Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer.

The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients' demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAFV600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAFV600E and BRAFnon-V600E and their analysis according to specific tumor localizations showed that all four BRAFnon-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.

The impact of adjuvant oxaliplatin and tumor sidedness on the overall survival of stage IIB colon cancer patients: a multicentre study.

The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Retinochoroidal vascular plexuses in patients with iron deficiency anaemia.

CLINICAL RELEVANCE: Optical coherence tomography angiography (OCT-A) may enable the identification of alteration in the retinochoroidal microvasculature in patients with iron deficiency anaemia. BACKGROUND: To investigate the presence of macular microvascular alterations in females with IDA by using OCT-A. METHODS: This is a cross-sectional comparative study. Forty patients with IDA and 35 age-matched healthy women underwent a complete ophthalmologic examination and OCT-A imaging. Foveal avascular zone parameters and the vessel density in the superficial (SCP) and deep capillary plexus (DCP) were calculated using automated software. All measurements were compared between groups. Correlations between the OCT-A metrics and haematological laboratory parameters were evaluated. RESULTS: Compared to healthy subjects, IDA patients revealed significantly decreased vessel density of the SCP in all parafoveal quadrants (p < 0.05). In contrast, vessel density analysis in DCP has shown no statistically significant difference in all parafoveal quadrants (p > 0.05). Although foveal vessel density in both SCP and DCP were higher in the IDA group, only the foveal vessel density in DCP was significantly higher than controls (p = 0.001). The mean values of the foveal avascular zone area and perimeter and choriocapillaris flow area were significantly lower in the IDA group (p < 0.05). The parafoveal vessel density in SCP, foveal avascular zone area, and choriocapillaris flow area were positively correlated with haematological parameters including haemoglobin, haematocrit, mean corpuscular haemoglobin, and mean corpuscular volume (p < 0.01). CONCLUSION: Patients with IDA had decreased parafoveal vessel density in the SCP, but not the DCP. Foveal avascular zone metrics and choriocapillaris flow area measurements were significantly lower in IDA.

Determination of therapeutic agents efficiencies of microsatellite instability high colon cancer cells in post-metastatic liver biochip modeling.

Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Biological properties of CMS1 (MSI-H type) can affect therapeutic efficiencies of agents used in the treatment of CRC, and therefore become a new predictive factor of the treatment. But, the predictive impact of MSI-H status for adjuvant chemotherapy remains controversial. This study will assess whether there is any unnecessary or inappropriate use of treatment agents recommended for adjuvant therapy of stage 2 and 3 of disease and for palliative or curative treatment of liver metastatic disease in microsatellite instability high group, a molecular subtype of colon cancer. Within this scope, the efficiencies of fluorouracil- and oxaliplatin-based chemotherapeutic agents will be shown on stage 3 microsatellite instability high colon tumor cell lines first, and then a microfluidic model will be created, imitating the metastasis of colon cancer to the liver. In the microfluidic chip model, we will create in liver tissue, where the metastasis of microsatellite instability high colon cancer will be simulated; the effectiveness of chemotherapeutic agents, immunotherapy agents, and targeted agents on tumor cells as well as drug response will be assessed according to cell viability through released biomarkers from the cells. The proposed hypothesis study includes the modeling and treatment of patient-derived post-metastatic liver cancer in microfluidics which has priority at the global and our region and consequently develop personal medication.

The Relationship between Insulin Resistance and Liver Damage in non-alcoholic Fatty Liver Patients.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is closely associated with diseases, such as obesity, diabetes mellitus, metabolic syndrome, which are characterized by insulin resistance. NAFLD is thought to be a manifestation of metabolic syndrome in the liver. Liver fibrosis has a high prognostic significance in non-alcoholic steatohepatitis (NASH). In this study, the relationship between insulin resistance and the histopathological changes in the liver was investigated in biopsy-proven NAFLD patients. METHODS: In this study, 85 biopsy-proven NAFLD patients (64 NASH, 21 non-NASH) and 40 healthy control subjects were enrolled. Insulin resistance was calculated using the "homeostasis model assessment of insulin resistance" (HOMA-IR). RESULTS: C reactive protein, total cholesterol, low-density lipoprotein, triglyceride, body mass index (BMI), HOMA-IR levels were significantly higher in the NAFLD group compared to the control group. In the NASH group, the HOMA-IR level was significantly higher than the non-NASH group (p=0.026). When NAFLD patients with advanced fibrosis (stage 3-4, n=27) and without fibrosis (stage 0-2, n=58) are compared, in advanced fibrosis group BMI (35.2±4.6 kg/m2 and 32.7±4.1 kg/m2, respectively; p=0.031) and HOMA-IR (6.3 [5.8-6.8] and 3.4 [2.6-4.8], respectively, p=0.001) levels were higher significantly. In the covariance analysis, when confounding factors, such as BMI, age and gender, were corrected, it was observed that the elevation of HOMA-IR level in the advanced fibrosis group continued statistically significantly. CONCLUSION: HOMA-IR levels were high in NAFLD patients with advanced fibrosis. HOMA-IR, which can be easily measured in daily practice, is an independent predictor for fibrosis.

The Effect of Type and Daily Doses of Insulin to Treatment Success in Type 2 Diabetes Patients who are Receiving Basal-bolus Insulin Therapy.

OBJECTIVES: The present study aims to compare different types of insulin concerning treatment success and insulin dose requirement in type 2 diabetes patients who were receiving basal-bolus insulin therapy and to evaluate the causes of treatment failure despite high doses of insulin. METHODS: In our retrospective study, 198 type 2 diabetes patients who were receiving basal-bolus insulin therapy included. Patients were divided into three groups according to the insulin types (Group 1: short and long-acting analogue insulin users (n=83), Group 2: short and long-acting human regular insulin users (n=58), Group 3: human regular insulin + long-acting analogue insulin users (57)). Demographic data and daily insulin doses were recorded from the patient follow-up files. These data and the rates of achievement of the target HbA1c levels were also compared between groups. In addition, insulin doses of the patients whose glycemic targets could and could not be achieved were compared. RESULTS: In this study, 123 (62.1%) of the 198 patients were female and 65 (47.9 %) were male. The mean age of the three groups was 55.81±8.1, 58.3±8.9, 58.3±8.8, respectively. HbA1C values were 8.72±1.65% in group 1, 9.0±1.98% in group 2 and 9.05±2.24% in group 3. The rates of achievement HbA1c value below 7% were 27.7% in analogue insulin group, 25.9% human regular insulin group and 31.6% in regular + analogue insulin group (p >0.05). There were no significant differences in daily basal and bolus insulin doses, total daily and per kg insulin doses and basal-bolus rates between groups. Higher total daily insulin doses were determined in patients who could not achieve target glycemic values than achieved it in group 1 and 2. Higher basal insulin doses were determined in patients who could not achieve target glycemic values than could achieved it in group 3. CONCLUSION: In our study, in which we did not find any significant difference in the dose analysis between analogue and regular insulin, the findings showed that high insulin doses might not be sufficient for glycemic control. The underlying causes should be investigated and correctible reasons should be eliminated in these patients.

The Relation between Homocysteine Levels in Patients with Acute Coronary Syndrome and Grace Score.

OBJECTIVES: This study investigated the correlation between homocysteine levels in patients with Acute Coronary Syndrome and GRACE Score. METHODS: This study included 191 cases -140 Non-ST MI cases and 51 MI with ST-elevation cases in Sisli Etfal Training and Research Hospital Coronary Intensive Care Unit between December 2008 and March 2010. Homocysteine was measured by immulite 2000 device, using kemiluminesans method and competitive immunoassay principle and a kit by DPC was used during the measurement. The reference range given by the producing company was between 5-15 Mmol/L for male and female adults. The patients were classified into three risk groups as low, medium and high on the basis of the criteria identified in GRACE risk score: age, heart rate, systolic blood pressure, serum creatine levels, Killip classification, cardiac arrest on admission, increased cardiac enzymes and ST segment depression. The relation between homocysteine levels in patients with Acute Coronary Syndrome and GRACE risk score was evaluated. RESULTS: In the Non-ST MI group, a statistically-moderate positive correlation was seen between homocysteine and GRACE risk score during the study (p<0.05). However, in the MI with ST-elevation group, no correlation was found between homocysteine and GRACE risk score (p>0.05). Overall, despite the low figures, a meaningful positive relation was observed between homocysteine and GRACE risk score in all cases. CONCLUSION: Homocysteine is independent of other classic risk factors for cardiovascular diseases. Therefore, we believe that routine plasma homocysteine levels should be checked when evaluating risk factors for Atherosclerotic Coronary Artery disease.

The Compatibility of Hemoglobin A1c with Oral Glucose Tolerance Test and Fasting Plasma Glucose.

OBJECTIVES: Diabetes mellitus (DM) is a chronic metabolic disease requiring lifelong medical care, and its prevalence is increasing worldwide. Early diagnosis of prediabetes and diabetes is significant in view of the mortality, morbidity and cost associated with them. Because of the difficulties in application and reproducibility of oral glucose tolerance test (OGTT), which is considered to be the gold standard in the diagnosis of DM, more feasible diagnostic tests are needed. This study aims to evaluate the validity of hemoglobin A1c (HbA1c) in predicting prediabetes and diabetes in the Turkish population and to evaluate the compatibility of HbA1c with other diagnostic tests. METHODS: The patients who were admitted to Health Sciences University Sisli Hamidiye Etfal Training and Research Hospital internal diseases and endocrinology outpatient clinics between 01.01.2013 and 30.06.2014 enrolled in this study. The participants were >18 years of age and were not diagnosed with prediabetes or DM earlier. The results of OGTT, fasting plasma glucose (FPG) and HbA1c tests were retrospectively screened, and the correlation of them was analyzed. RESULTS: In this study, 201 participants enrolled. Of these cases, 127 were women and 74 were men. Mean age of the group was 49.3±10.4 years. HbA1c was observed <5.7% in the 15%, 5.7-6.4% in the 60%, and ≥ 6.5% in the 25% of the cases. While FPG was <100 mg/dL in 24% of the participants, it was found to be between 100-126 mg/dL in 71% and ≥126 mg/dL in 5% of the participants. According to the OGTT data, 23% of the cases were healthy, 59% were prediabetic and 18% were diabetic. The sensitivity and specificity of HbA1c were calculated as 50% and 80%, respectively. While the sensitivity of FPG was 17% and specificity was 97%. CONCLUSION: The data obtained from our study show that HbA1c is a more sensitive test compared to FPG in the diagnosis of DM. Prospective studies with broad participation at national and international levels are needed to redefine HbA1c cut-off points for the diagnosis of DM and prediabetes. Thus, it will be possible to revise the diagnostic guidelines accordingly.

Determining INR Awareness of the Patients who Use Warfarin and Rates of Achieving the Target Dosage.

OBJECTIVES: Warfarin is the most frequently used therapy as an oral anticoagulant medication for reducing the risk of thromboembolic complications. However, poor adherence to therapy may cause ineffective INR levels with increased complication risk. In our study, we aimed to show the rates of INR awareness of patients with atrial fibrillation (AF) using warfarin and whether they achieved the targeted INR values. METHODS: In this study, 300 male (60%, n=180) and female (40%, n=120) patients over 18 years of age who applied to warfarin polyclinic and were receiving warfarin treatment due to AF were included. The levels of INR between 2-3 were estimated as effective. Same questionnaire was applied to all patients. RESULTS: Our study showed that 57% of the patients who used warfarin were not in the therapeutic range. We also determined that INR awareness was extremely low in the majority of the patients. In this study, 72.2% of the patients who used warfarin did not know the definition of INR, 68% of the patients did not know the side effects of the medicine, 75.7% of the patients did not know the precautions needed to be taken in daily life and 83.7% of the patients did not know the foods rich in vitamin K. Patients who knew the meaning of INR were more likely have INR levels in the effective range, but these rates were not statistically significant. There was no statistically significant relationship between the educational level, marital status, and INR control frequency of the patients with the achievement of targeted INR levels. CONCLUSION: At the beginning of the warfarin treatment, advantages and disadvantages should be balanced by the doctor. The patient and patient's relatives should be informed directly and comprehensibly about the effects and side effects of the medicine, as well as the interactions, pursuance and precautions need to be taken in daily life. Various modern methods should be enabled for surveillance and the patients who are not in the therapeutic range should be followed closer.

Immobilization of Purified Pectin Lyase from Pseudomonas putida onto Magnetic Lily Flowers (Lilium candidum L.) Nanoparticles and Applicability in Industrial Processes.

Pectinases are an important class of enzymes distributed in many higher plants and microorganisms. One of these enzymes is pectin lyase which has an important role in industrial applications such as clarification of fruit juices. Pectin lyase was purified with 73% yield from Pseudomonas putida bacteria and was 220.7-fold using three phase precipitation technique. Molecular weight of purified pectin lyase was determined as 32.88 kDa with SDS-polyacrylamide gel electrophoresis. The pectin lyase was immobilized covalently via the L-glutaraldehyde spacer to the cellulosic structures of lily flowers (Lilium candidum L.). The immobilized enzyme was then magnetized by modifying with γ-Fe3O4 nanoparticles and determined the most appropriate immobilization conditions as pH 6 and 30 °C. Purified pectin lyase was connected to magnetized support material after 60 min at the rate of 86.4%. The optimum pH and temperatures for the free and immobilized pectin lyase was found to be 6.0 and 40 °C. pH and thermal stabilities of the free and immobilized pectin lyase enzyme have been preserved at high-low temperatures and pH. The structural characterization of the immobilized pectin lyase was performed by SEM, FT-IR, and XRD chromatographic analyses and it was observed that the support materials structure was appropriated to immobilization with pectin lyase and to modify with Fe3O4 nanoparticles.

Evaluation of the efficacy in cosmetic products safety: Comparison with biochemical substrates.

Chemicals used in cosmetics must interact with the enzymes for their consumption after entering our bodies. The area at which the interaction realizes on the enzyme is known as the active center. This center is three dimensional and optically active. Considering the properties of the active regions, it is believed that the determination of the geometric properties of the chemicals may contribute to the safety evaluation of the chemical products. Obtainment of toxicological data of chemicals is a long and difficult process. It is an impossible process as the animal experiments have been prohibited. Since there are large number of chemical compounds available, it is not possible to conduct toxicological evaluation on all of them. Therefore, it is important to estimate whether chemicals are toxic through using molecular formulas. In this study, the similarities and differences between the unwanted chemicals used in cosmetic products and the geometric structures of the chemicals used in metabolism were determined by using Group Theory. The aim of the study is to estimate whether the chemicals will be toxic by taking advantage of point-group determinations. Molecular formulae of chemicals prohibited in cosmetics and substrates used in biological systems were used as materials. The point groups of the molecules were determined using these formulas. ChemDraw Professional 17 chemical drawing program was used to draw the formula structures of the molecules. Campus Licensed version of the program provided by Atatürk University was utilized. An Excel application which was developed to examine the molecules according to the Group Theory was also used.

The diagnostic value of late-night salivary cortisol for diagnosis of subclinical Cushing's syndrome.

INTRODUCTION: Late-night salivary cortisol is a frequently used and easily implemented diagnostically valuable test for the diagnosis of overt Cushing's syndrome. The use of late-night salivary cortisol in the diagnosis of subclinical Cushing's syndrome is somewhat controversial. In this study, we aimed to determine the diagnostic value of late-night salivary cortisol in diagnosing subclinical Cushing's syndrome and compare it with 24-hour urinary free cortisol levels (UFC). MATERIAL AND METHODS: The study consisted of 33 cases of subclinical Cushing's syndrome, 59 cases of non-functioning adrenal adenoma, and 41 control subjects. Late-night salivary cortisol and UFC were measured in all the cases. The diagnosis of subclinical Cushing's syndrome was based on combined results of 1 mg dexamethasone suppression test > 1.8 µg/dL and ACTH < 10 pg/mL. RESULTS: Mean late-night salivary cortisol levels in subjects with subclinical Cushing's syndrome were significantly higher than in subjects with non-functioning adrenal adenoma and the control group (p < 0.001). Using a cut-off value of 0.18 µg/dL, the sensitivity and specificity of late-night salivary cortisol for diagnosing subclinical Cushing's syndrome were determined as 82% and 60%, respectively. Using a cut-off value of 137 µg/day, the sensitivity and specificity of UFC was determined as 18% and 90%, respectively. CONCLUSIONS: Because the sensitivity of late-night salivary cortisol for the diagnosis of subclinical Cushing's syndrome is limited, using it as the sole screening test for subclinical Cushing's syndrome may lead to false negative results. However, using it as an adjunct test to other tests may be beneficial in the diagnosis of subclinical Cushing's syndrome. (Endokrynol Pol 2016; 67 (5): 487-492).

Evaluation of the efficiency and safety in cosmetic products.

Chemicals used in cosmetics have to interact with enzymes for beneficial or destroy purpose after they enter in our body. Active sections of enzymes that catalyze reactions have three dimensions and they are active optically. When these limitations of catalytic sections are considered, it may be considered that defining geometric specifications of chemical materials and functional groups they contain may contribute on safety evaluations of cosmetic products. In this study, defining similarities and differences of geometric structures of chemicals that are prohibited to be used in cosmetic products and chemical that are allowed to be used by using group theory and analyze of functional groups that are often encountered in these chemicals are aimed. Molecule formulas related to chemical material of, 276 pieces chemicals that are prohibited to be used in cosmetic products and 65 pieces chemicals that are allowed, are used as the material. Two and three-dimension structures of these formulas are drawn and types and quantity of functional groups they contain are defined. And as a method, freeware (Free Trial) version of "Chem-BioOffice Ultra 13.0 Suite" chemical drawing program to draw two and three-dimension of formulas, "Campus-Licensed" version that are provided for use by our university of "Autodesk 3DS Max" for three-dimension drawings are used. In order to analyze geometric specifications of drawn molecules according to Group Theory and define type and quantity of available functional groups, Excel applications developed by Prof. Dr. Yasar Demir are used.

The relationship between epicardial adipose tissue thickness and oxidative stress parameters in patients with isolated polycystic ovary syndrome.

PURPOSE: The aim of this study is to evaluate the correlation between epicardial adipose tissue thickness and oxidative stress parameters in patients with polycystic ovarian syndrome. METHODS: The study included 35 patients with PCOS and 35 healthy women. Transthoracic echocardiography was used to measure the epicardial adipose tissue thickness (EATT) of all patients. For all patients, serum TOS, TAS, hs-CRP, and insulin levels were measured according to the literature, and the HOMA-IR values were calculated. Independent samples t-test, Pearson's correlation analysis, multivariate logistic regression analysis, and receiver operator characteristic curve (ROC) analysis were used in the statistical analysis. RESULTS: Between the patient group and the control group, EATT was significantly higher in the PCOS group compared to the control group (5.4 ± 1.4 mm and 3.9 ± 1.6 mm, respectively; p < 0.001). Similarly, TOS, TAS, and hs-CRP levels were significantly higher in the PCOS group compared to the control group (p < 0.01 for all). The correlation analysis showed a significant positive correlation between EATT and TAS and hs-CRP (r = 0.349, p < 0.01 and r = 0.352, p < 0.01, respectively). Multivariate regression analysis showed a significant correlation between PCOS and EATT, TAS, and diastolic blood pressure (p < 0.05 for all). CONCLUSIONS: Epicardial adipose tissue may play a major role in PCOS pathogenesis by leading to an increase in oxidative stress.

Modified docetaxel and cisplatin in combination with capecitabine (DCX) as a first-line treatment in HER2-negative advanced gastric cancer.

BACKGROUND: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. MATERIALS AND METHODS: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with capecitabine 1650 mg/m2 (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. RESULTS: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. CONCLUSIONS: DCX regimen offers prominent anti-tumor activity and considered to be effective first- line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

Purification of paraoxonase enzyme from the sera of patients with Behcet's disease and analyzing the effects of the drugs containing imuran (azathioprine), prednisolone (methylprednisolone) and colchium (colchicine).

In this study, serum samples from 50 patients with the diagnosis of Behcet's disease and 20 healthy volunteers were analyzed. The study consists of three parts. In the first part, paraoxonase (PON) activities were determined in the serum samples of 50 patients with Behcet's disease and 20 healthy people. In the second part, equal volumes of serum samples from 50 patients were pooled and PON enzymes were purified by using Sepharose-4B-L-tyrosine tyrosine-1-naphtylamine affinity column. Optimum temperature, optimum pH, Vmax and Km values of the pure enzymes were determined. The same purification procedure was also performed in the serum samples of 20 healthy people. Electrophoretic mobility was observed (via SDS-PAGE) in the PON enzymes that were purified from the serum samples of patients with Behcet's disease and healthy people. In the third part, in vitro effects of drugs containing azathioprine, methylprednisolone and colchicine that have already been used for the treatment of Behcet's disease were tested on the PON enzymes of the patients with Behcet's disease and control group. IC50 values and Ki constant values were measured and inhibition types were determined for the drugs containing azathioprine, methylprednisolone and colchicine that have already been used for the treatment of the Behcet's disease and demonstrate in vitro inhibition effects.

Purification and some properties of carbonic anhydrase from Elephas trogontherii (Steppe elephant) bone.

Four isoenzymes of carbonic anhydrase (CA) were purified from Elephas Irogontherii (steppe elephant) bone (approx 0.3-0.5 million years old) from different locations (outer peripheral, cytosolic, inner peripheral and integral) using Sepharose 4B-L-tyrosine sulphanilamide affinity chromatography and their kinetics properties were investigated and compared with known CA isoenzymes. The purification degree of CAs was monitored by SDS-PAGE. Purification fold for outer peripheral, inner peripheral, cytosolic and integral CA was 395.6, 652.8, 1091 and 429.3 and the molecular mass (as determined by gel filtration chromatography) was 37, 36, 35, and 39 kDa, respectively. The optimal temperature for isozymes was 10-20, 30, 30 and 60 degrees C and optimal pH- was between 7.5-11, 7.5-10, 7.5-10 and 7.5 respectively. K(m) values (at optimum pH and 20 degrees C) for p-nitrophenyl acetate as substrate were 4.83, 6.80, 4.525 and 3.86 mM and the Vmax values for the same substrate were 0.00097, 0.0149, 0.00249 and 0.00072 micromol/L*min, respectively. I50 values of isoenzymes for the inhibitors of CA - sulphanilamide, KSCN, acetazolamide and NaN3 were also determined.

Identification of protease from Euphorbia amygdaloides latex and its use in cheese production.

In this research, protease enzyme was purified and characterized from milk of Euphorbia amygdaloides. (NH4)2SO4 fractionation and CM-cellulose ion exchange chromatography methods were used for purification of the enzyme. The optimum pH value was determined to be 5, and the optimum temperature was determined to be 60 degrees C. The V(max) and K(M) values at optimum pH and 25 degrees C were calculated by means of Linewearver-Burk graphs as 0.27 mg/L min(-1) and 16 mM, respectively. The purification degree was controlled by using SDS-PAGE and molecular weight was found to be 26 kD. The molecular weight of the enzyme was determined as 54 kD by gel filtration chromatography. These results show that the enzyme has two subunits. In the study, it was also researched whether purified and characterized protease can be collapsed to milk. It was determined that protease enzyme can collapse milk and it can be used to produce cheese.