Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CR...Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced intestinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12−/−mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.展开更多
BACKGROUND Chronic esophagitis can progress to esophageal cancer via"inflammationdysplasia-cancer"transformation,with nitric oxide(NO)serving as a critical mediator in this process.Traditional diagnostic met...BACKGROUND Chronic esophagitis can progress to esophageal cancer via"inflammationdysplasia-cancer"transformation,with nitric oxide(NO)serving as a critical mediator in this process.Traditional diagnostic methods(e.g.,endoscopic biopsy)for esophageal cancer transformation have low sensitivity and require long detection time,while existing fluorescent probes lack specificity and stability for real-time NO monitoring.High-performance fluorescent probes like DAF-FM,with NO-targeting ability,show potential for visual screening and efficacy evaluation but need systematic validation in esophageal cancer models.AIM To validate the applicability of the fluorescent probe DAF-FM for visual screening of esophageal cancer transformation,explore the underlying mechanism of NOregulated transformation,and evaluate the probe’s efficacy in monitoring therapeutic responses.METHODS Laser confocal imaging and flow cytometry were used to analyze DAF-FM’s NO concentration/time-dependent fluorescence response,lysosomal targeting(via Pearson coefficient),and cytotoxicity(with cholecystokinin-8 assay)in esophageal cells.Sprague-Dawley rat esophageal cancer models(normal,esophagitis,esophageal cancer,and drug/radiotherapy intervention)were established to monitor NO dynamics and tumor volume correlation.Clinical diagnostic comparison(50 suspected patients)with endoscopic biopsy/histopathology was conducted using Kolmogorov-Smirnov test and Student’s t-test(P<0.05).Western blot and quantitative realtime polymerase chain reaction were used to explore NO’s role in the nuclear factor-kappa B(NF-κB)pathway.RESULTS DAF-FM exhibited concentration/time-dependent fluorescence with NO(300μM NO:60-minute fluorescence intensity 458±15 arbitrary units,P<0.05)and specific lysosomal targeting(Pearson’s coefficient=0.82±0.03).It had low cytotoxicity(82.3%±4.1%cell viability at 50μM).In rat models,DAF-FM showed that NO was correlated with tumor volume(R²=0.87).Clinically,its sensitivity(92.5%)outperformed endoscopic biopsy(78.3%),with shorter detection time(30 minutes vs 48 hours,P<0.05).Mechanistically,NO regulated transformation via the NF-κB pathway(Pearson’s coefficient=0.78±0.05 between DAF-FM and NF-κB).CONCLUSION DAF-FM is a feasible tool for visual screening of esophageal cancer transformation,enabling real-time NO monitoring,high-sensitivity diagnosis,and therapeutic efficacy evaluation.It provides a new approach for esophageal cancer diagnosis and mechanism research.展开更多
BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the ...BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.展开更多
Epidermal growth factor receptor tyrosine kinase inhibitors effectively improve the prognosis of patients with epidermal growth factor receptor–mutant lung adenocarcinoma.However,acquired resistance inevitably develo...Epidermal growth factor receptor tyrosine kinase inhibitors effectively improve the prognosis of patients with epidermal growth factor receptor–mutant lung adenocarcinoma.However,acquired resistance inevitably develops with small cell lung cancer transformation emerging as a rare but increasingly frequent mechanism of tyrosine kinase inhibitor resistance.This transformation poses significant chal-lenges to the health of patients with lung cancer and complicates their clinical management.This article comprehensively reviews the di-agnostic,predictive,mechanistic,and therapeutic aspects of small cell lung cancer transformation to enhance our understanding and clin-ical awareness of this phenomenon.展开更多
Chronic uncontrolled inflammation is a major risk factor driving the occurrence of hepatocellular carcinoma(HCC),with over half of global cases attributed to hepatitis B virus(HBV)infection.Persistent inflammation fre...Chronic uncontrolled inflammation is a major risk factor driving the occurrence of hepatocellular carcinoma(HCC),with over half of global cases attributed to hepatitis B virus(HBV)infection.Persistent inflammation frequently progresses to cirrhosis and,ultimately,malignancy[1].Monitoring the key risk factors involved in the inflammatory-to-cancerous transformation in HCC is crucial for enabling timely intervention and improving patient survival rates.To address this challenge,we analyzed plasma samples collected from healthy volunteers and patients at various stages of HCC progression,including hepatitis,cirrhosis,and HCC(Approval No.:2021-IRBQYYS-021)(Tables S1–S5).展开更多
Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcino...Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).展开更多
Rat-1 cells were transfected with DNA from human esophageal cancer 2K, 4K, 6K, 7K. 8K. The transforming foci were obtained and the transforming cell lines were established. The cell lines can form larger colony in sof...Rat-1 cells were transfected with DNA from human esophageal cancer 2K, 4K, 6K, 7K. 8K. The transforming foci were obtained and the transforming cell lines were established. The cell lines can form larger colony in soft agar. Those nude mice injected subcutaneously with the cells suffered from larger fibrous sarcoma. This indicates that the cell lines have carcinogenicity. The experimental results suggest that human DNA sequence and human Ha-ras special 616Kb (BamHI) band are present in the DNA of the transforming cells. The over-expression of ras gene products P21 were found in the tissues of exophageal cancer, the tissues adjacent to tumor and the transforming cells.展开更多
1.New breakthroughs in cross-organ“brain-gut”strategies for the prevention and treatment of digestive diseases Refractory digestive diseases,represented by functional gastro-intestinal disorders and inflammation-to-...1.New breakthroughs in cross-organ“brain-gut”strategies for the prevention and treatment of digestive diseases Refractory digestive diseases,represented by functional gastro-intestinal disorders and inflammation-to-cancer transformation in the digestive tract,are associated with high incidence,com-plex pathogenesis,and considerable treatment challenges.These conditions are closely linked to acute and chronic stress-related injuries in the central nervous system.Single-modality therapies are insufficient to address the cross-organ nature of these dis-orders.Prof.Wei Wei(Wangjing Hospital,China Academy of Chinese Medical Sciences),Researcher Rong Peijing(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences),and Prof.Liu Fengbin(The First Affiliated Hospital of Guangzhou University of Chinese Medicine)pro-posed a novel strategy of“brain-gut coordination.”A mul-ticenter randomized controlled trial involving 1796 patients with functional gastrointestinal disorders demonstrated that this strategy significantly improved symptoms such as abdom-inal bloating,abdominal pain,and diarrhea,as well as anxiety and depression.展开更多
基金supported by National Nature Science Foundation of China(Grant Nos.:82320108022,82322076,and 822104466)Shanghai Rising-Star Program,China(Grant No.:20QA1409300)+1 种基金the National Funding Program for Postdoctoral Researchers,China(C gradeProgram No.:GZC20231707).
文摘Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced intestinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12−/−mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.
基金Supported by Natural Science Foundation of Fujian Province,No.2023J011787Quanzhou Science and Technology Program Project,No.2025QZC02DW.
文摘BACKGROUND Chronic esophagitis can progress to esophageal cancer via"inflammationdysplasia-cancer"transformation,with nitric oxide(NO)serving as a critical mediator in this process.Traditional diagnostic methods(e.g.,endoscopic biopsy)for esophageal cancer transformation have low sensitivity and require long detection time,while existing fluorescent probes lack specificity and stability for real-time NO monitoring.High-performance fluorescent probes like DAF-FM,with NO-targeting ability,show potential for visual screening and efficacy evaluation but need systematic validation in esophageal cancer models.AIM To validate the applicability of the fluorescent probe DAF-FM for visual screening of esophageal cancer transformation,explore the underlying mechanism of NOregulated transformation,and evaluate the probe’s efficacy in monitoring therapeutic responses.METHODS Laser confocal imaging and flow cytometry were used to analyze DAF-FM’s NO concentration/time-dependent fluorescence response,lysosomal targeting(via Pearson coefficient),and cytotoxicity(with cholecystokinin-8 assay)in esophageal cells.Sprague-Dawley rat esophageal cancer models(normal,esophagitis,esophageal cancer,and drug/radiotherapy intervention)were established to monitor NO dynamics and tumor volume correlation.Clinical diagnostic comparison(50 suspected patients)with endoscopic biopsy/histopathology was conducted using Kolmogorov-Smirnov test and Student’s t-test(P<0.05).Western blot and quantitative realtime polymerase chain reaction were used to explore NO’s role in the nuclear factor-kappa B(NF-κB)pathway.RESULTS DAF-FM exhibited concentration/time-dependent fluorescence with NO(300μM NO:60-minute fluorescence intensity 458±15 arbitrary units,P<0.05)and specific lysosomal targeting(Pearson’s coefficient=0.82±0.03).It had low cytotoxicity(82.3%±4.1%cell viability at 50μM).In rat models,DAF-FM showed that NO was correlated with tumor volume(R²=0.87).Clinically,its sensitivity(92.5%)outperformed endoscopic biopsy(78.3%),with shorter detection time(30 minutes vs 48 hours,P<0.05).Mechanistically,NO regulated transformation via the NF-κB pathway(Pearson’s coefficient=0.78±0.05 between DAF-FM and NF-κB).CONCLUSION DAF-FM is a feasible tool for visual screening of esophageal cancer transformation,enabling real-time NO monitoring,high-sensitivity diagnosis,and therapeutic efficacy evaluation.It provides a new approach for esophageal cancer diagnosis and mechanism research.
文摘BACKGROUND The emergence of secondary drug resistance when treating epidermal growth factor receptor(EGFR)mutated non-small cell lung cancer(NSCLC)using EGFRtyrosine kinase inhibitors(EGFR-TKIs),seriously affects the therapeutic efficacy and survival of patients.Here,we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.CASE SUMMARY A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma,and exhibited the development of a T790M mutation during initial TKI treatment.Following 3 mo of Osimertinib treatment,a mixed response was observed.Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer(SCLC)harboring RB1 and TP53 mutations,with loss of the original T790M mutation.A standard chemotherapy regimen with Anlotinib for SCLC was administered.Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression.The patient’s overall survival was 24 mo.CONCLUSION Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making.Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.
文摘Epidermal growth factor receptor tyrosine kinase inhibitors effectively improve the prognosis of patients with epidermal growth factor receptor–mutant lung adenocarcinoma.However,acquired resistance inevitably develops with small cell lung cancer transformation emerging as a rare but increasingly frequent mechanism of tyrosine kinase inhibitor resistance.This transformation poses significant chal-lenges to the health of patients with lung cancer and complicates their clinical management.This article comprehensively reviews the di-agnostic,predictive,mechanistic,and therapeutic aspects of small cell lung cancer transformation to enhance our understanding and clin-ical awareness of this phenomenon.
基金supported by Liaoning Province Science and Technology Plan Project,China(Grant No.:2022JH2/101300038)Liaoning Provincial Applied Basic Research Project,China(Grant No.:2022020255-JH2/1013)+6 种基金the National Natural Science Foundation of China of China(Grant Nos.:82104379/H3203 and 82104126/H3410)Liaoning Distinguished Professor Project(2017)Liaoning BaiQianWan Talents Program in 2019(A-37),ChinaLiaoning key Research and Development Program(2018),Chinathe Natural Science Funds of Liaoning Province,China(Grant No.:2021JH2/10300068)the Basic Scientific Research Project of Higher Education Department of Liaoning Province,China(Grant No.:LJ212410163036)Educational Commission of Liaoning Province of China,China(Grant No.:LJ212410163026).
文摘Chronic uncontrolled inflammation is a major risk factor driving the occurrence of hepatocellular carcinoma(HCC),with over half of global cases attributed to hepatitis B virus(HBV)infection.Persistent inflammation frequently progresses to cirrhosis and,ultimately,malignancy[1].Monitoring the key risk factors involved in the inflammatory-to-cancerous transformation in HCC is crucial for enabling timely intervention and improving patient survival rates.To address this challenge,we analyzed plasma samples collected from healthy volunteers and patients at various stages of HCC progression,including hepatitis,cirrhosis,and HCC(Approval No.:2021-IRBQYYS-021)(Tables S1–S5).
文摘Non-small cell lung cancer(NSCLC)is the most common form of lung cancer which remains the deadliest malignancy worldwide(Siegel et al.,2019).In general,NSCLC can be divided into several subtypes,including adenocarcinoma(ADC),squamous cell carcinoma(SCC),adeno-squamous cell carcinoma(AD-SCC)and large cell carcinoma(LCC).
文摘Rat-1 cells were transfected with DNA from human esophageal cancer 2K, 4K, 6K, 7K. 8K. The transforming foci were obtained and the transforming cell lines were established. The cell lines can form larger colony in soft agar. Those nude mice injected subcutaneously with the cells suffered from larger fibrous sarcoma. This indicates that the cell lines have carcinogenicity. The experimental results suggest that human DNA sequence and human Ha-ras special 616Kb (BamHI) band are present in the DNA of the transforming cells. The over-expression of ras gene products P21 were found in the tissues of exophageal cancer, the tissues adjacent to tumor and the transforming cells.
基金the Project of Map of Scientific and Technological Talents in the Field of Traditional Chinese Medicine (XMSB20240923106)。
文摘1.New breakthroughs in cross-organ“brain-gut”strategies for the prevention and treatment of digestive diseases Refractory digestive diseases,represented by functional gastro-intestinal disorders and inflammation-to-cancer transformation in the digestive tract,are associated with high incidence,com-plex pathogenesis,and considerable treatment challenges.These conditions are closely linked to acute and chronic stress-related injuries in the central nervous system.Single-modality therapies are insufficient to address the cross-organ nature of these dis-orders.Prof.Wei Wei(Wangjing Hospital,China Academy of Chinese Medical Sciences),Researcher Rong Peijing(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences),and Prof.Liu Fengbin(The First Affiliated Hospital of Guangzhou University of Chinese Medicine)pro-posed a novel strategy of“brain-gut coordination.”A mul-ticenter randomized controlled trial involving 1796 patients with functional gastrointestinal disorders demonstrated that this strategy significantly improved symptoms such as abdom-inal bloating,abdominal pain,and diarrhea,as well as anxiety and depression.
