- Email: [email protected]
Colon cancer and nutrition
Notes
464 Asthma and 5.lipoxygenase In this study, the authors examined the effects of a 5liposypqase rnhibitor on asthma induced by the inhalation of cold. dry air. 5-Lipoxygenase is a crucial enzyme in the pathway that converts arachidonic acid to bukotrienes. Leukotrienes are potent bronchoconstrictots and iuflammatory mediators that have been implicated h: asthmatic bronchocons~iction. The 5-Iypoxygenase inhibition A-64077 (800 mg) or placebo was administered 3 h before inhalation challenge with cold, dry air to 13 subjects in a randomized, double-blind, placebocontrolled, crossover design. The amount of cold, dry air required to reduce the FEVt by 10% was increased by 48% after administration of A-64077 compared with placebo. After placebo subjects required 27.5 I/min to produce a 10% decrease in FEV-1. whereas after treatment subjects required 39.8 l/mm. The effect exceeded the previously reported effets of cromolyn, terbutaline, and th?ophylline in this model. These data suggested that tcukotrienes may be involved in mediating asthmatic br~:~cho~onstrjction to cotd. dry air and that drugs blockjag the production of these agents, or antagonizing their site at the target organ may play a future role in the treatment of asthma.
E Ismet (1) BethIsrael Hospital, BostonMA.02215, USA Tomor, angkgtxesis acd fumagillin Angiogenesis, the growth of new blood capiharies, is a potential target for ~~~mpeutic inte~ention in cancer because solid tumors require continual neovascularization in order to expand in rize. Angiogenesis inhibitors could provide a relatively specific and non-toxic therapy since endothelial cell turnover Fates are extremely low in normal, non-growing tissues. We recently reported the synthesis of a new family of angiogenesis inhibitors (“angioinhibins”) which are analogues of fumagillin. a natural product of Aspergillus fumigatus Fresenius. This fungus was initially isolated from a contan.tnant found by chance in a routine culture of capillary e,-dothelial cells. The contaminant was thought to be interesJng because it produced a local gradient of endotheiiar ceil rounding, ie an effect which we have previously shown to be associated with capillary growth inhibition itt vitro and itt v&o. A compound was isolated from large-scale fungal cultures and shown to inhibit the growth of cultured endotheIia1 cells as well as both embryonic and tumor-induct neovas~u~a~~ation in vivo. The source of the anti-angiogenic activity was identified as fumagillin, an antibiotic previously used to treat amebiasis in man. Fumagillin inhibited tumor growth when tested in mice, however it was found to be toxic. Synthesis of fumagillin analogues resulted in identification of a potent angiogenesis inhibitor which is known as AGM-i470, (1) N En& J Wed (1990) 323, 1740
This analogue suppressed the growth of a wide variety of different murine tumors without any of the side-effects that are characteristic of conventional anti-cancer agents. The non-toxic quality of the angioinhibins may be critical for the treatment of tumors and other angiogeuic diseases (es. arthritis, diabetic retinopathy, psoriasis) which will most likely require life-long therapy. We hope to begin phase I clinical triais with angioinhibins wiikin the next two years. D fugher(2) The Children’s Hospital. MarvardMedicalSchGBI, Boston. MA 02115,USA Transport and storage of v3amin A The requirement of vitamin A ixtinoids) for visic?n has been recognized for decades. In iddision, vitamin +? is involved in fetal development and A:: the t’eguiatl~n ?.’ proliferation and differentiation of ceil; throughout He. Since this fat-soluble organic compnund
Notes 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95% confidence interval, 1.24 to 5.031, as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was strongly related to an increased incidence of coion cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95% con~dence interval, 1SO to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but thir relation was not statistically independent of meat 5ntake. The prospective data from this study provide eriocnce for the hypothesis that a high intake of animal far increases the risk of colon cancer, and they suppori existing recommendations that meats high in fat be rubstituted by fish and chicken. WC Willett (I) Hamrd School of Public Health. Bow 3 MA 02115, USA
(1) N E@
I Med (1990). 323, 1664
The earliest T-precursor cells in the thymus. The earliest T-precursor celis in the adult thymus hrve until recently been considered to be the 13% “triple negative” population
(2) ~Uf~~~(1991) 349. 71
464 Asthma and 5.lipoxygenase In this study, the authors examined the effects of a 5liposypqase rnhibitor on asthma induced by the inhalation of cold. dry air. 5-Lipoxygenase is a crucial enzyme in the pathway that converts arachidonic acid to bukotrienes. Leukotrienes are potent bronchoconstrictots and iuflammatory mediators that have been implicated h: asthmatic bronchocons~iction. The 5-Iypoxygenase inhibition A-64077 (800 mg) or placebo was administered 3 h before inhalation challenge with cold, dry air to 13 subjects in a randomized, double-blind, placebocontrolled, crossover design. The amount of cold, dry air required to reduce the FEVt by 10% was increased by 48% after administration of A-64077 compared with placebo. After placebo subjects required 27.5 I/min to produce a 10% decrease in FEV-1. whereas after treatment subjects required 39.8 l/mm. The effect exceeded the previously reported effets of cromolyn, terbutaline, and th?ophylline in this model. These data suggested that tcukotrienes may be involved in mediating asthmatic br~:~cho~onstrjction to cotd. dry air and that drugs blockjag the production of these agents, or antagonizing their site at the target organ may play a future role in the treatment of asthma.
E Ismet (1) BethIsrael Hospital, BostonMA.02215, USA Tomor, angkgtxesis acd fumagillin Angiogenesis, the growth of new blood capiharies, is a potential target for ~~~mpeutic inte~ention in cancer because solid tumors require continual neovascularization in order to expand in rize. Angiogenesis inhibitors could provide a relatively specific and non-toxic therapy since endothelial cell turnover Fates are extremely low in normal, non-growing tissues. We recently reported the synthesis of a new family of angiogenesis inhibitors (“angioinhibins”) which are analogues of fumagillin. a natural product of Aspergillus fumigatus Fresenius. This fungus was initially isolated from a contan.tnant found by chance in a routine culture of capillary e,-dothelial cells. The contaminant was thought to be interesJng because it produced a local gradient of endotheiiar ceil rounding, ie an effect which we have previously shown to be associated with capillary growth inhibition itt vitro and itt v&o. A compound was isolated from large-scale fungal cultures and shown to inhibit the growth of cultured endotheIia1 cells as well as both embryonic and tumor-induct neovas~u~a~~ation in vivo. The source of the anti-angiogenic activity was identified as fumagillin, an antibiotic previously used to treat amebiasis in man. Fumagillin inhibited tumor growth when tested in mice, however it was found to be toxic. Synthesis of fumagillin analogues resulted in identification of a potent angiogenesis inhibitor which is known as AGM-i470, (1) N En& J Wed (1990) 323, 1740
This analogue suppressed the growth of a wide variety of different murine tumors without any of the side-effects that are characteristic of conventional anti-cancer agents. The non-toxic quality of the angioinhibins may be critical for the treatment of tumors and other angiogeuic diseases (es. arthritis, diabetic retinopathy, psoriasis) which will most likely require life-long therapy. We hope to begin phase I clinical triais with angioinhibins wiikin the next two years. D fugher(2) The Children’s Hospital. MarvardMedicalSchGBI, Boston. MA 02115,USA Transport and storage of v3amin A The requirement of vitamin A ixtinoids) for visic?n has been recognized for decades. In iddision, vitamin +? is involved in fetal development and A:: the t’eguiatl~n ?.’ proliferation and differentiation of ceil; throughout He. Since this fat-soluble organic compnund
Notes 3.15). No association was found for vegetable fat. The relative risk of colon cancer in women who ate beef, pork, or lamb as a main dish every day was 2.49 (95% confidence interval, 1.24 to 5.031, as compared with those reporting consumption less than once a month. Processed meats and liver were also significantly associated with increased risk, whereas fish and chicken without skin were related to decreased risk. The ratio of the intake of red meat to the intake of chicken and fish was strongly related to an increased incidence of coion cancer (P for trend = 0.0005); the relative risk for women in the highest quintile of this ratio as compared with those in the lowest quintile was 2.49 (95% con~dence interval, 1SO to 4.13). A low intake of fiber from fruits appeared to contribute to the risk of colon cancer, but thir relation was not statistically independent of meat 5ntake. The prospective data from this study provide eriocnce for the hypothesis that a high intake of animal far increases the risk of colon cancer, and they suppori existing recommendations that meats high in fat be rubstituted by fish and chicken. WC Willett (I) Hamrd School of Public Health. Bow 3 MA 02115, USA
(1) N E@
I Med (1990). 323, 1664
The earliest T-precursor cells in the thymus. The earliest T-precursor celis in the adult thymus hrve until recently been considered to be the 13% “triple negative” population
(2) ~Uf~~~(1991) 349. 71