EC Treatment Research Articles

12455 Bone Mineral Density Improvement After Resolution Of Endogenous Cushing Syndrome

Abstract Disclosure: C. Plessias: None. N. Charoenngam: None. T. Rittiphairoj: None. T. Suenghataiphorn: None. T. Srikulmontri: None. P. Wattanachayakul: None. M. Kurt: None. Bone Mineral Density Improvement After Resolution of Endogenous Cushing Syndrome: a Meta-analysis and meta-regression Patients with endogenous Cushing syndrome (eCS) are known to have decreased bone mineral density (BMD) and are prone to fragility fractures. Treatment of eCS have been shown in multiple studies to result in improvement in BMD. However, the degree of BMD improvement after resolution of eCS remains inadequately explored due to limited sample sizes in existing studies. Through systematic review, meta-analysis, and meta-regression techniques, we aimed to identify all available evidence to evaluate BMD improvement after resolution of eCS. Potentially eligible studies were identified from the PubMed and EMBASE databases from inception to February 2024, utilizing a search strategy incorporating terms related to "Bone mineral density" and "Cushing syndrome". Eligible studies must include adult or pediatric patients diagnosed with any form of eCS, encompassing Cushing disease (CD), adrenal adenoma, mild autonomous cortisol secretion or ectopic ACTH-secreting tumors, who received treatment resulting in CS resolution. These studies must either present lumbar spine (LS) or femoral neck (FN) BMD measurements in the form of T-score, Z-score or actual BMD values before and after CS resolution, or report mean differences (MD) of BMD, or provide individual BMD data. Point estimates with corresponding standard errors were extracted from each study and combined using the generic inverse variance method. Meta-regression analysis was utilized to explore the impact of time after resolution of eCS on BMD improvement.A total of 5,085 records were identified from the databases. After systematic review, 14 studies, including a total of 386 patients, were deemed eligible for analysis. The meta-analysis demonstrated that resolution of eCS resulted in statistically significantly improvement of LS BMD (pooled MD: Z-score: +0.76, 95%CI 0.50 – 1.02, I2 76%; T-score: +0.87, 95%CI 0.55 – 1.19, I2 78%; actual BMD: +0.092 g/cm2, 95%CI 0.060 – 0.124, I2 74%) and FN BMD (pooled MD: Z-score: +0.54, 95%CI 0.32 – 0.76, I2 75%; T-score: +0.38, 95%CI 0.25 – 0.51, I2 0%; actual BMD: +0.041 g/cm2, 95%CI 0.021 – 0.062, I2 0%). The meta-regression analysis revealed a statistically significant association between follow-up time and improvements in LS T-score BMD (predicted LS T-score improvement = 0.42 + 0.062 × year, p = 0.027) and FN Z-score BMD (predicted FN Z-score improvement = 0.35 + 0.037 × year, p = 0.003), but not with LS Z-score and FN T-score.In summary, our study presents the extent of improvement in LS and FN BMD following the resolution of eCS based on all available data in the literature. These findings have clinical significance as they offer guidance for management of osteoporosis following the resolution of eCS. Presentation: 6/3/2024

The role of LncRNA TUG1 in DNA damage and malignant transformation induced by Helicobacter pylori and N-methyl-N′-nitro-N-nitrosoguanidine on human esophageal epithelial cells

N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) and Helicobacter pylori might synergistically promote the malignant transformation of human esophageal epithelial cells (HEECs) through inducing DNA double-strand breaks (DSBs) and inhibition of PAXX protein expression. The long noncoding RNA (lncRNA) TUG1 is associated with multiple cancers, and its overexpression can promote cancer by interfering with the functions of oncogenes. LncRNA TUG1 is also associated with DNA methyltransferase 1 (DNMT1) and the epithelial signaling pathway of H. pylori infection. To explore the role of LncRNA TUG1 in the malignant transformation of HEECs induced by H.pylori + MNNG, a stable strain of HEECs with LncRNA TUG1 knockdown (LncRNA TUG1-KD) was constructed using RNA interference technology with lentivirus as a vector. Set up negative controls LncRNA TUG1-NC (null carrier lentivirus was selected to transfect HEECs) and block controls (normal HEECs without exposure). H. pylori + MNNG were added to the LncRNA TUG1-KD and LncRNA TUG1-NC groups for 6 h and then passaged until their malignant transformation. From each group, cells in the early, intermediate, and late stages of malignant transformation were used for the alkaline comet assay and determination of protein expression, including γ-H2AX and PAXX, by western blotting assay to assess DNA damage and repair processes. Clone formation assay in soft agar and nude mouse xenograft model was used to assess malignancy. This study suggests that H. pylori + MNNG promotes the malignant transformation of HEECs by inducing DNA DSBs and inhibiting PAXX expression, and this effect may be alleviated by LncRNA TUG1 knockdown. It elucidates the pathogenesis of EC from the perspective of the combined effect of epigenetic and environmental carcinogens, offering new insights for the comprehensive prevention and treatment of EC.

GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation.

Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer-related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT-qPCR) was used to examine hub gene expression. ECA-109 and TE-12 cells were transfected using the pcDNA3.1 expression vector encoding GABRP. The cell counting kit-8 (CCK-8), cell scratch and Transwell assays were performed to assess the effect of GABRP on EC cell proliferation, migration and invasion. Epithelial-mesenchymal transition (EMT)-associated protein levels were measured by Western blotting. Subsequently, CFTR was knocked down to verify whether GABRP affected biological events in EC cells by targeting CFTR. Seven hub genes were identified, including GABRP, FLG, ENAH, KLF4, CD24, ABLIM3 and ABLIM1, which all could be used as diagnostic biomarkers for EC. The RT-qPCR results indicated that the expression levels of GABRP, FLG, KLF4, CD24, ABLIM3 and ABLIM1 were downregulated, whereas the expression level of ENAH was upregulated. Invitro functional assays demonstrated that GABRP overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, GABRP promoted the expression of CFTR, and CFTR knockdown significantly counteracted the influence of GABRP overexpression on biological events in EC cells. Overexpression of GABRP inhibited EC progression by increasing CFTR expression, which might be a new target for EC treatment.

Genetic testing of neoadjuvant therapy patients with esophageal cancer

BackgroundEsophageal cancer (EC) is a prevalent malignant tumor of the upper gastrointestinal tract in China, posing a serious threat to public health. Recent advances in cancer therapy have led to the application of neoadjuvant immunotherapy for esophageal cancer. However, the gene mutations in neoadjuvant immunotherapy of esophageal cancer remain unknown. The aim of this study was to investigate the gene mutation landscape in neoadjuvant treatment of esophageal cancer, and to provide more potential biomarkers and therapeutic targets for EC. MethodsNext-generation sequencing was performed on tumor tissue and plasma samples from 18 esophageal cancer patients in this study. The mutation profiles of 425 tumor genes were compared between pathological complete response (pCR) and non-pathological complete response (no-pCR) groups after neoadjuvant immunotherapy. The tumor mutational burden (TMB) values in tissue and plasma samples were also measured and the TMB differences between the pCR and no-pCR groups at baseline tissue (T0) were analyzed. ResultsWe found that TP53, NOTCH1 and FAT1 were the top three frequently mutated genes, with frequencies of 77.8 %, 61.1 %, and 44.4 %. Notably, the frequency of FAT1 mutations was significantly higher in the pCR group than in the no-pCR group. The mutation types in T0 and P0 samples were largely concordant, except for copy number variation (CNV). Moreover, the TMB in T0 samples was significantly higher than in P0 samples. While the TMB in the pCR group was higher than in the no-pCR group at T0, but this difference was not statistically significant. ConclusionsOur results revealed a mutational profile in patients with EC after neoadjuvant immunotherapy, and found the FAT1 gene has more significant mutations in pCR patients. We found esophageal cancer with pCR showed a trend toward higher TMB. Our findings may have implications for the subsequent diagnosis or treatment of EC.

LncRNA TRPM2-AS promotes endometrial carcinoma progression and angiogenesis via targeting miR-497-5p/SPP1 axis

BackgroundAnti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear.MethodsWe screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS’s function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC.ResultsWe found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes.ConclusionThe depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS’s role in regulating angiogenesis and provides a novel target for EC treatment.

Tumor mutational burden adjusted by neutrophil-to-lymphocyte ratio serves as a potential biomarker for atezolizumab-treated patients with extensive stage small cell lung cancer

BackgroundThere is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC.MethodsThe data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC.ResultsWe have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52–5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb).ConclusionOur findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.

GGTLC1 knockdown inhibits the progression of endometrial cancer by regulating the TGF-β/Smad signaling pathway

PurposeEndometrial cancer (EC) poses a serious risk to females worldwide; thus, a deep understanding of EC is urgently required. The role and mechanisms of gamma-glutamyltransferase light chain 1 (GGTLC1) in EC remain obscure. This study aims to elucidate the function and mechanisms underlying GGTLC1's involvement in EC. MethodsBioinformatic tools and databases were used to analyze GGTLC1 and its associated gene expression in EC tissues. Functional enrichment explorations and immune infiltration analyses were conducted, together with investigation into the methylation status of GGTLC1. Western blotting and Quantitative real-time PCR quantified expression levels. Additional experimental methodologies elucidated the role of GGTLC1 in EC progression. Transcriptome sequencing identified potential regulatory pathways for GGTLC1, and tumor growth was evaluated in vivo using HEC-1A cells in nude mice. ResultsGGTLC1 was upregulated and negatively correlated with immune cell infiltration and DNA methylation in EC. Cell migration and proliferation were reduced following GGTLC1 knockdown, together with arrest at the G0/G1 phase and an upsurge in apoptosis. Compared to the knockdown group, TGF-β/Smad signaling pathway was up-regulated in the negative control group of EC cells by transcriptome analysis. The levels of TGF-β, pSmad2, and pSmad3 followed the same decreasing trend, whereas Smad3 and Smad2 protein levels remained unchanged. ConclusionKnockdown of GGTLC1 attenuates EC development through the TGF-β/Smad pathway, positioning GGTLC1 as a promising target for EC treatment.

Combined treatment with amitraz and thymol to manage Varroa destructor mites (Acari: Varroidae) in Apis mellifera honey bee colonies (Hymenoptera: Apidae).

The parasitic mite Varroa destructor (Anderson and Trueman) is one of the greatest stressors of Apis mellifera (L.) honey bee colonies. When Varroa infestations reach damaging levels during fall, rapid control is necessary to minimize damage to colonies. We performed a field trial in the US Southeast to determine if a combination of registered treatments (Apivar, amitraz-based; and Apiguard, thymol-based) could provide rapid and effective control of Varroa. We compared colonies that received this combination treatment against colonies that received amitraz-based positive control treatments: (i) Apivar alone; or (ii) amitraz emulsifiable concentrate ("amitraz EC"). While not registered, amitraz EC is used by beekeepers in the United States in part because it is thought to control Varroa more rapidly and effectively than registered products. Based on measurements of Varroa infestation rates of colonies after 21 days of treatment, we found that the combination treatment controlled Varroa nearly as rapidly as the amitraz EC treatment: this or other combinations could be useful for Varroa management. At the end of the 42-day trial, colonies in the amitraz EC group had higher bee populations than those in the Apivar group, which suggests that rapid control helps reduce Varroa damage. Colonies in the combination group had lower bee populations than those in the amitraz EC group, which indicates that the combination treatment needs to be optimized to avoid damage to colonies.

An anoikis-related lncRNA signature may predict the prognosis, immune infiltration, and drug sensitivity in esophageal cancer

BackgroundEsophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications. MethodsTranscriptome and clinical data were obtained from TCGA database for EC samples. We identified anoikis-related genes and lncRNAs by Pearson correlation analysis. The risk score model hinged on prognostic lncRNAs filtered from multiple steps. Risk scores were calculated using the derived formula, and categorized patients into low- and high-risk groups. Model robustness was assessed through Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) curve, with clinical utility achieved via a constructed nomogram. We also explored the interplay between the risk score and immune cell infiltration, and investigated drug sensitivity. ResultsWe identified 2365 anoikis-related lncRNAs through co-expression analysis, including 1415 significant lncRNAs differentially expressed between normal and tumor samples. A risk score model was constructed from ten prognostic lncRNAs. The risk score model effectively stratified patients based on the median score, and its predictive capacity was validated through KM survival, ROC curve analyses, and the external GSE53622 dataset. The nomogram provided a practical tool for individualized prognosis evaluation. We unveiled significant correlations between specific immune cell subsets and the risk score. Eosinophils and common lymphoid progenitors exhibited positive associations, while endothelial cells and myeloid dendritic cells showed negative correlations. Drug sensitivity analysis revealed potential sensitive drugs for EC treatment that aligned with the risk subgroups. ConclusionThis study established an anoikis-related lncRNAs risk score model that may predict the prognosis, immune infiltration, and drug sensitivity in EC, in hope of facilitating tailored patient management.

ScRNA‐seq determines the characteristics of T cell marker genes to predict the prognosis of esophageal cancer

AbstractEsophageal cancer (EC) mainly includes two histological subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, which is of high morbidity and mortality. With the continuous development of medical technology, the treatment of EC has been greatly improved, but its prognosis is still unfavorable. Recent single‐cell RNA‐sequencing (scRNA‐seq) is expected to bring breakthroughs in the treatment of EC. First, we identified T cell marker genes and generated signature by analyzing scRNA‐seq data from Expression Omnibus (GEO) database and TCGA database. Then, an immune prognostic model was constructed using the least absolute shrinkage and selection operator. We found that the survival rate of ESCC varied significantly among the low‐ and high‐risk groups. Two genes from T cell signature, DCPS and CYB5R3, were expressed in ESCC cells. Collectively, our study proposed a novel prognostic signature for ESCC patients based on T cell marker genes.

Integrated system of electro-catalytic oxidation and microbial fuel cells for the treatment of recalcitrant wastewater

The emission of recalcitrant wastewater poses serious threats to the environment. In this study, an integrated approach combining electrocatalytic oxidation (EC) for pretreatment and microbial fuel cells (MFC) for thorough pollutant degradation is proposed to ensure efficient degradation of target substances, with low energy input and enhanced bioavailability of refractory organics. When phenol was used as the pollutant, an initial concentration of 2000 mg/L phenol solution underwent EC treatment under constant current-exponential attenuation power supply mode, resulting in a COD removal rate of 54.53%, and a phenol degradation rate of 99.83%. Intermediate products such as hydroquinone and para-diphenol were detected in the solution. After subsequent MFC treatment, only minor amounts of para-diphenol were left, and the degradation rate of phenol and its intermediate products reached 100%, with an output power density of 110.4 mW m−2. When coal chemical wastewater was used as the pollutant, further examination of the EC-MFC system performance showed a COD removal rate of 49.23% in the EC section, and a 76.21% COD removal rate in the MFC section, with an output power density of 181.5 mW m−2. Microbiological analysis revealed typical electrogenic bacteria (such as Pseudomonas and Geobacter), and specific degrading functional bacteria (such as Stenotrophomonas, Delftia, and Brevundimonas). The dominant microbial communities and their proportions adapted to environmental changes in response to the variation of carbon sources.

Differences in single gene expression patterns and signaling pathways between Black and White patients in high grade endometrioid endometrial cancer independent of BMI

ObjectiveEndometrial cancer (EC) incidence and mortality are increasing with striking racial disparities. Race and obesity are known risk factors for EC, however, their relationship and impact on tumor biology in higher grade endometrioid EC are unclear. The objective of this pilot study was to identify gene- and pathway-level changes in tumors from Black patients compared to White, both in general and in the context of dichotomized BMI. MethodsA single institution retrospective convenience sample was obtained for grade 2 or 3 endometrioid EC, equally distributed amongst Black and White patients. Tumor samples were analyzed with the Tempus Laboratories xT NGS-based genome profiling test. DESeq2 was applied to identify differentially expressed genes, and then subjected to ingenuity pathway analysis (IPA). Continuous variables were analyzed using unpaired t-tests, and categorical using Chi-squared and Fisher exact tests. Results39 representative cases were identified and analyzed from 2006 to 2021. Baseline clinicopathologic characteristics were similar. 157 genes were differentially expressed in tumors from Black patients compared to White regardless of BMI. IPA identified 81 significantly different pathways between Black and White patients with a BMI < 40 kg/m2, and 117 with a BMI ≥ 40 kg/m2. Of these, eleven pathways were consistently and significantly activated or deactivated regardless of BMI. ConclusionDifferences in gene expression and pathway activation in EC exist between race and BMI, which highlights the need for further research to better understand the implications of these differences on endometrioid EC progression, outcomes, and treatment in this historically underserved patient population.

Effect of water salinity and sodicity on soil least limiting water range

AbstractThis study aimed to evaluate the effects of water salinity and sodicity on the least limiting water range (LLWR) of two clay loam and sandy loam soils. The undisturbed soil samples were subjected to different water qualities, including three levels of sodium adsorption ratio (SAR, 1, 5, and 12) and electrical conductivity (EC, 1, 6, and 10 dS m−1). Our findings indicate that increasing EC at each SAR led to greater soil water retention. This was attributed to salinity affecting pore size distribution toward smaller pores by altering the diffuse double layer and causing soil particle flocculation. With increasing SAR levels at each EC level, soil water content at the wilting point also rose due to structural changes, clay swelling, and dispersion, resulting in more micropores and increased adsorptive surfaces in the soil. Additionally, soil volumetric water content at a 10% air‐filled porosity decreased, while values at a critical penetration resistance of 2 MPa increased with higher bulk density across all treatments. The LLWR showed a negative correlation with bulk density in clay loam soil across all SAR and EC treatments. The LLWR increased with higher water EC but decreased with increasing water SAR. The highest LLWR was observed at SAR = 1 and EC = 10 dS m−1, while the lowest occurred at SAR = 12 and EC = 1 dS m−1. The results revealed that elevated values of SAR in irrigation water reduced soil water accessibility for plants. However, as irrigation water salinity increased, the detrimental effects of SAR diminished.

Case report of radiotherapy combined with anlotinib and immunotherapy for a patient with esophageal cancer and esophageal fistula

BackgroundEsophageal cancer (EC) is a frequent gastrointestinal malignancy. The most common types of EC pathology worldwide are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Although surgical resection is still the main treatment modality for EC, most patients are already lost to surgery at the time of presentation due to the late stage. In recent years, the development of radiation therapy (RT) combined with targeted therapy (TT) and immunization therapy (IT) has brought more options for the treatment of EC. During radiation therapy, the radiation therapy area is very close to the trachea and esophagus, so radiation therapy may cause damage to the tissues of the trachea and esophagus, which is also known as a tracheoesophageal fistula (TF). We present the case of an EC patient who developed TF during radiation therapy and gradually improved after a combination of anlotinib and immunotherapy. MethodsThe patient was diagnosed with poorly differentiated ESCC by pathological biopsy and treated with “lobaplatin + Tegafur Gimeracil Oteracil Porassium Capsule” for 5 cycles. ResultsCT scan of the chest showed progression after treatment. During RT, the patient developed radiotherapy-related adverse effects, which were relieved by symptomatic support therapy. At the end of RT, the patient developed TF, but we chose to let the patient continue his radiation treatment plan with the anti-angiogenic drug “anlotinib.” ConclusionAfter radiation therapy, the patient continued to be treated with anlotinib and immunotherapy with camrelizumab, and the patient's lesion improved.

LncRNA FIRRE regulated endometrial cancer radiotherapy sensitivity via the miR-199b-5p/SIRT1/BECN1 axis-mediated autophagy

BackgroundEndometrial cancer (EC) poses a serious threat to women's health. Radiotherapy has been widely used for EC treatment. However, the mechanism of FIRRE in EC development and radioresistance remains unknown. MethodsMTT and colony formation assays determined cell proliferation. The degree of autophagy was tested by the measurement of autophagy-related genes and immunofluorescence staining of LC3. Molecular interactions were demonstrated via luciferase reporter assay, RIP, and Co-IP. The FIRRE role's was analyzed by in vivo xenograft tumor model. ResultsFIRRE and SIRT1 were upregulated in EC tumor tissues, whereas miR-199b-5p was reduced. FIRRE knockdown increased EC cell radiotherapy sensitivity by sponging miR-199b-5p and inhibiting autophagy. SIRT1 was targeted and negatively regulated by miR-199b-5p. SIRT1 could otherwise deacetylate BECN1 protein and participate in FIRRE-mediated autophagy. Silencing FIRRE increased sensitivity of EC radiotherapy in vivo. ConclusionFIRRE reduced EC cell radiotherapy sensitivity by stimulating autophagy via miR-199b-5p/SIRT1/BECN1 axis.

Impact of COVID-19 Pandemic on the Diagnostic and Therapeutic Management of Endometrial Cancer: A Monocentric Retrospective Comparative Study.

Endometrial cancer represents an ideal target to evaluate the impact of COVID-19 being the most frequent gynecological malignancy in Italy, generally detected at early stages and correlated with favorable oncological outcomes. The present comparative retrospective study carried out at Campus Bio-medico University Foundation in Rome aims to evaluate the impact of the COVID-19 pandemic on the presentation, diagnosis and treatment of EC. All women with a histological diagnosis of non-endometrioid and endometrioid endometrial cancer between 1 March 2018 and 31 October 2022 were included. The number of cases was higher in period 2 (95 vs. 64 cases). Time to diagnosis did not show statistically significant differences but in period 2, 92.06% of the diagnoses were made following abnormal uterine bleeding, while in period 1, only 67.02% were. The waiting time for the intervention was significantly shorter in period 2. Definitive histology, FIGO staging, surgical technique and adjuvant therapy did not show significant differences between the two periods. The study demonstrates that the impact of the COVID-19 pandemic did not have a direct effect on the diagnostic delay, tumor staging and type of therapy but rather on the presentation pattern of endometrial cancer.

BUB1, BUB1B, CCNA2, and CDCA8, along with miR-524-5p, as clinically relevant biomarkers for the diagnosis and treatment of endometrial carcinoma

BackgroundEndometrial carcinoma (EC) is a malignant tumor of the female reproductive tract that has been associated with increased morbidity and mortality. This study aimed to identify biomarkers and potential therapeutic targets for EC.MethodsA publicly available transcriptome data set comprising 587 EC cases was subjected to a comprehensive bioinformatics analysis to identify candidate genes responsible for EC occurrence and development. Next, we used clinical samples and cell experiments for validation.ResultsA total of 1,617 differentially expressed genes (DEGs) were identified. Analysis of patient survival outcomes revealed that BUB1, BUB1B, CCNA2, and CDCA8 were correlated with prognosis in patients with EC. Moreover, assessment of clinical samples confirmed that BUB1, BUB1B, CCNA2 and CDCA8 were strongly expressed in EC tissues. Additionally, bioinformatics and luciferase reporter assays confirmed that miR-524-5p can target and regulate these four genes. Overexpression of miR-524-5p significantly inhibited EC Ishikawa cells viability, migration and invasion. Inhibition of miR-524-5p showed the opposite results.ConclusionsExpression of miR-524-5p reduced the migration and invasion of Ishikawa EC cells, and decreased BUB1, BUB1B, CCNA2, and CDCA8 expression. miR-524-5p, as well as BUB1, BUB1B, CCNA2, and CDCA8, may be clinically relevant biomarkers for the diagnosis and treatment of EC.

Influence of Exogenous 24-Epicasterone on the Hormonal Status of Soybean Plants.

Brassinosteroids (BRs) are key phytohormones involved in the regulation of major processes of cell metabolism that guide plant growth. In the past decades, new evidence has made it clear that BRs also play a key role in the orchestration of plant responses to many abiotic and biotic stresses. In the present work, we analyzed the impact of foliar treatment with 24-epicastasterone (ECS) on the endogenous content of major phytohormones (auxins, salicylic acid, jasmonic acid, and abscisic acid) and their intermediates in soybean leaves 7 days following the treatment. Changes in the endogenous content of phytohormones have been identified and quantified by LC/MS. The obtained results point to a clear role of ECS in the upregulation of auxin content (indole-3-acetic acid, IAA) and downregulation of salicylic, jasmonic, and abscisic acid levels. These data confirm that under optimal conditions, ECS in tested concentrations of 0.25 µM and 1 µM might promote growth in soybeans by inducing auxin contents. Benzoic acid (a precursor of salicylic acid (SA)), but not SA itself, has also been highly accumulated under ECS treatment, which indicates an activation of the adaptation strategies of cell metabolism to possible environmental challenges.

ESOMIR: a curated database ofbiomarker genes andmiRNAs associated with esophageal cancer.

'Esophageal cancer' (EC) is a highly aggressive and deadly complex disease. It comprises two types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with Barrett's esophagus (BE) being the only known precursor. Recent research has revealed that microRNAs (miRNAs) play a crucial role in the development, prognosis and treatment of EC and are involved in various human diseases. Biological databases have become essential for cancer research as they provide information on genes, proteins, pathways and their interactions. These databases collect, store and manage large amounts of molecular data, which can be used to identify patterns, predict outcomes and generate hypotheses. However, no comprehensive database exists for EC and miRNA relationships. To address this gap, we developed a dynamic database named 'ESOMIR (miRNA in esophageal cancer) (https://esomir.dqweilab-sjtu.com)', which includes information about targeted genes and miRNAs associated with EC. The database uses analysis and prediction methods, including experimentally endorsed miRNA(s) information. ESOMIR is a user-friendly interface that allows easy access to EC-associated data by searching for miRNAs, target genes, sequences, chromosomal positions and associated signaling pathways. The search modules are designed to provide specific data access to users based on their requirements. Additionally, the database provides information about network interactions, signaling pathways and region information of chromosomes associated with the 3'untranslated region (3'UTR) or 5'UTR and exon sites. Users can also access energy levels of specific miRNAs with targeted genes. A fuzzy term search is included in each module to enhance the ease of use for researchers. ESOMIR can be a valuable tool for researchers and clinicians to gain insight into EC, including identifying biomarkers and treatments for this aggressive tumor. Database URL https://esomir.dqweilab-sjtu.com.

Long-term survival in esophagectomy for early-stage esophageal cancer versus endoscopic resection plus additional chemoradiotherapy: a systematic review and meta-analysis.

Esophagectomy is still advised as an additional treatment for patients with superficial esophageal cancer (EC, T1a-T1b) after endoscopic resection (ER). However, esophagectomy often deteriorates the general condition of EC patients. In recent years, adjuvant chemoradiotherapy (CRT) has been recognized as a reliable, non-surgical treatment that can improve the prognosis. How to combine ER with adjuvant therapy to bring maximal benefits to patients has become a hot clinical research hot topic. However, the current studies have mostly been conducted retrospectively, in single centers, and with small clinical samples; there have been few prospective and large sample size randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to compare the outcomes of adjuvant CRT versus esophagectomy in the treatment of early EC, and to provide a reference for clinical research and practice. A comprehensive and extensive literature search was performed via the databases of PubMed, Cochrane Library, Embase, and Web of Science online and all randomized cohort studies and retrospective cohort studies were collected. The quality of research was evaluated according to Cochrane's quality standards, and statistical analysis was conducted with Stata 13.0 and RevMan 5.3 software and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). A total of 9 cohort studies, including 790 patients, were included for meta-analysis. The long term effects of the esophagectomy group were better than those of the CRT after ER group [odds ratio (OR) =6.08, 95% confidence interval (CI): 1.96 to 18.84, P=0.002] in disease-free survival (DFS) [hazard ratio (HR) =0.24, 95% CI: 0.07 to 0.85, P=0.03] and overall survival (OS) (HR =1.02, 95% CI: 0.57 to 1.82, P=0.94). Other survival indicators showed no significant difference (P>0.05). The 2 groups showed no significant results in OS. Although we found that CRT may be suitable for patients with high-risk of relapse or unable to tolerate surgery, it cannot totally replace surgical treatment; further randomized trials are required to verify this view.