Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain tumors. However, the effects of RS for neuroepithelial tumors are still obscure. The present study investigates the radiological and histological changes after RS to elucidate the biological effect. There were seven cases (two males and five females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were located in the brainstem, another two in the cerebellum, and one each in the thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy. All cases were evaluated radiologically on MRI before and after RS. Four cases (3 astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were reoperated. These cases were examined using HE and immunohistochemical studies with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on the sections before and after RS. MRI demonstrated perifocal edema and intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting radionecrosis in most of the cases within 6 months after RS. In the central part of the RS, destructive changes were observed in the tumor cells and endothelial cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls were revealed. In the peripheral part, however, some tumors contained viable tumor cells intermingled with blood vessels showing endothelial and pericytic proliferations. The increase of MIB-1 staining index was found in only one case. The p21 immunoreactivity was increased in endothelial cells, although the p53 immunoreactivity was unchanged. These results suggested that radionecrosis occurred earlier and more frequently in neuroepithelial tumors after RS than after conventional radiation.
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PMID:Gamma knife radiosurgery for neuroepithelial tumors: radiological and histological changes. 1183 37

The clinical, histological, phenotypic and genotypic features of a lymphoblastoid natural killer (NK)-cell lymphoma presenting in the skin in a young caucasian woman are described. The disease behaved aggressively, but long-lasting remission was obtained by combination chemotherapy followed by autologous bone marrow transplantation. The blastoid cells were positive for terminal deoxynucleotidyl transferase, CD34, CD56 and CD4. Furthermore, the NK-cell receptor complex CD94/NKG2 was strongly expressed, as shown by examination with reverse transcription-polymerase chain reaction. The T-cell receptor (TCR)-gamma genes were in germline, and with the exception of CD4 all T-cell antigens were negative, including CD3, TCR-beta, TCR-delta, TIA-1, granzyme B and perforin. Epstein-Barr virus was negative, and no expression was seen of myeloid cell-associated markers. Molecular analysis showed no abnormalities of the CDKN2A (p16), CDKN2B (p15) or TNFRSF6 (Fas) genes. By contrast, a 34-bp deletion in exon 7 of the TP53 (p53) gene was detected. It is suggested that lymphoblastoid NK-cell lymphoma, which is a rare but distinctive disease, originates from NK cell precursors and may be associated with and possibly caused by alterations in the TP53 gene. Experience is too limited to warrant therapeutic suggestions. However, stem cell transplantation may be a useful option in younger patients.
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PMID:A case of lymphoblastoid natural killer (NK)-cell lymphoma: association with the NK-cell receptor complex CD94/NKG2 and TP53 intragenic deletion. 1184 84

The degree of DNA instability as determined by immunohistochemical staining with anti-single-stranded DNA antibody after acid hydrolysis (the DNA instability test) was used as a marker of malignancy. The test was applied to tissues of oral leukoplakia assessed histopathologically as hyperplasia (38 cases), mild (12 cases), moderate (11 cases) and severe (8 cases) dysplasia, and invasive squamous cell carcinoma (SCC, 20 cases). Tissues were subjected to immunohistochemical staining for proliferating cell nuclear antigen (PCNA), p53, DNA-fragmentation factor 45 (DFF45), analysis of various AgNORs parameters, and triple immunostaining for vascular endothelial growth factor (VEGF), CD34, and PCNA. The DNA instability test was positive in 20 (100%) SCC cases, 8 (100%) severe dysplasia cases, 8 (72.7%) moderate dysplasia cases, 6 (50.0%) mild dysplasia cases, and 9 (23.7%) hyperplasia cases, indicating malignancy. The proportion of lesions positive for PCNA, p53, DFF45, and values of AgNORs parameters steadily increased from hyperplasia to mild, moderate and severe dysplasia, and SCC, especially in those showing positive DNA instability test, indicative of malignancy. Based on these results, 44.9% of leukoplakia were malignant tissues, namely carcinoma in situ. The proportion of PCNA-positive vascular endothelial cells in the vicinity of VEGF-positive epithelial lesion was significantly higher than that of negative DNA instability lesions, as revealed by immunohistochemical triple staining for VEGF, CD34, and PCNA. Our results suggest that increased DNA instability, enhanced proliferative activity, p53 mutation, and induction of DFF45 and VEGF may allow cancer cell proliferation, enhance their survival by escaping apoptosis, and provide abundant nutrients during early-stage carcinogenesis of oral leukoplakia.
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PMID:Immunohistochemical detection of early-stage carcinogenesis of oral leukoplakia by increased DNA-instability and various malignancy markers. 1184 1

This study was designed to examine angiogenesis in rectal carcinoid tumors in relation to the clinicopathologic features. Seventy-seven rectal carcinoid tumors were studied clinicopathologically and experimentally. Cellular proliferation and microvessel density (MVD) were examined immunohistochemically. We used the antibodies MIB-1 for Ki-67, DO7 for p53, and NU-4A1 for CD34 expression in this study. Ki-67 labeling index (LI) of all lesions was below 3%, and the median Ki-67 LI of all lesions was 0.68+/-0.70% (mean +/- SD). A correlation was recognized between tumor size, metastasis and Ki-67 LI (p<0.05). Median MVD of all lesions was 25.9+/-13.1 (mean +/- SD). MVD was correlated with the tumor size (p<0.01), presence of depression (p<0.01), lymphatic (p<0.01) or venous (p<0.05) invasion, and existence of metastasis (p<0.01). But there was no significant relationship between MVD and Ki-67 LI. p53 protein was detected sporadically in only 1 case (1.3%) demonstrating both liver and lymph node metastases. Rectal carcinoid tumors are slow-growing tumors with a lower proliferative activity. Angiogenesis plays an important role in progression of rectal carcinoid tumors independent of the cellular proliferative activity.
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PMID:Clinical significance of angiogenesis in rectal carcinoid tumors. 1195 15

Angiogenesis is an essential requirement for the development, progression and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) plays an essential role in the development of angiogenesis of numerous solid malignancies, including colon cancer. The tumor suppressor gene p53 is a potent transcriptional regulator of genes which are involved in many cellular activities, including cell-cycle arrest, apoptosis and angiogenesis. In order to better understand the relation among p53 status, VEGF expression and microvessels count (MVC) in colon cancer, we evaluated immunoreactivity for CD34 endothelium-associated antigen, VEGF and p53 proteins in 43 cases of colon adenocarcinoma. Our results demonstrated an association between VEGF expression, p53 status and angiogenesis, suggesting that mutant p53 plays a central role in promoting angiogenesis in colon cancer progression.
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PMID:Neoangiogenesis in colon cancer: correlation between vascular density, vascular endothelial growth factor (VEGF) and p53 protein expression. 1195 38

The present case report describes a case of ganglioglioma with a distinct sarcomatous component in the left temporal lobe of a 59-year-old Japanese man. Neoplastic neuroglial tissue contained both benign and anaplastic glial components with a MIB-1 labeling index of 0.1% and 12.0%, respectively. Sarcomatous tissue adjacent to the anaplastic glial tissue was dominated by pleomorphic fibroblastic cells with a MIB-1 labeling index of 10.8%. They were immunoreactive for smooth muscle actin, type IV collagen, and alpha 1 antitrypsin, but not for desmin and CD34. Interestingly, some of the sarcomatous cells were double-positive for smooth muscle actin and GFAP. The p53 protein had accumulated in the anaplastic astrocytes and sarcomatous cells, but direct DNA sequencing of PCR products failed to detect any mutation in the p53 gene (from exon 4 to exon 10).
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PMID:Anaplastic ganglioglioma with sarcomatous component: an immunohistochemical study and molecular analysis of p53 tumor suppressor gene. 1203 Apr 14

Hypoxia encountered at high altitude, blood loss and erythroleukemia instigate stress erythropoiesis, which involves glucocorticoid-induced proliferation of erythroid progenitors (ebls). The tumour suppressor p53 stimulates hematopoietic cell maturation and antagonizes glucocorticoid receptor (GR) activity in hypoxia, suggesting that it may inhibit stress erythropoiesis. We report that mouse fetal liver ebls that lack p53 proliferate better than wild-type cells in the presence of the GR agonist dexamethasone. An important mediator of GR-induced ebl self-renewal, the c-myb gene, is induced to higher levels in p53(-/-) ebls by dexamethasone. The stress response to anemia is faster in the spleens of p53(-/-) mice, as shown by the higher levels of colony forming units erythroids and the increase in the CD34/c-kit double positive population. Our results show that p53 antagonizes GR-mediated ebl expansion and demonstrate for the first time that p53-GR cross-talk is important in a physiological process in vivo: stress erythropoiesis.
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PMID:The p53 tumour suppressor inhibits glucocorticoid-induced proliferation of erythroid progenitors. 1203 55

p53 suppressor gene mutations are a well known step which occurs in the late stages of the complex tumourigenesis of colorectal cancer. A deregulation of p53 protein function may be associated with increased neovascularization and aggressive tumour growth. In vitro studies have shown that these genetic alterations cause a loss of wild-type p53-induced anti-angiogenetic control and could possibly induce expression of the neoangiogenic vascular endothelial growth factor (VEGF). Therefore, this in vivo study was performed to assess p53 mutations, i.e. hot spots in exons 4-9, in primary colorectal cancers and in corresponding liver metastases in order to test whether there is an association between p53 mutated tumours with increased microvessel density (MVD) and VEGF overexpression. Twenty-two tissue samples taken from primary colorectal cancers and the corresponding liver metastases were immediately snap-frozen in liquid nitrogen and fixed in formaldehyde. After DNA extraction exons 4-9 were amplified and directly sequenced. Cryostat sections were stained immunohistochemically using antibodies against VEGF, CD34, and p53 protein. A modified semiquantitative Weidner score and interactive computerized image analysis was used to assess MVD. Overexpression of immunohistochemically detected p53 protein was found in 7 of the 11 primary tumours and liver metastases (64%). Sequencing showed 3 out of 11 primary tumours (27%) and 5 out of 11 liver metastases (46%) to have p53 point or frameshift mutations; these samples tested immunohistochemically positive for p53 protein. Two p53 mutations in samples of liver metastases were not detectable in the corresponding primaries. We detected one frameshift mutation in exon 4 that has not yet been described in the literature. Tumour samples with p53 mutations and increased VEGF immunoreactivity were associated with higher MVD (p<0.01 and p<0.05, respectively). However, there was no association detected immunohistochemically between p53 and MVD as well as p53 mutations and VEGF overexpression. Our data demonstrate specific genetic alterations in the coding regions of p53 suppressor gene in both primary colorectal cancers and corresponding liver metastases, these alterations are associated with an increase in MVD, but not in VEGF overexpression. In addition, a novel frameshift mutation in both colorectal cancer and metastasis is described.
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PMID:Association of p53 mutations, microvessel density and neoangiogenesis in pairs of colorectal cancers and corresponding liver metastases. 1211 17

This study examined the effect of preoperative low-dose tegafur treatment in human gastric carcinomas. Among 55 patients with gastric carcinoma, 33 received an oral administration of tegafur 600 mg/body/day for 7 days before. Formalin-fixed, paraffin-embedded specimens were immunostained for Ki-67, P53, P21, CD34, Bax, VEGF, and dThdPase and also examined by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling procedure. The apoptotic index (AI), Ki-67 labeling index (KI) and intratumoral microvessel density (IMVD) were counted. Mean AI and IMVD were 3.4+/-1.60 and 126.1+/-36.56 in the treated carcinomas, and 2.3+/-0.88 and 98.0+/-44.40 in the non-treated carcinomas, both values being significantly higher in the former (P<0.05). The treatment resulted in a significant increase of mean AI in the intestinal type, in the early, and in the P53-positive carcinomas (P<0.05), while the treatment brought a significant increase of IMVD in the diffuse type, in the early and in the P53-negative carcinomas (P<0.05, respectively). No significant difference was noted on the frequency of P53, P21, BAX, VEGF and dThdPase expressions between the two groups. Ki-67 expression did not correlate with any factors. Preoperative low-dose tegafur treatment resulted in a paradoxical effect; enhanced apoptosis and increased IMVD in human gastric carcinomas.
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PMID:Paradoxical effects by preoperative oral low-dose tegafur administration in human gastric carcinomas: enhanced apoptosis and increased intratumoral microvessel density. 1216 67

The biological behaviour of a gastrointestinal stromal tumor (GIST) cannot be easily predicted from preoperative clinical examination alone. As a result, there is little standardization in the surgical treatment of GIST. In this study, we analyzed the clinicopathology and immunohistochemistry of 20 cases of GIST to clarify factors associated with tumors showing malignant potential. Immunohistochemical analysis of KIT, CD34, vimentin, alpha-smooth muscle actin (SMA), s-100, p53, ki-67, bcl-2 and bax expression was performed on 20 surgically resected GIST. An apoptotic index (AI) was calculated for each sample using a TdT-mediated dUTP-biotin nick end-labeling method. With regard to bcl-2, t(14;18) translocations were also investigated using a polymerase chain reaction based method. Finally, the relationship between these biological results and clinicopathological data was analyzed. Of the 20 cases studied, two patients died due to lung or liver metastasis. All cases stained positive for vimentin, nine cases were positive for alpha-SMA and three cases positive for s-100. All cases were stained for both KIT and CD34, which tended to correlate with malignant potential. There was significant difference in frequency of bcl-2 overexpression (p<0.05) and trend in Ki-67 labeling index (p=0.098) between benign and malignant cases. However, with regard to bcl-2, no chromosomal t(14;18) translocations were detected in four analyzed cases. In GIST, overexpression of bcl-2 may play an important role in increasing malignant potential. Furthermore, Ki-67 L.I. and bcl-2 overexpression may be useful in predicting malignant potential, and therefore help to determine the surgical treatment, follow-up manner, and the necessity of adjuvant therapy.
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PMID:Biological analysis of gastrointestinal stromal tumors. 1237 34


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