Overcoming trastuzumab resistance in HER2-positive breast cancer using combination therapy

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) comprises around 20–30% of all BC subtypes and is correlated with poor prognosis. For many years, trastuzumab, a monoclonal antibody, has been used to inhibit the HER2 activity. Though, the main resistance to trastuzumab has challenged the use of this drug in the management of HER2-positive BC. Therefore, the determination of resistance mechanisms and the incorporation of new agents may lead to the development of a better blockade of the HER family receptor signaling. During the last few years, some therapeutic drugs have been developed for treating patients with trastuzumab-resistant HER2-positive BC that have more effective influences in the management of this condition. In this regard, the present study aimed at reviewing the mechanisms of trastuzumab resistance and the innovative therapies that have been investigated in trastuzumab-resistant HER2-positive BC subjects.     

The Footprints of Oxidative Stress and Mitochondrial Impairment in Arsenic Trioxide-Induced Testosterone Release Suppression in Pubertal and Mature F1-Male Balb/c Mice via the Downregulation of 3β-HSD, 17β-HSD,and CYP11a Expression

Biological Trace Element Research - Exposure to arsenic (AS) causes abnormalities in the reproductive system; however, the precise cellular pathway of AS toxicity on steroidogenesis in developing...     

Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer

Molecular Biology Reports - Reactive Oxygen Species Modulator 1 (ROMO1) plays a pivotal role in the regulation of mitochondrial structure integrity, and the production of reactive oxygen species...     

The activation of ezrin-radixin-moesin proteins is regulated by netrin-1 through Src kinase and RhoA/Rho kinase activities and mediates netrin-1-induced axon outgrowth

The receptor Deleted in Colorectal Cancer (DCC) mediates the attractive response of axons to the guidance cue netrin-1 during development. On netrin-1 stimulation, DCC is phosphorylated and induces the assembly of signaling complexes within the growth cone, leading to activation of cytoskeleton regulators, namely the GTPases Rac1 and Cdc42. The molecular mechanisms that link netrin-1/DCC to the actin machinery remain unclear. In this study we seek to demonstrate that the actin-binding proteins ezrin-radixin-moesin (ERM) are effectors of netrin-1/DCC signaling in embryonic cortical neurons. We show that ezrin associates with DCC in a netrin-1-dependent manner. We demonstrate that netrin-1/DCC induces ERM phosphorylation and activation and that the phosphorylation of DCC is required in that context. Moreover, Src kinases and RhoA/Rho kinase activities mediate netrin-1-induced ERM phosphorylation in neurons. We also observed that phosphorylated ERM proteins accumulate in growth cone filopodia, where they colocalize with DCC upon netrin-1 stimulation. Finally, we show that loss of ezrin expression in cortical neurons significantly decreases axon outgrowth induced by netrin-1. Together, our findings demonstrate that netrin-1 induces the formation of an activated ERM/DCC complex in growth cone filopodia, which is required for netrin-1-dependent cortical axon outgrowth.     

Addition of a volcanic rockdust to soils has no observable effects on plant yield and nutrient status or on soil microbial activity

Background and Aims

Rising costs and pressure on supplies of commercial mineral fertilizers and increasing markets for organically produced foods and feeds have led to a growing interest in soil amendments to supply plant nutrients. Rockdust is a by-product of quarrying and its effectiveness to supply plants with nutrients has been a contested issue and there have been no assessments of its effect on soil biota other than plants. The aim of this study was to assess the effect of a commercially-available volcanic rockdust application on crop growth and element concentrations for a wide range of macro and microelements and the response of soil microbial communities to rockdust due to the potential alteration in soil mineralogy.

Methods

A three-year controlled outdoor-growing experiment was conducted on three different soil types with two wheat cultivars in the first year following rockdust application and with forage species in the third year.

Results

Our results show that the tested rockdust had no positive or negative effect on plant growth or nutrient composition. In addition, the microbial response to added substrates, a sensitive measure of changes in soil environment, were unaltered by the rockdust.

Conclusions

As the rockdust had no nutrient or toxic effect it can probably be considered as an inert material which at least causes no harm but equally has no demonstrable ecological or agricultural benefit.     

Effect of Selenium Nanoparticle Supplementation on Tissue Inflammation,Blood Cell Count,and IGF-1 Levels in Spinal Cord Injury-Induced Rats

Biological Trace Element Research - Selenium is known to be a neuroprotective agent in respect to a number of neuronal diseases and pain. The aim of this study was to evaluate the neuroprotective...     

Up-regulated lncRNA-PVT1 expression in peripheral blood mononuclear cells of patients with coronary artery disease is correlated with decreased interleukin-10 production

Molecular Biology Reports - Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA, which has not been previously studied in the inflammatory responses of the...     

Induction of Apoptosis and Autophagy Using Ectopic DSCR1 Expression in Breast Cancer Cells

Down syndrome critical region 1 gene (DSCR1) is an anti-angiogenesis gene that inhibits the growth of tumor cells. In this study, the role of autophagy and apoptosis in DSCR1-induced cytotoxicity were investigated in MDA-MB-468 breast cancer cells. Lentivirus vector harboring DSCR1 (LV-DSCR1⁺) was constructed in HEK 293 cells and the optimal dosage of lentivirus vector for infection was determined by the MTT assay. After infection of cells using LV-DSCR1⁺, acridine orange and ethidium bromide staining was performed to investigation of apoptosis and autophagy. Expression of DSCR1 and marker genes for angiogenesis (VEGF), apoptosis (Bax and Bcl2) and autophagy (LC3 and Beclin) were determined by Real time PCR. The cellular morphological changes related to apoptosis and autophagy was happened after 48 hours of viral infection. Fragmented bright orange nucleuses and vacuoles were observed due to the cell apoptosis and autophagy after acridine orange and ethidium bromide staining. Upregulation of Bax, Lc3, DSCR1 and Beclin1 and downregulation of Bcl2 and VEGF was detected due to treatment with LV-DSCR1⁺. These results demonstrated that LV-DSCR1⁺ can induce apoptosis and autophagy, therefore suggesting that it may serves as an efficient tool to breast cancer treatment.