Chloroquine eliminates cancer stem cells through deregulation of Jak2 and DNMT1.

Triple negative breast cancer (TNBC) is known to contain a high percentage of CD44(+) /CD24(-/low) cancer stem cells (CSCs), corresponding with a poor prognosis despite systemic chemotherapy. Chloroquine (CQ), an antimalarial drug, is a lysotropic reagent which inhibits autophagy. CQ was identified as a potential CSC inhibitor through in silico gene expression signature analysis of the CD44(+) /CD24(-/low) CSC population. Autophagy plays a critical role in adaptation to stress conditions in cancer cells, and is related with drug resistance and CSC maintenance. Thus, the objectives of this study were to examine the potential enhanced efficacy arising from addition of CQ to standard chemotherapy (paclitaxel) in TNBC and to identify the mechanism by which CQ eliminates CSCs in TNBCs. Herein, we report that CQ sensitizes TNBC cells to paclitaxel through inhibition of autophagy and reduces the CD44(+) /CD24(-/low) CSC population in both preclinical and clinical settings. Also, we are the first to report a mechanism by which CQ regulates the CSCs in TNBC through inhibition of the Janus-activated kinase 2 (Jak2)-signal transducer and activator of transcription 3 signaling pathway by reducing the expression of Jak2 and DNA methyltransferase 1.

Pregnancy outcomes among solid organ transplant recipients in British Columbia.

OBJECTIVE: Since 1954, over 14 000 women have given birth after having had an organ transplantation. Unfortunately, some women and physicians remain misinformed about the feasibility and outcomes of pregnancy post transplantation. Our primary objective was to assess their perceptions and difficulties with regard to becoming pregnant. Our secondary objectives were to determine the incidence of pregnancies among transplant recipients in British Columbia and any maternal, graft, or fetal complications. METHODS: From 1997 to 2007 in British Columbia, there were over 500 female recipients of solid organ transplants. We surveyed recipients in this group who were of child-bearing age. RESULTS: One hundred forty of 295 (47%) eligible recipients responded: 44 of these women had attempted pregnancy after transplant, and 31 women gave birth to 47 children. One half of the respondents planned to have children post transplant; 108 of 140 (77%) had no children before transplant. One quarter of the respondents were advised against pregnancy by their physician, and 33% of these women found a new physician to support their pregnancy. Rates of miscarriage (27%), rejection (21%), and prematurity (65%) were higher than expected. Infections were rare, and no birth defects or noteworthy health problems in the offspring were reported. CONCLUSIONS: Overall, pregnancy appears to be safe following solid organ transplantation, but careful monitoring and counselling are recommended.

Opposites attract: a case of magnet ingestion.

Foreign-body ingestion is relatively common in the pediatric population and most objects pass through the gastrointestinal tract with minimal complications. Popular toy magnetic construction sets have resulted in numerous reports in the literature of serious complications including death following ingestion of multiple magnets. We report a case of a 5-year-old girl who presented to our emergency department with nonbilious vomiting and mild abdominal pain after accidentally ingesting 2 magnets 10 hours apart. Abdominal radiography showed the presence of 2 magnets, and a laparoscopy revealed multiple areas of bowel wall necrosis and perforation requiring subsequent laparotomy for repair of the bowel wall and retrieval of the magnets. This report aims to alert emergency care physicians of the necessity for early surgical referral with any multiple magnet ingestion to prevent severe complications.

Patterns of complementary and alternative medical therapy use in children diagnosed with autism spectrum disorders.

Previous studies suggest that complementary and alternative medical (CAM) therapy use in children with chronic illnesses is higher than in children in the general population. In this study, we investigated patterns of CAM therapy use in children diagnosed with autism spectrum disorders (ASD, n = 50) as compared to a control population of children with no ASD (n = 50). Over half of the parents in the ASD group reported using, or had used at least one CAM therapy for their child (52%) as compared to 28% of the control group (P = 0.024). Seventy percent of therapies used in the ASD group were biologically based therapies comprised of special diets or supplements, and parents felt that 75% of the therapies used were beneficial.

Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to regulate gastric acid secretion and intestinal motility. In the present study, the pattern of distribution of PACAP and PACAP type 1 receptor (PAC1) immunoreactivities were examined in the rat stomach and distal colon using a specific polyclonal antibody raised against rat/human PAC1. Western blot of the membrane preparations of NIH/3T3 cells transfected with the human PAC1 obtained by using rabbit polyclonal anti-PAC1 antibody showed a protein band with a molecular mass of approximately 50 kDa. NIH/3T3 cells transfected with the human PAC1 and incubated with the anti-PAC1 antibody displayed surface cell-type immunoreactivity, which was internalized following ligand exposure. In gastric or colonic longitudinal muscle/myenteric plexus (LMMP) whole mount preparations as well as cryostat sections, PACAP immunoreactivity was observed in cell bodies within the myenteric ganglia and nerve fibers in the muscle layers and mucosa. PAC1 immunoreactivity was confined mainly on the surface of the nerve cells. PACAP and PAC1 immunoreactivities showed a similar pattern of distribution in gastric and colonic tissues. Adjacent sections or LMMP whole mount preparations labeled with protein gene product 9.5 (PGP 9.5) revealed the neuronal identity of myenteric cells bearing PAC1. The neuronal localization of PACAP and PAC1 receptors supports their role in the neural regulation of gastric acid secretion and gastrointestinal motor function.