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)

Typical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall within the spectrum of neuroendocrine lung neoplasms. This paper investigates the immunohistochemical expression of the products of tumour suppressor genes p53 and retinoblastoma (RB), together with proliferation (PCNA and Ki67) and neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated that the phosphoprotein p53 and RB product can be immunolocalized on routine histological material. p53 protein was absent in all typical and atypical carcinoids, while it was abnormally expressed in eight SCLC and one borderline case. RB product was detected in all typical carcinoids and in two atypical carcinoids, while it was consistently absent in the other cases. PCNA-labelled cells were less than 4 per cent in typical carcinoids, about 40 per cent in atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index discriminates between typical and atypical carcinoids. Neuroendocrine differentiation was evaluated by a semi-quantitative method: a mean score value was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show that the decrease in neuroendocrine features from typical carcinoid to SCLC is paralleled by an increase in proliferative activity and by an altered expression of tumour suppressor gene products. The above findings have diagnostic relevance.
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PMID:Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms. 135 31

Recognition of premalignant lesions in the oral epithelium has the potential to increase survival rates for squamous cell carcinoma of the oral cavity. It has previously been reported that cytokeratin 19 (CK19), a 40-kd epithelial cytoskeletal protein within the suprabasal squamous epithelium, is a specific marker of moderate-to-severe dysplasia and carcinoma in situ in oral cavity squamous epithelium. In contrast, normal epithelium and hyperplastic lesions reportedly express CK19 only in the basal layer if at all. The authors chose to test and extend this hypothesis by studying suprabasal CK19 expression and dysplasia of the oral cavity and upper aerodigestive tract in paraffin-embedded specimens that had been fixed in alcohol, a superior fixative for the preservation of cytokeratins. The authors examined 56 alcohol-fixed, paraffin-embedded specimens including 37 from the oral cavity, using two antibodies specific for CK19 (Ks19.1 and 4.62), an antibody to the nuclear proliferation marker, proliferating cell nuclear antigen (PCNA) (19A2), and an antibody to the putative tumor suppressor gene, p53 (pAb1801). The lesions were classified as normal, hyperplasia, mild dysplasia, moderate dysplasia, severe dysplasia/carcinoma in situ, or invasive squamous cell carcinoma, following standard histologic criteria. Immunocytochemically stained sections were scored for the presence or absence of suprabasal CK19, suprabasal PCNA, and p53 positivity, regardless of location. The immunostaining patterns of the two anti-CK19 antibodies were essentially equivalent. Except for one laryngeal specimen, normal epithelium, when positive, showed CK19 expression only in scattered cells throughout the basal layer. Proliferating cell nuclear antigen-positive nuclei were found exclusively in the basal layer. In areas of hyperplasia, CK19 immunostaining was absent or confined to the basal layer in 20 of 38 specimens and was expressed in suprabasal cells in 18 of 38 hyperplastic specimens. Proliferating cell nuclear antigen immunostaining in all cases of hyperplasia was limited to the basal layer. Severe dysplasia and carcinoma in situ showed suprabasal CK19 staining in six of nine specimens and no CK19 staining in three of nine specimens. In contrast, suprabasal PCNA immunostaining was found in all dysplasia and carcinoma in situ cases. p53 expression was detected in three of nine severe dysplasia/CIS specimens and was immunocytochemically undetectable in all normal, hyperplasia, and mild to moderate dysplasia specimens. The authors conclude that suprabasal CK19 expression is neither a sensitive nor a specific marker of premalignancy in oral epithelium and cannot be used to distinguish hyperplasia from dysplasia. In contrast, a strong correlation between suprabasal expression of PCNA, a marker for proliferating cells, and dysplasia/carcinoma in situ was evident.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Markers for dysplasia of the upper aerodigestive tract. Suprabasal expression of PCNA, p53, and CK19 in alcohol-fixed, embedded tissue. 138 38

The MDA-468 human breast cancer cell line displays the unusual phenomenon of growth inhibition in response to pharmacological concentrations of EGF. This study was initiated with the objective of elucidating the cellular mechanisms involved in EGF-induced growth inhibition. Following EGF treatment the percentage of MDA-468 cells in G1 phase increased, together with a concomitant depletion in S and G2/M phase populations, as revealed by flow cytometry of DNA content. The apparent G1 block in the cell cycle was confirmed by treating the cells with vinblastine. DNA synthesis was reduced to about 35% of that measured in control, untreated cells after 48 h of EGF treatment, as measured by the incorporation of [3H]thymidine. DNA synthesis returned to normal following the removal of EGF from the growth-arrested cells. In order to locate the EGF-induced event responsible for the G1 arrest more precisely, we examined the expression of certain cell cycle-dependent genes by Northern blot analysis. EGF treatment did not alter either the induction of the early G1 marker, c-myc, or the expression of the late G1 markers, proliferating cell nuclear antigen, and thymidine kinase. However, EGF-treated cells revealed down regulation of p53 and histone 3.2 expression, which are expressed at the G1/S boundary and in S phase, respectively. These results indicate that EGF-induced growth inhibition in MDA-468 human breast cancer cells is characterized by a reversible cell cycle block at the G1/S boundary.
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PMID:EGF-dependent growth inhibition in MDA-468 human breast cancer cells is characterized by late G1 arrest and altered gene expression. 167 99

The expression of nine proto-oncogenes (c-myc, N-myc, c-fos, c-jun, p53, H-ras, N-ras, c-raf, hst) and other three genes (AFP, PCNA, GST-P) were investigated during spontaneous development to hepatocellular carcinomas (HCCs) in LEC rats. Expressions of c-myc, H-ras, N-ras, c-raf, p53, and PCNA genes were detected but did not significantly change during the development to HCCs in LEC rats. Expressions of N-myc, hst, and AFP genes were not detectable since 5 weeks after birth. Expression of c-fos gene was detected in one out of four HCCs. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. The high expression was decreased in HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development to HCCs in LEC rats. The increased expression of GST-P gene was observed in the liver tissues of LEC rats aged 8 months, and HCCs showed very high expression of GST-P gene. These observations suggest that both c-jun and GST-P genes may play a role in the spontaneous development to HCCs in LEC rats.
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PMID:[A study on expression of various oncogenes and tumor-associated genes in LEC rats spontaneously developing hepatitis and hepatoma]. 169 10

Our laboratory is studying genes involved in the regulation of the balance between cell growth and differentiation during embryonic development in Xenopus. We have analyzed the developmental expression of the proto-oncogenes c-myc, and KiRas 2B, the proliferating cell nuclear antigen (PCNA), and the tumor suppressor gene p53. These genes, usually expressed during cell proliferation, are expressed in the oocyte in large quantities, but the majority of their maternal RNAs are degraded by the gastrula stage. The expression of c-myc and the localization of the protein indicate that c-myc has the characteristics expected for a gene involved in the regulation of the mid-blastula transition, when zygotic expression is turned on in the embryo. Its expression during late development or during regeneration indicates that it enables the cells to remain competent for cycling during organogenesis. In vitro systems that reproduce the principal cellular functions during early development are used as model systems to understand the mechanisms involved in early embryogenesis.
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PMID:Genes and mechanisms involved in early embryonic development in Xenopus laevis. 197 4

We have studied the expressions of nine proto-oncogenes (c-myc, N-myc, c-fos, C-jun, p53, H-ras, N-ras, c-raf, hst) and two other genes (PCNA, GST-P) during the spontaneous development of hepatocellular carcinomas (HCCs) in LEC rats. Expression of c-myc, H-ras, N-ras, C-raf, p53 and PCNA genes was detected, but this did not significantly change during the development of HCCs in LEC rats. Expression of N-myc and hst genes was not detectable. Expression of c-fos gene was detected in one HCC case out of four. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. This high expression was decreased with the development of HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development of HCCs in LEC rats. The pattern of c-jun mRNA augmentation was different from that of GST-P mRNA. These observations suggest that c-jun gene may play a role in the spontaneous development of HCCs in LEC rats.
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PMID:Increased expression of c-jun gene during spontaneous hepatocarcinogenesis in LEC rats. 197 34

The hemopoietic growth factor interleukin 3 (IL-3) supports the survival and proliferation of multipotent and committed progenitor cells in vitro. To elucidate the molecular mechanisms triggered by IL-3 we studied the expression of cell cycle-related genes in a recently established human IL-3-dependent clone (M-07e). No changes in the level of expression of early (c-myc), mid (ornithine decarboxylase), or mid-late G1 (p53, c-myb) cell cycle genes were detected after restoration of IL-3 in deprived cells. The fact that only late G1-S-phase genes [proliferating cell nuclear antigen (PCNA) thymidine kinase (TK), histone H3] are modulated by IL-3 suggests that this factor may control human cell proliferation by acting at the G1-S boundary.
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PMID:Interleukin 3-dependent proliferation of the human Mo-7e cell line is supported by discrete activation of late G1 genes. 199 64

Flow cytometry (FCM) is a useful method for clinical research of oncogene products since it can analyze proteins quantitatively which are located at cell surfaces or inside of cells. Oncogene products are now under study by FCM not only as tumor markers but also as functioning proteins in carcinogenesis. The examples of oncogene products analyzed by FCM are ras, myc, p53, myb and fos; those of cell-proliferation-related proteins are Ki-67, PCNA and DNA polymerase alpha. In some diseases the relationship between these proteins and disease classification, stage, pathophysiology, or prognosis have been clarified. Using dual color FCM of H-ras p21 and DNA, we analyzed the expression of H-ras p21 in human multiple myeloma and leukemias and found that H-ras p21 levels in multiple myeloma strongly correlated to the prognosis of patients (p = 0.03). When AML cells were stimulated by adding G-CSF, it was found that many cells proliferated but some were dying. The percentage of dying cells was small in one AML case whose myeloblasts showed increased expression of H-ras p21 by G-CSF stimulation. Together with other papers reviewed, it is conceivable that H-ras p21 expression is related to cell proliferation and inhibition of cell autolysis. Thus FCM is useful in the classification of the role of oncogene products in carcinogenesis in clinical cases.
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PMID:[Application of flow cytometry to the study of hematologic disorders: analysis of oncogene products]. 214 49

Sinonasal melanoma is a rare malignancy. We present the clinicopathologic review of 18 cases seen at the British Columbia Cancer Agency between 1976 and 1992: 13 men and five women, mean age 66 years (range 32-88). Patients presented with nasal obstruction and bleeding (n = 8), obstruction alone (n = 4), bleeding alone (n = 5) or pain (n = 1). Those with bleeding presented with a shorter duration of symptoms than those with obstruction alone. All patients with obstruction alone died of their disease, while all patients with bleeding alone are alive or have died of an unrelated cause; four out of eight patients with both obstruction and bleeding are alive. There was no significant relationship between treatment modality and outcome. Histologic subtypes included epithelioid (n = 10), spindle-cell (n = 4), small-cell (n = 3) and pleomorphic (n = 1). Eight out of 11 cases from whom samples of paraffin-embedded tissue were available showed more prominent staining for HMB-45 than for S-100. In two cases, only rare (< 0.1%) cells stained for S-100. Cell type, mitotic rate and P53 expression were unrelated to disease outcome. Six out of seven patients with < or = 10% of cells showing intense staining for PCNA were alive or had died of an unrelated cause, while three out of four with > 10% staining died of their disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sinonasal malignant melanoma--a clinicopathologic analysis of 18 cases. 749 62

Thirty seven cases of recurrent gliomas with survival time from 3 month to 13 years were investigated morphologically and immunohistochemically to evaluate progression and transformation of tumors. Using antibodies against PCNA and p53 the proportion of positively marked cells (nuclei) to all tumor cells was assessed at both primary and secondary surgery. This was compared with morphology and survival time between first and second surgery. In 10 cases (27.0%) there were no positively marked cells. In the remaining 27 cases (73.0% of the whole group), the following indices (percents of positive cells) were calculated: for patients with survival below 1 year (mean = 9m) 28.3% PCNA-positive cells and 30.3% p53-positive cells at first operation. For recidiving tumors both indices were lower namely for PCNA 20.9% and for protein p53-26.7%. For patients with survival over 1 year (mean = 4.8y) the index after I operation for PCNA was 25.5% and was higher than found after II operation-22.3%. In contrary, the index for protein p53 was 20.1% after I operation and was lower as compared with the index after II operation-28.2%. Eleven of twelve fibrillary astrocytomas and all five gemistocytic astrocytomas at first operation underwent changes towards malignisation. The immunocytochemical results confirm the high phenotypic differentiation what is reflected in different indices for PCNA and p53 of tumors.
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PMID:PCNA and protein P53 in recurrent supratentorial glial brain tumors: studies on correlation between morphology and tumor progression. 749 34


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