Re: Re: Re: KS risks. 25 August 2004
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James J Whitehead,
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Re: Re: Re: Re: KS risks.

Dear Nicholas Bennette,

Please note that evidence exists in the papers I previousley presented on drug induced Kaposi sarcoma ( I am refereing to the Kidney transplant recipients not in this instance to gay men ) with a drug that creates ROS and reduces glutathione, that the recipients most likley to develope KS had the most advanced renal disease. Its well known that oxidative stress is occuring at increased levels amongst kidney dialysis patients and that disease progression in kidney dialysis is also linked to oxidative stress and is well known to be occuring in the kidney cells. Its interesting that TB and PCP is also linked in these patients. I would be interested in peoples opinions in the very significant rises in anal cancers and lung cancers ranging from 8 fold increases to 22 fold with gay men again being the most effected ?

"A component of phagocytic activation is the initiation of the oxidative burst, resulting in the generation of reactive oxygen species (ROS), which can be mutagenic to host cells if released beyond the phagolysosome and not inactivated. Our results demonstrate that cultured AIDS-KS cells possess decreased cytoprotective capabilities. Relative to either dermal fibroblasts, or human microvascular endothelial cells (HMECs), AIDS-KS cells contained significantly lower levels of glutathione, a tripeptide integral in both cytoprotection and maintenance of cellular thiol status. While HMECs increased catalase activity during culture in the cytokine-rich KS milieu (control medium supplemented with conditioned medium from MOT, an HTLV II-infected cell line), AIDS-KS cells demonstrated reduced catalase function under these conditions. Furthermore, HMEC cultures showed an inherent biochemical responsiveness, by increasing catalase activity following exposure to exogenous H2O2. In contrast, the catalase activity of AIDS-KS cells decreased following H2O2 challenge. Our results show that an inherent deficiency in cellular cytoprotection is present in AIDS-KS cells and suggest that oxidant stress may function in the development and progression of AIDS-KS." (2)

"Despite its recognition as the most prevalent HIV associated cancer, speculation still abounds regarding the pathogenesis of AIDS-related Kaposi's sarcoma (AIDS-KS). However, it has been established that both cytokines, e.g. IL-6, and HIV-associated products, e.g., Tat, are integral in AIDS-KS cellular proliferation. Further, both experimental and clinical evidence is accumulating to link reactive oxygen intermediates (ROI) with both cytokine induction (primarily via nuclear factor-kappa B[NF-kappa B] dependent routes) as well as the subsequent cytokine, tumor necrosis factor alpha (TNF alpha) stimulation of HIV replication. Features of AIDS- KS patients, such as retention of phagocytes, presence of sustained immunostimulation, and a frequent history of KS lesions arising at traumatized sites, make oxidant stress a viable clinical factor in AIDS-KS development. Time course nucleotide profile analyses show that AIDS-KS cells have an inherent, statistically significant, biochemical deficit, even prior to oxidant stress, due to 1) a more glycolytic bioenergetic profile, resulting in lower levels of high energy phosphates (impairing capacity for glutathione [GSH] synthesis and DNA repair); 2) lower levels of NADPH (compromising the activities of GSSG reductase and peroxidase function of catalase); and 3) reduced levels of GSH (impeding both GSH peroxidase and GSH-S-transferases). Following exposure to physiologically relevant levels of H2O2, only the human microvascular endothelial cells (a putative AIDS-KS progenitor cell) responded with bioenergetic adaptations that reflected co-ordination of energy generating and cytoprotective pathways, e.g., retention of the cellular energy charge, increased NAD+, and an accentuation of the ATP, NADPH, and total adenine nucleotide differences relative to AIDS-KS cells. Also, some of the AIDS-KS strains retained intracellular GSSG subsequent to oxidant challenge, inviting the formation of deleterious protein mixed disulfides. While the results of our study address some AIDS-KS issues, they also raise an etiological question, i.e., Does the inability to tolerate oxidant stress arise in conjunction with AIDS-KS neoplastic development, or is it pre-existing in the population at risk? Regardless, use of antioxidant therapy (low risk/ potentially high benefit) in both the "at risk" population as well as in those individuals with active disease may prove a useful preventative and/or treatment modality."

"The 6 control mice died on days 38, 38, 45, 45, 59, and 71, whereas NAC-treated mice died on days 79, 105, 108, 108, 111, and 114, with median survival times of 45 and 108 days, respectively. Kaplan-Meier plots of survival data (not shown), analyzed by log-rank (Mantel-Cox) test showed a significant difference between the two groups (2 = 12.168, P = 0.0005). " (8)

"KS is particularly frequent in HIV-infected patients, where the use of HAART has led to decreased KS tumor burdens in AIDS-KS patients (57 , 58) . However, these patients are at very high risk for recurrence of KS once HAART is discontinued because of toxicity or other reasons (59 , 60) . Furthermore, KS is becoming a leading cause of cancer death in areas of Africa that have high rates of endemic KS (KSHV/HHV8 infection) along with HIV-1 infection (9) . HAART is currently not an option for these patients largely because of economic factors. Therefore, identification of an inexpensive, nontoxic treatment for KS is urgently needed. The antiangiogenic activity of NAC on KS may partially fulfill this need. In addition, NAC (61) and thiols that are increased by NAC (62) have been shown to inhibit the replication of HIV-1, a major cofactor for KS. "(8)

"Previous studies in our laboratory have shown that AIDS-KS cells possess impaired oxygen intermediate scavenging capacities, thereby establishing conditions permissive for the intracellular retention of ROI." (3)

"Subsequent thiol redox modulation studies showed that only the normal fibroblast cultures showed a potentiation of TNF-alpha-mediated MnSOD upregulation following GSH depletion. In addition, provision of the GSH precursor, N-acetylcysteine during TNF-alpha challenge only diminished MnSOD activity and mitochondrial compartmentalization in the AIDS-KS cells, a finding that likely reflects the lower levels of reduced thiols in this cellular population. " (3)

"These results, which show in situ evidence of reactive species stress within AIDS-KS tumors and functional deficits attributable to nitrative stress in tumor-derived AIDS-KS lesional cells, imply that reactive species are intimately associated with AIDS-KS pathogenesis and provide insights for development of novel strategies for AIDS-KS clinical treatments."

Kaposi Sarcoma was declining donkeys years before combo came out.

"Prior to the AIDS epidemic, Kaposi's sarcoma (non-AIDS-KS) in Europe was mainly a disease of elderly Mediterranean men. In 1989 AIDS data from 15 European countries were collected to study proportional trends in AIDS- related Kaposi's sarcoma (AIDS-KS) in order to determine whether specific factors in Southern Europe might be important in the development of KS among AIDS patients. Another AIDS-related cancer, non-Hodgkin's lymphoma (NHL) was included as a malignancy control. Of 22,367 AIDS cases reported, 3,779 (16.9%) were KS and 741 (3.3%) were NHL. A significant, continuous fall in the percentage of AIDS-KS was seen for both homosexual men and other members of exposure groups during the period 1981-89 (p-trend less than 0.0001). The proportion with AIDS-KS decreased from 40.5% in 1983 to 26.5% in 1988 in homosexual men and from 12.2 to 3.6% in other exposure groups, respectively." (4)

"No significant change was observed in the proportion of NHL cases among any of the risk groups over time,

although a tendency towards a slight increase was noted for homosexual men.

Comparing proportional trends of KS and NHL geographically, no significant difference was found overall, by time or by exposure group. In conclusion, a specific decline is observed over time for AIDS-KS. However, if geographically-restricted factors are important in the development of non-AIDS-KS in Europe, the same factors do not appear to affect the risk of AIDS-KS." (4)

"To clarify further the epidemiology of AIDS-related Kaposi's sarcoma (KS) in San Francisco, we reviewed AIDS cases reported to the San Francisco Department of Public Health through August 31, 1990. Of the 7,119 patients reported, 2,346 (33%) had been diagnosed as having KS: 1,716 (73%) as their presenting clinical manifestation of AIDS and 648 (27%) as a later manifestation. Of these 2,364 KS patients, 2,075 (88%) were homosexual or bisexual men without histories of intravenous drug use, and 273 (12%) were homosexual or bisexual intravenous drug users. From 1981 to August 1989, the proportion of AIDS patients presenting with KS declined from 55 to 19% (p less than 0.001). However, the number of patients being diagnosed with KS has increased along with the overall number of AIDS patients, but this increase was less than the increase in number of patients with other opportunistic infections and malignancies. KS patients were less likely than patients without KS to be reported through an active surveillance system and less likely to be found through retrospective reviews of medical records, death certificates, and obituaries. We conclude that the proportion of AIDS patients with KS is continuing to decline in San Francisco and that this decline is not an artifact of the AIDS surveillance system."

On a personal note sadly like everyone else when I choose as an adult not to use combination therapy (because of side serious effects), my doctors and my government are happy to leave me with no treatment at all even though I have had whats called aids since 1998, thats no treatment for Kaposi Sarcoma, no treatment for muscle wasting and treatment to stop my cells commiting opoptosis. ( IE THE COMBO AND OR NOTHING STRATEGY)I could role of a hole list of aids defining diseases I have had but I will not bore everyone.

This is not about me, people are being denied access to life improving, anti wasting,life proloning treatments that are cheap and non toxic

These antioxidants and treatments suggested by leading researchers all over the world should be given to all so called hiv asymptomatic people in Africa and the west, they should also be made available to people with the many diseases that can sometimes be defined as aids. The failure of the medical professionals to provide access to these treatments in my opinion is inhumane and unethical. The risk versus gain ratio is obvious. Given the fact that very toxic drugs have been given already at great cost to human lives and the tax payer to healthy asymptomatics with no benefits accept side effects and whats called drug resistance. (The discredited big mistakes of Hit Hard Early Strategies of AZT then combo, but very profitable mistakes ).

One might be forgiven for thinking that medical and scientific research is being to dominated, influanced and run by and for the drug industry as opposed to saving and improving human lives. Having visited myself some of the worlds poorest countries and seen the total poverty, dirty water, bad housing, malnutrician, TB, children playing in open air sewers I know these peoples lives can be changed dramaticaly by addressing all of the problems associated with desperate poverty.

Given all the latest RE REVISED guidlines about delaying treatments and given the fact that non of the anti hiv treatments work in so-called aymptomatics why on earth are we delaying use of theses scientificaly validated cheap non toxic treatments.

Further more may I appeal to doctors and governments to stop adding import tax and Value Added Taxes on treatments to fight aids, cancer and any other life threatening diseases. Its rather mad that people are being denied access to these treatments, its very sad that the medical profession are violating peoples right to informed consent or choice and its insulting ,unethical and inhumane to charge people taxes on treatments to treat and prevent life threatening diseases.Patients are also been exposed to price fixing cartels where the price of vitamins like acetyl l carnitine can vary upto 8 fold in price between countries.

Thats before we get on to the subject of gross human rights violations being carried out around the world against people diagnosed with hiv and aids EG ,USA, Canada, Cuba, Australia, Russia and more than 70 countries.

As regards your comments about mixing antioxidants and amino acid and nutrient treatments with combo, yes I back that as well because I believe and if I can I will present evidence that they can help treat and prevent some of the side effects and successfully treat the wasting that still occurs despite a undectable viral load. And I appreciate all the information you have given me and opinions you have presented.

"Lung cancer in HIV positive HAART-users Sean Hosein for CATIE News "

One cancer in PHAs that has been the focus of attention is lung cancer. This cancer can arise from exposure to tobacco smoke.

Some studies have found higher-than-normal levels of cigarette usage in HIV positive people. Since HAART has had an impact on some HIV-related complications, researchers are interested in understanding the impact of HAART on lung cancer. To do this, researchers in London, England,reviewed information in their database of 8,400 PHAs.

Results In analysing data between 1986 and 2001, the researchers

found the following: 11 HIV positive people (one female, 10 males) were diagnosed with lung cancer, all of whom were tobacco smokers. Nine of the 11 developed lung cancer in the time HAART was available (1996 -2001). Six of the nine were taking HAART at the time cancer was diagnosed. The other three had sufficiently high CD4+ cell counts and did not require HAART at the time their cancers developed. The response of the tumours to anti-cancer therapy (radiation or chemotherapy) was not good, and half of the subjects did not survive beyond five months after their cancer diagnosis."

"The researchers found that in the time before HAART, the risk of developing lung cancer was about the same in HIV negative and HIV positive people. However, in the years since HAART has become available, the risk of developing lung cancer in HIV positive people has become about eight times greater than that in HIV negative people. " (57b)

"Between 2000 and 2002, the most common cause of death at the UK's largest HIV clinic, London's Kobler Centre, was cancer: non-hodgkin's lymphoma (NHL) and non-AIDS-defining cancers(such as lung ,testicular and anal cancer.(57b)

Cancer in Scotland: swings and roundabouts Scottish scientists, from universities of Strathclyde and Glasgow and the Scottish Cancer Registry, were surprised, last month, to find the risk of non-Aids defining cancers (such as lung, skin and liver cancer) up to 22 times higher in HIV positive people. Homosexual men topped the list as the group most likely to develop cancers of any kind. The UK’s first dedicated male-only cancer centre opened in Edinburgh last week - hailed as an example of innovation and reform which “puts the patient’s needs at the heart of the health service.”

Best Wishes

James J Whitehead.


1: J Cell Biochem. 1995 Nov;59(3):317-28.Cultured AIDS-related Kaposi's sarcoma (AIDS-KS) cells demonstrate impaired bioenergetic adaptation to oxidant challenge: implication for oxidant stress in AIDS-KS pathogenesis. Mallery SR, Bailer RT, Hohl CM, Ng-Bautista CL, Ness GM, Livingston BE, Hout BL, Stephens RE, Brierley GP. Department of Dentistry, College of Dentistry, Ohio State University, Columbus 43210-1241, USA.

2. 1: J Cell Biochem. 1994 Dec;56(4):568-81. Cultured AIDS-related Kaposi's sarcoma cells retain a proliferative bioenergetic profile but demonstrate reduced cytoprotective capabilities.

3.Journal of Cellular Biochemistry Volume 68, Issue 3 , Pages 339 - 354 Thiol redox modulation of tumor necrosis factor- responsiveness in cultured AIDS-related Kaposi's sarcoma cells S.R. Mallery 1 *, D.J. Landwehr 1, G.M. Ness 1, Y.M. Clark 1, C.M. Hohl 2 1Departments of Oral Surgery and Pathology, Colleges of Dentistry and Medicine, Ohio State University, Columbus, Ohio 43210 2Medical Biochemistry, Colleges of Dentistry and Medicine, Ohio State University, Columbus, Ohio 43210 Keywords glutathione • reactive oxygen intermediates • HIV • signal transduction • cytokines • redox state Published Online: 7 Dec 1998 Copyright © 1998 Wiley-Liss, Inc. 4.1: Int J Cancer. 1991 Jan 2;47(1):49-53. Kaposi's sarcoma and non-Hodgkin's lymphoma in European AIDS cases. No excess risk of Kaposi's sarcoma in Mediterranean countries. Casabona J, Melbye M, Biggar RJ. AIDS Epidemiology Section, Generalitat de Catalunya, Barcelona, Spain.

5. J Acquir Immune Defic Syndr. 1990;3 Suppl 1:S4-7. The epidemiology of AIDS-related Kaposi's sarcoma in San Francisco. Rutherford GW, Payne SF, Lemp GF. AIDS Office, Department of Public Health, San Francisco, CA 94102. md=Retrieve&db=pubmed&dopt=Abstrac t&list_uids=2395085

6.Carcinogenesis Advance Access originally published online on December 4, 2003 Carcinogenesis, Vol. 25, No. 4, 597-603, April 2004 Carcinogenesis vol.25 no.4 © Oxford University Press 2004; all rights reserved. MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION Implications for oxidative and nitrative stress in the pathogenesis of AIDS-related Kaposi's sarcoma

(8) Cancer Research Clinical Cancer Research Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics Molecular Cancer Research Cell Growth & Differentiation [Cancer Research 61, 8171-8178, November 15, 2001] © 2001 American Association for Cancer Research s.msnw?action=get_message&mview=0&I D_Message=8565&all_topics=0 57b.).(Positive Nation.Oct 2003.Issue 95)

57c).Positive Nation./issue96 2003.

Competing interests: Long term survivor hiv/oxidative stress/aids member of researcher Continuum Magazine