Due to the drawbacks of low specificity and high risk of side effects of traditional anti-tumor treatments in clinical practice,novel anti-tumor immunotherapy has received attention and has been gradually applied.Tumor immunotherapy is to enhance the anti-tumor immune response by regulating the body's immune system in order to achieve control and killing of tumors.Tumor immunotherapies include immune checkpoint blockade therapy,over-the-counter cellular immunotherapy and tumor vaccines.Among them,the tumor vaccine stimulates the immune system to produce specific immune cells or antibodies by delivering tumor cell-specific antigens thereby eliminating the tumor cells for the purpose of treating the tumor.In recent years,The field of mRNA vaccines is developing rapidly,and the required mRNA in the synthesis and preparation of the process has been developed and matured,laying a good foundation for the research of tumor mRNA vaccine.Because of the fact that mRNA is easily degraded and cannot enter the cell autonomously,this vaccine requires a suitable delivery vehicle to be successfully taken up by the cell to be effective.Therefore,the development of mRNA vaccine delivery systems has become critical for their better utilization,which is also an important part of whether mRNA vaccines can be developed and utilized for the clinical stage in the field of tumor therapy.This paper briefly introduced the immunotherapeutic methods for tumors,types of tumor vaccines and the mechanism of action and preparation methods of tumor mRNA vaccines,reviewed the research progress and related applications of mRNA vaccines and their common delivery systems in immunotherapy for tumor treatment,and summarized the tumor mRNA vaccines that entered into the phase of clinical trials with the aim of providing assistance for the research of mRNA vaccines for tumors in the future.

Gastric cancer is one of the most common malignant tumors,and over 70%of patients were diagnosed as advanced stage at the first visit in our country.For patients with locally advanced gastric cancer invading adjacent organs,the diagnosis and surgical treatment are quite difficult,and prognosis is poor.To further standardize the clinical research practice of locally advanced gastric cancer invading adjacent organs,this consensus was guided by evidence-based methodology,focusing on the progress of diagnosis and treatment in locally advanced gastric cancer invading adjacent organs,and the clinical studies with high level of evidence but not approved at present,and exploring the new modes of diagnosis,efficacy evaluation and other aspects.On the basis of literature retrieval,quality evaluation and evidence summary were carried out,and specific issues and hot topics such as the methods of diagnosis,peri-operative treatment,surgical treatment and other common concerns in the clinical application were discussed and investigated through multidisciplinary expert meetings,Delphi methods and other forms.The"Chinese expert consensus on clinical practice of locally advanced gastric cancer invading adjacent organs(2024 edition)"was completed by the investigation and summarization of the opinions of 35 experts from more than 10 different regions and 30 hospitals for 4 times,relying on Professional Committee on Gastric Cancer of Shanghai Anticancer Association,Professional Committee on Gastrointestinal Cancer of China Association for Promotion of Health Science and Technology,with a view to providing evidence reference and normative basis for frontline medical personnel in future clinical practice of locally advanced gastric cancer treatment,and laying a foundation for subsequent development of relevant industry guidelines.

Background and purpose:According to current consensus,adverse high-risk pathological features are only associated with adjuvant therapy for stage Ⅱ colorectal cancer(CRC).As important prognostic factors,we further explored the possibility of identifying patients with potential recurrence and poor prognosis based on these incorporating high-risk pathological features.Methods:This is a cohort study.A retrospective analysis was conducted on clinical data of CRC patients who underwent surgical treatment at the Second Department of Colorectal Surgery,Fudan University Affiliated Shanghai Cancer Center from 2008 to 2018.This study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center(approval No.:050432-4-2108*),and the study complies with the Declaration of Helsinki.A total of 9875 patients were enrolled,including 5859 males and 4016 females,aged[M(IQR)]60(16)years(range:16 to 94).Median follow-up time was 1779.0 days[95%CI:1750.1-1807.9].We used the Kaplan-Meier method to plot survival curves for different groups.Cox multivariate analysis was used to identify independent risk factors for 5-year overall survival(OS),disease-free survival(DFS)and recurrence-free survival(RFS).Finally,a column chart model was constructed to evaluate and stratify patient prognosis.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this cohort study.Results:According to the number of incorporating high-risk pathological features,patients were divided into five groups:Hr_0 group(0 incorporating high-risk pathological feature),Hr_1 group(1 incorporating high-risk pathological feature),Hr_2 group(2 incorporating high-risk pathological features),Hr_3 group(3 incorporating high-risk pathological features),and Hr_4 group(4 or more incorporating high-risk pathological features).The Kaplan-Meier survival curve results indicated significant differences in OS,DFS and RFS among different groups(all P<0.001).Subgroup analysis was conducted on stage Ⅱ colorectal cancer,and the survival curves of OS,DFS and RFS in different Hr groups overlapped with each other.Compared to the overall population,the survival differences in different groups were significantly reduced,indicating that stage Ⅱ colon cancer patients with incorporating high-risk pathological features may benefit from adjuvant chemotherapy.The independent prognostic factors for RFS included age,pT stage,pN stage and Hr group.The survival curves of OS,DFS and RFS indicated that the prognosis of Hr_4 group was significantly worse than that of stage Ⅲc patients;5.2%and 14.1%of stage Ⅰ and Ⅱ patients had two or more incorporating high-risk pathological features(Hr group≥2),respectively.Finally,a column chart model was constructed by incorporating the independent prognostic risk factors for CRC mentioned above.The calibration curve showed a good consistency between the actual observations and the predictions made by the nomogram,and the decision curve analysis(DCA)indicated that the model constructed in this study had good efficacy in stratifying recurrence.Conclusion:The number of incorporating high-risk pathological features is an independent prognostic factor for RFS in patients with stage Ⅰ-ⅢCRC.Combining it as a multiclass variable with age,pT and pN stage has good prognostic stratification and recurrence stratification efficacy,which is expected to guide clinical treatment.

Background and purpose:Silent information regulator proteins(sirtuins,SIRT)are a class Ⅲ histone deacetylases with nicotinamide adenine dinucleotide(NAD+)as coenzyme.YME1 like 1 ATPase(YME1L1)is essential for the maintenance of mitochondrial morphology,function and plasticity.Optic atrophy 1(OPA1)mainly mediates mitochondrial fusion.The aim of this study was to explore the expression of SIRT3 in the endocrine resistance of breast cancer,the relationship between SIRT3 and YME1L1 and OPA1,and the mechanism of SIRT3 in the endocrine resistance of breast cancer.Methods:4-hydroxytamoxifen was used to induce tamoxifen-resistant MCF-7/TAM cells.cell counting kit-8(CCK-8)was used to detect cell proliferation and verify drug resistance.The mitochondrial morphology was observed by transmission electron microscopy(TEM)and immunofluorescence staining.The expressions of SIRT3 and OPA1 were detected by real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.JC-1 staining was used to detect mitochondrial membrane potential,and dihydroethidium(DHE)staining was used to detect reactive oxygen species(ROS)to verify mitochondrial function.SIRT3 was knocked down in drug-resistant cells by RNA interference,and SIRT3 and YME1L1 wild type(WT),simulated acetylation state mutant(MUT K237Q),and simulated deacetylation state mutant(MUT K237R)were overexpressed in parental cells by overexpression plasmid.Immunoprecipitation assay(IP)and immunofluorescence(IF)were used to verify the interaction between SIRT3 and YME1L1.Results:RTFQ-PCR and Western blot results showed that SIRT3 gene expression and protein level was significantly higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in parental cells decreased the sensitivity of breast cancer cells to tamoxifen.Knockdown of SIRT3 in drug-resistant cells enhanced the sensitivity of drug-resistant cells to tamoxifen.DHE staining showed that the ROS level was lower in tamoxifen resistant cells than in parental cells at the same concentration.Transmission electron microscopy and fluorescence staining showed that the mitochondria of the drug-resistant cells were elongated compared with the parental cells.Western blot results showed that the expression level of L-OPA1 protein was higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in the parental cells resulted in enhanced mitochondrial function and longer mitochondrial morphology compared with the control cells.Western blot showed that the expression of L-OPA1 was upregulated.When SIRT3 was knocked down in drug-resistant cells,the opposite result was obtained.We further verified how SIRT3 regulated OPA1 protein,affected the morphology and function of mitochondria,and promoted drug resistance of breast cancer.Overexpression of YME1L1(wild-type and mutant plasmids)in parental cells showed that overexpression of YME1L1 in the simulated deacetylation state resulted in similar results as overexpression of SIRT3,and overexpression of YME1L1 in the acetylated state resulted in similar results as knockdown of SIRT3.IP assay confirmed the interaction between SIRT3 and YME1L1 in breast cancer cells.The acetylation level of YME1L1 was different at different SIRT3 expression levels.IF assay showed that YME1L1 was co-localized with SIRT3 in MCF-7 cells.Conclusion:SIRT3 is highly expressed in tamoxifen-resistant breast cancer cells.SIRT3 upregulates L-OPA1 expression by deacetylating YME1L1,thereby promoting mitochondrial fusion and enhancing mitochondrial function,and promotes tamoxifen resistance in breast cancer.

Background and purpose:Colorectal carcinoma(CRC)is a common malignant tumor with incidence and mortality rates second only to gastric cancer and esophageal cancer among digestive system malignancies.Increasing evidence suggests that immune cells play a significant role in the occurrence and development of CRC.The aim of this study was to construct a prognostic model related to immune cell-associated genes to predict the prognosis of CRC patients and enable precise management.Methods:Single-cell RNA sequencing(scRNA-seq)and bulk RNA sequencing(RNA-seq)data,along with clinical information for colorectal cancer,were downloaded from the Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)databases.Differential genes of immune cell subtypes were extracted,and genes related to prognosis were screened in TCGA data using Cox regression and LASSO regression,with external validation using GSE39582 and GSE41258.The prognostic model was used to analyze chemotherapy drug sensitivity,assess immunotherapy efficacy,analyze pathways related to risk scores,and perform clinical correlation analysis.Finally,the expression levels of model genes were validated in 10 fresh frozen CRC tissues with post-operative pathological examination and cell lines using real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and immunohistochemistry.All samples were approved by the Fudan University Shanghai Cancer Center Ethics Committee(No.050432-4-2108*).Results:We defined 16 cell clusters based on the scRNA-seq dataset(GSE161277)and labeled these clusters as different cell types using the R package celldex.Differential analysis of immune cell subtypes yielded 374 differentially expressed genes.Using univariate Cox and LASSO analyses,we constructed a 9-gene risk prognostic model in CRC.This risk model exhibited reliable prognostic prediction performance and played an important role in predicting anti-tumor drug sensitivity,immunotherapy efficacy,potential molecular mechanisms,and clinical characteristics.Patients with high-risk scores had a lower probability of benefiting from immunotherapy.Conclusion:We constructed a 9-gene risk prognostic model based on the heterogeneity of immune cells in the CRC tumor microenvironment,which predicted the survival and treatment outcomes of CRC patients.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Background and purpose:Transmembrane and coiled-coil domains 1(TMCO1)is a recently discovered endoplasmic reticulum calcium channel protein that has been found to be associated with the progression of various tumors,however,its role in cervical cancer has not yet been clarified.This study aimed to investigate the effects of TMCO1 on the proliferation and migration of cervical cancer HeLa cells.Methods:By transfecting cervical cancer HeLa cells with plasmids,cells with stable overexpression of TMCO1 and cells with stable knockdown of TMCO1 were obtained.Cell counting kit-8(CCK-8)assay,clone formation assay and EdU labeling assay were used to detect cell proliferation ability,transwell assay was used to detect cell migration ability,and proteomic analysis was performed on the cells that stably overexpressed TMCO1 and control cells.Results:TThe CCK-8 experiment and clone formation experiment showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased their proliferation ability(P＜0.05).EdU labeling experiments showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased the number of cells undergoing active DNA synthesis(P＜0.01).After knocking down TMCO1 in cervical cancer HeLa cells,the expression of cell cycle inhibitory protein p27 increased,and the phosphorylation of histone H3 decreased.Clonogenesis experiments showed that knocking down TMCO1 significantly inhibited the proliferation of cervical cancer HeLa cells(P＜0.001).EdU labeling experiments showed that after knocking down TMCO1 in cervical cancer HeLa cells,the number of cells undergoing active DNA synthesis was significantly reduced(P<0.05).Transwell experiment showed that overexpression of TMCO1 in cervical cancer HeLa cells significantly increased their migration ability(P＜0.001),while knocking down TMCO1 significantly inhibited the migration of cervical cancer HeLa cells(P＜0.001).The pathways related to extracellular matrix adhesion and PI3K-AKT signaling were significantly upregulated in the cells with stable overexpression of TMCO1,while ribosome related pathways were downregulated in proteomic analysis.Conclusion:Overexpression of TMCO1 significantly promotes the proliferation and migration of cervical cancer cells,while knockdown of TMCO1 significantly inhibits the proliferation and migration of cervical cancer HeLa cells.TMCO1 may affect the proliferation and migration of HeLa cells by regulating cell adhesion and signal transduction.

Background and purpose:Preoperative risk categorization of thymoma is useful for treatment decisions but remains challenging.This study focused on training radiomics models using contrast-enhanced computed tomography(CECT)images for thymoma risk categorization and validating the model's performance,reliability and generalizability in a relatively large cohort.Methods:This retrospective cohort study analyzed the clinical data of thymoma patients(Masaoka Koga Ⅰ-Ⅲ)who underwent thymectomy surgery at the Affiliated Chest Hospital of Shanghai Jiao Tong University School of Medicine from January 2008 to December 2017.The cohort was divided into a training group(80%)and a test group(20%)using stratified random selection.The gold standard for histologic types was based on surgically resected specimens.Low-risk histologic types included A,AB and B1.High-risk histologic types included B2 and B3.Radiomics features were extracted from manually segmented regions of interest on preoperative CECT images.Interobserver correlation and least absolute shrinkage and selection operator(LASSO)regression were used for feature selection.Model performance metrics included area under the curve(AUC)of receiver operating characteristic(ROC)curve,sensitivity and specificity.Clinical characteristics were added to the combined model.Results:A total of 478 patients(mean age 51.3±12.3 years,48.1%was male)were included.The AUC of the clinical model,the CECT-based model,and the model using both clinical and CECT features on the test set were 0.666,0.831 and 0.850,respectively.The best performing model had a sensitivity of 0.829 and a specificity of 0.764.Conclusion:CECT-based radiomics models showed good performance in risk categorization of thymomas.

Pancreatic cancer is a worldwide medical and health problem.Due to its high heterogeneity and malignant phenotype,the 5-year survival rate of pancreatic cancer is only 7.2%,which is a serious threat to human health.The biological mechanism and drug development research of pancreatic cancer often rely on the traditional two-dimensional culture models(cell lines)and patient-derived xenograft models.However,cell lines lack the three-dimensional environment and heterogeneity of the tumor,while xenograft models have the disadvantages of long culture time,low success rate and difficulty in carrying out high-throughput drug screening.There is an urgent need to develop three-dimensional culture models that can highly reflect the characteristics and molecular variation of pancreatic cancer.As a three-dimensional culture model developed in recent years,human-derived pancreatic cancer organoids are multicellular units extracted from tissue samples and embedded in extracellular matrix gels after mechanical and enzymatic digestion,which can reproduce the histological characteristics and organ characteristics of the original patient,and even have the functions of the original organ.With the continuous development and improvement of pancreatic cancer organoids culture system,its simple,economical and stable culture technology has been gradually established,which promotes the application of human pancreatic cancer organoids to high-throughput drug screening,individualized precision treatment and deeper pathogenesis and targeted drug development research.At the same time,human-derived pancreatic cancer organoids are also a novel semi-in vivo model for the study of clinical molecular typing of pancreatic cancer,especially for the study of etiology,molecular characteristics,histomorphology and somatic mutation burden of patients with high mutation rate and high heterogeneity.The construction of human pancreatic cancer organoid biobank with large sample size is a new platform for biology,basic medicine and clinical science oncology research,which provides a reliable resource for the in-depth study of the pathogenesis of pancreatic cancer and the development of treatment strategies.In summary,the research progress of human pancreatic cancer organoids promotes the application of laboratory models that recapitulate the characteristics of clinical patients,improves the connection between basic laboratory research and clinical patients,and provides clinical sources for drug screening,pathogenesis research,individualized treatment strategies and the construction of biobanks.Therefore,this article reviewed the latest research progress of human pancreatic cancer organoids,in order to provide reference for researchers engaged in the research of human pancreatic cancer organoids.

The current focus of materials science and biomedical science research lies in two-dimensional(2D)MXenes materials,which possess an array of distinctive material attributes.These include superior optical characteristics,a high specific surface area,remarkable hydrophilicity,facile surface functionalization modification and impressive electrochemical properties.These features endow MXenes with vast application potential across multiple domains,particularly in the biomedical realm where advancements in tumor diagnosis and therapy have garnered significant research interest.These advancements primarily center on the enhancement of imaging technology and treatment methodologies.Notably,MXenes exhibit an array of unique physical and chemical properties,including remarkable fluorescence quenching capabilities,superior X-ray attenuation performance and highly efficient photothermal conversion.In the realm of diagnostic technologies,MXenes materials have emerged as a promising candidate for multimodal imaging,encompassing fluorescence imaging,photoacoustic imaging,computed tomography and magnetic resonance imaging(MRI).These materials,through their composite design,offer the potential to transcend the limitations of single-mode diagnostic techniques,thereby fostering innovative approaches in tumor imaging.Furthermore,MXenes exhibit exceptional characteristics as combination therapy materials,particularly in targeted drug delivery and optical therapy for tumor treatment.By harnessing the diverse physical and chemical properties of MXenes,personalized treatment strategies can be realized through precise drug delivery,thereby mitigating the toxic side effects associated with systemic chemotherapy.Currently,a pressing challenge in cancer research lies in the rational design and modification of MXenes probes that possess both diagnostic and therapeutic capabilities.This article aimed to provide a comprehensive review of the latest advancements,opportunities and challenges associated with two-dimensional MXenes materials and their derivatives in the context of tumor diagnosis and treatment.Additionally,it delved into the material synthesis,surface modification and tumor imaging research conducted in this field.Furthermore,it examined the obstacles and limitations encountered in the utilization of MXenes in the present context.The research and development of MXenes materials were integral to nanotherapy,and their novel properties,biological effects and oncological application value were thoroughly analyzed,in order to offer more effective and safer therapeutic options for cancer patients.