Treatment Of Esophageal Squamous Cell Carcinoma Research Articles

Cancer-associated fibroblasts derived-exosomal circ_0076535 promotes esophageal squamous cell carcinoma progression

Background Esophageal cancer (EC) is a common malignant tumor of the digestive tract and an important health-related problem in many developing countries. Esophageal squamous cell carcinoma (ESCC) is the most common subtype of EC. The cancer-associated fibroblasts (CAFs) are the major stromal cells in ESCC microenvironment. They play important role in ESCC proliferation, metastasis, angiogenesis and chemotherapy resistance through paracrine processes. However, the roles of circRNAs enriched in CAF-derived exosmes have not been reported. Objective To explore the mechanisms of how CAF affects ESCC proliferation and metastasis through paracrine processes and to investigate the role of circRNAs enriched in CAF-derived exosomes. Methods Exosomes were isolated from the conditional medium of CAF using differential ultracentrifugation, and then validated by Nanosight analysis. Exosome secretion inhibitor-GW4869 validates the pro-carcinogenic role of exosomes. The qRT-PCR showed the highest expression of circ_0076535 in the exosomal CircRNA, and knockdown of it confirmed its function. Online bioinformatics tool was utilized to predict the potential target gene of circ_0076535, and captured miR-145-5p as the target gene with high predictive value. The targeting association between miR-145-5p and circ_0076535 is further confirmed by the dual luciferase reporter experiment. The stimulation of tumour development and EMT by the CAF-derived exosome circ_0076535 is further validated in vivo. Results In our research, we found that CAF-derived exosomes increased proliferation, migration, invasion and EMT in ESCC cells. Circ_0076535 was highly enriched in CAF-exosomes and transferred into ESCC cells directly depend on internalization of exosomes. CAF-exosomal circ_0076535 increased the level of circ_0076535 in ESCC cells and induced EMT. Mechanistic experiments revealed circ_0076535 acted as a sponge to absorb miR-145-5p and activated NF-κB signaling pathway. Conclusions Conclusively, CAF-exosomal circ_0076535 promoted the ESCC progression via miR-145-5p/NF-κB axis and expected to be a potential biomarker for early diagnosis and treatment of ESCC.

Elaiophylin targets EIF4B to suppress the growth of esophageal squamous cell carcinoma via the PI3K/AKT signaling pathway.

Elaiophylin is known to exert antitumor effects through certain signaling pathways; however, no reports regarding its effects on esophageal cancer are available. This study explored the effects of elaiophylin in esophageal squamous cell carcinoma (ESCC) cells. Transwell and immunofluorescence assays confirmed that elaiophylin inhibited the migration and proliferation of ESCC cells, and western blotting assays showed that it affected apoptosis-related gene expression in ESCC cells. Based on RNA-seq analyses, Single-cell RNA-seq, a human cancer pathway phosphorylation antibody array, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomics analyses, we found that elaiophylin was related to low expression of EIF4B and activation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. In both in vitro and in vivo experiments, ESCC cells treated with elaiophylin showed low EIF4B expression, which inhibited their proliferation and promoted apoptosis by activating the PI3K/AKT signaling pathway; EIF4B overexpression could reverse these effects of elaiophylin on ESCC cells. Therefore, our results indicate that elaiophylin targets EIF4B to inhibit ESCC cell proliferation via the PI3K/AKT signaling pathway. Targeting elaiophylin or the EIF4B/PI3K/AKT signaling pathway may produce new methods for ESCC treatment.

Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common forms of malignancy worldwide. However, there is currently a lack of effective chemotherapeutic drugs for ESCC. Ivermectin is a broad-spectrum antiparasitic drug with notable antitumor activity. However, the cellular and molecular mechanisms by which ivermectin inhibits cancer growth remain unclear. In this study, we elucidate the role of ivermectin in ESCC suppression by activating the endoplasmic reticulum (ER) stress and autophagy pathways. In transcriptome analyses, we find that activating transcription factor 4 (ATF4) and DNA damage inducible transcript 3 (DDIT3) are involved in the activation of ER stress by ivermectin. Moreover, ivermectin treatment suppresses the growth of ESCC xenograft tumors in nude mice. Taken together, our results establish the antitumor molecular role of ivermectin in targeting the ER stress-autophagy pathway and suggest that ivermectin is a potential drug candidate for the treatment of ESCC.

Co-targeting TMEM16A with a novel monoclonal antibody and EGFR with Cetuximab inhibits the growth and metastasis of esophageal squamous cell carcinoma.

The chloride channel transmembrane protein 16A (TMEM16A) possesses a calcium-activated property linked to tumor-promoting malignant phenotype and electrophysiological stability. Numerous studies have shown that TMEM16A exhibits aberrant amplification in various squamous cell carcinomas such as esophageal squamous cell carcinoma (ESCC) and is correlated with unfavorable outcomes of ESCC patients. Therefore, TMEM16A is considered as a promising therapeutic target for ESCC. Because of its intricate structure, the development of therapeutic antibodies directed against TMEM16A has not been documented. In this study, we produced a series of novel monoclonal antibodies targeting TMEM16A and identified mT16#5 as an antibody capable of inhibiting ESCC cells migration, invasion and TMEM16A ion channel activity. Additionally, based on the validation that TMEM16A was positively correlated with expression of EGFR and the interaction between them, the mT16#5 exhibited a synergistic inhibitory effect on ESCC metastasis and growth when administered in combination with Cetuximab in vivo. In terms of mechanism, we found that mT16A#5 inhibited the phosphorylation of PI3K, AKT and JNK. These results highlight the anti-growth and anti-metastasis capacity of the combination of mT16A#5 and Cetuximab in the treatment of ESCC by targeting TMEM16A and EGFR, and provide a reference for combinational antibody treatment in ESCC.

ΔNp63α promotes radioresistance in esophageal squamous cell carcinoma through the PLEC-KEAP1-NRF2 feedback loop.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly prevalent in China, exhibiting resistance to current treatments. ΔNP63α, the main isoform of p63, is frequently amplified in ESCC and contributes to therapeutic resistance, although the molecular mechanisms remain unknown. Here, we report that ΔNP63α is highly expressed in ESCC and is associated with radioresistance by reducing ROS level. Furthermore, ΔNP63α plays a critical role in radioresistance by directly transactivating the expression of PLEC. PLEC competitively interacts with KEAP1, resulting in the release of NRF2 from KEAP1 and its translocation from the cytosol to the nucleus, where it activates gene expression to facilitate ROS elimination. Additionally, radiotherapy-induced ROS also activates ΔNP63α expression via NRF2. Pharmacologic inhibition of NRF2 effectively improves radiosensitivity in nude mice. Collectively, our results strongly suggest that the ΔNp63α/PLEC/NRF2 axis plays a key role in radioresistance in ESCC, indicating that targeting NRF2 is a promising therapeutic approach for ESCC treatment.

Clinical efficacy of Endostar continuous infusion combined with concurrent chemoradiotherapy in the treatment of oesophageal squamous cell carcinoma.

To evaluate the effectiveness and safety of concurrent chemoradiotherapy using Endostar continuous infusion for treating oesophageal squamous cell carcinoma (OSCC). A total of 62 patients with oesophageal carcinoma were divided into three groups: the Endostar continuous infusion group (n = 27), the Endostar intravenous drip group (n = 21) and the concurrent chemoradiotherapy group (n = 14). All patients underwent oesophageal radiotherapy (56-60 Gy) alongside concurrent chemotherapy (4 mg of raltitrexed +100 mg of oxaliplatin, two cycles). In the Endostar continuous infusion group, 210 mg of Endostar was administered via infusion once every 3 weeks for 72 h, repeated for two cycles. The Endostar intravenous drip group received a dosage of 15 mg/day of Endostar, administered once daily for 14 days, repeated for two cycles. The objective response rate (ORR) (complete remission + partial remission), progression-free survival (PFS), 2-year overall survival (2y-OS) and adverse reactions were observed. In the Endostar continuous infusion, intravenous drip and concurrent chemoradiotherapy groups, the ORR was 100, 95.2 and 78.6%, respectively (p < 0.05). There was a statistically significant difference between the continuous infusion and concurrent chemoradiotherapy groups (p < 0.05). However, there was no statistically significant difference between the continuous infusion and intravenous drip groups or the intravenous drip and concurrent chemoradiotherapy groups (p > 0.05). The continuous infusion and intravenous drip groups had higher PFS rates than the concurrent chemoradiotherapy group (p < 0.05). Regarding the 2y-OS rate, no statistically significant difference was observed among the three groups (p > 0.05). Furthermore, there was no statistically significant difference in adverse reactions among the groups (p > 0.05). Concurrent chemotherapy based on endostatin is effective and safe in the treatment of OSCC. Continuous 3-day Endostar infusion treatment can significantly enhance both short-and long-term therapy efficacy in patients while maintaining a high level of safety.

Comparative Analysis of Concurrent Chemoradiotherapy Versus Chemotherapy Alone as First-Line Palliative Treatments for Advanced Esophageal Squamous Cell Carcinoma.

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan-Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43-0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29-0.93]), but not in stage IVB patients (HR: 0.76 [0.51-1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35-0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status.

TMSB4Y restrains sphingomyelin synthesis via de novo purine synthesis to exert a tumor suppressor function in male esophageal squamous cell carcinoma.

Y chromosome genes play a vital role in sex difference of cancer. The dysregulation and functional implications of Y chromosome genes in esophageal squamous cell carcinoma (ESCC) remains elusive. Here, we analyze the Y chromosome gene signature and identify TMSB4Y as an emerging prognostic predictor in male ESCC. Functional analyses show that TMSB4Y inhibits the proliferation, invasion and metastasis of male ESCC cells. Mechanistically, we demonstrate that TMSB4Y interacts with PAICS, wherein TMSB4Y disrupts the formation of the PAICS octamer to inhibit purine de novo synthesis, leading to a decrease in the AMP/ATP ratio, subsequently impeding AMPK phosphorylation. Furthermore, we uncover a regulatory cascade orchestrated by the TMSB4Y/PAICS-AMPK axis, which exerts a suppressive effect on sphingomyelin metabolism by inhibiting the expression of sphingomyelin synthases (SMSs). Notably, Malabaricone C, an inhibitor of SMS1 and SMS2, effectively suppresses male ESCC cell proliferation and xenograft tumor growth. Collectively, these findings reveal the regulation of sphingomyelin metabolism by TMSB4Y/PAICS-AMPK axis and underscore the potential of targeting SMSs as a promising therapeutic approach for the treatment of male ESCC.

Artificial intelligence enhances the management of esophageal squamous cell carcinoma in the precision oncology era

Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer with a poor prognosis. Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients. With the advancement of artificial intelligence (AI) technology and the proliferation of medical digital information, AI has demonstrated promising sensitivity and accuracy in assisting precise detection, treatment decision-making, and prognosis assessment of ESCC. It has become a unique opportunity to enhance comprehensive clinical management of ESCC in the era of precision oncology. This review examines how AI is applied to the diagnosis, treatment, and prognosis assessment of ESCC in the era of precision oncology, and analyzes the challenges and potential opportunities that AI faces in clinical translation. Through insights into future prospects, it is hoped that this review will contribute to the real-world application of AI in future clinical settings, ultimately alleviating the disease burden caused by ESCC.

The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

TRIM33 promotes glycolysis through regulating P53 K48-linked ubiquitination to promote esophageal squamous cell carcinoma growth

Esophageal squamous cell carcinoma (ESCC) is a common fatal malignant tumor of the digestive tract; however, its pathogenic mechanism is unknown and lacks specific molecular diagnosis and treatment. Therefore, it is particularly important to identify new tumor biomarkers to enhance the early diagnosis and molecular-targeted therapy of ESCC. Here, we found that the E3 ubiquitin ligase Tripartitemotif-containing33 (TRIM33) is highly expressed in ESCC tissues and cell lines, and is associated with adverse clinical outcomes. We determined that TRIM33 drives aerobic glycolysis to promote tumor growth in vivo and in vitro. In terms of mechanism, TRIM33 binds to p53 to inhibit its stability and promote the expression of downstream glycolysis target genes GLUT1, HK2, PKM2, and LDHA. In addition, TRIM33 promotes the polyubiquitination of P53 K48-linked and proteasome degradation. Further studies have shown that the K351 site of P53 is the key site mediating the ubiquitination of P53 K48-linked to promote aerobic glycolysis in ESCC and tumor cell growth. Our results reveal that the TRIM33-P53 signal axis regulates glycolysis during ESCC and may provide a new perspective for the diagnosis and treatment of ESCC.

Downregulation of chemokine (C‑C motif) ligand 5 induced by a novel 8‑hydroxyquinoline derivative (91b1) suppresses tumor invasiveness in esophageal carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a particularly aggressive form of cancer with high mortality. In the present study, a novel 8‑hydroxyquinoline derivative (91b1) was investigated for its anticancer activities in ESCC along with its associated mechanisms. The in vitro cytotoxic effect of 91b1 were evaluated across five ESCC cell lines using MTS assay, with cisplatin serving as a comparative standard. Changes in gene expression profile were identified by cDNA microarray and further validated by qualitative PCR and immunostaining. Additionally, protein levels of the most notably downregulated target in archival ESCC samples were also studied. 91b1 demonstrated comparable anticancer effect with cisplatin. Notably, chemokine ligand 5 (Ccl5) was identified as the most substantially downregulated gene, with its suppression at both mRNA and protein expression in ESCC cells, exhibiting a dose‑dependent manner. The recombinant human protein of CCL5 enhanced the invasion of ESCC cells using the Transwell assay. The upregulation of CCL5 protein was also detected in 50% of ESCC cell lines. CCL5 was also overexpressed in 76.9% of ESCC specimens. The overall results indicated that 91b1 could effectively induce anticancer effect on ESCC cells through downregulating CCL5 expression with suppression of tumor invasion. Overall, these findings suggested that 91b1 effectively inhibited ESCC cell proliferation and tumor invasion by downregulating CCL5 expression, highlighting its potential as a therapeutic agent for ESCC treatment.

ADAR promotes USP38 auto-deubiquitylation and stabilization in an RNA editing–independent manner in esophageal squamous cell carcinoma

Esophageal cancer is mainly divided into esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). China is one of the high-incidence areas of esophageal cancer, of which about 90% are ESCC. The deubiquitinase USP38 has been reported to play significant roles in several biological processes, including inflammatory responses, antiviral infection, cell proliferation, migration, invasion, DNA damage repair, and chemotherapy resistance. However, the role and mechanisms of USP38 in ESCC development remain still unclear. Furthermore, although many substrates of USP38 have been identified, few upstream regulatory factors of USP38 have been identified. In this study, we found that USP38 was significantly upregulated in esophageal cancer tissues. Knockdown of USP38 inhibited ESCC growth. USP38 stabilized itself through auto-deubiquitylation. In addition, we demonstrate that ADAR could enhance the stability of USP38 protein and facilitate USP38 auto-deubiquitylation by interacting with USP38 in an RNA editing-independent manner. ADAR inhibition of ESCC cell proliferation depended on USP38. In summary, these results highlight that the potential of targeting the ADAR-USP38 axis for ESCC treatment.

A spatiotemporal comparative analysis on tumor immune microenvironment characteristics between neoadjuvant chemotherapy and preoperative immunotherapy for ESCC

The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5’s antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.

CircJPH1 regulates the NF-κB/HERC5 axis to promote the malignant progression of esophageal squamous cell carcinoma through binding to XRCC6

Esophageal squamous cell carcinoma (ESCC) is a prevalent and malignant cancer with an unknown pathogenesis and a poor prognosis; therefore, the identification of effective biomarkers and targets is crucial for its diagnosis and treatment. Circular (circ)RNAs are prominent functional biomarkers and therapeutic targets in various diseases, particularly cancer, due to their widespread expression and regulatory mechanisms. Our study aimed to investigate the therapeutic potential of circRNA for ESCC. We identified Hsa_circ_0137111 for the first time as one of the most significantly up-regulated genes in ESCC sequencing and named it circJPH1. The results of the present study demonstrated an enhanced expression of circJPH1 in ESCC tissues. Moreover, circJPH1-knockdown could significantly inhibit the proliferation, migration, and invasion of ESCC cells, while its overexpression promoted these characteristics. In addition, circJPH1 promoted ESCC cell tumor growth in vivo. For the first time, mass spectrometry and RNA pull-down analysis revealed the interaction of X-ray repair cross-complementary 6 (XRCC6) protein with circJPH1, thereby promoting its nuclear translocation. Consequently, the nuclear factor kappa-B (NF-κB) signaling pathway was activated, leading to an up-regulation of HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5), thereby promoting ESCC progression. In summary, the present study elucidated the regulatory impact of circJPH1 on ESCC progression in vitro and in vivo, thereby indicating its potential role in ESCC treatment.

401. CLINICAL SIGNIFICANCE OF SIGNAL REGULATORY PROTEIN ALPHA AND CLUSTER OF DIFFERENTIATION 47 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background This study focuses on assessing the expression of Signal Regulatory Protein Alpha (SIRPα) and Cluster of Differentiation 47 (CD47) in Esophageal Squamous Cell Carcinoma (ESCC) and their impact on prognosis. Given the prominence of the CD47-SIRPα axis in cancer for inhibiting macrophage-mediated phagocytosis, this research aims to explore their role and significance in the development and treatment of ESCC. Methods In this study, 100 ESCC patients who underwent esophagectomy were included. Resected specimens were stained immunohistochemical staining for SIRPα and CD47. SIRPα expression was classified as high or low with cut-off value of 3%. CD47 expression was evaluated by Combined Positive Score (CPS) and Tumor Proportion Score (TPS) methods with setting a 10% threshold for high and low expression. The five-year survival rates were compared across groups over a median observation period of 61 months. This study reveals the correlation between these biomarkers and postoperative prognosis. Results Total 79 males and 21 females were included in this study and mean age was 68.7-year-old. The high SIRPα expression group (48 patients) revealed significantly worse 5-year overall survival rate than the low expression group (52 patients) (56.4 vs 82.8%, P=0.0098). For CD47, both evaluated by using CPS and TPS, the high expression group also showed significantly worse 5-year overall survival rate than its low group (48.8 vs 89.5%, P&amp;lt;0.0001, and 48.4 vs 87.5%, P&amp;lt;0.0001 respectively). Relapse free survival also showed significantly worse survival rate in high expression group of SIRPα and CD47. Conclusion The expression levels of SIRPα and CD47 serve as important biomarkers for predicting the prognosis of ESCC. They may influence prognosis by inhibiting macrophage-mediated tumor cell phagocytosis and modulating anti-tumor immune responses, offering new targets for ESCC treatment.

240. CACHEXIA INDEX AS A POTENTIAL BIOMARKER FOR SENSITIVITY OF NEOADJUVANT THERAPY AND PROGNOSIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Cancer cachexia has a negative impact on the clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). The cachexia index (CXI) is a potential biomarker for cancer cachexia, whereas its implications for ESCC prognosis and treatment outcomes have not been investigated. Methods In our study, 454 ESCC patients who had neoadjuvant therapy followed by surgery were included. Based on the exclusion criteria, a total of 224 patients were finally enrolled in this study. The CXI was determined as the serum albumin/neutrophil-lymphocyte ratio × the skeletal muscle index (based on CT image), which was classified as L3-CXI or pectoralis muscles-CXI depending upon the type of muscle involved. The patients were divided into high- and low-CXI groups using sex-specific medians as cutoff values for CXI. Results Tumor regression grade = 0,1 (sensitive to treatment) to neoadjuvant therapy was obtained in 61.6% and 46.4% of patients in the high-pretreatment L3-CXI and low-pretreatment L3-CXI groups, respectively (P = 0.023). ESCC patients with △L3-CXI &amp;lt;0 (L3-CXI decreased during treatment) had significantly shorter overall survival (P = 0.006) and disease-free survival (P = 0.002) than those with △L3-CXI ≥0. Multivariable analysis showed that △L3-CXI &amp;lt;0 was an independent negative prognostic factor for overall survival and disease-free survival. Conclusions In patients with ESCC, pretreatment CXI is a biomarker for treatment response, and △CXI can predict postoperative complications and survival outcomes. Patients could be clearly stratified by pretreatment CXI and △CXI categories, which provides a new nutritional assessment tool for clinical decision-making for patients with ESCC.

Efficacy and safety analysis on the combination of camrelizumab with nab-paclitaxel and cisplatin-based chemotherapy in first-line treatment of advanced or metastatic esophageal squamous cell carcinoma.

205 Background: Nab-paclitaxel has indicated good efficacy during the multi-line esophageal squamous cell carcinoma (ESCC) treatment. Our study summarized the efficacy and safety of the first-line combination treatment of camrelizumab with nab-paclitaxel and platinum in advanced or metastatic ESCC patients. This could provide evidence of the positive effects of using nab-paclitaxel. Methods: We included patients with advanced or metastatic ESCC who received camrelizumab in association with nab-paclitaxel and cisplatin for 3-6 cycles as first-line therapy. The patients were recruited from the First Hospital of Jilin University between August 2021 and December 2023. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), PFS, and OS rates at 12, 18, and 24 months, including safety. Results: 43 patients were included in this study, they were assessed based on the therapeutic effect, with 72.1% [95% CI,58.1%-86.1%]ORR and 100% DCR. The median PFS was 25.5 months, and the median OS was not achieved. The OS rates were 96.8%, 86.4%, and 78.6% at 12 months, 18 months, and 24 months, respectively. In contrast, the PFS rates were 90.1%, 75.8%, and 68.3%, respectively. Grade 3 or above treatment-related adverse reactions (TRAEs) occurred in nine patients (20.9%). No patient developed severe grade 5 TRAEs. Conclusions: During the first-line treatment of advanced or metastatic ESCC, applying nab-paclitaxel in associated with camrelizumab and cisplatin -based therapy showed a positive effect. Therefore, the results exhibit an extension of OS and PFS with manageable safety and no new TRAEs.

Current findings on the antitumor effects of metformin on esophageal squamous cell carcinoma (Review).

Esophageal squamous cell carcinoma (ESCC) is an intractable type of cancer that requires novel therapeutic modalities, since the therapeutic outcomes are often inadequate, even in response to multidisciplinary treatment. The antitumor effect of metformin, an antidiabetic drug, has been reported in esophageal cancer; however, its effects are diverse. Since various multidisciplinary therapies are used in ESCC, the antitumor effect of metformin is expected to be synergistic in some treatment strategies. The present review summarizes the antitumor effects of metformin and discusses its use in combination with existing therapies. The present study reviewed relevant studies where the molecular targets of metformin (AMPK and inflammatory system signals) were described, followed by the classification and organization of its antitumor effects, and subsequently summarized the current research on its antitumor effects, especially in ESCC. A number of studies have reported that metformin prevents the development of ESCC and exerts its antitumor effects through various pathways. In addition, metformin has been shown to inhibit tumor growth, induce apoptosis, inhibit cancer cell invasion, migration and angiogenesis into the tumor, and decrease tumor malignancy, such as metastasis. Furthermore, it may modulate host tumor immunity in a tumor-suppressive manner and is expected to improve prognosis following treatment for ESCC. Notably, metformin may be beneficial in combination with chemotherapy, such as cisplatin, and radiation. By contrast, it has been shown to potentially induce resistance to 5-fluorouracil. Finally, the effects of metformin in combination with other therapies are discussed in the present study, and perspectives on the potential benefits of metformin for future ESCC treatment are presented. In conclusion, the present review may be useful in improving the understanding of the wide range of antitumor effects of metformin. Although some concerning points remain, using metformin in ESCC treatment could be promising. Notably, more knowledge needs to be accumulated regarding the effects of metformin on ESCC.

Synaptotagmin 13 Could Drive the Progression of Esophageal Squamous Cell Carcinoma Through Upregulating ACRV1.

SYT13 is one of the atypical members of the synaptotagmin (SYT) family whose function has attracted considerable attention in recent years. Although SYT13 has been studied in several types of human cancers, such as lung cancer, its role in esophageal squamous cell carcinoma (ESCC) is still unclear. It was demonstrated that SYT13 is significantly upregulated in ESCC tissues compared with normal ones and correlated with higher degree of malignancy. Knockdown of SYT13 could inhibit ESCC cell proliferation and migration, while promoting cell apoptosis. Meanwhile, ESCC cells with relatively lower SYT13 expression grew slower invivo and finally formed smaller xenografts. Furthermore, acrosomal vesicular protein 1 was identified as a potential downstream target of SYT13, which regulates cell phenotypes of ESCC cells in cooperation with SYT13. All the in vitro and invivo results in this study identified that SYT13 silencing could be an effective strategy to inhibit the development of ESCC, which could be considered as a promising therapeutic target in the treatment of ESCC.