HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.

The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of 'tumor-initiating cells' retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demonstrated by in vitro mammosphere assays and the expression of stem cell marker aldehyde dehydrogenase (ALDH) as well as by generation of hyperplastic lesions in humanized fat pads of NOD (nucleotide-binding oligomerization domain)/SCID (severe combined immunodeficient) mice. Overexpression of HER2 in a series of breast carcinoma cell lines increases the ALDH-expressing 'cancer stem cell' population which displays increased expression of stem cell regulatory genes, increased invasion in vitro and increased tumorigenesis in NOD/SCID mice. The effects of HER2 overexpression on breast cancer stem cells are blocked by trastuzumab in sensitive, but not resistant, cell lines, an effect mediated by the PI3-kinase/Akt pathway. These studies provide support for the cancer stem cell hypothesis by suggesting that the effects of HER2 amplification on carcinogenesis, tumorigenesis and invasion may be due to its effects on normal and malignant mammary stem/progenitor cells. Furthermore, the clinical efficacy of trastuzumab may relate to its ability to target the cancer stem cell population in HER2-amplified tumors

An Early Drowning Detection System for Internet of Things (IoT) Applications

Drowning is the leading cause of injury or death for children and teenagers. Designing a drowning detection device by implementing an Internet of Thing (IoT) is needed. An Early Drowning Detection System (EDDS) is a system that gives an early alarm to the guardians (parents and lifeguard) if the detector triggered an abnormal heartbeat and the victims are submerged under the water for a long time. A microcontroller was used to control the signal received from a pulse sensor and time for the signal lost under the water before it is transmitted to the access point. The access point acts as a data forwarding to the database via an internet connection. Universal Asynchronous Receiver/Transmitter (UART) 433MHz radio frequency transceiver has been used to create the wireless communication between drowning detection device and monitoring hub. A triggered warning signal will be transmitted to the guardians via Android apps and web page

On the Web Platform Cornucopia

Peer reviewe

The management of bronchus intermedius complications after lung transplantation: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Airway complications following lung transplantation remain a significant cause of morbidity and mortality. The management of bronchial complications in Bronchus Intermedius (BI) is challenging due to the location of right upper bronchus. The aim of this study was to analyze the results of BI Montgomery T-tube stent in a consecutive patients with lung transplantations.</p> <p>Methods</p> <p>Between January 2007 and December 2010, 132 lung transplantations were performed at Foch Hospital, Suresnes, France. All the patients who had BI Montgomery T-tube after lung transplantation were included in this retrospective study. The demographic and interventional data and also complications were recorded.</p> <p>Results</p> <p>Out of 132 lung transplant recipients, 12 patients (9 male and 3 female) were entered into this study. The indications for lung transplantation were: cystic fibrosis 8 (67%), emphysema 3 (25%), and idiopathic pulmonary fibrosis 1 (8%). Most of the patients (83%) had bilateral lung transplantation. The mean interval between lung transplantation and interventional bronchoscopy was 11.5 ± 9.8 (SD) months. There was bronchial stenosis at the level of BI in 7 patients (58.3%). The Montgomery T-tube number 10 was used in 9 patients (75%). There was statistically significant difference in Forced Expiratory Volume in one second (FEV1) before and after stent placement (p = 0.01). The most common complication after stent placement was migration (33%).</p> <p>Conclusion</p> <p>BI complications after lung transplantation are still a significant problem. Stenosis or malacia following lung transplantation could be well managed with modified Montgomery T-tube.</p

Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness.published_or_final_versio

p16 Mutation Spectrum in the Premalignant Condition Barrett's Esophagus

Background: Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions. Methods and Findings: We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett’s esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations. Conclusions: The results of this study suggest the environment of the esophagus in BE patients can both generate an

Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience

<p>Abstract</p> <p>Background</p> <p>To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.</p> <p>Methods</p> <p>Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation.</p> <p>Results</p> <p>Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse.</p> <p>Conclusion</p> <p>When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.</p

Timeless standards for species delimitation

published_or_final_versio

Cellular Growth Kinetics Distinguish a Cyclophilin Inhibitor from an HSP90 Inhibitor as a Selective Inhibitor of Hepatitis C Virus

During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA) and heat-shock protein 90 (HSP90) which have each been reported to inhibit replication of hepatitis C virus (HCV). By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA), exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth