Browsing by Subject "Breast cancer."

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Open Access
Analysis of CHRNA5 expression in breast cancer cell lines in response to serum starvation and estrogen treatment
(2013) Açıkgöz, Azer Aylin
Breast cancer is a complex disease that can be classified into distinct molecular subtypes including Basal, Luminal A, Luminal B and HER2 positive. These molecular subtypes mainly differ in their hormone receptor expression and response to treatment. This makes the discovery of new molecular markers for further classification important. Cholinergic nicotinic acetylcholine receptors are ion channels involved in smoking behavior, neurodegenerative diseases and cancer. Cholinergic nicotinic receptor alpha 5 (CHRNA5) has been associated with nicotine addiction and recently with lung cancer yet its importance in breast cancer remains relatively unexplored. In the present study, a panel of 10 breast cancer cell lines were used for quantification of isoform-specific CHRNA5 expression using qPCR. Changes in CHRNA5 expression in response to serum starvation and estrogen treatment were assessed. qPCR showed that CHRNA5 was alternatively spliced, with at least five different isoforms in breast cancer cell lines. qPCR analysis for CHRNA5 expression in serum treated and serum starved cells were analyzed after outlier detection and exclusion; and statistical tests included ANCOVA using geometric mean of TPT1 and SDHA, as reference genes. Our results demonstrated that, CHRNA5 expression differed between different subtypes of breast cancer cell lines. CHRNA5 expression significantly responded to serum starvation in ZR75-1 and MDA-MB-157 cell lines, isoform specifically. Isoform expression of CHRNA5 exhibited significant alterations upon estrogen treatment in a dose and time-dependent manner. Expression of 1000bp variant, isoform2 and isoform3 of CHRNA5 significantly increased upon E2 treatment and total CHRNA5 and isoform2 CHRNA5 increased in expression at 24 hours when compared with 12 hours of treatment. Our findings show that CHRNA5 has multiple isoforms in breast cancer, with potential to be modulated by serum starvation and estrogen treatment in a cell-specific manner.
Open Access
Effects of biological compound Turkish propolis extract on breast cancer cells
(2013) Uğurlu, Deniz
Propolis is a resinous compound which is collected from various plants then combined with wax and bee enzymes by worker bees. There are many studies conducted on propolis or its active components aiming to find new treatment possibilities in diverse research fields such as immunology, infectious diseases, allergy, diabetes, ulcers, and oncology. Chemical analysis indicated that propolis is a multicomponent mixture of various compounds with prevalence of flavonoids and phenolic acids. Therefore it is important to investigate the propolis extract mechanisms of action in order to predict possible cytotoxic and may be therapeutic effects for cancer. The most common propolis extract is ethanol extract of propolis (EEP) whereas Turkish researchers were able to extract the propolis with dimethyl sulfoxide (DMSO) which can maximize the penetration of compounds from propolis to the cells as well as DMSO is a good solvent for flavonols (one of the most common compound in propolis). There are many studies conducted on propolis or its active components for treatment of cancer which reveals the potential of this biological compound in the development of novel anti-cancerous agents. However, anti-cancer activity of DMSO extract of Turkish propolis (DEP) on human breast cancer has not been investigated yet. The aim of this study was to investigate the anti-cancer effects of DMSO extract of Turkish propolis (DEP) on cancer cells. Inhibitory effects of propolis extracts collected from different regions of Turkey were analyzed on the growth of the human breast carcinoma cells. Two different propolis extracts were used to determine their cytotoxic effects of breast carcinoma cell lines using SRB staining and IC50 values were determined. The results showed that propolis is cytotoxic in dose-dependent manner (IC50 value of diverse from 25 ug/ml to 123 ug/ml). Real time monitoring (xCELLigence system) of propolis treated cells confirmed the cytotoxic effect of propolis, since increasing concentrations of propolis decreased the cell number in a dose- and cell line- dependent way. Furthermore, propolis treatment induces apoptosis in breast carcinoma cell lines. Propolis treated cells changed their adherent morphology to round cells and detached from the surface. Hoechst 33258 staining of propolis treated cells revealed the increasing number of cells displays DNA condensation. PARP-1, a 116 kDa nuclear enzyme, is cleaved in fragments of 89 and 24 kDa during apoptosis. Western blot analysis was performed to detect the PARP-1 cleavage in propolis treated cells. Decrease in the full-length PARP-1 protein levels supports our hypothesis that propolis shows its cytotoxic effect at least partially through induction of apoptosis. The effect of propolis on cell cycle was analyzed with flow cytometer after staining the cells with Propidium iodide (PI). Increase in the G2/M cell cycle arrest was observed in propolis treated cells compare to control DMSO treated MDA-MB-231 cells. In addition to cytotoxic effects, in vitro wound healing assay revealed that propolis treated MDA-MB-231 cells shows delayed invasion of the cells to the denuded area when compared to the DMSO control cells. In conclusion, propolis showed a cytotoxic effect on breast carcinoma cell lines by inducing apoptosis, G2/M arrest as well as delaying the invasion capacity of the cells which makes it a potent anti-tumorigenic compound that may be useful in cancer chemoprevention or therapy.
Open Access
Novel monoclonal antibodies targeting conformational ERBB2 epitopes
(2012) Ceran, Ceyhan
ERBB2 is a tyrosine kinase receptor which can act as homodimers or heterodimers with other members of the ERBB family. Nearly 30% of breast cancers overexpress ERBB2, which can be effectively targeted by anti-ERBB2 monoclonal antibodies. Trastuzumab directed against an epitope on subdomain IV of the extracellular domain (ECD) of ERBB2 is a clinically used therapeutics but the response rate is poor and acquired resistance is frequent. Pertuzumab that binds to subdomain II and inhibits receptor dimerization is another promising therapeutics under clinical trials. Anti-ERBB2 antibodies directed to novel epitopes are potentially useful tools for replacement and combinatorial therapies. We produced five new anti-ERBB2 antibodies, all directed against epitope(s) present only on the native ECD. They performed selective growth inhibitory effects depending on the level of ERBB2 expression and cellular background. When used alone, novel anti-ERBB2 antibodies displayed modest but significant growth inhibition on SK-BR-3, BT-474 and MDA-MB-361 cells with ERBB2 overexpression; while no detectable inhibition was observed on MCF-7 and T47D cells lacking ERBB2 amplification. When the antibodies were tested in combination with TNF-α, they acted synergistically on SK-BR-3 cells, producing upto 80% growth inhibition; but performed antagonistically on BT-474 cells. Detailed investigation of a representative antibody indicated G1-arrest as the main mechanism of the anti-proliferative effects exerted on SK-BR-3 cells. Antibody treatment induced permanent inhibition of DNA synthesis, leading to accumulation of cells at G1-phase; an effect which was accelerated in the presence of TNF-α. In addition, treated SK-BR-3 cells displayed inhibition of Akt and ERK1/2 phosphorylation leading to cyclin D1 accumulation and growth arrest, independently from TNF-α. Novel antibodies against conformational epitopes present on the extracellular domain of ERBB2 receptor may serve as new analytical and diagnostic tools, in addition to being potent anti-cancer bioactive molecules. Cell-dependent synergy and antagonism between anti-ERBB2 antibodies and TNF-α provide evidence for a complex interplay between ERBB2 and TNF-α signaling pathways. Such complexity may drastically affect the outcome of ERBB2-directed therapeutic interventions.
Open Access
A simulation model for breast cancer epidemiology in Turkey
(2014) Ada, Kumru
Breast cancer has a vital importance in women's life. In the world, breast cancer incidence and mortality rates are increasing. Considering the burden of disease, in 2012 1.67 million women got breast cancer and about 522,000 women died due to breast cancer. With this numbers, breast cancer ranks as the most common cancer among women in the world and the fifth cause of death from cancer overall. Breast cancer has a high incidence and mortality rates especially in developing countries, where late diagnosis of cancer is also increasing the disease burden. Lack of knowledge of the exact causes of breast cancer increases the importance of early detection. The most effective way of early detection is to apply mammography screening. Screening the accurate target population increases the rate of early detection of breast cancer and lessens the economic and health burden of disease. In this study, two simulation models were constructed in order to analyze the population-based mammography screening programs for Turkey. The first model was run for 10 years for validation purpose while the second one was run for the women born in 1980 during their lifetime to analyze several screening programs. The screening programs differ from each other in terms of beginning and final age of screening and screening frequency. Costs and health outcomes of the screening policies were examined and non-dominated screening policies are determined according to these performance measures.
Open Access
A simulation optimization for breast cancer screening in Turkey
(2014) Keyf, Dilek
Breast cancer is the most common cancer type among women in the world. 6.3 million women were diagnosed with breast cancer between 2007 - 2012 and 25% of cancers in women are breast cancer. Early diagnosis and early detection has an important role in survival from breast cancer. Mammographic screening is proved to be the only screening method that can reduce breast cancer mortality. Even though mammographic screening has this significant benefit, it is expensive and it can decrease life quality and it can generate false positive results. As a consequence, recommending an effective and costefficient mammographic screening policy in terms of starting and ending ages and screening frequencies has high importance. This study aims to optimize Ada’s Breast Cancer Simulation Model using Simulated Annealing. This model was run for Turkish women born in 1980 during their lifetime. The purpose of this study is to obtain an optimal or near optimal policy in terms of life years gained and cost for Turkish women. This study also aims to demonstrate the outcomes in terms of effectiveness and cost when different combinations of policy variables are used.