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

Pancreatic mucinous cystic tumors (MCT) are proliferations of mucin-producing epithelia supported by an ovarian-like stroma. They are classified into adenomas (MCA), borderline (MCB) and noninvasive or invasive carcinomas (MCC). The molecular mechanisms underlying their clinical behavior are poorly understood, partly due to the lack of cellular models. We report the establishment of MCC1, the first cell line from a pancreatic MCT, deriving from the highly dysplastic cell component of a noninvasive MCC. MCC1 has mutations in codon 12 of K-RAS (GGT>GAT), codon 58 of P16 (CGA>TGA) and codon 132 of P53 (AAG>AGG). The FHIT and DPC4 genes are unaltered. Immunohistochemistry shows abnormal expression of MUC1 and p53, loss of p16 and retention of Fhit and Dpc4 in both the cell line and the highly dysplastic cells of the primary lesion. The morphological and molecular features of MCC1 and its corresponding primary tumor are consistent with a model for non-invasive MCC, where K-RAS, P16, P53 and MUC1 alterations are pre-invasive changes associated with progression of malignancy of MCT from adenoma to carcinoma. MCC1 is sensitive to 5-fluorouracil, representing the first assessment of drug sensitivity for MCC. Finally, MCC1 is a suitable model for preclinical studies, as it grows in immunodeficient mice.
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PMID:Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion. 1568 69

Intraosseous benign notochordal cell tumor (BNCT) is a lesion postulated to be of notochordal cell origin. BNCT has recently been recognized as a potential precursor of classic chordoma, a rare malignant neoplasm usually presenting in the sacrococcygeal region, skull base, or mobile spine. Extra-axial chordoma is extremely rare, and only 2 cases of pulmonary chordoma have been reported previously. We describe herein 2 cases of hitherto-unreported lung tumors that were diagnosed as BNCT. The patients were a middle-aged asymptomatic man and woman who were each incidentally found to have a 15-mm pulmonary nodule on computed tomography. They underwent surgical resection of the tumors under a diagnosis of probable benign tumor of uncertain nature. Histopathologically, both tumors showed solid sheets of peculiar adipocyte-like univacuolated cells, multivacuolated cells, and less vacuolated cells with small, round nuclei and mildly eosinophilic cytoplasm. Mitosis was absent. These features were typical of BNCT. Immunohistochemically, the tumor cells in both cases were positive for brachyury, a transcription factor essential for notochordal cell differentiation and for other markers of notochordal cells including cytokeratins, vimentin, and S-100 protein. Postoperatively, extensive radiographic examination of the whole body revealed no evidence of a primary tumor elsewhere, and both patients are alive and well, with no evidence of disease 1 year after surgery. These 2 cases raise the possibility of a new explanation for the histogenesis of extra-axial chordomas: BNCT may be a precursor lesion of not only conventional axial chordoma but also of extra-axial chordoma.
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PMID:Pulmonary tumor with notochordal differentiation: report of 2 cases suggestive of benign notochordal cell tumor of extraosseous origin. 2171 81

Benign notochordal cell tumors (BNCTs) are tumors originating in the axial skeleton, where chordomas occur. Although very rare, some cases of extraosseous chordoma, such as in the soft tissue and lungs, have been reported. We report a case of a primary tumor showing the notochordal characteristics of BNCTs within the axial skeleton.An asymptomatic 57-year-old woman presented with an abnormal shadow on her chest radiograph; chest computed tomography revealed a well-defined round nodule. The resected sample tissue contained a jelly-like small nodule. Histologically, it was identified as a BNCT, based on minimal nuclear atypia, extremely low mitotic activity within the tumor cells lying in a sheet-like arrangement, and focal immunopositivity for brachyury.This is the third case report of BNCT originating in the lungs; BNCTs are considered asymptomatic tumors that are identified by using highly developed chest imaging technology; however, our findings also suggest that these notochordal tumors may potentially originate from extraosseous sites that lack ideal precursor cells. Our case suggests that notochordal tumors can arise from organs that are unrelated to known notochordal development.
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PMID:Extraosseous benign notochordal cell tumor originating in the lung: a case report. 2556 57

Patients diagnosed with triple-negative breast cancer (TNBC) have a high rate of tumor metastasis and a poor prognosis. The treatment option for these patients is currently chemotherapy, which results in very low response rates. Strategies that exploit the immune system for the treatment of cancer have now shown the ability to improve survival in several tumor types. Identifying potential targets for immune therapeutic interventions is an important step in developing novel treatments for TNBC. In this study, in silico analysis of publicly available datasets and immunohistochemical analysis of primary and metastatic tumor biopsies from TNBC patients were conducted to evaluate the expression of the transcription factor brachyury, which is a driver of tumor metastasis and resistance and a target for cancer vaccine approaches. Analysis of breast cancer datasets demonstrated a predominant expression of brachyury mRNA in TNBC and in basal vs luminal or HER2 molecular breast cancer subtypes. At the protein level, variable levels of brachyury expression were detected both in primary and metastatic TNBC lesions. A strong association was observed between nuclear brachyury protein expression and the stage of disease, with nuclear brachyury being more predominant in metastatic vs primary tumors. Survival analysis also demonstrated an association between high levels of brachyury in the primary tumor and poor prognosis. Two brachyury-targeting cancer vaccines are currently undergoing clinical evaluation; the data presented here provide rationale for using brachyury-targeting immunotherapy approaches for the treatment of TNBC.
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PMID:Brachyury, a vaccine target, is overexpressed in triple-negative breast cancer. 2758 Jun 59

Brachyury is a T-box transcription factor characterized as a driver of the epithelial-to-mesenchymal process, which is associated with poor prognosis of patients with breast cancer. The present study investigated expression of brachyury in breast cancer including primary tumor, metastatic and recurred tumor tissues, and the clinical significance and value of brachyury as a prognostic biomarker. This retrospective study included a series of 102 consecutive patients surgically resected between January 2005 and December 2011. Brachyury expression in tumor cell was evaluated using immunohistochemistry and scored as the immunoactivity. Of 102 patients, 62 primary tumors were positive for brachyury expression and 40 were negative. Multivariate analysis of disease-free survival (DFS) revealed brachyury expression, HER2 and lymphovascular invasion as independent prognostic factors [brachyury negative vs. positive hazard ratio (HR), 3.0; P=0.024; HER2 negative vs. positive HR, 4.9; P=0.003; lymphovascular invasion absent vs. present HR, 3.5; P=0.020]. These results were particularly observed in triple-negative breast cancer (TNBC), no recurrence or mortality occurred in brachyury negative group during the follow-up period, and therefore a significantly improved prognosis was demonstrated in these patients compared with the brachyury positive group [overall survival (OS), P=0.022; DFS, P=0.002]. Brachyury expression in metastatic lymph node/recurred tumors was not significantly associated with prognosis (OS, P=0.745; DFS, P=0.189). Therefore, Brachyury expression in primary tumor independently is a potential predictor of poor prognosis, particularly in TNBC, where it appears to serve a crucial function in recurrence and mortality. Brachyury vaccines under clinical trials are likely to be useful in patients with breast cancer.
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PMID:Prognostic significance of expression of epithelial-mesenchymal transition driver brachyury in breast cancer and its association with subtype and characteristics. 2939 64

Chordomas are slow-growing rare malignant neoplasms. The aim of this study was to establish a primary model of chordoma in the lumbosacral orthotopic area, to compare the growth rate to the subcutaneous site, and to show that this new graft site optimizes tumor growth and bony invasion. Eleven chordoma samples were transplanted subcutaneously in the flank and/or in contact with the lumbosacral region and grown into nude mice. Engraftment rate was significantly more successful in the lumbosacral environment compared with the flank at P0. Two xenografts from 2 patients showed bone invasion. One tumor was maintained through multiple rounds of serial transplantation, creating a model for study. Histological and immunostaining analysis confirmed that tumor grafts recapitulated the primary tumor from which they were derived, consisting of a myxoid chordoma expressing brachyury, cytokeratin AE1, EMA, and VEGF. Clear destruction of the bone by the tumor cells could be demonstrated. Molecular studies revealed PIK3CA and PTEN mutations involved in PI3K signaling pathway and most of the frequently reported chromosomal alterations. We present a novel orthotopic primary xenograft model of chordoma implanted for the first time in the lumbosacral area showing bone invasion, PIK3CA, and PTEN mutations that will facilitate preclinical studies.
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PMID:Development of a Novel Orthotopic Primary Human Chordoma Xenograft Model: A Relevant Support for Future Research on Chordoma. 3184 Nov 64