To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,10 more questions are ...To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,10 more questions are presented as follows.Question 15:Can tumor-induced erythrogenesis provide qualified red blood cells for carrying oxygen to distant organs?Question 16:Can we overcome tumor resistance to platinum-containing antineoplastic drugs by activating the sensitivity factors in the tumor?Question 17:How can a cancer cell stay dormant for years?Question 18:Why do cancer cells use distinct transcriptomic and proteomic programs to reach the same metastatic phenotype?Question 19:Why do some cancers regress spontaneously?Question 20:What are the regulatory mechanisms occurring in donor cells that determine selective sorting of biological content into vesicles and their biological consequences in recipient cells?Are the genetic transfer and exchange of biological messages between cells transient?Is the phenotypic manipulation of recipient cells temporary or prolonged and persistent?If extracellular vesicles possess immune-modulatory potential,how could they be exploited for immune interventions and cancer immunotherapy?Presumably the cargo of extracellular vesicles reflects the cells of their origin and can be used for cancer diagnosis,how could the uniform/stringent capture criteria be met universally for applying EVs in point-of-care diagnostics for cancer patients?Question 21:Can we use self-sampling technologies to monitor the tumor genetic alterations for more precise targeted therapy?Can we cure a heterogeneous tumor by sequentially targeting the driver molecules?Question 22:Can we postpone the onset of non-infection-related cancers?Question 23:How many types of cells can jointly form the tumor vasculature to provide blood supply for tumor progression?Question 24:How tumor cells transmit their epigenetic features to daughter cells and maintain the malignant phenotype?展开更多
Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC p...Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.展开更多
Conventional and targeted chemotherapies remain integral strategies to treat solid tumors. Despite the large number of anti-cancer drugs available, chemotherapy does not completely eradicate disease. Disease recurrenc...Conventional and targeted chemotherapies remain integral strategies to treat solid tumors. Despite the large number of anti-cancer drugs available, chemotherapy does not completely eradicate disease. Disease recurrence and the growth of drug resistant tumors remain significant problems in anti-cancer treatment. To develop more effective treatment strategies, it is important to understand the underlying cellular and molecular mechanisms of drug resistance. It is generally accepted that cancer cells do not function alone, but evolve through interactions with the surrounding tumor microenvironment. As key cellular components of the tumor microenvironment, fibroblasts regulate the growth and progression of many solid tumors. Emerging studies demonstrate that fibroblasts secrete a multitude of factors that enable cancer cells to become drug resistant. This review will explore how fibroblast secretion of soluble factors act on cancer cells to enhance cancer cell survival and cancer stem cell renewal, contributing to the development of drug resistant cancer.展开更多
Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and ...Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.展开更多
目的探究休眠的多倍体巨大肿瘤细胞(polyploid giant cancer cells,PGCC)对鼻咽癌(nasopharyngeal carcinoma,NPC)复发的影响,明确抑制自噬在阻止NPC复发中的作用。方法利用紫杉醇(paclitaxel,PTX)诱导NPC细胞来源的PGCC(NPC-PGCC)形成...目的探究休眠的多倍体巨大肿瘤细胞(polyploid giant cancer cells,PGCC)对鼻咽癌(nasopharyngeal carcinoma,NPC)复发的影响,明确抑制自噬在阻止NPC复发中的作用。方法利用紫杉醇(paclitaxel,PTX)诱导NPC细胞来源的PGCC(NPC-PGCC)形成,并利用光学显微镜、细胞免疫荧光、活/死细胞双染色实验对PGCC形态、多倍体特性、细胞活性等进行鉴定。采用转录组测序(RNA-seq)检测NPC-PGCC和二倍体NPC细胞CNE2的差异表达基因。采用基因本体论(gene ontology,GO)、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)对差异基因进行功能富集和通路注释分析。利用免疫蛋白印迹与细胞透射电镜实验评估NPC-PGCC细胞中的自噬水平。利用临床高度相关的裸鼠NPC复发模型研究自噬在NPC-PGCC形成中的作用及NPC-PGCC对NPC复发的影响。所有数据采用GraphPad Prism 6进行统计学分析,以P<0.05为差异具有统计学意义。结果紫杉醇诱导形成的NPC-PGCC具有休眠后爆炸性分裂的特征。NPC-PGCC和二倍体NPC细胞CNE2的差异基因GO富集、KEGG通路注释主要集中在自噬及其相关通路。NPC-PGCC细胞中的自噬水平显著增强。临床高度相关裸鼠NPC复发模型中,进行顺铂治疗的裸鼠原发肿瘤中PGCC数量高于其余各组;自噬抑制剂预处理后与顺铂联合治疗的裸鼠原发肿瘤中PGCC数量少,同时复发率显著低于其余各组。结论休眠多倍体巨大肿瘤细胞的形成机制与自噬有关,抑制自噬可通过抑制PGCC形成进而抑制NPC复发。展开更多
Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Ac...Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.展开更多
基金FAPESP(Sao Paulo Research Foundation, Proc.No.12/24574–3)CAPES(Coordination for the Improvement of Higher Education Personnel, Proc.No.BEX 7057/15-6)-Brazil
文摘To accelerate our endeavors to overcome cancer,Chinese Journal of Cancer has launched a program of publishing 150most important questions in cancer research and clinical oncology.In this article,10 more questions are presented as follows.Question 15:Can tumor-induced erythrogenesis provide qualified red blood cells for carrying oxygen to distant organs?Question 16:Can we overcome tumor resistance to platinum-containing antineoplastic drugs by activating the sensitivity factors in the tumor?Question 17:How can a cancer cell stay dormant for years?Question 18:Why do cancer cells use distinct transcriptomic and proteomic programs to reach the same metastatic phenotype?Question 19:Why do some cancers regress spontaneously?Question 20:What are the regulatory mechanisms occurring in donor cells that determine selective sorting of biological content into vesicles and their biological consequences in recipient cells?Are the genetic transfer and exchange of biological messages between cells transient?Is the phenotypic manipulation of recipient cells temporary or prolonged and persistent?If extracellular vesicles possess immune-modulatory potential,how could they be exploited for immune interventions and cancer immunotherapy?Presumably the cargo of extracellular vesicles reflects the cells of their origin and can be used for cancer diagnosis,how could the uniform/stringent capture criteria be met universally for applying EVs in point-of-care diagnostics for cancer patients?Question 21:Can we use self-sampling technologies to monitor the tumor genetic alterations for more precise targeted therapy?Can we cure a heterogeneous tumor by sequentially targeting the driver molecules?Question 22:Can we postpone the onset of non-infection-related cancers?Question 23:How many types of cells can jointly form the tumor vasculature to provide blood supply for tumor progression?Question 24:How tumor cells transmit their epigenetic features to daughter cells and maintain the malignant phenotype?
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 106-2320-B-255-005 and No.MOST 107-2320-B-255-003Chang Gung Medical Research Foundation,Taoyuan,Taiwan,No.CMRPF1G0011,No.CMRPF1G0251,No.CMRPF1I0031,No.CMRPF1H0051,and No.CMRPF1I0041Chang Gung University of Science and Technology,Taoyuan,Taiwan,No.ZRRPF3H0131
文摘Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.
文摘Conventional and targeted chemotherapies remain integral strategies to treat solid tumors. Despite the large number of anti-cancer drugs available, chemotherapy does not completely eradicate disease. Disease recurrence and the growth of drug resistant tumors remain significant problems in anti-cancer treatment. To develop more effective treatment strategies, it is important to understand the underlying cellular and molecular mechanisms of drug resistance. It is generally accepted that cancer cells do not function alone, but evolve through interactions with the surrounding tumor microenvironment. As key cellular components of the tumor microenvironment, fibroblasts regulate the growth and progression of many solid tumors. Emerging studies demonstrate that fibroblasts secrete a multitude of factors that enable cancer cells to become drug resistant. This review will explore how fibroblast secretion of soluble factors act on cancer cells to enhance cancer cell survival and cancer stem cell renewal, contributing to the development of drug resistant cancer.
文摘Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer treatment.Since tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the tumor.Based on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against therapy.We discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"popula-tions.Furthermore,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer cells.Beyond understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to treatment.More-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in tumors.Overall,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.
文摘目的探究休眠的多倍体巨大肿瘤细胞(polyploid giant cancer cells,PGCC)对鼻咽癌(nasopharyngeal carcinoma,NPC)复发的影响,明确抑制自噬在阻止NPC复发中的作用。方法利用紫杉醇(paclitaxel,PTX)诱导NPC细胞来源的PGCC(NPC-PGCC)形成,并利用光学显微镜、细胞免疫荧光、活/死细胞双染色实验对PGCC形态、多倍体特性、细胞活性等进行鉴定。采用转录组测序(RNA-seq)检测NPC-PGCC和二倍体NPC细胞CNE2的差异表达基因。采用基因本体论(gene ontology,GO)、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)对差异基因进行功能富集和通路注释分析。利用免疫蛋白印迹与细胞透射电镜实验评估NPC-PGCC细胞中的自噬水平。利用临床高度相关的裸鼠NPC复发模型研究自噬在NPC-PGCC形成中的作用及NPC-PGCC对NPC复发的影响。所有数据采用GraphPad Prism 6进行统计学分析,以P<0.05为差异具有统计学意义。结果紫杉醇诱导形成的NPC-PGCC具有休眠后爆炸性分裂的特征。NPC-PGCC和二倍体NPC细胞CNE2的差异基因GO富集、KEGG通路注释主要集中在自噬及其相关通路。NPC-PGCC细胞中的自噬水平显著增强。临床高度相关裸鼠NPC复发模型中,进行顺铂治疗的裸鼠原发肿瘤中PGCC数量高于其余各组;自噬抑制剂预处理后与顺铂联合治疗的裸鼠原发肿瘤中PGCC数量少,同时复发率显著低于其余各组。结论休眠多倍体巨大肿瘤细胞的形成机制与自噬有关,抑制自噬可通过抑制PGCC形成进而抑制NPC复发。
基金supported by grants of 81530093 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of China+23 种基金supported by grants of 31390431 from the National Natural Science Foundation of Chinasupported by grants of Natural Sciences Foundation of China(31301007 and 81272525)supported by grants of 81622010 from the National Natural Science Foundation of Chinasupported by grants of 81472717 and 81673474 from the National Natural Science Foundation of China81661128007, 81472653 and 81530080 from National Natural Science Foundation of Chinasupported by grants of 81400286 and 81530093 from the National Natural Science Foundation of Chinasupported by grants of 81400140 from the National Natural Science Foundation of Chinasupported by grants of 81503128 from the National Natural Science Foundation of China2016I2M-1-008 from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciencessupported by grants of 2014CB542103 from National Basic Research Program of China81502473 from National Natural Science Fund for Young Scholars of Chinasupported by US National Institutes of Health grants (CA217510, CA123088, CA099985, CA193136 and CA152470)supported by grants from the Canadian Institutes of Health Research(FRN 123516 and 152954)the Ontario Institute for Cancer Research(ORBiT)supported by NIH grant GM072744Ministry of Science and Technology of China grant 2016YFA0101100the Fundamental Research Fund for the Central University(No. 2017KFQWJX002) from Huazhong University of Science and TechnologyCore fund (Wang2016) for Development of Cell and Gene Therapy Centre of Academy of Medical Sciences,Zhengzhou UniversityThe MRC (MR/M015696/1)2017YFA0205400 from Ministry of Science and Technology of China2016ZX310190 and 2016ZX320014 from Central Public-interest Scientific Institution Basal Research Fund7162133 from Beijing Natural Science Foundation2016-I2M-4-001 from CAMS Innovation Fund for Medical Sciences2016-I2M-1-007 from the
文摘Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments,and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.
