Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoilei...Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoileitis can complicate established celiac disease or develop in patients de novo.Increased levels of tumor necrosis factor-alpha(TNF-α) in the small intestine of patients with untreated celiac disease are associated with a role in the immune pathogenesis of this disorder.No specific therapy has been shown to change the course of ulcerative jejunoileitis.We report a case of severe ulcerative jejunoileitis previously unresponsive to traditional therapies,including high dose corticosteroids and cyclosporine.The patient had a dramatic resolution of symptoms and a complete normalization of endoscopic findings after anti-TNF-α monoclonal antibody,infliximab(Remicade).展开更多
Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T...Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.展开更多
Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with an...Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.展开更多
[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extra...[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.展开更多
BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.H...BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.展开更多
Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens gener...Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.展开更多
Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal tumors.The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that f...Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal tumors.The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that for esophagus,duodenum and colon cancer(around 2%-4%).Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants[direct oral anticoagulants(DOACs)and warfarin],is thought to be the biggest risk factor for post-ESD bleeding.In fact,the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%,which is higher than that in patients not receiving anticoagulants.However,because clinical guidelines for management of ESD in patients receiving DOACs differ among countries,it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice.Given that the pharmacokinetics(e.g.,plasma DOAC level at both trough and T_(max))and pharmacodynamics(e.g.,anti-factor Xa activity)of DOACs are related to risk of major bleeding,plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.展开更多
Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity...Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.展开更多
Targeted treatment of cancer with monoclonal antibodies increases the benefit for patients. In order to improve the anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research fie...Targeted treatment of cancer with monoclonal antibodies increases the benefit for patients. In order to improve the anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research field. The emergence of various techniques to produce multi-specific recombinant antibody molecules has led to the selection of target combinations in various forms. To date, only a few multi-specific constructs have entered phase III clinical trials, in contrast to classical monoclonal antibodies. Some of the format options are outlined from a technical point of view. We focus on the achievements and prospects of the underlying technologies for generating biand multispecific antibodies.展开更多
Adoptive cellular therapy is rapidly improving immunotherapy in hematologic malignancies and several solid tumors.Remarkable clinical success has been achieved in chimeric antigen receptor(CAR)-T cell therapy which re...Adoptive cellular therapy is rapidly improving immunotherapy in hematologic malignancies and several solid tumors.Remarkable clinical success has been achieved in chimeric antigen receptor(CAR)-T cell therapy which represents a paradigm-shifting strategy for the treatment of hematological malignancies.However,many challenges such as resistance,antigen heterogeneity,poor immune cell infiltration,immunosuppressive microenvironment,metabolic obstructive microenvironment,and T cell exhaustion remain as barriers to broader application especially in solid tumors.Encouragingly,the development of new approaches such as multidimensional omics and biomaterials technologies was aided to overcome these barriers.Here,in this perspective,we focus on the most recent clinical advancements,challenges,and strategies of immune cellular therapy in solid tumor treatment represented by CAR-T cell therapy,to provide new ideas to further overcome the bottleneck of immune cell therapy and anticipate future clinical advances.展开更多
Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has...Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.展开更多
Objective:Inhibition of tumor angiogenesis has become a new targeted tumor therapy.In this study,we established a micellar carrier with a tumor neovascularization-targeting effect modified by the neovascularization-ta...Objective:Inhibition of tumor angiogenesis has become a new targeted tumor therapy.In this study,we established a micellar carrier with a tumor neovascularization-targeting effect modified by the neovascularization-targeting peptide NGR.Methods:The targeted polymer poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PEG-PLGA)modified with Asn–Gly–Arg(NGR)peptide was prepared and characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectrometry.NGR-PEG-PLGA was used to construct curcumin(Cur)-loaded micelles by the solvent evaporation method.The physicochemical properties of the micelles were also investigated.Additionally,we evaluated the antitumor efficacy of the polymer micelles(PM)using in vitro cytology experiments and in vivo animal studies.Results:The particle size of Cur-NGR-PM was 139.70±2.51 nm,and the drug-loading capacity was 14.37±0.06%.In vitro cytological evaluation showed that NGR-modified micelles showed higher cellular uptake through receptor-mediated endocytosis pathways than did unmodified micelles,leading to the apoptosis of tumor cells.Then,in vivo antitumor experiments showed that the modified micelles significantly inhibited tumor growth and were safe.Conclusions:NGR-modified micelles significantly optimized the therapeutic efficacy of Cur.This strategy offers a viable avenue for cancer treatment.展开更多
Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions.Many traditional Chinese medicine and its extracts have been appli...Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions.Many traditional Chinese medicine and its extracts have been applied in clinical tumor treatment.In this paper,the research progress in anti-tumor effects of plant-based traditional Chinese medicine and its extracts,animal-based traditional Chinese medicine and its extracts,and traditional Chinese medicine compound is reviewed.展开更多
Brain tumor significantly impacts the quality of life and changes everything for a patient and their loved ones.Diagnosing a brain tumor usually begins with magnetic resonance imaging(MRI).The manual brain tumor diagn...Brain tumor significantly impacts the quality of life and changes everything for a patient and their loved ones.Diagnosing a brain tumor usually begins with magnetic resonance imaging(MRI).The manual brain tumor diagnosis from the MRO images always requires an expert radiologist.However,this process is time-consuming and costly.Therefore,a computerized technique is required for brain tumor detection in MRI images.Using the MRI,a novel mechanism of the three-dimensional(3D)Kronecker convolution feature pyramid(KCFP)is used to segment brain tumors,resolving the pixel loss and weak processing of multi-scale lesions.A single dilation rate was replaced with the 3D Kronecker convolution,while local feature learning was performed using the 3D Feature Selection(3DFSC).A 3D KCFP was added at the end of 3DFSC to resolve weak processing of multi-scale lesions,yielding efficient segmentation of brain tumors of different sizes.A 3D connected component analysis with a global threshold was used as a post-processing technique.The standard Multimodal Brain Tumor Segmentation 2020 dataset was used for model validation.Our 3D KCFP model performed exceptionally well compared to other benchmark schemes with a dice similarity coefficient of 0.90,0.80,and 0.84 for the whole tumor,enhancing tumor,and tumor core,respectively.Overall,the proposed model was efficient in brain tumor segmentation,which may facilitate medical practitioners for an appropriate diagnosis for future treatment planning.展开更多
[Objectives]To explore the anti-tumor activity of the extracts of petroleum ether,ethyl acetate,n-butanol and aqueous solution from Mahoniae caulis.[Methods]The extracts were extracted with petroleum ether,ethyl aceta...[Objectives]To explore the anti-tumor activity of the extracts of petroleum ether,ethyl acetate,n-butanol and aqueous solution from Mahoniae caulis.[Methods]The extracts were extracted with petroleum ether,ethyl acetate,n-butanol and aqueous solution respectively,and then concentrated.The inhibitory effects of these extracts on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the IC 50 value was calculated.[Results]The four extracts inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol extract had the best anti-tumor activity.The IC 50 values of the n-butanol extract on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.23,0.25 and 0.58 mg/mL,respectively.[Conclusions]The ethanol extract of Mahoniae caulis under petroleum ether,ethyl acetate,n-butanol and aqueous solution had certain anti-tumor effect,and n-butanol extract had the best anti-tumor activity.展开更多
Objective:To investigate the therapeutic effects of matrine on CT26 tumor-bearing mice and its effect on the sterol regulatory element binding protein(SREBP)signaling pathway.Methods:A CT26 tumor-bearing mouse model w...Objective:To investigate the therapeutic effects of matrine on CT26 tumor-bearing mice and its effect on the sterol regulatory element binding protein(SREBP)signaling pathway.Methods:A CT26 tumor-bearing mouse model was established using CT26 cells.Different doses of matrine were orally administered to mice,and the tumor size and weight in each group of mice before and after administration were measured to calculate the tumor inhibition rate of matrine.Subsequently,tumor tissues were subjected to hematoxylin and eosin(HE)staining to observe morphological changes in tumor tissue,and quantitative polymerase chain reaction(qPCR)was performed to detect the expression of the genes of the lipid metabolism-related enzymes sterol regulatory element binding transcription factor 1(Srebf1),ATP citrate lyase(Acly),acetyl-Coenzyme A carboxylase alpha(Acc),and fatty acid synthase(Fasn)in tumor tissues before and after matrine intervention.Results:Compared to those in the model group,tumor-bearing mice in both the low and high-dose matrine groups showed significantly reduced tumor weights.HE staining showed that matrine significantly inhibited tumor cell proliferation in both the low and high-dose groups.The qPCR results showed that,compared with the model group,the expression levels of the genes of lipid metabolism-related enzymes Srebf1,Acly,Acc,and Fasn in tumor tissues were significantly downregulated in both the low and high-dose matrine groups.Conclusion:Matrine modulates the lipid metabolism pathway,affects tumor cell lipid metabolism,and exerts antitumor effects.展开更多
BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer...BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.展开更多
BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making i...BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.展开更多
文摘Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoileitis can complicate established celiac disease or develop in patients de novo.Increased levels of tumor necrosis factor-alpha(TNF-α) in the small intestine of patients with untreated celiac disease are associated with a role in the immune pathogenesis of this disorder.No specific therapy has been shown to change the course of ulcerative jejunoileitis.We report a case of severe ulcerative jejunoileitis previously unresponsive to traditional therapies,including high dose corticosteroids and cyclosporine.The patient had a dramatic resolution of symptoms and a complete normalization of endoscopic findings after anti-TNF-α monoclonal antibody,infliximab(Remicade).
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.
基金supported by National Natural Science Foundation of China(No.82003775)Talent Project established by Chinese Pharmaceutical Association Hospital Phamacy department.(No.CPA-Z05-ZC-2023-003)+2 种基金Outstanding Young Scholars Foundation of Harbin Medical University Cancer Hospital(No.JCQN2021-04)Heilongjiang Province postdoctoral research fund(No.LBH-Q20050)Special fund for clinical and basic research of medical research development fund(No.YXKY-WS013G).
文摘Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.
基金Natural Science Foundation of Chongqing,China,No.cstc2021jcyj-msxmX0501Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2022QNXM074.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.
基金Supported by Guangxi Key R&D Project(GuiKeAB18221095)Baise Scientific Research and Technology Development Plan of Baise City(BaiKe20211810)+1 种基金Open Project of Scientific Research in Guangxi Key Laboratory of Molecular Pathology of Hepatobiliary Diseases(GXZDSYS-005)Research Project of High-level Talents in Youjiang Medical University for Nationalities(01002018079).
文摘[Objectives]The anti-tumor activity of fractions from Buddleja officinalis Maxim.by petroleum ether,ethyl acetate,n-butanol and water solvent was studied.[Methods]The ethanol extract from B.officinalis Maxim.was extracted and then concentrated with petroleum ether,ethyl acetate,n-butanol and water,respectively,and the extracts were obtained.The inhibitory effects of the four different fractions on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the median inhibitory concentration(IC 50 value)was calculated.[Results]The four fractions inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol fraction had the best anti-tumor activity.The IC 50 values of the n-butanol fraction on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.08,1.58 and 0.12 mg/mL,respectively.[Conclusions]Petroleum ether,ethyl acetate,n-butanol and water fractions from the ethanol extract of B.officinalis Maxim.had certain anti-tumor effects,and the n-butanol fraction had the best anti-tumor activity.
基金Supported by the grants from the Asan Institute for Life Sciences,Asan Medical Center,Seoul,Korea,No.2019IF0593 and No.2020IP0039.
文摘BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.
基金This research was supported by the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(No.JNU1AF-CFTP-2022-a01223)Natural Science Foundation of Guangdong Province(2019A1515011763,2020A1515110639,2021A1515010994,2022A1515011695)Guangzhou Science and Technology Plan City-School Joint Funding Project(202201020084,202201020065).
文摘Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.
基金Supported by the Grant-in-Aid for Scientific Research in Japan,No.21K07949.
文摘Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD)for early-stage gastrointestinal tumors.The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%)than that for esophagus,duodenum and colon cancer(around 2%-4%).Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants[direct oral anticoagulants(DOACs)and warfarin],is thought to be the biggest risk factor for post-ESD bleeding.In fact,the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%,which is higher than that in patients not receiving anticoagulants.However,because clinical guidelines for management of ESD in patients receiving DOACs differ among countries,it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice.Given that the pharmacokinetics(e.g.,plasma DOAC level at both trough and T_(max))and pharmacodynamics(e.g.,anti-factor Xa activity)of DOACs are related to risk of major bleeding,plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81974500,81773678)the CAMS Innovation Fund for Medical Sciences(Grant No.:2022-I2M-2-001).
文摘Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
文摘Targeted treatment of cancer with monoclonal antibodies increases the benefit for patients. In order to improve the anti-tumor activity of monoclonal antibodies, multi-specific antibodies have entered the research field. The emergence of various techniques to produce multi-specific recombinant antibody molecules has led to the selection of target combinations in various forms. To date, only a few multi-specific constructs have entered phase III clinical trials, in contrast to classical monoclonal antibodies. Some of the format options are outlined from a technical point of view. We focus on the achievements and prospects of the underlying technologies for generating biand multispecific antibodies.
基金supported by grants from the National Natural Science Foundation of China(No.82203548)National Key Research and Development Program(No.2022YFE0141000)+1 种基金Henan Province Medical Science and Technology Research Project(No.LHGJ20220385)the Central Government of Henan Province guides local science and technology development fund projects(No.Z20221343036)。
文摘Adoptive cellular therapy is rapidly improving immunotherapy in hematologic malignancies and several solid tumors.Remarkable clinical success has been achieved in chimeric antigen receptor(CAR)-T cell therapy which represents a paradigm-shifting strategy for the treatment of hematological malignancies.However,many challenges such as resistance,antigen heterogeneity,poor immune cell infiltration,immunosuppressive microenvironment,metabolic obstructive microenvironment,and T cell exhaustion remain as barriers to broader application especially in solid tumors.Encouragingly,the development of new approaches such as multidimensional omics and biomaterials technologies was aided to overcome these barriers.Here,in this perspective,we focus on the most recent clinical advancements,challenges,and strategies of immune cellular therapy in solid tumor treatment represented by CAR-T cell therapy,to provide new ideas to further overcome the bottleneck of immune cell therapy and anticipate future clinical advances.
基金supported by the National Key Research and Development Plan,China(Grant No.:2022YFC3500202)the Natural Science Foundation of China(Grant Nos.:82172558,and 82205024)+4 种基金the Scientific and Technological Innovation Action Plan of Natural Science Foundation Project of Shanghai,China(Grant No.:22ZR1447400)the Scientific and Technological Innovation Action Plan,China(Grant No.:22ZR1447400)the Fundamental Research Funds for the Central Universities,China(Grant Nos.:020814380179,020814380174)the Distinguished Young Scholars of Nanjing,China(Grant No.:JQX20008)the School of Life Science(NJU)-Sipimo Joint Funds and Mountain Climbing Talents Project of Nanjing University,China(Grant No.:2015018).
文摘Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.
基金supported by Scientific Research Project of Tianjin Municipal Education Commission (No.2019KJ080).
文摘Objective:Inhibition of tumor angiogenesis has become a new targeted tumor therapy.In this study,we established a micellar carrier with a tumor neovascularization-targeting effect modified by the neovascularization-targeting peptide NGR.Methods:The targeted polymer poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PEG-PLGA)modified with Asn–Gly–Arg(NGR)peptide was prepared and characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectrometry.NGR-PEG-PLGA was used to construct curcumin(Cur)-loaded micelles by the solvent evaporation method.The physicochemical properties of the micelles were also investigated.Additionally,we evaluated the antitumor efficacy of the polymer micelles(PM)using in vitro cytology experiments and in vivo animal studies.Results:The particle size of Cur-NGR-PM was 139.70±2.51 nm,and the drug-loading capacity was 14.37±0.06%.In vitro cytological evaluation showed that NGR-modified micelles showed higher cellular uptake through receptor-mediated endocytosis pathways than did unmodified micelles,leading to the apoptosis of tumor cells.Then,in vivo antitumor experiments showed that the modified micelles significantly inhibited tumor growth and were safe.Conclusions:NGR-modified micelles significantly optimized the therapeutic efficacy of Cur.This strategy offers a viable avenue for cancer treatment.
基金Supported by Innovation and Entrepreneurship Training Program Project of College Student in 2021(202110600016)Key R&D Projects of Guangxi Science and Technology Department(GUIKE AB21196057)+2 种基金Guangxi Traditional Chinese Medicine Multidisciplinary Cross Innovation Team Project(GZKJ2309)National Administration of Traditional Chinese Medicine"12 th Five-Year Plan"Key Discipline of Traditional Chinese Medicine Ethnology(Zhuang Pharmacy)the"High-level Talent Cultivation and Innovation Team"Project of Guangxi University of Chinese Medicine(2022A008).
文摘Traditional Chinese medicine and its extracts have received widespread attention due to their significant anti-tumor effects and low adverse reactions.Many traditional Chinese medicine and its extracts have been applied in clinical tumor treatment.In this paper,the research progress in anti-tumor effects of plant-based traditional Chinese medicine and its extracts,animal-based traditional Chinese medicine and its extracts,and traditional Chinese medicine compound is reviewed.
基金supported by“Human Resources Program in Energy Technology”of the Korea Institute of Energy Technology Evaluation and Planning(KETEP),granted financial resources from theMinistry of Trade,Industry&Energy,Republic ofKorea(No.20204010600090).In addition,it was funded from the National Center of Artificial Intelligence(NCAI),Higher Education Commission,Pakistan,Grant/Award Number:Grant 2(1064).
文摘Brain tumor significantly impacts the quality of life and changes everything for a patient and their loved ones.Diagnosing a brain tumor usually begins with magnetic resonance imaging(MRI).The manual brain tumor diagnosis from the MRO images always requires an expert radiologist.However,this process is time-consuming and costly.Therefore,a computerized technique is required for brain tumor detection in MRI images.Using the MRI,a novel mechanism of the three-dimensional(3D)Kronecker convolution feature pyramid(KCFP)is used to segment brain tumors,resolving the pixel loss and weak processing of multi-scale lesions.A single dilation rate was replaced with the 3D Kronecker convolution,while local feature learning was performed using the 3D Feature Selection(3DFSC).A 3D KCFP was added at the end of 3DFSC to resolve weak processing of multi-scale lesions,yielding efficient segmentation of brain tumors of different sizes.A 3D connected component analysis with a global threshold was used as a post-processing technique.The standard Multimodal Brain Tumor Segmentation 2020 dataset was used for model validation.Our 3D KCFP model performed exceptionally well compared to other benchmark schemes with a dice similarity coefficient of 0.90,0.80,and 0.84 for the whole tumor,enhancing tumor,and tumor core,respectively.Overall,the proposed model was efficient in brain tumor segmentation,which may facilitate medical practitioners for an appropriate diagnosis for future treatment planning.
基金Supported by Guangxi Key Research and Development Plan Project(Gui Ke AB18221095)2023 Innovation Project of Youjiang Medical University for Nationalities Graduate Education(YXCXJH2023009)Scientific Research Project of High-level Talents of Youjiang Medical University for Nationalities(01002018079).
文摘[Objectives]To explore the anti-tumor activity of the extracts of petroleum ether,ethyl acetate,n-butanol and aqueous solution from Mahoniae caulis.[Methods]The extracts were extracted with petroleum ether,ethyl acetate,n-butanol and aqueous solution respectively,and then concentrated.The inhibitory effects of these extracts on the growth of three tumor cell lines in vitro were detected by CCK-8 method,and the IC 50 value was calculated.[Results]The four extracts inhibited the growth of the three tumor cell lines in vitro,among which the n-butanol extract had the best anti-tumor activity.The IC 50 values of the n-butanol extract on human gastric cancer(SGC-7901),human breast cancer(MCF-7)and human liver cancer(BEL-7404)cell lines were 0.23,0.25 and 0.58 mg/mL,respectively.[Conclusions]The ethanol extract of Mahoniae caulis under petroleum ether,ethyl acetate,n-butanol and aqueous solution had certain anti-tumor effect,and n-butanol extract had the best anti-tumor activity.
基金This work was supported by grants from the Natural Science Foundation of Fujian province(No.2020J011181).
文摘Objective:To investigate the therapeutic effects of matrine on CT26 tumor-bearing mice and its effect on the sterol regulatory element binding protein(SREBP)signaling pathway.Methods:A CT26 tumor-bearing mouse model was established using CT26 cells.Different doses of matrine were orally administered to mice,and the tumor size and weight in each group of mice before and after administration were measured to calculate the tumor inhibition rate of matrine.Subsequently,tumor tissues were subjected to hematoxylin and eosin(HE)staining to observe morphological changes in tumor tissue,and quantitative polymerase chain reaction(qPCR)was performed to detect the expression of the genes of the lipid metabolism-related enzymes sterol regulatory element binding transcription factor 1(Srebf1),ATP citrate lyase(Acly),acetyl-Coenzyme A carboxylase alpha(Acc),and fatty acid synthase(Fasn)in tumor tissues before and after matrine intervention.Results:Compared to those in the model group,tumor-bearing mice in both the low and high-dose matrine groups showed significantly reduced tumor weights.HE staining showed that matrine significantly inhibited tumor cell proliferation in both the low and high-dose groups.The qPCR results showed that,compared with the model group,the expression levels of the genes of lipid metabolism-related enzymes Srebf1,Acly,Acc,and Fasn in tumor tissues were significantly downregulated in both the low and high-dose matrine groups.Conclusion:Matrine modulates the lipid metabolism pathway,affects tumor cell lipid metabolism,and exerts antitumor effects.
基金Supported by the National Natural Science Funds of China,No.81974448Guangdong Medical Research Foundation,No.B2019126Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324135005013.
文摘BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.
基金National Key R&D Program of China,No.2022YFF1203300.
文摘BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.
