2024 |
Feng H, Xu D, Jiang C, Chen Y, Wang J, Ren Z, et al., 'LINC01559 promotes lung adenocarcinoma metastasis by disrupting the ubiquitination of vimentin', BIOMARKER RESEARCH, 12 (2024) [C1]
|
|
Nova |
2024 |
Gu J, Cao H, Chen X, Zhang XD, Thorne RF, Liu X, 'RNA m6A modifications regulate crosstalk between tumor metabolism and immunity.', Wiley Interdiscip Rev RNA, 15 e1829 (2024) [C1]
|
|
|
2024 |
Zheng SM, Feng YC, Zhu Q, Li RQ, Yan QQ, Teng L, et al., 'MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.', Cancer Res, OF1-OF15 (2024) [C1]
|
|
|
2024 |
Xu L, Xiang W, Yang J, Gao J, Wang X, Meng L, et al., 'PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer', JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 43 (2024) [C1]
|
|
Nova |
2023 |
Li RQ, Zhao XH, Zhu Q, Liu T, Hondermarck H, Thorne RF, et al., 'Exploring neurotransmitters and their receptors for breast cancer prevention and treatment.', Theranostics, 13 1109-1129 (2023) [C1]
|
|
Nova |
2023 |
Feng J, Gong Z, Sun Z, Li J, Xu N, Thorne RF, et al., 'Microbiome and metabolic features of tissues and feces reveal diagnostic biomarkers for colorectal cancer', Frontiers in Microbiology, 14 (2023) [C1]
Microbiome and their metabolites are increasingly being recognized for their role in colorectal cancer (CRC) carcinogenesis. Towards revealing new CRC biomarkers, we compared 16S ... [more]
Microbiome and their metabolites are increasingly being recognized for their role in colorectal cancer (CRC) carcinogenesis. Towards revealing new CRC biomarkers, we compared 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC¿MS) metabolite analyses in 10 CRC (TCRC) and normal paired tissues (THC) along with 10 matched fecal samples (FCRC) and 10 healthy controls (FHC). The highest microbial phyla abundance from THC and TCRC were Firmicutes, while the dominant phyla from FHC and FCRC were Bacteroidetes, with 72 different microbial genera identified among four groups. No changes in Chao1 indices were detected between tissues or between fecal samples whereas non-metric multidimensional scaling (NMDS) analysis showed distinctive clusters among fecal samples but not tissues. LEfSe analyses indicated Caulobacterales and Brevundimonas were higher in THC than in TCRC, while Burkholderialese, Sutterellaceaed, Tannerellaceaea, and Bacteroidaceae were higher in FHC than in FCRC. Microbial association networks indicated some genera had substantially different correlations. Tissue and fecal analyses indicated lipids and lipid-like molecules were the most abundant metabolites detected in fecal samples. Moreover, partial least squares discriminant analysis (PLS-DA) based on metabolic profiles showed distinct clusters for CRC and normal samples with a total of 102 differential metabolites between THC and TCRC groups and 700 metabolites different between FHC and FCRC groups. However, only Myristic acid was detected amongst all four groups. Highly significant positive correlations were recorded between genus-level microbiome and metabolomics data in tissue and feces. And several metabolites were associated with paired microbes, suggesting a strong microbiota-metabolome coupling, indicating also that part of the CRC metabolomic signature was attributable to microbes. Suggesting utility as potential biomarkers, most such microbiome and metabolites showed directionally consistent changes in CRC patients. Nevertheless, further studies are needed to increase sample sizes towards verifying these findings.
|
|
Nova |
2023 |
Du X, Wei H, Zhang B, Pang LK, Zhao R, Zhang XD, Yao W, 'Unveiling the prognostic implications of RPLP1 upregulation in osteosarcoma.', Am J Cancer Res, 13 4822-4831 (2023) [C1] |
|
Nova |
2023 |
Gao E, Sun X, Thorne RF, Zhang XD, Li J, Shao F, et al., 'NIPSNAP1 directs dual mechanisms to restrain senescence in cancer cells', Journal of Translational Medicine, 21 (2023) [C1]
Background: Although the executive pathways of senescence are known, the underlying control mechanisms are diverse and not fully understood, particularly how cancer cells avoid tr... [more]
Background: Although the executive pathways of senescence are known, the underlying control mechanisms are diverse and not fully understood, particularly how cancer cells avoid triggering senescence despite experiencing exacerbated stress conditions within the tumor microenvironment. Methods: Mass spectrometry (MS)-based proteomic screening was used to identify differentially regulated genes in serum-starved hepatocellular carcinoma cells and RNAi employed to determine knockdown phenotypes of prioritized genes. Thereafter, gene function was investigated using cell proliferation assays (colony-formation, CCK-8, Edu incorporation and cell cycle) together with cellular senescence assays (SA-ß-gal, SAHF and SASP). Gene overexpression and knockdown techniques were applied to examine mRNA and protein regulation in combination with luciferase reporter and proteasome degradation assays, respectively. Flow cytometry was applied to detect changes in cellular reactive oxygen species (ROS) and in vivo gene function examined using a xenograft model. Results: Among the genes induced by serum deprivation, NIPSNAP1 was selected for investigation. Subsequent experiments revealed that NIPSNAP1 promotes cancer cell proliferation and inhibits P27-dependent induction of senescence via dual mechanisms. Firstly, NIPSNAP1 maintains the levels of c-Myc by sequestering the E3 ubiquitin ligase FBXL14 to prevent the proteasome-mediated turnover of c-Myc. Intriguingly, NIPSNAP1 levels are restrained by transcriptional repression mediated by c-Myc-Miz1, with repression lifted in response to serum withdrawal, thus identifying feedback regulation between NIPSNAP1 and c-Myc. Secondly, NIPSNAP1 was shown to modulate ROS levels by promoting interactions between the deacetylase SIRT3 and superoxide dismutase 2 (SOD2). Consequent activation of SOD2 serves to maintain cellular ROS levels below the critical levels required to induce cell cycle arrest and senescence. Importantly, the actions of NIPSNAP1 in promoting cancer cell proliferation and preventing senescence were recapitulated in vivo using xenograft models. Conclusions: Together, these findings reveal NIPSNAP1 as an important mediator of c-Myc function and a negative regulator of cellular senescence. These findings also provide a theoretical basis for cancer therapy where targeting NIPSNAP1 invokes cellular senescence.
|
|
|
2023 |
La T, Chen S, Zhao XH, Zhou S, Xu R, Teng L, et al., 'LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells.', Adv Sci (Weinh), 10 e2204599 (2023) [C1]
|
|
Nova |
2023 |
Geng H, Feng C, Sun Z, Fan X, Xie Y, Gu J, et al., 'Chloride intracellular channel 1 promotes esophageal squamous cell carcinoma proliferation via mTOR signalling.', Transl Oncol, 27 101560 (2023) [C1]
|
|
Nova |
2023 |
Cao L, Wang R, Liu G, Zhang Y, Thorne RF, Zhang XD, et al., 'Glycolytic Pfkp acts as a Lin41 protein kinase to promote endodermal differentiation of embryonic stem cells.', EMBO Rep, 24 e55683 (2023) [C1]
|
|
Nova |
2022 |
Li D, Hu LN, Zheng SM, La T, Wei LY, Zhang XJ, et al., 'High nerve density in breast cancer is associated with poor patient outcome', FASEB BioAdvances, 4 391-401 (2022) [C1]
Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerv... [more]
Active crosstalk between the nervous system and breast cancer cells has been experimentally demonstrated in vitro and in animal models. However, low frequencies of peripheral nerve presence in human breast cancers reported in previous studies (~30% of cases) potentially negate a major role of the nervous system in breast cancer development and progression. This study aimed to clarify the incidence of nerves within human breast cancers and to delineate associations with clinicopathological features. Immunohistochemical staining was conducted in formalin-fixed paraffin-embedded breast cancer tissue sections using antibodies against the pan-neuronal markers protein gene product 9.5 and growth-associated protein 43, and the sympathetic nerve-specific marker tyrosine hydroxylase. Nerve trunks and isolated nerve fibers were quantitated. The chi-squared test was used to determine the associations between nerve counts and clinicopathological parameters. The log-rank test was used to compare differences in patient progression-free survival (PFS) and overall survival (OS). The overall frequency of peripheral nerves in breast cancers was 85%, a markedly higher proportion than reported previously. Of note, most nerves present in breast cancers were of the sympathetic origin. While high density of nerve trunks or isolated nerve fibers was associated with poor PFS and OS of patients, high nerve trunk density appeared also to predict poor patient PFS independently of lymph node metastasis. Innervation of breast cancers is a common event correlated with poor patient outcomes. These findings support the notion that the nervous system plays an active role in breast cancer pathogenesis.
|
|
Nova |
2022 |
Gao H, Kan S, Ye Z, Feng Y, Jin L, Zhang X, et al., 'Development of in silico methodology for siRNA lipid nanoparticle formulations', Chemical Engineering Journal, 442 (2022) [C1]
|
|
Nova |
2022 |
Mamun MMA, Khan MR, Zhu Y, Zhang Y, Zhou S, Xu R, et al., 'Stub1 maintains proteostasis of master transcription factors in embryonic stem cells', Cell Reports, 39 (2022) [C1]
The pluripotency and differentiation states of embryonic stem cells (ESCs) are regulated by a set of core transcription factors, primarily Sox2, Oct4, and Nanog. Although their tr... [more]
The pluripotency and differentiation states of embryonic stem cells (ESCs) are regulated by a set of core transcription factors, primarily Sox2, Oct4, and Nanog. Although their transcriptional regulation has been studied extensively, the contribution of posttranslational modifications in Sox2, Oct4, and Nanog are poorly understood. Here, using a CRISPR-Cas9 knockout library screen in murine ESCs, we identify the E3 ubiquitin ligase Stub1 as a negative regulator of pluripotency. Manipulation of Stub1 expression in murine ESCs shows that ectopic Stub1 expression significantly reduces the protein half-life of Sox2, Oct4, and Nanog. Mechanistic investigations reveal Stub1 catalyzes the polyubiquitination and 26S proteasomal degradation of Sox2 and Nanog through K48-linked ubiquitin chains and Oct4 via K63 linkage. Stub1 deficiency positively enhances somatic cell reprogramming and delays differentiation, whereas its enforced expression triggers ESC differentiation. The discovery of Stub1 as an integral pluripotency regulator strengthens our understanding of ESC regulation beyond conventional transcriptional control mechanisms.
|
|
Nova |
2022 |
Wang Y, Feng YC, Gan Y, Teng L, Wang L, La T, et al., 'LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma', JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 41 (2022) [C1]
|
|
Nova |
2022 |
Yang Y, Zhu Y, Zhou S, Tang P, Xu R, Zhang Y, et al., 'TRIM27 cooperates with STK38L to inhibit ULK1-mediated autophagy and promote tumorigenesis', EMBO JOURNAL, 41 (2022) [C1]
|
|
Nova |
2022 |
Chen Q, Yang B, Liu X, Zhang XD, Zhang L, Liu T, 'Histone acetyltransferases CBP/p300 in tumorigenesis and CBP/p300 inhibitors as promising novel anticancer agents', THERANOSTICS, 12 4935-4948 (2022) [C1]
|
|
Nova |
2022 |
Zhu Y, Jin L, Shi R, Li J, Wang Y, Zhang L, et al., 'The long noncoding RNA glycoLINC assembles a lower glycolytic metabolon to promote glycolysis', Molecular Cell, 82 542-554.e6 (2022) [C1]
Non-covalent complexes of glycolytic enzymes, called metabolons, were postulated in the 1970s, but the concept has been controversial. Here we show that a c-Myc-responsive long no... [more]
Non-covalent complexes of glycolytic enzymes, called metabolons, were postulated in the 1970s, but the concept has been controversial. Here we show that a c-Myc-responsive long noncoding RNA (lncRNA) that we call glycoLINC (gLINC) acts as a backbone for metabolon formation between all four glycolytic payoff phase enzymes (PGK1, PGAM1, ENO1, and PKM2) along with lactate dehydrogenase A (LDHA). The gLINC metabolon enhances glycolytic flux, increases ATP production, and enables cell survival under serine deprivation. Furthermore, gLINC overexpression in cancer cells promotes xenograft growth in mice fed a diet deprived of serine, suggesting that cancer cells employ gLINC during metabolic reprogramming. We propose that gLINC makes a functional contribution to cancer cell adaptation and provide the first example of a lncRNA-facilitated metabolon.
|
|
Nova |
2022 |
Wang PL, Teng L, Feng YC, Yue YM, Han MM, Yan Q, et al., 'The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119 (2022) [C1]
|
|
Nova |
2022 |
Marsland M, Dowdell A, Jiang CC, Wilmott JS, Scolyer RA, Zhang XD, et al., 'Expression of NGF/proNGF and Their Receptors TrkA, p75(NTR) and Sortilin in Melanoma', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (2022) [C1]
|
|
Nova |
2021 |
Wang R, Cao L, Thorne RF, Zhang XD, Li J, Shao F, et al., 'LncRNA GIRGL drives CAPRIN1-mediated phase separation to suppress glutaminase-1 translation under glutamine deprivation.', Sci Adv, 7 (2021) [C1]
|
|
Nova |
2021 |
Chen S, Thorne RF, Zhang XD, Wu M, Liu L, 'Non-coding RNAs, guardians of the p53 galaxy', Seminars in Cancer Biology, 75 72-83 (2021) [C1]
The TP53 gene is arguably the most important tumor suppressor gene known, contributing multifaceted roles to the process of tumor development. Its protein product p53, is a crucia... [more]
The TP53 gene is arguably the most important tumor suppressor gene known, contributing multifaceted roles to the process of tumor development. Its protein product p53, is a crucial sequence-specific transcription factor which regulates the expression of a large network of protein-coding genes, as well as thousands of noncoding RNAs (ncRNAs), notably microRNAs and long ncRNAs (lncRNAs). Through a variety of direct and indirect mechanisms, ncRNAs in turn modulate p53 levels and activity. Here the numbers of studies are steadily building which link the contributions of dysregulated ncRNAs to tumorigenesis via their participation throughout the p53 regulatory network. In this review, we will examine how the principal forms of ncRNAs, namely microRNAs, lncRNAs and circular RNAs (circRNAs) function as either effectors or regulators amongst the diversity of p53's cellular responses. We first discuss the more recently discovered connections between miRNAs and p53 signaling before focusing on the remarkable diversity of crosstalk evident between lncRNAs and p53, and subsequently, developing reports linking circRNAs to p53. Highlighted throughout the review are the mechanistic impacts of dysregulated ncRNAs on p53 functions as well as the possible prognostic implications of these interactions. We also describe the emerging connections between ncRNAs and the often-perplexing functions of mutant p53. Finally, in the context of p53 therapeutic approaches, we describe some of the challenges in ncRNA research and their potential for translation.
|
|
Nova |
2021 |
Li M, Thorne RF, Shi R, Zhang XD, Li J, Li J, et al., 'DDIT3 Directs a Dual Mechanism to Balance Glycolysis and Oxidative Phosphorylation during Glutamine Deprivation', Advanced Science, 8 (2021) [C1]
Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened meta... [more]
Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened metabolic activity within tumor tissues can result in glutamine deficiency, necessitating metabolic reprogramming responses. Here, dual mechanisms involving the stress-responsive transcription factor DDIT3 (DNA damage induced transcript 3) that establishes an interrelationship between glycolysis and mitochondrial respiration are revealed. DDIT3 is induced during glutamine deprivation to promote glycolysis and adenosine triphosphate production via suppression of the negative glycolytic regulator TIGAR. In concert, a proportion of the DDIT3 pool translocates to the mitochondria and suppresses oxidative phosphorylation through LONP1-mediated down-regulation of COQ9 and COX4. This in turn dampens the sustained levels of reactive oxygen species that follow glutamine withdrawal. Together these mechanisms constitute an adaptive survival mechanism permitting tumor cells to survive metabolic stress induced by glutamine starvation.
|
|
|
2021 |
Teng L, Feng YC, Guo ST, Wang PL, Qi TF, Yue YM, et al., 'The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis', NATURE COMMUNICATIONS, 12 (2021) [C1]
|
|
Nova |
2021 |
Nabil WNN, Xi Z, Song Z, Jin L, Zhang XD, Zhou H, et al., 'Towards a framework for better understanding of quiescent cancer cells', Cells, 10 1-19 (2021) [C1]
Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, ca... [more]
Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, cancer recurrence and metastasis. QCCs are also therapeutically challenging due to their resistance to most conventional cancer treatments that selectively act on proliferating cells. Considering the significant impact of QCCs on cancer progression and treatment, better understanding of appropriate experimental models, and the evaluation of QCCs are key questions in the field that have direct influence on potential pharmacological interventions. Here, this review focuses on existing and emerging preclinical models and detection methods for QCCs and discusses their respective features and scope for application. By providing a framework for selecting appropriate experimental models and investigative methods, the identification of the key players that regulate the survival and activation of QCCs and the development of more effective QCC-targeting therapeutic agents may mitigate the consequences of QCCs.
|
|
Nova |
2021 |
La T, Chen S, Guo T, Zhao XH, Teng L, Li D, et al., 'Visualization of endogenous p27 and Ki67 reveals the importance of a c-Myc-driven metabolic switch in promoting survival of quiescent cancer cells', THERANOSTICS, 11 9605-9622 (2021) [C1]
|
|
Nova |
2021 |
Zhang C, Shen L, Zhu Y, Xu R, Deng Z, Liu X, et al., 'KDM6A promotes imatinib resistance through YY1-mediated transcriptional upregulation of TRKA independently of its demethylase activity in chronic myelogenous leukemia', THERANOSTICS, 11 2691-2705 (2021) [C1]
|
|
Nova |
2021 |
Feng YC, Zhao XH, Teng L, Thorne RF, Jin L, Zhang XD, 'The pan-cancer lncRNA MILIP links c-Myc to p53 repression', MOLECULAR & CELLULAR ONCOLOGY, 8 (2021)
|
|
|
2021 |
Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al., 'Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)', AUTOPHAGY, 17 1-382 (2021)
|
|
|
2021 |
Chen J, Nelson C, Wong M, Tee AE, Liu PY, La T, et al., 'Targeted Therapy of
|
|
Nova |
2021 |
Lan Q, Liu PY, Bell JL, Wang JY, Huttelmaier S, Zhang XD, et al., 'The Emerging Roles of RNA m
|
|
Nova |
2021 |
Shuai T, Khan MR, Zhang XD, Li J, Thorne RF, Wu M, Shao F, 'lncRNA TRMP-S directs dual mechanisms to regulate p27-mediated cellular senescence', MOLECULAR THERAPY-NUCLEIC ACIDS, 24 971-985 (2021) [C1]
|
|
Nova |
2021 |
Sang B, Zhang YY, Guo ST, Kong LF, Cheng Q, Liu GZ, et al., 'Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence (vol 115, pg E11661, 2018)', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 118 (2021)
|
|
|
2020 |
Yu S, Wang F, Bi Y, Wang P, Zhang R, Bohatko-Naismith J, et al., 'Autophagy regulates the Wnt/GSK3ß/ß-catenin/cyclin D1 pathway in mesenchymal stem cells (MSCs) exposed to titanium dioxide nanoparticles (TiO
|
|
Nova |
2020 |
Sun X, Thorne RF, Zhang XD, He M, Li J, Feng S, et al., 'LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1a-FOXO4-p21-dependent signaling axis', EMBO Reports, 21 (2020) [C1]
|
|
Nova |
2020 |
Wei LY, Zhang XJ, Wang L, Hu LN, Zhang XD, Li L, Gao JN, 'A six-epithelial mesenchymal transition gene signature may predict metastasis of triple-negative breast cancer', OncoTargets and Therapy, 13 6497-6509 (2020) [C1]
Purpose: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favourable outcomes of patients with triple-negative breast cancer (TNBC). Howe... [more]
Purpose: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favourable outcomes of patients with triple-negative breast cancer (TNBC). However, a proportion of TNBC patients with the residual disease do not relapse and achieve long-term survival. The aim of this study was to identify biomarkers that predict clinical outcomes in these patients. Patients and Methods: A retrospective series of 10 TNBC patients who displayed non-pCR to NACT were included in the discovery cohort. Total RNA from pre-NACT core biopsies and paired surgical specimens were subjected to the Affymetrix Human Transcriptome Array. Gene set enrichment analysis (GSEA) was used to identify signal pathways and gene signatures associated with metastasis. The Cox proportional hazard model and Kaplan¿Meier survival curves were employed to assess the prognostic value of the identified signature in two independent TNBC datasets included in Gene Expression Omnibus (GEO). Results: The epithelial¿mesenchymal transition (EMT) pathway was markedly more enriched in pre-(NES = 1.92; p.adjust = 0.019) and post-NACT samples (NES = 2.02; p. adjust = 0.010) from patients who developed metastasis after NACT. A subset of 6 EMT genes including LUM, SFRP4, COL6A3, MMP2, CXCL12, and HTRA1 were expressed constantly at higher levels in samples from patients who progressed to metastatic disease. The potential of the 6-EMT gene signature to predict TNBC metastasis after NACT was validated with a GEO dataset (HR=0.36, p=0.0008, 95% CI: 0.200¿0.658). Moreover, the signature appeared of predictive value in another GEO dataset of TNBC patients who received surgery followed by adjuvant chemotherapy (HR = 0.46, 95% CI: 0.225¿0.937). Conclusion: Expression analysis of the 6-EMT gene signature at diagnosis may be of predictive value for metastasis in TNCB patients who did not achieve pCR to NACT and for patients treated with surgery in combination with adjuvant therapy.
|
|
Nova |
2020 |
Feng YC, Liu XY, Teng L, Ji Q, Wu Y, Li JM, et al., 'c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis', Nature Communications, 11 (2020) [C1]
|
|
Nova |
2020 |
Xu CL, Sang B, Liu GZ, Li JM, Zhang XD, Liu LX, et al., 'SENEBLOC, a long non-coding RNA suppresses senescence via p53-dependent and independent mechanisms', Nucleic Acids Research, 48 3089-3102 (2020) [C1]
|
|
Nova |
2020 |
Thorne RF, Wang Y, Zhang Y, Jing X, Zhang XD, de Bock CE, Oliveira CS, 'Evaluating nuclear translocation of surface receptors: recommendations arising from analysis of CD44', Histochemistry and Cell Biology, 153 77-87 (2020) [C1]
|
|
Nova |
2020 |
Liu X, Feng S, Zhang XD, Li J, Zhang K, Wu M, Thorne RF, 'Non-coding RNAs, metabolic stress and adaptive mechanisms in cancer.', Cancer Letters, 491 60-69 (2020) [C1]
|
|
Nova |
2020 |
La T, Jin L, Liu XY, Song ZH, Farrelly M, Feng YC, et al., 'Cylindromatosis is required for survival of a subset of melanoma cells.', Oncology Research, 28 385-398 (2020) [C1]
|
|
Nova |
2019 |
Li Q, Wang Y, Wu S, Zhou Z, Ding X, Shi R, et al., 'CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress', CELL METABOLISM, 30 157-+ (2019) [C1]
|
|
Nova |
2019 |
Liu PY, Tee AE, Milazzo G, Hannan KM, Maag J, Mondal S, et al., 'The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.', Nature communications, 10 5026 (2019) [C1]
|
|
Nova |
2019 |
Lei FX, Jin L, Liu XY, Lai F, Yan XG, Farrelly M, et al., 'RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors (vol 9, 679, 2018)', CELL DEATH & DISEASE, 10 (2019)
|
|
|
2019 |
Wong M, Sun Y, Xi Z, Milazzo G, Poulos RC, Bartenhagen C, et al., 'JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma', NATURE COMMUNICATIONS, 10 (2019) [C1]
|
|
Nova |
2019 |
Yari H, Jin L, Teng L, Wang Y, Wu Y, Liu GZ, et al., 'LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription', NATURE COMMUNICATIONS, 10 (2019) [C1]
|
|
Nova |
2019 |
Gao W, An C, Xue X, Zheng X, Niu M, Zhang Y, et al., 'Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1-Binding Proteins in Laryngeal Squamous Cell Carcinoma', PROTEOMICS, 19 (2019) [C1]
|
|
Nova |
2019 |
Yu S, Mu Y, Zhang X, Li J, Lee C, Wang H, 'Molecular mechanisms underlying titanium dioxide nanoparticles (TiO2NP) induced autophagy in mesenchymal stem cells (MSC)', Journal of Toxicology and Environmental Health - Part A: Current Issues, 82 997-1008 (2019) [C1]
|
|
Nova |
2018 |
Wang YF, Liu F, Sherwin S, Farrelly M, Yan XG, Croft A, et al., 'Cooperativity of HOXA5 and STAT3 Is Critical for HDAC8 Inhibition-Mediated Transcriptional Activation of PD-L1 in Human Melanoma Cells', Journal of Investigative Dermatology, 138 922-932 (2018) [C1]
Although the expression of programmed death-ligand 1 (PD-L1) is an important mechanism by which cancer cells evade the immune system, PD-L1 expression in cancer cells is commonly ... [more]
Although the expression of programmed death-ligand 1 (PD-L1) is an important mechanism by which cancer cells evade the immune system, PD-L1 expression in cancer cells is commonly associated with patients¿ responses to treatment with anti-programmed death 1/PD-L1 antibodies. However, how PD-L1 expression is regulated in melanoma cells remains to be fully elucidated. Here we report that the class I histone deacetylase (HDAC) HDAC8 controls transcriptional activation of PD-L1 by a transcription complex consisting of transcription factors homeobox A5 and signal transducer and activator of transcription 3. Inhibition of HDAC8 upregulated PD-L1 in melanoma cells. This was due to an increase in the activity of a fragment of the PD-L1 gene promoter that is enriched with binding sites for both homeobox A5 and signal transducer and activator of transcription 3. Indeed, knockdown of homeobox A5 or signal transducer and activator of transcription 3 abolished upregulation of PD-L1 by HDAC8 inhibition. Moreover, homeobox A5 and signal transducer and activator of transcription 3 were physically associated and appeared interdependent in activating PD-L1 transcription. Functional studies showed that HDAC8-mediated regulation of PD-L1 expression participated in modulating anti-melanoma T-cell responses. Collectively, these results identify HDAC8 as an important epigenetic regulator of PD-L1 expression, with implications for better understanding of the interaction between melanoma cells and the immune system.
|
|
Nova |
2018 |
Sang B, Zhang YY, Guo ST, Kong LF, Cheng Q, Liu GZ, et al., 'Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence', Proceedings of the National Academy of Sciences of the United States of America, 115 E11661-E11670 (2018) [C1]
Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in c... [more]
Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mito-gen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc¿mediated cell proliferation and Mcl-1¿mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)¿mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.
|
|
Nova |
2018 |
Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD, Wu M, 'GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.', Nature Cell Biology, 20 492-502 (2018) [C1]
|
|
Nova |
2018 |
La T, Liu GZ, Farrelly M, Cole N, Feng YC, Zhang YY, et al., 'A p53-responsive miRNA network promotes cancer cell quiescence', Cancer Research, 78 6666-6679 (2018) [C1]
Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show... [more]
Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show that two p53-responsive miRNAs utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or miRNA-455-3p reduced, whereas its overexpression increased, the proportion of quiescent cells in the population, indicating that these miRNAs promote cancer cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455-3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted CDK2-associated cullin domain 1 (CAC1), which enhanced CDK2-mediated phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment. Significance: Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment.
|
|
Nova |
2018 |
Wang CY, Guo ST, Croft A, Yan XG, Jin L, Zhang XD, Jiang CC, 'BAG3-dependent expression of Mcl-1 confers resistance of mutant KRAS colon cancer cells to the HSP90 inhibitor AUY922', Molecular Carcinogenesis, 57 284-294 (2018) [C1]
Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance rem... [more]
Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance remains an obstacle for the potential application of the inhibitor in the treatment of the disease. Here we report that Mcl-1 is important for survival of colon cancer cells in the presence of AUY922. Mcl-1 was upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922-induced apoptosis. This was due to its increased stability mediated by Bcl-2-associated athanogene domain 3 (BAG3), which was also increased in resistant colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic endoplasmic reticulum (ER) stress. Functional investigations demonstrated that inhibition of Mcl-1, BAG3, or HSF1 triggered apoptosis in resistant colon cancer cells, and rendered AUY922-naïve colon cancer cells more sensitive to the inhibitor. Together, these results identify that the HSF1-BAG3-Mcl-1 signal axis is critical for protection of mutant KRAS colon cancer cells from AUY922-induced apoptosis, with potential implications for targeting HSF1/BAG3/Mcl-1 to improve the efficacy of AUY922 in the treatment of colon cancer.
|
|
Nova |
2018 |
Faulkner S, Jobling P, Rowe CW, Rodrigues Oliveira SM, Roselli S, Thorne RF, et al., 'Neurotrophin Receptors TrkA, p75
Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor k... [more]
Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75NTR, and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75NTR was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75NTR, and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75NTR, and sortilin as potential therapeutic targets in thyroid cancer.
|
|
Nova |
2018 |
Sahoo SS, Zhang XD, Hondermarck H, Tanwar PS, 'The Emerging Role of the Microenvironment in Endometrial Cancer', CANCERS, 10 (2018) [C1]
|
|
Nova |
2018 |
Xiang S, Gu H, Jin L, Thorne RF, Zhang XD, Wu M, 'LncRNA IDH1-AS1 links the functions of c-Myc and HIF1a via IDH1 to regulate the Warburg effect', Proceedings of the National Academy of Sciences of the United States of America, 115 E1465-E1474 (2018) [C1]
The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1a, which is essential for driving glycolysis under hypoxia, is oft... [more]
The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1a, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two major regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1a in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased a-KG and decreased ROS production and subsequent HIF1a down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1a. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment.
|
|
Nova |
2018 |
Lei FX, Jin L, Liu XY, Lai F, Yan XG, Farrelly M, et al., 'RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors article', Cell Death and Disease, 9 (2018) [C1]
|
|
Nova |
2018 |
Zhang YY, Tabataba H, Liu XY, Wang JY, Yan XG, Farrelly M, et al., 'ACTN4 regulates the stability of RIPK1 in melanoma', ONCOGENE, 37 4033-4045 (2018) [C1]
|
|
Nova |
2017 |
Liu X, Cao H, Li J, Wang B, Zhang P, Dong Zhang X, et al., 'Autophagy induced by DAMPs facilitates the inflammation response in lungs undergoing ischemia-reperfusion injury through promoting TRAF6 ubiquitination.', Cell Death Differ, 24 683-693 (2017) [C1]
|
|
Nova |
2017 |
Croft A, Guo ST, Sherwin S, Farrelly M, Yan XG, Zhang XD, Jiang CC, 'Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells', Biochemical and Biophysical Research Communications, 485 47-53 (2017) [C1]
The 4-phosphatase Inositol polyphosphate 4-phosphatase II (INPP4B) is a regulator of the PI3K signalling pathway and functions to suppress or promote activation of downstream kina... [more]
The 4-phosphatase Inositol polyphosphate 4-phosphatase II (INPP4B) is a regulator of the PI3K signalling pathway and functions to suppress or promote activation of downstream kinases depending on cell type and context. Here we report the identification of a novel small transcript variant of INPP4B (INPP4B-S) that has a role in promoting proliferation of colon and breast cancer cells. INPP4B-S differed from full length INPP4B (INPP4B-FL) by the insertion of a small exon between exons 15 and 16 and the deletion of exons 20¿24. Nevertheless, INPP4B-S retained all the functional domains of INPP4B-FL and was similarly located to the cytoplasm. Overexpression of INPP4B-S increased, whereas selective knockdown of INPP4B-S reduced the rate of proliferation in HCT116 and MCF-7¿cells. These results warrant further investigation of the role INPP4B-S in activation of downstream kinases and in regulation of cancer pathogenesis.
|
|
Nova |
2017 |
Guo ST, Guo XY, Wang J, Wang CY, Yang RH, Wang FH, et al., 'MicroRNA-645 is an oncogenic regulator in colon cancer', ONCOGENESIS, 6 (2017) [C1]
|
|
Nova |
2017 |
Wang JY, Liu GZ, Wilmott JS, La T, Feng YC, Yari H, et al., 'Skp2-mediated stabilization of MTH1 promotes survival of melanoma cells upon oxidative stress', Cancer Research, 77 6226-6239 (2017) [C1]
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is reg... [more]
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. In melanoma cell lines and patient specimens, we observed a positive correlation of Skp2 and MTH1 expression. Mechanistic investigations showed that Skp2 limited DNA damage and apoptosis triggered by oxidative stress and that MAPK upregulated Skp2 and MTH1 to render cells more resistant to such stress. Collectively, our findings identify Skp2-mediated K63-linked polyubiquitination as a critical regulatory mechanism responsible for MTH1 upregulation in melanoma, with potential implications to target the MAPK/Skp2/MTH1 pathway to improve its treatment.
|
|
Nova |
2017 |
Yu S, Bohatko-Naismith J, Zhang X, Zhou X, Wang P, Wang H, 'Cellular responses in titanium dioxide nanoparticle cytotoxicity studies: parts of the map waiting to be composed', Journal of Medicinal Chemistry and Toxicology, 2 1-9 (2017) [C1]
|
|
Nova |
2017 |
Wong M, Tee AEL, Milazzo G, Bell JL, Poulos RC, Atmadibrata B, et al., 'The histone methyltransferase DOT1L promotes neuroblastoma by regulating gene transcription', Cancer Research, 77 2522-2533 (2017) [C1]
|
|
Nova |
2016 |
Chen J, Jiang CC, Jin L, Zhang XD, 'Regulation of PD-L1: A novel role of pro-survival signalling in cancer', Annals of Oncology, 27 409-416 (2016) [C1]
Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling pro... [more]
Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes. However, only a proportion of patients respond to the treatments. Further understanding of the regulation of PD-L1 expression could be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors and epigenetic factors. In this review, we summarise the recent progress of the regulation of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation. Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible factor-1a and signal transducer and activation of transcription-3 act on the promoter of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513, miR-197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD-L1 expression and cell proliferation.
|
|
Nova |
2016 |
Yanwang C, Guo ST, Yuwang J, Liu F, Zhang YY, Yari H, et al., 'Inhibition of HSP90 by AUY922 preferentially kills mutantkrascolon cancer cellsbyactivatingbim through ER stress', Molecular Cancer Therapeutics, 15 448-459 (2016) [C1]
Oncogenic mutations of KRAS pose a great challenge in the treatment of colorectal cancer. Here we report that mutant KRAS colon cancer cells are nevertheless more susceptible to a... [more]
Oncogenic mutations of KRAS pose a great challenge in the treatment of colorectal cancer. Here we report that mutant KRAS colon cancer cells are nevertheless more susceptible to apoptosis induced by the HSP90 inhibitor AUY922 than those carrying wild-type KRAS. Although AUY922 inhibited HSP90 activity with comparable potency in colon cancer cells irrespective of their KRAS mutational statuses, those with mutant KRAS were markedly more sensitive to AUY922-induced apoptosis. This was associated with upregulation of the BH3-only proteins Bim, Bik, and PUMA.However, only Bim appeared essential, in that knockdown of Bim abolished, whereas knockdown of Bik or PUMA only moderately attenuated apoptosis induced by AUY922. Mechanistic investigations revealed that endoplasmic reticulum (ER) stress was responsible for AUY922-induced upregulation of Bim, which was inhibited by a chemical chaperone or overexpression of GRP78. Conversely, siRNA knockdown of GRP78 or XBP-1 enhanced AUY922-induced apoptosis. Remarkably, AUY922 inhibited the growth of mutant KRAS colon cancer xenografts through activation of Bim that was similarly associated with ER stress. Taken together, these results suggest that AUY922 is a promising drug in the treatment of mutant KRAS colon cancers, and the agents that enhance the apoptosis-inducing potential of Bimmaybe useful to improve the therapeutic efficacy.
|
|
Nova |
2016 |
Yang RH, Tian RF, Ren QL, Chui HY, Guo ST, Zhang XD, Song X, 'Serum protein profiles of patients with lung cancer of different histological types', Asia-Pacific Journal of Clinical Oncology, 12 70-76 (2016) [C1]
Aims: To compare serum protein expression profiles between lung cancer patients and healthy individuals, and to examine whether there are differences in serum protein expression p... [more]
Aims: To compare serum protein expression profiles between lung cancer patients and healthy individuals, and to examine whether there are differences in serum protein expression profiles among patients with lung cancers of different histological types and whether the characteristic expression of serum proteins may assist in differential diagnosis of various subtypes of lung cancers. Methods: Blood samples were collected from 123 lung cancer patients before commencement of treatment who attended Shanxi Cancer Hospital, China, between 2008 and 2013. Blood samples from 60 healthy individuals were also collected in the same period. Serum protein expression profiles were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The differences in the serum protein spectrums of lung cancer patients with different histological subtypes were analyzed by one-way Analysis of Variance and receiver operating characteristic curves. Results: A cluster of 48 protein mass-to-change ratio (M/Z) peaks was differentially expressed between sera of lung cancer patients and healthy individuals. The M/Z 1205, 4673, 1429 and 4279 peaks were differentially expressed among patients with lung squamous cell carcinomas, adenocarcinomas and small-cell lung carcinomas. Conclusion: These results reinforce the notion that profiling of serum proteins may be of diagnostic value in lung cancer, and suggest that the differences in serum protein profiles may be useful in differential diagnosis of lung cancers of varying histological subtypes.
|
|
Nova |
2016 |
Wang JY, Jin L, Yan XG, Sherwin S, Farrelly M, Zhang YY, et al., 'Reactive Oxygen Species Dictate the Apoptotic Response of Melanoma Cells to TH588', Journal of Investigative Dermatology, 136 2277-2286 (2016) [C1]
The effect of MTH1 inhibition on cancer cell survival has been elusive. Here we report that although silencing of MTH1 does not affect survival of melanoma cells, TH588, one of th... [more]
The effect of MTH1 inhibition on cancer cell survival has been elusive. Here we report that although silencing of MTH1 does not affect survival of melanoma cells, TH588, one of the first-in-class MTH1 inhibitors, kills melanoma cells through apoptosis independently of its inhibitory effect on MTH1. Induction of apoptosis by TH588 was not alleviated by MTH1 overexpression or introduction of the bacterial homolog of MTH1 that has 8-oxodGTPase activity but cannot be inhibited by TH588, indicating that MTH1 inhibition is not the cause of TH588-induced killing of melanoma cells. Although knockdown of MTH1 did not impinge on the viability of melanoma cells, it rendered melanoma cells sensitive to apoptosis induced by the oxidative stress inducer elesclomol. Of note, treatment with elesclomol also enhanced TH588-induced apoptosis, whereas a reactive oxygen species scavenger or an antioxidant attenuated the apoptosis triggered by TH588. Indeed, the sensitivity of melanoma cells to TH588 was correlated with endogenous levels of reactive oxygen species. Collectively, these results indicate that the cytotoxicity of TH588 toward melanoma cells is not associated with its inhibitory effect on MTH1, although it is mediated by cellular production of ROS.
|
|
Nova |
2016 |
Wang CY, Guo ST, Wang JY, Yan XG, Farrelly M, Zhang YY, et al., 'Reactivation of ERK and Akt confers resistance of mutant BRAF colon cancer cells to the HSP90 inhibitor AUY922', Oncotarget, 7 49597-49610 (2016) [C1]
Oncogenic mutations of BRAF occur in approximately 10% of colon cancers and are associated with their resistance to clinically available therapeutic drugs and poor prognosis of th... [more]
Oncogenic mutations of BRAF occur in approximately 10% of colon cancers and are associated with their resistance to clinically available therapeutic drugs and poor prognosis of the patients. Here we report that colon cancer cells with mutant BRAF are also resistant to the heat shock protein 90 (HSP90) inhibitor AUY922, and that this is caused by rebound activation of ERK and Akt. Although AUY922 triggered rapid reduction in ERK and Akt activation in both wild-type and mutant BRAF colon cancer cells, activation of ERK and Akt rebounded shortly in the latter leading to resistance of the cells to AUY922-induced apoptosis. Reactivation of ERK was associated with the persistent expression of mutant BRAF, which, despite being a client of HSP90, was only partially degraded by AUY922, whereas reactivation of Akt was related to the activity of the HSP90 co-chaperone, cell division cycle 37 (CDC37), in that knockdown of CDC37 inhibited Akt reactivation in mutant colon cancer cells treated with AUY922. In support, as a HSP90 client protein, Akt was only diminished by AUY922 in wild-type but not mutant BRAF colon cancer cells. Collectively, these results reveal that reactivation of ERK and Akt associated respectively with the activity of mutant BRAF and CDC37 renders mutant BRAF colon cancer cells resistant to AUY922, with implications of co-targeting mutant BRAF and/or CDC37 and HSP90 in the treatment of mutant BRAF colon cancers.
|
|
Nova |
2016 |
Liu PY, Sokolowski N, Guo ST, Siddiqi F, Atmadibrata B, Telfer TJ, et al., 'The BET bromodomain inhibitor exerts the most potent synergistic anticancer effects with quinone-containing compounds and anti-microtubule drugs', Oncotarget, 7 79217-79232 (2016) [C1]
BET bromodomain inhibitors are very promising novel anticancer agents, however, single therapy does not cause tumor regression in mice, suggesting the need for combination therapy... [more]
BET bromodomain inhibitors are very promising novel anticancer agents, however, single therapy does not cause tumor regression in mice, suggesting the need for combination therapy. After screening a library of 2697 small molecule compounds, we found that two classes of compounds, the quinone-containing compounds such as nanaomycin and anti-microtubule drugs such as vincristine, exerted the best synergistic anticancer effects with the BET bromodomain inhibitor JQ1 in neuroblastoma cells. Mechanistically, the quinone-containing compound nanaomycin induced neuroblastoma cell death but also activated the Nrf2-antioxidant signaling pathway, and the BET bromodomain proteins BRD3 and BRD4 formed a protein complex with Nrf2. Treatment with JQ1 blocked the recruitment of Nrf2 to the antioxidant responsive elements at Nrf2 target gene promoters, and JQ1 exerted synergistic anticancer effects with nanaomycin by blocking the Nrf2-antioxidant signaling pathway. JQ1 and vincristine synergistically induced neuroblastoma cell cycle arrest at the G2/M phase, aberrant mitotic spindle assembly formation and apoptosis, but showed no effect on cell survival in normal non-malignant cells. Importantly, co-treatment with JQ1 and vincristine synergistically suppressed tumor progression in neuroblastoma-bearing mice. These results strongly suggest that patients treated with BET bromodomain inhibitors in clinical trials should be co-treated with vincristine.
|
|
Nova |
2016 |
Jin L, Chen J, Liu XY, Jiang CC, Zhang XD, 'The double life of RIPK1.', Mol Cell Oncol, 3 e1035690 (2016) [C1]
|
|
Nova |
2016 |
Jiang CC, Croft A, Tseng HY, Guo ST, Jin L, Hersey P, Zhang XD, 'Repression of microRNA-768-3p by MEK/ERK signalling contributes to enhanced mRNA translation in human melanoma', Oncogene, (2016)
|
|
|
2016 |
Wang JY, Jiang CC, Yan XG, Jin L, Zhang XD, 'TH588 Potently Kills Melanoma Cells Grown in 3-Dimensional Culture Through Apoptosis Induced by ROS', Archives in Cancer Research, 4
|
|
|
2016 |
Zhang Z, Li HM, Zhou C, Li Q, Ma L, Zhang Z, et al., 'Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells', Journal of Experimental and Clinical Cancer Research, 35 1-13 (2016) [C1]
Background: Hsp90 proteins are important therapeutic targets for many anti-cancer drugs in clinical trials. Geldanamycin (GA) was identified as the first natural inhibitor of Hsp9... [more]
Background: Hsp90 proteins are important therapeutic targets for many anti-cancer drugs in clinical trials. Geldanamycin (GA) was identified as the first natural inhibitor of Hsp90, increasing evidence suggests that GA was not a good choice for clinical trials. In this study, we investigated two new non-benzoquinone geldanamycin analogs of Hsp90 inhibitors, DHQ3 and 17-demethoxy-reblastatin (17-DR), to explore the molecular mechanisms of their anti-cancer activity in vivo and vitro. Methods: MTT and colony formation assays were used to measure cell viability. Flow cytometry, DAPI staining, ATP assay, electron microscopy, western blots, siRNAs transfection and immunofluorescence were used to determine the molecular mechanism of DHQ3- or 17-DR-induced different forms of death in human breast cancer MDA-MB-231 cells. Malachite green reagent was used to measure ATPase activity of the analogs. Results: DHQ3 and 17-DR presented efficiently inhibitory effect in MDA-MB-231 cell lines, and DHQ3 induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade. And DHQ3-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), but not by a caspase inhibitor z-VAD-fmk. On the other hand, 17-DR induced apoptosis in MDA-MB-231 cells, indicating a caspase-dependent killing mechanism. We further demonstrated that down-regulation of RIP1 and RIP3 by siRNA protected against DHQ3 but not 17-DR induced cell death. These results were confirmed by electron microscopy. DHQ3 and 17-DR induced the degradation of Hsp90 client proteins, and they showed strong antitumor effects in MDA-MB-231 cell-xenografted nude mice. Conclusions: These findings supported that DHQ3 and 17-DR induce different forms of death in some cancer cell line via activation of different pathways. All of the results provided evidence for its anti-tumorigentic action with low hepatotoxicity in vivo, making them promising anti-breast cancer agents.
|
|
Nova |
2016 |
Ye Y, Ge YM, Xiao MM, Guo LM, Li Q, Hao JQ, et al., 'Suppression of SHIP2 contributes to tumorigenesis and proliferation of gastric cancer cells via activation of Akt', Journal of Gastroenterology, 51 230-240 (2016) [C1]
Background: The Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is implicated in diabetes, arthrosclerosis, and cancer. However, the role of SHIP2 in human gastric canc... [more]
Background: The Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is implicated in diabetes, arthrosclerosis, and cancer. However, the role of SHIP2 in human gastric cancer remains unclear. Methods: The expression levels of SHIP2 in gastric cancer tissues, a panel of gastric cancer cell lines, and normal gastric epithelial cells were analyzed by immunohistochemistry (IHC), Western blot, and real-time quantitative RT-PCR (qRT-PCR). Gastric cancer cells with either overexpressed SHIP2 or co-overexpressed SHIP2 and Akt were analyzed to determine cell proliferation, colony formation, apoptosis, cell migration, and invasion assays. Normal gastric epithelial cells with knockdown SHIP2 or co-knockdown SHIP2 and Akt were subjected by anchorage-independent growth assays. The effect of SHIP2 on tumor growth in vivo was detected by xenograft tumorigenesis assays. Results: SHIP2 was commonly downregulated in gastric cancer compared with normal gastric mucosa, and overexpression of SHIP2 inhibited cell proliferation, induced apoptosis, suppressed cell motility and invasion in gastric cancer cells in vitro, and retarded the growth of xenograft gastric tumors in vivo, while knockdown of SHIP2 in normal gastric epithelial cells promoted anchorage-independent growth. Moreover, overexpression of SHIP2 inactivated Akt, and upregulated p21, p27, and the pro-apoptotic protein Bim. Restoring Akt activation in gastric cancer cells largely blocked the inhibition of PI3K/Akt signaling by SHIP2 and reversed the inhibitory effect of SHIP2 on tumorigenesis and proliferation. Conclusions: This study demonstrates, for the first time, that SHIP2 is frequently downregulated in gastric cancer, and reduced SHIP2 expression promotes tumorigenesis and proliferation of gastric cancer via activation of the PI3K/Akt signaling.
|
|
Nova |
2016 |
Meng XX, Xu HX, Yao M, Dong Q, Zhang XD, 'Implication of unfolded protein response and autophagy in the treatment of BRAF inhibitor resistant melanoma', Anti-Cancer Agents in Medicinal Chemistry, 16 291-298 (2016) [C1]
The continuous activation of the mitogen-activated protein kinase signaling cascade, typified by the BRAFV600E mutation, is one of the key alterations in melanoma. Accordingly, tw... [more]
The continuous activation of the mitogen-activated protein kinase signaling cascade, typified by the BRAFV600E mutation, is one of the key alterations in melanoma. Accordingly, two BRAF inhibitors (BRAFi), vemurafenib and dabrafenib are utilized to treat melanoma and resulted in an excellent clinical outcome. However, the clinical success is not long-lasting, and the BRAFi resistance and disease progression inevitably occurs in nearly all patients. Endoplasmic reticulum stress-induced unfolded protein response and autophagy have emerged as potential pro-survival mechanisms adopted by melanoma cells in response to BRAFi. In this review, we discuss the role of unfolded protein response and autophagy that are implicated in the development of BRAFi-resistant melanoma and the corresponding strategy aiming at overcoming the intractable clinical problem.
|
|
Nova |
2016 |
Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Arozena AA, et al., 'Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356', Autophagy, 12 443 (2016)
|
|
|
2016 |
Sutton SK, Carter DR, Kim P, Tan O, Arndt GM, Zhang XD, et al., 'A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner', Oncotarget, 7 52166-52178 (2016) [C1]
There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAFV600E/K mutation. In melanoma cells, loss of TRIM16 expre... [more]
There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAFV600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease.
|
|
Nova |
2016 |
Guo ST, Chi MN, Yang RH, Guo XY, Zan LK, Wang CY, et al., 'INPP4B is an oncogenic regulator in human colon cancer', Oncogene, 35 3049-3061 (2016) [C1]
Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we ... [more]
Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum-and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.
|
|
Nova |
2016 |
Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Arozena AA, et al., 'Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)', Autophagy, 12 1-222 (2016) [C1]
|
|
Nova |
2015 |
Roselli S, Pundavela J, Demont Y, Faulkner S, Keene S, Attia J, et al., 'Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion', Oncotarget, 6 10473-10486 (2015) [C1]
The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed... [more]
The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion.
|
|
Nova |
2015 |
Tay KH, Liu X, Chi M, Jin L, Jiang CC, Guo ST, et al., 'Involvement of vacuolar H
Targeting the sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) signalling axis is emerging as a promising strategy in the treatment of cancer. However, the effect of such an appr... [more]
Targeting the sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) signalling axis is emerging as a promising strategy in the treatment of cancer. However, the effect of such an approach on survival of human melanoma cells remains less understood. Here, we show that the sphingosine analogue FTY720 that functionally antagonises S1PRs kills human melanoma cells through a mechanism involving the vacuolar H+-ATPase activity. Moreover, we demonstrate that FTY720-triggered cell death is characterized by features of necrosis and is not dependent on receptor-interacting protein kinase 1 or lysosome cathepsins, nor was it associated with the activation of protein phosphatase 2A. Instead, it is mediated by increased production of reactive oxygen species and is antagonized by activation of autophagy. Collectively, these results suggest that FTY720 and its analogues are promising candidates for further development as new therapeutic agents in the treatment of melanoma.
|
|
Nova |
2015 |
Luan Q, Jin L, Jiang CC, Tay KH, Lai F, Liu XY, et al., 'RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy.', Autophagy, 11 975-994 (2015) [C1]
|
|
Nova |
2015 |
Liu PY, Erriquez D, Marshall GM, Tee AE, Polly P, Wong M, et al., 'Erratum: Effects of a novel long noncoding RNA, lncUSMycN, on N-Myc expression and neuroblastoma progression (Journal of the National Cancer Institute (2014) 106:7 (dju113) DOI: 10.1093/jnci/dju113)', Journal of the National Cancer Institute, 107 (2015)
|
|
|
2015 |
Chen J, Zhang XD, Proud C, 'Dissecting the signaling pathways that mediate cancer in PTEN and LKB1 double-knockout mice', Science Signaling, 8 (2015) [C1]
Double knockout of PTEN and LKB1 - genes encoding phosphatase and tensin homolog and liver kinase B1, respectively - leads to the spontaneous development of cancer in mice. PTEN c... [more]
Double knockout of PTEN and LKB1 - genes encoding phosphatase and tensin homolog and liver kinase B1, respectively - leads to the spontaneous development of cancer in mice. PTEN converts phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (4,5)-bisphosphate (PIP2), whereas LKB1 activates the 5' adenosine monophosphate-activated protein kinase (AMPK). The kinase AKT and the kinase complex mTORC1 may play key roles in carcinogenesis and are components of signaling pathways that also contain PTEN and LKB1. We propose that via activation of AKT and mTORC1, the double knockout of PTEN and LKB1 contributes to distinct cell-specifi c aspects of tumor development and progression. Whereas mTORC1 promotes cancer initiation and progression through cell growth, survival, and proliferation, independent induction of the immune inhibitory molecule PD-L1 by activated AKT enables the tumors to evade immunosurveillance.
|
|
Nova |
2015 |
Meng X-X, Yao M, Zhang XD, Xu H-X, Dong Q, 'ER stress-induced autophagy in melanoma', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 42 811-816 (2015) [C1]
|
|
Nova |
2015 |
Jiang C, Chi MN, Guo ST, Wilmott JS, Guo X Y, Yan X G, et al., 'INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas', Oncotarget, 6 39891-39907 (2015) [C1]
|
|
Nova |
2015 |
Liu XY, Lai F, Yan XG, Jiang CC, Guo ST, Wang CY, et al., 'RIP1 kinase is an oncogenic driver in melanoma', Cancer Research, 75 1736-1748 (2015) [C1]
Although many studies have uncovered an important role for the receptor-binding protein kinase RIP1 in controlling cell death signaling, its possible contributions to cancer patho... [more]
Although many studies have uncovered an important role for the receptor-binding protein kinase RIP1 in controlling cell death signaling, its possible contributions to cancer pathogenesis have been little explored. Here, we report that RIP1 functions as an oncogenic driver in human melanoma. Although RIP1 was commonly upregulated in melanoma, RIP1 silencing inhibited melanoma cell proliferation in vitro and retarded the growth of melanoma xenografts in vivo. Conversely, while inducing apoptosis in a small proportion of melanoma cells, RIP1 overexpression enhanced proliferation in the remaining cells. Mechanistic investigations revealed that the proliferative effects of RIP1 overexpression were mediated by NF-¿B activation. Strikingly, ectopic expression of RIP1 enhanced the proliferation of primary melanocytes, triggering their anchorageindependent cell growth in an NF-¿B-dependent manner. We identified DNA copy-number gain and constitutive ubiquitination by a TNFa autocrine loop mechanism as two mechanisms of RIP1 upregulation in human melanomas. Collectively, our findings define RIP1 as an oncogenic driver in melanoma, with potential implications for targeting its NF-¿B-dependent activation mechanism as a novel approach to treat this disease.
|
|
Nova |
2015 |
Zou X, Zhang M, Sun Y, Zhao S, Wei Y, Zhang X, et al., 'Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells', ONCOLOGY REPORTS, 34 1895-1904 (2015) [C1]
|
|
Nova |
2014 |
Liu PY, Erriquez D, Marshall GM, Tee AE, Polly P, Wong M, et al., 'Effects of a novel long noncoding RNA, lncUSMycN, on N-Myc expression and neuroblastoma progression.', J Natl Cancer Inst, 106 (2014) [C1]
|
|
Nova |
2014 |
Liu YL, Lai F, Wilmott JS, Yan XG, Liu XY, Luan Q, et al., 'Noxa upregulation by oncogenic activation of MEK/ERK through CREB promotes autophagy in human melanoma cells', Oncotarget, 5 11237-11251 (2014) [C1]
Reduction in the expression of the anti-survival BH3-only proteins PUMA and Bim is associated with the pathogenesis of melanoma. However, we have found that the expression of the ... [more]
Reduction in the expression of the anti-survival BH3-only proteins PUMA and Bim is associated with the pathogenesis of melanoma. However, we have found that the expression of the other BH3-only protein Noxa is commonly upregulated in melanoma cells, and that this is driven by oncogenic activation of MEK/ERK. Immunohistochemistry studies showed that Noxa was expressed at higher levels in melanomas than nevi. Moreover, the expression of Noxa was increased in metastatic compared to primary melanomas, and in thick primaries compared to thin primaries. Inhibition of oncogenic BRAFV600E or MEK downregulated Noxa, whereas activation of MEK/ERK caused its upregulation. In addition, introduction of BRAFV600E increased Noxa expression in melanocytes. Upregulation of Noxa was due to a transcriptional increase mediated by cAMP responsive element binding protein, activation of which was also increased by MEK/ERK signaling in melanoma cells. Significantly, Noxa appeared necessary for constitutive activation of autophagy, albeit at low levels, by MEK/ERK in melanoma cells. Furthermore, it was required for autophagy activation that delayed apoptosis in melanoma cells undergoing nutrient deprivation. These results reveal that oncogenic activation of MEK/ERK drives Noxa expression to promote autophagy, and suggest that Noxa has an indirect anti-apoptosis role in melanoma cells under nutrient starvation conditions.
|
|
Nova |
2014 |
Zhang Q, Zhang Y, Zhang P, Chao Z, Xia F, Jiang C, et al., 'Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in human breast cancer cells', Genes and Cancer, 5 100-112 (2014)
Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, has been proposed as a specific antitu... [more]
Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, has been proposed as a specific antitumor agent. Autophagy is a process that regulates the balance between protein synthesis and protein degradation. Autophagy in mammalian systems occurs under basal conditions and can be stimulated by stresses, including starvation, oxidative stress. Therefore, we hypothesized that 3-BrPA could induce autophagy. In the present study, we explored the mechanism of 3-BrPA and its combined action with chloroquine. Our results demonstrate that in MDA-MB-435 and in MDA-MB-231 cells, 3-BrPA induces autophagy, which can be inhibited by chloroquine. Furthermore, the combined treatment synergistically decreased the number of viable cells. Interestingly, the combined treatment triggered apoptosis in MDA-MB-435 cells, while it induced necroptosis in MDA-MB-231 cells. ROS mediated cell death when 3-BrPA and CQ were co-administered. Finally, CQ enhanced the anticancer efficacy of 3-BrPA in vivo. Collectively, our results show that 3-BrPA triggers autophagy, increasing breast cancer cell resistance to 3-BrPA treatment and that CQ enhanced 3-BrPA-induced cell death in breast cancer cells by stimulating ROS formation. Thus, inhibition of autophagy may be an innovative strategy for adjuvant chemotherapy of breast cancer
|
|
|
2014 |
Cheng X, Liu H, Jiang C-C, Fang L, Chen C, Zhang X-D, Jiang Z-W, 'Connecting endoplasmic reticulum stress to autophagy through IRE1/JNK/beclin-1 in breast cancer cells.', Int J Mol Med, 34 772-781 (2014)
|
|
|
2014 |
Gong J, Fang L, Liu R, Wang Y, Xing J, Chen Y, et al., 'UPR decreases CD226 ligand CD155 expression and sensitivity to NK cell-mediated cytotoxicity in hepatoma cells', EUROPEAN JOURNAL OF IMMUNOLOGY, 44 3758-3767 (2014) [C1]
|
|
Nova |
2014 |
Croft A, Tay KH, Boyd SC, Guo ST, Jiang CC, Lai F, et al., 'Oncogenic activation of MEK/ERK primes melanoma cells for adaptation to endoplasmic reticulum stress', Journal of Investigative Dermatology, 134 488-497 (2014) [C1]
Cancer cells commonly undergo chronic endoplasmic reticulum (ER) stress, to which the cells have to adapt for survival and proliferation. We report here that in melanoma cells int... [more]
Cancer cells commonly undergo chronic endoplasmic reticulum (ER) stress, to which the cells have to adapt for survival and proliferation. We report here that in melanoma cells intrinsic activation of the ER stress response/unfolded protein response (UPR) is, at least in part, caused by increased outputs of protein synthesis driven by oncogenic activation of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) and promotes proliferation and protects against apoptosis induced by acute ER stress. Inhibition of oncogenic BRAF V600E or MEK-attenuated activation of inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6) signaling of the UPR in melanoma cells. This was associated with decreased phosphorylation of eukaryotic initiation factor 4E (eIF4E) and nascent protein synthesis and was recapitulated by knockdown of eIF4E. In line with this, introduction of BRAF V600E into melanocytes led to increases in eIF4E phosphorylation and protein production and triggered activation of the UPR. Similar to knockdown of glucose-regulated protein 78 (GRP78), inhibition of XBP1 decelerated melanoma cell proliferation and enhanced apoptosis induced by the pharmacological ER stress inducers tunicamycin and thapasigargin. Collectively, these results reveal that potentiation of adaptation to chronic ER stress is another mechanism by which oncogenic activation of the MEK/ERK pathway promotes the pathogenesis of melanoma. © 2014 The Society for Investigative Dermatology.
|
|
Nova |
2014 |
Wu P, Cheng YW, Wang JY, Zhang XD, Zhang LJ, 'Inhibition of MEK sensitizes gastric cancer cells to TRAIL-induced apoptosis', Neoplasma, 61 136-143 (2014) [C1]
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has long been believed to be highly selective in inducing apoptosis in cancer cells, has turned out to be a ... [more]
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has long been believed to be highly selective in inducing apoptosis in cancer cells, has turned out to be a molecule that induces a far more diverse range of effects. The aim of this study was to investigate whether or not ERK1/2 pathway is involved in antitumor effects of TRAIL on gastric cancer cells. In addition to activate the extrinsic and intrinsic apoptotic pathway, TRAIL also triggered the activation of ERK1/2. Inhibition of ERK1/2 signaling by MEK inhibitor U0126 promoted cell death via increased activation of caspases, drop in mitochondrial membrane potential and downregulation of XIAP, cIAP2 and Mcl-1. These results indicate that TRAIL-induced rapid activation of ERK1/2 may be a survival mechanism to struggle against TRAIL assault at the early stage, and inhibition of ERK1/2 signaling can sensitize gastric cancer cells to TRAIL-induced apoptosis.
|
|
Nova |
2014 |
Wu PY, Zhang XD, Zhu J, Guo XY, Wang JF, 'Low expression of microRNA-146b-5p and microRNA-320d predicts poor outcome of large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone', Human Pathology, 45 1664-1673 (2014) [C1]
Although diffuse large B-cell lymphoma (DLBCL) encompasses a biologically and clinically diverse set of diseases, increasing evidence has pointed to an important role of microRNAs... [more]
Although diffuse large B-cell lymphoma (DLBCL) encompasses a biologically and clinically diverse set of diseases, increasing evidence has pointed to an important role of microRNAs (miRs) in the pathogenesis of DLBCL. We report here that low expression of miR-146b-5p and miR-320d is associated with poor prognosis of DLBCL patients treated with the standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen and that this is related to the inhibitory effect of these miRs on DLBCL cell proliferation. Analysis of a retrospective cohort of 106 primary nodal DLBCL samples from patients who were treated with CHOP showed that, when the median survival period (40.8 months) was used as the cutoff point, miR-146b-5p and miR-320d were expressed at lower levels in DLBCLs with poor prognosis. Indeed, whereas low expression of miR-146b-5p was correlated with reduced progression-free survival, low expression of miR-320d was associated with decreases in both progression-free survival and overall survival. Moreover, miR-146b-5p and miR-320d were expressed at significantly lower levels in DLBCLs with the MYC t(8;14) translocation. Functional studies demonstrated that overexpression of miR-146b-5p or miR-320d inhibited DLBCL cell proliferation, wheareas knockdown of miR-146b-5p or miR-320d promoted proliferation of DLBCL cells. Taken together, these results suggest that low expression of miR-146b-5p and miR-320d may be predictive of compromised responses of a subset of DLBCL patients to treatment with the CHOP regimen and that restoration of these miRs may be useful to improve the therapeutic efficacy of CHOP. © 2014 Elsevier Inc.
|
|
Nova |
2014 |
Yang F, Xu N, Li D, Guan L, He Y, Zhang Y, et al., 'A Feedback Loop between RUNX2 and the E3 Ligase SMURF1 in Regulation of Differentiation of Human Dental Pulp Stem Cells', JOURNAL OF ENDODONTICS, 40 1579-1586 (2014) [C1]
|
|
Nova |
2014 |
Dong L, Jin L, Tseng HY, Wang CY, Wilmott JS, Yosufi B, et al., 'Oncogenic suppression of PHLPP1 in human melanoma', Oncogene, 33 4756-4766 (2014) [C1]
Akt is constitutively activated in up to 70% of human melanomas and has an important role in the pathogenesis of the disease. However, little is known about protein phosphatases t... [more]
Akt is constitutively activated in up to 70% of human melanomas and has an important role in the pathogenesis of the disease. However, little is known about protein phosphatases that dephosphorylate and thereby inactivate it in melanoma cells. Here we report that suppression of pleckstrin homology domain and leucine-rich repeat Ser/Thr protein phosphatase 1 (PHLPP1) by DNA methylation promotes Akt activation and has an oncogenic role in melanoma. While it is commonly downregulated, overexpression of PHLPP1 reduces Akt activation and inhibits melanoma cell proliferation in vitro, and retards melanoma growth in a xenograft model. In contrast, knockdown of PHLPP1 increases Akt activation, enhances melanoma cell and melanocyte proliferation, and results in anchorage-independent growth of melanocytes. Suppression of PHLPP1 involves blockade of binding of the transcription factor Sp1 to the PHLPP1 promoter. Collectively, these results suggest that suppression of PHLPP1 by DNA methylation contributes to melanoma development and progression.
|
|
Nova |
2014 |
Tay KH, Luan Q, Croft A, Jiang CC, Jin L, Zhang XD, Tseng H-Y, 'Sustained IRE1 and ATF6 signaling is important for survival of melanoma cells undergoing ER stress', CELLULAR SIGNALLING, 26 287-294 (2014) [C1]
|
|
Nova |
2014 |
Chi M, Chen J, Ye Y, Tseng H-Y, Lai F, Tay KH, et al., 'Adipocytes Contribute to Resistance of Human Melanoma Cells to Chemotherapy and Targeted Therapy', CURRENT MEDICINAL CHEMISTRY, 21 1255-1267 (2014) [C1]
|
|
Nova |
2014 |
Becker TM, Boyd SC, Mijatov B, Gowrishankar K, Snoyman S, Pupo GM, et al., 'Mutant B-RAF-Mcl-1 survival signaling depends on the STAT3 transcription factor', ONCOGENE, 33 1158-1166 (2014) [C1]
|
|
Nova |
2014 |
Jiang CC, Croft A, Tseng HY, Guo ST, Jin L, Hersey P, Zhang XD, 'Repression of microRNA-768-3p by MEK/ERK signalling contributes to enhanced mRNA translation in human melanoma', Oncogene, 33 2577-2588 (2014) [C1]
Increased global protein synthesis and selective translation of mRNAs encoding proteins contributing to malignancy is common in cancer cells. This is often associated with elevate... [more]
Increased global protein synthesis and selective translation of mRNAs encoding proteins contributing to malignancy is common in cancer cells. This is often associated with elevated expression of eukaryotic translation initiation factor 4 (eIF4E), the rate-limiting factor of cap-dependent translation initiation. We report here that in human melanoma downregulation of miR-768-3p as a result of activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway has an important role in the upregulation of eIF4E and enhancement in protein synthesis. Melanoma cells displayed increased nascent protein production and elevated eIF4E expression, which was associated with the downregulation of miR-768-3p that was predicted to target the 3'-untranslated region of the eIF4E mRNA. Overexpression of miR-768-3p led to the downregulation of the endogenous eIF4E protein, reduction in nascent protein synthesis and inhibition of cell survival and proliferation. These effects were efficiently reversed when eIF4E was co-overexpressed in melanoma cells. On the other hand, introduction of anti-miR-768-3p into melanocytes upregulated endogenous eIF4E protein expression and increased global protein synthesis. Downregulation of miR-768-3p appeared to be mediated by activation of the MEK/ERK pathway, in that treatment of BRAF V600E melanoma cells with the mutant BRAF inhibitor PLX4720 or exposure of either BRAF V600E or wild-type BRAF melanoma cells to the MEK inhibitor U0126 resulted in the upregulation of miR-768-3p and inhibition of nascent protein synthesis. This inhibition was partially blocked in cells cointroduced with anti-miR-768-3p. Significantly, miR-768-3p was similarly downregulated, which was inversely associated with the expression levels of eIF4E in fresh melanoma isolates. Taken together, these results identify downregulation of miR-768-3p and subsequent upregulation of eIF4E as an important mechanism in addition to phosphorylation of eIF4E responsible for MEK/ERK-mediated enhancement of protein synthesis in melanoma. © 2014 Macmillan Publishers Limited.
|
|
Nova |
2014 |
Wu P, Zhu XP, Zhang XD, Zhang LJ, 'Activation of caspase-4 was involved in TRAIL-induced apoptosis of gastric cancer cells', Chinese Pharmacological Bulletin, 30 1437-1441 (2014)
Aim: To investigate the potential involvement of caspase-4 in TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis in gastric cancer cells.... [more]
Aim: To investigate the potential involvement of caspase-4 in TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis in gastric cancer cells.
|
|
|
2014 |
Ye Y, Li Q, Ge YM, Zhang XD, Zhang LJ, 'The effects of PIB5PA on migration and invasion of human melanoma cells', Tumor, 34 487-493 (2014) [C1]
Objective: To investigate the effects of phosphatidylinositol 4, 5-bisphosphate 5-phosphatase A (PIB5PA) on the migration and invasion of human melanoma Mel-FH cells. Methods: Euk... [more]
Objective: To investigate the effects of phosphatidylinositol 4, 5-bisphosphate 5-phosphatase A (PIB5PA) on the migration and invasion of human melanoma Mel-FH cells. Methods: Eukaryotic expression recombinant vector pF-5xUAS-SV40-PIB5PA which carried a 4-hydroxytamoxifen (4-OHT)-inducible lentiviral expression system was constructed and infected into melanoma Mel-FH cells. Mel-FH.PIB5PA cells were successfully obtained via dual antibiotic selection of puromycin and hygromycin B. The optimum concentration and acting time of 4-OHT on the expression of PIB5PA of Mel-FH.PIB5PA cells were detected by Western blotting. The migration and invasion of Mel-FH.PIB5PA cells were determined by wound healing and Transwell chamber assay, respectively. The expression levels of phospho-protein kinase B (p-AKT), phospho-focal adhesion kinase (p-FAK), matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 were measured by Western blotting. Results: The addition of 10 nmol/L 4-OHT for 16 h readily induced PIB5PA overexpression in Mel-FH.PIB5PA cells. The exogenous expression of PIB5PA significantly inhibited migration and invasion of Mel-FH.PIB5PA cells as compared with Mel-FH.PIB5PA cells without treatment of 4-OHT (P < 0.05), and reduced the expression levels of p-AKT, p-FAK, MMP-2, MMP-9, TIMP-1, TIMP-2, MMP-2/ TIMP-2 and MMP-9/TIMP-1 proteins (all P < 0.05). Conclusion: Over-expression of PIB5PA can inhibit the abilities of migration and invasion of human melanoma Mel-FH cells in vitro , which may be associated with inactivity of AKT and FAK, and down-regulation of the relative expression levels of MMP-2/TIMP-2 and MMP-9/TIMP-1. Copyright© 2014 by TUMOR.
|
|
Nova |
2014 |
Chi M, Ye Y, Zhang XD, Chen J, 'Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway', Drug Design, Development and Therapy, 8 255-262 (2014) [C1]
There is currently no curative treatment for melanoma once the disease spreads beyond the original site. Although activation of the PI3K/Akt pathway resulting from genetic mutatio... [more]
There is currently no curative treatment for melanoma once the disease spreads beyond the original site. Although activation of the PI3K/Akt pathway resulting from genetic mutations and epigenetic deregulation of its major regulators is known to cause resistance of melanoma to therapeutic agents, including the conventional chemotherapeutic drug dacarbazine and the Food and Drug Administration-approved mutant BRAF inhibitors vemurafenib and dabrafenib, the role of extracellular stimuli of the pathway, such as insulin, in drug resistance of melanoma remains less understood. Objective: To investigate the effect of insulin on the response of melanoma cells to dacarbazine, and in particular, the effect of insulin on the response of melanoma cells carrying the BRAFV600E mutation to mutant BRAF inhibitors. An additional aim was to define the role of the PI3K/Akt pathway in the insulin-triggered drug resistance. Methods: The effect of insulin on cytotoxicity induced by dacarbazine or the mutant BRAF inhibitor PLX4720 was tested by pre-incubation of melanoma cells with insulin. Cytotoxicity was determined by the MTS assay. The role of the PI3K/Akt pathway in the insulin-triggered drug resistance was examined using the PI3K inhibitor LY294002 and the PI3K and mammalian target of rapamycin dual inhibitor BEZ-235. Activation of the PI3K/Akt pathway was monitored by Western blot analysis of phosphorylated levels of Akt. Results: Recombinant insulin attenuated dacarbazine-induced cytotoxicity in both wild-type BRAF and BRAFV600E melanoma cells, whereas it also reduced killing of BRAFV600E melanoma cells by PLX4720. Nevertheless, the protective effect of insulin was abolished by the PI3K and mTOR dual inhibitor BEZ-235 or the PI3K inhibitor LY294002. Conclusion: Insulin attenuates the therapeutic efficacy of dacarbazine and PLX4720 in melanoma cells, which is mediated by activation of the PI3K/Akt pathway and can be overcome by PI3K inhibitors. © 2014 Chi et al.
|
|
Nova |
2014 |
Dong Y, Yin S, Jiang C, Luo X, Guo X, Zhao C, et al., 'Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-ß-D- glucose-induced senescence-like growth arrest in human cancer cells', Autophagy, 10 296-310 (2014)
Growing evidence has demonstrated that autophagy plays important and paradoxical roles in carcinogenesis, while senescence is considered to be a crucial tumor-suppressor mechanism... [more]
Growing evidence has demonstrated that autophagy plays important and paradoxical roles in carcinogenesis, while senescence is considered to be a crucial tumor-suppressor mechanism in cancer prevention and treatment. In the present study we demonstrated that both autophagy and senescence were induced in response to penta-1,2,3,4,6-O-galloyl-ß-D-glucose (PGG), a chemopreventive polyphonolic compound, in multiple types of cancer cells. Analysis of these 2 events over the experimental time course indicated that autophagy and senescence occurred in parallel early in the process and dissociated later. The long-term culture study suggested that a subpopulation of senescent cells may have the capacity to reenter the cell cycle. Inhibition of autophagy by either a chemical inhibitor or RNA interference led to a significant reduction of PGG-induced senescence, followed by induction of apoptosis. These results suggested that autophagy promoted senescence induction by PGG and that PGG might exert its anticancer activity through autophagy-mediated senescence. For the first time, these findings uncovered the relationships among autophagy, senescence, and apoptosis induced by PGG. In addition, we identified that unfolded protein response signaling played a pivotal role in the autophagy-mediated senescence phenotype. Furthermore, our data showed that activation of MAPK8/9/10 (mitogenactivated protein kinase 8/9/10/c-Jun N-terminal kinases) was an essential upstream signal for PGG-induced autophagy. Finally, the key in vitro results were validated in vivo in a xenograft mouse model of human HepG2 liver cancer. Our findings provided novel insights into understanding the mechanisms and functions of PGG-induced autophagy and senescence in human cancer cells. © 2014 Landes Bioscience.
|
|
|
2014 |
Zhan Z, Xie X, Cao H, Zhou X, Zhang XD, Fan H, Liu Z, 'Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination.', Autophagy, 10 257-268 (2014) [C1]
|
|
Nova |
2014 |
Oliveira CS, de Bock CE, Molloy TJ, Sadeqzadeh E, Geng XY, Hersey P, et al., 'Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma', BMC Cancer, 14 (2014) [C1]
Background: Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control... [more]
Background: Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control of proliferation. Overexpression of MIF has been reported in a number of cancer types and it has previously been shown that MIF is upregulated in melanocytic tumours with the highest expression levels occurring in malignant melanoma. However, the clinical significance of high MIF expression in melanoma has not been reported. Methods: MIF expression was depleted in human melanoma cell lines using siRNA-mediated gene knockdown and effects monitored using in vitro assays of proliferation, cell cycle, apoptosis, clonogenicity and Akt signalling. In silico analyses of expression microarray data were used to correlate MIF expression levels in melanoma tumours with overall patient survival using a univariate Cox regression model. Results: Knockdown of MIF significantly decreased proliferation, increased apoptosis and decreased anchorage-independent growth. Effects were associated with reduced numbers of cells entering S phase concomitant with decreased cyclin D1 and CDK4 expression, increased p27 expression and decreased Akt phosphorylation. Analysis of clinical outcome data showed that MIF expression levels in primary melanoma were not associated with outcome (HR = 1.091, p = 0.892) whereas higher levels of MIF in metastatic lesions were significantly associated with faster disease progression (HR = 2.946, p = 0.003 and HR = 4.600, p = 0.004, respectively in two independent studies). Conclusions: Our in vitro analyses show that MIF functions upstream of the PI3K/Akt pathway in human melanoma cell lines. Moreover, depletion of MIF inhibited melanoma proliferation, viability and clonogenic capacity. Clinically, high MIF levels in metastatic melanoma were found to be associated with faster disease recurrence. These findings support the clinical significance of MIF signalling in melanoma and provide a strong rationale for both targeting and monitoring MIF expression in clinical melanoma.
|
|
Nova |
2014 |
Sutton SK, Koach J, Tan O, Liu B, Carter DR, Wilmott JS, et al., 'TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells', ONCOTARGET, 5 10127-10139 (2014) [C1]
|
|
Nova |
2013 |
Li Y, Liu H, Huang Y-Y, Pu L-J, Zhang X-D, Jiang Z-W, Jiang C-C, '[Effects of cisplatin combined with heparanase inhibitor on proliferation and invasion of human nasopharyngeal carcinoma cells].', Yao Xue Xue Bao, 48 609-614 (2013)
|
|
|
2013 |
Wroblewski D, Jiang CC, Croft A, Farrelly ML, Zhang XD, Hersey P, 'OBATOCLAX and ABT-737 induce ER stress responses in human melanoma cells that limit induction of apoptosis.', PLoS One, 8 e84073 (2013) [C1]
|
|
Nova |
2013 |
Ye Y, Li Q, Hu WL, Tseng HY, Jin L, Zhang XD, et al., 'Loss of PI(4,5)P
Past studies have shown that the inositol polyphosphate 5-phosphatase, phosphatidylinositol 4,5-bisphosphate 5-phosphatase (PIB5PA), is commonly downregulated or lost in melanomas... [more]
Past studies have shown that the inositol polyphosphate 5-phosphatase, phosphatidylinositol 4,5-bisphosphate 5-phosphatase (PIB5PA), is commonly downregulated or lost in melanomas, which contributes to elevated activation of phosphatidylinositol 3-kinase (PI3K)/Akt in melanoma cells. In this report, we provide evidence that PIB5PA deficiency plays a role in resistance of melanoma cells to RAF/mitogen-activated protein kinase kinase (MEK) inhibitors. Ectopic expression of PIB5PA enhanced apoptosis induced by the RAF inhibitor PLX4720 in BRAFV600E and by the MEK inhibitor U0126 in both BRAFV600E and wild-type BRAF melanoma cells. This was due to inhibition of PI3K/Akt, as co-introduction of an active form of Akt (myr-Akt) abolished the effect of over-expression of PIB5PA on apoptosis induced by PLX4720 or U0126. While overexpression of PIB5PA triggered activation of Bad and down-regulation of Mcl-1, knockdown of Bad or overexpression of Mcl-1 recapitulated, at least in part, the effect of myr-Akt, suggesting that regulation of Bad and Mcl-1 is involved in PIB5PA-mediated sen-sitization of melanoma cells to the inhibitors. The role of PIB5PA deficiency in BRAF inhibitor resistance was confirmed by knockdown of PIB5PA, which led to increased growth of BRAFV600E melanoma cells selected for resistance to PLX4720. Consistent with its role in vitro, overexpression of PIB5PA and the MEK inhibitor selumetinib cooperatively inhibited melanoma tumor growth in a xenograft model. Taken together, these results identify loss of PIB5PA as a novel resistance mechanism of melanoma to RAF/MEK inhibitors and suggest that restoration of PIB5PA may be a useful strategy to improve the therapeutic efficacy of the inhibitors in the treatment of melanoma. © 2013 Neoplasia Press, Inc. All rights reserved.
|
|
Nova |
2013 |
Wroblewski D, Mijatov B, Mohana-Kumaran N, Lai F, Gallagher SJ, Haass NK, et al., 'The BH3-mimetic ABT-737 sensitizes human melanoma cells to apoptosis induced by selective BRAF inhibitors but does not reverse acquired resistance', CARCINOGENESIS, 34 237-247 (2013) [C1]
|
|
Nova |
2013 |
Wu P, Wang JY, Zhang XD, Zhu XF, Zhang LJ, 'Tunicamycin enhances the sensitivity to TRAIL in gastric cancer cells by up-regulation of TRAIL-R2', Tumor, 33 15-20 (2013)
Objective: To investigate the promoting effect of TM (tunicamycin) on apoptosis of gastric cancer cells induced by TRAIL [TNF (tumor necrosis factor)-related apoptosis-inducing li... [more]
Objective: To investigate the promoting effect of TM (tunicamycin) on apoptosis of gastric cancer cells induced by TRAIL [TNF (tumor necrosis factor)-related apoptosis-inducing ligand], and to explore its possible mechanism. Methods: The effect of treatment with TM (1 µmol/L)/TRAIL (100 µg/L) alone or in combination for 3, 6, 16, 24 and 36 h on the apoptotic rate of SGC-7901 cells was detected by FCM (flow cytometry) using propidium iodide DNA staining. The cell surface expression levels of different types of TRAIL receptors including TRAIL-R1, TRAIL-R2, TRAIL-R3 and TRAIL-R4 before and after TM treatment were detected by FCM, and the expression level of TRAIL-R2 mRNA was detected by RFQ-PCR (real-time fluoregenic quantitative-PCR). The expression levels of GRP78 (78-kDa glucoseregulated protein) and CHOP (CCAAT/enhancer- binding protein homologous protein) proteins were detected by Western blotting. The splicing of XBP1 (X-box binding protein 1) mRNA was detected by RT-PCR. Results: Treatment with TM alone induced minimal level of apoptosis of SGC-7901 cells. The apoptosis rate of SGC-7901 cells was increased significantly after treatment with TM in combination with TRAIL. TM could markedly up-regulate cell surface expression level of TRAIL-R2 on cell surface. In contrast, TM did not induce any changes in the expressions of TRAIL-R1, TRAIL-R3 and TRAIL-R4. The expression level of TRAIL-R2 mRNA of SGC-7901 cells induced by TM treatment was up-regulated in a time-independent manner. The results of up-regulation of GRP78 and the splicing of XBP1 mRNA demonstrated the activation of UPR (unfolded protein response) induced by TM. Treatment with TM also resulted in a remarkable increase in the expression of CHOP protein. Conclusion: TM enhances TRAILinduced apoptosis in gastric cancer cells by up-regulation of TRAIL-R2 expression via UPR. CHOP may be responsible for this effect involved in up-regulation of TRAIL-R2. Copyright © 2013 by TUMOR.
|
|
|
2013 |
Wu P, Cheng YW, Zhang XD, Zhu XF, Zhang LJ, 'Role of inhibitor of apoptosis proteins in TRAIL-induced apoptosis of gastric cancer cells', Chinese Pharmacological Bulletin, 29 850-853 (2013)
Aim: To explore the role of inhibitor of apoptosis proteins (IAP) in regulating the sensitivity of gastric cancer cells to tumor necrosis factor-related apoptosis-inducing ligand ... [more]
Aim: To explore the role of inhibitor of apoptosis proteins (IAP) in regulating the sensitivity of gastric cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Methods: Apoptotic cells were determined by the propidium iodide method using flow cytometry. The activation of caspase-3 and PARP cleavage were conducted by Western blot analysis. Expressions of XIAP, Survivin, cIAP1 and cIAP2 before and after treatment with TRAIL were also measured by Western blot analysis. Results: TRAIL induced apoptosis in gastric cancer cells. BGC-823 cells were more sensitive to TRAIL than SGC-7901 cells. Caspse-3 activation and PARP cleavage were detected early after exposure to TRAIL. IAP family members were constitutively overexpressed in the two cell lines. The expression of XIAP was significantly downregulated in BGC-823 cells, compared with that in SGC-7901 cells, after TRAIL treatment. The expression of Survivin and cIAP1 remained unchanged. The expression of cIAP2 was slightly lowered in the two cell lines. Conclusions: TRAIL-induced apoptosis of gastric cancer cells appears to be determined at the level of the effector caspase-3. XIAP protects gastric cancer cells from TRAIL-indued apoptosis.
|
|
|
2013 |
Guo ST, Jiang CC, Wang GP, Li YP, Wang CY, Guo XY, et al., 'MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer', ONCOGENE, 32 1910-1920 (2013) [C1]
|
|
Nova |
2013 |
Chen J, Chi M, Chen C, Zhang XD, 'Obesity and melanoma: Exploring molecular links', Journal of Cellular Biochemistry, 114 1955-1961 (2013) [C1]
|
|
Nova |
2013 |
Li Y, Liu H, Huang YY, Pu LJ, Zhang XD, Jiang CC, Jiang ZW, 'Suppression of endoplasmic reticulum stress-induced invasion and migration of breast cancer cells through the downregulation of heparanase (Retracted article. See vol. 48, pg. 188, 2021)', INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 31 1234-1242 (2013) [C1]
|
|
Nova |
2013 |
Chen J, Shao R, Zhang XD, Chen C, 'Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics', International Journal of Nanomedicine, 2013 2677-2688 (2013) [C1]
|
|
Nova |
2013 |
Liu PY, Xu N, Malyukova A, Scarlett CJ, Sun YT, Zhang XD, et al., 'The histone deacetylase SIRT2 stabilizes Myc oncoproteins', CELL DEATH AND DIFFERENTIATION, 20 503-514 (2013) [C1]
|
|
Nova |
2013 |
Sun X-J, Liu H, Zhang P, Zhang X-D, Jiang Z-W, Jiang C-C, 'miR-10b Promotes Migration and Invasion in Nasopharyngeal Carcinoma Cells', ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 14 5533-5537 (2013) [C1]
|
|
Nova |
2013 |
Carlino MS, Gowrishankar K, Saunders CAB, Pupo GM, Snoyman S, Zhang XD, et al., 'Antiproliferative effects of continued mitogen-activated protein kinase pathway inhibition following acquired resistance to BRAF and/or MEK inhibition in melanoma', Molecular Cancer Therapeutics, 12 1332-1342 (2013) [C1]
Inhibitors of the mitogen-activated protein kinases (MAPK), BRAF, and MAP-ERK kinase (MEK) induce tumor regression in the majority of patients with BRAF-mutant metastatic melanoma... [more]
Inhibitors of the mitogen-activated protein kinases (MAPK), BRAF, and MAP-ERK kinase (MEK) induce tumor regression in the majority of patients with BRAF-mutant metastatic melanoma. The clinical benefit of MAPK inhibitors is restricted by the development of acquired resistance with half of those who benefit having progressed by 6 to 7 months and long-term responders uncommon. There remains no agreed treatment strategy on disease progression in these patients. Without published evidence, fears of accelerated disease progression on inhibitor withdrawal have led to the continuation of drugs beyond formal disease progression. We now show that treatment with MAPK inhibitors beyond disease progression can provide significant clinical benefit, and the withdrawal of these inhibitors led to a marked increase in the rate of disease progression in two patients. We also show that MAPK inhibitors retain partial activity in acquired resistant melanoma by examining drug-resistant clones generated to dabrafenib, trametinib, or the combination of these drugs. All resistant sublines displayed a markedly slower rate of proliferation when exposed to MAPK inhibitors, and this coincided with a reduction in MAPK signaling, decrease in bromodeoxyuridine incorporation, and S-phase inhibition. This cytostatic effect was also associated with diminished levels of cyclin D1 and p-pRb. Two shortterm melanoma cultures generated from resistant tumor biopsies also responded to MAPK inhibition, with comparable inhibitory changes in proliferation and MAPK signaling. These data provide a rationale for the continuation of BRAF and MEK inhibitors after disease progression and support the development of clinical trials to examine this strategy. ©2013 AACR.
|
|
|
2013 |
Song L, Liu H, Ma L, Zhang X, Jiang Z, Jiang C, 'Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced apoptosis in human nasopharyngeal carcinoma cells', ONCOLOGY LETTERS, 6 1031-1038 (2013) [C1]
|
|
Nova |
2013 |
Chen J, Zhang XD, Jiang Z, 'The Application of Fungal Beta-glucans for the Treatment of Colon Cancer', ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 13 725-730 (2013) [C1]
|
|
Nova |
2013 |
Bowden NA, Ashton KA, Vilain RE, Avery-Kiejda KA, Davey RJ, Murray HC, et al., 'Regulators of Global Genome Repair Do Not Respond to DNA Damaging Therapy but Correlate with Survival in Melanoma', PLOS ONE, 8 (2013) [C1]
|
|
Nova |
2013 |
Ye Y, Jin L, Wilmott JS, Hu WL, Yosufi B, Thorne RF, et al., 'PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma', NATURE COMMUNICATIONS, 4 (2013) [C1]
|
|
Nova |
2013 |
Lai F, Guo ST, Jin L, Jiang CC, Wang CY, Croft A, et al., 'Cotargeting histone deacetylases and oncogenic BRAF synergistically kills human melanoma cells by necrosis independently of RIPK1 and RIPK3', CELL DEATH & DISEASE, 4 (2013) [C1]
|
|
Nova |
2013 |
Hu W, Jin L, Jiang CC, Long GV, Scolyer RA, Wu Q, et al., 'AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma.', Cell Death and Disease, 4 e914 (2013) [C1]
|
|
Nova |
2013 |
Huang YY, Liu H, Li Y, Pu LJ, Zhang XD, Jiang CC, Jiang ZW, '2-DG sensitizes nasopharyngeal carcinoma cells to TRAIL induced apoptosis', Chinese Pharmacological Bulletin, 29 1119-1124 (2013)
Aim: To determine whether 2-DG (2-deoxy-D-glucose) can synergize with tumors necrosis factor-related apotosis-inducing ligand (TRAIL) which is used in nasopharyngeal carcinoma tre... [more]
Aim: To determine whether 2-DG (2-deoxy-D-glucose) can synergize with tumors necrosis factor-related apotosis-inducing ligand (TRAIL) which is used in nasopharyngeal carcinoma treatment and wish to find new targets for human nasopharyngeal carcinoma chemotherapy. Methods: Nasopharyngeal carcinoma cells CNE-2 were incubated with varying concentrations of 2-DG (0, 0.625, 1.25, 2.5, 5, 10 mmol·L-1) with or without TRAIL (200 µg·L -1). Cell viability was measured by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2-5 diphenyltetrazolium bromide) assay. Then propidium iodide (PI) staining was used to measure apoptotic cells in Flow Cytometry (FCM). CNE-2 cells were treated with 2-DG (5 mmol·L-1) (with or without TRAIL) for different time points (0, 6, 16, 24 h). Western blot was used to measure the protein expression of glucose-regulated protein 78 (GRP-78) and Caspase-3. Results: Combining 2-DG with TRAIL resulted in enhanced cell death compared with the individual use of each agent, 2-DG induced apoptosis cells hardly reached 10% and 2-DG markedly up-regulated GRP-78 and Caspase-3 expression. With the combination of 2-DG and TRAIL, the apoptotic rate of CNE-2 cells reached 78.9%. Conclusion: These results indicate that 2-DG sensitizes nasopharyngeal carcinoma cells to TRAIL induced apoptosis by up-regulation of GRP-78 and Caspase-3.
|
|
|
2012 |
Song L, Ma L, Zhang X, Jiang Z, Liu H, Jiang C, '[Effect of tunicamycin combined with cisplatin on proliferation and apoptosis of human nasopharyngeal carcinoma cells in vitro].', Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 32 766-771 (2012)
To study the effects of tunicamycin (a glycosylation inhibitor) combined with cisplatin on the proliferation and apoptosis of human nasopharyngeal carcinoma cells and explore the ... [more]
To study the effects of tunicamycin (a glycosylation inhibitor) combined with cisplatin on the proliferation and apoptosis of human nasopharyngeal carcinoma cells and explore the molecular mechanism. Nasopharyngeal carcinoma CNE-1 and CNE-2 cells cultured in vitro were treated with different concentrations of tunicamycin with or without cisplatin. The inhibition of cell proliferation was examined using MTT assay and colony formation assay, and the cell apoptosis was analyzed using flow cytometry with propidium iodide staining. The expressions of Bax, Bcl-2, and GRP78 in cells treated with 3 µmol/L tunicamycin with or without 6.00 µmol/L cisplatin were measured with Western blotting. Treatment with tunicamycin or cisplatin obviously inhibited the proliferation of CNE-1 and CNE-2 cells. Treatment with 3 µmol/L tunicamycin for 24, 36 and 48 h resulted in a viability of 72.13%, 51.97%, and 37.56% in CNE-1 cells and 85.61%, 56.95%, and 43.66% in CNE-2 cells, respectively, and the combined treatment with 6 µmol/L cisplatin lowered the cell viability to 67.97%, 47.76%, and 34.68% in CNE-1 cells and 56.89%, 37.05%, and 29.30% in CNE-2 cells, respectively. Tunicamycin at 0.3 µmol/L combined with 0.6 µmol/L cisplatin showed an obviously enhanced inhibitory effect on colony formation of CNE-1 and CNE-2 cells. Tunicamycin treatment (3 µmol/L) of CNE-1 and CNE-2 cells for 48 h induced an apoptosis rate of only 8.89% and 8.67%, but when combined with 6 µmol/L cisplatin, the cell apoptosis rate increased to 37.02% and 32.25%, significantly higher than that in cells with cisplatin treatment alone (7.25% and 6.36%, respectively). Compared with tunicamycin and cisplatin alone, the combined treatment significantly increased Bax expression and decreased Bcl-2 expression in the cells; tunicamycin up-regulated the expression of GRP-78 and enhanced the activity of caspase-3. Tunicamycin can inhibit the proliferation of CNE-1 and CNE-2 cells and enhance cisplatin-induced cell death, the mechanism of which may involve excessive endoplasmic reticulum stress response and increased activity of caspase-3.
|
|
|
2012 |
Tseng HY, Chen L, Ye Y, Tay KH, Jiang CC, Guo ST, et al., 'The melanoma-associated antigen MAGE-D2 suppresses TRAIL receptor 2 and protects against TRAIL-induced apoptosis in human melanoma cells', Carcinogenesis, 33 1871-1881 (2012) [C1]
|
|
Nova |
2012 |
Xu W-H, Zhang A-M, Ren M-S, Zhang XD, Wang F, Xu X-C, et al., 'Changes of treg-associated molecules on CD4 +CD25 +treg cells in myasthenia gravis and effects of immunosuppressants', Journal of Clinical Immunology, 32 975-983 (2012) [C1]
|
|
Nova |
2012 |
Lai FS, Jiang CC, Farrelly ML, Zhang XD, Hersey P, 'Evidence for upregulation of Bim and the splicing factor SRp55 in melanoma cells from patients treated with selective BRAF inhibitors', Melanoma Research, 22 244-251 (2012) [C1]
|
|
Nova |
2012 |
Wroblewski D, Zhang XD, Hersey P, 'Induction of Bim by the BRAF inhibitor PLX4720 sensitizes human melanoma cells to the BH3 mimetic ABT-737', CANCER RESEARCH, 72 (2012)
|
|
|
2012 |
Lucas KM, Mohana-Kumaran N, Lau D, Zhang XD, Hersey P, Huang DC, et al., 'Modulation of NOXA and MCL-1 as a strategy for sensitizing melanoma cells to the BH3-Mimetic ABT-737', Clinical Cancer Research, 18 783-795 (2012) [C1]
|
|
Nova |
2012 |
Zhan Z, Li Q, Wu P, Ye Y, Tseng HY, Zhang L, Zhang XD, 'Autophagy-mediated HMGB1 release antagonizes apoptosis of gastric cancer cells induced by vincristine via transcriptional regulation of Mcl-1', Autophagy, 8 109-121 (2012) [C1]
|
|
Nova |
2012 |
Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al., 'Guidelines for the use and interpretation of assays for monitoring autophagy', Autophagy, 8 445-544 (2012) [C1]
|
|
Nova |
2012 |
Tay KH, Jin L, Tseng HY, Jiang CC, Ye Y, Thorne RF, et al., 'Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress', Cell Death and Disease, 3 (2012) [C1]
|
|
Nova |
2011 |
Kiejda KA, Bowden NA, Croft AJ, Scurr LL, Kairupan CF, Ashton KA, et al., 'P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation', BMC Cancer, 11 203-219 (2011) [C1]
|
|
Nova |
2011 |
Jiang CC, Lai F, Thorne RF, Yang F, Liu H, Hersey P, Zhang XD, 'MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to apoptosis induced by the RAF inhibitor PLX4720', Clinical Cancer Research, 17 721-730 (2011) [C1]
|
|
Nova |
2011 |
Hou LL, Jin L, Han CC, Cheng B, Wang L, Zhang XD, Zhang LJ, 'Role of dysregulation of Bim in resistance of melanoma cells to endoplasmic reticulum stress-induced apoptosis', Chinese Journal of Oncology, 33 494-498 (2011)
Objective: To establish a model of ER stress-induced apoptosis with tunicamycin and to examine whether Bim is dysregulated and its potential role in resistance of melanoma cells t... [more]
Objective: To establish a model of ER stress-induced apoptosis with tunicamycin and to examine whether Bim is dysregulated and its potential role in resistance of melanoma cells to apoptosis under endoplasmic reticulum(ER) stress. Methods: A model of ER stress-induced apoptosis was established with tunicamycin. Apoptotic cells were quantitated using the annexin V/propidium iodide method by flow cytometry. Hoechst staining was also used to confirm the apoptotic cell death. Western blotting was used to measure the activation of caspase-3 and -9, and the expression of Bim, GRP78, CHOP, and Foxol at the protein level. The expression of Bim, CHOP and Foxol at the mRNA level was quantitated by qPCR. The siRNA technique was used to inhibit the expression of Bim. Results: Treatment of the melanoma cells with tunicamycin did not induce significant apoptosis and activation of caspase cascade, whereas it caused marked activation of caspase-3 and -9, and apoptosis in HEK293 cells which were used as a control. With exposure to tunicamycin (3 µmol/L) for 12, 24, 36 hours the Bim protein levels were not increased in Mel-RM and MM200 cells. Its mRNA levels were 0.37 ± 0.05, 0.13 ± 0.02 and 0.02 ± 0.01 in Mel-RM cells, while 0.41 ± 0.06, 0.16 ± 0.04 and 0.21 ± 0.03 in MM200 cells, respectively. The expression of Bim mRNA was significantly reduced compared with that in the control groups of the two cell lines (P < 0.01). siRNA knockdown of Bim protected HEK293 cells against activation of caspase-3. The cell apoptosis of Bim siRNA group was(5.69 ± 0.38)%, significantly lower than that of the siRNA control group (40.32 ± 1.64)% and blank control group (35.46 ± 2.01)% (P < 0.01). In the melanoma cells after exposure to tunicamycin (3 µmol/L) for 6, 12, 24, and 36 hours the transcription factor CHOP at mRNA level were significantly increased and the expressions at protein level were also up-regulated. The expressions of another transcription factor Foxol at mRNA level significantly decreased and the expressions at protein level were down-regulated, too. Conclusions: The lack of Bim up-regulation contributes to the resistance of melanoma cells to ER stress-induced apoptosis and may be a mechanism by which melanoma cells adapt to ER stress conditions. Transcription factors CHOP and Foxol may be responsible for the dysregulation of Bim in melanoma cells upon ER stress.
|
|
|
2011 |
Liu H, Jiang CC, Cheng X, Fang L, Chen C, Zhang XD, Jiang ZW, 'Effects of resveratrol on proliferation and apoptosis in human melanoma cells', Chinese Pharmacological Bulletin, 27 998-1002 (2011)
Aim: To investigate the effect of resveratrol (Res) on the proliferation and apoptosis in human melanoma cells. Methods: Mel-RM and MM200 cells were treated with different concent... [more]
Aim: To investigate the effect of resveratrol (Res) on the proliferation and apoptosis in human melanoma cells. Methods: Mel-RM and MM200 cells were treated with different concentrations of Res. Cell viability was measured using the MTT assay. Apoptosis induced by Res was examined using the propidium iodide (PI) staining in flow cytometry. Mitochondrial membrane potential (¿¿m) in Mel-RM and MM200 cells was detected by JC-1 staining. Activation of Caspase-3 was detected by special kit. Results: Cell viability was inhibited by Res with the increasing concentration. 80, 160 µmol·L-1 Res could induces obvious apoptosis in melanoma Mel-RM and MM200 cells. JC-1 staining results showed that Res could decrease the mitochondrial membrane potential in Mel-RM and MM200 cells. It also induced the activation of Caspases-3. Conclusions: Res can inhibit the proliferation and induce apoptosis in melanoma Me1-RM and MM200 cells. The effect might be associated with the reduction of ¿¿m and the activation of Caspase-3.
|
|
|
2011 |
Hersey P, Smalley KSM, Weeraratna A, Bosenberg M, Zhang XD, Haass NK, et al., 'Meeting report from the 7th international melanoma congress, Sydney, November, 2010', Pigment Cell and Melanoma Research, 24 e1-e15 (2011)
The 2010 7th International Melanoma Congress sponsored by the Society for Melanoma Research and held in Sydney, Australia, was held together with the International Melanoma and Sk... [more]
The 2010 7th International Melanoma Congress sponsored by the Society for Melanoma Research and held in Sydney, Australia, was held together with the International Melanoma and Skin Cancer Centers group and the International Melanoma Pathology Study Group. As a consequence, there were over 900 registrants that included a wide range of clinicians (surgeons, medical oncologists, dermatologists) specialising in the management of melanoma as well as scientists and students carrying out laboratory-based research in melanoma. There was a general consensus that this grouping of clinicians, pathologists and scientists was mutually advantageous and plans are afoot to continue this grouping in future meetings. The meeting was dominated by the advances being made in treatment of melanoma with selective BRAF inhibitors but interest in epithelial mesenchymal transition and phenotypic changes in melanoma was apparent in many of the talks. The authors have attempted to capture many of the new developments in melanoma research but apologize to those speakers and poster presenters who had equally important findings not captured in these summaries.
|
|
|
2011 |
Sadeqzadeh E, De Bock CE, Zhang XD, Shipman KL, Scott NM, Song C, et al., 'Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products', Journal of Biological Chemistry, 286 28181-28191 (2011) [C1]
|
|
Nova |
2011 |
Jin L, Hu WL, Jiang CC, Wang JX, Han CC, Chu P, et al., 'MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma', Proceedings of the National Academy of Sciences, 108 15840-15845 (2011) [C1]
|
|
Nova |
2011 |
Wilmott JS, Zhang XD, Hersey P, Scolyer RA, 'The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers', Pathology, 43 657-671 (2011) [C1]
|
|
Nova |
2011 |
Dong L, Jiang CC, Thorne RF, Croft A, Yang F, Liu H, et al., 'Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress', Oncogene, 30 3716-3726 (2011) [C1]
|
|
Nova |
2010 |
Tseng H-Y, Jiang CC, Croft A, Croft A, Thorne RF, Yang F, et al., 'Contrasting effects of Nutlin-3 on TRAIL - and Docetaxel-induced Apoptosis due to upregulation of TRAIL-R2 and Mcl-1 in human melanoma cells', Molecular Cancer Therapeutics, 9 3363-3374 (2010) [C1]
|
|
Nova |
2010 |
Jiang CC, Lai F, Tay KH, Croft A, Rizos H, Becker TM, et al., 'Apoptosis of human melanoma cells induced by inhibition of B-RAF(V600E) involves preferential splicing of bim(S)', Cell Death & Disease, 1 e69 (2010) [C1]
|
|
Nova |
2010 |
Cheng X, Liu H, Fang L, Su F, Song LL, Ma LY, et al., '2-DG enhances chemosensitivity of breast cancer cells to adriamycin', Chinese Pharmacological Bulletin, 26 1371-1376 (2010)
Aim: To determine whether 2-DG can synergize with chemotherapeutic agent Adriamycin(ADM) which is commonly used in breast cancer treatment and wish to find new targets for human b... [more]
Aim: To determine whether 2-DG can synergize with chemotherapeutic agent Adriamycin(ADM) which is commonly used in breast cancer treatment and wish to find new targets for human breast cancer chemotherapy. Methods Sk-Br-3 breast cancer cells were incubated with varying concentrations of ADM(0.625, 1.25,2.5,5 and 10 mg·L-1) with or without 2-DG (1.25,2.5,5,10 and 20 mmol·L-1). Cell viability was measured using the MTT(3-(4,5-dimethylthiazol-2-y1)-2-5 diphenyltetrazolium bromide) assay. Then propidium iodide (PI) staining measured apoptotic cells in Flow Cytometry (FCM). Sk-Br-3 cells were treated with 2-DG (10 mmol·L-1) (with or without ADM) for different time points (0,9,24,36 h). Western blot measured proteins GRP-78 and caspase-3 expression. Results: Combining 2-DG with ADM resulted in enhanced cell death compared with the individual use of each agent, 2-DG induced apoptotic cells < 10% and 2-DG markedly up-regulated GRP-78 expression. With the combination of 2-DG and ADM, the apoptotic rate of Sk-Br-3 cells reached 58.11%. Conclusion: These results indicate that 2-DG acts synergistically with chemotherapeutic agents in causing breast cancer cell death and the class of chemicals most sensitive appear to be those which cause DNA damage.
|
|
|
2010 |
Bowden NA, Ashton KA, Kiejda KA, Zhang XD, Hersey P, Scott R, 'Nucleotide excision repair gene expression after cisplatin treatment in melanoma', Cancer Research, 70 7918-7926 (2010) [C1]
|
|
Nova |
2010 |
Thorne RF, Ralston KJ, De Bock CE, Mhaidat NM, Zhang XD, Boyd AW, Burns GF, 'Palmitoylation of CD36/FAT regulates the rate of its post-transcriptional processing in the endoplasmic reticulum', Biochimica et Biophysica Acta - Molecular Cell Research, 1803 1298-1307 (2010) [C1]
|
|
Nova |
2010 |
Zhuang L, Scolyer RA, Murali R, McCarthy SW, Zhang XD, Thompson JF, Hersey P, 'Lactate dehydrogenase 5 expression in melanoma increases with disease progression and is associated with expression of Bcl-XL and Mcl-1, but not Bcl-2 proteins', Modern Pathology, 23 45-53 (2010) [C1]
|
|
Nova |
2010 |
Yang F, Tay KH, Dong L, Thorne RF, Jiang CC, Yang E, et al., 'Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIPL from degradation by the E3 ligase itch in human melanoma cells', Cell Death and Differentiation, 17 1354-1367 (2010) [C1]
|
|
Nova |
2010 |
Mao ZG, Jiang CC, Thorne RF, Hersey P, Zhang XD, 'TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4', Apoptosis, 15 1211-1222 (2010) [C1]
|
|
Nova |
2009 |
Liu H, Jiang CC, Lavis CJ, Croft A, Dong L, Tseng H-Y, et al., '2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2', Molecular Cancer, 8 Article no. 122 (2009) [C1]
|
|
Nova |
2009 |
Jiang CC, Yang F, Thorne RF, Zhu BK, Hersey P, Zhang XD, 'Human melanoma cells under endoplasmic reticulum stress acquire resistance to microtubule-targeting drugs through XBP-1-mediated activation of Akt', Neoplasia, 11 436-447 (2009) [C1]
|
|
Nova |
2009 |
Jiang CC, Wroblewski D, Yang F, Hersey P, Zhang XD, 'Human melanoma cells under endoplasmic reticulum stress are more susceptible to apoptosis induced by the BH3 mimetic obatoclax', Neoplasia, 11 945-955 (2009) [C1]
|
|
Nova |
2009 |
Hersey P, Watts RN, Zhang XD, Hackett J, 'Metabolic approaches to treatment of melanoma', Clinical Cancer Research, 15 6490-6494 (2009) [C1]
|
|
Nova |
2009 |
Yang F, Liu H, Zhang XD, Jiang ZW, 'Inhibition of MEK sensitizes human breast carcinoma cells to endoplasmic reticulum pathway's apoptosis', Chinese Pharmacological Bulletin, 25 (2009)
Aim: To investigate the inhibition of MEK/ERK pathway affecting the sensitivity of human breast carcinoma cells SK-BR-3 to endoplasmic reticulum (ER) stress-induced apoptosis and ... [more]
Aim: To investigate the inhibition of MEK/ERK pathway affecting the sensitivity of human breast carcinoma cells SK-BR-3 to endoplasmic reticulum (ER) stress-induced apoptosis and wish to find new targets for human breast carcinoma chemotherapy. Methods: Different concentrations(0, 1.5, 3, 6, 9 and 12 µmol;·L-1) tunicamycin (TM) treated human breast carcinoma cells SK-BR-3 for 48 h, then propidium iodide (PI) staining measured apoptotic cells in Flow Cytometry(FCM). Different times(0, 6, 12, 24 and 36 h) of TM (3 µmol;·L-1) treated SK-BR-3 cells, Western blot measured proteins GRP78, ERK1/2 and pERK expression. MEK inhibitor U0126 (20 µmol;·L-1) pretreated cells for 1 h before treatment with TM (3 µmol;·L-1) in different concentrations and times, measured above identical indexes and compared with their diversities of treatment with U0126 or not. Results: TM induced apoptotic cells <20% and TM markedly up-regulated GRP78 expression. Combination of U0126 and TM induced apoptotic cells to 78%. TM did not induce further activation of ERK1/2 in SK-BR-3 cells. U0126 down-regulated GRP78 expression and blocked TM-induced up-regulation of GRP78. Conclusion: U0126 sensitizes human breast carcinoma cells SK-BR-3 to ER stress-induced apoptosis. U0126 inhibits TM-induced unfolded protein response (UPR).
|
|
|
2009 |
Jiang CC, Mao ZG, Kiejda KA, Hersey P, Zhang XD, 'Glucose-regulated protein 78 antagonizes cisplatin and adriamycin in human melanoma cells', Carcinogenesis, 30 197-204 (2009) [C1]
|
|
Nova |
2009 |
Zhang LJ, Chen S, Wu P, Hu CS, Thorne RF, Luo CM, et al., 'Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER stress in gastric cancer cells', Cancer Letters, 274 40-46 (2009) [C1]
|
|
Nova |
2009 |
Zhuang L, Scolyer RA, Lee CS, McCarthy SW, Cooper WA, Zhang XD, et al., 'Expression of glucose-regulated stress protein GRP78 is related to progression of melanoma', Histopathology, 54 462-470 (2009) [C1]
|
|
Nova |
2009 |
Hersey P, Zhang XD, 'Treatment combinations targeting apoptosis to improve immunotherapy of melanoma', Cancer Immunology, Immunotherapy, 58 1749-1759 (2009) [C1]
|
|
Nova |
2009 |
Zhang X-H, Li SC, Fong K-Y, Thumboo J, 'The Impact of Health Literacy on Health-Related Quality of Life (HRQoL) and utility assessment among patients with rheumatic diseases', Value in Health, 12 S106-S109 (2009) [C1]
|
|
|
2008 |
Kiejda KA, Zhang XD, Adams LJ, Scott R, Vojtesek B, Lane DP, Hersey P, 'Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin', Clinical Cancer Research, 14 1659-1668 (2008) [C1]
|
|
Nova |
2008 |
Mhaidat NM, Thorne RF, Zhang XD, Hersey P, 'Involvement of endoplasmic reticulum stress in Docetaxel-induced JNK-dependent apoptosis of human melanoma', Apoptosis, 13 1505-1512 (2008) [C1]
|
|
Nova |
2008 |
Hersey P, Zhang XD, 'Adaptation to ER stress as a driver of malignancy and resistance to therapy in human melanoma', Pigment Cell and Melanoma Research, 21 358-367 (2008) [C1]
|
|
Nova |
2008 |
Liu H, Jiang ZW, Tong XH, Zhang XD, 'Inhibitory effects of heparan sulfate proteoglycan on transplanted breast cancer in C
Aim: To observe the anti-tumor activity and the mechanism of heparan sulfate proteoglycan (HSPG) on C3H mice transplanted tumors. Methods: Tumor model was established and randomly... [more]
Aim: To observe the anti-tumor activity and the mechanism of heparan sulfate proteoglycan (HSPG) on C3H mice transplanted tumors. Methods: Tumor model was established and randomly divided into five groups. HSPG groups (5, 10, 50 mg·kg-1), positive group and control group, intraperitoneal injection was performed once a day for 22 days and the volume of tumors was measured. Mice were treated on 24th day, then tumor weight was examined, thymus index, and spleen index were calculated, the apoptosis was determined by TdT-mediated Dutp nick end labeling (TUNEL) assay in situ, the expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemistry. Results: The tumor volume in HSPG groups was reduced without the decrease of thymus index, spleen index. TUNEL assay in situ showed numerous heavy blue apoptosis cells in the HSPG groups significantly higher than in control groups. The tumors in HSPG groups showed significantly lower VEGF expression than those in control group. Conclusion: HSPG had significant anti-tumor effects on C3H mice transplantable breast cancer. The mechanisms may be associated with the effects of inducing tumor cell apoptosis and inhibiting the VEGF expression.
|
|
|
2008 |
Chen LH, Jiang CC, Watts R, Thorne RF, Kiejda KA, Zhang XD, Hersey P, 'Inhibition of endoplasmic reticulum stress-induced apoptosis of melanoma cells by the ARC protein', Cancer Research, 68 834-842 (2008) [C1]
|
|
Nova |
2008 |
Jiang CC, Lucas K, Kiejda KA, Wade M, Debock CE, Thorne RF, et al., 'Up-regulation of Mcl-1 is critical for survival of human melanoma cells upon endoplasmic reticulum stress', Cancer Research, 68 6708-6717 (2008) [C1]
|
|
Nova |
2008 |
Mhaidat NM, Thorne RF, De Bock CE, Zhang XD, Hersey P, 'Melanoma cell sensitivity to docetaxal-induced apoptosis is determined by class III beta-tubulin levels', FEBS Letters, 582 267-272 (2008) [C1]
|
|
|
2008 |
Zhu B-K, Wang P, Zhang XD, Jiang CC, Chen LH, Kiejda KA, et al., 'Activation of Jun N-terminal kinase is a mediator of vincristine-induced apoptosis of melanoma cells', Anti-Cancer Drugs, 19 189-200 (2008) [C1]
|
|
Nova |
2008 |
Zhang LJ, Hao YZ, Hu CS, Ye Y, Xie QP, Thorne RF, et al., 'Inhibition of apoptosis facilitates necrosis induced by cisplatin in gastric cancer cells', Anti-Cancer Drugs, 19 159-166 (2008) [C1]
|
|
Nova |
2007 |
Zhuang L, Lee CS, Scolyer RA, McCarthy SW, Zhang XD, Thompson JF, Hersey P, 'Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma', Modern Pathology, 20 416-426 (2007) [C1]
|
|
|
2007 |
Mhaidat NM, Zhang XD, Jiang CC, Hersey P, 'Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway', Clinical Cancer Research, 13 1308-1314 (2007) [C1]
|
|
|
2007 |
Yu FW, Jiang CC, Kiejda KA, Gillespie S, Zhang XD, Hersey P, 'Apoptosis induction in human melanoma cells by inhibition of MEK is caspase-independent and mediated by the Bcl-2 family members PUMA, Bim, and Mcl-1', Clinical Cancer Research, 13 4934-4942 (2007) [C1]
|
|
|
2007 |
Mhaidat NM, Wang Y, Kiejda KA, Zhang XD, Hersey P, 'Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2', Molecular Cancer Therapeutics, 6 752-761 (2007) [C1]
|
|
|
2007 |
Mhaidat NM, Thorne RF, Zhang XD, Hersey P, 'Regulation of docetaxel-induced apoptosis of human melanoma cells by different isoforms of protein kinase C', Molecular Cancer Research, 5 1073-1081 (2007) [C1]
|
|
|
2007 |
Mhaidat NM, Zhang XD, Allen J, Kiejda KA, Scott R, Hersey P, 'Temozolomide induces senescence but not apoptosis in human melanoma cells', British Journal of Cancer, 97 1225-1233 (2007) [C1]
|
|
|
2007 |
Jiang CC, Li HC, Gillespie S, Kiejda KA, Mhaidat N, Yu FW, et al., 'Tunicamycin sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by up-regulation of TRAIL-R2 via the unfolded protein response', Cancer Research, 67 5880-5888 (2007) [C1]
|
|
|
2007 |
Jiang CC, Li HC, Gillespie S, Yu FW, Kiejda KA, Zhang XD, Hersey P, 'Inhibition of MEK sensitizes human melanoma cells to endoplasmic reticulum stress-induced apoptosis', Cancer Research, 67 9750-9761 (2007) [C1]
|
|
|
2007 |
Chen LH, Jiang CC, Kiejda KA, Wang YF, Thorne RF, Zhang XD, Hersey P, 'Thapsigargin sensitizes human melanoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-R2 through the unfolded protein response', Carcinogenesis, 28 2328-2336 (2007) [C1]
|
|
|
2006 |
Zhuang L, Lee CS, Scolyer RA, McCarthy SW, Zhang XD, Thompson JF, et al., 'Progression in melanoma is associated with decreased expression of death receptors for tumor necrosis factor-related apoptosis-inducing ligand', Human Pathology, 37 1286-1294 (2006) [C1]
|
|
Nova |
2006 |
Yu F, Watts RN, Zhang XD, Borrow JM, Hersey P, 'Involvement of BH3-only proapoptotic proteins in mitochondrial-dependent Phenoxodiol-induced apoptosis of human melanoma cells', Anti-Cancer Drugs, 17 1151-1161 (2006) [C1]
|
|
|
2006 |
Gillespie S, Borrow J, Zhang XD, Hersey P, 'Bim plays a crucial role in synergistic induction of apoptosis by the histone deacetylase inhibitor SBHA and TRAIL in melanoma cells', Apoptosis, 11 2251-2265 (2006) [C1]
|
|
|
2006 |
Zhang XD, Wu JJ, Gillespie S, Borrow JM, Hersey P, 'Cross resistance of melanoma to trail-induced apoptosis and chemotherapy', Update on Cancer Therapeutics, 1 435-441 (2006) [C1]
|
|
|
2006 |
Hersey P, Zhuang L, Zhang XD, 'Current strategies in overcoming resistance of cancer cells to apaptosis melanoma as a model', International Review of Cytology - A Survey of Cell Biology, 251 131-158 (2006) [C1]
|
|
Nova |
2006 |
Zhang XD, Wu JJ, Gillespie S, Borrow J, Hersey P, 'Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin', Clinical Cancer Research, 12 1355-1364 (2006) [C1]
|
|
Nova |
2005 |
Wu JJ, Zhang XD, Gillespie S, Hersey P, 'Selection for TRAIL resistance results in melanoma cells with high proliferative potential', FEBS Letters, 579 1940-1944 (2005) [C1]
|
|
|
2005 |
Zhuang L, Lee CS, Scolyer RA, McCarthy SW, Palmer AA, Zhang XD, et al., 'Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma', Journal of Clinical Pathology, 58 1163-1169 (2005) [C1]
|
|
|
2005 |
Allen JD, Zhang XD, Scott CL, Boyle GM, Hersey P, Strasser A, 'Is Apaf-1 expression frequently abrogated in melanoma?', CELL DEATH AND DIFFERENTIATION, 12 680-681 (2005)
|
|
|
2005 |
Gillespie S, Zhang XD, Hersey P, 'Variable expression of protein kinase CE in human melanoma cells regulates sensitivity to TRAIL-induced apoptosis', Molecular Cancer Therapeutics, 4 668-676 (2005) [C1]
|
|
|
2004 |
Zhang XY, Zhang (Ext) XD, Borrow JM, Nguyen T, Hersey P, 'Translational Control of Tumor Necrosis Factor-related Apoptosis-inducing Ligand Death Receptor Expression in Melanoma Cells', Journal of Biological Chemistry, 279 10606-10614 (2004) [C1]
|
|
Nova |
2004 |
Waterhouse D, Dragowska WH, Gelmon KA, Mayer LD, Bally MB, 'Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model', Cancer Biology & Therapy, 3 197-204 (2004)
|
|
|
2004 |
Zhang (Ext) XD, Gillespie SK, Hersey P, 'Staurosporine induces apoptosis of melanoma by both caspase-dependant and -independant apoptotic pathways', Molecular Cancer Therapeutics, 3 187-197 (2004) [C1]
|
|
|
2004 |
Zhang (Ext) XD, Gillespie SK, Borrow JM, Hersey P, 'The histone deacetylase inhibitor suberic bishydroxamate regulates the expression of multiple apoptotic mediators and induces mitochondria-dependent apoptosis of melanoma cells', Molecular Cancer Therapeutics, 3 425-435 (2004) [C1]
|
|
|
2004 |
Gillespie SK, Zhang XD, Hersey P, 'Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor-related apoptosis-inducing ligand-induced aopootsis in melanoma cells', Molecular Cancer Therapeutics, 3 1651-1658 (2004) [C1]
|
|
|
2003 |
Hersey P, Zhang XD, 'Resistance of follicular lymphoma cells to chemotherapy is more than just Bcl-2', CANCER BIOLOGY & THERAPY, 2 541-543 (2003)
|
|
|
2003 |
Xu DZ, Gillespie SK, Borrow JM, Hersey P, 'The histone deacetylase inhibitor suberic bishydroxamate: a potential sensitizer of melanoma to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis', Biochemical Pharmacology, 66 1537-1545 (2003) [C1]
|
|
|
2003 |
Hersey P, Zhang (Ext) XD, 'Overcoming resistance of cancer cells to apoptosis', Journal of Cellular Physiology, 196 9-18 (2003) [C1]
|
|
|
2003 |
Zhang XD, Borrow JM, Zhang XY, Nguyen T, Hersey P, 'Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria', ONCOGENE, 22 2869-2881 (2003)
|
|
|
2001 |
Zhang X, Zhang X, Gray C, Nguyen T, Hersey P, 'Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of human melanoma is regulated by Smac/DIABLO release from mitochondria', Cancer Research, 61 7339-7348 (2001) [C1]
|
|
|
2001 |
Franco A, Zhang X, Van Berkel E, Sanders J, Zhang X, Thomas W, et al., 'The role of NF-kB in TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of melanoma cells', The Journal of Immunology, 166 5337-5345 (2001) [C1]
|
|
|
2001 |
Nguyen T, Zhang XD, Hersey P, 'Relative Resistance of Fresh Isolates of Melanoma to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis', Cancer Research, 7 (2001)
In previous studies, we have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) could induce varying degrees of apoptosis in approximately two-thirds of hu... [more]
In previous studies, we have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) could induce varying degrees of apoptosis in approximately two-thirds of human melanoma lines. In the present study, we have examined the sensitivity of fresh isolates and early passages of melanoma cells to TRAIL-induced apoptosis from eight patients. We found that fresh isolates were relatively resistant to TRAIL-induced apoptosis and that this appeared to be associated with low TRAIL death receptor (TRAIL-R) expression. TRAIL-R expression was also undetectable in tissue sections from the same melanoma. We attempted to create a model for these findings by generation of TRAIL-resistant melanoma lines from TRAIL-sensitive lines grown for prolonged periods in TRAIL. The resulting TRAIL-resistant melanoma cell lines had low TRAIL-R expression, and sensitivity to TRAIL was increased rapidly by pretreatment with proteasome inhibitors known to inhibit activation of nuclear factor-¿:B. However, the latter treatment had no significant effect on the sensitivity of fresh isolates to TRAIL. The levels of the inhibitors of apoptosis, Flice-like inhibitory protein and Bcl-2, also did not relate to resistance to TRAIL-induced apoptosis. These results suggest that down-regulation of TRAIL-R on melanoma cells may be the primary determinant of resistance of fresh isolates to TRAIL, and the basis for this requires further investigation. © 2001, American Association for Cancer Research. All rights reserved.
|
|
|
2001 |
Nguyen T, Zhang X, Hersey P, 'Relative resistance of fresh isolates of melanoma to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis', Clinical Cancer Research, 7 966s-973s (2001) [C1]
|
|
|
2001 |
Hersey P, Zhang X, 'How melanoma cells evade trail-induced apoptosis', Nature Reviews Cancer, 1 142-150 (2001) [C1]
|
|
|
2000 |
Zhang X, Nguyen T, Thomas W, Sanders J, Hersey P, 'Mechanisms of resistance of normal cells to TRAIL induced apoptosis vary between different cell types', FEBS Letters, 482 193-199 (2000) [C1]
|
|
|
2000 |
Zhang X, Franco A, Nguyen T, Gray C, Hersey P, 'Differential Localization and Regulation of Death and Decoy Receptors for TNF-Related Apoptosis-Inducing Ligand (TRAIL) in Human Melanoma Cells', The Journal of Immunology, 164 No 8 3961-3970 (2000) [C1]
|
|
|
2000 |
Thomas W, Zhang X, Franco A, Nguyen T, Hersey P, 'TNF-Related Apoptosis-Inducing Ligand-Induced Apoptosis of Melanoma is Associated with Changes in Mitochondrial Membrane Potential and Perinuclear Clustering of Mitochondria', The Journal of Immunology, 165 No 10 5612-5620 (2000) [C1]
|
|
|
2000 |
Nguyen T, Thomas W, Zhang X, Gray C, Hersey P, 'Immunologically-mediated tumour cell apoptosis: the role of TRAIL in T cell and cytokine-mediated responses to melanoma', Forum: Trends in Experimental and Clinical Medicine, 10 243-252 (2000) [C3]
|
|
|
1999 |
Zhang XD, Franco A, Myers K, Gray C, Nguyen T, Hersey P, 'Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma', CANCER RESEARCH, 59 2747-2753 (1999)
|
|
|
1999 |
Zhang XD, Hersey P, 'Expression of catenins and p120(cas) in melanocytic nevi and cutaneous melanoma: Deficient alpha-catenin expression is associated with melanoma progression', PATHOLOGY, 31 239-246 (1999)
|
|
|
1998 |
Zhang XD, Coventry BJ, Jamieson GG, Gill PG, 'The utility of the proliferative index in pretreatment biopsy specimens of esophageal squamous cell carcinoma.', Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus, 11 215-220 (1998)
|
|
|
1998 |
Zhang XD, Schiller GD, Gill PG, Coventry BJ, 'Lymphoid cell infiltration during breast cancer growth: A syngeneic rat model', IMMUNOLOGY AND CELL BIOLOGY, 76 550-555 (1998)
|
|
|
1997 |
Yang ZJ, Yuan HP, Zou P, Tong WD, Qu SX, Zhang XD, 'Osteogenic responses to extraskeletally implanted synthetic porous calcium phosphate ceramics: an early stage histomorphological study in dogs', JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 8 697-701 (1997)
|
|
|