Effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with esophageal squamous cell carcinoma: a prospective multicenter observational cohort study.

Background: Camrelizumab has been demonstrated to be a feasible treatment option for locally advanced esophageal squamous cell carcinoma (ESCC) when combined with neoadjuvant chemotherapy. This trial was conducted to investigate the effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with ESCC in daily practice. Methods: This prospective multicenter observational cohort study was conducted at 13 tertiary hospitals in Southeast China. Patients with histologically or cytologically confirmed ESCC [clinical tumor-node-metastasis (cTNM) stage I-IVA] who had received at least one dose of camrelizumab-containing neoadjuvant therapy were eligible for inclusion. Results: Between June 1, 2020 and July 13, 2022, 255 patients were enrolled and included. The median age was 64 (range, 27 to 82) years. Most participants were male (82.0%) and had clinical stage III-IVA diseases (82.4%). A total of 169 (66.3%) participants underwent surgical resection; 146 (86.4%) achieved R0 resection, and 36 (21.3%) achieved pathological complete response (pCR). Grades 3-5 adverse events (AEs) were experienced by 14.5% of participants. Reactive cutaneous capillary endothelial proliferation occurred in 100 (39.2%) of participants and all were grade 1 or 2. Conclusions: Camrelizumab-containing neoadjuvant therapy has acceptable effectiveness and safety profiles in real-life ESCC patients.

Lobectomy versus segmentectomy for stage IA3 (T1cN0M0) non-small cell lung cancer: a meta-analysis and systematic review.

Background: Segmentectomy has been proven to have better survival and perioperative efficacy than lobectomy for non-small cell lung cancer (NSCLC) up to 2 cm. Whether this result is applicable to stage T1cN0M0 NSCLC (2.1 to 3 cm) remains controversial. Methods: We conducted a comprehensive search across seven databases to identify relevant studies comparing lobectomy and segmentectomy procedures. Our primary focus was on survival indicators (overall survival [OS] and disease-free survival [DFS]), while for secondary outcomes, operative outcomes, hospitalization outcomes, recurrences, and complications were considered. Results: After screening, the final analysis included 10 studies (involving 22113 patients in the lobectomy group and 1627 patients in the segmentectomy group). The lobectomy procedure achieved better OS (hazard ratio [HR]: 1.19 [1.07~1.33]) and DFS (HR: 1.37 [1.10~1.71]), which were proven in all subgroups. The OS rate at 2-5 years and DFS rate at 4-5 years were higher in the lobectomy group. The advantages of OS and DFS in the lobectomy group increased over the survival time. More lymph node dissections, intraoperative blood loss and total complications were found in the lobectomy group. Similar hospital stays, 90-day mortality and conversion thoracotomy were found between the two groups. Conclusion: Lobectomy appeared to be the better choice for patients with stage T1cN0M0 NSCLC with better survival (OS and DFS). However, the complications needed to be taken seriously. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identification CRD42023445013.

PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation and thus affect the malignant progression of esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor of the digestive tract with complex pathogenesis. There is a pressing need to search for ESCC targeted therapy sites and explore its pathogenesis. Prothymosin alpha (PTMA) is abnormally expressed in numerous tumors and has a significant regulatory effect on tumor malignant progression. However, the regulatory role and mechanism of PTMA in ESCC have not yet been reported. Methods: We first detected the PTMA expression in ESCC patients, subcutaneous tumor xenograft models of ESCC, and ESCC cells. Subsequently, PTMA expression in ESCC cells was inhibited by cell transfection, and cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and Western blot. A dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect reactive oxygen species (ROS) level in cells, and MitoSOX fluorescent probe, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl carbocyanine iodide (JC-1) staining, mitochondrial complex kit, and Western blot were used to detect the expression of mitochondrial oxidative phosphorylation. Next, the combination between PTMA and high mobility group box 1 (HMGB1) was detected using Co-immunoprecipitation (co-IP) and immunofluorescence (IF) techniques. Finally, the expression of PTMA was inhibited and the expression of HMGB1 was overexpressed in cells via cell transfection, and the regulatory effect of PTMA and HMGB1 binding on mitochondrial oxidative phosphorylation in ESCC was determined through related experiments. Results: The expression of PTMA in ESCC was abnormally elevated. The inhibition of PTMA expression in ESCC cells significantly decreased the activity of ESCC cells and increased their apoptosis. Moreover, interference with PTMA can induce ROS aggregation in ESCC cells by inhibiting mitochondrial oxidative phosphorylation, which may be achieved by binding to HMGB1. Conclusions: PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation, thereby affecting the malignant progression of ESCC.

PHLDA3 activated by BARX2 transcription, suppresses the malignant development of esophageal squamous cell carcinoma by downregulating PI3K/AKT levels.

BACKGROUND: Low pleckstrin homology-like domain family A, member 3 (PHLDA3) expression has been reported to be associated with cancer specificity and disease-free survival in esophageal squamous cell carcinoma (ESCC), and was an independent predictor of postoperative recurrence. However, the specific mechanisms involved are still unclear. This paper aimed to explore the role and its mechanisms of PHLDA3 in ESCC. MATERIALS AND METHODS: PHLDA3 and BarH-like homeobox 2 (BARX2) expressions in ESCC were predicted by Gene Expression Profiling Interactive Analysis (GEPIA) analysis and determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western Blot. Western blot detected the expression of proteins associated with migration, angiogenesis and phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway. The University of California Santa Cruz Genomics Institute (UCSC) database predicted that the relationship of BARX2 and PHLDA3 promoter and JASPAR identified the possible binding sites. Dual luciferase gene reporter verified PHLDA3 promoter activity, and the relationship of both was determined by chromatin immunoprecipitation (CHIP). Cell counting kit (CCK)-8, 5-ethynyl-2'-deoxyuridine (EDU) and colony formation were used to assess cell proliferation. Wound healing and transwell were used to detect cell migration and invasion ability. Tube formation assay was applied to assess angiogenesis. Mice were injected with transfected KYSE30 cells under the right axilla. Body weight and tumor volume and mass were recorded for each group of mice. Immunohistochemistry was performed to detect KI67 level in tumor tissues. RESULTS: Both PHLDA3 and BARX2 were downregulated in ESCC. The upregulated PHLDA3 suppressed PI3K/AKT expression. In addition, BARX2 bound to the PHLDA3 promoter and transcriptionally activated PHLDA3. PHLDA3 overexpression inhibited ESCC cell proliferation, migration, invasion and angiogenesis, but this effect was reversed by BARX2 knockdown. In addition, BARX2 overexpression inhibited ESCC cell proliferation, migration, invasion and angiogenesis, but this effect was reversed by PHLDA3 knockdown. CONCLUSION: PHLDA3 was transcriptionally activated by BARX2 and inhibited malignant progression of ESCC by downregulating PI3K/AKT levels.

Cysteinyl-tRNA Synthetase 1 Promotes Ferroptosis-Induced Cell Death via Regulating GPX4 Expression.

Esophageal squamous cell carcinoma (ESCC) has still been considered to be the most common malignant tumors in China. Emerging evidence indicates that cysteinyl-tRNA synthetase 1 (CARS1) has been considered as a ferroptosis-related gene in ESCC. However, the roles and molecular mechanisms of CARS1 in ferroptosis-induced cell death of ESCC are still largely unknown. In our study, we investigated an aberrantly upregulated gene in ESCC tumor tissues CARS1 significantly inhibited cell proliferation, and the ability of migration and invasion promoted the relative level of MDA and ROS and decreased GPX4 expression level in two ESCC cell lines. Mechanistically, both the ferroptosis inhibitor ferrostatin-1 and its inducer erastin were further used and indicated that CARS1 participated in the ferroptosis-induced cell death. Together, these results revealed that CARS1 has a critical function in the progression of ESCC by promoting ferroptosis-induced cell death.

Synergistic solidification of lead-contaminated soil by magnesium oxide and microorganisms.

Although microbially induced carbonate precipitation (MICP) technology effectively promotes the remediation of heavy metal contaminated soils in low concentrations, the high concentration of heavy metals has a toxic effect on microorganisms, which leads to the decline of carbonate yield and makes the soil strength and environmental safety after remediation no up to the standard. This study describes the synergistic curing effect of MgO and microorganisms on soil contaminated with high concentrations of heavy metals. The experimental results with MgO showed 2-6 times increase in unconfined compressive strength (UCS) compared to bio-cemented samples without MgO. Toxicity characteristic leaching procedure experiments indicated that Pb-contaminated soil at 10,000 mg/kg with quantitative MgO for synergistic solidification could meet the international solid waste disposal standards, which leachable Pb2+ are less than 5 mg/L. In addition, the microscopic results showed that the introduction of MgO promoted the formation of magnesium calcite and dolomite, improved the solidification efficiency of heavy metal contaminants, and demonstrated the presence of Pb2+ in carbonate minerals. This study suggests that MgO and microorganisms have broad application prospects for synergistic solidification of Pb2+ soil.