Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and pote...Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.展开更多
Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autoph...Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.展开更多
The androgenetic alopecia(AGA)is the most prevalent clinical manifestation of hair loss,believed to be associated with excessive dihydrotestosterone(DHT)caused by typeⅡ5α-reductase(5αR2).The utilization of oral fin...The androgenetic alopecia(AGA)is the most prevalent clinical manifestation of hair loss,believed to be associated with excessive dihydrotestosterone(DHT)caused by typeⅡ5α-reductase(5αR2).The utilization of oral finasteride(FNS),which selectively inhibits 5αR2,is frequently constrained by its adverse effects.Topical FNS formulations can mitigate adverse effects but often exhibit limited dermal permeability.Nanocarriers show great potential in augmenting the cutaneous permeation of loaded FNS due to their inherent properties of selective accumulation within the hair follicles(HFs).In this study,hollow mesoporous silica nanoparticles(HMSN)with varying sizes were utilized as the nanocarriers for FNS,following mixing with the Carbopol hydrogel(F@H/Gel)for direct topical application.Specifically,the influence of size on the targeted delivery of FNS to HFs,and its enhanced therapeutic efficacy for the AGA mice model was evaluated.Results showed that the HMSN,with a diameter of approximately 300 nm,exhibited significant enhancement in FNS retention within skin and HFs,as well as remarkably accelerated hair regrowth on an AGA mouse model.In conclusion,this FNS topical formulation has proved to be a viable approach in offering a secure and efficient treatment modality for AGA.展开更多
Vascular stents play an important role in the minimally invasive treatment of vascular diseases,such as vascular stenosis,vascular aneurysm,vascular dissection and vascular atherosclerotic plaque disease.Bare metal st...Vascular stents play an important role in the minimally invasive treatment of vascular diseases,such as vascular stenosis,vascular aneurysm,vascular dissection and vascular atherosclerotic plaque disease.Bare metal stents were initially fabricated;however,the incidence of complications such as thrombosis,inflammation,restenosis,vascular injury,displacement and endoleakage is still high after implantation.To overcome these complications,several strategies for designing functional vascular stents have been carried out.Drug-eluting stents,biodegradable stents and bionic stents were manufactured and investigated.This review aims to comprehensively analyze the vascular diseases suitable for stent implantation treatment,tissue reactions after implantation,the materials and manufacturing techniques used to fabricate vascular stents,the various application scenarios in which they could be used to treat vascular lesions and the development process of vascular stents.Future development trends of vascular stents are expected to prioritize their performance,biocompatibility,and clinical accessibility.The design of vascular stents may be transformed or improved to better fulfill the rehabilitation requirements of vascular disease patients.Finally,various application scenarios may be used to treat vascular or even nonvascular diseases via endovascular access.展开更多
BACKGROUND Cancer-associated fibroblasts(CAFs),crucial components of the tumor microenvironment in primary and metastatic tumors,can impact the activity of cancer cells and contribute to their progression.Given their ...BACKGROUND Cancer-associated fibroblasts(CAFs),crucial components of the tumor microenvironment in primary and metastatic tumors,can impact the activity of cancer cells and contribute to their progression.Given their extensive interactions with cancer cells and other stromal cells,we aimed to evaluate the prognostic value of CAFs in patients with liver cancer(LC).AIM To investigate the association between CAF expression and clinicopathological characteristics as well as overall survival(OS)in patients with LC,including hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).METHODS We performed a meta-analysis of cohort studies with available data on the effects of CAF expression on both clinicopathological characteristics and OS via hazard ratios(HRs)and risk ratios with 95%confidence intervals(CIs).Studies were subgrouped on the basis of CAF markers and cancer type,and the subgroup effects of CAF expression on both HCC and iCCA were analyzed through meta-regression.The Newcastle-Ottawa Scale was used to evaluate the included studies to guarantee their quality and minimize the possibility of bias.RESULTS Nine trials were selected and included a total of 1518 patients.According to our primary meta-analysis,the expression of CAFs in LC patients was significantly associated with a decrease in OS(LC:HR:1.62;95%CI:1.34-1.97;P<0.001;HCC:HR:1.67;95%CI:1.34-2.07;P<0.001;iCCA:HR:1.47;95%CI:0.97-2.23;P=0.07);nevertheless,it was not significantly associated with almost all clinicopathologic characteristics,including tumor size,venous infiltration,alpha-fetoprotein level,and differentiation grade.According to the subgroup analysis of smooth muscle actin(SMA)markers in both HCC patients and iCCA patients,high CAF expression in HCC(HR:2.29;95%CI:1.01-5.22;P=0.048)and iCCA(HR:2.04;95%CI:1.09-3.81;P=0.025)patients was a significant indicator of poor OS.Moreover,the clinicopathological characteristics were also verified by the SMA marker,which had a nearly significant effect on the venous infiltration of iCCA(risk ratio:2.70;95%CI:0.97-7.49;P=0.057).CONCLUSION High CAF expression,evaluated by both mixed markers and SMAs,is significantly associated with poor OS in patients with LC,including both HCC patients and iCCA patients.However,further research is necessary since how CAF expression and clinicopathologic features are related is yet unknown.展开更多
A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antit...A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antitumor responses.These triads ensure that CD8^(+)T cells receive the necessary help from CD4^(+)T cells,mediated via the same DC,to effectively targeting and destroying cancer cells.The article’s novel insight suggests a shift in focus from increasing the number of immune cells to optimizing their interactions within the tumor microenvironment.This groundbreaking study not only underscores the critical roles of CD4^(+)T cells and DCs,but also highlights the intricate interplay among immune cell subsets within the tumor microenvironment.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown...Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.展开更多
Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly red...Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma(HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients.However,the role of TRIM3 in liver cancer remains unknown.This study aimed to investigate the function of TRIM3 in liver cancer cells.Methods:The protein levels of TRIM3 in five liver cancer cell lines(SK-Hep1,Hep3 B,Huh7,HepG2,Bel-7402) and one normal liver cell line(L02) were detected with Western blotting.HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3(LV-TRIM3),whereas Huh7 and Hep3 B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA(siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were examined.The effect ofTRIM3 on tumor growth and metastases in nude mice was also investigated.Results:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell lines.Cell cycle analysis showed that TRIM3 overexpression induced G_0/G_1 phase arrest in HepG2 and Bel-7402 cells.Moreover,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3.Contrarily,silencing TRIM3 expression in Huh7 and Hep3 B cells by siTRIM3 led to significantly decreased percentages of both cells in the G_0/G_1 phase and promoted cell proliferation,colony formation,migration,and invasion.In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis.Conclusions:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G_0/G_1 phase.展开更多
Chuankezhi(CKZ),a new Chinese medicine,plays an important role in immunoregulation.Cytokineinduced killer(CIK)cells have been commonly used for immunotherapy in recent years.In this study,we aimed to investigate the i...Chuankezhi(CKZ),a new Chinese medicine,plays an important role in immunoregulation.Cytokineinduced killer(CIK)cells have been commonly used for immunotherapy in recent years.In this study,we aimed to investigate the immunoregulatory effect of CKZ on CIK cells.Peripheral blood monocytes were isolated from healthy donors,and CIK cells were generated by culturing monocytes with interferon-gamma(IFN-γ)and interleukin 2.Different concentrations of CKZ were added on day 2.After incubation for 14days in culture,the antitumor effects of CIK cells were measured by cytotoxicity assay.Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype,intracellular cytokine production,and apoptosis.The effect of CKZ on the antitumor activity of CIK cells in nude mice was also investigated.CKZ increased the percentage of CD3+CD56+CIK cells but did not significantly change the percentage of CD4+,CD8+,or CD4+CD25+CIK cells.CKZ-conditioned CIK cells showed a greater ability to kill tumor cells,as well as a higher frequency of IFN-γand TNF-αproduction,compared with the CIK cells in the control group.CKZ also suppressed the apoptosis of CIK cells in vitro.Furthermore,CKZ combined with CIK cells had a stronger suppressive effect on tumor growth in vivo than the CIK,CKZ,or normal saline control groups.Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.展开更多
On March 5th, a novel immunosuppressive molecule,Siglec-15, was reported in Nature Medicine by Professor Lieping Chen1. Siglec-15 was reported in a wide variety of tumors. The molecule is not a simple replica of PD-1/...On March 5th, a novel immunosuppressive molecule,Siglec-15, was reported in Nature Medicine by Professor Lieping Chen1. Siglec-15 was reported in a wide variety of tumors. The molecule is not a simple replica of PD-1/PD-L1.Rather, the expressions of Siglec-15 and PD-L1 are mutually exclusive1, suggesting that Siglec-15 antibodies may be effective on tumors that are not responsive to anti-PD-1/PDL1 therapy. Siglec-15 potentially serves as a complementary therapeutic target and offers alternative treatments for many anti-PD-l/PD-Ll therapy unresponsive patients. This discovery generated a huge response.展开更多
Background:Protein tyrosine kinase 6(PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis.However,PTK6 expression status and its role in cervical squamous cell cancer are unknown.This study aim...Background:Protein tyrosine kinase 6(PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis.However,PTK6 expression status and its role in cervical squamous cell cancer are unknown.This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen,early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues.The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed,paraffin-embedded,early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections.Results:The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues.Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells.The level of PTK6 expression was significantly associated with tumor grade(P = 0.020).The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression(81.3%vs.96.2%,P = 0.008).Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival(hazard ratio = 5.999,95%confidence interval 1.622-22.191,P< 0.05).Conclusions:PTK6 is overexpressed in cervical squamous ceil cancer.Increased PTK6 expression is associated with reduced 5-year overall survival.PTK6 expression is an independent prognostic predictor for cervical cancer.展开更多
BACKGROUND Recent evidence indicates that malignant ascites may be associated with the high malignancy and poor prognosis of gastric cancer(GC)with peritoneal metastasis(PM),but no robust consensus has been reached un...BACKGROUND Recent evidence indicates that malignant ascites may be associated with the high malignancy and poor prognosis of gastric cancer(GC)with peritoneal metastasis(PM),but no robust consensus has been reached until now.AIM To evaluate the prognostic significance of malignant ascites in GC patients with PM.METHODS Two independent authors conducted database searches.The searches were performed in the EMBASE,PubMed,and Cochrane Library databases,and the terms used to search included stomach neoplasms,GC,ascites,peritoneal effusion,survival,and survival analysis.Outcomes included overall survival and hazard ratios with 95%confidence intervals(CIs).Three pairs of comparisons for measuring survival were made:(1)Patients with ascites vs those without ascites;(2)Patients with massive ascites vs those with mild to moderate ascites;and(3)Patients with massive ascites vs those with no to moderate ascites.RESULTS Fourteen articles including fifteen studies were considered in the final analysis.Among them,nine studies assessed the difference in prognosis between patients with and without malignant ascites.A pooled HR of 1.63(95%CI:1.47-1.82,P<0.00001)indicated that GC patients with malignant ascites had a relatively poor prognosis compared to patients without ascites.We also found that the prognosis of GC patients with malignant ascites was related to the volume of ascites in the six other studies.CONCLUSION GC patients with malignant ascites tend to have a worse prognosis,and the volume of ascites has an impact on GC outcomes.展开更多
Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved n...Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.展开更多
BACKGROUND Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(cHCCCCA)is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis.AIM To develo...BACKGROUND Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(cHCCCCA)is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis.AIM To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA.METHODS Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets.Radiomics features were extracted from portal venous phase computed tomography(CT)images using the least absolute shrinkage and selection operator Cox regression and random forest analysis.A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression.Nomogram performance was assessed in terms of the C-index as well as calibration,decision,and survival curves.RESULTS CT and clinical data of 118 patients were included in the study.The radiomics score,vascular invasion,anatomical resection,total bilirubin level,and satellite lesions were found to be independent predictors of overall survival(OS)and were therefore included in an integrative nomogram.The nomogram was more strongly associated with OS(hazard ratio:8.155,95%confidence interval:4.498-14.785,P<0.001)than a model based on the radiomics score or only clinical factors.The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875,respectively.Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk(6.1 vs 81.6 mo,P<0.001).CONCLUSION This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.展开更多
Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small...Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.展开更多
Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Somatic copy number alterations(SCNAs)have been used to predict responses to therapies in many cancers,including lung cancer.However,li...Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Somatic copy number alterations(SCNAs)have been used to predict responses to therapies in many cancers,including lung cancer.However,little is known about whether they are predictive of radiotherapy outcomes.We aimed to understand the prognostic value and biological functions of SCNAs.Methods:We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy.Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response.Our results were validated in 20 patients with lung adenocarcinoma(LUAD)receiving radiotherapy.Results:SCNAs were a better predictor of progression-free survival(PFS)in LUAD(P=0.024)than in lung squamous carcinoma(P=0.18)in patients treated with radiotherapy.Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD.Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels(P=0.022).Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS.Additionally,high SCNA may activate the cell cycle pathway and induce tumorigenesis.Conclusions:SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy,in combination with TNM,with the aim of predicting long-term PFS.Therefore,SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.展开更多
Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received i...Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.展开更多
In vitro amplified human leukocyte antigen(HLA)-haploidentical donor immune cell infusion(HDICI)is not commonly used in children.Therefore,our study sought to evaluate its safety for treating childhood malignancies.Be...In vitro amplified human leukocyte antigen(HLA)-haploidentical donor immune cell infusion(HDICI)is not commonly used in children.Therefore,our study sought to evaluate its safety for treating childhood malignancies.Between September 2011 and September 2012,12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center.The median patient age was 5.1 years(range,1.7-8.4 years).Of the 12 patients,9 had high-risk neuroblastoma(NB)[7 showed complete response(CR),1 showed partial response(PR),and 1 had progressive disease(PD)after multi-modal therapies],and 3 had Epstein-Barr virus(EBV)-positive lymphoproliferative disease(EBV-LPD).The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×108immune cells/kg body weight:71 infusions with natural killer(NK)cells,8 with cytokine-induced killer(CIK)cells,and 13 with cascade primed immune cells(CAPRIs);83 infusions with immune cells from the mothers,whereas 9 with cells from the fathers.Twenty cases(21.7%)of fever,including 6 cases(6.5%)accompanied with chills and 1(1.1%)with febrile convulsion,occurred during infusions and were alleviated after symptomatic treatments.Five cases(5.4%)of mild emotion changes were reported.No other adverse events occurred during and after the completion of HDIDIs.Neither acute nor chronic graft versus host disease(GVHD)was observed following HDICIs.After a median of 5.0 months(range,1.0-11.5 months)of follow-up,the 2 NB patients with PR and PD developed PD during HDICIs.Of the other 7 NB patients in CR,2 relapsed in the sixth month of HDICIs,and 5 maintained CR with disease-free survival(DFS)ranging from 4.5 to 11.5 months(median,7.2months).One EBV-LPD patient achieved PR,whereas 2 had stable disease(SD).Our results show that HDICI is a safe immunotherapy for childhood malignancies,thus warranting further studies.展开更多
Immune checkpoint inhibitors(ICIs)targeting cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 receptor/ligand have revolutionized cancer treatment,achieving unprecedented efficacy in numerous malign...Immune checkpoint inhibitors(ICIs)targeting cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 receptor/ligand have revolutionized cancer treatment,achieving unprecedented efficacy in numerous malignancies.Despite the excellent therapeutic effects of ICIs,medications,such as pembrolizumab,ipilimumab,nivolumab,atezolizumab,avelumab,and durvalumab,typically cause a broad spectrum of toxicity events termed as immune-related adverse events(ir AEs).Out of all ir AEs,ophthalmic adverse events occur infrequently and are not comprehensively recognized.The current understanding of ophthalmic ir AEs is mainly derived from case reports and case series.In this review,based on relevant articles in the literature and current evidence,we summarize the incidences,manifestations,diagnoses,underlying mechanisms,treatments,and outcomes of ophthalmic ir AEs and discuss possible management strategies.A better understanding of these features is critical for managing patients with ICI-associated ophthalmic adverse events.展开更多
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09201018–028)the nuclear energy development projects of China during the 13thFive Year Plan periodthe key research and development project of the Sichuan Provincial Department of Science and Technology(No.18ZDYF1466)。
文摘Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.
基金the National Natural Science Foundation of China(Nos.22307009,82374155,82073997,82104376)the Sichuan Science and Technology Program(Nos.2023NSFSC1108,2024NSFTD0023)+1 种基金the Postdoctoral Research Project of Sichuan Provincethe Xinglin Scholar Research Promotion Project of Chengdu University of TCM.
文摘Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.
基金funded by the National Natural Science Foundation of China Regional Innovation and Development Joint Fund(Sichuan)(No.U21A20417)the National Natural Science Foundation of China(No.31930067)。
文摘The androgenetic alopecia(AGA)is the most prevalent clinical manifestation of hair loss,believed to be associated with excessive dihydrotestosterone(DHT)caused by typeⅡ5α-reductase(5αR2).The utilization of oral finasteride(FNS),which selectively inhibits 5αR2,is frequently constrained by its adverse effects.Topical FNS formulations can mitigate adverse effects but often exhibit limited dermal permeability.Nanocarriers show great potential in augmenting the cutaneous permeation of loaded FNS due to their inherent properties of selective accumulation within the hair follicles(HFs).In this study,hollow mesoporous silica nanoparticles(HMSN)with varying sizes were utilized as the nanocarriers for FNS,following mixing with the Carbopol hydrogel(F@H/Gel)for direct topical application.Specifically,the influence of size on the targeted delivery of FNS to HFs,and its enhanced therapeutic efficacy for the AGA mice model was evaluated.Results showed that the HMSN,with a diameter of approximately 300 nm,exhibited significant enhancement in FNS retention within skin and HFs,as well as remarkably accelerated hair regrowth on an AGA mouse model.In conclusion,this FNS topical formulation has proved to be a viable approach in offering a secure and efficient treatment modality for AGA.
基金supported by Natural Science Foundation of China(No.31930067)Natural Science Foundation of Sichuan Province(No.23NSFSC5880)+2 种基金Chengdu Medical Research Project(No.2022004)Natural Science Foundation of Clinical Medical College and Affiliated Hospital of Chengdu University(No.Y202206)Postdoctoral Research and Development Fund of West China Hospital,Sichuan University(No.2023HXBH052).
文摘Vascular stents play an important role in the minimally invasive treatment of vascular diseases,such as vascular stenosis,vascular aneurysm,vascular dissection and vascular atherosclerotic plaque disease.Bare metal stents were initially fabricated;however,the incidence of complications such as thrombosis,inflammation,restenosis,vascular injury,displacement and endoleakage is still high after implantation.To overcome these complications,several strategies for designing functional vascular stents have been carried out.Drug-eluting stents,biodegradable stents and bionic stents were manufactured and investigated.This review aims to comprehensively analyze the vascular diseases suitable for stent implantation treatment,tissue reactions after implantation,the materials and manufacturing techniques used to fabricate vascular stents,the various application scenarios in which they could be used to treat vascular lesions and the development process of vascular stents.Future development trends of vascular stents are expected to prioritize their performance,biocompatibility,and clinical accessibility.The design of vascular stents may be transformed or improved to better fulfill the rehabilitation requirements of vascular disease patients.Finally,various application scenarios may be used to treat vascular or even nonvascular diseases via endovascular access.
基金Supported by the Sichuan Science and Technology Program,No.2024NSFSC1936.
文摘BACKGROUND Cancer-associated fibroblasts(CAFs),crucial components of the tumor microenvironment in primary and metastatic tumors,can impact the activity of cancer cells and contribute to their progression.Given their extensive interactions with cancer cells and other stromal cells,we aimed to evaluate the prognostic value of CAFs in patients with liver cancer(LC).AIM To investigate the association between CAF expression and clinicopathological characteristics as well as overall survival(OS)in patients with LC,including hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).METHODS We performed a meta-analysis of cohort studies with available data on the effects of CAF expression on both clinicopathological characteristics and OS via hazard ratios(HRs)and risk ratios with 95%confidence intervals(CIs).Studies were subgrouped on the basis of CAF markers and cancer type,and the subgroup effects of CAF expression on both HCC and iCCA were analyzed through meta-regression.The Newcastle-Ottawa Scale was used to evaluate the included studies to guarantee their quality and minimize the possibility of bias.RESULTS Nine trials were selected and included a total of 1518 patients.According to our primary meta-analysis,the expression of CAFs in LC patients was significantly associated with a decrease in OS(LC:HR:1.62;95%CI:1.34-1.97;P<0.001;HCC:HR:1.67;95%CI:1.34-2.07;P<0.001;iCCA:HR:1.47;95%CI:0.97-2.23;P=0.07);nevertheless,it was not significantly associated with almost all clinicopathologic characteristics,including tumor size,venous infiltration,alpha-fetoprotein level,and differentiation grade.According to the subgroup analysis of smooth muscle actin(SMA)markers in both HCC patients and iCCA patients,high CAF expression in HCC(HR:2.29;95%CI:1.01-5.22;P=0.048)and iCCA(HR:2.04;95%CI:1.09-3.81;P=0.025)patients was a significant indicator of poor OS.Moreover,the clinicopathological characteristics were also verified by the SMA marker,which had a nearly significant effect on the venous infiltration of iCCA(risk ratio:2.70;95%CI:0.97-7.49;P=0.057).CONCLUSION High CAF expression,evaluated by both mixed markers and SMAs,is significantly associated with poor OS in patients with LC,including both HCC patients and iCCA patients.However,further research is necessary since how CAF expression and clinicopathologic features are related is yet unknown.
文摘A recent publication by Espinosa-Carrasco et al.1has illuminated the critical roles of intratumoral immune triads-a unique cluster of CD4^(+)T cells,CD8^(+)T cells,and dendritic cells(DCs)-in mediating effective antitumor responses.These triads ensure that CD8^(+)T cells receive the necessary help from CD4^(+)T cells,mediated via the same DC,to effectively targeting and destroying cancer cells.The article’s novel insight suggests a shift in focus from increasing the number of immune cells to optimizing their interactions within the tumor microenvironment.This groundbreaking study not only underscores the critical roles of CD4^(+)T cells and DCs,but also highlights the intricate interplay among immune cell subsets within the tumor microenvironment.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by grants from the key program of the National Basic Research Program of China (973 program) (Grant No. 2012CB9333004)the National Natural Science Foundation of China (Grant No. 81401888)
文摘Vascular endothelial growth factor(VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors(VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells(DCs), macrophages, and lymphocytes further express certain types of VEGF receptors.VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness.This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.
基金primarily supported by grants from the National Natural Science Foundation of China(Nos.81472387 and 81402560)Guangdong Province Science and Technology Plan Project(No.2012A030400059)
文摘Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma(HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients.However,the role of TRIM3 in liver cancer remains unknown.This study aimed to investigate the function of TRIM3 in liver cancer cells.Methods:The protein levels of TRIM3 in five liver cancer cell lines(SK-Hep1,Hep3 B,Huh7,HepG2,Bel-7402) and one normal liver cell line(L02) were detected with Western blotting.HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3(LV-TRIM3),whereas Huh7 and Hep3 B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA(siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were examined.The effect ofTRIM3 on tumor growth and metastases in nude mice was also investigated.Results:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell lines.Cell cycle analysis showed that TRIM3 overexpression induced G_0/G_1 phase arrest in HepG2 and Bel-7402 cells.Moreover,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3.Contrarily,silencing TRIM3 expression in Huh7 and Hep3 B cells by siTRIM3 led to significantly decreased percentages of both cells in the G_0/G_1 phase and promoted cell proliferation,colony formation,migration,and invasion.In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis.Conclusions:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G_0/G_1 phase.
基金National NaturalScience Foundation of China(No.u0772002,No.30700985,No.30973398)Guangdong Natural Science Foundation(No.925100890).
文摘Chuankezhi(CKZ),a new Chinese medicine,plays an important role in immunoregulation.Cytokineinduced killer(CIK)cells have been commonly used for immunotherapy in recent years.In this study,we aimed to investigate the immunoregulatory effect of CKZ on CIK cells.Peripheral blood monocytes were isolated from healthy donors,and CIK cells were generated by culturing monocytes with interferon-gamma(IFN-γ)and interleukin 2.Different concentrations of CKZ were added on day 2.After incubation for 14days in culture,the antitumor effects of CIK cells were measured by cytotoxicity assay.Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype,intracellular cytokine production,and apoptosis.The effect of CKZ on the antitumor activity of CIK cells in nude mice was also investigated.CKZ increased the percentage of CD3+CD56+CIK cells but did not significantly change the percentage of CD4+,CD8+,or CD4+CD25+CIK cells.CKZ-conditioned CIK cells showed a greater ability to kill tumor cells,as well as a higher frequency of IFN-γand TNF-αproduction,compared with the CIK cells in the control group.CKZ also suppressed the apoptosis of CIK cells in vitro.Furthermore,CKZ combined with CIK cells had a stronger suppressive effect on tumor growth in vivo than the CIK,CKZ,or normal saline control groups.Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.
文摘On March 5th, a novel immunosuppressive molecule,Siglec-15, was reported in Nature Medicine by Professor Lieping Chen1. Siglec-15 was reported in a wide variety of tumors. The molecule is not a simple replica of PD-1/PD-L1.Rather, the expressions of Siglec-15 and PD-L1 are mutually exclusive1, suggesting that Siglec-15 antibodies may be effective on tumors that are not responsive to anti-PD-1/PDL1 therapy. Siglec-15 potentially serves as a complementary therapeutic target and offers alternative treatments for many anti-PD-l/PD-Ll therapy unresponsive patients. This discovery generated a huge response.
文摘Background:Protein tyrosine kinase 6(PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis.However,PTK6 expression status and its role in cervical squamous cell cancer are unknown.This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen,early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues.The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed,paraffin-embedded,early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections.Results:The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues.Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells.The level of PTK6 expression was significantly associated with tumor grade(P = 0.020).The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression(81.3%vs.96.2%,P = 0.008).Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival(hazard ratio = 5.999,95%confidence interval 1.622-22.191,P< 0.05).Conclusions:PTK6 is overexpressed in cervical squamous ceil cancer.Increased PTK6 expression is associated with reduced 5-year overall survival.PTK6 expression is an independent prognostic predictor for cervical cancer.
基金Supported by the National Natural Science Foundation of China,No.81672577
文摘BACKGROUND Recent evidence indicates that malignant ascites may be associated with the high malignancy and poor prognosis of gastric cancer(GC)with peritoneal metastasis(PM),but no robust consensus has been reached until now.AIM To evaluate the prognostic significance of malignant ascites in GC patients with PM.METHODS Two independent authors conducted database searches.The searches were performed in the EMBASE,PubMed,and Cochrane Library databases,and the terms used to search included stomach neoplasms,GC,ascites,peritoneal effusion,survival,and survival analysis.Outcomes included overall survival and hazard ratios with 95%confidence intervals(CIs).Three pairs of comparisons for measuring survival were made:(1)Patients with ascites vs those without ascites;(2)Patients with massive ascites vs those with mild to moderate ascites;and(3)Patients with massive ascites vs those with no to moderate ascites.RESULTS Fourteen articles including fifteen studies were considered in the final analysis.Among them,nine studies assessed the difference in prognosis between patients with and without malignant ascites.A pooled HR of 1.63(95%CI:1.47-1.82,P<0.00001)indicated that GC patients with malignant ascites had a relatively poor prognosis compared to patients without ascites.We also found that the prognosis of GC patients with malignant ascites was related to the volume of ascites in the six other studies.CONCLUSION GC patients with malignant ascites tend to have a worse prognosis,and the volume of ascites has an impact on GC outcomes.
文摘Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.
文摘BACKGROUND Combined hepatocellular carcinoma(HCC)and cholangiocarcinoma(cHCCCCA)is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis.AIM To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA.METHODS Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets.Radiomics features were extracted from portal venous phase computed tomography(CT)images using the least absolute shrinkage and selection operator Cox regression and random forest analysis.A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression.Nomogram performance was assessed in terms of the C-index as well as calibration,decision,and survival curves.RESULTS CT and clinical data of 118 patients were included in the study.The radiomics score,vascular invasion,anatomical resection,total bilirubin level,and satellite lesions were found to be independent predictors of overall survival(OS)and were therefore included in an integrative nomogram.The nomogram was more strongly associated with OS(hazard ratio:8.155,95%confidence interval:4.498-14.785,P<0.001)than a model based on the radiomics score or only clinical factors.The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875,respectively.Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk(6.1 vs 81.6 mo,P<0.001).CONCLUSION This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.
基金Supported by a grant from the key Scientific Foundation of Shanxi Province (No. 051096-2)
文摘Objective: The aim of the study was to evaluate the safety and therapeutic effects of autologous dendritic cells co-cultured with cytokine-induced killer cells (DC-CIK) combined with chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Methods: Fifty patients with advanced NSCLC (stages III to IV), who had received therapies in our Center (Department of Biotherapy, Affiliated to Cancer Hospital of Shanxi Medical University, Taiyuan, China) from August 2008 to January 2010, were treated by DC-CIK + chemotherapy as the combined treatment group; fifty advanced NSCLC patients treated with chemotherapy at the same time served as controls. The immunologic function, short-term therapeutic effects, the 1-year survival rate, the life quality, the chemotherapy side effects were compared between the two groups, the safety and therapeutic effects of DC-CIK cells therapy were observed too. Results: There was no obvious change of subsets of T cells in peripheral blood before and after therapy in DC-CIK + chemotherapy group, and IFN-γ was improved after therapy in this group (P < 0.05); in chemotherapy alone group, the ratios of CD3+CD4+, CD3+CD8+, CD3-CD56+ cells and the secretion of IL-2, TNF-α decreased significantly after therapy (P < 0.05); the ratios of CD3+CD8+, CD3+CD56+ were improved after cell culture (P < 0.05). The disease control rate (DCR) of DC-CIK + chemotherapy group was higher than that in the chemotherapy alone group (78.0% vs 56.0%, P < 0.05); the 1-year survival rates of DC-CIK + chemotherapy group and chemotherapy alone group were 50% and 44% respectively, had no significant difference. Compared with chemotherapy alone group, the occurrence of chemotherapy side effects (including bone marrow suppression, nausea and vomiting, peripheral nerve toxicity) was less in the DC-CIK + chemotherapy group (P < 0.05). The physical and appetite were better in DC-CIK + chemotherapy group after therapy. Conclusion: To compare with simple chemotherapy, DC-CIK + chemotherapy for advanced NSCLC is safe and effective, and it can improve patients' life quality and remission rate, and prolong their survival time.
基金This work was supported by grants from the National Key Technology R&D Program(Grant No.2018YFC1313400)National Natural Science Foundation of China(Grant No.81974246)+1 种基金Scientific Research Program of Tianjin Education Commission(Grant No.2019KJ185)Tianjin Research Innovation Project(Grant No.2020YJSB164)for postgraduate students.
文摘Objective:Lung cancer is the most common cause of cancer-related deaths worldwide.Somatic copy number alterations(SCNAs)have been used to predict responses to therapies in many cancers,including lung cancer.However,little is known about whether they are predictive of radiotherapy outcomes.We aimed to understand the prognostic value and biological functions of SCNAs.Methods:We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy.Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response.Our results were validated in 20 patients with lung adenocarcinoma(LUAD)receiving radiotherapy.Results:SCNAs were a better predictor of progression-free survival(PFS)in LUAD(P=0.024)than in lung squamous carcinoma(P=0.18)in patients treated with radiotherapy.Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD.Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels(P=0.022).Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS.Additionally,high SCNA may activate the cell cycle pathway and induce tumorigenesis.Conclusions:SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy,in combination with TNM,with the aim of predicting long-term PFS.Therefore,SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.
文摘Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.
文摘In vitro amplified human leukocyte antigen(HLA)-haploidentical donor immune cell infusion(HDICI)is not commonly used in children.Therefore,our study sought to evaluate its safety for treating childhood malignancies.Between September 2011 and September 2012,12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center.The median patient age was 5.1 years(range,1.7-8.4 years).Of the 12 patients,9 had high-risk neuroblastoma(NB)[7 showed complete response(CR),1 showed partial response(PR),and 1 had progressive disease(PD)after multi-modal therapies],and 3 had Epstein-Barr virus(EBV)-positive lymphoproliferative disease(EBV-LPD).The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×108immune cells/kg body weight:71 infusions with natural killer(NK)cells,8 with cytokine-induced killer(CIK)cells,and 13 with cascade primed immune cells(CAPRIs);83 infusions with immune cells from the mothers,whereas 9 with cells from the fathers.Twenty cases(21.7%)of fever,including 6 cases(6.5%)accompanied with chills and 1(1.1%)with febrile convulsion,occurred during infusions and were alleviated after symptomatic treatments.Five cases(5.4%)of mild emotion changes were reported.No other adverse events occurred during and after the completion of HDIDIs.Neither acute nor chronic graft versus host disease(GVHD)was observed following HDICIs.After a median of 5.0 months(range,1.0-11.5 months)of follow-up,the 2 NB patients with PR and PD developed PD during HDICIs.Of the other 7 NB patients in CR,2 relapsed in the sixth month of HDICIs,and 5 maintained CR with disease-free survival(DFS)ranging from 4.5 to 11.5 months(median,7.2months).One EBV-LPD patient achieved PR,whereas 2 had stable disease(SD).Our results show that HDICI is a safe immunotherapy for childhood malignancies,thus warranting further studies.
文摘Immune checkpoint inhibitors(ICIs)targeting cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 receptor/ligand have revolutionized cancer treatment,achieving unprecedented efficacy in numerous malignancies.Despite the excellent therapeutic effects of ICIs,medications,such as pembrolizumab,ipilimumab,nivolumab,atezolizumab,avelumab,and durvalumab,typically cause a broad spectrum of toxicity events termed as immune-related adverse events(ir AEs).Out of all ir AEs,ophthalmic adverse events occur infrequently and are not comprehensively recognized.The current understanding of ophthalmic ir AEs is mainly derived from case reports and case series.In this review,based on relevant articles in the literature and current evidence,we summarize the incidences,manifestations,diagnoses,underlying mechanisms,treatments,and outcomes of ophthalmic ir AEs and discuss possible management strategies.A better understanding of these features is critical for managing patients with ICI-associated ophthalmic adverse events.
