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OBJECTIVES: Various molecular changes in Fibroblast Growth Factor Receptor 4 gene that is known with its oncogenic transformation activity are known to result with different gene variants. To investigate the potential candidate variant of c.1162G>A that is known to have a role in cancer progression and retinal development in the tumor development and progression in patients diagnosed with retinoblastoma who had no RB1 gene mutation. MATERIAL&METHODS: c.1162G>A variant was bi-directionally sequenced using the Sanger sequencing in 49 retinoblastoma patients with no mutation in RB1 gene, in their first degree 13 healthy relatives, and in 146 individuals who were matched for sex and age in the control group. RESULTS: c.1162G>A variant was found positive in about 55% of patients, and mutation was detected in 54% of healthy relatives of the patients in our study. Mutation was detected in 48% individuals in the evaluation of the c.1162G>A mutation in healthy controls. Although c.1162G>A allele frequency was detected as 30% in general population in different databases, we demonsrated the frequency as 50% in Turkish population in our study. CONCLUSIONS: c.1162G>A allele was significantly higher in patients who were diagnosed with retinoblastoma before the month 24, and in advanced stage patients. In conclusion, these results suggested that c.1162G>A polymorphism might have a role in aggressive tumor progression, and in tumor development. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The most frequently diagnosed malignant ocular tumor of infancy and childhood is Retinoblastoma. Due to the mutation on the q14 on chromosome 13 causes the retinoblastoma. There are two types of basic gene mutations: genetic and sporadic. This cancer is initiated by RB1 mutation, responsible for the cell cycle regulation and genome stability in the cells of the retina in children under 5 years old. The retinoblastoma comprises about 40% inherited mutations, 10% of germline mutations of RB1 inherited from an affected parent, and 30% from de-novo germline mutations. MATERIAL&METHODS: Methylation of the RB1 gene on promoter region is unknown. The results obtained by MLPA analysis and sequence analysis were investigated for RB1 gene methylation in patients without RB1 mutation. The methylation determination is done with OneStep qMethyl-PCR Kit using a Real-Time PCR system. Methylation changes were investigated in peripheral blood samples of 60 patients with retinoblastoma, 18% of the patients (11/60) had bilateral and 82% of patients (49/60) had unilateral disease and 52 healthy controls. RESULTS: The mean methylation levels of 60 retinoblastoma patients and 52 healthy controls were 35% and 34%, respectively. Mann Whitney U test was compared between the patient and healthy controls and no statistically significant difference was detected between the two groups (p = 0.882). CONCLUSIONS: The promoter methylation levels in RB1 gene patients having familial history was believed to be large deletion and duplication and small indel absence mutations in the RB1 gene are not effective especially in the etiology of heritable retinoblastoma. [ABSTRACT FROM AUTHOR]

OBJECTIVES: According to TUIK-Turkish statistics, every year around 2790 OvarianCancer cases have been reported in Turkey. In order to have effective treatment of OvarianCancer as well as to follow the treatment process and to diagnose in early stage, there is need for disease-specific and sensitive biomarkers. This study aims to determine whether miR1260a and miR1260b molecules can be non-invasive biomarkers for sporadic and familial OvarianCancer cases compared with healthy controls. MATERIAL&METHODS: The expression levels of miR1260a and miR1260b were investigated in 150 patients with familial and sporadic OvarianCancer, and 100 healthy controls matched with patients for age, gender, ethnicity. RESULTS: It was seen that there was a statistically significant difference (p = 0.000) for expression levels of both miRNAs between the ovarian cancer patients and the healthy control group. According to healthy controls, it was found that the expression of miR-1260a and miR-1260b in OvarianCancer patients increased between 16.1-43.21 fold. STRING analysis was performed to understand the interactions of these molecules with other genes. It was found that miR-1260a has relationship with the ribosomal protein family known to have effect on the cellular stage of translation and miR-1260b is associated with the proteins CHEK2 and CDK4. CONCLUSIONS: The significant expression of miR-1260 and miR-1260b in peripheral blood lymphocytes of patients with ovarian cancer compared to healthy controls was shown first. The miR-1260 and miR-1260b molecules may be responsible for the etiology of ovarian cancer. It is thought that miR1260 and miR1260b molecules may be used as non-invasive biomarkers for diagnosis and prognosis of OvarianCancer. [ABSTRACT FROM AUTHOR]

OBJECTIVES: B-cell Non-Hodgkin's lymphoma (B-NHL) is one of the increasing cancer species over the world. DICER1 gene is a member of ribonuclease type III family and it plays a crucial role in biogenesis of miRNAs that regulates the gene expression in posttranscriptional level. In addition, studies have showed that the germline mutations in DICER1 exon 11 may be hazardous because they result in frame shift and exon 25 mutations play role in biogenesis of miRNA. BAFF is expressed by immune system cells such as monocytes, macrophages, dendritic cells, a subtype of T-lymphocytes and B-lymphocytes. Studies, that has been done till now, show high levels BAFF gene expression in malignant B-cells of patients with B-NHL. MATERIAL&METHODS: In our study, DICER1 c.+3473A>G (rs3742330) and BAFF c.-871C>T (rs9514828) single nucleotide polymorphisms in DNA materials, that were isolated from peripheral blood samples of 60 patients that were diagnosed B-cell non-Hodgkin's lymphoma and 30 healthy people matched with patients by age, sex and ethnicity, were examined with PCR-RFLP method. RESULTS: The detection of mutation existence in exon11 and 25 in DICER1 gene was examined by SANGER sequencing analysis. Chi-Square and Fisher tests were used for evaluation of the results between control and patient groups. No significant results were found between the two groups (p > 0, 05). CONCLUSIONS: In our study, the presence of mutations and polymorphisms related to DICER1 and BAFF genes was not found in patients with B cell non- Hodgkin lymphoma. It is thought that the disease may be related to other factors in the patient group in our study. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Ovarian cancer is one of the most lethal gynecological malignancy among women. Many miRNAs have been determined to act as oncogenes, tumor suppressors, and even modulators of cancer stem cells and metastasis. Based on the findings obtained from the microarray study previously, we conclude that the miR-16-5p, miR-17-5p, miR-638 might be important in the etiology of ovarian cancer and, should be validated in large patients cohorts with ovarian cancer and healthy control group. The aim of this study was to validate and determine whether three molecules, miR-16-5p, miR-17-5p, miR-638, are any biomarker in the early diagnosis and prognosis of patients with high-risk ovarian cancer. MATERIAL&METHODS: In the study, peripheral blood samples of 142 patients with ovarian cancer and 97 healthy controls which were ethnicity, age and gender matched were used. For gene expression analysis, Real-Time PCR methods were performed. RESULTS: miRNA gene expression levels increased more than 2 times in the patient groups compared to healthy controls and statistically significant (p<0.05). The p value obtained for each miRNA was determined as miR-16-5p, p<0.001; miR-17-5p, p<0.001, miR-638, p=0.005. In addition, we compared the clinical data of patients with miRNAs; There was a significant difference between the smoking status of the patients and the increased expression level of miR- 17-5p(p=0.007). In addition, miR-638 was expressed at significantly higher levels in distant metastasis-positive patients than in distant metastasis-negative patients(p=0.03). CONCLUSIONS: The findings suggest that these miRNAs were associated with metastasis. miR-16-5p, miR-17-5p, and miR-638 may be potential biomarkers to detect ovarian cancer and indicate its progression. [ABSTRACT FROM AUTHOR]

OBJECTIVES: miRNAs play an important role in the early diagnosis of ovarian cancer, prognosis and chemotherapy sensitivity. Our study was aimed to validate and investigate the expression of miR-423-5p and miR-664b-5p, among the miRNAs found to be important for ovarian cancer etiology in our previous study in the large cohorts of the peripheral blood of familial and sporadic ovarian cancer patients (150 cases) and healthy individuals 100 cases) MATERIAL&METHODS: Expression analysis was performed using the Real- Time PCR and the results were statistically evaluated with the SPSS v21.0. RESULTS: When the expression results of ovarian cancer patients were evaluated, it was found that the expression of miR-423-5p increased by 2.35 times and miR-664b-5p expression increased 2.47 times in ovarian cancer patients compared to the healthy control group. In the subgroup of ovarian cancer patients in comparison with the control group, the miR-423-5p expression level was higher in patients both ovarian and breast cancer diagnosis although the level of miR- 423-5p was found as decreased in the patients with diagnosed both ovarian and endometrial carcinoma. In the subgroup of ovarian cancer patients in comparison with the control group, the miR-664b-5p expression level was 1.95 fold higher in patients both ovarian and breast cancer diagnosis although the level of miR-664b- 5p was found 0.27 fold decreased in the patients with diagnosed both ovarian and endometrial carcinoma. CONCLUSIONS: The increased expression level of both miR-423-5p and miR- 664b-5p suggests that they may be a possible biomarker for ovarian carcinoma. The decreased miR-664b-5p expression might be a biomarker for BRCA associated cancers. [ABSTRACT FROM AUTHOR]

The expression of the FOXO3a gene, and its role in acute myeloid leukemia and chronic myeloid leukemia were investigated in the present study. We analyzed 101 patients diagnosed with AML, and CML, and 34 healthy individuals. The cDNAs obtained from the blood samples of patients, and healthy controls were analyzed by the Real-Time PCR using specific primers, and probes for the FOXO3a and ACTB genes. A 50-fold decrease in FOXO3a expression levels was detected in CML patients, and 8-fold decrease was detected in AML patients compared with the levels in the healthy controls. Significant difference was detected between the patients, and healthy controls (p= 0.000). However, there was no statistically significant difference between the CML and AML patient groups for FOXO3a expression level. The decrease in FOXO3a gene expression in all CML (51/51), and AML patients (50/50) was remarkable. The FOXO3a gene expression was downregulated in 91.8% (124/135) of all individuals included in the study. The present study might be an important report on emphasizing the expression profiles of FOXO3a gene in AML, and CML patients. Whether the FOXO3a gene is a valuable biomarker for early diagnosis and prognosis in CML and AML patients need to be investigated in larger study groups. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disease caused by a mutation in the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) gene resulting in progressive systemic skeletal dysplasia. There is currently no effective treatment available for this skeletal condition. Thus, the development of a new therapy stands as an unmet challenge in reversing or alleviating the progression of the disease. Our research, which could be a game-changer, hypothesizes that ex vivo lentiviral (LV) gene therapy (GT) could produce the supraphysiological level of active GALNS enzyme by hematopoietic stem cells (HSCs) transduced with LVs carrying the native GALNS gene under two different promoters (CBh and COL2A1), impacting bone and cartilage abnormalities in MPS IVA. We conditioned newborn knock-out (Galns -/- ) MPS IVA mice with busulfan and intravenously transplanted LV-modified HSCs isolated from the bone marrow of Galns -/- donor mice. Transplanted mice were autopsied at 16 weeks, and tissues were collected to assess the therapeutic efficacy of modified HSCs in MPS IVA mice. Although HSC-LV-CBh-hGALNS provided a higher GALNS enzyme activity in plasma, HSC-LV-COL2A1-hGALNS stably corrected heart and bone abnormalities better under a low level of GALNS enzyme. Our findings suggest that ex vivo LV-GT may potentially treat MPS IVA.

Mucopolysaccharidosis type IVA (MPS IVA) is caused by a deficiency of the galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme responsible for the degradation of specific glycosaminoglycans (GAGs). The progressive accumulation of GAGs leads to various skeletal abnormalities (short stature, hypoplasia, tracheal obstruction) and several symptoms in other organs. To date, no treatment is effective for patients with bone abnormalities. To improve bone pathology, we propose a novel combination treatment with the adeno-associated virus (AAV) vectors expressing GALNS enzyme and a natriuretic peptide C (CNP; NPPC gene) as a growth-promoting agent for MPS IVA. In this study, an MPS IVA mouse model was treated with an AAV vector expressing GALNS combined with another AAV vector expressing NPPC gene, followed for 12 weeks. After the combination therapy, bone growth in mice was induced with increased enzyme activity in tissues (bone, liver, heart, lung) and plasma. Moreover, there were significant changes in bone morphology in CNP-treated mice with increased CNP activity in plasma. Delivering combinations of CNP and GALNS gene therapies enhanced bone growth in MPS IVA mice more than in GALNS gene therapy alone. Enzyme expression therapy alone fails to reach the bone growth region; our results indicate that combining it with CNP offers a potential alternative., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Glycosaminoglycans (GAGs) are sulfated polysaccharides comprising repeating disaccharides, uronic acid (or galactose) and hexosamines, including chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate. Hyaluronan is an exception in the GAG family because it is a non-sulfated polysaccharide. Lysosomal enzymes are crucial for the stepwise degradation of GAGs to provide a normal function of tissues and extracellular matrix (ECM). The deficiency of one or more lysosomal enzyme(s) results in the accumulation of undegraded GAGs, causing cell, tissue, and organ dysfunction. Accumulation of GAGs in various tissues and ECM results in secretion into the circulation and then excretion in urine. GAGs are biomarkers of certain metabolic disorders, such as mucopolysaccharidoses (MPS) and mucolipidoses. GAGs are also elevated in patients with various conditions such as respiratory and renal disorders, fatty acid metabolism disorders, viral infections, vomiting disorders, liver disorders, epilepsy, hypoglycemia, myopathy, developmental disorders, hyperCKemia, heart disease, acidosis, and encephalopathy. MPS are a group of inherited metabolic diseases caused by the deficiency of enzymes required to degrade GAGs in the lysosome. Eight types of MPS are categorized based on lack or defect in one of twelve specific lysosomal enzymes and are described as MPS I through MPS X (excluding MPS V and VIII). Clinical features vary with the type of MPS and clinical severity of the disease. This chapter addresses the historical overview, synthesis, degradation, distribution, biological role, and method for measurement of GAGs., (Copyright © 2024. Published by Elsevier Inc.)

MicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi's sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi's sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi's sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b-3p) which have not been described in the literature in the context of Kaposi's sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi's sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi's sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tuncer, Celik, Akdeniz Odemis, Kılıc Erciyas, Sukruoglu Erdogan, Avsar, Kuru Turkcan and Yazici.)

Purpose: The purpose of this study was to evaluate the soluble Apo-2L (sApo-2L) levels in the ascitic fluid and to study its potential in detecting malignant ascites and soluble CD200 (sCD200,sOX-2) levels so as to predict its clinical usage for detecting stage 4 metastatic endometrial, ovarian and breast cancer in serum samples., Methods: Ascitic fluid from 53 and blood from 25 subjects without known malignancy on admission were collected. There were 14 breast cancer (BC), 17 ovarian cancer (OC) and 19 endometrial cancer (EC) patients diagnosed later on. Blood samples for sApo-2L, sCD200, liver function tests and CEA, CA-19.9 and CA-125 were always taken and assayed in the morning., Results: Significantly low levels of sApo-2L were observed in peritoneal fluid from OC and EC patients compared to benign peritoneal fluid from control individuals. Positive correlation was observed between sApo-2L and aspartate aminotransferase (AST) in benign peritoneal fluid and sCD200, and creatinine and sCD200 and platelets in OC patients; also, sCD200 and CEA in EC patients and sCD200 and blood urea nitrogen (BUN) in healthy subjects., Conclusions: Our data indicate that low proteomics pattern of sApo-2L but not sCD200 is a good biochemical marker. Further decline in the level of sApo-2L was seen in EC compared to OC. Since higher levels of sApo-2L were seen with higher levels of AST, the liver might be involved in its metabolism. The positive correlation detected between sCD200 and creatinine, platelets, CEA and BUN needs to be elucidated.

Pro-inflammatory factors regulated by TRAIL in vivo may lead to the development of novel therapeutic strategies for diseases as diverse as infection, autoimmunity and allergy. In this study we aimed to investigate the relationship between IFN treatment response, HCV viral load and sApo 2L levels. Eleven HCV-treatment naive HCV-infected patients were treated with pegIFN alfa-2a. Intensive serum circulating Apo 2L levels were monitored at study visits on day 0 (pretreatment), and in weeks 4, 6 and 12. HCV-RNA and sApo 2L levels decreased gradually with PegIF-alfa 2 treatment and the differences were significant between day 0 and week 4 (p 0.001, p 0.005 and p 0.01, p 0.005 respectively); between day 0 and week 12 (p 0.001, p 0.005 and p 0.001, p 0.000 respectively); between weeks 6 and 12 (p 0.01, p 0.05 and p 0.01, p 0.05 respectively). We suggest that decreased levels of circulating Apo 2L may reflect its increased binding to its ligand expressed on hepatocytes or lymphocytes under the influence of PegIFN treatment.

Background: CD200 (OX-2) is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum (s OX-2), which acts to regulate inflammatory and acquired immune responses., Material and Methods: We planned this study to evaluate the sOX-2 levels of type 2 diabetic foot (group B), and compare it with that of healthy controls (group A). The patient group had the following values: DM period: 27.9±10.3 year [mean ±SD], HbA1c: 9.52±2.44% [mean ±SD]., Results: Blood samples for sCD200 measurement were always taken in the morning between 8 and 10 A.M.. The results were reported as means of duplicate measurements. Concentrations of sOX-2 in the serum samples were quantified using an ELISA kit. Serum hs-CRP levels were measured using an hs-CRP assay kit. The sOX-2 level in group B was 173.8±3.1 and in group A was 70.52±1.2 [p<0.0001). In subgroup analysis of T2DM-DFI patients, we noticed that sOX-2 levels were higher in WGS (Wagner grading system) I and II patients than in WGS III and IV patients. The HbA1c, BUN, creatinine, hs-CRP levels, and sedimentation rates were higher in the patient group (p<0.0001, p<0.001, p<0.001, p<0.005, and p<0.0001, respectively)., Conclusions: We suggest that there are vascular, immunologic, and neurologic components in DFI, whereas autoimmune diseases and inflammatory skin disorders have only an immunologic component. This is possibly evidence of a pro-inflammatory effect seen in DFI as a vascular complication.