Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular cla...Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology,metastasis,immune microenvironment,and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes.Additionally,advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease.Herein,we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.展开更多
Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than eve...Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stressresponsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment （TMEN）. Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thor- ough and personalized.展开更多
Tumor infiltrating lymphocytes (TIL) were cultured with “moxibustion serum”(MS), and the results were examined by flow cytometry. The results indicated that MS could enhance the proliferation of TIL,accelerate it to...Tumor infiltrating lymphocytes (TIL) were cultured with “moxibustion serum”(MS), and the results were examined by flow cytometry. The results indicated that MS could enhance the proliferation of TIL,accelerate it to reach the exponential growth phase, and assist recombinant interleukin 2 (rIL-2) to enhance successively the percentage of CD3^+ positive cells, maintain the number of CD4^+ positive T cells, promote greatly the percentage of CD8^+ positive T cells among TILs, and reverse the CD4^+/CD8^+ ratio. Such cooperative effects rely on relative specificity of acupoints. It is suggested that MS is beneficial to the growth of TIL both in the aspects of proliferation and phenotypes.展开更多
A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal bio...A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.展开更多
AIM To investigate the effect of cryopreservation at 50℃ on the human hepatoma SMMC 7721 cell line. METHODS With 15% DMSO as cryopreservant, the SMMC 7721 cells were cryopreserved at 50℃, then thawed and re...AIM To investigate the effect of cryopreservation at 50℃ on the human hepatoma SMMC 7721 cell line. METHODS With 15% DMSO as cryopreservant, the SMMC 7721 cells were cryopreserved at 50℃, then thawed and recultured. The survival rate, mitotic index and LDH isoenzymes were compared between pre and post cryopreservation. RESULTS The survival rate could reach over 95%. Thirteen hours after the thaw, the mitotic index of cryopreserved SMMC 7721 cells decreased by 1 09%. The mode scope of chromosome number (46～53) after cryopreservation tended to transfer to that of normal human cells, and the percentage of metaphases containing 46 chromosomes changed from 0% to 16%. LDH isoenzymes changed from H like model (LDH3 (29 3%)>LDH4 (26 8%)>LDH2 (25 3%)>LDH5 (14 9%)>LDH1 (3 6%) to M like model (LDH4 (48 3%)>LDH5 (28 3%)>LDH3 (18 9%)>LDH2 (4 4%)>LDH1 (0%)). CONCLUSION ① 50℃ cryopreservation can be a convenient method for the cryopreservation of cell lines; ② 50℃ cryopreservation is likely involved in the changes of malignant phenotypes of human hepatoma SMMC 7721 cell line and may induce the differentiation of malignant cells.展开更多
Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy ...Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.展开更多
基金supported by grants from the Jilin Scientific and Technological Development Program(CN)(No.20190303146SF)General Program of National Natural Science Foundation of China(No.81874052)
文摘Small cell lung cancer(SCLC)is a highly malignant tumor with a very poor prognosis;therefore,more effective treatments are urgently needed for patients afflicted with the disease.In recent years,emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology,metastasis,immune microenvironment,and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes.Additionally,advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease.Herein,we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.
文摘Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stressresponsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment （TMEN）. Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thor- ough and personalized.
文摘Tumor infiltrating lymphocytes (TIL) were cultured with “moxibustion serum”(MS), and the results were examined by flow cytometry. The results indicated that MS could enhance the proliferation of TIL,accelerate it to reach the exponential growth phase, and assist recombinant interleukin 2 (rIL-2) to enhance successively the percentage of CD3^+ positive cells, maintain the number of CD4^+ positive T cells, promote greatly the percentage of CD8^+ positive T cells among TILs, and reverse the CD4^+/CD8^+ ratio. Such cooperative effects rely on relative specificity of acupoints. It is suggested that MS is beneficial to the growth of TIL both in the aspects of proliferation and phenotypes.
基金supported,in part or whole,by the National Natural Science Foundation of China(Nos.32171395,U19A2006,and 12132004)the Sichuan Science and Technology Program(Nos.2021YJ0130,2022NSFSC0048,and 2023NSFSC0715,China)the Joint Funds of Center for Engineering Medicine(Nos.ZYGX2021YGLH010,ZYGX2021YGLH017,and ZYGX2021YGLH204,China)。
文摘A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.
文摘AIM To investigate the effect of cryopreservation at 50℃ on the human hepatoma SMMC 7721 cell line. METHODS With 15% DMSO as cryopreservant, the SMMC 7721 cells were cryopreserved at 50℃, then thawed and recultured. The survival rate, mitotic index and LDH isoenzymes were compared between pre and post cryopreservation. RESULTS The survival rate could reach over 95%. Thirteen hours after the thaw, the mitotic index of cryopreserved SMMC 7721 cells decreased by 1 09%. The mode scope of chromosome number (46～53) after cryopreservation tended to transfer to that of normal human cells, and the percentage of metaphases containing 46 chromosomes changed from 0% to 16%. LDH isoenzymes changed from H like model (LDH3 (29 3%)>LDH4 (26 8%)>LDH2 (25 3%)>LDH5 (14 9%)>LDH1 (3 6%) to M like model (LDH4 (48 3%)>LDH5 (28 3%)>LDH3 (18 9%)>LDH2 (4 4%)>LDH1 (0%)). CONCLUSION ① 50℃ cryopreservation can be a convenient method for the cryopreservation of cell lines; ② 50℃ cryopreservation is likely involved in the changes of malignant phenotypes of human hepatoma SMMC 7721 cell line and may induce the differentiation of malignant cells.
文摘Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 - 30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.
