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Gerardo A Vitiello, Timothy G Bowler, Mengyuan Liu, Benjamin D Medina, Jennifer Q Zhang, Nesteene J Param, Jennifer K Loo, Rachel L Goldfeder, Frederic Chibon, Ferdinand Rossi, Shan Zeng, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common human sarcoma, frequently characterized by an oncogenic mutation in the KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes. We performed RNA sequencing of 75 human GIST tumors from 75 patients, comprising the largest cohort of GISTs sequenced to date, in order to discover differences in the immune infiltrates of KIT and PDGFRA-mutant GIST. Through bioinformatics, immunohistochemistry, and flow cytometry, we found that PDGFRA-mutant GISTs harbored more immune cells with increased cytolytic activity when compared to KIT-mutant GISTs...
February 14, 2019: Journal of Clinical Investigation
Welda E H Tjhoi, Kai Li, Chun-Hui Shou, Wei-Li Yang, Ji-Ren Yu
RATIONALE: The efficiency and tolerance of long-term adjuvant imatinib treatment for patient who underwent complete resection of a localized recurrent gastrointestinal stromal tumor (GIST) was unknown. PATIENT CONCERNS: A 45-year-old man underwent complete resection of an intestinal GIST in August 2001. Four years later, a giant (11 × 8 × 6 cm) recurrent GIST located in the retroperitoneum was detected. DIAGNOSIS: The recurrent tumor was positive for CD117 by immunohistochemistry...
February 2019: Medicine (Baltimore)
Hanan M Alghamdi, Samir S Amr, Mohamed A Shawarby, Salwa S Sheikh, Ahmed A Alsayyah, Ali M Alamri, Mona H Ismail, Ahmed Almarhabi, Munir A Alrefaee, Muhammad I Ahmed
OBJECTIVES: To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data. METHODS: Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning. Results: The median age of patients was 54 years  (range; 17-81 years)...
February 2019: Saudi Medical Journal
Da Meng, Richard D Carvajal
Metastatic melanoma is a heterogenous disease that has served as a model for the development of both targeted therapy and immunotherapy. KIT-mutated melanoma represents a rare subset, most commonly arising from acral, mucosal, and chronically sun-damaged skin. Additionally, KIT alterations are enriched in the triple wild-type subtype of cutaneous melanoma. Activating alterations of KIT-a transmembrane receptor tyrosine kinase important for cell development, growth, and differentiation-have been shown to be critical to oncogenesis across many tumor subtypes...
February 1, 2019: American Journal of Clinical Dermatology
Fiona H Tan, Tracy L Putoczki, Stanley S Stylli, Rodney B Luwor
Human malignancies are often the result of overexpressed and constitutively active receptor and non-receptor tyrosine kinases, which ultimately lead to the mediation of key tumor-driven pathways. Several tyrosine kinases (ie, EGFR, FGFR, PDGFR, VEGFR), are aberrantly activated in most common tumors, including leukemia, glioblastoma, gastrointestinal stromal tumors, non-small-cell lung cancer, and head and neck cancers. Iclusig™ (ponatinib, previously known as AP24534) is an orally active multi-tyrosine kinase inhibitor and is currently approved by the US Food and Drug Administration for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, specifically targeting the BCR-ABL gene mutation, T315I...
2019: OncoTargets and Therapy
Masaaki Iwatsuki, Kazuto Harada, Shiro Iwagami, Kojiro Eto, Takatsugu Ishimoto, Yoshifumi Baba, Naoya Yoshida, Jaffer A Ajani, Hideo Baba
Gastrointestinal stromal tumors (GIST) are rare and mesenchymal in origin with a yearly incidence of 10-15 cases per million people. If it is technically resectable, surgical resection is the mainstay of therapy regardless of tumor location,. Although complete (R0) resection can be achieved in up to 85% of patients with primary disease, approximately 50% of patients experience recurrence or metastases within 5 years of primary resection. Moreover, prior to 2000, the prognosis of patients with advanced, inoperable GIST was poor because the molecular mechanism had not sufficiently been elucidated, thus effective therapy was lacking...
January 2019: Annals of gastroenterological surgery
Jwa Hoon Kim, Min-Hee Ryu, Changhoon Yoo, Heejung Chae, Hana Na, Moyoul Beck, Beom Su Kim, Moon-Won Yoo, Jeong Hwan Yook, Byung Sik Kim, Ki-Hun Kim, Chan Wook Kim, Yoon-Koo Kang
The long-term effects of tyrosine kinase inhibitors (TKIs), including imatinib, and surgical intervention on advanced gastrointestinal stromal tumor (GIST) were evaluated. All 379 patients had metastatic or recurrent GIST and started 400 mg/d imatinib at the Asan Medical Center in periods 1 and 2 [2001-2007 (33.2%) and 2008-2014 (66.8%), respectively]. Men constituted 60.4%; median patient age and tumor size at the initiation of imatinib were 58.6 (14.6-85.5) years and 51 (0-324) mm, respectively, without differences between periods except for older age and less preimatinib surgery in period 2...
January 28, 2019: Cancer Medicine
Kenji Nanishi, Fumihiro Taniguchi, Aya Mizuno, Hirotaka Furuke, Sachie Tanaka, Tatsuya Kumano, Shuhei Komatsu, Kenichiro Imura, Katsumi Shimomura, Jun Ikeda, Kenichiro Takashina, Yasuhiro Shioaki, Eito Ikeda
A 67-year-old man presented with abdominal pain and fever. Many abdominal tumors were detected by enhanced computed tomography(CT). The largest tumor, measuring 20 cm, had perforated the ileum and formed an abscess. Emergency surgery was performed to remove multiple tumors in the peritoneal cavity as much as possible. Immunostaining showed c-kit and CD34 positivity, and the tumors were diagnosed as gastrointestinal stromal tumor(GIST). During postoperative imatinib therapy for the residual tumor, low-dose intermittent administration was required due to side effects, but the disease was controlled for over 91months...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Saki Kishibe, Takashi Fujimoto, Masaya Satake, Akinori Hattori, Takebumi Usui, Kentaro Yamaguchi, Shunichi Shiozawa, Kazuhiko Yoshimatsu, Takeshi Shimakawa, Takao Katsube, Toshihiro Hattori, Yoshihiko Naritaka
A 60-year-old woman was admitted for abdominal distention, abdominal pain, and anorexia. Abdominal CT showed a 30×20 cm mass with contrast effect. gastrointestinal stromal tumor(GIST) of the omentum or the mesenterium was suspected. Peritoneal nodules were also recognized. We performed palliative surgery. The tumor was considered to have originatedfrom the greater omentum andinvolvedthe marginal artery of the transverse colon. We performedpartial excision of the transverse colon andresection of the tumor. Immunohistochemically, the tumor cells were c-kit(+), CD34(+), S100(-), andDOG1(-), with 1 fission image for 50 fields of view with high magnification...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yosuke Ariyoshi, Noriaki Koizumi, Rie Yasuoka, Kenji Nakamura, Hiroshi Fujiki, Atsushi Shiozaki, Hitoshi Fujiwara, Chouhei Sakakura
A 58-year-old man was followed up for esophageal submucosal tumor at our hospital. Esophagogastroduodenoscopy showed the tumor was located on the left side of the thoracic esophagus and had gradually increased in size. Endoscopic ultrasonography revealed an 18×11.5mm hypoechoic tumor connected to the fourth layer of the esophagus and fine needle biopsy revealed c-kit(+), desmin(-)and a-SMA(-). Double-contrast barium study detected a tumor of diameter 20 mm in the middle-lower thoracic esophagus. We diagnosed an esophageal gastrointestinal stromal tumor(GIST)and performed mediastinoscope-assisted transhiatal esophagectomy with gastric tube reconstruction...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Seiji Inoue, Masaya Nakauchi, Kazuhiro Matsuo, Sayaka Amano, Ai Goto, Makoto Tomatsu, Kenichi Nakamura, Susumu Shibasaki, Kenji Kikuchi, Shinichi Kadoya, Kazuki Inaba, Yutaro Kato, Tsunekazu Hanai, Atsushi Sugioka, Ichiro Uyama
A 60-year-old male was admitted to our hospital on account of a duodenal submucosal tumor on the opposite side of Vater's papilla identified on a screening gastroduodenoscopy. The tumor was diagnosed as a duodenal gastrointestinal stromal tumor(GIST)due to positive c-kit and DOG1tests. Gastroduodenography and enhanced computed tomography showed a 50mm tumor widely invadingthe descendingportion of the duodenum close to the papilla of Vater and indicated the need for extended resection includingpancreaticoduodenectomy to achieve curation...
December 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Yanli Nie, Wenjia Sun, Zhihua Xiao, Shengwei Ye
RATIONALE: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is characterized by KIT mutations. Patientsresistant to 1st-line imatinib therapy are usually given sunitinib assecond-line treatment, which provides a median progression-free survival of 8 to 12 months. We report the 1st case of metastatic jejunum GIST with a KIT exon 11 deletion that showed complete response (CR) to sunitinib for more than 3 years. PATIENT CONCERNS: A 34-year-old man with advanced jejunum GIST was surgically treated upon initial diagnosis, and was histologically found to carry a high recurrence risk...
January 2019: Medicine (Baltimore)
Matthew L Hemming, Matthew A Lawlor, Jessica L Andersen, Timothy Hagan, Otari Chipashvili, Thomas G Scott, Chandrajit P Raut, Ewa Sicinska, Scott A Armstrong, George D Demetri, James E Bradner
Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm characterized by activating mutations in the related receptor tyrosine kinases KIT and PDGFRA. GIST relies on expression of these unamplified receptor tyrosine kinase (RTK) genes through a large enhancer domain, resulting in high expression levels of the oncogene required for tumor growth. Although kinase inhibition is an effective therapy for many GIST patients, disease progression from kinase resistance mutations is common and no other effective classes of systemic therapy exist...
January 10, 2019: Cancer Research
Riccardo Ricci, Maurizio Martini, Gloria Ravegnini, Tonia Cenci, Massimo Milione, Paola Lanza, Francesco Pierconti, Donatella Santini, Sabrina Angelini, Alberto Biondi, Fausto Rosa, Sergio Alfieri, Gennaro Clemente, Roberto Persiani, Alessandra Cassano, Maria A Pantaleo, Luigi M Larocca
BACKGROUND: Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) constitute a small KIT/PDGFRA-WT GIST subgroup featuring DNA methylation which, although pervasive, appears nevertheless not randomly distributed. Although often indolent, these tumors are mostly chemorefractory in aggressive cases. Promoter methylation-induced O6 -methylguanine DNA methyltransferase (MGMT) inactivation improves the efficacy of alkylating agents in gliomas, colorectal cancer and diffuse large B cell lymphoma...
January 7, 2019: Clinical Epigenetics
Mircea Florin Costache, Bogdan Filip, Dragoş Viorel Scripcariu, Nicolae Danilă, Viorel Scripcariu
Background: Gastrointestinal stromal tumors are some of the most common mesenchymal tumors of the gut. The aim of this study is to asses the clinical manifestation and treatment of gastric GISTs. Methodology: We performed a retrospective 5-year multicenter study conducted on a prospective collected database, which includes all the patients diagnosed with GIST in which surgery was performed. We selected all the pateients with gastric GISTs and we analyzed the clinical manifestation, treatment and prognostic factors...
November 2018: Chirurgia
Jung Lim Kim, Dae-Hee Lee, Soyeon Jeong, Bo Ram Kim, Yoo Jin Na, Seong Hye Park, Min Jee Jo, Yoon A Jeong, Sang Cheul Oh
Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR‑ABL, c‑KIT, and PDGFR kinases, and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancers. However, the possible anticancer effects of imatinib in gastric cancer have not yet been explored. The present study evaluated the in vitro effects of imatinib on gastric cancer cells and determined the molecular mechanism underlying these effects. We determined that imatinib induced mitochondria‑mediated apoptosis of gastric cancer cells by involving endoplasmic reticulum (ER) stress‑associated activation of c‑Jun NH2‑terminal kinase (JNK)...
December 19, 2018: Oncology Reports
Wei-Guang Zhang, Liang-Bi Xu, Yi-Ning Xiang, Chen-Hong Duan
BACKGROUND: Plexiform fibromyxoma is a rare, special type of mesenchymal tumor. The most common presenting symptoms are anemia, hematemesis, and hematochezia, without sex or age predilection. The reported cases have mainly occurred in the gastric antrum and pylorus region, with some cases in the duodenum. CASE SUMMARY: We report here a case of plexiform fibromyxoma in the upper segment of the jejunum, which was continuously followed up for 3 years after surgical removal...
December 6, 2018: World Journal of Clinical Cases
Daniel Paramythiotis, Anestis Karakatsanis, Diamantoula Pagkou, Petros Bangeas, Niki Mantha, Sofia Lypiridou, Antonis Michalopoulos
INTRODUCTION: Gastrointestinal schwannomas are benign, slow-growing and usually asymptomatic tumors. In some cases bleeding, epigastric pain and palpable mass may be occurring. Preoperative diagnosis is challenging due to the difficulty of differentiation from other submucosal tumors. Diagnosis is most often provided through the histology report. CASE PRESENTATION: In this study we report two cases of gastric tumors with the suspicion of a GIST preoperatively but histologically confirmed to be gastric schwannomas...
2018: International Journal of Surgery Case Reports
Bharat Rekhi
Gastrointestinal stromal tumor (GIST) constitutes the commonest mesenchymal tumor of the gastrointestinal tract, invariably immunoreactive for CD117(KIT); originates from the interstitial cells of Cajal; mostly driven by KIT or PDGFRA-activating mutations and is histopathologically characterized by spindle, cell, epithelioid, and rarely pleomorphic morphology.1 Discovered on GIST-1 (DOG1) is another useful immunohistochemical marker for diagnosing GISTs, including those lacking CD117 immunoexpression, characterized by PDGFRA mutation and epithelioid cytomorphology...
December 17, 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
Fangxi Xue, Zhaoxia Liu, Jian Xu, Xiaoguang Xu, Xingtian Chen, Feng Tian
BACKGROUND: Gastrointestinal stromal tumor (GIST) threatens the health of middle-aged and older people with high recurrence rate and low survival rate. In this study, Neferin (Nef) was hoped to control growth and migration of GIST cell line GIST-T1. METHODS: Cell viability, proliferation, apoptosis, and migration were determined by cell counting kit-8 (CCK-8) assay, bromodeoxyuridine (BrdU) assay, Annexin V-FITC/PI double staining method, and Transwell assay, respectively...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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