A natural antisense lncRNA controls breast cancer progression by promoting tumor suppressor gene mRNA stability.

The human genome encodes thousands of long noncoding RNA (lncRNA) genes; the function of majority of them is poorly understood. Aberrant expression of a significant number of lncRNAs is observed in various diseases, including cancer. To gain insights into the role of lncRNAs in breast cancer progression, we performed genome-wide transcriptome analyses in an isogenic, triple negative breast cancer (TNBC/basal-like) progression cell lines using a 3D cell culture model. We identified significantly altered expression of 1853 lncRNAs, including ~500 natural antisense transcript (NATs) lncRNAs. A significant number of breast cancer-deregulated NATs displayed co-regulated expression with oncogenic and tumor suppressor protein-coding genes in cis. Further studies on one such NAT, PDCD4-AS1 lncRNA reveal that it positively regulates the expression and activity of the tumor suppressor PDCD4 in mammary epithelial cells. Both PDCD4-AS1 and PDCD4 show reduced expression in TNBC cell lines and in patients, and depletion of PDCD4-AS1 compromised the cellular levels and activity of PDCD4. Further, tumorigenic properties of PDCD4-AS1-depleted TNBC cells were rescued by exogenous expression of PDCD4, implying that PDCD4-AS1 acts upstream of PDCD4. Mechanistically, PDCD4-AS1 stabilizes PDCD4 RNA by forming RNA duplex and controls the interaction between PDCD4 RNA and RNA decay promoting factors such as HuR. Our studies demonstrate crucial roles played by NAT lncRNAs in regulating post-transcriptional gene expression of key oncogenic or tumor suppressor genes, thereby contributing to TNBC progression.

Diagnostic role of endoscopic ultrasonography-guided fine needle aspiration of gallbladder lesions.

BACKGROUND/AIMS: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a well-established diagnostic technique for examining various organs of the gastrointestinal tract and pancreas, but little is known about its use in the diagnostic work-up of GB lesions. The objective of this retrospective study was to evaluate the efficacy of EUS-FNA of GB lesions. METHODOLOGY: Twenty-eight patients who underwent EUS-FNA for evaluation of GB lesions were enrolled. The pathological results and complications were assessed. RESULTS: EUS-FNA of GB was performed in 13 patients and that of enlarged lymph nodes was done in 18. Of the 13 GB lesions sampled by EUS-FNA, 10 were diagnosed as malignant and 3 were negative for malignant cells. Of the latter 3, two were false negatives for malignancy. All 14 metastatic lymphadenopathy cases were diagnosed with EUS-FNA of lymph nodes. EUS-FNA could differentiate adenocarcinomas and other malignant diseases. Cholecystitis occurred in one patient after EUS-FNA of the GB. CONCLUSIONS: EUS-FNA is a feasible, safe and reliable method for obtaining samples from GB lesions. EUS-FNA of lymph nodes is complementary to EUS-FNA of the GB and provides nodal stage as well as histological diagnosis.

Efficacy and tolerability of split-dose PEG compared with split-dose aqueous sodium phosphate for outpatient colonoscopy: a randomized, controlled trial.

BACKGROUND AND AIMS: Adequate bowel cleansing is essential for a high-quality, effective, and safe colonoscopy. The aims of this study were to compare the efficacy and tolerability of split-dose polyethylene glycol with aqueous sodium phosphate for outpatients who underwent scheduled colonoscopy. METHODS: In this prospective trial, 207 outpatients (aged between 18 and 65 years, with normal renal function, at low risk for renal damage) were randomized to receive split-dose preparation of PEG (2 L/2 L) (N = 103) or NaP (45 mL/45 mL, 12 h apart) (N = 104) without strict diet restriction the day before colonoscopy. The bowel cleansing efficacy of preparations was rated according to the Ottawa scale and the patient tolerability was assessed using a patient questionnaire. RESULTS: There was no significant difference between the two groups for the mean total score using the Ottawa bowel preparation scale (P = 0.181). Significantly greater residual colonic fluid was observed in the split-dose PEG group (1.24 ± 0.49) than in the NaP group (1.04 ± 0.53) (P = 0.007). Patient compliance, preference, and acceptance of a two preparation regimen were similar with no significant differences (P = 0.095, P = 0.280 and P = 0.408, respectively). The overall incidence of adverse events was not significantly different between the two groups; however, the split-dose PEG group tended to have fewer adverse events (52/103 [50.5%], 66/104 [63.5%], P = 0.059) and had significantly less nausea and vomiting (P = 0.036). CONCLUSIONS: Split-dose PEG, compared with split-dose NaP, is associated with more residual colonic fluid, but produces equivalent colon cleansing efficacy and results in less nausea and vomiting, which might improve patient tolerability (clinical trial registration number NCT01229800).

The efficacy of the combination therapy with oral and topical mesalazine for patients with the first episode of radiation proctitis.

BACKGROUND/AIMS: Radiation proctitis is a common complication of pelvic radiation for which an optimal treatment remains undetermined. We assessed the efficacy of oral and topical mesalazine combination therapy for patients with naive radiation proctitis. METHODS: A total of 23 patients with radiation proctitis were enrolled in the study over a period of 2 years. Three of these patients were excluded due to severe bleeding during the study. Twenty patients (mean age 60.3 years; two males, 18 females) were treated with oral mesalazine (3 × 1 g per day) plus a daily mesalazine suppository (1 g per day at bedtime) for 4 weeks. The efficacy of treatment was assessed according to the Subjective Objective Management Analytic (SOMA) scale for alleviation of clinical symptoms of rectal toxicity and sigmoidoscopic findings. RESULTS: The mean bleeding score improved significantly from 2.10 to 1.70 (p = 0.002) with mesalazine treatment. However, scores were not improved for pain (0.30-0.20, p = 0.163), tenesmus (0.50-0.45, p = 0.577), or stool frequency (0.35-0.30, p = 0.577). The improvements in the mean telangiectasia score (1.80-1.45, p = 0.005), bleeding point score (1.60-1.05, p < 0.001), and friable mucosa score (1.35-1.00, p = 0.005) were all statistically significant. No side-effects were noted in any of the patients. CONCLUSIONS: The combination of oral and topical mesalazine therapy for radiation proctitis may be a safe and effective treatment for naive radiation proctitis, especially for hemorrhagic proctitis. A large, randomized controlled trial is required to confirm the results of this pilot study.

A phase II study of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced non-small cell lung cancer.

BACKGROUND: More than 50% of all advanced non-small cell lung cancer (NSCLC) is diagnosed in patients older than 65 years. Chemotherapy in elderly patients has not been standardized even though cisplatin-based chemotherapy has been used in patients with advanced NSCLC as primary therapy. We investigated the efficacy and safety of combination chemotherapy with docetaxel and carboplatin for elderly patients with advanced NSCLC. METHODS: Chemotherapy-naïve patients (age > or = 65 years) with stage IIIB or IV NSCLC were enrolled. Patients received docetaxel (75 mg/m(2) on D1) and carboplatin (AUC of 5mg/ml/min on D1) every 3 weeks. The end points included the response rate, progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: A total of 43 patients was enrolled between March 2005 and December 2008, and 38 patients were evaluable. The median age was 74 years old (range, 65-84 years) and 39 patients (90.6%) had an ECOG PS of 0 or 1. Squamous cell carcinoma was observed in 18 patients (41.8%) and 24 patients (55.8%) had an increased Charlson comorbidity index score (CCI > or = 1). The median number of treatment cycles was five (range, 1-8) and the relative dose intensity was 90.4% for docetaxel and 92.7% for carboplatin. The overall response rate was 46.5% (95% CI, 31.6-61.4) for with one complete response and 19 partial responses. The median follow-up duration was 14.4 months. The median PFS was 6.9 months (95% CI, 6.25-7.55) and the median OS was 13.1 months (95% CI, 10.20-16.07). The 1-year survival rate was 60%. In grade 3 or 4 hematological toxicities, neutropenia (37.2%), anemia (18.6%) and thrombocytopenia (4.6%) were shown. The non-hematological toxicities were tolerable. CONCLUSIONS: The combination chemotherapy with docetaxel and carboplatin was effective with tolerable toxicities in elderly patients with advanced non-small cell lung cancer.

Non-ischemic cardiomyopathy attributed to adult myotonic dystrophy.

In patients with myotonic dystrophy (MD), impairment of the conduction system is a common and progressive finding. However, only a few cases of MD with cardiomyopathy have been reported. Herein we report a case of MD with progressive non-ischemic cardiomyopathy and severe electrocardiographic abnormalities.