Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving resear...Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.展开更多
Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-...Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.展开更多
The recent study by Chen et al highlights the paradoxical role of the histone deacetylase inhibitor(HDACi)Trichostatin A(TSA)in esophageal squamous cell carcinoma(ESCC),revealing its promotion of epithelial-mesenchyma...The recent study by Chen et al highlights the paradoxical role of the histone deacetylase inhibitor(HDACi)Trichostatin A(TSA)in esophageal squamous cell carcinoma(ESCC),revealing its promotion of epithelial-mesenchymal transition(EMT)and tumor migration via the BRD4/c-Myc/endoplasmic reticulum(ER)-stress pathway.While HDACis are traditionally considered anti-tumor agents,these findings underscore the need for alternative therapeutic strategies.In this commentary,we discuss the potential of traditional medicine-derived com-pounds,such as berberine,curcumin,and resveratrol,in modulating epigenetic regulators and mitigating TSA-induced oncogenic pathways.Additionally,we emphasize the prognostic significance of histone acetylation markers,particularly acetylated histone H3,which could serve as predictive biomarkers for ESCC progression and HDACi therapy responsiveness.Further,we explore the role of ER stress in tumor aggressiveness and suggest that compounds like quercetin and baicalein,known for their ER stress-alleviating properties,warrant further inves-tigation.Integrating traditional medicine-based interventions with biomarker-driven targeted therapy may enhance ESCC treatment efficacy while minimizing HDACi-associated risks.We advocate for future research focusing on the inter-play between epigenetic modulation,natural compounds,and biomarker identification to refine personalized therapeutic strategies for ESCC.展开更多
One of the most prevalent malignant tumors worldwide,stomach cancer still has a high incidence and fatality rate in China,and the number of young people developing early-onset gastric cancer is steadily increasing.The...One of the most prevalent malignant tumors worldwide,stomach cancer still has a high incidence and fatality rate in China,and the number of young people developing early-onset gastric cancer is steadily increasing.The 5-year survival rate of stomach cancer is typically 30%–35%,the prognosis is bad,the patients’quality of life is low,and the progression of advanced gastric cancer cannot be effectively managed despite the use of surgical surgery,chemotherapy,and other medicines.We urgently need molecular biomarkers with high specificity and sensitivity to increase the early gastric cancer detection rate,extend patient survival,and improve patient quality of life.The initial diagnosis of gastric cancer primarily depends on gastroscopy and biopsy,and invasive procedures cause significant discomfort to patients.Similar to this,treating advanced and metastatic stomach cancer is a pressing issue that requires attention.More and more immune checkpoint molecules have been discovered,and corresponding inhibitors are gradually being applied to clinical diagnosis and treatment.Recently,some non-coding RNAs have begun to be used as new targets for the treatment of gastric cancer.Some non-coding RNAs are highly present in the serum or urine of gastric cancer patients and can be used as diagnostic markers or prognostic indicators.Many clinical trials targeting non-coding RNAs have also shown good therapeutic effects.In general,targeting non-coding RNAs has shown good therapeutic effects.The biomarkers for gastric cancer detection and treatment are reviewed in this article,focusing on the new non-coding RNAs used in diagnosis,prognosis,and treatment.Patients with stomach cancer should have access to more precise and efficient diagnosis and treatment choices as a result of ongoing technological advancements and thorough research.展开更多
Objective:Microscopically positive resection margins(R1)in gastric cancer have been associated with poor outcomes,but evidence regarding its prognostic significance across different stages remains inconsistent.This st...Objective:Microscopically positive resection margins(R1)in gastric cancer have been associated with poor outcomes,but evidence regarding its prognostic significance across different stages remains inconsistent.This study investigated the impact of R1 resection on survival outcomes and evaluated the prognostic significance of detailed pathological characteristics of margin involvement.Methods:This retrospective study analyzed 10,165 patients who underwent curative-intent gastrectomy for gastric cancer between 2007 and 2021.Propensity score matching was performed at a 1:3 ratio between R1(n=45)and R0(n=130)cases.For R1 margins,detailed pathological assessment included involvement length,proportion,depth,and histological features.Survival outcomes were evaluated across all stages,and the impact of subsequent resection was analyzed.Results:After propensity score matching,R1 resection showed significantly lower 5-year overall survival rates compared to R0 resection across all stages(stageⅠ:60.0%vs.90.9%,P=0.008;stageⅡ:40.0%vs.83.3%,P=0.001;stageⅢ:20.0%vs.35.4%,P<0.001).In R1 cases,tumor involvement length≤1 cm(P<0.001),proportion≤10%(P=0.012),and mucosal-only involvement(P=0.004)were associated with better survival.Patients who underwent subsequent resection to achieve R0 status showed better survival than those with persistent R1 resection(53.8%vs.26.7%,P<0.001)and comparable survival to matched R0 cases(53.8%vs.46.9%,P=0.320).Conclusions:R1 resection significantly impairs survival across all stages of gastric cancer,with the extent and depth of microscopic involvement influencing prognosis.When R1 status is discovered postoperatively,subsequent resection should be considered to improve survival outcomes.展开更多
Objectives:Gastric cancer(GC)is often associated with high invasiveness,epithelial-mesenchymal transition(EMT),and resistance to 5-fluorouracil(5-FU),highlighting the need for novel therapeutic targets.This study expl...Objectives:Gastric cancer(GC)is often associated with high invasiveness,epithelial-mesenchymal transition(EMT),and resistance to 5-fluorouracil(5-FU),highlighting the need for novel therapeutic targets.This study explored whether diallyl disulfide(DADS)upregulates retinoic acid-related orphan receptor alpha(RORα)to weaken the protein kinase C alpha(PKCα)/RORα-mediated RORα/β-catenin pathway,thereby inhibiting GC cell invasion,epithelial-mesenchymal transition(EMT),and enhancing 5-FU sensitivity.Methods:Human GC cell lines MGC-803 and SGC7901 were treated with DADS,RORαagonist SR1078/antagonist T0901317,and PKCαagonist TPA/antagonist GO6976.Cell proliferation(MTT),migration(scratch assay),invasion(Transwell),protein expression(Western blot),protein interactions(coimmunoprecipitation),and localization(immunofluorescence)were detected.Apoptosis and 5-FU sensitivity-related proteins were examined.Experiments were triplicated;statistics used t-test/ANOVA(p<0.05).Results:DADS/SR1078 inhibited GC cell proliferation/migration/invasion,upregulated RORα/E-cadherin,downregulated nuclearβ-catenin/TGF-β1/Rac1/Vimentin,and weakened EMT(reversed by T0901317).DADS/TPA upregulated RORα/p-RORα/PKCα/p-PKCα,promoted PKCα-RORαbinding,and downregulated RORα/β-catenin target genes(counteracted by GO6976).DADS upregulated caspase-3 and downregulated Bcl-2/P-gp/XIAP via RORα,promoting apoptosis and 5-FU sensitivity.Conclusion:DADS inhibits GC progression and enhances 5-FU sensitivity by PKCα/RORα-mediated downregulation of RORα/β-catenin signaling,paralleling SR1078/TPA effects.It may act as a novel RORαagonist for GC therapy.展开更多
BACKGROUND Radiotherapy is widely employed in colorectal cancer(CRC)treatment,but the occurrence of radioresistance severely limits the clinical benefit to patients and significantly contributes to treatment failure a...BACKGROUND Radiotherapy is widely employed in colorectal cancer(CRC)treatment,but the occurrence of radioresistance severely limits the clinical benefit to patients and significantly contributes to treatment failure and recurrent metastasis.AIM To explore the role and underlying mechanism of the lncRNA FTX in radiotherapy resistance in CRC.METHODS LncRNA FTX expression in colorectal parent cells(HT29 and HCT116)and radioresistant cells(HT29R and HCT116R)was determined by real-time quantitative PCR,and the viability of HT29R-shFTX and HCT116R-shFTX cells under ionizing radiation was evaluated using the cell counting kit-8 assay and colony formation experiment.The levels of glutathione and reactive oxygen species in cells after irradiation were determined,and the association between ferroptosis and lncRNA FTX expression in cancer cells was tested.A dual-luciferase assay was used to validate gene interactions.A xenotransplantation mouse model was established to explore the effects of FTX on the CRC tumor radiosensitivity in vivo.RESULTS FTX was upregulated in radioresistant CRC cells,and FTX knockdown inhibited cell survival and increased cell ferroptotic death in response to ionizing radiation.Moreover,lncRNA FTX restricted the SLC7A11 expression by sponging with miR-625-5p,and inhibition of the lncRNA FTX or SLC7A11 significantly increased cellular oxidant levels and DNA damage to ionizing radiation in cancer cells.However,SLC7A11 overexpression reversed the effects of decreased FTX levels on ferroptosis and high oxidation levels in cancer cells exposed to ionizing radiation.CONCLUSION Inhibition of the lncRNA FTX/miR-625-5p/SLC7A11 axis can induce ferroptosis and disturb intracellular redox balance,further sensitizing CRC cells to ionizing radiation,suggesting its potential as a therapeutic target for improving CRC response to radiation therapy.展开更多
1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effect...1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effects.Over the past decade,a promising alternative has emerged:cancer immunotherapy,which leverages the body's immune system to identify and eradicate cancer cells[1].展开更多
Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified n...Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.展开更多
AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent ...AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995.Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS:The rate of lymph node metastasis in cases where the depth of invasion was<500 μm,500-2 000 μm,or >2 000 μm was 9%(2/23),19%(7136),and 33%(15/46), respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren's classification,and lymphatic invasion.In multivariate analysis, tumor size(>4 cm vs≤2 cm,odds ratio=4.80, P=0.04)and depth of invasion(>2 000 μm vs ≤500 μm, odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis.Combining the depth and size in cases where the depth of invasion was less than 500 μm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2 000 μm. CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 μm in depth.展开更多
AIM： To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. METHODS： We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A...AIM： To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. METHODS： We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR （MS-PCR）, as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues. RESULTS： Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MSPCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%, respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively. CONCLUSION： The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.展开更多
OBJECTIVE： To study the anticancer mechanism of polyphyllin I （PPI）, a Traditional Chinese Medicine, on the ovarian cancer cell line HO-8910PM in vitro. METHODS： Transwell chamber invasive assays were used to inve...OBJECTIVE： To study the anticancer mechanism of polyphyllin I （PPI）, a Traditional Chinese Medicine, on the ovarian cancer cell line HO-8910PM in vitro. METHODS： Transwell chamber invasive assays were used to investigate the inhibitory capacity of PPI on HO-8910PM metastasis. Gene expression profiling chips was used to screen differentially ex- pressed genes between experiment group and con- trol group. Reverse transcription PCR and Western blotting were used to determine mRNA and pro- tein levels. RESULTS： With increasing PPI concentration, the metastatic capacity of cells decreased, with signifi- cance differences between the experimental and control groups （P〈0.01） as well as between two concentration groups. Gene expression profiling identified 123 differentially expressed genes, of which 70 were downregulated and 53 were upregu- lated. The genes were involved in multiple signal transduction pathways, including apoptosis, prolif- eration and metastasis. Real-time PCR （RT-PCR） showed that differential genes PIK3C2B, Caspase 9and WntSA were downregulated with increasing PPI, showing an evident dose-effect relationship. The c-Jun was an exception. As the PPI dosage in- creased and the exposure time was extended, c-Jun relative expression showed an upward trend. There were significant differences between the ex- periment and control （P〈0.05）. Western blot analy- ses showed that PPI treatment decreased levels of Caspase 9, WntSA and PIK3C2B and increased acti- vated Caspase 9,c-Jun and p-c-Jun expression levels. CONCLUSION＂ PPI has strong antitumor and anti transfer activity. It can activate c-Jun expression and the JNK signaling pathway, elicit cell apoptosis via the mitochondrial-mediated Caspase activation pathway, and finally inhibit tumor growth and mi- gration in vitro. The downregulation of PIK3C2B and Wnt5A jointly inhibit the proliferation and me- tastasis of HO-8910PM. PPI may be a novel treat- ment for ovarian cancer.展开更多
Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethyle...Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.展开更多
There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer.A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protoco...There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer.A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)],peritonectomy,hyperthermic intraperitoneal chemoperfusion (HIPEC) and early postoperative intraperitoneal chemotherapy has been developed.In this article,we assess the indications,safety and eff icacy of this treatment,review the relevant studies and introduce our experiences.The aims of NIPS are stage reduction,the eradication of peritoneal free cancer cells,and an increased incidence of complete cytoreduction (CC-0) for PC.A complete response after NIPS was ob-tained in 15 (50%) out of 30 patients with PC.Thus,a signif icantly high incidence of CC-0 can be obtained in patients with a peritoneal cancer index (PCI) ≤ 6.Using a multivariate analysis to examine the survival benef it,CC-0 and NIPS are identified as significant indicators of a good outcome.However,the high morbidity and mortality rates associated with peritonectomy and perioperative chemotherapy make stringent patient selection important.The best indications for multidisciplinary therapy are localized PC (PCI≤6) from resectable gastric cancer that can be completely removed during a peritonectomy.NIPS and complete cytoreduction are essential treatment modalities for improving the survival of patients with PC from gastric cancer.展开更多
Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic opti...Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA(ct DNA) could provide diagnostic information. In this review, we provide an overview of the current status of bloodbased tests for diagnosis of pancreatic cancer and the potential utility of ct DNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ct DNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.展开更多
Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus(Pim)family proteins that exhibit serine/threonine kinase activity.Similar to the other Pim kinases(Pim-1 and Pim-2),Pim-3 is involve...Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus(Pim)family proteins that exhibit serine/threonine kinase activity.Similar to the other Pim kinases(Pim-1 and Pim-2),Pim-3 is involved in many cellular processes,including cell proliferation,survival,and protein synthesis.Although Pim-3is expressed in normal vital organs,it is overexpressed particularly in tumor tissues of endoderm-derived organs,including the liver,pancreas,and colon.Silencing of Pim-3 expression can retard in vitro cell proliferation of hepatocellular,pancreatic,and colon carcinoma cell lines by promoting cell apoptosis.Pim-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack,and therefore,Pim-3 can exhibit its kinase activity once it is expressed.Pim-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors(e.g.,Ets-1)and post-translational modifiers(e.g.,translationally-controlled tumor protein),respectively.Pim-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse model.Furthermore,a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice,without inducing any major adverse effects.Thus,Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer.展开更多
Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast...Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.展开更多
Object: The authors studied the influence of CO2 pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. Method: They set up a simulation o...Object: The authors studied the influence of CO2 pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. Method: They set up a simulation of pneumoperitoneum under different CO2 pressure, and then measured the variation of intracellular pH (pHi) at different time and the activity of protein kinase C (PKC) and protein phosphatase 2a (PP2a) at the end of the pneumoperitoneum. After 1 week, the concentration of cancer cells in the culture medium was calculated. Result: When the pressure of CO2 pneumoperitoneum was 0, 10, 20, 30 mmHg respectively, the average pHi was 7.273, 7.075, 6.783, 6.693 at the end of the pneumoperitoneum; PKC activity was 159.4, 168.5,178.0, 181.6 nmol/(g.min) and PP2a was 4158.3, 4066.9, 3984.0, 3878.5 nmol/(g.min) respectively. After 1 week, the cancer cells concentration was 2.15×105, 2.03×105, 2.20×105, 2.18×105 L-1. Conclusion: CO2 pneumoperitoneum could promote acidosis in cancer cells, inducing the activation of protein kinase C and deactivation of protein phosphatase 2a, but it could not accelerate the mitosis rate of the cancer cells.展开更多
Colorectal cancers (CRCs) with a high level of microsatellite instability (MSI-H) are clinicopathologically distinct tumors characterized by predominance in females, proximal colonic localization, poor differentiation...Colorectal cancers (CRCs) with a high level of microsatellite instability (MSI-H) are clinicopathologically distinct tumors characterized by predominance in females, proximal colonic localization, poor differentiation, mucinous histology, tumor-infiltrating lymphocytes, a Crohn’s-like lymphoid reaction and a favorable prognosis. In terms of their molecular features, MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations, including DNA mismatch repair deficiency, target microsatellite mutations, BRAF mutations, a CpG island methylator phenotype-high (CIMP-H) status, and a low level of genomic hypomethylation. The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences; for example, in Eastern Asian countries, relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries. Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy, there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs. Here, we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs, as well as several putative prognostic or predictive molecular markers, including HSP110 expression, beta2-microglobulin mutations, myosin 1a expression, CDX2/CK20 expression, SMAD4 expression, CIMP status and LINE-1 methylation levels.展开更多
AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from ga...AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.展开更多
基金supported by Key Research and Development Plan of Hunan Province(2024DK2006)the Fundamental Research Funds for the Central Universities of Central South University(1053320221769)+2 种基金Hunan Provincial Respiratory Disease Rehabilitation and Nursing Engineering Research Center Innovation Capacity Building Project(No.202012)the Zhangjiajie Science and Technology Development Key Special Project(No.202304)the National Key Clinical Specialty Major Scientific Research Project(No.20230382).
文摘Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.
基金funded by the Natural Science Foundation of Guangdong Province(grant number 2022A1515012315)Guangdong Medical Science and Technology Research Fund Project(grant number A2023185)+2 种基金the Discipline Construction Project of Guangdong Medical University(grant number 4SG22005G)the 2023 Provincial Basic and Applied Basic Research Fund Enterprise Joint Fund Project(grant number 2023A1515220149)Southern Medical University Shunde Hospital 2023 Research Initiation Programme Project(SRSP2023016).
文摘Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors,but the currently used immune checkpoint inhibitors targeting programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),and cytotoxic T-lymphocyte antigen-4(CTLA-4)show limited clinical efficacy in many breast cancers.B7H3 has been widely reported as an immunosuppressive molecule,but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program(TCGA)and the Gene Expression Omnibus(GEO)databases.MicroRNAs were selected using the TarBase,miRTarBase,and miRBase databases.The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays,which identified the specific action sites of interaction.The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR(qPCR).In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis.Additionally,the regulatory impact of hsa-miR-214-3p on B7H3 was examined.Enzyme-linked immunosorbent assays(ELISA)and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells(PBMCs)on immune cells and associated cytokines.Results:In breast cancer tissues,the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p,as well as with the regulatory effects on breast cancercell behavior.Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3.Importantly,our research identified,for the first time,two binding sites for hsa-miR-214-3p on the 3’UTR of B7H3,both of which exert similar effects independently.Co-culture experiments revealed that hsamiR-214-3p obstructs the suppressive function of B7H3 on CD8^(+)T cells and natural killer cells.Conclusions:This study confirms the existence of two hsa-miR-214-3p binding sites on the 3’UTR of B7H3,reinforcing the role of hsamiR-214-3p as a regulatory factor for B7H3.In breast cancer,hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3.These findings suggest new potential targets for the clinical treatment of breast cancer.
文摘The recent study by Chen et al highlights the paradoxical role of the histone deacetylase inhibitor(HDACi)Trichostatin A(TSA)in esophageal squamous cell carcinoma(ESCC),revealing its promotion of epithelial-mesenchymal transition(EMT)and tumor migration via the BRD4/c-Myc/endoplasmic reticulum(ER)-stress pathway.While HDACis are traditionally considered anti-tumor agents,these findings underscore the need for alternative therapeutic strategies.In this commentary,we discuss the potential of traditional medicine-derived com-pounds,such as berberine,curcumin,and resveratrol,in modulating epigenetic regulators and mitigating TSA-induced oncogenic pathways.Additionally,we emphasize the prognostic significance of histone acetylation markers,particularly acetylated histone H3,which could serve as predictive biomarkers for ESCC progression and HDACi therapy responsiveness.Further,we explore the role of ER stress in tumor aggressiveness and suggest that compounds like quercetin and baicalein,known for their ER stress-alleviating properties,warrant further inves-tigation.Integrating traditional medicine-based interventions with biomarker-driven targeted therapy may enhance ESCC treatment efficacy while minimizing HDACi-associated risks.We advocate for future research focusing on the inter-play between epigenetic modulation,natural compounds,and biomarker identification to refine personalized therapeutic strategies for ESCC.
基金funded by the National Key Research and Development Project,grant number 2021YFE0192100Natural Science Foundation of Hunan Province,grant numbers 2021JJ30694,2023JJ30529+4 种基金Innovation and Entrepreneurship Training Program for College Students in Hunan Province,grant number S202210555254Key Projects of Hunan Provincial Education Department,grant number 21A0285Natural Science Foundation of Hunan Provincial and Municipal Co-Funding,grant number 2022JJ50029Key Projects of Shaoyang Science and Technology Bureau,grant number 2021GZ031Innovation and Entrepreneurship Training Program for College Students of the University of South China,grant numbers D202405212006326156,D202405210948392932,D202405211329047648,D202405221955420827.
文摘One of the most prevalent malignant tumors worldwide,stomach cancer still has a high incidence and fatality rate in China,and the number of young people developing early-onset gastric cancer is steadily increasing.The 5-year survival rate of stomach cancer is typically 30%–35%,the prognosis is bad,the patients’quality of life is low,and the progression of advanced gastric cancer cannot be effectively managed despite the use of surgical surgery,chemotherapy,and other medicines.We urgently need molecular biomarkers with high specificity and sensitivity to increase the early gastric cancer detection rate,extend patient survival,and improve patient quality of life.The initial diagnosis of gastric cancer primarily depends on gastroscopy and biopsy,and invasive procedures cause significant discomfort to patients.Similar to this,treating advanced and metastatic stomach cancer is a pressing issue that requires attention.More and more immune checkpoint molecules have been discovered,and corresponding inhibitors are gradually being applied to clinical diagnosis and treatment.Recently,some non-coding RNAs have begun to be used as new targets for the treatment of gastric cancer.Some non-coding RNAs are highly present in the serum or urine of gastric cancer patients and can be used as diagnostic markers or prognostic indicators.Many clinical trials targeting non-coding RNAs have also shown good therapeutic effects.In general,targeting non-coding RNAs has shown good therapeutic effects.The biomarkers for gastric cancer detection and treatment are reviewed in this article,focusing on the new non-coding RNAs used in diagnosis,prognosis,and treatment.Patients with stomach cancer should have access to more precise and efficient diagnosis and treatment choices as a result of ongoing technological advancements and thorough research.
文摘Objective:Microscopically positive resection margins(R1)in gastric cancer have been associated with poor outcomes,but evidence regarding its prognostic significance across different stages remains inconsistent.This study investigated the impact of R1 resection on survival outcomes and evaluated the prognostic significance of detailed pathological characteristics of margin involvement.Methods:This retrospective study analyzed 10,165 patients who underwent curative-intent gastrectomy for gastric cancer between 2007 and 2021.Propensity score matching was performed at a 1:3 ratio between R1(n=45)and R0(n=130)cases.For R1 margins,detailed pathological assessment included involvement length,proportion,depth,and histological features.Survival outcomes were evaluated across all stages,and the impact of subsequent resection was analyzed.Results:After propensity score matching,R1 resection showed significantly lower 5-year overall survival rates compared to R0 resection across all stages(stageⅠ:60.0%vs.90.9%,P=0.008;stageⅡ:40.0%vs.83.3%,P=0.001;stageⅢ:20.0%vs.35.4%,P<0.001).In R1 cases,tumor involvement length≤1 cm(P<0.001),proportion≤10%(P=0.012),and mucosal-only involvement(P=0.004)were associated with better survival.Patients who underwent subsequent resection to achieve R0 status showed better survival than those with persistent R1 resection(53.8%vs.26.7%,P<0.001)and comparable survival to matched R0 cases(53.8%vs.46.9%,P=0.320).Conclusions:R1 resection significantly impairs survival across all stages of gastric cancer,with the extent and depth of microscopic involvement influencing prognosis.When R1 status is discovered postoperatively,subsequent resection should be considered to improve survival outcomes.
基金supported by The National Natural Scientific Foundation of China(No.81973532,No.81374013)The Natural Science Foundation of Hunan Province of China(No.2020JJ4522,No.2020JJ4529)+4 种基金The Patency Foundation of Innovation Platform of Hunan Provincial University of China(No.17K081)The Scientific Research Foundation ofHealth and Family Planning Committee of Hunan Province of China(No.A2015-2,No.B2015-182)The Scientific Research Foundation of Hunan Province Education Department of China(No.19C1610)Science and Technology Project of Jiangxi Provincial Administration of Traditional Chinese Medicine(No.2021B715)The Scientific Research Foundation of University of South China(No.220XNK002).
文摘Objectives:Gastric cancer(GC)is often associated with high invasiveness,epithelial-mesenchymal transition(EMT),and resistance to 5-fluorouracil(5-FU),highlighting the need for novel therapeutic targets.This study explored whether diallyl disulfide(DADS)upregulates retinoic acid-related orphan receptor alpha(RORα)to weaken the protein kinase C alpha(PKCα)/RORα-mediated RORα/β-catenin pathway,thereby inhibiting GC cell invasion,epithelial-mesenchymal transition(EMT),and enhancing 5-FU sensitivity.Methods:Human GC cell lines MGC-803 and SGC7901 were treated with DADS,RORαagonist SR1078/antagonist T0901317,and PKCαagonist TPA/antagonist GO6976.Cell proliferation(MTT),migration(scratch assay),invasion(Transwell),protein expression(Western blot),protein interactions(coimmunoprecipitation),and localization(immunofluorescence)were detected.Apoptosis and 5-FU sensitivity-related proteins were examined.Experiments were triplicated;statistics used t-test/ANOVA(p<0.05).Results:DADS/SR1078 inhibited GC cell proliferation/migration/invasion,upregulated RORα/E-cadherin,downregulated nuclearβ-catenin/TGF-β1/Rac1/Vimentin,and weakened EMT(reversed by T0901317).DADS/TPA upregulated RORα/p-RORα/PKCα/p-PKCα,promoted PKCα-RORαbinding,and downregulated RORα/β-catenin target genes(counteracted by GO6976).DADS upregulated caspase-3 and downregulated Bcl-2/P-gp/XIAP via RORα,promoting apoptosis and 5-FU sensitivity.Conclusion:DADS inhibits GC progression and enhances 5-FU sensitivity by PKCα/RORα-mediated downregulation of RORα/β-catenin signaling,paralleling SR1078/TPA effects.It may act as a novel RORαagonist for GC therapy.
基金Supported by the National Natural Science Foundation of China,No.81960506Science and Technology Fund Project of Guizhou Provincial Health Commission,No.gzwkj2022-299Key Projects of Zunyi Science and Technology Fund,No.zunshikeheHZzi(2023)24 and No.zunshikeheHZzi(2024)9.
文摘BACKGROUND Radiotherapy is widely employed in colorectal cancer(CRC)treatment,but the occurrence of radioresistance severely limits the clinical benefit to patients and significantly contributes to treatment failure and recurrent metastasis.AIM To explore the role and underlying mechanism of the lncRNA FTX in radiotherapy resistance in CRC.METHODS LncRNA FTX expression in colorectal parent cells(HT29 and HCT116)and radioresistant cells(HT29R and HCT116R)was determined by real-time quantitative PCR,and the viability of HT29R-shFTX and HCT116R-shFTX cells under ionizing radiation was evaluated using the cell counting kit-8 assay and colony formation experiment.The levels of glutathione and reactive oxygen species in cells after irradiation were determined,and the association between ferroptosis and lncRNA FTX expression in cancer cells was tested.A dual-luciferase assay was used to validate gene interactions.A xenotransplantation mouse model was established to explore the effects of FTX on the CRC tumor radiosensitivity in vivo.RESULTS FTX was upregulated in radioresistant CRC cells,and FTX knockdown inhibited cell survival and increased cell ferroptotic death in response to ionizing radiation.Moreover,lncRNA FTX restricted the SLC7A11 expression by sponging with miR-625-5p,and inhibition of the lncRNA FTX or SLC7A11 significantly increased cellular oxidant levels and DNA damage to ionizing radiation in cancer cells.However,SLC7A11 overexpression reversed the effects of decreased FTX levels on ferroptosis and high oxidation levels in cancer cells exposed to ionizing radiation.CONCLUSION Inhibition of the lncRNA FTX/miR-625-5p/SLC7A11 axis can induce ferroptosis and disturb intracellular redox balance,further sensitizing CRC cells to ionizing radiation,suggesting its potential as a therapeutic target for improving CRC response to radiation therapy.
基金supported by Australian Centre for AI in Medical Innovation(ACAMI)funded by the Victoria State Government,National University of Singapore(NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine,NUHSRO/2021/044/Kickstart/09/LOA,and 230173-A0001)National Medical Research Council(MOH-001388-00,CG21APR1005,MOH-001500-00,and MOH-001609-00)+1 种基金Singapore Ministry of Education(MOE-000387-00 and MOET32023-0005)National Research Foundation(NRF-000352-00)。
文摘1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effects.Over the past decade,a promising alternative has emerged:cancer immunotherapy,which leverages the body's immune system to identify and eradicate cancer cells[1].
基金supported by grants from the Ministry of Science and Technology,Taiwan(MOST108-2314-B-182-006,MOST109-2314-B-182-071:Lee-Yung Shih)the Ministry of Health and Welfare,Taiwan(MOHW110-TDU-B-212-134011:Lee-Yung Shih)+3 种基金Chang Gung Memorial Hospital(CMRPG3D1524,OMRPG3E0031:Lee-Yung Shih)the Grant-in-Aid for the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP19H05656:Seishi Ogawa,22K16320:Yotaro Ochi)the Japan Agency for Medical Research and Development(AMED)(JP19cm0106501h0004,JP19ck0106250h0003:Seishi Ogawa)the Ministry of Education,Culture,Sports,Science and Technology of Japan(MEXT)(hp200138,hp210167:Seishi Ogawa)。
文摘Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.
文摘AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995.Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS:The rate of lymph node metastasis in cases where the depth of invasion was<500 μm,500-2 000 μm,or >2 000 μm was 9%(2/23),19%(7136),and 33%(15/46), respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren's classification,and lymphatic invasion.In multivariate analysis, tumor size(>4 cm vs≤2 cm,odds ratio=4.80, P=0.04)and depth of invasion(>2 000 μm vs ≤500 μm, odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis.Combining the depth and size in cases where the depth of invasion was less than 500 μm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2 000 μm. CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 μm in depth.
基金the Korea Research Foundation Grant, No.KRF-2003-03-E00199
文摘AIM： To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. METHODS： We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR （MS-PCR）, as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues. RESULTS： Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MSPCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%, respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively. CONCLUSION： The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.
基金Supported by Grant from the Zhejiang Province Natural Science Fund of Youth in China(No.LQ12H16015)
文摘OBJECTIVE： To study the anticancer mechanism of polyphyllin I （PPI）, a Traditional Chinese Medicine, on the ovarian cancer cell line HO-8910PM in vitro. METHODS： Transwell chamber invasive assays were used to investigate the inhibitory capacity of PPI on HO-8910PM metastasis. Gene expression profiling chips was used to screen differentially ex- pressed genes between experiment group and con- trol group. Reverse transcription PCR and Western blotting were used to determine mRNA and pro- tein levels. RESULTS： With increasing PPI concentration, the metastatic capacity of cells decreased, with signifi- cance differences between the experimental and control groups （P〈0.01） as well as between two concentration groups. Gene expression profiling identified 123 differentially expressed genes, of which 70 were downregulated and 53 were upregu- lated. The genes were involved in multiple signal transduction pathways, including apoptosis, prolif- eration and metastasis. Real-time PCR （RT-PCR） showed that differential genes PIK3C2B, Caspase 9and WntSA were downregulated with increasing PPI, showing an evident dose-effect relationship. The c-Jun was an exception. As the PPI dosage in- creased and the exposure time was extended, c-Jun relative expression showed an upward trend. There were significant differences between the ex- periment and control （P〈0.05）. Western blot analy- ses showed that PPI treatment decreased levels of Caspase 9, WntSA and PIK3C2B and increased acti- vated Caspase 9,c-Jun and p-c-Jun expression levels. CONCLUSION＂ PPI has strong antitumor and anti transfer activity. It can activate c-Jun expression and the JNK signaling pathway, elicit cell apoptosis via the mitochondrial-mediated Caspase activation pathway, and finally inhibit tumor growth and mi- gration in vitro. The downregulation of PIK3C2B and Wnt5A jointly inhibit the proliferation and me- tastasis of HO-8910PM. PPI may be a novel treat- ment for ovarian cancer.
文摘Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.
文摘There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer.A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)],peritonectomy,hyperthermic intraperitoneal chemoperfusion (HIPEC) and early postoperative intraperitoneal chemotherapy has been developed.In this article,we assess the indications,safety and eff icacy of this treatment,review the relevant studies and introduce our experiences.The aims of NIPS are stage reduction,the eradication of peritoneal free cancer cells,and an increased incidence of complete cytoreduction (CC-0) for PC.A complete response after NIPS was ob-tained in 15 (50%) out of 30 patients with PC.Thus,a signif icantly high incidence of CC-0 can be obtained in patients with a peritoneal cancer index (PCI) ≤ 6.Using a multivariate analysis to examine the survival benef it,CC-0 and NIPS are identified as significant indicators of a good outcome.However,the high morbidity and mortality rates associated with peritonectomy and perioperative chemotherapy make stringent patient selection important.The best indications for multidisciplinary therapy are localized PC (PCI≤6) from resectable gastric cancer that can be completely removed during a peritonectomy.NIPS and complete cytoreduction are essential treatment modalities for improving the survival of patients with PC from gastric cancer.
文摘Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA(ct DNA) could provide diagnostic information. In this review, we provide an overview of the current status of bloodbased tests for diagnosis of pancreatic cancer and the potential utility of ct DNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ct DNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.
基金Supported by the National Science Foundation of China(in part),No.30973476 and No.812727
文摘Pim-3 is a member of the provirus integration site for Moloney murine leukemia virus(Pim)family proteins that exhibit serine/threonine kinase activity.Similar to the other Pim kinases(Pim-1 and Pim-2),Pim-3 is involved in many cellular processes,including cell proliferation,survival,and protein synthesis.Although Pim-3is expressed in normal vital organs,it is overexpressed particularly in tumor tissues of endoderm-derived organs,including the liver,pancreas,and colon.Silencing of Pim-3 expression can retard in vitro cell proliferation of hepatocellular,pancreatic,and colon carcinoma cell lines by promoting cell apoptosis.Pim-3 lacks the regulatory domains similarly as Pim-1 and Pim-2 lack,and therefore,Pim-3 can exhibit its kinase activity once it is expressed.Pim-3 expression is regulated at transcriptional and post-transcriptional levels by transcription factors(e.g.,Ets-1)and post-translational modifiers(e.g.,translationally-controlled tumor protein),respectively.Pim-3 could promote growth and angiogenesis of human pancreatic cancer cells in vivo in an orthotopic nude mouse model.Furthermore,a Pim-3 kinase inhibitor inhibited cell proliferation when human pancreatic cancer cells were injected into nude mice,without inducing any major adverse effects.Thus,Pim-3 kinase may serve as a novel molecular target for developing targeting drugs against pancreatic and other types of cancer.
文摘Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs.
基金Project supported by Research and Development Funds of Second Affiliated Hospital, School of Medicine, Zhejiang University, China
文摘Object: The authors studied the influence of CO2 pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. Method: They set up a simulation of pneumoperitoneum under different CO2 pressure, and then measured the variation of intracellular pH (pHi) at different time and the activity of protein kinase C (PKC) and protein phosphatase 2a (PP2a) at the end of the pneumoperitoneum. After 1 week, the concentration of cancer cells in the culture medium was calculated. Result: When the pressure of CO2 pneumoperitoneum was 0, 10, 20, 30 mmHg respectively, the average pHi was 7.273, 7.075, 6.783, 6.693 at the end of the pneumoperitoneum; PKC activity was 159.4, 168.5,178.0, 181.6 nmol/(g.min) and PP2a was 4158.3, 4066.9, 3984.0, 3878.5 nmol/(g.min) respectively. After 1 week, the cancer cells concentration was 2.15×105, 2.03×105, 2.20×105, 2.18×105 L-1. Conclusion: CO2 pneumoperitoneum could promote acidosis in cancer cells, inducing the activation of protein kinase C and deactivation of protein phosphatase 2a, but it could not accelerate the mitosis rate of the cancer cells.
基金Supported by The National R&D Program for Cancer Control funded by the Ministry of Health and Welfare,South Korea,No.0720540the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP),No.2011-0030768+1 种基金Priority Research Centers Program through the NRF grant funded by the Ministry of Education,Science and Technology(MEST),South Korea,No.2009-0093820the Mid-career Researcher Program through the NRF grant funded by MEST,No.2011-0015646
文摘Colorectal cancers (CRCs) with a high level of microsatellite instability (MSI-H) are clinicopathologically distinct tumors characterized by predominance in females, proximal colonic localization, poor differentiation, mucinous histology, tumor-infiltrating lymphocytes, a Crohn’s-like lymphoid reaction and a favorable prognosis. In terms of their molecular features, MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations, including DNA mismatch repair deficiency, target microsatellite mutations, BRAF mutations, a CpG island methylator phenotype-high (CIMP-H) status, and a low level of genomic hypomethylation. The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences; for example, in Eastern Asian countries, relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries. Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy, there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs. Here, we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs, as well as several putative prognostic or predictive molecular markers, including HSP110 expression, beta2-microglobulin mutations, myosin 1a expression, CDX2/CK20 expression, SMAD4 expression, CIMP status and LINE-1 methylation levels.
文摘AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.
