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Advanced Renal cell carcinoma

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https://www.readbyqxmd.com/read/28224821/lenvatinib-for-use-in-combination-with-everolimus-for-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-following-one-prior-anti-angiogenic-therapy
#1
Aine O'Reilly, James Larkin
In patients with mRCC options for second line therapies, following progression on anti-angiogenic agents, that demonstrate a survival advantage in clinical trials have been limited. Recently a number of agents have demonstrated efficacy in this setting. Here in we profile one such therapy, the combination of lenvatinib and everolimus, and discuss the expanded options for therapy available in this setting. Areas covered: In this review, we discuss current algorithms for treatment of mRCC in both the first-line and second-line setting...
March 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28222071/combination-of-the-histone-deacetylase-inhibitor-vorinostat-with-bevacizumab-in-patients-with-clear-cell-renal-cell-carcinoma-a-multicentre-single-arm-phase-i-ii-clinical-trial
#2
Roberto Pili, Glenn Liu, Sreenivasulu Chintala, Hendrick Verheul, Shabnam Rehman, Kristopher Attwood, Martin A Lodge, Richard Wahl, James I Martin, Kiersten Marie Miles, Silvia Paesante, Remi Adelaiye, Alejandro Godoy, Serina King, James Zwiebel, Michael A Carducci
BACKGROUND: Class II histone deacetylase (HDAC) inhibitors induce hypoxia-inducible factor-1 and -2α degradation and have antitumour effects in combination with vascular endothelial growth factor (VEGF) inhibitors. In this study, we tested the safety and efficacy of the HDAC inhibitor vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients previously treated with different drugs including sunitinib, sorafenib, axitinib, interleukin-2, interferon, and temsirolimus...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28221861/inhibiting-histone-deacetylase-as-a-means-to-reverse-resistance-to-angiogenesis-inhibitors-phase-i-study-of-abexinostat-plus-pazopanib-in-advanced-solid-tumor-malignancies
#3
Rahul Aggarwal, Scott Thomas, Nela Pawlowska, Imke Bartelink, Jennifer Grabowsky, Thierry Jahan, Amy Cripps, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Charles J Ryan, Pamela N Munster
Purpose This phase I trial evaluated epigenetic modulation of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor by using a histone deacetylase abexinostat in combination with pazopanib to enhance response and reverse resistance. Patients and Methods Pazopanib was administered once a day on days 1 to 28 and abexinostat was administered orally twice a day on days 1 to 5, 8 to 12, and 15 to 19 (schedule A) or on days 1 to 4, 8 to 11, and 15 to 18 (schedule B). Dose escalation (3 + 3 design) in all solid tumors was followed by dose expansion in renal cell carcinoma (RCC)...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28214486/robotic-inferior-vena-cava-surgery
#4
Victor J Davila, Cristine S Velazco, William M Stone, Richard J Fowl, Haidar M Abdul-Muhsin, Erik P Castle, Samuel R Money
OBJECTIVE: Inferior vena cava (IVC) surgery is uncommon and has traditionally been performed through open surgical approaches. Renal cell carcinoma with IVC extension generally requires vena cavotomy and reconstruction. Open removal of malpositioned IVC filters (IVCF) is occasionally required after endovascular retrieval attempts have failed. As our experience with robotic surgery has advanced, we have applied this technology to surgery of the IVC. We reviewed our institution's experience with robotic surgical procedures involving the IVC to determine its safety and efficacy...
March 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28212559/the-selective-mek1-inhibitor-selumetinib-enhances-the-antitumor-activity-of-everolimus-against-renal-cell-carcinoma-in-vitro-and-in-vivo
#5
Yun Zou, Jianfeng Wang, Xuejiao Leng, Jiwei Huang, Wei Xue, Jin Zhang, Yiran Huang
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212363/vegf-inhibitors-in-renal-cell-carcinoma
#6
Pankit Vachhani, Saby George
The arrival of targeted therapies-vascular endothelial growth factor (VEGF) pathway inhibitors and mammalian target of rapamycin (mTOR) inhibitors-and programmed death 1 (PD-1) inhibitors has transformed the management of renal cell carcinoma (RCC). Once considered fatal, with a median survival of approximately 1 year, these agents have nearly tripled overall survival and have raised hopes of a possible cure for advanced RCC. This review begins with a brief discussion of the seminal von Hippel-Lindau/hypoxia-inducible factor axis in RCC...
December 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28210496/the-additional-utility-of-apparent-diffusion-coefficient-values-of-clear-cell-renal-cell-carcinoma-for-predicting-metastasis-during-clinical-staging
#7
Rika Yoshida, Takeshi Yoshizako, Araki Hisatoshi, Hiroshi Mori, Yukihisa Tamaki, Noriyoshi Ishikawa, Hajime Kitagaki
BACKGROUND: The apparent diffusion coefficient (ADC) value is known to be an indicator of tumor activity. The ADC value of high-grade clear-cell renal cell carcinoma (RCC) is significantly lower than that of low-grade clear-cell RCC. PURPOSE: To investigate the utility of ADC values of clear-cell RCC by comparing ADC values between groups with T1a RCC (tumor size ≤ 4 cm) without metastasis and the group with metastasis. MATERIAL AND METHODS: A retrospective review was performed on 51 patients with 51 RCCs who underwent 1...
January 2017: Acta Radiologica Open
https://www.readbyqxmd.com/read/28203091/expression-of-microrna-30c-via-lentivirus-vector-inhibits-the-proliferation-and-enhances-the-sensitivity-of-highly-aggressive-ccrcc-caki-1-cells-to-anticancer-agents
#8
Honglin Yang, Erlin Song, Guorong Shen, Tonghua Zhu, Tingwang Jiang, Hao Shen, Liping Niu, Biao Wang, Zhaoyang Lu, Jianping Qian
The clear cell renal cell carcinoma (ccRCC) is one of the most fatal urologic tumors, and the prognosis remains very poor for advanced or metastatic ccRCC. This study reveals the roles of microRNA (miR)-30c in regulating a highly aggressive ccRCC cell line proliferation by targeting MTA-1, which is a key mediator for human cancer metastasis. Results from quantitative real-time polymerase chain reaction showed that the expression of MTA-1, the target of miR-30c, was significantly higher in metastatic ccRCC specimens than in nonmetastatic ccRCC or nontumor specimens...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28195104/well-differentiated-neuroendocrine-tumor-of-the-kidney-report-of-a-rare-case-with-review-of-literature
#9
Kavita Mardi, Lalita Negi, Srijan Srivastava
Neuroendocrine tumors (NETs) are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC) are exceedingly rare. Renal carcinoids are typically slow-growing tumors and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. We herein report a rare cases of well-differentiated NET (carcinoid) in a 39-year-old male along with the immunohistochemical features...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28187463/preoperative-albumin-to-globulin-ratio-predicts-survival-in-clear-cell-renal-cell-carcinoma-patients
#10
Zhen Chen, Yingjie Shao, Hongwei Yao, Qianfeng Zhuang, Kun Wang, Zhaoyu Xing, Xianlin Xu, Xiaozhou He, Renfang Xu
In this retrospective analysis, we evaluated associations between albumin to globulin ratio (AGR), clinicopathological characteristics, and survival in 592 patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC) prior to nephrectomy. We found that low AGR was associated with more aggressive tumor behavior; patients with low AGR had poorer overall survival (OS) and cancer-specific survival (CSS) in Kaplan-Meier survival analyses both before and after propensity score matching, which was used to compensate for differences in baseline clinicopathological characteristics...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28184919/upregulation-of-mir-21-expression-is-a-valuable-predicator-of-advanced-clinicopathological-features-and-poor-prognosis-in-patients-with-renal-cell-carcinoma-through-the-p53-p21%C3%A2-cyclin%C3%A2-e2%C3%A2-bax-caspase-3-signaling-pathway
#11
Zhihong Liu, You Lu, Yingmin Xiao, Yipin Lu
In the present study, we investigated whether the upregulation of miR-21 expression is a predictor of advanced clinicopathological features and poor prognosis in patients with renal cell carcinoma (RCC). It was found that the expression of miR-21 not only had a significant effect on the clinicopathological features and survival in patients with RCC, but also exerted an important influence on the occurrence rate of RCC. In addition, miR-21 expression was lower in the human kidney HRPTEpiC cell line than that noted in RCC A-498 cells...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28183697/safety-and-antitumor-activity-of-the-multi-targeted-pan-trk-ros1-and-alk-inhibitor-entrectinib-rxdx-101-combined-results-from-two-phase-1-trials-alka-372-001-and-startrk-1
#12
Alexander Drilon, Salvatore Siena, Sai-Hong Ignatius Ou, Manish Patel, Myung Ju Ahn, Jeeyun Lee, Todd M Bauer, Anna F Farago, Jennifer J Wheler, Stephen V Liu, Robert Doebele, Laura Giannetta, Giulio Cerea, Giovanna Marrapese, Michele Schirru, Alessio Amatu, Katia Bencardino, Laura Palmeri, Andrea Sartore-Bianchi, Angelo Vanzulli, Sara Cresta, Silvia Damian, Matteo Duca, Elena Ardini, Gang Li, Jason Christiansen, Karey Kowalski, Ann Johnson, Rupal Patel, David Luo, Edna Chow-Maneval, Zachary Hornby, Pratik S Multani, Alice T Shaw, Filippo G De Braud
Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two Phase 1 studies in patients with advanced or metastatic solid tumors, including patients with active CNS disease. Here we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring NTRK1/2/3, ROS1, or ALK gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the RP2D...
February 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28183256/current-and-emerging-treatments-for-metastatic-renal-cell-carcinoma
#13
Carla Cavaliere, Carmine D Aniello, Chiara Della Pepa, Salvatore Pisconti, Massimiliano Berretta, Gaetano Facchini
In the last decades the treatment of mRCC, metastatic Renal Cell Carcinoma, has become more and more complex due to the approval of a great number of effective systemic treatments that have significantly improved the prognosis of patients suffering from such disease. An increasing knowledge of the genetic aberrations and the molecular pathways alterations that underlie RCC, has promoted the development of several novel agents, known as target therapies (TTs). Even though TTs are not curative and all patients eventually progressed, an adequate sequencing of these drugs can provide a significant benefit in terms of PFS, Progression Free Survival, and hopefully OS, Overall Survival...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183189/what-advances-have-been-made-in-immune-therapy-for-renal-cell-carcinoma
#14
Elena Verzoni, Paolo Grassi, Raffaele Ratta
No abstract text is available yet for this article.
February 10, 2017: Future Oncology
https://www.readbyqxmd.com/read/28178674/plasma-cytokine-and-angiogenic-factors-associated-with-prognosis-and-therapeutic-response-to-sunitinib-vs-everolimus-in-advanced-non-clear-cell-renal-cell-carcinoma
#15
Pavlos Msaouel, Amado J Zurita, Shixia Huang, Eric Jonasch, Nizar M Tannir
No biomarkers are available to predict relative clinical benefit from targeted therapies in patients with non-clear cell renal cell carcinoma (nccRCC). To identify candidate predictive markers, we investigated a set of cytokines and angiogenic factors (CAFs) in previously untreated patients with nccRCC participating in the phase II ESPN trial comparing first-line sunitinib to everolimus. Pre-treatment concentrations of 30 CAFs were measured in plasma from 37 patients treated with everolimus (n=16) or sunitinib (n=21), and associated with progression-free (PFS) and overall survival (OS) after adjusting for potential confounders...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178644/clinicalpathological-and-prognostic-significance-of-survivin-expression-in-renal-cell-carcinoma-a-meta-analysis
#16
Zhichen Pu, Guang-Zhen Wu, QiFei Wang
BACKGROUND: In recent years, survivin expression had been investigated as a prognostic biomarker for renal cell carcinoma (RCC), however, the results were conflicting. This study was aimed to explore the association between survivin expression and clinicalpathological features and the prognostic value for cancer-specific survival (CSS) and overall survival (OS) in RCC. RESULTS: Eleven studies with 1,697 subjects were included in this meta-analysis. The results showed that survivin expression was associated with higher tumor grade (OR=4...
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28166200/upregulation-of-marcks-in-kidney-cancer-and-its-potential-as-a-therapeutic-target
#17
C-H Chen, L W R Fong, E Yu, R Wu, J F Trott, R H Weiss
Targeted therapeutics, such as those abrogating hypoxia inducible factor (HIF)/vascular endothelial growth factor signaling, are initially effective against kidney cancer (or renal cell carcinoma, RCC); however, drug resistance frequently occurs via subsequent activation of alternative pathways. Through genome-scale integrated analysis of the HIF-α network, we identified the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) as a potential target molecule for kidney cancer...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28164615/renal-cancer-diagnosed-by-noninvasive-methods-from-body-fluids-by-quantitative-methylation-specific-pcr-qmsp
#18
Radu Minciu, Anca Tudor, Gheorghe Pupca, Livius Daminescu, Raluca Dumache
BACKGROUND: Renal cell carcinoma (RCC) represents the 9th most common malignancy in the world, having an incidence peak in the range of 60 to 70 years of age. Most of these malignancies are detected in an advanced stage. Thus, there is an urgent need for developing new tools composed of biomarkers. METHODS: In the present study we measured the promoter methylation of the Ras association domain family 1A gene (RASSF1A) by quantitative methylation-specific PCR (qMSP) in paired urine samples from 13 RC patients and from 13 corresponding controls...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28164557/the-detection-of-urinary-podocytes-from-drug-induced-glomerular-thrombotic-microangiopathy-in-advanced-cancer-patients
#19
Joichi Usui, Chie Yokoyama, Masahiro Hagiwara, Kai Hirayasu, Takahiro Kojima, Takayuki Yoshino, Hiroyuki Nishiyama, Masanori Hara, Kunihiro Yamagata
BACKGROUND: Focusing on glomerular thrombotic microangiopathy (TMA), we detected urinary podocytes to evaluate podocyte damage following glomerular endothelial cell injury. METHODS: We analyzed the relationship between urinary podocytes as biomarkers for podocyte injuries and clinical manifestations in five patients of anti-cancer-drug-induced glomerular TMA. RESULTS: Cancer in all five patients was advanced, including 4 cases of renal cell carcinoma treated with tyrosine kinase inhibitor, and one with intrahepatic bile duct carcinoma treated with gemcitabine...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28162771/experimental-murine-model-of-renal-cancer
#20
B Padilla-Fernández, M B García-Cenador, P Rodríguez-Marcos, J F López-Marcos, P Antúnez-Plaza, J M Silva-Abuín, D López-Montañés, F J García-Criado, M F Lorenzo-Gómez
INTRODUCTION: The objective of this study was to determine the reproducibility in a murine model of renal tumours of various histological strains that could be useful for investigating the response to target drugs. MATERIAL AND METHODS: Development and analysis of the "in vivo" model: tumour xenograft of renal cell carcinomas with Balb/c nude athymic mice. Nontumourous human renal tissue was implanted in the interscapular region of 5 mice, chromophobe renal cell carcinoma was implanted in 5 mice (which, after checking its growth, was prepared for implantation in another 10 mice) and Fuhrman grade 2 clear cell renal cell carcinoma (CCRCC) was implanted in 5 mice (which was also subsequently implanted in 10 mice)...
February 2, 2017: Actas Urologicas Españolas
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