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https://www.readbyqxmd.com/read/29467128/macrophages-and-cd8-t-cells-mediate-the-anti-tumor-efficacy-of-combined-cd40-ligation-and-imatinib-therapy-in-gastrointestinal-stromal-tumors
#1
Jennifer Q Zhang, Shan Zeng, Gerardo A Vitiello, Adrian M Seifert, Benjamin D Medina, Michael J Beckman, Jennifer Loo, Juan Santamaria-Barria, Joanna H Maltbaek, Nesteene J Param, John A Moral, Julia N Zhao, Vinod Balachandran, Ferdinand Rossi, Cristina R Antonescu, Ronald P DeMatteo
Tyrosine kinase inhibition of gastrointestinal stromal tumors (GIST) is effective but typically culminates in resistance and is rarely curative. Immunotherapy has potential application to GIST, as we previously showed that T-cell checkpoint blockade increases the antitumor effects of imatinib. Here, we showed that ligation of CD40 using an agonistic antibody (anti-CD40) activated tumor-associated macrophages (TAMs) in vivo in a knock-in mouse model of GIST harboring a germline mutation in Kit exon 11. Activated TAMs had greater TNF production and NFkappaB signaling and directly inhibited tumor cells in vitro...
February 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29451912/expression-of-cell-cycle-regulators-and-frequency-of-tp53-mutations-in-high-risk-gastrointestinal-stromal-tumors-prior-to-adjuvant-imatinib-treatment
#2
Michaela Angelika Ihle, Sebastian Huss, Wiebke Jeske, Wolfgang Hartmann, Sabine Merkelbach-Bruse, Hans-Ulrich Schildhaus, Reinhard Büttner, Harri Sihto, Kirsten Sundby Hall, Mikael Eriksson, Peter Reichardt, Heikki Joensuu, Eva Wardelmann
Despite of multitude investigations no reliable prognostic immunohistochemical biomarkers in GIST have been established so far with added value to predict the recurrence risk of high risk GIST besides mitotic count, primary location and size. In this study, we analyzed the prognostic relevance of eight cell cycle and apoptosis modulators and of TP53 mutations for prognosis in GIST with high risk of recurrence prior to adjuvant treatment with imatinib. In total, 400 patients with high risk for GIST recurrence were randomly assigned for adjuvant imatinib either for one or for three years following laparotomy...
2018: PloS One
https://www.readbyqxmd.com/read/29451118/a-spatial-memory-signal-shows-that-the-parietal-cortex-has-access-to-a-craniotopic-representation-of-space
#3
Mulugeta Semework, Sara C Steenrod, Michael E Goldberg
Humans effortlessly establish a gist-like memory of their environment whenever they enter a new place, a memory that can guide action even in the absence of vision. Neurons in the lateral intraparietal area (LIP) of the monkey exhibit a form of this environmental memory. These neurons respond when a monkey makes a saccade that brings the spatial location of a stimulus that appeared on a number of prior trials, but not on the present trial, into their receptive fields (RFs). The stimulus need never have appeared in the neuron's RF...
February 16, 2018: ELife
https://www.readbyqxmd.com/read/29449894/personalization-of-regorafenib-treatment-in-metastatic-gastrointestinal-stromal-tumours-in-real-life-clinical-practice
#4
Margherita Nannini, Maria Concetta Nigro, Bruno Vincenzi, Elena Fumagalli, Giovanni Grignani, Lorenzo D'Ambrosio, Giuseppe Badalamenti, Lorena Incorvaia, Raffaella Bracci, Silvia Gasperoni, Maristella Saponara, Lidia Gatto, Valentina Indio, Annalisa Astolfi, Valerio Di Scioscio, Paolo G Casali, Giuseppe Tonini, Massimo Aglietta, Antonio Russo, Guido Biasco, Maria A Pantaleo
Background: Regorafenib (REG) has now been approved as the standard third-line therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the recommended dose and schedule of 160 mg once daily for the first 3 weeks of each 4-week cycle. However, it has a relevant toxicity profile that mainly occurs within the first cycles of therapy, and dose and schedule adjustments are often required to reduce the frequency or severity of adverse events and to avoid early treatment discontinuation...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29448300/identification-of-preoperative-factors-associated-with-outcomes-following-surgical-management-of-intra-abdominal-recurrent-or-metastatic-gist-following-neoadjuvant-tyrosine-kinase-inhibitor-therapy
#5
Christina L Roland, Brian K Bednarski, Kelsey Watson, Keila E Torres, Janice N Cormier, Wei-Lien Wang, Alexander J Lazar, Neeta Somaiah, Kelly K Hunt, Barry W Feig
BACKGROUND: The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy. METHODS: We identified 107 patients with metastatic or recurrent GIST treated with TKIs and surgical resection (2002-2012). Patients that underwent palliative or incomplete resection were excluded...
February 15, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29443783/giant-gist-of-the-stomach-a-successful-case-of-safe-resection-with-preoperative-simulation-using-three-dimensional-ct-angiography-case-report
#6
Kentaro Matsuo, Masaya Inoue, Yasutsugu Shirai, Tatsuki Kataoka, Shuji Kagota, Kohei Taniguchi, Sang-Woong Lee, Kazuhisa Uchiyama
RATIONALE: We report a very rare case of safely resectable giant gastrointestinal stromal tumor (GIST) with preoperative three-dimensional computed tomography (3D-CT) angiography in spite of no neoadjuvant treatment. PATIENT'S CONCERN: A 71-year-old woman presented to our hospital with an abdominal giant tumor. As this giant tumor could not be accurately diagnosed by preoperative investigation, we had to perform her surgical treatment without neoadjuvant treatment...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29443772/primary-leiomyosarcoma-in-the-colon-a-case-report
#7
Jing Yang
RATIONALE: Leiomyosarcoma (LMS) is a common type of soft tissue sarcoma. Primary colonic LMS in general is a very rare entity, accounting for 1% to 2% of gastrointestinal malignancies. PATIENT CONCERNS: We report a case of 55-year-old female who presented with a sudden onset of sharp right lower quadrant abdominal pain. Electronic colonoscopy showed a normal lumen. However, an abdominal computed tomography scan revealed a mass of soft tissue attenuation inseparable from the ascending colon which appeared as a gastrointestinal stromal tumor (GIST)...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29441371/gastrointestinal-stromal-tumor-of-the-esophagus-current-issues-of-diagnosis-surgery-and-drug-therapy
#8
REVIEW
Jun Hihara, Hidenori Mukaida, Naoki Hirabayashi
Gastrointestinal stromal tumors (GISTs) often arise in the stomach and small intestine, while esophageal GISTs are rare. Due to their rarity, clinicopathological data on esophageal GISTs are extremely limited, and this results in a lack of clear recommendations concerning optimal surgical management for esophageal GISTs. It is difficult to distinguish esophageal GIST from leiomyoma, the most frequent esophageal mesenchymal tumor, prior to resection, because the two types of tumors appear similar on computed tomography (CT), endoscopic ultrasound (EUS), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29441368/neoadjuvant-therapy-for-gastrointestinal-stromal-tumor
#9
REVIEW
Takashi Ishikawa, Tatsuo Kanda, Hitoshi Kameyama, Toshifumi Wakai
Molecular-targeting therapy using tyrosine kinase inhibitor imatinib mesylate is effective for metastasis/recurrent gastrointestinal stromal tumors (GISTs). Likewise, imatinib would be effective in the neoadjuvant therapy for high-risk GIST. Neoadjuvant therapy may have the potential to increase the complete resection rate and to avoid the surgical rupture by decreasing the tumor size. Thereby, it is expected that improvement of recurrence rate and survival rate can be obtained by neoadjuvant therapy. Neoadjuvant therapy is also expected to be favored from the viewpoint of organ/function preservation by tumor shrinkage...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29435684/recurrence-free-survival-after-resection-of-gastric-gastrointestinal-stromal-tumors-classified-according-to-a-strict-definition-of-tumor-rupture-a-population-based-study
#10
Toto Hølmebakk, Ivar Hompland, Bodil Bjerkehagen, Stephan Stoldt, Øyvind Sverre Bruland, Kirsten Sundby Hall, Kjetil Boye
BACKGROUND: In gastrointestinal stromal tumors (GISTs), rupture is a high-risk feature and an indication for adjuvant treatment; however, the independent impact of rupture on prognosis is uncertain and the term is inconsistently defined. In the present study, a previously proposed definition of 'tumor rupture' was applied on a population-based cohort of gastric GISTs. METHODS: Patients undergoing surgery for non-metastatic gastric GISTs from 2000 to 2015 were identified in the regional sarcoma database of Oslo University Hospital...
February 12, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29435627/wide-surgical-margin-improves-the-outcome-for-patients-with-gastrointestinal-stromal-tumors-gists
#11
Jan Åhlén, Fredrik Karlsson, Johan Wejde, Inga-Lena Nilsson, Catharina Larsson, Robert Bränström
BACKGROUND: Surgical resection is still the main treatment for gastrointestinal stromal tumor (GIST), and R0 excision, regardless of surgical margins, is considered sufficient. METHODS: A cohort of 79 consecutive GIST cases treated at the Karolinska University Hospital, who were without metastasis at diagnosis and who had not received any pre-or postoperative treatment with tyrosine kinase inhibitors, was included. Surgical margins were evaluated at the time of surgery and classified as wide, marginal or intralesional...
February 12, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29434135/multiple-synchronous-sporadic-gastrointestinal-stromal-tumors-in-the-stomach-and-jejunum
#12
Mami Tokunaga, Sohachi Nanjo, Hiroki Yoshita, Haruka Fujinami, Tohru Watanabe, Yoko Ishii, Saito Kobayashi, Momoko Akashi, Hiroaki Takagi, Hiroshi Mihara, Shinya Kajiura, Takayuki Ando, Isaya Hashimoto, Shozo Hojo, Tomoyuki Okumura, Toshiro Sugiyama
A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins...
February 9, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29433465/strengthening-health-data-on-a-rare-and-heterogeneous-disease-sarcoma-incidence-and-histological-subtypes-in-germany
#13
Meike Ressing, Eva Wardelmann, Peter Hohenberger, Jens Jakob, Bernd Kasper, Katharina Emrich, Andrea Eberle, Maria Blettner, Sylke Ruth Zeissig
BACKGROUND: The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries. METHODS: Pooled data from the German Centre for Cancer Registry Data with a primary diagnosis occurring in 2013 were used...
February 12, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29431674/what-s-the-fox-got-to-do-with-the-kitten-regulating-the-lineage-specific-transcriptional-landscape-in-gist
#14
Donna M Lee, Anette Duensing
Transcriptional regulation of the KIT receptor tyrosine kinase, a master regulator in gastrointestinal stromal tumors (GIST) and their precursors, the interstitial cells of Cajal (ICC), is part of a positive feedback loop involving the transcription factor ETV1. A new study now shows that the forkhead box (FOX) family transcription factor FOXF1 not only is an upstream regulator of ETV1 and hence ICC/GIST lineage-specific gene transcription, but also functions as lineage-specific pioneer factor with an active role in chromatin rearrangement to facilitate ETV1 binding and transcriptional activity...
February 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431007/author-accepted-manuscript-associative-strength-or-gist-extraction-which-matters-when-drm-lists-have-two-critical-lures
#15
Helena M Oliveira, Pedro B Albuquerque, Magda Saraiva
No abstract text is available yet for this article.
January 1, 2018: Quarterly Journal of Experimental Psychology: QJEP
https://www.readbyqxmd.com/read/29423012/ccdc26-knockdown-enhances-resistance-of-gastrointestinal-stromal-tumor-cells-to-imatinib-by-interacting-with-c-kit
#16
Ke Cao, Minhuan Li, Ji Miao, Xiaofeng Lu, Xing Kang, Hao Zhu, Shangce Du, Xue Li, Qian Zhang, Wenxian Guan, Ying Dong, Xuefeng Xia
Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are involved in diseases such as cancer. However, little is known about the role of lncRNAs in gastrointestinal stromal tumors (GIST). In the present study, we explored the biological function of the lncRNA coiled-coil domain-containing 26 (CCDC26) in imatinib resistance of GIST. We found that human GIST-882 cells with lower CCDC26 expression were less sensitive to imatinib compared with GIST-T1 cells with higher CCDC26 expression. CCDC26 expression decreased in a time-dependent manner in the presence of imatinib...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29422251/systematic-review-of-current-prognostication-systems-for-primary-gastrointestinal-stromal-tumors
#17
REVIEW
Chun Yuet Khoo, Xun Chai, Richard Quek, Melissa C C Teo, Brian K P Goh
BACKGROUND: The advent of tyrosine kinase inhibitors as adjuvant therapy has revolutionized the management of GIST and emphasized the need for accurate prognostication systems. Numerous prognostication systems have been proposed for GIST but at present it remains unknown which system is superior. The present systematic review aims to summarize current prognostication systems for primary treatment-naive GIST. METHODS: A literature review of the Pubmed and Embase databases was performed to identify all published articles in English, from the 1st January 2002 to 28th Feb 2017, reporting on clinical prognostication systems of GIST...
January 9, 2018: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29420824/differentiating-true-and-false-schematic-memories-in-older-adults
#18
Christina E Webb, Nancy A Dennis
Objective: While schemas aid memory for schematically related information, the gist induced by the schema can also lead to high rates of false memories, especially in older adults. The neural mechanisms that support and differentiate true and false memories in aging are not well understood. The current study sought to clarify this, using a novel scene paradigm to investigate the role of schemas on true and false memories in older adults. Methods: Healthy older adults encoded schematic scenes (e...
February 6, 2018: Journals of Gerontology. Series B, Psychological Sciences and Social Sciences
https://www.readbyqxmd.com/read/29415160/genital-autoinoculation-with-vaccinia-a-look-at-two-cases
#19
Julie R Whittington, Nanette L Rollene, Richard S Gist
Introduction: Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. Materials and Methods: We report two unusual cases of genital autoinoculation following smallpox vaccination. Results: Both patients' lesions resolved without sequelae within 20 d. Conclusions: We advocate for thorough education on this potential vaccination adverse event...
February 5, 2018: Military Medicine
https://www.readbyqxmd.com/read/29413424/gastrointestinal-stromal-tumors-the-gist-of-precision-medicine
#20
REVIEW
Lin Mei, Steven C Smith, Anthony C Faber, Jonathan Trent, Steven R Grossman, Constantine A Stratakis, Sosipatros A Boikos
The discovery of activated KIT mutations in gastrointestinal (GI) stromal tumors (GISTs) in 1998 triggered a sea change in our understanding of these tumors and has ushered in a new paradigm for the use of molecular genetic diagnostics to guide targeted therapies. KIT and PDGFRA mutations account for 85-90% of GISTs; subsequent genetic studies have led to the identification of mutation/epimutation of additional genes, including the succinate dehydrogenase (SDH) subunit A, B, C, and D genes. This review focuses on integrating findings from clinicopathologic, genetic, and epigenetic studies, which classify GISTs into two distinct clusters: an SDH-competent group and an SDH-deficient group...
January 2018: Trends in Cancer
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