The Role of Sex-specific Long Non-coding RNAs in Cancer Prevention and Therapy.

The functions of a large number of non-coding genes in human DNA have yet to be accurately identified. Long non-coding RNA (lncRNA) measuring 10 kb or less in length regulates transcription or post-transcriptional events. The lncRNAs have attracted increased attention of researchers in recent years. In this review, we summarize the recently published lncRNAs which are known to influence cancer development and progression. We also discuss recent studies investigating tumor-specific lncRNA expression. These lncRNAs provide very useful information that allows prediction of the degree of malignancy and a survival rate in cancer patients as clinically relevant biomarkers. Because symptoms and progression of cancer differ from onset to death between males and females, it is important to consider the gender of the patient when diagnosing cancer and predicting the progression. Considering the importance of gender difference, we also examine the influence of sex hormones involved in the expression and regulation of lncRNAs as biomarkers. Many of the lncRNAs examined in this review have been studied in cancers occurring in the female or male reproductive organs, but the association between lncRNAs and sex hormones has also been reported in common organs such as the lung, renal and colon. Although lncRNAs have not yet been widely used as definitive cancer indicators, recent studies have demonstrated the potential role of lncRNAs as biomarkers and therapeutic targets reflecting sex-specificity in a number of different cancers.

CCL8 mediates crosstalk between endothelial colony forming cells and triple-negative breast cancer cells through IL-8, aggravating invasion and tumorigenicity.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a poor prognosis for which no effective therapeutic measures are currently available. The present study aimed to investigate whether interactions with endothelial colony-forming cells (ECFCs) promote aggressive progression of TNBC cells. Herein, using an indirect co-culture system, we showed that co-culture increased the invasive and migratory phenotypes of both MDA-MB-231 TNBC cells and ECFCs. Through a cytokine antibody array and RT-PCR analysis, we revealed that co-culture markedly induced secretion of the chemokine C-C motif ligand (CCL)8 from ECFCs and that of interleukin (IL)-8 from MDA-MB-231 cells. CCL8 was crucial for ECFC-induced IL-8 secretion and invasion of MDA-MB-231 cells as well as for MDA-MB-231-enhanced MMP-2 secretion and angiogenesis of ECFCs. We suggest c-Jun as a transcription factor for CCL8-induced IL-8 expression in MDA-MB-231 cells. IL-8 was important for co-culture-induced CCL8 and MMP-2 upregulation and invasion of ECFCs. Notably, our findings reveal a positive feedback loop between CCL8 and IL-8, which contributes to the aggressive phenotypes of both ECFC and TNBC cells. Using an MDA-MB-231 cell-based xenograft model, we show that tumor growth and metastasis are increased by co-injected ECFCs in vivo. Increased expression of IL-8 was observed in tissues with bone metastases in mice injected with conditioned media from co-cultured cells. High IL-8 levels are correlated with poor recurrence-free survival in TNBC patients. Together, these results suggest that CCL8 and IL-8 mediate the crosstalk between ECFCs and TNBC, leading to aggravation of tumorigenicity in TNBC.

Sex-Biased Molecular Signature for Overall Survival of Liver Cancer Patients.

Sex/gender disparity has been shown in the incidence and prognosis of many types of diseases, probably due to differences in genes, physiological conditions such as hormones, and lifestyle between the sexes. The mortality and survival rates of many cancers, especially liver cancer, differ between men and women. Due to the pronounced sex/gender disparity, considering sex/ gender may be necessary for the diagnosis and treatment of liver cancer. By analyzing research articles through a PubMed literature search, the present review identified 12 genes which showed practical relevance to cancer and sex disparities. Among the 12 sex-specific genes, 7 genes (BAP1, CTNNB1, FOXA1, GSTO1, GSTP1, IL6, and SRPK1) showed sex-biased function in liver cancer. Here we summarized previous findings of cancer molecular signature including our own analysis, and showed that sexbiased molecular signature CTNNB1High, IL6High, RHOAHigh and GLIPR1Low may serve as a female-specific index for prediction and evaluation of OS in liver cancer patients. This review suggests a potential implication of sex-biased molecular signature in liver cancer, providing a useful information on diagnosis and prediction of disease progression based on gender.

Relationship between the endoscopic withdrawal time and adenoma/polyp detection rate in individual colonic segments: a KASID multicenter study.

BACKGROUND AND AIMS: Appropriate colonoscopy withdrawal times for individual colonic segments are not well known. The relationship between withdrawal time and adenoma detection rate (ADR)/polyp detection rate (PDR) in individual colonic segments was examined in this study. METHODS: This was a prospective observational study involving 724 patients who underwent colonoscopy screening or surveillance colonoscopy from October 2015 to February 2017 at 10 university hospitals. RESULTS: In the right side of the colon, the ADR (33.2% vs 13.7%, P < .001), PDR, serrated polyp detection rate, and number of adenomas per colonoscopy (APC) were significantly higher when the colonoscopy withdrawal time was ≥2 minutes compared with <2 minutes. When the withdrawal time was ≥4 minutes in the proximal colon and ≥3 minutes in the left segment of the colon, the ADR, PDR, and APC were significantly higher compared with withdrawal times of <4 minutes and <3 minutes, respectively. Multivariate analyses showed that the ADR was significantly associated with withdrawal times of ≥2 minutes in the right side of the colon (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.72-5.15; P < .001), ≥4 minutes in the proximal colon (OR, 4.48; 95% CI, 3.15-6.36; P < .001), and ≥3 minutes in the left segment of the colon (OR, 2.92; 95% CI, 1.74-4.91; P < .001). CONCLUSIONS: The PDR and ADR appeared to be significantly increased when the withdrawal time was ≥2 minutes in the right-sided colon segment, ≥4 minutes in the proximal colon, and ≥3 minutes in the left-sided colon segment compared with shorter withdrawal times.

Quality of care in inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 2(nd) Asian Organization of Crohn's and Colitis (AOCC) meeting in Seoul.

BACKGROUND/AIMS: The quality of care in inflammatory bowel disease (IBD) has not been systematically estimated. The aim of this study was to investigate the current status of quality of IBD care in Asian countries. METHODS: A questionnaire-based survey was conducted between March 2014 and May 2014. The questionnaire was adopted from "An adult inflammatory bowel disease physician performance measure set" developed by the American Gastroenterological Association. If the respondent executed the performance measure in more than 70% of patients, the measure was regarded as well performed. RESULTS: A total of 353 medical doctors from Asia completed the survey (116 from Korea, 114 from China, 88 from Japan, 17 from Taiwan, 8 from Hong-Kong, 4 from India, 3 from Singapore, and 1 each from the Philippines, Malaysia and Indonesia). The delivery of performance measures, however, varied among countries. The documentation of IBD and tuberculosis screening before anti-tumor necrosis factor therapy were consistently performed well, while pneumococcal immunization and prophylaxis of venous thromboembolisms in hospitalized patients were performed less frequently in all countries. Physician awareness was positively associated with the delivery of performance measures. Variations were also noted in reasons for non-performance or low performance of quality measures, and the two primary reasons cited were consideration of the measure to be unimportant and lack of time. CONCLUSIONS: The delivery of performance measures varies among physicians in Asian countries, and reflects variations in the quality of care among the countries. This variation should be recognized to improve the quality of care in Asian countries.

Importance of Patients' Knowledge of Their Prescribed Medication in Improving Treatment Adherence in Inflammatory Bowel Disease.

GOALS: To investigate the association between treatment nonadherence and patients' knowledge of the prescribed medication among individuals with inflammatory bowel disease (IBD), and evaluate the impact of nonadherence on relapse. BACKGROUND: The patient's knowledge of the prescribed medication has been identified as an important predictor of treatment adherence in chronic diseases. However, this association has not been examined in IBD. STUDY: In this prospective study, at baseline, 138 patients with IBD completed a self-reported survey on demographic data, knowledge of the prescribed medication, and candidate factors related to the degree of treatment adherence. To investigate the impact of nonadherence among patients in remission, relapse was analyzed for 18 months after enrollment. RESULTS: Nonadherence was observed in 50 (36.2%) of the 138 subjects. In multivariate analysis, nonadherence was significantly associated with younger age (less than 30 y) at participation [odds ratio (OR), 5.88; 95% confidence interval (CI), 1.51-22.94; P=0.011], longer intervals between outpatient clinic visits (≥3 mo) (OR, 30.31; 95% CI, 3.06-300.17; P=0.004), and limited knowledge of the prescribed medication (OR, 5.61; 95% CI, 1.60-19.67; P=0.038). Nonadherent patients had a significantly greater risk of relapse of IBD than adherent patients (relative risk, 2.9; 95% CI, 2.25-3.79; P=0.045). CONCLUSION: Younger age, longer intervals between outpatient clinic visits, and limited knowledge of the prescribed medication tended to be associated with nonadherence to treatment, which consequently also affects the risk of relapse.

Associations of colorectal cancer incidence with nutrient and food group intakes in korean adults: a case-control study.

This study aimed to examine the associations between intakes of various nutrients and food groups and colorectal cancer risk in a case-control study among Koreans aged 20 to 80 years. A total of 150 new cases and 116 controls were recruited with subjects' informed consent. Dietary data were collected using the food frequency questionnaire developed and validated by the Korea Centers for Disease Control and Prevention. Multivariate logistic regression models were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for colorectal cancer incidence. High intakes of total lipid (ORT3 vs T1 = 4.15, 95% CI: 1.33-12.96, p for trend = 0.034), saturated fatty acid (ORT3 vs T1 = 2.96, 95% CI: 1.24-7.04, p for trend = 0.016) and monounsaturated fatty acid (ORT3 vs T1 = 3.04, 95% CI: 1.23-7.54, p for trend = 0.018) were significantly associated with increased incidence of colorectal cancer. High dietary fiber (ORT3 vs T1 = 0.22, 95% CI: 0.08-0.56, p for trend = 0.002) and vitamin C (ORT3 vs T1 = 0.38, 95% CI: 0.14-1.05, p for trend = 0.021) intakes were significantly associated with reduced colorectal cancer incidence. From the food group analysis, bread (ORT3 vs T1 = 2.26, 95% CI: 0.96-5.33, p for trend = 0.031), red meat (ORT3 vs T1 = 7.33, 95% CI: 2.98-18.06, p for trend < 0.001), milk·dairy product (ORT3 vs T1 = 2.42, 95% CI: 1.10-5.31, p for trend = 0.071) and beverage (ORT3 vs T1 = 3.17, 95% CI: 1.35-7.48, p for trend = 0.002) intakes were positively associated with colorectal cancer risk. On the other hand, high intake of traditional rice cake (ORT3 vs T1 = 0.35, 95% CI: 0.14-0.86, p for trend = 0.024) was linked with lower colorectal cancer incidence. In conclusion, eating a diet high in total lipid, saturated fatty acids and monounsaturated fatty acids is associated with higher incidence of colorectal cancer, whereas a diet high in dietary fiber and vitamin C was found to lower the incidence in Korean adults. Interestingly high traditional rice cake consumption is associated inversely with colorectal cancer incidence, warranting a future study.

The use of low-volume polyethylene glycol containing ascorbic acid versus 2 L of polyethylene glycol plus bisacodyl as bowel preparation for colonoscopy.

OBJECTIVE: Low-volume polyethylene glycol (PEG) bowel preparations have been developed to improve compliance for colonoscopy. Our study aimed to compare the efficacy and tolerability of low-volume PEG containing ascorbic acid for colonoscopy against 2 L of PEG plus bisacodyl. METHODS: We prospectively enrolled consecutive inpatients who had not undergone polypectomy at the index colonoscopy and were subsequently referred for polypectomy at our hospital. A total of 62 patients were randomized to receive either low-volume PEG containing ascorbic acid (n = 31) or 2 L of PEG plus bisacodyl (n = 31) as a split-dose regimen in inpatients. The efficacy of preparation was determined using the Ottawa Bowel Preparation Score (OBPS) and a 4-point scale. Adverse events, tolerability, and willingness were evaluated using a questionnaire. RESULTS: Based on the OBPS and 4-point scale, we determined that the efficacy of low-volume PEG containing ascorbic acid was comparable to that of the 2 L of PEG plus bisacodyl (p = 0.071 for OBPS, p = 0.056 for the 4-point scale). Adverse events were comparable between the two groups (p = 1.000). A greater proportion of patients in the low-volume PEG containing ascorbic acid (90.6%) and the 2L of PEG plus bisacodyl (96.9%) were willing to repeat the same preparation for subsequent colonoscopy. CONCLUSION: Low-volume PEG containing ascorbic acid had comparable efficacy and tolerability to 2 L of PEG plus bisacodyl, when given as a split dose, for colonoscopy in inpatients. Split-dose low-volume PEG containing ascorbic acid is a good alternative for bowel preparation for colonoscopy in inpatients.

[Caustic injury of upper gastrointestinal tract: 20 year experience at a tertiary referral center].

BACKGROUND/AIMS: Caustic ingestion can cause severe injury to upper gastrointestinal tract. There were few studies about clinical characteristics and treatments of caustic injury in Korea. We investigated the changes in clinical features of caustic injury over the past 20 years including pattern of endoscopic mucosal injury and treatment modality. METHODS: This study was a retrospective review of medical records from patients with caustic injury from September 1993 through December 2012. Patients were classified into two groups based on the year when caustic ingestion occurred: patients who visited the hospital from 1993 to 2002 (early group) and patients who visited the hospital from 2003 to 2012 (late group). RESULTS: A total 140 patients were included (early group [n=50] vs. late group [n=90]). Annual number of caustic ingestions did not show decreasing tendency over the past 20 years. Alkali ingestion increased (20.0% vs. 65.6%, p<0.001) and cases with more than grade 2b of esophageal mucosal injury decreased (41.3% vs. 20.7%, p=0.012) in late group. There were no differences between two groups in sex, age, proportion of accidental ingestion, and systemic/gastrointestinal complications. Use of gastric lavage (p<0.01) and broad spectrum antibiotics (p=0.03) decreased in late group. However, there was no difference in use of steroid between two groups. CONCLUSIONS: In this study, overall caustic ingestion did not decrease and ingestion of alkali agents increased over the past 20 years. Tighter legislation on caustic agents is required and we need to be alert to the best management of caustic injury.

Isolated terminal ileal ulcerations in asymptomatic individuals: natural course and clinical significance.

BACKGROUND: Although isolated terminal ileal ulcerations (ITIUs) are occasionally observed on colonoscopic examination of asymptomatic individuals, their clinical course and guidelines for treatment are unclear. OBJECTIVE: To evaluate the clinical course and significance of ITIUs in asymptomatic individuals. DESIGN: Single-center retrospective analysis. SETTING: University hospital. PATIENTS AND INTERVENTIONS: All patients diagnosed with ITIUs on colonoscopy from July 2001 to December 2007 were identified. Patients with colorectal symptoms, a history of nonsteroidal anti-inflammatory drug consumption, a history of colorectal surgery, oral or genital ulcerations, and coincidental ulceration in the ileocecal valve or colon were excluded. MAIN OUTCOME MEASUREMENTS: Colonoscopic findings and clinical courses of patients were analyzed. RESULTS: Of the 148 included patients, 93 were followed (mean duration, 29.9 months). Of these, 62 showed resolution of ITIU on follow-up colonoscopy, including 60 who resolved without any treatment and 2 who resolved after antituberculosis medication. Follow-up colonoscopy continued to show ITIUs in the remaining 31 patients, only 1 of whom developed typical Crohn's disease, whereas the other 30 showed no significant changes in the lesions (n = 22), partial improvement (n = 6), or waxing and waning endoscopic appearance (n = 2). LIMITATIONS: Retrospective design, relatively short-term follow-up. CONCLUSIONS: Most ITIUs incidentally observed in asymptomatic individuals resolve without any treatment. Even if these lesions persist, it is unusual for them to progress or to cause any symptoms.

Screening colonoscopy in asymptomatic average-risk Koreans: analysis in relation to age and sex.

BACKGROUND AND AIMS: Although the incidence of colorectal cancer is rising in Asian countries, there are no guidelines for its screening in this region due in part to the lack of epidemiological data regarding colorectal neoplasms. This study aimed to evaluate the prevalence of colorectal neoplasms in average-risk Koreans and to assess the effectiveness of screening colonoscopy in Korea. METHODS: The prevalence of colorectal neoplasms was assessed by primary screening colonoscopy in 5,086 consecutive asymptomatic adults (males 70.5%; age 20-84 years) with no risk factors for colorectal cancer. RESULTS: The overall prevalence of colorectal neoplasms in the 5,086 subjects was 21.9% and this increased linearly with age. Among the 2,435 subjects aged >or=50 years (males 66.7%; mean age 57.7 years), the prevalence of all colorectal neoplasms was 30.2% (males 35.9% vs females 18.7%; P < 0.001), while advanced neoplasms accounted for only 4.1% (males 5.1% vs females 2.0%; P < 0.001). The prevalence of advanced neoplasms in Korean men of a specific age group was similar to that of Korean women in the 10-years older age group. Also, Koreans in a specific age group showed a prevalence of advanced neoplasms similar to that of Westerners in the 10-years younger age group. CONCLUSIONS: Colonoscopy is a useful modality for colorectal cancer screening in Korea, as established in Western countries. However, the screening colonoscopy may begin at an older age for Koreans than for Westerners. Similarly, the optimal starting age for screening in Korean women may be higher than that in men by 10 years.