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https://www.readbyqxmd.com/read/28334729/slug-transcription-factor-a-pro-survival-and-prognostic-factor-in-gastrointestinal-stromal-tumour
#1
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
#2
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 20, 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
#3
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-vitro-and-in-vivo-study
#4
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...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28293832/the-mechanistic-role-of-the-calcium-activated-chloride-channel-ano1-in-tumor-growth-and-signaling
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28192400/oncogenic-signaling-by-kit-tyrosine-kinase-occurs-selectively-on-the-golgi-apparatus-in-gastrointestinal-stromal-tumors
#13
Y Obata, K Horikawa, T Takahashi, Y Akieda, M Tsujimoto, J A Fletcher, H Esumi, T Nishida, R Abe
Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM)...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#14
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28185561/optimized-pipeline-of-mutect-and-gatk-tools-to-improve-the-detection-of-somatic-single-nucleotide-polymorphisms-in-whole-exome-sequencing-data
#15
Ítalo Faria do Valle, Enrico Giampieri, Giorgia Simonetti, Antonella Padella, Marco Manfrini, Anna Ferrari, Cristina Papayannidis, Isabella Zironi, Marianna Garonzi, Simona Bernardi, Massimo Delledonne, Giovanni Martinelli, Daniel Remondini, Gastone Castellani
BACKGROUND: Detecting somatic mutations in whole exome sequencing data of cancer samples has become a popular approach for profiling cancer development, progression and chemotherapy resistance. Several studies have proposed software packages, filters and parametrizations. However, many research groups reported low concordance among different methods. We aimed to develop a pipeline which detects a wide range of single nucleotide mutations with high validation rates. We combined two standard tools - Genome Analysis Toolkit (GATK) and MuTect - to create the GATK-LODN method...
November 8, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28163271/intestinal-gastrointestinal-stromal-tumor-in-a-cat
#16
Akihisa Suwa, Tetsuya Shimoda
A 12-year-old, 3.6-kg, spayed female domestic shorthaired cat had a 2-month history of anorexia and weight loss. Abdominal ultrasonography and computed tomography revealed an exophytic mass originating from the jejunum with very poor central and poor peripheral contrast enhancement. On day 14, surgical resection of the jejunum and mass with 5-cm margins and an end-to-end anastomosis were performed. Histopathological examination revealed the mass was a transmural, invasive cancer showing exophytic growth and originating from the small intestinal muscle layer...
February 4, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28144126/transanal-endoscopic-operation-for-benign-rectal-lesions-and-t1-carcinoma
#17
Mathieu D'Hondt, Emi Yoshihara, Lieven Dedrye, Koen Vindevoghel, Frederiek Nuytens, Hans Pottel
BACKGROUND AND OBJECTIVES: Transanal endoscopic operation (TEO) is a minimally invasive technique used for local excision of benign and selected malignant rectal lesions. The purpose of this study was to investigate the feasibility, safety, and oncological outcomes of the procedure and to report the experience in 3 centers. METHODS: Retrospective review of a prospectively collected database was performed of all patients with benign lesions or ≤cT1N0 rectal cancer who underwent TEO with curative intent at 3 Belgian centers (2012 through 2014)...
January 2017: JSLS: Journal of the Society of Laparoendoscopic Surgeons
https://www.readbyqxmd.com/read/28133332/-multidisciplinary-treatment-for-high-risk-gist-of-the-stomach
#18
Tomo Ishida, Shigeyuki Tamura, Atsushi Takeno, Kohei Murakami, Yohei Nose, Ryota Mori, Yasuo Oneda, Ryuichi Kuwahara, Takuya Sakamoto, Atsushi Naito, Yoshiteru Katsura, Yoshiaki Ohmura, Yoshinori Kagawa, Yutaka Takeda, Takeshi Kato
A 59-year-old man underwent total gastrectomy(with D2 dissection)and cholecystectomy for gastric cancer and a submucosal tumor of the stomach. The specimen was immunohistochemically positive for c-kit, the Ki-67 label index was 10%, and the mitotic count was 20/HPF. Finally, the patient was diagnosed with high-risk gastrointestinal stromal cancer with normal type gastric cancer. After discharge from hospital, we started administration of TS-1 as adjuvant therapy for the gastric cancer. As multiple recurrences of the GIST in the abdomen developed, the patient underwent 3 radical local resections...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133239/-a-case-of-small-intestinal-gastrointestinal-stromal-tumor-gist-with-synchronous-colonic-cancer-and-gastric-cancer-at-a-different-time
#19
Yukika Tsukamoto, Hisami Oshima, Takashi Katsumori, Hiromitsu Hamaguchi, Shinichi Yamamoto, Tomohiro Iwanaga, Susumu Ohkawara
The patient was a 70-year-old woman with a gastrointestinalstromaltumor (GIST)of the small intestine and synchronous colonic cancer, who underwent laparoscopic right colectomy and resection of the small intestine. We started imatinib therapy because GIST belongs to a high-risk group, according to the modified Fletcher classification. Gastric cancer was diagnosed 2 years after the start of imatinib therapy. Only 4 of the 12 GIST cases seen at our institution over the last 5 years were complicated by another cancer...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28098915/somatic-mutational-spectrum-analysis-in-a-prospective-series-of-104-gastrointestinal-stromal-tumors
#20
David Guenat, Olivier Deroo, Sandrine Magnin, Loïc Chaigneau, Franck Monnien, Christophe Borg, Christiane Mougin, Jean-François Emile, Jean-Luc Prétet
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis. All patients with GISTs diagnosed at the University Hospital of Besançon between August 2005 and October 2014 were prospectively included in the present study...
January 17, 2017: Oncology Reports
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