No abstract available.
Humans ; Infant, Newborn* ; Mothers* ; Vitamin E* ; Vitamins*

PURPOSE: Activity of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factor for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferase(GST) are enzymes which reduce the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of glutathione S-transferase mu(GSTM1) were reported as risk factors of bladder tumor. Since the cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of N-acetyltransferase type 2(NAT2) and GSTM1 are risk factors of bladder tumor and to evaluate the effects of their interaction on bladder tumor development. MATERIALS AND METHODS: 113 bladder tumor and 221 non-cancer patients, hospitalized in the Chungbuk National University Hospital, Samsung Medical Center, and Asan Medical Center from March to December 1996 participated in this case-control study. Questionnaire interview was done and the genotypes of NAT2 and GSTM1 were identified using PCR methods with DNA extracted from the venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. RESULTS: The frequencies of slow, intermediate, and rapid acetylators were 7.1%, 37.5%, and 55.4% for the cases, and 11.0%, 43.4%, and 45.7% for the controls, respectively. The risk of bladder tumor was not associated with the increase of NAT2 activity (chi2trend=3.16, p-value>0.05). GSTM1 was deleted in 69.6% of the cases and 55.9% of the controls (Chi2=5.86, p-value<0.05), and the odds ratio (95% CI) was 1.81 (1.12 - 2.93). Smoking history turned out to be insignificant as a risk factor of bladder tumor (OR=1.34, 95%CI: 0.78 - 2.31), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder tumor. Medical history of tuberculosis and bronchial asthma were significant risk factors for bladder tumor, and their ORs (95% CI) were 3.61 (1.57-8.26) and 4.15 (1.61-10.75), respectively. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion (OR: 1.80, 95% CI: 1.07-3.05), and histories of tuberculosis (OR: 2.99, 95% CI: 1.22-7.32) and of bronchial asthma (OR: 3.38, 95% CI: 1.24-9.22) were the significant risk factors for bladder tumor, but slow acetylation was not. CONCLUSIONS: These results suggest that GSTM1 deletion may be a significant risk factor of bladder tumor. The medications for tuberculosis and bronchial asthma could possibly cause bladder tumor, or immune mechanism might be involved in the development of bladder tumor.
Acetylation ; Asthma ; Carcinogens ; Case-Control Studies ; Chungcheongbuk-do ; Chungcheongnam-do ; DNA ; Genotype ; Glutathione Transferase* ; Glutathione* ; Humans ; Metabolism ; Occupations ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Surveys and Questionnaires ; Risk Factors ; Smoke ; Smoking ; Tuberculosis ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Xenobiotics

PURPOSE: Cancer development depends on activities of enzymes involved in metabolisms of various carcinogenic xenobiotics. N-acetyltransferase(NAT) and glutathione S-transferases(GST) are enzymes, reducing the toxicity of activated carcinogenic metabolites. Carcinogens of bladder cancer can not be fully explained by single risk factor and many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1, and GSTT1 were risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer occurrence. MATERIALS AND METHODS: One hundred and thirteen bladder cancer and 221 non-cancer patients hospitalized in the Chungbuk National University Hospital participated in the present case-control study. Questionnaire interview was performed and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. Effects of the polymorphism of NAT2, GSTM1 and GSTT1 and their interaction on bladder cancer were statistically analyzed after controlling other risk factors. RESULTS: The frequencies of slow, intermediate, and rapid acetylators were 7.1%, 37.5%, and 55.4% for the cases, and 11.0%, 43.4%, and 45.7% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity(x2trend=3.16, p>0.05). GSTM1 was deleted in 69.6% of the cases and 55.9% of the controls(x2=5.86, P<0.05), and the mean odds ratio(95% CI) was 1.81 (1.12 - 2.93). The GSTT1 deletion, the rate of which were 42.0% for the bladder cancer patients and 45.9% for the controls, showed the protective effect against bladder cancer, but was not statistically significant. Smoking history turned out to be insignificant as a risk factor of bladder cancer(OR=1.34, 95%CI: 0.78 - 2.31), and occupation was not analyzed due to the extremely small number of occupational history related to the increase of bladder cancer. Medical histories of tuberculosis and bronchial asthma were significant risk factors for bladder cancer, and their average ORs(95% CI) were 3.61(1.57-8.26) and 4.15(1.61-10.75), respectively. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion (OR: 1.80, 95% CI: 1.07-3.05), and histories of tuberculosis(OR: 2.99, 95% CI: 1.22-7.32) and of bronchial asthma(OR: 3.38, 95% CI: 1.24-9.22) were the significant risk factors for bladder cancer, but slow acetylation and GSTT1 deletion were not. CONCLUSIONS: These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer, and GSTT1 deletion may have the protective effect against bladder tumor development. Since tuberculosis and bronchial asthma, in the present study, appeared to be involved in the development of bladder tumor, possible associated relationships are under experimental investigation in every aspect.
Acetylation ; Asthma ; Carcinogens ; Case-Control Studies ; Chungcheongbuk-do ; DNA ; Genotype ; Glutathione ; Humans ; Metabolism* ; Occupations ; Polymerase Chain Reaction ; Surveys and Questionnaires ; Risk Factors ; Smoke ; Smoking ; Tuberculosis ; Urinary Bladder Neoplasms* ; Urinary Bladder* ; Xenobiotics*

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.
Alzheimer Disease ; Biomarkers* ; Cerebrospinal Fluid* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Parkinson Disease ; Pathology ; Therapeutic Uses

OBJECTIVETo evaluate the effects of Huafenqinutang combined with vardenafil for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with erectile dysfunction.

METHODSOne hundred and thirty-eight cases diagnosed as CP/CPPS with erectile dysfunction were randomized into trial group (70 cases) and control group (68 cases) for treatment with Huafenqinutang for 8 weeks, and in the former group, vardenaffil was added since the fifth weeks. All the cases were evaluated according to NIH-CPSI and IIEF-5 scores at 4 weeks and 8 weeks, respectively.

RESULTSAt the end of the fourth weeks, NIH-CPSI score was 13.1-/+4.7 in the trial group and 13.3-/+4.5 in the control group, which were comparable between the two groups (P>0.05) but significantly decreased compared with the pre-treatment scores in both groups (P<0.01). IIEF-5 score was also similar between the two groups (14.1-/+3.3 vs 14.3-/+5.0, P>0.05) but significantly increased compared with the pre-treatment scores in both groups (P<0.01). At the end of the eighth week, NIH-CPSI score was 7.8-/+2.2 and IIEF-5 score 20.1-/+4.4 in the trial group, which were significantly different from those at the end of the fourth week (P<0.01). In the control group, NIH-CPSI score was 12.7-/+2.3 and IIEF-5 score 14.3-/+4.5 at the eighth week, similar to those at the end of the fourth week (P>0.05). There were significant differences in NIH-CPSI and IIEF-5 scores between the 2 groups (P<0.01), and the change of NIH-CPSI score was negatively correlated with IIEF-5 score in the trial group (r=-0.89, P<0.01).

CONCLUSIONFor patients with CP/CPPS with erectile dysfunction, Huafenqinutang treatment in combination with vardenafil can effectively improve the erectile functions and decrease the NIH-CPSI score to favor the recovery from CP/CPPS.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Male ; Middle Aged ; Pelvic Pain ; drug therapy ; Phytotherapy ; Piperazines ; therapeutic use ; Prostatitis ; drug therapy ; Sulfones ; therapeutic use ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride

Background: Sentinel lymph node (SLN) mapping has been suggested as an alternative surgical technique to full lymphadenectomy for early-stage endometrial cancer. However, the survival outcomes of SLN mapping compared with lymphadenectomy have not been established via a prospective study. Methods A multi-center, single-blind, randomized controlled trial has been designed to determine the prognostic value of SLN mapping alone compared with conventional lymphadenectomy for patients with clinical stage I-II endometrial cancer. Eligible participants will be randomly assigned in a 1:1 ratio between the group to undergo SLN mapping using indocyanine green and the conventional lymph node dissection group. A high-risk group will undergo a 2-step SLN mapping procedure. The primary endpoint is the 3-year disease-free survival (DFS). The secondary endpoints are 3-year overall survival (OS), 5-year DFS, 5-year OS after surgery, pattern of recurrence, immediate surgical outcomes, success rate of SLN mapping, postoperative lymph-related complications, postoperative quality of life, and postoperative cost effectiveness. The role of pathologic ultrastaging of SLNs will also be assessed.

Metastatic malignant tumors involving the thyroid gland are not as unusual as was once believed. They may in fact be more common than primary cancer of the thyroid, especially if careful screening is performed at autopsy. The origins of primary neoplasms that metasta size to the thyoid are myriad, but reports obviously indicate predminantly cancers of the kidney, breast, and lung and malignant melanoma. Occasienally, metastatic lesions from several gastrointestinal neoplasms such as colo-retal and esophageal carcinoma are seen, but metastasis from gastric cancer is very rare. We have seen one case of thyroid cancer metastasized from the stomach cancer. It simultaneously spread to the breast also and confirmed with gastrofiberscopic biopsy, fine needle aspiration cytology of the thyroid and excisonal biopsy of the breast. We report this case with reriew of literature.
Autopsy ; Biopsy ; Biopsy, Fine-Needle ; Breast* ; Gastrointestinal Neoplasms ; Kidney ; Lung ; Mass Screening ; Melanoma ; Neoplasm Metastasis* ; Stomach Neoplasms* ; Thyroid Gland* ; Thyroid Neoplasms

PURPOSE: To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. RESULTS: The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. CONCLUSION: Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients.
Brachytherapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Electrons ; Follow-Up Studies ; Glycolysis ; Gynecology ; Humans ; Hysterectomy ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Obstetrics ; Pelvis ; Positron-Emission Tomography and Computed Tomography ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; ROC Curve ; Uterine Cervical Neoplasms*

PURPOSE: To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. RESULTS: The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. CONCLUSION: Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance in early uterine cervical cancer patients. More effective systemic treatments might be needed to reduce distant metastasis in these patients.
Brachytherapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Electrons ; Follow-Up Studies ; Glycolysis ; Gynecology ; Humans ; Hysterectomy ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Obstetrics ; Pelvis ; Positron-Emission Tomography and Computed Tomography ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; ROC Curve ; Uterine Cervical Neoplasms*

PURPOSE: S100A8 is a member of the S100 protein family containing 2EF-hand calcium-binding motifs. S100 proteins are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. Altered expression of this protein is associated with various diseases and cancers. The present study aimed to evaluate whether S100A8 has prognostic value for non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A total of 103 primary NMIBC samples obtained by transurethral resection were evaluated. mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results were compared with clinico-pathological parameters. The Kaplan-Meier method was applied to plot the curves for progression-free survival. The multivariate Cox regression model was used to identify the independent prognostic factors for progression. RESULTS: mRNA expression levels of S100A8 were significantly related to the progression of NMIBC. Kaplan-Meier estimates demonstrated significant differences in tumor progression according to the level of S100A8 expression (log-rank test, p<0.001). The multivariate Cox regression model revealed that the S100A8 mRNA expression level (hazard ratio: 12.538; 95% confidence interval: 2.245-70.023, p=0.004) was an independent predictor for disease progression of NMIBC. CONCLUSIONS: Expression levels of S100A8 might be a useful prognostic marker for disease progression of NMIBC.
Calgranulin A ; Cell Cycle ; Disease Progression ; Disease-Free Survival ; Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger ; S100 Proteins ; Biomarkers, Tumor ; Urinary Bladder ; Urinary Bladder Neoplasms