Microcystins (MCYSTs) isolated from blue-green algae,are hepatotoxic polypeptides.It will induce severe intrahepatic hemorrhage and liver necrosis at low concentrations in rats and mice.MCYST- LR is one of MCYSTs whic...Microcystins (MCYSTs) isolated from blue-green algae,are hepatotoxic polypeptides.It will induce severe intrahepatic hemorrhage and liver necrosis at low concentrations in rats and mice.MCYST- LR is one of MCYSTs which consists of 2 variable L- amino acids(leucine and arginine),3 D-amino acids and 2 unusualamino acids(including Adda).MCYSTs bind to protein phosphatase 1 and 2A,and strongly inhibit their activities.The resultant increase of phosphoprotein was referred to be involved in tumor-promoting activity in liver.According to the above results and animal study,MCYST-LR is a potent liver tumor promoter.There were 9 positive from 30 samples of pond-ditch water in high endemic county-Haimen by high-peformance liquid chromatograph and 3 already confirmed by liquid chromograph/mass spectrometer.The quantities of MCYSTs were different between drinking water of liver cancer cases and controls groups.122±0.057and 0.072±0.044μg/200ml respectively) by ELISA. It is not easy to remove by conventional water treatment procedures.The relationship between MCYSTs and oncogenes and anti-oncogenes are under studying.展开更多
Cancer clusters have long been a focus of interest because of the possibility of identifying etiologic agents. Only on rare occasions, however, have such cluster investigations been successful. One major difficulty in...Cancer clusters have long been a focus of interest because of the possibility of identifying etiologic agents. Only on rare occasions, however, have such cluster investigations been successful. One major difficulty in cluster investigations, particularly in the area of breast cancer, is the long latent period. There have been a number of publications providing a discouraging picture regarding cancer cluster investigations. The possibility of learning from a cluster investigation, however, is greatly increased if the cancer involved is relatively rare and if it has a short latent period. Inflammatory breast cancer(IBC) fits these criteria and is worth pursuing because of the strong evidence that environmental factors play a major role. In this report we describe our experience with several clusters and the lessonslearned which are now being utilized to improve investigation of future IBC clusters. The first IBC cluster that we evaluated was in 2000, when we were asked to investigate an apparent cluster of IBC in Castro Valley, California where three women in an office setting of 24 people were diagnosed with IBC in a ten month period from May 1999 to March 2000. Our investigation of this striking cluster did not yield a specific trigger for this cluster but it did indicate that the women involved all had at least two IBC risk factors that may well have made them susceptible to getting IBC. We are now investigating another apparent cluster in Texas and are aware of several others requiring careful consideration. We see a need for a consistent protocol for the evaluation of IBC clusters focusing on the laboratory investigation of environmental triggers, primarily infectious agents and chemical carcinogens.展开更多
Cobalamin uptake into cells is mediated by the CD320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor express...Cobalamin uptake into cells is mediated by the CD320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor expression is up regulated. Delivering drugs or toxins via this receptor provides increased targeting to cancer cells while minimizing toxicity to the normal tissues. Saporin conjugated monoclonal antibodies to the extracellular domain of TCblR were effectively internalized to deliver a toxic dose of Saporin to some cancer cell lines propagating in culture. Antibody concentration of 2.5 nM was effective in producing optimum inhibition of cell proliferation. The cytotoxic effect of mAb-Saporin appears to be dictated primarily by the level of receptor expression and therefore normal primary cells expressing low levels of CD320 were spared while tumor cell lines with higher CD320 expression were destroyed. Targeting the pathway for cellular uptake of vitamin B12 via the CD320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over expresses this receptor.展开更多
In recent years,traditional Chinese medicine(TCM)has made great progress in the prevention and treatment of cancer.It has gradually revealed its characteristics and advantages in clinical practice,including alleviatin...In recent years,traditional Chinese medicine(TCM)has made great progress in the prevention and treatment of cancer.It has gradually revealed its characteristics and advantages in clinical practice,including alleviating clinical symptoms,prolonging survival time,decreasing the adverse effects of chemotherapy,and improving living quality.However,clinical TCM treatment of cancer lacks systematic theoretical guidance,because ancient TCM has not formed a recognized theoretical system of cognitive cancer,and there still are different opinions on the pathogenesis of cancer.Due to the complexity of cancer,the essence of cancer pathogenesis has not been described accurately by using common pathogenic factors,such as pathogenic wind,cold,dampness,summer heat,dryness,and fire.Ancient and modern TCM physicians have a similar understanding that the occurrence of cancer is related to toxin.In the 1990s,the thought of cancerous toxin was first proposed by Prof Zhou Zhongying,a TCMmaster based onmore than 60 years of clinical practice,who used“pandemic Qi(Li-Qi)is a specific pathogenic factor of epidemic disease”in Wenyi Lun(Treatise on Pestilence)for references.The pathogenesis theory of cancerous toxin was gradually established under the guidance of the thought of cancerous toxin.It holds that the cancerous toxin,a special pathogenic factor of cancer,is the key pathogenesis of the occurrence of malignant tumors.According to the pathogenesis theory of cancerous toxin,the basic pathogenesis of malignant tumors is the accumulation of pathogenic factors and cancerous toxin,and the deficiency of the vital Qi(Zheng-Qi).Therefore,the treatment principle involves eliminating pathogenic factors,resolving cancerous toxin,and supporting the vital Qi.The anticancer detoxification methods and the classification of Chinese medicinal herbs with anticancer detoxification effects were put forward.System theory has much in common with the concepts in the theory system of TCM,such as the universal relation theory,asking for a concrete analysis of concrete conditions,the humanism thought,and so on.This article aims to describe,review,and analyze the pathogenesis theory of cancerous toxin based on system theory for clinical practices.展开更多
Epidermal growth factor （EGF） may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, w...Epidermal growth factor （EGF） may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, we found that EGF treatment could activate Ras-related C3 botulinum toxin substrate 1 （Racl）, PI3K/Akt and p21- actived kinase （PAK1） along with cell migration. Ectopic expression of PAK1 K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAK1 activation and cell migration. Furthermore, expression of dominant-negative Racl （T17N） could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which abolished the EGF-induced ROS generation, cell migration, as well as activation of PI3K/Akt and PAK, but not Racl. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Racl, generation of ROS and subsequent activation of PI3K/Akt and PAK1.展开更多
“炎-癌转化”是宫颈由高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染发展至宫颈癌的重要机制之一。持续性宫颈HR-HPV感染作为宫颈癌的重要诱因,其引起的局部非可控性炎症微环境是宫颈癌发生的内在机制。“炎-癌转化...“炎-癌转化”是宫颈由高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染发展至宫颈癌的重要机制之一。持续性宫颈HR-HPV感染作为宫颈癌的重要诱因,其引起的局部非可控性炎症微环境是宫颈癌发生的内在机制。“炎-癌转化”的宏观及微观病理过程均与中医“湿热蕴毒”的病机演变相契合,湿热聚结为“炎-癌转化”的驱动因素;湿热久蕴致脾虚肝郁为其病机演变特征;湿热久稽,肝脾失调,瘀滞蕴结胞门,终成“癌毒”。持续性宫颈HR-HPV感染所致的“炎-癌转化”进程主要责之于中医的湿、热、虚、毒病理因素。调控持续性宫颈HR-HPV感染炎性微环境为宫颈癌防治的重要途径。临证时以清热燥湿、健脾疏肝为核心治法,攻伐有道、内外同调,以截断“炎-癌转化”的进程。基于“湿热蕴毒”探讨持续性宫颈HR-HPV感染“炎-癌转化”进程,可为中医防治宫颈癌及中医药干预“炎-癌转化”提供思路。展开更多
文摘Microcystins (MCYSTs) isolated from blue-green algae,are hepatotoxic polypeptides.It will induce severe intrahepatic hemorrhage and liver necrosis at low concentrations in rats and mice.MCYST- LR is one of MCYSTs which consists of 2 variable L- amino acids(leucine and arginine),3 D-amino acids and 2 unusualamino acids(including Adda).MCYSTs bind to protein phosphatase 1 and 2A,and strongly inhibit their activities.The resultant increase of phosphoprotein was referred to be involved in tumor-promoting activity in liver.According to the above results and animal study,MCYST-LR is a potent liver tumor promoter.There were 9 positive from 30 samples of pond-ditch water in high endemic county-Haimen by high-peformance liquid chromatograph and 3 already confirmed by liquid chromograph/mass spectrometer.The quantities of MCYSTs were different between drinking water of liver cancer cases and controls groups.122±0.057and 0.072±0.044μg/200ml respectively) by ELISA. It is not easy to remove by conventional water treatment procedures.The relationship between MCYSTs and oncogenes and anti-oncogenes are under studying.
文摘Cancer clusters have long been a focus of interest because of the possibility of identifying etiologic agents. Only on rare occasions, however, have such cluster investigations been successful. One major difficulty in cluster investigations, particularly in the area of breast cancer, is the long latent period. There have been a number of publications providing a discouraging picture regarding cancer cluster investigations. The possibility of learning from a cluster investigation, however, is greatly increased if the cancer involved is relatively rare and if it has a short latent period. Inflammatory breast cancer(IBC) fits these criteria and is worth pursuing because of the strong evidence that environmental factors play a major role. In this report we describe our experience with several clusters and the lessonslearned which are now being utilized to improve investigation of future IBC clusters. The first IBC cluster that we evaluated was in 2000, when we were asked to investigate an apparent cluster of IBC in Castro Valley, California where three women in an office setting of 24 people were diagnosed with IBC in a ten month period from May 1999 to March 2000. Our investigation of this striking cluster did not yield a specific trigger for this cluster but it did indicate that the women involved all had at least two IBC risk factors that may well have made them susceptible to getting IBC. We are now investigating another apparent cluster in Texas and are aware of several others requiring careful consideration. We see a need for a consistent protocol for the evaluation of IBC clusters focusing on the laboratory investigation of environmental triggers, primarily infectious agents and chemical carcinogens.
文摘Cobalamin uptake into cells is mediated by the CD320 receptor for transcobalamin-bound cobalamin. Optimum receptor expression is associated with proliferating cells and therefore, in many cancers this receptor expression is up regulated. Delivering drugs or toxins via this receptor provides increased targeting to cancer cells while minimizing toxicity to the normal tissues. Saporin conjugated monoclonal antibodies to the extracellular domain of TCblR were effectively internalized to deliver a toxic dose of Saporin to some cancer cell lines propagating in culture. Antibody concentration of 2.5 nM was effective in producing optimum inhibition of cell proliferation. The cytotoxic effect of mAb-Saporin appears to be dictated primarily by the level of receptor expression and therefore normal primary cells expressing low levels of CD320 were spared while tumor cell lines with higher CD320 expression were destroyed. Targeting the pathway for cellular uptake of vitamin B12 via the CD320 receptor with toxin-antibody conjugates appears to be a viable treatment strategy for certain cancers that over expresses this receptor.
基金supported by the National Natural Science Foundation of China(No.81973737)National Key R&D Program of China(No.2022YFC3500200 and 2022YFC3500201)+2 种基金Innovation Team and Talents Cultivation Program of National Administration of TraditionalChinese Medicine(No.ZYYCXTD-C-202208)NATCM’s Project of High-level Construction of Key TCM Disciplines,Qing Lan Project of Jiangsu Higher Education Institutions,Jiangsu Postgraduate Practice Innovation Plan(No.SJCX22_0706)General Project of Universities’Philosophy and Social Science in Jiangsu Province.
文摘In recent years,traditional Chinese medicine(TCM)has made great progress in the prevention and treatment of cancer.It has gradually revealed its characteristics and advantages in clinical practice,including alleviating clinical symptoms,prolonging survival time,decreasing the adverse effects of chemotherapy,and improving living quality.However,clinical TCM treatment of cancer lacks systematic theoretical guidance,because ancient TCM has not formed a recognized theoretical system of cognitive cancer,and there still are different opinions on the pathogenesis of cancer.Due to the complexity of cancer,the essence of cancer pathogenesis has not been described accurately by using common pathogenic factors,such as pathogenic wind,cold,dampness,summer heat,dryness,and fire.Ancient and modern TCM physicians have a similar understanding that the occurrence of cancer is related to toxin.In the 1990s,the thought of cancerous toxin was first proposed by Prof Zhou Zhongying,a TCMmaster based onmore than 60 years of clinical practice,who used“pandemic Qi(Li-Qi)is a specific pathogenic factor of epidemic disease”in Wenyi Lun(Treatise on Pestilence)for references.The pathogenesis theory of cancerous toxin was gradually established under the guidance of the thought of cancerous toxin.It holds that the cancerous toxin,a special pathogenic factor of cancer,is the key pathogenesis of the occurrence of malignant tumors.According to the pathogenesis theory of cancerous toxin,the basic pathogenesis of malignant tumors is the accumulation of pathogenic factors and cancerous toxin,and the deficiency of the vital Qi(Zheng-Qi).Therefore,the treatment principle involves eliminating pathogenic factors,resolving cancerous toxin,and supporting the vital Qi.The anticancer detoxification methods and the classification of Chinese medicinal herbs with anticancer detoxification effects were put forward.System theory has much in common with the concepts in the theory system of TCM,such as the universal relation theory,asking for a concrete analysis of concrete conditions,the humanism thought,and so on.This article aims to describe,review,and analyze the pathogenesis theory of cancerous toxin based on system theory for clinical practices.
基金supported by grants from the National Natural Science Foundation of China (No. 30872926)the Program for AdvancedTalents within Six Industries of Jiangsu Province (08-D) to Dr. Luo Gu+1 种基金the Science Development Foundation of Nanjing Medical University (No. 2010NJMUZ35)the Research Program funded by Schoolof Basic Medical Science, Nanjing Medical University to Dr. Jun Du
文摘Epidermal growth factor （EGF） may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, we found that EGF treatment could activate Ras-related C3 botulinum toxin substrate 1 （Racl）, PI3K/Akt and p21- actived kinase （PAK1） along with cell migration. Ectopic expression of PAK1 K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAK1 activation and cell migration. Furthermore, expression of dominant-negative Racl （T17N） could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which abolished the EGF-induced ROS generation, cell migration, as well as activation of PI3K/Akt and PAK, but not Racl. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Racl, generation of ROS and subsequent activation of PI3K/Akt and PAK1.
文摘“炎-癌转化”是宫颈由高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)感染发展至宫颈癌的重要机制之一。持续性宫颈HR-HPV感染作为宫颈癌的重要诱因,其引起的局部非可控性炎症微环境是宫颈癌发生的内在机制。“炎-癌转化”的宏观及微观病理过程均与中医“湿热蕴毒”的病机演变相契合,湿热聚结为“炎-癌转化”的驱动因素;湿热久蕴致脾虚肝郁为其病机演变特征;湿热久稽,肝脾失调,瘀滞蕴结胞门,终成“癌毒”。持续性宫颈HR-HPV感染所致的“炎-癌转化”进程主要责之于中医的湿、热、虚、毒病理因素。调控持续性宫颈HR-HPV感染炎性微环境为宫颈癌防治的重要途径。临证时以清热燥湿、健脾疏肝为核心治法,攻伐有道、内外同调,以截断“炎-癌转化”的进程。基于“湿热蕴毒”探讨持续性宫颈HR-HPV感染“炎-癌转化”进程,可为中医防治宫颈癌及中医药干预“炎-癌转化”提供思路。
