Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Microsatellite Repeats ; Mutation ; Neoplasm Grading ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Pathology, Molecular ; Receptor, Fibroblast Growth Factor, Type 3 ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology

To evaluate the relationship between p27Kip1 low expression in breast cancer and its prognostic implication in breast carcinoma patients. Methods All data that were associated with the study of the relationship between p27Kip1 and the prognosis for breast cancer was pooled from Cochrane library, PubMed, Embase and Medlinebase. The outcome was measured using the risk ratio (RR). Data pooling was performed by RevMan 4. 2. Results 6457 patients from 20 studies were included in this meta-analysis. RR estimate of overall survival (OS) for patients with low level p27Kip1 was 2.07 [1.66,2.60] (P<0.01). For disease free survival (DFS), the pooled RR was 1.27 [1.10,1.47] (P<0.05). The combined RR estimate of relapse free survival (RFS) for patients with low level of p27Kip1 was 1.49 [0.92, 2.42] (P >0.05). In patients with lymph node negative breast carcinoma, the combined RR for OS and RFS were 1.98 [1.34,2.91] (P <0.01) and 1.28 [0.45,3.65] (P > 0.05), respectively. Among the patients with lymph node positive breast carcinoma, the combined RR for OS and RFS was 1.92 [1.31, 2.82] (P=0.0009) and 1.35 [0.96,1.89] (P>0.05) respectively. Conclusions Low level of p27Kip1 appears to be an independent prognostic factor to OS and DFS of breast cancer patients but not to RFS. Additional studies with large patient number and widely accepted practical methods are required to derive the precise prognostic significance of p27Kip1 expression in breast cancer patients.
Biomarkers, Tumor ; analysis ; Breast Neoplasms ; diagnosis ; genetics ; metabolism ; pathology ; Carcinoma ; diagnosis ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; genetics ; metabolism ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Lymphatic Metastasis ; diagnosis ; physiopathology ; Neoplasm Staging ; methods ; Prognosis

OBJECTIVETo detect the expression of skp2 and p27kip1 in human renal cell carcinoma (RCC) using tissue chip technique, and evaluate the relationship between the proteins and the biological behavior of RCC.

METHODSTissue chip technique and immunohistochemical SP method was used to detect the expression of skp2 and p27kip1 in normal and tumor tissues.

RESULTSThe positivity rate of Skp2 in RCC was significantly higher than that in normal renal tissues (P=0.025). The positivity rate of Skp2 expression in RCC was significantly correlated to poor differentiation of the tumor (P=0.002), and was not associated with the patients gender, age, tumor size, lymph node metastasis and stages of RCC (P>0.05). The positivity rate of p27kip1 in RCC was significantly lower than that in normal renal tissues (P=0.007). The positivity rate of p27kip1 expression was inversely correlated to the malignancy and stage of RCC (P<0.05), but not with the patients' age, gender, lymph node metastasis and tumor size (P>0.05). An inverse correlation was noted between Skp2 and p27kip1 expressions (r= -0.273, P=0.014).

CONCLUSIONOverexpression of Skp2 protein may lead to decreased p27kip1 level in RCC, indicating its involvement in the carcinogenesis and development of RCC.

Adult ; Aged ; Carcinoma, Renal Cell ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p27 ; biosynthesis ; Female ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; S-Phase Kinase-Associated Proteins ; biosynthesis ; Tissue Array Analysis ; Young Adult

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.
Adenocarcinoma, Follicular/diagnosis/metabolism ; Carcinoma, Papillary, Follicular/diagnosis/metabolism ; Cyclin D1/analysis ; Cyclin-Dependent Kinase Inhibitor p27/analysis ; Diagnosis, Differential ; Galectin 3/analysis ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/analysis ; Keratin-19/analysis ; Keratins/analysis ; Sensitivity and Specificity ; Thyroid Gland/chemistry/*pathology ; Thyroid Nodule/*diagnosis/metabolism ; Tumor Markers, Biological/*analysis

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) that is a critical factor in carcinogenesis, but precise mechanism of its action remains to be elucidated. Here we evaluated the inhibitory effect of celecoxib on cell growth of human oral squamous cell carcinoma (OSCC) YD-10B, which was established to be used as in vitro OSCC model, and identified celecoxib-regulated protein by proteomics techniques. Celecoxib (IC50=37 micrometer) inhibited the growth of YD-10B cells with the decrease of COX-2 protein expression. Its inhibition could be linked in the arrest of G1 phase with increased levels of p(27)protein, a specific CDK inhibitor. Using proteomics, the 10- to 20-fold increase of heterogeneous nuclear ribonuclear protein C (hnRNP C), which has been suggested to be related with the translation of p(27)mRNA, was observed in celecoxib-treated YD-10B cells. In summary, celecoxib has a potential to induce the protein expression of hnRNP C and its increase subsequently induce the translation of p(27)mRNA, which trigger the inhibition of cell growth via p(27)-regulated cell cycle arrest in YD-10B cells. In addition, YD-10B cells could be useful to study the pathological mechanism of OSCC.
Tumor Cells, Cultured ; Tongue Neoplasms/metabolism/pathology ; Sulfonamides/*pharmacology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Pyrazoles/*pharmacology ; Proteomics/methods ; Male ; Immunoblotting ; Humans ; Heterogeneous-Nuclear Ribonucleoprotein Group C/analysis/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Cyclooxygenase Inhibitors/pharmacology ; Cyclooxygenase 2/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/analysis/metabolism ; Cell Survival/drug effects ; Cell Proliferation/*drug effects ; Cell Line, Tumor ; Cell Cycle/drug effects ; Carcinoma, Squamous Cell/metabolism/pathology ; Aged ; Actins/metabolism

To evaluate the expression of cyclin dependent kinase inhibitor P27(Kip1) in leukemia and to investigate its clinical significance, the P27(Kip1) protein in bone marrow or peripheral blood samples from 82 cases of leukemia was measured by Western blot and enhanced chemoluminescence (ECL). The results showed that the expression of P27(Kip1) protein in ALL was higher than that in ANLL (P = 0.033) and also that in CML (P = 0.008). P27(Kip1) expression in CLL was higher than that in CML too (P = 0.017). In acute leukemia, the effective rate (CR and PR) of initial chemical therapy in the group of P27(Kip1) > 0.655 was higher than that in the group of P27(Kip1) < or = 0.655, P = 0.041. For ANLL and ALL patients, the survival time in the group of P27(Kip1) > 0.655 was longer than that in the group of P27(Kip1) < or = 0.655, P = 0.0065. There were similar statistical significance for ANLL and ALL patients, P = 0.0271 and P = 0.0266 respectively. There was a negative correlation between chromosomal abnormalities and P27(Kip1) expression in ALL patients (r = -0.775, P = 0.04). The expression of P27(Kip1) protein appeared nothing to do with sex, age, white blood cell number, blast cell number in peripheral blood, serum LDH or uric acid. In conclusion, the expression level of P27(Kip1) protein is in relation to the effect of initial chemical therapy and survival time, so that the lower P27(Kip1) expression may associated with poor prognosis in acute leukemia.
Adolescent ; Adult ; Aged ; Blotting, Western ; Cell Cycle Proteins ; analysis ; Child ; Child, Preschool ; Chromosome Aberrations ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Leukemia ; drug therapy ; genetics ; metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; genetics ; metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; metabolism ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; metabolism ; Survival Rate ; Tumor Suppressor Proteins ; analysis

Adult ; Aged ; Cell Cycle Proteins ; analysis ; Coal Mining ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Immunohistochemistry ; Lung ; chemistry ; pathology ; Male ; Middle Aged ; Occupational Diseases ; metabolism ; Pneumoconiosis ; metabolism ; Tumor Suppressor Proteins ; analysis