In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST tho...In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST (2017 edition) was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.展开更多
Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis o...Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.展开更多
Background: The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one...Background: The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods: We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination: The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient's follow-up will be ended until December, 2023. Trial registration: ClinicalTrials.gov, identifier: NCT02867839. Registered on August 4, 2016.展开更多
Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuv...Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.展开更多
Objective: Currently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G(Ig G) is widely expressed in many cancers, and it promotes c...Objective: Currently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G(Ig G) is widely expressed in many cancers, and it promotes cancer progression. This study explored the role of cancer-derived Ig G(CIg G) in colorectal cancer.Methods: First, using a monoclonal antibody to CIg G, we examined the expression levels of CIg G in colorectal cancer cell lines by western blot and immunofluorescence analyses and in tissue specimens by immunohistochemistry. Second, the variable region gene was amplified by nested polymerase chain reaction(PCR), and PCR products were sequenced and analyzed. Third, we investigated the effect of CIg G on colorectal cancer cells by cell proliferation, wound healing, migration and invasion assays, and colony formation assay. Fourth, we performed in vivo tumorigenicity experiments to explore the effect of CIg G on tumorigenicity. Finally, we used RNA-seq analysis and co-immunoprecipitation experiments to further clarify possible mechanisms of CIg G.Results: We found that CIg G is widely expressed in colorectal cancer cells, and the overexpression of CIg G indicates significantly poor colorectal cancer prognosis. Furthermore, CIg G knockdown significantly inhibits the proliferation, migration and invasion ability of cells, and tumor growth in vivo. RNA-seq analysis indicated that CIg G knockdown results primarily in changes in expression of apical junction and epithelial-mesenchymal transition-related genes. CIg G may be involved in colorectal cancer invasion and metastasis through interacting with E-cadherin.Conclusions: CIg G is a potential human oncogene in colorectal cancer and that it has potential for application as a novel target in targeted therapy and a marker for prognostic evaluation.展开更多
Objective:This intervention has been shown to be clinically efficacious and safe.The aim of this study was to determine the effect of different intervention times on the efficacy of gastroparesis external application ...Objective:This intervention has been shown to be clinically efficacious and safe.The aim of this study was to determine the effect of different intervention times on the efficacy of gastroparesis external application prescription versus placebo for the treatment of gastrointestinal tumor postoperative,postsurgical gastroparesis.Methods:A multicenter,randomized,double-blind,placebo controlled phaseⅢclinical trial was designed to demonstrate superiority and conducted at four grade 3A hospitals in Beijing.Patients diagnosed with gastrointestinal tumor postsurgical gastroparesis and local cold syndrome in the abdomen were enrolled and received conventional treatment(nutritional support,gastrointestinal decompression,and prokinetic medication).Treatment and control groups respectively received gastroparesis external application prescription or placebo acupoint application over a treatment course of 14 days or until the primary efficacy endpoint(clinical efficiency)was achieved.Results:A total of 120 patients were enrolled in the treatment and control groups(n Z 60 per group),and 15 patients dropped out of the study because of skin allergies(n Z 7)or poor efficacy(nZ8).The efficacy among patients in Class B of Group A(treatment group)was marginally better than that of Group B(control group)(64.28%vs.55.56%)although the difference between the two groups was not significant.However,the efficacy among patients in Class C of Group A was significantly better than that of Group B(79.49%vs.43.33%).For Group A,the time for patients in the three classes to achieve the efficacy endpoint increased significantly with disease progression(3.00,6.78,and 8.29 days for Class A,B,and C,respectively).Conclusions:Gastroparesis external application prescription can effectively treat gastrointestinal tumor postsurgical gastroparesis and may be more efficacious in progressive disease compared placebo.Patients with gastrointestinal tumor postsurgical gastroparesis should therefore undergo intervention at an earlier stage.展开更多
The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid mod...The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid(PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z’ factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore,the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.展开更多
Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at t...Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.展开更多
Colorectal cancer(CRC)has become a major threat to human health.Recent years,improvements have been seen in the treatment of advanced CRC with immune checkpoint inhibitors(ICIs).Nonetheless,sensitivity to ICIs notably...Colorectal cancer(CRC)has become a major threat to human health.Recent years,improvements have been seen in the treatment of advanced CRC with immune checkpoint inhibitors(ICIs).Nonetheless,sensitivity to ICIs notably varies among patients,thus greatly limiting clinical applications of ICIs in CRC.Hence,the identification of biomarkers that can accurately distinguish between ICI-sensitive and drug-resistant patients is of utmost importance.Such biomarkers are essential for selecting appropriate treatment regimens and achieving precision therapy(Figure 1).The biomarkers discussed below provide insights into the advancements made in this field(Table 1).展开更多
Digestive tract tumors,ranging from esophageal to colorectal cancers(CRCs),pose a substantial challenge in oncology because of their high global incidence and mortality.1,2 The heterogeneity of these malignancies unde...Digestive tract tumors,ranging from esophageal to colorectal cancers(CRCs),pose a substantial challenge in oncology because of their high global incidence and mortality.1,2 The heterogeneity of these malignancies underscores the complexity of their etiology,which is influenced by a combination of genetic,epigenetic,and environmental factors.3 Unraveling the molecular complexities and clinical implications of these tumors is of growing importance,as they provide insights that can inform the development of more effective diagnostic,therapeutic,and preventative approaches.The Special Issue,titled“Basic research and clinical practice on gastrointestinal cancer”,aims to highlight the recent advances in molecular mechanisms and clinical research in the field of digestive tract oncology.We hope that by presenting these findings we can foster collaboration and dialog among experts in the field,ultimately leading to innovative perspectives on the diagnosis and treatment of these cancers.展开更多
Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction.However,the current titanium(Ti)staple will remain in the human body permanently,resulting in some adverse effects.In this st...Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction.However,the current titanium(Ti)staple will remain in the human body permanently,resulting in some adverse effects.In this study,we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium(Mg)alloy wires.The wire surface was modified by micro-arc oxidation treatment(MAO)and then coated with poly-L-lactic acid(PLLA)to achieve a moderate degradation rate matching the tissue healing process.The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples.The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid(SCF).Furthermore,24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon.The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days.All animals did not have anastomotic leakage and stenosis,and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects.The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.展开更多
Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of re...Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.展开更多
Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively exp...Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy.Methods:Data were collected from seven prospective hospital databases in China from July 2002 to May 2018.Binary logistic regression models were used to predict lymph node metastasis.The cut-off value for LNe was determined using X-tile 3.6.1.Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model.Results:A total of 482 patients were included,of whom 459 had complete overall survival(OS)information.Using the percentile method,the total number of lymph nodes examined(TLNe)was 14-16(40th-60th percentile),and the proportion of patients with lymph node metastasis reached a maximum of 48.1%.Cox multivariate analysis showed that the odds ratio(OR)remained the highest when TLNe was 14-16(OR=3.379,P=0.003).The 3-year and 5-year OS were 85.4% and 77.8%,respectively.Negative lymph nodes examined(NLNe)of≤6 was an independent risk factor for 3-year and 5-year OS(3-year OS 71.1%vs.85.9%,P=0.004;5-year OS 66.3%vs.74.3%,P=0.035).Subgroup analysis for patients with ypN+showed that higher 3-year and 5-year OS were achieved when the TLNe was>10,78.8%vs.54.0%(P=0.005),and 60.8%vs.36.0%(P=0.012),respectively.Patients with ypN0M0 had a higher 5-year OS when the TLNe was>19(P=0.055).Conclusion:The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.展开更多
文摘In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST (2017 edition) was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.
基金supported by grants from the National Natural Science Foundation of China (No. 81372291).
文摘Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.
基金supported by the National Science Foundation of China (No. 81374016 and 81402308)Beijing Municipal Science & Technology Commission (No. D141100000414002)
文摘Background: The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods: We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination: The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient's follow-up will be ended until December, 2023. Trial registration: ClinicalTrials.gov, identifier: NCT02867839. Registered on August 4, 2016.
基金supported by Shenzhen Sanming Project(No.SZSM201612051)。
文摘Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.
基金supported by grants from the National Natural Science Foundation of China (No. 8157101395)Beijing Natural Science Foundation (No. 7182171)
文摘Objective: Currently, no satisfactory targets for colorectal cancer or markers for immunotherapy and diagnosis and prognosis are available. Immunoglobulin G(Ig G) is widely expressed in many cancers, and it promotes cancer progression. This study explored the role of cancer-derived Ig G(CIg G) in colorectal cancer.Methods: First, using a monoclonal antibody to CIg G, we examined the expression levels of CIg G in colorectal cancer cell lines by western blot and immunofluorescence analyses and in tissue specimens by immunohistochemistry. Second, the variable region gene was amplified by nested polymerase chain reaction(PCR), and PCR products were sequenced and analyzed. Third, we investigated the effect of CIg G on colorectal cancer cells by cell proliferation, wound healing, migration and invasion assays, and colony formation assay. Fourth, we performed in vivo tumorigenicity experiments to explore the effect of CIg G on tumorigenicity. Finally, we used RNA-seq analysis and co-immunoprecipitation experiments to further clarify possible mechanisms of CIg G.Results: We found that CIg G is widely expressed in colorectal cancer cells, and the overexpression of CIg G indicates significantly poor colorectal cancer prognosis. Furthermore, CIg G knockdown significantly inhibits the proliferation, migration and invasion ability of cells, and tumor growth in vivo. RNA-seq analysis indicated that CIg G knockdown results primarily in changes in expression of apical junction and epithelial-mesenchymal transition-related genes. CIg G may be involved in colorectal cancer invasion and metastasis through interacting with E-cadherin.Conclusions: CIg G is a potential human oncogene in colorectal cancer and that it has potential for application as a novel target in targeted therapy and a marker for prognostic evaluation.
基金This study was supported by“Clinical Study of TCM Treating Gastroparesis and Other Tumor Postsurgical Complications”(Project No.:D131100002213003)a key project of the Beijing Municipal Science and Technology Commission and Combining traditional Chinese and Western medicine:Cancer Collaborative Innovation Center of Beijing University of Chinese Medicine(Project No.:2013-XTCX-05).
文摘Objective:This intervention has been shown to be clinically efficacious and safe.The aim of this study was to determine the effect of different intervention times on the efficacy of gastroparesis external application prescription versus placebo for the treatment of gastrointestinal tumor postoperative,postsurgical gastroparesis.Methods:A multicenter,randomized,double-blind,placebo controlled phaseⅢclinical trial was designed to demonstrate superiority and conducted at four grade 3A hospitals in Beijing.Patients diagnosed with gastrointestinal tumor postsurgical gastroparesis and local cold syndrome in the abdomen were enrolled and received conventional treatment(nutritional support,gastrointestinal decompression,and prokinetic medication).Treatment and control groups respectively received gastroparesis external application prescription or placebo acupoint application over a treatment course of 14 days or until the primary efficacy endpoint(clinical efficiency)was achieved.Results:A total of 120 patients were enrolled in the treatment and control groups(n Z 60 per group),and 15 patients dropped out of the study because of skin allergies(n Z 7)or poor efficacy(nZ8).The efficacy among patients in Class B of Group A(treatment group)was marginally better than that of Group B(control group)(64.28%vs.55.56%)although the difference between the two groups was not significant.However,the efficacy among patients in Class C of Group A was significantly better than that of Group B(79.49%vs.43.33%).For Group A,the time for patients in the three classes to achieve the efficacy endpoint increased significantly with disease progression(3.00,6.78,and 8.29 days for Class A,B,and C,respectively).Conclusions:Gastroparesis external application prescription can effectively treat gastrointestinal tumor postsurgical gastroparesis and may be more efficacious in progressive disease compared placebo.Patients with gastrointestinal tumor postsurgical gastroparesis should therefore undergo intervention at an earlier stage.
基金supported by grants from the National Natural Science Foundation of China (No.82174086)the Beijing Natural Science Foundation (No.7222273)+3 种基金the Beijing Xisike Clinical Oncology Research Foundation (Nos.Y-xsk2021-0004 and Y-XD202001-0172)the Youth Talents Promotion Project of China Association of Chinese Medicine (No.2020-QNRC2-08)the Clinical Medicine Plus X-Young Scholars Project of Peking University (No.BMU2021MX009)the Peking University People’s Hospital Research and Development Funds (No.RDY2020-18)。
文摘The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid(PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z’ factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore,the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.
基金supported by National Key Research and Development Program of China(No.2017YFC1308800)Industry-University-Research Innovation Fund in Ministry of Education of the People’s Republic of China(No.2018A01013)。
文摘Objective:The goal of this study was to get preliminary insight on the intra-tumor heterogeneity in colitisassociated cancer(CAC)and to reveal a potential evolutionary trajectory from ulcerative colitis(UC)to CAC at the single-cell level.Methods:Fresh samples of tumor tissues and adjacent UC tissues from a CAC patient with pT3N1M0 stage cancer were examined by single-cell RNA sequencing(scRNA-seq).Data from The Cancer Genome Atlas(TCGA)and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with patient prognosis.Results:Ultimately,4,777 single-cell transcriptomes(1,220 genes per cell)were examined,of which 2,250(47%)and 2,527(53%)originated from tumor and adjacent UC tissues,respectively.We defined the composition of cancer-associated stromal cells and identified six cell clusters,including myeloid,T and B cells,fibroblasts,endothelial and epithelial cells.Notable pathways and transcription factors involved in these cell clusters were analyzed and described.Moreover,the precise cellular composition and developmental trajectory from UC to UCassociated colon cancer were graphed,and it was predicted that CD74,CLCA1,and DPEP1 played a potential role in disease progression.Conclusions:scRNA-seq technology revealed intra-tumor cell heterogeneity in UC-associated colon cancer,and might provide a promising direction to identify novel potential therapeutic targets in the evolution from UC to CAC.
基金supported by the National Natural Science Foundation of China(Grant No.82272841).
文摘Colorectal cancer(CRC)has become a major threat to human health.Recent years,improvements have been seen in the treatment of advanced CRC with immune checkpoint inhibitors(ICIs).Nonetheless,sensitivity to ICIs notably varies among patients,thus greatly limiting clinical applications of ICIs in CRC.Hence,the identification of biomarkers that can accurately distinguish between ICI-sensitive and drug-resistant patients is of utmost importance.Such biomarkers are essential for selecting appropriate treatment regimens and achieving precision therapy(Figure 1).The biomarkers discussed below provide insights into the advancements made in this field(Table 1).
基金the Beijing Xisike Clinical Oncology Research Foundation(No.Y-xsk2021-0004).
文摘Digestive tract tumors,ranging from esophageal to colorectal cancers(CRCs),pose a substantial challenge in oncology because of their high global incidence and mortality.1,2 The heterogeneity of these malignancies underscores the complexity of their etiology,which is influenced by a combination of genetic,epigenetic,and environmental factors.3 Unraveling the molecular complexities and clinical implications of these tumors is of growing importance,as they provide insights that can inform the development of more effective diagnostic,therapeutic,and preventative approaches.The Special Issue,titled“Basic research and clinical practice on gastrointestinal cancer”,aims to highlight the recent advances in molecular mechanisms and clinical research in the field of digestive tract oncology.We hope that by presenting these findings we can foster collaboration and dialog among experts in the field,ultimately leading to innovative perspectives on the diagnosis and treatment of these cancers.
基金This work was supported by the National Natural Science Foundation of China(51971062,81901056)the Natural Science Foundation of Jiangsu(BK20190649)+2 种基金the Science and Technology Project of Jiangsu Province(BE2019679)the Technological Innovation of key Industry of Suzhou(SYG202116)the open research fund of Jiangsu Key Laboratory for Advanced Metallic Materials(AMM2021A01).
文摘Staplers have been widely used in the clinical treatment of gastrointestinal reconstruction.However,the current titanium(Ti)staple will remain in the human body permanently,resulting in some adverse effects.In this study,we developed a type of biodegradable staple for colonic anastomosis using 0.3 mm diameter magnesium(Mg)alloy wires.The wire surface was modified by micro-arc oxidation treatment(MAO)and then coated with poly-L-lactic acid(PLLA)to achieve a moderate degradation rate matching the tissue healing process.The results of tensile tests on isolated porcine colon tissue anastomosed by Mg and Ti staples showed that the anastomotic property of Mg staples was almost equal to that of Ti staples.The in vitro degradation tests indicated the dual-layer coating effectively enhanced the corrosion resistance and maintained the tensile force of the coated staple stable after 14-day immersion in the simulated colonic fluid(SCF).Furthermore,24 beagle dogs were employed to conduct a comparison experiment using Mg-based and clinical Ti staples for 90-day implantation by ent-to-side anastomosis of the colon.The integrated structure of Mg-based staples was observed after 7 days and completely degraded after 90 days.All animals did not have anastomotic leakage and stenosis,and 12 dogs with Mg-based staples fully recovered after 90 days without differences in visceral ion levels and other side effects.The favorable performance makes this Mg-based anastomotic staple an ideal candidate for colon reconstruction.
文摘Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.
文摘Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy.Methods:Data were collected from seven prospective hospital databases in China from July 2002 to May 2018.Binary logistic regression models were used to predict lymph node metastasis.The cut-off value for LNe was determined using X-tile 3.6.1.Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model.Results:A total of 482 patients were included,of whom 459 had complete overall survival(OS)information.Using the percentile method,the total number of lymph nodes examined(TLNe)was 14-16(40th-60th percentile),and the proportion of patients with lymph node metastasis reached a maximum of 48.1%.Cox multivariate analysis showed that the odds ratio(OR)remained the highest when TLNe was 14-16(OR=3.379,P=0.003).The 3-year and 5-year OS were 85.4% and 77.8%,respectively.Negative lymph nodes examined(NLNe)of≤6 was an independent risk factor for 3-year and 5-year OS(3-year OS 71.1%vs.85.9%,P=0.004;5-year OS 66.3%vs.74.3%,P=0.035).Subgroup analysis for patients with ypN+showed that higher 3-year and 5-year OS were achieved when the TLNe was>10,78.8%vs.54.0%(P=0.005),and 60.8%vs.36.0%(P=0.012),respectively.Patients with ypN0M0 had a higher 5-year OS when the TLNe was>19(P=0.055).Conclusion:The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.