Mustafa Yildirim

The role of High Mobility Group Box 1 (HMGB1) in colorectal cancer

Background HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in colorectal carcinoma. Material/Methods The study included 110 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection and biopsy in Antalya Education and Research Hospital between 2008 and 2012. HMGB1 expression was examined via immunohistochemical method. Results HMGB1 expression was evaluated as negative in 32 (44.4%) of the patients and as positive in 40 (55.6%) patients. There was no relation between the HMGB1 expression and sex, age, tumor invasion depth, and histological type. However, a significant relation was detected between the HMGB1 expression and lymph node status, metastasis status, and stage (p:<0.001, p:<0.001, p:<0.001, respectively). Similar results were obtained for the relations between the HMGB1 and histological grade, perineural invasion, lymphovascular invasion, and lymphocytic response (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). Conclusions The results of our study demonstrate that HMGB1 overexpression has a significant role in tumor progression (especially migration of tumor cells) and tumor ability to metastasize in colorectal cancers; thus, it corroborates the idea that it might be an important prognostic factor.

Prognostic Significance of Basic Laboratory Methods in Non- Small-Cell-Lung Cancer

BACKGROUND In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. MATERIALS AND METHODS Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. RESULTS A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). CONCLUSIONS Molecular methods have been changing rapidly in todays world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods.

Loss of tight junction proteins (Claudin 1, 4, and 7) correlates with aggressive behavior in colorectal carcinoma

Background Tight junction proteins in the cell organize paracellular permeability and they play a critical role in apical cell-to-cell adhesion and epithelial polarity. Claudins are major integral membrane proteins of tight junctions, especially Claudin 1, 4, and 7, which are known as the impermeability Claudins. In this study, we investigated the importance of loss of Claudin 1, 4, and 7 expression, and their relation to tumor progression in colorectal cancer patients. Material/Methods Loss of Claudin 1, 4, and 7 expression was examined by immunohistochemical method in 70 patients diagnosed with colorectal cancer. Cases with loss of Claudin expression in <1/3 of tumor cells were classified as mild loss, whereas cases with loss of Claudin expression ≥1/3 of tumor cells were classified as moderate-to-marked loss in order to evaluate the relation between loss of Claudin 1, 4, and 7 expression and clinicopathologic data. Results The severe suppression of Claudin 1, 4, and 7 expression was found to be significantly related to the depth of tumor invasion, positive regional lymph nodes, histological grade, lymphovascular invasion, perineural invasion, and lymphocytic response. Additionally, severity of loss in Claudin 4 expression was found to have a relation with distant metastasis. Conclusions Claudin 1, 4, and 7 are important building blocks of paracellular adhesion molecules. Their decreased expression in colorectal cancer seems to have critical effects on cell proliferation, motility, invasion, and immune response against the tumor.

Non-Hodgkin lymphoma and pesticide exposure in Turkey.

BACKGROUND Non-Hodgkin lymphoma (NHL) is a solid tumour of lymphocytes, important elements in the immune system. According to 2006 data, in Turkey the incidence was 6.5 per 100,000 in males, and 4.4 in females. The relationship between the use of pesticides and development of NHL has been extensively investigated in many studies, and it has been demonstrated that the risk of NHL is increased by exposure to such compounds. Antalya is a region of intensive agricultural activity. In this study, the relationship between the incidence of lymphoma in Antalya and the amount of pesticides employed was investigated. MATERIALS AND METHODS The study used data from 1995 to 2010 on the patients from the databank of TR Ministry of Health, Antalya Provincial Health Directorate, Cancer Registration Center and the patients who were histopathologically diagnosed with NHL during these years. RESULTS The relationship between the amount of pesticide used and the incidence was studied with the Spearman correlation analysis and the p value was found as 0.05. The correlation coefficient was 0.497. An increase in the NHL incidence over the years was identified, with a 2.42-fold increment found from 1995 to 2005 and a 2.77 fold elevation from 1995 to 2010. The use of pesticides increased 1.89 fold over the same period. CONCLUSIONS Our study investigated the relationship of the pesticides used with NHL patients diagnosed during the same year. Since the time elapsing after exposure to pesticides until the development of cancer is not clear, no comparison can be made at present. We believe that the increase in use of pesticides since 1995 may be associated with the increase in the incidence of NHLand therefore that further studies on the issue including measurements of serum pesticide levels, are required.

Effect of Adhesive Thickness on Transverse Low-Speed Impact Behavior of Adhesively Bonded Similar and Dissimilar Clamped Plates

This study investigates the effect of adhesive thickness on the transverse low-speed impact behavior of adhesively bonded similar (Al–Al, St–St) and dissimilar (Al–St, St–Al) clamped plates using the three-dimensional explicit finite element method. The contact force and plastic dissipation histories are studied for various impact energies and adhesive thicknesses. The residual plastic strains in both adhesive layer and the two plates increase with increasing impact energy. The central transverse deflections become maximal in Al–Al, moderate in Al–St, St–Al and minimal in St–St bonded plates. The back plates of all configurations deform noticeably. The stiff steel plate results in a shorter contact time, a higher contact force, a lower plastic dissipation energy and the impact energy is absorbed by the adhesive layer rather than by the front and back plates, whereas Al–Al plates dissipate it as much as the adhesive layer. The total contact time gets longer with increasing impact energy. St–St bonded plates experience larger damaged regions in both plates and adhesive layer than those in Al–Al bonded plates. The adhesive thickness has only a minor effect on the magnitude of the contact force and contact time, whereas a stiffer (St) front or back plate affects considerably the contact force and total contact time. Increasing the adhesive thickness decreases apparently residual plastic strains in plates and the adhesive layer, the central transverse deflection. A thick adhesive layer results in a minor increase in the kinetic energy of impactor, a shorter total contact time, a lower plastic dissipation energy and smaller damaged areas on the back faces of the lower plate, along the adhesive–plate interfaces.

Prognostic significance of p53 in gastric cancer: a meta- analysis.

BACKGROUND Gastric cancer is one of the frequently seen cancers in the world and it is the second most common reason for death due to cancer. The prognostic role of expression of p53 detected by immunohistochemistry in gastric cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. MATERIALS AND METHODS We systematically searched for studies investigating the relationships between expression of p53 detected by immunohistochemistry and prognosis of gastric cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival and disease-free survival. RESULTS A total of 4.330 patients from 21 studies were included in the analysis. Our results showed tissue p53 overexpression in patients with gastric cancer to be associated with poor prognosis in terms of overall survival (HR, 1.610; 95% CI, 1.394 -5.235; p: <0.001). Pooled hazard ratio for disease free survival showed that p53 positivity or negativity were not statitistically significant (HR, 1.219; 95%CI, 0.782-1.899; p:0.382). CONCLUSIONS The present meta-analysis indicated overexpression of p53 detected by immunohistochemistry to be associated with a poor prognosis in patients with gastric cancer.

Transverse Low-Speed Impact Behavior of Adhesively Bonded Similar and Dissimilar Clamped Plates

This study concentrates on the transverse low-speed impact behavior of adhesively bonded similar and dissimilar clamped plates using the three-dimensional explicit finite element method. The contact force and plastic dissipation histories of the adhesively bonded dissimilar plates, such as aluminum–aluminum (Al–Al), aluminum–steel (Al–St), steel–aluminum (St–Al) and steel–steel (St–St) layered structures, were studied for different values of the impactor mass, radius and velocity (impact energies). The residual plastic strains in both adhesive layer and plates increased with increasing impact energies. The impactor radius had only a minor effect on the contact force histories for all configurations. The peak transverse deflection in the impact region was maximal in Al–Al, decreased in Al–St, St–Al plates and became minimal in St–St bonded plates. Impact effect was evident in the back plates of all four configurations. Al–Al plates dissipated impact energy as much as the adhesive layer, whereas the adhesive layer rather than plates absorbed the impact energy in Al–St, St–Al and St–St bonded plates and this state became evident in the St–St bonded plates. The number and locations of the steel plates considerably affected impact force history, impact time as well as the plastic dissipation level; thus, the contact force increased, the contact time shortened and the dissipated energy decreased. As the impact energy was increased the impact period got longer. Damage areas in the adhesive layer were minimal in Al–Al bonded plates but maximal in St–St bonded plates.

Multiple Myeloma: Relationship to Antioxidant Esterases

Objective: To investigate the status of the oxidant/antioxidant balance in patients with multiple myeloma compared to healthy controls. Materials and Methods: This study was conducted on 40 multiple myeloma patients and 40 healthy controls of matched age and sex. Serum total thiol, oxidative stress index (OSI), total oxidant status (TOS), and total antioxidant status (TAS) were measured using colourimetric methods; paraoxonase-1 and arylesterase enzyme activities were also quantified. Results: Serum paraoxonase-1 and arylesterase activities and total thiol levels were significantly lower (p = 0.0001, p = 0.036 and p < 0.0001, respectively), whereas TOS and OSI levels were significantly higher (p < 0.0001 for both parameters) in multiple myeloma patients compared to controls. However, no significant differences in TAS were identified when the two groups were compared. Conclusions: Our findings indicate an impaired oxidative/antioxidative balance in multiple myeloma. We recommend further studies with larger groups to investigate the possible relationship between oxidative stress and the aetiopathogenesis of multiple myeloma.

Esophageal cancer, gastric cancer and the use of pesticides in the southwestern of Turkey.

BACKGROUND Esophageal and gastric cancer generally have a poor prognosis and may share common risk factors. It has been demonstrated that the pesticide usage may contribute to development of many cancer types. In this study, the relation between amount of pesticides used in agriculture and esophageal and gastric cancer incidence was researched. MATERIALS AND METHODS Findings from the data bank of the Ministry of Health Provincial Health Directorate Cancer Records Center between the years of 1998-2010 were used. All patients who were diagnosed with gastric and esophageal cancer histopathologically were included. Data for annual pesticide usage were obtained from Provincial Agriculture Directorate for the same time period. Statistical analysis was performed using the Spearman test. RESULTS One thousand eight hundred and ninety-six patients were involved in the study, 1,233 males (65%) and 663 females (35%), 230 with esophageal cancer (12.1%) and 1,666 with gastric cancer (87.9%). No statistically significant relation was apparent between pesticide amount used and esophageal cancer (p: 0.87). CONCLUSIONS In our study, there was no relationship between pesticide usage and esophageal or gastric cancer. However, the time between pesticide usage and cancer development was not known, qualifying the comparison.

Free Vibration Analysis and Optimal Design of a Clamped-free Single Lap Joint with Unidirectional Laminated Narrow Plates

In this study the three-dimensional free vibration analysis and modal stress analysis of an adhesively bonded composite single lap joint having unidirectional laminated narrow plates and subjected to clamped-free condition are carried out. The first ten natural frequencies and mode shapes of the adhesive joint are considered. The effects of fiber angle, fiber volume fraction, overlap length, and plate thickness on the natural frequencies and the mode shapes of the adhesive joint are investigated using the back-propagation artificial neural network (ANN) method. A series of free vibration and stress analyses is carried out using the finite element method for random values of the fiber angle, the fiber volume fraction, the overlap length, and the plate thickness so that the proposed ANN model can be trained successfully to predict the first ten natural frequencies as well as the corresponding modal strain energies. The ANN models indicate that the fiber angle is a more dominant parameter than the fiber volume fraction on the natural frequencies and the corresponding mode shapes of the adhesive joint, and the plate thickness and the overlap length are important geometrical design parameters whereas the adhesive thickness has a minor effect. In addition, genetic algorithm is combined with the present ANN model to achieve the optimal joint design which satisfies maximum natural frequency and minimum modal strain energy conditions for each natural frequency and mode shape of the adhesively bonded composite single lap joint.