AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcino...AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.展开更多
Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytos...Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.展开更多
基金Supported by Hong Kong Wang Kuan Cheng GrantInner Mongolia Stem Cell Grant, No. kjk10jhg
文摘AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.
基金funded by"Beijing Natural Science Foundation,grant number 6224060","Young Elite Scientists Sponsorship Program by BAST,grant number",BYESS2023192"Program of Beijing Municipal Education Commission,grant number KM202310020006"+1 种基金"Bejing University of Agriculture science and Technology innovation Sparkling support plan,grant number,BUA-HHXD2022007""2022 Research and Innovation ability improvement plan for young teachers of Beijing University of Agriculture,grant number QJKC2022028".
文摘Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.
