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Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Subject(s)
Humans , Benzydamine , Esophageal Neoplasms/drug therapy , Esophageal Squamous Cell Carcinoma/drug therapy , Molecular Docking Simulation , Phosphorylation , Cell Proliferation , Cell Line, Tumor , Apoptosis , Cyclin-Dependent Kinase 2ABSTRACT
Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.
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<p><b>OBJECTIVE</b>To estimate the cost-effectiveness of esophageal cancer endoscopic screening once-in-a-lifetime and to predict the optimal screening age for people in high-risk areas of rural China.</p><p><b>METHODS</b>A Markov model was constructed to predict and compare the effect of four esophageal cancer endoscopic screening modalities which varied with different screening ages. Long-term epidemiological effectiveness and cost-effectiveness were predicted by simulation of the model.</p><p><b>RESULTS</b>Compared with the control group, strategies starting at 40, 45, 50 and 55 year-old had saved life-years of 629.51, 769.88, 738.98 and 533.21 years per 100 000 people, respectively, of which the strategy starting at 45 year-old saved the maximum life years. All strategies were cost-effective and starting at 40 year-old cost the most per life-year saved. Among all alternatives, strategies starting age at 45 year-old and 50 year-old were incremental cost-effective, and the incremental cost-effective ratios were 34 962.87 and 3 346.43 RMB per life year saved, respectively.</p><p><b>CONCLUSIONS</b>The strategy starting at 40 year-old implemented at present and other strategies were cost-effective in high-risk areas of rural China. However, the 45-year-old group is more aligned with the principle of cost-effectiveness. Considering the cost-effectiveness of different strategies and social economic status, 45 year-old is regarded as the optimal starting age of esophageal cancer once-in-a-lifetime endoscopic screening and is recommended in areas lacking health resources. The strategy of starting age at 40 year-old which could obtain better screening effects would be preferable in wealthy regions.</p>
Subject(s)
Adult , Humans , Middle Aged , Age Factors , Case-Control Studies , China , Cost-Benefit Analysis , Early Detection of Cancer , Esophageal Neoplasms , Diagnosis , Esophagoscopy , Economics , Markov Chains , Rural PopulationABSTRACT
Objective: To analyze the survival rate of stomach cancer patients and its variation during different periods in Linzhou city, Henan Province, from 1988 to 2004, and evaluate the level of secondary prevention and diagnosis of stomach cancer in this area. Methods: All of the incidence and death records of stomach cancer from 1988 to 2004 were collected and matched from Linzhou Cancer Registry. The records that were identified as duplicate cases or had only death certificate (DCO) were excluded. The tumor cause eliminated life tables in this area were calculated and linked to the data of incidence and death of stomach cancer. FivE-year observed survival rates and fivE-year relative survival rates in three periods (1990-1994, 1995-1999, and 2000-2004) were calculated using period survival analysis mehod. The relative survival curves in the three periods were plotted. Results:The 5-year relative survival rate of stomach cancer was 26.66% during 1990-1994, 32.01% during 1995-1999, and 40.43% during 2000-2004 in Linzhou city. It showed a gradually increasing trend. The 5-year survival rates were higher in males than those in females. During 1990-1994 and 1995-1999, the 5-year survival rates of gastric cardia cancer were higher than those of non-cardia cancer. During 2000-2004 period, the 5-year survival rate of gastric cardia cancer was lower than that of non-cardia cancer. Conclusion: The survival rates of stomach cancer in Linzhou city are increasing gradually since 1990s in 20 century. It indicates that the levels of secondary prevention and clinical diagnosis and treatment on stomach cancer kept increasing in this area.
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Objective: To study early diagnosis and treatment of multi-primary esophageal cancer and esophageal and cardiac double primary cancer. Methods: The data of 71 cases patients of multi-primary esophageal, double primary esophageal and cardiac cancer were collected. The diagnosis was made by dye staining through gastroscopy and X-ray. Pathological examination after operation was analyzed. Results: 14 patients were diagnosed by X-ray(14/71), 69 by endoscopy (69/71), 54 early foci and 6 early stage patients were found. All of them were operated. The resection rate is 100% with no operative death. 3-year survival rate was 40 5%. Conclusion: Routine X-ray examination of esophagus or stomach, and esophageal dye-staining and/or biopsy through endoscopy are important measures for early diagnosis of multi-primary cancer or esophageal and double primary cardiac cancer prompt surgery is advised.
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Objective To reseach the way of rising resectable rate,reducing operative mortality,enhancing long-term effect and higher life quality in postoperation for cancers of esophagus and gastric cardia.Method Operation outcome of 2837 cases for cancers of esophagus and gastric cardia and followed-up were analysed.Results Overall resectability was 98.7%,and postoperative mortality was 0 92% in the group.Survival rates of 3 and 5 years were 48.9% and 33.7%,respectively.Factors affecting long-term survival were those of depth of tumor invasion and lymph nodes metastasis and oncologic staging.It was higher for cervical lymph nodes metastasis within 3 years after operation.Conclusions Early discovery and timely treatment,an appropriate enlarging resectable field and comprehensive therapies are the key to improve the long-term survival.
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The Campylobacter carrier rate of the bile was 23. 64%,14. 29%,7. 14%,6. 64%,5.88%, 5.55% and 3. 63% in the quails, cats, dogs, pigs, chickens, ducks and oxen respectively. The survival time of Campylobacter in the bile in vitro ranged from 4 to 7 weeks. The Campylobacter carrier rate of the intestinal content was higher than that of the bile in all the domestic animals and fowls. It is believed that the domestic animals and fowls may be an important source of Campylobacter infection in human beings according to our findings.