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Item Haptoglobin Levels in Turkish Patients with Bladder Cancer and its Association with Clinicopathological Features(ASIAN PACIFIC ORGANIZATION CANCER PREVENTION) Piriniççi, N; Geçit, I; Gunes, M; Kemik, AS; Yüksel, MB; Kaba, M; Ceylan, K; Aslan, MAlthough alteration in the haptoglobin phenotype has been reported in patients with bladder cancer, serum haptoglobin levels have not been evaluated. We hypothesized that serum haptoglobin can be used as a biomarker. The aim of this study was to evaluate the expression of haptoglobin in bladder cancer and to determine the relationship with clinicopathological features. A total of 68 serum specimens obtained before surgery were used to investigate haptoglobin expression using the sandwich ELISA technique. Serum haptoglobin levels were higher in the patients with bladder cancer compared to healthy controls (p<0.0001). Additionally, the levels of haptoglobin protein increased with increasing tumor grades (p<0.001) and were significantly higher in patients with metastatic disease and the presence of lymphovascular involvement, lymph node metastases and increasing tumor burden (p<0.0001). This study suggests that elevated haptoglobin levels are associated with a higher stage, grade, and extent of distant metastasis and larger tumor size. Haptoglobin may therefore provide a useful diagnostic and treatment biomarker for patients with bladder cancer.Item Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells(WILEY) Karabulut, B; Erten, C; Gul, MK; Cengiz, E; Karaca, B; Kucukzeybek, Y; Gorumlu, G; Atmaca, H; Uzunoglu, S; Sanli, UA; Baran, Y; Uslu, RDocetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.Item Transfection of Leishmania tropica with Green Fluorescent Protein (gfp) Gene and Investigation of the In Vitro Drug Effect(ANKARA MICROBIOLOGY SOC) Ertabaklar, H; Çaliskan, SÖ; Kolli, B; Ertug, S; Özbilgin, A; Malatyali, E; Chang, KPCutaneous leishmaniasis (CL) is a parasitic disease transmitted by vector sand flies Phlebotomus and Lutzomyia. This disease is characterized by long time non-healing skin lesions, and caused by Leishmania species. CL is the most common infection in Eastern and Southeastern Anatolia in Turkey and L. tropica is known as the main agent of the disease. Number of cases is increasing in our country in time because of malnutrition, migration, travel, low socioeconomic level and ecological changes. For the treatment, the pentavalent antimonials are often used as intralesionally for many years, and it was reported that resistant cases have increased in recent years. New treatment methods and anti-Leishmanial activity of new agents have been investigated because of side effects, resistance development and toxic reactions of the present drugs. These studies are first carried out in vitro and afterwards with in vivo experimental animal models. Reporter gene technology has been used to investigate a variety of purposes like biological events in microorganisms and the efficacy and resistance of drugs in recent years. The major areas that green fluorescent protein (gfp) used are that they can be incorporated into different genes to determine the amount of expression of these genes in different organisms and can be used as markers in living cells. Especially gfp gene, which encodes the green fluorescent protein, is widely used nowadays. Gene-based assays have several advantages like being easy to follow-up, inexpensive and have improved biosecurity. The aim of the present study was to perform the transfection of L. tropica with enhanced gfp (egfp) and in vitro usefulness of gfp-transfectants as a drug screening model in comparison to the conventional methods. Promastigotes of L. tropica were transfected with p6.5/egfp by electroporation and selected for tunicamycin-resistance as previously described. L. tropica promastigotes transfected with gfp and in vitro effect of meglumine animoniate was assessed using different methods such as fluorescence microscopy, fluorometer and XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide) assay. The use of gfp-transfected Leishmania strains was found more rapid and more sensitive by fluorescent microscopy and fluorometry than conventional assays for the evaluation of potential anti-leishmanial agents. Consequently, stable gfp-transfected Leishmania species will be used in vitro and in vivo for screening of anti-leishmanial drugs and vaccine development as well as for understanding the biology of the host-parasite interactions at the cellular level. As a result ot this study, gfp transfected model using a Turkish L. tropica isolate was established to be used in further studies.Item Relationship of Tumor-Associated Macrophage Population Detected by CD68 PG-M1, CD68 KP1, and CD163 with Latent EBV Infection and Prognosis in Classical Hodgkin Lymphoma(FEDERATION TURKISH PATHOLOGY SOC) Mavili, HS; Isisag, A; Tan, A; Miskioglu, M; Saka Baraz, L; Nese, NObjective: To evaluate the quantity of tumor-associated macrophages (TAMs) in cases of Hodgkin Lymphoma of classical type (cHL), and to reveal possible associations between TAM intensity and latent Epstein-Barr virus (EBV) infection, overall survival, progression-free survival, prognostic indices, and clinicopathological parameters. Materials and Methods: A total 46 cases of cHL with complete clinical records were selected and re-evaluated histopathologically. Staining for CD68 (PG-M1; KP1 clones) and CD163 was evaluated and the cut-off values were defined. Also, all cases were evaluated using the chromogen in situ hybridization (CISH) method with EBER (Epstein-Barr virus-encoded RNA) probes for the presence of possible EBV infection. Results: It was found that high expression levels of PG-M1 and high International Prognostic Scores (IPS) were associated with shortened overall survival (p=0.047, p=0.013). Cases with 2 or less areas of nodal region involvement were observed to have longer progression-free survival period (p=0.043). Higher expression levels of CD68 PG-M1, CD68 KP1, and CD163 were found to show significant associations with the presence of some clinical parameters such as the presence of B symptoms, spleen involvement, and the presence of EBV infection. Conclusions: Our findings suggest that increase of PG-M1+ TAM is associated with shortened overall survival, while higher expressions of all immunohistochemical markers are statistically significantly associated with the presence of EBV infection and clinical parameters mentioned above. These findings indicate that highlighting the TAM rate via macrophage markers in cases of cHL could be helpful in determining the prognostic risk groups and the relevant results should be mentioned in pathology reports.Item Oxidative DNA damage: the thyroid hormone-mediated effects of insulin on liver tissue(HUMANA PRESS INC) Altan, N; Sepici-Dinçel, A; Sahin, D; Kocamanoglu, N; Kosova, F; Engin, AThyroid hormone affects glucose homeostasis with its actions between the skeletal muscle and liver and the altered oxidative and non-oxidative glucose metabolism. In our study three chemicals are considered biomarkers associated with oxidative stress for protein modifications were measured; 8-hydroxy-2-deoxyyguanosine (8-OHdG), a major lesion that can be generated by reactive oxygen species for DNA damage, protein carbonyl content (PCO), products of protein oxidation and advanced oxidation protein products (AOPPs) a dithyrosine containing cross-linked protein products. The purpose of the recent study was to determine the effects of insulin and T4 or their combination in diabetic, thyroidectomized, or diabetic-thyroidectomized rats and possible relations with oxidative DNA and protein damages. For this purpose, rats were assigned to eight groups: Group 1; control, Group 2; diabetes, Group 3; diabetes + insulin, Group 4; surgically thyroidectomized control, Group 5; thyroidectomized + diabetes, Group 6; thyroidectomized + diabetes + insulin, Group 7; thyroidectomized + diabetes + insulin + thyroid hormone, levothyroxin sodium, 2.5 mu g/kg and Group 8; thyroidectomized + diabetes + insulin + thyroid hormone, levothyroxin sodium, 5.0 mu g/kg for 5 weeks. After the genomic DNA of liver tissues was extracted, the ratio of 8-OHdG to deoxyguanosine and liver tissue protein oxidation markers was determined. The main findings of our recent study were the increased 8-OHdG levels during the diabetes, hypothyroidism, and hypothyroidism with diabetes, which can be regulated in different percentages with the treatment of 2.5 and 5.0 mu g/kg doses of thyroid hormone and the altered protein carbonyl and AOPP levels of liver tissue. Consequently, it was observed that the DNA and protein damage induced by oxidative stress in diabetes could be regulated by dose-dependent thyroid hormone-mediated effects to insulin treatment.Item Evaluation of Heterozygous Deletion of TP53 Gene in Pleural Fluid Samples: A Case Series of 11 Patients(DERMAN MEDICAL PUBL) Dirican, N; Bagci, Ö; Uz, E; Ozturk, Ö; Bircan, HA; Dirican, AWe described heterozygous deletion of tumor protein 53 (TP53) gene in 11 patients including 2 patients with non- malignant diseases (pneumonia) and 9 patients with malignant diseases [including small cell lung cancer (n = 3), non-small cell lung carcinoma (n = 4), non-Hodgkin's lymphoma (n= 1), and gastric carcinoma (n= 1)]. Chromosomal aberrant status was analyzed by fluorescence in situ hybridization with centromere specific and 17p13.1 locus specific probes. In 3 of 9 cancer patients we did not find malignant pleural effusion with histological examination and/or closed pleural biopsy. Heterozygous deletion of TP53 gene was found to be significantly higher in patients with malignant disease when compared to the patients with benign pleural fluid. As a result, we suggest that heterozygous deletion of TP53 may have indicator value for malignancy; however further studies are warranted to confirm this suggestion in large patient cohorts.Item Prognostic Significance of Hemoglobin/Prognostic Nutritional Index and Hemoglobin/Red Blood Cell Distribution in Rectal Cancer(AVES) Tuncel, ET; Parvizi, M; Kut, E; Aydin, M; Kasap, EBackground: We aimed to investigate the effect of hemoglobin/prognostic nutritional index and hemoglobin/red blood cell distribution, which are indicators of inflammation and nutrition, on prognosis and survival in patients with rectal cancer. Methods: The retrospective study reviewed medical records of 138 patients with rectal cancer who were followed up between 2010 and 2021. The effects of hemoglobin/red blood cell distribution, hemoglobin/prognostic nutritional index, tumor stage, and lymph node status on survival and prognosis were evaluated using univariate and multivariate analyses. Overall survival and disease-free survival were calculated for both groups. Results: Survival and prognosis were found to be significantly better in nonanemic patients with the hemoglobin/prognostic nutritional index higher than the cut-off value than in anemic patients with a normal or lower hemoglobin/prognostic nutritional index. Similarly, survival and prognosis were found to be significantly better in nonanemic patients with a hemoglobin/red blood cell distribution higher than the cut-off value than in anemic patients with a normal or lower hemoglobin/red blood cell distribution. Conclusion: The results indicated that nutrition and inflammatory markers have independent prognostic significance in rectal cancer. These markers are simple, inexpensive, and useful biomarkers commonly used in clinical practice, and they were found to predict overall survival and disease-free survival independently.Item Evaluation of 601 children with multisystem inflammatory syndrome (Turk MISC study)(SPRINGER) Yilmaz, D; Keles, YE; Emiroglu, M; Duramaz, BB; Ugur, C; Kocabas, BA; Celik, T; Ozdemir, H; Bayturan, S; Turel, O; Erdeniz, EH; Cakici, O; Taskin, EC; Erbas, IC; Genceli, M; Sari, EE; Caymaz, C; Kizil, MC; Sutcu, M; Demirbuga, A; Alkan, G; Bagci, Z; Dayar, GT; Ozkan, EA; Yilmaz, AT; Akca, M; Yesil, E; Kara, SS; Akturk, H; Yasar, B; Umit, Z; Uygun, H; Erdem, N; Buyukcam, A; Oncel, EK; Oz, SKT; Cetin, HS; Anil, AB; Yilmaz, R; Zengin, N; Uzuner, S; Albayrak, H; Borakay, O; Topal, S; Arslan, G; Yazar, A; Ozer, A; Kendirli, T; Kara, EM; Demirkol, D; Battal, F; Kosker, M; Akcan, OM; Kihtir, HS; Gul, D; Zararci, K; Alakaya, M; Kula, N; Celik, E; Petmezci, E; Evren, G; Aksay, AK; Konca, C; Sert, A; Arslan, D; Bornaun, H; Tekeli, O; Bal, A; Sahin, IO; Demir, S; Sap, F; Akyol, MB; Tanidir, IC; Donmez, YN; Ucar, T; Coban, S; Arga, G; Torun, SH; Karpuz, D; Celik, SF; Varan, C; Elmali, F; Oncel, S; Belet, N; Hatipoglu, N; Karabulut, ND; Turgut, M; Somer, A; Kuyucu, N; Dinleyici, EC; Ciftci, E; Kara, APurpose Due to its link with the 2019 coronavirus, the multisystem inflammatory syndrome in children (MISC) has garnered considerable international interest. The aim of this study, in which MISC patients were evaluated multicenter, and the data of the third period of the Turk-MISC study group, to compare the clinical and laboratory characteristics and outcomes of MISC patients who did and did not require admission to an intensive care unit (ICU).Methods This retrospective multicenter observational study was carried out between June 11, 2021, and January 01, 2022. The demographics, complaints, laboratory results, system involvements, and outcomes of the patients were documented.Results A total of 601 patients were enrolled; 157 patients (26.1%) required hospitalization in the intensive care unit (ICU). Median age was 8 years (interquartile range (IQR) 4.5-11.3 years. The proportion of Kawasaki disease-like features in the ICU group was significantly higher than in the non-ICU group (56.1% vs. 43.2% p = 0.006). The ICU group had considerably lower counts of both lymphocytes and platelets (lymphocyte count 900 vs. 1280 cells x mu L, platelet count 153 vs. 212 cells x 10(3)/ mu L, all for p< 0.001). C-reactive protein, procalcitonin, and ferritin levels were significantly higher in the ICU group (CRP 164 vs. 129 mg/L, procalcitonin 9.2 vs. 2.2 mu g/L, ferritin 644 vs. 334 mu g/L, all for p< 0.001). Being between ages 5-12 and older than 12 increased the likelihood of hospitalization in the ICU by four [95% confidence intervals (CI)1.971-8.627] and six times (95% CI 2.575-14.654), respectively, compared to being between the ages 0-5. A one-unit increase in log d-dimer (mu g/L) and log troponin (ng/L) was also demonstrated to increase the need for intensive care by 1.8 (95% CI 1.079-3.233) and 1.4 times (95% CI 1.133-1.789), respectively. Conclusion: By comparing this study to our other studies, we found that the median age of MISC patients has been rising. Patients requiring an ICU stay had considerably higher levels of procalcitonin, CRP, and ferritin but significantly lower levels of lymphocyte and thrombocyte. In particular, high levels of procalcitonin in the serum might serve as a valuable laboratory marker for anticipating the need for intensive care.Item Impact of renal function or folate status on altered plasma homocysteine levels in hypothyroidism(JAPAN ENDOCRINE SOC) Özmen, B; Özmen, D; Parildar, Z; Mutaf, I; Turgan, N; Bayindir, OHyperhomocysteinemia is an independent risk factor for coronary, peripheral and cerebrovascular diseases. Moderately elevated total homocysteine (tHcy) levels have been reported in patients with overt hypothyroidism. Plasma tHcy concentration is affected by several physiological factors and is elevated tinder conditions of impaired folate and cobalamin status and in renal failure. The aim of this Study was to assess plasma tHcy concentrations and to evaluate the role of potential determinants of plasma tHcy levels in hypothyroid patients. Fasting plasma tHcy, serum homocysteine-related vitamins folate and vitamin B-12, serum cystatin C (CysC) and creatinine, were determined in 22 hypothyroid patients and compared with 25 healthy control subjects. Creatinine clearance (CCr) was calculated using the Cockroft-Gault formula. Plasma tHcy levels were determined by HPLC with fluorescence detection and serum CysC by automated particle enhanced immunoturbidimetry. Plasma tHcy, creatinine levels were significantly higher, and serum CysC levels, and creatinine clearance values were lower in hypothyroid patients than in control subjects. Folate levels were lower in hypothyroidic group compared to the control group. There were no differences in vitamin 13, levels between hypothyroid and control groups. Positive correlation was noted between tHcy and creatinine levels in hypothyroid patients (r = 0.596); however, an inverse correlation was found between tHcy and folate levels (r = -0.705) in hypothyroid patients. In conclusion, tHcy was increased in hypothyroidism, and this increase was more strongly associated with changes in serum folate than in serum creatinine and CysC, suggesting an altered folate status.Item Tumor Microenvironment in Head and Neck Squamous Cell Carcinomas(GALENOS YAYINCILIK) Eskiizmir, GRecent studies about solid tumors demonstrated that tumor microenvironment has an important role in tumor progression, aggressivity, and metastasis process, in addition to genetic aberrations and molecular alterations of cancer cells. Therefore, the crosstalks between cancerous and noncancerous cells and metabolic changes in tumor microenvironment cause significant detrimental effects. The purpose of this review is to present the role and effect of noncancerous cells and their crosstalks with cancer cells, metabolic changes in tumor microenvironment, and to discuss the clinical significance of all these factors with respect to the current literature.Item Evaluation of proinflammatory cytokine and neopterin levels in women with papillary thyroid carcinoma(SAGE PUBLICATIONS LTD) Beksac, K; Sonmez, C; Cetin, B; Kismali, G; Sel, T; Tuncer, Y; Kosova, FIntroduction: Papillary thyroid cancer is a disease that has been associated with chronic inflammation. The purpose of this study is to measure the production of the proinflammatory cytokines IL-1 beta, IL-6 and IL-8 and neopterin, which is a novel biomarker for cellular immune response in papillary thyroid cancer. Materials and methods: The serum IL-1 beta, IL-6, IL-8 and neopterin values of 31 papillary thyroid cancer patients undergoing bilateral total thyroidectomy were measured before and 20 days after surgery. The values were compared with those of 39 healthy controls. Results: Serum IL-1 beta levels were similar across groups. IL-6 (p<0.001), IL-8 (p = 0.015) and neopterin levels (p = 0.002) were higher in presurgical samples and returned to normal following surgery. Conclusions: The proinflammatory cytokines IL-6 and IL-8, but not IL-1 beta, were produced in greater amounts in papillary thyroid cancer. Serum neopterin seems to be a valid biological marker supporting the presence of papillary thyroid cancer.Item N-terminal ProBNP levels can predict cardiac failure after cardiac surgery(JAPANESE CIRCULATION SOCIETY) Cerrahoglu, M; Iskesen, I; Tekin, C; Onur, E; Yildirim, F; Sirin, BHBackground The aim of this study was to evaluate, the relationship between the preoperative N-terminal proB-type natriuretic peptide (NT-proBNP) level and the need for the inotropic support in the early postoperative period of patients undergoing coronary artery bypass graft surgery. Methods and Results The patients were divided into 2 groups: NT-proBNP level < 220pg/ml (group A, n=26) or > 220 pg/ml (group B, n=26). The normal value for NT-proBNP level was accepted as < 220 pg/ml. The cardiac output was measured on arrival in intensive care and at the 16(th) hour. The groups were compared with respect to early postoperative hemodynamic measurements, urinary output, use of inotropic agents and requirement for additional cardiac-assist devices. Left ventricular ejection fraction, cardiac output and cardiac index were lower in group B and inotropic agents were used for a longer period of time and at higher doses in this group (p < 0.05). Conclusion Measurement of the NT-proBNP level in the period before cardiac surgery can indicate the postoperative prognosis of the patient and may be a predictor of the need for postoperative inotropic treatment.Item IL-2R, IL-6 and IL-8 Levels in Behcet's Disease(DERI ZUHREVI HASTALIKLAR DERNEGI) Inanir, I; Onur, E; Pirildar, T; Gündüz, K; Var, ABackground and Design: Immunological factors are considered to have an important role in the multifactorial ethiopathogenesis of Behcet's disease (BD). Especially, Th1 cells function by expressing proinflammatory cytokines and neutrophil-attracting chemokines. Levels of IL-2R, IL-6 and IL-8 were evaluated in patients with BD in this study. Material and Method: Sixty-six patients with BD (36 with inactive and 30 with active) composed the study group and 22 subjects the control group. Cytokine analyses were done with ELISA method by using commercial kits. ESR and CRP levels were also measured. Results: IL-2R, IL-6 and IL-8 levels in all patients, including the inactive ones, were not different from those in controls. CRP and ESR levels in patients were higher than in controls. IL-8 and CRP levels were increased in patient with active BD (p<0.05) when compared to those with inactive BD. Conclusion: Our study demonstrated elevated levels of serum IL-8, a chemokine activating monunuclear cells and neutrophils, in patients with active BD. IL-8 may be considered as an activity marker for BD. (Turkderm 2010; 44: 213-5)