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https://www.readbyqxmd.com/read/29334307/regorafenib-regresses-an-imatinib-resistant-recurrent-gastrointestinal-stromal-tumor-gist-with-a-mutation-in-exons-11-and-17-in-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#1
Kentaro Miyake, Kei Kawaguchi, Tasuku Kiyuna, Masuyo Miyake, Kentaro Igarashi, Zhiying Zhang, Takashi Murakami, Yunfeng Li, Scott D Nelson, Irmina Elliott, Tara Russell, Arun Singh, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chisima, Itaru Endo, Fritz C Eilber, Robert M Hoffman
Gastrointestinal stromal tumor (GIST) is a rare type of sarcoma. The aim of this study was to determine drug sensitivity for a regionally-recurrent case of GIST using a patient-derived orthotopic xenograft (PDOX) model. The PDOX model was established in the anterior wall of the stomach. GIST PDOX models were randomized into 5 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration (p.o.), daily, for 3 weeks); G3, sunitinib group (p.o., daily, for 3 weeks); G4, regorafenib (p...
January 15, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29327492/a-five-gene-signature-may-predict-sunitinib-sensitivity-and-serve-as-prognostic-biomarkers-for-renal-cell-carcinoma
#2
Yuan-Lei Chen, Guang-Ju Ge, Chao Qi, Huan Wang, Huai-Lan Wang, Li-Yang Li, Gong-Hui Li, Li-Qun Xia
Sunitinib resistance is, nowadays, the major challenge for advanced renal cell carcinoma patients. Illuminating the potential mechanisms and exploring effective strategies to overcome sunitinib resistance are highly desired. We constructed a reliable gene signature which may function as biomarkers for prediction of sunitinib sensitivity and clinical prognosis. The gene expression profiles were obtained from The Cancer Genome Atlas database. By performing GEO2R analysis, numerous differentially expressed genes (DEGs) were found to be associated with sunitinib resistance...
January 12, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29312652/tyrosine-kinase-inhibitor-sensitive-pdgfr%C3%AE-mutations-in-gist-two-cases-and-review-of-the-literature
#3
Pieter A Boonstra, Jourik A Gietema, Albert J H Suurmeijer, Matthew R Groves, Fernando de Assis Batista, Ed Schuuring, Anna K L Reyners
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal malignancies of the gastrointestinal tract. Most GISTs harbor a c-KIT (80%) or a PDGFRα (10%) mutation that leads to constitutive activation of the tyrosine kinase receptor. Response to treatment with tyrosine kinase inhibitors (TKIs) is dependent on mutational status of the tumor. The most common mutation in PDGFRα, D842V, is known to be imatinib resistant. Almost all other PDGFRα mutations are imatinib sensitive. We describe two patients with a PDGFRα exon 18 mutated GIST responding to treatment with TKIs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310342/efficacy-and-safety-of-regorafenib-for-advanced-gastrointestinal-stromal-tumor-after-failure-with-imatinib-and-sunitinib-treatment-a-meta-analysis
#4
Zhenan Zhang, Tao Jiang, Wensheng Wang, Daxun Piao
AIMS: This meta-analysis aimed to evaluate the safety and efficacy of regorafenib as a treatment for patients with advanced (metastatic and/or unresectable) gastrointestinal stromal tumor (AGIST) after developing resistance to imatinib and sunitinib. METHODS: A literature search of databases such as PubMed, Embase, and Cochrane library was conducted up to February 2017. The pooled percentages and the corresponding 95% confidence intervals (CIs) were calculated using the Stata 11...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29310178/re-a-phase-ii-study-of-intermittent-sunitinib-in-previously-untreated-patients-with-metastatic-renal-cell-carcinoma
#5
M Pilar Laguna
No abstract text is available yet for this article.
January 2018: Journal of Urology
https://www.readbyqxmd.com/read/29290991/early-and-late-effects-of-pharmacological-alk-inhibition-on-the-neuroblastoma-transcriptome
#6
Shana Claeys, Geertrui Denecker, Robrecht Cannoodt, Candy Kumps, Kaat Durinck, Frank Speleman, Katleen De Preter
Background: Neuroblastoma is an aggressive childhood malignancy of the sympathetic nervous system. Despite multi-modal therapy, survival of high-risk patients remains disappointingly low, underscoring the need for novel treatment strategies. The discovery of ALK activating mutations opened the way to precision treatment in a subset of these patients. Previously, we investigated the transcriptional effects of pharmacological ALK inhibition on neuroblastoma cell lines, six hours after TAE684 administration, resulting in the 77-gene ALK signature, which was shown to gradually decrease from 120 minutes after TAE684 treatment, to gain deeper insight into the molecular effects of oncogenic ALK signaling...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290798/ultrasound-molecular-imaging-of-vegfr-2-in-clear-cell-renal-cell-carcinoma-tracks-disease-response-to-antiangiogenic-and-notch-inhibition-therapy
#7
Juan D Rojas, Fanglue Lin, Yun-Chen Chiang, Anna Chytil, Diana C Chong, Victoria L Bautch, W Kimryn Rathmell, Paul A Dayton
Metastatic clear-cell renal cell carcinoma (ccRCC) affects thousands of patients worldwide each year. Antiangiogenic therapy has been shown to have beneficial effects initially, but resistance is eventually developed. Therefore, it is important to accurately track the response of cancer to different therapeutics in order to appropriately adjust the therapy to maximize efficacy. Change in tumor volume is the current gold standard for determining efficacy of treatment. However, functional variations can occur much earlier than measurable volume changes...
2018: Theranostics
https://www.readbyqxmd.com/read/29289530/a-vascular-endothelial-growth-factor-dependent-sprouting-angiogenesis-assay-based-on-an-in-vitro-human-blood-vessel-model-for-the-study-of-anti-angiogenic-drugs
#8
Joris Pauty, Ryo Usuba, Irene Gayi Cheng, Louise Hespel, Haruko Takahashi, Keisuke Kato, Masayoshi Kobayashi, Hiroyuki Nakajima, Eujin Lee, Florian Yger, Fabrice Soncin, Yukiko T Matsunaga
Angiogenesis is the formation of new capillaries from pre-existing blood vessels and participates in proper vasculature development. In pathological conditions such as cancer, abnormal angiogenesis takes place. Angiogenesis is primarily carried out by endothelial cells, the innermost layer of blood vessels. The vascular endothelial growth factor-A (VEGF-A) and its receptor-2 (VEGFR-2) trigger most of the mechanisms activating and regulating angiogenesis, and have been the targets for the development of drugs...
December 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29287894/-monitoring-of-hypertension-in-patients-orally-treated-by-angiogenesis-inhibitor-in-daily-practice
#9
Lisa Belaid, Sahar Bayat-Makoei, Brigitte Laguerre, Cécile Vigneau
OBJECTIVE: The aim of this study is to measure the monitoring and the incidence of renovascular effects of angiogenesis inhibitors in real population. METHOD: Are included in this descriptive, monocentric, practical study, patients of 18 years old and more, orally treated by angiogenesis inhibitors and monitored in consultation by clinician nurses. The main interest variable is the incidence of hypertension at three months of treatment. RESULTS: From January, 2011 to July, 2014, 324 patients have been included, whose 53% are men...
December 26, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29287262/dna-binding-of-sunitinib-spectroscopic-evidence-via-circular-dichroism-and-nuclear-magnetic-resonance
#10
Eszter Kiss, Arash Mirzahosseini, Ágnes Hubert, Attila Ambrus, László Őrfi, Péter Horváth
Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable...
December 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29286028/-isolated-pancreatic-metastases-of-renal-cell-carcinoma
#11
G A Shatveryan, N K Chardarov, N N Bagmet, N P Ratnikova, A L Bedzhanyan, K N Petrenko, L O Polishchuk, G A Karagyozyan
AIM: To present own experience of surgical treatment of isolated pancreatic metastases of renal cell carcinoma. MATERIAL AND METHODS: There are 3 cases of pancreatic metastases of renal cell carcinoma. They were diagnosed in women aged 55, 66 and 67 years in 9, 11 and 23 years after nephrectomy respectively. RESULTS: The tumors were placed in head (60 mm), body (10 and 5 mm) and tail (30 mm) of the pancreas. There were 2 distal pancreatectomy with splenectomy and 1 pancreatoduodenectomy...
2017: Khirurgiia
https://www.readbyqxmd.com/read/29285109/acute-kidney-injury-in-cancer-patients-and-impedance-cardiography-assisted-renal-replacement-therapy-experience-from-the-onconephrology-unit-of-a-chinese-tertiary-hospital
#12
Tao Wang, Yan Zhang, Qingxia Li, Shumin Jia, Changjin Shi, Kai Niu, Bing Liu
Acute kidney injury (AKI) in cancer patients may disrupt anticarcinogenic treatment and greatly increase associated mortality rates. The present study reported on the management of cancer patients with AKI and, from the nephrologic viewpoint, on the significance of fine volume control during the continuous renal replacement therapy (CRRT). The records of 117 cancer patients with AKI treated over three years were reviewed and their data were compared with those of 120 healthy controls. AKI was defined according to the Kidney Disease: Improving Global Outcomes criteria with serum creatinine levels determined on initial admission and for the diagnosis of AKI...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29284153/role-of-ret-protein-tyrosine-kinase-inhibitors-in-the-treatment-ret-driven-thyroid-and-lung-cancers
#13
REVIEW
Robert Roskoski, Abdollah Sadeghi-Nejad
RET is a transmembrane receptor protein-tyrosine kinase that is required for the development of the nervous system and several other tissues. The mechanism of activation of RET by its glial-cell derived neurotrophic factor (GDNF) ligands differs from that of all other receptor protein-tyrosine kinases owing to the requirement for additional GDNF family receptor-α (GFRα) co-receptors (GFRα1/2/3/4). RET point mutations have been reported in multiple endocrine neoplasia (MEN2A, MEN2B) and medullary thyroid carcinoma...
December 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29283974/the-role-of-distal-tubule-and-collecting-duct-sodium-reabsorption-in-sunitinib-induced-hypertension
#14
Jeannine Witte, Josephine Lampe, Anna Koenen, Ines Urbaneck, Antje Steinbach, Rainer Rettig, Olaf Grisk
OBJECTIVE: Antiangiogenic receptor tyrosine kinase inhibitors (RTKI) induce arterial hypertension which may limit their use. Renal fractional sodium excretion (FENa) is reduced in early RTKI-induced hypertension, whereas fractional lithium excretion is unaltered. Therefore, we tested the hypothesis that activated distal tubule and collecting duct sodium reabsorption contributes to RTKI-induced hypertension. METHODS: Amiloride-sensitive and hydrochlorothiazide (HCTZ)-sensitive fractional sodium reabsorption (FRNa) and renal epithelial sodium channel (ENaC) as well as sodium chloride cotransporter (NCC) abundances were determined in sunitinib-treated and control rats...
December 27, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29283445/simultaneous-analysis-of-oral-anticancer-drugs-for-renal-cell-carcinoma-in-human-plasma-using-liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry
#15
Shinya Takasaki, Masaki Tanaka, Masafumi Kikuchi, Masamitsu Maekawa, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano
An analytical method using high performance liquid chromatography/electrospray ionization tandem mass spectrometry has been developed and validated for simultaneous measurement of four tyrosine kinase inhibitors used for renal cell carcinoma and their metabolites in human plasma. Despite their similar structures, it is difficult to measure plasma levels of these compounds simultaneously using optimal MS parameters for each compound because a quantitative range exceeding 50,000-fold is required. To overcome this problem, we used a linear range shift technique using in-source collision-induced dissociation...
December 28, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29275383/solid-pseudopapillary-tumour-frantz-s-tumour-of-the-pancreas-in-childhood-successful-management-of-late-liver-metastases-with-sunitinib-and-chemoembolisation
#16
Mauricio Antonio Escobar, John Mason McClellan, William Thomas
The patient is a girl aged 17 years who originally presented at age 11 years with a solid pseudopapillary tumour (SPT) in the head of the pancreas treated by an R0 pylorus-preserving Whipple procedure. The patient underwent surveillance CT every 3 months for the first year followed by MRI every 6 months. She was noted to have a new liver lesion in Couinaud segment VI highly suspicious for metastasis at 30 months. Liver wedge biopsy confirmed metastatic SPT. Two months later two new lesions were noted in Couinaud segment VII...
December 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29274030/fatigue-among-patients-with-renal-cell-carcinoma-receiving-adjuvant-sunitinib-or-sorafenib-patient-reported-outcomes-of-ecog-acrin-e2805-trial
#17
Fengmin Zhao, David Cella, Judith Manola, Robert S DiPaola, Lynne I Wagner, Naomi S B Haas
BACKGROUND: E2805 was a phase III trial to test whether adjuvant sunitinib or sorafenib could improve disease-free survival compared to placebo in patients with renal cell carcinoma. Patient-reported outcomes (PRO), focusing on fatigue, were evaluated as a secondary endpoint. PATIENTS AND METHODS: A total of 463 patients participated in the PRO study. Fatigue was measured by the FACIT Fatigue scale and PROMIS Fatigue SF1 measure at baseline, week 10, and week 22...
December 23, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29259007/amplification-of-oncolytic-vaccinia-virus-widespread-tumor-cell-killing-by-sunitinib-through-multiple-mechanisms
#18
Minah Kim, Maximilian Nitschké, Barbara Sennino, Patrizia Murer, Brian J Schriver, Alexander M Bell, Aishwarya Subramanian, Corry E McDonald, Jiahu Wang, Howard Cha, Marie-Claude Bourgeois-Daigneault, David H Kirn, John C Bell, Naomi De Silva, Caroline J Breitbach, Donald M McDonald
Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors (PNET) that developed spontaneously and progress as in humans...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29248607/involvement-of-mitogen-activated-kinase-kinase-7-intracellular-signalling-pathway-in-sunitinib-induced-cardiotoxicity
#19
Samantha Louise Cooper, Hardip Sandhu, Afthab Hussain, Christopher Mee, Helen Maddock
The tyrosine kinase inhibitor Sunitinib is used to treat cancer and is linked to severe adverse cardiovascular events. Mitogen activated kinase kinase 7 (MKK7) is involved in the development of cardiac injury and is a component of the c-Jun N-terminal kinase (JNK) signal transduction pathway. Apoptosis signal-regulating kinase 1 (ASK1) is the upstream activator of MKK7 and is specifically inhibited by 2,7-dihydro-2,7-dioxo-3H-naphtho[1,2,3-de]quinoline-1-carboxylic acid ethyl ester (NQDI-1). This study investigates the role of ASK1, MKK7 and JNK during Sunitinib-induced cardiotoxicity...
December 14, 2017: Toxicology
https://www.readbyqxmd.com/read/29239846/molecular-subtypes-of-clear-cell-renal-cell-carcinoma-are-associated-with-outcome-during-pazopanib-therapy-in-the-metastatic-setting
#20
Annelies Verbiest, Gabrielle Couchy, Sylvie Job, Jessica Zucman-Rossi, Laure Caruana, Evelyne Lerut, Raymond Oyen, Aurélien de Reyniès, Brigitte Laguerre, Nathalie Rioux-Leclercq, Agnieszka Wozniak, Steven Joniau, Hendrik Van Poppel, Kathleen Van Den Eynde, Benoit Beuselinck
BACKGROUND: We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment...
November 7, 2017: Clinical Genitourinary Cancer
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