Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its wid...Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.展开更多
Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial ...Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.展开更多
Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has...Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.展开更多
Seashell has been applied as an indicator for ocean research and element analysis of the seashell is used to track biological or environmental evolution. In this work, laser-induced breakdown spectroscopy （LIBS） was...Seashell has been applied as an indicator for ocean research and element analysis of the seashell is used to track biological or environmental evolution. In this work, laser-induced breakdown spectroscopy （LIBS） was applied for elementary analysis of an ezo scallop-shell, and a graphite enrichment method was used as the assistance. It was found that LIBS signal intensity of Ca fluctuated less than 5%, in spite of the sampling positions, and Sr/Ca was related to the shell growth. A similar variation was also found when using a direct LIBS analysis on the shell surface, and it might be more practicable to track shell growth by investigating Sr/Ca ratio with Sr ionic line at 421.6 nm. The obtained results prove that calcium （Ca） is qualified as an internal reference for shell analysis, and LIBS is a potential analytical method for seashell study.展开更多
Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan(CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-coli...Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan(CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA(ds DNA) from the intestine, leading to cyclic-GMP-AMP synthase(c GAS)-stimulator of interferon genes(STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination(HR) repair and downregulate ds DNA-c GAS-STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.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
Alpha-fetoprotein-producing gastric or gastro-esophageal junction(AFP-G/GEJ)cancer,a rare gastric cancer subtype,exhibits increased angiogenesis and more immunosuppression than non-AFP-G/GEJ cancer.The potential benef...Alpha-fetoprotein-producing gastric or gastro-esophageal junction(AFP-G/GEJ)cancer,a rare gastric cancer subtype,exhibits increased angiogenesis and more immunosuppression than non-AFP-G/GEJ cancer.The potential benefits of anti-angiogenic agents and immunotherapy for this specific subtype remain unknown.This multi-center,single-arm,phase 2 trial(ClinicalTrials.gov NCT04609176)evaluated the antitumor activity,safety,and biomarkers of camrelizumab plus apatinib and S-1 and oxaliplatin(SOX),followed by maintenance treatment with camrelizumab plus apatinib,as a first-line treatment in patients with AFP-G/GEJ adenocarcinoma.Primary endpoint was the confirmed objective response rate(ORR)per RECIST v1.1 in the full analysis set.Secondary endpoints were disease control rate(DCR),progression-free survival(PFS),overall survival(OS),duration of response,time to response,and safety.Between December 4,2020,and August 4,2023,36 patients were enrolled and treated.The trial met its primary endpoint with a confirmed ORR of 66.7%(95%Cl:49.0-81.4).The DCR was 88.9%(95%Cl:73.9-96.9).With a median follow-up of 11.7 months(range:3.2-37.9),the median PFS reached 7.8 months(95%Cl:4.9-12.3)and the median OS reached 18.0 months(95%Cl:10.5-NR).No new safety concerns were identified.In exploratory analysis,patients with durable clinical benefit exhibited higher pre-treatment(PD-1+)CD8+T cell densities and effective scores.First-line treatment with camrelizumab plus apatinib and SOX,followed by maintenance treatment with camrelizumab plus apatinib,is effective and safe in AFP-G/GEJ adenocarcinoma.Further studies are necessary to validate these findings.展开更多
The authors discovered that Fig.4H and Fig.S3H in the published article contained incorrect images during the process of using AI tools to check published images.After carefully checking the original data,this was due...The authors discovered that Fig.4H and Fig.S3H in the published article contained incorrect images during the process of using AI tools to check published images.After carefully checking the original data,this was due to their unintended negligence during the extraction and handling of a large volume of experimental data in the process of assembling figures.The authors have replaced the incorrect images with the correct representative images.The updated Fig.4H and Fig.S3H are provided below.The original data of the figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.展开更多
Background:Glecirasib,an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12(KRAS G12C),has exhibited clinical activity in non-small-cell lung cancer(NSCLC)and colorect...Background:Glecirasib,an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12(KRAS G12C),has exhibited clinical activity in non-small-cell lung cancer(NSCLC)and colorectal cancer(CRC).Here,we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma(PDAC)and other solid tumors(excluding NSCLC and CRC)that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited.Methods:We conducted and analyzed two open-label,phase I/II trials in adult patients with KRAS G12C mutant solid tumors,in which glecirasib was administered orally.The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment.We performed a pooled analysis of all patients,excluding NSCLC and CRC,from both trials.The primary end-point in the pooled population was objective response rate(ORR).Efficacy and safety were assessed in patients who received at least one dose of glecirasib.Results:As of June 30,2024,the pooled analysis included 54 patients who were treated with glecirasib:32 PDACs,8 biliary tract cancers(BTCs),4 small intestinal cancers,3 gastric cancers,2 appendiceal cancers,and 5 other tumors.At baseline,24 received≥two prior lines of systemic therapy.Of the 53 efficacyevaluable patients,the confirmed ORR was 50.9%(95%confidence interval[CI],36.8%-64.9%),with an ORR of 46.9%(95%CI,29.1%-65.3%)in PDAC patients.Among other solid tumors,ORR was 71.4%(5/7)in BTC,100%(4/4)in small intestinal cancer,and 66.7%(2/3)in gastric cancer.Median progression-free survival and median overall survival were 6.9 and 10.8 months,respectively,in the overall population,and 5.5 and 10.8 months,respectively,in patients with PDAC.Treatment-related adverse events(TRAEs)of any grade occurred in 94.4%patients,with grade≥3 TRAEs in 27.8%.No fatal TRAEs or TRAEs leading to treatment discontinuation occurred.Conclusions:Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors(beyond NSCLC and CRC),warranting further expedited clinical development in this patient population.Trial registration:ClinicalTrials.gov identifier:NCT05009329 and NCT05002270.展开更多
Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit ca...Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.展开更多
Chemical substitution during growth is a well-established method to manipulate electronic states of quantum materials, and leads to rich spectra of phase diagrams in cuprate and iron-based superconductors. Here we rep...Chemical substitution during growth is a well-established method to manipulate electronic states of quantum materials, and leads to rich spectra of phase diagrams in cuprate and iron-based superconductors. Here we report a novel and generic strategy to achieve nonvolatile electron doping in series of(i.e.11 and 122 structures) Fe-based superconductors by ionic liquid gating induced protonation at room temperature. Accumulation of protons in bulk compounds induces superconductivity in the parent compounds, and enhances the Tclargely in some superconducting ones. Furthermore, the existence of proton in the lattice enables the first proton nuclear magnetic resonance(NMR) study to probe directly superconductivity. Using Fe S as a model system, our NMR study reveals an emergent high-Tcphase with no coherence peak which is hard to measure by NMR with other isotopes. This novel electric-fieldinduced proton evolution opens up an avenue for manipulation of competing electronic states(e.g.Mott insulators), and may provide an innovative way for a broad perspective of NMR measurements with greatly enhanced detecting resolution.展开更多
Carbon nanotube reinforced bioglass composites have been successfully synthesized by two comparative sintering techniques, i.e., spark plasma sintering （SPS） and conventional compaction and sinteirng. The composites...Carbon nanotube reinforced bioglass composites have been successfully synthesized by two comparative sintering techniques, i.e., spark plasma sintering （SPS） and conventional compaction and sinteirng. The composites show improved mechanical properties, with SPS technique substantially better than conventional compact and sintering approach. Using SPS, compared with the 45S5Bioglass matrix, the maximum flexural strength and fracture toughness increased by 159% and 105%, respectively. Enhanced strength and toughness are attributed to the interfacial bonding and bridging effects between the carbon nanotubes and bioglass powders during crack propagations.展开更多
Ceramics of Bi0.9Ba0.1Fe0.925TixO3 (x = 0.0625, 0.08125, 0.0875, and 0.11) were prepared according to two doping strategies: one is called single-step doping in which Ba and Ti were doped together in calcination, whil...Ceramics of Bi0.9Ba0.1Fe0.925TixO3 (x = 0.0625, 0.08125, 0.0875, and 0.11) were prepared according to two doping strategies: one is called single-step doping in which Ba and Ti were doped together in calcination, while the other one is called two-step doping in which Ba and Ti were doped in calcination and sintering, respectively. Compared with samples prepared with single-step doping, those prepared with two-step doping have obviously different XRD patterns and small grains, and are dramatically improved in dielectric loss, resistivity, and remnant magnetization. A low dielectric loss of 0.05 at 10(3) Hz, a high resistivity of 4x10(12) Omega.cm, and a large remnant magnetization of 1.5 emu/g, have been obtained simultaneously for Bi0.9Ba0.1Fe0.925Ti0.11O3 prepared with two-step doping. The contrast between these two doping strategies clearly reveals the importance of establishing a proper doping strategy when two or more elements are co-doped to BiFeO3.展开更多
基金supported by the National Natural Science Foundation of China(82072675,82273197,82173933)Fundamental Research Funds for the Central Universities(020814380160).
文摘Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.
基金supported by grants from Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120)General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391)+1 种基金National Key Research and Development Program of China (Grant No. 2016YFC1303800)Guangdong Provincial Applied S&T R&D Program (Grant No. 2016B020237006)
文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.
基金supported by the National Key Research and Development Plan,China(Grant No.:2022YFC3500202)the Natural Science Foundation of China(Grant Nos.:82172558,and 82205024)+4 种基金the Scientific and Technological Innovation Action Plan of Natural Science Foundation Project of Shanghai,China(Grant No.:22ZR1447400)the Scientific and Technological Innovation Action Plan,China(Grant No.:22ZR1447400)the Fundamental Research Funds for the Central Universities,China(Grant Nos.:020814380179,020814380174)the Distinguished Young Scholars of Nanjing,China(Grant No.:JQX20008)the School of Life Science(NJU)-Sipimo Joint Funds and Mountain Climbing Talents Project of Nanjing University,China(Grant No.:2015018).
文摘Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.
基金financially supported by National Natural Science Foundation of China(No.41506113)Natural Science Foundation of Shandong Province(No.ZR2014DP010)
文摘Seashell has been applied as an indicator for ocean research and element analysis of the seashell is used to track biological or environmental evolution. In this work, laser-induced breakdown spectroscopy （LIBS） was applied for elementary analysis of an ezo scallop-shell, and a graphite enrichment method was used as the assistance. It was found that LIBS signal intensity of Ca fluctuated less than 5%, in spite of the sampling positions, and Sr/Ca was related to the shell growth. A similar variation was also found when using a direct LIBS analysis on the shell surface, and it might be more practicable to track shell growth by investigating Sr/Ca ratio with Sr ionic line at 421.6 nm. The obtained results prove that calcium （Ca） is qualified as an internal reference for shell analysis, and LIBS is a potential analytical method for seashell study.
基金supported by National Natural Science Foundation of China(81871944,81572389,81922067)Jiangsu 333 project(BRA2016517,China)+2 种基金Natural Science Foundation of Jiangsu Province(BK20190306,China)Jiangsu Province Key Medical Talents(ZDRCA2016026,China)Priority Academic Program Development of Jiangsu Higher Education Institutions and Fundamental Research Funds for the Central Universities(14380114,China)。
文摘Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan(CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA(ds DNA) from the intestine, leading to cyclic-GMP-AMP synthase(c GAS)-stimulator of interferon genes(STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination(HR) repair and downregulate ds DNA-c GAS-STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.
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.
基金Capital's Funds for Health Improvement and Research(2024-1-1021)Beijing Natural Science Foundation(Z20J00105)+2 种基金National Natural Science Foundation of China(82272627)Beijing Natural Science Foundation(L234003)the Beijing Xisike Clinical Oncology Research Foundation(Y-HR2020ZD-0773)。
文摘Alpha-fetoprotein-producing gastric or gastro-esophageal junction(AFP-G/GEJ)cancer,a rare gastric cancer subtype,exhibits increased angiogenesis and more immunosuppression than non-AFP-G/GEJ cancer.The potential benefits of anti-angiogenic agents and immunotherapy for this specific subtype remain unknown.This multi-center,single-arm,phase 2 trial(ClinicalTrials.gov NCT04609176)evaluated the antitumor activity,safety,and biomarkers of camrelizumab plus apatinib and S-1 and oxaliplatin(SOX),followed by maintenance treatment with camrelizumab plus apatinib,as a first-line treatment in patients with AFP-G/GEJ adenocarcinoma.Primary endpoint was the confirmed objective response rate(ORR)per RECIST v1.1 in the full analysis set.Secondary endpoints were disease control rate(DCR),progression-free survival(PFS),overall survival(OS),duration of response,time to response,and safety.Between December 4,2020,and August 4,2023,36 patients were enrolled and treated.The trial met its primary endpoint with a confirmed ORR of 66.7%(95%Cl:49.0-81.4).The DCR was 88.9%(95%Cl:73.9-96.9).With a median follow-up of 11.7 months(range:3.2-37.9),the median PFS reached 7.8 months(95%Cl:4.9-12.3)and the median OS reached 18.0 months(95%Cl:10.5-NR).No new safety concerns were identified.In exploratory analysis,patients with durable clinical benefit exhibited higher pre-treatment(PD-1+)CD8+T cell densities and effective scores.First-line treatment with camrelizumab plus apatinib and SOX,followed by maintenance treatment with camrelizumab plus apatinib,is effective and safe in AFP-G/GEJ adenocarcinoma.Further studies are necessary to validate these findings.
文摘The authors discovered that Fig.4H and Fig.S3H in the published article contained incorrect images during the process of using AI tools to check published images.After carefully checking the original data,this was due to their unintended negligence during the extraction and handling of a large volume of experimental data in the process of assembling figures.The authors have replaced the incorrect images with the correct representative images.The updated Fig.4H and Fig.S3H are provided below.The original data of the figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.
文摘Background:Glecirasib,an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12(KRAS G12C),has exhibited clinical activity in non-small-cell lung cancer(NSCLC)and colorectal cancer(CRC).Here,we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma(PDAC)and other solid tumors(excluding NSCLC and CRC)that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited.Methods:We conducted and analyzed two open-label,phase I/II trials in adult patients with KRAS G12C mutant solid tumors,in which glecirasib was administered orally.The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment.We performed a pooled analysis of all patients,excluding NSCLC and CRC,from both trials.The primary end-point in the pooled population was objective response rate(ORR).Efficacy and safety were assessed in patients who received at least one dose of glecirasib.Results:As of June 30,2024,the pooled analysis included 54 patients who were treated with glecirasib:32 PDACs,8 biliary tract cancers(BTCs),4 small intestinal cancers,3 gastric cancers,2 appendiceal cancers,and 5 other tumors.At baseline,24 received≥two prior lines of systemic therapy.Of the 53 efficacyevaluable patients,the confirmed ORR was 50.9%(95%confidence interval[CI],36.8%-64.9%),with an ORR of 46.9%(95%CI,29.1%-65.3%)in PDAC patients.Among other solid tumors,ORR was 71.4%(5/7)in BTC,100%(4/4)in small intestinal cancer,and 66.7%(2/3)in gastric cancer.Median progression-free survival and median overall survival were 6.9 and 10.8 months,respectively,in the overall population,and 5.5 and 10.8 months,respectively,in patients with PDAC.Treatment-related adverse events(TRAEs)of any grade occurred in 94.4%patients,with grade≥3 TRAEs in 27.8%.No fatal TRAEs or TRAEs leading to treatment discontinuation occurred.Conclusions:Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors(beyond NSCLC and CRC),warranting further expedited clinical development in this patient population.Trial registration:ClinicalTrials.gov identifier:NCT05009329 and NCT05002270.
基金supported by National Natural Science Foundation of China(Nos.81673436,21472091,81872877,81673437)Mountain-Climbing Talents Project of Nanjing University,the Open Fund of State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University(No.KF-GN-201703,China)+1 种基金Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica(No.JKLPSE201802,China)the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD,China)
文摘Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099.Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system.SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.
基金supported by the Ministry of Science and Technology of China(2015CB921700,2016YFA0300504,2016YFA0301004,2016YFA0300401 and 2017YFA0302903)the National Natural Science Foundation of China(11374364,11522429,11374011 and 11534005)
文摘Chemical substitution during growth is a well-established method to manipulate electronic states of quantum materials, and leads to rich spectra of phase diagrams in cuprate and iron-based superconductors. Here we report a novel and generic strategy to achieve nonvolatile electron doping in series of(i.e.11 and 122 structures) Fe-based superconductors by ionic liquid gating induced protonation at room temperature. Accumulation of protons in bulk compounds induces superconductivity in the parent compounds, and enhances the Tclargely in some superconducting ones. Furthermore, the existence of proton in the lattice enables the first proton nuclear magnetic resonance(NMR) study to probe directly superconductivity. Using Fe S as a model system, our NMR study reveals an emergent high-Tcphase with no coherence peak which is hard to measure by NMR with other isotopes. This novel electric-fieldinduced proton evolution opens up an avenue for manipulation of competing electronic states(e.g.Mott insulators), and may provide an innovative way for a broad perspective of NMR measurements with greatly enhanced detecting resolution.
文摘Carbon nanotube reinforced bioglass composites have been successfully synthesized by two comparative sintering techniques, i.e., spark plasma sintering （SPS） and conventional compaction and sinteirng. The composites show improved mechanical properties, with SPS technique substantially better than conventional compact and sintering approach. Using SPS, compared with the 45S5Bioglass matrix, the maximum flexural strength and fracture toughness increased by 159% and 105%, respectively. Enhanced strength and toughness are attributed to the interfacial bonding and bridging effects between the carbon nanotubes and bioglass powders during crack propagations.
基金the National Natural Science Foundation of China，the National High-tech R&D Program of China
文摘Ceramics of Bi0.9Ba0.1Fe0.925TixO3 (x = 0.0625, 0.08125, 0.0875, and 0.11) were prepared according to two doping strategies: one is called single-step doping in which Ba and Ti were doped together in calcination, while the other one is called two-step doping in which Ba and Ti were doped in calcination and sintering, respectively. Compared with samples prepared with single-step doping, those prepared with two-step doping have obviously different XRD patterns and small grains, and are dramatically improved in dielectric loss, resistivity, and remnant magnetization. A low dielectric loss of 0.05 at 10(3) Hz, a high resistivity of 4x10(12) Omega.cm, and a large remnant magnetization of 1.5 emu/g, have been obtained simultaneously for Bi0.9Ba0.1Fe0.925Ti0.11O3 prepared with two-step doping. The contrast between these two doping strategies clearly reveals the importance of establishing a proper doping strategy when two or more elements are co-doped to BiFeO3.
