Biomedical subjects

Hakan Bozcuk

Publications and source records attributed to Hakan Bozcuk.

10 recordsLinked to original sources

PubMed2006

Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study.

We have explored the action of zoledronic acid, which has an apoptotic effect and is used as an agent for treating skeletal metastases and osteoporosis, in the presence of vinblastine, and whether this effect is associated with MRP-1 (multidrug resistance protein-1) expression. HEK (human embryonic kidney) 293 cells were transfected to form the multidrug resistant cell line designated 293MRP (MRP-1 expressing HEK293 cells). Both lines were treated with varying concentrations of vinblastine and zoledronic acid. Apoptosis was determined by the TUNEL (deoxyuridine triphosphate nick end-labeling) method. The type of treatment, MRP-1 expression status, and the type of treatment with respect to MRP-1 expression status significantly affected (P < 0.001) the degree of apoptosis. The largest increase in cytotoxicity was noted in HEK293 cells, when 100 micromol zoledronic acid was added to 4 microg/ml vinblastine (an increment of 80.3%, P < 0.001). This preliminary work shows that zoledronic acid acts synergistically with vinblastine to induce apoptosis in an MRP-1 dependent way.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Does music exposure during chemotherapy improve quality of life in early breast cancer patients? A pilot study.

BACKGROUND: Adjuvant chemotherapy is associated with poor quality of life (qol) in breast cancer patients. We tested the effect of listening to music during chemotherapy on quality of life in these patients. MATERIAL/METHODS: We tested in a prospective cohort the changes in qol scores as assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and the influence of listening to non-preferred music at the chemotherapy unit on these parameters in a mixed linear model by repeated measures analysis of variance (RMANOVA). RESULTS: For the whole cohort, musical intervention was not associated with a change in any dimension of quality of life. However; the music effect significantly interacted with patient age; patients > 45 years old had improved insomnia and appetite loss scores after musical intervention (F = 6.76, P = 0.019 and F = 11.22, P = 0.004, respectively). CONCLUSIONS: Our results show that brief, non-preferred music exposure at the time of chemotherapy administration does not improve quality of life in patients with early breast cancer. Nonetheless, there is still a possibility that a subgroup will benefit from this approach as suggested by the interaction of the music effect with patient age.

Adult↗

PubMed2005

Does maintenance/consolidation chemotherapy have a role in the management of small cell lung cancer (SCLC)? A metaanalysis of the published controlled trials.

BACKGROUND: The role of maintenance/consolidation chemotherapy was assessed in the management of small cell lung cancer (SCLC) via a metaanalytic approach. METHODS: The Medline and Cochrane databases were searched for relevant randomized clinical trials that compared maintenance chemotherapy with follow-up. Quality of trials was assessed by European Lung Cancer Working Party (ELCWP) score. Odds ratios and rate differences were used as the effect size. Mantel-Haenszel tests with fixed and random effect models were conducted for 1- and 2-year overall survival (OAS) and progression-free survival (PFS). RESULTS: Fourteen relevant randomized clinical trials to date, encompassing 2550 patients, with trial sizes ranging from 36 to 610, were identified. Both 1- and 2-year mortality were reduced with maintenance/consolidation chemotherapy. With the fixed model, odds ratios for 1- and 2-year OAS were 0.67 (95% confidence interval [CI] = 0.56-0.79), P < 0.001, and also 0.67 (95% CI = 0.53-0.86), P < 0.001. Likewise, 1- and 2-year PFS were better with maintenance/consolidation chemotherapy, with odds ratios of 0.49 (95% CI = 0.37-0.63), P < 0.001, and 0.64 (95% CI = 0.45-0.92), P < 0.015. The random model gave similar results. In accordance, maintenance chemotherapy improved 1- and 2-year OAS by 9% (from 30-39%) and 4% (from 10-14%), respectively. Similarly, 1- and 2-year PFS were also improved. CONCLUSION: Maintenance/consolidation chemotherapy improves survival in SCLC. New randomized clinical trials are needed to further refine the place of this approach in the management of SCLC.

Adult↗

PubMed2005

Cluster analysis of p-glycoprotein, c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non-small cell lung cancer.

BACKGROUND: Various biomarkers have prognostic value in non-small cell lung cancer (NSCLC). We aimed to identify the roles of P53, c-erb- B2 and p-glycoprotein (pgp) as prognostic factors, independently or in conjunction with each other, in operable NSCLC. MATERIAL/METHODS: Seventy operable NSCLC cases were retrospectively evaluated for P53, c-erb-B2 and pgp expression patterns by immunohistochemistry. An unsupervised hierarchical cluster analysis of the 3 biomarkers was conducted. Univariate and multivariate survival analyses were made in relation to cluster affiliation. RESULTS: Cluster analysis yielded two distinct subgroups; group A of high biomarker expressors (n=26, 37%), and group B (n=44, 63%) of low expressors. Cluster affiliation with regard to tumor histology (interaction term) was independently associated with Recurrence- free survival (RFS) and Overall survival (OAS) with a Hazard Ratio (HR) of 5.88, P=0.003, and HR=4.68, P=0.012, respectively. The median OAS times for cluster A and B in the squamous cell carcinoma subgroup were 328 and 596 days, whereas the corresponding figures in the non-squamous cell carcinoma subgroup were non-measurable and 298 days. CONCLUSIONS: In operable NSCLC there may be different relationships of P53, c-erb-B2 and pgp with patient outcome for different tumor histologies. The prognostic utility of cluster affiliation with regard to these biomarkers, and in relation to tumor histology, deserves further testing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

An application of a genetic algorithm in conjunction with other data mining methods for estimating outcome after hospitalization in cancer patients.

BACKGROUND: We investigated which factors predicted the risk of in-hospital mortality in a general population of cancer patients with non-terminal disease and whether employing the genetic algorithm technique would be useful in this regard. MATERIAL/METHODS: A total of 201 cancer patients, including all cases of in-hospital mortality over a 2-year period, as well as a control group of subjects discharged during the same period, all having an Eastern Cooperative Oncology Group (ECOG) performance status of of < or =3 at the time of admission, were retrospectively evaluated. Indicators of in-hospital mortality were determined by multivariate logistic regression, recursive partitioning analysis, neural network, and genetic algorithm (GA) techniques. The performance of the different techniques were compared by a number of measures, including receiver operating curve (ROC) analysis. RESULTS: All four analysis methods selected a combination of six explanatory variables to explain the risk of in-hospital mortality: lactate dehydrogenase (LDH), alanine transaminase (ALT), hemoglobin (Hb), white blood cell counts (Wbc), type of cancer, and reason for admission. Compared with the other 3 methods, GA selected the least number of explanatory variables, i.e. LDH and reason for admission, with similar fraction of cases explained (78.6%), and yielded a fitness score of 0.52. CONCLUSIONS: LDH is an important indicator of in-hospital mortality for hospitalized cancer patients not in terminal stage. GA reliably predicted in-hospital mortality and was shown to be as efficient as the other data mining techniques employed in this study. Its use in a clinical setting for prognostication in oncology appears promising.

Adolescent↗

PubMed2004

Fundamental principals of tumor necrosis factor-alpha gene therapy approach and implications for patients with lung carcinoma.

Apoptosis, known as programmed cell death, is defined as a cell's preferred form of death under hectic conditions through genetically conserved and complex pathways. There is a decisive balance between stimulatory and inhibitory signaling pathways to maintain homeostasis in cells. In order to shift the balance towards apoptosis, the modulation of both apoptotic and anti-apoptotic pathways represents an attractive target for cancer therapeutics. Currently, chemotherapy and radiotherapy are among the most commonly used treatment modalities against lung cancer. Tumor suppressor gene, p53, is required in order for both of these treatment methods to work as anti-tumor agents. As a result, tumors lacking p53 display resistance to both chemotherapy and radiotherapy. However, death ligands induce apoptosis regardless of p53 status of cells. Thus, these methods constitute a complementary therapeutic approach to currently employed conventional treatment modalities. At present, death ligands are being evaluated as potential cancer therapeutic agents. Since resistance to tumor necrosis factor (TNF)-alpha-mediated apoptosis represented an obstacle for the treatment of patients with lung carcinoma in the earlier attempts, an extensive research was recently initiated to understand molecular mechanism of TNF-alpha signaling. NF-kappaB transcription factors have been demonstrated to modulate the apoptotic program, mostly as blockers of apoptosis in different cell types. In this review, we concentrate on the current progress in the understanding of TNF-alpha-mediated apoptosis for lung carcinoma. Representative models of NF-kappaB-inhibiting gene therapy strategies from various labs including ours are also provided as examples of up-to-date approaches to defeat TNF resistance. In order to give the reader better understanding and appreciation of such approaches, previously unpublished in vivo assays are also incorporated into this review. Current progress in clinical trials using adenovirus-mediated delivery of TNF-alpha is also discussed.

Antineoplastic Agents↗

PubMedDate not supplied

Tumour necrosis factor-alpha, interleukin-6, and fasting serum insulin correlate with clinical outcome in metastatic breast cancer patients treated with chemotherapy.

INTRODUCTION: To assess the relationship of various growth factors and cytokines with the clinical outcome in metastatic breast cancer patients receiving chemotherapy. METHODS: Consecutive, metastatic breast cancer patients with measurable disease and receiving palliative chemotherapy were prospectively evaluated for the predictors of progression free survival (PFS) and overall survival (OAS) in relation to serum insulin, insulin resistance, interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha). RESULTS: Estrogen receptor (ER) status, serum IL-6 and serum TNF- were the independent determinants of PFS, with RR=0.28 (0.13-0.60), P=0.001, RR=2.48 (1.24-5.61), P=0.012, and RR=0.48 (0.23-1.01), P=0.053, respectively. The factors related with OAS in the multivariate analysis were histological grade (RR=7.88 (2.33-26.62), P=0.001), ER status (RR=0.18 (0.06-0.57), P=0.003), serum insulin (RR=0.87 (0.77-0.97), P=0.016), and serum IL-6 (RR=5.99 (1.89-18.97), P=0.002). CONCLUSIONS: We show for the first time that fasting serum insulin and TNF-alpha levels are independent predictors for OAS and PFS, respectively, in metastatic breast cancer patients. In addition, we also confirm that IL-6 is a poor prognosticator in this group. These results suggest that insulin and TNF-alpha are important biomolecules that may be directly involved in vivo in the progression of metastatic breast cancer.

Adult↗

PubMedDate not supplied

Quality of life in patients with advanced non-small cell lung cancer.

Quality of life (QOL) has been shown to improve with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), but the determinants of this improvement have not been thoroughly explored. Fifty consecutive NSCLC patients starting chemotherapy with measurable disease and with an Eastern Co-operative Oncology Group (ECOG) performance status of <or=2 were evaluated for change in QOL by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). The status of global QOL before chemotherapy influenced the degree of change in physical functioning (F = 8.71, P =.001), global QOL (F = 23.82, P <.001), and fatigue (F = 7.92, P =.001), whereas age of the patient was again linked with the change in global QOL (F = 4.68, P =.014), and type of chemotherapy administration (1st vs. 2nd line) was associated with the change in fatigue (F = 7.82, P =.001). Our findings show that patient age and baseline QOL assessed by EORTC-QLQ-C30, but not ECOG performance status, may help predict the amount of improvement in certain aspects of QOL in patients with advanced NSCLC undergoing chemotherapy. Conversely, in this cohort, patients who are likely to have deteriorating QOL on chemotherapy may benefit from closer follow-up and nursing care to optimize supportive measures.

Adult↗

PubMedDate not supplied

Different clinical features of primary and secondary tumors in patients with multiple malignancies.

Clinical features of the first and second primaries in patients with multiple malignancies have not been extensively studied. We compared patient and treatment characteristics of the primary malignancy in 48 consequent multiple primary cancer patients with those of the second primary in the same cohort. The second primaries comprised fewer breast cancers; 29.2% of primaries as opposed to 10.4% of second tumors were breast cancer (P = 0.049). In addition, primary tumors tended to be at a lower TNM stage than secondary tumors (P = 0.060). The median overall survival after the diagnosis of the first primary for the whole cohort was 22.3 years (95% CI, 2.0-42.5) and the median time to presentation of the second malignancy was 38 months after the diagnosis of the first primary (range, 0 to 384). Therefore, the prognosis of cancers in the multiple malignancy group appears to be good and they appear to have an indolent clinical behavior. Thus, we recommend a long screening time for secondary tumors after a curative treatment in patients with common cancers, taking into account the different occurrence patterns of second primaries with respect to first primaries.

Adult↗

PubMedDate not supplied

The value of low-dose intraperitoneal immunoglobulin administration in the treatment of peritoneal dialysis-related peritonitis.

BACKGROUND: Peritonitis is a major complication of continuous ambulatory peritoneal dialysis (CAPD). The value of immunomodulatory therapeutic approaches and, especially, methods aimed at augmenting opsonization in the treatment of peritoneal dialysis (PD)-related peritonitis is unclear. In this study, the effect of intraperitoneal (IP) immunoglobulin (Ig) usage, as an approach for strengthening opsonization, was evaluated in CAPD peritonitis. METHODS: The study included 24 patients with CAPD peritonitis. The patients were divided into two groups, A and B, each consisting of 12 patients. There were no significant differences between the groups in terms of age, gender, CAPD duration, and peritonitis rate. Empiric antibiotic treatment was a 2-week IP ampicillin+sulbactam/netilmycin combination. Group B was additionally given low-dose IP IgG (2 mL = 320 mg) with every exchange. The dialysate leucocyte counts were obtained in both groups until the number was <100 cells/microL to monitor the response to peritonitis treatment. RESULTS: In group A, the number of exchanges done until the dialysate leucocyte counts decreased to <100/mL was 13.9 +/- 1.4 and for group B 6.6 +/- 0.4 (p<0.001). The reduction in neutrophils was significantly faster in group B compared to group A (p<0.001). The number of exchanges until abdominal pain completely disappeared was 12.5 +/- 1.7 in group A and 5.6 +/- 0.7 in group B (p<0.001). CONCLUSIONS: The results of this study show that low-dose, continuous IP IgG administration in the treatment of PD-related peritonitis is safe and effective in shortening the treatment time.

Anti-Bacterial Agents↗