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https://www.readbyqxmd.com/read/29054093/the-role-of-pazopanib-on-tumour-angiogenesis-and-in-the-management-of-cancers-a-review
#1
REVIEW
Dinesh Kumar Chellappan, Jestin Chellian, Zhao Yin Ng, Yan Jinn Sim, Chiu Wei Theng, Joyce Ling, Mei Wong, Jia Hui Foo, Goh Jun Yang, Li Yu Hang, Saranyah Nathan, Yogendra Singh, Gaurav Gupta
Pazopanib is a relatively new compound to be introduced into the chemotherapy field. It is thought to have decent anti-angiogenic properties, which gives an additional hope for the treatment of certain types of cancers. A systematic review solely discussing about pazopanib and its anti-angiogenic effect is yet to be published to date, despite several relevant clinical trials being conducted over the recent years. In this review, we aim to investigate the mechanism of pazopanib's anti-angiogenic effect and its effectiveness in treating several cancers...
October 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29051480/nox4-functions-as-a-mitochondrial-energetic-sensor-coupling-cancer-metabolic-reprogramming-to-drug-resistance
#2
Karthigayan Shanmugasundaram, Bijaya K Nayak, William E Friedrichs, Dharam Kaushik, Ronald Rodriguez, Karen Block
The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2)...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29050225/hcarg-commd5-inhibits-erbb-receptor-driven-renal-cell-carcinoma
#3
Hiroyuki Matsuda, Carole G Campion, Kyoko Fujiwara, Jin Ikeda, Suzanne Cossette, Thomas Verissimo, Maiko Ogasawara, Louis Gaboury, Kosuke Saito, Kenya Yamaguchi, Satoru Takahashi, Morito Endo, Noboru Fukuda, Masayoshi Soma, Pavel Hamet, Johanne Tremblay
Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed in renal proximal tubules, where it contributes to the control of cell proliferation and differentiation. HCaRG accelerates tubular repair by facilitating re-differentiation of injured proximal tubular epithelial cells, thus improving mouse survival after acute kidney injury. Sustained hyper-proliferation and de-differentiation are important hallmarks of tumor progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain a more differentiated phenotype, while several of them undergo autophagic cell death...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044643/fidaxomicin-versus-vancomycin-as-a-first-line-treatment-for-clostridium-difficile-associated-diarrhea-cdad-in-specific-patient-populations-a-pharmacoeconomic-evaluation
#4
Kelly R Reveles, Jennifer L Backo, Frank A Corvino, Marko Zivkovic, Kelly C Broderick
OBJECTIVES: The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the United States (US) hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a US hospital perspective...
October 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29044535/incidence-and-histologic-features-of-mixed-renal-tumors
#5
Neil J Kocher, Chris Rjepaj, Erik Lehman, Jay D Raman
BACKGROUND AND OBJECTIVES: Guidelines for management of renal cell carcinoma (RCC) incompletely address the implications of mixed renal tumor histology. We investigate the incidence of mixed renal tumors identified at renal surgery and determine the association with pathologic features. METHODS: Institutional kidney tumor database was reviewed to identify 536 patients who underwent partial or radical nephrectomy. Clinical, demographic, and pathologic data were collected...
October 16, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29038551/a-novel-machine-learning-approach-reveals-latent-vascular-phenotypes-predictive-of-renal-cancer-outcome
#6
Nathan Ing, Fangjin Huang, Andrew Conley, Sungyong You, Zhaoxuan Ma, Sergey Klimov, Chisato Ohe, Xiaopu Yuan, Mahul B Amin, Robert Figlin, Arkadiusz Gertych, Beatrice S Knudsen
Gene expression signatures are commonly used as predictive biomarkers, but do not capture structural features within the tissue architecture. Here we apply a 2-step machine learning framework for quantitative imaging of tumor vasculature to derive a spatially informed, prognostic gene signature. The trained algorithms classify endothelial cells and generate a vascular area mask (VAM) in H&E micrographs of clear cell renal cell carcinoma (ccRCC) cases from The Cancer Genome Atlas (TCGA). Quantification of VAMs led to the discovery of 9 vascular features (9VF) that predicted disease-free-survival in a discovery cohort (n = 64, HR = 2...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038151/obesity-and-cancer-evidence-impact-and-future-directions
#7
REVIEW
Graham A Colditz, Lindsay L Peterson
BACKGROUND: Mounting evidence, particularly from prospective epidemiologic studies but with additional support from animal models and mechanistic studies, supported conclusions in 2016 by the International Agency for Research on Cancer (IARC)(3) in their review of the preventive effects of weight control on cancer risk. CONTENT: The workgroup concluded that obesity is causally related to cancer at 13 anatomic sites (esophagus: adenocarcinoma; gastric cardia; colon and rectum; liver; gallbladder; pancreas; breast: postmenopausal; uterine endometrial; ovary; kidney: renal cell; meningioma; thyroid; and multiple myeloma)...
October 16, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29027306/fenton-reaction-induced-renal-carcinogenesis-in-mutyh-deficient-mice-exhibits-less-chromosomal-aberrations-than-the-rat-model
#8
Guang Hua Li, Shinya Akatsuka, Shan Hwu Chew, Li Jiang, Takahiro Nishiyama, Akihiko Sakamoto, Takashi Takahashi, Mitsuru Futakuchi, Hiromu Suzuki, Kunihiko Sakumi, Yusaku Nakabeppu, Shinya Toyokuni
Oxidative stress including iron excess has been associated with carcinogenesis. The level of 8-oxoguanine, a major oxidatively modified base in DNA, is maintained very low by three distinct enzymes, encoded by OGG1, MUTYH and MTH1. Germline biallelic inactivation of MUTYH represents a familial cancer syndrome called MUTYH-associated polyposis. Here, we used Mutyh-deficient mice to evaluate renal carcinogenesis induced by ferric nitrilotriacetate (Fe-NTA). Although the C57BL/6 background is cancer-resistant, a repeated intraperitoneal administration of Fe-NTA induced a high incidence of renal cell carcinoma (RCC; 26...
October 13, 2017: Pathology International
https://www.readbyqxmd.com/read/29022072/effect-of-pathological-high-risk-features-on-cancer-specific-mortality-in-non-metastatic-clear-cell-renal-cell-carcinoma-a-tool-for-optimizing-patient-selection-for-adjuvant-therapy
#9
Marco Bandini, Ariane Smith, Emanuele Zaffuto, Raisa S Pompe, Michele Marchioni, Umberto Capitanio, Felix K Chun, Anil B Kapoor, Shahrokh F Shariat, Francesco Montorsi, Alberto Briganti, Pierre I Karakiewicz
PURPOSE: Adjuvant therapies for non-metastatic renal cell carcinoma (nmRCC) are being tested to improve outcomes in patients with high-risk (hR) nmRCC. The objective of the current study is to test the ability of three hR features to identify patients who are at the highest risk of cancer-specific mortality (CSM) after partial or radical nephrectomy. METHODS: Within the Surveillance Epidemiology and End Results (SEER) database (1988-2013), we identified 23,632 nm "clear cell" RCC partial or radical nephrectomy patients with hR features: Fuhrman grade (FG) 3 or 4 or pathological classifications T3a or T3b or lymph node invasion (LNI), or combination of these...
October 11, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/29021969/-k-means-and-cluster-models-for-cancer-signatures
#10
Zura Kakushadze, Willie Yu
We present *K-means clustering algorithm and source code by expanding statistical clustering methods applied in https://ssrn.com/abstract=2802753 to quantitative finance. *K-means is statistically deterministic without specifying initial centers, etc. We apply *K-means to extracting cancer signatures from genome data without using nonnegative matrix factorization (NMF). *K-means' computational cost is a fraction of NMF's. Using 1389 published samples for 14 cancer types, we find that 3 cancers (liver cancer, lung cancer and renal cell carcinoma) stand out and do not have cluster-like structures...
September 2017: Biomolecular Detection and Quantification
https://www.readbyqxmd.com/read/29021138/glutamine-addiction-in-kidney-cancer-suppresses-oxidative-stress-and-can-be-exploited-for-real-time-imaging
#11
Omran Abu Aboud, Samy Habib, Josephine F Trott, Benjamin Stewart, Sitai Liang, Abhijit J Chaudhari, Julie L Sutcliffe, Robert H Weiss
Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28993059/perioperative-blood-transfusion-adversely-affects-prognosis-after-nephrectomy-for-renal-cell-carcinoma
#12
Yasmin Abu-Ghanem, Dorit E Zilberman, Zohar Dotan, Issac Kaver, Jacob Ramon
BACKGROUND: It has been previously suggested that perioperative blood transfusion (PBT) may induce adverse oncological outcomes following cancer surgery. The aim of the current study is to evaluate the effect of PBT on the prognosis of patients who underwent nephrectomy due to renal cell carcinoma (RCC). METHODS: Study included 1,159 patients who underwent radical nephrectomy or partial nephrectomy (PN) between the years 1987 and 2013. Univariate and multivariate models were used to evaluate the association of PBT with cancer-specific survival (CSS), disease-free survival, and overall survival (OS)...
October 6, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28991230/alu-rna-accumulation-induces-epithelial-to-mesenchymal-transition-by-modulating-mir-566-and-is-associated-with-cancer-progression
#13
F Di Ruocco, V Basso, M Rivoire, P Mehlen, J Ambati, S De Falco, V Tarallo
Alu sequences are the most abundant short interspersed repeated elements in the human genome. Here we show that in a cell culture model of colorectal cancer (CRC) progression, we observe accumulation of Alu RNA that is associated with reduced DICER1 levels. Alu RNA induces epithelial-to-mesenchymal transition (EMT) by acting as a molecular sponge of miR-566. Moreover, Alu RNA accumulates as consequence of DICER1 deficit in colorectal, ovarian, renal and breast cancer cell lines. Interestingly, Alu RNA knockdown prevents DICER1 depletion-induced EMT despite global microRNA (miRNA) downregulation...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28989104/epidemiology-of-malignant-cutaneous-granular-cell-tumors-a-united-states-population-based-cohort-analysis-using-the-surveillance-epidemiology-and-end-results-seer-database
#14
Fatima N Mirza, Charles T Tuggle, Cheryl K Zogg, Humza N Mirza, Deepak Narayan
BACKGROUND: Malignant cutaneous granular cell tumors (mcGCT) are rare and associated with substantial morbidity and mortality. The literature includes single-institution studies. OBJECTIVE: To examine the incidence, secondary malignancies, treatment, overall survival (OS), and disease-specific survival (DSS) of patients with mcGCT. METHODS: A population-based cohort analysis was conducted in the Surveillance, Epidemiology, and End Results (SEER) database, 1973-2013, for patients diagnosed with mcGCT...
October 5, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28985870/polymeric-micelles-loaded-with-1-2-diaminocyclohexane-platinum-ii-against-colorectal-cancer
#15
Takako Nirei, Soichiro Ishihara, Toshiaki Tanaka, Tomomichi Kiyomatsu, Kazushige Kawai, Keisuke Hata, Hioaki Nozawa, Toshiaki Watanabe
BACKGROUND: We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model. MATERIALS AND METHODS: The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28)...
October 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28984199/roles-of-alternative-splicing-in-modulating-transcriptional-regulation
#16
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
#17
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/28978168/the-correlation-between-renal-transplantation-and-liver-carcinoma-a-meta-analysis
#18
Hong Yongzhi, Xu Min, Yu Bo, Chen Pin, Shi Xueqiang
OBJECTIVE: Much of the related researches have reported the correlation between renal transplantation and different tumors in the post transplant recipients. However, there are not exact essays revealed that renal transplantation is definite causation for liver carcinoma, thus we systematically evaluated the association between renal transplantation and the risk of liver carcinoma in this meta-analysis from all available researches. METHODS: All useful data were collected through searching of PubMed and Web of Science until the date of 31 September 2015...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976794/multicenter-validation-of-enhancer-of-zeste-homolog-2-expression-as-an-independent-prognostic-marker-in-localized-clear-cell-renal-cell-carcinoma
#19
Thai Huu Ho, Payal Kapur, Jeanette E Eckel-Passow, Alana Christie, Richard W Joseph, Daniel J Serie, John C Cheville, R Houston Thompson, Farrah Homayoun, Vandana Panwar, James Brugarolas, Alexander S Parker
Purpose Enhancer of zeste homolog 2 (EZH2), a chromatin remodeler, is implicated in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However, the effect of EZH2 on outcomes in localized ccRCC is unclear, and molecular biomarkers are not currently integrated into prognostic models or adjuvant therapy trials. Methods We performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in three independent cohorts: a cohort from The Cancer Genome Atlas (n = 532), a cohort from University of Texas Southwestern Medical Center (n = 122), and a cohort from Mayo Clinic (n = 1,338)...
October 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28975613/extracellular-vesicles-isolated-from-human-renal-cell-carcinoma-tissues-disrupt-vascular-endothelial-cell-morphology-via-azurocidin
#20
Kentaro Jingushi, Motohide Uemura, Naomi Ohnishi, Wataru Nakata, Kazutoshi Fujita, Takuya Naito, Risa Fujii, Naomi Saichi, Norio Nonomura, Kazutake Tsujikawa, Koji Ueda
Cancer-associated extracellular vesicles (EVs) are intimately involved in establishment of tumor microenvironment and occurrence of metastasis. However, previous studies have mainly relied on experiments with cultured cell lines or mouse models, making it difficult to gain a full understanding of EV functions in human body. Hence, we extracted EVs directly from surgically resected viable clear cell renal cell carcinoma (ccRCC) tissues and adjacent normal renal tissues (n = 20). Quantitative LC/MS analysis identified 3,871 tissue-exudative EV (Te-EV) proteins, among which azurocidin (AZU1) was highly enriched in tumor Te-EVs (p = 2...
October 4, 2017: International Journal of Cancer. Journal International du Cancer
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