Publications by authors named "Muge Akmansu"

38 Publications

Submandibular gland cancers: prognostic factors and survival analysis.

Eur Arch Otorhinolaryngol 2020 Aug 24;277(8):2307-2313. Epub 2020 Mar 24.

Department of Otorhinolaryngology and Head & Neck Surgery, Gazi University School of Medicine, Beşevler, 06500, Ankara, Turkey.

Purpose: The aim of this study is to evaluate prognosis and prognostic factors affecting oncological outcome.

Methods: Records of the subjects managed for a submandibular gland cancer (SGC) between January 1997 and June 2014 were retrospectively reviewed. Survival outcomes were analyzed. All subjects had a minimum follow up of 5 years or until death.

Results: Of 24 subjects (13 male, 11 female), 16 (64.6%) were adenoid cystic carcinoma (ACC). Eight patients had clinically positive neck nodes and 2 of the 16 clinically negative necks were also positive histologically. None of the subjects had distant metastases at presentation. The Kaplan-Meier 5-year estimated locoregional control (LRC), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) were 62.5%, 83.3%, 58.3% and 66.7%, respectively. American Joint Committee on Cancer (AJCC) overall stage and extra glandular extension (EGE) proved to be significant predictors of LRC. Only smoking was found to be a significant factor related with lower DMFS and only EGE significantly lowered DFS. Positive nodal stage and positive surgical margin were proved to be significant predictors of OS.

Conclusion: Surgery alone is effective in subjects with early stage, noninvasive and low-grade cancers. Despite aggressive treatment, locoregional recurrence was common in subjects who were at advanced stage.
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http://dx.doi.org/10.1007/s00405-020-05924-wDOI Listing
August 2020

Results of Chordoma Patients Treated by Different Approaches in a Single Institution.

Turk Neurosurg 2020 ;30(3):366-370

Gazi University, School of Medicine, Department of Radiation Oncology, Ankara, Turkey.

Aim: To discuss the optimal and recent treatment options based on clinical review of 16 chordoma patients.

Material And Methods: Data of the patients diagnosed and treated between 1999 and 2017 in Gazi University School of Medicine has been collected through patients’ files and the electronic database of hospital records. Statistical analysis was applied to evaluate the correlation between the progression free survival and treatment modalities.

Results: Nine of the 16 patients were women (56.3%). Half of the patients had intracranially located tumors, whereas the other 50% of the sample had spinal (n=5) and sacral (n=3) chordomas. The median follow-up time was 51.7 months. Recurrence was observed in 50% of patients, while the median recurrence time equaled to 27.6 months. Multivariate analysis results showed that age, gender tumor size, intra or extracranial location of tumor, treatment modalities, subtotal or grosstotal resection of tumor, radiotherapy dose, and techniques were not associated with recurrence. On the other hand, 2 patients are still under chemoterapy (imatinib, bevacizumab) without evident of recurrent disease.

Conclusion: Despite the fact that surgery remains to be the cornerstone of treatment, total resection is not reasonable for all patients with chordomas. For this reason, adjuvant treatment for ensuring local control is highly important. If the residual tumor is of a small volume, SBRT may provide more advantages. Targeted treatment or chemotheapeutic agents may also be benificial for maintanence therapy. As the clinical awareness about chordomas is based on our series, aggressive multi-modality treatment options should be applied in the adjuvant therapy.
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http://dx.doi.org/10.5137/1019-5149.JTN.24406-19.4DOI Listing
October 2020

Failure of Concurrent Chemoradiotherapy for Organ Preservation in Laryngeal Cancer: Survival Outcomes and Recurrence Patterns.

Ear Nose Throat J 2019 Aug 15;98(7):E92-E96. Epub 2019 Apr 15.

4 Department of Otorhinolaryngology, Head & Neck Surgery, Lösev Ankara Hospital, Ankara, Turkey.

Although definitive chemoradiation (CRT) has been used for locally advanced laryngeal cancer for more than 2 decades, studies focusing on CRT failures in advanced laryngeal cancer are scarce. In this study, we aimed to determine the failure patterns and the survival outcomes in the patients who had recurrence after concurrent CRT for laryngeal cancer. Clinical records of the patients who had definitive concurrent CRT for laryngeal cancer between 2001 and 2014 at a tertiary referral center were reviewed. The end points of the study were 1-, 2-, and 3-year overall survival (OS) and disease-specific survival (DSS).In our results, there were 48 failures and the mean time period from the first diagnosis of disease to the diagnosis of recurrence was 18.0 months (range 2-72; standard deviation: 15.6). The most common recurrence pattern was local recurrence in 21 (47.9%) patients followed by regional recurrence in 11 (22.9%) patients. The 1 and 3 years OS rates were 41.7%, and 19.2% for the entire cohort, and 64.5%, and 29.7% for the patients who had not systemic recurrence at presentation of recurrence, respectively. The 1 and 3 years DSS rates were 43.5%, and 20.0% for the entire cohort, and 69.0%, and 31.8% for the patients who had not systemic recurrence at presentation of recurrence, respectively. All patients who had systemic recurrence initially (n = 13) died within 9 months (median = 4 months, range: 1-9 months). This study reveals that survival outcomes are unfavorable in the CRT failures and careful patient selection is critical to minimize failures. In the presence of systemic recurrence, disease course is aggressive.
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http://dx.doi.org/10.1177/0145561319839788DOI Listing
August 2019

Primary Signet Ring Cell Carcinoma of the Prostate: A Rare Case Report.

J Clin Med 2018 Aug 15;7(8). Epub 2018 Aug 15.

Department of Urology, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara 06030, Turkey.

Primary prostatic signet ring cell carcinoma is a rare form of cancer with a poor prognosis, which is generally treated with a traditional prostate adenocarcinoma therapy. This case report presents a 70-year-old diagnosed with primary prostatic signet ring cell carcinoma, treated with a combination of radiotherapy and hormone therapy and a 16 month survival without an evidence of the disease at follow up.
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http://dx.doi.org/10.3390/jcm7080218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112034PMC
August 2018

The evaluation of the feasibility of carotid sparing intensity modulated radiation therapy technique for comprehensive breast irradiation.

Phys Med 2017 Apr 22;36:60-65. Epub 2017 Mar 22.

Medical School of Gazi University, Department of Radiation Oncology, Ankara, Turkey.

Purpose: To investigate the feasibility of carotid sparing intensity modulated radiation therapy (CS-IMRT) to minimize the radiation dose to carotid arteries for comprehensive irradiation of breast cancer patients who have risk factors for atherosclerosis. The dose distribution of CS-IMRT technique and the conventional irradiation technique were also compared.

Patients And Methods: Ten patients who were previously treated with comprehensive three-dimensional conformal radiation therapy (3DCRT) were selected. DICOM data were used to contour the carotid artery and to create the virtual CS-IMRT plans for each patient. 3DCRT and CS-IMRT plans were compared in terms of conformity index, homogeneity index, and the doses to organ at risk and carotid arteries.

Results: The homogeneity and conformity indices were better with CS-IMRT plans compared to 3DCRT plan. The homogeneity index was 1.13 vs 1.11 (p=0.007) for 3DCRT and CS-IMRT and the conformity index was 0.96 vs 0.97 (p=0.006) for 3DCRT and CS-IMRT. The radiation dose to the carotid arteries were reduced by applying CS-IMRT without compromising the target volume coverage. When the carotid artery was considered as organ at risk for CS-IMRT planning, the median of V50 was decreased to 0% from 12.5% compared to 3DCRT plans (p=0.017). The median of the maximum dose to the carotid artery was decreased under 50Gy with CS-IMRT.

Conclusions: CS-IMRT can significantly reduce the unnecessary radiation dose to the carotid arteries compared with conventional 3DCRT technique while maintaining target volume coverage. CS-IMRT technique can be considered for breast cancer patient with high risk of atherosclerosis.
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http://dx.doi.org/10.1016/j.ejmp.2017.01.008DOI Listing
April 2017

Comparison of three different concurrent chemoradiation regimens for treatment of laryngeal cancer.

Eur Arch Otorhinolaryngol 2016 Sep 18;273(9):2795-803. Epub 2015 Dec 18.

Department of Otorhinolaryngology and Head and Neck Surgery, Gazi University School of Medicine, Beşevler, 06500, Ankara, Turkey.

During last decades, laryngeal organ preservation strategies have emerged. The data about the oncological outcomes mainly come from multi-institutional prospective studies. In this study, we aimed to determine the oncological outcomes of different organ preservation regimens applied in routine practice. Patients who had definitive concurrent chemoradiation (CRT) for treatment of laryngeal cancer between January 2001 and June 2013 were retrospectively reviewed. There were 139 subjects who met the inclusion criteria. Three groups were defined: group A (n = 59) consisted of subjects who had concurrent cisplatin and radiotherapy (RT), group B (n = 47) consisted of subjects who had cisplatin/docetaxel-based concurrent CRT, and group C (n = 33) had induction chemotherapy before concurrent cisplatin and RT. The Kaplan-Meier estimated 5-year overall survival, disease-specific survival, disease-free survival, and local recurrence-free survival (LRFS) rates for the whole study group were 66.5, 69.2, 69.6, and 88.9 %, respectively. None of these survival rates were statistically different when the treatment arms were compared. The 3- and 5-year LRFS rates were significantly lower in subjects with a T4a tumor (p = 0.030). According to our results, the oncological outcomes of three different platinum-based concurrent chemotherapy schemes were similar and high local control rates could be achieved with the use of these protocols. Neoadjuvant chemotherapy before concurrent CRT was not superior to conventional concurrent treatment.
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http://dx.doi.org/10.1007/s00405-015-3854-8DOI Listing
September 2016

Oral glutamine supplementation reduces radiotherapy- induced esophagitis in lung cancer patients.

Asian Pac J Cancer Prev 2015 ;16(1):53-8

Department of Radiation Oncology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey E-mail :

Background: The purpose of this study was to assess the the efficacy of oral glutamine (GLN) in prevention of acute radiation-induced esophagitis in patients with lung cancer and determine the predictive role of clinical and dosimetric parameters.

Materials And Methods: Thirty-two patients diagnosed with lung cancer were studied prospectively. Sixteen patients (50%) received prophylactic powdered GLN orally in doses of 10g/8h. Patients were treated 2 Gy per fraction daily, 5 days a week. We evaluated the grading of esophagitis daily at the end of each fraction of each treatment day until a cumulative dose of 50 Gy was reached. The primary end point was radiation-induced esophagitis.

Results: All patients tolerated GLN well. Toxicity grade, weight loss, serum cytokine levels and esophageal transit times exhibited statistically significant improvement in the GLN receiving group. GLN suppressed the inflammation related to the disease and treatment and reduced toxicity with statistical significance.

Conclusions: This study suggests a benefical role of oral GLN use in prevention and/or delay of radiation-induced esophagitis, in terms of esophageal transit time and serum immunological parameters, as well as weight loss.
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http://dx.doi.org/10.7314/apjcp.2015.16.1.53DOI Listing
October 2015

HPV-associated p16 INK4A expression and response to therapy and survival in selected head and neck cancers.

Asian Pac J Cancer Prev 2015 ;16(1):253-8

Department of Radiation Oncology, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey E-mail :

Background: Development of squamous cell cancer of head and neck (SCCHN) is associated with human papillomavirus (HPV) infection, which in turn is closely related with expression of p16 INK4A. Loss of p16 INK4A expression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated p16 INK4A as a prognostic marker of treatment response and survival in our SCCHN patients with laryngeal, hypopharyngeal or nasopharyngeal cancers.

Materials And Methods: 131 patients diagnosed with SCCHN between January 2,2006 and July 17, 2010 were examined for p16 INK4A. The median age was 60 years (15-82 years). Fifty one patients were stage I-II and 80 were stage III-IV. Immunohistochemical expression of p16 INK4A was analyzed in pretreatment paraffin-embedded tumor blocks. The influence of p16 INK4A status on disease-free survival, and overall survival after treatment was evaluated.

Results: P16 INK4A positivity was found in 58 patients (44%). Tumor-positivity for p16INK4A was correlated with improved disease free survival (70.1 months vs 59 months) and improved overall survival (2, 3 and 5-year values; 77% vs 72%, 70% vs 63% and, 63% vs 55%; respectively). On multivariate analysis, stage was determined as independent prognostic factor for disease-free survival.

Conclusions: Stage was the major prognostic factor on treatment response and survival in our patients. P16 INK4A status predicts better outcome in laryngeal, hypopharyngeal or nasopharyngeal cancer cases treated with surgery plus adjuvant radiochemotherapy as well as with definitive radiation therapy and/or chemotherapy.
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http://dx.doi.org/10.7314/apjcp.2015.16.1.253DOI Listing
October 2015

Prognostic significance of expression of CD133 and Ki-67 in gastric cancer.

Asian Pac J Cancer Prev 2014 ;15(19):8215-9

Department of Radiation Oncology, Konya Training and Research Hospital, Konya, Turkey E-mail :

CD133 is one of the most important stem cell markers in solid cancers and Ki-67 is a marker that reflects cell proliferation. The relationships between the expression of CD133 and Ki-67 and prognosis in gastric carcinoma are unknown and need exploring. We examined 50 gastric cancer patients retrospectively in the Radiation Oncology Department of the Faculty of Medicine, Gazi University. CD133 and Ki-67 expression was examined using immunohistochemical staining. The survival rate in patients with CD133 positive expression was significantly worse than that in the patients with negative expression (p=0.04). Expression of CD133 had a positive correlation with that of Ki-67 (r=0.350; p=0.014). Multivariate analysis revealed that the expression of CD133 was an independent prognostic factor in gastric cancer (p=0.02). Conclusion, expression of CD133 may be a useful prognostic marker in gastric cancer.
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http://dx.doi.org/10.7314/apjcp.2014.15.19.8215DOI Listing
June 2015

Role of vascular endothelial growth factor in clinically localized prostate cancer treated with radiation therapy.

Balkan Med J 2014 Mar 1;31(1):43-9. Epub 2014 Mar 1.

Department of Radiation Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.

Background: Anti-vascular endothelial growth factor (Anti-VEGF) agents are a promising approach to increase the efficacy of treatment for treatment-resistant prostate cancer.

Aims: To correlate vascular endothelial growth factor (VEGF) expression and outcome following radiation therapy in the treatment of clinically localized prostate cancer.

Study Design: Retrospective observational study.

Methods: Forty-one patients and clinically localized disease that were treated with radiation therapy were analyzed. For VEGF expression, immunoreactivity scores (IRS) were calculated using percent scores and intensity scores. Twenty-four patients were classified as having low (0 to 4 IRS) and 17 patients were classified as having high (5 to 8 IRS) VEGF expression.

Results: The median age was 71 years, median follow-up was 5.4 years and median radiation therapy dose was 70 Gy. VEGF expression was calculated as low in 24 patients and high in 17 patients. Higher VEGF expression was observed in 6/26 patients with a low Gleason score versus 11/15 patients with a high Gleason score (p=0.02). Biochemical failure (BF) was observed in 2/24 patients with low VEGF expression versus 7/17 patients with high VEGF expression (p=0.01). In univariate analysis, having a higher Gleason score (p<0.01), being in the high risk group (p=0.03) and having higher VEGF expression (p=0.01) predicted BF after definitive radiation therapy. The biochemical failure-free survival rate at 5 years tended to be different (91% vs. 53%) when patients were grouped according to VEGF expression (p=0.06).

Conclusion: In attempt to define patients with clinically localized disease that are not sensitive to standard treatment modalities, cellular and/or molecular biological markers may be required.
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http://dx.doi.org/10.5152/balkanmedj.2014.13055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116003PMC
March 2014

Practice patterns for oropharyngeal cancer in radiation oncology centers of Turkey.

Tumori 2014 May-Jun;100(3):284-8

Aims And Background: The aim of the study was to review the current clinical practices of radiation oncologists involved in the treatment of oropharyngeal cancer.

Methods And Study Design: The daily practices of radiation oncology centers for patients diagnosed with oropharyngeal cancer in 2010 were evaluated by a two-part questionnaire that separately assessed the information of the participating center and the charts of the treated patients.

Results: A total of 22 centers participated in the study, and 105 oropharyngeal cancer patients reported for our review. The use of positron emission tomography was a common practice in staging and radiotherapy planning. Multidisciplinary head and neck cancer clinics were available in 14 (64%) centers and were absent in 8 centers. Thirty-six of the 105 patients were not evaluated by a multidisciplinary clinic before the initiation of therapy, and adjuvant radiotherapy administration was found to be higher in this group. Percutaneous endoscopic gastrostomy tube placement was not a routine practice in any of the centers. Seventy-five patients received chemotherapy - 46 concurrently with radiotherapy and 29 as induction chemotherapy. Two centers administered conventional radiotherapy alone, 20 centers conformal radiotherapy, and 7 centers were able to provide intensity-modulated radiotherapy.

Conclusions: Across all the centers there were small differences in the pretreatment evaluation of patients with oropharyngeal cancer. The greatest difference was in the technical delivery of radiation, with most of the centers using conformal radiotherapy despite the increasing availability of intensity-modulated radiotherapy. The use of chemotherapy has more readily adopted the current international standards in the treatment of oropharyngeal cancer.
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http://dx.doi.org/10.1700/1578.17204DOI Listing
November 2014

Effects of β-glucan on colon anastomotic healing in rats given preoperative irradiation.

J Invest Surg 2014 Jun 19;27(3):155-62. Epub 2013 Dec 19.

1Department of General Surgery, Faculty of Medicine, Harran University , Sanlıurfa , Turkey.

Background: Radiation therapy is an essential therapeutic modality in the management of a wide variety of tumors. We aimed to investigate the short-term effects of pelvic irradiation on the healing of colon anastomoses and to determine the potential protective effects of β-glucan in this situation.

Material And Methods: Sixty Wistar albino rats were randomized into three experimental groups: a control group (n = 20), an irradiation (IR) group (n = 20), and an irradiation+β-glucan (IR+β-glucan) group (n = 20). Only segmental colonic resection and anastomosis were performed on the control group. The IR group underwent the same surgical procedure as the control group 5 days after pelvic irradiation. In the IR+β-glucan group, the same procedure was applied as in the IR group after β-glucan administration. The groups were subdivided into subgroups according to the date of euthanasia (third [n = 10] or seventh [n = 10] postoperative [PO] day), and anastomotic colonic segments were resected to evaluate bursting pressures and biochemical and histopathological parameters.

Results: Bursting pressure values were significantly lower in the IR group (p < .001). Malondialdehyde (MDA) levels were significantly higher in the IR group, whereas β-glucan significantly decreased MDA levels on the third PO day (p < .001). Granulation tissue formation scores were significantly lower in the IR+β-glucan group compared with the control group and the IR group (p < .001).

Conclusions: The results of this study indicate that irradiation has negative effects on the early healing of colon anastomoses. The administration of β-glucan ameliorates these unfavorable effects by altering bursting pressures and biochemical parameters.
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http://dx.doi.org/10.3109/08941939.2013.865820DOI Listing
June 2014

The effects of Pycnogenol(®) on colon anastomotic healing in rats given preoperative irradiation.

Int J Surg 2013 18;11(9):983-8. Epub 2013 Jun 18.

Department of Gastroenterological Surgery, Turkiye Yuksek Ihtisas Teaching and Research Hospital, Ankara, Turkey. Electronic address:

Pycnogenol(®) has excellent radical scavenging properties and enhances the production of antioxidative enzymes which contributes to the anti-inflammatory effect of the extract. Irradiation delivered to the abdominal region, typically results in severe damage to the intestinal mucosa. The effects of ionizing radiation are mediated by the formation of free radicals through radiolysis. Irradiation has local effects on tissues. These local effects of irradiation on the bowel are believed to involve a two-stage process which includes both short and long term components. In our study we aimed to investigate the short term effects of Pycnogenol(®) on the healing of colon anastomoses in irradiated bowel. Sixty male Wistar-Albino rats were used in this study. There were three groups: Group I, control group (n = 20); group II which received preoperative irradiation (n = 20); group III which received per oral Pycnogenol(®) before irradiation (n = 20). Only segmeter colonic resection and anastomosis was performed to the control group (Group I). The other groups (Group II, III) underwent surgery on the 5th day after pelvic irradiation. On postoperative days 3 and 7, half of the rats in each group were sacrificed and then relaparotomy was performed. There was no statistical difference between groups with respect to biochemical parameters. Bursting pressure was significantly higher in the Control and Group III compared with the Group II. In conclusion, the present study showed that preoperative irradiation effect negatively on colonic anastomoses in rats by means of mechanical parameters and administration of Pycnogenol(®) preoperatively ameliorates this unfavorable effect.
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http://dx.doi.org/10.1016/j.ijsu.2013.06.004DOI Listing
July 2014

18F-FDG PET/CT findings of radiotherapy-related myocardial changes in patients with thoracic malignancies.

Nucl Med Commun 2013 Sep;34(9):855-9

Department of Nuclear Medicine, Izmir University, Izmir, Turkey.

Objective: The purpose of this study was to investigate myocardial findings of F-fluorodeoxyglucose PET/computed tomography (F-FDG PET/CT) after thoracic radiotherapy.

Methods: F-Fluorodeoxyglucose PET/CT examination was performed in 38 patients at least 4 months after radiotherapy. Patients with known cardiac diseases, high cardiovascular risk factors, or diabetes mellitus were excluded.

Results: On visual analysis, 28 patients were seen to have regional myocardial F-FDG uptake (74%), five patients were seen to have diffuse myocardial F-FDG uptake (13%), and five patients were seen to have no significant myocardial F-FDG uptake (13%). Regions of interest were drawn on irradiated and nonirradiated segments of the myocardium. The standardized uptake value measurements of the 28 patients with regional myocardial F-FDG uptake revealed significantly higher values in the irradiated segments in comparison with nonirradiated segments (P<0.001).

Conclusion: Annular or focal increased F-FDG uptake in irradiated myocardial segments may be observed after thoracic radiotherapy. These myocardial uptake regions were not consistent with the vascular territory of coronary arteries, and the patients had no prior myocardial infarction or coronary artery disease. The patients with a history of thoracic radiotherapy, who showed increased F-FDG uptake on PET/CT, especially in the basal myocardium, should be followed up cautiously for the early diagnosis of cardiac events.
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http://dx.doi.org/10.1097/MNM.0b013e328362f824DOI Listing
September 2013

Lymph node ratio assessment of brain metastasis in early breast cancer cases.

Asian Pac J Cancer Prev 2013 ;14(3):1665-7

Department of Radiation Oncology , Rize Recep Tayyip Erdogan University Hospital, Rize, Turkey.

Background: Ten to 30% of early breast cancer (EBC) patients develop brain metastasis (BM) during their follow-up. In this study, we aimed to evaluate importance of the lymph node ratio (LNR) in development of BM in EBC cases.

Materials And Methods: Ninety patients whom had axillary metastases in lymph nodes at their initial diagnosis and developed BM during 5-year follow-up were detected in 950 EBC patients. LNR values were calculated for all patients and after categorization into 4 molecular sub-types as luminal A, luminal B HER-2 (+), HER-2 overexpressing and basal- like. Comparison was with control group patients who had similar characteristics.

Results: In the comparison of all molecular sub-types of LNR, 54.9% and 28.4% values were found in patients with and without BM respectively (p<0.001). In the comparison of the LNR with control groups, a statistically significant differences were found with luminal A with BM (p=0.001), luminal B HER-2 (p=0.001), HER-2 overexpressing (p=0.027) and basal-like groups (p<0.001). In the evaluation of patients with BM, the highest ratio was found in the basal-like group (67.9%) and there was a statistically significant difference between this group and the others (p=0.048).

Conclusions: EBC patients developing BM within 5 years follow- up had significantly higher LNRs for all molecular sub-types, especially in the basal-like group. Larger scale studies are now needed for evaluating LNR prognostic importance for EBC regarding BM development.
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http://dx.doi.org/10.7314/apjcp.2013.14.3.1665DOI Listing
January 2014

Radiotherapy applications of patients with malignant mesothelioma: A single center experience.

Rep Pract Oncol Radiother 2012 9;18(2):82-6. Epub 2012 Aug 9.

Gazi University Medical Faculty, Department of Chest Disease, Ankara, Turkey.

Background: In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms.

Aim: The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma.

Materials And Methods: Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy.

Results: Prophylactic radiation was applied to 27 patients with 4-15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6-18 MV photon and/or 4-12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases.

Conclusion: Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes.
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http://dx.doi.org/10.1016/j.rpor.2012.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863306PMC
January 2014

Cetuximab concomitant with second-line radiation therapy in patients with locally advanced recurrent squamous cell head and neck cancer.

Case Rep Oncol 2010 Sep 17;3(3):480-8. Epub 2010 Dec 17.

Department of Radiation Oncology, Gazi University School of Medicine, Ankara, Turkey.

We presented 9 recurrent head and neck carcinoma patients. Priorly all of them had received radiochemotherapy. We used cetuximab and irradiation concomitantly. Overall survival analysis of the patients was performed using the Kaplan-Meier method on SPSS version 15.0. Based on this calculation, mean follow-up duration is 12.8 months. Mean survival time is 19.8 months and annual mean survival rate is 59.3%.
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http://dx.doi.org/10.1159/000323204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100271PMC
September 2010

Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide.

Clin Neurol Neurosurg 2010 Oct 2;112(8):662-7. Epub 2010 Jun 2.

Department of Medical Oncology, Mersin State Hospital, Mersin, Turkey.

Background: Temozolomide is the major drug in the treatment of malignant gliomas. Radiation induced necrosis can behave radiologically and clinically like a recurrent tumor. The major problem is the differentiation between recurrence and radiation injury especially in early phases of treatment. The aim of this study was to evaluate the patients receiving temozolomide showing early clinical or radiological progression and impact of early necrosis on follow-up.

Patients And Methods: We retrospectively evaluated medical records of 67 patients with malignant glioma receiving temozolomide. All patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide. In case of any radiological or clinical progression, MRI spectroscopy evaluation was used to confirm tumoral progression.

Results: Radiological or clinical progression was observed in 17 (25.4%) patients. Early radiation induced necrosis was diagnosed in 4 of 17 patients (23.5%) by surgery (n=3) and MRI spectroscopy (n=1). The observed incidence of pseudoprogression was 4 in 67 (6%) patients. Patients with diagnosis of early radiation injury had median progression-free survival of 7 months compared to 5 months in patients without radiation damage (p=0.004). However, there was no statistically significant difference in terms of overall survival between groups.

Conclusion: Temozolomide can cause early radiation induced injury which can mimic progressive tumor. Although the discrimination between two entities results in the accurate evaluation of response to therapy and benefits those patients, it did not affect overall survival. MRI spectroscopy is a valuable tool to define early radiation necrosis and should be further evaluated in larger prospective studies.
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http://dx.doi.org/10.1016/j.clineuro.2010.05.003DOI Listing
October 2010

The histopathologic evaluation of soft tissue changes in rabbit extremity after different dose-fractionation schemes of interstitial high dose rate (HDR) brachytherapy.

Rep Pract Oncol Radiother 2010 17;15(6):165-71. Epub 2010 Oct 17.

Gazi University Medical School, Department of Pathology, Turkey.

Background: The use of HDR in the treatment of soft tissue sarcoma had been on the rise. However, there was limited study to evaluate the effect of different fractionation schemes on soft tissue and the optimal HDR scheme.

Aims: We aimed to assess the histopathologic changes on soft tissue after different HDR brachytherapy doses.

Methods: The subjects were divided into three groups. Each group included 10 limbs. Group A had only an applicator without radiation, group B received a total of 24 Gy at 6 Gy per fraction, twice a day, and group C received a total of 13.5 Gy in a single fraction. The histopathologic findings were grouped into soft tissue pathology-1 (edema, inflammation, endothelial proliferation, necrosis) and soft tissue pathology-2 (atrophy, calcification, vascular hyalinization, fibrosis) (STP-1-2).

Results: The highest mean grade values of STP-1 and STP-2 were observed in group C (0.95 and 1.45) in comparison to group A (0.45 and 0.85) and group B (0.65 and 0.9). The difference in STP-1 was found significant only between groups A and C and the difference in STP-2 was found both between groups A and C and groups B and C.

Conclusion: In our experimental study it was shown that the fractionated interstitial HDR had both lower rate and severity of toxicity in comparison to a single high dose fraction. Before using a single fractionated regimen in the clinic, the increased morbidity related to the irreversible early toxicities or progressive late toxicities should be kept in mind.
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http://dx.doi.org/10.1016/j.rpor.2010.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863242PMC
December 2013

Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: a long-term analysis.

Tumori 2009 Mar-Apr;95(2):191-7

Kutahya Evliya Celebi Governement Hospital, Department of Radiation Oncology, Kutahya, Turkey.

Aims And Background: Glioblastoma is the most common primary brain tumor in adults. The standard treatment is surgery and radiotherapy. In this study, the results of radiotherapy plus concomitant and adjuvant temozolomide are reported. In addition, the efficiency of adjuvant temozolomide is evaluated.

Methods And Study Design: Forty-one patients were analyzed. All patients received radiotherapy (2 Gy daily fractionation dose, median 60 Gy total doses) and concomitant temozolomide (at a daily dose of 75 mg/m2/day, 7 days per week) after surgery. Thirty-one patients received an average of 6 cycles (range, 1-8 cycles) of adjuvant temozolomide after radiotherapy, every 28 days for 5 days at a dose of 200 mg/m2/day. The primary end point was overall survival.

Results: The median overall survival was 16.7 months. The overall survival significantly increased in the adjuvant temozolomide group compared to the group with no adjuvant therapy (18.9 vs 9.8 months). The difference in overall survival between adjuvant temozolomide cycles of < or = and > 3 was significant (8.7 vs 20 months). On multivariate analyses, the important prognostic factors were type of surgery and application of adjuvant temozolomide for at least 4 cycles. Grade III/IV toxicity was seen in 4% and 6.5% of patients during concomitant and adjuvant therapy, respectively.

Conclusions: The study confirmed the effectiveness of radiotherapy plus temozolomide in newly diagnosed glioblastoma. It was established that the application of adjuvant temozolomide for at least 4 cycles is required to obtain a benefit from adjuvant therapy. However, further studies are needed to confirm these data.
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July 2009

Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study.

Support Care Cancer 2010 Jun 31;18(6):691-8. Epub 2009 May 31.

Department of Radiation Oncology, Hacettepe University, Ankara 06100, Turkey.

Introduction: In this prospective study, the efficacy and safety of radiotherapy combined with zoledronic acid was evaluated.

Materials And Methods: Breast cancer patients with painful bone metastases were randomized to either high- or reduced-dose radiotherapy. All patients received zoledronic acid (4 mg) every 28 days from the beginning of radiotherapy. Analgesic and pain scores in addition to visual analog score (VAS) for treatment satisfaction and whole-body bone scintigraphy were evaluated.

Results And Conclusion: No significant differences could be found in analgesic or pain scores and bone scintigraphy results between the groups. Our results suggest that reduced-dose radiotherapy produces similar response rates and response durations when used concomitantly with zoledronic acid.
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http://dx.doi.org/10.1007/s00520-009-0663-xDOI Listing
June 2010

Primary cardiac angiosarcoma: a case report.

Tumori 2008 Nov-Dec;94(6):892-7

Kutahya Evliya Celebi Government Hospital, Department of Radiation Oncology, Kutahya, Turkey.

Primary tumors of the heart are rarely seen. Cardiac angiosarcomas are malignant tumors that almost always have a poor prognosis. We describe a 29-year-old man with primary cardiac angiosarcoma with multiple site metastases. The therapeutic approach includes surgery, chemotherapy and radiotherapy alone or in combination. New techniques of radiotherapy and combined chemotherapeutic agents may relieve symptoms and prolong a patient's life. We discuss the diagnosis and treatment of cardiac angiosarcoma in the light of a case report.
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April 2009

Concomitant chemoradiotherapy with cisplatin and docetaxel followed by surgery and consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer.

Med Oncol 2010 Mar 26;27(1):152-7. Epub 2009 Feb 26.

Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.

Aims: To evaluate preoperative concomitant chemoradiation using cisplatin plus docetaxel followed by consolidation chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC).

Patients And Methods: Medical records of patients with locally advanced unresectable NSCLC (stage IIIA and IIIB) treated with concomitant chemoradiotherapy using cisplatin + docetaxel combination followed by consolidation chemotherapy were retrospectively evaluated. All the patients were consecutively treated. Chemotherapy consisted of weekly cisplatin 20 mg/m(2) and docetaxel 20 mg/m(2) during radiotherapy. Radiotherapy dose was 58-66 Gy given in 2 Gy fractions, 5 days per week. The patients were subsequently referred to surgery if adequately downstaged. Consolidation chemotherapy using cisplatin and docetaxel both at doses 75 mg/m(2) every 3 weeks followed local therapy in all patients.

Results: A total of 54 patients were evaluated (49 males, 5 females with a median age of 58 years; 41 [75.9%] stage IIIB and 13 [24.1%] IIIA). Twelve patients (22.2%) achieved pathologic complete response and 20 (37%) partial response. Downstaging was possible in 32 patients (59.3%). Twenty-six patients (48.1%) were operated after concomitant chemoradiotherapy (pneumonectomy [n = 2], lobectomy [n = 12], and wedge resection [n = 12]). Toxicity was tolerable. Median progression-free survival and overall survival (OS) for the entire cohort were 14 and 22 months, respectively. In resected patients (n = 26), median PFS and OS have not been reached with a median follow-up duration of 24 months.

Conclusion: Preoperative concomitant chemoradiation using weekly cisplatin and docetaxel followed by surgery and consolidation chemotherapy is effective and well tolerated in patients with unresectable locally advanced NSCLC.
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http://dx.doi.org/10.1007/s12032-009-9186-zDOI Listing
March 2010

Temozolomide in newly diagnosed malignant gliomas: administered concomitantly with radiotherapy, and thereafter as consolidation treatment.

Onkologie 2008 Jun 27;31(6):309-13. Epub 2008 May 27.

Department of Medical Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.

Background: Surgical resection followed by radiotherapy used to be the standard treatment in malignant gliomas. Recently, temozolomide has become a cornerstone in the treatment of these patients. We evaluated retrospectively the efficacy and the toxicity of temozolomide which was administered concomitantly with radiotherapy, and thereafter as consolidation treatment.

Patients And Methods: Medical records of 64 patients with malignant glioma were reviewed. Postoperatively, temozolomide was given at a dose of 75 mg/m(2)/day concomitantly with cranial radiotherapy. After 4 weeks of rest, patients were treated with temozolomide 200 mg/m(2) on days 1-5 every 28 days for 6 cycles.

Results: 62 patients were evaluable for response and toxicity. Objective response rate was 38.7% including 7 (11.3%) complete responses, and 17 (27.4%) partial responses. Median progression-free survival, and overall survival have not yet been reached in the grade III astrocytoma group at a median follow-up of 19 months. In the glioblastoma multiforme group, median progression-free survival, and median overall survival were 10 and 19 months, respectively. 2-year survival rates were 80% and 19% for the grade III astrocytoma, and for the glioblastoma multiforme groups, respectively. Toxicity was mild to moderate with rare grade 4 toxicities.

Conclusion: Our data suggest that temozolomide is an active regimen for malignant gliomas. It was more effective in younger patients with better performance status.
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http://dx.doi.org/10.1159/000127252DOI Listing
June 2008

Gelatinase B expression as a prognostic factor in patients with stage II/III rectal carcinoma treated by postoperative adjuvant therapy.

Am J Clin Oncol 2008 Feb;31(1):55-63

Radiation Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.

Objective: The matrix-metalloproteinases (MMPs) are thought to be critically involved in tumor invasion and metastasis. This retrospective study was aimed both to examine the gelatinase expression status in patients with rectal cancer and to investigate their prognostic value on survival.

Methods: Sixty patients who underwent postoperative adjuvant chemoradiotherapy for Stage II and III rectal carcinoma were included. Expressions of MMP-2, MMP-9, and tissue inhibitors of MMP (TIMP-1 and TIMP-2) were analyzed by immunohistochemistry in paraffin-embedded primary rectal cancers and graded for the intensity and the percentage of cells stained. The relation between the expression of the markers studied and clinicopathologic features were evaluated for the primary study endpoint. The data were also analyzed using a multivariate Cox proportional hazards model for prognosis as a secondary endpoint.

Results: Positive MMP-9 expression was observed in 70% of the tumors. The ratio of tumors with positive MMP-9 expression was increased according to N stage (P = 0.005), AJCC stage (P = 0.005), and tumor differentiation (P = 0.017). Overall survival was reduced in poorly differentiated tumors and tumors with positive MMP-9 expression (P = 0.002). Disease-free survival was lower in patients with positive MMP-9 expression (P = 0.007). Multivariate analysis indicated that positive MMP-9 expression was an independent predictor of reduced overall survival (P = 0.0103) and reduced disease-free survival (P = 0.0360). The other markers studied were associated with neither any clinicopathologic feature nor any survival parameter.

Conclusion: MMP-9 expression was observed in the tumors of patients with Stage II and III rectal carcinoma in comparable values and was characterized by poor overall survival and disease-free survival.
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http://dx.doi.org/10.1097/COC.0b013e318068b4e2DOI Listing
February 2008

The results of three different treatment modalities in patients with locally advanced nasopharyngeal carcinoma.

Med Oncol 2008 15;25(3):269-73. Epub 2007 Dec 15.

Gazi University Medical School, Department of Medical Oncology, Gazi Hospital, Ankara 06500, Turkey.

The aim of the study was to evaluate the toxicity and efficacy of 62 patients with locally advanced nasopharyngeal carcinoma (NPC) (stage III, IVA, IVB) treated by three different modalities. Cisplatin was given weekly 35 mg/m(2)/day or every 3 weeks 100 mg/m(2)/day during radiotherapy (RT) in all patients. Patients were classified into following three groups: The patients in the group 1 (n=23) were treated only with concurrent chemoradiotherapy (CCRT). In the group 2 (n=15), before the CCRT, neoadjuvant chemotherapy, consisting of intravenous cisplatin and docetaxel on day 1, every 3 weeks treatment cycles was administered. In the group 3 (n=24), adjuvant chemotherapy, consisting of cisplatin on day 1 and 5-fluorouracil on day 1 to 5 every 3 weeks was used after CCRT. Three arms were treated with the same RT technique and dose. There was no difference for age, sex, and stage among the groups. Radiotherapy was administered in planned dose for all patients. A total of 82% patients completed planned chemotherapy concurrent with RT. The treatment related adverse effects were mild or moderate in intensity. There was no statistical difference between the groups regarding the treatment responses. Complete response rate of RT was 73.9%, 86.7%, and 87.5%, respectively. Median progression free survival (PFS) and overall survival (OS) were 13, 12, 9 months and 22, 20, 15 months for groups 1, 2, 3, respectively. No difference was observed in median OS and PFS among three groups. In our study, the efficacy and toxicity of neoadjuvant and/or adjuvant chemotherapy with CCRT and CCRT alone were found similar.
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http://dx.doi.org/10.1007/s12032-007-9029-8DOI Listing
December 2008

Metastatic gastrointestinal stromal tumor with long-term response after treatment with concomitant radiotherapy and imatinib mesylate.

Anticancer Drugs 2007 Sep;18(8):969-72

Department of Medical Oncology, Selcuk University Faculty of Medicine, Konya, Turkey.

Total surgical excision of the tumor is considered to be the only hope in treatment of malignant mesenchymal tumors. The roles of radiotherapy and/or chemotherapy have not yet been established. We report here a case of metastatic gastrointestinal stromal tumors with a dramatic long duration of response after treatment with concurrent radiotherapy and imatinib mesylate. The patient had a long-term complete response at the radiotherapy region with concomitant imatinib therapy although previous metastatic sides persisted with partial response.
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http://dx.doi.org/10.1097/CAD.0b013e3280e94982DOI Listing
September 2007

Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation.

Adv Ther 2007 May-Jun;24(3):648-61

Department of Surgery, Gazi University Faculty of Medicine, Anakara Turkey.

Intestinal mucosal damage and bacterial translocation are clinical problems that may be caused by the use of ionizing radiation. Glutamine (Gln) support reduces the mucosal barrier in several ways. This study was undertaken to investigate the effect of timing of Gln-enriched enteral nutrition (EN) on bacterial translocation and mucosal damage due to radiotherapy (RT). A rat model of whole body irradiation was designed in which a single dose of 485 cGy was given. A total of 50 rats were randomly assigned to the following 5 groups, each of which comprised 10 rats: (1) balanced rat chow given for 8 days without RT (group 1); (2) balanced rat chow given 4 days before and 4 days after RT (group 2); (3) Gln-enriched EN given 4 days before RT (group 3); (4) Gln;enriched EN given 4 days after RT (group 4); and (5) Gln-enriched EN given 4 days before and 4 days after RT (group 5). Mesenteric lymph node and ileum samples were removed for evaluation of bacterial translocation (BT) and histopathologic investigation, respectively. BT and intestinal mucosal injury scores in all rats that received RT were higher than in rats without RT. No difference was seen in parameters between groups 3 and 4 (P>.05, P>.016, respectively); BT and intestinal mucosal injury scores of group 5 were significantly lower than those of groups 3 and 4 (P<.05, P<.016, respectively). Meanwhile, the BT and mesenteric injury scores of group 5 were significantly lower than those of group 2 (P<.05, P<.016, respectively). As a result, intestinal injury due to RT was significantly decreased by Gln-enriched EN support given before and after whole body RT.
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http://dx.doi.org/10.1007/BF02848790DOI Listing
September 2007

Evaluation of nutritional status in cancer patients receiving radiotherapy: a prospective study.

Am J Clin Oncol 2006 Apr;29(2):183-8

Gazi University Faculty of Medicine, Department of Radiation Oncology, Ankara, Turkey.

Objectives: The purpose of the present study was to evaluate the nutritional status of cancer patients receiving radiotherapy (RT) and to assess the possible contributions of nutritional support to patients with malnutrition.

Methods: Prospectively, 207 patients referred to our outpatient radiotherapy department were included. The patients were classified according to tumor site (head/neck, breast, lung, stomach, or colorectal). Nutritional status at the onset, at the end of RT, and 3 and 6 months after irradiation was evaluated with the subjective global assessment (SGA). All of the patients were supported with additional portions of meal or standard enteral feeding formula during and after the irradiation period as long as they were in the moderately or severely malnourished groups, respectively.

Results: At the onset, malnutrition was present in 31% of all patients, and it increased to 43% at the end of RT. This difference predominated in head/neck cancer patients. Malnutrition ratios in head/neck cancer patients at the onset and after RT were 24% and 88%, respectively. By a 6-month follow-up, the ratio of patients with malnutrition decreased to 8%. Nutritional status of all groups was found to improve during the 6-month follow-up period, except for the breast cancer group, which included no patients with severe malnutrition at any time.

Conclusion: The results of the present study may be helpful in planning an appropriate nutritional support for cancer patients undergoing radiotherapy according to the irradiation site.
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http://dx.doi.org/10.1097/01.coc.0000198745.94757.eeDOI Listing
April 2006

The effect of vitamin A pretreatment on radiation induced alteration in neutrophil functions.

Mol Cell Biochem 2006 Jun 14;286(1-2):103-5. Epub 2006 Feb 14.

Department of Biochemistry, Faculty of Science and Art, Gazi University, Ankara, Turkey.

The aim of this investigation was to determine whether pre-administration of vitamin A will be effective in preventing the radiation-induced decline in MPO-H2O2 system and the end product of reactive nitrogen species (NOx) in guinea pig. Animals were subjected to 612 cG of radiation and polimorfonuclear leukocytes were isolated and then NOx and myeloperoxidase activity were measured. In irradiated animals, a marked decrease in NOx level and myeloperoxidase activity have been found compared to control (p = 0.001 and p < 0.000 respectively). The application of vitamin A significantly improved the radiation-induced decrease (for both p < 0.00). In conclusion pre-treatment of vitamin A is efficient to protect against radiation induced alteration in polimorfonuclear leukocyte.
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http://dx.doi.org/10.1007/s11010-005-9099-xDOI Listing
June 2006
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