Pauling noble prize winner

Pauling Therapy References

1. NLM CIT. ID: 91067711
2.
3. TITLE: Immunological evidence for the accumulation of lipoprotein(a)
in
4. the atherosclerotic lesion of the hypoascorbemic guinea pig.
5. AUTHOR: Rath M; Pauling L
6. ADDRESS:
7. Linus Pauling Institute of Science and Medicine, Palo Alto, CA
8. 94306-2025.
9. PUBLICATION TYPES:
10. JOURNAL ARTICLE
11. LANGUAGE: Eng
12. REGISTRY NUMBERS:
13. 0 (Antibodies)
14. 0 (Lipoprotein(a))
15. 0 (Lipoproteins)
16. ABSTRACT:
17. Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein.
18. Lp(a) has been found in the plasma of humans and other primates,
19. but until now only in a few other species. The mechanism by
which
20. it exerts its atherogenicity is still poorly understood. We
21. observed that Lp(a) has been found in the plasma of several
22. species unable to synthesize ascorbate and not in other species.
23. We have now detected apoprotein(a) in the plasma of the guinea
24. pig. We induced atherosclerosis in this animal by dietary
25. ascorbate depletion and, using SDS/PAGE and subsequent
26. immunoblotting, we identified Lp(a) as accumulating in the
27. atherosclerotic plaque. Most importantly, adequate amounts of
28. ascorbate (40 mg per kg of body weight per day) prevent the
29. development of atherosclerotic lesions in this animal model and
30. the accumulation of Lp(a) in the arterial wall. We suggest an
31. analogous mechanism in humans because of the similarity between
32. guinea pigs and humans with respect to both the lack of
33. endogenous ascorbate production and the role of Lp(a) in human
34. atherosclerosis.
35. MAIN MESH HEADINGS:
36. Lipoproteins/ANALYSIS/*METABOLISM
37. Atherosclerosis/COMPLICATIONS/*METABOLISM/PATHOLOGY
38. Ascorbic Acid Deficiency/COMPLICATIONS/*METABOLISM
39. ADDITIONAL MESH SUBJECTS:
40. Support, Non-U.S. Gov't
41. Muscle, Smooth, Vascular/METABOLISM/PATHOLOGY
42. Guinea Pigs
43. Female
44. Electrophoresis, Polyacrylamide Gel
45. Blotting, Western
46. Aorta/METABOLISM/PATHOLOGY
47. Antibodies
48. Animal
49. SOURCE: Proc Natl Acad Sci U S A 1990 Dec;87(23):9388-90
50.
51. NLM CIT. ID: 91031571
52.
53. TITLE: Lipoprotein(a) in the arterial wall.
54. AUTHOR: Beisiegel U; Rath M; Reblin T; Wolf K; Niendorf A
55. ADDRESS:
56. Medizinische Kernklinik und Poliklinik, Universitatskrankenhaus
57. Eppendorf, Hamburg, F.R.G.
58. PUBLICATION TYPES:
59. JOURNAL ARTICLE
60. LANGUAGE: Eng
61. REGISTRY NUMBERS:
62. 0 (Apoproteins)
63. 0 (Lipoprotein(a))
64. 0 (Lipoproteins)
65. 0 (Triglycerides)
66. 57-88-5 (Cholesterol)
67. ABSTRACT:
68. We compared CHD patients with healthy blood donors to confirm
the
69. role of Lp(a) as an independent risk factor. More important, we
70. performed biochemical and immunohistochemical studies to
evaluate
71. the potential mechanism by which Lp(a) causes CHD. We measured
72. the Lp(a) concentration in comparison with other lipoprotein
73. parameters in fresh human arterial wall biopsies and, in autopsy
74. tissue, we localized apo (a) and apo B, as well as fibrin, with
75. immunohistochemical methods in different vessel areas. Density
76. gradient ultracentrifugation was used to analyse lipoprotein
77. fractions isolated from human arterial wall. Lp(a) accumulates
in
78. the intima, preferentially in plaque areas, dependent on the
79. serum Lp(a) level. Most of the Lp(a) can be located
80. extracellularly, but apo(a) can also be detected in foam cells.
A
81. strong co-localization has been observed for apo(a) and apo B;
82. only a few areas containing only apo B were detected. Moreover,
a
83. striking co-localization for apo(a) and fibrin was found. The
84. possibilities for the pathways by which Lp(a) enters the
arterial
85. wall and accumulates extracellularly are discussed on the basis
86. of the present data and recent data published by other groups.
87. MAIN MESH HEADINGS:
88. Lipoproteins/*ANALYSIS
89. Endothelium, Vascular/*CHEMISTRY
90. Coronary Disease/*METABOLISM
91. Aorta/*CHEMISTRY
92. ADDITIONAL MESH SUBJECTS:
93. Triglycerides/ANALYSIS
94. Support, Non-U.S. Gov't
95. Proteins/ANALYSIS
96. Middle Age
97. Lipids/ANALYSIS
98. Immunohistochemistry
99. Human
100. Cholesterol/ANALYSIS
101. Apoproteins/ANALYSIS
102. SOURCE: Eur Heart J 1990 Aug;11 Suppl E:174-83
103.
104. NLM CIT. ID: 90349583
105.
106. TITLE: Hypothesis: lipoprotein(a) is a surrogate for ascorbate
107. [published erratum appears in Proc Natl Acad Sci U S A 1991 Dec
108. 15;88(24):11588]
109. AUTHOR: Rath M; Pauling L
110. ADDRESS:
111. Linus Pauling Institute of Science and Medicine, Palo Alto, CA
112. 94306.
113. PUBLICATION TYPES:
114. JOURNAL ARTICLE
115. LANGUAGE: Eng
116. REGISTRY NUMBERS:
117. 0 (Antioxidants)
118. 0 (Lipoprotein(a))
119. 0 (Lipoproteins)
120. 50-81-7 (Ascorbic Acid)
121. ABSTRACT:
122. The concept that lipoprotein(a) [Lp(a)] is a surrogate for
123. ascorbate is suggested by the fact that this lipoprotein is
found
124. generally in the blood of primates and the guinea pig, which
have
125. lost the ability to synthesize ascorbate, but only rarely in the
126. blood of other animals. Properties of Lp(a) that are shared with
127. ascorbate, in accordance with this hypothesis, are the
128. acceleration of wound healing and other cell-repair mechanisms,
129. the strengthening of the extracellular matrix (e.g., in blood
130. vessels), and the prevention of lipid peroxidation. High plasma
131. Lp(a) is associated with coronary heart disease and other forms
132. of atherosclerosis in humans, and the incidence of
cardiovascular
133. disease is decreased by elevated ascorbate. Similar observations
134. have been made in cancer and diabetes. We have formulated the
135. hypothesis that Lp(a) is a surrogate for ascorbate in humans and
136. other species and have marshaled the evidence bearing on this
137. hypothesis.
138. MAIN MESH HEADINGS:
139. Lipoproteins/*PHYSIOLOGY
140. Cardiovascular Diseases/*PHYSIOPATHOLOGY
141. Ascorbic Acid/*METABOLISM
142. ADDITIONAL MESH SUBJECTS:
143. Wound Healing
144. Neoplasms/PHYSIOPATHOLOGY
145. Human
146. Evolution
147. Disease Models, Animal
148. Diabetes Mellitus/PHYSIOPATHOLOGY
149. Atherosclerosis/PHYSIOPATHOLOGY
150. Antioxidants/METABOLISM
151. Animal
152. SOURCE: Proc Natl Acad Sci U S A 1990 Aug;87(16):6204-7
153.
154. NLM CIT. ID: 90312898
155.
156. TITLE: Morphological detection and quantification of lipoprotein(a)
157. deposition in atheromatous lesions of human aorta and coronary
158. arteries [published erratum appears in Virchows Arch A Pathol
159. Anat Histopathol 1991;418(1):86]
160. AUTHOR: Niendorf A; Dietel M; Beisiegel U; Arps H; Peters S
161. Wolf K; Rath M
162. ADDRESS:
163. Institut fur Pathologie, Universitat Hamburg, Federal Republic
164. of Germany.
165. PUBLICATION TYPES:
166. JOURNAL ARTICLE
167. LANGUAGE: Eng
168. REGISTRY NUMBERS:
169. 0 (Apolipoproteins A)
170. 0 (Apolipoproteins B)
171. 0 (Lipoprotein(a))
172. 0 (Lipoproteins)
173. ABSTRACT:
174. Lipoprotein(a), as an atherogenic particle, represents an
175. independent risk factor for coronary heart disease. In the
176. present study the morphological distribution of apoprotein (a)
177. and apoprotein B within the arterial wall is described.
178. Apoprotein B, a constituent of very low-density lipoprotein,
179. low-density lipoprotein and lipoprotein(a) has previously been
180. demonstrated in atheromatous lesions. Lipoprotein(a) possesses
an
181. additional protein, designated apoprotein (a). Autopsy material
182. (n = 74) from the left coronary artery and from the thoracic
183. aorta has been examined by means of immunohistochemistry and
both
184. apoprotein (a) and apoprotein B were detected, primarily
185. associated with the extracellular matrix and accumulating in
186. lesions in the arterial wall. The staining pattern for both
187. antigens was almost always found to be congruent, suggesting
that
188. the detection of (a)-antigen has to be attributed at least in
189. part to the presence of lipoprotein(a). It is concluded that
both
190. low-density lipoprotein and lipoprotein(a) have an important
role
191. in the pathogenesis of atherosclerosis.
192. MAIN MESH HEADINGS:
193. Lipoproteins/*METABOLISM
194. Coronary Disease/*METABOLISM/PATHOLOGY
195. Atherosclerosis/*METABOLISM/PATHOLOGY
196. Arteriosclerosis/*METABOLISM
197. Aortic Diseases/*METABOLISM/PATHOLOGY
198. ADDITIONAL MESH SUBJECTS:
199. Tissue Distribution
200. Middle Age
201. Infant, Newborn
202. Infant
203. Immunohistochemistry
204. Human
205. Coronary Vessels/METABOLISM/PATHOLOGY
206. Comparative Study
207. Child, Preschool
208. Child
209. Apolipoproteins B/METABOLISM
210. Apolipoproteins A/METABOLISM
211. Aorta/METABOLISM/PATHOLOGY
212. Aged, 80 and over
213. Aged
214. Adult
215. Adolescence
216. SOURCE: Virchows Arch A Pathol Anat Histopathol 1990;417(2):105-11


Is Vitamin C Harmful to Cancer Patients?
Stephen Lawson
LPI Administrative Officer
Linus Pauling Institute


In a recent presentation at the American Cancer Society meeting, Dr. David
Golde of Memorial Sloan-Kettering Cancer Center speculated that
supplemental vitamin C may be harmful to cancer patients. Dr. Golde had
previously shown how vitamin C gets into and accumulates in cancer cells.
Golde and others are concerned that the extra vitamin C in cancer cells may
enhance their growth or protect them from the cell-killing free radicals
produced by radiation and some chemotherapeutic drugs.
While different cancer cells may respond differently to vitamin C, it is
important to view these concerns in the context of the experimental cell
culture, small animal, and human clinical studies. In some cell culture and
small animal studies, vitamin C has enhanced cancer cell growth. Dr. Chan
Park has found that the growth of leukemic cells from some leukemia
patients put into culture was enhanced by vitamin C. The growth of cells
taken from other leukemia patients was either inhibited or unaffected by
vitamin C. It is unknown whether similar effects would have been observed
in the same patients taking supplemental vitamin C. Dr. Joel Schwartz of the
National Institutes of Health has published studies in which supplemental
vitamin C enhanced the growth of tumors induced in hamsters by a chemical
carcinogen. Interestingly, the growth of tumors was significantly inhibited by
supplemental vitamin E and by a mixture of antioxidants, including beta-
carotene, vitamin E, and vitamin C.
Studies published by LPI scientists since the 1970s have demonstrated that
supplemental vitamin C delayed the onset of tumors in mice that developed
spontaneous mammary tumors, in mice exposed to ultraviolet radiation, and
in guinea pigs implanted with liver cancer cells. In these experiments,
vitamin C did not appreciably affect the growth rate of tumors once they
formed. Other studies published by Dr. Constance Tsao and her colleagues
at LPI showed that supplemental vitamin C (sometimes combined with
oxidation products of vitamin C) inhibited the growth of human colon, lung,
and mammary tumors implanted into mice. LPI investigations also
demonstrated that vitamin C and its derivatives have anticancer effects
against a number of cancer cell lines in culture.
What about clinical studies on vitamin C in cancer patients? Dr. Pauling and
his medical collaborator, Dr. Ewan Cameron, former Chief of Surgery at Vale
of Leven Hospital in Scotland, published numerous papers on the response
of cancer patients given large doses of supplemental vitamin C as an adjunct
to the appropriate conventional treatment for cancer. In their book Cancer
and Vitamin C, they concluded that supplemental vitamin C is of benefit to
most cancer patients. The benefit ranged from an increased sense of well-
being to a prolongation of survival time in terminal patients to rare complete
regressions. However, two clinical studies carried out by Drs. Edward
Creagan and Charles Moertel of the Mayo Clinic and published in 1979 and
1985 showed no benefit from supplemental vitamin C on survival time. As
Drs. Cameron and Pauling pointed out, however, the patients in the first
Mayo Clinic study had undergone extensive chemotherapy that damaged
their immune systems prior to the use of vitamin C. In the second study
supplemental vitamin C was abruptly stopped after only about two months.
There was also evidence that some of the patients in the placebo group were
taking extra vitamin C, thus muddying the differences between groups.
When Cancer and Vitamin C was first published in 1979, Drs. Cameron and
Pauling noted that little information was available on the interaction between
vitamin C and chemotherapeutic drugs. They cautioned that patients
undergoing aggressive chemotherapy expected to be curative should refrain
from taking large doses of vitamin C at the same time in case the vitamin
interfered with the drug action. There is some evidence that vitamin C
increases the activity of liver enzymes that detoxify xenobiotics, including
drugs. When the chemotherapy was merely palliative, they did not believe
that the use of concurrent vitamin C was contraindicated. They believed that
vitamin C potentiates radiation, and even many clinicians who disagree on
this point nevertheless agree that supplemental vitamin C given after
radiation ameliorates radiation sickness.
In the early 1990s, Dr. Pauling published two papers with Dr. Abram Hoffer,
who developed a regimen for use in cancer patients that includes B vitamins,
vitamin E, large doses of vitamin C, beta-carotene, selenium, zinc, and other
substances. The statistical analysis of their data revealed that about 40% of
the cancer patients survived five years or more after the initiation of the
regimen. (A new book by Dr. Hoffer, Vitamin C & Cancer, features major
contributions by Linus Pauling and further discussion of these results.) Only
about 10% of the patients treated by Dr. Cameron in Scotland with vitamin
C alone survived as long, although all of the Scottish study patients had
terminal cancer. These studies, as well as Dr. Cameron's studies in Scotland,
were not designed as placebo- controlled, randomized, double-blind trials
because of ethical concerns and practical problems concerning appropriate
placebos.
Interestingly, Dr. Hoffer's regimen is remarkably similar to that
recommended by Dr. Kedar Prasad of the University of Colorado and his
colleagues, who advocate the use of a combination of B vitamins, large
doses of calcium ascorbate (vitamin C), vitamin E, and beta-carotene for
cancer patients undergoing either chemotherapy or radiation. Dr. Prasad
acknowledges the accumulation of antioxidant vitamins in cancer cells, but
argues that this has favorable biochemical effects, including the inhibition of
oncogenes and the induction of factors that inhibit cell growth, favor
differentation, or induce apoptosis (programmed cell death). In an extensive
and well-referenced recent review published in the Journal of the American
College of Nutrition, Dr. Prasad presented results from cell culture
experiments demonstrating that the killing effect of many cancer drugs or
radiation on mouse and human cancer cells is enhanced in the presence of
vitamins C or E. Of course, cell culture studies (or animal studies) cannot
always predict what will happen in humans. In another extensive review
published in Alternative Medicine Review in 1999, Drs. Lamson and Brignall
reached conclusions similar to those of Dr. Prasad. These authors noted that
"considerable data exists showing increased effectiveness of many cancer
therapeutic agents, as well as a decrease in adverse effects, when given
concurrently with antioxidants."
A Finnish non-randomized clinical study published in Anticancer Research in
1992 by Dr. Jaakkola and colleagues showed that the provision of B
vitamins, large doses of vitamins C and E, beta-carotene, fatty acids, and
minerals in combination with chemotherapy and radiation to patients with
small-cell lung cancer resulted in significantly prolonged survival, especially
when started early. These patients were compared to patients in other
studies who were treated only with chemotherapy and radiation. Another
clinical study by Dr. Emmanuel Cheraskin published in 1968 showed that the
response to radiation among women with cervical carcinoma was enhanced
by daily supplements of 750 mg of vitamin C given during radiation.
What can we conclude about vitamin C and cancer? While the theoretical
speculation by Dr. Golde seems plausible, there is no clinical evidence that
supplemental antioxidant vitamins, including vitamin C, harm cancer
patients. Indeed, much of the recent cell culture and clinical research
suggests that a combination of antioxidant vitamins and minerals as an
adjunct to conventional therapy may have benefit. This is a complex issue,
however, and there is clearly more to learn from controlled clinical trials
about the use of these modalities in treating cancer before definitive
conclusions can be drawn.
For more information on vitamin C, see the Linus Pauling
Institute's Micronutrient Information Center.