Evaluation Expression of the Caspase-3 and Caspase-9 Apoptotic Genes in Schizophrenia Patients

Ebubekir Dirican(Ebubekir Dirican ),Halil Özcan(Halil Özcan ),Sevgi Karabulut Uzunçakmak(Sevgi Karabulut Uzunçakmak ),Uğur Takım(Uğur Takım ) 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.1

Objective: Apoptosis is programmed cell death that occurs by several pathways. Caspase-3 is induced by active caspase-9 via the intrinsic pathway. The aim of this research was to explore the expression of caspase-3 and caspase-9 in schizophrenia patients and healthy samples. Methods: RNA was isolated from the peripheral blood of 39 schizophrenia patients’ and healthy samples. After cDNA synthesis, real time PCR (RT-PCR) was used to analyse caspase-3 and caspase-9 gene expression. The severity of psychopathological symptoms of schizophrenia was evaluated using the Positive and Negative Symptoms Scale for schizophrenia (PANSS) and Clinical Global Impressions (CGI). Results: The expression of caspase-3 and caspase-9 genes was higher in schizophrenia patients than in healthy samples (p = 0.012, p = 0.002, respectively). The increase in caspase-3 gene expression was significant with being male, smoking and with a duration of less than 6 years (p = 0.047, p = 0.049, p = 0.034, respectively). On the other hand, the increase in caspase-9 gene expression was significant in patients who is smoke, have children, and are under 33 years old (p = 0.040, p = 0.043, p = 0.045, respectively). A significant positive correlation was detected between the caspase-3 and caspase-9 gene expression (r = 0.3218, p = 0.049). Conclusion: Our findings indicate that caspase-3 and caspase-9 gene expression may activate cell death mechanisms by intrinsic apoptotic genes. Furthermore, caspase-3 and caspase-9 may play essential roles in different ways in schizophrenia. Hence there is a need to further study the apoptotic mechanism with expanded patient populations.

A New Inflammatory Prognostic Index, Based on C-reactive Protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases

Dirican, Nigar,Dirican, Ahmet,Anar, Ceyda,Atalay, Sule,Ozturk, Onder,Bircan, Ahmet,Akkaya, Ahmet,Cakir, Munire Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.12

Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein ${\times}$ NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.

Prognostic and Predictive Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma: Second Line Sunitinib Treatment Following IFN-alpha

Dirican, Ahmet,Kucukzeybek, Yuksel,Erten, Cigdem,Somali, Isil,Demir, Lutfiye,Can, Alper,Payzin, Kadriye Bahriye,Bayoglu, Ibrahim Vedat,Akyol, Murat,Yildiz, Yasar,Koseoglu, Mehmet,Alacacioglu, Ahmet,Ta Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Background: Long-term survival is a problem with locally advanced and metastatic renal cell carcinomas. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, but data on sunitinib use as a second line treatment in metastatic renal cell carcinoma (mRCC) are limited. Prognostic and predictive value of peripheral blood markers has been shown for many cancers. Materials and Methods: Efficacy and safety profiles of sunitinib after interferon alpha (IFN-${\alpha}$) were evaluated based on retrospective data for 23 patients with mRCC. Hematological parameters (neutrophils, lymphocytes, platelets, mean platelet volume, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio) were recorded at the time of metastasis. It was evaluated whether hematological parameters were prognostic and predictive factors. Results: Median progression-free survival (PFS) time was 16.5 months (95%CI: 0-34.5). Median overall survival (OS) time was 25.7 months (95%CI: 10.8-40.0). Most common side effects were neutropenia (52.2%), stomatitis (26.1%) and hand-food syndrome (26.1%). PFS was found 3.13 vs 17.1 months in patients with neutrophil / lymphocyte ratio (NLR)>3 vs $NLR{\leq}3$ (p:0.012). Median OS was 6.96 vs 27.1 months in patients with NLR>3 vs $NLR{\leq}3$ (p:0.001).While 75% of patients who responded to sunitinib had $NLR{\leq}3$, in 72% of patients with no response to sunitinib NLR>3 was detected (p:0.036). The association between the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria and NLR was statistically significant (p:0.022). Conclusions: Data on second line sunitinib treatment following cytokine in mRCC are limited. In our study, we observed second line sunitinib treatment following IFN-${\alpha}$ to be effective and tolerable. NLRappeared to have prognostic and predictive value.

Treatment of Metastatic Colorectal Cancer With or Without Bevacizumab: Can the Neutrophil/Lymphocyte Ratio Predict the Efficiency of Bevacizumab?

Dirican, Ahmet,Varol, Umut,Kucukzeybek, Yuksel,Alacacioglu, Ahmet,Erten, Cigdem,Somali, Isil,Can, Alper,Demir, Lutfiye,Bayoglu, Ibrahim Vedat,Akyol, Murat,Yildiz, Yasar,Koyuncu, Betul,Coban, Eyup,Tarh Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. Materials and Methods: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. Results: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). Conclusions: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab-based treatments in mCRC patients.

REIDEMEISTER TORSION AND ORIENTABLE PUNCTURED SURFACES

Dirican, Esma,Sozen, Yasar Korean Mathematical Society 2018 대한수학회지 Vol.55 No.4

Let ${\Sigma}_{g,n,b}$ denote the orientable surface obtained from the closed orientable surface ${\Sigma}_g$ of genus $g{\geq}2$ by deleting the interior of $n{\geq}1$ distinct topological disks and $b{\geq}1$ points. Using the notion of symplectic chain complex, the present paper establishes a formula for computing Reidemeister torsion of the surface ${\Sigma}_{g,n,b}$ in terms of Reidemeister torsion of the closed surface ${\Sigma}_g$, Reidemeister torsion of disk, and Reidemeister torsion of punctured disk.

Detection of PIK3CA Gene Mutations with HRM Analysis and Association with IGFBP-5 Expression Levels in Breast Cancer

Dirican, Ebubekir,Kaya, Zehra,Gullu, Gokce,Peker, Irem,Ozmen, Tolga,Gulluoglu, Bahadir M.,Kaya, Handan,Ozer, Ayse,Akkiprik, Mustafa Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Breast cancer is the second most common cancer and second leading cause of cancer deaths in women. Phosphatidylinositol-3-kinase (PI3K)/AKT pathway mutations are associated with cancer and phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene mutations have been observed in 25-45% of breast cancer samples. Insulin growth factor binding protein-5 (IGFBP-5) can show different effects on apoptosis, cell motility and survival in breast cancer. We here aimed to determine the association between PIK3CA gene mutations and IGFBP-5 expressions for the first time in breast cancer patients. Frozen tumor samples from 101 Turkish breast cancer patients were analyzed with high resolution melting (HRM) for PIK3CA mutations (exon 9 and exon 20) and 37 HRM positive tumor samples were analyzed by DNA sequencing, mutations being found in 31. PIK3CA exon 9 mutations (Q546R, E542Q, E545K, E542K and E545D) were found in 10 tumor samples, exon 20 mutations (H1047L, H1047R, T1025T and G1049R) in 21, where only 1 tumor sample had two exon 20 mutations (T1025T and H1047R). Moreover, we detected one sample with both exon 9 (E542Q) and exon 20 (H1047R) mutations. 35% of the tumor samples with high IGFBP-5 mRNA expression and 29.4% of the tumor samples with low IGFBP-5 mRNA expression had PIK3CA mutations (p=0.9924). This is the first study of PIK3CA mutation screening results in Turkish breast cancer population using HRM analysis. This approach appears to be a very effective and reliable screening method for the PIK3CA exon 9 and 20 mutation detection. Further analysis with a greater number of samples is needed to clarify association between PIK3CA gene mutations and IGFBP-5 mRNA expression, and also clinical outcome in breast cancer patients.

Clinical Characteristics of Patients with Bronchioloalveolar Carcinoma: A Retrospective Study of 44 Cases

Dirican, Nigar,Baysak, Aysegul,Cok, Gursel,Goksel, Tuncay,Aysan, Tulin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background: Bronchioloalveolar carcinoma (BAC) is considered a subtype of adenocarcinoma of the lung. Recently BAC has been variously termed adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant invasive adenocarcinoma, and invasive mucinous adenocarcinoma. The aim of the study was to analyze and detect prognostic factors of patients with BAC over a 7-year period. Materials and Methods: This retrospective single-center study included 44 patients with BAC. The impact on survival of fifteen variables (gender, age, smoking status, cough, dyspnea, hemoptysis, fever, chest pain, sputum, metastasis number, Karnofsky performance status, pT, pN, TNM stage, cytotoxic chemoterapy) were assessed. Results: Median age was 55 years (38-83). Most patients were male (63.6%) and stage IV (59.1%). Twenty-one patients (47.7%) received cytotoxic chemotherapy (platinum-based regimens) for metastatic disease. Objective response rate was 33.3% (4 partial, 3 complete responses). Stable disease was observed in nine in patients (42.8%). Disease progression was noted in 5 (23.8%). The median OS for all patients was 12 months (95%CI, 2.08-22.9 months). Independent predictors for overall survival were: Karnofsky performance status (HR:3.30, p 0.009), pN (HR:3.81, p 0.018), TNM stage (HR:6.49, p 0.012) and hemoptysis (HR:2.31, p 0.046). Conclusions: Karnofsky performance status, pN, TNM stage and hemoptysis appear to have significant impact on predicting patient survival in cases of BAC.

Mutations in PIK3CA Sensitize Breast Cancer Cells to Physiologic Levels of Aspirin

Dirican, Ebubekir Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5

Reidemeister torsion and orientable punctured surfaces

Esma Dirican,Yasar Sozen 대한수학회 2018 대한수학회지 Vol.55 No.4

Let $\Sigma_{g,n,b}$ denote the orientable surface obtained from the closed orientable surface $\Sigma_g$ of genus $g\geq2$ by deleting the interior of $n\geq 1$ distinct topological disks and $b\geq 1$ points. Using the notion of symplectic chain complex, the present paper establishes a formula for computing Reidemeister torsion of the surface $\Sigma_{g,n,b}$ in terms of Reidemeister torsion of the closed surface $\Sigma_{g},$ Reidemeister torsion of disk, and Reidemeister torsion of punctured disk.

Relation of ATPase6 Mutations and Telomere Length in Schizophrenia Patients

Sevgi Karabulut Uzuncakmak(Sevgi Karabulut Uzuncakmak ),Ebubekir Dirican(Ebubekir Dirican ),Halil Ozcan(Halil Ozcan ),Ugur Takim(Ugur Takim ) 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.1

Objective: Schizophrenia is a serious mental disorder. Mutations in mitochondrial genes can change energy metabolism. Telomere is a tandem sequence at the end of chromosomes. Shorter telomere length has been shown in schizophrenia. The aim of this study was to determine the relationship between ATPase6 gene mutations and telomere length in schizophrenia patients. Methods: Blood samples of 34 patients and 34 healthy controls were used. In this study conventional PCR, Sanger sequencing technic and real-time PCR were utilized. Results: Five different mutations (A8860G, A8836, G8697A, C8676T, and A8701G) in the ATPase6 gene were identified in schizophrenia patients. The most seen mutation was A8860G (94%). Telomere length analysis indicated the relation of ATPase6 gene mutations and telomere length variations (p = 0.001). Patients carrying the A8860G mutation had shorter telomere lengths than patients carrying other mutations. Comparing telomere length between schizophrenia patients and healthy controls revealed that the mean telomere length of schizophrenia patients was shorter than healthy controls (p = 0.006). The demographic analysis demonstrated a significant relationship between marital status and telomere length (p = 0.011). Besides that, the duration of the illness is another factor that impacts telomere length (p = 0.044). There is no significant relation between telomere length and other clinical and demographic characteristics including education status, age, gender, etc. Conclusion: In conclusion, telomere length and ATPase6 gene mutations have a significant relation. Studies with larger patient populations and investigation of other mitochondrial gene mutations will make the clearer link between telomere length and mitochondrial mutations.