Profiling and targeting HER2-positive breast cancer using trastuzumab emtansine.

PurposeThis article reviews the mechanism of action of trastuzumab emtansine (T-DM1), existing clinical data relating to its use for human growth factor receptor 2 (HER2)-positive breast cancer, potential pathways of resistance, and ongoing studies evaluating this novel agent.BackgroundThe development of HER2-targeted therapies has dramatically improved clinical outcomes for patients with any stage of HER2-positive breast cancer. Although the positive effect of these treatments cannot be overstated, treatment resistance develops in the vast majority of those diagnosed with stage IV HER2-positive breast cancer. Moreover, HER2-directed therapies are most effective when combined with cytotoxic chemotherapy. The need for chemotherapy leads to significant adverse effects and a clear decrease in quality of life for those dealing with a chronic incurable disease. T-DM1 is a recently developed, novel antibody-drug conjugate in which highly potent maytanisinoid chemotherapy is stably linked to the HER2-targeted monoclonal antibody, trastuzumab.ResultsPreclinical and phase 1-3 clinical data support the significant antitumor activity of T-DM1. Importantly, several randomized studies also now demonstrate its clear superiority in terms of tolerability compared with standard chemotherapy-containing regimens. Its role in the treatment of trastuzumab-resistant metastatic breast cancer has now been established on the basis of the results of two phase 3 randomized studies, EMILIA (An Open-label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine + Lapatinib in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer) and TH3RESA (A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy). The most common toxicities seen with T-DM1 are thrombocytopenia and an elevation in liver transaminases. Significant cardiac toxicity has not been demonstrated. Both in vitro cell line-based studies as well as exploratory analyses of archived tumor samples from the clinical trials are seeking to understand potential mechanisms of resistance to T-DM1. Ongoing studies are also evaluating the use of T-DM1 in the first-line metastatic, neoadjuvant, and adjuvant settings, as well as in combination with other targeted therapies.ConclusionT-DM1 represents the first successfully developed antibody drug conjugate for the treatment of HER2-positive advanced breast cancer

Comparison of temperament and character personality traits in opiate and stimulant addicts

Background: Phenomenon of addiction as one of the social problems has a high prevalence, especially among youth. The aim of the present study was to compare personality traits based on the temperament and character inventory in opiate and stimulant addicts in Tehran.  Methods: In the present quasi-experimental study, 60 male addicts (30 opiate and 30 stimulant addicts) who referred to addiction treatment centers in the suburbs of Tehran were selected through convenience sampling method and were studied using Temperament and Character Inventory (TCI). The participants were sorted according to their age and education.    Results: There was a significant difference between the two groups with regard to harm avoidance, reward dependence, cooperativeness, and self-transcendence traits. Thus, opiate addicts had higher levels of harm avoidance, reward dependence, and cooperativeness, and stimulant addicts had higher levels of self-transcendence. The significance level was set at P<0.01.  Conclusion: The obtained results showed that there was a significant difference between opiate and stimulant addicts. Opiate addicts gained higher scores, compared with stimulant addicts, in Temperament and Character Inventory variables. The obtained results also showed that stimulant addicts were suffering from more severe disorders than opiate addicts. Based on the means of the values of the TCI, personality traits reflecting personality disorders are detectable and predictable in substance abusers. This new understanding is important in the prevention and treatment of addiction

An applicable master plan to develop city’s information technology infrastructure

AbstractNowadays, communication devices are widespread exponentially. People use some of these devices in daily life like as using mobile to access for shopping from Internet and pay by credit cards or student email their homework to their teacher. In other words, Internet network plays significant roles in people’s life. Therefore, some features such as access to Internet from everywhere, connection bandwidth and minimum necessary devices to connect and use network are important in make better satisfaction of people.In this article, a master plan of infrastructure is suggested that city which built base on this infrastructure, people in city can connect to Data center from anywhere with simple and usual tools like PDA, Notebook and also cell phones and also superior manager can use the information to make proper decisions and as a result they can offer a fast and appropriate sort of management. In this instruction, people can easily connect to Metropolitan Area Network (MAN) then use IT subsystems like Ecommerce, E-learning, E-health and others and enjoy from IT subsystem advantages in city. In this design, there are some important factors that we must attend to them because they affect the result, some of them such as speared of access point to MAN, independent from especial hardware requirement, Network Bandwidth and simple using structure for people. So, in the result, the useful information of people is saved in Data center and people or organization can reach these data easily and use people data in time

Attribution of ghrelin to cancer; Attempts to unravel an apparent controversy

Ghrelin is an endogenous peptide hormone mainly produced in the stomach. It has been known to regulate energy homeostasis, stimulate secretion of growth hormone, and mediate many other physiologic effects. Various effects attributed to ghrelin contribute to many aspects of cancer development and progression. Accordingly, a large body of evidence has emerged about the association of ghrelin with several types of cancer in scales of cell-line, animal, and human studies. However, existing data are controversial. This controversy occurs in two main domains: one is the controversial results in local effects of ghrelin on different types of human cancer cell-lines; the second is the apparent disagreement in the results o

Effectiveness of life skills training on self-efficacy and emotional intelligence among high school students in Urmia

  Background: Life skills are the abilities to have adaptive and positive behaviors that enable human beings to deal effectively with the demands and challenges of life. The aim of the present study was to examine the effectiveness of teaching life skills on self-efficacy and emotional intelligence among high school students.  Methods: A quasi-experimental study was conducted on 462 male high school students of Silvana area in Urmia city, selected via multi-stage cluster sampling method. These students studied in two different schools. Three classes were selected randomly from each high school and all the students of these classes completed the self-efficacy and emotional intelligence inventory. Participants who scored low on effectiveness of life skills training were selected for the study; among them 30 students were selected randomly and assigned randomly into two experimental and control groups (15 students each). The experimental group received life skills education but the control group did not receive any education. Both groups completed the Sherer's Self-Efficacy Scale and Bar-On Emotional Intelligence-Inventory in baseline and follow up phases. The data were analyzed using descriptive statistics (the mean and standard of deviation) and Multivariate analysis of covariance (MANCOVA). Statistical analysis was perfumed using IBM SPSS Statistics for Windows, Version 22.0.  Results: The results of the study indicated that teaching life skills significantly increased mean±SD scores of self-efficacy (68.2±7.35, 55.4±9.96) and emotional intelligence (106.6±15.05, 94.8±11.33) in the experimental and control group, respectively (P=0.001). there were significant correlations between self-efficacy and academic achievement (r=0.518, P=0.01)  Conclusion: Teaching life skills can improve students' self-efficacy and emotional intelligence and the education officials should pay attention to teaching these life skills to the students

Analysing Gas-Liquid Flow in PEM Electrolyser Micro-Channels

PEM water electrolysis is a key component for closing the loop of the renewable energy eco-system. In particular, these high response water electrolysers are suitable for fluctuating power sources. Conventional PEM water electrolysers are typically operated at a current density of around 1 A/cm2 and are fairly expensive. One means of increasing the hydrogen yield to cost ratio of such systems, is to increase the operating current density. However, at high current densities, management of heat and mass transfer in the anode current collector and channel becomes crucial. This entails that further understanding of the gas-liquid flow in both the porous media and the channel is necessary for insuring proper oxygen, water and heat management of the electrolysis cell. In this work, the patterns of vertical upward gas-liquid flow in a 5×1×94 mm micro-channel are experimentally analysed. A sheet of titanium felt is used as a permeable wall for permeation of air through a column of water similar to the phenomenon encountered at the anode. The transparent setup is operated ex-situ and the gas-liquid flow regimes are identified using a camera.</jats:p