Tumor Hypoxia and Ozone Therapy

Author: Kornel Kusznieruk

Affiliation: University of Western Ontario
Date Published: Tuesday October 24th, 2006 @ 23:30:29 EST

From Category: Immunology


This paper describes the importance of increasing oxygen content in tumors and provides some possible ways of doing this.


Tumors are a rapidly expanding mass originating from one transformed cell. This rapid
expansion does not allow for proper vascularization to occur. At the size of 2-3 mm3 the
tumor would hypothetically stop growing because of its need for a blood supply to
provide oxygen and nutrients (1). Unfortunately, the tumor can coerce the host
endothelial cells to enter the growing mass and provide life support. This is
accomplished, in part, by release of chemoattractant compounds from the growing tumor
or from immune system cells which have entered the growing tumor. These compounds
activate neighboring endothelial cells to migrate to the tumor, to cut through host tissue so that they can arrive at the tumor, and to start proliferating and forming new blood vessels for the tumor. This process is called angiogenesis (2).

Although the host-derived endothelium allows the tumor to grow, its vascular structure is
much different from that of normal tissue. The tumor has no intratumor lymphatics, this
does not permit fluid draining from tumour tissue and as a result high interstitial fluid
pressure develops (3). The high interstitial pressure inhibits drugs from penetrating the
whole tumor tissue, as well as forcing death of some tumor cells. This alteration of
interstitial pressure combined with the rapid rate of tumor cell proliferation ends up
forming a situation where the growing tumor is vascularized, but only to the limited
extend that it needs for it’s own survival. Tumor blood vessels do not contain smooth
muscle lining, are resistant to control by the nervous system, and grow in a disorganized
manner compared to vasculature in non-tumor tissue (3). An example of the difference
between tumor and non-tumor vasculature is that the former relies on tumor secretion of
vascular endothelial growth factor (VEGF) for its survival, whereas the former is
insensitive to withdrawl of VEGF (4).

Tumors contain areas of hypoxia (4a). The cause of this is multifactorial and includes
poor tumor perfusion by the blood (5), clotting of tumor blood vessels due to activated
clotting factors on tumor endothelium (6), and the rapid rate of tumor growth. Hypoxia,
and poor perfusion have been shown to negatively correlate with prognosis (7, 8).
Cancer cells under hypoxic environments secrete matrix metalloproteases, which allow
them to metastasize (9). In addition, hypoxia programs cancer cells and macrophages to
secrete VEGF, a protein that stimulates angiogenesis as well as immune suppression (10).
Hypoxia activates hypoxia inducible factor (HIF-1) a nuclear transcription factor which is important in promotion of angiogenesis (11). Besides local hypoxia, late stage cancer patients have lower systemic hemoglobin levels compared to healthy controls, this is due in part to lower renal production of erythropoietin (11a). Lower hemoglobin implies less oxygen transport and therefore reduced tumor oxygenation. Studies aimed at increasing hemoglobin levels by administration of erythropoietin have shown increased efficacy of radiotherapy and chemotherapy (11b).

An important consideration of tumor hypoxia is the role it plays in protection of tumors
from anti-tumor defense systems. For example, tumor necrosis factor alpha (TNF-α) is a
cytokine secreted by activated macrophages and T cells, which as the name implies has
antitumor activity. Interestingly, the cytotoxicity of TNF-α to tumor cells is reduced
under hypoxic conditions (12). Hypoxia also stimulates production of soluble TNF
receptors which hypothetically may block systemic activities of this cytokine (13). This
may explain the poor efficacy of systemic TNF-α therapy which was attempted in the
1980s (reviewed in 13a). If TNF-α can not kill cancer cells, then it is possible that
immune effectors which use intracellular signalling similar to TNF-α will not be able to
work either. Such mediators include the Fas signalling pathway (13b). Since Fas ligand
and TNF-α are used by T cells in killing of target cells, the poor efficacy of
immunotherapy may be explained by hypoxia.

In accordance with the above point: lymphokine activated killer (LAK) cells are effective
in killing certain types of tumor cells in vitro and in vivo but the ability to generate these cells is depressed under conditions of hypoxia. Furthermore, the ability of estabilished LAK cells to kill tumor targets is decreased under conditions of hypoxia similar to those found inside the tumor (14). Proliferation of lymphocytes in response to interleukin-2 is also inhibited during hypoxia (15).

In 1953 the impact of tumor oxygenation on efficacy of radiation therapy was described
by Gray et al (16). Since then a great number of studies confirming that tumor sensitivity to radiotherapy positively correlates with tumor oxygenation (reviewed in 17). Several other interventions such as etoposide, doxorubicin, camptothecin and vincristine therapy are oxygen dependent (17a).

The Problem
Tumor hypoxia:
1. Stimulates angiogenesis
2. Suppresses immune function by:
a) Blocking TNF-α toxicity
b) Blocking systemic TNF-α activity by shed receptors
c) Blocking lymphocyte proliferation
d) Blocking LAK cell generation and activity
e) Induces production of the immune-suppressive cytokine VEGF
3. Stimulates resistance to radio- and chemotherapy.

Available Solutions

Hyperbaric Chambers

Methods of increasing tumor oxygenation have been described. One such method
involves exposing a patient to higher oxygen tension by use of a hyperbaric chamber.
This approach has shown marginal increases in oxygenation of some tumors although
clinical efficacy is a matter of debate. A randomized trial of squamous cell sarcoma
patients treated with radiotherapy in the presence of air or hyperbaric oxygen
demonstrated a significantly greater number of patients achieving clinical response in the hyperbaric oxygen group (18). Another randomized study assessing the ability of
hyperbaric oxygen to increase efficacy of radiotherapy in cervical carcinoma patients
demonstrated no beneficial effects (19). In addition to questionable clinical efficacy
hyperbaric oxygen is a costly and sometimes dangerous procedure, which is not
commonly used.


Inhalation of carbogen, a mixture of 95% oxygen and 5% carbon dioxide has also been
shown to increase tumor oxygenation both in animal models (20,21) and in the clinical
situation (22-24). An explanation for this effect is that carbon dioxide has vasodilatory
functions in this setting which allows for better tumor perfusion of the high concentration of inhaled oxygen (25). Therapeutic benefits of carbogen therapy are mixed although some radiosensitizing effects have been observed alone (26-28), or in combination with nicotinamide in Phase I/II trials (29). Phase III trials are needed.

Proposed Solutions

Hypertonic Saline

Patients suffering from hemorragic shock often incur organ failure due to hypo-perfusion
and lose of oxygen. Hypertonic solutions have originally been found useful in the
treatment of traumatized patients with hemorrhagic shock. In 1980 Velasco et al
demonstrated that an injection of 7.5% NaCl in hemorrhaged dogs restored arterial
pressure and cardiac output while increasing survival compared to dogs receiving
isotonic saline (30). In the same year, his group published human study in which 12
patients with hypovolaemic shock refractory to volume replacement, corticosteroid and
dopamine infusions were administered a bolus of 100-400 ml of 7.5% NaCl. 11 of the 12
patients responded with rise in arterial pressure and the resumption of urine flow, the
effects lasting for several hours (31). This treatment has been shown to increase oxygen
content of organs in part by causing intratissue fluid to enter blood vessels, and increase blood vessel volume. These effects were postulated to be due to the temporary disruption of osmotic balance, as well, as erythrocytes losing their volume and being able to squeeze through areas which previously have not been perfused. Hypertonic saline therapy has not been associated with toxicity and has been used extensively in the clinical setting (33,34). The hemodynamic-stabilizing effects of saline have even been shown benefitial a hamster model of endotoxemia (35).

This stimulates the question of whether infusions of hypertonic saline may be used in
conjunction or alone for increasing tumor oxygenation. An added benefit to this
approach is immunostimulation! It has been demonstrated in mouse and human that
hypertonic saline therapy increases T cell proliferation and IL-2 production, while
suppressing production of PGE-2 and also suppresses IL-4 production (36-40). IL-4 and
PGE-2 have both been shown to suppress antitumor immune responses (41,42).
Another interesting approach to cancer therapy, which has not been attempted is the
combination of hypertonic saline infustion with systemic interleukin-2. One of the big
problems with clinical administration of IL-2 is induction of a shock-like state called the vascular-leak syndrome (43). Along these lines, a randomized trial was conducted
examining crystalloid vs colloid resuscitation. No clear benefitial effect was
demonstrated (44).

Although therapy with hypertonic saline seems absurdly simple, we must not forget that
cisplatin therapy would have most likely been abandoned had Cvitkovic et al not found
that rapid fluid administration can spare the host of this drug’s nephrotoxic effects

Ozone Therapy/Stressed Cell Therapy


There are some areas in which ideas practiced in alternative medicine may have clinical
relevance, I believe the area of ozone therapy is one of them.

Ozone therapy is administered through several routes:
1. Directly intravenously,
2. Intrarectally,
3. Exposing patient blood to ozone ex-vivo followed by subsequent re-infusion

The first method was described by Lacoste in 1951 who used it to treat vascular
insuffiency and gangrene (47). Intravenous administration of ozone is possible since
both ozone and oxygen are very soluble in blood (48), however this technique is
considered out-dated and is hardly used today. Rectal administration has been used with
some efficacy for AIDS associated diarrhea (49), although, by far, the safest and most
widely method of ozone therapy is the third one mention: autohematherapy.

Vasocare therapy, invented by Anthony Bolten of Vasogen, is analogous to
autohematherapy, with the exception that UV irradation and/or heat is added to the
patient cells before reintroduction. In contrast to traditional ozone therapy, the effects of Vasocare have been extensively analysized scientifically with several patents and papers available in the public domain. I will clump together Vasocare and traditional autohematherapy for purposes of this discussion.

Clinical Effects

Reports of ozone therapy are largely anectodal due to it being primarily practiced in
alternative medicine. In this field it is a panacea, irresponsibly claimed by detractors to be a cure for everything from AIDS to diabetes (50,51). Reports such has these have
severely damaged the credibility of ozone therapy, even placing it on the National Cancer
Institute’s list of questionable treatments for cancer (52).

With that said, I will examine the credible literature on this topic. Anacedotally reported, treatment of peripheral limb ischemia has been successful with autohematherapy (53,54).

Recently, Tylicki et al treated 12 patients with lower limb atherosclerotic ischemia. Of
these, 11 had prolonged ability to walk on a threadmill post-treatment (55). In another
pilot study symptoms of atherosclerotic vasculopathy were improved (56). Utility of
Vasocare treatment was demonstrated in peripheral vascular disease in a two centered
double-blind study by Baird and Belch in the United Kingdom where the treatment group
reported a greater than 50% increase in walking distance compared to controls (57).
Vasogen has currently received approval for a Phase III pivotal trial in peripheral arterial disease (58).

Vasogen has also demonstrated efficacy of Vasocare therapy in autoimmune diseases
both in animal models and in humans, unfortunately, these studies have not been
published in the peer reviewed literature but only as patents (59-61). More relevant to
our discussion, Vasogen noticed some anti-leukemia effects in its trial on graft versus
host disease, this is the basis for an ongoing trial of Vasocare in chronic lymphocytic
leukemia (62).


It is postulated that these effects are mediated in part by the ability of the treatment to increase tissue oxygenation, while at the same time having an anti-inflammatory effect
(reviewed in 63). Erythrocytes in patients receiving autohematherapy are postulated to
be better oxygen carriers than controls due to an increase in 2,3 diphosphoglycerate (64). A randomized trial comparing autohematherapy to hyperbaric oxygen demonstrated that
only autohematherapy decreases blood viscosity while increasing erythrocyte filterability
(65). Both of these changes would hypothetically increase tumor oxygenation. Another
mechanism of ozone therapy may be induction of nitric oxide (NO). NO possesses many
effects, but one of the well known ones is vasodilation (66). In Vasogen mentions in two
of their patents, that Vasocare blocks platelet aggregation and induces NO (67,68).
Once again, these effects could hypothetically increase tumor oxygenation.
Ozone therapy may also have direct effects on cancer cells. In the 1920s Warburg
postulated cancer cells preferentially utilize anaerobic metabolism (69). Others after him have claimed that high concentrations of oxygen can specifically kill tumor cells,
although this was for the most part proven wrong. Interestingly, ozone can preferentially
inhibit various primary human tumor cells while sparing normal tissue, in vitro (70).
Similar results were obtained in leukemic cell lines (71).


Ozone therapy has been used for millions of treatments without toxicity (cited in 72).
Under a different form (Vasocare) ozone therapy is now entering Phase III trials. The
combination of ozone therapy with radio, chemo and immune therapies should increase
efficacy of these treatments by overcoming tumor hypoxia. Future studies in this area are
definitely warranted.


1. Folkman J. Tumor angiogenesis. Adv Cancer Res. 1985;43:175-203

2. Tumour angiogenesis / edited by Roy Bicknell, Claire E. Lewis, and Napoleone
Ferrara. Oxford, [England] ; New York : Oxford University Press, 1997.

3. Jain RK. Haemodynamic and transport barriers to the treatment of solid tumours.
Int J Radiat Biol. 1991 Jul-Aug;60(1-2):85-100

4. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature
blood vessels in established human tumors follows vascular endothelial growth factor
withdrawal. J Clin Invest. 1999 Jan;103(2):159-65.

4a. Williams KJ, Cowen RL, Stratford IJ. Hypoxia and oxidative stress. Tumour
hypoxia—therapeutic considerations. Breast Cancer Res. 2001;3(5):328-31

5. Fenton BM, Lord EM, Paoni SF. Intravascular HBO saturations, perfusion and
hypoxia in spontaneous and transplanted tumor models.
Int J Cancer. 2001 Sep 1;93(5):693-8.

6. Gouin-Thibault I, Achkar A, Samama MM. The thrombophilic state in cancer patients.
Acta Haematol. 2001;106(1-2):33-42

7. Dunst J, Ahrens S, Paulussen M, Burdach S, Jurgens H. Prognostic impact of tumor
perfusion in MR-imaging studies in Ewing tumors. Strahlenther Onkol. 2001

8. Rudat V, Stadler P, Becker A, Vanselow B, Dietz A, Wannenmacher M, Molls M,
Dunst J, Feldmann HJ. Predictive value of the tumor oxygenation by means of pO2
histography in patients with advanced head and neck cancer. Strahlenther Onkol. 2001

9. Canning MT, Postovit LM, Clarke SH, Graham CH. Oxygen-mediated regulation of
gelatinase and tissue inhibitor of metalloproteinases-1 expression by invasive cells. Exp
Cell Res. 2001 Jul 1;267(1):88-94.

10. Semenza GL. HIF-1: using two hands to flip the angiogenic switch.
Cancer Metastasis Rev. 2000;19(1-2):59-65

11. Pugh CW, Gleadle J, Maxwell PH. Hypoxia and oxidative stress in breast cancer.
Hypoxia signalling pathways. Breast Cancer Res. 2001;3(5):313-7.

11a. Kurzrock R. The role of cytokines in cancer-related fatigue. Cancer. 2001 Sep
15;92(6 Suppl):1684-8.

11b. Littlewood TJ. The impact of hemoglobin levels on treatment outcomes in patients
with cancer. Semin Oncol. 2001 Apr;28(2 Suppl 8):49-53.

12. Naldini A, Cesari S, Bocci V. Effects of hypoxia on the cytotoxicity mediated by
tumor necrosis factor-alpha. Lymphokine Cytokine Res. 1994 Aug;13(4):233-7.

13. Scannell G, Waxman K, Kaml GJ, Ioli G, Gatanaga T, Yamamoto R, Granger GA.
Hypoxia induces a human macrophage cell line to release tumor necrosis factor-alpha and
its soluble receptors in vitro. J Surg Res. 1993 Apr;54(4):281-5.

13a). Balkwill FR. Tumour necrosis factor and cancer. Prog Growth Factor Res.

13b) Natoli G, Costanzo A, Guido F, Moretti F, Levrero M. Apoptotic, non-apoptotic,
and anti-apoptotic pathways of tumor necrosis factor signalling. Biochem Pharmacol.
1998 Oct 15;56(8):915-20.

14. Ishizaka S, Kimoto M, Tsujii T. Defect in generation of LAK cell activity under
oxygen-limited conditions. Immunol Lett. 1992 May;32(3):209-14.

15. Loeffler DA, Juneau PL, Masserant S. Influence of tumour physico-chemical
conditions on interleukin-2-stimulated lymphocyte proliferation. Br J Cancer. 1992

16. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen
dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol
26:638-48, 1953.

17. Hill RP. Cellular basis of radiotherapy. In: Tannock IF, Hill RP, editors. The basic
science of oncology. 2nd ed. New York: McGraw-Hill; pp259-275, 1992.

17a). Tomida A, Tsuruo T. Drug resistance mediated by cellular stress response to the
microenvironment of solid tumors. Anticancer Drug Des. 1999 Apr;14(2):169-77.

18. Haffty BG, Hurley R, Peters LJ. Radiation therapy with hyperbaric oxygen at 4
atmospheres pressure in the management of squamous cell carcinoma of the head and
neck: results of a randomized clinical trial. Cancer J Sci Am. 1999 Nov-Dec;5(6):341-7.

19. Dische S, Saunders MI, Sealy R, Werner ID, Verma N, Foy C, Bentzen SM.
Carcinoma of the cervix and the use of hyperbaric oxygen with radiotherapy: a report of a
randomised controlled trial. Radiother Oncol. 1999 Nov;53(2):93-8.

20. Hartmann KA, van der Kleij AJ, Carl UM, Hulshof MC, Willers R, Sminia P. Effects
of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat
rhabdomyosarcoma R1H.
Int J Radiat Oncol Biol Phys. 2001 Nov 15;51(4):1037-44.

21. Horsman MR, Khalil AA, Nordsmark M, Grau C, Overgaard J. Relationship between
radiobiological hypoxia and direct estimates of tumour oxygenation in a mouse tumour
model. Radiother Oncol. 1993 Jul;28(1):69-71.

22. Powell ME, Collingridge DR, Saunders MI, Hoskin PJ, Hill SA, Chaplin DJ.
Improvement in human tumour oxygenation with carbogen of varying carbon dioxide
concentrations. Radiother Oncol. 1999 Feb;50(2):167-71.

23. Aquino-Parsons C, Green A, Minchinton AI. Oxygen tension in primary
gynaecological tumours: the influence of carbon dioxide concentration. Radiother Oncol.
2000 Oct;57(1):45-51.

24. Partridge SE, Aquino-Parsons C, Luo C, Green A, Olive PL. A pilot study
comparing intratumoral oxygenation using the comet assay following 2.5% and 5%
carbogen and 100% oxygen. Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):575-80.

25. Griffiths JR, McIntyre DJ, Howe FA, McSheehy PM, Ojugo ASE, Rodrigues LM,
Wadsworth P, Price NM, Lofts F, Nicholson G, Smid K, Noordhuis P, Peters GJ, Stubbs
M. Issues of normal tissue toxicity in patient and animal studies—effect of carbogen
breathing in rats after 5-fluorouracil treatment.
Acta Oncol. 2001;40(5):609-14.

26. Martinez JC, Villar A, Cabezon MA, de Serdio JL, Fuentes C, Espineira M, Perez
MD, Gil J, Artazkoz JJ, Borque C, Suner M, Saavedra JA. Hyperfractionated
chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise
developed treatment schedule for advanced head-and-neck cancer.
Int J Radiat Oncol Biol Phys. 2001 May 1;50(1):47-53.

27. Marcial VA, Pajak TF, Kramer S, Davis LW, Stetz J, Laramore GE, Jacobs JR, Al-
Sarraf M, Brady LW. Radiation Therapy Oncology Group (RTOG) studies in head and
neck cancer. Semin Oncol. 1988 Feb;15(1):39-60.

28. Dische S, Rojas A, Rugg T, Hong A, Michael BD. Carbogen breathing: a system for
use in man. Br J Radiol. 1992 Jan;65(769):87-90.

29. Hoskin PJ, Saunders MI, Dische S. Hypoxic radiosensitizers in radical radiotherapy
for patients with bladder carcinoma: hyperbaric oxygen, misonidazole, and accelerated
radiotherapy, carbogen, and nicotinamide. Cancer. 1999 Oct 1;86(7):1322-8.

30. Velasco IT, Pontieri V, Rocha e Silva M Jr, Lopes OU. Hyperosmotic NaCl and
severe hemorrhagic shock. Am J Physiol. 1980 Nov;239(5):H664-73.

31. de Felippe J Jr, Timoner J, Velasco IT, Lopes OU, Rocha-e-Silva M Jr. Treatment of
refractory hypovolaemic shock by 7.5% sodium chloride injections. Lancet. 1980 Nov

32. Mazzoni MC, Borgstrom P, Intaglietta M, Arfors KE. Capillary narrowing in
hemorrhagic shock is rectified by hyperosmotic saline-dextran reinfusion. Circ Shock.
1990 Aug;31(4):407-18.

33. Shires, G. T., A. E. Barber, H. P. Illner. 1995. Current status of resuscitation:
solutions including hypertonic saline. Adv. Surg. 28:133

34. Wade, C. E., G. C. Kramer, J. J. Grady, T. C. Fabian, R. N. Younes. 1997. Efficacy of
hypertonic 7. 5% saline and 6% dextran-70 in treating trauma: a meta-analysis of
controlled clinical studies. Surgery 122:609.

35. de Carvalho H, Matos JA, Bouskela E, Svensjo E. Vascular permeability increase
and plasma volume loss induced by endotoxin was attenuated by hypertonic saline with
or without dextran.
Shock. 1999 Jul;12(1):75-80.

36. Coimbra R, Junger WG, Hoyt DB, Liu FC, Loomis WH, Evers MF. Hypertonic
saline resuscitation restores hemorrhage-induced immunosuppression by decreasing
prostaglandin E2 and interleukin-4 production. J Surg Res. 1996 Aug;64(2):203-9.

37. Junger WG, Coimbra R, Liu FC, Herdon-Remelius C, Junger W, Junger H, Loomis
W, Hoyt DB, Altman A. Hypertonic saline resuscitation: a tool to modulate immune
function in trauma patients?
Shock. 1997 Oct;8(4):235-41.

38. Coimbra R, Junger WG, Liu FC, Loomis WH, Hoyt DB. Hypertonic/hyperoncotic
fluids reverse prostaglandin E2 (PGE2)-induced T-cell suppression. Shock. 1995

39. Junger WG, Hoyt DB, Hamreus M, Liu FC, Herdon-Remelius C, Junger W, Altman
A. Hypertonic saline activates protein tyrosine kinases and mitogen-activated protein
kinase p38 in T-cells. J Trauma. 1997 Mar;42(3):437-43;

40. Junger WG, Liu FC, Loomis WH, Hoyt DB. Hypertonic saline enhances cellular
immune function.
Circ Shock. 1994 Apr;42(4):190-6.

41. Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in
human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev. 1996

42. Young MR. Eicosanoids and the immunology of cancer. Cancer Metastasis Rev.
1994 Dec;13(3-4):337-48.

43. Cotran RS, Pober JS, Gimbrone MA Jr, Springer TA, Wiebke EA, Gaspari AA,
Rosenberg SA, Lotze MT. Endothelial activation during interleukin 2 immunotherapy. A
possible mechanism for the vascular leak syndrome. J Immunol. 1988 Mar

44. Pockaj BA, Yang JC, Lotze MT, Lange JR, Spencer WF, Steinberg SM, Topalian
SL, Schwartzentruber DJ, White DE, Rosenberg SA. A prospective randomized trial
evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak
syndrome associated with interleukin-2 therapy. J Immunother. 1994 Jan;15(1):22-8.

45. Cvitkovic E, Spaulding J, Bethune V, Martin J, Whitmore WF. Improvement of cisdichlorodiammineplatinum
(NSC 119875): therapeutic index in an animal model.
Cancer. 1977 Apr;39(4):1357-61.

46. Gonzales-Vitale JC, Hayes DM, Cvitkovic E, Sternberg SS. The renal pathology in
clinical trials of cis-platinum (II) diamminedichloride. Cancer. 1977 Apr;39(4):1362-71.
47. Lacoste: Traitement des insuffisances vascuilaires pa l’ozone. Gaz med de France

48. Rokitansky O: Klinik und biochemie der ozon therapy. Hospitals 1982;52:643 nd

49. Carpendale MT, Freeberg J, Griffiss JM. Does ozone alleviate AIDS diarrhea?
J Clin Gastroenterol. 1993 Sep;17(2):142-5.




53. Rokitansky O. Klinik und Biochemie der Ozontherapie. Hospitalis 1982;52643-7.

54. Werkmeister H. Dekubitalgeschwure und die Behandlung mit der Ozon-
Unterdruckbegasung. In: Beck, Viebahn-hnsler eds. Ozon-Handbuch. Grundlagen.
Pravention. Therapie. Landsberg/Lech: Ecomed, 1995, V-7-7.1 1-V-7.1, 22.

55. Tylicki L, Niew glowski T, Biedunkiewicz B, Burakowski S, Rutkowski B.
Beneficial clinical effects of ozonated autohemotherapy in chronically dialysed patients
with atherosclerotic ischemia of the lower limbs--pilot study. Int J Artif Organs. 2001

56. Di Paolo N, Bocci V, Garosi G, Borrelli E, Bravi A, Bruci A, Aldinucci C,
Capotondo L. Extracorporeal blood oxygenation and ozonation (EBOO) in man.
preliminary report. Int J Artif Organs. 2000 Feb;23(2):131-41.


58. Visioli F. VasoCare. Vasogen.
Curr Opin Investig Drugs. 2001 Sep;2(9):1247-9.

59. US Patent # 6,258,357

60. US Patent # 6,204,058

61. US Patent # 5,980,954


63. Bocci V. Ozone as a bioregulator. Pharmacology and toxicology of ozonetherapy
today. J Biol Regul Homeost Agents. 1996 Apr-Sep;10(2-3):31-53.

64. Viebahn-Hansler R. Einfluss auf den rythrozytenstoffwechsel. In: Ozon-Handbuch.
Grundlagen-Prevention-Therapie. Landsberg/Lech:Ecomed, 1995, 1-15.

65. Verrazzo G, Coppola L, Luongo C, Sammartino A, Giunta R, Grassia A, Ragone R,
Tirelli A.Hyperbaric oxygen, oxygen-ozone therapy, and rheologic parameters of blood
in patients with peripheral occlusive arterial disease.
Undersea Hyperb Med. 1995 Mar;22(1):17-22.

66. Lind L. Evaluation of endothelium-dependent vasodilation in humans. Blood Press.

67. US Patent # 5,834,030

68. US Patent # 5,591,457

69. Warburg, O. (1924) Biochem Z. 152, 319-344.

70. Sweet F, Kao MS, Lee SC, Hagar WL, Sweet WE. Ozone selectively inhibits growth
of human cancer cells. Science. 1980 Aug 22;209(4459):931-3.

71. Canadian Patent # 2192602

72. Bocci V. Biological and clinical effects of ozone. Has ozone therapy a future in
medicine? Br J Biomed Sci. 1999;56(4):270-9.

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1 Comment | Add Comment

jonnyboy said...

Created 2008-06-21 21:56:06 EST

Funny that you are discussing ozone therapy and vasogen.  If the company would have stuck to protocols that HAVE BEEN successful so many times in places outside of North America, then maybe they would have done better in their trials. 

It is sad to see great technology go to waste like that. 

I hope that Vasogen will get a second chance.

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