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Background SMAD4 is a potent tumor suppressor. SMAD4 loss increases genomic instability and plays a critical role in the DNA damage response that leads to skin cancer development. We aimed to investigate SMAD4 methylation effects on mRNA and protein expression of SMAD4 in cancer and healthy tissues from patients with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and basosquamous skin cancer (BSC). Methods and results The study included 17 BCC, 24 cSCC and nine BSC patients. DNA and RNA were isolated from cancerous and healthy tissues following punch biopsy. Methylation-specific polymerase chain reaction (PCR) and real-time quantitative PCR methods were used to examine SMAD4 promoter methylation and SMAD4 mRNA levels, respectively. The percentage and intensity of staining of the SMAD4 protein were determined by immunohistochemistry. The percentage of SMAD4 methylation was increased in the patients with BCC (p = 0.007), cSCC (p = 0.004), and BSC (p = 0.018) compared to the healthy tissue. SMAD4 mRNA expression was decreased in the patients with BCC (p˂0.001), cSCC (p˂0.001), and BSC (p = 0.008). The staining characteristic of SMAD4 protein was negative in the cancer tissues of the patients with cSCC (p = 0.00). Lower SMAD4 mRNA levels were observed in the poorly differentiated cSCC patients (p = 0.001). The staining characteristics of the SMAD4 protein were related to age and chronic sun exposure. Conclusions The mRNA expression level of the SMAD4 gene and its changing protein expression are particularly important for the early diagnosis and prognosis of cSCC. Trial Registration The name of the trial register: SMAD4 Methylation and Expression Levels in Non-melanocytic Skin Cancers; SMAD4 Protein Positivity.

Cancer is the name given to all malignant tumors, the main reason for which is uncontrolled growth, and the tumor, which has become a mass as a result of uncontrolled cell proliferation, also attacks the surrounding cells and envelops the whole body (metastasis) in the later stages of the disease. Although cancer is an important health problem, it is not a common disease in childhood. On the other hand, statistics show that cancer affects one in three adults, causes up to 20% of all deaths, and covers about 10% of treatment costs in developed countries. Although it is known that cancer develops under the influence of genetic and environmental factors, environmental factors are more prominent in the formation of some types of cancer. Breast cancer is one of the cancer types known to have tumor suppressor genes in its etiology. These tumor suppressor genes are BRCA1 and BRCA2 genes. Studies have shown that these two genes are particularly effective in the development of familial breast cancers. These types of cancers occur much earlier than non-familial cancers. The research, two genes; It has shown that it is especially effective in the development of familial breast cancers.

Oxidative stress plays a role in the pathogenesis of bone loss, causing low bone mineral density (BMD) and associated osteoporotic fractures. In our study, we aimed to investigate the relationship of SOD1 50-bp insertion( Ins)/deletion( Del) polymorphism that is involved in oxidative stress metabolism, Cu and Zn element concentrations, and plasma viscosity level, with postmenopausal osteoporosis and related vertebral fractures. The study included 167 voluntary individuals. The 50- bp Ins/Del polymorphism of SOD1 was determined by allele-specific PCR. Plasma Cu and Zn levels were measured by atomic absorption spectrophotometry (AAS). The plasma viscosity was determined using the Harkness Capillary Viscometer device. In our study, the distribution of SOD1 promoter 50-bp Ins/Del polymorphism did not indicate a significant difference between the groups and in postmenopausal osteoporosis patients with and without fractures (p > 0.05). The Ins/Ins genotype was found to be common in individuals in both groups. The Cu and Zn levels of the study group were found to be between the normal reference values (p > 0.05). It was determined that plasma viscosity increased significantly in the group of osteoporotic patients and in patients with postmenopausal osteoporosis with fractures (p < 0.01). In addition, plasma viscosity was found to significantly increase in patients with Ins/Ins genotype and fractures (p < 0.01). Postmenopausal osteoporosis and associated vertebral fracture were found not to be directly related to SOD1 50-bp polymorphism and Cu and Zn element levels. Plasma viscosity levels were found to increase due to the increase in oxidative stress products. Further studies are needed to clarify the roles and relationships of SOD genes and trace elements in the development of postmenopausal osteoporosis and vertebral fracture.

Survivin is a bifunctional protein which regulates cell division and inhibits apoptosis. Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Expression of survivin has been shown to be responsible for apoptosis and resistance to ionizing radiation. The aim of the present study was to investigate the association between −31 G/C promoter polymorphism, survivin protein and glial tumour grading, and to compare survivin versus Ki-67 as a marker. In this study, DNA was isolated from paraffin-embedded sections of 29 patients diagnosed with glial tumours. Survivin gene promoter −31 G/C polymorphism was investigated using PCR-RFLP. For the analysis, 10 µm sections were stained with survivin protein and Ki-67 antibody. Immunohistochemical staining was performed. Survivin showed a positive correlation with Ki-67 (r = 0.604; p = 0.001). The tumour grades correlated with survivin; however, the relationship was not statistically significant (r = 0.345; p > 0.05). We found a significant correlation between tumour grades and Ki-67 (r = 0.663; p

WOS:000461542500005 PubMed ID: 30880750 Background and Aim of Study: The role of E-cadherin (CDH1) gene-160 C>A (rsl 6260) promoter polymorphism in colorectal cancer (CRC) still remains inconclusive. The aim of this study is to investigate the associations between the CDH1 -160 C>A polymorphism with the susceptibility and clinicopathological development of CRC in the Turkish patients. To our knowledge, this is the first report examining the role of CDH1 polymorphism in Turkish CRC patients. Materials and Methods: A total of 92 colorectal carcinoma cases (including 62 colon and 30 rectal cancer patients) and the corresponding adjacent normal tissues as controls were studied. The polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Clinicopathological features including patient's age, gender, tumor stage, and tumor location (colon/ rectum) were compared statistically with the polymorphism status. Results: There was no significant difference in both genotype and allele frequencies of the CDH1 polymorphism between colorectal tumor cases and normal samples (P = 0.472 and 0.508, respectively). Furthermore, no significant associations were observed between the CDH1 polymorphism status and age, gender, tumor stage, and tumor location of the colorectal tumor cases (all P>0.05). Conclusions: These results indicate that CDH1 -160 C>A polymorphism does not contribute to the genetic susceptibility of CRC and the polymorphism may not be a direct effect on the progression of the disease in Turkish CRC patients. Istanbul University Cerrahpasa Medical Faculty Hospital, Istanbul, Turkey This study was financially supported by Istanbul University Cerrahpasa Medical Faculty Hospital, Istanbul, Turkey

Background/aim: Activity of the prestin gene may have a role in the pathogenesis of salicylate-induced ototoxicity. We investigated DNA methylation for prestin gene exon 1 in salicylate-injected guinea pigs.Materials and methods: Fifteen guinea pigs (30 ears) underwent audiological evaluation including 1000 Hz probe-tone tympanometry and a distortion product otoacoustic emission (DPOAE) test. The animals were randomly divided into three groups. Groups 2 (8 ears) and 3 (14 ears) were injected with intramuscular saline and sodium salicylate (200 mg/kg), respectively twice daily for 2 weeks. Group 1 (8 ears) received no injection. DPOAE measurements were performed at baseline; after 1, 2, 4, and 8 h (acute effect); and after 1 and 2 weeks (chronic effect). After audiological measurements, the animals were sacrificed for DNA isolation.Results: While a significant decrease (P < 0.01) was found for the acute effect in all frequencies in Group 3 according to baseline measurements, there was no difference in terms of chronic effect. DNA methylation increased during the acute phase of salicylate administration, whereas it returned to initial levels during the chronic phase.Conclusion: Salicylate-induced changes in DPOAE responses may be related to prestin-gene methylation. These results may have important implications for salicylate ototoxicity.

Coronary artery disease (CAD) is one of the frequent cardiovascular mortality causes in the world. Common risk factors explain only about half the risk of CAD. The healthy familial predisposition to CAD, combined with advances in genetic analysis, has led to a number of studies in recent years making an effort to identify the genetic factors that influence the risk. The approach taken by most studies was to examine the association of naturally occurring genetic polymorphisms in candidate genes with risk of or severity of CAD. Endothelial nitric oxide synthase (eNOS) is important for vascular and tissue protection and is found in endothelial cells that encompass the entire vasculature, including the vessels in the heart. Nitric oxide (NO) is produced in a catabolic reaction in the endothelial cells, neurons, glia and macrophages by nitric oxide synthase (NOS) isoenzymes. eNOS is a subgroup of this family of enzymes that catalyses the production of nitric oxide (NO) from L-arginine and oxygen, which leads to vascular relaxation by activating the guanylate cyclase. This finally induces smooth muscle relaxation. The aim of this study was to investigate the allelic frequency and the genotypic distribution of the variable number of tandem repeat 27 (27 VNTR) gene polymorphism in intron 4 of the eNOS (eNOS 4a/b) gene in Thrace region, to compare CAD patients with appropriate healthy controls and to correlate the genetic findings with CAD subtypes. The study group included 281 (153 subjects with CAD and 128 controls) patients. The eNOS polymorphism was identified with a polymerase chain reaction. Genotypes were defined as aa, ab and bb according to the presence of a and b alleles. In this case–control study, we found that there was sensible correlation between eNOS gene intron 4a/b VNTR polymorphism and the risk of CAD in Thrace region of Turkey. However, there was no major difference for the genotype distribution and the allelic frequency among the CAD subtypes. Further studies on the interaction of such genes are needed to clarify the association between eNOS 4a/b polymorphism and CAD patients.

Nanoparticle research is currently an area of intense scientific research, due to a wide variety of potential applications in biomedical, optical, and electronic fields. Nanoparticles are of great scientific interest as they are effectively a bridge between bulk materials and atomic or molecular structures. Superoxide dismutase (SOD), Glutamine synthetase (GS), Catalase (CAT) are some of the defense mechanisms against cellular oxidative stress, especially against free oxygen radicals. In this study, we aimed to investigate that Ag, SiO2 and ZnO nanoparticles affect cancer cell lines (HT-29) and relationship between SOD, GS and CAT. We investigated that alterations in gene expressions of SOD, GS and CAT caused by exposure to nanoparticles in HT-29 cells. The difference between the Ct values (ΔCt) of the gene of interest was calculated for each experimental sample. As a result of Ag, SiO2 and ZnO nanoparticle application, there was a 2-fold increase in SOD and CAT expression in the first 24 hours compared to control. As a result of 48 hours of application, it was observed that Ag nanoparticles caused 4-fold increase in SOD and 6-fold statistically significant increase in CAT and GS expression of SiO2 nanoparticles. Consequently, after 48 hours of nanoparticle application, SiO2, CAT and GS expression were more effective than 24-hour application. Our results suggest that nanoparticles may cause increased oxidative stress in colon cells and may have therapeutic properties by affecting cancer cells in these aspects.

Genetic determinations of human essential (primary) hypertension are discussed by reviewing the candidate genes. Angiotensinogen (AGT) gene, coding the precursor of potent vasoactive hormone angiotensin II, in renin-angiotensin-system (RAS) has been reported to be associated with the onset of hypertension. The aim of this study was to investigate the role of variation in the 174 and 235 sites in exon 2 in AGT gene in the developing of primary hypertension in Turkish subjects from Trakya region. Our study involved 136 subjects, 84 hypertensive and 52 gender and age matched controls. T174M and M235T polymorphisms of the AGT gene were investigated using allele specific polymerase chain reaction (PCR) assay, and restriction fragment length polymorphism (RFLP). The frequency of genotypes of the variant T174M in the patients with primary hypertension was TT=%73.8, TM=%26.2, and MM=%0.0, that were not different from the controls TT=%73.1, TM=%25.0, and MM=%1.9. And for M235T; the genotype frequencies in patients with primary hypertension were MM=%19.0 MT=%54.8, and TT=%26.2, which were again not significantly different from that of the controls MM=%26.9 MT=%46.2 and TT=%26.9. In conclusion this study shows that T174M and M235T variants of the AGT gene were not associated with primary hypertension in Turkish subjects from Trakya region.

Hypertension is immensely common in Turkish subjects in Trakya region. The renin angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and appears important in the pathogenesis of hypertension. Angiotensin I-converting enzyme (ACE) is a key component of RAS. Insertion/Deletion (I/D) polymorphism of the ACE gene has been implicated in the pathogenesis of cardiovascular diseases. In addition to this, the association between ACE I/D polymorphism and hypertension is controversial, when numerous studies have addressed the role of ACE I/D polymorphism in the development of hypertension, there were different studies showed that no correlation has been found between ACE I/D polymorphism and in the development of hypertension. The objective of our study was to investigate the relation between the ACE gene I/D polymorphism and primary hypertension in Turkish subjects in Trakya region. We analyzed the ACE gene I/D polymorphism in 79 patients with primary hypertension as a primary hypert...

The low plasma nitric oxide concentrations and reduced vascular reactivity are considered major proatherogenic mechanisms in cardiovascular diseases. The present study aimed to assess the allelic frequency and the genotypic distribution of the Glu298Asp gene polymorphism at exon 7 of endothelial nitric oxide synthase (eNOS) gene in Turkish ischemic stroke patients compared to appropriate healthy controls, and to correlate the genetic findings with stroke subtypes. The study population included 146 (75 males, 71 females) patients with ischemic stroke which were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and 133 (34 males, 99 females) healthy subjects. The eNOS polymorphism was identified with a PCR followed by RFLP with the restriction enzyme BanII. Genotypes were defined as GG, GT, and TT according to the presence of the G and T alleles. In this case-control study, we did not find any significant difference in either the genotypic distribution or allelic frequency of Glu298Asp gene polymorphism between the patients and the controls. In addition, there was also no significant difference for the genotype distribution and the allelic frequency among the stroke subtypes. The results suggested the lack of the association between the Glu298Asp gene polymorphism and ischemic stroke or subtypes of ischemic stroke in the Turkish population.

Recent studies suggest that infection with high risk human papillomavirus (HPV) is a common event in colon tumors. Infection by oncogenic HPV may result in functional inactivation of the p53 protein in absence of mutations. Thus far no studies have been made to examine the frequency of p53 mutations in HPV-associated colon cancer. The purpose of this study was to investigate the interrelationship between p53 mutations and HPV infection. The 'hot-spot' region of the p53 gene for mutations was analyzed by PCR-SSCP and direct sequencing in HPV-positive tumor samples. Only 2 mutations were identified in 56 samples. This rate was much lower than reported for sporadic colon tumors. Our results indicate an inverse relationship between p53 mutations and HPV infection and suggest that p53 inactivation caused by HPV infection may play a role in the pathogenesis of colon cancer.