Trastuzumab (Herceptin (R)): Monoclonal antibody in the treatment of HER2/neu-overexpressing breast cancer in the metastatic and (neo)adjuvant situation

Trastuzumab (Herceptin (R)) is a humanized monoclonal antibody that specifically targets HER2/neu (human epidermal growth factor receptor-2) breast cancer cells, which are overexpressed in about 25-30% of breast carcinomas. After phase I and II trials, several phase III studies of trastuzumab alone or in combination with various chemotherapies were conducted. Patients with HER2/neu overexpression levels of 3+ determined by immunohistochemical assay or gene amplification (fluorescence in situ hybridization) derive most clinical benefit from trastuzumab. Taking into consideration efficacy and side effect profile, the combination of trastuzumab and paclitaxel showed an improvement of all clinical parameters, including overall survival, for the first time in the history of palliative breast cancer therapy. The application of trastuzumab has meanwhile become an established part of systemic therapy of metastastic breast cancer, and excellent data of its application in the adjuvant setting now exist (NSABP-B31, NCCTG-N9831, HERA), with significantly better relapse-free survival in the treatment arms with trastuzumab. Ongoing trials investigate the role of trastuzumab in the neoadjuvant setting. Trastuzumab is generally well tolerated. Cardiotoxicity is the main concern, thus monitoring of cardiac function is recommended

Local Resection of Primary Tumor in Upfront Stage IV Breast Cancer

Background: This study aimed to identify the association of local surgery of the primary tumor in metastatic breast cancer (MBC) patients with overall survival (OS) and prognostic factors. Patients and Methods: Patients with primary MBC (1990-2006) were included in our retrospective analysis (n = 236). 83.1% had surgery for the primary tumor. OS was evaluated using Kaplan-Meier estimates. Predictive factors for OS were determined. Results: Median follow-up was 123 months for all patients still alive at the time of analysis. In univariate analysis, patients with surgery of the primary tumor had significantly prolonged OS (28.9 vs. 23.9 months). Within the surgery group, patients with MBC limited to 1 organ system had a better outcome (39.3 vs. 24.9 months), as did asymptomatic patients. Independent risk factors for shorter OS were hormone receptor negativity, symptoms, and involvement of > 1 organ system. Conclusion: Patient selection for local therapy was confounded by a more favorable profile and a lesser tumor burden before surgery, which might implicate a bias. Nevertheless, our univariate results indicate that local surgery of the primary tumor in MBC patients could be considered as part of the therapeutic regimen in selected patients. However, larger patient numbers are needed to prove these findings in the multivariate model. (C) 2016 S. Karger GmbH, Freibur

The Reality in the Surveillance of Breast Cancer Survivors—Results of a Patient Survey

Background: International guidelines for the surveillance of breast cancer patients recommend a minimized clinical follow-up including routine history and physical examination and regularly scheduled mammograms. However, the abandonment of scheduled follow-up examinations in breast cancer survivors remains a contradiction to established follow-up guidelines for other solid tumours.Patients and Methods: We report the patients’ view on the basis of a survey performed in two separate geographical areas in Germany. The questionnaires were sent out to 2.658 patients with a history of breast cancer.Results: A total of 801 patients (30.1%) responded to the questionnaire. The results of the survey can be summarized in two major categories: First, necessity for surveillance was affi rmed by a majority (>95%), and 47.8% of the organized patients answered that there was a need for more intensive diagnostic effort during follow-up. The main expectation from an intensified follow-up was the increased feeling of security as expressed by >80% of the women. Second, the present survey indicates that most of the regularly scheduled follow-up visits were expanded using extensive laboratory and imaging procedures exceeding the quantity of examinations recommended in the present follow-up guidelines.Conclusion: Despite the fact that only one third of the patients responded to the questionnaire, the survey indicates that a majority of physicians who treated these patients still do not accept the present follow-up guidelines. To some extent this may be explained by the observation that patients and possibly also their doctors trust that intensified follow-up increases diagnostic security and survival. Since considerable changes in the treatment options of breast cancer have been made during the last decades a new trial of investigations in follow-up is warranted

ADVANCE system testing: Can coverage of pertussis vaccination be estimated in European countries using electronic healthcare databases: An example

Introduction: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing healthcare databases in Europe. The objective of this paper was to assess the feasibility of using electronic healthcare databases to estimate dose-specific acellular pertussis (aP) and whole cell pertussis (wP) vaccine coverage. Methods: Seven electronic healthcare databases in four European countries (Denmark (n = 2), UK (n = 2), Spain (n = 2) and Italy (n = 1)) participated in this study. Children were included from birth and followed up to age six years. Vaccination exposure was obtained from the databases and classified by type (aP or wP), and dose 1, 2 or 3. Coverage was estimated using period prevalence. For the 2006 birth cohort, two estimation methods for pertussis vaccine coverage, period prevalence and cumulative incidence were compared for each database. Results: The majority of the 2,575,576 children included had been vaccinated at the country-specific recommended ages. Overall, the estimated dose 3 coverage was 88–97% in Denmark (birth cohorts from 2003 to 2014), 96–100% in the UK (2003–2014), 95–98% in Spain (2004–2014) and 94% in Italy (2006–2007). The estimated dose 3 coverage per birth cohort in Denmark and the UK differed by 1–6% compared with national estimates, with our estimates mostly higher. The estimated dose 3 coverage in Spain differed by 0–2% with no consistent over- or underestimation. In Italy, the estimates were 3% lower compared with the national estimates. Except for Italy, for which the two coverage estimation methods generated the same results, the estimated cumulative incidence coverages were consistently 1–10% lower than period prevalence estimates. Conclusion: Thi

FUmanoid team description 2009

Abstract. This document describes hardware and software of the robots developed by the "FUmanoid" Team for the RoboCup competitions to be held in Graz, Austria 2009. The robot has 22 actuated degrees of freedom based on Dynamixel RX28, and RX64 servos. Central Processing, including Machine vision, Planning and control is performed using a Gumstix Verdex 6LP which is an ARM based 600MHz platform. Planning algorithms are organized in a new structure called Concurrent Scenario based Planning (CSBP). This paper explains the software and hardware used for the robot as well as control and stabilization methods developed by our team

Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease

ABSTRACT: BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients