A novel NRF2/ARE inhibitor gossypol induces cytotoxicity and sensitizes chemotherapy responses in chemo-refractory cancer cells.

NRF2/ARE signaling pathway is a principal regulator of cellular redox homoeostasis. The stress-induced transcription factor, NRF2, can shield cells from the oxidative damages via binding to the consensus antioxidant-responsive element (ARE) and driving several cyto-protective genes expression. Increasing evidence indicated that aberrant activation of NRF2 in malignant cells may support their survival through various pathways to detoxify chemotherapy drugs, attenuate drug-induced oxidative stress, or induce drug efflux, all of which are crucial in developing drug resistance.

A Novel Signature for Predicting Prognosis of Smoking-Related Squamous Cell Carcinoma.

Tobacco smoking is an established risk factor for squamous cell carcinoma (SCC). We obtained smoking-related SCC, including cervical SCC (CSCC), esophageal SCC (ESCC), head and neck SCC (HNSC), and lung SCC (LUSC), from The Cancer Genome Atlas (TCGA) database to investigate the association between smoking status (reformed and current smoking) and prognosis. We found that reformed smokers had a better prognosis than current smokers in CSCC ( = 0.

c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation.

NRF2, a redox sensitive transcription factor, is up-regulated in head and neck squamous cell carcinoma (HNSCC), however, the associated impact and regulatory mechanisms remain unclear. The protein expression of NRF2 in HNSCC specimens was examined by IHC. The regulatory effect of c-MYC on NRF2 was validated by ChIP-qPCR, RT-qPCR and western blot.

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

Purpose: To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes.

Methods: A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation.

Results: Four studies including 527 patients eligible for inclusion in meta-analysis were identified.

Improvement of overactive bladder symptoms: Is correction of the paravaginal defect in anterior vaginal wall prolapse necessary?

Background: To explore the relationship between overactive bladder (OAB) symptoms and paravaginal defects (PVDs), and to identify the necessity of PVD repair by transvaginal mesh (TVM) for the treatment of OAB symptoms.

Methods: A retrospective clinical study of 30 women with advanced cystocele with limited apical and posterior vaginal wall prolapse was conducted to identify any changes in OAB symptoms following a single Perigee procedure. Prolapse was assessed using the pelvic organ prolapse quantification (POP-Q) system, and paravaginal defects were identified by sonography.

The Impact of the National Essential Medicines Policy on Rational Drug Use in Primary Care Institutions in Jiangsu Province of China.

Background: Essential medicine policy is a successful global health policy to promote rational drug use. The aim of this study was to evaluate the impact of the National Essential Medicines Policy (NEMP) on the rational drug use in primary care institutions in Jiangsu Province of China.

Methods: In this exploratory study, a multistage, stratified, random sampling was used to select 3400 prescriptions from 17 primary care institutions who implemented the NEMP before (Jan 2010) and after the implementation of the NEMP (Jan 2014).

Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.

Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation.

Delayed postcoital vaginal cuff dehiscence with small bowel evisceration after robotic-assisted staging surgery.

Objective: We report a rare case of vaginal cuff dehiscence with small bowel evisceration at 7 months post robotic-staging surgery.

Case Report: A 41-year-old woman was sent to the emergency room with sudden onset of abdominal pain, vaginal bleeding, and vaginal protruding mass after sexual activity. She had a history of synchronous uterine and ovarian cancer treated with robotic-staging surgery 7 months before.

Multimorbidity in the community-dwelling elderly in urban China.

Objectives: The primary objective of the study was to investigate the prevalence and patterns of multimorbidity in the community-dwelling elderly in urban China.

Methods: By a cluster random sampling method, 2452 persons aged 60 years and older were enrolled as the subjects in an urban community in Nanjing, China. Data on 13 chronic diseases were collected by interviews, physical check-ups and support by physicians.

Pills-related severe adverse events: A case report in Taiwan.

Objective: To review and evaluate the potential adverse effects of these oral contraceptives (OCP) to overweight women.

Case Report: A 19-year-old college student, with a body mass index (BMI) of 35.2 kg/m(2), who received 2 months of OCP containing cyproterone and ethinyl estradiol for polycystic ovary syndrome (PCOS)-related menstrual problems was complicated with a thromboembolism-related life-threatened disease.

Complication reports for robotic surgery using three arms by a single surgeon at a single institution.

Background: The aim of this study is to evaluate perioperative complications related to robotic-assisted laparoscopic surgery for management of gynaecologic disorders.

Materials And Methods: Eight hundred and fifty-one women who underwent robotic procedures between December 2011 and April 2015 were retrospectively included for analysis. Patient demographics, surgical outcomes and complications were evaluated.

Integrative bioinformatic analyses of an oncogenomic profile reveal the biology of endometrial cancer and guide drug discovery.

A major challenge in personalized cancer medicine is to establish a systematic approach to translate huge oncogenomic datasets to clinical situations and facilitate drug discovery for cancers such as endometrial carcinoma. We performed a genome-wide somatic mutation-expression association study in a total of 219 endometrial cancer patients from TCGA database, by evaluating the correlation between ~5,800 somatic mutations to ~13,500 gene expression levels (in total, ~78, 500, 000 pairs). A bioinformatics pipeline was devised to identify expression-associated single nucleotide variations (eSNVs) which are crucial for endometrial cancer progression and patient prognoses.

Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model.

We have designed and synthesized certain novel oxime- and amide-bearing coumarin derivatives as nuclear factor erythroid 2 p45-related factor 2 (Nrf2) activators. The potency of these compounds was measured by antioxidant responsive element (ARE)-driven luciferase activity, level of Nrf2-related cytoprotective genes and proteins, and antioxidant activity. Among them, (Z)-3-(2-(hydroxyimino)-2-phenylethoxy)-2H-chromen-2-one (17a) was the most active, and more potent than the positive t-BHQ in the induction of ARE-driven luciferase activity.

Novel Nrf2/ARE activator, trans-Coniferylaldehyde, induces a HO-1-mediated defense mechanism through a dual p38α/MAPKAPK-2 and PK-N3 signaling pathway.

The induction of detoxifying enzymes and antioxidant proteins by chemopreventive agents protects cells from oxidizing substances capable of damaging DNA integrity and initiating carcinogenesis. Coniferyl aldehyde, a naturally occurring substance, has been found in many foods and edible plants. We and others previously demonstrated that trans-coniferylaldehyde (t-CA) has potential antimutagenic and antioxidant properties.

Comparison of robotic approach, laparoscopic approach and laparotomy in treating epithelial ovarian cancer.

Background: The purpose of this study was to evaluate the feasibility of robotic surgery and compare its surgical outcomes with those of laparoscopic surgery and laparotomy, with regard to performing staging surgery to manage ovarian cancer.

Methods: One hundred and thirty-eight women who received surgical staging procedures for treatment of stage IA-IIIC epithelial ovarian cancer and borderline tumours were retrospectively included in the study. All enrolled cases were reviewed for patient demographics, peri-operative parameters, complications and survival.

Gene expression profiling for analysis acquired oxaliplatin resistant factors in human gastric carcinoma TSGH-S3 cells: the role of IL-6 signaling and Nrf2/AKR1C axis identification.

Oxaliplatin treatment is a mainstay of treatment for advanced gastrointestinal tract cancer, but the underlying mechanisms of acquired oxaliplatin resistance remain largely obscured. We previously demonstrated that increased DNA repair capacity and copper-transporting ATPase 1 (ATP7A) level contributed to oxaliplatin resistance in the human gastric carcinoma cell line TSGH-S3 (S3). In the present study, we applied gene array technology to identify additional resistance factors in S3 cells.

Adlay ( yì yĭ; "soft-shelled job's tears"; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes.

Adlay ( yì yĭ "soft-shelled job's tears", the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop that has long been used in traditional Chinese medicine (TCM) and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases.

4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling.

The Nrf2/ARE pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and has been considered a potential target for cancer chemoprevention because it eliminates harmful reactive oxygen species or reactive intermediates generated from carcinogens. The objectives of this study were to identify novel Nrf2/ARE activators and to investigate the mechanistic signaling pathway involved in the activation of Nrf2-mediated cytoprotective effects against oxidative-induced cell injury. A stable ARE-driven luciferase reporter cell line was established to screen a potentially cytoprotective compound.

Antimutagenic constituents of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) with potential cancer chemopreventive activity.

Adlay has long been used in traditional Chinese medicine and as a nourishing food. The acetone extract of adlay hull had previously been demonstrated to possess potent antimutagenic activity. The aims of this study were to identify the antimutagenic constituents from adlay hull by using Ames antimutagenic activity-guide isolation procedures and to investigate their chemopreventive efficacies in cultured cells.

Investigations of survivin: the past, present and future.

Survivin is a member of the inhibitors-of-apoptosis protein (IAPs) family. It promotes cell survival through interference with multiple cell cycle-related proteins such as INCENP and Aurora B kinase. Survivin also inhibits cell death through interference with both caspase-dependent and -independent cell apoptosis.

Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells.

Background: Survivin is a dual functioning protein. It inhibits the apoptosis of cancer cells by inhibiting caspases, and also promotes cancer cell growth by stabilizing microtubules during mitosis. Since the molecular chaperone Hsp90 binds and stabilizes survivin, it is widely believed that down-regulation of survivin is one of the important therapeutic functions of Hsp90 inhibitors such as the phase III clinically trialed compound 17-AAG.

Assignment of the 1H, 13C and 15N resonances of the calponin homology-2 domain of alpha-actinin-4.

We report the assignment of the 110 amino acid second calponin homology domain of human alpha-actinin-4. The two calponin homology domains of alpha-actinin combine to regulate F-actin binding.

Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers.

Background: Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent) and paclitaxel (microtubule stabilizer) in cancers.