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Kinase targeting and clear cell carcinoma

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https://www.readbyqxmd.com/read/29422973/chloroquine-affects-autophagy-to-achieve-an-anticancer-effect-in-ec109-esophageal-carcinoma-cells-in-vitro
#1
Yan Cai, Jiajing Cai, Qiang Ma, Yuan Xu, Jiang Zou, Lei Xu, Dongsheng Wang, Xiaolan Guo
Esophageal carcinoma is a malignancy that severely threatens human health, with a high incidence rate and a low 5-year survival rate. Resistance to chemotherapy frequently emerges during its treatment, partly due to the induction of autophagy. Therefore, targeting autophagy may be a promising therapeutic approach for the treatment of esophageal carcinoma. In the present study, it was investigated how chloroquine (CQ) can influence the growth ability and biological behaviors of EC109 esophageal squamous carcinoma cells in vitro, as well as the potential molecular mechanisms behind its activity...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29391889/significant-expression-of-chk1-and-p53-in-bladder-urothelial-carcinoma-as-potential-therapeutic-targets-and-prognosis
#2
Linfeng Zheng, Yuping Zhu, Lei Lei, Wenyong Sun, Guoping Cheng, Shifeng Yang
Checkpoint kinase 1 (CHK1) and p53 are involved in cell-cycle checkpoint, and cellular response to DNA damage. CHK1 and p53 are overexpressed in bladder urothelial carcinoma (BUC); however, a clear elucidation on their interaction and influence in the progress of BUC is absent. The aim of the present study was to examine the correlation between CHK1 and p53 in BUC, and analyze their value as therapeutic targets and prognostic indicators in BUC. A clinically annotated cohort of 110 patients with BUC was identified retrospectively...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29368125/overview-of-current-and-future-first-line-systemic-therapy-for-metastatic-clear-cell-renal-cell-carcinoma
#3
REVIEW
David M Gill, Andrew W Hahn, Peter Hale, Benjamin L Maughan
Treatment of metastatic clear cell renal cancer (mccRCC) has seen substantial progress over the last 20 years, with many regulatory approvals since 2006 culminating in a substantial increase to overall survival (OS). Six therapies are currently available for first-line use, with additional treatments currently being tested in this setting, some of which are expected to be approved soon based on new data from the CABOSUN and CheckMate-214 trials. Based on the available evidence, we strongly believe that vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) therapy over mechanistic target or rapamycin (mTOR; formerly known as mammalian target of rapamycin) inhibitor therapy is the most effective first-line option regardless of risk category assignment...
January 24, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29343969/the-putative-tumor-suppressor-mir-199a-regulated-by-snail-modulates-clear-cell-renal-cell-carcinoma-aggressiveness-by-repressing-rock1
#4
Xiao Zhang, Peng Li, Zhen Ding, Huili Wang, Junye Wang, Lei Han, Shangwei Ding
Background: Aberrant expression of miR-199a has been frequently reported in cancer studies; however, its role in renal cell carcinoma (RCC) has not been examined in detail. Results: Here, we showed that miR-199a was downregulated in RCC and associated with poor prognostic phenotype. Using luciferase and western blot assays we identified that Rho-associated coiled coil-containing protein kinases 1 (ROCK1) was a direct target gene for miR-199a. miR-199a regulated proliferation, invasion, and apoptosis of clear cell renal cell carcinoma (ccRCC) cells by modulating ROCK1 expression...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29325268/-clinical-significance-of-targeting-drug-based-molecular-biomarkers-expression-in-ovarian-clear-cell-carcinoma
#5
M J Li, H R Li, X Cheng, R Bi, X Y Tu, F Liu, L H Chen
Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues...
December 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/29163707/n-myc-downstream-regulated-gene-2-restrains-glycolysis-and-glutaminolysis-in-clear-cell-renal-cell-carcinoma
#6
Wei Shi, Xinyuan Xu, Fei Yan, Bao Wang, Hang Zhao, Aaron Chan, Zhen Ren, Yongzheng Ma, Fuli Wang, Jianlin Yuan
Glycolysis and glutaminolysis are heavily involved in the metabolic reprogramming of cancer cells. The activation of oncogenes and inactivation of tumor suppressor genes has a marked effect on the cellular metabolic processes glycolysis and glutaminolysis. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene that previous studies have demonstrated can inhibit the growth, proliferation and metastasis of clear cell renal cell carcinoma (ccRCC) cells. However, the function of NDRG2 in ccRCC metabolism remains unknown...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29158991/ndufa4l2-is-associated-with-clear-cell-renal-cell-carcinoma-malignancy-and-is-regulated-by-elk1
#7
Lei Wang, Zhiqiang Peng, Kaizhen Wang, Yijun Qi, Ying Yang, Yue Zhang, Xinyuan An, Shudong Luo, Junfang Zheng
Background: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated...
2017: PeerJ
https://www.readbyqxmd.com/read/29144835/modern-systemic-therapy-for-metastatic-renal-cell-carcinoma-of-the-clear-cell-type
#8
Mamta Parikh, Primo N Lara
In the last 30 years, there have been many advances in the treatment of metastatic renal cell carcinoma of the clear cell type. Renal cell carcinoma has long been understood to have a component of immune mediation and has been responsive to immune-based therapies; in addition to early cytokine therapy, newer checkpoint inhibition therapies have also demonstrated activity. Molecular characterization of the genome of clear cell renal cell carcinoma enabled identification of the roles of angiogenesis and hypoxic stress...
November 16, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#9
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29119970/hispidulin-mediates-apoptosis-in-human-renal-cell-carcinoma-by-inducing-ceramide-accumulation
#10
Hui Gao, Ming-Quan Gao, Jian-Jun Peng, Mei Han, Kai-Li Liu, Yan-Tao Han
Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Hispidulin (10, 20 μmol/L) decreased the viability of ccRCC cells in dose- and time-dependent manners without affecting that of normal tubular epithelial cells...
November 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29089775/practical-management-of-adverse-events-associated-with-cabozantinib-treatment-in-patients-with-renal-cell-carcinoma
#11
REVIEW
Benjamin S Gerendash, Patricia A Creel
Cabozantinib is an oral tyrosine-kinase inhibitor whose targets include VEGFR, MET, and AXL. Cabozantinib is approved for the treatment of patients with advanced clear-cell renal-cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the pivotal Phase III trial of second-line RCC, cabozantinib was associated with a significant improvement in overall survival, progression-free survival, and antitumor response compared with everolimus. Adverse events (AEs) were common for patients receiving cabozantinib, but were effectively managed with supportive care and dose modifications, as discontinuations of cabozantinib due to an AE were infrequent...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29077169/clinical-significance-of-sccro-dcun1d1-in-prostate-cancer-and-its-proliferation-inhibiting-effect-on-lncap-cells
#12
Z-H Zhang, J Li, F Luo, Y-S Wang
OBJECTIVE:   SCCRO/DCUN1D1/DCN1 (squamous cell carcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin neddylation) is considered as an oncogene, but its role in the prostate cancer (PC) is still not clear. The current study aims to investigate the expression of SCCRO in PC tumor tissues, further its clinical significance, and proliferation inhibiting effect on PC cells in vitro. PATIENTS AND METHODS: RT-PCR was used to detect the expression of SCCRO in PC tissue and corresponding adjacent normal tissues from 160 cases, and its relationship with clinical pathological characteristics was analyzed...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29063069/targeting-met-in-cancer-therapy
#13
REVIEW
Hong-Nan Mo, Peng Liu
MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile...
September 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29061793/the-anti-tumor-effect-of-cabozantinib-on-ovarian-clear-cell-carcinoma-in-vitro-and-in-vivo
#14
Makiko Nakatani, Hidemichi Watari, Takashi Mitamura, Lei Wang, Yutaka Hatanaka, Kanako C Hatanaka, Kohei Honda, Toshiyuki Nomura, Hiroshi Nishihara, Shinya Tanaka, Noriaki Sakuragi
BACKGROUND: Several reports have shown that the overexpression of the MET proto-oncogene, receptor tyrosine kinase (MET), was more frequently observed in clear cell carcinoma (CCC) than in non-CCC. We evaluated the antitumor activity of cabozantinib, that targets MET. MATERIALS AND METHODS: A gene expression analysis of tumors from human ovarian cancers was carried out by transcriptome sequencing. An in vitro 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay (MTT assay) and in vivo experiments were performed to determine the activity of cabozantinib...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/28984199/roles-of-alternative-splicing-in-modulating-transcriptional-regulation
#15
Jin Li, Yang Wang, Xi Rao, Yue Wang, Weixing Feng, Hong Liang, Yunlong Liu
BACKGROUND: The ability of a transcription factor to regulate its targets is modulated by a variety of genetic and epigenetic mechanisms. Alternative splicing can modulate gene function by adding or removing certain protein domains, and therefore affect the activity of protein. Reverse engineering of gene regulatory networks using gene expression profiles has proven valuable in dissecting the logical relationships among multiple proteins during the transcriptional regulation. However, it is unclear whether alternative splicing of certain proteins affects the activity of other transcription factors...
October 3, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28978636/ezh2-modifies-sunitinib-resistance-in-renal-cell-carcinoma-by-kinome-reprogramming
#16
Remi Adelaiye-Ogala, Justin Budka, Nur P Damayanti, Justine Arrington, Mary W Ferris, Chuan-Chih Hsu, Sreenivasulu Chintala, Ashley R Orillion, Kiersten Marie Miles, Li Shen, May Elbanna, Eric Ciamporcero, Sreevani Arisa, Piergiorgio Pettazzoni, Giulio F Draetta, Mukund Seshadri, Bradley A Hancock, Milan Radovich, Janaiah Kota, Michael Buck, Heike Keilhack, Brian P McCarthy, Scott A Persohn, Paul R Territo, Yong Zang, Joseph Irudayaraj, Andy W Tao, Peter Hollenhorst, Roberto Pili
Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represent a major hurdle in improving the management of clear cell renal cell carcinoma (ccRCC). Recent reports suggest that drug resistance is driven by tumor adaptation via epigenetic mechanisms that activate alternative survival pathways. The histone methyl transferase EZH2 is frequently altered in many cancers including ccRCC. To evaluate its role in ccRCC resistance to RTKi, we established and characterized a spontaneously metastatic, patient-derived xenograft (PDX) model that is intrinsically resistant to the RTKI sunitinib but not to the VEGF therapeutic antibody bevacizumab...
October 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28975890/identification-and-validation-of-novel-prognostic-markers-in-renal-cell-carcinoma
#17
Maj Rabjerg
Kidney cancer (Renal Cell Carcinoma (RCC)) is one of the most deadly malignancies due to frequent late diagnosis and poor treatment options. Histologically, RCC embraces a wide variety of different subtypes with the clear cell variant (ccRCC) being the most common, accounting for 75-90% of all RCCs. At present, the surveillance protocols for follow-up of RCC patients after radical nephrectomy are based on the American Joint Committee on Cancers (AJCC) pathological tumor-node-metastasis (TNM) classification system...
October 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28974261/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-57-66-edited-by-chinese-journal-of-cancer
#18
EDITORIAL
(no author information available yet)
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 57. What are the major stresses that drive the formation, progression, and metastasis of a cancer? Question 58. What is the mechanism responsible for altering an acidic intracellular pH and a basic extracellular pH in normal tissue cells to a basic intracellular pH and an acidic extracellular pH in cancer cells, a fundamental and yet largely ignored phenomenon? Question 59...
October 3, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28952411/clinical-development-of-mtor-inhibitors-for-renal-cancer
#19
REVIEW
Michele Ghidini, Fausto Petrelli, Antonio Ghidini, Gianluca Tomasello, Jens Claus Hahne, Rodolfo Passalacqua, Sandro Barni
Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. In the last 10 years, clinical trials have established multitargeted tyrosine kinase inhibitors (TKIs) as the standard first-line treatment in patients with metastatic disease. Multiple agents are now available for treatment in subsequent lines.The mammalian target of rapamycin (mTOR) inhibitors (e.g., everolimus alone or with lenvatinib) are among the most effective options. Areas covered: This paper provides a complete and updated overview on mTOR inhibitors for the treatment of advanced RCC...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28951458/phgdh-as-a-key-enzyme-for-serine-biosynthesis-in-hif2%C3%AE-targeting-therapy-for-renal-cell-carcinoma
#20
Hirofumi Yoshino, Nijiro Nohata, Kazutaka Miyamoto, Masaya Yonemori, Takashi Sakaguchi, Satoshi Sugita, Toshihiko Itesako, Satoshi Kofuji, Masayuki Nakagawa, Rajvir Dahiya, Hideki Enokida
Continuous activation of hypoxia-inducible factor (HIF) is important for progression of renal cell carcinoma (RCC) and acquired resistance to anti-angiogenic multi-kinase and mTOR inhibitors. Recently, HIF2α antagonists PT2385 and PT2399 were developed and are being evaluated in a Phase I clinical trial for advanced or metastatic clear cell RCC (ccRCC). However, resistance to HIF2α antagonists would be expected to develop. In this study, we identified signals activated by HIF2α deficiency as candidate mediators of resistance to the multi-kinase inhibitor sunitinib...
September 26, 2017: Cancer Research
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