Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases

Dilek Unal,Mehmet Fatih Unal,Mehmet Alikasifoglu,Arda Cetinkaya 대한신경정신의학회 2016 PSYCHIATRY INVESTIGATION Vol.13 No.4

ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity. Methodsaa121 ADHD patients aged 6–18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners’ Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group. ResultsaaAlthough there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis. ConclusionaaClinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.

Are Neutrophil/Lymphocyte and Platelet/Lymphocyte Rates in Patients with Non-Small Cell Lung Cancer Associated with Treatment Response and Prognosis?

Unal, Dilek,Eroglu, Celalettin,Kurtul, Neslihan,Oguz, Arzu,Tasdemir, Arzu Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Background: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Ninety-four patients with non-metastatic NSCLC were included and separated into two groups according to median valuse of NLR and PLR (low:<3.44 or high:${\geq}3.44$ and low:<194 or high${\geq}194$, respectively). Results: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. Conclusions: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy.

ABO Blood Groups are Not Associated with Treatment Response and Prognosis in Patients with Local Advanced Non-Small Cell Lung Cancer

Unal, Dilek,Eroglu, Celalettin,Kurtul, Neslihan,Oguz, Arzu,Tasdemir, Arzu,Kaplan, Bunyamin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Background: Lung cancer is the leading cause of cancer death, late diagnosis being the main obstacle to improving the outcomes with stage at diagnosis as an important prognostic factor. Relationships between ABO blood groups and risk of benign or malignant diseases have been observed and in this study, we aimed to investigate whether they might affect prognosis and response to chemoradiotherapy in patients with local advanced non-small cell lung cancer (NSCLC). Materials and Methods: Eighty-one patients with non-metastatic local advanced NSCLC were included in the study. ABO blood groups were A in 45 (55.6%), B in 7 (8.6%), AB in 8 (9.9%), and O in 21 (25.9%) patients. The patients were also divided two groups according to blood group A (45 patients) and non-A (B, AB and O; 36 patients). Response to chemoradiotherapy was complete remission in 10 (12.3%), disease regression in 42 (51.9%), stable disease in 12 (14.8%), and disease progression in 17 (21.0%) patients. Results: There was no significant difference among ABO blood group categories or between patients with A blood group and those with non-A blood group in terms of responses to chemoradiotherapy (p>0.05). There were also no significant differences regarding overall and disease-free survival rates. Conclusion: The ABO blood group system has no significant effect on prognosis and response to chemoradiotherapy in patients with non-metastatic NSCLC.

Is Human Kallikrein 11 in Non-small Cell Lung Cancer Treated Chemoradiotherapy Associated with Survival?

Dilek Unal,Celalettin Eroglu,Arzu Tasdemir,Hatice Karaman,Neslihan Kurtul,Arzu Oguz,Sema Sezgin Goksu,Bunyamin Kaplan 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Purpose Involvement of human kallikreins (hKs) in human cancers has been reported and several hKs are promising biomarkers of various cancers. The aim of this study was to evaluate the prognostic significance of hK11 expression in patients with non-metastatic non-small cell lung cancer (NSCLC). Materials and Methods The study included 44 patients with NSCLC. hK11 expression was determined by immuno- histochemical staining. Results The estimation of disease-free and overall survival by Kaplan-Meier was 11 months and 17 months, respectively. The estimation of overall survival by Kaplan-Meier was significantly higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (20 months vs. 11 months, p=0.032). Although not statistically different, the estimation of disease-free survival by Kaplan-Meier was higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (12 months vs. 9 months, p=0.113). Multivariate Cox regression analysis showed that the overall survival rates were significantly associated with response to chemoradiotherapy and the degree of staining with hK11. Conclusion The stronger hK11 expression in NSCLC appears to be associated with better survival rates. hK11 may be a prognostic biomarker of NSCLC.

Lack of any Association between Season of Diagnosis and Survival of Gastric Cancer Cases in Kayseri, Turkey

Unal, Dilek,Oguz, Arzu,Acmaz, Banu,Goksu, Sema Sezgin,Arslan, Alaettin,Eroglu, Celalettin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Background: The influence of season of diagnosis on cancer survival has been an interesting issue for many years. Most studies have shown a possible association between seasonality and survival in some cancers. We aimed to investigate whether there is an association between season of diagnosis and survival in patients with gastric cancer. Materials and Methods: We reviewed retrospectively the files of 279 histologically proven gastric cancer patients. According to diagnosis date, the patients were grouped into 4 seasons of diagnosis groups, spring, summer, autumn, and winter. Results: There was no significant differences when the overall survival rates of the patients were compared according to the patients' season of diagnosis (p: 0.871). Median overall survival rates were 22.0 (14.5-29.5) months for the patients who were diagnosed in spring, 24.0 (12.4-35.6) for summer, 18.0 (9.96-26.0) for autumn and 21.0 (16.3-25.7) for winter. Median disease-free survival rates were 66.0 (44.1-68.1) months for the patients who were diagnosed in spring, 28.0 (17.0-39.0) for summer, 22.0 (0-46.4) for autumn and 23.0 (17.5-28.5) for winter. While the rate was best for the patients diagnosed in spring the differences were not statistically significant (p= 0.382). Conclusions: On the basis of the above results the season was not suggested as contributing to prognosis in gastric cancer cases in Kayseri, Turkey.

Mothers' Knowledge and Attitudes about HPV Vaccination to Prevent Cervical Cancers

Kose, Dilek,Erkorkmaz, Unal,Cinar, Nursan,Altinkaynak, Sevin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: Cervical cancer which is one of the most preventable cancers is an important public health problem worldwide, and especially in developing countries. The aim of this study was to determine knowledge and attitudes about the HPV vaccination of mothers with 0- to 18-year old children. Materials and Methods: Written approval was taken from the local authorities. The study subjects consisted of 799 mothers who agreed to participate. The data were collected via a "Personal Information Form" which included 30 questions that were prepared by the researchers themselves in line with the literature. The data were collected by face to face interviews with the mothers. Analyses were performed using commercial software. Results: The mean age of the mothers who participated in the study was $32.0{\pm}6.52$, and 88.1% reported no information about HPV, and 83.5% no information about HPV vaccination. Only 0.7% of the mothers had daughters who had HPV vaccination, and 44.3% of the mothers who had sons were found out to be indecisive about having HPV vaccination. There was a significant corelation between the educational status of the mothers and their knowledge about HPV vaccination (p<0.05). However, there was no significant correlation in terms of economic conditions (p>0.05). Conclusions: This study suggested that mothers had very little information on HPV and HPV vaccination. Knowledge of the disease and its vaccination is an essential factor for the success of the vaccination program. It is of great importance that mothers are trained in this subject by health professionals.

Lack of any Association between Blood Groups and Lung Cancer, Independent of Histology

Oguz, Arzu,Unal, Dilek,Tasdemir, Arzu,Karahan, Samet,Aykas, Fatma,Mutlu, Hasan,Cihan, Yasemin Benderli,Kanbay, Mehmet Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Introduction: Lung cancer, the leading cause of cancer deaths, is divided into 2 main classes based on its biology, therapy and prognosis: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Many cases are at an advanced stage at diagnosis, which is a major obstacle to improving outcomes. It is important to define the high risk group patients for early diagnosis and chance of cure. Blood group antigens are chemical components on erythrocyte membranes but they are also expressed on a variety of epithelial cells. Links between ABO blood groups with benign or malignant diseases, such as gastric and pancreas cancers, have been observed for a long time. In this study, we aimed to investigate any possible relationship between lung cancer histological subtypes and ABO-Rh blood groups. Materials and Methods: The files of 307 pathologically confirmed lung cancer patients were reviewed retrospectively. Cases with a serologically determined blood group and Rh factor were included and those with a history of another primary cancer were excluded, leaving a total of 221. The distribution of blood groups of the lung cancer patients were compared with the distribution of blood groups of healthy donors admitted to the Turkish Red Crescent Blood Service in our city in the year 2012. Results: There was no significant difference between patients with lung cancer of either type and the control group in terms of distribution of ABO blood groups and Rh factor (p: 0.073). There was also no relationship with non small cell cancer histological subtypes. Conclusions: In this study, we found no relationship between the ABO-Rhesus blood groups and NSCLC and SCLC groups. To our knowledge this is the first analysis of ABO blood groups in SCLC patients.

Season of Diagnosis and Survival of Advanced Lung Cancer Cases - Any Correlation?

Oguz, Arzu,Unal, Dilek,Kurtul, Neslihan,Aykas, Fatma,Mutlu, Hasan,Karagoz, Hatice,Cetinkaya, Ali Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Introduction: The influence of season at diagnosis on cancer survival has been an intriguing issue for many years. Most studies have shown a possible correlation in between the seasonality and some cancer type survival. With short expected survival, lung cancer is an arena that still is in need of new prognostic factors and models. We aimed to investigate the effect of season of diagnosis on 3 months, 1 and 2 years survival rates and overall survival of non small cell lung cancer patients. Materials and Methods: The files of non small cell lung cancer patients that were stages IIIB and IV at diagnosis were reviewed retrospectively. According to diagnosis date, the patients were grouped into 4 season groups, autumn, winter, spring and summer. Results: A total of 279 advanced non small cell lung cancer patients' files were reviewed. Median overall survival was 15 months in the entire population. Overall 3 months, 1 and 2 years survival rates were 91.0%, 58.2% and 31.2% respectively. The season of diagnosis was significantly correlated with 3 months survival rates, being diagnosed in spring being associated with better survival. Also the season was significantly correlated with T stage of the disease. For 1 and 2 years survival rates and overall survival, the season of diagnosis was not significantly correlated. There was no correlation detected between season and overall survivals according to histological subtypes of non small cell lung cancer. Conclusion: As a new finding in advanced non small cell lung cancer patients, it can be concluded that being diagnosed in spring can be a favorable prognostic factor for short term survival.

Hepatitis B and C Seroprevalence in Solid Tumors - Necessity for Screening During Chemotherapy

Oguz, Arzu,Aykas, Fatma,Unal, Dilek,Karahan, Samet,Uslu, Emine,Basak, Mustafa,Karaman, Ahmet Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Background: Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solid malignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detected which may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was to determine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoing chemotherapy and consequences during follow-up. Materials and Methods: The files of 914 patients with solid malignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively. All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNA and HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities that were chosen were determined. Results: Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detected in 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients received prophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liver failure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis was not encountered. Conclusions: Just as with hematological malignancies, screening for HBV and HCV should also be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy for HBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCV infection on patients undergoing chemotherapy is still not well characterized.

Prognostic Value of SPARC Expression in Unresectable NSCLC Treated with Concurrent Chemoradiotherapy

Kurtul, Neslihan,Eroglu, Celalettin,Unal, Dilek,Tasdemir, Erdem Arzu,Orhan, Okan,Zararsiz, Gokmen,Baran, Munevver,Kaplan, Bunyamin,Kontas, Olgun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Background: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. Materials and Methods: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel ($20mg/m^2$) and cisplatin ($20mg/m^2$). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. Results: Median overall survival was $16{\pm}2.73$ (11.55-20.46) months for low expression vs $7{\pm}1.79$ months (7.92-16.08) months for high expression (p=0.039), while median local control was $13{\pm}2.31$ (8.48-17.5) months for low expression vs $6{\pm}0.85$ (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was $10{\pm}2.31$ (5.48-14.5) months for low expression vs $6{\pm}1.10$ (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. Conclusions: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.