Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis.

Objectives: The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness. Methods: We systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311). Results: From the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events. Conclusions: Patients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.

The role of SLC39A4 in the prognosis, immune microenvironment, and contribution to malignant behavior in vivo and in vitro of cervical cancer.

BACKGROUND: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. METHODS: The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. RESULTS: SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. CONCLUSION: In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

S100A10 Overexpression Correlates with Adverse Prognosis, Tumor Microenvironment, and Aggressive Behavior In Vitro and In Vivo of Cervical Cancer.

Background: The incidence of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is increasing in women. S100A10 overexpression is commonly reported in various malignancies and is closely associated with tumor cell characteristics and prognosis. Methods: The expression of S100A10 and its prognostic relevance were assessed utilizing RNA-seq data from The Cancer Genome Atlas. S100A10 regulation of CESC cell growth and migration was investigated using CCK-8, colony-forming, and Transwell-based approaches. Xenograft model mice were used to examine the in vivo effects of S100A10, and differentially expressed genes (DEGs) linked to S100A10 were identified to explore its functional role in oncogenesis. Associations between S100A10 levels, chemosensitivity, and the immune microenvironment were assessed, and the mutational and methylation status of S100A10 was evaluated using the cBioPortal and MethSurv databases, respectively. Results: S100A10 was upregulated in CESC samples, and higher S100A10 mRNA levels were associated in poor prognostic outcomes. The area under the curve for S100A10 when diagnosing CESC was 0.935, and S100A10 was found to regulate tumor cell proliferation and metastasis both in vitro and in vivo. Overall, 1125 DEGs enriched in crucial CESC progression-associated signaling pathways were identified. S100A10 expression was also associated with the intratumoral immune microenvironment and immune checkpoint activity. Patients expressing elevated S100A10 levels exhibited distinct chemotherapeutic susceptibility, and methylation of the S100A10 gene was correlated with patient survival outcomes. Conclusion: In summary, this research demonstrated that S100A10 plays a crucial role in regulating CESC development, prognosis, and the intratumoral immune microenvironment. Thus, S100A10 shows potential as a prognostic or diagnostic tool and as a potential target for CESC immunotherapy.

SERPINB7 as a prognostic biomarker in cervical cancer: Association with immune infiltration and facilitation of the malignant phenotype.

Purpose: The purpose of this study was to investigate the expression patterns, predictive significance, and roles in the immune microenvironment of Serpin Family-B Member 7 (SERPINB7) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Methods: The expression of SERPINB7 and its prognostic relevance were evaluated using RNA-seq data from The Cancer Genome Atlas. SERPINB7 regulation of CESC cell growth and metastasis was investigated using MTT, scratch, and Transwell assays. In vivo effects of SERPINB7 were examined in xenograft model mice and differentially expressed genes (DEGs) associated with SERPINB7 were identified to explore its functional role in oncogenesis. Associations between SERPINB7 levels, chemosensitivity, and immune infiltration were assessed, and mutations and methylation of SERPINB7 were evaluated using the cBioPortal and MethSurv databases, respectively. Results: SERPINB7 was up-regulated in CESC samples as well as in other tumors, and patients with higher SERPINB7A mRNA levels exhibited shorter overall survival. The area under the curve for the use of SERPINB7 in CESC diagnosis was above 0.9, and the gene was shown to regulate tumor cell proliferation and metastasis in vitro and in vivo. Overall, 398 DEGs enriched in key CESC progression-related signaling pathways were identified. SERPINB7 expression was additionally correlated with intratumoral immune infiltration and immune checkpoint activity. Patients expressing higher SERPINB7 levels exhibited distinct chemosensitivity profiles, and methylation of the SERPINB7 gene was linked to CESC patient prognostic outcomes. Conclusion: SERPINB7 was found to be a crucial regulator of CESC progression, prognosis, and the tumor immune microenvironment, highlighting its potential as a diagnostic and prognostic biomarker and target for CESC immunotherapy.

TPM3: a novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) has become increasingly prevalent in younger women. Tropomyosin 3 (TPM3), a thin filament actin-binding protein, has been implicated in various malignancies. In this study, TPM3 expression was evaluated using RNA-seq data from The Cancer Genome Atlas (TCGA), and its relationship with CESC prognosis was examined with receiver operating characteristic (ROC) curves. The effects of TPM3 on cellular proliferation and migration were examined in CESC cell lines using Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays, while in vivo effects were assessed in mouse xenograft models. Furthermore, differentially expressed genes (DEGs) associated with TPM3 were investigated to determine their tumorigenic functions. Associations between TPM3, chemosensitivity, and immune infiltration were analyzed, as were links between mutations, methylation, and prognosis using the cBioPortal and MethSurv databases. Upregulation of TMP3 mRNA and protein levels was observed in CESC samples, with elevated mRNA levels associated with reduced overall survival. TPM3 showed an area under the curve (AUC) of 0.946 for CESC diagnosis and was found to regulate tumor proliferation and metastasis in vitro and in vivo. Overall, 3099 DEGs were identified and found to be enriched in key CESC progression-related signaling pathways. TPM3 expression was also correlated with intratumoral immune cell infiltration and immune checkpoint activity. Patients with higher TPM3 expression showed distinctive chemosensitivity profiles, and TPM3 gene methylation was linked to poorer CESC patient prognostic outcomes. In conclusion, TPM3 is a key regulator of CESC progression, prognosis, and the tumor immune microenvironment, suggesting its potential as a diagnostic or prognostic biomarker and target for CESC immunotherapy.

The action of topical application of Vitamin B12 ointment on radiodermatitis in a porcine model.

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-ß in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.

Adenylate kinase 7 is a prognostic indicator of overall survival in ovarian cancer.

ABSTRACT: Ovarian cancer (OC), a common malignant heterogeneous gynecological tumor, is the primary cause of cancer-related death in women worldwide. Adenylate kinase (AK) 7 belongs to the adenylate kinase (AK) family and is a cytosolic isoform of AK. Recent studies have demonstrated that AK7 is expressed in several human diseases, including cancer. However, there is a scarcity of reports on the relationship between AK7 and OC. Here, we compared the expression of AK7 in normal and cancerous ovarian tissues from The Cancer Genome Atlas database and used the c2 test to assess the correlation between AK7 levels and the clinical symptoms of OC. Finally, the prognostic significance of AK7 in OC was determined using the Kaplan-Meier analyses and Cox regression and performed gene set enrichment analysis to detect any relevant signaling pathways. We found that AK7 levels were substantially downregulated in OC than that in normal ovarian tissues (P < .001). Low AK7 levels were related to the patients' age (P = .0093) in OC. The median overall survival (OS) of patients with low AK7-expressing OC was shorter than patients with high AK7-expressing OC (P = .019). The Cox regression analysis (multivariate) identified low AK7 levels were independently related to the prognosis of OC (HR 1.34; P = .048). Our study demonstrated that the downregulated levels of AK7 could serve as an independent prognostic indicator for the OS in OC. Additionally, gene set enrichment analysis revealed that EMT, apical junction, TGF-b signaling, UV response, and myogenesis were associated in the low AK7 expression phenotype (NOM P < .05).

Elevated high mobility group A2 expression in liver cancer predicts poor patient survival

BACKGROUND: liver cancer is a malignant tumor with a high morbidity and mortality that endangers human health. High mobility group A2 (HMGA2) is a chromosome associated protein that participates in embryogenesis, tissue development, tumorigenesis and development. OBJECTIVE: to explore the relationship between HMGA2 expression and the clinicopathological parameters and survival of liver cancer patients using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (HCC) data. METHODS: RNA-sequencing data and the corresponding clinical characteristics of the patients were downloaded from the Atlas database. The Chi-squared test was used to assess the relationship between HMGA2 expression and clinical variables. Cox regression analysis was used to compare survival rates between the high- and low-expressing groups; the p-values and Kaplan-Meier survival curves were compared using the log-rank test. RESULTS: RNA-seq data from 373 cases of liver cancer cases were analyzed. HMGA2 was overexpressed in liver cancer and significantly associated with gender (p = 0.0357), T classification (p = 0.0063), clinical classification (p = 0.0026) and overall survival (p = 0.0386). According to the multivariate analysis, HMGA2 could independently predict overall survival in liver cancer. CONCLUSIONS: HMGA2 independently predicts poor prognosis in liver cancer and serves as a molecular marker to determine disease prognosis

No disponible

Elevated high mobility group A2 expression in liver cancer predicts poor patient survival.

BACKGROUND: liver cancer is a malignant tumor with a high morbidity and mortality that endangers human health. High mobility group A2 (HMGA2) is a chromosome associated protein that participates in embryogenesis, tissue development, tumorigenesis and development. OBJECTIVE: to explore the relationship between HMGA2 expression and the clinicopathological parameters and survival of liver cancer patients using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (HCC) data. METHODS: RNA-sequencing data and the corresponding clinical characteristics of the patients were downloaded from the Atlas database. The Chi-squared test was used to assess the relationship between HMGA2 expression and clinical variables. Cox regression analysis was used to compare survival rates between the high- and low-expressing groups; the p-values and Kaplan-Meier survival curves were compared using the log-rank test. RESULTS: RNA-seq data from 373 cases of liver cancer cases were analyzed. HMGA2 was overexpressed in liver cancer and significantly associated with gender (p = 0.0357), T classification (p = 0.0063), clinical classification (p = 0.0026) and overall survival (p = 0.0386). According to the multivariate analysis, HMGA2 could independently predict overall survival in liver cancer. CONCLUSIONS: HMGA2 independently predicts poor prognosis in liver cancer and serves as a molecular marker to determine disease prognosis.

Polymer brushes-containing coordination polymer networks on monolith for rapid solid phase extraction of multi-class drug residues in meat samples.

A new solid phase extraction sorbent, based on poly(methacrylic acid) brushes-containing coordination polymer networks on monolith, was in-situ synthesized in a commercial syringe filter via surface grafting. Extraction of twenty model analytes, including nine sulfonamides, eight steroid hormones, and three quinolones, could be efficiently achieved by the monolithic hybrid filter due to multi-interactions. Through simple filtering steps, fast extraction (60 s of adsorption and 60 s of desorption) could be achieved. Furthermore, the monolithic hybrid filter was used to analyze the model compounds in chicken meat samples in combination with ultra-performance liquid chromatography-tandem mass spectrometry. Compared with other adsorption sorbents in reported literatures, the proposed monolithic hybrid filter allowed for shorter purification time, simplified sample pretreatment procedure, and comparable LODs and LOQs of 0.1-3 µg kg-1 and 0.4-10 µg kg-1, respectively. The recoveries for all analytes ranged from 83.9% to 103% with inter-day relative standard deviation lower than 10%. The results demonstrated that the developed analytical method was highly efficient and operationally convenient, and had a great potential for high throughput analysis of multi-residues.