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)

A 64-year-old woman experienced an episode of disorientation in relation to time, place, and people, as well as of visual defect and impaired balance. Physical examination showed a bitemporal hemianopsia and truncal ataxia. Computerized tomography of the skull revealed a sellar mass consistent with the diagnosis of pituitary adenoma. The patient progressively lost consciousness and died. At postmortem examination, a pituitary neoplasm with arachnoid metastases was present. Metastatic cervical lymph nodes were also detected. Histologic aspects of the primary tumor and of lymph node metastases were quite similar. Immunohistochemical investigation revealed the epithelial origin of the neoplasm and failed to disclose endocrine activity. At ultrastructural examination, the cells of the primary tumor and of the metastases lacked specific granules. These findings support the evidence of a primary metastasizing pituitary carcinoma.
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PMID:Endocrine inactive pituitary carcinoma metastasizing to cervical lymph nodes: a case report. 381 1

The case of a 52-year-old woman with acromegaly, diabetes insipidus, and visual impairment caused by a metastatic growth hormone-releasing hormone (GRH)-produced pancreatic tumor is reported. Serum growth hormone (GH) and somatomedin C levels were elevated to 14 ng/ml (normal < 5 ng/ml), and 3.20 U/ml (normal < 1.88 U/ml), respectively. Paradoxical increases were observed in GH levels after glucose tolerance and thyrotropin-releasing hormone-stimulation tests. Biopsy of a pituitary tumor observed on computerized tomography scans and magnetic resonance studies revealed a metastatic cancer. When circulating GRH levels were measured, a marked increase in plasma GRH (1145 pg/ml; normal < 4-1 pg/ml) was observed. The patient died of cachexia due to metastases. Postmortem examination revealed that a primary tumor, a malignant endocrine lesion, was present in the pancreas, with metastatic tumors in the pituitary, lung, liver, and adrenal glands. Synthesis and production of GRH by the tumor was demonstrated by Northern blotting and immunohistochemical analysis. The pituitary gland showed hyperplastic, but not adenomatous changes. The authors stress the importance of both exploration for an ectopic source of GRH and the search for a GH-producing pituitary adenoma when unusual signs and symptoms are seen in patients with acromegaly.
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PMID:Acromegaly, diabetes insipidus, and visual loss caused by metastatic growth hormone-releasing hormone-producing malignant pancreatic endocrine tumor in the pituitary gland. Case report. 767 23

MRI provides additional information about tumor location, extent, and margins. MRI was used in 158 patients with CNS tumors for treatment planning from 1985-89 and they were studied in a prospective manner. The most common site was cerebrum (73 pts), then extradural spinal axis (21 pts) posterior fossa (17 pts), brain stem (14 pts) and pituitary (13 pts), etc. The most common histological primary tumor was glioblastoma multiform (25 pts), then low grade astrocytoma (22 pts), anaplastic astrocytoma (14 pts), pituitary tumor (13 pts), medulloblastoma (9 pts), ependymoma (7 pts), and germ cell tumors (6 pts). Twenty-nine patients had metastasis to the brain. A majority of the patients with CNS tumors had the studies using Gadolinium-DTPA. Of the patients with CNS tumors, 120 (76%) had better information based on the MRI, which improved the treatment planning (using the three dimensional images) and field arrangement. In 89 patients (56%) the MRI was very decisive in the treatment volume and field arrangement. In 31 patients (20%) the MRI was beneficial and confirmed the treatment plan. MRI provides important additional information for radiation therapy planning.
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PMID:Use of magnetic resonance imaging in central nervous system tumors. 773 Jul 30

Pituitary carcinomas are defined by their metastatic growth. Most of them also invade into surrounding tissues. They should be classified by the site of their metastases (cerebrospinal, systemic, or combined) and by the presumable cell type of origin, respectively with the hormone being demonstrable by immunohistochemistry (adrenocorticotrophic hormone [ACTH], prolactin [PRL], growth hormone [GH], hormone-negative). Pituitary carcinomas develop from invasive adenomas. Nearly all tumors had been treated by surgery or X-ray before they metastasized. Since 1976, 37 cases demonstrated with modern methods were reported: 23 had metastasized into the brain or meninges, 10 showed extracerebral metastases, and 4 showed both types of metastases. In our collection of pituitary tumors, three carcinomas (0.13%) were identified: two with systemic metastases (one ACTH secreting and one PRL secreting) and one with meningeal dissemination and ACTH production. The diagnosis of pituitary carcinomas should be based on four criteria: a demonstrable metastasis, identification of the primary tumor as a pituitary tumor, similarity between the structure and immunohistological marker expression of metastasis and primary tumor, and exclusion of an alternative primary tumor.
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PMID:Pituitary Carcinomas. 1211 77

The prognosis of breast cancer patients is related to the degree of metastasis. However, the mechanisms by which epithelial tumor cells escape from the primary tumor and colonize at a distant site are not entirely understood. Here, we analyzed expression levels of pituitary tumor-transforming gene-1 (PTTG1), a relatively uncharacterized oncoprotein, in patient-derived breast cancer tissues with corresponding normal breast tissues. We found that PTTG1 is highly expressed in breast cancer patients, compared with normal tissues. Also, PTTG1 expression levels were correlated with the degree of malignancy in breast cancer cell lines; the more migratory and invasive cancer cell lines MDA-MB-231 and BT549 displayed the higher expression levels of PTTG1 than the less migratory and invasive MCF7 and SK-BR3 and normal MCF10A cell lines. By modulating PTTG1 expression levels, we found that PTTG1 enhances the migratory and invasive properties of breast cancer cells by inducing epithelial to mesenchymal transition, as evidenced by altered morphology and epithelial/mesenchymal cell marker expression patterns and up-regulation of the transcription factor Snail. Notably, down-regulation of PTTG1 also suppressed cancer stem cell population in BT549 cells by decreasing self-renewing ability and tumorigenic capacity, accompanying decreasing CD44(high) CD24(low) cells and Sox2 expression. Up-regulation of PTTG1 had the opposite effects, increasing sphere-forming ability and Sox2 expression. Importantly, PTTG1-mediated malignant tumor properties were due, at least in part, to activation of AKT, known to be a key regulator of both EMT and stemness in cancer cells. Collectively, these results suggest that PTTG1 may represent a new therapeutic target for malignant breast cancer.
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PMID:PTTG1 oncogene promotes tumor malignancy via epithelial to mesenchymal transition and expansion of cancer stem cell population. 2251 56

ABSTRACT BACKGROUND. Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the cancer/testis antigens (CTAs) Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. METHODS. We used RT-PCR, immunofluorescence, flow cytometry, ELISA and cytotoxicity assays to determine the expression levels and immunogenicity of SP17, AKAP4 and PTTG1 in human NSCLC cell lines and primary tumors. RESULTS. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in NSCLC cancer cell lines and primary tumor tissues from patients, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes (CTLs) from patients' peripheral blood mononuclear cells (PBMCs). CONCLUSIONS. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in NSCLC patients. Based on our findings, further studies are warranted to explore the feasibility of developing CTA-specific immunotherapeutic strategies for NSCLC patients.
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PMID:Selective expression and immunogenicity of the cancer/testis antigens SP17, AKAP4 and PTTG1 in non-small cell lung cancer: new candidates for active immunotherapy. 2481 38

Glioma which has strong proliferation and angiogenesis ability is the most common and malignant primary tumor in central nervous system. Pituitary tumor transforming gene (PTTG) is found in pituitary tumor, and plays important role in cell proliferation, cell cycle, cell apoptosis, and angiogenesis. However, the role of PTTG in glioma is still incompletely investigated. Here, we explored the correlation between PTTG and glioma grade, as well as micro-vessel density (MVD). In addition, siRNA was used to silence PTTG expression in glioma cell lines including U87MG, U251, and SHG44. Cell proliferation, apoptosis, invasion, and angiogenesis were studied both in vitro and in vivo. Our results demonstrated that PTTG expression was significantly up-regulated in glioma, and had positive correlation with glioma grade and MVD. Silencing of PTTG inhibited glioma cell proliferation, migration/invasion, and angiogenesis, induced cell apoptosis, suppressed cell invasion, and arrested cell cycle at G0/G1 stage. Silencing of PTTG could also inhibit tumor growth, invasion, and angiogenesis in vivo. Our data indicated that PTTG might be a potential target for glioma treatment.
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PMID:Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment. 2590 89

Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome.
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PMID:E2F1-mediated human POMC expression in ectopic Cushing's syndrome. 2793 5