Carboxylesterase-overexpressing hTERT-immortalized human adipose stem cells in prostate tumor growth inhibition by irinotecan.

INTRODUCTION: Effective chemotherapy has not yet to be developed for castration-resistant prostate cancer (CRPC). Cell-mediated enzyme prodrug therapy (EPT), including a combination of carboxylesterase (CE) and irinotecan (CPT-11), could be a possible treatment option. This study explored a cell-mediated EPT, including a combination of CE and irinotecan (CPT-11), to inhibit CRPC tumor growth using rabbit CE-overexpressing human TERT-immortalized adipose-derived stem cells (hTERT-ADSC.CE). MATERIALS AND METHODS: An hTERT ADSC.CE cell line was established by transfection with a lentiviral vector (CLV-Ubic) encoding the rabbit CE gene. To determine the in vitro suicide effects of hTERT-ADSC.CE, cell cultures were performed using various concentrations of CPT-11 (0.01-5 µM), and to determine the in vitro cytotoxic effects of hTERT-ADSC.CE cells, PC3 and hTERT-ADSC.CE cells were co-cultured. For the in vivo model, PC3 cells (1 × 106 cells) were injected subcutaneously into the flanks of nude mice and hTERT-ADSC.CE cells were injected via an intracardiac route, followed by the continuous treatment using CPT-11 for 2 weeks. The final change in tumor volume was measured and immunohistochemical analysis was performed. RESULTS: The directional and selective migration of hTERT-ADSC.CE cells toward PC3 cells was significantly stimulated by PC3 cells in vitro. The number of apoptotic PC3 cells significantly increased in the presence of hTERT-ADSC.CE and CPT-11 compared to CPT-11 alone. In the in vivo study, the inhibitory effects of hTERT-ADSC.CE combined with CPT-11 were higher than those of CPT-11 monotherapy. After treatment with CPT-11 alone or ADSC.CE in combination with CPT-11, the removed tumor tissues showed hyperchromatic nuclei and apoptotic bodies. CE-overexpressing ADSCs potentiated the inhibition of tumor growth in CRPC-bearing mice in the presence of CPT-11 prodrugs. CONCLUSIONS: This report suggests that cell-mediated EPT including CE and CPT-11 may be efficacious in treating CRPC.

Improvement of damaged cavernosa followed by neuron-like differentiation at injured cavernous nerve after transplantation of stem cells seeded on the PLA nanofiber in rats with cavernous nerve injury.

This study investigated the differentiation of transplanted transplanted mesenchymal stem cells MSCs into neuron-like cells, repair of erectile dysfunction (ED), and synergy of MSCs seeded to nanofibrous scaffolds with after transplantation around the injured cavernous nerve (CN) of rats. The synthesized polymer was electrospun in a rotating drum to prepare nanofiber meshes (NMs). Human MSCs were prepared and confirmed. Eight-week-old male Sprague-Dawley rats were divided into five groups of six each: group 1-sham operation; group 2-CN injury; group 3-MSCs treatment after CN injury; group 4-nanofibrous scaffold treatment after CN injury; and group 5-post-CN injury treatment combining a nanofibrous scaffold and MSCs (nano-MSCs). In the latter group, the damaged CN was instantly surrounded by an MSC-containing a nanofibrous scaffold in the aftermath of injury. Morphological analysis and immuno-histochemical staining in relation to nerves (Tuj1, NF, MAP2, MBP and peripherin), endothelium (vWF), smooth muscle (SMA), neurofilament (NF), and apoptosis (TUNEL) were performed. We evaluated the mean proportion expressed as a percentage of the ratio of muscle to collagen of penile cavernous smooth-muscle cells as well as the expression of cavernous SMA, NF, vWF, and TUNEL makers. Compared to the group free of CN injury, erectile function was markedly reduced in the group with CN injury at 2 and 4 weeks (p < 0.05). By contrast, compared to the sham operation group, erectile function was better in the group with MSC transplantation (p < 0.05). Similarly, by comparison to the group solely with hMSCs, erectile function was better in the group with nano-MSC transplantation (p < 0.05). Transplantation of MSCs demonstrated the neuronal differentiation. By contrast to MSCs on their own, neuronal differentiation was more significantly expressed in nano-MSCs. The mean proportion expressed as a percentage of the ratio of muscle to collagen of penile cavernous smooth-muscle cells, the expression of cavernous SMA, NF, vWF, and apoptosis improved in the cavernosum after transplantation. NMs showed synergy with MSCs for the repair of erectile dysfunction. Transplanted MSCs differentiated into neuron-like cells and repaired erectile dysfunction in the rats with CN injury. Transplanted MSCs increased the mean percentage of the collagen area of the caversnosum as well as the expression levels of cavernous neuronal, endothelial, smooth-muscle markers, and apoptosis.

The Prognostic Model of Pre-Treatment Complete Blood Count (CBC) for Recurrence in Early Cervical Cancer.

The aim of the present study was to investigate the prognostic role of the pre-treatment complete blood count (CBC) profile as a predictive marker of survival, recurrence, and death in early stage squamous cell carcinoma and adenocarcinoma of the cervix. The pre-treatment CBC profiles of the patients from nine tertiary medical centers in South Korea who were treated surgically for early stage cervical cancer were reviewed. Statistical models by the Akaike's information criterion (AIC) were developed using CBC profiles to calculate individuals' risk scores for clinical outcomes. A total of 1443 patients were included in the study and the median follow-up was 63.7 months with a range of 3-183 months. Univariate analyses identified the components of CBC that were significantly related to clinical outcomes including white blood cell (WBC), hemoglobin, neutrophil, and platelet levels. The models developed using CBC profiles and the conventional clinical predictive factors provided individuals' risk scores that were significantly better in predicting clinical outcomes than the models using the conventional clinical predictive factors alone. Pre-treatment CBC profiles including WBC, hemoglobin, neutrophil, lymphocyte, and platelet levels were found to be a potential biomarker for survival prognosis in early cervical cancer.

Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028).

PURPOSE: We aimed to develop and validate individual prognostic models in a large cohort of cervical cancer patients that were primarily treated with radical hysterectomy. MATERIALS AND METHODS: We analyzed 1,441 patients with early-stage cervical cancer treated between 2000 and 2008 from the Korean Gynecologic Oncology Group multi-institutional cohort: a train cohort (n=788) and a test cohort (n=653). Models predicting the risk for overall survival (OS), disease- free survival (DFS), lymphatic recurrence and hematogenous recurrence were developed using Cox analysis and stepwise backward selection and best-model options. The prognostic performance of each model was assessed in an independent patient cohort. Model-classified risk groups were compared to groups based on traditional risk factors. RESULTS: Independent risk factors for OS, DFS, lymphatic recurrence, and hematogenous recurrence were identified for prediction model development. Different combinations of risk factors were shown for each outcome with best predictive value. In train cohort, area under the curve (AUC) at 2 and 5 years were 0.842/0.836 for recurrence, and 0.939/0.882 for OS. When applied to a test cohort, the model also showed accurate prediction result (AUC at 2 and 5 years were 0.799/0.723 for recurrence, and 0.844/0.806 for OS, respectively). The Kaplan-Meier plot by proposed model-classified risk groups showed more distinctive survival differences between each risk group. CONCLUSION: We developed prognostic models for OS, DFS, lymphatic and hematogenous recurrence in patients with early-stage cervical cancer. Combining weighted clinicopathologic factors, the proposed model can give more individualized predictions in clinical practice.

Comparison of laparoscopic and abdominal radical hysterectomy in early stage cervical cancer patients without adjuvant treatment: Ancillary analysis of a Korean Gynecologic Oncology Group Study (KGOG 1028).

OBJECTIVE: We compared two groups of early stage cervical cancer patients treated with different surgical methods without adjuvant treatment using retrospective multicenter data previously collected for Korean Gynecologic Oncology Group (KGOG) study designed for developing prognostic models. METHOD: We initially assessed data from the multi-institutional cohort with early stage (IB-IIA) cervical cancer patients treated with radical hysterectomy without adjuvant treatment between 2000 and 2008. Propensity score matching was performed to compare disease-free survival (DFS) and overall survival (OS) of patients with laparoscopic to abdominal radical hysterectomy. Additionally, survival comparison was performed in patients with tumor size <2 cm. RESULTS: After matching, 119 patients with laparoscopic radical hysterectomy were compared with 357 patients with abdominal radical hysterectomy (median follow-up of 63.9 months). Inferior DFS was observed in the laparoscopy group (HR 2.738 [95% CI 1.326-5.650], p = 0.005) with a significant difference in pelvic (HR 5.110 [95% CI 1.817-14.473], p < 0.001) and hematogenous recurrence (HR 3.171 [95% CI 1.059-9.494], p = 0.03), but OS was not significantly different between two groups (p = 0.624). In subgroup analysis in the patient with tumor size <2 cm (laparoscopy 62 vs. laparotomy 186, median follow-up of 69.1 months), laparoscopy was associated with lower rate of DFS (HR 12.987 [95% CI 1.451-116.244], p = 0.003), but no significant difference in OS was observed between groups. Regarding OS, number of events is lacking, and inferior DFS in the laparoscopy group may be compensated by better response to radiation therapy in pelvic recurrence. CONCLUSIONS: In this analysis, laparoscopic radical hysterectomy was associated with lower rates of DFS but not OS in early stage cervical cancer patients without adjuvant treatment. Further larger scale studies are needed.

Effect of highly concentrated hyaluronic acid/chondroitin sulphate instillation on ureteric stent-induced discomfort after ureteroscopic lithotripsy: a multicentre randomised controlled pilot study.

OBJECTIVE: To investigate the effectiveness and safety of instilling highly concentrated hyaluronic acid (HA)/chondroitin sulphate (CS) on ureteric stent-related pain, urinary symptoms, and quality of life (QoL) of patients who underwent ureteroscopic lithotripsy for ureteric stones followed by ureteric stent placement. PATIENTS AND METHODS: Eligible patients were randomly allocated to receive intravesical instillation with HA/CS or normal saline just after ureteric stent placement. Just before stent removal on postoperative day 7, the patients completed the Ureteric Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS) QoL question, and a pain visual analogue scale (VAS). RESULTS: In total, 92 patients (46 each in the treatment and control arms) completed the study. The groups did not differ in terms of age or stent indwelling time. Compared with the control group, the treatment group had significantly lower USSQ urinary symptom domain scores (24.6 vs 32.5; P < 0.001), better IPSS QoL scores (3.5 vs 4.4, P = 0.018), and lower VAS pain scores (2.0 vs 3.2; P < 0.001). They also had lower total body pain subscores (16.7 vs 22.0; P = 0.01) and lower additional pain subscores due to urinary tract infections (2.1 vs. 3.2; P = 0.01) in the USSQ. CONCLUSIONS: Highly concentrated HA/CS effectively improved urinary symptoms and pain, and reduced the need for additional medication or procedures after ureteric stent placement.

Association Between Ambient Temperature and Lower Urinary Tract Symptoms: A Hospital-Based Cross-Sectional Analysis.

OBJECTIVES: To date, there is no overall agreement as to risk of ambient temperature for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Thus, we focused on ambient temperature as an environmental factor affecting LUTS and attempted to explain the temperature differences in LUTS severity in cases in real clinical practice. METHODS: This was a multicenter, cross-sectional survey. The study involved 1612 men aged 40 years and older who visited 23 university hospitals in 10 major areas in South Korea between September 2010 and December 2011. The participants who had good overall mental and physical health, and complaint of LUTS were included. Korea Meteorological Administration data were used to determine daily average temperatures and daily temperatures on the interview dates at each site. RESULTS: The average age of the 1612 men was 66.57 ± 10.03 years. The mean International Prostate Symptom Score (IPSS) and symptom duration were 18.51 ± 6.77 and 3.79 ± 3.89 years, respectively. Daily average temperature and temperature difference ranged from -13.1 to 28.5 °C and 0 to 20.6 °C, respectively. Age was a significant risk factor for IPSS, symptom duration, prostate volume (PV), maximal urinary flow rate (Qmax), average urinary flow rate (Qave) and total voiding volume (P < 0.001) but not QOL. Logistic regression analysis after adjustment for age and PV revealed that Qave and total voiding volume were increased as the temperature declined. However, IPSS and Qmax did not show a statistically significant difference as the temperature declined. CONCLUSION: Our findings did not demonstrate an increased clinically significant risk of LUTS severity in connection with ambient temperature in clinical practice.

Association between ambient temperature and lower urinary tract symptoms: a community-based survey.

PURPOSE: The aim of this study was to evaluate the individual change of International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in each patient by temperature conditions. MATERIALS AND METHODS: The severity of lower urinary tract symptoms (LUTS) was explored using the IPSS and OABSS questionnaires that were completed by 2.486 subjects (923 males and 1.563 females) aged 60 years and older. Korea Meteorological Administration data was used to determine daily average temperature and daily temperature difference on the interview dates at each site. RESULTS: The mean IPSS and mean age for males was 13.45±8.24 and 75.03±6.20 years, respectively. The mean OABSS and mean age for females was 4.41±3.10 and 73.74±6.03years, respectively. Daily average temperature and daily temperature difference ranged from-3.4-28.3oC and 2.2-16.9oC, respectively. Age was a significantly risk factor for IPSS, OABSS, and QoL (P<0.001, <0.001, and 0.005, respectively). After multiple regression analysis, daily average temperatures did not show a statistically significant change in IPSS and OABSS. Only daily temperature differences were associated with male LUTS. CONCLUSIONS: While LUTS could be worsened in low temperatures generally, IPSS and OABSS were not affected by daily average temperature conditions. Daily temperature differences may be more influential than daily average temperatures.

Association between ambient temperature and lower urinary tract symptoms: a community-based survey

ABSTRACT Purpose The aim of this study was to evaluate the individual change of International prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) in each patient by temperature conditions. Materials and Methods The severity of lower urinary tract symptoms (LUTS) was explored using the IPSS and OABSS questionnaires that were completed by 2.486 subjects (923 males and 1.563 females) aged 60 years and older. Korea Meteorological Administration data was used to determine daily average temperature and daily temperature difference on the interview dates at each site. Results The mean IPSS and mean age for males was 13.45±8.24 and 75.03±6.20 years, respectively. The mean OABSS and mean age for females was 4.41±3.10 and 73.74±6.03years, respectively. Daily average temperature and daily temperature difference ranged from-3.4-28.3oC and 2.2-16.9oC, respectively. Age was a significantly risk factor for IPSS, OABSS, and QoL (P<0.001, <0.001, and 0.005, respectively). After multiple regression analysis, daily average temperatures did not show a statistically significant change in IPSS and OABSS. Only daily temperature differences were associated with male LUTS. Conclusions While LUTS could be worsened in low temperatures generally, IPSS and OABSS were not affected by daily average temperature conditions. Daily temperature differences may be more influential than daily average temperatures.

Management of Endometrial Hyperplasia With a Levonorgestrel-Releasing Intrauterine System: A Korean Gynecologic-Oncology Group Study.

OBJECTIVE: The aim of the study was to evaluate the efficacy of the levonorgestrel intrauterine system (LNG-IUS) for treatment of endometrial hyperplasia (EH). METHODS: A prospective multicenter study was conducted from November 2010 to March 2014. Patients with histologically confirmed EH were treated with LNG-IUS. At 3, 6, and 9 months after LNG-IUS insertion, follow-up endometrial aspiration biopsies with the LNG-IUS in the uterus were undertaken. At the 12th month of follow-up, endometrial tissues were obtained via 2 methods: endometrial aspiration biopsy with the LNG-IUS in the uterus, followed by dilatation and curettage (D&C) after LNG-IUS removal. The primary outcome was the regression rate at 12 months after LNG-IUS insertion, and the secondary outcome was the consistency of the results between the endometrial aspiration biopsy and the D&C. RESULTS: The study population comprised 75 patients, including 37 with simple hyperplasia without atypia; 3 with atypical simple hyperplasia; 23 with complex hyperplasia without atypia, and 12 with atypical complex hyperplasia. Of these patients treated with the LNG-IUS, 38 (50.7%) were followed up at 12 months after LNG-IUS insertion. The complete regression rate at 12 months was 94.7% (36/38): 100% (6/6) of patients with atypical EH and 93.7% (30/32) with EH without atypia. In all of the cases (100%, 36/36), patients achieved complete regression within 3 months of LNG-IUS insertion. A comparison of the pathologic results from endometrial aspiration biopsy and D&C was carried out for 15 patients. In the histologic results by endometrial aspiration biopsy, 14 patients were diagnosed as "normal endometrium" and 1 as "insufficient tissue for pathologic evaluation." Among the 14 cases of normal endometrium by endometrial aspiration biopsy, 1 was diagnosed as "residual EH" by D&C, and the 1 case with insufficient tissue was diagnosed as normal endometrium by D&C. CONCLUSIONS: Levonorgestrel intrauterine system is an effective and favorable method for treatment of EH.

Bladder recovery by stem cell based cell therapy in the bladder dysfunction induced by spinal cord injury: systematic review and meta-analysis.

BACKGROUND: Bladder dysfunction induced by spinal cord injury (SCI) can become problematic and severely impair the quality of life. Preclinical studies of spinal cord injury have largely focused on the recovery of limb function while neglecting to investigate bladder recovery. OBJECTIVE: The present study was performed to investigate and review the effect of stem cell-based cell therapy on bladder recovery in SCI. METHODS: We conducted a meta-analysis of urodynamic findings of experimental trials that included studies of stem cell-based cell therapy in SCI. Relevant studies were searched using MEDLINE, EMBASE and Cochrane Library (January 1990 - December 2012). Final inclusion was determined by a urodynamic study involving detailed numerical values. Urodynamic parameters for analysis included voiding pressure, residual urine, bladder capacity and non-voiding contraction (NVC). Meta-analysis of the data, including findings from urodynamic studies, was performed using the Mantel-Haenszel method. RESULTS: A total of eight studies were included with a sample size of 224 subjects. The studies were divided into different subgroups by different models of SCI. After a stem cell-based cell therapy, voiding pressure (-6.35, p <0.00001, I2 = 77%), NVC (-3.58, p <0.00001, I2 = 82%), residual urine (-024, p = 0.004, I2 = 95%) showed overall significant improvement. Bladder capacity showed improvement after treatment only in the transection type (-0.23, p = 0.0002, I2 = 0%). CONCLUSION: After stem cell-based cell therapy in SCI, partial bladder recovery including improvement of voiding pressure, NVC, and residual urine was demonstrated. Additional studies are needed to confirm the detailed mechanism and to obtain an ideal treatment strategy for bladder recovery.

Measuring the improvement in health-related quality of life using King's health questionnaire in non-obese and obese patients with lower urinary tract symptoms after alpha-adrenergic medication: a preliminary study.

BACKGROUND: The efficacy of medical treatment among obese men with lower urinary tract symptoms (LUTS) has been less clear, especially regarding the improvement of QoL. We aimed to investigate the difference in efficacy and consequent satisfaction of life quality after medical treatment of male LUTS according to obesity. METHODS: An 8-week prospective study was performed for a total of 140 patients >50 years old with International Prostate Symptom Scores (IPSS) > 12 points and prostate volume > 20 mL. Obesity was determined by either body mass index (BMI) or waist circumference (WC). Patients were divided into 2 groups according to BMI or WC. Patients received tamsulosin at a dose of 0.4 mg daily for 8 weeks. The changes from baseline in the IPSS, maximal urinary flow rate (Qmax), post-void residual volume, questionnaire of quality of life (QoL), and King's Health Questionnaire (KHQ) were analyzed. RESULTS: Of the 150 enrolled patients, 96 completed the study. Seventy-five patients (78.1%) had BMI ≥ 23 kg/m2, and 24 (25.0%) had WC > 90 cm. Overall, the IPSS, IPSS QoL, and total KHQ showed significant improvement. Obese (BMI ≥ 23 kg/m2) and non-obese (BMI < 23 kg/m2) both showed improvement of the IPSS and IPSS QoL scores, but only the obese (BMI ≥ 23 kg/m2) group showed improvement of the total KHQ score (P < 0.001 vs. P = 0.55). Only the obese (WC > 90 cm) group showed improvement of the IPSS and total KHQ scores (P < 0.001). CONCLUSIONS: Our preliminary study showed the different efficacy of an alpha-blocker for improvement of LUTS and life quality according to obesity. Obese patients, defined by BMI or WC, showed the tendency toward a more favorable improvement of LUTS and life quality. TRIAL REGISTRATION: Current Controlled Trials 2010-058. Registered 2 September 2010 in Soonchunhyang University Hospital.

Association between the hemodialysis adequacy and sexual dysfunction in chronic renal failure: a preliminary study.

BACKGROUND: The core question of the study was whether adequately achieved HD affected the sexual dysfunction in women on hemodialysis (HD) with chronic renal failure (CRF). METHODS: Thirty-seven female patients on HD, including 18 women with adequate HD and 19 women with non-adequate HD, and 36 healthy controls were included in this study. Demographic and clinical variables, including the sexual hormones estradiol and testosterone, were recorded. Sexual function was assessed according to the Female Sexual Function Index (FSFI) and results were compared between groups. Adequate HD was defined as an average urea clearance of over 1.3 (Kt/V) over three consecutive months. RESULTS: All domains of the FSFI questionnaire, with the exception of satisfaction, were higher in the control group than in the HD group. In comparing the adequate and non-adequate HD groups, there was no difference in any of the six domains of the FSDI questionnaire. Among the clinical variables, the number of menopausal women was higher in the HD group than in the control group (P = 0.023). Estradiol and testosterone levels were higher in the control group than in the HD group (P = 0.003, 0.027, respectively). The number of menopausal women and estradiol and testosterone levels showed no differences between the adequate and non-adequate HD groups. Correlation analysis between Kt/V and FSFI showed no significant relationship, but estrogen did show a significant relationship with FSFI (correlation coefficient = 0.399, P = 0.001). CONCLUSIONS: HD adequacy alone does not have a significant impact on sexual dysfunction. Other treatments options should be considered to treat sexual dysfunction in women with CRF.

Liver recurrence in early endometrial cancer with focal myometrial invasion.

Endometrial cancer is the most common malignancy of the female genital tract. The cancer spreads by direct extension, transtubal dissemination, lymphatic dissemination, and/or by hematogenous spread, usually results in lung metastasis, but may less commonly involve liver, brain, and bone. Here, we describe a patient with stage IA endometrial cancer who developed liver recurrence 17 months after surgery.

Management of endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: single arm, prospective multicenter study: Korean gynecologic oncology group study (KGOG2006).

A prospective multicenter trial has been commenced in Korea to investigate the treatment efficacy of the levonorgestrel-releasing intrauterine system in patients with endometrial hyperplasia. The levonorgestrel-releasing intrauterine system is an alternative to oral progesterone without the disadvantages of oral progestogens. Therefore, we hypothesize that if the therapeutic efficacy of the levonorgestrel-releasing intrauterine system is similar to or greater than that of oral progesterone, the levonorgestrel-releasing intrauterine system could become the standard treatment for endometrial hyperplasia patients who do not want a hysterectomy. The levonorgestrel-releasing intrauterine system is inserted into uteri of patients with histologically confirmed endometrial hyperplasia. An office endometrial aspiration biopsy and transvaginal ultrasound are conducted every 3 months at an outpatients clinic. The primary endpoint is the response rate. The secondary endpoint is to estimate the consistency of the results of the office endometrial aspiration biopsy during the levonorgestrel-releasing intrauterine system being placed in uterus and a dilatation and curettage procedure.

Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12.

OBJECTIVE: We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: This multicenter case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75 years). RESULTS: Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend = 0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C > T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18-4.85) and 3.19 (1.43-7.13)]. Low vitamin B12 and the MTHFR 677 C > T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17-5.42) and 2.40 (1-5.73)] vs. wild-type or heterozygous status with high vitamin levels. CONCLUSION: Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.

Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea.

Cervical cancer is one of the most common gynecological malignancies in Korea, although the incidence has been declining in recent years. This study explored whether antioxidant vitamin intakes influenced the risk of cervical cancer. The association between antioxidant vitamin intakes and cervical cancer risk was calculated for 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models. Cases reported statistically lower mean dietary intakes of vitamin A, beta -carotene, and vitamin C than did controls. Total intakes of vitamins A and E, which included both dietary and supplement intake, were also lower in cases. Those patients in the highest quartiles of dietary vitamin A, beta -carotene, and vitamin C intakes had statistically significantly lower cervical cancer risks than those in the lowest quartiles for vitamin A, beta -carotene, and vitamin C: odds ratio (OR) = 0.36 [95% confidence interval (CI) = 0.19-0.69), OR = 0.48 (CI = 0.26-0.88), and OR = 0.36 (CI = 0.18-0.69), respectively. Total intakes of vitamins A, C, and E were strongly inversely associated with cervical cancer risk: OR = 0.35 (CI = 0.19-0.65), OR = 0.35 (CI = 0.19-0.66), and OR = 0.53 (CI = 0.28-0.99), respectively. The findings support a role for increased antioxidant vitamin intake in decreasing the risk of cervical cancer. These associations need to be assessed in large prospective studies with long-term follow-up.

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women.

The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 case-control samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.

Functional polymorphism in manganese superoxide dismutase and antioxidant status: their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVE: Manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, plays a key role in protecting cells from oxidative stress. Furthermore, the MnSOD rs4880 polymorphism is associated with enzyme activity. The authors evaluated the interaction between MnSOD genotypes and cervical carcinogenesis risk and the modulating effects of serum antioxidant nutrient status (beta-carotene, lycopene, zeaxanthin/lutein, retinol, alpha-tocopherol and gamma-tocopherol). METHODS: Cases and controls for this study were recruited between June 2006 and July 2007 (263 controls, 84 cervical intraepithelial neoplasia (CIN), 94 CIN 2/3, and 99 cases of cervical cancer). The MnSOD polymorphism at rs4880T/C was examined using SNaPshot assays. Serum antioxidant vitamin concentrations were measured by reverse-phase gradient high-pressure liquid chromatography. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated after adjusting for age, menopause, parity, oral contraceptive use, smoking and alcohol consumption. RESULTS: No association was found between the MnSOD rs4880 polymorphism and cervical cancer. However, genotypes significantly modified the risk of cervical cancer in association with the serum statuses of micronutrients (P(interaction)<0.05 for beta-carotene, lycopene, zeaxanthin/lutein, alpha-tocopherol, and gamma-tocopherol). Decreased CIN1 risk in association with the MnSOD rs4880 variant genotype was also observed particularly for subjects with higher beta-carotene and gamma-tocopherol levels. Similar results were observed for lycopene and alpha-tocopherol in relation to the risk of CIN2/3. CONCLUSION: Our findings suggest that a higher antioxidant micronutrients status may decrease the risk of CIN and cervical cancer and modify the effect of the MnSOD polymorphism on disease risk.

Surgical practice patterns in endometrial cancer: results of the Korean Gynecologic Oncology Group survey.

OBJECTIVE: This study was undertaken to document current practice patterns for the surgical treatment of endometrial cancer in Korea. METHODS: Questionnaires were distributed to 131 Korean gynecologic oncologists, all members of the Korean Gynecologic Oncology Group. Questions addressed extent of hysterectomy procedure, pelvic (PEN) or paraaortic (PAN) lymph node dissection, ovarian preservation, and omentectomy. RESULTS: Completed questionnaires were returned by 64.1% (84/131) of the oncologists at 50 institutes. Extrafascial hysterectomy (EH) was used by 32% of respondents and modified radical hysterectomy (MRH) or radical hysterectomy (RH) by 17%. Hysterectomy procedures were selectively employed based on tumor-related factors by 51% of the respondents. Laparoscopic hysterectomy was routinely utilized by 49% and was more commonly used by younger surgeons with 10 years of experience or less. PEN dissection was routinely utilized by 67% and was used selectively based on tumor-related factors by 33%. PAN dissection/biopsy was used either routinely (43%) or selectively based on tumor-related factors (43%). PAN dissection/biopsy had never been employed by 12% of the respondents. Sixty-nine percent of respondents stated that grossly normal looking ovaries can be preserved during surgery in young aged patients with early stage disease, and 29% stated that bilateral oophorectomy should be performed irrespective of age or stage. Omentectomy was routinely performed by 11% of respondents, and was selectively performed when extrauterine spread was present by 41%. CONCLUSION: Surgical procedures for the treatment of endometrial cancer are still not standardized among Korean gynecologic surgeons. Clinical trials to determine the benefits of the different surgical procedures should be developed.