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)

The aim of the present study is to study the relationship between cyclin D1 and the clinicopathological features of oral squamous cell carcinomas. The cyclin D1 and p53 expression in oral squamous cell carcinomas from 56 patients (45 men, 11 women) was studied by immunohistochemistry using monoclonal antibodies. The correlation between cyclin D1 and the clinicopathological features of the oral cancers was evaluated. Cyclin D1 expression was found in 63% of oral squamous cell carcinomas; it was often weak but was more frequently positive in high-grade lesions (P=0.019). The expression was positively correlated with p53 expression (P= 0.06). Radiation therapy did not alter the expression of either cyclin D1 or p53 proteins. Expression of these proteins was not related to the age, gender or survival of the patients, or to stages of the tumors. The cyclin D1 expression was more frequently seen in patients with squamous cell carcinomas of oropharynx, palate, floor of mouth and gingiva. To conclude, cyclin D1 was frequently expressed in oral squamous cell carcinomas. This expression was related to the grade of the tumors and was not similar in various regions in the oral cavity, which may indicate the different tumor biology of cancers from these regions.
 ...
PMID:Cyclin D1 expression in oral squamous cell carcinomas: clinicopathological relevance and correlation with p53 expression. 1076 94

Esophageal squamous cell carcinoma (ESCC) is a frequent form of cancer that shows striking variations in geographic distribution, reflecting exposure to specific environmental factors that are still poorly defined. ESCC develops as the result of a sequence of histopathological changes that typically involves esophagitis, atrophy, mild to severe dysplasia, carcinoma in situ and finally, invasive cancer. Genetic changes associated with the development of ESCC include mutation of the p53 gene, disruption of cell-cycle control in G1 by several mechanisms (inactivation of p16MTS1, amplification of Cyclin D1, alterations of RB), activation of oncogenes (e.g., EGFR, c-MYC) and inactivation of several tumor suppressor genes. Loss of heterozygosity on chromosome 17q25 has been linked with tylosis, a rare autosomal dominant syndrome associated with high predisposition to ESCC. Whether this locus is also involved in sporadic ESCC remains to be elucidated. Chronic esophagitis is a frequent occurrence in populations at high risk of ESCC. These lesions often show focal accumulation of p53 protein and in some instances, patches of positive cells in esophagitis area at the margins of tumors were found to contain a mutation in the p53 gene. This observation is consistent with field cancerization in the esophagus and suggests that esophagitis may represent an interesting target for early detection of ESCC as well as for intervention strategies.
 ...
PMID:Genetic steps in the development of squamous cell carcinoma of the esophagus. 1076 43

Expression of cell cycle modulators at the G1-S boundary, the retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D1 as well as Ki-67 was investigated with 39 extrahepatic bile duct carcinomas (BDC). The Ki-67 labeling index (LI) was higher in cases with poor differentiation, lymph node metastasis and stage III or IV. Cyclin D1 overexpression was seen in 14 cases (35.8%). This phenomenon could be observed more frequently in cases of hilar carcinoma and with poor differentiation, perineural invasion, lymphatic invasion and lymph node metastasis. Furthermore, Ki-67 LI was higher in cyclin D1 overexpressing cases. p27 expression showed inverse relationships with Ki-67 LI, lymph node metastasis and aberrant p53 expression. Although p16 and p21 expression significantly correlated with lymph node metastasis and cyclin D1 overexpression, respectively, they were not related to Ki-67 LI. pRb expression was observed in all cases. Although the LI was lower in carcinoma of upper and middle bile ducts, no correlation was established between pRb expression and other clinicopathological parameters including Ki-67 LI. Aberrant p53 expression was observed in 13 cases (33.3%) and Ki-67 LI was significantly higher in these cases. These findings suggest that p27 and cyclin D1 strongly correlate with BDC proliferation and reflect the biological aggressiveness of this carcinoma.
 ...
PMID:Expression and clinical significance of the G1-S modulators in carcinoma of the extrahepatic bile duct. 1076 77

Tumour growth is regulated by a balance between proliferation, growth arrest and programmed cell death (apoptosis). Until recently, the majority of the studies dealing with oncogenesis has been focused on the regulation of cell proliferation. There is now growing understanding that control of growth arrest and apoptosis play key roles in the development of human cancer and in cancer treatment. Some of the more heavily studied proteins of importance for the control of growth arrest and apoptosis are p53, p21, bcl-2 and bax. Alterations in the p53 protein may lead to malignant transformation and defect therapy response, most likely as a result of defective p53-dependent apoptosis. In addition, p21 (WAF1/CIP1) is involved in cell-cycle arrest and probably in induction of p53-dependent apoptosis. Proteins belonging to the bcl-2 family are also important for normal apoptosis. Overexpression of bcl-2 protein is thought to reduce the apoptotic capacity, while bax protein seems to be necessary for induction of apoptosis. In this study, we have immunostained tissues from 93 primary colon carcinomas and have examined the expression of p53, p21 (WAF1/CIP1), bcl-2 bax, pRb and cyclin D1 for evaluation of their roles in colon-cancer progression. A highly significant association between p53 accumulation and downregulation of p21 (WAF1/CIP1) was seen. We also found a strong association between reduced/absent p21 and the development of metastases and death due to cancer disease. Cyclin D1, bcl-2 and bax protein failed to have independent prognostic impacts. Bcl-2 and bax protein levels showed an inverse relationship. The results of the present study indicate that reduced p21 protein levels play an important role in progression of colon cancer. We concluded that evaluation of p21 expression in primary colon carcinomas at the time of surgery might be a valuable tool in defining patients with a high risk of developing metastases.
 ...
PMID:Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. 1078 80

The effects of gamigeonsim-tang (GGT) on cellular proliferation and expression of cell cycle-related genes were investigated in human smooth muscle cell HISM. HISM cells were treated with an aqueous extract of GGT. Cellular proliferation was investigated by an immunocytometric analysis of PCNA expression and a flow cytometric analysis of the cell cycle progression. Reduced expression of PCNA and a significant accumulation of G1 phase cells were observed following treatment, indicating that GGT inhibits cellular proliferation of human smooth muscle cells. To explore whether GGT affects the transcription of cell cycle-regulating genes, we evaluated mRNA expression of p53, p21Waf1 PCNA, Cyclin D1, Cdc2, Histone H3, c-Myc, and c-Fos using a quantitative RT-PCR analysis. While increased expressions of two negative cell cycle regulators, p53 and p21Waf1 were found, reduced expressions of cell cycle stimulators, PCNA, c-Fos, and c-Myc, were identified following treatment. Taken together, our study demonstrates that GGT inhibits cellular proliferation of human smooth muscle cell through the up- and down-regulation of growth-inhibiting and growth-promoting genes, respectively.
 ...
PMID:Inhibition of human smooth muscle cell proliferation by gamigeonsim-tang through the transcriptional regulation of cell cycle-controlling genes. 1079 17

Studies on cell cycle regulation and cancer genetics have revealed that multiple cell cycle regulatory proteins play key roles in oncogenesis. These can be categorized in three sets. First; p16INK4-Cyclin D1-RB pathway, which controls G1 to S progression of the cell cycle, second; p53 pathway, which is involved in DNA damage repair, and third; p27KIP1 CDK inhibitor, a negative regulator of cell cycle, and decreased expression of which has been correlated to poor prognosis in cancer patients. Among these, p16INK4, RB and p53 are tumor suppressor genes, and p27 has been pointed out to be haplo-insufficient for tumor suppression. Involvement of these cell cycle regulatory proteins in lung cancer will be discussed.
 ...
PMID:[Deregulation of cell cycle control in lung cancer]. 1082 44

Malignant uveal melanoma is the commonest primary intraocular tumour in adults. It metastasizes frequently and 50% of patients die within 10 years of diagnosis. The expression of cyclin D1, p53, and MDM2 in uveal melanoma and their relationship to metastasis-free 5-year survival was determined, in order to investigate whether these proteins help to distinguish those patients with a favourable prognosis from those with a poorer one. Ninety-six eyes enucleated for uveal melanomas were immunohistochemically analysed for the protein expression of cyclin D1 and related cell-cycle markers, p53 and MDM2. The evaluation of the specimens was undertaken by two independent pathologists without knowledge of the outcome. Statistical analysis of clinical, morphological, and immunohistological features was performed. A 'favourable outcome' was defined as survival of at least 5 years after diagnosis, without metastases (n=57). An 'unfavourable outcome' was defined as death from metastases within the first 5 years after diagnosis of uveal melanoma (n=39). Cyclin D1 positivity (>15% positive tumour cells) as well as p53 positivity (>15% positive tumour cells) was associated with an unfavourable outcome (for cyclin D1: odds ratio=4. 2, 95% confidence interval 1.5-11.8, p=0.006; for p53: odds ratio=3. 2, 95% confidence interval 1.1-9.3, p=0.03). In addition, cyclin D1 positivity was associated with the presence of extraocular extension of the tumour (p=0.01), with the mixed or epithelioid cell type (p=0. 02), and with the tumour cell MIB-1 positivity (p=0.0001). MDM2 immunoreactivity of the tumour cells showed a potential correlation with clinical outcome (odds ratio=2.1, 95% confidence interval 0.8-5. 8, p=0.13). Multiple logistic regression models showed that cyclin D1 positivity is an independent prognostic factor after control for other prognostic markers. The expression of cyclin D1 in uveal melanoma is associated with a more aggressive course and histologically unfavourable disease. This could serve as a further independent prognostic factor in uveal melanoma.
 ...
PMID:The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma. 1086 67

Depsipeptide, FR901228, a novel cyclic peptide inhibitor of histone deacetylase with a unique cytotoxicity profile is currently in phase I clinical trials. Here we demonstrate that, in addition to G2/M arrest, FR901228 causes G1 arrest with Rb hypophosphorylation. In vitro kinase assays demonstrated no direct inhibition of CDK activity, however, an inhibition was observed in CDKs extracted from cells exposed to FR901228. Cyclin D1 protein disappeared between 6 and 12 hours after treatment with FR901228, whereas cyclin E was upregulated. While it did not induce wt p53, FR901228 did induce p21(WAF1/CIP1)in a p53-independent manner. Cell clones lacking p21 were not arrested in G1 phase, but continued DNA synthesis and were arrested in G2/M phase following FR901228 treatment. Finally, FR901228 blunted ERK-2/MAPK activation by EGF whereas early signal transduction events remained intact since overall cellular tyrosine phosphorylation after EGF stimulation was unaffected. Thus, FR901228, while not directly inhibiting kinase activity, causes cyclin D1 downregulation and a p53-independent p21 induction, leading to inhibition of CDK and dephosphorylation of Rb resulting in growth arrest in the early G1 phase. In contrast to the G1 arrest, the G2/M arrest is p21-independent, but is associated with significant cytotoxicity.
 ...
PMID:P21-dependent g(1)arrest with downregulation of cyclin D1 and upregulation of cyclin E by the histone deacetylase inhibitor FR901228. 1095 88

Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55% of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p=0.81), high levels of protein expression (>50% of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p=0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p>0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p=0.029 and p=0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival.
 ...
PMID:Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Aberdeen Colorectal Initiative. 1096 85

Cyclin D1, P53 and P21 (WAF1) are cell cycle regulating proteins, playing a crucial role in oncogenesis of a large number of human malignancies, and loss of activity of P53 and P21 (WAF1) proteins seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. To find out their mutual relations we investigated the expression of cyclin D1, P53 and P21 (WAF1) in 122 colorectal cancers by immunohistochemistry. Positivity for cyclin D1 was found in all the cases (100%), positivity for P53 in 96 cases (70%) and positivity for P21 in 48 cases (39%). Statistical analysis revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and also between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity. These data suggest that in colorectal cancer induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. Wild-type P53, which is undetectable by immunohistochemistry, induces transcriptionally P21 (WAF1) and in tumours it may cause its accumulation, while mutations of the P53 may result in a sufficient increase of intracellular protein having no ability to transactivate P21 (WAF1). Moreover P21 (WAF1) as the main cyclin-dependent kinases (CDKs) inhibitor may also inhibit the activity of the cyclins, thus overexpression of P21 (WAF1) may result in reduced level of cyclin D1.
 ...
PMID:Comparative evaluation of the expression of cell cycle regulating proteins: cyclin D1, P53 and P21 (WAF1) in colorectal cancer. 1097 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>