Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an...Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an invading pathogen with reactive oxygen species (ROS). Although cancer cells can be similarly killed by ROS, development of oxidant-producing chemotherapies has been limited by their inherent nonspecificity and potential toxicity to healthy cells. In this paper, we describe the targeting of an ROS-generating molecule selectively to tumor cells using folate as the tumor-targeting ligand. For this purpose, we exploit the ability of 9,10-phenanthraquinone (PHQ) to enhance the continuous generation of H<sub>2</sub>O<sub>2</sub> in the presence of ascorbic acid to establish a con-stitutive source of ROS within the tumor mass. We report here that incubation of folate receptor-expressing KB cells in culture with folate-PHQ plus ascorbate results in the death of the cancer cells with an IC<sub>50</sub> of ~10 nM (folate-PHQ). We also demonstrate that a cleavable spacer linking folate to PHQ is significantly inferior to a noncleavable spacer, in contrast to most other folate-targeted therapeutic agents. Unfortunately, no evidence for folate-PHQ mediated tumor regression in murine tumor models is obtained, suggesting that unanticipated impediments to generation of cytotoxic quantities of ROS in vivo are encountered. Possible mechanisms and potential solutions to these unanticipated results are offered.展开更多
Cocoa （Theobroma cacao L.） is the major input into the chocolate manufacturing industry, particularly the fine or flavor of the indigenous variety Trinitario, which is the hybrid of Crillo and Forastero. One key pro...Cocoa （Theobroma cacao L.） is the major input into the chocolate manufacturing industry, particularly the fine or flavor of the indigenous variety Trinitario, which is the hybrid of Crillo and Forastero. One key problem encountered by researchers is the inability to differentiate the various phenological stages of the cocoa reproductive cycle and to assess or predict the yield. This study sets out to map the various stages of the reproductive biology of cacao and to develop a set of photographic illustrations that appropriately describe the floral biology and development stages of Caribbean free cocoa as a tool for agronomist and farmers. It used a modified version of the codification of the ＂extended BBCH＂ scale （Biologische Bundesantalt, Bundessortenamt and Chemische Industrie, Germany）, which is a numerical system that differentiates between principal, secondary and tertiary growth stages. The phases and all floral stages to fruit development are described and illustrated in a set of photographs, which can now be used for training and referencing purposes. This is the first attempt to undertake and document this study.展开更多
G-enomic imprinting is an epigenetic mechanism that produces functional differences between the paternal and mammal genomes and plays an essential role in mammalian development and growth. There are a number of genes ...G-enomic imprinting is an epigenetic mechanism that produces functional differences between the paternal and mammal genomes and plays an essential role in mammalian development and growth. There are a number of genes in our genomes that are subject to genomic imprinting where one parent＇s copy of the gene is expressed while the other is silent. Silencing of one allele predetermines that any function ascribed to that gene are now dependant on the single active copy. Possession of only a single active allele can lead to deleterious health consequences in humans. If imprinted genes are crucial in mammalian development, one would also expect mutations in these genes to cause diseases. Since imprinting is an epigenetic mechanism, mistakes in maintaining epigenetic mark also cause imprinting disorders. Here we in this review focus on the current understanding of this unique genetic mechanism more than two decades after the first description of the imprinting phenomenon was given by McGrath and Solter. Although the possible molecular mechanisms by which imprinting is imposed and maintained are being identified, we have a long way to go in understanding the molecular mechanisms that regulate the expression of these oddly behaving genes, the function of imprinting and the evolution. Post genomic technologies might ultimately lead to a better understanding of the ＇imprinting effects＇.展开更多
文摘Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an invading pathogen with reactive oxygen species (ROS). Although cancer cells can be similarly killed by ROS, development of oxidant-producing chemotherapies has been limited by their inherent nonspecificity and potential toxicity to healthy cells. In this paper, we describe the targeting of an ROS-generating molecule selectively to tumor cells using folate as the tumor-targeting ligand. For this purpose, we exploit the ability of 9,10-phenanthraquinone (PHQ) to enhance the continuous generation of H<sub>2</sub>O<sub>2</sub> in the presence of ascorbic acid to establish a con-stitutive source of ROS within the tumor mass. We report here that incubation of folate receptor-expressing KB cells in culture with folate-PHQ plus ascorbate results in the death of the cancer cells with an IC<sub>50</sub> of ~10 nM (folate-PHQ). We also demonstrate that a cleavable spacer linking folate to PHQ is significantly inferior to a noncleavable spacer, in contrast to most other folate-targeted therapeutic agents. Unfortunately, no evidence for folate-PHQ mediated tumor regression in murine tumor models is obtained, suggesting that unanticipated impediments to generation of cytotoxic quantities of ROS in vivo are encountered. Possible mechanisms and potential solutions to these unanticipated results are offered.
文摘Cocoa （Theobroma cacao L.） is the major input into the chocolate manufacturing industry, particularly the fine or flavor of the indigenous variety Trinitario, which is the hybrid of Crillo and Forastero. One key problem encountered by researchers is the inability to differentiate the various phenological stages of the cocoa reproductive cycle and to assess or predict the yield. This study sets out to map the various stages of the reproductive biology of cacao and to develop a set of photographic illustrations that appropriately describe the floral biology and development stages of Caribbean free cocoa as a tool for agronomist and farmers. It used a modified version of the codification of the ＂extended BBCH＂ scale （Biologische Bundesantalt, Bundessortenamt and Chemische Industrie, Germany）, which is a numerical system that differentiates between principal, secondary and tertiary growth stages. The phases and all floral stages to fruit development are described and illustrated in a set of photographs, which can now be used for training and referencing purposes. This is the first attempt to undertake and document this study.
文摘G-enomic imprinting is an epigenetic mechanism that produces functional differences between the paternal and mammal genomes and plays an essential role in mammalian development and growth. There are a number of genes in our genomes that are subject to genomic imprinting where one parent＇s copy of the gene is expressed while the other is silent. Silencing of one allele predetermines that any function ascribed to that gene are now dependant on the single active copy. Possession of only a single active allele can lead to deleterious health consequences in humans. If imprinted genes are crucial in mammalian development, one would also expect mutations in these genes to cause diseases. Since imprinting is an epigenetic mechanism, mistakes in maintaining epigenetic mark also cause imprinting disorders. Here we in this review focus on the current understanding of this unique genetic mechanism more than two decades after the first description of the imprinting phenomenon was given by McGrath and Solter. Although the possible molecular mechanisms by which imprinting is imposed and maintained are being identified, we have a long way to go in understanding the molecular mechanisms that regulate the expression of these oddly behaving genes, the function of imprinting and the evolution. Post genomic technologies might ultimately lead to a better understanding of the ＇imprinting effects＇.
