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https://www.readbyqxmd.com/read/28817826/the-safety-and-efficacy-of-the-s1-temozolomide-regimen-in-patients-with-metastatic-neuroendocrine-tumors
#1
Jiuda Zhao, Hong Zhao, Yihebali Chi
<br><br>Purpose Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1 plus temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75...
August 17, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28811127/attenuation-of-sunitinib-induced-cardiotoxicity-through-the-a3-adenosine-receptor-activation
#2
Hardip Sandhu, Samantha Cooper, Afthab Hussain, Christopher Mee, Helen Maddock
Sunitinib is an anti-cancer tyrosine kinase inhibitor associated with severe cardiotoxic adverse effects. Using rat Langendorff heart model and human acute myeloid leukemia 60 (HL60) cell line we detected the involvement of protein kinase C (PKC) α during Sunitinib-induced cardiotoxicity and the effect of Sunitinib on cancer progression. The cardioprotective and anti-cancer properties of the A3 adenosine receptor agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were investigated...
August 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28810837/phase-i-dose-escalation-study-of-pazopanib-combined-with-bevacizumab-in-patients-with-metastatic-renal-cell-carcinoma-or-other-advanced-tumors
#3
Sylvie Négrier, David Pérol, Rastislav Bahleda, Antoine Hollebecque, Etienne Chatelut, Helen Boyle, Philippe Cassier, Séverine Metzger, Ellen Blanc, Jean-Charles Soria, Bernard Escudier
BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors...
August 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28805145/pdgf-vegf-related-receptor-affects-transglutaminase-activity-to-control-cell-migration-during-crustacean-hematopoiesis
#4
Kingkamon Junkunlo, Chadanat Noonin, Kenneth Söderhäll, Irene Söderhäll
The platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor whose ligand is PDGF, is crucial in the transduction of extracellular signals into cells and mediates numerous processes, such as cell proliferation, differentiation, survival and migration. We demonstrate the important roles of a receptor tyrosine kinase related to the PDGF/VEGF family protein (PVR) in controlling hematopoietic progenitor cell migration by affecting extracellular transglutaminase (TGase) activity. Pl_PVR1, GenBank accession number KY444650, is highly expressed in hemocytes and the hematopoietic tissue (HPT)...
August 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#5
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28796048/clinicopathologic-study-of-succinate-dehydrogenase-deficient-gastrointestinal-stromal-tumors-a-single-institutional-experience-in-china
#6
Weizhen Liu, Xiangyu Zeng, Xiuli Wu, Jun He, Jinbo Gao, Xiaoming Shuai, Guobin Wang, Peng Zhang, Kaixiong Tao
Gastrointestinal stromal tumors (GISTs) that are not driven by kinase mutations, as are most GISTs, often show loss of function of the succinate dehydrogenase (SDH) complex and are considered SDH-deficient GISTs. SDH-deficient GISTs share many distinct characteristics compared with conventional GISTs. However, data regarding these characteristics, particularly among Asian people, are relatively limited. The objective of this study was to characterize the clinicopathologic characteristics, treatment, and prognosis of these uncommon GISTs...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28795288/novel-agents-in-the-treatment-of-thymic-malignancies
#7
REVIEW
Claire Merveilleux du Vignaux, Jean-Michel Maury, Nicolas Girard
The management of thymic tumours is a paradigm of multidisciplinary collaboration. Chemotherapy may be administered part of curative-intent sequential strategy integrating subsequent surgery or radiotherapy, or as an exclusive treatment if local treatment is not achievable. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. Given the limited activity of cytotoxic agents in the advanced, refractory setting, novel and innovative agents are needed...
August 10, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28789709/comparison-of-efficacy-safety-and-quality-of-life-between-sorafenib-and-sunitinib-as-first-line-therapy-for-chinese-patients-with-metastatic-renal-cell-carcinoma
#8
Wen Cai, Wen Kong, Baijun Dong, Jin Zhang, Yonghui Chen, Wei Xue, Yiran Huang, Lixin Zhou, Jiwei Huang
BACKGROUND: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma (mRCC) in China. This study aimed to compare the efficacy, safety, and quality of life (QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy. METHODS: Clinical data of patients with mRCC who received sorafenib (400 mg twice daily; 4 weeks) or sunitinib (50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved...
August 8, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28782406/severe-sunitinib-induced-myelosuppression-in-a-patient-with-a-cyp-3a4-polymorphism
#9
Nirav D Patel, Kanishka Chakrabory, Garrett Messmer, Koyamangalath Krishnan, John B Bossaer
Sunitinib, an oral vascular endothelial growth factor receptor, is a first-line option for metastatic renal cell carcinoma and widely used in clinical practice. Despite the proven benefit of sunitnib in metastatic renal cell carcinoma, patients may suffer from a variety of adverse events including hypertension, fatigue, hypothyroidism, hand-foot skin reactions, rash, depigmentation, and myelosuppression. Myelosuppression is usually mild, transient and resolves during the two weeks at the end of each cycle where no drug is taken...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28781298/primary-cardiac-leiomyosarcoma-a-27-month-survival-with-surgery-and-chemotherapy
#10
Koji Nakashima, Haruhiko Inatsu, Kazuo Kitamura
The patient was a 39-year-old man hospitalized due to the presence of a cardiac mass and heart failure. Emergency tumor resection and mitral valve replacement were performed. The pathological findings of the tumor led to a diagnosis of cardiac leiomyosarcoma. After the operation, multiple metastases were found. The patient underwent three courses of chemotherapies: adriamycin, ifosfamide, dacarbazine, and mesna (MAID therapy), gemcitabine plus docetaxel, and sunitinib. During MAID therapy, the patient underwent resection of gastrointestinal metastases twice due to gastrointestinal hemorrhaging...
August 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28781191/phase-i-study-of-dalteparin-in-combination-with-sunitinib-in-patients-with-metastatic-clear-cell-renal-carcinoma
#11
Madelon Q Wentink, Henk M W Verheul, Sumanta K Pal, Saby George, Johannes Voortman, Pongwut Danchaivijitr, Remi Adelaiye, Diane Poslinski, Adrienne Groman, Alan Hutson, Roberto Pili
BACKGROUND: Based on the tumor-driven concomitant activation of angiogenesis and coagulation we conducted a phase I combination study of sunitinib with the low molecular weight heparin dalteparin in patients with metastatic clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: Patients received standard treatment with sunitinib (50 mg daily, 4 weeks on, 2 weeks off). During the second week of no sunitinib in the first cycle (week 6) patients received dalteparin monotherapy (in escalating doses)...
July 14, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28768491/succinate-dehydrogenase-deficiency-in-a-pdgfra-mutated-gist
#12
Martin G Belinsky, Kathy Q Cai, Yan Zhou, Biao Luo, Jianming Pei, Lori Rink, Margaret von Mehren
BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor mutually exclusive gain of function mutations in the receptor tyrosine kinase (RTK) KIT (70-80%) or in the related receptor PDGFRA (~10%). These GISTs generally respond well to therapy with the RTK inhibitor imatinib mesylate (IM), although initial response is genotype-dependent. An alternate mechanism leading to GIST oncogenesis is deficiency in the succinate dehydrogenase (SDH) enzyme complex resulting from genetic or epigenetic inactivation of one of the four SDH subunit genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHX)...
August 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28761748/new-treatment-options-for-metastatic-renal-cell-carcinoma
#13
REVIEW
Alejo Rodriguez-Vida, Thomas E Hutson, Joaquim Bellmunt, Michiel H Strijbos
During the last decade, the treatment of advanced or metastatic renal cell carcinoma (RCC) was revolutionised with the advent of antiangiogenic drugs and tyrosine-kinase inhibitors. Several agents targeting the vascular endothelial growth factor (VEGF) pathway (sunitinib, bevacizumab, pazopanib, axitinib) or the mammalian target of rapamycin pathway (temsirolimus, everolimus) were since then progressively approved for first-line or later-line use in the treatment of patients with advanced RCC and became the new standard of care...
2017: ESMO Open
https://www.readbyqxmd.com/read/28756150/a-marine-sponge-alkaloid-derivative-4-chloro-fascaplysin-inhibits-tumor-growth-and-vegf-mediated-angiogenesis-by-disrupting-pi3k-akt-mtor-signaling-cascade
#14
Sonia Sharma, Santosh Kumar Guru, Sudhakar Manda, Ashok Kumar, Mubashir J Mintoo, Venna Deva Prasad, Parduman R Sharma, Dilip M Mondhe, Sandip B Bharate, Shashi Bhushan
Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives for the treatment and management of breast cancer. Here we first time report the molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4-CF) for its anticancer and antiangiogenesis potential. It simultaneously targets multiple cancer and angiogenesis dynamics, such as proliferation, chemotaxis cell migration, and invasion, growth factors signaling cascade, autophagy and apoptosis in HUVEC and MDAMB-231 breast cancer cells...
July 26, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28756136/addressing-the-best-treatment-for-non-clear-cell-renal-cell-carcinoma-a-meta-analysis-of-randomised-clinical-trials-comparing-vegfr-tkis-versus-mtori-targeted-therapies
#15
Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Francesco Massari, Davide Bimbatti, Emanuela Fantinel, Vincenzo De Marco, Antonio Benito Porcaro, Guido Martignoni, Walter Artibani, Giampaolo Tortora
AIM: Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous group of malignancies that profoundly differ in terms of morphology, genetic profile, clinical behaviour and prognosis. The optimal treatment algorithm for nccRCC is still unknown and derived mainly from evidence available for ccRCC, being therefore represented by targeted agents against vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to compare the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of nccRCC patients...
July 27, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28754878/acquired-tumor-cell-resistance-to-sunitinib-by-increased-invasion-and-epithelial-mesenchymal-transition-in-ll-2-murine-lung-cancer
#16
Yang Du, Jia-Qi Liu, Jie Tang, Jun Ge, Ye Chen, Ke Cheng, Jing Ding, Zhi-Ke Li, Ji-Yan Liu
OBJECTIVE: This study aims to investigate biological behavior changes in a murine lung cancer cell characterized by acquired resistance to sunitinib, a potent inhibitor of multiple-targeted receptor tyrosine kinase. METHODS: A lung cancer cell line resistant to sunitinib (LL/2-R) was developed from its parental cell line (LL/2-P). Differences in biological characteristics and associated molecular profiles between these two cells were compared in vitro and in vivo...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753786/tumor-xenografts-of-human-clear-cell-renal-cell-carcinoma-but-not-corresponding-cell-lines-recapitulate-clinical-response-to-sunitinib-feasibility-of-using-biopsy-samples
#17
Yiyu Dong, Brandon J Manley, Maria F Becerra, Almedina Redzematovic, Jozefina Casuscelli, Daniel M Tennenbaum, Ed Reznik, Song Han, Nicole Benfante, Ying-Bei Chen, Maria E Arcila, Omer Aras, Martin H Voss, Darren R Feldman, Robert J Motzer, Nicola Fabbri, John H Healey, Patrick J Boland, Mohit Chawla, Jeremy C Durack, Chung-Han Lee, Jonathan A Coleman, Paul Russo, A Ari Hakimi, Emily H Cheng, James J Hsieh
BACKGROUND: Parallel development of preclinical models that recapitulate treatment response observed in patients is central to the advancement of personalized medicine. OBJECTIVE: To evaluate the use of biopsy specimens to develop patient-derived xenografts and the use of corresponding cell lines from renal cell carcinoma (RCC) tumors for the assessment of histopathology, genomics, and treatment response. DESIGN, SETTING, AND PARTICIPANTS: A total of 74 tumor specimens from 66 patients with RCC were implanted into immunocompromised NOD-SCID IL2Rg(-/-) mice...
August 25, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28753585/overriding-tki-resistance-of-renal-cell-carcinoma-by-combination-therapy-with-il-6-receptor-blockade
#18
Kei Ishibashi, Tobias Haber, Ines Breuksch, Susanne Gebhard, Takashi Sugino, Hitoshi Kubo, Junya Hata, Tomoyuki Koguchi, Michihiro Yabe, Masao Kataoka, Soichiro Ogawa, Hiroyuki Hiraki, Tomohiko Yanagida, Nobuhiro Haga, Joachim W Thüroff, Dirk Prawitt, Walburgis Brenner, Yoshiyuki Kojima
Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28748721/real-world-costs-and-outcomes-in-metastatic-renal-cell-carcinoma-patients-treated-with-targeted-therapies-a-cohort-study-from-the-french-health-insurance-database
#19
Rana Maroun, Laetitia Fleury, Gaelle Nachbaur, Franck Maunoury, Jean-Louis Vanhille, Isabelle Durand-Zaleski
OBJECTIVES: The objective of this study was to describe treatment patterns, survival, healthcare use and costs in patients with metastatic renal cell carcinoma (mRCC) in a real-world setting. RESEARCH DESIGN AND METHODS: We used the National Health Insurance (NHI) claims database for the Ile-de-France region to perform a retrospective cohort analysis of patients with mRCC treated by a first-line targeted therapy. Treatment naïve patients were identified combining the 10th revision of the International Classification of Diseases (ICD-10) codes (C64 & C77-C79) and a first prescription of targeted therapies...
August 7, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28748331/eligibility-for-phase-3-clinical-trials-of-systemic-therapy-in-real-world-patients-with-metastatic-renal-cell-cancer-managed-in-a-rural-region
#20
Carsten Nieder, Mohsan A Syed, Astrid Dalhaug, Adam Pawinski, Jan Norum
Previous research has identified disparities between urban and rural cancer care, including clinical trial access. Therefore, we addressed three different questions in patients with metastatic renal cell cancer managed according to national guidelines in a rural Norwegian standard practice setting. (1) How many patients would have been eligible for three recent landmark randomized clinical trials? (2) Is survival different between eligible and non-eligible patients receiving first-line systemic therapy? (3) Is survival different between eligible patients and published trial results? We performed a retrospective analysis of 101 consecutive patients (2006-2016)...
September 2017: Medical Oncology
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