Research progress on the mechanism of traditional Chinese medicine intervening in esophageal cancer by microRNA regulation / 中国药房

Esophageal cancer （EC） is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA （miRNA） is an important regulator in tumor occurrence and development， and can participate in malignant biological behaviors such as tumor cell proliferation， invasion， metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects， wide range of effects， and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine （including curcumin， Tussilago farfara polysaccharides， Atractylodes macrocephala polysaccharides and ophiopogonin B） and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p （miR-532-3p）， miR-551b-3p， miR-99a， miR-34a， miR-199a-3p and miR-377； and the active ingredients/parts of traditional Chinese medicine （including chrysin and Actinidia arguta extract）， and Chinese herbal formulas （including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction） could down-regulate the expressions of miRNAs such as miR-199a-3p， miR-451 and miR-21， which could regulate the expressions of signaling pathways （phosphoinositide 3-kinase/protein kinase B， etc.） or their downstream protein（zinc-finger and homeobox protein 1， etc.） or enzymes（thymidine kinase-1， etc.）， inhibit the proliferation， invasion and metastasis of EC cells and induce apoptosis， thereby ultimately achieving the purpose of preventing the disease from aggravating.

Comparison of the Recent Efficacy of Robot-assisted and Thoracic Laparoscopic Minimally Invasive Mckeown Radical Resection of Esophageal Cancer based on Propensity Score Matching / 中山大学学报(医学科学版)

ObjectiveTo explore the safety and efficacy of robot-assisted minimally invasive esophagectomy （robot-assisted minimally invasive esophagectomy， RAMIE） and thoracic laparoscopy combined with minimally invasive esophageal resection （minimal invasive esophagectomy， MIE）. MethodsThe data of 188 patients treated with Da Vinci robot assisted minimally invasive esophageal resection （RAMIE） from April 2021 to December 2022 were analyzed. In the RAMIE group， 69 patients， 49 males and 20 female， age （67.2 ± 7.2）； 119 in the MIME group， respectively， 89 males and 30 female， age （69.1 ± 7.0）. At 1 ∶ 1， including 58 patients in the RAMIE group and 58 patients in the MIE group. The t-test， Wilcoxon rank-sum test， χ2 test， and so on. ResultsAfter PSM treatment， the clinical data between the two groups. There was no significant difference in operation time， postoperative tube days， and total number of lymph node dissection between the RAMIE and MIE groups （P <0.05）； the RAMIE group was better in terms of intraoperative bleeding and the MIE group， statistically significant （P <0.05）； the MIE group was better in drainage flow and lymph node dissection for three days （P <0.05）. In terms of postoperative complications， there was no statistical difference between RAMIE and MIE groups （P>0.05）. ConclusionThe recent efficacy of robot-assisted minimally invasive esophagectomy is comparable to that of thoracic laparoscopy and minimally invasive Mckeown esophagectomy； robotic-assisted minimally invasive esophagectomy can reduce intraoperative bleeding and have more advantages in left recurrent laryngeal nerve lymph node dissection.

Diagnosis and treatment pathway of neoadjuvant immunotherapy for esophageal cancer in Henan province / 中国胸心血管外科临床杂志

@#Esophageal cancer is a highly prevalent tumor species in Henan province, which brings heavy medical burden to families and society. Surgical treatment plays a dominant role in the treatment of non-advanced esophageal cancer. However, cancer cells in esophageal cancer lesions are highly invasive, postoperative recurrence and metastasis rates are pretty high. More effective systemic and comprehensive treatment is urgently needed to improve the prognosis. We invited 52 doctors in esophageal surgery, oncology, pathology, imaging, and radiation therapy of 32 hospitals at all levels in Henan province, to repeatedly negotiate and fully discuss in combination with evidence and clinical practice experience. Finally, “diagnosis and treatment pathway of neoadjuvant immunotherapy for esophageal cancer in Henan province” was formulated. In this treatment pathway, seven recommendations were proposed from seven perspectives including target population, patient evaluation, protocol selection, surgical timing, postoperative management, organ preservation, and general principles to offer reference for medical personnel related to esophageal cancer surgery.

Take A Calm View on Heat Wave of Organ Preservation in Esophageal Cancer Treatment / 肿瘤防治研究

The esophagus plays an extremely important physiological function in human body, and esophageal cancer is a highly lethal disease among all the malignancies. Esophagectomy is still the main treatment for locally advanced esophageal cancer. Ensuring the efficacy of oncology plays a crucial role in exploring organ preservation in the treatment of esophageal cancer. We should always be aware of the inherent difficulties and potential harms of organ preservation for esophageal cancer treatment and seek a personalized and reasonable balance between ensuring cure and preserving organs, provide the best treatment design for esophageal cancer patients, to achieve maximum therapeutic effect without sacrificing the life quality of patients.

Application progress of artificial intelligence in the diagnosis of esophageal cancer / 中国胸心血管外科临床杂志

@#Esophageal cancer is an aggressive malignancy with high morbidity and poor prognosis. Symptoms of early esophageal cancer are insidious and difficult to detect, while advanced esophageal obstruction, lesion infiltration and metastasis seriously affect patients’ quality of life. Early detection and treatment can help to increase the survival chance of patients. Recently, artificial intelligence (AI) has shown remarkable success in diagnosis of esophageal cancer, highlighting the great potential of new AI-assisted diagnostic modalities. This paper aims to review recent progress of AI in the diagnosis of esophageal cancer and to prospect its clinical application.

Interpretation of the updates of the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023) / 中国胸心血管外科临床杂志

@#Esophageal cancer is the seventh most common cancer worldwide. On August 29, 2023, National Comprehensive Cancer Network (NCCN) released the NCCN esophageal and esophagogastric junction cancers clinical practice guidelines in oncology (version 3. 2023). This article aims to highlight the key updates in treatment and follow-up recommendations between the version 3 and the version 2 in 2023, providing the latest guidance for the management of esophageal cancer in our country.

Chinese Medicine Regulates Signaling Pathways Related to Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer is a common malignant tumor of the digestive tract. At present， the pathogenesis of esophageal cancer has not been fully clarified. Although surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy have achieved good clinical results in the treatment of esophageal cancer， there are still many complications and severe adverse reactions. As an important part of traditional Chinese medicine （TCM）， in recent years， many basic experiments and clinical studies have proved that Chinese medicine has a good effect in treating esophageal cancer. At the same time， the multi-component and multi-target characteristics of Chinese medicine and unclear pathogenesis of esophageal cancer determine that there are some problems such as unclear mechanisms of Chinese medicine in preventing and treating esophageal cancer. It is necessary to start with modern medicine and reveal the mechanism of Chinese medicine in preventing and treating diseases from the aspects of molecular biology and network pharmacology. It is believed in TCM that the occurrence of esophageal cancer is mostly attributed to stagnation of liver Qi， phlegm stasis and Qi stagnation， fluid consumption and heat accumulation， the decline of healthy Qi， and the cementation of cancer toxicity. According to the literature review， Chinese medicinal compounds mainly include tonic formulae （such as Liu Junzitang）， drying and moistening formulas （such as Qigesan）， and heat-clearing formulas （such as Fufang Kushen injection）. Chinese medicinal monomers mainly include drugs potent in attacking poison and killing insects， clearing heat， activating blood and resolving stasis， and regulating Qi， which is consistent with the etiology and pathogenesis of esophageal cancer in TCM. It is also found that Chinese medicine can promote cell apoptosis and autophagy， block cell cycle， and reverse cell resistance by regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， neurogenic locus notch homolog protein （Notch）， Wnt/β-catenin， mitogen-activated protein kinase （MAPK）， nuclear factor-κB （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and other related signaling pathways， but there is no systematic summary. This study systematically summarized the relevant signaling pathways of Chinese medicine in regulating esophageal cancer， which is helpful to clarify the relevant mechanisms of Chinese medicine in the process of esophageal cancer occurrence， development， invasion， and metastasis， so as to provide new targets and new perspectives for the treatment of esophageal cancer and promote the modernization of TCM.

Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention：A Review / 中国实验方剂学杂志

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Self-expanding Metal Stents in Malignant Obstruction of the Esophagus: A 25-Year Multicentric Study

Background: Self-expanding metal prostheses improve dysphagia in patients with incurable esophageal cancer (EC). New stents have been introduced, and chemoradiotherapy has been implemented for EC, changing patients' risk profiles. It is unknown whether this has affected palliation with stents. Patients and methods: Retrospective study in three centers in Medellín-Colombia; patients undergoing placement of palliative esophageal prostheses for malignant dysphagia (1997-2022). Major and minor complications after implantation, the influence of oncological therapies, and survival were evaluated for 1997-2009 (n = 289) and 2010-2022 (n = 318). Results: 607 patients underwent esophageal prostheses; 296 (48.8%) became complicated. It was higher in the second period (52.5% vs. 48.1%), as were major complications (20.8% vs. 14.2%, p = 0.033), with no differences in minor complications (33.9% vs 31.8%, p = 0.765). Also, 190 (31.3%) patients presented with recurrent dysphagia, stable in both periods. Migration increased over time (from 13.1% to 18.2%, p = 0.09). The most common minor adverse event was pain, increasing over time (from 24.9% to 33.95%, p < 0.01), and associated factors were chemoradiotherapy, absence of fistula, and squamous cell carcinoma. Acid reflux decreased in the second group (p = 0.038). Twelve percent of patients required another intervention for feeding. Survival was not impacted by time and use of stents. Conclusions: Stents are an alternative in non-surgical malignant dysphagia, although recurrent dysphagia has not decreased over time. Minor stent-related complications are increasing in association with the implementation of chemoradiotherapy.

Antecedentes: Las prótesis metálicas autoexpandibles mejoran la disfagia en pacientes con cáncer esofágico (CE) incurable. En las últimas décadas se han introducido nuevos tipos de stents y se ha implementado la quimiorradioterapia para el CE, generando cambios en los perfiles de riesgo de los pacientes. Se desconoce si estos cambios han afectado la paliación con stents. Pacientes y métodos: Estudio retrospectivo en tres centros de Medellín-Colombia; pacientes sometidos a colocación de prótesis esofágicas paliativas para disfagia maligna (1997-2022). Se evaluaron en dos períodos: 1997-2009 (n = 289) y 2010-2022 (n = 318), complicaciones mayores y menores después del implante, la influencia de las terapias oncológicas y la sobrevida. Resultados: Se evaluaron 607 pacientes sometidos a prótesis esofágicas. 296 (48,8%) se complicaron, y fue mayor en el segundo periodo (52,5% frente a 48,1%), al igual que las complicaciones mayores (20,8% frente a 14,2%, p = 0,033), sin diferencias en complicaciones menores (33,9% frente a 31,8%, p = 0,765). 190 (31,3%) pacientes presentaron disfagia recurrente, estable en ambos períodos. La migración aumentó con el tiempo (de 13,1% a 18,2%, p = 0,09). El evento adverso menor más frecuente fue dolor, que aumentó con el tiempo (de 24,9% a 33,95%, p < 0,01), y los factores asociados fueron quimiorradioterapia, ausencia de fístula y carcinoma de células escamosas. El reflujo ácido disminuyó en el segundo grupo (p = 0,038). El 12% de pacientes requirieron otra intervención para alimentarse. No se impactó la sobrevida con el tiempo y uso de stents. Conclusiones: Los stents son una alternativa en la disfagia maligna no quirúrgica, aunque la disfagia recurrente no ha disminuido con el tiempo. Las complicaciones menores relacionadas con el stent van en aumento, asociadas a la implementación de la quimiorradioterapia.

Morbilidad y mortalidad de pacientes operados de cáncer de esófago / Morbidity and Mortality of Patients Operated on for Esophageal Cancer

Introducción: El tratamiento principal del cáncer esofágico es la esofagectomía. Objetivo: Determinar la morbilidad y mortalidad de los pacientes operados de cáncer esofágico. Métodos: Se realizó un estudio observacional, descriptivo y transversal en 87 pacientes operados de cáncer esofágico en el Servicio de Cirugía General del Hospital Provincial Docente Saturnino Lora de Santiago de Cuba durante el período comprendido de 2014 a 2018. Resultados: Dos pacientes en estadio II (100,0 por ciento) recibieron tratamiento quirúrgico curativo y 12 en estadio III (17,9 por ciento). Recibieron tratamiento quirúrgico paliativo 55 (82,1 por ciento) enfermos en estadio III y 18 (100,0 por ciento) en estadio IV. Predominó la técnica transhiatal de Denk-Sloan-Orringer aplicada en 10 (71,4 por ciento) pacientes. La gastrostomía predominó como proceder paliativo para alimentación en 53 (76,2 por ciento) pacientes. Se reportaron 45 complicaciones; el 53,3 por ciento de tipo médica, en las que prevalecieron las respiratorias: bronconeumonía (13,3 por ciento) y distrés respiratorio (11,1 por ciento). En cambio, el 46,7 por ciento de las complicaciones fueron de tipo quirúrgicas: infección del sitio operatorio (20,0 por ciento), seguida de la fuga anastomótica (15,6 por ciento). Fallecieron 16 (18,4 por ciento) pacientes del total de la serie. Las causas de muerte predominantes fueron el distrés respiratorio (31,3 por ciento) y la disfunción múltiple de órganos (25,0 por ciento). Conclusiones: La esofagectomía abierta o mínimamente invasiva se erige como el tratamiento quirúrgico de elección para el tratamiento del cáncer esofágico con intención curativa, proceder con elevada morbilidad y mortalidad a escala mundial. Los resultados de esta investigación coinciden con los reportados en la literatura médica nacional y extranjera(AU)

Introduction: The main treatment for esophageal cancer is esophagectomy. Objective: To determine the morbidity and mortality of patients operated on for esophageal cancer. Methods: An observational, descriptive and cross-sectional study was carried out with 87 patients operated on for esophageal cancer in the general surgery service of Hospital Provincial Docente Saturnino Lora, of Santiago de Cuba, during the period from 2014 to 2018. Results: Curative surgical treatment was received by 2 patients (100.0 percent) in stage II and 12 patients (17.9 percent) in stage III. Palliative surgical treatment was received by 55 ill patients (82.1 percent) in stage III and 18 ill patients (100.0 percent) in stage IV. There was a predominance of the Denk-Sloan-Orringer transhiatal technique, applied in 10 (71.4 percent) patients. Gastrostomy predominated in 53 (76.2 percent) patients as a palliative procedure for feeding. Forty-five complications were reported, 53.3 percent of which were medical, with respiratory complications prevailing: bronchopneumonia (13.3 percent) and respiratory distress (11.1 percent). On the other hand, 46.7 percent of the complications were surgical: surgical site infection (20.0 percent), followed by anastomotic leak (15.6 percent). Out of the total series, 16 (18.4 percent) patients died. The predominant causes of death were respiratory distress (31.3 percent) and multiple organ dysfunction (25.0 percent). Conclusions: Open or minimally invasive esophagectomy stands out as the surgical treatment of choice for esophageal cancer with curative purposes, being a procedure with high morbidity and mortality worldwide. The results of this research coincide with those reported in the national and foreign medical literature(AU)

Realgar inhibits proliferation, invasion and induces cellular ferroptosis in esophageal cancer cells / 中国药理学通报

Aim To investigate the effects of realgar on the proliferation, invasion and ferroptosis of esophageal cancer cells. Methods Different concentrations of realgar(0, 10,20, 40, 60, 80, 100 μmol·L-1)or realgar 1/2IC

KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Pathologic assessment of esophageal cancer following neoadjuvant therapy / 中国胸心血管外科临床杂志

@#China is a country with a high incidence of esophageal cancer. Most patients are already in the locally advanced stage when first diagnosed. Preoperative neoadjuvant therapy followed by surgery has become the standard treatment mode for them. Closely related to prognosis, the evaluation of tumor response is essential. Response evaluation criteria in solid tumors is the gold standard to evaluate tumor response, but the lesions must meet the measurement standards. Tumor regression grading (TRG) systems are designed to classify regressive changes after neoadjuvant treatment based on histopathological results to reveal prognostic information. Concentrating on pathologic assessment of esophageal cancer following neoadjuvant therapy, this article reviews histopathological changes, commonly used TRG systems and current debate.

Macroscopic Clinical Medication Pattern of Traditional Chinese Medicine for Esophageal Cancer in Recent Ten Years Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo explore the macroscopic medication pattern of traditional Chinese medicine （TCM） in treating esophageal cancer （EC） and provide medication references for the clinical application of TCM in EC treatment. MethodRelevant literature on TCM treatment of EC was retrieved from three major Chinese databases： China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP. Information about Chinese herbal medicines was entered into Excel to establish a prescription database for EC. The data were standardized， summarized， and subjected to frequency analysis， association rules， and cluster analysis of medication in the prescriptions. Based on the TCM classification of EC syndromes， clinical indications corresponding to each syndrome were identified， and high-frequency drugs and drug pairs were analyzed correspondingly with syndromes. ResultA total of 136 prescriptions containing 240 Chinese herbal medicines were screened， with a cumulative frequency of 1 853 times. The top 5 frequently used Chinese herbal medicines were Glycyrrhizae Radix et Rhizoma， Poria， Atractylodis Macrocephalae Rhizoma， Astragali Radix， and Pinelliae Rhizoma. In terms of functions， the Chinese herbal medicines were mainly deficiency-tonifying， urination-promoting and dampness-draining， deficiency-tonifying， deficiency-tonifying， and phlegm-resolving and cough and dyspnea-relieving ones. The statistical analysis of flavor， property， and meridian tropism showed that Chinese herbal medicines were mainly bitter and sweet， warm， cold， and neutral， and acted on the spleen， lung， and stomach meridians. Association rule analysis yielded nine potential drug combinations， and cluster analysis of high-frequency drugs resulted in four combination categories. The four TCM syndromes for EC corresponded to respective clinical indications， treatment drugs， and drug pairs. ConclusionTonifying deficiency， reinforcing healthy Qi， descending adverse Qi， resolving phlegm， activating blood， and resolving stasis are the basic principles of TCM treatment for EC， which are supplemented by clearing heat and dissipating mass while focusing on regulating and smoothing the qi movement. The drug combinations obtained from high-frequency drug and association rule analysis provide references for different TCM syndrome treatments of EC， offering valuable insights for clinical medication.

Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Analysis of Significant Genes and Pathways in Esophageal Cancer Based on Gene Expression Omnibus Database / 中国医学科学杂志(英文版)

Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes, and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis, protein-protein interaction (PPI) network, and survival analysis based on the Gene Expression Omnibus (GEO) database.Methods By screening with highly expressed genes, we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis, PPI network, and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.

Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

Correlation Between Peripheral Blood Biomarkers and Immune Checkpoint Inhibitors in Treatment of Advanced Esophageal Cancer / 肿瘤防治研究

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.

Effects of X-ray volume imaging registration methods on position verification for radiotherapy in treatment of middle/lower-segment esophageal cancer / 中国辐射卫生

@#<b>Objective</b> To compare the set up errors derived from different registration methods of the X-ray volume imaging (XVI) system for radiotherapy in the treatment of middle/lower-segment esophageal cancer, and to provide a reference for radiation treatment of esophageal cancer. <b>Methods</b> We randomly selected 63 patients with middle/lower-segment esophageal cancer, and obtained their reconstructed XVI images at the first therapy to perform automatic registration with gray-value and bone registration methods. We acquired and compared the three translation errors (along <i>x</i> [left to right], <i>y</i> [head to feet], and <i>z</i> [front to back] axes) and three rotation errors (around the <i>x</i>, <i>y</i>, and <i>z</i> axes) derived from the two registration methods. <b>Results</b> Gray-value registration had significantly smaller translation errors along the <i>x</i> and <i>z</i> axes than bone registration (<i>x</i> azes <i>t</i> = −2.78, <i>z</i> azes <i>t</i> = −2.15, <i>P</i> < 0.05), but there was no significant difference along the <i>y</i> axes (<i>P</i> > 0.05). The rotation errors around the three axes were all smaller than 1°, and were smaller with gray-value registration than with bone registration, but without significant differences (<i>P</i> > 0.05). <b>Conclusion</b> We recommend gray-value registration for radiotherapy in the treatment of middle/lower-segment esophageal cancer. Manual verification or fine-tuning is recommended after automatic registration in clinical practice. Besides translation errors, rotation errors should also be paid attention to.

Ethyl Acetate Extract of Qigesan Intervenes in Migration and Invasion of Esophageal Cancer Cells via Inhibiting TGF-β1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Qigesan （QGS） in intervening in the migration and invasion of esophageal carcinoma TE-1 cells. MethodMicroarray technology was used to screen differentially expressed genes （DEGs） in the normal group and the QGS group， and the ontological functions and signaling pathways of DEGs were analyzed. The thiazolyl tetrazolium （MTT） assay was used to detect the effect of QGS on the viability of TE-1 cells. In the subsequent experiments for verification， a blank group， a transforming growth factor-β1 （TGF-β1） group， a TGF-β1 + QGS group， and a TGF-β1 + SB431542 group were set up. The cell morphology in each experimental group was observed by microscopy. The migration and invasion abilities of cells were detected by wound healing assay， and the mRNA expression levels of E-Cadherin， vimentin， Smad2， and Smad7 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of E-Cadherin， vimentin， p-Smad2/3， Smad2/3， and Smad7 was detected by Western blot. ResultThere were 1 487 DEGs between the QGS group and the blank group， including 1 080 down-regulated ones （accounting for 72.63%） and 407 up-regulated ones. The down-regulated genes were mainly involved in biological processes such as cytoskeletal protein binding， ATP binding， adenylate nucleotide binding， and adenylate ribonucleotide binding， and the involved Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways included TGF-β signaling pathway， cell cycle， extracellular matrix-receptor interaction protein， tumor pathways， and oocyte meiosis. The up-regulated genes were mainly involved in RNA binding， DNA binding， transcriptional regulator activity， transcriptional activator activity， and nucleotide binding， and the KEGG pathways involved mainly included mitogen-activated protein kinase （MAPK） signaling pathway， bladder cancer， renal cell carcinoma， cancer pathways， and p53 signaling pathway. Compared with the blank group， the inhibition rate of cell viability of TE-1 cells increased after QGS （20， 30， 40， 60， 80 mg·L-1） intervention for 12， 24， 36， 48， 60 h （P<0.05）， and the inhibition rate was time- and dose-dependent. Compared with the blank group， the TGF-β1 group showed lengthened cells with fibroblast phenotype. Compared with the TGF-β1 group， the TGF-β1 + QGS group showed shortened cells with normal morphology and epithelial phenotype. The cell morphology in the TGF-β1 + SB431542 group was similar to that of the TGF-β1 + QGS group. Compared with the blank group， the TGF-β1 group showed potentiated ability of cell migration and invasion （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group showed inhibited and weakened migration and invasion abilities of cells （P<0.05）. However， there was no significant difference in migration and invasion abilities between the TGF-β1 + QGS group and the TGF-β1 + SB431542 group. The mRNA expression levels of vimentin and Smad2 in the TGF-β1 group were higher （P<0.05）， and the mRNA expression levels of E-Cadherin and Smad7 were lower （P<0.05） than those in the blank group. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1+ SB431542 group exhibited decreased expression levels of vimentin and Smad2 mRNA （P<0.05）， and elevated expression levels of E-Cadherin and Smad7 mRNA （P<0.05）. Compared with the blank group， the TGF-β1 group showed up-regulated protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and reduced protein expression levels of E-Cadherin and Smad7 （P<0.05）. Compared with the TGF-β1 group， the TGF-β1 + QGS group and the TGF-β1 + SB431542 group displayed decreased protein expression levels of vimentin， p-Smad2/3， and Smad2/3 （P<0.05）， and increased protein expression levels of E-Cadherin and Smad7 （P<0.05）. ConclusionThe ethyl acetate extract of QGS inhibits the epithelial-mesenchymal transition （EMT） of TE-1 cells through the TGF-β1 pathway to reduce the migration and invasion of TE-1 cells.