Objective:Robotic gastrectomy(RG)is increasingly used in the treatment of gastric cancer.However,studies on patients with clinical serosa-invasive(cT4a)gastric cancer remain scarce.This study aimed to compare the shor...Objective:Robotic gastrectomy(RG)is increasingly used in the treatment of gastric cancer.However,studies on patients with clinical serosa-invasive(cT4a)gastric cancer remain scarce.This study aimed to compare the shortand long-term outcomes of RG and laparoscopic gastrectomy(LG)in the treatment of stage cT4a gastric cancer.Methods:A retrospective analysis was conducted on the clinical data of patients with stage cT4a gastric cancer diagnosed and treated at eight high-volume tertiary teaching hospitals in China from 2016 to 2019.Propensity score matching(PSM)analysis and inverse probability of treatment weighting(IPTW)analysis was used to adjust for the imbalance in baseline characteristics.The primary research endpoint was the 3-year overall survival(OS)and disease-free survival(DFS).The secondary research endpoint was intraoperative outcomes and postoperative complications.Results:After IPTW and PSM adjustments,baseline characteristics between the RG and LG groups were comparable[standardized mean difference(SMD)<0.10].Post-PSM analysis revealed that the RG group exhibited longer operative time(P<0.001),lower postoperative complication rates(P<0.001),shorter postoperative hospital stays(P=0.037),and earlier initiation of adjuvant chemotherapy(P=0.041)compared with the LG group.Survival analysis demonstrated comparable 3-year OS(P=0.110)and DFS(P=0.088)in the PSM cohort,whereas the IPTW cohort showed superior OS(P=0.030)and DFS(P=0.046)for RG.No significant differences were observed in overall recurrence rates or recurrence sites between groups.Conclusions:For patients with stage cT4a gastric cancer,compared with the LG group,the RG group had shorter postoperative hospital stay,lower incidence of postoperative complications,earlier postoperative adjuvant chemotherapy,and no worse long-term efficacy.展开更多
Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeu...Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.展开更多
Tumor tissues contain both tumor and non-tumor cells,which include infiltrated immune cells and stromal cells,collectively called the tumor microenvironment(TME).Single-cell RNA sequencing(sc RNAseq)enables the examin...Tumor tissues contain both tumor and non-tumor cells,which include infiltrated immune cells and stromal cells,collectively called the tumor microenvironment(TME).Single-cell RNA sequencing(sc RNAseq)enables the examination of heterogeneity of tumor cells and TME.In this review,we examined sc RNAseq datasets for multiple cancer types and evaluated the heterogeneity of major cell type composition in different cancer types.We further showed that endothelial cells and fibroblasts/myofibroblasts in different cancer types can be classified into common subtypes,and the subtype composition is clearly associated with cancer characteristic and therapy response.展开更多
To improve the long-term therapeutic efficacy of colorectal cancer,we propose a synergistic treatment strategy involving dualpathway,multistep induction of long-term hyperimmunity combined with photothermal-chemothera...To improve the long-term therapeutic efficacy of colorectal cancer,we propose a synergistic treatment strategy involving dualpathway,multistep induction of long-term hyperimmunity combined with photothermal-chemotherapy.To implement this strategy,infinite coordination polymer nanoparticles(SN38-Mn(II)-EGCG ICP NPs)were prepared by coordinating SN38,EGCG,and Mn2+.These nanoparticles were then coated with polydopamine(PDA)and grafted with folate-PEG-thiol(FA-PEG-SH)onto their surfaces,producing tumor-targeting folate-modified PDA infinite coordination polymer nanocomposites(ICP@FAPDA nanocomposites).These nanocomposites exhibit a particle size of 94.9±1.6 nm with a high drug loading capacity(83.3%±1.5%),drug release under acidic conditions while maintaining stability in physiological environments.Furthermore,each component within the nanocomposites serves multiple functions.Notably,the incorporation of multiple components triggers a powerful antitumor immune effect and establishes enduring immune memory through a dual-pathway and multistep approach,which is produced with the activation of the cGAS-STING pathway and immunogenic cell death(ICD)by a four-component multistep process.Under a low-dose regimen,this approach induces dual-pathway hyperimmunity effect and generates ultra-long immunological memory,marked by a ninefold increase in CD8+T cell infiltration,a fourfold increase in CD4+T lymphocytes,a fourfold reduction in Treg cells,and a fivefold increase in memory T cells.The remarkable therapy efficacy is achieved by hyperimmunity effect combination of SN38 and EGCG chemotherapy and photothermal therapy.In vivo studies demonstrated that mice treated with ICP@FA-PDA nanocomposites achieved complete eradication of cancer within 21 days,with no recurrence observed within 60 days.These nanocomposites hold significant promise and potential for future clinical translation.展开更多
In the original version of this article1 given name of first author Junjun She was supplied and published incorrectly as Junyun She.The original article has been corrected.
A recent study published in Nature by Delannoy-Bruno et al.1 described the role of formulated fibre snacks on the obese gut microbiome utilizing mouse-human co-clinical trial,and demonstrated that precise dietary fibr...A recent study published in Nature by Delannoy-Bruno et al.1 described the role of formulated fibre snacks on the obese gut microbiome utilizing mouse-human co-clinical trial,and demonstrated that precise dietary fibre intervention directed at the obese gut microbiome modulates the host’s physiological state.Epidemiological and observational studies2 have long linked a diet rich in fibre to protection against chronic diseases.Dietary fibre functions as a prebiotic that can be utilized by gut microbes.Given accumulating evidence showing roles of gut microbes in health and disease,there is renewed interest in harnessing fibre as a prebiotic to promote a healthy gut microbiome.Dietary fibres are safe,inexpensive,and readily incorporated into our diet.However,the development of evidenced-based fibre preparations that selectively induce the abundance of desirable gut microbes pose a huge challenge,as fibre and the gut microbiome are complex identities that remain poorly characterized.This is confounded by their dynamic interactions and inter-and intra-personal variations.展开更多
基金supported by Fujian Provincial Medical“Building High-level Hospitals,High-level Clinical Medical Centers and Key Clinical Specialty Projects”([2021]No.76)Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare(No.[2022]954)。
文摘Objective:Robotic gastrectomy(RG)is increasingly used in the treatment of gastric cancer.However,studies on patients with clinical serosa-invasive(cT4a)gastric cancer remain scarce.This study aimed to compare the shortand long-term outcomes of RG and laparoscopic gastrectomy(LG)in the treatment of stage cT4a gastric cancer.Methods:A retrospective analysis was conducted on the clinical data of patients with stage cT4a gastric cancer diagnosed and treated at eight high-volume tertiary teaching hospitals in China from 2016 to 2019.Propensity score matching(PSM)analysis and inverse probability of treatment weighting(IPTW)analysis was used to adjust for the imbalance in baseline characteristics.The primary research endpoint was the 3-year overall survival(OS)and disease-free survival(DFS).The secondary research endpoint was intraoperative outcomes and postoperative complications.Results:After IPTW and PSM adjustments,baseline characteristics between the RG and LG groups were comparable[standardized mean difference(SMD)<0.10].Post-PSM analysis revealed that the RG group exhibited longer operative time(P<0.001),lower postoperative complication rates(P<0.001),shorter postoperative hospital stays(P=0.037),and earlier initiation of adjuvant chemotherapy(P=0.041)compared with the LG group.Survival analysis demonstrated comparable 3-year OS(P=0.110)and DFS(P=0.088)in the PSM cohort,whereas the IPTW cohort showed superior OS(P=0.030)and DFS(P=0.046)for RG.No significant differences were observed in overall recurrence rates or recurrence sites between groups.Conclusions:For patients with stage cT4a gastric cancer,compared with the LG group,the RG group had shorter postoperative hospital stay,lower incidence of postoperative complications,earlier postoperative adjuvant chemotherapy,and no worse long-term efficacy.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82003807,82173394)the Shaanxi Province Science Foundation,China(Grant No.:2023-GHZD-19)+1 种基金the Medical Foundation-Clinical Integration Program of Xi'an Jiaotong University,China(Grant No.:YXJLRH2022043)the Xi'an Jiaotong University Free Exploration and Innovation-Teacher Project Foundation,China(Grant No.:xzy012023104).
文摘Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.
基金partially supported by NIH grants(Grant Nos.R01CA249175 and U19AI118610)。
文摘Tumor tissues contain both tumor and non-tumor cells,which include infiltrated immune cells and stromal cells,collectively called the tumor microenvironment(TME).Single-cell RNA sequencing(sc RNAseq)enables the examination of heterogeneity of tumor cells and TME.In this review,we examined sc RNAseq datasets for multiple cancer types and evaluated the heterogeneity of major cell type composition in different cancer types.We further showed that endothelial cells and fibroblasts/myofibroblasts in different cancer types can be classified into common subtypes,and the subtype composition is clearly associated with cancer characteristic and therapy response.
基金supported by National Natural Science Foundation of China(82202308,81870380,and 82173394)China National Postdoctoral Program for Innovative Talents(BX20220247)+2 种基金China Postdoctoral Science Foundation(2021M702619)Natural Science Basic Research Plan in Shaanxi Province of China(2021TD-41 and 2020KWZ-020)Institutional Foundation of The First Affiliated Hospital of Xi’an Jiaotong University(2021QN-12).
文摘To improve the long-term therapeutic efficacy of colorectal cancer,we propose a synergistic treatment strategy involving dualpathway,multistep induction of long-term hyperimmunity combined with photothermal-chemotherapy.To implement this strategy,infinite coordination polymer nanoparticles(SN38-Mn(II)-EGCG ICP NPs)were prepared by coordinating SN38,EGCG,and Mn2+.These nanoparticles were then coated with polydopamine(PDA)and grafted with folate-PEG-thiol(FA-PEG-SH)onto their surfaces,producing tumor-targeting folate-modified PDA infinite coordination polymer nanocomposites(ICP@FAPDA nanocomposites).These nanocomposites exhibit a particle size of 94.9±1.6 nm with a high drug loading capacity(83.3%±1.5%),drug release under acidic conditions while maintaining stability in physiological environments.Furthermore,each component within the nanocomposites serves multiple functions.Notably,the incorporation of multiple components triggers a powerful antitumor immune effect and establishes enduring immune memory through a dual-pathway and multistep approach,which is produced with the activation of the cGAS-STING pathway and immunogenic cell death(ICD)by a four-component multistep process.Under a low-dose regimen,this approach induces dual-pathway hyperimmunity effect and generates ultra-long immunological memory,marked by a ninefold increase in CD8+T cell infiltration,a fourfold increase in CD4+T lymphocytes,a fourfold reduction in Treg cells,and a fivefold increase in memory T cells.The remarkable therapy efficacy is achieved by hyperimmunity effect combination of SN38 and EGCG chemotherapy and photothermal therapy.In vivo studies demonstrated that mice treated with ICP@FA-PDA nanocomposites achieved complete eradication of cancer within 21 days,with no recurrence observed within 60 days.These nanocomposites hold significant promise and potential for future clinical translation.
文摘In the original version of this article1 given name of first author Junjun She was supplied and published incorrectly as Junyun She.The original article has been corrected.
基金This work was supported by RGC Theme-based Research Scheme Hong Kong(T21-705/20-N)RGC-CRF Hong Kong(C4039-19GF)+2 种基金RGC-GRF(24100520,14101917,14108718)Heath and Medical Research Fund(06170686,08190706)Vice-Chancellor’s Discretionary Fund Chinese University of Hong Kong.
文摘A recent study published in Nature by Delannoy-Bruno et al.1 described the role of formulated fibre snacks on the obese gut microbiome utilizing mouse-human co-clinical trial,and demonstrated that precise dietary fibre intervention directed at the obese gut microbiome modulates the host’s physiological state.Epidemiological and observational studies2 have long linked a diet rich in fibre to protection against chronic diseases.Dietary fibre functions as a prebiotic that can be utilized by gut microbes.Given accumulating evidence showing roles of gut microbes in health and disease,there is renewed interest in harnessing fibre as a prebiotic to promote a healthy gut microbiome.Dietary fibres are safe,inexpensive,and readily incorporated into our diet.However,the development of evidenced-based fibre preparations that selectively induce the abundance of desirable gut microbes pose a huge challenge,as fibre and the gut microbiome are complex identities that remain poorly characterized.This is confounded by their dynamic interactions and inter-and intra-personal variations.
