Mustafa Degirmenci

Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells

In the present study, we aimed to evaluate the possible synergistic, cytotoxic effects of combination treatment of gossypol and zoledronic acid, in human ovarian cancer cell lines, OVCAR-3 and MDAH-2774, and to elucidate the role of this novel combination treatment on angiogenesis-related molecules in ovarian cancer. The XTT cell viability assay was used for showing cytotoxicity. Both DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used for demonstrating apoptosis. To elucidate the angiogenic molecules affected by combination treatment, mRNA levels of angiogenic molecules were measured using the Human Angiogenesis RT2 ProfilerTM PCR Array (SuperArray, Frederick, MD) in ovarian cancer cell lines, OVCAR-3 and MDAH-2774.The combined treatment resulted in significant, synergistic cytotoxicity, and induced apoptosis. This effect was observed to happen in a dose- and time-dependent manner. Moreover, the combination treatment of 10 microM gossypol and 5 microM zoledronic acid resulted in significant down-regulation (>or= thee-fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3 and MDAH-2774 cells as compared to the untreated control. However, this effect was different in the two ovarian cancer cell lines observed. Gossypol, in combination with zoledronic acid, may provide a rational treatment option for ovarian cancer, not only by direct inhibition of cell proliferation, but also inhibition of angiogenesis-related molecules.

Medication Errors in Chemotherapy Preparation and Administration: a Survey Conducted among Oncology Nurses in Turkey

BACKGROUND Medication errors in oncology may cause severe clinical problems due to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed to investigate unintentional medication errors and underlying factors during chemotherapy preparation and administration based on a systematic survey conducted to reflect oncology nurses experience. MATERIALS AND METHODS This study was conducted in 18 adult chemotherapy units with volunteer participation of 206 nurses. A survey developed by primary investigators and medication errors (MAEs) defined preventable errors during prescription of medication, ordering, preparation or administration. The survey consisted of 4 parts: demographic features of nurses; workload of chemotherapy units; errors and their estimated monthly number during chemotherapy preparation and administration; and evaluation of the possible factors responsible from ME. The survey was conducted by face to face interview and data analyses were performed with descriptive statistics. Chi-square or Fisher exact tests were used for a comparative analysis of categorical data. RESULTS Some 83.4% of the 210 nurses reported one or more than one error during chemotherapy preparation and administration. Prescribing or ordering wrong doses by physicians (65.7%) and noncompliance with administration sequences during chemotherapy administration (50.5%) were the most common errors. The most common estimated average monthly error was not following the administration sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most important underlying reasons for medication errors were heavy workload (49.7%) and insufficient number of staff (36.5%). CONCLUSIONS Our findings suggest that the probability of medication error is very high during chemotherapy preparation and administration, the most common involving prescribing and ordering errors. Further studies must address the strategies to minimize medication error in chemotherapy receiving patients, determine sufficient protective measures and establishing multistep control mechanisms.

Effectiveness of Online Education in Teaching Breast Self- Examination

BACKGROUND This research evaluated the effectiveness of an online education model in teaching breast self- examination to university staff and students. MATERIALS AND METHODS 1,679 women participated in a breast self-examination online training program. Breast self-examination knowledge evaluation forms developed by Maurer (1997) were used in the research and were evaluated on a 100 point scale. Paired t-test and McNemars Test statistics were employed. RESULTS The participants scored an average of 46.5 (14.0%) on knowledge on breast self-examination before training, but 77.4 (11.0%) one month after education and 76.7 (9.52%) after six months. There was a clear significant difference between these knowledge levels (p<0.05). Similarly, while the rate for systematic practice of breast self-examination among women was 30.8% before training it increased to 47.8% afterwards. Again the difference was significant (p<0.05). CONCLUSIONS Online education is an effective method for teaching breast self-examination to women.

Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with breast cancer

Purpose Cytotoxic treatment may cause weight gain and important alterations in the metabolic status of breast cancer (BC) patients. The aim of this study was to investigate the changes in metabolic and anthropometric parameters of patients with BC who received adjuvant chemotherapy. Methods All consecutive women treated with adjuvant TAC (docetaxel 75 mg/m2, doxorubicine 50 mg/m2, cyclophosphamide 500 mg/m2) chemotherapy for node-positive breast carcinoma at our Institution between 2008 and 2010 were included. Results Among 104 patients, 84 of them were stage II and 20 of them were stage III. When we compared the measurements between 1st and 6th adjuvant chemotherapy, we observed statistically significant increases in weight and serum triglyceride levels, and decreases in high density lipoprotein, apolipoprotein A-1, transferrin, albumin and prealbumin levels. An elevation of follicle stimulating hormone, luteinizing hormone together with the decrease of estradiol was detected. Waist-to-hip ratio has also increased significantly. In subgroup analyses, we observed dramatic changes in body mass index in pre-menopausal women whereas no significant change was seen in the post-menopausal group. Conclusions Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with BC and these changes are more profound in pre-menopausal patients.

Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell lines.

PurposeDocetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines.MethodsThe XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISAPlus Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis.ResultsDTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone.ConclusionsThese results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects.

Zoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell lines.

Our aim was to investigate the possible synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and zoledronic acid (ZA), in PC-3 hormone-refractory prostate cancer cells (HRPC), as well as their docetaxel-resistant sublines. We established a docetaxel-resistant cell line (PC-3R) from PC-3 prostate cancer cells, by intermittent exposure to increasing concentrations of docetaxel in vitro. We then examined the effect of ZA and docetaxel on cell proliferation in both PC-3 and PC-3R prostate cancer cells. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 enzyme activity were measured to verify apoptosis. According to our results, docetaxel and ZA were found to be synergistically cytotoxic and apoptotic in both PC-3 and docetaxel-resistant PC-3R cells, in a dose- and time-dependent manner. Combined treatment with docetaxel and ZA synergistically inhibited PC-3 cell growth in vitro through an enhanced induction of cell death, compared with either agent alone; this result was also evident on PC-3R cells. Moreover, we have also demonstrated that apoptosis was induced in prostate cancer cells exposed to these drugs by a concentration-dependent increase in DNA fragmentation and caspase 3/7 enzyme activity. We concluded that ZA, either with docetaxel or not, might still exert some cytotoxicity even in docetaxel-resistant cells. From the clinical perspective, when the clinician decided to change the treatment in the post-docetaxel setting, continuing or combination with ZA may be an effective therapeutic approach for the treatment of HRPC patients.

First-line mono-chemotherapy in frail elderly patients with metastatic colorectal cancer.

BACKGROUND Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. MATERIALS AND METHODS We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. RESULTS Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. CONCLUSIONS Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status.

Hormone receptor status and survival of medullary breast cancer patients. A Turkish cohort

Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p<0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p<0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p>0.05). Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.

Evaluating Depression, Anxiety, Sexuality and Quality of Life in Metastatic Lung Cancer Patients

Introduction: Lung cancer (LC) affects psychosexual outcome and quality of life (QoL) of the patients because of short survival period and aggressive treatment modalities. The aim of our study was to investigate anxiety, depression, QoL and sexual satisfaction levels of LC patients. Methods: The data for metastatic LC patients treated with first or second-line chemotherapy were collected by using four forms completed during face-to-face interviews. The forms consist of socio-demographic characteristics, the Beck Depression Inventory (BDI), Golombok-Rust Inventory of Sexual Satisfaction (GRISS) and European Organization for Research on Treatment of Cancer Questionnaires Quality of Life-C30 (EORTCQoL-C30). Results: Forty-four LC patients were participated in this study. The total Beck scores of patients for anxiety and depression were very high (15.60 ± 12.30 and 16.02 ± 11.39; respectively). When we evaluated GRISS scores of our metastatic LC patients with respect to their anxiety or depression levels, we could not find any statistical significance. In the metastatic LC patients whose anxiety and depression scores were high, physical, cognitive, emotional and social functioning of EORTC-QLQ-C30 was found statistically significantly low. Statistical significance in terms of role functioning was only found in the patients with high anxiety scores. Conclusion: Metastatic LC patients had high anxiety and depression levels, decreased sexual satisfaction and impaired QoL.

Evaluation Of Clinicopathological Features Of Breast Cancer According To The Molecular Subtypes

Objective: Breast cancer is the most common malignancy observed among women worldwide. Breast cancer is a heterogeneous tumor, with different responses to therapy even among tumors of similar histology and stage. In this study we aimed to compare the clinical and pathological features of breast cancer according to the molecular subtypes. Methods: We retrospectively reviewed the 292 cases with breast cancer, who were diagnosed and treated at the Izmir Tepecik Education and Research Hospital between 2011 and 2014. Descriptive and inferential analyses between different intrinsic subtypes were performed. Results: A total of 292 females with invasive breast cancer were included in this study. The mean age of the patients was 55.5±12.8 years (28-85 years) which was similar to mean ages of patients with different tumor types. We identified 90 (30.8%) cases of luminal A, 87 (29.8%) luminal B, 78 (26.7%) HER2+, and 37 (12.7%) triple negative. The mean Ki-67 proliferation index was found to be 5 (1-12) in Luminal A group, 28.4 (15-80) in Luminal B group, 24.1 (1-95) in Her2 positive group and 43 (1-85) in triple negative group. The mean follow-up period was 22.5±10.9 months. Mean mortality rate was found as 10.6% (n = 31) in all patients. The least survival rate was determined in triple negative patients (78.4%, n=29). The highest survival rate was assessed (as compatible with the literature) in the luminal A group (n= 83, 92.2%). HER2-positive cases had second highest survival rate with tailored treatment (n= 71, 91%). Conclusion: Histopathologic features or histological grade of breast cancer alone are not reliable prognostic factors. It must be always considered that breast cancer is a heterogeneous tumor. Therefore in breast cancer, tailored therapy according to the molecular subtypes of tumor, seems to provide the highest benefit for patients.