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Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group (p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups (p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study. [ABSTRACT FROM AUTHOR]

To evaluate effects of halofuginone (H) on radiation-induced lung injury (RILI), 60 rats were divided into six groups: Group (G) 1 control, G2 radiotherapy (RT) only, G3 and G4 2. 5 and 5 μg H and G5 and G6 RT + 2.5 and 5 μg H groups, respectively. A single dose of 12 Gy RT was given to both lungs. H was applied intraperitoneally with daily doses, until animals were killed at 6 and 16 weeks after RT. At 6th and 16th weeks of RT, five rats from each group were killed. Lung tissues were dissected for light and electron microscopy. Chronic inflammation, fibrosis and transforming growth factor-beta (TGF)-β scores of all study groups were significantly different at 6th and 16th week (p < 0.001). Chronic inflammation, fibrosis and TGF-β scores of G2 were higher than G5 and G6 at 6th and 16th weeks of RT. At 16th week, fibrosis and TGF-β scores of G5 were higher than G6 (p = 0.040 and 0.028, respectively). Electron microscopical findings also supported these results. Therefore, H may ameliorate RILI. The effect of the H was more prominent at higher dose and after long-term follow-up. These findings should be clarified with further studies. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the effects of β-hydroxy-β-methylbutyrate, L-glutamine, and L-arginine (HMB/Glu/Arg) on radiation-induced acute inflammation and mucosal atrophy in the oral mucosa.Methods: Twenty-eight rats were divided into four groups. group (G) 1 was defined as control group, and G2 was the radiation therapy (RT) group. G3 and G4 were HMB/Glu/Arg control and 17 Gy RT plus HMB/Glu/Arg groups, respectively. A single dose of 17 Gy RT was given to the head and neck area, and the active supplement consisting of 5.2 g of HMB, 29.6 g arginine, and 29.6 g of glutamine which was equivalent to 60 kg adult dose was calculated for each rat and administrated orally. HMB/Glu/Arg started from the day of RT and continued until the animals were sacrificed 7 days after the RT. The extent of acute inflammation and mucosal atrophy for each rat was quantified with image analysis of histological sections of the oral mucosa.Results: There were significant differences in terms of epithelial thickness, subepithelial edema, inflammation, and congestion between all groups (p values were <0.001, 0.003, <0.001, and 0.001 for each parameter, respectively). Using HMB/Glu/Arg alone led to hypertrophic changes in the epithelial layer. Moreover, when used with RT, HMB/Glu/Arg reversed radiation-induced epithelial atrophy (p, 0.006) and decreased radiation-induced inflammation at a significant level (p, 0.007).Conclusion: Concomitant use of HMB/Glu/Arg appears to ameliorate the radiation-induced acute inflammation and mucosal atrophy which represent the early phase of acute oral mucositis; however, this finding should be clarified with further clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: The assessment of Health-Related Quality of Life (HRQoL) in cancer patients has become increasingly important during the past decades. The aim of this study was to evaluate the HRQoL in patients treated for low-grade glioma (LGG).Methods and Materials: Forty-three adult patients with LGG were evaluated prospectively between September 2006 and December 2010. We assessed HRQoL at baseline (after surgery before radiotherapy), at the end of radiotherapy and during follow-up (every 3 months for the first 2 years and every 6 months between 2 and 5 years), using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC-C30), Brain Cancer Module-20 (BN-20), Mini Mental State Examination (MMSE) and Hospital Anxiety and Depression Scale (HADS).Results: We demonstrated changes in global score (p = 0.004), and future uncertainty (p < 0.001), communication deficit (p = 0.007), headache (p < 0.001), drowsiness (p = 0.002) and hair loss (p < 0.001), and recall score (p = 0.0029) during follow-up. All complaints of LGG patients showed improvement, except for the hair loss. Although the baseline cognitive function scores was not significantly different, the third-year cognitive function scores of patients who used antiepileptic drugs had lower when compared to patients who did not use (p < 0.001). The baseline and follow-up anxiety and depression scores did not differ significantly.Conclusion: Our results suggested that there were improvement in HRQoL in LGG patients during follow-up and antiepileptic drugs had negative effect on cognitive functions. [ABSTRACT FROM AUTHOR]

Background: 5-hydroxytryptamine receptor type-3 (5-HT3) antagonists are widely used for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) and regarded to have a high safety profile. However, several electrocardiographic changes and cardiac arrhythmias have been reported due to administration of 5-HT3 antagonists. Only prolongation of QT interval has been investigated as an index of potential for life-threatening arrhythmias in adult patients using 5-HT3 antagonists. Recently, increase in transmural dispersion of repolarization (TDR) has been proposed as a more reliable determinant of arrhythmogenic potential. Aim: To assess the effects of palonosetron, a second-generation 5-HT3 antagonist, on the T-wave peak to T-wave end (TpTe) interval which has been proposed as a reliable index of spatial TDR. Patients and Methods: A total of 50 consecutive cancer patients (aged: 57 ± 12 years) who were scheduled to receive emetogenic chemotherapy were included to the study. Baseline12-lead electrocardiography (ECG) recordings were obtained. Then, all patients received 8 mg intravenous dexamethasone followed by a single dose of 0.25 mg intravenous palonosetron administered over 30 seconds. A second ECG was performed 30 minutes after the administration of palonosetron. Indices of cardiac repolarization and TDR before and after the administration of palonosetron were compared. Results: In comparison with baseline there was no statistically significant change in any of the heart rate-corrected parameters, including QTc (lead V5), QTmaxc, QTminc, QTcd, TpTe (V5), TpTemax, TpTemin, TpTed and TpTe/QT (V5). Conclusions: Palonosetron does not have any significant effect on QTc and TpTe intervals. It might be the drug of choice for prophylaxis of CINV in cancer patients receiving chemotherapy with known cardiotoxic potential or who have pre-existing cardiac disease that predispose them to drug-induced arrhythmias. [ABSTRACT FROM AUTHOR]

Background: This study explores the mechanisms of colorectal cancer (CRC) through bioinformatics and in vitro experiments. The goal is to find differentially expressed genes (DEGs) and miRNA-gene interactions, especially between miR-16-5p and BIRC5, in order to find biomarkers that can be used to diagnose, predict, and treat CRC., Methods and Results: Microarray data (GSE52060) from the GEO database was analysed using R software, applying LIMMA for log2 transformation and quantile normalization. Significant DEGs were identified, and miRNA targets were predicted with miRWalk v.3 and validated in CRC cell lines. Statistical analyses were conducted using R and GraphPad Prism. BIRC5's impact on survival was analysed via GEPIA2, and correlated genes were identified using Correlation AnalyzeR. The treatment of miR-16-5p mimic significantly reduced BIRC5 expression in HT-29, SW480, and HCT116 cells in a dose-dependent manner. Correlational analyses revealed a strong negative association between miR-16-5p levels and BIRC5 expression, emphasizing miR-16-5p's role as a tumor suppressor. While BIRC5 inhibits apoptosis and regulates cell division, miR-16-5p impacts apoptosis, the cell cycle, and angiogenesis. GEPIA2 analysis indicated that BIRC5 expression had no significant impact on CRC survival outcomes., Conclusions: This study demonstrates miR-16-5p's regulatory role on BIRC5 in CRC cells and its therapeutic potential. Restoring miR-16-5p or targeting BIRC5 could improve CRC treatment strategies. To learn more about how miR-16-5p and BIRC5 can be used to diagnose and predict CRC, more clinical testing is needed. This will help us learn more about how CRC works at the molecular level., Competing Interests: Declarations. Ethical approval and consent to participate: This study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Non-Interventional Ethics Committee of Biruni University (Approval Number: 2024-BİAEK/05–05; Date of Approval: 12 December 2024). Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth type 2S (CMT2S) typically present before age 10. Genetic factors account for up to 50 % of neuropathies, which often display varied symptoms. Mutations in the IGHMBP2 gene are associated with both CMT2S and SMARD1, resulting in a rare clinical condition marked by axonal neuropathy, spinal muscular atrophy, respiratory distress, and muscle weakness., Method: Detailed family histories and medical data were collected. Segregation analysis was performed using Sanger sequencing and whole exome sequencing. Additionally, a review of molecularly confirmed patients was conducted. Protein tertiary structures expressed in the IGHMBP2 gene were tested for topological and conformational changes using modeling programs and in-silico tools., Results: We identified a novel homozygous nonsense mutation (c.2568&#95;2569del p.Gly857Alafs*27) in a family with a member showing neuropathy. This report details the clinical and genetic findings of the affected individuals, including a Turkish patient with neuropathy, and compares them with literature cases., Conclusion: Understanding the clinical impact of the (c.2568&#95;2569del p.Gly857Alafs*27) mutation will enhance our knowledge of IGHMBP2 gene defects role in neuropathy. This study aims to highlight this severe recessive disease caused by pathogenic IGHMBP2 gene mutations and to examine the mutation spectrum and phenotype differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Inherited retinal diseases (IRDs) constitute a heterogeneous group of clinically and genetically diverse conditions, standing as a primary cause of visual impairment among individuals aged 15-45, with an estimated incidence of 1:2000. Our study aimed to comprehensively evaluate the genetic variants underlying IRDs in the Turkish population. This study included 50 unrelated Turkish IRD patients and their families. Genomic DNA was extracted from each participant, and candidate variants were identified via next-generation sequencing to determine their pathogenicity. We detected variants in 58% of the patients, of which six novel variants were identified. Among these, 16 cases exhibited variants associated with retinitis pigmentosa and Stargardt disease, while 13 presented variants linked to other retinal diseases. The spectrum of identified variants included 21 homozygous cases and five compound heterozygous variants, both indicative of autosomal recessive inheritance. Three cases revealed heterozygous variants suggestive of autosomal dominant inheritance, and two cases featured hemizygous variants suggestive of X-linked inheritance. Importantly, no matches with copy number variants were detected in our analysis. This study comprehensively portrays clinical and genetic profiles within the Turkish population affected by IRDs. Identifying novel variants and delineating inheritance patterns contribute to a deeper understanding of the genetic diagnosis of IRDs, paving the way for more precise diagnostic and therapeutic interventions., (© 2025 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

Purpose: Although chemotherapy is one of the standard treatments for gastric cancer, the disease's resistance mechanisms continue to limit the survival rates. B7H6 ( NCR3LG1 ), an immune checkpoint belonging to the B7 family, is significantly overexpressed in gastric cancer. This work investigated the possibility of using B7H6 suppression to improve the effectiveness of the widely used chemotherapy medication docetaxel., Materials and Methods: In this study, MKN-45 gastric cancer cells were transfected for 24 h with siRNA targeting B7H6 , and then, docetaxel was added at optimal inhibitory doses (IC25 and IC50). To assess the impact of this combination therapy, cellular viability, proliferation, and migration were assessed using MTT assay, colony-forming unit assay, and wound-healing assay, respectively. Additionally, apoptosis and cell cycle status were evaluated by flow cytometry. Moreover, using qRT-PCR, the gene expression of B7H6 and indicators associated with apoptosis was also examined., Results: The sensitivity of MKN-45 cells to docetaxel was greatly increased by the siRNA-mediated knockdown of B7H6 , resulting in a decrease in the drug's IC50 value. When compared to each therapy alone, the combination of B7H6 siRNA plus docetaxel at IC50 levels exhibited a significant increase in apoptosis rate. The volume of cells arrested at the sub-G1 and G2-M phase was shown to rise when B7H6 siRNA transfection was combined with docetaxel. Furthermore, the combination treatment significantly decreased the ability of cells to migrate and form colonies., Conclusions: B7H6 suppression increases the susceptibility of MKN-45 gastric cancer cells to docetaxel treatment, resulting in decreased cellular proliferation and increased rates of apoptosis. The present work underscores the possibility of enhancing treatment results in gastric cancer by merging conventional chemotherapy with gene-silencing approaches.

Background: We analyzed a dose escalation of 36.25 Gy to the entire prostate and a dose increment up to 40 Gy with 1.25 Gy increments to intraprostatic lesion (IPL) using simultaneous integrated boost (SIB) in five fractions., Materials and Methods: Eighteen low- and intermediate-risk prostate cancer patients treated with 1.5T MR-Linac were retrospectively evaluated. The same planning computed tomography (CT) images generated four plans: no SIB, 37.5 Gy SIB, 38.75 Gy SIB, and 40 Gy SIB. In four plans, planning target volume (PTV) doses, organ at risk (OAR) doses, and PTV-SIB homogeneity index (HI), gradient index (GI) and conformity index (CI) were compared., Results: All plans met the criteria for PTV and PTV-SIB coverage. PTV 40 Gy plan has higher maximum PTV and PTV-SIB doses than other plans. The PTV HI was significantly higher in the SIB 40 Gy plan (0.135 ± 0.007) compared to SIB 38.75 Gy plan (0.099 ± 0.007; p = 0.001), SIB 37.5 Gy (0.067 ± 0.008; p < 0.001), and no SIB plan (0.049 ± 0.010; p < 0.001), while there were no significant differences in HI, GI and CI for PTV-SIB between three plans. Four rectum and bladder plans had similar dosimetric parameters. The urethra D5 was significantly higher in SIB 40 Gy plan compared to no SIB plan (37.7 ± 1.1 Gy vs . 37.0 ± 0.7 Gy; p = 0.009) and SIB 37.5 Gy plan (36.9 ± 0.8 Gy; p = 0.008). There was no significant difference in monitor units between the four consecutive plans., Conclusions: Ultra-hypofractionated dose escalation to IPL up to 40 Gy in 5 fractions with a 1.5-T MR-linac is dosimetrically feasible, potentially paving the way for clinical trials., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (© 2024 Greater Poland Cancer Centre.)

Introduction: Alport syndrome (AS) is an inherited, rare, progressive kidney disease that affects the eye and ear physiology. Pathogenic variants of COL4A5 account for 85% of all cases, while COL4A3 and COL4A4 account for the remaining 15%., Methods: Targeted next-generation sequencing of the COL4A3 , COL4A4 , and COL4A5 genes was performed in 125 Turkish patients with AS. The patients were compared to 45 controls and open-access population data., Results: The incidence of AS variants in patients was found as 21.6%. 27 variants were identified as pathogenic/likely pathogenic, 28 as variant of uncertain significance, and 52 as benign/likely benign. We also found 31 novel variants (14 in COL4A3 , 6 in COL4A4 , and 11 in COL4A5 ) of which 27 were classified as pathogenic/likely pathogenic. Pathogenic/likely Pathogenic variants were most commonly found in the COL4A5 gene, consistent with the literature. This study contributed novel variants associated with AS to the literature., Conclusion: Genetic testing is a crucial part for the diagnosis and management of AS. Studies on the genetic etiology of AS are limited for the Turkish population. We believe that this study will contribute to the literature and the clinical decision-making process of patients with AS and emphasize the importance of genetic counseling., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)