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,nine more questions ar...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,nine more questions are presented as followed.Question 6.Why do nasopharyngeal carcinomas rarely metastasize to the brain?Question 7.Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node?Question 8.What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis?Question 9.How does chronic hepatitis prevent liver metastasis from colorectal cancer?Question 10.How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis?Question 11.Why do cancers rarely metastasize to the small bowel?Question 12.Why do glioblastomas rarely metastasize outside the central nervous system?Question 13.Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas,these tumors are the most therapeutically refractory among all human cancers.What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy,since even a surgical resection of greater than 99%of tumor tissues is invariably associated with recurrence?Question 14.The blood–brain barrier(BBB)effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain.What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?展开更多
Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complex...Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis—a “passive approach”. On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells;on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the “active approach”. On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain “mysteries” behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.展开更多
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,nine more questions are presented as followed.Question 6.Why do nasopharyngeal carcinomas rarely metastasize to the brain?Question 7.Can distant spread of cancer cells be blocked by inhibiting the remodeling of high endothelial venules in the sentinel lymph node?Question 8.What sort of live-imaging techniques can be developed to directly observe the dynamic processes of metastasis?Question 9.How does chronic hepatitis prevent liver metastasis from colorectal cancer?Question 10.How many types of host cells contribute to forming the pre-metastatic niche in the lung favorable for metastasis?Question 11.Why do cancers rarely metastasize to the small bowel?Question 12.Why do glioblastomas rarely metastasize outside the central nervous system?Question 13.Despite increased understanding of the molecular genetic events leading to the development and progression of high-grade gliomas,these tumors are the most therapeutically refractory among all human cancers.What then would be the most effective therapeutic approaches to treat what in essence can be regarded as a whole brain malignancy,since even a surgical resection of greater than 99%of tumor tissues is invariably associated with recurrence?Question 14.The blood–brain barrier(BBB)effectively limits a wide variety of potential therapeutic agents from reaching glioma cells widely dispersed in the brain.What therapeutic approaches can be used to breach the BBB and allow therapeutic agents to seek out and kill these tumor cells?
文摘Heat shock proteins (HSPs) serve to correct proteins’ conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis—a “passive approach”. On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells;on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the “active approach”. On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain “mysteries” behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.
