Search results for "Breast"

Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer

2007

Interleukin-7-receptor-signaling plays a pivotal role in T-cell development and maintenance of T-cell memory. We studied IL-7Ralpha (CD127) expression in PBMCs obtained from patients with breast cancer and examined IL-7 receptor-mediated downstream effects defined by STAT5 phosphorylation (p-STAT5). Reduced numbers of IL-7Ralpha-positive cells were identified in CD4+ T-cells as well as in a CD8+ T-cell subset defined by CD8alpha/alpha homodimer expression in patients with breast cancer. PBMCs obtained from healthy donors (n = 19) and from patients with breast cancer (n = 19) exhibited constitutive p-STAT5 expression in the range of 0-6.4% in CD4+ T-cells and 0-4% in CD8+ T-cells. Stimulatio…

Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer

2019

AbstractThe article gives an overview of current treatment options for metastatic hormone receptor-positive and HER2-negative breast cancer. The focus is on combined therapies, e.g., with CDK4/6 inhibition compared with purely endocrine-based therapies in the pre- and postmenopause, presenting the latest study results. The addition of a CDK4/6 inhibitor to endocrine-based therapy with an aromatase inhibitor or fulvestrant leads to a marked improvement in progression-free survival and is independently beneficial whether palbociclib, ribociclib or abemaciclib is involved. The particular clinical status of inhibition of cyclin-dependent kinases argues for its use in the first-line treatment of…

Prognostic significance of Focal Adhesion Kinase (FAK) in node-negative breast cancer.

2015

552 Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase playing an important role as a key mediator for signal transduction. We examined the subtype specific prognostic signifi...

Non-pegylated liposomal doxorubicin plus cyclophosphamide as first-line therapy in elderly women with HER2 negative metastatic breast cancer.

2022

Background. The use of anthracyclines in metastatic breast cancer (MBC) is limited by cumulative dose-dependent cardiotoxicity mostly in elderly women with comorbidities. The aim of this observational retrospective study was to evaluate the efficacy of non-pegylated liposomal doxorubicin (Myocet®) and cyclophosphamide in elderly women as HER2 negative first-line MBC treatment. Methods. 84 elderly women >70 years of age (median age 78 years) with MBC HER2 negative were enrolled. Performance Status in 58 patients was ECOG-0 and in 26 patients was ECOG-1. Results. The drug was well tolerated, with overall response rates were >40%, median overall survival was 16.2 months (95%CI:14.6- 18.8…

Effect of cadmium on MDA-MB231 breast cancer cells

2006

Interleukin-30 feeds breast cancer stem cells via CXCL10 and IL23 autocrine loops and shapes immune contexture and host outcome

2021

BackgroundBreast cancer (BC) progression to metastatic disease is the leading cause of death in women worldwide. Metastasis is driven by cancer stem cells (CSCs) and signals from their microenvironment. Interleukin (IL) 30 promotes BC progression, and its expression correlates with disease recurrence and mortality. Whether it acts by regulating BCSCs is unknown and could have significant therapeutic implications.MethodsHuman (h) and murine (m) BCSCs were tested for their production of and response to IL30 by using flow cytometry, confocal microscopy, proliferation and sphere-formation assays, and PCR array. Immunocompetent mice were used to investigate the role of BCSC-derived IL30 on tumor…

CtIP silencing as a novel mechanism of tamoxifen resistance in breast cancer.

2007

AbstractAcquired resistance to the antiestrogen tamoxifen constitutes a major clinical challenge in breast cancer therapy. However, the mechanisms involved are still poorly understood. Using serial analysis of gene expression, we identified CtIP, a BRCA1- and CtBP-interacting protein, as one of the most significantly down-regulated transcripts in estrogen receptor α–positive (ER+) MCF-7 tamoxifen-resistant breast cancer cells. We further confirmed the association of CtIP down-regulation with tamoxifen resistance in an additional ER+ breast cancer line (T47D), strengthening the relevance of the phenomenon observed. In additional studies, we found CtIP protein expression in a majority of ER+ …

Patterns of Innate or Acquired Resistance to Anticancer Drugs: Our Experience to Overcome It

2021

Drug resistance, which is often of a multiple type, can be defined as the ability of cancer cells to obtain resistance to both conventional and novel chemotherapy agents. It remains a major problem to solve in cancer therapy. The mechanisms of resistance are multifactorial, and in our cellular models of acute myeloid leukemia, hepatocellular carcinoma, and triple-negative breast cancer, it involves the NF-κB pathway. In our opinion, multitarget molecules can be considered as privileged compounds capable of attacking and reversing the resistant phenotype. In the phenomena of both innate and acquired drug resistance that we have been studying since 1998 to today and up to 2016 under the guida…

Mid-region parathyroid hormone-related protein (PTHrP) binds chromatin of MDA-MB231 breast cancer cells and isolated oligonucleotides “in vitro”

2006

We have previously shown that PTHrP(38-94)-amide restrains growth and invasion "in vitro", causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231 whose tumorigenesis was also attenuated "in vivo". PTHrP(38-94)-amide contains the domain implicated in the nuclear import of PTHrP. Although the nucleus was identified as a destination for mid-region PTHrP, evidence for direct DNA-binding capability is lacking to date. Here, we examined the localization of PTHrP(38-94)-amide within MDA-MB231 cells and within metaphase spread preparations and characterized its DNA-binding properties, employing a combination of immunocytochemical, cytoge…

Targeted sequencing in a phase III trial of luminal breast cancer: Identification of novel targets.

2017

505 Background: The International Cancer Genome Consortium and The Cancer Genome Atlas have had a global transformative impact on our understanding of cancer. These programs have mapped the genomic landscape of common and rare tumors setting the scene for a comprehensive change in the approach to cancer diagnosis and treatment. However, the task remains incomplete until these mutational events are linked to clinical outcomes in the context of current therapeutic intervention to drive future stratified medicine approaches. Methods: We performed targeted sequencing in patients from the Tamoxifen Exemestane Adjuvant Multicentre trial. DNA was extracted and a 101 gene panel analysed using a no…