Diagnostic value of serum autotaxin level in colorectal cancer.

Background: Autotaxin (ATX) is a nucleotide enzyme linked to cell growth, differentiation and migration. This study investigated serum levels of ATX in colorectal cancer (CRC). Methods: The study involved stage I-III CRC diagnosed between December 2020 and 2021, excluding those with neoadjuvant or adjuvant therapy, or metastasis. Healthy volunteers were controls. Serum ATX levels were measured by ELISA and compared. Results: This study included 129 patients (91 in the patient group and 38 in the control group). The optimal cutoff value of ATX for CRC was 169.98 ng/ml, and sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 91.2% (95% CI: 89.4-96.2), 78.9% (95% CI: 62.7-90.4), 4.33 and 0.11, respectively. Conclusion: The serum ATX level is a useful biomarker for CRC.

What is this summary about? Here, we summarize the results from 'The diagnostic value of serum autotaxin level in colorectal cancer' study, published in Biomarkers in Medicine. This study examined a biomarker that could enable the early diagnosis of colorectal cancer. Autotaxin (ATX) plays a key role in inflammatory and neoplastic processes. In our study, serum ATX levels were measured in patients with colorectal cancer. What are the results? Serum ATX levels were higher in patients with colorectal cancer than in healthy volunteers. ATX levels were not associated with tumor stage. However, ATX levels were lower in mucinous adenocarcinomas. The ATX levels were higher in females than males. Although our study sample was small, we observed that ATX was more sensitive and specific than carcinoembryonic antigen in detecting colorectal cancer. What do these results mean? Serum ATX levels are promising biomarkers for colorectal cancer diagnosis and patient surveillance.

Molecular profiling of TAM tyrosine kinase receptors and ligands in endometrial carcinoma: An in silico-study.

OBJECTIVES: TAM Receptors (TYRO3, AXL, and MerTK) and their ligands on tumor-associated macrophages are promising therapeutic targets for most solid cancers. However, in endometrial cancer, the most common invasive gynecologic malignancy, the TAM receptor-mediated activation pathway, its molecular mechanisms, and its pathophysiology are unknown. The goal of this research; to uncover the comprehensive genetic profile of TAM receptors and ligands in endometrial cancer. MATERIAL AND METHODS: Mutation and expression profiles of the Uterine Corpus Endometrial Carcinoma (UCEC) cohort (n = 509) were obtained using bioinformatics tools providing data from The Cancer Genome Atlas (TCGA). PolyPhen-2 and SNAP tools were used to predict the oncogenic/pathogenic properties of the identified mutations for UCEC. STRING network analysis was performed to better understand the functional relationships of the mutant proteins in cellular processes. Furthermore to the mutation profile, gene expression and survival profiles were also determined. Finally, the correlation between target genes and macrophage infiltration was investigated using the tool TIMER. RESULTS: A total of 229 mutations were detected in 6 genes, and 81 missense mutations are pathogenic. In the UCEC cohort, the expression level of MerTK, AXL, GAS6, and PROS1 was statistically significantly lower in the patient group, while the expression level of CD47 was higher in the patient group than in the healthy group (p < 0.01). Protein-protein interaction analysis identified target genes, SRC protein responsible for important cellular mechanisms such as cell proliferation, adhesion and migration, ITGB3, ITGAV and THSB1 proteins involved in endothelial mesenchymal transition and tumor metabolism reprogramming, and FOLR1 involved in DNA replication and damage repair. CONCLUSION: We believe that TAM receptors and their ligands may be attractive molecular targets for the treatment of endometrial carcinoma because they act as pleiotropic inhibitors of immune cells, effectively regulate phagocytic clearance of apoptotic cells, and make the tumor microenvironment a more suitable niche for the tumour.

Identification of novel TUBB1 variants in patients with macrothrombocytopenia.

Background/aim: Macrothrombocytopenia is an autosomal-dominant disorder characterized by increased platelet size and a decreased number of circulating platelets. The membrane skeleton and the link between actin filaments of the skeleton and microtubules, which consist of alpha and beta tubulin [including the tubulin beta-1 chain (TUBB1)] heterodimers, are important for normal platelet morphology, and defects in these systems are associated with macrothrombocytopenia. Materials and methods: In this study, we sequenced the exons of the TUBB1 gene using DNA isolated from the peripheral blood samples of healthy controls (n = 47) and patients with macrothrombocytopenia (n = 37) from Turkey. The TUBB1 expression levels in fractioned blood samples from patients and healthy controls were analyzed by RT-qPCR and Western blot. Microtubule organization of the platelets in the peripheral blood smears of patients, and in mutant TUBB1-transfected HeLa cells, were analyzed by immunofluorescence staining. Results: A new TUBB1 c.803G>T (p.T178T) variant was detected in all of the control and patient samples. Importantly, we found 3 new heterozygous TUBB1 variants predicting amino acid substitutions: G146R (in 1 patient), E123Q (in 1 patient), and T274M (in 4 patients); the latter variant was associated with milder thrombocytopenia in cancer patients treated with paclitaxel. Ectopic expression of TUBB1 T274M/R307H variant in HeLa cells resulted in irregular microtubule organization. Conclusion: Further clinical and functional studies of the newly identified TUBB1 variants may offer important insights into their pathogenicity in macrothrombocytopenia.

Genetic Analysis of Afibrinogenemia and Hypofibrinogenemia: Novel Mutations in the FGB Gene in the Turkish Population.

INTRODUCTION: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels <1.5 g/L. OBJECTIVE: In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. METHODS: We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the FGB gene using the DNA isolated from the peripheral blood samples of patients and controls. RESULTS AND CONCLUSION: We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same patient of Turkish descent. Furthermore, there was a novel heterozygous guanine-to-adenine nucleotide change in exon 3. This caused the change of arginine amino acid to threonine amino acid at position 136 (p.A136T) in a protein, which has not been described in the literature before.

Variables determining the development of colistin-associated renal impairment.

AIM: The aim of this study was to identify the predictors of acute renal injury associated with colistin treatment. METHODS: The patients who received treatment with colistin for more than 3 days were included in this retrospective cohort study. Acute renal injury was defined by the RIFLE (Risk Injury Failure Loss End stage renal disease) criteria. Patients whose serum creatinine levels increased at least 1.5-fold compared with baseline value were considered as cases with renal injury. The independent variables determining the development of acute renal injury were investigated by survival analysis. RESULTS: A total of 112 cases [67 (59.8 %) were male, median age 64 (range: 18-93) years] were included in the study. Acute renal injury occurred in 66 (58.9 %) patients. Renal injury developed in first 7 days of the colistin therapy in 52 (78.8 %) cases and at day 8-23 in 14 (21.2 %) cases. On the day with highest levels of creatinine, 25 (22.3 %), 17 (15.2 %), and 33 (29.5 %) cases were in 'Risk', 'Injury', and 'Failure' group, respectively, according to RIFLE criteria. We identified three independent risk factors predicting acute colistin-induced renal injury: advanced age, low serum albumin levels, and high serum total bilirubin levels [odds ratio (confidence interval) = 1.022 (1.006-1.037), 0.643 (0.415-0.994), and 1.129 (1.014-1.257), respectively]. CONCLUSIONS: The advanced age, low serum albumin levels, and high serum total bilirubin levels are independent risk factors for colistin-induced nephrotoxicity.

Novel mutations of integrin αIIb and ß3 genes in Turkish children with Glanzmann's thrombasthenia.

Glanzmann's thrombasthenia (GT) is an inherited disorder of platelet aggregation, characterized by qualitative and quantitative defect on platelet αIIbß3 integrin (GpIIb/IIIa), resulting in lifelong bleeding tendency due to defective platelet plug formation. The αIIb gene (ITGA2B) and ß3 gene (ITGB3) are closely located at chromosome 17q21.31-32. ITGA2B consist of 30 exons and encoding α chain, whereas ITGB3 has 15 exons and encoding ß chain. Until now, according to the Human Gene Mutation Database (HGMD), 138 mutations at ITGA2B gene and 101 mutations at ITGB3 gene have been identified. We aimed to determine whether there was any mutation in the ITGA2B and ITGB3 genes, and a correlation between clinical phenotype and genotype in Turkish GT patients. We examined 20 patients with GT followed at the Department of Pediatric Hematology, Meram Faculty of Medicine, for Clinical and Laboratory Findings and Molecular Genetic Analysis. Peripheral blood was collected from patients, and a written informed consent for genetic analysis was obtained from parents. DNA was isolated from by proteinase K and phenol/chloroform extraction. ITGA2B and ITGB3 genes were screened by polymerase chain reaction. There were 12 females and 8 males with a median age of 15.25 years. Major clinical presentations of these patients were mucocutaneous bleedings. The most common bleeding type was epistaxis (85%). Life-threatening bleedings were seen in five patients. Seven (35%) patients showed various mutations in the ITGA2B or ITGB3 genes. We detected four novel mutations in three different regions and two mutations defined previously within the ITGA2B gene. These changes are at exon 4; c.570 T > G alteration, at exon 13 c.1277 T > A, c.1291 T > G alterations, at exon 19 c.1921A > G alterations. And from the start point of exon 14, behind 107 bases, we detected a heterozygous alteration at Thymine to Guanine. According to PolyPhen Database Program and NCBI Multiple Alignment Tool Database, four transitions are conserved at evolutionary process, so we can say that these transitions are novel mutations. c. 468T > G alteration at exon 4 and c. 1378 T > A alteration at exon 13 were reported to HGMD previously. Screening the exons of the ITGB3 gene from the same patient groups, we reported a novel missense mutation at exon 5, at nucleotide 680. No correlation was found between clinical phenotype and genotype. These mutations were described for the first time in Turkish population, and all novel mutations are not defined previously. Furthermore, collaborative studies are needed for the population point of view.

Use of PET-CT for the assessment of treatment results in patients with sarcoidosis.

BACKGROUND AND AIM: Sarcoidosis is a multisystem disease of unknown origin. Determining the involvement and the response to the treatment is important. The aim of this study was to identify the effects of methylprednisolone and indomethacine on metabolic activity and pulmonary function test parameters in patients with sarcoidosis. MATERIAL AND METHODS: A total of 24 pulmonary sarcoidosis patients were enrolled in the study. All the patients underwent spirometry and [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan before treatment and were divided into two groups according to the necessity of corticosteroid treatment or not. Patients who did not have corticosteroid indication were treated with indomethacine. Symptomatic patients and patients who did not respond to indomethacine treatment received methylprednisolone. Patients were followed up on a monthly basis to determine the response. FDG uptakes as the disease activity were re-evaluated before ending the treatment at the sixth month. RESULTS: Mean age of patients (16 male, 8 female) was 39.79 (9.3) years. Besides mediastinum and pulmonary parenchyma, extrapulmonary sites were also involved in patients with pulmonary sarcoidosis (distant lymph nodes (upper abdominal, supraclavicular, inguinal, and axillary), liver, and spleen). Although maximum standard uptake values of methylprednisolone group regressed significantly (p < 0.001) after treatment, indomethacine group did not have significant regression (p = 0.345). Despite metabolic regressions, spirometry values of patients did not significantly increase (p > 0.005). CONCLUSION: FDG PET-CT may be useful for determining activity and the efficacy of treatments. Methylprednisolone is effective in reducing metabolic activity but does not lead to improvement in functional parameters.