Treatment Of Esophageal Carcinoma Research Articles

Gallic acid from Terminalia chebula inhibited the growth of esophageal carcinoma cells by suppressing the Hippo signal pathway.

Objective(s):To explore the molecular mechanism of gallic acid (GA) from Terminalia chebula in suppressing the growth of esophageal carcinoma (EC).Materials and Methods:Human EC cells (EC9706 and KYSE450) were treated with different concentrations of GA (10, 20, and 40 μg/ml), which were subjected to 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, plate clone formation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining, and Western blotting. EC mice were divided into Model, 0.3% GA, and 1% GA groups to observe the tumor volume and the expressions of YAP, TAZ, Ki-67, and Caspase-3 in tumor tissues. Results:GA decreased cell viability and colony formation of EC9706 and KYSE450 cells, which was more obvious as the concentration increased. In addition, GA promoted cell apoptosis in a concentration-dependent manner with the up-regulation of pro-apoptotic proteins (Bax, cleaved caspase-3, and cleaved caspase-9) and nuclear YAP/TAZ, as well as the down-regulation of anti-apoptotic protein Bcl-2 and the levels of p-YAP and p-TAZ. Moreover, GA decreased the growth of xenograft tumor in vivo, with the reduction in the tumor volume and the reduction of YAP and TAZ expressions in the tumor tissues. In addition, Ki-67 expression in GA groups was lower than those in the Model group, with the increase in caspase-3 expression in the tumor tissues. Changes aforementioned were obviously shown in the 0.3% GA group. Conclusion:GA blocked the activity of the Hippo pathway to suppress cell proliferation of EC and facilitate cell apoptosis, which is expected to be a novel strategy for treatment of EC.

A nanomicelle with miR-34a and doxorubicin reverses the drug resistance of cisplatin in esophageal carcinoma cells by inhibiting SIRT1 signal pathway.

BackgroundEsophageal carcinoma (EC) is one of the most deadly malignant tumors in the world. Surgery, combined with chemotherapy or radiotherapy, is the traditional strategy for the treatment of EC. Cisplatin (CDDP) is a common chemotherapy drug widely used to treat EC due to its powerful anti-tumor effect. However, CDDP is subject to intrinsic or acquired resistance in EC cells, which badly hinders the efficacy of chemotherapy. The resistance phenomenon is mostly caused by the p53 mutant in the EC and the low efficiency of the drug delivery system.MethodsIn this study, a specially designed nanomicelle was used to promote the anti-tumor effect of chemotherapy drugs against the CDDP-resistant EC cells. The nanomicelle consisted of miR-34a, doxorubicin (DOX), polyethylene glycol (PEG), and other excipients in an appropriate ratio.ResultsThe results showed that the nanomicelle could exert significant cell proliferation inhibition and apoptosis-inducing effects in the CDDP-resistant EC cells. The endogenous expression of miR-34a in the CDDP-resistant EC cells was promoted by the incubation with the nanomicelle. After incubation with the nanomicelle, the expression of protein SIRT1 was inhibited, and the expression of caspase3 was promoted significantly in the CDDP-resistant EC cells.ConclusionsOur results indicate that the specially designed nanomicelle can exert promising anti-tumor effects by introducing miR-34a to inhibit SIRT1 signaling pathway and enhance the efficiency of the drug delivery system.

Xiaoaiping injection as adjunct therapy for patients with advanced esophageal carcinoma: A protocol for a systematic review and meta-analysis.

Background:Esophageal carcinoma (EC) is one of the worst malignant digestive neoplasms with a strong tendency of invasion and metastasis. Despite the improvement of diagnostic and therapeutic methods in the past decades, the prognosis of EC remains unsatisfactory. Xiaoaiping injection (XAPI), a famous traditional Chinese herbal medicine, has been widely applied as a promising adjunctive drug for EC. However, the exact effects and safety of XAPI have yet to be systematically investigated. We aimed to summarize the efficacy and safety of XAPI for the treatment of advanced EC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials.Methods:Relevant randomized controlled trials (RCTs) were searched from Cochrane Library, PubMed, Google Scholar, Web of Science, Excerpt Medica Database, Medline, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Scientific Journal Database and Wanfang Database. Papers in English or Chinese published from January 2000 to May 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate, overall survival, Disease-free survival, quality of life, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the studies was also evaluated.Results:The results of this study will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice.Conclusion:Our study will draw an objective conclusion of the effects of XAPI combined with conventional treatment for advanced EC and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for EC patients.INPLASY registration number:INPLASY202050094.

Combination of DCE-MRI and DWI in Predicting the Treatment Effect of Concurrent Chemoradiotherapy in Esophageal Carcinoma.

Background Concurrent chemoradiotherapy (CCRT) is the main treatment for esophageal cancer, but the response to treatment varies from individual to individual. MR imaging methods, such as diffusion-weighted (DW) MRI and the use of dynamic contrast-enhanced (DCE) MRI, have the potential to provide additional biomarkers that could evaluate the effect of CCRT in patients with esophageal carcinoma. Materials and Methods Fifty-six patients with esophageal carcinoma, verified by histopathology, underwent MRI examination before and at midtreatment (4th week, radiotherapy 30–40 Gy) using the Siemens 3.0 T MR System. Parameter maps of apparent diffusion coefficient (ADC), and DCE maps of volume transfer constant (Krans), rate contrast (kep), and extracellular fluid space (ve), were computed using a Siemens Company Multimodality Workplace (MMWP) model. Comparison of histogram parameters and their diagnostic performance was determined using the Mann–Whitney U test and receiver operating characteristic (ROC) analysis. Results 56 patient MRI scans were available for analysis at baseline and at the third week, respectively. Pretreatment Krans, pretreatment kep, pretreatment ADC (P < 0.05), and during-treatment Krans (P < 0.05) and ΔKrans and ΔADC (P < 0.05) were significantly different after CCRT. Based on the binary logistic model, the ROC analysis demonstrated that the combined predictors demonstrated a high diagnostic performance with an AUC of 0.939. The sensitivity and specificity were 98.6% and 73.8%, respectively. Conclusion The combination of DCE and DWI can be used as an early biomarker in the prediction of the effect of CCRT three weeks after treatment in esophageal carcinoma.

PRR11 and SKA2 promote the proliferation, migration and invasion of esophageal carcinoma cells.

Proline-rich protein 11 (PRR11) together with its upstream adjacent gene, spindle and kinetochore associated 2 (SKA2), represent a classic, head-to-head gene pair. The role of the PRR11 and SKA2 gene pair has been described in various types of cancer, including breast cancer, non-small cell lung cancer, hepatocellular carcinoma and ovarian carcinoma. However, its role in esophageal carcinoma (ESCC) remains unclear. The mRNA expression levels of PRR11 and SKA2 were examined in ESCC surgical specimens. In addition, the role of PRR11 and SKA2 in the proliferation and migratory and invasive capacities of EC9706 and EC109 cell lines was examined. The results from the present study demonstrated that PRR11 and SKA2 expression levels were upregulated in ESCC tissues compared with adjacent normal tissues. Furthermore, PRRl1 and SKA2 knockdown significantly inhibited the proliferation and migratory and invasive capacities of ESCC cells. Conversely, PRRl1 and SKA2 overexpression significantly promoted the proliferation and migratory and invasive capacities of ESCC cell lines via activation of the AKT signaling pathway and certain markers of epithelial-mesenchymal transition, including Snail and N-cadherin. The results from the present study suggested that the PRR11 and SKA2 gene pair may represent a potential target in the diagnosis and treatment of ESCC.

Tolerance and efficacy of dose escalation using IMRT combined with chemotherapy for unresectable esophageal carcinoma: Long-term results of 51 patients

PurposeThe optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60Gy delivered with intensity-modulated radiotherapy (IMRT). Materials and methodsAll consecutive patients that received a definitive CRT>50Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. ResultsA total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60Gy (54–66) and 48Gy (44.8–56) delivered in 30 (27–35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4Gy (IC 95%: 4.8–19.8), the median volumes receiving up to 20Gy (V20) and 30Gy (V30) were 13.5% (3.0–46.0) and 4.6% (0.7–19.8) respectively. The mean dose delivered to the heart was 13.9Gy (IC 95%:0.3–31.3) with a median V40 of 3.3% (0.0–25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9–4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). ConclusionWe demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.

PRDX2 plays an oncogenic role in esophageal squamous cell carcinoma via Wnt/β-catenin and AKT pathways

To investigate the role of PRDX2 in esophageal carcinoma (ESCA). The expression of PRDX2 was detected in ESCA tissues. And PRDX2 expression in two ESCA cell lines was knocked down. Cell proliferation, metastasis and invasion were detected in these cells. Here, we found that PRDX2 expression was significantly increased in ESCA tissues and was associated with a poor prognosis in ESCA patients. In addition, PRDX2 expression was significantly associated with pathological grading, infiltration degree and 5-year survival time in ESCA patients. Next, we knocked down PRDX2 expression by PRDX2-shRNA transfection in two ESCA cell lines, Eca-109 and TE-1. Proliferation analysis indicated that in vitro PRDX2 knockdown decreased growth and clone formation of ESCA cells. Scratch and transwell assays indicated that cell migration and invasion were significantly inhibited by PRDX2 knockdown. In addition, PRDX2 knockdown inhibited cell cycle of ESCA cells and down-regulated Cyclin D1-CDK4/6. Moreover, PRDX2 knockdown regulated proteins involved in mitochondrial-dependent apoptosis, including increased Bax and Caspase9/3 and decreased Bcl2. Mechanism investigation indicated that PRDX2 knockdown led to inactivation of Wnt/β-catenin and AKT pathways. Our data suggest that PRDX2 may function as an oncogene in the development of ESCA via regulating Wnt/β-catenin and AKT pathways. Our study fills a gap in the understanding of the role of PRDX2 in ESCA and provides a potential target for ESCA treatment.

Effect of TTLL6 expression on CDDP sensitivity of EC109/CDDP cells in hypoxia/acidosis microenvironment.

Multidrug resistance is a major obstacle to the effective treatment of esophageal carcinoma. It occurs more readily in hypoxia and acidosis microenvironment. TTLL6 is one of Tubulin tyrosine ligase-like family members. In this study, the effect of TTLL6 on the regulation of cisplatin (CDDP) sensitivity was evaluated in CDDP-resistant esophageal carcinoma (EC) cells both in vitro and in vivo. In hypoxia/acidosis condition, overexpression of TTLL6 in EC109/CDDP cells significantly lowered the IC50 of CDDP and increased the CDDP-induced apoptosis; while knockdown of TTLL6 expression in EC109/CDDP cells exhibited the opposite effects. Further study showed that, mechanistically, TTLL6 was inversely correlated with ERBB2 and TOPOIIA, and positively correlated with apoptosis-associated factor Caspase 9. Furthermore, animal model confirmed that TTLL6 negatively regulated the growth of xenograft tumor after chemotherapy. Alternated expression of TTLL6 also regulated the expression of ERBB2, TOPOIIA and Caspase 9 in EC109/CDDP cells in vivo. In conclusion, our results suggest that TTLL6 could reverse the drug resistant of EC109/CDDP cells, it might provide a potential treatment strategy for the clinical reversing the chemotherapy resistance.

Adjuvant radiotherapy for patients with pathologic node-negative esophageal carcinoma: A population based propensity matching analysis.

BackgroundThe impact of adjuvant treatment for esophageal carcinoma with tumor‐negative lymph nodes after upfront radical esophagectomy is still uncertain. This study investigated the effects of postoperative radiotherapy in pT1‐3N0 esophageal carcinoma after radical resection.MethodWe retrospectively identified pT1‐3N0M0 esophageal carcinoma patients between 2000 and 2016 from the Surveillance, Epidemiology, and End Results database. Patients with upfront esophagectomy were categorized as having received surgery alone (SA) and surgical resection followed by adjuvant radiotherapy (SA + RT). Propensity score matching, univariate and multivariate analysis were performed to compare overall survival (OS) and cause‐specific survival (CSS).ResultsA total of 2862 patients were identified, of whom 274 received SA + RT and 2588 received SA. The median follow‐up was 60.4 months (95%CI, 58.7–62.1 months). The five‐year OS and CSS were better for SA group compared with SA + RT group (P < 0.001, respectively). Furthermore, after matching, the OS and CSS were still significantly better for SA patients. For T subgroup analysis, postoperative radiotherapy was an independent prognostic factor only for pT1 patients with worse OS, without survival differences for pT2 and pT3 patients. However, after multivariate cox analysis, postoperative radiotherapy can provide significantly better OS for pT3 patients with tumor length ≥5 cm (P = 0.03; 95%CI, 0.29–0.94).ConclusionsAmong pT1‐3N0M0 esophageal carcinoma patients, postoperative radiotherapy can provide significantly better OS for pT3 patients with tumor length ≥5 cm. However, there are no survival benefits for pT1‐2 patients after SA + RT procedure. This finding may have significant implications on the use of adjuvant radiation in patients with pN0 disease.

RETRACTED: Silencing lncRNAs PVT1 Upregulates miR-145 and Confers Inhibitory Effects on Viability, Invasion, and Migration in EC

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is correlated to various malignant tumors. Consequently, we explored effects of lncRNA PVT1 on esophageal carcinoma (EC) targeting microRNA-145 (miR-145). EC tissues, adjacent normal tissues, and EC-related cell lines were collected and cultured. Expression of lncRNA PVT1, miR-145, fascin-1 (FSCN1), and related genes with intervening expression of PVT1 and miR-145 was determined. Bioinformatic website, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) were carried to verify target relationship among lncRNA PVT1, FSCN1, and miR-145. Scratch test, Transwell assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry were performed for detection of migration, invasion, viability, and apoptosis of transfected cells, respectively. Finally, tumor formation in nude mice was measured. After database analysis, lncRNA PVT1, miR-145, and FSCN1 were selected for study. lncRNA PVT1 and FSCN1 can bind to miR-145. After overexpressing miR-145 or inhibiting lncRNA PVT1, EC cell viability, migration, and invasion were inhibited, while volume and weight of tumor formation in nude mice decreased. Expression of lncRNA PVT1, FSCN1, Bcl-2, CD147, VEGFR2, and MTA1 decreased and expression of miR-145 and Bax increased. Silencing lncRNA PVT1 can upregulate miR-145, which is a tumor suppressor in EC via knockdown of FSCN1. Thus, we might provide a potential theoretical basis for EC treatment.

Efficacy of chemo-radiotherapy versus radiotherapy alone in the treatment of esophageal carcinoma

Background: The treatment of esophageal carcinoma may demand multiple approaches including combination of radiotherapy and chemotherapy, particularly cases which are considered unresectable, such as upper third esophageal cancers, locally advanced middle and lower third cancers. Methods: This was a prospective, randomized, open-label, single-center study conducted between December 2014 and July 2016. Patients of either sex aged more than 18 years with the confirmed diagnosis of previously untreated advanced esophageal carcinoma were included in the study. Eligible patients were randomized to receive one of the treatments (chemo-radiotherapy [cisplatin] or radiotherapy alone). Response criteria included dysphasia free survival (DySF), disease free survival (DFS), and overall survival (OS). Tolerability was also assessed. Results: A total of 31 patients (chemo-radiotherapy, n=13; radiotherapy alone, n=18) were enrolled in this study. At one year, the probability of remaining dysphagia free was 40% and 20%, respectively for chemo-radiotherapy and radiotherapy alone groups; and the probability of OS was 64% versus 21%, respectively. The median DFS was 12 months and 5 months for chemo-radiotherapy and radiotherapy alone group, respectively. There were no significant differences in both the groups in EBRT, total treatment duration and duration of EBRT. No patient reported thrombocytopenia or nephrotoxicity. Conclusions: Concurrent chemo-radiotherapy with cisplatin can improve dysphasia and OS in patients with esophageal carcinoma.

Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1.

Accumulating evidence has established that long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is a tumor regulator in many cancers. Here, we aimed to investigate the possible function of lncRNA PVT1 in esophageal carcinoma (EC) via targeting of microRNA‐145 (miR‐145). Initially, microarray‐based gene expression profiling of EC was employed to identify differentially expressed genes. Moreover, the expression of lncRNA PVT1 was examined and the cell line presenting with the highest level of lncRNA PVT1 expression was selected for subsequent experiments. We then proceeded to examine interaction among lncRNA PVT1, FSCN1, and miR‐145. The effect of lncRNA PVT1 on viability, migration, invasion, apoptosis, and tumorigenesis of transfected cells was examined with gain‐of‐function and loss‐of‐function experiments. We observed that lncRNA PVT1 was robustly induced in EC. lncRNA PVT1 could bind to miR‐145 and regulate its expression, and FSCN1 is a target gene of miR‐145. Overexpression of miR‐145 or silencing of lncRNA PVT1 was revealed to suppress cell viability, migration, and invasion abilities, while also stimulating cell apoptosis. Furthermore, our in vivo results showed that overexpression of miR‐145 or silencing of lncRNA PVT1 resulted in decreased tumor growth in nude mice. In conclusion, our research reveals that down‐regulation of lncRNA PVT1 could potentially promote expression of miR‐145 to repress cell migration and invasion, and promote cell apoptosis through the inhibition of FSCN1. This highlights the potential of lncRNA PVT1 as a therapeutic target for EC treatment.

Investigation into the expression levels of MAGEA6 in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues.

Esophageal carcinoma (EC) is the sixth most deadly of all cancers. It is among the most malignant cancers due to its highly aggressive nature and low survival rate. The incidence of EC is high in Asia, particularly in Southern areas including China, Iran and Japan. There is a large body of evidence to suggest an association between the melanoma antigen gene (MAGE) family and the initiation of cancer; however, there is no clear evidence to suggest an association between EC and MAGE. Discovery of the chemical and physiological processes relevant to the occurrence of EC is vital for clinicians to diagnose and treat this highly aggressive cancer. The present study focused on the association of EC with the expression of MAGE family member A6 (MAGEA6) at the mRNA and protein levels using gene chip, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The expression of MAGEA6 in human esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) tissue samples were compared with those in paracancerous tissue. The result of the gene chip assay revealed that as the generation grew, there was a significant increase in MAGEA6 transcription in the esophageal epithelial cell line, SHEE Different ESC cell lines also exhibited a significantly higher transcription of MAGEA6 compared with the HaCaT cell line, as determined via reverse transcription-quantitative PCR. An higher positive rate of MAGEA6 expression in ESCC and EAC tissues was also revealed when compared with paracancerous tissues, as determined via immunohistochemistry. The results indicated that MAGEA6 is highly transcribed and expressed in the development of EC and may therefore serve as a novel biomarker for the diagnosis or treatment of EC.

Screening of differentially expressed genes of esophageal squamous cell carcinoma with cDNA microarray.

e13005 Background: Esophageal Carcinoma (EC) is one of the most common malignant tumors in digestive system and is the sixth leading cause of cancer-related mortality worldwide. To find out the genes related with the occurrence and development of EC can help to elucidate the pathogenesis and molecular mechanism of it. The aim of the present study was to find out differentially expressed genes of EC in different stages(cancerous tissue, paraneoplastic tissue, normal mucosa tissue) by cDNA microarray technique, so that to provide new molecular biomarker and approach for the treatment and diagnosis of EC, and contribute to comprehensively knowing the mechanism of EC occurrence and development. Methods: The whole RNA of 21 cases of EC cancerous tissue, paraneoplastic tissue and normal mucosa tissue were extracted, then using agarose gel electrophoresis to make quality control, Agilent human genome 4*44K gene chip was applied to screen differentially expressed genes. Results: 2659 differential expression genes between cancerous tissue and normal mucosa tissue were screened, included 1328 up-regulated genes and 1331 down-regulated genes; 2505 differential expression genes between cancerous tissue and paraneoplastic tissue were screened, included 1286 up-regulated genes and 1218 down-regulated genes. 48 significant up-regulation genes and 11 significant down-regulation genes were reported in association with EC for the first time. Through GO classification, screened differentially expressed genes mainly were involved in the following function and process: catalytic activity, signal transduction, molecular transport and combination, enzymatic activity regulation, transcription activity regulation, protein transportation function, cell growth and apoptosis, and so on. Conclusions: The screened differential expression genes of EC in different stages may provide experimental basis for further illuminating the occurrence mechanism of esophageal squamous carcinoma.

MiRNA‑30a‑3p inhibits metastasis and enhances radiosensitivity in esophageal carcinoma by targeting insulin‑like growth factor 1 receptor.

It has been demonstrated that microRNAs (miRNAs) serve important roles in various biological processes, such as tumorigenesis. In the present study, the role of miR-30a-3p in the pathogenesis of esophageal carcinoma (EC) was investigated. Reverse transcription-quantitative polymerase chain reaction was performed to determine the levels of miR-30a-3p expression in EC tissues and cell lines. Then, the effects of miR-30a-3p on the migration, invasion and radiosensitivity of EC cells were investigated using scratch-wound, Transwell and radiosensitivity assays, respectively. A dual-luciferase reporter assay was performed to determine potential interactions between miR-30a-3p and the 3′-untranslated region (3′-UTR) of insulin-like growth factor 1 receptor (IGF-1R). The results demonstrated that the levels of miR-30a-3p expression in EC tissues and cell lines were significantly decreased compared with those in paired healthy tissues and a human esophageal epithelial cell line. Upregulation of miR-30a-3p expression significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT), and enhanced radiosensitivity in EC cells. Analysis of luciferase activity demonstrated that miR-30a-3p interacted with the 3′-UTR of IGF-1R, and knockdown of IGF-1R induced similar effects on the migration, invasion, EMT and radiosensitivity of EC cells. The results indicated that miR-30a-3p suppressed metastasis and enhanced the radiosensitivity of EC cells via downregulation IGF-1R, suggesting that miR-30a-3p may be a potential therapeutic target in the treatment of EC.

Analysis of the function of MAGE-A in esophageal carcinoma by bioinformatics.

Background:Melanoma-associated antigen-A (MAGE-A) was recognized as high-expressed in many solid tumors including esophageal carcinoma (EC), nevertheless, was reported to be low/not-expressed in normal tissues. Thus, it was considered as an extraordinary appropriate target for treatment especially in immunotherapy. Therefore, it demanded more detail knowledge on the precise function of MAGE-A.Methods:In this study, we used the data from the Cancer Genome Atlas dataset (TCGA-ESCA) to analyze the expression and survival for MAGE A3/4/11 (the subtype of MAGE-A) using the online tool of UALCAN. Furthermore, the high-throughput sequencing data of the patients with esophageal squamous-cell carcinoma (ESCC) from TCGA dataset were performed to analyze the correlation test, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of MAGE A3/4/9/11 using LinkeDomics (online tool) and ClueGO (inner software of Cytoscape). Finally, relative gene expressions of MAGE A3/4/9/11 were verified by quantitative real-time PCR (q-PCR) in the patients with EC.Results:MAGE A3/4/11 was high-expressed in tissues of patients with ESCC, and there was no difference in survival time for patients between the high-expressed with the low/medium-expressed. The Go enrichment analysis showed that the 4 MAGE-A subtypes (MAGE-A3/4/9/11) were enriched in the regulation of the adaptive immune response, translational initiation, interleukin-4 production, response to type I interferon, and skin development, respectively. The KEGG results showed that they were enriched in T cell receptor signaling pathway (MAGE-A3), Th1 and Th2 differentiation, antigen processing and presentation (MAGE-A4), cytokine-cytokine receptor interaction (MAGE-A9), and chemokine signaling pathway (MAGE-A11).Conclusion:MAGE A3/4/9/11 was high-expressed in EC, and were enrolled in the regulation of immune response. They may consider as candidate immune target for EC treatment and provided the messages for further research in the function of MAGE-A.

Differences in Esophageal Cancer Surgery in Terms of Surgical Approach and Extent of Lymphadenectomy: Findings of an International Survey

IntroductionEsophagectomy and lymphadenectomy are essential parts of the multimodal treatment of esophageal carcinoma with curative intent. Treatment regimens vary globally and are subject to debate. A global survey was designed to gain insight into current practice.MethodsFifty-seven international expert upper gastrointestinal surgeons received a personal invitation to participate in the survey, which focused on demographics and experience; extent of lymphadenectomy in adeno and squamous cell carcinoma; use of classification systems; neoadjuvant therapy; surgical approach; and specimen handling.ResultsThe response rate was 88% (50/57 surgeons), with a mean age of 51.6 years and a median number of 15 years of experience in esophageal surgery. The variety in the extent of lymphadenectomy in proximal, middle and distal squamous cell carcinoma, and Siewert I, II and III adenocarcinoma, was considerable. The number of different combinations of lymph node (LN) stations that were resected in the same tumor was high, while the number of surgeons who removed the exact same combination of LN stations was low. Illustrative is Siewert I adenocarcinoma, in which 27 unique combinations of LN stations were resected, with a maximum of two surgeons performing the exact same dissection. Use of neoadjuvant therapy, surgical approach, and specimen handling also show great variety among participants.ConclusionThere is no uniform, worldwide strategy for surgical treatment of esophageal cancer. The extent of lymphadenectomy shows great variation for both histologic types. An international observational study is needed to provide evidence on the distribution pattern of lymph node metastases in esophageal cancer and the necessary extent of lymphadenectomy.

Chinese guidelines for diagnosis and treatment of esophageal carcinoma 2018 (English version).

Chinese guidelines for diagnosis and treatment of esophageal carcinoma 2018 (English version).

Changes in quality of life following initial treatment of oesophageal carcinoma: a cohort study from Sri Lanka

BackgroundOesophageal carcinoma is one of the leading cancers in Sri Lanka. Recent advances in treatment modalities have drastically improved the survival of these patients. However, the quality of life (QoL) among the survivors needs to be reviewed in order to recognise the need for advocating more focussed rehabilitation for oesophageal carcinoma in Sri Lanka.MethodsA prospective cohort study was conducted among 51 incident cases of oesophageal carcinoma recruited consecutively from the National Cancer Institute, Maharagama. Data were collected on their QoL using EORTC QLQ-C30 and EORTC-OES18 questionnaires validated for Sri Lankan oesophageal carcinoma patients, before and one month after the completion of initial treatment. Scoring was based on the EORTC manual. Comparison of baseline and follow-up scores was done using paired t test at significance level of 0.05.ResultsResponse rate was 80%. The majority consisted of squamous cell carcinoma of stage IV. On a scale of 0–100, the overall QoL (mean score = 49.8; SD = 22); and role (42.2; SD = 34), physical (53.1; SD = 29), emotional (53.4; SD = 26) and social (57.2; SD = 23) functioning were relatively low at diagnosis. The scores of functioning scales further deteriorated (difference > 5 points) following the initial treatment (p < 0.05). Dysphagia (mean = 54; SD = 27) was the main symptom at diagnosis, which improved significantly (p < 0.05) in contrast to dry mouth (mean = 39.2; SD = 34) that worsened (p < 0.05) following initial treatment. Family support and financial difficulties were adversely affected (p < 0.05) during the initial treatment.ConclusionsThe deterioration of several dimensions of QoL of oesophageal carcinoma patients following the initial treatment highlights the need for more targeted tertiary preventive strategies that address the issues identified.

Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking.

Patients with esophageal carcinoma (ESCA) have a poor prognosis and high mortality rate. Although standard therapies have had effect, there is an urgent requirement to develop novel options, as increasing drug tolerance has been identified in clinical practice. In the present study, differentially expressed genes (DEGs) of ESCA were identified in The Cancer Genome Atlas and Genotype-Tissue Expression databases. Functional and protein-protein interaction (PPI) analyses were performed. The Connectivity Map (CMAP) was selected to predict drugs for the treatment of ESCA, and their target genes were acquired from the Search Tool for Interactions of Chemicals (STITCH) by uploading the Simplified Molecular-Input Line-Entry System structure. Additionally, significant target genes and ESCA-associated hub genes were extracted using another PPI analysis, and the corresponding drugs were added to construct a network. Furthermore, the binding affinity between predicted drug candidates and ESCA-associated hub genes was calculated using molecular docking. Finally, 827 DEGs (|log2 fold-change|≥2; q-value <0.05), which are principally involved in protein digestion and absorption (P<0.005), the plasminogen-activating cascade (P<0.01), as well as the ‘biological regulation’ of the Biological Process, ‘membrane’ of the Cellular Component and ‘protein binding’ of the Molecular Function categories, were obtained. Additionally, 11 hub genes were obtained from the PPI network (all degrees ≥30). Furthermore, the 15 first screen drugs were extracted from CMAP (score <−0.85) and the 9 second screen drugs with 70 target genes were extracted from STITCH. Furthermore, another PPI analysis extracted 51 genes, and apigenin, baclofen, Prestwick-685, menadione, butyl hydroxybenzoate, gliclazide and valproate were selected as drug candidates for ESCA. Those molecular docking results with a docking score of >5.52 indicated the significance of apigenin, Prestwick-685 and menadione. The results of the present study may lead to novel drug candidates for ESCA, among which Prestwick-685 and menadione were identified to be significant new drug candidates.