Chronic inflammation has been considered an important risk factor for development of prostate cancer. Toll-like receptors (TLRs) recognize microbial moieties or endogenous molecules and play an important role in the triggering and promotion of inflammation. In this study, we examined whether expression of TLR4 and TLR5 was associated with progression of prostate transformation in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The expression of TLR4 and TLR5 was evaluated by immunohistochemisty in formalin-fixed paraffin-embedded prostate tissue from wild-type (WT) and TRAMP mice. Normal prostate tissue from WT mice showed strong expression of TLR4 and TLR5. However, TLR4 expression in the prostate tissue from TRAMP mice gradually decreased as pathologic grade became more aggressive. TLR5 expression in the prostate tissue from TRAMP mice also decreased in low-grade prostate intraepithelial neoplasia (PIN), high-grade PIN and poorly differentiated adenocarcinoma. Overall, our results suggest that decreased expression of TLR4 and TLR5 may contribute to prostate tumorigenesis.
Adenocarcinoma/etiology/*genetics ; Animals ; Cell Transformation, Neoplastic ; Disease Progression ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Prostatic Neoplasms/etiology/*genetics ; Toll-Like Receptor 4/*genetics/metabolism ; Toll-Like Receptor 5/*genetics/metabolism

Adenocarcinoma, Clear Cell ; etiology ; pathology ; Brenner Tumor ; etiology ; pathology ; Carcinosarcoma ; etiology ; pathology ; Cell Transformation, Neoplastic ; Cystadenocarcinoma, Serous ; etiology ; pathology ; Epithelial Cells ; metabolism ; pathology ; Female ; Genes, p53 ; Humans ; Mutation ; Neoplasms, Glandular and Epithelial ; etiology ; genetics ; metabolism ; pathology ; Ovarian Neoplasms ; etiology ; genetics ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; genetics ; metabolism

Adenocarcinoma ; genetics ; metabolism ; Angiomyolipoma ; etiology ; Antibiotics, Antineoplastic ; therapeutic use ; Astrocytoma ; etiology ; Brain Neoplasms ; etiology ; Breast Neoplasms ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Kidney Neoplasms ; etiology ; Lung Neoplasms ; genetics ; metabolism ; Mutation ; Sirolimus ; therapeutic use ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Tuberous Sclerosis ; complications ; drug therapy ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

BACKGROUND/AIMS: Barrett's esophagus is a premalignant lesion of the esophagus in which normal squamous epithelium is replaced by intestinalized columnar epithelium. In Korea, adenocarcinoma associated with Barrett's esophagus is rare compared with that of Western country. The purpose of this study was to investigate the immunohistochemical expression of p53 and Ki-67 in Barrett's esophagus which had predictive value for cancer risk in Korea. METHODS: Ninety five patients (43 male and 52 female, median age 44, range 21-75) who have been suspected to have Barrett's esophagus by endoscopic assessment were enrolled in this study. Alcian blue (pH 2.5) and high ion diamine stain for the evaluation of specialized intestinal metaplasia (SIM) and immunohistochemical stain for p53 and Ki-67 were done. RESULTS: 57.9% (55/95) of biopsies from the columnar lined esophagus showed SIM, but no dyspalsia. 56.4% (31/55) of Barrett's esophagus showed sulfomucin positive colonic metaplasia. The p53 expression was observed in 10.9% (6/55) of the patients of Barrett's esophagus and all of them showed colonic metaplasia. Ki-67 labeling index showed no difference significantly. CONCLUSIONS: In Korea, 10.9% of Barrett's esophagus had p53 mutation and moreover all of them had colonic metaplasia. Consequently, we expect that these patients have high risk of developing dysplasia and adenocarcinoma and need careful follow-up.
Adenocarcinoma/etiology/genetics ; Adult ; Aged ; Barrett Esophagus/complications/*metabolism ; Esophageal Neoplasms/etiology/genetics ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Male ; Middle Aged ; Risk Factors ; Tumor Suppressor Protein p53/*metabolism

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.
Adenocarcinoma ; ethnology ; etiology ; genetics ; Alcohol Drinking ; adverse effects ; Asia ; epidemiology ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Squamous Cell ; ethnology ; etiology ; genetics ; Esophageal Neoplasms ; ethnology ; etiology ; genetics ; European Continental Ancestry Group ; genetics ; Gastroesophageal Reflux ; complications ; Genetic Predisposition to Disease ; Humans ; Incidence ; Obesity ; complications ; Polymorphism, Single Nucleotide ; Risk Factors ; Smoking ; adverse effects ; United States ; epidemiology

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A or C-->T) rather than a transversion mutation (G-->T or G-->C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.
Adenocarcinoma/drug therapy/etiology/*genetics/pathology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics ; Female ; Humans ; Incidence ; Lung Neoplasms/drug therapy/etiology/*genetics/pathology ; Male ; Middle Aged ; *Mutation ; Mutation Rate ; Proportional Hazards Models ; Proto-Oncogene Proteins/*genetics ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/genetics ; Smoking/adverse effects/*genetics ; Treatment Outcome ; ras Proteins/*genetics

OBJECTIVETo investigate the transcription level and protein expression of HIF-1alpha and VEGF in SW480 cell line and colorectal adenocarcinoma, and to determine whether HIF-1alpha plays a role in angiogenesis through its regulation of VEGF.

METHODSHIF-1alpha mRNA expression was analyzed by in situ hybridization. HIF-1alpha and VEGF protein expressions were determined by immunochemical streptavidin/peroxidase (SP) in SW480 cells and colorectal carcinoma tissue samples and Western blot, using proteins extracted from SW480 cells. Tumor tissue microvessel density (MVD) was determined by CD34 immunostaining of colorectal carcinomas.

RESULTSThe levels of HIF-1alpha mRNA changed significantly in response to different oxygen concentrations and an addition of genistein in SW480 cells. Immunocytochemistry revealed that the levels of HIF-1alpha, VEGF protein expression in SW480 cells were significantly higher under hypoxia than those in nomoxia (P < 0.01, P < 0.05 respectively). However, addition of genistein, an inhibitor of HIF-1alpha, suppressed such responses to hypoxia. Western blot analysis showed that SW480 cells exposed to hypoxia expressed a high level of HIF-1alpha protein, compared to a weak expression in nomoxia. The addition of genistein in hypoxia suppressed the over-expression of HIF-1alpha. The positive rates of HIF-1alpha mRNA by in situ hybridization in colorectal adenomas and adenocarcinomas were 38.9% (7/18) and 67.7% (42/62), respectively. The percentage of HIF-1alpha mRNA positive cells varied significantly from colorectal adenomas to adenocarcinomas at different Duke stages (P < 0.05), and HIF-1alpha mRNA was higher in adenocarcinomas than in adenomas (P < 0.01). The positive rates of HIF-1alpha and VEGF protein expression in adenocarcinomas were 43.5% (27/62) and 37.1% (23/62), respectively. The expression of VEGF elevated as the Duke tumor staging increased. The conformation rate of HIF-1alpha and VEGF was 74.2% (46/62). MVD was significantly higher in HIF-1alpha and/or VEGF positive tumors than those without (P < 0.01 and P < 0.05 respectively). Among the four groups, i.e. HIF-1alpha+/VEGF+, HIF-1alpha+/VEGF-, HIF-1alpha+/VEGF- and HIF-1alpha-/VEGF-, the difference of MVD was highly significant (P < 0.01). HIF-1alpha expression was correlated significantly with VEGF expression and microvessel density.

CONCLUSIONSThese findings suggest hypoxia induces the expression of HIF-1alpha and VEGF in colorectal adenocarcinoma. HIF-1alpha may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinoma.

Adenocarcinoma ; blood supply ; metabolism ; pathology ; Colorectal Neoplasms ; blood supply ; metabolism ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Microcirculation ; pathology ; Neovascularization, Pathologic ; etiology ; RNA, Messenger ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

Adenocarcinoma ; etiology ; prevention & control ; surgery ; Adenomatous Polyposis Coli ; complications ; genetics ; surgery ; Adolescent ; Adult ; Colectomy ; methods ; Colonic Neoplasms ; etiology ; prevention & control ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pedigree

OBJECTIVETo assess the relationship between the XRCC1 polymorphism and susceptibility to lung cancer in non-smoking female on the basis of a hospital-based case-control study.

METHODSGenotypes were determined by PCR-restriction fragment length polymorphism in 50 patients with lung cancer and 50 controls. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression model to study the relationship between different genotypes and risk of lung cancer in non-smoking women. Furthermore, a multiplicative interaction between exposure to cooking oil smoke and the variant XRCC1 399Gln allele on risk of lung adenocarcinoma was evaluated.

RESULTSIndividuals carrying Gln/Gln genotype were at an increased risk to suffer from lung adenocarcinoma as compared with those with the Arg/Arg genotype (OR: 14.12; 95% CI: 2.14 approximately 92.95, adjusted for age and cooking oil smoke). The OR of lung adenocarcinoma for the variant XRCC1 399Gln allele with exposure to cooking oil smoke was 6.29 (95% CI 1.99 approximately 19.85).

CONCLUSIONThe above described findings indicate that Arg 399Gln polymorphism in the XRCC1 is associated with risk of lung adenocarcinoma but not with risk of squamous-cell carcinoma of the lung in non-smoking women.

Adenocarcinoma ; etiology ; genetics ; Adult ; Aged ; Air Pollution, Indoor ; adverse effects ; Carcinoma, Squamous Cell ; genetics ; Case-Control Studies ; Cooking ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms ; etiology ; genetics ; Middle Aged ; Polymorphism, Genetic ; Risk Assessment ; Smoking ; adverse effects ; X-ray Repair Cross Complementing Protein 1

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage