No abstract available.
Cyclins*

No abstract available.
Cyclins* ; Hematologic Neoplasms* ; Phosphotransferases*

BACKGROUND: Aberrations of cell cycle-related genes have been reported to contribute to the formation and development of various human tumors. To investigate the gastric carcinogenesis, the expression of cell cycle-related genes (p53, p21wafl/cipl, cyclin D1 and Rb protein) compared to the morphological changes of gastric epithelial lesions were studied. METHODS: The expression of p53, p21wafl/cipl, cyclin D1 and Rb protein was immunohistochemically studied in a series of surgical specimens including the 36 normal/regenerating lesions and the 127 gastric epithelial proliferative lesions (GEPLs). The gastric epithelial proliferative lesions consisted of 25 regenerating epithelia with atypias (REAs), 27 low grade gastric dysplasias (LGDs), 17 high grade dysplasias (HGDs), 24 early gastrc carcinomas (EGCs), and 34 advanced gastric carcinomas (AGCs). RESULTS:The frequency of p53 protein overexpression was significantly associated with histologic grades of GEPLs (p=0.031); occurring in 4% of REAs, in 14.8% of LGDs, in 23.5% of HGDs, in 41.7% of EGCs and 58.9% of AGCs. The p21 wafl/cipl immunohistochemical reaction showed superficial eccentric positivity, representing an inverse correlation with histologic grades of GEPLs (p=0.04); occurring in 83.4% of normal/regenerating lesions, in 80% of REAs, in 74.1% of LGDs, in 29.4% of HGDs, 20.8% of EGCs and 8.8% of AGCs. Although Cyclin D1 and Rb proteins were expressed highly in the GEPLs, the frequency of both proteins were insignificantly associated with histologic grades of GEPLs (p=0.092). However, cases with both the Rb and cyclin D1 positivity were increased with statistical significance along histologic grades of GEPLs (p=0.044). CONCLUSIONS: The altered expression of p53, p21, Rb, and cyclin D1 was considered to be related to dysplastic progression and advancement of malignancy in GEPLs. Therefore, immunohistochemical studies of cell cycle related proteins and a combined analysis may be useful for estimating and following up cases of GEPLs.
Carcinogenesis ; Cell Cycle ; Cyclin D1* ; Cyclins* ; Humans ; Retinoblastoma Protein

BACKGROUND/AIMS: Gastric carcinoma is a major cause of morbidity and mortality in Korea. It evolves through dysplasia to an invasive adenocarcinoma. The carcinogenesis of dysplasia and adenocarcinoma in the stomach was investigated by examining the levels of mutant p53 protein, p21(waf1/cip1), and cyclin D1 expression in gastric dysplasia and invasive adenocarcinoma. METHODS: Formalin- fixed paraffin-embedded tumors were examined immunohistochemically using the monoclonal antibodies to the 53 protein, p21(waf1/cip1) and cyclin D1. RESULTS: Mutant p53 protein, p21(waf1/cip1) and cyclin D1 expression were found in 66.6% (12/18), 72.2% (13/18) and 33.8% (6/18) of dysplasia, and 45.0% (9/20), 15.0% (3/20) and 30.0% (6/20) of invasive adenocarcinoma, respectively. CONCLUSIONS: These results suggest that p21(waf1/cip1), which is controlled by the p53 protein, plays a more important role in the carcinogenesis of the stomach than cyclin D1.
Adenocarcinoma* ; Antibodies, Monoclonal ; Carcinogenesis ; Cyclin D1* ; Cyclins* ; Korea ; Mortality ; Stomach*

No abstract available.
Breast Neoplasms* ; Breast* ; Cyclin D1* ; Cyclins* ; Survival Rate*

BACKGROUND AND OBJECTIVES: The p16, cyclin D1, their partners Cdk4/Cdk6, and pRb constitute a G1 regulatory pathway commomly targeted in tumorigenesis. Genetical, immunochemical, and functional analyses show abnormalities of this pathway in various tumors including head and neck squmaous cell carcinoma. To investigate the clinicopathologic meanings of p16 protein and the relationship between p16 and cyclin D1 in head and neck squmous cell carcinoma. MATERIAL AND METHOD: Formalin-fixed paraffin-embeded tumor materials that were obtained from 37 patient with head and neck squmaous cell carcinoma were analyzed by immunohistochemical staining method using antiserum that were directed against p16 and cyclin D1. RESULTS: 1) Deletion of p16 was found in 67.6% (25/37) of the patients with head and neck squamous cell carcinoma. The deletion was not associated with the clinicopathologic parameters (eg. T and N stages, cell differentiation). 2) Deletion of p16 protein and overexpression of cyclin D1 were identified in 76% (28/37) of the patients with head and neck squmaous cell carcinoma. But deletion of p16 was not affected by the overexpression of cyclin D1 in head and neck squmaous cell carcinoma. CONCLUSION: Deletion of p16 and overexpression of cyclin D1 were identified in head and neck squmaous cell carcinoma. These may abrogate the G1 regulatory pathway. These data suggested that combination of these abnormalities may be important in head and neck turmorigenesis.
Carcinogenesis ; Carcinoma, Squamous Cell* ; Cyclin D1* ; Cyclins* ; Head* ; Humans ; Neck*

OBJECTIVE: To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells. METHODS: C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 microM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 microM fluoxetine, and the expression of Bcl-xL protein was measured using western blot. RESULTS: As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsalpha and Bcl-xL) and down-regulated 77 genes (including Galphai2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsalpha mRNA and a decrease in Galphai2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased. CONCLUSION: These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsalpha expression but also induces Bcl-xL expression, thus inhibiting apoptosis.
Animals ; Apoptosis ; bcl-X Protein ; Cyclins ; Fluoxetine ; Gene Expression ; Glioma ; Rats ; RNA, Messenger

p27kip1, a cyclin dependent kinase inhibitor, has been recognized as a negative regulator of cell cycle. To investigate the role of p27kip1 on progression of cancer and apoptotic pathway, we analyzed p27kip1 expression using immunohistochemical stain in 40 cases of prostatic adenocarcinoma and apoptotic index by TUNEL method in 30 cases of prostatic adenocarinoma. Both were correlated with Gleason grade and Gleason score. Loss of p27kip1 expression was more frequent in prostatic adenocarcinomas of higher score (Gleason score 7 to 10) (60.7%) than in those of lower score (Gleason score 4 to 6) (33.3%) (p<0.05). The value of mean apoptotic index of carcinoma was 1.13+/-0.26, 1.80+/-0.91, 2.06+/-0.79, and 2.12+/-0.82 in grade 2, 3, 4, and 5, respectively, and was positively correlated with grade of carcinoma (p<0.05). Mean apoptotic index of higher Gleason score (score 7 to 10; 2.05+/-0.63) was also significantly increased than in lower Gleason score (score 4 to 6; 1.34+/-0.39) (p<0.05). Mean apoptotic index in cases with and without p27kip1 expression was 1.92+/-0.86 and 1.89+/-0.81, respectively (p>0.05). These results suggest that loss of p27kip1 expression and increased apoptotic index may be the morphologic markers to predict the behavior of prostatic adenocaricnoma. The role of p27kip1 on apoptotic pathway seems to be meager in this study and needs further study.
Adenocarcinoma* ; Cell Cycle ; Cyclins ; In Situ Nick-End Labeling ; Neoplasm Grading ; Phosphotransferases

Recently, cell cycle regulators have been suggested as new prognostic factors of the lung cancer. In this study, we evaluated the expression of cyclin D1, p21, and p53 using the X2-test, with regard to the stage of the patients, histologic type, and histologic differentiation in the 135 cases of non-small cell lung carcinomas (NSCLC). To evaluate the confounding effects among cyclin D1, p21, and p53 on X2-test analysis, we used the Mantel-Haenzel test. The NSCLC in this study included 82 cases of squamous cell carcinoma and 53 cases of adenocarcinoma. Each nuclear staining of cyclin D1, p21, and p53 was observed in 65 cases (48.1%), in 54 cases (40.0%), and in 81 cases (60.0%) of NSCLCs, respectively. Only p53 expression was significantly associated with the stage (stage I, II, IIIa) (p<0.05) and squamous cell carcinoma (p<0.05). On the other hand, cyclin D1 expression was significantly associated with the histologic differentiation. The confounding effects among cyclin D1, p21, and p53 revealed that only p21 expression changed the relationship between p53 and stage. In this regard, further study is needed.
Adenocarcinoma ; Carcinoma, Squamous Cell ; Cell Cycle ; Cyclin D1* ; Cyclins* ; Hand ; Humans ; Lung Neoplasms ; Lung* ; Prognosis*

PURPOSE: Cyclin D1 plays critical roles in the progression of cells through the G1 phase of the cell cycle, which has been implicated as a putative protooncogene, while p53 protein affects different phase checkpoint pathways in the normal cell cycle, which mutations occur in poor prognosis of cancer. We attempted to determine their significance for tumor behavior and prognosis of transitional cell carcinoma(TCCa) of the bladder in human. MATERIALS AND METHODS: Formalin fixed-paraffin embedded tissue specimens from 102 patients with TCCa of the urinary bladder were examined. Nuclear expression was detected by immunohistochemical analysis with a standard avidin-biotin immunoperoxidase method, using the monoclonal antibody cyclin D1 and p53(DO7). RESULTS: Cyclin D1 and p53 protein immunostaining of the nucleus was observed in 49 tumors(48.0%) and 55 tumors(53.9%) respectively. Overexpression of cyclin D1 showed significant inverse correlation with the histological grade and significant correlation with recurrence. Overexpression of p53 protein showed a significant correlation with the histological grade and stage(p<0.01). 65.3% (32 out of 49 tumors), of the cyclin D1 positive tumors exhibited expression for p53 protein(p<0.05). Patients with TCCa coexpressing cyclin D1 and p53 protein had a significantly poorer prognosis than those expressing neither cyclin D1 nor p53 protein(p<0.001). CONCLUSIONS: Cyclin D1 in bladder TCCa is closely related to early tumor differentiation and associated with recurrence. Simultaneous overexpression of both cyclin D1 and p53 protein is related to more aggressive tumor behavior and poorer prognosis. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroup of patients who should be treated with more aggressive therapies.
Carcinoma, Transitional Cell* ; Cell Cycle ; Cyclin D1* ; Cyclins* ; Formaldehyde ; G1 Phase ; Humans ; Prognosis ; Recurrence ; Urinary Bladder*