BackgroundDeveloping novel strategies against treatment-resistant triple negative breast cancer (TNBC) cells remains a significant challenge. The ErbB family, including epidermal growth factor receptor (EGFR), plays key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSC) which are believed to be responsible for tumor initiation and maintenance. Ixabepilone is a new generation microtubule-stabilizing agent, which has been expected to be more efficacious than conventional taxanes. Here we aim to investigate whether the EGFR monoclonal antibody Cetuximab, in combination with Ixabepilone, is more effective in eliminating CSC populations compared to chemotherapy alone in TNBC.MethodsRepresentative TNBC cell lines (MDA-MB-231 and SUM159) were used to evaluate breast CSC populations. We used fluorescence-activated cell sorter analysis (CD44+ and CD24-/low, or Aldefluor+) and a self-renewal assay called mammosphere formation efficiency (MSFE) to measure CSC population size after treatment with Cetuximab, or Cetuximab plus Ixabepilone in vitro.ResultsAlthough there was no significant decrease in cell viability, Cetuximab reduced MSFE and the CSC population in breast cancer cells in vitro and in vivo through inhibition of autophagy. Also, SUM159 and MDA-MB-231 orthotopic tumors demonstrated partial response to Centuximab or Ixabepilone monotherapy; however, the effect of the combination treatment was significant only in SUM159 tumors (p <0.0001), when compared to Ixabepilone alone.ConclusionsOverall, our findings demonstrate that EGFR-targeted therapy by Cetuximab effectively reduces the CSC population in TNBC tumors. However, combination therapy with Ixabepilone may be effective only in a small subset of TNBCs, warranting further investigation of alternative approaches to target multiple pathways for TNBC treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0662-4) contains supplementary material, which is available to authorized users.

This study found hidden personal costs of caregiving among fathers of adults with schizophrenia; strategies are needed for supporting these fathers.

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Our findings indicate that Autism Spectrum Disorder manifests as a distinct behavioral phenomenon in Down syndrome. Hence it is important for professionals to consider the possibility of a dual diagnosis which will entitle the child to a more specialized and effective educational and intervention services.

Background: Adolescence is a distinctive stage of various changes and is noted as peak age for onset of many psychiatric disorders, especially linked to stress and depression. Several genetic variations are being increasingly known to be linked with stress and depression. The polymorphisms in two such genes, the BDNF and SLC1A3, have been reported to be linked with either depression/stress or with suicidal behaviour. These genes have not been validated in Indian population, and therefore there is a need to investigate these genes in Indian population. The present study was undertaken to test whether the known polymorphisms SLC1A3 C3590T, SLC1A3 C869G and BDNF G196A are associated or not with stress or depression in an eastern Indian population. Methods: A case-control association study was performed with 108 cases having variable levels of stress and depression and 205 matched controls. Detection of stress and depression was done by using standard instruments as PSS and CES-D, respectively and demographic profile was obtained for each individual on the basis of personal data sheet. Genotyping for the selected polymorphisms was performed by PCR followed by restriction digestion. Results: The SNP SLC1A3 C3590T was found to be associated with stress and depression (p = 0.0042, OR = 2.072). Therefore, the T allele increases the risk by more than two folds for stress and depression in the present population. The other allele of SLC1A3, G869C, as well as BDNF G196A were not associated with stress or depression in the population studied. Conclusion: SLC1A3 C3590T is a predisposition factor for stress and depression in an eastern Indian population, whereas SLC1A3 G869C and BDNF G196A were not found to be a risk factor. Therefore, presence of T allele of SLC1A3 C3590T, may predict the development of stress and depression in an individual. This may also help in the understanding of pathophysiology of the disease. However, these findings warrant a wider study in Indian populations and would be of significance in understanding the predisposition of stress and depression in this population.