Browsing by Author "Uslu R."

Now showing 1 - 20 of 42
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    Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine/threonine protein phosphatase inhibitors
    (1999) Uzunoglu S.; Uslu R.; Tobu M.; Saydam G.; Terzioglu E.; Buyukkececi F.; Omay S.B.
    To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Cal-A on the proliferation/differentiation of HL60 and K562 cells. Okadaic acid and Cal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells.
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    Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells
    (2000) Aydin H.H.; Selvi N.; Saydam G.; Tobu M.; Uzunoglu S.; Uslu R.; Buyukkececi F.; Omay S.B.
    Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL 60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2 A upregulation.
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    Treatment of Metastatic Breast Cancer with Capecitabine: Efficacy and Toxicity; [Metastatik Meme Kanserinin Tedavisinde Capecitabine: Etkinlik ve Toksisite]
    (2003) Sezgin V.C.; Şanli U.A.; Karabulut B.; Uslu R.; Müezzinoǧlu G.G.; Göker E.; Özdemir N.
    Capecitabine is an oral fluoropyrimidine that mimics continuous infusion 5-fluorouracil. As an oral agent, capecitabine is more convenient for patients and medical oncologists, and avoids the complications associated with venous access. Clinical trials have demonstrated the efficacy and tolerability of capecitabine in anthracycline and taxane pretreated metastatic breast cancer. In this study, we evaluated efficacy and tolerability of capecitabine in anthracycline and taxane pretreated metastatic breast cancer retrospectively. A total of 42 patients received oral capecitabine 2000 mg/m2/daily, on days 1-14 of each 3-week treatment cycle. Complete response not achieved. The partial and stable response rate were %19, %45,2 respectively. Median progression free survival time was 5 months. Additionally, cerbB2 subgroup analysis was performed. Progression free survival was longer in cerbB2 negative group than cerbB2 positive group. Difference between two groups was statistically significant. Oral capecitabine monotherapy demonstrated an acceptable safety profile. There was a low incidence of grade 3-4 adverse event. Capecitabine therapy, has antitumor activity and an acceptable safety profile in this setting.
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    Necrotising myofasiitis after chemotherapy: A case report; [Kemoterapi sonrasinda gelişen nekrotizan miyofasiitis: Olgu sunumu]
    (2004) Karabulut B.; Kirçelli F.; Sezgin V.C.; Müezzinoǧlu G.G.; Şanli U.A.; Uslu R.; Gökmen E.; Göker E.
    Nekrotising myofasciitis (NMF) is a rare infection that involves subcutaneus tissues, especially fascia and the muscular tissues. It can happen on the basis of immunosupression, tumour, surgery and injection which impair tissue integrity in cancer patients. A 37 year old male, diagnosed as nasopharyngeal carcinoma was accepted to the emergency servise 15 days after chemotherapy with pain in his gluteal region, that later turned to a necrotising lesion involving proximal left lower limb, left lower part of the abdomen and distal right lower limb. No etiological factor was found although all microbiological, pathological and rheumatological tests were done. NMF was taken under control with broad spectrum antibiotics and prompt surgical exploration and removal.
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    Potential predictive factors for response to weekly paclitaxel treatment in patients with metastatic breast cancer
    (E.S.I.F.T. srl, 2005) Sezgin C.; Karabulut B.; Uslu R.; Sanli U.A.; Goksel G.; Zekioglu O.; Ozdemir N.; Goker E.
    The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS. © E.S.I.F.T. srl - Firenze.
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    The efficacy and tolerability of intermediate high dose interferon alpha 2B treatment as an adjuvant therapy of high risk malignant melanoma; [Yüksek riskli malign melanomun adjuvan tedavisinde orta yüksek doz i̇nterferon alfa-2B tedavisinin etkinliǧi ve tolerabilitesi]
    (2005) Karabulut B.; Sezgin V.C.; Göksel G.; Şanli U.A.; Uslu R.; Göker E.
    There are still ongoing clinical trials and debates about adjuvant treatment of malignant melanoma. Between 1995 and 2004, fourty-nine patients with high risk operated non-metastatic malignant melanoma who had been treated with intermediate dose of interferon alpha were enrolled to the study. Twenty-three patients had regional lymph node metastasis at the time of diagnosis. Patients were treated with interferon alpha 2b (10 million units/day, five times a week for four weeks) as an induction therapy, followed by interferon alpha 2b (10 million units/day interferon three times a week for eleven months) as a maintanence therapy. The median follow-up time was 35 months (range 2-101 months). In this period, 7(14%) of patients had local recurrence, 12 (24%) of patients had regional lymph node metastasis and 20 (41%) of patients had distant metastasis. The 5-years overall survival, disease free survival and distant metastasis free survival rate of patients were 68%, 32% and 54% respectively. Therapy was well tolerated, no grade 4 toxicity related to therapy was observed. Comparing to natural history of malignant melanoma, these results are found to be encouraged.
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    Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors
    (2005) Sezgin C.; Karabulut B.; Uslu R.; Sanli U.A.; Goksel G.; Yuzer Y.; Goker E.
    Objective. Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. Material and methods. Sixty-seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. Results. The overall response rate was 5%. Thirty-one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression-free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status (PS) =2, and in patients with primary tumour location in the body or tail of the pancreas (p <0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PS =2 had worse results than the patients with PS =0-1 (p <0.05). Conclusions. Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine. © 2005 Taylor & Francis.
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    Serum Her-2/neu and survivin levels and their relationship to histological parameters in early-stage breast cancer
    (Cambridge Medical Publications, 2007) Goksel G.; Taneli F.; Uslu R.; Ulman C.; Dinc G.; Coskun T.; Kandiloglu A.R.
    This study was conducted to investigate the serum levels of her-2/neu and survivin in patients with early-stage breast cancer and their relationship with known histological parameters. Forty-one patients with early-stage breast cancer were investigated. Serum samples were collected from patients on their first admission before adjuvant chemotherapy, and from healthy controls. Serum her-2/neu and survivin levels were determined using an enzyme-linked immunosorbent assay. There was no difference in the levels of serum her-2/neu and survivin between the breast cancer patients and the control group. Serum her-2/neu concentration showed moderate correlations with disease stage and the Ki-67 level, and the serum survivin level showed a moderate correlation with progesterone receptor concentration. Serum levels of her-2/neu and survivin were not significantly related to age and histological parameters in patients with early-stage breast cancer. However, much research continues on the prognostic value of serum her-2/neu and survivin levels, and important new knowledge may ultimately emerge. Copyright © 2007 Cambridge Medical Publications.
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    A survey of functional living and social support in patients with cancer; [Kanserli bireylerin fonksiyonel durumlari ve algiladiklari sosyal desteǧin incelenmesi]
    (2008) Dedeli Ö.; Fadiloǧlu Ç.; Uslu R.
    Objectives: The aim of the study was to investigate functional living and social support in patients with cancer. Methods: The research was carried out on 105 patients diagnosed with cancer in the Daily Chemotherapy Units and Cancer Polyclinic of Tülay Aktaş Oncology Hospital during July and August 2007. The forms containing patients' demographic information were prepared by the researcher and Functional Living Index-Cancer and Cancer Patient Social Support Scale were used as the data tools. Data were collected during personal interviews with patients, and were evaluated on computer using SPSS 13.0 packet program. Mean, percentage, Pearson correlation, chi-square, independent sample t test, and Kruskal-Wallis test were used in the statistical analysis. Results: The mean age of patients was 46.3±12.8, 59.0% of which were women. The average Functional Living Index-Cancer score was poor (92.3±7.2), but the average Cancer Patient Social Support Scale score was good (142.4±14.2). Only the general well-being subscale of the Functional Living Index-Cancer was associated with each subscale of the Cancer Patient Social Support Scale, and the statistical correlation was significant. Conclusion: Although cancer patients had impaired functional status, their social support was good. We suggest social support is as beneficial as care for cancer patients' general well-being.
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    Profiling of angiogenic cytokines produced by hormone- And drug-refractory prostate cancer cell lines, PC-3 and DU-145 before and after treatment with gossypol
    (2008) Karaca B.; Kucukzeybek Y.; Gorumlu G.; Erten C.; Gul M.K.; Cengiz E.; Atmaca H.; Uzunoglu S.; Sanli U.A.; Karabulut B.; Uslu R.
    In this study, we aimed to investigate the angiogenic cytokine profiles of hormone- and drug- refractory prostate carcinoma cell lines, PC-3 and DU-145. We also studied the effect of gossypol, a natural polyphenolic cotton-seed extract, on the angiogenic cytokine profile of these cell lines. XTT cell proliferation assay was used for the assessment of cytotoxicity. For apoptosis, both histone-DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used. Angiogenic cytokine profiles of supernatants from both cell lines, before and after treatment with gossypol, were investigated using the human angiogenesis antibody array I®. It was shown that the two different hormone- and drug-resistant prostate cancer cell lines, PC-3 and DU-145, constitutively express some important angiogenic cytokines, which are known to regulate tumorigenic- ity and angiogenesis in hormone-refractory prostate cancer. However, PC-3 and DU-145 cells have distinct angiogenic cytokine profiles. In addition, these two cells lines respond differently to gossypol treatment in terms of cytotoxicity and angiogenic cytokine secretion. After treatment with 10 μM of gossypol, there was a 1.5-fold decrease in angiogenin and IL-8 levels and a 1.7- and 1.8-fold decrease in ENA-78 and GRO-α levels respectively, in DU-145 cells. For PC-3 cells, there were 1.6- and 1.8-fold decreases in IL-8 and VEGF levels, respectively. We conclude that PC-3 and DU-145 cells secrete significant amounts of different angiogenic cytokines that may explain their aggressive nature and metastatic potential. Gossypol treatment affects angiogenic cyto- kine secretion from these two cell lines in a different manner. By expanding our knowledge of the heterogeneous biological behavior of these two cell lines, novel treatment approaches can be developed for the treatment of prostate cancer.
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    Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line, DU-145
    (2008) Kucukzeybek Y.; Gul M.K.; Cengiz E.; Erten C.; Karaca B.; Gorumlu G.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.
    Background. The management of hormone-refractory prostate cancer (HRPC) still remains as an important challenge of daily oncology practice. Docetaxel has proved to be a first line treatment choice. All-trans retinoic acid (ATRA) could potently inhibit the growth of prostate cancer cells in vitro and its combination with various anticancer agents results in increased cytotoxicity. Based on these data, our aim was to examine the synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and ATRA, in hormone- and drug refractory human DU-145 prostate cancer cells. Furthermore, we have searched for the underlying mechanisms of apoptosis by demonstrating apoptosis-related genes. Methods. XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. For detecting the mechanism of apoptosis induced by docetaxel-ATRA combination, OligoGeArray® which consists of 112 apoptosis related genes was used. Results. Our results revealed that docetaxel and ATRA were synergistically cytotoxic and apoptotic in DU-145 cells, in a dose- and time dependent manner. It was also shown by our studies that apoptosis was induced in DU-145 prostate carcinoma cells with significant cytotoxicity, no matter which agent applied first. We have found out that docetaxel-ATRA combination significantly downregulates survivin (BIRC5), myeloid cell leukemia-1 (MCL-1) and lymphotoxin β-receptor (LTβR) genes, which all three have pivotal roles in regulation of apoptosis and cell cycle progression. Conclusion. In conclusion, we strongly suggest that docetaxel and ATRA combination is a good candidate for this challenging era of daily oncologic practice. Also, the combination of docetaxel and ATRA might allow a reduction in docetaxel doses and by this way may diminish docetaxel adverse effects while maintaining the therapeutic effect in patients with HRPC. © 2008 Kucukzeybek et al; licensee BioMed Central Ltd.
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    Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide
    (2009) Erten C.; Karaca B.; Kucukzeybek Y.; Gorumlu G.; Cengiz E.; Gul M.K.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.
    OBJECTIVE To evaluate the effects of combined treatment with docetaxel and octreotide, a somatostatin analogue, on human hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145, and on some growth factors related to tumour growth and angiogenesis in prostate cancer. MATERIALS AND METHODS A cell proliferation assay was used to assess the cytotoxicity of the drugs. To verify apoptosis, both DNA fragmentation (by enzyme-linked immunosorbent assay) and caspase 3/7 activity were measured. We also investigated the effect of combined docetaxel and octreotide on growth factors secreted from prostate cancer cells using a human growth factor antibody array. RESULTS The combination of docetaxel and octreotide resulted in significant synergistic cytotoxic activity and apoptosis, which was dose- and time-dependent. The combined treatment also resulted in significantly less secretion of stem cell factor and platelet-derived growth factor-AB in PC-3 cells, and transforming growth factor-β and basic fibroblast growth factor in DU-145 cells, than in untreated controls. CONCLUSION Octreotide, a somatostatin analogue, combined with docetaxel might provide a rationale treatment option for hormone-refractory prostate cancer cells, not only by direct inhibition of cell proliferation but also by inhibiting the secretion of growth factors. © 2009 BJU International.
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    Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells
    (2009) Atmaca H.; Gorumlu G.; Karaca B.; Degirmenci M.; Tunali D.; Cirak Y.; Purcu D.U.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.
    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 Profiler™ 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 μM gossypol and 5 μM zoledronic acid resulted in significant down-regulation (≥ 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.
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    Enhancement of taxane-induced cytotoxicity and apoptosis by gossypol in human breast cancer cell line MCF-7
    (2009) Karaca B.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.
    Purpose: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer, like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells. Materials and methods: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays. Results: We identified strong synergistic cytotoxic and apoptotic activity of gossypol with taxanes among all other studied cytotoxic drugs. Conclusion: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer. © 2009 Zerbinis Medical Publications.
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    The effect of racemic gossypol and AT-101 on angiogenic profile of OVCAR-3 cells: A preliminary molecular framework for gossypol enantiomers
    (2009) Varol U.; Karaca B.; Tunali D.; Degirmenci M.; Cirak Y.; Purcu D.U.; Uzunoglu S.; Sezgin C.; Karabulut B.; Sanli U.A.; Uslu R.
    Aim: To compare the effect of racemic gossypol with its (-)/(-) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3. Methods: Cell viability assay (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) was used to detect cytotoxicity of gossypol enantiomers. DNA fragmentation by an enzyme-linked immunosorbent (ELISA) assay was used to evaluate the rate of apoptosis. The mRNA expression levels of angiogenic molecules were investigated by Human Angiogenesis RT2 Profiler™ PCR Array (SuperArray, Frederick, MD). Results: Both racemic form and AT-101 resulted in a significant cytotoxicity and induced apoptosis. This effect was observed in a dose- and time dependent manner. However, AT-101 was much more potent. In addition, the treatment of 10 μM of racemic gossypol alone and 3 μM of AT-101 alone resulted in significant down-regulation (≥ 3 fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3, but altered gene profiles were different by the treatment of each enantiomer. Conclusion: The efficacy of two gossypol enantiomers in OVCAR-3 cells showed distinction. AT-101 was much more potent than racemic gossypol, not only by means of cell death and apoptosis, but also by modulation of angiogenic molecules released from OVCAR-3 cells. Further studies with endothelial cells should be done to verify the anti-angiogenic effect of gossypol enantiomers in cancer treatment.
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    Apoptosis-mediated cytotoxic effects of ibandronic acid on hormone-and drug-refractory prostate cancer cells and human breast cancer cells
    (SAGE Publications Ltd, 2010) Kucukzeybek Y.; Gorumlu G.; Cengiz E.; Karabulut B.; Sezgin C.; Atmaca H.; Sanli U.A.; Uzunoglu S.; Uslu R.
    Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immuno sorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 μM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings. © 2010 Field House Publishing LLP.
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    Radiosensitization of hormone-refractory prostate cancer cells by gossypol treatment
    (2010) Akagunduz O.; Karaca B.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Haydaroglu A.; Uslu R.
    Purpose: Many drugs have been tested to increase the sensitivity of prostate cancer cells to radiotherapy. Gossypol, a natural polyphenols compound extracted from the cotton plant, is one of the agents the efficacy of which has been investigated in the treatment of prostate cancer for this purpose. The main aim of this study was to investigate the best gossypol application with irradiation, when gossypol was applied either sequentially (24 h before and after irradiation) or concurrently in PC-3 hormone-refractory and radioresistant prostate cancer cells. Methods: The XTT viability assay was used to evaluate the cytotoxicity of different concentrations of gossypol in PC-3 cells. Irradiation was applied to PC-3 cells via 6 MV photon linear accelerator and delivered 24 h before, 24 h after radiation or at the same time with gossypol administration. Results: Gossypol caused radiosensitization of PC-3 cells that are known to be radioresistant, with high Bcl-2 levels. Among different applications of gossypol and irradiation (before, after and concurrent) in prostate cancer cells, the best results were observed by the application of gossypol 24 h before irradiation. Conclusion: Our study suggests that gossypol represents a promising novel anticancer treatment for radiosensitization of human hormone-refractory prostate cancer cells. © 2010 Zerbinis Medical Publications.
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    Comparison of XTT and Alamar blue assays in the assessment of the viability of various human cancer cell lines by AT-101 (-/- gossypol)
    (2010) Uzunoglu S.; Karaca B.; Atmaca H.; Kisim A.; Sezgin C.; Karabulut B.; Uslu R.
    This study compared the two different commercially available in vitro viability assays: XTT and Alamar blue (AB), to detect anti-proliferative effects of AT-101, a cotton plant extract, on six different human carcinoma cell lines including: prostate (PC-3 and DU-145), breast (MCF-7 and MDA-MB-231), and ovary (OVCAR-3 and MDAH 2774) in a time- and dose-dependent manner. Cells were exposed to AT-101 in the concentration range of 2.540 M for 24, 48, and 72h. The AB assay was slightly more sensitive than the XTT assay in the evaluation of AT-101 at 24h, suggesting that the AB assay might be used for detecting early changes in cell viability as compared to the XTT assay. Moreover, the AB assay showed less intra-assay variability as compared to the XTT. The non-toxic, non-radioactive AB metabolism assay allows rapid assessment of large numbers of samples, with simple equipment and at reduced cost for continuous monitoring of cancer cell viability, and, thus, should be accepted as a suitable alternative viability method. © 2010 Informa Healthcare USA, Inc.
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    Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: A paradigm of synergistic molecular targeting treatment for ovarian cancer
    (2010) Karabulut B.; Karaca B.; Varol U.; Muslu U.; Cakar B.; Atmaca H.; Ksm A.; Uzunoglu S.; Uslu R.
    Background. Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA) induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods. XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR), myeloid cell leukemia-1 (MCL-1), tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), TNFRSF1A-associated death domain protein (TRADD). Results. We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF), TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions. These are the preliminary molecular results of a novel combination treatment of ATRA and zoledronic acid, with fewer side effects as compared to conventional cytotoxic agents. With additional experimental analysis, it may serve as a good option for the treatment of refractory and elderly ovarian cancer patients, for whom there exists very limited choice of treatment. © 2010 Karabulut et al; licensee BioMed Central Ltd.
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    Overcoming drug resistance in hormone-and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination
    (2010) Cengiz E.; Karaca B.; Kucukzeybek Y.; Gorumlu G.; Gul M.K.; Erten C.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.
    Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose-and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated C3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers. © Springer Science+Business Media B.V. 2009.