Search results for "GASTROINTESTINAL STROMAL TUMORS"

GIST: Particular aspects related to cell cultures, xenografts, and cytogenetics

2006

In less than half a decade, gastrointestinal stromal tumors (GIST) have emerged from historical anonymity to become a model of kinase-targeted therapies. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT or PDGFRA tyrosine kinase genes, and such mutations have predictive and prognostic value. In this regard, the in vitro and in vivo models have provided valuable tools for understanding the molecular pathology of this interesting neoplasm. This review charts particular aspects in the field of cell cultures and tumor xenografts in nude mice in GIST and their implication in the establishment of appropriate models for discovering and testing therapy. The cytogenetic featu…

1535P Exploring the dynamic crosstalk between immune system and genetics in a cohort of 116 completely resected gastrointestinal stromal tumors (GIST…

2021

German Survey on EUS-Guided Diagnosis and Management of Gastrointestinal Stromal Tumors (GISTs) - Evidence or "Gut-Feeling"?

2015

To examine practice patterns of endosonographers in diagnosing and managing gastrointestinal stromal tumors (GISTs) in Germany.A modified published survey (Ha et al., Gastrointest Endosc 2009) was sent to endosonographic ultrasound (EUS) customers in Germany. The survey was also publicized on the homepage of an EUS interest group. To avoid duplicate opinions, participants were asked to return one survey per institution.142 centers of roughly 850 German EUS centers responded. 25 % were from University hospitals and 74 % from community hospitals. 61 % performed 2 EUS scans for suspected subepithelial lesions/week. Although 97 % of respondents believed that tissue acquisition with CD117 immuno…

Design of antitumor drugs targeting c-kit receptor by a new mixed ligand-structure based method

2020

An important challenge, in the medicinal chemistry field, is the research of novel forceful drugs to overcome tumor-acquired resistance. The c-Kit tyrosine kinase receptor (TKR) represents a suitable target for the carcinogenesis control of gastro-intestinal stromal (GIST), leukemia, and mastocytosis tumors; nevertheless, several hotspot mutations of the protein limit the efficacy of a few clinical administered TKRs inhibitors. In this study, a new in silico protocol based on ligand and structure-based combined method is proposed, with the aim to identify a set of new c-Kit inhibitors able to complex c-Kit mutated proteins. A recent and freely available web-server DRUDIT is used for the lig…

Imaging of Gastrointestinal Stromal Tumors: From Diagnosis to Evaluation of Therapeutic Response

2016

Once considered an obscure tumor entity with poor prognosis, gastrointestinal stromal tumors (GISTs) are nowadays recognized as the most common mesenchymal tumors of the alimentary tract. GISTs differ from other mesenchymal neoplasms at pathology since 90% of them exhibit strong immunohistochemical staining for KIT, a tyrosinase kinase growth factor receptor. In the early 2000s, the ability of imatinib mesylate, a tyrosine kinase inhibitor, to inhibit KIT established a new paradigm for cancer treatment. A reduction in lesion size may not be observed or may appear many months after therapy; thus, tumor response criteria alternative to the Response Evaluation Criteria in Solid Tumors were dev…

Predictive Factors of Response to Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs): A Multi-Institutional Study

2019

Imatinib 400 mg is the standard of care for medical treatment of advanced GISTs. In the majority of cases, however, GISTs eventually develop resistance to imatinib. The optimal second line treatment has not been established yet and imatinib dose escalation (800 mg) or sunitinib represent two feasible options. The objective of this retrospective, multi-institutional, study is to analyze the validity of several parameters as possible predictive factors of response to sunitinib after imatinib failure. We reviewed 128 metastatic GISTs treated with sunitinib between January 2007 to June 2017. Primary tumour site, metastatic site, c-KIT/PDGFR-α mutational status, PET-FDG status and type…

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestin…

2021

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase ( KIT) exon 11 PV were included in the study. We analyzed the t…

Into the wild of long non-coding RNA in gastrointestinal stromal tumors (GISTs) to explore new prognostic/predictive biomarkers

2015

Background: Long Non-coding RNAs (lncRNA) are emerging as essential regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies have described lncRNAs alterations in patients with solid tumors. In particular, in Gastrointestinal Stromal Tumors (GIST), upregulation of HOTAIR has been associated with aggressiveness, metastasis, and poor patients’ survival. In order to gain more detailed insight on the molecular role of lncRNAs in GIST, we analyzed in vivo the expression levels of lncRNAs H19 and MALAT1 in surgically resected patients. Material and Methods: The expression of the lnc-RNAs H19 and MALAT1 was evaluat…

Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis

2015

We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line. All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits. 64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7–10.9) and 5 months (95% CI 3.6–6.7) respectively (P = 0.012). No difference wa…

Cardiovascular Toxicity in Cancer Patients Treated with Tyrosine Kinase Inhibitors: A Real-World Single-Center Experience

2019

<b><i>Background:</i></b> Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. <b><i>Methods:</i></b> A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with…