scholarly journals Gastrointestinalni tumor zeluca (GIST) kao uzrok masivnog krvarenja iz gornjih partija digestivnog trakta

2007 ◽  
Vol 54 (1) ◽  
pp. 169-171 ◽  
Author(s):  
V.R. Djukic ◽  
A.R. Karamarkovic ◽  
S. Mijatovic ◽  
M. Micev ◽  
V.M. Bumbasirevic ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Response To Treatment ◽  
Gastric Gist ◽  
Adjuvant Imatinib ◽  
Mesenchymal Tumors ◽  
Promising Treatment ◽  
Histopathology Examination

Gastrointestinal stromal tumors GIST are rare mesenchymal tumors of the gastrointestinal tract characterized by expression of a receptor that activates tyrosine kinase called C- kit. Since malignant GIST has an extremely poor prognosis even after surgical resection. The development of a tyrosine kinase inhibitor, STI571/imatinib mesylate/Gleevec, Glivec which inhibits the BCR-ABL, PDGF-R alpha, and C-Kit receptors, has changed the management of unrespectable malignant GIST and has improved the survival of patients with metastaic disease. We report a 32 year old male patient with subcardiale gastric GIST and massive gastrointestinale bleeding. The patient underwent total gastrectomy, D2 lymphadenestomy, distal pancreatectomy and splenectomy on 02.02. 2004. Histopathology examination of the primary tumor revealed a strong C-Kit expression and CD 34 +++, Ki67 20 and so called "Pure GIST" was approved Liver metastasis was detected on ultrasound and CT 12 months later and segmentectomy S7 was performed on 23.03.2005. Postoperative course was uneventful. HP examination - malignant 35 x 30 mm sarcoma like tumor of mesenchymal origin. The patient received adjuvant imatinib -mesylate Gleevec Novartis Pharma Basel 400 mg a day. The initial complete response to treatment continued to 24 months postoperatively Imatinib is a recent and very promising treatment extirpation remains the only curative treatment of malignant GIST as evidenced by our patient.

Molecular Targeting of Platelet-Derived Growth Factor B by Imatinib Mesylate in a Patient With Metastatic Dermatofibrosarcoma Protuberans

2002 ◽  
Vol 20 (17) ◽  
pp. 3586-3591 ◽  
Author(s):  
Brian P. Rubin ◽  
Scott M. Schuetze ◽  
Janet F. Eary ◽  
Thomas H. Norwood ◽  
Sohail Mirza ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Dermatofibrosarcoma Protuberans ◽  
Response To Therapy ◽  
Platelet Derived Growth Factor ◽  
Response To Treatment ◽  
Resected Specimen ◽  
Factor B

PURPOSE: Dermatofibrosarcoma protuberans is caused by activation of the platelet-derived growth factor B (PDGFB) receptor, a transmembrane tyrosine kinase. We investigated the response of dermatofibrosarcoma protuberans to the tyrosine kinase inhibitor imatinib mesylate. PATIENTS AND METHODS: A patient with unresectable, metastatic dermatofibrosarcoma protuberans received imatinib mesylate (400 mg bid). Response to therapy was assessed by [18F]fluorodeoxyglucose (FDG) positron emission tomography, magnetic resonance imaging, and histopathologic and immunohistochemical evaluation. RESULTS: The patient was treated for 4 months with imatinib mesylate. The hypermetabolic uptake of FDG fell to background levels within 2 weeks of treatment, and the tumor volume shrank by over 75% during the 4 months of therapy, allowing for resection of the mass. There was no residual viable tumor in the resected specimen, indicating a complete histologic response to treatment with imatinib mesylate. CONCLUSION: Imatinib mesylate is highly active in dermatofibrosarcoma protuberans. The dramatic response seen in this patient demonstrates that inhibition of PDGFB receptor tyrosine kinase activity can significantly impact viability of at least one type of solid tumor.

Relationship between Clinical/Hematological Response and Increase of Plamacells in the Bone Marrow of Patients with Chronic Myelogenous Leukemia Imatinib Mesylate Treatment (631).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4552-4552
Author(s):  
Alessandro Poggi ◽  
Ivana Pierri ◽  
Silvia Catellani ◽  
Francesca Olcese ◽  
Antonella Marasco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
B Lymphocytes ◽  
Chronic Myelogenous Leukemia ◽  
Peripheral Blood ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Response To Treatment ◽  
Imatinib Treatment

Abstract Tyrosine kinase inhibitors, such as imatinib mesylate (Gleevec, Novartis, formerly known as STI571) are the first line treatment of Chronic Myelogenous Leukemia (CML) and of a rare form of gastroenteric stromal cancer. It has been recently reported that in the latter case, tumor cells are refractory to imatinib antiproliferative effect in vitro and the response to the drug in vivo is due to immunocompetent cells, able to produce cytokines with antineoplastic activity. In this study, 20 CML patients, prior and during treatment with imatinib mesylate, underwent bone marrow (BM) aspirates every 6 months, including: morphologic and phenotypic analysis, cytogenetic and biomolecular evaluation, compared to peripheral blood. Plasma from BM and peripheral blood was also recovered for cytokyne-chemokine dosage. We report that in 12 out of 20 CML patients a significant increase in the percentage of BM lymphoplasmocytoid cells was observed upon treatment with imatinib mesylate, with >10% (range 10–16%) of CD20+CD126+cells. Among this population, two third of cells coexpressed IgM and one third was IgD+, while a smaller fraction of IgM+CD126+CD20– (3–4%) or IgD+CD126+CD20- (2–3%) cells was also found. The lasting 8 patients had<5% of CD20 +CD126+ lymphocytes (range2–4%), 2/3 coexpressing IgM and 1/3 coexpressing IgD. All patients with increased number of CD126+ B lymphocytes underwent hematologic remission, 7 of them with complete molecular and cytogenetic remission. On the other hand, among the patients with low or undetectable CD20+CD126+cells, only 4 underwent hemathological remission and none of them displayed stable cytogenetyc and molecular remission. In two patients relapsed after six months of treatment, the fraction of BM CD20+CD126+ lymphocytes decreased from 16% and 11% to 7 and 5%, respectively, with undetectable IgM+ CD126+CD20- or IgD+ CD126+CD20- cells. These data suggest that this population of lymphoplasmocytoid B cells depends on or contribute to the pharmacological response; by the way, this phenomenon might help in monitoring the outcome of disease and the response to treatment. To check this item and understand the biochemical mechanisms substaining the observed increase in BM lymphoplasmocitoid cells on imatinib treatment, we wonder if the production of cytokines able to induce B lymphocytes differentiation, such as interleukin (IL)-4, IL-6 (whose receptor is CD126), IL-3, IL10 or IL-21 was affected by imatinib administration. To this aim, both soluble cytokines (by ELISPOT) and their mRNA (by real time polymerase chain reaction) were evaluated in the BM of these patients: moreover, the expression of MCP-1, SDF-1, IP-10 and IL-8 were also measured, to verify whether the increse in BM CD20+ CD126+ lymphocytes was due to a redistribution rather than to “in situ” differentiation. Preliminary results seem to indicate that the latter hypothesis is unlikely; in addition, when CD20+ CD126+ were increased in the BM, they also raised in the peripheral blood. These immunological events might have a role in the response to tyrosine kinase inhibitor and need further investigations.

scholarly journals Anorectal Gastrointestinal Stromal Tumor: A Case Report and Literature Review

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Sanjeev Singhal ◽  
Anu Singhal ◽  
Rahul Tugnait ◽  
Vineet Varghese ◽  
Bishwanath Tiwari ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Anal Canal ◽  
Imatinib Mesylate ◽  
Abdominoperineal Resection ◽  
Tumor Size ◽  
Kinase Inhibitor ◽  
Biological Behavior ◽  
High Power Field ◽  
Mesenchymal Tumors ◽  
Large Tumor

Gastrointestinal stromal tumors or “GIST” are mesenchymal neoplasms expressing KIT(CD117) tyrosine kinase and showing the presence of activating mutations in KIT orPDGFRα(platelet-derived growth factor alpha). GIST of anal canal is an extremely rare tumor, accounting for only 3% of all anorectal mesenchymal tumors and 0.1–0.4% of all GIST. GIST with large tumor size and high mitotic activity are highly malignant, but the biological behavior of anorectal GIST is less clear. Abdominoperineal resection (APR) or conservative surgery is the best treatment option. Imatinib mesylate, a tyrosine kinase inhibitor, has shown promising results in its management. We present a case of anorectal GIST diagnosed by computed tomography (CT) scan, magnetic resonance imaging (MRI), and colonoscopy with biopsy. The patient underwent abdominoperineal resection (APR) and was confirmed on histopathology to have anal canal GIST with tumor size more than 5 cm in maximum dimension and mitotic figures more than 5/50 high power field (HPF). The CD117—immunoreactive score—was 3+ in spindled cells. Therefore the patient was put on adjuvant imatinib mesylate 400 mg daily.

Cystic acne due to imatinib therapy for chronic myelocytic leukemia

2018 ◽  
Vol 25 (4) ◽  
pp. 972-974 ◽  
Author(s):  
Andrew Hwang ◽  
Andrew Iskandar ◽  
Michael del Rosario ◽  
Constantin A Dasanu
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Imatinib Mesylate ◽  
Side Effect ◽  
Medical Literature ◽  
Kinase Inhibitor ◽  
Imatinib Therapy ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Cutaneous Reactions

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of several malignancies. Its use, however, is associated with a number of toxic effects including adverse cutaneous reactions. Herein, we present a case of facial cystic acne in a patient receiving imatinib therapy for chronic myelocytic leukemia. This side effect resolved with cessation of therapy. To the best of our knowledge, this clinical entity has never been previously reported in the medical literature.

Gastrointestinal Stromal Tumors (GISTs): From Science to Targeted Therapy

2008 ◽  
Vol 23 (2) ◽  
pp. 96-110 ◽  
Author(s):  
R. Sarmiento ◽  
P. Bonginelli ◽  
F. Cacciamani ◽  
F. Salerno ◽  
G. Gasparini
Keyword(s):  
Targeted Therapy ◽  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitor ◽  
Mesenchymal Tumors ◽  
Treatment Scenario ◽  
Stromal Tumors ◽  
Imatinib Resistant ◽  
Review Reports ◽  
Molecular Patterns

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs represent a distinct category of tumors characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a majority of patients. KIT is useful not only for the diagnosis but also for targeted therapy of this disease. Imatinib, a tyrosine kinase inhibitor, is widely used in advanced and metastatic GISTs. This agent revolutionized the treatment strategy of advanced disease and is being tested in the neoadjuvant and adjuvant settings with encouraging results. New therapeutic agents like sunitinib have now been approved, enriching the treatment scenario for imatinib-resistant GISTs. The present review reports on the peculiar characteristics of this disease through its biology and molecular patterns, focusing on the predictive value of KIT mutations and their correlation with clinical outcome as well as on the activity of and resistance to approved targeted drugs.

The Tyrosine Kinase Inhibitor Adaphostin (NSC 680410), but Not Imatinib Mesylate, Inhibits Survival and Src Tyrosine Kinase Family- Triggered Signaling Pathways of MM Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3352-3352
Author(s):  
Klaus Podar ◽  
Melissa Simoncini ◽  
Yu-Tzu Tai ◽  
Martin Sattler ◽  
Kenji Ishitsuka ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Signaling Pathways ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
K562 Cells ◽  
Parp Cleavage ◽  
Src Tyrosine Kinase ◽  
Kinase Family ◽  
Long Term Treatment

Abstract The tyrosine kinase inhibitor adaphostin is a member of the tyrophostin family of small molecules that interfere with peptide binding rather, than targeting the kinase ATP-binding site. Adaphostin has therefore been examined as an alternative to the 2-phenylaminopyrimidine derivate imatinib mesylate, with remarkable efficacy in the treatment of chronic myeloic leukemia (CML). Previous studies show that adaphostin induces apoptosis: (1) in Bcr/Abl+ cells more rapidly than imatinib mesylate; (2) in imatinib mesylate resistant cells; and (3) in Bcr/ Abl - cells. Imatinib mesylate has minimal, if any activity in MM; the efficacy of adaphostin in multiple myeloma (MM) is unknown. Here we compare the effects of adaphostin and imatinib mesylate against human MM cells. Our results show concentration-dependent apoptosis in MM.1S, U266, OPM-2, INA-6, RPMI8226 and RPMI-Dox40 MM cells after treatment with adaphostin, but not with imatinib mesylate. Imatinib mesylate induced more than 50% apoptosis in K562 cells using concentrations as low as 1mM, which served as a positive control. Moreover, adaphostin, but not imatinib mesylate, induced caspase-9, caspase-8, and PARP cleavage, as well as downregulation of Mcl-1, in MM cells. Further results demonstrated that adaphostin induces peroxide production and DNA strand breaks after long-term treatment. Importantly MM cell proliferation induced by MM cell binding to BMSCs was abrogated by adaphostin- treatment. IL-6 and IGF-1 signaling and sequelae triggered by these cytokines are important growth, survival, and drug resistance factors in MM; conversely, adaphostin but not imatinib mesylate, inhibited phosphorylation of Src tyrosine kinase family, Akt-1, and ERK. Taken together, our studies in MM cells show that (1) adaphostin- inhibits IGF-1- and IL-6- triggered signaling pathways as well as (2) induces reactive oxygen species and apoptosis. These studies therefore provide the preclinical framework for its clinical evaluation to improve patient outcome in MM.

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