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https://www.readbyqxmd.com/read/28333125/clarity-reveals-dynamics-of-ovarian-follicular-architecture-and-vasculature-in-three-dimensions
#1
Yi Feng, Peng Cui, Xiaowei Lu, Brian Hsueh, Fredrik Möller Billig, Livia Zarnescu Yanez, Raju Tomer, Derek Boerboom, Peter Carmeliet, Karl Deisseroth, Aaron J W Hsueh
Optimal distribution of heterogeneous organelles and cell types within an organ is essential for physiological processes. Unique for the ovary, hormonally regulated folliculogenesis, ovulation, luteal formation/regression and associated vasculature changes lead to tissue remodeling during each reproductive cycle. Using the CLARITY approach and marker immunostaining, we identified individual follicles and corpora lutea in intact ovaries. Monitoring lifetime changes in follicle populations showed age-dependent decreases in total follicles and percentages of advanced follicles...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#2
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#3
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#4
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28267243/overall-survival-of-1st-line-axitinib-in-metastatic-renal-cell-carcinoma-japanese-subgroup-analysis-from-phase-ii-study
#5
Mototsugu Oya, Yoshihiko Tomita, Satoshi Fukasawa, Nobuo Shinohara, Tomonori Habuchi, Brian I Rini, Yosuke Fujii, Yoichi Kamei, Yoshiko Umeyama, Angel H Bair, Hirotsugu Uemura
Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6 months in treatment-naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and updated safety in 44 Japanese patients and compared with 169 non-Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first-line metastatic RCC were explored using a Cox proportional hazard model in all patients...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28256961/gemcitabine-mono-therapy-versus-gemcitabine-plus-targeted-therapy-in-advanced-pancreatic-cancer-a-meta-analysis-of-randomized-phase-iii-trials
#6
Alessandro Ottaiano, Monica Capozzi, Chiara De Divitiis, Alfonso De Stefano, Gerardo Botti, Antonio Avallone, Salvatore Tafuto
BACKGROUND: Prognosis of advanced pancreatic cancer is dismal and the novel targeted therapies, albeit successfully used to treat many advanced tumors, have shown modest results. We performed a meta-analysis in order to quantify the effect size on survival of adding targeted therapy to single agent gemcitabine. METHODS: Randomized phase III trials comparing gemcitabine mono-therapy versus gemcitabine plus a targeted agent in first-line treatment of advanced pancreatic cancer designed on survival as primary outcome were selected...
March 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28253548/patterns-of-care-among-patients-receiving-sequential-targeted-therapies-for-advanced-renal-cell-carcinoma-a-retrospective-chart-review-in-the-usa
#7
Sumanta K Pal, James E Signorovitch, Nanxin Li, Miriam L Zichlin, Zhimei Liu, Sameer R Ghate, Jose Ricardo Perez, Nicholas J Vogelzang
OBJECTIVES: To assess real-world treatment patterns of targeted therapies after failure of first-line tyrosine kinase inhibitors in patients with advanced renal cell carcinoma. METHODS: A large, retrospective review of medical charts of patients with advanced renal cell carcinoma in the USA was carried out. Descriptive statistics were used to summarize physicians' and patients' characteristics, treatment sequences, and reasons for treatment choices. P-values were calculated using χ(2) -tests for categorical variables and Wilcoxon rank-sum tests for continuous variables...
March 2, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28246756/-first-line-therapy-in-advanced-renal-cell-carcinoma-a-randomized-open-label-phase%C3%A2-iii-study-evaluating-the-efficacy-and-safety-of-pembrolizumab-mk-3475-in-combination-with-axitinib-compared-to-sunitinib-monotherapy-as-first-line-treatment-for-locally-advanced
#8
https://www.readbyqxmd.com/read/28245539/-a-case-of-hydrocephalus-due-to-brain-metastasis-from-renal-cell-carcinoma-successfully-treated-with-axitinib
#9
Soichiro Shimura, Dai Koguchi, Satoru Minamida, Yoshinori Taoka, Masatsugu Iwamura
We report a case of hydrocephalus due to brain metastasis from renal cell carcinoma treated with axitinib. A 65-year-old man had undergone right radical nephrectomy for renal cell carcinoma in 2010. The pathological diagnosis indicated clear cell carcinoma G3, pT1a. After adjuvant treatment with interferon-α, computed tomography, in 2011, revealed multiple lung metastases. He was administered sorafenib. Because of progressive lung metastases, sunitinib was administered. The lung metastases were progressive and bone scan revealed multiple bone metastases...
January 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28230776/effects-and-side-effects-of-using-sorafenib-and-sunitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma
#10
REVIEW
Caroline Randrup Hansen, Daniela Grimm, Johann Bauer, Markus Wehland, Nils E Magnusson
In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect. Studies have compared newer targeted drugs to sorafenib and sunitinib in terms of PFS, OS, quality of life and safety profiles...
February 21, 2017: International Journal of Molecular Sciences
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
#11
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/28174388/-a-case-of-renal-cell-carcinoma-with-high-everolimus-blood-concentrations-and-hyperglycemia-due-to-everolimus-induced-hepatic-dysfunction
#12
Shinya Takasaki, Masafumi Kikuchi, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
We report the case of a patient who had renal cell carcinoma with high everolimus blood concentrations and hyperglycemia due to everolimus-induced hepatic dysfunction. A 74-year-old man who underwent right nephrectomy for renal cell carcinoma was administered everolimus for multiple lung metastases. Everolimus caused grade 3 hepatic dysfunction and hyperglycemia; hence, high blood levels of everolimus were observed. Although the patient was re-administrated everolimus after recovering from hepatic dysfunction, hepatic function test values worsened again...
January 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28161830/combined-vegf-and-pdgf-inhibition-for-neovascular-amd-anti-angiogenic-properties-of-axitinib-on-human-endothelial-cells-and-pericytes-in-vitro
#13
Jakob Siedlecki, Christian Wertheimer, Armin Wolf, Raffael Liegl, Claudia Priglinger, Siegfried Priglinger, Kirsten Eibl-Lindner
PURPOSE: Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma...
February 4, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28153029/new-treatment-options-for-metastatic-renal-cell-carcinoma-with-prior-anti-angiogenesis-therapy
#14
REVIEW
Kevin Zarrabi, Chunhui Fang, Shenhong Wu
Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28143997/targeted-therapy-for-metastatic-renal-cell-carcinoma
#15
REVIEW
Andika Afriansyah, Agus Rizal Ah Hamid, Chaidir A Mochtar, Rainy Umbas
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC...
October 2016: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28108609/visualization-and-quantification-of-browning-using-a-ucp1-2a-luciferase-knock-in-mouse-model
#16
Liufeng Mao, Baoming Nie, Tao Nie, Xiaoyan Hui, Xuefei Gao, Xiaoliang Lin, Xin Liu, Yong Xu, Xiaofeng Tang, Ran Yuan, Kuai Li, Peng Li, Ke Ding, Yu Wang, Aimin Xu, Jian Fei, Weiping Han, Pentao Liu, Lise Madsen, Karsten Kristiansen, Zhiguang Zhou, Sheng Ding, Donghai Wu
Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28106614/study-of-intrapatient-variability-and-reproducibility-of-quantitative-tumor-perfusion-parameters-evaluated-with-dynamic-contrast-enhanced-ultrasonography
#17
Nathalie Lassau, Bénédicte Coiffier, Laura Faivre, Baya Benatsou, Sophie Bidault, Elizabeth Girard, Bernard Asselain, Stéphanie Pitre-Champagnat, Serge Koscielny
OBJECTIVES: Dynamic contrast-enhanced (DCE) ultrasonography (US) is a functional imaging technique enabling quantitative assessment of solid tumor perfusion in metastatic patients treated with antiangiogenic therapies.The objective of this prospective single-center study was to evaluate in real-life conditions (in routine clinical practice) the intrapatient variability and reproducibility of DCE-US parameters. MATERIALS AND METHODS: Each patient provided written informed consent and had 2 DCE-US examinations (preprandial and postprandial) at baseline, day 15, and 1 month after treatment initiation...
March 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#18
Emilie Patras de Campaigno, Emmanuelle Bondon-Guitton, Guy Laurent, Francois Montastruc, Jean-Louis Montastruc, Maryse Lapeyre-Mestre, Fabien Despas
AIMS: The aims of the present study were to evaluate the risk of cardiac failure (CF) associated with 15 anticancer protein kinase inhibitors (PKIs) through a case/noncase analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: In order to evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the World Health Organization safety report database (VigiBase®). We realised a literature review to identify 21 protein kinases (PKs) that were possibly involved in CF caused by PKIs...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28096936/treatment-options-in-advanced-renal-cell-carcinoma-after-first-line-treatment-with-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors
#19
REVIEW
Naveen S Basappa
Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago and since then, a number of therapeutic options have been developed. Vascular endothelial growth factor-targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28093138/re-efficacy-and-safety-of-axitinib-in-elderly-patients-with-metastatic-renal-cell-carcinoma
#20
Tomas L Griebling
No abstract text is available yet for this article.
February 2017: Journal of Urology
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