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Advanced Renal cell carcinoma

May Garrett, Timothy Taylor, Diane R Mould, Michael A Amantea, Ying Chen, Antonella Ingrosso, Yazdi K Pithavala
PURPOSE: Axitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors 1-3, is approved for second-line treatment of advanced renal cell carcinoma. Axitinib is partially metabolized by cytochrome P450 1A2, which is induced by chronic heavy smoking. The effect of smoking on axitinib pharmacokinetics was evaluated in a non-small-cell lung cancer (NSCLC) patient population with a large number of active and ex-smokers. METHODS: Data were pooled from six clinical studies-serial pharmacokinetics from two healthy volunteer studies (n = 58) and sparse pharmacokinetics from four NSCLC studies (n = 152)-for a nonlinear mixed effects modeling (NONMEM v7...
October 25, 2016: Cancer Chemotherapy and Pharmacology
Qiang Ma, Zhiqiang Peng, Lei Wang, Yanming Li, Kaizhen Wang, Junfang Zheng, Zhiyong Liang, Tonghua Liu
MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found that miR-19a correlated with poor prognosis of ccRCC patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression. Both the microarray screening result and TCGA KIRC dataset analysis showed that miR-19a was significantly upregulated in ccRCC tissues, and further analysis of TCGA data revealed that the upregulated level of miR-19a was strongly associated with advanced T stage and poor prognosis of ccRCC patients...
October 24, 2016: International Journal of Oncology
Bridgette A Kanz, Megan H Pollack, Romany Johnpulle, Igor Puzanov, Leora Horn, Alicia Morgans, Jeffrey A Sosman, Suthee Rapisuwon, R Martin Conry, Zeynep Eroglu, Douglas B Johnson
BACKGROUND: Anti-PD-1 therapy is increasingly used in various advanced malignancies. Patients with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether anti-PD-1 therapy is safe or effective in this setting. Further, these patients are often not candidates for other anti-cancer therapies, highlighting their need for active treatment options. METHODS: We performed a retrospective analysis of patients from multiple centers with advanced solid tumors and baseline organ dysfunction who received anti-PD-1 therapy...
2016: Journal for Immunotherapy of Cancer
A Antar, Z K Otrock, J El-Cheikh, M A Kharfan-Dabaja, G Battipaglia, R Mahfouz, M Mohty, A Bazarbachi
FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma...
October 24, 2016: Bone Marrow Transplantation
Neil M D'Souza, Penny Fang, Jennifer Logan, Jinzhong Yang, Wen Jiang, Jing Li
Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies...
2016: Frontiers in Oncology
Handoo Rhee, John Blazak, Chui Ming Tham, Keng Lim Ng, Benjamin Shepherd, Malcolm Lawson, John Preston, Ian Vela, Paul Thomas, Simon Wood
BACKGROUND: In this study, we prospectively evaluate the diagnostic potential of a gallium-68 (68Ga) prostate-specific membrane antigen (PSMA)-binding ligand and positron emission tomography (PET) in detecting metastatic lesions in patients with renal tumour. The secondary aim was to determine whether the findings would result in the alteration of patient management. RESULTS: Ten patients with renal lesion and potential metastatic disease on conventional imaging were recruited...
December 2016: EJNMMI Research
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Hilaire C Lam, Julie S Nijmeh, Elizabeth P Henske
In just the past five years, dramatic changes have occurred in the clinical management of Tuberous Sclerosis Complex (TSC). Detailed knowledge about the role of the TSC proteins in regulating the activity of the mammalian Target of Rapamycin Complex 1 (mTORC1) underlies this paradigm-shifting progress. Advances continue to be made in understanding the genetic pathogenesis of the different tumours that occur in TSC, including pivotal discoveries using next-generation sequencing (NGS). For example, the pathogenesis of angiofibromas is now known to involve UV-induced mutations, and the pathogenesis of multifocal renal cell carcinoma (RCC) in TSC is now known to result from distinct second-hit mutations...
October 18, 2016: Journal of Pathology
Wenting Ma, Le Tao, Xuefei Wang, Qinyi Liu, Wei Zhang, Qiuying Li, Chunfeng He, Dongying Xue, Jie Zhang, Cheng Liu
AIMS: Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism. METHODS: Mice underwent UUO followed by vehicle or sorafenib treatment...
October 17, 2016: Cellular Physiology and Biochemistry
Baijun Dong, Yujing Gao, Xunlei Kang, Hongchang Gao, Jin Zhang, Hua Guo, Mingjian J You, Wei Xue, Jinke Cheng, Yiran Huang
Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC...
October 12, 2016: Oncotarget
Ajay Gupta, Siddhartha Baxi, Christopher Hoyne
INTRODUCTION: Comprehensive oncology services have recently been introduced in the Northern Territory (NT) enabling delivery of concurrent chemo-radiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LAHNSC). The purpose of this study is to assess feasibility, compliance and toxicity of CCRT in remote Australia. METHODS: Chart review was conducted for all patients >18 years, with biopsy-proven LAHNSC, receiving curative intent CCRT between January 2010 and September 2012...
July 1, 2016: Journal of Medical Radiation Sciences
Ming Guo, Yunsong Cao, Jingzhe Yang, Jingfeng Zhang
PURPOSE: The purpose of this study was to conduct network meta-analysis to assess drug resistances of the Food and Drug Administration-approved drugs for advanced renal cell carcinoma. MATERIALS AND METHODS: Database searches were conducted to identify randomized controlled trials reporting results for eligible treatments. After searching for PubMed, MEDLINE, EMBASE, and ISI Web of Science, 22 studies (n = 7854 patients) were included for the comparison of drug resistance in the present meta-analysis...
October 2016: Journal of Cancer Research and Therapeutics
Norbert Marschner, Michael Staehler, Lothar Müller, Arnd Nusch, Johanna Harde, Michaela Koska, Martina Jänicke, Peter J Goebell
INTRODUCTION: Because "real-life" patients often do not meet the strict eligibility criteria of clinical trials, we assessed the trial eligibility of patients with advanced or metastatic renal cell carcinoma (mRCC) in routine practice and compared the survival of "trial-ineligible" and potentially "trial-eligible" patients. PATIENTS AND METHODS: The present prospective, multicenter German cohort study is recruiting patients from 110 oncology/urology outpatient centers and hospitals at initiation of systemic first-line treatment...
September 8, 2016: Clinical Genitourinary Cancer
Brian I Rini, Arnulf Stenzl, Romauld Zdrojowy, Mikhail Kogan, Mikhail Shkolnik, Stephane Oudard, Steffen Weikert, Sergio Bracarda, Simon J Crabb, Jens Bedke, Joerg Ludwig, Dominik Maurer, Regina Mendrzyk, Claudia Wagner, Andrea Mahr, Jens Fritsche, Toni Weinschenk, Steffen Walter, Alexandra Kirner, Harpreet Singh-Jasuja, Carsten Reinhardt, Tim Eisen
BACKGROUND: In a phase 2 study in patients with metastatic renal cell carcinoma, overall survival was associated with T-cell responses against IMA901, a vaccine consisting of ten tumour-associated peptides. In this phase 3 trial, we aimed to determine the clinical effect of adding IMA901 to sunitinib, the standard first-line treatment in metastatic renal cell carcinoma with postulated favourable immunomodulatory effects. METHODS: The IMPRINT study is an open-label, randomised, controlled, phase 3 trial done at 124 clinical sites in 11 countries...
October 3, 2016: Lancet Oncology
Fouad Ghazi Souki, Michael Demos, Lilibeth Fermin, Gaetano Ciancio
Advanced renal cell carcinoma (RCC) resection has important anesthetic management implications, particularly when tumor extends, suprahepatic, into the right atrium. Use of transesophageal echocardiogram (TEE) is essential in identifying tumor extension and guiding resection. Latest surgical approach avoids venovenous and cardiopulmonary bypass yet requires special precautions and interventions on the anesthesiologist's part. We present a case of Level IV RCC resected without cardiopulmonary bypass and salvaged by TEE guidance and detection of residual intracardiac tumor...
October 2016: Annals of Cardiac Anaesthesia
Yongkun Sun, Wei Niu, Feng Du, Chunxia Du, Shuting Li, Jinwan Wang, Li Li, Fengqing Wang, Yu Hao, Chuan Li, Yihebali Chi
BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. METHODS: Anlotinib (5-16 mg) was orally administered in patients with solid tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 2-week on/1-week off (2/1)...
October 4, 2016: Journal of Hematology & Oncology
Steven S Yu, David I Quinn, Tanya B Dorff
Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib's designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016...
2016: OncoTargets and Therapy
Jung Hoon Kim, Bum Jun Kim, Hyeong Su Kim, Jung Han Kim
Cancer immunotherapy is at dawn of the Renaissance after the Medieval Dark Ages. Recent advances of understanding tumor immunology and molecular drug development are leading us to the epoch of cancer immunotherapy. Some types of immunotherapy have shown to provide survival benefit for patients with solid tumors such as malignant melanoma, renal cell carcinoma, or non-small cell lung cancer. Several studies have suggested that immune checkpoint inhibition might be effective in some patients with gastrointestinal cancers...
2016: Journal of Cancer
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
P Xian, Y Li, H Zhou, H Luo, N Liu, J Y Dai
Objective: To evaluate the effect of Sunitinib therapy on immune function of patient with advanced renal cell carcinoma. Methods: A total of 27 patient with advanced renal cell carcinoma who received Sunitinib therapy in Chongqing Cancer Hospital from July 2010 to July 2014 were recruited in a prospective cohort study.Nineteen were male patients and 8 were female patients aged from 36 to 75 years with mean age of (58±7)years.Twenty-five cases were renal clear cell carcinoma, the other two cases were papillary renal cell carcinoma and Xp11...
October 1, 2016: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
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