This issue of Cancer Biology & Medicine, a premium Chinese international scientific journal in this field, focuses on cooperation between Chinese and German cancer research, particularly between the Tianjin Medica...This issue of Cancer Biology & Medicine, a premium Chinese international scientific journal in this field, focuses on cooperation between Chinese and German cancer research, particularly between the Tianjin Medical University Cancer Institute & Hospital and the German Cancer Research Center(DKFZ) with its networking partners. This editorial provides a brief overview on DKFZ’s research strategy with a focus on how a national integrated cancer research and care ecosystem is evolving that benefits patients and society.展开更多
Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly can...Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.展开更多
AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospec...AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.展开更多
Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stim...Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stimulation by signal factors and/or growth factors,organoids self-assemble to replicate the morphological and structural characteristics of the corresponding organs.They provide an extraordinary platform for investigating organ development and mimicking pathological processes.Organoid biobanks derived from a wide range of carcinomas have been established to represent different lesions or stages of clinical tumors.Importantly,genomic and transcriptomic analyses have confirmed maintenance of intra-and interpatient heterogeneities in organoids.Therefore,this technology has the potential to revolutionize drug screening and personalized medicine.In this review,we summarized the characteristics and applications of organoids in cancer research by the establishment of organoid biobanks directly from tumor organoids or from genetically modified non-cancerous organoids.We also analyzed the current state of organoid applications in drug screening and personalized medicine.展开更多
The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the re...The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes.展开更多
This review is aimed at presenting some of the recent developments in translational cancer imaging research,with a focus on novel,recently established,or soon to be established cross-sectional imaging techniques for c...This review is aimed at presenting some of the recent developments in translational cancer imaging research,with a focus on novel,recently established,or soon to be established cross-sectional imaging techniques for computed tomography(CT),magnetic resonance imaging(MRI),and positron-emission tomography(PET)imaging,including computational investigations based on machine-learning techniques.展开更多
Objective:Breast cancer is the most common cancer in women,causing significant mortality in the world,which contributed 11.7%to the overall cancer-related mortality in Afghanistan.In 2018,3062 new breast cancer cases ...Objective:Breast cancer is the most common cancer in women,causing significant mortality in the world,which contributed 11.7%to the overall cancer-related mortality in Afghanistan.In 2018,3062 new breast cancer cases were reported accounting for 29.7%of all cancers in women in the country.However,a comprehensive diagnostic and therapeutic system is lacking in Afghanistan.In this paper,we reported the implementation of a project aiming to establish a comprehensive breast cancer center in Herat province of Afghanistan.Methods:From July 2017,a two-year-program initiated at Kimia Hospital in Herat.This first free diagnostic and therapeutic breast cancer project planned by the Afghanistan Surgeons Society-West and the Verein für Afghanistan-Förderung e.V.,as well supported by three international foundations.The target populations of this project were women presenting with breast problems at Kimia Hospital in Herat and healthcare staff involved in breast cancer diagnosis and management.Results:A group of six medical personnel chosen to represent the breast cancer core team for breast cancer diagnosis and management were trained in India.These caregivers established the breast cancer service and tumor board.During a period of 20 months,a total of 632 women with breast problems presented to Kimia Hospital of whom 44(7.0%)were diagnosed with breast cancer.Diagnosis was established by a physical examination,ultrasonography,mammography,biopsy and histopathology.Treatment included surgery,radiotherapy and chemotherapy.Twelve seminars for 512 healthcare workers,1000 brochures and a movie were prepared for awareness-raising actions.For continuation of this project,potential resource providers were identified.A database was developed to record project findings.Conclusion:Implementation of this comprehensive breast cancer project resulted in significant achievements in healthcare staff capacity building,diagnosis and management of breast cancer patients in Herat province.Data obtained in this project offer Afghan government,public health authorities,and the community the opportunity of improving diagnosis and treatment of breast cancer in Afghanistan.展开更多
Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are...Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are scarce.Therefore,we conducted a randomized controlled trial investigating the effects of aerobic or resistance exercise concomitant to neoadjuvant chemotherapy(NACT)on tumor size.Methods In the BENEFIT study(German title:Bewegung bei neoadjuvanter chemotherapie zur verbesserung der fitness),patients with breast cancer scheduled for NACT were randomly assigned to supervised resistance training(RT,n=60)or aerobic training(AT,n=60)twice weekly during NACT or to a waitlist control group(WCG,n=60).The primary outcome,“change in tumor size”,as well as the secondary clinical outcomes pathologic complete response(pCR),type of surgery(breast conserving/mastectomy),axillary lymph node dissection(ALND,yes/no),premature discontinuation of chemotherapy(yes/no),and relative dose intensity(RDI)were derived from clinical records.Due to the highly skewed distribution,the primary outcome was categorized.Multiple(ordinal)logistic regression analyses were performed.Results Overall,there was no significant difference in post-intervention tumor size between RT or AT and WCG.However,there was a significant effect modification by hormone receptor(HR)status(P_(interaction)=0.030).Among patients with HR+tumors,results suggest a beneficial effect of AT on tumor shrinkage(odds ratio(OR)=2.37,95%confidence interval(95%CI):0.97‒5.78),on pCR(OR=3.21,95%CI:0.97‒10.61);and on ALND(OR=3.76,95%CI:0.78‒18.06)compared to WCG.The effects of RT were slightly less pronounced.For HR−subtypes,beneficial effects on RDI were found for AT(OR=3.71,95%CI:1.20‒11.50)and similarly for RT(OR=2.58,95%CI:0.88‒7.59).Both AT and RT had favorable effects on premature discontinuation of chemotherapy(OR(no vs.yes)=2.34,95%CI:1.10‒5.06),irrespective of tumor receptor status.Conclusion While there was no significant effect on the primary outcome in the overall group,aerobic and resistance exercise concomitant to NACT seem to beneficially affect tumor shrinkage and pCR,reduce the need for ALND among patients with HR+breast cancers,and prevent low RDI among patients with HR–breast cancers.These results warrant confirmation in further trials.展开更多
BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnose...BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.展开更多
Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of R...Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.Methods:We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles,mutational profiles,cancer immunotherapy and drug sensitivity.By combining RFX1 expression with persistent tumor mutational burden,we proposed a novel nomogram clinical prediction model and validated its predictive performance,and the correlation between high expression and poor prognosis.Results:Compared to tumor mutational burden(TMB),persistent tumor mutational burden(pTMB)is an independent predictor of prognosis in patients with colon cancer.The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB.Among them,patients in the RFX1^(high)/pTMB^(high) subgroup had the worst quality of survival and prognosis,whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis(p<0.0001).Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients(Hazard Ratio[HR]=1.58,95%Confidence Interval[CI]:1.10–2.25,p=0.012),which remained independently predictive in multivariate analysis after covariate adjustment(HR=1.52,95%CI:1.04–2.22,p=0.031).Conclusion:A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.G...BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).展开更多
BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHO...BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.展开更多
Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest i...Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest in cannabinoids like cannabichromene(CBC)and delta-9-tetrahydrocannabinol(THC)for their therapeutic properties,we evaluated their cytotoxic effects on urothelial carcinoma(UC)cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures(EVOCs).Methods:C.sativa strains were screened for their cytotoxicity against UC cell lines(HTB-4 and HTB-9)using XTT assays.Their phytocannabinoid content was analyzed using high-performance liquid chromatography.We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle,migration assays to determine cell migration,and EVOCs to evaluate the cytotoxic effect on UC.Gene expression was determined by quantitative polymerase chain reaction.Results:Three commercial C.sativa strains,PARIS,DQ,and sCBD,were found to have the most potent anticancer effects on bladder cancer cells.All extracts contain CBC and THC at different concentrations.In XTT assays on UC cell lines,PARIS had a half-maximal inhibitory concentration(IC50)of 21.58 mg/mL,while DQ and sCBD had similar cytotoxic activity with IC_(50) values for 48-h treatment of 17.99 mg/mL and 17.88 mg/mL,respectively.DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G_(2)/M phase within the cell population.In EVOCs,the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.Conclusion:The findings suggest that C.sativa strains PARIS,DQ,and sCBD,containing CBC and THC,exhibit significant anticancer activity against UC cell lines and ex vivo models.These results underscore the therapeutic potential of CBC-and THC-rich C.sativa extracts in bladder cancer treatment.展开更多
Background:Non-small cell lung cancer(NSCLC)is the cancer with the highest incidence and mortality rate worldwide.This study aimed to investigate the predictive value of clinicopathological and radiological characteri...Background:Non-small cell lung cancer(NSCLC)is the cancer with the highest incidence and mortality rate worldwide.This study aimed to investigate the predictive value of clinicopathological and radiological characteristics for event-free survival(EFS),major pathological response(MPR),and pathological complete response(pCR)in patients with NSCLC undergoing neoadjuvant chemoimmunotherapy.Methods:A retrospective analysis was performed on the clinical data of 180 patients with NSCLC who received neoadjuvant chemoimmunotherapy between October 2019 and December 2023.The primary endpoint was EFS,and the secondary endpoint was the pathological response rate.Fisher exact test and the nonparametricMann-Whitney U test were used to compare categorical and continuous data between the pCR/MPR and non-pCR/non-MPR groups.The Kaplan-Meier method was used to estimate EFS curves,and Cox regression analysis was performed to compare the differences in EFS between patients with or without pCR or MPR.Results:Sex(p=0.004),smoking history(p=0.025),and clinical stage(p=0.002)were identified as predictors of pCR and MPR.In our study,pCR was observed in 38.12%and MPR in 44.75%of the patients.Through the multivariate logistic regression model,age and pathological response were found to predict the 1-and 2-year EFS rates,demonstrating satisfactory predictive power(area under the curve,0.866 and 0.736,respectively).Patients with pCR or MPR exhibited longer EFS compared with those without pCR or MPR,as determined by Cox analysis.Conclusions:Sex,smoking history,and clinical stage were identified as predictors of pCR and MPR in patients with NSCLC.Survival analysis revealed that age and pathological response were key prognostic factors for EFS.展开更多
Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks...Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.展开更多
Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expen...Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.展开更多
Cancer is characterized by abnormal cell proliferation.Cyclins and cyclin-dependent kinases(CDKs)have been recognized as essential regulators of the intricate cell cycle,orchestrating DNA replication and transcription...Cancer is characterized by abnormal cell proliferation.Cyclins and cyclin-dependent kinases(CDKs)have been recognized as essential regulators of the intricate cell cycle,orchestrating DNA replication and transcription,RNA splicing,and protein synthesis.Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers,rendering cyclins and CDKs attractive therapeutic targets.Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use,fueling the development of CDK-targeted therapies.With this enthusiasm for finding novel CDK-targeting anti-cancer agents,there have also been exciting advances in the field of targeted protein degradation through innovative strategies,such as using proteolysis-targeting chimera,heat shock protein 90(HSP90)-mediated targeting chimera,hydrophobic tag-based protein degradation,and molecular glue.With a focus on the translational potential of cyclin-and CDK-targeting strategies in cancer,this review presents the fundamental roles of cyclins and CDKs in cancer.Furthermore,it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs,detailing the underlying mechanisms of action for each approach.A comprehensive overview of the structure and activity of existing CDK degraders is also provided.By examining the structure‒activity relationships,target profiles,and biological effects of reported cyclin/CDK degraders,this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.展开更多
Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC...Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.展开更多
Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the dia...Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan(CNY; 1 CNY = 0.155 USD) based on the2011 value and inflated using the year-specific health care consumer price index for China.Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002(25,111 CNY) to 2011(46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ,39,302 CNY for stage Ⅱ,40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases(P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy(P < 0.05).Drugs contributed to 45.02% of the overall expenditure.Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.展开更多
文摘This issue of Cancer Biology & Medicine, a premium Chinese international scientific journal in this field, focuses on cooperation between Chinese and German cancer research, particularly between the Tianjin Medical University Cancer Institute & Hospital and the German Cancer Research Center(DKFZ) with its networking partners. This editorial provides a brief overview on DKFZ’s research strategy with a focus on how a national integrated cancer research and care ecosystem is evolving that benefits patients and society.
文摘Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.
基金Supported by Zentrum für Geriatrische Onkologie und Biologie in der Metropolregion Rhein Neckar(ZOBEL)
文摘AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.31671421,82030079,and 82003187).
文摘Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stimulation by signal factors and/or growth factors,organoids self-assemble to replicate the morphological and structural characteristics of the corresponding organs.They provide an extraordinary platform for investigating organ development and mimicking pathological processes.Organoid biobanks derived from a wide range of carcinomas have been established to represent different lesions or stages of clinical tumors.Importantly,genomic and transcriptomic analyses have confirmed maintenance of intra-and interpatient heterogeneities in organoids.Therefore,this technology has the potential to revolutionize drug screening and personalized medicine.In this review,we summarized the characteristics and applications of organoids in cancer research by the establishment of organoid biobanks directly from tumor organoids or from genetically modified non-cancerous organoids.We also analyzed the current state of organoid applications in drug screening and personalized medicine.
基金The study was supported by funding from the NIDDK(DK098277)to Douglas W.Strandfrom the National Nature Scientific Foundation of China(NSFC No.81372772)to Dr.Ming Jiang,the Scientific Research Foundation for Jiangsu Specially-Appointed Professor(Sujiaoshi[2012]No.34),to Dr.Ming Jiang,Department of Education in Jiangsu Province,China and the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China.
文摘The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes.
文摘This review is aimed at presenting some of the recent developments in translational cancer imaging research,with a focus on novel,recently established,or soon to be established cross-sectional imaging techniques for computed tomography(CT),magnetic resonance imaging(MRI),and positron-emission tomography(PET)imaging,including computational investigations based on machine-learning techniques.
基金supported by the Hospital Partnerships by Germany's Federal Ministry of Economic Cooperation and Development(BMZ)the Else Kroner-Fresenius-Stiftung and the Foundation Wienbeck,Germany.
文摘Objective:Breast cancer is the most common cancer in women,causing significant mortality in the world,which contributed 11.7%to the overall cancer-related mortality in Afghanistan.In 2018,3062 new breast cancer cases were reported accounting for 29.7%of all cancers in women in the country.However,a comprehensive diagnostic and therapeutic system is lacking in Afghanistan.In this paper,we reported the implementation of a project aiming to establish a comprehensive breast cancer center in Herat province of Afghanistan.Methods:From July 2017,a two-year-program initiated at Kimia Hospital in Herat.This first free diagnostic and therapeutic breast cancer project planned by the Afghanistan Surgeons Society-West and the Verein für Afghanistan-Förderung e.V.,as well supported by three international foundations.The target populations of this project were women presenting with breast problems at Kimia Hospital in Herat and healthcare staff involved in breast cancer diagnosis and management.Results:A group of six medical personnel chosen to represent the breast cancer core team for breast cancer diagnosis and management were trained in India.These caregivers established the breast cancer service and tumor board.During a period of 20 months,a total of 632 women with breast problems presented to Kimia Hospital of whom 44(7.0%)were diagnosed with breast cancer.Diagnosis was established by a physical examination,ultrasonography,mammography,biopsy and histopathology.Treatment included surgery,radiotherapy and chemotherapy.Twelve seminars for 512 healthcare workers,1000 brochures and a movie were prepared for awareness-raising actions.For continuation of this project,potential resource providers were identified.A database was developed to record project findings.Conclusion:Implementation of this comprehensive breast cancer project resulted in significant achievements in healthcare staff capacity building,diagnosis and management of breast cancer patients in Herat province.Data obtained in this project offer Afghan government,public health authorities,and the community the opportunity of improving diagnosis and treatment of breast cancer in Afghanistan.
基金supported by an intramural proof of concept grant of the NCT Heidelberg.
文摘Background The potential of exercise as a concurrent therapy for actively treated primary tumors has been suggested by emerging preclinical and observational studies.However,clinical trials regarding this question are scarce.Therefore,we conducted a randomized controlled trial investigating the effects of aerobic or resistance exercise concomitant to neoadjuvant chemotherapy(NACT)on tumor size.Methods In the BENEFIT study(German title:Bewegung bei neoadjuvanter chemotherapie zur verbesserung der fitness),patients with breast cancer scheduled for NACT were randomly assigned to supervised resistance training(RT,n=60)or aerobic training(AT,n=60)twice weekly during NACT or to a waitlist control group(WCG,n=60).The primary outcome,“change in tumor size”,as well as the secondary clinical outcomes pathologic complete response(pCR),type of surgery(breast conserving/mastectomy),axillary lymph node dissection(ALND,yes/no),premature discontinuation of chemotherapy(yes/no),and relative dose intensity(RDI)were derived from clinical records.Due to the highly skewed distribution,the primary outcome was categorized.Multiple(ordinal)logistic regression analyses were performed.Results Overall,there was no significant difference in post-intervention tumor size between RT or AT and WCG.However,there was a significant effect modification by hormone receptor(HR)status(P_(interaction)=0.030).Among patients with HR+tumors,results suggest a beneficial effect of AT on tumor shrinkage(odds ratio(OR)=2.37,95%confidence interval(95%CI):0.97‒5.78),on pCR(OR=3.21,95%CI:0.97‒10.61);and on ALND(OR=3.76,95%CI:0.78‒18.06)compared to WCG.The effects of RT were slightly less pronounced.For HR−subtypes,beneficial effects on RDI were found for AT(OR=3.71,95%CI:1.20‒11.50)and similarly for RT(OR=2.58,95%CI:0.88‒7.59).Both AT and RT had favorable effects on premature discontinuation of chemotherapy(OR(no vs.yes)=2.34,95%CI:1.10‒5.06),irrespective of tumor receptor status.Conclusion While there was no significant effect on the primary outcome in the overall group,aerobic and resistance exercise concomitant to NACT seem to beneficially affect tumor shrinkage and pCR,reduce the need for ALND among patients with HR+breast cancers,and prevent low RDI among patients with HR–breast cancers.These results warrant confirmation in further trials.
基金Supported by National Key Technology Research and Developmental Program of China,No.2022YFC2704400 and No.2022YFC2704405.
文摘BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.
基金sponsored by the National Natural Science Foundation of China(82002507)Shanghai Sailing Program(20YF1430100)Shanghai Hospital Development Center(SHDC2023CRT004).
文摘Objective:The plastic role of regulatory factor X1(RFX1)in colon cancer progression and its impact on the tumor microenvironment remain poorly understood.The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer.Methods:We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles,mutational profiles,cancer immunotherapy and drug sensitivity.By combining RFX1 expression with persistent tumor mutational burden,we proposed a novel nomogram clinical prediction model and validated its predictive performance,and the correlation between high expression and poor prognosis.Results:Compared to tumor mutational burden(TMB),persistent tumor mutational burden(pTMB)is an independent predictor of prognosis in patients with colon cancer.The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB.Among them,patients in the RFX1^(high)/pTMB^(high) subgroup had the worst quality of survival and prognosis,whereas those in the RFX1low/pTMBlow subgroup had a relatively better prognosis(p<0.0001).Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients(Hazard Ratio[HR]=1.58,95%Confidence Interval[CI]:1.10–2.25,p=0.012),which remained independently predictive in multivariate analysis after covariate adjustment(HR=1.52,95%CI:1.04–2.22,p=0.031).Conclusion:A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer.
文摘BACKGROUND Colorectal cancer is the third most common malignancy and the fourth leading cause of cancer-related deaths worldwide.Several studies have shown an association between gut microbiota and colorectal cancer.Gut microbiota is unique and can be influenced by geographic factors and habits.This study aimed to determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer.AIM To determine the diversity and composition of colonic mucosal microbiota in patients with and without colorectal cancer in Indonesia.METHODS This case-control study included 59 subjects(35 colorectal cancer patients and 24 non-colorectal cancer patients indicated for colonoscopy at Dr.Cipto Mangunkusumo Gastrointestinal Endoscopy Center and Fatmawati Hospital.Microbiota examination was performed using 16S rRNA sequencing.Bioinformatics analysis was performed using the wf-metagenomics pipeline from EPI2Me-Labs(Oxford Nanopore Technologies platform).RESULTS Patients with colorectal cancer had a higher median index value on the Shannon index(3.28 vs 2.82,P>0.05)and a lower value on the Simpson index(0.050 vs 0.060,P>0.05).Significant differences in beta diversity were observed at the genus(P=0.002)and species levels(P=0.001).Firmicutes,Proteobacteria,Bacteroidetes,and Fusobacteria were the dominant phyla.The genera Bacteroides,Campylobacter,Peptostreptococcus,and Parvimonas were found more frequently in colorectal cancer,while Faecalibacterium,Haemophilus,and Phocaeicola were more frequently found in non-colorectal cancer.The relative abundance of Fusobacterium nucleatum,Bacteroides fragilis,Enterococcus faecalis,Campylobacter hominis,and Enterococcus faecalis species was significantly elevated in patients with colorectal cancer.Meanwhile,Faecalibacterium prausnitzii,Faecalibacterium duncaniae,and Prevotella copri were more commonly found in non-colorectal cancer.CONCLUSION Patients with colorectal cancer exhibit distinct differences in the composition and diversity of their colonic mucosal microbiota compared to those with non-colorectal cancer.This study was reviewed and approved by the Ethics Committee of Faculty of Medicine,Universitas Indonesia(No.KET-1517/UN2.F1/ETIK/PPM.00.02/2023).
基金Supported by the Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)Wenzhou Science&Technological Project,No.Y20240103.
文摘BACKGROUND Deoxycholic acid(DCA),a secondary bile acid,is associated with colorectal carcinogenesis,but its mechanisms remain unclear.AIM To investigate how DCA regulates apoptosis in colorectal cancer(CRC)cells.METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting,flow cytometry,confocal microscopy,and other methods.RESULTS DCA significantly induced apoptosis,with rates increasing to 7.2%±1.5%in SW480 cells and 14.3%±0.6%in DLD-1 cells after treatment,compared to 4.7%±1.0%and 11.6%±0.8%in controls(P<0.05).Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP,with a significant increase in the Cleaved-PARP/PARP ratio(P<0.001).DCA treatment also increased the intracellular reactive oxygen species(ROS)levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold,respectively(P<0.01),while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy.Additionally,cytosolic and mitochondrial Ca^(2+)levels increased 1.3-fold and 1.2-fold,respectively,in SW480 cells(P<0.01),and 1.1-fold and 1.1-fold,respectively,in DLD-1 cells compared with controls(P<0.05).p-CaMKII protein levels were also elevated(P<0.01),indicating activation of the Ca^(2+)-CaMKII signaling pathway.Pharmacological inhibition with BAPTAAM(1μM)reduced mitochondrial Ca^(2+)accumulation and ROS levels in SW480 cells(P<0.05),and suppressed apoptosis.CONCLUSION DCA activates the Ca^(2+)-CaMKII pathway,leading to ROS-mediated apoptosis in CRC cells,providing insights for potential therapeutic targets.
文摘Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest in cannabinoids like cannabichromene(CBC)and delta-9-tetrahydrocannabinol(THC)for their therapeutic properties,we evaluated their cytotoxic effects on urothelial carcinoma(UC)cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures(EVOCs).Methods:C.sativa strains were screened for their cytotoxicity against UC cell lines(HTB-4 and HTB-9)using XTT assays.Their phytocannabinoid content was analyzed using high-performance liquid chromatography.We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle,migration assays to determine cell migration,and EVOCs to evaluate the cytotoxic effect on UC.Gene expression was determined by quantitative polymerase chain reaction.Results:Three commercial C.sativa strains,PARIS,DQ,and sCBD,were found to have the most potent anticancer effects on bladder cancer cells.All extracts contain CBC and THC at different concentrations.In XTT assays on UC cell lines,PARIS had a half-maximal inhibitory concentration(IC50)of 21.58 mg/mL,while DQ and sCBD had similar cytotoxic activity with IC_(50) values for 48-h treatment of 17.99 mg/mL and 17.88 mg/mL,respectively.DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G_(2)/M phase within the cell population.In EVOCs,the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.Conclusion:The findings suggest that C.sativa strains PARIS,DQ,and sCBD,containing CBC and THC,exhibit significant anticancer activity against UC cell lines and ex vivo models.These results underscore the therapeutic potential of CBC-and THC-rich C.sativa extracts in bladder cancer treatment.
基金Supported by a grant from Beijing Municipal PublicWelfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,No.JYY2023-14).
文摘Background:Non-small cell lung cancer(NSCLC)is the cancer with the highest incidence and mortality rate worldwide.This study aimed to investigate the predictive value of clinicopathological and radiological characteristics for event-free survival(EFS),major pathological response(MPR),and pathological complete response(pCR)in patients with NSCLC undergoing neoadjuvant chemoimmunotherapy.Methods:A retrospective analysis was performed on the clinical data of 180 patients with NSCLC who received neoadjuvant chemoimmunotherapy between October 2019 and December 2023.The primary endpoint was EFS,and the secondary endpoint was the pathological response rate.Fisher exact test and the nonparametricMann-Whitney U test were used to compare categorical and continuous data between the pCR/MPR and non-pCR/non-MPR groups.The Kaplan-Meier method was used to estimate EFS curves,and Cox regression analysis was performed to compare the differences in EFS between patients with or without pCR or MPR.Results:Sex(p=0.004),smoking history(p=0.025),and clinical stage(p=0.002)were identified as predictors of pCR and MPR.In our study,pCR was observed in 38.12%and MPR in 44.75%of the patients.Through the multivariate logistic regression model,age and pathological response were found to predict the 1-and 2-year EFS rates,demonstrating satisfactory predictive power(area under the curve,0.866 and 0.736,respectively).Patients with pCR or MPR exhibited longer EFS compared with those without pCR or MPR,as determined by Cox analysis.Conclusions:Sex,smoking history,and clinical stage were identified as predictors of pCR and MPR in patients with NSCLC.Survival analysis revealed that age and pathological response were key prognostic factors for EFS.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
文摘Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
基金co-supported by the National Natural Science Foundation of China (No. 81773521)CAMS Innovation Fund for Medical Sciences (No. 2017-I2M-1006, No. 2016-12M-2-004)+4 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2018RC330001)the National Key Projects of Research and Development of China (No. 2018 YFC1315000)China Scholarship Council (No. 201908110180)the Sanming Project of Medicine in Shenzhen (No. SZSM201911015)the Cancer Screening Program in Urban China funded by National Health Commission of People’s Republic of China
文摘Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.
基金supported by the Zhejiang Provincial Nat ural Science Foundation of China(Nos.LZ23C060002 and LZ24H160004)the National Natural Science Foundation of China(Nos.32270746,82203247,82203415,82272637,82204429,and 82073332)+2 种基金the National Key Research and Development Program of China(No.2022YFE0107800)the Medical Interdisciplinary Innovation Program 2024,Zhejiang University School of Medicine,and the Fundamental Research Funds for the Central Universities(No.K20220228)It is add-itionally supported by the National Institute of Health(No.R01-CA200992-03).
文摘Cancer is characterized by abnormal cell proliferation.Cyclins and cyclin-dependent kinases(CDKs)have been recognized as essential regulators of the intricate cell cycle,orchestrating DNA replication and transcription,RNA splicing,and protein synthesis.Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers,rendering cyclins and CDKs attractive therapeutic targets.Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use,fueling the development of CDK-targeted therapies.With this enthusiasm for finding novel CDK-targeting anti-cancer agents,there have also been exciting advances in the field of targeted protein degradation through innovative strategies,such as using proteolysis-targeting chimera,heat shock protein 90(HSP90)-mediated targeting chimera,hydrophobic tag-based protein degradation,and molecular glue.With a focus on the translational potential of cyclin-and CDK-targeting strategies in cancer,this review presents the fundamental roles of cyclins and CDKs in cancer.Furthermore,it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs,detailing the underlying mechanisms of action for each approach.A comprehensive overview of the structure and activity of existing CDK degraders is also provided.By examining the structure‒activity relationships,target profiles,and biological effects of reported cyclin/CDK degraders,this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.
基金supported by the grants from the Beijing Hope Run Special Fund(#LC2012YF44)National Natural Science Foundation of China(No.81402740)+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education(No.20131106120014)The National Health and Family Planning Committee of P.R.China
文摘Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.
基金supported by the National Health and Family Plan Commission of P. R. China
文摘Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan(CNY; 1 CNY = 0.155 USD) based on the2011 value and inflated using the year-specific health care consumer price index for China.Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002(25,111 CNY) to 2011(46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ,39,302 CNY for stage Ⅱ,40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases(P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy(P < 0.05).Drugs contributed to 45.02% of the overall expenditure.Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.
