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

Non-squamous cell carcinoma is a rare but distinct neoplasm of the upper aerodigestive tract. Among these carcinomas, basaloid-squamous cell carcinoma (BSCC) has frequently been confused with adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma of the upper aerodigestive tract. In this study, we examined immunohistochemically the expression of differentiation-related substances, including cytokeratin (CK) subtypes, p53 and p27, and cell adhesion-related molecules E-cadherin and alpha-catenin to clarify the biological features of these neoplasms. We studied seven cases of BSCC of the oesophagus, five cases of ACC and seven cases of mucoepidermoid carcinoma. Squamous cell carcinoma and adenocarcinoma of the oesophagus and trachea were also studied for comparison. Among the cytokeratin subtypes examined, CK14, CK17 and CK19 immunoreactivity was detected in BSCC. ACC and mucoepidermoid carcinoma were immunopositive for CK8, CK14 and CK17 and for CK8, CK14, CK17 and CK19, respectively. These findings suggest that CK subtypes, especially CK8, CK14 and CK17, are useful in differentiating these malignancies. BSCC was more frequently associated with decreased E-cadherin and alpha-catenin immunoreactivity than ACC and mucoepidermoid carcinoma. Nuclear p53 immunoreactivity was detected more frequently in BSCC (5 out of 7) than in ACC (2 out of 5) and mucoepidermoid carcinoma (4 out of 7). There were no significant differences in p27 immunoreactivity among these carcinomas. Carcinoembryonic antigen (CEA) immunoreactivity was detected in mucoepidermoid carcinoma (2 out of 7), SCC (8 out of 11) and adenocarcinoma (9 out of 9), but it was not detected in BSCC (7) or ACC (5). Carbohydrate antigen 19-9 (CA19-9) immunoreactivity was detected only in mucoepidermoid carcinoma (4 out of 7) and adenocarcinoma, but not in BSCC, ACC, or SCC. These findings indicate that BSCC, ACC and mucoepidermoid carcinoma are distinct neoplasms arising in the upper aerodigestive tract. In addition, decreased expression of E-cadherin and alpha-catenin proteins and increased p53 expression in BSCC may be correlated with aggressive behaviour.
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PMID:Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract. 1081 Apr 23

The aim of the study was to verify a relationship between P53 protein expression and prognosis in laryngeal cancer. P53 protein levels were studied by immunohistochemical staining of 80 primary laryngeal SCC. Forty five tumours (56.3%) had a positive staining for P53 protein. There was no correlation between P53 overexpression and disease-free survival. No prognostic significance of P53 protein expression in laryngeal cancer was found.
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PMID:[Protein P53 in laryngeal cancer--no evidence of prognostic value]. 1135 78

Cervical lymph node metastasis is the most common recurrence pattern of head and neck squamous cell carcinoma (HNSCC), and it is usually treated with radiation therapy and/or neck dissection. There has long been a desire for markers useful in predicting radiosensitivity to enable assignment of patients with recurrent head and neck cancer to clinical trials to improve their survival rates and quality of life. A total of 43 cases of HNSCC treated with whole or elective neck irradiation (total dose, 26-70 Gy; median, 60 Gy) for recurrent metastatic SCC in neck lymph nodes after neck dissection between 1992 and 1999 were the subject of this study. The relationship between radiosensitivity and clinicopathological and histopathological factors, including the Ki-67-labeling index for cell proliferation, p53 immunoreactivity and microvessel density (MVD), in surgical neck lymph node specimens were investigated by univariate and multivariate analysis. Of the 43 patients, 31 had recurrent tumors in neck lymph nodes after radiotherapy. Univariate analysis revealed significant associations between radiosensitivity and both high grade of keratinization (p=0.033) and low MVD (p=0.004), and marginally significant associations between radiosensitivity and grade of differentiation of the cancer in the lymph nodes (p=0.070). Multivariate analysis showed that only MVD had predictive value (p=0.016). Tumors with a high MVD possessed a significantly better neck control rate than tumors with a low MVD (p=0.004) by Kaplan-Meier analysis. MVD can be used as a good predictive marker for radiosensitivity of metastatic HNSCCs in cervical lymph nodes after neck dissection.
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PMID:Microvessel density predicts the radiosensitivity of metastatic head and neck squamous cell carcinoma in cervical lymph nodes. 1171 80

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and gamma-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 +/- 70 mm(3) at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 +/- 220 mm(3). Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 +/- 12.7 days) compared to those in the empty vector group (67.3 +/- 6.8 days). After treatment with 5-FU (5 microg/day), PLM (50 microg/day), CDDP (10 microg/day) and gamma-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 +/- 22.7, 123.0 +/- 22.1, 136.3 +/- 24.0 and 143.0 +/- 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 +/- 14.8, 85.7 +/- 13.3, 97.5 +/- 16.0 and 100.7 +/- 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21(waf1/cip1) and suppressed expression of Bcl-2, Bcl-X(L) and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and gamma-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.
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PMID:Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and gamma-rays regulating expression of the BCL-2 family proteins, COX-2 and p21. 1174 42

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism.
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PMID:Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies. 1174 30

A natural animal model for human head and neck squamous cell carcinoma (H/N SCC) has not been described. The domestic cat has a high spontaneous occurrence of oropharyngeal SCC, which is similar to the human disease in aggressiveness and incurability. We have developed a cell line (SCCF1) from a laryngeal SCC of a cat. Keratinocytes were maintained in culture for greater than 50 passages. SCCF1 had strong cytokeratin immunohistochemical staining, weak vimentin staining, and no p53 staining. Ultrastructual features included cytokeratin filaments and desmosomes, as well as features of anaplasia (irregular cytoplasmic and nuclear margins, surface filopodia, and abnormal intermediate filament production). Karyotype analysis revealed aneuploidy, with a stemline chromosomal number of 34. The cells grew logarithmically for 6 d until confluency. SCCF1 expressed parathyroid hormone-related protein (PTHrP) messenger ribonucleic acid (mRNA) and protein, and secreted the protein into the medium. Treatment of SCCF1 with transforming growth factor-beta increased PTHrP production but did not affect PTHrP mRNA stability. Reverse transcriptase-polymerase chain reaction was used to amplify a 282-base pair region of feline PTHrP mRNA, encoding portions of the pre-pro and coding regions. The complementary deoxyribonucleic acid (cDNA) was cloned and sequenced. The cDNA and the predicted amino acid sequences had a high degree of homology to human and canine PTHrP. RT-PCR was used to confirm alternate splicing of PTHrP mRNA for translation of PTHrP 1-139 and PTHrP 1-141. The SCCF1 cell line will permit mechanistic experiments on genetic dysregulation in neoplastic keratinocytes of the feline oropharynx, and development of an in vitro model for H/N cancer.
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PMID:Feline head and neck squamous cell carcinoma cell line: characterization, production of parathyroid hormone-related protein, and regulation by transforming growth factor-beta. 1177 73

AIM:To determine the extent of apoptosis and its possible relationship with the changes of p53, Waflp21, bcl-2, and c-myc at different stages of esophageal carcinogenesis.METHODS:Two hundred and forty-one esophageal biopsy samples from symptom-free subjects and 38 surgically resected esophageal carcinoma tissues from a high-risk population for esophageal cancer in Henan, China were used in this study.Apoptotic cells and apoptotic bodies were identified by well-established morphological criteria. The extent of apoptosis and its possible relationship with the rate of cell proliferation (PCNA) and changes of p53, Waf1p21, bcl-2,and c-myc were analyzed in samples with esophageal precancerous and cancerous lesions.RESULTS:The apoptotic cells, identified morphologically, were located in the same proliferative compartment of hyperproliferative cell population in the esophageal epithelia as the cells immunostaining-positive for p53, bcl-2, c-myc and PCNA.The apoptotic indices (total number of apoptotic cells and apoptotic bodies per mm(2) of the tissue section) were low in the normal epithelia,and increased significantly as the lesions progressed from BCH to DYS and to SCC.The extent of apoptosis correlated well with the cell proliferation indices based on PCNA. The total number of positive cells for p53 stain was much higher than that of apoptotic cells. No difference in apoptotic indices was found between p53-positive and p53-negative samples. Waf1p21-positive cells resided in cell layers were higher in number than p53 and PCNA-positive cells. The number of immunostaining positive cells for Waflp21 increased slightly from normal to BCH,but decreased in DYS and SCC. Positive staining samples for bcl-2 and c-myc increased as the lesions progressed from BCH to DYS and to SCC. No apparent correlation between apoptosis and Waf1p21, bcl-2 or c-myc expression was observed.CONCLUSION:The extent of apoptosis was low in normal esophageal epithelium and increased as the lesions progressed. The apoptotic cells were located in the same hyperproliferative cell compartment as cells immunostaining-positive for p53, bcl-2,c-myc and PCNA,but no apparent correlation between apoptosis and these parameters was observed,possibly due to the complexities of molecular changes in esophageal carcinogenesis.
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PMID:Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China. 1181 1

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

Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.
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PMID:Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms. 1196 27

The correlation between inactivation of the TP53 gene through mutation or the presence of high-risk human papillomavirus (HPV) DNA and intrinsic paclitaxel sensitivity was studied in 27 gynaecological cancer cell lines. IC(50) values, as a measure of drug sensitivity, were determined using a 96-well clonogenic assay. TP53 mutations were investigated with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. HPV status was studied with PCR using HPV consensus primers. TP53 mutations were found in 7/11 vulvar SCC cell lines. Only 2/9 endometrial and 1/7 ovarian cancer cell lines carried TP53 mutations. One vulvar and one endometrial cancer cell line were HPV-positive; both carrying HPV type-16 DNA. Thus, TP53 was functionally normal in 3/11 vulvar, 6/9 endometrial and 6/7 ovarian cancer cell lines. The IC(50) values for paclitaxel were 0.60-2.9, 0.49-2.3 and 0.40-3.4 nM in the vulvar, endometrial and ovarian cancer cell lines, respectively. No correlation could be demonstrated between inactivation of the TP53 gene and paclitaxel sensitivity in vitro; the cell lines were evaluated as one group or according to their anatomical origin or histology. Previous reports have given inconclusive results, partly due to the cell types used, i.e. normal, cancerous or transformed cells. Our results support the view that paclitaxel sensitivity of tumour-derived cancer cell lines is not related to the TP53 status.
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PMID:Mutations of TP53 do not correlate with the sensitivity to paclitaxel--a study using 27 gynaecological cancer cell lines. 1217 96


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