Evidence-based complementary and alternative medicine : eCAM, 2005
Echinacea has been viewed as an immunoenhancing herb since it became commercially available sever... more Echinacea has been viewed as an immunoenhancing herb since it became commercially available several years ago. Indeed, its medicinal significance is responsible for billions of dollars in worldwide sales annually. Unfortunately, most of the 'evidence' for the purported medicinal efficacy of Echinacea has been anecdotal and, moreover, to this day, there is no formal proof on how to achieve the best results-whether it should be consumed daily throughout life as a prophylactic; consumed by either young or old; or consumed after diseases, such as cancer, have taken hold. Our work over the past 5 years has led to conclusive answers to some of these questions, at least in mice. Our results have shown that daily consumption of Echinacea is indeed prophylactic, extends the life span of aging mice, significantly abates leukemia and extends the life span of leukemic mice. Given that humans are 97% genetically common with mice and that virtually all our basic physiology is identical, i...
Journal of complementary & integrative medicine, 2011
In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract... more In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract (Afexa Life Sciences, Inc.) of North American ginseng, Panax quinquefolius, significantly enhanced the absolute levels of cells acting at the first line of defense in tumor combat, i.e., natural killer (NK) cells. The present study evaluated the effect of CVT-E002, on life span when administered intraperitoneally to leukemic, infant/juvenile mice. The extract was administered to groups of mice daily for 14 days in several dosing groups up to 50mg/day from age 7 to 21 days. The tumor was administered intraperitoneally under sterile conditions, in a laminar flow hood at 7 days of age (0.5 x 10(6) leukemic cells), immediately preceding the first CVT-E002 injection for each dose group. The data revealed that CVT-E002 significantly extends the life of leukemic, young mice in a dose-specific manner, i.e., 20 mg/day was effective in extending life, while lower doses of 5, 10 mg as well as high...
On the basis of our previous findings that erythroleukemia-bearing mice of different ages respond... more On the basis of our previous findings that erythroleukemia-bearing mice of different ages responded positively to immunotherapy [indomethacin +/- recombinant interleukin (rIL-2)] in vivo [stimulated natural killer (NK) cells and increased life span], we aimed, in the present study, to determine if changes in these parameters could be correlated to change in erythroleukemia cell numbers. Infant (< 3 weeks old), young adult (5-8 weeks) and aged (> 10 months) DBA/2 mice were injected with erythroleukemia cells. Some mice remained untreated for the 10-day duration of the tumor-bearing period, while others were treated with either indomethacin alone for the 10 days from tumor inoculation, rIL-2 alone for the last 4 days of the 10-day tumor-bearing period, or with both indomethacin and rIL-2 as above. In all cases, both treated and untreated mice were killed at 10 days after tumor inoculation. Cytospot preparations from single cell suspensions of spleen and bone marrow, in all cases, were stained with MacNeal's tetrachrome hematologic stain and the relative and absolute number of erythroleukemia cells in these organs were determined using light microscopy. The results show that indomethacin- and/or rIL-2 treated leukemic infant and young adult mice have significantly lower numbers of erythroleukemia cells in both the spleen and bone marrow relative to untreated, leukemic mice of corresponding age. Leukemic aged mice, however, show no change in erythroleukemia cell numbers in either organ, regardless of treatment, paralleling our observations of a lack of immunotherapeutic value of these agents on NK cell production/function in aged mice.
We previously showed that immunotherapy using indomethacin combined with rIL-2 in vivo was very e... more We previously showed that immunotherapy using indomethacin combined with rIL-2 in vivo was very effective in stimulating natural killer (NK) cells and in increasing the life span of young adult mice bearing a tumor of hemopoietic origin. The aim of the present study was to test the efficacy and universality, with respect to age, of this treatment in tumor-bearing mice. DBA/2 mice (10-16 months old) were injected with 5 x 10(6) erythroleukemia cells and remained either: (i) untreated (control); (ii) treated with indomethacin (5 micrograms/ml drinking water) for 9 days from tumor onset; (iii) treated with rIL-2 (24 x 10(3) U/injection) twice a day for the last 4 days of the 9-day tumor-bearing period, or (iv) treated with both indomethacin and rIL-2 concomitantly. Some mice from each group (above) were killed after 9 days of tumor growth, while the others were allowed to survive. Spleen and bone marrow cells were collected from the mice of each group and NK (ASGM-1+) cells were quantitated using an immunoperoxidase technique combined with light microscopy. NK cell-mediated activity was assessed using a standard chromium release assay. The results show that although NK cell numbers increase in the presence of the growing tumor, neither indomethacin alone, rIL-2 alone, nor the combination could further increase the numbers of these cells. Furthermore, indomethacin and/or rIL-2 could not induce NK cell-mediated activity in such mice. Moreover, tumor-bearing aged mice treated as above did not have a significantly longer life span than untreated (control) tumor-bearing mice. The present results indicate an age-dependent resistance to a form of immunotherapy already proven very effective in young adult mice. Furthermore, the results of this and our previous studies suggest that immunotherapy, which may be highly effective in one age group, should not be presumed effective throughout life.
The postulate made by some investigators that functional NK cells are of pre-T lineage remains hi... more The postulate made by some investigators that functional NK cells are of pre-T lineage remains highly controversial. The present study tested this possibility by adoptive transfer of fetal thymocytes, rich in pre-T cells, into aged syngeneic mice which show thymic involution and low or no splenic NK activity. Splenic NK activity of aged CBA/J mice at 1 or 3 days after intravenous injection of fetal thymocytes was measured with a 4-hr chromium-release assay. Another group received saline only and a third group received either thymocytes as above or saline, and were subsequently injected with the interferon inducer, poly(I:C), 12 hr prior to removal of their spleens for the NK assay. The results revealed that reconstitution with fetal thymocytes did not restore NK activity in aged mice at 1 or 3 days after thymocyte inoculation. Poly(I:C) treatment caused an elevation of NK activity in both thymocyte-injected and control mice. The spleens of aged hosts given young adult splenocytes, on the other hand, had significantly elevated NK activity over controls. Collectively, the results demonstrate that while the adult spleen contains functional NK cells, the fetal thymus, rich in pre-T cells, does not contain functional NK cells or NK precursors as detected by maturation into functional NK cells within 3 days in the aged secondary hosts.
Evidence-based complementary and alternative medicine : eCAM, 2005
Echinacea has been viewed as an immunoenhancing herb since it became commercially available sever... more Echinacea has been viewed as an immunoenhancing herb since it became commercially available several years ago. Indeed, its medicinal significance is responsible for billions of dollars in worldwide sales annually. Unfortunately, most of the 'evidence' for the purported medicinal efficacy of Echinacea has been anecdotal and, moreover, to this day, there is no formal proof on how to achieve the best results-whether it should be consumed daily throughout life as a prophylactic; consumed by either young or old; or consumed after diseases, such as cancer, have taken hold. Our work over the past 5 years has led to conclusive answers to some of these questions, at least in mice. Our results have shown that daily consumption of Echinacea is indeed prophylactic, extends the life span of aging mice, significantly abates leukemia and extends the life span of leukemic mice. Given that humans are 97% genetically common with mice and that virtually all our basic physiology is identical, i...
Journal of complementary & integrative medicine, 2011
In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract... more In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract (Afexa Life Sciences, Inc.) of North American ginseng, Panax quinquefolius, significantly enhanced the absolute levels of cells acting at the first line of defense in tumor combat, i.e., natural killer (NK) cells. The present study evaluated the effect of CVT-E002, on life span when administered intraperitoneally to leukemic, infant/juvenile mice. The extract was administered to groups of mice daily for 14 days in several dosing groups up to 50mg/day from age 7 to 21 days. The tumor was administered intraperitoneally under sterile conditions, in a laminar flow hood at 7 days of age (0.5 x 10(6) leukemic cells), immediately preceding the first CVT-E002 injection for each dose group. The data revealed that CVT-E002 significantly extends the life of leukemic, young mice in a dose-specific manner, i.e., 20 mg/day was effective in extending life, while lower doses of 5, 10 mg as well as high...
On the basis of our previous findings that erythroleukemia-bearing mice of different ages respond... more On the basis of our previous findings that erythroleukemia-bearing mice of different ages responded positively to immunotherapy [indomethacin +/- recombinant interleukin (rIL-2)] in vivo [stimulated natural killer (NK) cells and increased life span], we aimed, in the present study, to determine if changes in these parameters could be correlated to change in erythroleukemia cell numbers. Infant (< 3 weeks old), young adult (5-8 weeks) and aged (> 10 months) DBA/2 mice were injected with erythroleukemia cells. Some mice remained untreated for the 10-day duration of the tumor-bearing period, while others were treated with either indomethacin alone for the 10 days from tumor inoculation, rIL-2 alone for the last 4 days of the 10-day tumor-bearing period, or with both indomethacin and rIL-2 as above. In all cases, both treated and untreated mice were killed at 10 days after tumor inoculation. Cytospot preparations from single cell suspensions of spleen and bone marrow, in all cases, were stained with MacNeal's tetrachrome hematologic stain and the relative and absolute number of erythroleukemia cells in these organs were determined using light microscopy. The results show that indomethacin- and/or rIL-2 treated leukemic infant and young adult mice have significantly lower numbers of erythroleukemia cells in both the spleen and bone marrow relative to untreated, leukemic mice of corresponding age. Leukemic aged mice, however, show no change in erythroleukemia cell numbers in either organ, regardless of treatment, paralleling our observations of a lack of immunotherapeutic value of these agents on NK cell production/function in aged mice.
We previously showed that immunotherapy using indomethacin combined with rIL-2 in vivo was very e... more We previously showed that immunotherapy using indomethacin combined with rIL-2 in vivo was very effective in stimulating natural killer (NK) cells and in increasing the life span of young adult mice bearing a tumor of hemopoietic origin. The aim of the present study was to test the efficacy and universality, with respect to age, of this treatment in tumor-bearing mice. DBA/2 mice (10-16 months old) were injected with 5 x 10(6) erythroleukemia cells and remained either: (i) untreated (control); (ii) treated with indomethacin (5 micrograms/ml drinking water) for 9 days from tumor onset; (iii) treated with rIL-2 (24 x 10(3) U/injection) twice a day for the last 4 days of the 9-day tumor-bearing period, or (iv) treated with both indomethacin and rIL-2 concomitantly. Some mice from each group (above) were killed after 9 days of tumor growth, while the others were allowed to survive. Spleen and bone marrow cells were collected from the mice of each group and NK (ASGM-1+) cells were quantitated using an immunoperoxidase technique combined with light microscopy. NK cell-mediated activity was assessed using a standard chromium release assay. The results show that although NK cell numbers increase in the presence of the growing tumor, neither indomethacin alone, rIL-2 alone, nor the combination could further increase the numbers of these cells. Furthermore, indomethacin and/or rIL-2 could not induce NK cell-mediated activity in such mice. Moreover, tumor-bearing aged mice treated as above did not have a significantly longer life span than untreated (control) tumor-bearing mice. The present results indicate an age-dependent resistance to a form of immunotherapy already proven very effective in young adult mice. Furthermore, the results of this and our previous studies suggest that immunotherapy, which may be highly effective in one age group, should not be presumed effective throughout life.
The postulate made by some investigators that functional NK cells are of pre-T lineage remains hi... more The postulate made by some investigators that functional NK cells are of pre-T lineage remains highly controversial. The present study tested this possibility by adoptive transfer of fetal thymocytes, rich in pre-T cells, into aged syngeneic mice which show thymic involution and low or no splenic NK activity. Splenic NK activity of aged CBA/J mice at 1 or 3 days after intravenous injection of fetal thymocytes was measured with a 4-hr chromium-release assay. Another group received saline only and a third group received either thymocytes as above or saline, and were subsequently injected with the interferon inducer, poly(I:C), 12 hr prior to removal of their spleens for the NK assay. The results revealed that reconstitution with fetal thymocytes did not restore NK activity in aged mice at 1 or 3 days after thymocyte inoculation. Poly(I:C) treatment caused an elevation of NK activity in both thymocyte-injected and control mice. The spleens of aged hosts given young adult splenocytes, on the other hand, had significantly elevated NK activity over controls. Collectively, the results demonstrate that while the adult spleen contains functional NK cells, the fetal thymus, rich in pre-T cells, does not contain functional NK cells or NK precursors as detected by maturation into functional NK cells within 3 days in the aged secondary hosts.
Uploads