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Kinase targeting and clear cell carcinoma

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https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#1
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29645088/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#2
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29554941/when-tyrosine-kinase-inhibitor-sunitinib-can-be-discontinued-in-metastatic-renal-cell-carcinoma-to-pancreas-a-case-report
#3
Yassir Sbitti, Adil Debbagh, Khaoula Slimani, Mohamed Mahi, Hassan Errihani, Mohamed Ichou
BACKGROUND: Long-term survival with durable response remains possible in the area of targeted therapies. Discontinuation of sunitinib could improve quality of life and reduce treatment costs in metastatic renal cell carcinoma with long-term disease stabilization. We discuss a case of successful interruption of antiangiogenic therapy in a patient with persisting evidence of metastases. The discontinuation of antiangiogenic therapy seems to be an option, even in indolent oligo-metastatic renal cell carcinoma with long disease stabilization before sunitinib...
March 20, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29549930/pyrvinium-sensitizes-clear-cell-renal-cell-carcinoma-response-to-chemotherapy-via-casein-kinase-1%C3%AE-dependent-inhibition-of-wnt-%C3%AE-catenin
#4
Long Cui, Juan Zhao, Jingjing Liu
BACKGROUND: Aberrant Wnt/β-catenin activation has been shown to play essential roles in cancer, including renal cell carcinoma (RCC). In this work, we demonstrate that Wnt/β-catenin inhibition by a Food and Drug Administration-approved drug, pyrvinium, effectively targets clear cell RCC and enhances chemotherapy agent's efficacy. MATERIALS AND METHODS: We performed in vitro cell culture assays and in vivo xenograft tumor model to evaluate the effects of pyrvinium alone and its combination with paclitaxel, and analyzed the underlying mechanism(s) of pyrvinium's action in RCC...
March 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29531214/lasp1-promotes-nasopharyngeal-carcinoma-progression-through-negatively-regulation-of-the-tumor-suppressor-pten
#5
Qingzu Gao, Lihua Tang, Ling Wu, Kaitao Li, Hui Wang, Weidong Li, Juan Wu, Mingyi Li, Shuang Wang, Liang Zhao
LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells...
March 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29527128/crosstalk-between-vegfr-and-other-receptor-tyrosine-kinases-for-tki-therapy-of-metastatic-renal-cell-carcinoma
#6
REVIEW
Yongchang Lai, Zhijian Zhao, Tao Zeng, Xiongfa Liang, Dong Chen, Xiaolu Duan, Guohua Zeng, Wenqi Wu
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel-Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29502423/systemic-administration-of-sirna-with-anti-hb-egf-antibody-modified-lipid-nanoparticles-for-the-treatment-of-triple-negative-breast-cancer
#7
Ayaka Okamoto, Tomohiro Asai, Yusuke Hirai, Kosuke Shimizu, Hiroyuki Koide, Tetsuo Minamino, Naoto Oku
Triple-negative breast cancer is one of intractable cancers that are not sensitive to the treatment with existing molecular-targeted drugs. Recently, there has been much interest in RNA interference-mediated treatment of triple-negative breast cancer. In the present study, we have developed lipid nanoparticles encapsulating siRNA (LNP-siRNA) decorated with an Fab' antibody against heparin-binding EGF-like growth factor (αHB-EGF LNP-siRNA). αHB-EGF LNP-siRNA targeting polo-like kinase 1 (PLK1) was prepared and evaluated for its anticancer effect using MDA-MB-231 human triple-negative breast cancer cells overexpressing HB-EGF on their cell surface...
March 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29487224/second-line-treatment-landscape-for-renal-cell-carcinoma-a-comprehensive-review
#8
REVIEW
Nizar M Tannir, Sumanta K Pal, Michael B Atkins
The management of advanced clear-cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second-line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, and AXL; and lenvatinib, a small-molecule TKI of VEGF and fibroblast growth factor receptors that is used in combination with everolimus, an inhibitor of the mechanistic target of rapamycin...
February 27, 2018: Oncologist
https://www.readbyqxmd.com/read/29479523/renal-cell-carcinoma-in-von-hippel-lindau-disease-from-tumor-genetics-to-novel-therapeutic-strategies
#9
REVIEW
Emily Kim, Stefan Zschiedrich
von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by mutations in the VHL tumor-suppressor gene, leading to the dysregulation of many hypoxia-induced genes. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous VHL gene inactivation, ccRCCs evolve through additional genetic alterations, resulting in both intratumor and intertumor heterogeneity...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29472550/pim1-mediates-epithelial-mesenchymal-transition-by-targeting-smads-and-c-myc-in-the-nucleus-and-potentiates-clear-cell-renal-cell-carcinoma-oncogenesis
#10
Bin Zhao, Lei Liu, Jun Mao, Zhiwei Zhang, Qifei Wang, Quanlin Li
Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to date, the potential regulatory roles and molecular mechanisms by which PIM1 affects the development and progression of cancers, including clear-cell renal-cell carcinoma (ccRCC), remain largely unknown...
February 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29464464/pazopanib-related-tumor-lysis-syndrome-in-metastatic-clear-cell-renal-cell-carcinoma-a-case-report
#11
Michael W van Kalleveen, Maudy Walraven, Mathijs P Hendriks
Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by rapid cell death as a result of anti-tumor therapy. In the era of targeted therapy it has increasingly been observed in solid malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe the case of a 58-year old man with the medical history of a memorial sloan kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell carcinoma (mRCC) who developed TLS within six days after initiating therapy with the tyrosine kinase inhibitor (TKI) pazopanib...
February 20, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29422973/chloroquine-affects-autophagy-to-achieve-an-anticancer-effect-in-ec109-esophageal-carcinoma-cells-in-vitro
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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 histopathologic studies are performed to prove, localize, treat, and monitor disease progression. Improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (<1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
January 2018: Endocrine Practice
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