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https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#1
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28424409/clinical-genomic-profiling-to-identify-actionable-alterations-for-investigational-therapies-in-patients-with-diverse-sarcomas
#2
Roman Groisberg, David S Hong, Vijaykumar Holla, Filip Janku, Sarina Piha-Paul, Vinod Ravi, Robert Benjamin, Shreyas Kumar Patel, Neeta Somaiah, Anthony Conley, Siraj M Ali, Alexa B Schrock, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Shiraj Sen, Cynthia Herzog, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: There are currently no United States Food and Drug Administration approved molecularly matched therapies for sarcomas except gastrointestinal stromal tumors. Complicating this is the extreme diversity, heterogeneity, and rarity of these neoplasms. Few therapeutic options exist for relapsed and refractory sarcomas. In clinical practice many oncologists refer patients for genomic profiling hoping for guidance on treatment options after standard therapy. However, a systematic analysis of actionable mutations has yet to be completed...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420839/solitary-gastric-metastasis-from-a-stage-ia-serous-ovarian-carcinoma-a-case-report-with-literature-review
#3
Keishi Mizuguchi, Hiroshi Minato, Isao Yoshida, Junpei Iwadare, Kayo Kayahashi, Yuki Mitani, Kazuyoshi Watanabe
Gastric metastasis from ovarian cancer is exceptionally rare and generally occurs in advanced stages. A 71-year-old woman presented with a solitary gastric submucosal mass 8 years after the diagnosis of a stage IA ovarian serous adenocarcinoma. Endoscopy showed a tumor covered with normal gastric mucosa. Initially, a gastrointestinal stromal tumor was suspected, but biopsy revealed a histology of invasive micropapillary carcinoma, similar to the histological findings of the previously resected ovarian tumor...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28403213/m-copa-suppresses-endolysosomal-kit-akt-oncogenic-signalling-through-inhibiting-the-secretory-pathway-in-neoplastic-mast-cells
#4
Yasushi Hara, Yuuki Obata, Keita Horikawa, Yasutaka Tasaki, Kyohei Suzuki, Takatsugu Murata, Isamu Shiina, Ryo Abe
Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28402935/mirna-profiling-of-gastrointestinal-stromal-tumors-by-next-generation-sequencing
#5
Ugne Gyvyte, Simonas Juzenas, Violeta Salteniene, Juozas Kupcinskas, Lina Poskiene, Laimutis Kucinskas, Sonata Jarmalaite, Kristina Stuopelyte, Ruta Steponaitiene, Georg Hemmrich-Stanisak, Matthias Hübenthal, Alexander Link, Sabine Franke, Andre Franke, Dalia Pangonyte, Vaiva Lesauskaite, Limas Kupcinskas, Jurgita Skieceviciene
Deregulation of miRNAs has been observed virtually in all major types of cancer, whereas the miRNA signature in GIST is not well characterized yet. In this study the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and differentially expressed miRNAs as well as isomiRNAs were defined. Highly significantly deregulated miRNAs were selected for validation by Taq-Man low-density array in replication group of 40 paired samples. Validated miRNAs were further subjected to enrichment analysis, which revealed significantly enriched KEGG pathways in the main GIST associated pathways...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383420/can-laparoscopic-surgery-be-applied-in-gastric-gastrointestinal-stromal-tumors-located-in-unfavorable-sites-a-study-based-on-the-nccn-guidelines
#6
Chang-Ming Huang, Qing-Feng Chen, Jian-Xian Lin, Mi Lin, Chao-Hui Zheng, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Qi-Yue Chen, Long-Long Cao, Ru-Hong Tu
This article investigated the feasibility of laparoscopic surgery in unfavorable site gastric gastrointestinal stromal tumors (GISTs).We identified 214 patients who underwent primary gastric GIST resection at our institution (January 2006-December 2014) from a prospectively collected database. These patients were divided into a Favorable group (140 cases) and an Unfavorable group (74 cases) according to the 2014 version of the National Comprehensive Cancer Network Clinical Guidelines (NCCN guidelines).The wedge resection rate of the Favorable group was higher than that of the Unfavorable group, and most procedures were performed laparoscopically (P < 0...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28377632/integrated-analysis-of-gene-expression-and-copy-number-identified-potential-cancer-driver-genes-with-amplification-dependent-overexpression-in-1-454-solid-tumors
#7
Keiichi Ohshima, Keiichi Hatakeyama, Takeshi Nagashima, Yuko Watanabe, Kaori Kanto, Yuki Doi, Tomomi Ide, Yuji Shimoda, Tomoe Tanabe, Sumiko Ohnami, Shumpei Ohnami, Masakuni Serizawa, Koji Maruyama, Yasuto Akiyama, Kenichi Urakami, Masatoshi Kusuhara, Tohru Mochizuki, Ken Yamaguchi
Identification of driver genes contributes to the understanding of cancer etiology and is imperative for the development of individualized therapies. Gene amplification is a major event in oncogenesis. Driver genes with tumor-specific amplification-dependent overexpression can be therapeutic targets. In this study, we aimed to identify amplification-dependent driver genes in 1,454 solid tumors, across more than 15 cancer types, by integrative analysis of gene expression and copy number. Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28362562/ten-year-progression-free-and-overall-survival-in-patients-with-unresectable-or-metastatic-gi-stromal-tumors-long-term-analysis-of-the-european-organisation-for-research-and-treatment-of-cancer-italian-sarcoma-group-and-australasian-gastrointestinal-trials
#8
Paolo G Casali, John Zalcberg, Axel Le Cesne, Peter Reichardt, Jean-Yves Blay, Lars H Lindner, Ian R Judson, Patrick Schöffski, Serge Leyvraz, Antoine Italiano, Viktor Grünwald, Antonio Lopez Pousa, Dusan Kotasek, Stefan Sleijfer, Jan M Kerst, Piotr Rutkowski, Elena Fumagalli, Pancras Hogendoorn, Saskia Litière, Sandrine Marreaud, Winette van der Graaf, Alessandro Gronchi, Jaap Verweij
Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued...
March 31, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28334729/slug-transcription-factor-a-pro-survival-and-prognostic-factor-in-gastrointestinal-stromal-tumour
#9
Olli-Pekka Pulkka, Bengt Nilsson, Maarit Sarlomo-Rikala, Peter Reichardt, Mikael Eriksson, Kirsten Sundby Hall, Eva Wardelmann, Aki Vehtari, Heikki Joensuu, Harri Sihto
BACKGROUND: The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown. METHODS: Influence of SLUG expression on cell proliferation and viability were investigated in GIST48 and GIST882 cell lines. The association between tumour SLUG expression in immunohistochemistry and recurrence-free survival (RFS) was studied in two clinical GIST series, one with 187 patients treated with surgery alone, and another one with 313 patients treated with surgery and adjuvant imatinib...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28317407/using-molecular-diagnostic-testing-to-personalize-the-treatment-of-patients-with-gastrointestinal-stromal-tumors
#10
Amber E Bannon, Lillian R Klug, Christopher L Corless, Michael C Heinrich
The diagnosis and treatment of gastrointestinal stromal tumor (GIST) has emerged as a paradigm for modern cancer treatment ('precision medicine'), as it highlights the importance of matching molecular defects with specific therapies. Over the past two decades, the molecular classification and diagnostic work up of GIST has been radically transformed, accompanied by the development of molecular therapies for specific subgroups of GIST. This review summarizes the developments in the field of molecular diagnosis of GIST, particularly as they relate to optimizing medical therapy...
March 27, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28314314/familial-gastrointestinal-stromal-tumor-with-germline-kit-mutations-accompanying-hereditary-breast-and-ovarian-cancer-syndrome
#11
Yuki Sekido, Seiji Ohigashi, Tsuyoshi Takahashi, Naoki Hayashi, Koyu Suzuki, Seiichi Hirota
BACKGROUND: Familial gastrointestinal stromal tumor (GIST) is a rare disease with germline mutations in the c-kit gene (KIT) or platelet-derived growth factor receptor alpha gene (PDGFRA). We had encountered multiple GISTs in the stomach and small intestine during a screening of ovarian cancer for a woman with hereditary breast and ovarian cancer syndrome (HBOC) with breast cancer susceptibility gene II (BRCA2) mutations. The aim of this study was to examine this case in detail. CASE REPORT: A 65-year-old woman diagnosed with HBOC harboring BRCA2 mutations was found to have multiple tumors in the stomach and small intestine by abdominal screening...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in%C3%A2-vitro-and-in%C3%A2-vivo-study
#12
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
June 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28293832/the-mechanistic-role-of-the-calcium-activated-chloride-channel-ano1-in-tumor-growth-and-signaling
#13
Anke Bill, Larry Alex Gaither
Multiple studies have described the high expression and amplification of Anoctamin 1 (ANO1) in various cancers, including, but not limited to breast cancer, head and neck cancer, gastrointestinal stromal tumors and glioblastoma. ANO1 has been demonstrated to be critical for tumor growth in breast and head and neck cancers through its regulation of EGFR signaling and pathway modulators like MAPK and protein kinase B. However, the discovery of ANO1 as a calcium activated chloride channel came as a surprise to the field and has given rise to many questions...
March 15, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28268936/assessing-the-population-representativeness-of-colorectal-cancer-treatment-clinical-trials
#14
Zhe He, Zhiwei Chen, Thomas J George, Gloria Lipori, Bian
The generalizability (external validity) of clinical trials has long been a concern for both clinical research community as well as the general public. Results of trials that do not represent the target population may not be applicable to the broader patient population. In this study, we used a previously published metric Generalizability Index for Study Traits (GIST) to assess the population representativeness of colorectal cancer (CRC) treatment trials. Our analysis showed that the quantitative eligibility criteria of CRC trials are in general not restrictive...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28258440/comprehensive-characterization-of-genes-associated-with-the-tp53-signal-transduction-pathway-in-various-tumors
#15
Shumpei Ohnami, Keiichi Ohshima, Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Junko Saito, Akane Naruoka, Keiichi Hatakeyama, Tohru Mochizuki, Masakuni Serizawa, Sumiko Ohnami, Masatoshi Kusuhara, Ken Yamaguchi
The TP53 signal transduction pathway is an attractive target for cancer treatments. In this study, we conducted a comprehensive molecular evaluation of 907 patients with cancer in Japan to identify genomic alterations in the TP53 pathway. TP53 mutations were frequently detected in many cancers, except melanoma, thymic tumors, gastrointestinal stromal tumors, and renal cancers. The frequencies of non-synonymous single nucleotide variants (SNVs) in the TP53 family members TP63 and TP73 were relatively low, although genes with increased frequencies of SNVs were as follows: PTEN (11...
March 3, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28243730/-gastrointestinal-stromal-tumors-of-the-stomach-and-precursor-lesions
#16
E Wardelmann, W Hartmann, M Trautmann, J Sperveslage, S Elges, E Hekeler, S Huss
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract although they are much less frequent than epithelial tumors. In more than 60% of cases they occur in the stomach. Especially small lesions measuring ≤1 cm in diameter, so-called microscopic GIST can occur multifocally, frequently in the proximal stomach wall and sometimes as an incidental finding in a gastrectomy specimen resected for gastric cancer. The multicentricity of GIST alone is not proof of a metastatic behavior or a syndromal or hereditary disease...
February 27, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28240510/gastric-cancer-and-gastrointestinal-stromal-tumors-could-be-causes-of-non-helicobacter-pylori-non-nsaids-peptic-ulcers-in-thailand
#17
Pattama Kiatpapan, Ratha korn Vilaichone, Peranart Chotivitayatarakorn, Varocha Mahachai
Background and aim: H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) remain the major causes of peptic ulcer disease. Nevertheless, non- H. pylori non-NSAIDs peptic ulcers or idiopathic peptic ulcer disease (IPUD) constitute a growing problem associated with many complications. Gastric cancer and gastrointestinal stromal tumor (GIST) have also been reported as a cause of IPUD. This study was aimed to investigate prevalence and clinical characteristics of IPUD in Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings, history of H...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28227142/assessing-the-population-representativeness-of-colorectal-cancer-treatment-clinical-trials
#18
Zhe He, Zhiwei Chen, Thomas J George, Gloria Lipori, Jiang Bian, Zhe He, Zhiwei Chen, Thomas J George, Gloria Lipori, Bian, Zhiwei Chen, Zhe He, Thomas J George, Gloria Lipori
The generalizability (external validity) of clinical trials has long been a concern for both clinical research community as well as the general public. Results of trials that do not represent the target population may not be applicable to the broader patient population. In this study, we used a previously published metric Generalizability Index for Study Traits (GIST) to assess the population representativeness of colorectal cancer (CRC) treatment trials. Our analysis showed that the quantitative eligibility criteria of CRC trials are in general not restrictive...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28222971/cancer-biology-of-small-gastrointestinal-stromal-tumors-2%C3%A2-cm-what-is-the-risk-of-malignancy
#19
K Søreide
INTRODUCTION: The identification of small (<2 cm) gastrointestinal stromal tumors (GISTs) is increasingly recognized. The malignancy potential is not absent. However, data on risk is scarce. The aim was to review the existing data on perceived risk of small GISTs in population-based studies. METHODS: A combined review of small GISTs (<2 cm) in a population-based dataset compared with a systematic review of available population-based studies. RESULTS: About one in every four (27%) patient has a small GIST, of which 79% were incidental in presentation, and all had a low-risk mitoses index (<5/hpf)...
February 9, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28197362/prognostic-impact-of-the-expression-of-ncr1-and-ncr3-nk-cell-receptors-and-pd-l1-on-advanced-non-small-cell-lung-cancer
#20
Laetitia Fend, Sylvie Rusakiewicz, Julien Adam, Bérangère Bastien, Anne Caignard, Meriem Messaoudene, Christina Iribarren, Isabelle Cremer, Aurélien Marabelle, Christophe Borg, Michaela Semeraro, Luc Barraud, Jean-Marc Limacher, Alexander Eggermont, Guido Kroemer, Laurence Zitvogel
The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantified NCR1 (which codes for NKp46) and NCR3 (which codes for NKp30), as well as that of three NCR3 splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C)...
2017: Oncoimmunology
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