Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

57 cases of malignant fibrous histiocytomas (MFH) were examined, immunohistochemically for the presence of p-53-tumour suppressor gene with monoclonal antibody DO-7 (Dako) and for the presence of Ki-67 antigen using monoclonal antibody MIB-1 (Dianova). The statistical relationship between the overexpression of p-53 and grading parameters (mitoses, cellularity, necrosis) and expression of Ki-67 antigen as well as survival time, was determined. The presence of p-53 antigen was found in 29.8% of grade II and grade III tumours, but not in MFH of grade I. The p-53 positive cases demonstrated a significantly higher mitotic index (p < 0.05), higher Ki-67 index (p < 0.05) and shorter survival time (p < 0.05) in comparison to p-53 negative cases. Differences concerning cellularity and extent of necrosis, between p-53 positive and p-53 negative tumours were not found (p > 0.05). The prognostic role of p-53 overexpression in MFH is discussed.
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PMID:P-53 positivity and high proliferative index: factors of bad prognosis in malignant fibrous histiocytomas. 890 Sep 26

Apoptosis and cell proliferation occur simultaneously in tumour tissue with tumour suppressor gene, p53 being one of the key players in the complex relationship between these two key phenomena. We, as well as several other groups, have earlier demonstrated the association of p53 immunopositivity with increased degree of cell proliferation in astrocytic tumours. Here we have studied the extent of apoptosis in 62 primary human astrocytic tumours [25 Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28 Glioblastoma multiforme (GBM)] in relation to tumour grade, proliferative status and p53 protein expression. Apoptosis was measured by the TUNEL assay while, cell proliferation (MIB-1 index) and p53 protein immunoreactivity were evaluated by immunohistochemical staining using MIB-1 and DO-1 monoclonal antibodies respectively. The apoptotic index (AI) was greater in GBM than in AA or DA, and more in tumours with p53 immunopositivity than in those without. The most striking observation was the strong correlation between Apoptotic index (AI) and proliferation index (PI) in p53 negative GBM (r=0.766, P < 0.005). However this was not observed in p53 +ve GBM or in low grade DA either p53 positive or negative. Taking p53 negativity in IHC as evidence of a functional gene/protein, this extends the link between proliferation and apoptosis, hitherto observed only in cultured cells with functional p53, to a subset of solid tumours.
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PMID:Apoptosis and proliferation: correlation with p53 in astrocytic tumours. 1598 Oct 97

Tumours of the gastrointestinal (GI) tract, of which 70% arise in the colorectum, are a major cause of morbidity and mortality worldwide. Transformation from normal to malignant mucosa is a multistep process involving specific gene mutations and is called the adenoma-carcinoma sequence. Histologically, adenomas are of three types (tubular, tubulovillous and villous) and the extent of mucosal cellular abnormality of three grades (mild, moderate and severe). Cellular proliferation is a marker of malignant potential in many tissues. In the colon, cellular proliferation is partly controlled by the CDX-2 gene, a homeobox gene expressed in differentiated cells of the intestine that has proto-oncogenic potential in murine models. In the stomach, CDX-2 is expressed in intestinal metaplasia and decreasing expression through tumourogenesis shows its tumour suppressor potential. Down-regulation in colorectal cancer cell lines is also observed. This is a retrospective study of colorectal adenomas, and haematoxylin and eosin (H&E) and immunocytochemical staining for CDX-2 and MIB-1 (a cell proliferation marker) are performed on each case. Comment is made on the morphological features (adenoma type and dysplasia severity) and the grade of CDX-2 and MIB-1 expression. This study showed that dysplasia severity is linked to cellular proliferation (P=0.011) but adenoma type was not (P=0.54). CDX-2 was not linked to the morphological features discussed (P=0.11 and P=0.16) and CDX-2 and MIB-1 expression showed no correlation. Increased cell proliferation (MIB-1 expression) was seen in increasingly dysplastic adenomatous lesions of the colorectum. CDX-2 had no link to morphological features or cell proliferation of the dysplastic mucosa.
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PMID:CDX-2 and MIB-1 expression in the colorectum: correlation with morphological features of adenomatous lesions. 1687 98

Prolactinoma is the most common pituitary tumour in adults. Macroprolactinomas, particularly in men, may occasionally exhibit a very aggressive clinical course as evidenced by progressive growth, invasion through bone into the sphenoid sinus, cavernous sinus, suprasellar region or the nasopharynx. Some may even progress to pituitary carcinoma with craniospinal or systemic metastases. Aggressive tumours have low cure rates despite appropriate medical and surgical treatment. The mechanisms underlying this aggressive biological behaviour have not yet been fully clarified. Recent immunohistochemical, molecular and genetic studies have provided some insight in this respect. Invasive prolactinomas may be associated with a high Ki-67/MIB-1 labelling index indicating increased cell proliferation, although this is not a universal finding. The AA polymorphism in the cyclin adenine (A)/guanine (G) gene is more frequently detected in invasive prolactinomas. Increased expression of the polysialylated neural cell adhesion molecule (NCAM) and reduced expression of the E-cadherin/catenin complex implies a contribution of altered cell-to-cell adhesion and cellular migration. Extracellular matrix components (ECM), matrix metalloproteinases (MMPs) and their inhibitors play important roles in the context of angiogenesis and invasion. The induction of fibroblast growth factor and vascular endothelial growth factor via oestrogen-induced overexpression of novel genes (PTTG, hst and Edpm5) enhance cell growth, proliferation and angiogenesis contributing to invasiveness in prolactinomas. Although mutations in proto-oncogenes like Ras are uncommon, loss of tumour suppressor genes at loci 11q13, 13q12-14, 10q and 1p seem to be associated with invasiveness. Of the described mechanisms, only reduced E-cadherin/catenin expression and overexpression of hst gene seem to be relatively specific markers for prolactinoma invasiveness compared with other pituitary adenomas. Further research is needed to clarify the molecular mechanisms behind the aggressive course of some prolactinomas to predict those with a potentially poor clinical outcome, and to devise treatments that will eventually enable the cure of these challenging tumours.
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PMID:What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. 1728 3