To investigate the expression of CD10 in tumor-associated fibroblasts (TAF) in colorectal adenomas and its relation to cancerization and recurrence of adenoma.Tissue samples of low-grade adenoma (=50), high-grade adenoma (=50) and colorectal adenocarcinoma (=50) were collected, and tissue samples at the distal margin of corresponding colorectal lesions were taken as controls. The expression of CD10 in the stromal TAFs, and the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells were detected by immunohistochemistry (Envision). The correlation of CD10 expression in stromal TAFs with the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells was analyzed by Spearmen. One hundred samples of low-grade colorectal adenoma were collected, including 57 non-recurrent cases and 43 recurrent cases (16 cases of recurrent adenoma and 27 cases of recurrent adenocarcinoma); the expression of stromal TAF CD10 were determined and compared among groups.There was no TAF in normal colorectal mucosa. The expression rates of TAF CD10 in low-grade adenoma, high-grade adenoma and colorectal adenocarcinoma were 22%, 50% and 78%, respectively (all<0.05). The expression of Ki-67 and β-catenin in low-grade adenoma, high-grade adenoma, colorectal adenocarcinoma was on a rising trend (all<0.01). The expression of CyclinD1 in high-grade adenoma was higher than that in colorectal adenocarcinoma and low-grade adenoma (all>0.05). The expression of p53 in colorectal adenocarcinoma and high-grade adenoma was higher than that in low grade adenoma (all<0.01). The expression of TAF CD10 was correlated with the expression of p53, Ki-67 and β-catenin-nucleus(=0.264、0.307、0.320, all<0.01),but not correlated with CyclinD1 and β-catenin-membrane (=0.012、-0.073, all>0.05). The TAF CD10 level was significantly higher in low-grade adenoma with recurrence than that in those without recurrence (<0.05).The expression of CD10 in recurrent colorectal adenocarcinoma was higher than that in recurrent adenoma (<0.05).The expression of TAF CD10 is increased gradually in the process of adenoma-cancer, indicating that it may play an important role in the canceration of adenoma. Adenomas with high expression of CD10 TAF are likely to be recurrent and cancerized, and detection of TAF CD10 combined with p53, Ki-67 and β-catenin may be of value in predicting canceration or recurrence of colorectal adenoma.
Adenocarcinoma ; chemistry ; genetics ; Adenoma ; chemistry ; genetics ; Biomarkers, Tumor ; analysis ; Cancer-Associated Fibroblasts ; chemistry ; Carcinogenesis ; chemistry ; Colorectal Neoplasms ; chemistry ; genetics ; Cyclin D1 ; analysis ; Disease Progression ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; chemistry ; Neprilysin ; analysis ; Predictive Value of Tests ; Tumor Suppressor Protein p53 ; analysis ; beta Catenin ; analysis

PURPOSE: The effect of cyclin D1 overexpression on breast cancer outcomes and prognosis is controversial, even though amplification of the cyclin D1 gene, CCND1, has been shown to be associated with early relapse and poor prognosis. In this study, we examined the relationship between cyclin D1 overexpression and disease-specific survival (DSS). We also analyzed survival in patients who experienced recurrence. METHODS: We retrospectively analyzed data from patients diagnosed with ductal carcinoma between April 2005 and December 2010. We examined clinicopathologic factors associated with cyclin D1 overexpression and analyzed the influence of cyclin D1 on recurrence-free survival and DSS. RESULTS: We identified 236 patients diagnosed with primary breast cancer who completed all phases of their primary treatment. Cyclin D1 overexpression was significantly associated with longer DSS (5-year DSS, 89.9% in patients without cyclin D1 overexpression vs. 98.9% in patients with cyclin D1 overexpression; p=0.008). Multivariate analysis also found that patients with cyclin D1 overexpressing tumors had significantly longer disease-specific survival than patients whose tumors did not overexpress cyclin D1, with a hazard ratio for disease-specific mortality of 7.97 (1.17-54.22, p=0.034). However, in the group of patients who experienced recurrence, cyclin D1 overexpression was not significantly associated with recurrence-free survival. Cyclin D1 overexpression was significantly associated with increased survival after disease recurrence, indicating that cyclin D1 overexpression might be indicative of more indolent disease progression after metastasis. CONCLUSION: Cyclin D1 overexpression is associated with longer DSS, but not recurrence-free survival, in patients with breast cancer. Longer postrecurrence survival could explain the apparent inconsistency between DSS and recurrence-free survival. Patients with cyclin D1-overexpressing tumors survive longer, but with metastatic disease after recurrence. This information should spark the urgent development of tailored therapies to cure these patients.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Cyclin D1* ; Cyclins* ; Disease Progression ; Genes, bcl-1 ; Humans ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Recurrence* ; Retrospective Studies

OBJECTIVETo investigate the effects of peroxisome proliferator-activated receptor-gamma (PPARγ) agonist rosiglitazone on the expression of cyclin D1 in lung tissue, and the proliferation of airway smooth muscle cells (ASMCs) in mice with bronchial asthma.

METHODSThirty clean BALB/c mice were randomly divided into control group (n = 10), asthma group (n = 10), and rosiglitazone treatment group (n = 10). A mouse model of asthma was established by ovalbumin (OVA) sensitization and challenge. The treatment group received rosiglitazone (5 mg/kg) by gavage 1 hour before each challenge and the control group received saline instead of OVA sensitization and challenge. Leukocytes and eosinophils in bronchoalveolar lavage fluid (BALF) were counted under a microscope. Airway structural changes were observed by hematoxylin-eosin staining. Protein and mRNA expression levels of cyclin D1 were measured by immunohistochemical staining and RT-PCR. Perimeter of the basement membrane (Pbm), total bronchial wall area (WAt), airway smooth muscle area (WAm), and number of nuclei in ASMCs (N) were determined using image analysis software, and WAt/Pbm, WAm/Pbm, and N/Pbm were calculated.

RESULTSCompared with the control group, the asthma group showed significant increases in the total number of leukocytes and percentage of eosinophils in BALF, as well as in the mRNA and protein expression of cyclin D1, but changes in these indices were significantly reduced in the rosiglitazone treatment group (P < 0.05). In addition, compared with the control group, the asthma group had significantly increased WAt/Pbm, WAm/Pbm, and N/Pbm, but rosiglitazone significantly decreased these ratios (P < 0.05).

CONCLISONSRosiglitazone may delay the process of airway remodeling by inhibiting the proliferation of ASMCs, so it can be used for preventing and treating chronic asthma.

Airway Remodeling ; Animals ; Asthma ; drug therapy ; pathology ; Bronchi ; pathology ; Bronchoalveolar Lavage Fluid ; cytology ; Cell Proliferation ; Cyclin D1 ; analysis ; genetics ; Female ; Lung ; chemistry ; pathology ; Mice ; Mice, Inbred BALB C ; Myocytes, Smooth Muscle ; physiology ; PPAR gamma ; physiology ; RNA, Messenger ; analysis ; Thiazolidinediones ; pharmacology

OBJECTIVETo investigate the effects of matrine on the proliferation and apoptosis of human rhabdomyosarcoma RD cells in vitro, and to explore the mechanism of matrine inducing apoptosis of RD cells.

METHODSMTT assay was used to measure the proliferation inhibition rates of RD cells that were treated with matrine (final concentrations= 0.5, 1.0, 1.5, and 2.0 mg/mL). Flow cytometry was used to evaluate the apoptosis of RD cells treated with the four concentrations of matrine. RT-PCR was used to measure the mRNA expression of cyclin D1 and survivin in RD cells treated with 0.5, 1.0, and 1.5 mg/mL of matrine.

RESULTSThe RD cells treated with various concentrations of matrine showed significantly higher proliferation inhibition rates and apoptotic rates than those that were not treated with matrine (P<0.01), and with increased matrine concentration, the proliferation inhibition rate of RD cells increased gradually, thus exhibiting a dose dependence. The mRNA expression of cyclin D1 and survivin was seen in all RD cells, but was significantly lower in RD cells treated with matrine than in those that were not treated with matrine (P<0.01). There were significant differences in cyclin D1 mRNA level among the RD cells treated with 0.5, 1.0, and 1.5 mg/mL of matrine (P<0.05), while there was significant difference in survivin mRNA level between the RD cells treated with 0.5 and 1.5 mg/mL of matrine (P<0.05).

CONCLUSIONSMatrine can significantly inhibit proliferation and induce apoptosis of RD cells, which may be related to downregulating the mRNA expression of cyclin D1 and survivin.

Alkaloids ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin D1 ; genetics ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; Quinolizines ; pharmacology ; RNA, Messenger ; analysis ; Rhabdomyosarcoma ; drug therapy ; pathology

OBJECTIVEMyriocin (ISP-1) is a new type of immune inhibitor extracted from cordyceps sinensis. This study was to observe the effects of ISP-1 on the expression of cell cycle regulatory protein D1 (cyclinD1) in high glucose-induced hypertrophy rat glomerular mesangial cells (GMCs).

METHODSRat GMCs were cultured in vitro and divided into three groups: high glucose (450 mg/dL D-glucose), normal glucose (100 mg/dL D-glucose, control) and ISP-1 (450 mg/dL D-glucose plus 100 μg/mL ISP-1). The protein expression of cyclinD1 was detected by flow cytometry.

RESULTSThe expression of cyclinD1 in GMCs in the high glucose group increased significantly in a time-dependent manner compared with that in the control group. ISP-1 treatment significantly inhibited the up-regulated expression of cyclinD1 induced by high concentration glucose, and the expression of cyclinD1 was restored to the level of the control group 48 and 72 hrs after ISP-1 treatment.

CONCLUSIONSHigh concentration of glucose can up-regulate the expression of cyclinD1 in GMCs. ISP-1 may inhibit the up-regulated expression of cyclinD1, which might contribute to the protective effect of ISP-1 against GMC hypertrophy induced by high glucose.

Animals ; Cyclin D1 ; analysis ; Fatty Acids, Monounsaturated ; pharmacology ; G1 Phase ; Glucose ; toxicity ; Hypertrophy ; Mesangial Cells ; chemistry ; pathology ; Rats ; Rats, Sprague-Dawley

Since endocrine disrupting chemicals (EDCs) may interfere with the endocrine system(s) of our body and have an estrogenicity, we evaluated the effect(s) of bisphenol A (BPA) on the transcriptional levels of altered genes in estrogen receptor (ER)-positive BG-1 ovarian cancer cells by microarray and real-time polymerase-chain reaction. In this study, treatment with 17beta-estradiol (E2) or BPA increased mRNA levels of E2-responsive genes related to apoptosis, cancer and cell cycle, signal transduction and nucleic acid binding etc. In parallel with their microarray data, the mRNA levels of some altered genes including RAB31_MEMBER RAS ONCOGENE FAMILY (U59877), CYCLIN D1 (X59798), CYCLIN-DEPENDENT KINASE 4 (U37022), IGF-BINDING PROTEIN 4 (U20982), and ANTI-MULLERIAN HORMONE (NM_000479) were significantly induced by E2 or BPA in this cell model. These results indicate that BPA in parallel with E2 induced the transcriptional levels of E2-responsive genes in an estrogen receptor (ER)-positive BG-1 cells. In conclusion, these microarray and real-time polymerase-chain reaction results indicate that BPA, a potential weak estrogen, may have estrogenic effect by regulating E2-responsive genes in ER-positive BG-1 cells and BG-1 cells would be the best in vitro model to detect these estrogenic EDCs.
Anti-Mullerian Hormone ; Apoptosis ; Benzhydryl Compounds ; Cell Cycle ; Cyclin D1 ; Cyclin-Dependent Kinase 4 ; Endocrine Disruptors ; Estrogens ; Genes, ras ; Humans ; Insulin-Like Growth Factor Binding Protein 4 ; Microarray Analysis ; Ovarian Neoplasms ; Phenols ; Receptors, Estrogen ; RNA, Messenger ; Signal Transduction

OBJECTIVECyclinD1 and p21CIP1 are major proteins to regulate lung cell proliferation and involved in lung development and lung injury reparation. This study aimed to explore the expression manners of CyclinD1 and p21CIP1 at canalicular, saccular and alveolar stages during lung development in Sprague-Dawley rats.

METHODSLung tissues were obtained from fetal rats of 20 and 21 days gestational ages, and neonatal rats at 0, 3, 7, 14 and 21 days (n=6). Lung tissues were used for histopathology and the protein analysis of CyclinD1 and p21CIP1 (immunohistochemistry and Western blot).

RESULTSThe strongest expression of CyclinD1 and the weakest expression of p21CIP1 occurred at 20-21 days gestation (canalicular stage). At the canalicular stage, CyclinD1 was mainly expressed in epithelial cells, and the expression of p21CIP1was negative. At the saccular stage, the expression of CyclinD1 decreased significantly and the p21CIP1 expression increased significantly. Positive expression of CyclinD1 and p21CIP1 was found in epithelial cells and interstitial cells. At the alveolar stage, the CyclinD1 expression was the lowest and the p21CIP1 expression was the highest. The positive expression of CyclinD1 was found in interstitial cells and that of p21CIP1 was found in epithelial cells.

CONCLUSIONSThe location and quantity of CyclinD1 and p21CIP1 expression are different at various stages during lung development in rats. A strongest CyclinD1 expression found in the canalicular stage may be associated a high lung cell proliferation. A strongest p21CIP1 expression found in the alveolar stage may be associated with alveolar maturity.

Animals ; Blotting, Western ; Cyclin D1 ; analysis ; Cyclin-Dependent Kinase Inhibitor p21 ; analysis ; Female ; Immunohistochemistry ; Lung ; chemistry ; embryology ; Male ; Rats ; Rats, Sprague-Dawley

PURPOSE: The aim of this study was to determine the expressions of Rb, p16, and cyclin D1 in soft tissue sarcomas, and we also wanted to identify the prognostic factors according to the clinicalpathologic features. MATERIALS AND METHODS: We reviewed the charts and radiographic films of 66 sarcoma patients. Tissue samples were collected from these patients. Immunochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p16, Rb, and cyclin D1 proteins. RESULTS: The median duration of overall survival was 47.8 months (range, 20.0 to 70.7 months) and the 5 years survival rate was 39%. As for the correlation between the degree of immunohistochemical staining for Rb protein and the histological tumor grades, there was a significant difference with a p-value of 0.019. However, no significant correlation was shown for p16 and cyclin D1. The overall survival duration of the Rb negative group (staining cell <20%) and the heterogeneous group (cell staining 20 to 80%) was 53.5+/-6.6 months and the overall survival duration of the Rb homogeneous group was 18.3+/-6.4 months, and there was a significant difference with a p-value of 0.016. However, no significant difference was shown between the survival rate according to the p16 and cyclin D1 expressions. On the multivariate analysis that was done with Rb, p16, the tumor size, grade and site, and patient age, the Rb gene expression was the most significant independent prognostic factor with a risk ratio of 3.01 (p=0.04). CONCLUSION: The expression of Rb protein was correlated with the histologic grade and overall survival of patients with soft tissue sarcomas.
Cyclin D1 ; Cyclins ; Genes, Retinoblastoma ; Humans ; Immunochemistry ; Multivariate Analysis ; Odds Ratio ; Proteins ; Retinoblastoma Protein ; Sarcoma ; Survival Rate ; X-Ray Film

The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Transitional Cell/*metabolism/mortality/pathology ; Cyclin D1/*metabolism ; Cyclin-Dependent Kinase Inhibitor p16/*metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Recurrence ; Retinoblastoma Protein/*metabolism ; Survival Rate ; Tumor Suppressor Protein p53/*metabolism ; Urinary Bladder Neoplasms/*metabolism/mortality/pathology

BACKGROUNDSurvivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug.

METHODSSurvivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin) cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM). The protein expression levels of survivin, LRP, cyclin-D(1), caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo.

RESULTSSurvivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug-resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth.

CONCLUSIONSSurvivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3. Anti-tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas.

Adenocarcinoma ; drug therapy ; pathology ; Animals ; Apoptosis ; Caspase 3 ; analysis ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Cyclin D1 ; analysis ; Drug Resistance, Neoplasm ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Microtubule-Associated Proteins ; antagonists & inhibitors ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; RNA, Messenger ; analysis ; RNA, Small Interfering ; genetics ; Vault Ribonucleoprotein Particles ; genetics