Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are i...Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.展开更多
Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stim...Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stimulation by signal factors and/or growth factors,organoids self-assemble to replicate the morphological and structural characteristics of the corresponding organs.They provide an extraordinary platform for investigating organ development and mimicking pathological processes.Organoid biobanks derived from a wide range of carcinomas have been established to represent different lesions or stages of clinical tumors.Importantly,genomic and transcriptomic analyses have confirmed maintenance of intra-and interpatient heterogeneities in organoids.Therefore,this technology has the potential to revolutionize drug screening and personalized medicine.In this review,we summarized the characteristics and applications of organoids in cancer research by the establishment of organoid biobanks directly from tumor organoids or from genetically modified non-cancerous organoids.We also analyzed the current state of organoid applications in drug screening and personalized medicine.展开更多
Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease and its incidence rate is rapidly rising.However,effective therapies for the treatment of IPF are still lacking.Phosphodiesterase 4(PDE4)inhibitors were ...Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease and its incidence rate is rapidly rising.However,effective therapies for the treatment of IPF are still lacking.Phosphodiesterase 4(PDE4)inhibitors were reported to be potential anti-fibrotic agents.Herein,structure-based hit-to-lead optimization of natural isoaurostatin(8.98μmol/L)resulted in several potent inhibitors of PDE4 with half maximal inhibitory concentration(IC_(50))values ranging from 35 nmol/L to 126 nmol/L.Co-crystal structures revealed that isoaurostatin compounds exhibited different binding patterns from the classic PDE4 inhibitor rolipram and the analogues would favor to be Z configurations other than the corresponding E isomers.Finally,lead 2–9 showed remarkable in vitro/in vivo anti-fibrotic effects indicating its potential as a novel anti-IPF agent.展开更多
Objective:To evaluate the effectiveness of incorporating ideological and political education into anesthesiology residency training,using the Mini Clinical Evaluation Exercise combined with Direct Observation of Proce...Objective:To evaluate the effectiveness of incorporating ideological and political education into anesthesiology residency training,using the Mini Clinical Evaluation Exercise combined with Direct Observation of Procedural Skills.Methods:Sixty resident physicians undergoing standardized training in the Anesthesiology Department of Jiangsu Cancer Hospital from December 2023 to June 2024 were randomly assigned to a control group and an observation group,with 30 residents in each.The control group received traditional clinical skill training,while the observation group received additional ideological and political education on the basis of control group.Both groups were evaluated using Mini Clinical Evaluation Exercise and Direct Observation of Procedural Skills.Patient satisfaction with the residents was rated anonymously,and student feedback on the training model was collected via a questionnaire.Results:The residents in the observation group demonstrated superior performance in doctor-patient communication,humanistic care,and professional competence compared to the control group(P<0.05).Patient satisfaction scores were also higher in the observation group(P<0.05).Conclusion:Integrating ideological and political education into standardized anesthesiology residency training can significantly enhance residents’communication skills,humanistic care,and professional competence,leading to higher patient satisfaction.展开更多
Worldwide, colorectal cancer(CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy,radiotherapy and immun...Worldwide, colorectal cancer(CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy,radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines(CHMs) for the prevention and treatment of CRC.CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapyinduced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic,and suggests novel directions for new drug discovery against CRC.展开更多
Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We pr...Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.展开更多
Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the im...Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.展开更多
As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of ...As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.展开更多
Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutroph...Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.展开更多
Herein,we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled byβ-cyclodextrin(β-CD)based host-vip recognitions.This nanovaccine can generate significant titers...Herein,we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled byβ-cyclodextrin(β-CD)based host-vip recognitions.This nanovaccine can generate significant titers of antibodies and improve the therapeutic effect against melanoma,suggesting the immunogenicity of peptide antigens can be improved by loading with this carrier.The novel vaccine carrier provides a platform for the transport of various antigens especially T cell-independent antigens.展开更多
The liver is the largest solid organ,and it is involved in multiple biological processes,including energy metabolism,protein synthesis,and detoxification1.Under physiological or pathological conditions,the liver can r...The liver is the largest solid organ,and it is involved in multiple biological processes,including energy metabolism,protein synthesis,and detoxification1.Under physiological or pathological conditions,the liver can regrow to normal size even after resection of 90%of the liver volume because of its strong regeneration ability2.Changes in diet,viral infection(HBV and/or HCV)。展开更多
Translational Cancer Research （Transl Cancer Res; TCR; Print ISSN： 2218-676X; Online ISSN 2219-6803; www. thetcr.org） launched in August 2013 a special issue on Applications of Nanotechnology in Radiation Research ...Translational Cancer Research （Transl Cancer Res; TCR; Print ISSN： 2218-676X; Online ISSN 2219-6803; www. thetcr.org） launched in August 2013 a special issue on Applications of Nanotechnology in Radiation Research inviting Prof. Rao V.L. Papineni from University of Kansas Medical Center, Pataje G.S. Prasanna from National Cancer Institute and Mansoor M. Ahmed, National Cancer Institute to serve as the vip Editors.展开更多
Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonf...Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.展开更多
Epigenetic dysregulation is a key factor leading to oncogenesis and tumor progression1. To date, seven agents in three epigenetic target classes have been approved by the U.S. Food and Drug Administration for the trea...Epigenetic dysregulation is a key factor leading to oncogenesis and tumor progression1. To date, seven agents in three epigenetic target classes have been approved by the U.S. Food and Drug Administration for the treatment of diverse malignancies. Despite this approval for clinical application, the mechanisms of many epigenetic modulators are not completely understood, because many genes are epigenetically regulated.展开更多
Viewing cancer as a large,evolving population of heterogeneous cells is a common perspective.Because genomic instability is one of the fundamental features of cancer,this intrinsic tendency of genomic variation leads ...Viewing cancer as a large,evolving population of heterogeneous cells is a common perspective.Because genomic instability is one of the fundamental features of cancer,this intrinsic tendency of genomic variation leads to striking intratumor heterogeneity and functions during the process of cancer formation,development,metastasis,and relapse.With the increased mutation rate and abundant diversity of the gene pool,this heterogeneity leads to cancer evolution,which is the major obstacle in the clinical treatment of cancer.Cells rely on the integrity of DNA repair machineries to maintain genomic stability,but these machineries often do not function properly in cancer cells.The deficiency of DNA repair could contribute to the generation of cancer genomic instability,and ultimately promote cancer evolution.With the rapid advance of new technologies,such as single-cell sequencing in recent years,we have the opportunity to better understand the specific processes and mechanisms of cancer evolution,and让s relationship with DNA repair.Here,we review recent findings on how DNA repair affects cancer evolution,and discuss how these mechanisms provide the basis for critical clinical challenges and therapeutic applications.展开更多
Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chr...Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver repair.Methods:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted mice.Immunohistochemistry and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the disease.The cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ hybridization.Results:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient mice.Furthermore,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse model.DEN-induced HCCs exhibited a similar histological phenotype and genomic profile as human HCCs.Conclusions:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.展开更多
Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective...Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.展开更多
A facile and efficient strategy was established for the construction of RC-529 and its derivatives.Four conjugates of RC-529 derivatives with Tn antigen were synthesized and all elicited strong and T celldependent imm...A facile and efficient strategy was established for the construction of RC-529 and its derivatives.Four conjugates of RC-529 derivatives with Tn antigen were synthesized and all elicited strong and T celldependent immune responses in mice without requiring external adjuvants.In addition,all antisera induced by these conjugates could specifically recognize,bind to and kill Tn-overexpressing cancer cells.Thus,RC-529 shows promise as a useful platform for the development of new vaccine carriers with self-adjuvanting properties for the treatment of cancer.Moreover,preliminary structure-activity relationship analysis provides convincing support for further optimization of,and additional investigation into RC-529.展开更多
Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer ...Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer includes two major types： hepatocellular carcinoma （HCC, about 80%） and cholangiocarcinoma （CCA, about 15%）. Many etiological factors contribute to HCC development, such as hepatitis B virus （HBV）, hepatitis C virus （HCV）, aflatoxin B1 （AFB1）, alcohol, and metabolic diseases3. By contrast, the major risk factors for CCA are liver flukes （Opisthorchis viverrini and Clonorchis sinensis） and primary sclerosing cholangitis4,展开更多
Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), whic...Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients. Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast Cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and survival data were available for up to 17 years. Overall survival (OS) was analyzed through the Kaplan-Meier method stratified by E-cadherin, LVD, VEGF-D, and response to chemotherapy. The differences in OS curves were compared using the log-rank test. Results: The median OS for patients with high LVD was 6.63 years (95% CI: 4.06 to 10.14), compared to median at 10 years not reached in those with low LVD (p = 0.03). There was a trend towards a longer median OS in patients with high E-cadherin (10.14, 95% CI: 6.63 to 11.67), compared with those with low E-cadherin (6.26, 95% CI: 3.42 to undeterminable). VEGF-D levels showed no correlation with survival. Conclusion: Low LVD significantly predicts better survival. High E-cadherin expression, as with non-IBC breast cancer and several other malignancies, tends to be associated with a better prognosis.展开更多
文摘Somatic stem cells （SSCs）, being essential in maintaining homeostasis of normal tissue, replenish dying cells and regenerate damaged tissues for organism. On the other hand, with the self-renewed ability, SSCs are ideal cellular targets to be acquired in multiple mutations transforming SSCs to cancer stem cells （CSCs） which cause malignancies and even recurrence after cancer treatment if CSCs fail to be eradicated （1）.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.31671421,82030079,and 82003187).
文摘Organoids are three-dimensional culture systems generated from embryonic stem cells,induced pluripotent stem cells,and adult stem cells.They are capable of cell proliferation,differentiation,and self-renewal.Upon stimulation by signal factors and/or growth factors,organoids self-assemble to replicate the morphological and structural characteristics of the corresponding organs.They provide an extraordinary platform for investigating organ development and mimicking pathological processes.Organoid biobanks derived from a wide range of carcinomas have been established to represent different lesions or stages of clinical tumors.Importantly,genomic and transcriptomic analyses have confirmed maintenance of intra-and interpatient heterogeneities in organoids.Therefore,this technology has the potential to revolutionize drug screening and personalized medicine.In this review,we summarized the characteristics and applications of organoids in cancer research by the establishment of organoid biobanks directly from tumor organoids or from genetically modified non-cancerous organoids.We also analyzed the current state of organoid applications in drug screening and personalized medicine.
基金supported by the Natural Science Foundation of China(Nos.22277019,82150204,22307031,22377023,22077143,and 82003594)Key Project of Guangdong Natural Science Foundation(No.2016A030311033)+2 种基金Fundamental Research Funds for Hainan University(Nos.KYQD(ZR)-21031,KYQD(ZR)-21108,KYQD(ZR)-23003,and XTCX2022JKA01)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Science Foundation of Hainan Province(Nos.KJRC2023B10,824YXQN420,and 324MS018)。
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease and its incidence rate is rapidly rising.However,effective therapies for the treatment of IPF are still lacking.Phosphodiesterase 4(PDE4)inhibitors were reported to be potential anti-fibrotic agents.Herein,structure-based hit-to-lead optimization of natural isoaurostatin(8.98μmol/L)resulted in several potent inhibitors of PDE4 with half maximal inhibitory concentration(IC_(50))values ranging from 35 nmol/L to 126 nmol/L.Co-crystal structures revealed that isoaurostatin compounds exhibited different binding patterns from the classic PDE4 inhibitor rolipram and the analogues would favor to be Z configurations other than the corresponding E isomers.Finally,lead 2–9 showed remarkable in vitro/in vivo anti-fibrotic effects indicating its potential as a novel anti-IPF agent.
基金supported by the The Educational Research Project of Nanjing Medical University(SLYB 2023-02).
文摘Objective:To evaluate the effectiveness of incorporating ideological and political education into anesthesiology residency training,using the Mini Clinical Evaluation Exercise combined with Direct Observation of Procedural Skills.Methods:Sixty resident physicians undergoing standardized training in the Anesthesiology Department of Jiangsu Cancer Hospital from December 2023 to June 2024 were randomly assigned to a control group and an observation group,with 30 residents in each.The control group received traditional clinical skill training,while the observation group received additional ideological and political education on the basis of control group.Both groups were evaluated using Mini Clinical Evaluation Exercise and Direct Observation of Procedural Skills.Patient satisfaction with the residents was rated anonymously,and student feedback on the training model was collected via a questionnaire.Results:The residents in the observation group demonstrated superior performance in doctor-patient communication,humanistic care,and professional competence compared to the control group(P<0.05).Patient satisfaction scores were also higher in the observation group(P<0.05).Conclusion:Integrating ideological and political education into standardized anesthesiology residency training can significantly enhance residents’communication skills,humanistic care,and professional competence,leading to higher patient satisfaction.
基金supported by the grants of National Natural Science Foundation of China (No. 81703803 and 81720108033)Natural Science Foundation of Guangdong Province(No. 2017A030310464),which paid for planning and collection of literature+1 种基金by the Project of Guangzhou University of Chinese Medicine (No. QNYC20190103)Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine (No.2018B030322011),which paid for writing and submitting the article for publication。
文摘Worldwide, colorectal cancer(CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy,radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines(CHMs) for the prevention and treatment of CRC.CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapyinduced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic,and suggests novel directions for new drug discovery against CRC.
文摘Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.
文摘Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.
基金the National Natural Science Foundation of China(No.82073308 and No.81773211)the High-level startup fund of Nanjing Medical University(No.KY109RC2019010).
文摘As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.
基金jointly supported by the National Natural Science Foundation of China(Grant Nos.81972735,82030079,and 81972656)Beijing Natural Science Foundation(Grant No.7212108)+2 种基金Michigan Medicine and PKU-HSC JI(Grant No.BMU2020JI005)Baidu Foundation(Grant No.2020BD015)Ying Shi Foundation。
文摘Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.
基金the Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine(No.20188030322011)the National Natural Science Foundation of China(No.81773580)。
文摘Herein,we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled byβ-cyclodextrin(β-CD)based host-vip recognitions.This nanovaccine can generate significant titers of antibodies and improve the therapeutic effect against melanoma,suggesting the immunogenicity of peptide antigens can be improved by loading with this carrier.The novel vaccine carrier provides a platform for the transport of various antigens especially T cell-independent antigens.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81970459)。
文摘The liver is the largest solid organ,and it is involved in multiple biological processes,including energy metabolism,protein synthesis,and detoxification1.Under physiological or pathological conditions,the liver can regrow to normal size even after resection of 90%of the liver volume because of its strong regeneration ability2.Changes in diet,viral infection(HBV and/or HCV)。
文摘Translational Cancer Research （Transl Cancer Res; TCR; Print ISSN： 2218-676X; Online ISSN 2219-6803; www. thetcr.org） launched in August 2013 a special issue on Applications of Nanotechnology in Radiation Research inviting Prof. Rao V.L. Papineni from University of Kansas Medical Center, Pataje G.S. Prasanna from National Cancer Institute and Mansoor M. Ahmed, National Cancer Institute to serve as the vip Editors.
文摘Human endogenous retroviruses(HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K(HML6) and HERV-K(HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K(HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are twoedged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.
文摘Epigenetic dysregulation is a key factor leading to oncogenesis and tumor progression1. To date, seven agents in three epigenetic target classes have been approved by the U.S. Food and Drug Administration for the treatment of diverse malignancies. Despite this approval for clinical application, the mechanisms of many epigenetic modulators are not completely understood, because many genes are epigenetically regulated.
基金supported by the National Natural Science Foundation of China(Grant Nos.81672981 and 81972240).
文摘Viewing cancer as a large,evolving population of heterogeneous cells is a common perspective.Because genomic instability is one of the fundamental features of cancer,this intrinsic tendency of genomic variation leads to striking intratumor heterogeneity and functions during the process of cancer formation,development,metastasis,and relapse.With the increased mutation rate and abundant diversity of the gene pool,this heterogeneity leads to cancer evolution,which is the major obstacle in the clinical treatment of cancer.Cells rely on the integrity of DNA repair machineries to maintain genomic stability,but these machineries often do not function properly in cancer cells.The deficiency of DNA repair could contribute to the generation of cancer genomic instability,and ultimately promote cancer evolution.With the rapid advance of new technologies,such as single-cell sequencing in recent years,we have the opportunity to better understand the specific processes and mechanisms of cancer evolution,and让s relationship with DNA repair.Here,we review recent findings on how DNA repair affects cancer evolution,and discuss how these mechanisms provide the basis for critical clinical challenges and therapeutic applications.
基金supported by the grants from the National Natural Science Foundation of China(Grant No.81902401,81972656,31671421,81970107,81600083)the National 135 Major Project of China(Grant No.2018ZX10723204,2018ZX10302205)+3 种基金the Natural Science Foundation of Tianjin(Grant No.19JCQNJC09000)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT32034)CAMS Innovation Fund for Medical Sciences(Grant No.2016-12M-1-003)supported by the China Scholarship Council(Grant No.201906940003)。
文摘Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver repair.Methods:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted mice.Immunohistochemistry and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the disease.The cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ hybridization.Results:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient mice.Furthermore,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse model.DEN-induced HCCs exhibited a similar histological phenotype and genomic profile as human HCCs.Conclusions:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.
基金financially supported by the National Natural Science Foundation of China (No. 82030079, 82341005, 81972656 and 82173035)the National Science and Technology Major Project of China (No. 2022YFC3400 901)Sino-Russian Math Center in PKU。
文摘Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.
基金supported by the National Natural Science Foundation of China(Nos.81773580,82003594)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme to Guochao Liao(2019)+1 种基金the Department of education of Guangdong Province,China(No.2020KZDZX1057)the Science and Technology Planning Program of Guangzhou City,China(No.202008040004)。
文摘A facile and efficient strategy was established for the construction of RC-529 and its derivatives.Four conjugates of RC-529 derivatives with Tn antigen were synthesized and all elicited strong and T celldependent immune responses in mice without requiring external adjuvants.In addition,all antisera induced by these conjugates could specifically recognize,bind to and kill Tn-overexpressing cancer cells.Thus,RC-529 shows promise as a useful platform for the development of new vaccine carriers with self-adjuvanting properties for the treatment of cancer.Moreover,preliminary structure-activity relationship analysis provides convincing support for further optimization of,and additional investigation into RC-529.
基金supported,in part,by the Precision Medical Research Program from Ministry of Science and Technology of China(Grant No.YL 2017YFC0908400)National Science and Technology Major Project for Infectious Disease and Funding(Grant No.YL 17-163-12-ZT-005-095-01)+2 种基金Science and Technology Commission in Ministry of National Defense of China(Grant No.YL 17-163-12-ZT-005-095-01)Xinwei Wang was supported by the intramural research program of the Center for Cancer Research,National Cancer Institute of the United StatesJunfang Ji was supported by the Thousand Young Talents Plan of China,National Natural Science Foundation of China(Grant No.81672905)
文摘Introduction Primary liver cancer, the second most common cause of cancer related death worldwide, presents ethnic, etiological, sex, and geographical diversity2 （Figure 1A）. At the histological level, liver cancer includes two major types： hepatocellular carcinoma （HCC, about 80%） and cholangiocarcinoma （CCA, about 15%）. Many etiological factors contribute to HCC development, such as hepatitis B virus （HBV）, hepatitis C virus （HCV）, aflatoxin B1 （AFB1）, alcohol, and metabolic diseases3. By contrast, the major risk factors for CCA are liver flukes （Opisthorchis viverrini and Clonorchis sinensis） and primary sclerosing cholangitis4,
文摘Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients. Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast Cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and survival data were available for up to 17 years. Overall survival (OS) was analyzed through the Kaplan-Meier method stratified by E-cadherin, LVD, VEGF-D, and response to chemotherapy. The differences in OS curves were compared using the log-rank test. Results: The median OS for patients with high LVD was 6.63 years (95% CI: 4.06 to 10.14), compared to median at 10 years not reached in those with low LVD (p = 0.03). There was a trend towards a longer median OS in patients with high E-cadherin (10.14, 95% CI: 6.63 to 11.67), compared with those with low E-cadherin (6.26, 95% CI: 3.42 to undeterminable). VEGF-D levels showed no correlation with survival. Conclusion: Low LVD significantly predicts better survival. High E-cadherin expression, as with non-IBC breast cancer and several other malignancies, tends to be associated with a better prognosis.
