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Objective: This study was designed to evaluate the five-year overall survival (OS) rate and postoperative survival time of patients diagnosed with oral squamous cell carcinoma (OSCC), as well as examine the clinical and pathological factors influencing survival outcomes in OSCC patients. Methods: Data were collected from OSCC patients who underwent their first radical surgical intervention in the Department of Maxillofacial Surgery at the First Affiliated Hospital of Chongqing Medical University between April 2014 and December 2016. Follow-up was conducted until March 2022. Results: The study included a total of 162 patients. The observed 5-year OS rate was 59.3%. Approximately 45.7% of OSCC patients experienced postoperative recurrence or metastasis, with a 5-year overall disease-free survival rate of 49.4%. There was no significant difference in the impact of sex, age, smoking, alcohol consumption, primary tumour location, depth of invasion or primary tumour size on the 5-year survival rate (p > 0.05). Univariate analysis revealed that clinical stage (Hazard Ratio = 2.239, p = 0.004), perineural invasion (PNI) (Hazard Ratio = 1.712, p = 0.03), lymph node metastasis (pN) (Hazard Ratio = 2.119, p = 0.002), pathological differentiation (Hazard Ratio = 2.715, p < 0.001), and recurrence or metastasis (Hazard Ratio = 10.02, p < 0.001) were significant factors influencing survival. Multivariate analysis further indicated that pathological differentiation (Hazard Ratio = 2.291, p = 0.001), PNI (Hazard Ratio = 1.765, p = 0.031) and recurrence or metastasis (Hazard Ratio = 9.256, p < 0.001) were independent risk factors of survival. Intriguingly, 11 OSCC patients were diagnosed with oesophageal squamous cell carcinoma (ESCC) within 1-4 years following surgery. Conclusion: The survival prognosis of OSCC patients is significantly associated with clinical stage, PNI, lymph node metastasis, pathological differentiation, and recurrence or metastasis. Pathological differentiation, PNI and recurrence or metastasis are independent risk factors affecting survival. Routine clinical screening for ESCC may be recommended for OSCC patients with a history of alcohol consumption and tobacco use. [ABSTRACT FROM AUTHOR]

Artesunate (ART), an effective antimalarial semisynthetic derivative of artemisinin, exhibits antitumour properties, but the mechanism(s) involved remain elusive. In this study, we investigated the antitumour effects of ART on human oesophageal squamous cell carcinoma (ESCC) cell lines. Treatment of ESCC cell lines with ART resulted in the production of excessive reactive oxygen species (ROS) that induced DNA damage, reduced cell proliferation and inhibited clonogenicity via G1-S cell cycle arrest and/or apoptosis in vitro. The administration of ART to nude mice with ESCC cell xenografts inhibited tumour formation in vivo. However, the cytotoxicity of ART strongly differed among the ESCC cell lines tested. Transcriptomic profiling revealed that although the expression of large numbers of genes in ESCC cell lines was affected by ART treatment, these genes could be functionally clustered into pathways involved in regulating cell cycle progression, DNA metabolism and apoptosis. We revealed that p53 and Cdk4/6-p16-Rb cell cycle checkpoint controls were critical determinants required for mediating ART cytotoxicity in ESCC cell lines. Specifically, KYSE30 cells with p53Mut/p16Mut were the most sensitive to ART, KYSE150 and KYSE180 cells with p53Mut/p16Nor exhibited intermediate responses to ART, and Eca109 cells with p53Nor/p16Nor exhibited the most resistance to ATR. Consistently, perturbation of p53 expression using RNA interference (RNAi) and/or Cdk4/6 activity using the inhibitor palbociclib altered ART cytotoxicity in KYSE30 cells. Given that the p53 and Cdk4/6-cyclin D1-p16-Rb genes are commonly mutated in ESCC, our results potentially shed new light on neoadjuvant chemotherapy strategies for ESCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and efficacy of chemoradiotherapy or radiotherapy combined with nimotuzumab in the treatment of unresectable oesophageal squamous cell carcinoma (ESCC) in elderly patients. Methods: This study retrospectively analysed 54 cases of elderly patients (aged over 70 years) with unresectable ESCC in our centre between December 2016 and November 2019. The patients were treated with a radiation dose of 50–61.6 Gy (25–30 fractions) combined with nimotuzumab for targeted therapy with or without chemotherapy according to each patient's condition. The patients were observed for quality of life, safety, side effects and survival before and after the treatment. Results: Among the 54 patients, 26 were treated with nimotuzumab combined with chemoradiotherapy and 28 were treated with nimotuzumab combined with radiotherapy. Toxicities were mainly oesophagitis (≥ Grade 2, 38.9%), myelosuppression (≥ Grade 3, 24.1%) and hypoproteinaemia (any grade, 94.4%). The rates of complete response, partial response, disease stability and disease progression were 11.1% (6/54), 81.5% (44/54), 3.7% (2/54) and 3.7% (2/54), respectively, and the overall objective response rate was 92.6% (50/54). The median follow-up time was 35.1 months, and the 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 61.1% (1 year OS) and 35.2% (2 year OS), 42.6% (1 year PFS) and 16.7% (2 year PFS), respectively. The median OS and PFS rates were 16.0 and 10.0 months, respectively. Conclusion: Nimotuzumab combined with chemoradiotherapy or radiotherapy was well tolerated in elderly patients with unresectable ESCC. This combination can achieve a good treatment response and enhance survival. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. Methods: RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. Results: One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. Conclusions: The newly identified SNHG16–EIF4A3–RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre. Methods: This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics. Results: Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P<0.001) and pTNM stage (P<0.001), and similar results were found in VI. Moreover, survival analysis showed that pT stage (P<0.001), pN stage (P=0.001), pTNM stage (p<0.001), VI (P=0.001) and LI (P<0.001) were associated with DFS in ESCC. Furthermore, multivariate analysis suggested that pT stage (RR=1.4, P =0.032), pN stage (RR=1.9, P<0.001) and LI (RR=1.5, P=0.008) were independent predictive factors for DFS. Finally, relapse was observed in 110 patients (lymph node metastasis, 78 and distant, 32) and 147 patients with cancer-related deaths. Subanalysis showed that LI-positive patients had higher lymph node metastasis, although there was no significant difference (32.1% vs. 15.6%, P=0.100). Conclusions: LI and VI were common in ESCC; they were all survival predictors for patients with ESCC, and LI was independent. Patients with positive LI were more likely to suffer lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: Tumour-associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumours. Epithelial-mesenchymal transition (EMT) is a mechanism for tumour invasion and metastasis. In this study, we aimed to determine whether TAMs can induce EMT for the invasion and metastasis of Kazakh oesophageal squamous cell cancer (ESCC). Methods: CD163 was used as a marker for TAMs, and the density of TAMs in tumour nest and surrounding stroma was quantified using immunohistochemistry (IHC). IHC staining was used to evaluate the expression of E-cadherin (epithelial marker) and vimentin (mesenchymal marker) in Kazakh ESCC and cancer-adjacent normal tissues (CANs). Additionally, 6-well transwell plates (0.4 μm) were used to establish the co-culture system of ESCC (EC109 or EC9706) cells and macrophages. Real-time quantitative polymerase chain reaction (qPCR) and western blot experiments were used to determine whether ESCC cells undergo EMT transformation after co-culture with macrophages. Transwell assays were used to detect the migration and invasion of the ESCC cells. Results: The distribution of CD163-positive TAMs in cancer tissues was closely related to EMT in Kazakh ESCC. The expression of vimentin in the ESCC cells was significantly upregulated, the expression of E-cadherin was significantly downregulated, and the invasion and migration of the ESCC cells were significantly enhanced after tumour-associated macrophages were added to the co-culture. Conclusions: Tumour-associated macrophages promote EMT in ESCC, which may be one of the important factors involved in the invasion and progression of Kazakh ESCC. [ABSTRACT FROM AUTHOR]

Background: Oesophageal submucosal tumours are usually benign. We report a rare case of esophageal squamous cell carcinoma presenting as a submucosal tumour.Case Presentation: A 58-year-old man undergoing screening oesophago-gastroduodenoscopy was found to have a smooth-surfaced 0.6-cm sized submucosal tumour in the oesophagus 30 cm from the incisor. Endoscopic ultrasonography showed the tumour to be located in the muscularis mucosa; the lesion was heterogeneously hypoechoic and had a clear boundary. With a provisional diagnosis of leiomyoma, the tumour was removed by endoscopic submucosal dissection. Pathological examination showed it to be a moderately differentiated infiltrating squamous cell carcinoma, with normal overlying squamous epithelium. Immunohistochemistry indicated that it was caused by malignant transformation in mucosal glandular duct epithelium. Positron emission tomography-computer tomography showed no tumour spread to any other site. The patient was treated by oesophageal resection.Conclusion: The clinician should be aware that oesophageal submucosal tumours with smooth overlying mucosa may not always be benign; malignancy must be ruled out. [ABSTRACT FROM AUTHOR]

Background: Oesophageal squamous cell carcinoma (OSCC) is a highly aggressive carcinoma with a poor survival rate. One of the most commonly used chemotherapeutic drugs, cisplatin, displays varied and often poor efficacy in vivo. Therefore, alternative, cost-effective and more efficacious treatments are required. Metformin has been previously shown to reduce proliferative rates in various carcinoma cell lines. We report for the first time, the effect of metformin on OSCC cell proliferation and show that it antagonises cisplatin-induced but not copper-bis (thiosemicarbazone)-induced cytotoxicity in OSCC cells. Methods: Cell proliferation and stage of the cell cycle were quantified by trypan blue counts and flow cytometry, respectively. All cytotoxicity measurements were made using the tetrazolium based MTT assay. Metabolic alterations to cells were determined as follows: glycolysis via a lactate dehydrogenase assay, reducing equivalents by MTT reduction and reduced intracellular thiols by monobromobimane-thiol fluorescence, and glutathione depletion using buthionine sulfoximine. Inductively coupled plasma mass spectrometry was used to quantify cisplatin-DNA adduct formation. Results: Metformin was found to reduce cell proliferation significantly in all OSCC cell lines, with an accumulation of cells in G0/G1 phase of the cell cycle. However, metformin significantly protected OSCC cells against cisplatin toxicity. Our results indicate that a major mechanism of metformin-induced cisplatin resistance results from a significant increase in glycolysis, intracellular NAD(P)H levels with a concomitant increase in reduced intracellular thiols, leading to decreased cisplatin-DNA adduct formation. The glutathione synthesis inhibitor buthionine sulfoximine significantly ablated the protective effect of metformin. We subsequently show that the copper-bis (thiosemicarbazones), Cu-ATSM and Cu-GTSM, which are trapped in cells under reducing conditions, cause significant OSCC cytotoxicity, both alone and in combination with metformin. Conclusions: This is the first study showing that metformin can be used to decrease cell proliferation in OSCC cells. However, metformin protects against cisplatin cytotoxicity by inducing a reducing intracellular environment leading to lower cisplatin-DNA adduct formation. As such, we advise that caution be used when administering cisplatin to diabetic patients treated with metformin. Furthermore, we propose a novel combination therapy approach for OSCC that utilises metformin with metformin-compatible cytotoxic agents, such as the copper-bis (thiosemicarbazones), Cu-ATSM and Cu-GTSM. [ABSTRACT FROM AUTHOR]

Background: Metastasis suppressor-1 (MTSS1) has been proposed to function as a cytoskeletal protein with a role in cancer metastasis. Recent studies have demonstrated the clinical significance of MTSS1 in certain type of cancers, yet the clinical relevance of MTSS1 in oesophageal squamous cell carcinoma (ESCC) has not been reported.Methods: In this study, we assessed the expression levels of MTSS1 in tumours and its matched adjacent non-tumour tissues obtained from 105 ESCC patients. We also used ESCC cells with differing MTSS1 expression and assessed the influence of MTSS1 on ESCC cells.Results: Down-regulation of MTSS1 expression was observed both in oesophageal tumour tissues and ESCC cancer cell lines. We also reported that MTSS1 expression was associated with tumour grade (p = 0.024), lymph node metastasis (p = 0.010) and overall survival (p = 0.035). Patients with high levels of MTSS1 transcripts had a favorable prognosis in comparison with those who had reduced or absent expression levels. Using over-expression and knockdown approach, we created sublines from ESCC cells and further demonstrated that MTSS1 expression in ESCC cells significantly influenced the aggressiveness of the oesophageal cancer cells, by reducing their cellular migration and in vitro invasiveness.Conclusion: MTSS1 serves as a potential prognostic indicator in human ESCC and may be an important target for cancer therapy. [ABSTRACT FROM AUTHOR]