Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens. Immunohistochemistry with specific anti-KIT and anti-SCF antibodies was performed on paraffin-embedded tissue sections in order to localize the relative protein expression in epithelial compartments. Approximately 10% of patients expressed KIT in their adenoma or primary tumor. The majority of KIT-positive carcinomas co-expressed SCF. Real-time RT-PCR showed expression of c-kit and SCF transcripts in all cDNA specimens examined. A significant association between the co-expression of KIT/SCF and a worse clinical outcome was found. In conclusion, KIT expression was observed in a proportion of premalignant and malignant colonic lesions, while it was virtually absent in normal colon mucosa. Moreover, the majority of KIT-positive carcinomas co-expressed SCF, suggesting the possibility of aberrant signaling by an autocrine loop, as confirmed by the negative prognostic value of this association. Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy.
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PMID:KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes. 1696 80

Gastro-intestinal stromal tumors (GIST), an abdominal sarcoma entity are characterized by a gain-of-function mutation in c-kit proto-oncogen (CD117). Initial treatment should aim at complete removal of the primary tumor (R0 resection) which almost never develops lymphatic metastases. Distant metastatic spread involves mainly the peritoneal cavity and the liver. In patients with metastatic disease, treatment with tyrosinkinase inhibitor imatinib mesylate (Glivec) is indicated and very effective. Systemic chemotherapy and external beam radiation must be considered ineffective. Patients requiring multivisceral resection to remove their primary tumor rapidly develop tumor recurrence and could potentially benefit from preoperative treatment with imatinib. Primary tumors are classified into four risk categories according to their size and mitotic activity. Whether there is an advantage of adjuvant treatment is currently under investigation within international randomized trials. Patients who develop an extensive remission of metastatic disease should be evaluated individually for resection of the tumor remnants. Even resection of single progressive lesions (with newly developed mutations) should be considered in carefully selected patients, if the remaining tumor can be controlled by continued imatinib treatment.
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PMID:[Gastrointestinal stromal tumors]. 1725 58

Cancer of unknown primary site (CUP) ranks as the fourth most common cause of cancer deaths and represents both a diagnostic and a management challenge. In CUP, the regression or dormancy of the primary tumor, the development of early, uncommon, systemic metastases, and the resistance to therapy are hallmarks of this heterogeneous clinical entity. Still, no consensus exists on whether CUP is simply a group of metastatic tumors with unidentified primaries or a distinct entity with specific genetic/phenotypic aberrations that define it as "primary metastatic disease." In this review, we present karyotypic analyses as well as the single-gene, single-protein studies done on the expression of oncogenes, tumor- or metastasis-suppressor genes, as well as angiogenesis effectors. These studies show frequent expression of oncoproteins, lack of activating epidermal growth factor receptor/c-Kit mutations or amplification, uncommon presence of tumor- or metastasis-suppressor gene mutations and highly active angiogenesis in CUP. Informative as they may be, these data have been observed in several solid tumors of known primary and failed to identify a CUP-specific molecular signature. The latter, if it exists, probably consists of a multigene expression pattern not captured by single-gene studies. Gene and protein microarray technologies offer promise for the unraveling of complex genetic programs that would either identify each CUP's primary tissue of origin or instead define the CUP-specific molecular signature. Confirmation of one of the two hypotheses would either improve primary disease-oriented therapy or develop CUP-oriented treatments targeting molecular aberrations that drive neoplastic growth/dissemination.
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PMID:Cancer of unknown primary site: missing primary or missing biology? 1747 Jun 84

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 developement 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 unresectable 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 uneventfull. 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 monts postoperatively Imatinib is a recent and very promising tretemenextirpation remains the only curative treatment of malignant GIST as evideneced by our patient.
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PMID:[Gastrointestinal gastric tumor (GIST) as a cause of massive hemorrhage from the upper digestive tract]. 1763 80

Malignant solitary fibrous tumor (MSFT) is a rare neoplasm. Three cases of MSFT with unusual features, including 1 pleural and 2 extrapleural, are reported. A 64-year-old woman with a large right thoracic MSFT and episodes of severe hypoglycemia experienced resolution of her hypoglycemia immediately after resection of the MSFT. A 27-year-old woman with primary retroperitoneal MSFT had pulmonary metastases 10 months after resection of the primary tumor. A 54-year-old man with an intracranial solitary fibrous tumor suffered from multiple pulmonary metastases and local recurrence 21 and 28 months after resection of the primary tumor, respectively. All 3 cases of solitary fibrous tumor displayed malignant features. The tumor cells in each case were positive for CD34 and Bcl-2, but negative for cytokeratin, smooth muscle actin, S-100, and c-kit. In addition, the tumor cells in the case with concomitant hypoglycemia were strongly positive for insulin-like growth factor-II. The histopathologic diagnostic criteria for MSFT, the differential diagnosis with other spindle cell tumors, and the mechanism of MSFT-derived hypoglycemia via insulin-like growth factor-II are discussed.
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PMID:Malignant solitary fibrous tumor: report of 3 cases with unusual features. 1934 55

We report a patient who long had a complete response by chemotherapy with imatinib mesilate(IM)for locally recurrent gastrointestinal stromal tumor(GIST)of the stomach. On July 2000, a 58-year-old woman was pointed out to have anemia in the course of surveillance for malignant melanoma of skin. Endoscopic examination revealed continuous bleeding from a submucosal tumor with ulceration on the posterior wall of the stomach. After endoscopic homeostasis failed, emergency laparotomy was performed and a biopsy was also done. The diagnosis made was GIST from immunohistological findings of positive c-kit, positive CD34, negative HMB45, and negative S100. After diagnosis, total gastrectomy, distal pancreatectomy, and splenectomy were performed. On September 2003, a local recurrence was recognized, and then chemotherapy by 400 mg IM daily was started. After beginning with a dose of IM 400 mg daily, the reduction of the tumor was monitored. The IM dose then had to be reduced to 300 mg daily. Because of the adverse side effects of IM, systemic edema and body weight increased. After reduction of IM, the adverse reactions resolved promptly, and a complete response of the primary tumor has been maintained for 4 years 3 months.
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PMID:[A case of recurrent gastrointestinal stromal tumor of the stomach with complete response to imatinib mesilate]. 1954 18

The CD117 (KIT) protein is overexpressed in many human neoplasms including adenoid cystic carcinoma of salivary glands. To evaluate the function of c-kit-activating mutations in adenoid cystic carcinoma of the salivary gland, we studied 14 cases (13 primary, 1 cervical lymph node metastasis) from our institution. KIT protein expression was evaluated by immunohistochemistry using formalin-fixed paraffin-embedded tissue. Mutational analyses of c-kit extracellular (exon 9), juxtamembrane (exon 11) and tyrosine kinase domains (exons 13 and 17) were performed by polymerase chain reaction, clonal selection and DNA sequencing. All 14 cases demonstrated strong KIT expression by immunohistochemistry. Molecular analysis was successful in 8 of 14 cases, and c-kit missense point mutations were detected in seven of eight cases (88%) including seven in exon 11, two in exon 9, two in exon 13 and two in exon 17. Eight silent point mutations were detected in five cases. Two cases contained missense mutations in more than one exon. Different mutations were found in the primary tumor and the cervical lymph node metastasis of one patient. Point mutations in domains similar to those described in gastrointestinal stromal tumors were detected, including Pro551Leu and Lys558Glu (5' end of exon 11), Leu576Phe (3' end of exon 11), Val643Ala (exon 13) and Asn822Ser (exon 17). Additional novel point mutations in exons 9, 11, 13 and 17 were also identified. This study is the first to report c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. Identification of such potential gain-of-function mutations in exon 11, and less frequently in exons 9, 13 and 17, suggests that KIT may be involved in the pathogenesis of adenoid cystic carcinoma of salivary glands. Our study raises a prospect of correlation of c-kit mutation and a potential treatment of adenoid cystic carcinoma with tyrosine kinase inhibitor (imatinib).
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PMID:Identification of c-kit gene mutations in primary adenoid cystic carcinoma of the salivary gland. 2051 80

The present study evaluates the protein expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and cKIT in a wide number of desmoids tumors and their role in determining treatment options. Fifty-nine cases classified as muscle aponeurotic fibromatosis were selected. Samples were grouped by tumor location in: head and neck, extremity and abdominal/trunk; type of resection of the primary tumor (complete resection with adequate margins, marginal resection and resection with inadequate margins); type of treatment (exclusive surgery, surgery followed by radiation therapy and surgery followed by tamoxifen or cyclooxygenase inhibitor). A tissue microarray (TMA) was built and the immunohistochemical reactions were performed against ERalpha, ERbeta, PR, and c-kit. All cases were negative for ERalpha, PR and c-KIT. 53/59 cases were positive for ERbeta. No significant difference was observed among clinical variables and the ERbeta status. The estimated 5 and 10 year local recurrence free survival (LRFS) for the patients with complete or marginal resection was 75% and 75%, respectively. Tumor location (p = 0.006) and type of resection (p = 0.001) were predictive of local relapse in the univariate analysis. All patients treated with post-operative tamoxifen were LRFS (p = 0.035). Head and neck and extremities lesions showed higher recurrence rates compared to abdominal/trunk lesions. Marginal resection was associated with local recurrence. In conclusion, although this is a retrospective study, the results presented can contribute to better understanding of the mechanisms under desmoid tumor development and can propose tamoxifen as a therapeutic option to be tested in prospective trials.
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PMID:Evaluation of estrogen receptor alpha, estrogen receptor beta, progesterone receptor, and cKIT expression in desmoids tumors and their role in determining treatment options. 2030 41

Approximately 50% of mucosal melanomas affect the head and neck region representing approximately 9% of all malignant head and neck tumors. The pathogenesis of this disease is unknown. Mucosal melanomas are characterized by an aggressive biological behavior, leading to a 5-year survival rate of less than 25%. Data for this review were identified by searches of Medline, Current Contents, PubMed, and references from relevant articles using the terms 'mucosal melanoma,' 'head and neck melanoma,' 'c-kit mutation in melanoma,' and 'c-kit inhibitors'. Therapy aims for the complete surgical excision of the primary tumor, whereas sentinel node biopsy is not established and present data do not support the addition of radiotherapy. Mutilating operations of larger tumors should be avoided, as they do not inhibit the frequent development of distant metastasis. C-kit mutations and amplifications are found in approximately 15-30% of mucosal and acral-lentiginous melanomas. Therefore, the use of so-called targeted therapies addressing molecular structures in mucosal melanomas seem to represent new promising treatment tools. In this study, we review the literature regarding epidemiology, molecular pathology, and therapy of mucosal melanomas of the head and neck emphasizing c-kit protein inhibiting treatment modalities for tumors carrying c-kit mutations.
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PMID:Mucosal melanomas of the head and neck: new aspects of the clinical outcome, molecular pathology, and treatment with c-kit inhibitors. 2189 3

Progress in molecular biology has facilitated a new classification for melanoma. Melanomas today are considered as a heterogeneous group of tumors. The different subtypes are characterized by specific genetic alterations, including mutations in kinase, such as B-RAF or c-kit. New medications like vemurafenib have been developed and are available for the systemic therapy of advanced melanomas in subpopulations identified by mutation tests. In addition, interferon therapy holds the highest promises to dates in subpopulations of patients characterized by microscopic lymph node involvement and ulceration of the primary tumor. These developments are the first steps resulting in a personalized treatment approach for individuals affected by melanoma.
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PMID:[Therapeutic approaches in Melanoma - a paradigm for personalized medicine]. 2281 27


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