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Kinase targeting and clear cell carcinoma

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https://www.readbyqxmd.com/read/29163707/n-myc-downstream-regulated-gene-2-restrains-glycolysis-and-glutaminolysis-in-clear-cell-renal-cell-carcinoma
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28947862/a-review-on-eph-ephrin-angiogenesis-and-lymphangiogenesis-in-gastric-colorectal-and-pancreatic-cancers
#16
Julia Rudno-Rudzińska, Wojciech Kielan, Ewelina Frejlich, Krzysztof Kotulski, Wojciech Hap, Krzysztof Kurnol, Przemysław Dzierżek, Marcin Zawadzki, Agnieszka Hałoń
Erythroprotein-producing human hepatocellular carcinoma receptors (Eph receptors) compose a subfamily of transmembrane protein-tyrosine kinases receptors that takes part in numerous physiological and pathological processes. Eph family receptor-interacting proteins (Ephrins) are ligands for those receptors. Eph/ephrin system is responsible for the cytoskeleton activity, cell adhesion, intercellular connection, cellular shape as well as cell motility. It affects neuron development and functioning, bone and glucose homeostasis, immune system and correct function of enterocytes...
August 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28867195/simultaneous-targeting-pi3k-and-perk-pathways-promotes-cell-death-and-improves-the-clinical-prognosis-in-esophageal-squamous-carcinoma
#17
Shao-Qi Wang, Xiao Wang, Kai Zheng, Kai-Sheng Liu, Shao-Xiang Wang, Cong-Hua Xie
PI3K pathway is an important anti-tumor target, but its effect and mechanism is not clear in esophageal squamous cell carcinoma (ESCC). By analysis of the Cancer Genome Atlas (TCGA) datasets, we found that PI3Ks level were significantly upregulated in human esophageal cancer tissues compared with that in non-cancer tissues. The alteration of PI3K can significantly affect the overall patient survival in ESCC but not in esophageal adenocarcinoma (EAC). We found that the classic PI3K inhibitor LY294002 obviously inhibited the canonical mammalian target of rapamycin (mTOR) pathway and restrained the growth of ESCC with less toxicity to normal cells...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28819401/identification-and-validation-of-soluble-carrier-family-expression-signature-for-predicting-poor-outcome-of-renal-cell-carcinoma
#18
Wan Fangning, Ma Chunguang, Zhang Hailiang, Shi Guohai, Zhu Yao, Dai Bo, Shen Yijun, Zhu Yiping, Ye Dingwei
The soluble carrier (SLC) family plays an important role in cell metabolism. The purpose of the current study was to screen SLCs as potential prognostic factors in clear cell renal cell carcinoma (ccRCC). A total of 509 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort were enrolled in this study. The expression profile of SLCs was obtained from the TCGA RNAseq database. Metadata of the TCGA cohort, including age, sex, TNM stage, tumor grade, American Joint Committee on Cancer stage, laterality, and overall survival, were collected...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28802060/taurine-upregulated-gene-1-functions-as-a-master-regulator-to-coordinate-glycolysis-and-metastasis-in-hepatocellular-carcinoma
#19
Yang-Hsiang Lin, Meng-Han Wu, Ya-Hui Huang, Chau-Ting Yeh, Mei-Ling Cheng, Hsiang-Cheng Chi, Chung-Ying Tsai, I-Hsiao Chung, Ching-Ying Chen, Kwang-Huei Lin
Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of Taurine upregulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion and glycolysis via suppression of miR-455-3p...
August 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28756136/addressing-the-best-treatment-for-non-clear-cell-renal-cell-carcinoma-a-meta-analysis-of-randomised-clinical-trials-comparing-vegfr-tkis-versus-mtori-targeted-therapies
#20
REVIEW
Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Francesco Massari, Davide Bimbatti, Emanuela Fantinel, Vincenzo De Marco, Antonio Benito Porcaro, Guido Martignoni, Walter Artibani, Giampaolo Tortora
AIM: Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous group of malignancies that profoundly differ in terms of morphology, genetic profile, clinical behaviour and prognosis. The optimal treatment algorithm for nccRCC is still unknown and derived mainly from evidence available for ccRCC, being therefore represented by targeted agents against vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to compare the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of nccRCC patients...
September 2017: European Journal of Cancer
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