Decline in radioiodine use but not total thyroidectomy in thyroid cancer patients treated in the United Arab Emirates - A retrospective study

xlomafota13 shared this article with you from Inoreader Decline in radioiodine use but not total thyroidectomy in thyroid cancer patients treated in the United Arab Emirates - A retrospective study Via radioactive iodine Ann Med Surg (Lond). 2021 Mar 4;64:102203. doi: 10.1016/j.amsu.2021.102203. eCollection 2021 Apr. ABSTRACT OBJECTIVES: To assess the trend of clinicopathological features and treatment modalities in patients with thyroid cancer (TC) in the largest oncology center in the United Arab Emirates (UAE). METHODS: A retrospective analysis of patients with TC presenting to a tertiary care hospital in Al Ain, UAE between September 2008 and December 2018 identified using ICD 9 & 10 codes was performed. Data on demographics, histopathology, surgical extent, and use of Radioiodine (RAI) were extracted. Exact logistic and ordinal logistic regressions were performed to analyze the annual trend in features and management of TC, and logistic regression analysis was performed to identify predictors of total thyroidectomy and RAI use. RESULTS: A total of 762 patients were included in the analysis (mean age: 39.6 ± 12.6 years, 45 (60%) women). The majority (92.2%) were diagnosed with papillary thyroid cancer (PTC) and 83.9% had tumor size of <4 cm. All patients underwent surgery (93.8% total thyroidectomy, 6.2% lobectomy) and 77.4% received RAI therapy overall with a significant (p < 0.001) decline from 100% in 2008 to 60% in 2018. In multivariate analysis, nationality, and lymph node (LN) involvement were significant predictors of total thyroidectomy, while nationality, LNs, year of diagnosis, and tumor size significantly predicted RAI use. CONCLUSI ON: Most patients in our cohort were diagnosed with localized PTC with no significant change in the extent of surgical approach but a substantial decline in RAI therapy administration over time. Nationality and LN involvement were significant predictors of surgical extent and RAI use. PMID:33747499 | PMC:PMC7970029 | DOI: 10.1016/j.amsu.2021.102203 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DNA repair pathway activation features in follicular and papillary thyroid tumors, interrogated using 95 experimental RNA sequencing profiles

xlomafota13 shared this article with you from Inoreader DNA repair pathway activation features in follicular and papillary thyroid tumors, interrogated using 95 experimental RNA sequencing profiles Via radioactive iodine Heliyon. 2021 Mar 13;7(3):e06408. doi: 10.1016/j.heliyon.2021.e06408. eCollection 2021 Mar. ABSTRACT DNA repair can prevent mutations and cancer development, but it can also restore damaged tumor cells after chemo and radiation therapy. We performed RNA sequencing on 95 human pathological thyroid biosamples including 17 follicular adenomas, 23 follicular cancers, 3 medullar cancers, 51 papillary cancers and 1 poorly differentiated cancer. The gene expression profiles are annotated here with the clinical and histological diagnoses and, for papillary cancers, with BRAF gene V600E mutation status. DNA repair molecular pathway analysis showed strongly upregulated pathway activation levels for most of the differential pathways in the papillary cancer and moderately upregulated pattern in the follicular cancer, when compared to the follicular adenomas. This was observed for the BRCA1, ATM, p53, excision repair, and mismatch repair pathways. This finding was validated using independent thyroid tumor expression dataset PRJEB11591. We also analyzed gene expression patterns linked with the radioiodine resistant thyroid tumors (n = 13) and identified 871 differential genes that according to Gene Ontology analysis formed two functional groups: (i) response to topologically incorrect protein and (ii) aldo-keto reductase (NADP) activity. We also found RNA sequencing reads for two hybrid transcripts: one in-frame fusion for well-known NCOA4-RET translocation, and another frameshift fusion of ALK oncogene with a new partner ARHGAP12. The latter could probably support increased expression of truncated ALK downstream from 4th exon out of 28. Both fusions were found in papillary thyroid cancers of follicular histologic subtype with node metastases, one of them (NCOA4-RET) for the radioactive iodine resistant tumor. The differences in DNA repair activation patterns may help to improve therapy of different thyroid cancer types under investigation and the data communicated may serve for finding additional markers of radioiodine resistance. PMID:33748479 | PMC:PMC7970325 | DOI:10.1016/j.heliyon.2021.e06408 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The assessment of the Long Term Hematologic Effects in Differentiated Thyroid Cancer Patients Treated with Radioactive Iodine

xlomafota13 shared this article with you from Inoreader The assessment of the Long Term Hematologic Effects in Differentiated Thyroid Cancer Patients Treated with Radioactive Iodine Via radioactive iodine Turk J Haematol. 2021 Mar 22. doi: 10.4274/tjh.galenos.2021.2021.0092. Online ahead of print. ABSTRACT OBJECTIVE: Radioactive iodine (RAI) therapy may cause hematological abnormalities. The aim of the study is to evaluate long-term hematological changes in differentiated thyroid cancer (DTC) patients after RAI therapy. MATERIALS AND METHODS: One thousand three hundred eighty nine patients with DTC who were treated with RAI were retrospectively evaluated. Complete blood cell c ounts before the RAI therapy and last follow up and hematologic malignancy development were obtained from the electronic records. RESULTS AND CONCLUSION: In the long term analysis, thrombocytopenia and lymphopenia were observed significantly over 60 years of age. We suggested that, these cytopenias should be surveyed more carefully in this group of age. Thrombocytopenia was observed more frequently in men. Leukopenia, thrombocytopenia and lymphopenia were observed significantly with >175 mCI doses. Thrombocytopenia and lymphopenia were observed significantly with multiple dose administration. The higher frequency of anemia, thrombocytopenia, leukopenia, neutropenia, and lymphopenia were found in patients with advanced stage disease. However patients with advanced stage disease had higher doses and multiple doses than patients with early stage disease. The rate of hematological malignancy was found to be higher than the general population. PMID:33749216 | DOI:10.4274/tjh.galenos.2021.2021.0092 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Estrogen administration attenuates post-stroke depression by enhancing CREB/BDNF/TrkB signaling in the rat hippocampus

xlomafota13 shared this article with you from Inoreader Estrogen administration attenuates post-stroke depression by enhancing CREB/BDNF/TrkB signaling in the rat hippocampus Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):433. doi: 10.3892/etm.2021.9850. Epub 2021 Feb 26. ABSTRACT A previous study demonstrated that 17β-estradiol (E2), which is an antidepressant, can ameliorate post-stroke depression (PSD); however, the underlying mechanisms governing this remain largely unknown. Therefore, the present study developed a PSD model in rats, which was induced by left middle cerebral artery occlusion followed by exposure to chronic mild stress for 2 weeks. The results revealed that the activity of the cAMP response element-binding protein (CREB), a cellular transcription factor, and the associated brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling were all attenuated in the hippocampus in PSD rats. The depression-like behaviors were significantly improved after treatment with E2, along with increased CREB and the BDNF/TrkB signaling activity. These results provide novel insight into the molecular basis o f PSD, and suggest the potential involvement of CREB/BDNF/TrkB signaling in E2-mediated improvement of PSD in rats. PMID:33747172 | PMC:PMC7967838 | DOI:10.3892/etm.2021.9850 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Underlying mechanisms of the effect of minocycline against Candida albicans biofilms

xlomafota13 shared this article with you from Inoreader Underlying mechanisms of the effect of minocycline against <em>Candida albicans</em> biofilms Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):413. doi: 10.3892/etm.2021.9857. Epub 2021 Feb 25. ABSTRACT Minocycline (MH) is a broad-spectrum antimicrobial agent and semisynthetic tetracycline derivative, which has been widely used in the clinic due to its efficacy. Having the strongest anti-microbial effect, MH exceeded the traditional scope of antibiotics and its previously unknown antifungal activity is also gradually being discovered. To preliminarily investigate the inhibitory effect of MH on Candida albicans (C. albicans), changes of cell growth, hyphal formation and transition, biofilm production and signaling pathway gene expression of C. albicans in the presence of MH were assessed in the present study. An XTT reduction assay was performed to quantitatively detect the metabolic activity of biofilms and evaluate the inhibition of MH on this. The results suggested that biofilm formation was clearly inhibited by 67% (P<0. 0001) in the presence of 250 µg/ml MH, while mature biofilms were not significantly affected. In addition, MH inhibited the transition from yeast to hypha in a dose-dependent manner. Furthermore, reverse transcription-quantitative PCR revealed that several hyphae- and adhesion-specific genes associated with the Ras/cyclic (c)AMP/protein kinase A (PKA) pathway were differentially expressed following MH treatment, including downregulation of ras family GTPase (RAS1), adenylyl cyclase-associated protein 1 (CAP1), thiamin pyrophosphokinase 1 (TPK1), adenylate cyclase (CDC35), transcription factor (TEC1), agglutinin-like protein 3 (ALS3) and hyphal wall protein 1 (HWP1) and upregulation of EFG1 (enhanced filamentous growth protein 1 gene) and PDE2 (high-affinity phosphodiesterase gene). The most obviously changed genes were TPK1, HWP1 and RAS1, downregulated by 0.33-, 0.48- and 0.55-fold, respectively. It was s uggested that MH is associated with alterations in the morphology of C. albicans, such as the repression of hypha and biofilm formation of cells, and MH affected the Ras/cAMP pathway to regulate the expression of cAMP-associated genes. PMID:33747154 | PMC:PMC7967842 | DOI:10.3892/etm.2021.9857 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Laminar shear stress upregulates the expression of PPARs in vascular endothelial cells under high free fatty acid-induced stress

xlomafota13 shared this article with you from Inoreader Laminar shear stress upregulates the expression of PPARs in vascular endothelial cells under high free fatty acid-induced stress Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):438. doi: 10.3892/etm.2021.9855. Epub 2021 Feb 26. ABSTRACT Shear stress has been reported to result in various metabolic effects in endothelial cells (ECs), which in turn contribute to the regulation of their vascular functions. Peroxisome proliferator-activated receptors (PPARs) have been reported to regulate lipid metabolism and have been implicated in metabolic disorders. The present study assessed the effects of laminar shear stress on the expression of PPARs in ECs in the presence of high concentrations of free fatty acids (FFAs). Human aortic ECs (HAECs) were treated with a high concentrations of palmitic acid (PA) and exposed to high shear stress (HSS) or low shear stress (LSS). Western blotting and ELISA were performed to quantify protein expression and assess prostacyclin production. The results revealed that long-term application of HSS to PA-treated HAECs induced PPAR-α, -δ and -γ protein exp ression. Additionally, LSS induced higher levels of PPAR-α protein expression in PA-treated HAECs compared with those after HSS. HAECs exposed to HSS also released prostacyclin (PGI2). However, HAECs treated with high concentrations of PA also produced high levels of PGI2 in the perfusion media in response to HSS compared with the static PA group. HSS also reduced the static PA-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1. The results demonstrated that HAECs increases the expression of all three peroxisome proliferator-activated receptor isoforms in response to shear metabolic stress at high FFA concentrations. The present study may provide preliminary insights into the potential roles of PPARs as an effective treatment method against metabolic disturbances that can result in EC dysfunction. PMID:33747175 | PMC:PMC7967849 | DOI:10.3892/etm.2021.9855 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mutational landscape and potential therapeutic targets for sporadic pancreatic neuroendocrine tumors based on target next-generation sequencing

xlomafota13 shared this article with you from Inoreader Mutational landscape and potential therapeutic targets for sporadic pancreatic neuroendocrine tumors based on target next-generation sequencing Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):415. doi: 10.3892/etm.2021.9859. Epub 2021 Feb 25. ABSTRACT Pancreatic neuroendocrine tumor (PNET), a heterogenous type of neoplasm with limited treatment options, is relatively rare and to date, the genetic background has remained to be fully elucidated. The present study aimed to determine the mutational landscape of PNET with and without liver metastasis, as well as its clinical application value for treatment. Fresh tumor tissues were collected from 14 patients with PNET following surgery, 4 of whom had developed liver metastasis. Subsequently, targeted next-generation sequencing of 612 cancer-associated genes and comprehensive analysis were performed on the tumor tissues. The results identified 63 somatic mutations in 53 genes in the 14 patients with PNET, amongst which menin 1 was identified as the most recurrently mutated gene. The analysis also identified several novel recurrently mutated genes, inc luding adrenoceptor alpha 2B, ARVCF delta catenin family member, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase and neuregulin 1. Among the 53 mutated genes, 11 were enriched in the PI3K/AKT signaling pathway (adjusted P=7.12x10-5). In addition, 4 patients with PNET with liver metastasis had distinctly different mutational profiles compared with those without liver metastasis; 13 genes were discovered to be exclusively mutated in the liver metastasis group of the patients with PNET, including ATRX chromatin remodeler, thioredoxin reductase 2, anus kinase 3, ARVCF delta catenin family member, integrin subunit alpha V and RAD50 double strand break repair protein. In addition, two potentially actionable alterations in BRCA2 DNA repair-associated (p.Q548Q) and neurofibromin 1 (p.Q1188X) were identified using the OncoKB database. In conclusion, the present study generated a comprehensive mutational profile of 14 patients with PNET and further described the features of patients with liver metastasis, which highlights potential targets for drug development of PNET. PMID:33747156 | PMC:PMC7967861 | DOI:10.3892/etm.2021.9859 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-383 promotes reactive oxygen species-induced autophagy via downregulating peroxiredoxin 3 in human glioma U87 cells

xlomafota13 shared this article with you from Inoreader MicroRNA-383 promotes reactive oxygen species-induced autophagy via downregulating peroxiredoxin 3 in human glioma U87 cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):439. doi: 10.3892/etm.2021.9870. Epub 2021 Feb 26. ABSTRACT Peroxiredoxin 3 (PRDX3) is an abundant and effective enzyme, which aids in the removal of H2O2 in the mitochondria, thereby inhibiting cell autophagy. PRDX3 is a target protein of microRNA (miRNA/miR)-383, the overexpression of which has been found to inhibit the growth of glioma cells. We hypothesized that miR-383 serves an antitumor role by inhibiting oxidative stress during tumor growth. In the current study, human glioma U87 cells were transfected with pre-/short hairpin (sh)-PRDX3 vectors and miR-383 mimics/inhibitors. Apoptosis and reactive oxygen species (ROS) production were detected using flow cytometry. Autophagy was examined using acridine orange staining, and the expression of cytoplasmic autophagy-related proteins [autophagy-related protein 9 (ATG9), Ras-related protein Rab-1A (Rab1) and p62] was determined using western blot analysis. The interaction between miR-383 and PRDX3 was assessed using a dual-luciferase assay. The results indicated that both sh-PRDX3 and miR-383 mimics promoted apoptosis and increased the level of mitochondrial ROS, whilst acridine orange staining revealed that sh-PRDX3 promoted autophagy in U87 cells compared with that in the control cells. The detection of autophagic proteins indicated that sh-PRDX3 and miR-383 mimics increased the protein expression level of ATG9 and RAB1, and inhibited that of p62. On the contrary, the effect of miR-383 mimics was opposite to that of pre-PRDX3 in U87 cells. Reverse transcription-quantitative PCR and western blot assays revealed that miR-383 was negatively associated with PRDX3 in U87 cells. miR-383 was indicated to interact with PRDX3, as demonstrated using a dual-luciferase assay. In conclusion, the present study demonstrated that miR-383 induced cell apoptosis and mitochondrial ROS production by downregulating PRDX3 in U87 ce lls, thereby promoting oxidative stress-induced autophagy. PMID:33747176 | PMC:PMC7967820 | DOI:10.3892/etm.2021.9870 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperresponsiveness of human gingival fibroblasts from patients with aggressive periodontitis against bacterial lipopolysaccharide

xlomafota13 shared this article with you from Inoreader Hyperresponsiveness of human gingival fibroblasts from patients with aggressive periodontitis against bacterial lipopolysaccharide Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):417. doi: 10.3892/etm.2021.9861. Epub 2021 Feb 25. ABSTRACT The present study aimed to investigate whether gingival fibroblasts (GFs) of patients with aggressive periodontitis (AgP) are more sensitive to lipopolysaccharide (LPS) stimulation than GFs of control subjects. AgP causes rapid periodontal destruction, including the production of cytokines [i.e. interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α] and matrix metalloproteinases (MMP)-1, -3 and -9 in AgP GFs. LPS upregulates IL-1β, IL-6, TNF-α, MMP-1, MMP-3, MMP-9 and mitochondrial reactive oxygen species (mtROS). Fibroblasts are known to be associated with immune responses to bacterial virulence factors, but the precise mechanisms underlying this severe periodontal disease are unclear. In the present study, primary human GFs of four patients with AgP and four healthy subjects were challenged in vitro with LPS from Porphyromonas gingivalis (P. gingivalis). The generation of mtROS in GFs was assessed using MitoSOX Red. The expression of genes encoding inflammatory cytokines and MMPs in GFs was analyzed using reverse transcription-quantitative polymerase chain reaction, and the expression of proteins was analyzed using ELISA and Western blotting. Human GFs of patients with AgP exhibited higher levels of mtROS, and higher mRNA and protein expression levels of proinflammatory cytokines, including IL-1β, IL-6, MMP-1, MMP-3 and MMP-9 compared with healthy human GFs following stimulation with LPS from P. gingivalis. In the present study, it was demonstrated that GFs of patients with AgP display hyperreactivity when challenged with LPS. PMID:33747158 | PMC:PMC7967859 | DOI:10.3892/etm.2021.9861 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Resveratrol protects against high glucose-induced oxidative damage in human lens epithelial cells by activating autophagy

xlomafota13 shared this article with you from Inoreader Resveratrol protects against high glucose-induced oxidative damage in human lens epithelial cells by activating autophagy Via Experimental and therapeutic medicine Exp Ther Med. 2021 May;21(5):440. doi: 10.3892/etm.2021.9871. Epub 2021 Feb 26. ABSTRACT In the pathogenesis of diabetic cataract, high glucose levels induce oxidative damage in human lens epithelial cells (HLECs). Resveratrol has been demonstrated to be a potent antioxidant in various disease conditions; however, limited information is available on its effects on oxidative damage associated with the pathogenesis of diabetic cataract in HLECs. The present study aimed to determine whether resveratrol prevents high glucose-induced oxidative damage to human lens epithelial cells by activating autophagy. In the present study, HLECs treated with high glucose were used as a cellular model of diabetic cataract and treated with resveratrol for 24 h. Flow cytometry was performed to detect the cellular reactive oxygen species (ROS) content. Autophagy marker protein levels were determined by western blotting. Immunofluorescence assay was performe d to analyze in vitro microtubule-associated protein 1 light chain 3 β (LC3B) protein expression. Autophagosome formation in HLECs was observed using transmission electron microscopy. The results demonstrated that high glucose suppressed HLEC viability and proliferation rate compared with normal glucose levels (5 mM), which were significantly reversed by resveratrol treatment. High glucose also increased the ROS content compared with ROS content in normal HLECs, which was reduced following resveratrol treatment. Further experiments demonstrated that resveratrol significantly reversed the high glucose-decreased protein levels of LC3II and beclin-1 proteins and the high glucose-increased protein levels of LC3I and p62 in HLECs. In conclusion, resveratrol inhibited the high glucose-induced oxidative damage in HLECs by promoting autophagy through the activation of the p38 mitogen-activated protein kinase signaling pathway. These results provide a theoretical basis for the applic ation of resveratrol in diabetic cataract prevention and treatment. PMID:33747177 | PMC:PMC7967869 | DOI:10.3892/etm.2021.9871 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.