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)

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumours. Malignant mesothelioma (MM) of the pleura is a highly invasive tumour with a poor prognosis. In the present study, microvascular quantification was undertaken on 25 specimens of mesothelioma and 15 specimens of non-neoplastic mesothelium (NNM), by staining for the antigens CD34 and CD31. Areas of highest intratumoural microvascular density (IMD) were identified and counted either manually (mIMD) or on a computerized image analysis system (CIAS; iIMD). The two IMDs were significantly correlated with each other (r = 0.736; P < 0.001). The average IMD for MM was significantly (P < 0.001) higher than in NNM. Moreover, each unit increment in iIMD for MM, when regarded as a continuous variable, was significantly (P = 0.001) associated with an increased hazard of about 4 per cent. When regarded as a categorical variable, the patients in the highest tertile (> 58 vessels/field) had a significantly (P < 0.01; log-rank test) shorter survival than patients in the lowest tertile (< 45 vessels/field). This association was independent of the age of the patient and of the histological type or grade of the MM. No association was noted with p53 immunoexpression. Although the mean vascular area of blood vessels measured on the CIAS did not correlate with survival, assessment of IMDs can be an important independent prognostic indicator in malignant mesothelioma.
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PMID:Evaluation of tumour angiogenesis as a prognostic marker in malignant mesothelioma. 927 33

Despite controversy regarding its histogenesis, meningeal hemangiopericytoma (HPC) is a well-defined clinicopathologic entity exhibiting high rates of recurrence and late extracranial metastasis. It must be distinguished from several benign neoplasms, particularly fibrous meningioma (FM) and solitary fibrous tumor (SFT). To determine the immunoprofile of HPC, we studied 27 meningeal examples, including 13 low-grade and 14 high-grade tumors. For comparison, 20 FMs and eight SFTs of the meninges were also evaluated. The immunotype of HPC included vimentin (85%), factor XIIIa (78%) in individual scattered cells, Leu-7 (70%), and CD34 (33%) in a weak, patchy pattern. Focal desmin and cytokeratin positivity was only occasionally encountered (20% each). The SFT shared a similar immunophenotype, except that CD34 expression (100%) was characteristically strong and diffuse. The FM characteristically expressed epithelial membrane antibody (EMA) (80%) and S-100 protein (80%); CD34 reactivity (60%) was patchy and weak. Both within and among all three tumor types, MIB-1 labeling indices varied widely. Specifically, they were unrelated to tumor grade in HPC. Significant reactivity for p53 protein was detected in 52% of HPCs, 17% of SFTs, and 5% of FMs. Meningeal HPC exhibits a distinct antigenic profile, one enabling the exclusion of other entities in nearly all cases. The rare expression of desmin or cytokeratin in HPC suggests either the occurrence of divergent differentiation or, less likely, the possibility that its distinctive morphology is but a phenotype shared by several types of meningeal sarcoma.
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PMID:The immunophenotypic spectrum of meningeal hemangiopericytoma: a comparison with fibrous meningioma and solitary fibrous tumor of meninges. 935 73

Cell cycle control subsequent to gamma irradiation or growth factor starvation has been studied in immative hematopoietic cells of 19 previously untreated chronic myeloid leukemia (CML) patients in chronic phase compared with 18 normal controls. CD34-positive cells were cultured for seven days in the presence of optimal concentrations of appropriate growth factors. At day 7 of culture both S-phase fraction and differentiation were identical in normal and leukemic cells. In normal cells the proportion of S-phase cells was reduced by irradiation with 500 rad from 40 +/- 3% to 16 +/- 2%. In contrast, in CML cells a reduction of S-phase cells from 35 +/- 2% to 25 +/- 3% was observed. Moreover, irradiated CML cells arrested at a smaller number of cells in G2. Similarly, a significantly higher proportion of CML cells remained in S phase after withdrawal of growth factors. Semiquantitative PCR of p21 (waf1/cip1) induction by gamma irradiation provided no evidence for a major functional deficiency of p53 response to irradiation in these cells. Our results demonstrate an abnormal cell cycle arrest in chronic-phase CML cells both after gamma irradiation and after growth factor removal. This observation might have important implications for understanding the pathogenesis of both hyperplasia of chronic phase and the development of blast crisis in CML. The molecular mechanisms underlying these abnormalities in bcr-abl-positive cells remain to be clarified.
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PMID:Deficient cell cycle control in myeloid cells of patients with newly diagnosed chronic myeloid leukemia. 938 81

Prompt reconstitution of hematopoiesis after cytoreductive therapy is essential for patient recovery and may have a positive impact on long-term prognosis. We examined the role of the p53 tumor suppressor gene in hematopoietic recovery in vivo after treatment with the cytotoxic drug 5-fluorouracil (5-FU). We used p53 knock-out (p53-/-) and wild-type (p53+/+) mice injected with 5-FU as the experimental model. Analysis of the repopulation ability and clonogenic activity of hematopoietic stem cells (HSCs) and their lineage-committed descendants showed a greater number of HSCs responsible for reconstitution of lethally irradiated recipients in p53-/- bone marrow cells (BMCs) recovering after 5-FU treatment than in the corresponding p53+/+ BMCs. In post-5-FU recovering BMCs, the percentage of HSC-enriched Lin- Sca-1(+) c-Kit+ cells was about threefold higher in p53-/- than in p53+/+ cells. Although the percentage of the most primitive HSCs (Lin- Sca-1(+) c-Kit+ CD34(low/-)) did not depend on p53, the percentage of multipotential HSCs and committed progenitors (Lin- Sca-1(+) c-Kit+ CD34(high/+)) was almost fourfold higher in post-5-FU recovering p53-/- BMCs than in their p53+/+ counterparts. The pool of HSCs from 5-FU-treated p53-/- BMCs was exhausted more slowly than that from the p53+/+ population as shown in vivo using pre-spleen colony-forming unit (CFU-S) assay and in vitro using long-term culture-initiating cells (LTC-ICs) and methylcellulose replating assays. Clonogenic activity of various lineage-specific descendants was significantly higher in post-5-FU regenerating p53-/- BMCs than in p53+/+ BMCs, probably because of their increased sensitivity to growth factors. Despite all these changes and the dramatic difference in sensitivity of p53-/- and p53+/+ BMCs to 5-FU-induced apoptosis, lineage commitment and differentiation of hematopoietic progenitors appeared to be independent of p53 status. These studies suggest that suppression of p53 function facilitates hematopoietic reconstitution after cytoreductive therapy by: (1) delaying the exhaustion of the most primitive HSC pool, (2) stimulating the production of multipotential HSCs, (3) increasing the sensitivity of hematopoietic cells to growth factors, and (4) decreasing the sensitivity to apoptosis.
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PMID:Role of p53 in hematopoietic recovery after cytotoxic treatment. 953 12

Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on oesophageal carcinoma and the connection between VEGF and p53. One hundred and nine resected oesophageal squamous cell carcinomas were examined. VEGF expression was analysed by immunohistochemical staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF positive. A significant correlation was found between the VEGF expression and both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001). With regard to p53, we compared the expression of VEGF with the mutation of p53, examined using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who we have reported previously. The VEGF expression was significantly correlated to p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density (MVD) was counted, and endothelial cells were stained immunohistochemically using anti-CD34 monoclonal antibody against 29 cases with invasion limited to the submucosal layer. The average MVD had a tendency to correlate to VEGF expression (P = 0.1626). The prognoses of patients with VEGF-positive primary tumours were significantly worse than for those with VEGF-negative primary tumours (P = 0.0077). We have assumed that VEGF contributes to aggressive characteristics in oesophageal carcinomas and that VEGF expression might be affected by p53 status.
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PMID:In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis. 963 53

The major vault lung resistance protein LRP is a cytoplasmic protein involved in drug resistance, especially in acute myeloid leukemia. We looked for LRP overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66% of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+) in 33% of the cases. No correlation was seen between LRP overexpression and FAB type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts. Furthermore, in the 18 cases treated with anthracycline-AraC intensive chemotherapy and the 7 cases treated with low dose AraC, the response rate was not significantly different in LRP+ and LRP- patients. Survival was also similar in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more frequent in MDS than in de novo AML and, as in AML, is only partially correlated with PGP expression. In our experience, however, LRP was not a prognostic factor for response to chemotherapy and survival in MDS.
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PMID:Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes. 964 68

Acral myxoinflammatory fibroblastic sarcoma is a unique low-grade tumor of modified fibroblasts. It characteristically occurs in the distal extremities and has a propensity to recur locally. Forty-four cases that occurred in 22 males and 22 females from 20 to 91 years of age (median, 53 years) were studied. The lesions, which were 1-6 cm (median, 3 cm), occurred in the hands (64%), the feet (20%), the ankles (11%), and the wrists (5%). The patients usually had a long history of a painless mass (median duration, 1 year). Clinically they were suspected to be ganglion cysts, tenosyonovitis, or giant cell tumors of tendon sheath. Initial histologic diagnoses, in most cases, included pigmented villonodular tenosynovitis or various reactive fibroinflammatory processes. Histologically, the lesions were multinodular, poorly delineated, and characterized by a prominent myxoid matrix containing numerous inflammatory cells, including polymorphonuclear leukocytes, eosinophils, lymphocytes, and plasma cells, as well as fibrosis. Amidst the prominent inflammation, and sometimes obscured by it, were scattered, large, bizarre tumor cells with vesicular nuclei, prominent inclusion-like nucleoli, and abundant eosinophilic cytoplasm, which was homogeneous to vacuolated and often contained intracytoplasmic inflammatory cells. Ultrastructurally, the bizarre tumor cells had features of modified fibroblasts, including an abundance of intermediate filaments and dilated rough endoplasmic reticulum. Immunohistochemically, the neoplastic cells revealed strong positivity for vimentin (25 of 25), focal positivity for CD68 antigen (17 of 25) and CD34 (7 of 25); the tumor cells did not express neuroectodermal, epithelial, or lymphoid markers. The Ki67 labeling index with MIB1 was less than 1% in 20 of 25 cases; p53 immunoreactivity (20-90%) was observed in 7 of 25 primary tumors and in 2 of 3 local recurrences. Follow-up information was available in 36 of 44 cases (median, 5 years). Most excisions were either intralesional or marginal. Ten patients underwent amputation, usually after repeated local recurrences. Radiation therapy and chemotherapy were administered in five and two cases, respectively. Twenty-four cases (67%) had at least one local recurrence. A histologically proven lymph node metastasis developed in one patient, whereas another was stated to have lung metastases, although these were not documented histologically. At last follow-up, 23 patients were alive and well, 11 were alive with disease, and 2 were dead of other causes without evidence of tumor. The prominent inflammation and fibrosis seen histologically in acral myxoinflammatory fibroblastic sarcoma simulate a reactive process. The presence of myxoid foci and scattered bizarre cells, which are occasionally multivacuolated, may cause confusion with malignant fibrous histiocytoma and liposarcoma. Based on the protracted clinical course, a high rate of local recurrence (sometimes necessitating amputation), and a low rate of metastasis, we believe these tumors are low-grade sarcomas. The intimate relationship with the synovium, the frequent association with tenosynovitis, and the prominent inflammatory infiltrate suggest that inflammation may play a role in the pathogenesis of acral myxoinflammatory fibroblastic sarcoma.
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PMID:Acral myxoinflammatory fibroblastic sarcoma: a low-grade tumor of the hands and feet. 970 71

Activation of the angiogenic process occurs during tumorigenesis, as does disturbance of cell proliferation and apoptosis. Seeking a potential correlation, we investigated tumor cell apoptosis, proliferation, and angiogenesis in the adenoma-carcinoma sequence of colorectal carcinogenesis using an in situ apoptosis detection kit and MIB-1 and anti-CD34 antibodies in 27 adenomas with low dysplasia, 17 adenomas with high dysplasia, and 26 carcinomas in adenoma, as well as assessed p53 and bcl-2 expressions. The results showed that the potential for apoptosis was augmented, paralleling the increment of proliferation, in adenomas with low dysplasia but diminished when adenomas progressed from low dysplasia to high dysplasia and cancer. A gradual increment of microvessel density was observed during the progression with an increase during transition from low dysplasia to high dysplasia and cancer. Correlation coefficient test showed an inverse correlation between apoptotic index and microvessel density when all of the lesions were taken into account. No apparent impact of aberrant p53 on angiogenesis or bcl-2 on apoptosis was observed in this study. These results suggest that the angiogenesis initiates during transition from low dysplasia to high dysplasia and cancer, which may, in turn, contribute to the reduction of tumor cell apoptosis during colorectal carcinogenesis.
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PMID:Changes of angiogenesis and tumor cell apoptosis during colorectal carcinogenesis. 991 11

Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression. Results from this study suggest that angiogenesis increases as histological abnormality increases in the oral mucosa. The expression of apoptosis regulatory proteins also appears to be altered in a histologically dependent manner. The correlation seen between CD34 expression, cyclin D1 and TUNEL reactive cells suggests that increased angiogenesis, decreased apoptosis and deregulated proliferation occur simultaneously during tumor progression in the oral mucosa. Presence of a mutant p53, increased bcl-2 expression and altered bax expression are also involved in this complex process.
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PMID:Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation. 993 Mar 69

We studied the relationship between angiogenesis (using the CD34 antibody), the presence of human papilloma virus (HPV) infection, HPV E6 protein expression and the accumulation of p53 protein at various phases of tumour progression in the uterine cervix. Expression of CD34, p53 and HPV E6 protein was evaluated by immunocytochemistry. Presence of the mutant p53 was detected using a mutant specific ELISA, and the type of HPV was determined by the Polymerase Chain Reaction. A total of 230 cervical tissue samples were analyzed and included 40 cases of apparently normal cervical epithelium, 37 low grade squamous intraepithelial lesions (SILs), 43 high grade SILs, 36 well-differentiated squamous cell carcinomas (DSCC), 31 moderately differentiated (MDSCC) and 43 poorly differentiated carcinomas (PDSCC). There was an excellent correlation between the extent of angiogenesis and histological abnormality (r = 0.912, p = 0.000004). The least extent of angiogenesis was seen in normal cervical tissue and low grade SILs where the mean (low power) intra lesional vascular density (ILVD) was 12 +/- 1.13 and 25.66 +/- 5.20, respectively. In high grade squamous intraepithelial lesions (SILs), the mean ILVD value was 80.84 +/- 25.57. In well-differentiated squamous cell carcinomas (WDSCC's) the mean value was 144.22 +/- 28.67 while in moderately differentiated squamous cell carcinomas (MDSCC's) the mean value was 166.29 +/- 34.95 and in poorly differentiated tumours (PDSCC's) 192.42 +/- 27.98. The extent of angiogenesis also correlated to presence of HPV (r = 0.505, p = 0.00001). Increased CD34 expression was associated with the presence of HPV types 16 and 18. A similar correlation was also evident in HPV, 16/18 infected cases expressing the E6 protein (r = 0.612, p = 0.000001). CD34 expression also correlated well with p53 accumulation (r = 0.859, p = 0.000002). Presence of HPV infection significantly correlated with the extent of histological abnormality (r = 0.467, p = 0.00001). Expression of E6 also showed this significant correlation (r = 0.644, p = 0.00002). Accumulation of p53 was significantly more elevated in HPV 16-infected lesions (r = 0.518, p = 0.00001) and E6-expressing cells (r = 0.650, p = 0.000004). Only 12 of the 230 cases analyzed showed presence of the mutant p53 protein. Angiogenesis appears to increase with histological abnormality in the uterine cervix. Angiogenesis also appears to be influenced by high risk HPV infection, the expression of the E6 transforming protein and the p53 tumour suppressor protein.
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PMID:Increased angiogenesis in the uterine cervix associated with human papillomavirus infection. 1022 Jul 96


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