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https://www.readbyqxmd.com/read/27930642/adjuvant-treatment-for-renal-cell-carcinoma-do-we-finally-have-a-major-breakthrough
#1
Devin N Patel, Robert A Figlin, Hyung L Kim
Clinical parameters can be used to identify patients at greatest risk for recurrence following nephrectomy for clinically localized renal cell carcinoma (RCC). Molecular tools are being developed to improve risk stratification. An increasing list of available treatments for metastatic RCC continues to provide hope that an effective adjuvant therapy will be identified for patients with high-risk, clinically localized disease. In a phase 3 adjuvant therapy trial (S-TRAC), sunitinib increased median disease-free survival in patients with clear cell RCC who were at very high risk...
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930578/short-term-and-long-term-efficacy-of-7-targeted-therapies-for-the-treatment-of-advanced-hepatocellular-carcinoma-a-network-meta-analysis-efficacy-of-7-targeted-therapies-for-ahcc
#2
Meng Niu, Duo Hong, Teng-Chuang Ma, Xiao-Wei Chen, Jin-Hang Han, Jun Sun, Ke Xu
BACKGROUND: A variety of targeted drug therapies in clinical trials have been proven to be effective for the treatment of hepatocellular carcinoma (HCC). Our study aims to compare the short-term and long-term efficacies of different targeted drugs in advanced hepatocellular carcinoma (AHCC) treatment using a network meta-analysis approach. METHODS: PubMed, Embase, Ovid, EBSCO, and Cochrane central register of controlled trials were searched for randomized controlled trials (RCTs) of different targeted therapies implemented to patients with AHCC...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27929442/synthesis-and-antitumor-activity-of-5-bromo-7-azaindolin-2-one-derivatives-containing-a-2-4-dimethyl-1h-pyrrole-3-carboxamide-moiety
#3
Jun Zhang, Weiyi Shen, Xiaoning Li, Yun Chai, Senjun Li, Kai Lv, Huiyuan Guo, Mingliang Liu
We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds exhibit broad-spectrum antitumor potency, and the most active compound 23p (IC50: 2.357-3.012 μM) was found more potent than Sunitinib (IC50: 31.594-49.036 μM) against HepG2, A549 and Skov-3, respectively...
December 6, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27928797/-changes-of-diagnosis-and-treatment-for-gastrointestinal-stromal-tumors-during-a-18-year-period-in-four-medical-centers-of-china
#4
Haibo Qiu, Peng Zhang, Xingyu Feng, Tao Chen, Xiaowei Sun, Jiang Yu, Zhijing Chen, Yong Li, Kaixiong Tao, Guoxin Li, Zhiwei Zhou
OBJECTIVE: To elucidate the historic and current diagnosis and treatment status of gastrointestinal stromal tumor (GIST) in the Chinese population based on four high volume databases. METHODS: Clinicopathological data of GIST patients with follow-up information between January 1998 and December 2015 from Sun Yat-sen University Cancer Center, Union Hospital of Huazhong University of Science and Technology, Southern Medical University Nanfang Hospital and Guangdong General Hospital were retrospectively analyzed...
November 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27927774/autophagy-inhibition-enhances-sunitinib-efficacy-in-clear-cell-ovarian-carcinoma
#5
Lindsay DeVorkin, Matthew Hattersley, Paul Kim, Jenna Ries, Jaeline Spowart, Michael S Anglesio, Samuel M Levi, David G Huntsman, Ravi K Amaravadi, Jeffrey D Winkler, Anna V Tinker, Julian J Lum
: Clear cell ovarian carcinoma (CCOC) is an aggressive form of epithelial ovarian cancer that exhibits low response rates to systemic therapy and poor patient outcomes. Multiple studies in CCOC have revealed expression profiles consistent with increased hypoxia, and our previous data suggests that hypoxia is correlated with increased autophagy in CCOC. Hypoxia-induced autophagy is a key factor promoting tumor cell survival and resistance to therapy. Recent clinical trials with the molecular-targeted receptor tyrosine kinase (RTK) inhibitor sunitinib have demonstrated limited activity...
December 7, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27926489/suppression-of-immune-regulatory-cells-with-combined-therapy-of-celecoxib-and-sunitinib-in-renal-cell-carcinoma
#6
Qi Zhao, Jianming Guo, Guomin Wang, Yiwei Chu, Xiaoyi Hu
OBJECTIVE: To observe the the potential benefit of sunitinib in combination with cyclooxygenase-2(COX-2) inhibitor in renal cell carcinoma therapy. METHODS: 769-p cell lines were treated with sunitinib, celecoxib, or in combination at different concentrations respectively. We investigated the expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in 769-p and cell proliferation in vitro. BALB/c mice implanted with Renca cells were divided into 4 groups and administered orally by gavage with sunitinib, COX-2 inhibitor (celecoxib) monotherapy or combination, and PBS respectively...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924664/assessment-of-ethnic-differences-in-sunitinib-outcome-between-caucasian-and-asian-patients-with-metastatic-renal-cell-carcinoma-a-meta-analysis
#7
Xiaoyan Liu, Marta Fiocco, Jesse J Swen, Henk-Jan Guchelaar
BACKGROUND: An increasing number of studies have reported ethnic differences in sunitinib outcome in metastatic renal cell carcinoma (mRCC) patients. However, a comprehensive analysis is still lacking. Therefore, we systematically collected available published data and performed a meta-analysis to compare sunitinib efficacy and toxicity in Asian and Caucasian mRCC patients. METHODS: Data were extracted from published results from clinical trials, expanded access program and real-world clinical practice...
December 7, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27924459/patient-reported-outcomes-and-quality-of-life-with-sunitinib-versus-placebo-for-pancreatic-neuroendocrine-tumors-results-from-an-international-phase-iii-trial
#8
Aaron Vinik, Andrew Bottomley, Beata Korytowsky, Yung-Jue Bang, Jean-Luc Raoul, Juan W Valle, Peter Metrakos, Dieter Hörsch, Rajiv Mundayat, Arlene Reisman, Zhixiao Wang, Richard C Chao, Eric Raymond
OBJECTIVE: The objective of this analysis was to compare patient-reported outcomes and health-related quality of life (HRQoL) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive, well-differentiated pancreatic neuroendocrine tumors (NCT00428597). PATIENTS AND METHODS: Patients received sunitinib 37.5 mg (n = 86) or placebo (n = 85) on a continuous daily-dosing schedule until disease progression, unacceptable adverse events (AEs), or death...
December 6, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27923360/tumour-response-in-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors-assessment-of-intra-tumour-heterogeneity
#9
EDITORIAL
Viktoria Stühler, Jens Bedke
Intra-tumour heterogeneity is a common molecular phenomenon in metastatic clear cell renal carcinoma (mRCC), representing the genetic complexity of a tumour with multiple metastatic sites. The present commentary discusses the observed phenomena of phenotypic intra-tumour heterogeneity in mRCC patients treated with the tyrosine kinase inhibitors sunitinib or pazopanib. Here, drug response can be different on the level of each evaluated metastasis in the individual patient. This questions the currently used radiologic staging systems of RECIST criteria and demands for a modification of radiologic response assessment with the consequence of a patient-tailored therapy in the clinical setting...
December 7, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27922693/a-novel-pdgf-receptor-inhibitor-eluting-stent-attenuates-in-stent-neointima-formation-in-a-rabbit-carotid-model
#10
Chen Huang, Haijun Mei, Min Zhou, Xiaobing Zheng
A novel drug-eluting stent (DES) is required to target vascular smooth muscle cells (SMCs) without harming endothelial cells (ECs). Platelet-derived growth factor (PDGF) is critical for the proliferation and migration of SMCs. Sunitinib [a PDGF receptor (PDGFR) tyrosine kinase inhibitor]‑eluting stents may therefore inhibit neointimal formation. The aim of the present study was to examine the stent‑based delivery of sunitinib in a rabbit carotid model; in addition, the effects of sunitinib were evaluated in vitro...
December 5, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27921054/a-rare-case-of-sunitinib-induced-exfoliative-esophagitis
#11
Swapna Gayam, Ashwini Anumandla
Sunitinib is a chemotherapeutic agent that has been approved for renal cell carcinoma and gastrointestinal stromal tumors resistant to imatinib. It is usually well tolerated and severe gastrointestinal side effects are rare. There are very few reports of sunitinib causing severe esophagitis, and only one of them was previously reported as exfoliative esophagitis. We describe a case of severe sunitinib-induced exfoliative esophagitis that resulted in overt gastrointestinal bleed.
August 2016: ACG Case Reports Journal
https://www.readbyqxmd.com/read/27921007/long-term-response-to-nivolumab-and-acute-renal-failure-in-a-patient-with-metastatic-papillary-renal-cell-carcinoma-and-a-pd-l1-tumor-expression-increased-with-sunitinib-therapy-a-case-report
#12
Juan Ruiz-Bañobre, Urbano Anido, Ihab Abdulkader, José Antúnez-López, Rafael López-López, Jorge García-González
INTRODUCTION: Papillary renal cell carcinoma (PRCC), which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal cell carcinoma...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27920695/metastatic-alveolar-soft-part-sarcoma-responsive-to-pazopanib-after-progression-through-sunitinib-and-bevacizumab-two-cases
#13
William L Read, Felicia Williams
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with a propensity for lung metastases and indolent progression. ASPS is not responsive to chemotherapy, but there are case reports and small series describing benefit from drugs targeting the VEGF pathway. These drugs include sunitinib, cediranib and bevacizumab. There is no established second-line treatment for persons with ASPS progressing through first-line targeted therapy. We report two individuals with metastatic ASPS who obtained disease stabilization from sunitinib lasting over a year...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27919134/-a-case-of-metastatic-tubulocystic-carcinoma-of-the-kidney-treated-with-molecularly-targeted-therapy
#14
Fumihiko Urabe, Jun Miki, Takafumi Yanagisawa, Takahiro Kimura, Masataka Nakano, Masafumi Suzuki, Koichi Kishimoto, Shin Egawa
A 51-year-old man who presented with gross hematuria and back pain was found to have a right renal mass accompanied with lung and osseous metastases. The patient underwent transabdominal right nephrectomy. The histopathological examination revealed the tumor to be tubulocystic carcinoma of the kidney. After the patient received sunitinib therapy, contrast enhanced computed tomography revealed that the metastatic tumor size was stable in the bone and decreased in the lung. Unfortunately, 9 months after nephrectomy, bone scintigraphy revealed an increase in the size of the metastatic tumor in the bone...
November 2016: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/27919126/-a-case-of-renal-cell-carcinoma-with-malignant-pleural-effusion-showing-marked-response-to-axitinib
#15
Yu Ishizuya, Takuya Okusa, Koji Hatano, Yasutomo Nakai, Masashi Nakayama, Ken-Ichi Kakimoto, Kazuo Nishimura
A 36-year-old woman had undergone left radical nephrectomy followed by interferon-α and sunitinib for the treatment of renal cell carcinoma with para-aortic lymph node and lung involvements (papillary renal cell carcinoma, G3, cT3aN1M1) in the previous hospital. She was referred to our hospital for further treatment and received serial molecular targeted agents (everolimus, sorafenib, sunitinib) and radiation therapy for right ischial and femoral bone metastases. Then she was found to have multiple metastatic lesions in the lungs and carcinomatous pleural effusion associated with dyspnea...
October 2016: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/27904651/sunitinib-in-the-treatment-of-metastatic-renal-cell-carcinoma
#16
REVIEW
Thomas A Schmid, Martin E Gore
Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27901483/meta-analysis-on-the-association-of-vegfr1-genetic-variants-with-sunitinib-outcome-in-metastatic-renal-cell-carcinoma-patients
#17
Xiaoyan Liu, Jesse J Swen, Epie Boven, Daniel Castellano, Hans Gelderblom, Ron H J Mathijssen, Cristina Rodríguez-Antona, Jesus García-Donas, Brian I Rini, Henk-Jan Guchelaar
VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900022/conversion-of-aspergilloma-to-chronic-necrotizing-pulmonary-aspergillosis-following-treatment-with-sunitinib-a-case-report
#18
Yeon Wook Kim, Hyun Woo Lee, Jaeyoung Cho, Han-Sol Choi, Jungsil Lee, Sung Soo Park, Eun Young Heo, Kwang Nam Jin, Deog Kyeom Kim
Semi-invasive or invasive aspergillosis occurring following chemotherapy with sunitinib is a rare condition with unknown incidence and prognosis. Here, we report a case involving a 59-year-old male who had a history of underlying stable aspergilloma and was newly diagnosed with metastatic renal cell carcinoma. Following surgical resection for renal cell carcinoma and adjuvant chemotherapy with sunitinib for 8 months, the patient presented with hemoptysis. Chest computed tomography revealed an increased soft tissue mass and air crescent sign of the underlying aspergilloma, combined with consolidation and bronchial artery hypertrophy around the lesion...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896475/an-exploratory-association-of-polymorphisms-in-angiogenesis-related-genes-with-susceptibility-clinical-response-and-toxicity-in-gastrointestinal-stromal-tumors-receiving-sunitinib-after-imatinib-failure
#19
Gloria Ravegnini, Margherita Nannini, Corrado Zenesini, Vittorio Simeon, Giulia Sammarini, Milena Urbini, Lidia Gatto, Maristella Saponara, Guido Biasco, Maria A Pantaleo, Nicola Venturoli, Patrizia Hrelia, Sabrina Angelini
The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and metastasis. The most important actors in the angiogenic pathway are VEGFA and its receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we hypothesized that germline variants may affect sunitinib efficacy (TTP and OS) and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in 54 GIST patients, treated with second-line sunitinib and 147 healthy controls...
November 28, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27893461/dual-modulation-of-mcl-1-and-mtor-determines-the-response-to-sunitinib
#20
Mohamed Elgendy, Amal Kamal Abdel-Aziz, Salvatore Lorenzo Renne, Viviana Bornaghi, Giuseppe Procopio, Maurizio Colecchia, Ravindran Kanesvaran, Chee Keong Toh, Daniela Bossi, Isabella Pallavicini, Jose Luis Perez-Gracia, Maria Dolores Lozano, Valeria Giandomenico, Ciro Mercurio, Luisa Lanfrancone, Nicola Fazio, Franco Nole, Bin Tean Teh, Giuseppe Renne, Saverio Minucci
Most patients who initially respond to treatment with the multi-tyrosine kinase inhibitor sunitinib eventually relapse. Therefore, developing a deeper understanding of the contribution of sunitinib's numerous targets to the clinical response or to resistance is crucial. Here, we have shown that cancer cells respond to clinically relevant doses of sunitinib by enhancing the stability of the antiapoptotic protein MCL-1 and inducing mTORC1 signaling, thus evoking little cytotoxicity. Inhibition of MCL-1 or mTORC1 signaling sensitized cells to clinically relevant doses of sunitinib in vitro and was synergistic with sunitinib in impairing tumor growth in vivo, indicating that these responses are triggered as prosurvival mechanisms that enable cells to tolerate the cytotoxic effects of sunitinib...
November 28, 2016: Journal of Clinical Investigation
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