The Effectiveness of aCombination Therapy in an

Advanced Uterine Cancer withNeopiasic Infiitrative Lesions

by Prof. Serge JurasunasAbstract

Tumors of the uterine funduscomprise the most common group ofgynecologic malignancies. Advanceddisease states have a poor prognostic andoperations, and other chemotherapy orradiation therapy are often not beneficial.Inoperable large tumors may not respondto chemotherapy radiation. Cancerpatients, in particular, have shown agreater desire to explore other forms oftreatments include complementary andalternative medicine (CAM).

IntroductionA 62-year-old Caucasian female

with a diagnosis of uterine carcinomain an advanced stage of 6 cm wideinvolving hemorrhage was diagnosedby resonance magnetic imaging(RMI) and biopsy in May 2007. Thepatient exhibited extensive infiltrationof neopiasic lesions to the wall ofthe rectum. There was possibleinvasion to bladder and several large

Figure 1 : Patient Before Treatment

adenopathies of about 2 cm localizedto the iliac territory, ganglions, andperitoneal area, as shown by the RMI(Figure 1). She came in to our Instituteon June 2007 in a poor physicalcondition from chemotherapy withadverse toxic effects of fatigue,vomiting, depression, poor appetite,pains, and bleeding hemorrhage.

Antineoplasic drugs treatmentmay decrease large but non-resistant

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Combination Therapy in Advanced Uterine Cancer Lesions

tumors to some extent and mayreduce some adenopathies but neverin the totality, while at the same time,chemotherapy increases oxidativestress, boosts inflammatory mediatorsto stimulate tumor growth, and/orincreases resistance.

Persistence oxidative stressincreases cancer survival,increases angiogenic factors, andinhibits apoptosis.^ Additionally,chemotherapy induces a numberof adverse toxic effects that in turnmay decrease its effectiveness.^Radiation therapy may burn tissues tosome extent with damaging effect tobladder.

One similar case came to us. Thispatient had had only radiation therapy,which developed extensive burninginflammation to the genital organs andabdomen. She also suffered from leftkidney infection and from an inabilityto control her bladder. Not only didthe radiation worsen her condition,but by inducing inflammation, it alsocontributed to metastasis invasion.Inflammatory mediators, such asNFKB or CSFl, are mostly boostedby oxidative stress, over-expressedin many cancers, and contribute toincreased cancer survival.

The TreatmentWe built up a protocol, based on

16 years of clinical experience, thatconsisted of a combination therapy(CT) that might target cancer cells inseveral directions. As with mosf ofour patients, and especially advancedcases, we first included Ukrain, anatural chemotherapeutic drug madefrom an extract of the chelidoniummajus plant that has demonstratedstrong cytostatic activity against cancercells.''^ Many clinical investigationssuggest that as single drug or incombination with conventionaltherapy, Ukrain shows beneficialeffects on many tumors, includingthose in the colon, pancreas, ovary,rectum, breast, etc.*̂ ^

Ukrain has an immunologica! effectwhen prescribed at lower dose andmay be defined as a potent "biologicalresponse modifier."'' At larger doses,it possesses selective cytoloxic effectto cancer cells'* when administered totumor patients by IV injection. Ukrainusually hardens the consistency ofthe tumor and demarcates it from thesurrounding tissue.'*' The observationby laser-scanner microscopy revealsthat a much higher Ukrain uptake canbe seen in a cell nucleus of a malignant

Table 1: Products and Their Posology

Antiangiogenic therapy

Natural anticancer drug

Immunomodulator

Antioxidant therapy(multiple action to targetcancer cells)

Liquid Cartilage Extract as angiogenic inhibitor of tumor'sblood vessels1 vial (frozen) of 30 ml per day

Ukrain, a natural drug containing an extract of theceiandrine plant {chelidonium majus), one injection of 5ml IM or IV, three times per week

Biobran MGN3, an arabinoxylan extract of rice bran withstrong efficiency to activate immune cells,3g per day

Anoxe, a compound rich in antioxidants extract frommodified herbs and seed with low molecular weightcontain full range of quickly absorbed antioxidants, 18gto 24g per day

cell compared toa normal cell (Figures2 and 3):" immunomodulating effectsat 5 mg; malignocytolitic effect at 20mg.

We have been using Ukrain nowfor over 20 years and have observedsatisfactory results in many types ofcancer such breast, liver, pancreaticcancer, colon, etc. In advancedcancer cases, when chemotherapyhas shown no beneficial effects andpatients are dismissed from hospital,Ukrain increases the median survival.Such results can be observed withpancreatic cancer patients with amedian survival up to three to fouryears. Better results are obtainedon large tumor and disseminatedlesions when Ukrain is included ina combination therapy as support toconventional treatment. A male patientof 38 years, a nurse at hospital withan advanced cancer in the pancreas,liver, and lung and multiple lesions,with a prognosis of six months to live,actually lived an additional two-and-a-half years with a good quality oflife, and we managed to reduce andeliminate several large lesions anddecrease very high tumor markersto normal through the followingapproach:

• An antiangiogenic therapy,which is a main goal in any cancerapproach, using a liquid cartilageextract (LCE) known as Comitris,which has demonstrated strongefficacy to inhibit vascularization oftumor blood vessels'^'^

By inhibiting the VEGF and matrixmetalloproteinase (MMP 2 - 9 - 1 2 )often expressed in tumors and involvedin both migration of endothelial cellsand tumor invasion,'"' an angiogenictherapy increases the effectivenessof chemotherapy as demonstrated invarious clinical studies with animalsor humans.

• An immunomodulator madefrom a derivate, processed dietaryfiber, which consists of a modifiedarabinoxylan derived from rice brancultivated on shitake mushroom

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Combination Therapy in Advanced Uterine Cancer Lesions

mycelia enzymes that demonstratesstrong ability to modulate the immunesystem, enhancing T-cells, B-cells,macrophages, and particularly NaturalKiller (NK)cells'MFigure 4)

The compound Biobran MGn3may increase the NK cells' activityfrom 80% to 3607o.''' Biobran hasdemonstrated the efficiency in thetreatment of various form of cancer byenhancing the immune cells function,restoring NK cells against cancercells.'^'"

• An antioxidant therapy madefrom modified vegetables and seedsrich in antioxidants known as Anoxe,which contain low molecular enzymes(Superoxide dismutase, catalase) anda full range of antioxidants such asvitamins A, C, E, betacarotene, tannin,riboflavin, flavonoids, polyphenols,glutathione and act as SOD molecule(7,3 X 1,000 unit/g)

The modified antioxidantcompound is quickly absorbed by

the body for immediate therapeuticapplication.'" Anoxe has demonstratedproperties that reduce or eliminateReactive Oxygen Species (ROS)'̂and has strong anti-inflammatory andCOX-l/COX-2 inhibitory properties''^in contrast to other treatments,particularly Vioxx, with no adverse/effects (Figure 5).

Growing evidence suggests thatinhibition of COX-2 might havean important role in the delay ofprogression in established cancer, andCOX-2 inhibitors may be consideredas novel agents in addition tostandard treatment, while the enzymeSuperoxide dismutase may inhibitmetastasis promotion and suppresstumor growth.- '̂

• Finally, an aggressive diet wassuggested that includes whole grains,cereals, steam vegetables, shitakemushrooms, barley soup, onions, kefir,sesame oil, fresh daily vegetables, andfruit juices.

Figure 6: After Treatment

Duration of TreatmentThe patient followed the whole

treatment and diet during five monthswith regular monthly consultation tocheck on her health condition andimprovement, including any adversetoxic effects. We performed severalalternative check-ups, includingperipheral blood analysis, oxidativestress status, and electromagneticfield computerize test. As with allour cancer patients, the patient filledout a monthly "Evaluation of CancerPatients" to check on energy levelsand any eventual adverse toxiceffects.

ResultsAfter two months of treatment, the

patient increased her quality of life andwas feeling stronger and experiencingless adverse toxic effects.

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Combination Therapy in Advanced Uterine Cancer Lesions

The good new is that the largetumor decreased by 50% size (3cm), and at the end of four months(9/27/2007), a new RMI shown acomplete therapeutic response witha total regression of the large tumor.Additionally, we observed a completeregression of all the adenopathiesfrom the wall of the rectum andvaginal canal (Figure 6). The patientis free from bleeding hemorrhage.Hospital oncologists were completelyastonished by such a quick result,which could not be have beenachieved by chemotherapy alone.Because of this unexpected result,they told the patient that radiationtreatment was no longer necessary.

CommentsThe result obtained in four months,

as verified by hospital check-up andmedical imagery made before andafter, is indeed quite impressive.This treatment eliminated the needfor radiation therapy, which has acontroversial role in uterine cancerand, in many cases, may induceinflammation that in turn stimulateangiogenesis and increase metastasisexpansion. Therefore, we have clearlydemonstrated the synergistic effect ofour combination therapy to increasechemotherapy's effectiveness.

The antioxidant compound Anoxedecreases oxidative stress and inhibitsCOX2 activity, which in turn maydecrease angiogenic factors. Manynew lines of research demonstrate thatoverexpressed COX 2 is linked with

Figure 4: NK Immunorestoration of Cancer Patients by aModifier Arabinoxyian Rice Bran

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5 50-$• 4 0 -

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^M Before Treatment

JH After Treatment

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1 ̂ i Ju10 Prostate 12 Breast 5 Multiple Myeloma 5 Leukemia

The figure demonstrates the baseline values of cytotoxic responses of NK cells in 32patients at one to two weeks after treatment. Patients demonstrate overall significantlow level In NK function - treatment with MGn3 result in significant increase in NKactivity up to tenfold.

Figure 5: Anti-fnflammatory and COX-1 and COX-2iniiibitory Property of Anoxe

Biosctive Natural Products Laborstory - Naöonal Food Safety and Toxicology Center - Michigan State Univ. - USA

Anti-inflammatory activities of NR-m & NR-wNR-w COX-1 and COX-2 inhibitory activity

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NR-m NR-w npro asp tmQ COX-1 21 OOW 7B BB 70.56 64 14 51 *2• COX-2 55 5 92 1 9S 24 59.2

tumor resistance to chemotherapyand radiation including prostateand breast cancer. By providingless resistance, and by conjointlyattacking the tumor via cytotoxicityof the natural anticancer drug Ukrain,high doses of antioxidants, and lessvascularization, the tumor starts toshrink and can be more vulnerableto immune cells' activity increase bythe immunostimulant Biobran. Theresult is an increase in the numberof cancer cells destroyed jointlyby chemotherapy and the immunesystem.

Usually chemotherapy decreasesthe concentration of plasma vitamins- antioxidants that in turn impairimmune function, mainly decreasingNK cells' activity. The low molecularantioxidant compound Anoxe thatcontains a full range of antioxidantsmay restore the immune cells' activityand prevent Infections that may beresponsible for increasing mortality incancer patients.

ConciusionOverall, in this case, we have

clinically demonstrated that acombination therapy (Table 1)that targets cancer cells in severaldirections may be useful when usedsimultaneously with conventionaltreatment to reduce and/or eliminatesolid tumors and, at the same time,decrease adverse toxic effects andincrease patients' quality of life.

Serge JurasunasHoliterapias InstituteRua da Misericordia, 137- 1°1200-272 Lisbon, PortugalPhone +351-21-3471117Fax +351-21-3471119info@sergejurasunas.com

Serge lurasunas is an internationally knowndoctor of complementary and altemativemedicine with over 35 years of experiencein the field of medicine. He runs a clinicof integrative medicine in Portugal wherecancer patients from various countries receivecomplementary care and conventionaltreatments.

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Combination Therapy in Advanced Uterine Cancer Lesions

NotesShdi t(̂ r E, Williams (A, Hudson RM, et al. Oxidativestress interfere with cancer chemotherapyinhibition of lymphonw cells and apoptosis andphagcx-ytosifi. Blood. 2000 July 1;96 (1): 307-313.Toyokami S, Okamada K, Yocho ), Hiaitt, Persisten!oxiddtive stress in cancer. FEBS. 1995;358:13.Conkiin KA. Chemolherdpy-associated oxidativestress-impact on chemotherapy effectiveness. IntgCancer Thee. 2004; 3:294-300.Lohninger A, Hamler F. Chelidomium majus I.(Ukrainl In the treatment of cancer patienis. DrugsExp Clin Res. 1992;18 Suppl:73-7.Uglyarutsa KN, Nefyodow LI, Karayedovd LM,Nowicky JW, Br^osko W. Clinical aspects of tancprtreatment and new biochemical mechanisms of thedfufi Ukrain.

Susak YM, Zewskow VS, Yaremchuk OY,Kravchenco OB, Yatsk IM, Korsh OB. Comparingchemotherapy and X-rays therapy with Ukrainmnnolhprapy for colorectal cancer. Dmgs Clin.Res. Î996;22;115-122.Ernsi E, Scnidi K. Ukrain: a new cancer cure? Asystematic review of randomized clinical trials.BMC Cancer. 2005; 5: 69.Liepins A, Nowicky )W. Modulation of immuneeffectors cell cytolytic activity and tumor growthinhibition in vivo by Ukrain INSC - 631570).Drugs Expl. Clin Res. I996;XXII isuppÜ: 31-32.Nowicky |W, Nowicky W. Liepens A. Cytostalicand cytotoxic effects of Ukrain on malignant cells.VIII Mediterranean Congress of chemotherapy.Athens, Greece, tournai of Chemotherapy. 24-29May 1992; 5 (Supplement n");! 797-1993.

Figure 2: Straight to the Heart - Ukrain Targets Malignant Tumor Cell NucleiProf Dr Andrejs Liepins Memorial University of Newfoundland Faculty of Medicine, St. John's, Newfoundland,

CANADAA1B3V6

Figure 3: Effects of Ukrain

10. Nowicky |W, Greif M, Hamler F, Hitismayr W,Staub. Microscopic UV - Mafking through affinity.lournal of Tumor Marker Oncology. 1998; 3 (4):463-1998.

11. Hohenwater O, Stutzenbeger K. Katinger H,Liepens A, Nowicky |W. Selective inhibition of Invitro cell growth by the anti tumor drug Ukrain.Drugs Bxpl CImic Rfs. 1992;XVIII:I.

12. Lee A. Langet R. Shark Cartilage conlarns inhibitorsof angiogenesis. Science. 1983;221il 185-1167.

13. Berbari P, Thibodean A, Germain L. Saint-CyrM, Gandeau P, Elhbouri S, Dupont E, GarrelDR, Elboris. Antiangiogenic effects oí the oraladministration of liquid cartilage extracts inhuman./. Sur Res. 1999 Nov;87 111; 108-13.

14. Shen |R, Tsai ML, Chung Wl. Effects of U-995 apolent shark cartilage - derived angiogenesisinhibitor on anti-angiogenesis and anti-tumoractivities. Anticancer Res. 1998 Nov/Dec. 18;6A:4435-41.

15. Ghoneum M. Enhancement of Human NaturalKiller cell activity by modified arabinoxylan fromrice bran (MGN3). Int. Immunotherapy IV. 1998;2:89-99.

16. Ghomeum M. NK immunorestoration of cancerpatients MGN3: A modified arabinoxylan rice branstudy of 32 patients followed up to four years.

17. Ghoneum M, Marmatulia G, NKimmunomodulatory function in 27 cancer patientsbyMGN3; A modified arabinoxylan from rice bran.Abstraa. 87'" Ann Meeting American Associationfor Cancer Research.

18. Jura^unas S. Therapeutic application of a new lowmolecular antioxidant compound ¡Anoxe} in ROSactivity. Abs!. Inst. Symposium on Reactive Oxygenand Nitrogen Species: Diagnostic, Preventive andtherapeutic values. Si. Petersburg, Russia. |uly8-12,2002.

19. lonescu)G,IurasunasS, Weber D. Effect of naturallike compounds on redox potenfial and tree radicalgeneration in venous blood and plasmas. Researc hDept. of Specialkiinic Neukirchen (Germany).2005.

20. Nair MG, Nelson, Jurasunas S. Anti-inflammatoryand COXl. COX2. Inhibitory property of Anoxe:Bioactive Natural Product lab. National FoodSafety and Toxicology Center. Michigan SlateUniversity, USA.

21. Safford SE, Oberley TD, Urano M, St. Clair DK.Suppression of fibrosarcoma metastasis by elevatedexpression of manganese Superoxide dismutase.Cancer Res. l994;54:4261-4262.

Yellow fluorescence of Ukrain in tumortissue.

Pathotogicai sample (gastricadenocarcinoma) under UV light. 12hours after 20 mg Ukrain IV injection.

Lymphatic nodes of the same patientshow fluorescent points.

Examination malignant tissue at theselocations, next to unaffected tissue

Exutcerated mamma-ca in 58-year-oldpatient.

After the flrst injection with Ukrain visiblefluorescence in the tumor area.

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