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Akihiro Miura, Eigo Kojima, Kouichi Tashiro, Takehiro Tajima, Makiko Matsumura, Nobuo Yanagisawa, Yoshihiro Ohno
A 67-year-old man visited our hospital with an enlarging abdominal mass several months after he had first noticed his symptoms. An elastic firm tumor was palpated on the left side of the abdomen upon physical examination. The blood test results were normal. Contrast-enhanced computed tomography of the abdomen revealed a 10-cm-diameter homogeneous low-density cystic tumor located at the dorsal portion of the gastric corpus. Enhancement of a few net-like structures was noted, but most of the lesion was not enhanced...
2018: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
M L Hemming, M C Heinrich, S Bauer, S George
Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma of the gastrointestinal tract and, in the vast majority of cases, is characterized by activating mutations in KIT or, less commonly, PDGFRA. Mutations in these type III receptor tyrosine kinases (RTKs) account for over 85% of GIST cases, and the majority of KIT primary mutations respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib. However, drug resistance develops over time, most commonly due to secondary kinase mutations...
August 8, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Pramod Nepal, Shinichiro Mori, Yoshiaki Kita, Kan Tanabe, Kenji Baba, Yasuto Uchikado, Hiroshi Kurahara, Takaaki Arigami, Masahiko Sakoda, Kosei Maemura, Shoji Natsugoe
BACKGROUND: Rectal gastrointestinal stromal tumor (GIST) is a very rare tumor of gastrointestinal tract. Surgical management of rectal GIST requires special attention for preserving of anal and urinary functions. Transanal minimal invasive surgery (TAMIS) is a well-developed minimally invasive technique for local excision of benign and early malignant rectal tumors; however, the application of TAMIS for rectal GIST is rarely and inadequately reported. We report the novel application of TAMIS for rectal GIST with considerations for anal and urinary functions...
August 11, 2018: World Journal of Surgical Oncology
Heidi M Namløs, Kjetil Boye, Skyler J Mishkin, Tale Barøy, Susanne Lorenz, Bodil Bjerkehagen, Eva W Stratford, Else Munthe, Brian A Kudlow, Ola Myklebost, Leonardo A Meza-Zepeda
Molecular analysis of circulating tumour DNA (ctDNA) has a large potential for clinical application by capturing tumour-specific aberrations through non-invasive sampling. In gastrointestinal stromal tumour (GIST), analysis of KIT and PDGFRA mutations is important for therapeutic decisions, but the invasiveness of traditional biopsies limits the possibilities for repeated sampling. Using targeted next-generation sequencing, we have analysed circulating cell-free DNA from 50 GIST patients. Tumour-specific mutations were detected in 16 of 44 plasma samples (36%) from treatment-naïve patients and in 3 of 6 (50%) patients treated with tyrosine kinase inhibitors...
August 10, 2018: Molecular Cancer Therapeutics
Kazuaki Seita, Fumihiko Yoneyama, Keiko Kimura, Yuichiro Kato, Hidehiko Otsuji, Hiroshi Kouno
A 66-year-old man was referred to our hospital after being diagnosed with a pelvic tumor. A subsequent transperineal biopsy revealed spindle cells with CD34·c-kit(+). An enhanced computed tomography scan showed a giant rectal-derived tumor in the pelvis. The tumor was pressing on the urinary bladder and the prostate, and appeared to invade the posterior wall ofthese organs. The patient was diagnosed with rectal GIST, and neoadjuvant therapy with 400mg/day imatinib was initiated. Three months later, the tumor reduction rate was at 33...
June 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Kazuya Akahoshi, Masafumi Oya, Tadashi Koga, Yuki Shiratsuchi
Gastrointestinal stromal tumors (GISTs) are the most common malignant subepithelial lesions (SELs) of the gastrointestinal tract. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Pathologically, diagnosis of a GIST relies on morphology and immunohistochemistry [KIT and/or discovered on gastrointestinal stromal tumor 1 (DOG1) is generally positive]. The prognosis of this disease is associated with the tumor size and mitotic index...
July 14, 2018: World Journal of Gastroenterology: WJG
Haohai Jiang, Weiwei Shao, Yuanjin Wang, Ronghui Xu, Linsen Zhou, Xiangming Mu
The D816X (X = V, H, Y or F) missense mutation constitutively activates c-Kit kinase in gastrointestinal stromal tumor (GIST) and has been observed to cause acquired resistance against first-line and second-line kinase inhibitors. In the present study, the allosteric mechanism of D816X-induced c-Kit conformational change is investigated at molecular level. The Asp816 residue is located at the activation loop (A-loop) of c-Kit and the mutation can eliminate a negative formal charge from the loop region by substituting the acidic asparagic acid residue with neutral valine, histidine, tyrosine or phenylalanine...
July 10, 2018: Journal of Molecular Graphics & Modelling
X Liu, K-M Chu
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. However, the development of molecular markers, especially circulating biomarkers, remains largely undone for the prognosis of GIST. We discussed the clinical-pathological characteristics of GIST and identified potential biomarkers for guidance of therapy and prognosis of GIST. Around 90% of GISTs contain mutations in KIT or PDGFRA and the remaining 10% of GISTs are wild-type. Recent studies have indicated that various DNAs and miRNAs could serve as potential biomarkers for prognosis of GIST, including KIT, PDGFRA, other DNAs (such as BRAF, SDH, SETD2 and ROR2), and microRNAs (miRNAs)...
July 12, 2018: Clinical & Translational Oncology
Kentaro Miyake, Kei Kawaguchi, Masuyo Miyake, Ming Zhao, Tasuku Kiyuna, Kentaro Igarashi, Zhiying Zhang, Takashi Murakami, Yunfeng Li, Scott D Nelson, Michael Bouvet, Irmina Elliott, Tara A Russell, Arun S Singh, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chishima, Shree Ram Singh, Itaru Endo, Fritz C Eilber, Robert M Hoffman
Gastrointestinal stromal tumor (GIST) is a refractory disease in need of novel efficacious therapy. The aim of our study was to evaluate the effectiveness of tumor-targeting Salmonella typhimurium A1-R ( S. typhimurium A1-R) using on a patient derived orthotopic xenograft (PDOX) model of imatinib-resistant GIST. The GIST was obtained from a patient with regional recurrence, and implanted in the anterior gastric wall of nude mice. The GIST PDOX mice were randomized into 3 groups of 6 mice each when the tumor volume reached 60 mm3 : G1, control group; G2, imatinib group (oral administration [p...
June 2018: Heliyon
Amitabh Thacoor
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The stomach is most commonly affected. Advances in immunopathology have identified a mutation in the c-KIT proto-oncogene, leading to the development of the tyrosine-kinase inhibitor Imatinib as targeted therapy for advanced disease. Surgery, however, remains the only curative treatment of resectable primary GIST. This review article aims at reviewing the management of primary GISTs, investigating recurrences, exploring the role of surgery in metastatic disease and looking into combined surgery and molecular therapy for GISTs...
June 2018: Journal of Gastrointestinal Oncology
Seiichi Hirota
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal (GI) tract. GISTs account for approximately 80% of the clinically relevant GI mesenchymal tumors. Although most GISTs show spindle cell morphology, 10-15% of GISTs show pure epithelioid configuration. Therefore, not only spindle cell tumors but also epithelioid cell ones developing in the GI tract are subject to the differential diagnoses of GISTs. GISTs are basically positive for KIT, a receptor tyrosine kinase (RTK) encoded by protooncogene c -kit , by immunohistochemistry, but approximately 5% of GISTs are only weakly or barely positive for KIT...
2018: Translational Gastroenterology and Hepatology
Xin Wu, Jian Li, Wentong Xu, Jing Gao, Yanyan Li, Lin Shen
AIM: To determine whether imatinib adjuvant treatment improved recurrence-free survival (RFS) in gastrointestinal stromal tumor (GIST) with intermediate risk. MATERIALS & METHODS: Patients who had undergone complete tumor resection with intermediate risk were enrolled. RESULTS: A total of 99 patients received imatinib adjuvant therapy and 93 patients only received observation. The RFS in patients who received adjuvant therapy was superior to RFS in control group (p = 0...
July 2018: Future Oncology
Yi Qian, Lei Yu, Xue-Hui Zhang, Qing-Yun Yuan-Zi, Ping Zhao, Lu-Ning Sun, Yong-Qing Wang
Platelet-derived Growth Factor Receptor (PDGFR) is one of the families of Receptor Tyrosine Kinases (RTKs), which have attracted increasing attention as a potential target of antitumor therapy in cancer. PDGFR family members consist of PDGFR-α, PDGFR-β, CSF-1R, KIT and FLT3. Tyrosine Kinase Inhibitors (TKIs) are a kind of small molecule inhibitors targeting RTKs. TKIs prevent and block vital pathways by targeting signaling molecules which are necessary for cell survival. At present, about 11 kinds of TKIs targeting PDGFR family members have been approved for the treatment of diseases like chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), renal cell carcinoma (RCC), etc...
June 28, 2018: Current Drug Metabolism
Yoshiyuki Suehara, Keisuke Akaike, Kenta Mukaihara, Aiko Kurisaki-Arakawa, Daisuke Kubota, Taketo Okubo, Hiroyuki Mitomi, Keiko Mitani, Michiko Takahashi, Midori Toda-Ishii, Youngji Kim, Yu Tanabe, Tatsuya Takagi, Takuo Hayashi, Kaoru Mogushi, Kazuo Kaneko, Takashi Yao, Tsuyoshi Saito
Our group has previously demonstrated that pfetin, encoded by the KCTD12 gene, is a strong prognostic biomarker for gastrointestinal stromal tumors (GISTs). However, the underlying mechanisms that control pfetin expression remain unknown. To elucidate the regulatory mechanisms of KCTD12 in GIST, in addition to a possible association between KCTD12 alterations and protein expression, we examined 76 patients with GISTs for KCTD12 mutations by PCR-direct sequence, and compared these results with clinicopathologic data...
June 5, 2018: Oncotarget
Akihiro Hayashi, Mirai Edano, Kazunori Maeda, Atsushi Yanagitani, Kiwamu Tanaka, Hajime Isomoto
Abdominal ultrasonography revealed a low echoic mass in the upper abdomen of a 65-year-old man. He was referred to our department, where abdominal CT revealed a tumor with a 30-mm contrast effect on the distal side of the inferior part of the duodenum. Endoscopy revealed a submucosal tumor in the same region, and ultrasonic endoscopy showed a low echoic mass with a clear boundary derived from the muscle layer. The duodenum was partially resected based on a diagnosis of suspected gastrointestinal stromal tumors (GIST), and the skin tumor was simultaneously resected...
2018: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
Lin Mei, Wei Du, Michael Idowu, Margaret von Mehren, Sosipatros A Boikos
Gastrointestinal stromal tumors (GISTs) originate from interstitial cells of Cajal and account for over 5,000 newly diagnosed cases in the United States. The discovery of activated KIT and PDGFRA mutations and introduction of imatinib revolutionized the treatment strategy and opened up the new era of target therapy for solid tumors. Although surgery remains the primary modality of treatment for curative purpose, almost half of the patients experienced disease recurrence. Tailoring (neo)-adjuvant treatment with imatinib is ongoing to meet the need for an effective therapy...
2018: Frontiers in Oncology
Matthew L Hemming, Matthew A Lawlor, Rhamy Zeid, Tom Lesluyes, Jonathan A Fletcher, Chandrajit P Raut, Ewa T Sicinska, Frédéric Chibon, Scott A Armstrong, George D Demetri, James E Bradner
Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease...
June 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Valeria Pellegrino, Luisa V Muscatello, Giuseppe Sarli, Giancarlo Avallone
Tissue microarray (TMA) is a time- and cost-saving technique allowing the simultaneous immunohistochemical evaluation of multiple tissue samples. The aim of this study was to assess the efficacy of TMA at classifying canine gastrointestinal spindle cell tumors as gastrointestinal stromal tumor (GIST), smooth muscle tumor (SMT), and non-GIST/non-SMT based on the expression of α-smooth muscle actin (α-SMA), desmin, and CD117. Thirty-four cases were investigated on TMAs, sampling 2 cores each. Immunohistochemistry was performed on TMAs and full sections, and the results were compared...
January 1, 2018: Veterinary Pathology
Tinya Abrams, Anu Connor, Christie Fanton, Steven B Cohen, Thomas Huber, Kathy Miller, E Erica Hong, Xiaohong Niu, Janine Kline, Marjorie Ison-Dugenny, Sarah Harris, Dana Walker, Klaus Krauser, Francesco Galimi, Zhen Wang, Majid Ghoddusi, Keith Mansfield, Si Tuen Lee-Hoeflich, Jocelyn Holash, Nancy Pryer, William Kluwe, Seth A Ettenberg, William R Sellers, Emma Lees, Paul Kwon, Judith A Abraham, Siew C Schleyer
Purpose: c-KIT overexpression is well recognized in cancers such as gastrointestinal stromal tumors (GIST), small cell lung cancer (SCLC), melanoma, non-small cell lung cancer (NSCLC), and acute myelogenous leukemia (AML). Treatment with the small-molecule inhibitors imatinib, sunitinib, and regorafenib resulted in resistance (c-KIT mutant tumors) or limited activity (c-KIT wild-type tumors). We selected an anti-c-KIT ADC approach to evaluate the anticancer activity in multiple disease models. Experimental Design: A humanized anti-c-KIT antibody LMJ729 was conjugated to the microtubule destabilizing maytansinoid, DM1, via a noncleavable linker (SMCC)...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Juan Manuel Sanchez-Hidalgo, Manuel Duran-Martinez, Rafael Molero-Payan, Sebastian Rufian-Peña, Alvaro Arjona-Sanchez, Angela Casado-Adam, Antonio Cosano-Alvarez, Javier Briceño-Delgado
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs (> 95%) are positive for the KIT protein (CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment...
May 14, 2018: World Journal of Gastroenterology: WJG
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