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

Construction and evaluation of measures of identification of sound elements in words in kindergarten,

Thesis (M.A.)--Boston Universit

Do diverse groups cheat less than homogenous groups?

This thesis provides empirical evidence to test the hypothesis that diverse groups cheat less than homogenous groups. The thesis explores both whether or not diversity provides more than just varied perspectives and the benefit of equal opportunity. The research is carried out in an academic setting and is based on an experiment with 688 Second and Third year Auditing students. It uses an experimental task designed to identify instances of dishonesty by individuals in different groups through the completion of a short mathematical assessment. Social psychological theories which are relevant for understanding group composition, social norms, conformity and self-awareness are considered as possible explanations for the manner in which diversity might affect the ethicality of an individual’s decisions within a group. Using a two-way ANOVA the results show that variations in the composition of a group (in terms of diversity or homogeneity) have a significant effect on the frequency of dishonest behaviour by individuals within the respective group. In particular, when students were observed those who were members of diverse groups had test scores which were not significantly different from students writing in homogenous groups. Conversely, unobserved students in homogenous groups had test scores which were significantly higher than in unobserved diverse groups. These results should be relevant for accounting practitioners and corporate governance policymakers - given the emphasis placed on diversity of management groups in terms of codes of best practice - as well as for academics interested in better understanding the dynamics of student groups

Who is the accused? The interrogation of Aḥmad Ibn Ḥanbal

ABSTRACT The miḥna (218-234 H.) was a defining event of Islamic spiritual authority. Its importance was evident to contemporaries, the inquisitors and their victims, and each side recorded the events. This study compares these accounts. It concentrates on three components that appear in both narratives: how each side told the story to the wide public; how they perceived the torture of Ibn Ḥanbal; how they described and understood the dialogue between Ibn Ḥanbal and his inquisitors. Interestingly, the depictions of these events bear a strong resemblance. The aim of this study is to trace how shared factual descriptions end up promoting opposing ideologies.La Miḥna (218-234 H) fue un acontecimiento definitorio de la autoridad espiritual islámica. Su importancia fue evidente para sus contemporáneos, tanto los inquisidores como sus víctimas, y ambos lados recogieron los acontecimientos producidos. Este artículo compara estas narraciones. Se concentra en tres elementos que aparecen en ambos relatos: cómo cada lado contó la historia a un público amplio; cómo percibieron la tortura de Ibn Ḥanbal; cómo describieron y comprendieron el diálogo entre Ibn Ḥanbal y sus inquisidores. Es interesante señalar que los relatos de ambos lados de estos acontecimientos tienen un gran parecido. El objeto de este estudio es detectar de qué modo las descripciones de hechos comunes acaban apoyando ideologías opuestas

The Significant Other in Marital and Family Therapy

The significant other (SO) is derived from the social behaviorism of G. H. Mead which is comparable to contemporary cognitive behaviorism. The SO is defined as an analytical concept by examining interaction in social acts; it includes attributes associated with the family member\u27s role-reciprocity, meanings, affect, self-concept and modeling; and it is associated with concepts such as transformation, attribution and social interchange. The process by which the therapist becomes an SO to the family members individually and jointly, and how he or she utilizes transformation, attribution and social interchange are outlined

Use of the metastatic breast cancer progression (MBC-P) questionnaire to assess the value of progression-free survival for women with metastatic breast cancer.

While overall survival (OS) has historically been the primary endpoint for clinical trials in oncology, progression-free survival (PFS) has gained acceptance as a valuable surrogate endpoint. However, there are no known published reports about the value of PFS from the patient's perspective. We developed a questionnaire that included items regarding quality of life (QoL) and the importance of different treatment outcomes and presented hypothetical scenarios for which respondents were asked to indicate their preferences concerning treatments as they relate to PFS. 282 women with metastatic breast cancer (MBC), ranging in age from 21 to 80 years completed an online version of this questionnaire. The majority of women (66 %) had been diagnosed with MBC within the previous 3 years and 56 % had been told their MBC had progressed. When asked to rank five treatment characteristics from most important to least important, respondents ranked "extending PFS" as the second most important treatment outcome after OS. When presented with a hypothetical scenario of two women receiving different treatments, respondents preferred the treatment that resulted in longer PFS (16 vs. 12 months), even when OS and side effects were assumed to be equal. Specifically, when asked to consider which woman within the hypothetical scenario had better QoL, physical functioning, and emotional well-being, respondents more often chose the woman who experienced longer PFS (QoL: 40 vs. 6 %; physical functioning: 32 vs. 8 %; emotional well-being: 58 vs. 6 %) compared to the woman within the hypothetical scenario who had a shorter time of progression. Respondents rated their own QoL highest after being told their MBC was responding to treatment (mean score 76.6) versus after the initial diagnosis of breast cancer and MBC (68.5 and 60.3). These findings suggest that extending PFS is an important treatment outcome and, from a patient perspective, improves overall QoL, physical functioning, and emotional well-being

A Communal Bridge: The Detroit Jewish News, The Detroit Jewish Welfare Federation And The Detroit Jewish Community In 1942

While many historians writing about Jews in America focus on dissonance and disorganization during the 1940s among national Jewish leadership and national Jewish organizations which accounts (partially) for their inability to effectively advocate for European Jewry, Zionism, and other Jewish causes, this was not necessarily true on a local level. Jews in Detroit were effective in raising funds for these causes, supporting institutional infrastructure, battling anti-Semitism, and participating in the war effort. An important part of that was a unique partnership entered into between the nascent Detroit Jewish News and the established Detroit Jewish Federation, the most important part of the Jewish communal infrastructure in Detroit. The Jewish News became a key communications tool between leadership and Detroit Jews, serving as an advocate and an informative and educational bridge. The arrangement allowed the Jewish News to quickly overtake its competition and become the “newspaper of record “ among Detroit Jews