• Indonesia
• Nasopharyngeal carcinoma
• P16
• smoking status

• Adult
• Aged
• Case-Control Studies
• Cyclin-Dependent Kinase Inhibitor p16/metabolism
• Follow-Up Studies
• Humans
• Incidence
• Male
• Middle Aged
• Nasopharyngeal Neoplasms/etiology
• Nasopharyngeal Neoplasms/metabolism
• Nasopharyngeal Neoplasms/pathology
• Prognosis
• Smoking/adverse effects
• Smoking/epidemiology
• Smoking/metabolism

• meta-analysis
• nasopharynx cancer
• p16
• prognosis

• Cyclin-Dependent Kinase Inhibitor p16/metabolism
• Humans
• Lymphatic Metastasis
• Nasopharyngeal Neoplasms/metabolism
• Nasopharyngeal Neoplasms/pathology
• Neoplasm Staging
• Prognosis
• Progression-Free Survival
• Survival Rate

Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G₁ arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a critical role in NPC pathogenesis. This study evaluated the preclinical activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) models. Over 95% cell growth inhibition was observed at 96 hours after ribociclib treatment. (IC₅₀ concentrations: HK1 = 1.42 ± 0.23 µM; HK1-LMP1 = 2.18 ± 0.70 µM and C666-1 = 8.26 ± 0.92 µM). HK1 and C666-1 cells were chosen for analysis of ribociclib on kinase signaling, apoptosis and cell cycle. Treatment with ribociclib for 48 hours consistently showed a dose-dependent reduction in phosphorylated and total RB expression and G₁ cycle arrest was only observed. Combining ribociclib with the alpha-specific PI3K inhibitor alpelisib showed a synergistic effect in two NPC PDX models in nude mice. The co-treatment induced a significant reduction in tumor volume in both xeno-666 and xeno-2117 compared with ribociclib treatment alone and control (p < 0.01). In summary, ribociclib is active in NPC models and the effect on growth inhibition was augmented when combined with alpelisib. This study supports the clinical evaluation of ribociclib in NPC.

In addition to their canonical roles in regulating cell cycle transition and transcription, cyclin-dependent kinases (CDKs) have been shown to coordinate DNA damage response pathways, suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human malignancies. Here, we report that roniciclib (BAY1000394), a potent pan-CDK inhibitor, displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma (NPC) models. Proliferation of the NPC cell lines HONE-1, CNE-2, C666-1, and HK-1 was effectively curbed by roniciclib treatment, with IC₅₀ values between 11 and 38 nmol/L. These anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1, 2, 3, and 4 and transcriptional CDKs 7 and 9, ultimately resulting in arrest at G1/S and G2/M, downregulation of the transcriptional apparatus, and repression of anti-apoptotic proteins. Considerably enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0 μmol/L cisplatin; this combination therapy achieved a response over 250% greater than either drug alone. Although roniciclib chemosensitized NPC cells to cisplatin, it did not sensitize untransformed (NP69) cells. The administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin, whereas combining these two agents produced far greater tumor suppression than either of the monotherapies. In summary, these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses, thus justifying further evaluation of this combinatorial approach in clinical settings.

Nasopharyngeal carcinoma (NPC) is an uncommon malignancy arising from the nasopharynx epithelium, and is endemic to east and southeast parts of Asia where they account for 70% of worldwide incidence. Researchers from the Cancer Science Institute of Singapore examined the anti-tumor effects of roniciclib—a small-molecule drug that blocks a family of enzymes known as cyclin-dependent kinases (CDKs) which are classically involved in cell cycle progression and transcription—in cell lines and mouse models of nasopharyngeal carcinoma. Because CDK/cyclin complexes have a putative role in DNA repair, roniciclib was combined with cisplatin, a DNA-damaging agent which is currently used in chemotherapy of NPC. The authors found that roniciclib had potent anti-NPC effects when given alone, whereas the combination of roniciclib and cisplatin proved to be highly synergistic and restrained tumor growth to a greater extent than either drugs given alone. Interestingly, roniciclib appeared to selectively enhance the anti-cancer effects of cisplatin in cancerous cells while this “chemo-sensitizing” phenomenon was not seen in non-cancerous cells, suggesting that giving both drugs together could improve the effectiveness of standard chemotherapy without incurring additional toxicities. These findings suggest that roniciclib should be evaluated clinically in patients with NPC.

Radioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma (NPC). SHP-1 is involved in cancer progression, but its role in radioresistance and senescence of NPC is not well understood. This study aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC cells.

SHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells using lentiviruses. Cells were irradiated to observe their radiosensitivity by colony forming assay. BrdU incorporation assay and flow cytometry were used to monitor cell cycle. A β-galactosidase assay was used to assess senescence. Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1γ, CDK4, cyclin D1, cyclin E, and p16 protein expressions.

Compared with CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence (+107 %, P < 0.001), increased radiosensitivity, higher proportion of cells in G0/G1 (+33 %, P < 0.001), decreased expressions of CDK4 (−44 %, P < 0.001), cyclin D1 (−41 %, P = 0.001), cyclin E (−97 %, P < 0.001), Rb (−79 %, P < 0.001), and pRb (−76 %, P = 0.001), and increased expression of p16 (+120 %, P = 0.02). Furthermore, SHP-1 overexpression resulted in radioresistance, inhibition of cellular senescence, and cell cycle arrest in the S phase. Levels of p53 and p21 were unchanged in both cell lines (all P > 0.05).

SHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of NPC cells. Down-regulating SHP-1 may be a promising therapeutic approach for treating patients with NPC.

• cyclin D1
• cyclin E
• quantum dot
• tissue chip
• urothelial bladder carcinoma

The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy, with or without concurrent chemotherapy. However, resistance to radiotherapy is not uncommon. The aim of the present study was to establish a radioresistant NPC cell line to study the molecular mechanisms of radioresistance by measuring the expression of cell cycle control proteins src homology 2 domain-containing phosphatase (SHP)-1/2, p16, CDK4 and cyclin D1. Human nasopharyngeal carcinoma CNE-2 cells were cultured, divided into two groups (CNE-2S1 and CNE-2S2) and irradiated with a dose of 6 Gy x5 or 2 Gy x15, respectively. The cells were subcultured between doses of irradiation. The surviving sublines (CNE-2S1 and CNE-2S2 clones) were then passaged for three months and their radiosensitivity was determined. The cell cycle distribution and protein expression of SHP-1/2, p16, CDK4 and cyclin D1 in parental and progenitor cell lines were measured. Small interfering (si)RNA-mediated knockdown of SHP-1 and SHP-2 in the NPC cells was used to further examine their roles in radiosensitivity and cell cycle distribution. CNE-2S1, a radio-resistant cell line, had a significantly higher percentage of cells in S phase and a lower percentage of cells in G1 phase, enhanced expression levels of SHP-1, CDK4 and cyclin D1, and reduced expression of p16, respectively, as compared with the parent cells. Stable suppression of SHP-1 mRNA in CNE-2 cells resulted in increased radiosensitivity compared with the parental cells, a decrease in the number of cells in S phase and an increase in the expression of p16. The results suggested that the SHP-1/p16/cyclin D1/CDK4 pathway may have a role in regulating radiosensitivity and cell cycle distribution in nasopharyngeal cells.

• Cell cycle
• Checkpoints
• DNA damage responses
• Epstein–Barr virus
• NPC

• 14-3-3 Proteins/analysis
• Adult
• Aged
• Biomarkers, Tumor/analysis
• Carcinoma
• Case-Control Studies
• Cell Line, Tumor/chemistry
• Cyclin-Dependent Kinase 2/analysis
• Cyclin-Dependent Kinase 4/analysis
• Cyclin-Dependent Kinase Inhibitor p16
• Epstein-Barr Virus Nuclear Antigens/analysis
• Exoribonucleases/analysis
• Female
• Humans
• Male
• Middle Aged
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms/chemistry
• Nasopharynx/chemistry
• Neoplasm Proteins/analysis
• Young Adult

Recently, there have been a number of studies on the association between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk. However, the results of previous reports remain controversial and ambiguous. Thus, we performed a meta-analysis to explore more precisely the association between cyclin D1 G870A polymorphism and the risk of nasopharyngeal carcinoma. No significant association was found between cyclin D1 G870A polymorphism and nasopharyngeal carcinoma risk in total population analysis. In the subgroup meta-analysis by ethnicity, a negative association was shown in Caucasian subgroup, and no significant association in any genetic models among Asians was observed. In summary, positive results have been shown on the search for polymorphic variants influencing the risk of NPC. This meta-analysis provides evidence of the association between CCND1 G870A polymorphism and NPC risk, supporting the hypothesis that CCND1 870A allele probably acts as an important NPC protective factor in Caucasians but not in Asians. Since the results of our meta-analysis are preliminary and may be biased by the relatively small number of subjects, they still need to be validated by well-designed studies using larger samples in the future.

Since scarce data exist on the pathogenesis of nasopharyngeal carcinoma in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population.

Formalin-fixed paraffin-embedded tumor tissue samples from 107 patients, diagnosed with locally-advanced nasopharyngeal carcinoma and treated with chemotherapy or chemo-radiotherapy, were analyzed by immunohistochemistry for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-AKT, phospho-mTOR, and phospho-GSK-3β. EBER status was assessed by in situ hybridization. The majority of the cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2) months.

Biomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK-3β, and Fascin-1. WHO II+III tumors were more frequently EBER & PTEN positive and VEGF-A negative. Advanced age was significantly associated with positive phospho-GSK-3β and ERCC1 expression; male gender with positive phospho-AKT and phospho-p44/42MAPK; and worse performance status (1 or 2) with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier disease stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for disease-free survival (p=0.034) and EBER as a positive one for overall survival (p=0.048). In multivariate analysis, advanced age and stage, poor performance status, and positive ERCC1 emerged as predictors of worse disease-free and overall survival, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better overall survival (p=0.043).

Our study is the first to examine the activation and interaction of established biomolecules and signaling pathways in Caucasian NPC patients in an effort to reveal new therapeutic targets.

Nasopharyngeal carcinoma (NPC) is an uncommon cancer, which has a distinctive ethnic and geographic distribution. Etiology of NPC is considered to be related with a complex interaction of environmental and genetic factors as well as Epstein-Barr virus infection. Since NPC is located in the silent painless area, the disease is usually therefore diagnosed at the advanced stages; hence early detection of NPC is difficult. Furthermore, understanding in molecular pathogenesis is still lacking, pondering the identification of effective prognostic and diagnostic biomarkers. Dysregulation of signaling molecules in intracellular signal transduction, which regulate cell proliferation, apoptosis, and adhesion, underlines the basis of NPC pathogenesis. In this paper, the molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression. The important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.

• Adult
• Aged
• Carcinoma
• Cell Line, Tumor
• Cell Proliferation
• DNA-Binding Proteins/genetics
• DNA-Binding Proteins/metabolism
• Disease Progression
• Enhancer of Zeste Homolog 2 Protein
• Female
• Gene Silencing
• Humans
• Male
• Middle Aged
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms/metabolism
• Nasopharyngeal Neoplasms/mortality
• Nasopharyngeal Neoplasms/pathology
• Nasopharynx/metabolism
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Neoplasm Staging
• Polycomb Repressive Complex 2
• Prognosis
• RNA, Messenger/metabolism
• Transcription Factors/genetics
• Transcription Factors/metabolism
• Up-Regulation

Malignant gliomas are the most common in central nervous system cancer. Genome-wide association study identifies that CDKN2A was a susceptibility loci for glioma. The CDKN2A/cyclin-dependent kinase 4, 6/Retinoblastoma protein (Rb) pathway is thought to play a crucial role in malignant gliomas pathogenesis. We have investigated the expression of CDKN2A for potential correlations with malignant gliomas grade and potential role of CDKN2A on malignant gliomas pathogenesis.

Tumour tissue samples from 61 patients suffering from malignant gliomas were investigated. The expression levels of CDKN2A were detected using immunohistochemical staining and western blot. Overexpression and knockdown of CDKN2A were performed in human glioma cell lines. Subsequently, colony formation, growth curves and CDKN2A-Cyclin-Rb pathway were analyzed.

Here we show that a lower expression of CDKN2A and a higher expression of cyclin D1 in the patients with high-grade malignant gliomas than low-grade gliomas, respectively. Moreover, overexpression of CDKN2A inhibits growth of glioma cell lines by suppression of cyclin D1 gene expression.

Our study suggests that CDKN2A as a malignant gliomas suppressor gene, appears to be useful for predicting behaviour of high-grade malignant gliomas. CDKN2A-Cyclin-Rb pathway plays a key role on malignant gliomas formation and that therapeutic targeting of this pathway may be useful in malignant gliomas treatment.

• Cell Transformation, Neoplastic/genetics
• Chemoradiotherapy
• Combined Modality Therapy
• Cyclin-Dependent Kinase Inhibitor p16
• Disease Progression
• Herpesvirus 4, Human/genetics
• Humans
• Molecular Targeted Therapy
• Nasopharyngeal Neoplasms/drug therapy
• Nasopharyngeal Neoplasms/epidemiology
• Nasopharyngeal Neoplasms/genetics
• Nasopharyngeal Neoplasms/radiotherapy
• Neoplasm Proteins/genetics
• Radiotherapy, Intensity-Modulated
• Tumor Suppressor Protein p53/genetics
• Up-Regulation/genetics
• Viral Matrix Proteins/genetics

• Cell Cycle/genetics
• Cell Cycle Proteins/genetics
• Cell Cycle Proteins/metabolism
• Cyclin D1/genetics
• Cyclin D1/metabolism
• Cyclin-Dependent Kinase 4/genetics
• Cyclin-Dependent Kinase 4/metabolism
• Cyclin-Dependent Kinase Inhibitor p16/genetics
• Cyclin-Dependent Kinase Inhibitor p16/metabolism
• Cyclin-Dependent Kinase Inhibitor p19/genetics
• Cyclin-Dependent Kinase Inhibitor p19/metabolism
• Cyclin-Dependent Kinase Inhibitor p27/genetics
• Cyclin-Dependent Kinase Inhibitor p27/metabolism
• E2F6 Transcription Factor/genetics
• E2F6 Transcription Factor/metabolism
• Epstein-Barr Virus Infections/genetics
• Epstein-Barr Virus Infections/metabolism
• Epstein-Barr Virus Infections/virology
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Herpesvirus 4, Human/genetics
• Herpesvirus 4, Human/physiology
• Host-Pathogen Interactions
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Kaplan-Meier Estimate
• Logistic Models
• Nasopharyngeal Neoplasms/genetics
• Nasopharyngeal Neoplasms/metabolism
• Nasopharyngeal Neoplasms/virology
• Oligonucleotide Array Sequence Analysis/methods
• RNA, Viral/genetics
• RNA, Viral/metabolism
• Retinoblastoma Protein/genetics
• Retinoblastoma Protein/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Tissue Array Analysis

MicroRNAs (miRNAs) are a family of small non-coding RNA molecules of about 20–23 nucleotides in length, which negatively regulate protein-coding genes at post-transcriptional level. Using a stem-loop real-time-PCR method, we quantified the expression levels of 270 human miRNAs in 13 nasopharyngeal carcinoma (NPC) samples and 9 adjacent normal tissues, and identified 35 miRNAs whose expression levels were significantly altered in NPC samples. Several known oncogenic miRNAs, including miR-17-92 cluster and miR-155, are among the miRNAs upregulated in NPC. Tumour suppressive miRNAs, including miR-34 family, miR-143, and miR-145, are significantly downregulated in NPC. To explore the roles of these dysregulated miRNAs in the pathogenesis of NPC, a computational analysis was performed to predict the pathways collectively targeted by the 22 significantly downregulated miRNAs. Several biological pathways that are well characterised in cancer are significantly targeted by the downregulated miRNAs. These pathways include TGF-Wnt pathways, G1-S cell cycle progression, VEGF signalling pathway, apoptosis and survival pathways, and IP3 signalling pathways. Expression levels of several predicted target genes in G1-S progression and VEGF signalling pathways were elevated in NPC tissues and showed inverse correlation with the down-modulated miRNAs. These results indicate that these downregulated miRNAs coordinately regulate several oncogenic pathways in NPC.

• nasopharyngeal carcinoma (npc)
• epstein
• barr virus (ebv)
• lmp1
• tumorigenesis
• review

• Apoptosis/genetics
• Cadherins/genetics
• Carcinogenicity Tests/methods
• Carcinoma, Squamous Cell/epidemiology
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Cell Proliferation
• Cyclin E/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease/epidemiology
• Herpesvirus 4, Human/genetics
• Humans
• Male
• Molecular Biology
• NF-kappa B p50 Subunit/genetics
• Nasopharyngeal Neoplasms/epidemiology
• Nasopharyngeal Neoplasms/genetics
• Nasopharyngeal Neoplasms/pathology
• Oncogene Proteins/genetics
• Proto-Oncogene Proteins/genetics
• Sensitivity and Specificity
• Signal Transduction/genetics
• beta Catenin/genetics

• R01 CA093708-01A3 NCI NIH HHS
• R01 CA093708-02 NCI NIH HHS
• R01 CA093708 NCI NIH HHS
• R01 CA 093708-01A3 NCI NIH HHS
• R01 CA093708-04 NCI NIH HHS
• R01 CA093708-03 NCI NIH HHS

• Animals
• Antineoplastic Agents/pharmacology
• Apoptosis
• Cell Line, Tumor
• Cell Survival/drug effects
• Cisplatin/pharmacology
• Cyclin D1/antagonists & inhibitors
• DNA Fragmentation
• Drug Resistance, Neoplasm/genetics
• Humans
• Mice
• NF-kappa B/antagonists & inhibitors
• NF-kappa B/metabolism
• Pancreatic Neoplasms/metabolism
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-myc/metabolism
• RNA, Small Interfering/genetics

• R01 CA100864 NCI NIH HHS

• R01 CA070297 NCI NIH HHS
• R01 CA087767 NCI NIH HHS

AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma.

METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading.

RESULTS: The expression rates of abnormal cyclin D1 in gallbladder carcinoma (68.3%)and gallbladder adenoma(57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G₁, G₂ and G₃ and among Nevin stagings S₁-S₂, S₃ and S₄-S₅ of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S₁-S₂ (80.0% and 90.0%) and S₃ (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S₄-S₅ (33.3% and 38.8%) (P<0.05), and those in pathologic grades G₁ (54.5% and 81.8%) and G₂ (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G₃ (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r = -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin D1 had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05).

CONCLUSION: Cyclin D1 may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.

• Gallbladder carcinoma
• Cyclin D1
• p16 protein
• Retinoblastoma protein
• Tumor metastasis

• Adenoma/metabolism
• Carcinoma/metabolism
• Carcinoma/secondary
• Cholecystitis/metabolism
• Cyclin D1/metabolism
• Cyclin-Dependent Kinase Inhibitor p16/metabolism
• Gallbladder Neoplasms/metabolism
• Gallbladder Neoplasms/secondary
• Humans
• Immunoenzyme Techniques
• Mutation
• Neoplasm Staging
• Prognosis
• Retinoblastoma Protein/metabolism

• Adenocarcinoma/metabolism
• Adenocarcinoma/mortality
• Adenocarcinoma/therapy
• Adult
• Aged
• Combined Modality Therapy
• Cyclin D1/metabolism
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/therapy
• Female
• Fibroblast Growth Factor 3
• Fibroblast Growth Factors/metabolism
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Ki-67 Antigen/metabolism
• Male
• Middle Aged
• Proto-Oncogene Proteins/metabolism
• Survival Analysis
• Tumor Suppressor Protein p53/metabolism

• cell cycle
• gl/s transition
• cyclin
• tissue microarray
• protein
• renal cell carcinoma

• Actuarial Analysis
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/mortality
• Carcinoma, Renal Cell/pathology
• Cell Cycle/genetics
• Cyclin D
• Cyclin D1/genetics
• Cyclin D1/metabolism
• Cyclin E/genetics
• Cyclin E/metabolism
• Cyclins/genetics
• Cyclins/metabolism
• Female
• Humans
• Immunohistochemistry
• Kidney Neoplasms/genetics
• Kidney Neoplasms/mortality
• Kidney Neoplasms/pathology
• Male
• Microfilament Proteins/genetics
• Microfilament Proteins/metabolism
• Middle Aged
• Multivariate Analysis
• Muscle Proteins
• Oligonucleotide Array Sequence Analysis/methods
• Survival Analysis
• Time Factors