Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.

/pdf/notch-signaling-simplicity-in-design-versatility-in-function-1gqwuqw3i9.pdf

Notch signaling: simplicity in design, versatility in function

Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell com...

Notch Signaling in Development, Tissue Homeostasis, and Disease

Characterization of Therapeutic Antibodies and Related Products

Recent progress in development of siRNA delivery vehicles for cancer therapy

Published by Elsevier B.V. on behalf of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Guidelines for the Prevention, Detection, and Management of Heart Failure in Australia 2018

Mammalian cell culture systems are used predominantly for the production of therapeutic monoclonal antibody (mAb) products. A number of alternative platforms, such as Pichia engineered with a humanized N-linked glycosylation pathway, have recently been developed for the production of mAbs. The glycosylation profiles of mAbs produced in glycoengineered Pichia are similar to those of mAbs produced in mammalian systems. This report presents for the first time the comprehensive characterization of an anti-human epidermal growth factor receptor 2 (HER2) mAb produced in a glycoengineered Pichia, and a study comparing the anti-HER2 from Pichia, which had an amino acid sequence identical to trastuzumab, with trastuzumab. The comparative study covered a full spectrum of preclinical evaluation, including bioanalytical characterization, in vitro biological functions, in vivo anti-tumor efficacy and pharmacokinetics in both mice and non-human primates. Cell signaling and proliferation assays showed that anti-HER2 fro...

Glycoengineered Pichia produced anti-HER2 is comparable to trastuzumab in preclinical study

Aims: 

2 dimensional (2D) strain analysis detects subclinical left ventricular (LV) systolic dysfunction. Our aim was to evaluate changes in LV systolic and diastolic function in breast cancer patients early after anthracycline chemotherapy, and to identify predisposing factors. Methods and Results: 

140 patients were assessed by detailed echocardiography before and within seven days post treatment. LV ejection fraction (LVEF), global longitudinal strain (GLS), strain rate and radial and circumferential strain were assessed. Additionally, left atrial volumes and LV diastolic parameters were evaluated. LVEF although reduced after treatment, remained within the normal range (60 ± 3% vs. 59 ± 3%, p = 0.04). Triplane GLS was significantly reduced after treatment (-20.0 ± 1.6% vs. -19.1 ± 1.8%, p   11% reduction in GLS compared to before therapy) occurred in 22% (29/135). Impaired diastolic function grade significantly increased from 46% to 57% (p   11% reduction in GLS. Conclusion: 

Twenty two percent of patients had subclinical LV dysfunction by GLS, whilst none had cardiotoxicity defined by LVEF, demonstrating that GLS is more sensitive for detection of subclinical LV systolic dysfunction immediately after anthracycline therapy. Diastolic dysfunction increased, particularly in the group with reduced GLS, demonstrating the close pathophysiological relationship between systolic and diastolic function.

/pdf/anthracyclines-induce-early-changes-in-left-ventricular-x4fcbqclx2.pdf

Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study

Introduction Plasma cell leukemia (PCL) is a rare but aggressive variant of multiple myeloma (MM) with a poor prognosis. Due to the limited number of prospective clinical trials studying PCL, treatment options are often extrapolated from data available for the treatment of MM. Venetoclax has recently demonstrated antimyeloma activity in patients with relapsed/refractory MM carrying the t(11;14) translocation. However, few cases have reported the analogous efficacy of venetoclax in PCL. Case Report A 64-year-old Caucasian male developed relapsed PCL despite treatment with hyperCD (hyperfractionated cyclophosphamide and dexamethasone) and Dara-KRd (daratumumab, carfilzomib, lenalidomide, dexamethasone). Due to the refractory nature of his disease and the presence of a t(11:14) translocation, the patient was subsequently initiated on venetoclax 400 mg daily and dexamethasone 4 mg once weekly. Management and outcome The patient achieved a complete response by International Myeloma Working Group criteria three months after initiating venetoclax-dexamethasone, including a repeat bone marrow biopsy that showed no abnormal plasma cells. He successfully underwent consolidation with melphalan-based autologous stem cell transplantation. He remains disease-free 9 months after venetoclax initiation. Discussion Combination all-oral therapy with venetoclax and dexamethasone can induce deep hematologic responses in patients with relapsed/refractory PCL carrying the t(11;14) translocation.

Complete response following treatment of plasma cell leukemia with venetoclax and dexamethasone: A case report

Ngoc Hoa, et al., Time Trend of Mortality from Esophagus Cancer During 2005-2014 in the Nghe An Province, Viet Nam. Biomed MS.ID.006524. To describe the time trend of esophageal cancer (EC) mortality that occurred in Nghe An province during 2005-2014. Methods: Mortality due to EC and all causes were annually collected from the A6 death register system using the “Validated mortality registration forms” from 2005 to 2014. There was a mandatory monthly active mortality registration by 480 state health stations following the A6 death register system. Age-standardized rates (ASR) of mortality and mortality rate ratio and 95% confidence interval (MRR (95%CI)) by time-period were estimated. Results: Among 140,670 reported deaths, 639 were due to EC (Men 527, women 112). The mortality rate (WHO-ASR) per 100,000 was 4.70 in men and 0.77 in women, giving the men to women ratio was 6.1. Mortality from EC was significantly increased during the 10 years, 2013-2014 vs. 2005-2006, MRR (95%CI): 2.79 (1.95, 3.99), p for trend < 0.05. Conclusion: We observed an increased time trend of mortality due to EC; men are responsible for over 80% of this fatal disease, therefore, a program of primary and secondary prevention against EC focused on men is highly needed in the Nghe An province.

Time Trend of Mortality from Esophagus Cancer During 2005-2014 in the Nghe An Province, Viet Nam

Le. Premature Mortality due to Breast Cancer in a Mountainous Province of Vietnam from 2005 to 2018. Biomed

Premature Mortality due to Breast Cancer in a Mountainous Province of Vietnam from 2005 to 2018

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