R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd

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1 R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd Dear Dr. Gilbard and Dr Hammon, Florina, 29 / 4 / 9 EX-VIVO TEST SCREEN We send you the results from the analysis made about a patient (??????????????) suffering from breast carcinoma. The that was sent to us for analysis was a of ml of whole blood that contained EDTA-Ca as anti-coagulant, all packed with water ice. In our laboratory we made the following : We isolated the malignant cells using Oncoquick with a membrane that isolates malignant cells from normal cells after centrifugation and positive and negative selection using multiple cell markers. The results during the isolation procedure are presented below : Table of markers: CD45 positive cells (Hematologic origin cells) CD45 negative cells (non Hematologic origin) CD15 NEGATIVE CD34 NEGATIVE CD3 NEGATIVE CD99 NEGATIVE BCR-ABL NEGATIVE EpCam POSITIVE CD34 NEGATIVE VHL mut. NEGATIVE CD19 NEGATIVE CD19 NEGATIVE CD133 POSITIVE CD31 PSMA MUC-1 CD44 CD63 NEGATIVE NEGATIVE NEGATIVE POSITIVE NEGATIVE Index of marker : CD45: Hematologic origin cell marker, CD15: Hematologic malignancy marker, CD3: Hematologic malignancy marker, CD34: hematological stem cell and blast cell marker, epithelioid sarcoma marker, CD19: hematology B cell origin marker Bcr-Abl: Hematologic malignancy marker, CD99: Sarcoma marker, VHL: renal carcinoma marker, CD19: Lung cancer cell marker (NSCLC) MUC-1: lung cancer cell marker (SCLC), CD63: melanoma cell marker, CD44, CD133: tumour stem cell marker, PSMA: prostate cancer specific tumour stem cell marker, CD31: endothelial cell membrane marker. Conclusion: We notice that after isolation procedure there are remaining malignant cells. The concentration of the isolated population is 3.3 cells/ 7.5 ml (SD +/-,3 cell) (1% was CD44+ve, approx. 5% was CD133+ve). Regardly, Dr Papasotiriou Ioannis MD Head of molecular medicine dpt of R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Index of circulating cells number: (upper limit : progress of disease, lower than limit: beginning of disease or stable of disease when the patient is on treatment plan) Breast cancer: 5cell/7.5ml, Prostate cancer cells/ml, Sarcoma: 15cells/6.5ml, Colon cancer: 5cells/ml, Lung cancer (Lc=, r=.99): 1cell/ml. *This test will NOT DETECT cancers of the brain or other cancers that have been encapsulated by the body or are not releasing cancer cells into the blood stream. This is not a stand alone test, we still recommend using biopsy, blood markers and/or appropriate scans with this test when cancer is suspected or known to exist. AT

2 R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd Dear Dr. Gilbard and Dr. Hammon, Florina, 29 / 4 / 9 EX-VIVO TEST We send you the results from the analysis made about a patient (??????????) suffering from breast carcinoma stage. The that was sent to us for analysis was a of ml of whole blood that contained EDTA-Ca as anti-coagulant, packed with water ice. In our laboratory we made the following : We isolated the malignant cells using Oncoquick with a membrane that isolates malignant cells from normal cells. Then we centrifuged at 35g for 1 min and we collected the supernatant with the malignant cells. Then we proceed to isolation of malignant cells from mononuclear cells by negative selection. Then we developed forty eight cell cultures in a fetal calf serum media. In each culture of the well plate we added a biological modifier substance (H2O2, ascorbic acid, mistletoe, quercetin, indol-3-carbinol, c-statin, Ukrain, Poly MVA, Co enzyme Q1, IP6, pancreatic enzymes, salvestrol, Uncaria Tomentosa, annonaceous acetogenins, cesium chloride, amygdalin-b17-, artesunate, maitake, lycopene, curcumin, green tee extract, ellagic acid, N-acetyl-cysteine, UltraTreinols Plus, prolamine iodine, Grape seed supreme, Dim avail, Ganoderma, Astragalus Complex, Vitanox, Echinacea Premium Blend, Burdock complex, Vitamin E (tocopherol), superoxide dismutase (SOD), PME, selenium, aloe vera, acemannan, Acai berry, Avemar pulvis, AHCC-Active Hexose Correlated Compound, sodium bicarbonate, Thymex, OPC, Intenzyme, Oncoplex, cruciferous, Larrea) that is used in clinical application. Then we developed those cultures and we harvested a every 24 hours and made the following assays. In the culture that it contains all substance we measure the apoptotic ability using the oncogen apoptosis kit In the culture that it contains the Ukrain we measure the inhibition of tyrosin kinase catalytic ability from growth factors receptor (EGF-r, IGF-r,) and the production of cytokines PBMC In the culture that contains quercetin we measure the inhibition of EGF and IGF. In the culture that contains indol-3-carbinol we measure the inhibition of VEGF and FGF and PDGF In the culture that it contains the mistletoe we measure the inhibition of tyrosin kinase catalytic ability from growth factors receptor (EGF-r, IGF-r,) and the production of cytokines and the increase of PBMC In the culture that it contains the H2O2 we measure viability of the culture in 4 days of treatment. In the culture that it contains the ascorbic acid we measure the catalytic activity of GSH and GSSG (redox reaction) and the induction of cytochrome C (apoptosis). In the culture that it contains the Poly MVA we measure the catalytic activity of GSH and GSSG (redox reaction) and the induction of cytochrome C (apoptosis) In the culture that it contains the artesunate we measure the catalytic activity of GSH and GSSG (redox reaction for free radical since artesunate bind free radicals with iron molecule ), the inhibition of VEGF, FGF and PDGF (since it act to the angiogenesis cascade reactions) and the induction of cytochrome C (apoptosis).

3 RESULTS: 1. We notice that in culture that contains the ascorbic acid we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by 65%. 2. We notice that in culture that contains the Poly MVA we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by %. 3. We notice that in culture that contains Astragalus complex we have inhibition of EGF-r by less than 5% and for IGF-r by <5% and we notice no increase of cytokine production. 4. We notice that in the culture that contains quercetin we have inhibition of EGF by 5% and IGF by 45% 5. We notice that in the culture that contains indol-3-carbinol we have inhibition of VEGF by less than 5%, of FGF by 5%, and PDGF by 5% 6. We notice that in culture that contains mistletoe we have inhibition of EGF-r by less than 5% and for IGF-r by 5% and we notice no increase of cytokine production, and there is no increase of PBMC. 7. We notice that in culture that contains the c-statin we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by 35%. 8. We notice that in culture that contains Ukrain we have inhibition of EGF-r by less than 5% and for IGF-r by 5% and we notice no increase of cytokine production, and there is no increase of PBMC. 9. We notice that in culture that contains the H2O2 we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by less than 5% and the viability of the culture remain stable. 1. We notice that in culture that contains the Co enzyme Q1 we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by less than 5% and the viability of the culture remain stable. 11. We notice that in culture that contains the polysaccharide Ganoderma we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c and the viability of the culture remain stable. 12. We notice that in culture that contains the IP6 we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by less than 5% and the viability of the culture remain stable. 13. We notice that in culture that contains the pancreatic enzymes we have by less than 5% and the viability of the culture remain stable. 14. We notice that in culture that contains the salvestrol we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by 45% and the viability of the culture reduced by 35%. 15. We notice that in culture that contains the Uncaria tomentosa we have by less than 5% 16. We notice that in culture that contains the cesium chloride we have no 17. We notice that in culture that contains the prolamine iodine we have no 18. We notice that in culture that contains the Grape Seed Supreme we have no 19. We notice in culture that contains the annonaceous acetogenins we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by less than 5%. We notice that in culture that contains the Dim Avail we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c and the viability of the culture remain stable.

4 21. We notice that in culture that contains the amygdalin-b17- we have no and the viability of the culture remain stable 22. We notice that in culture that contains maitake we have inhibition of EGF-r by less than 5% and for IGF-r by 5% and we notice no increase of cytokine production, and there is no increase of PBMC. 23. We notice that in culture that contains the curcumin (turmeric) we have no 24. We notice that in culture that contains the lycopene we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c and the viability of the culture remain stable. 25. We notice that in culture that contains the green tea extract we have no and the viability of the culture remain stable 26. We notice that in culture that contains super artemisinin, there is inhibition of redox reaction and increase of intracellular free radicals, there is increase of cytochrome c (apoptosis) by 55% and the inhibition rate of VEGF is %, of FGF is 35% and of PDGF is %. 27. We notice that in culture that contains the UltraTreinols Plus we have no 28. We notice that in culture that contains the ellagic acid we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c and the viability of the culture remain stable. 29. We notice that in culture that contains the Vitanox we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c and the viability of the culture remain stable. 3. We notice that in culture that contains the N-acetyl-cysteine we have no 31. We notice that in culture that contains the Echinacea Premium Blend we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c 32. We notice that in culture that contains the Burdock complex we have no 33. We notice that in culture that contains the vitamin E we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c and the viability of the culture remain stable. 34. We notice that in culture that contains the superoxide dismutase we have no 35. We notice that in culture that contains the aloe vera extract we have no 36. We notice that in culture that contains selenium we have inhibition of EGF-r by less than 5% and for IGF-r by 5% and we notice no increase of cytokine production, and there is no increase of PBMC and NK. 37. We notice that in culture that contains acemannan we have inhibition of EGF-r by less than 5% and for IGF-r by <5% and we notice no increase of cytokine production, and there is no increase of PBMC and NK. 38. We notice that in culture that contains AHCC we have inhibition of EGF-r by less than 5% and for IGF-r by 5% and we notice no increase of cytokine production, and there is no increase of PBMC and NK.

5 39. We notice that in culture that contains the Avemar pulvis we have increase of the cascade of caspase (especially 3 and 9) and cytochrome-c by 5% and the viability of the culture reduced by 25%.. We notice that in culture that contains the anti-oxidant Acai berry we no have 41. We notice that in culture that contains the PME we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c. 42. We notice that in culture that contains the Cruciferous complete we have no. 43. We notice that in culture that contains the Thymex we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c. 44. We notice that in culture that contains the OPC we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c. 45. We notice that in culture that contains the Intenzyme we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c. 46. We notice that in culture that contains the Oncoplex we have no increase of the cascade of caspase (especially 3 and 9) and cytochrome-c. 47. We notice that in culture that contains the Sodium Bicarbonate 5% we have no 48. We notice that in culture that contains Larrea Plus we have inhibition of EGF-r by less than 5% and for IGF-r by 5% and we notice no increase of cytokine production, and there is no increase of PBMC and NK. CONCLUSION: It seems that this specific population of malignant cell have greater sensitivity in quercetin, in Avemar pulvis, in c-statin, in super artemisinin, in Poly-MVA, in salvestrol and in ascorbic acid and less in hydrogen peroxide (H2O2), Co enzyme Q1, IP6, N-acetyl-cysteine, pancreatic enzymes, cesium chloride, ellagic acid, vitamin E (tocopherol), maitake, in Ukrain, in indol 3-carbinol, Uncaria tomentosa (Samento), in selenium, Ganoderma, in curcumin (turmeric), in artesunate, in Vitanox, in superoxide dismutase, UltraTreinols Plus, in mistletoe, Acai berry, in AHCC-Active Hexose Correlated Compound, in amygdalin-(b17), in Oncoplex, in Dim Avail, in Astragalus complex, in acemannan, in Burdock complex, aloe vera extract, prolamine iodine, Echinacea Premium Blend, in Grape Seed Supreme, in Thymex, in PME, in OPC, sodium bicarbonate, Intenzyme, cruciferous, in Larrea Plus, annonaceous acetogenins (paw-paw), lycopene and in green tea extract. Regardly, Dr Papasotiriou Ioannis MD Head of molecular medicine dpt of R.G.C.C.-RESEARCH GENETIC CANCER CENTRE *This test and the recommendations are not designed to replace traditional oncological treatment and or care. It is only intended to support the immune system & nutritional needs during standard traditional oncological care and treatment. These statements and recommendations have not been evaluated by the FDA. These recommendations are not intended to diagnose, treat, cure, or prevent any disease. ATMC

6 R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd Dear Dr. Gilbard and Dr. Hammon, EX-VIVO TEST Florina, 29 / 4 / 9 We send you the results from the analysis made about a patient (?????????????) suffering from breast carcinoma stage.. The that was sent to us for analysis was a of ml of whole blood that contained EDTA-Ca as anti-coagulant, all packed with water ice. In our laboratory we made the following : We isolated the malignant cells using Oncoquick with a membrane that isolates malignant cells from normal cells after centrifugation and positive and negative selection using anti-epcam as cell marker and anti-cd45. We develop six (6) different cultures from malignant cells (one with xanthone compound from Mangosteen product, one compound from Larrea Plus (chaparral) product shown as (vitamin C on the graph), one with the mineral mixture from salve product Virxcan (shown as minerals on the graph), one with the vitamin A compound for Bio-Ae-Mulsion product, one with the cholecalciferol (vitamin D 3 ) from Bio-D- Mulsion product, and one without any additional compound inside the media as control). From each culture we test the expression of caspase 3 and the concentration of cytochrome c in the extracellular matter (measurement of apoptosis induction) The results are presented below : Malignant cell cultures compared analysis Xantrone vitanin c minerals vitamin a vitamin d normal Casp 9 Cyt-c Conclusion : We notice that Larrea Plus can induce apoptosis for the specific cancer cells becoming from patient above. Regardly, Dr Papasotiriou Ioannis MD Head of molecular medicine dpt of R.G.C.C.-RESEARCH GENETIC CANCER CENTRE *This test and the recommendations are not designed to replace traditional oncological treatment and or care. It is only intended to support the immune system & nutritional needs during standard traditional oncological care and treatment. These statements and recommendations have not been evaluated by the FDA. These recommendations are not intended to diagnose, treat, cure, or prevent any disease. ATMC

7 R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd Florina, 29 / 4 / 9 Dear Dr. Gilbard and Dr. Hammon, EX-VIVO TEST We send you the results from the analysis made about a patient (?????????????) suffering from breast carcinoma. The that was sent to us for analysis was a of ml of whole blood that contained EDTA-Ca as anti-coagulant, all packed with water ice. In our laboratory we made the following : We isolated the malignant cells using Oncoquick with a membrane that isolates malignant cells from normal cells after centrifugation and positive and negative selection using anti-epcam as cell marker. We develop two (2) different cultures from malignant cells (one with Argentyn23[Ag+] in the culture media in concentration AUC- and one without Argentyn23[Ag-]) from the blood of patient above. From the culture that include thalidomide [Ag+] to the media in the culture with malignant cells, we measure the activity of caspase 3 and cytochrome c. From both cultures we make compare analysis of IL2, IL6, IFNa and IFNgamma production rate. The results are presented below : Malignant cell cultures compared analysis IL-2 IL-6 IFNa IFNg Ag- Ag+ In the culture Ag+ we notice no increase of caspase 3 activity by less than 5% and cytochrome c Conclusion : We notice that the Argentyn 23 (Hydrosol Silver) cannot induce apoptosis for the specific cancer cells becoming from patient above and it cannot induce immune response (immuno-therapy options) Regardly, Dr Papasotiriou Ioannis MD Head of molecular medicine dpt of R.G.C.C.-RESEARCH GENETIC CANCER CENTRE *This test and the recommendations are not designed to replace traditional oncological treatment and or care. It is only intended to support the immune system & nutritional needs during standard traditional oncological care and treatment. These statements and recommendations have not been evaluated by the FDA. These recommendations are not intended to diagnose, treat, cure, or prevent any disease. ATMC

8 R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd Dear Dr. Gilbard and Dr. Hammon, EX-VIVO TEST Florina, 29 / 4 / 9 We send you the results from the analysis made about a patient (??????????????) suffering from breast carcinoma stage. The that was sent to us for analysis was a of ml of whole blood that contained EDTA-Ca as anti-coagulant, all packed with water ice. In our laboratory we made the following : We isolated the malignant cells using Oncoquick with a membrane that isolates malignant cells from normal cells after centrifugation and positive and negative selection using epithelial cell marker. We develop two (2) different cultures from malignant cells (one with thalidomide[th+] in the culture media in concentration AUC- and one without thalidomide[th-]) from the blood of patient above. From the culture that include thalidomide [th+] to the media in the culture with malignant cells, we measure the activity of caspase 3 and cytochrome c. From both cultures we make compared analysis of VEGF, PDGF, FGF and MMPs inhibition rate. The results are presented below : Malignant cell cultures compared analysis VEGF PDGF FGF MMPs thth+ In the culture th+ we notice increase of caspase 3 activity and cytochrome c by 35% (apoptosis induction) Conclusion : We notice that the thalidomide can inhibit the neovascularization and it can induce the apoptosis to the cancer cell becoming from the patient above, but it cannot inhibit the invasion activity of the cancer cells. Regardly, Dr Papasotiriou Ioannis MD Head of molecular medicine dpt of R.G.C.C.-RESEARCH GENETIC CANCER CENTRE *This test and the recommendations are not designed to replace traditional oncological treatment and or care. It is only intended to support the immune system & nutritional needs during standard traditional oncological care and treatment. These statements and recommendations have not been evaluated by the FDA. These recommendations are not intended to diagnose, treat, cure, or prevent any disease. ATMC

9 R.G.C.C.-RESEARCH GENETIC CANCER CENTRE Ltd Dear Dr. Gilbard and Dr. Hammon, EX-VIVO TEST Florina, 29 / 4 / 9 We send you the results from the analysis made about a patient (?????????????) suffering from breast carcinoma stage. The that was sent to us for analysis was a of ml of whole blood that contained EDTA-Ca as anti-coagulant, all packed with water ice. In our laboratory we made the following : We isolated the malignant cells using Oncoquick with a membrane that isolates malignant cells from normal cells after centrifugation and positive selection using epithelial cell marker and negative selection using anti-cd45 particles (isolated 3.3 cells/7.5 ml SD +/-.3 cell). Then we developed cell cultures in a fetal calf serum media and at the same time we developed colony cultures in soft agar. In each culture of the well plate we added a chemotherapeutic substance that is used in clinical application. Then we developed those cultures and we harvested a every 24 hours for 6 days and made the following assays. There was made an isolation of the genomic DNA using the kit Invisorb of INVITEK. We isolated mrna using the mrna Magprep blood isolation kit of NOVAGEN. We traced the mrna and the genes of MDR1 ( multi drug resistant 1 ), MRP and LRP using the technique of Northern Blot.(resistance in drugs used in chemotherapies) We tracked the mrna and the gene of topoisomerase I and II a & b using the technique of Northern Blot. ( sensitivity in cytostatic inhibitors of topoisomerase ) We tracked the quantity of the mrna of the tubulin using the RT-PCR.( sensitivity in cytostatics of the kind of taxanes and the products of the alkaloids of Vinca ) We defined the activity of the enzyme complex of the glutathione-s- transferases (GST kit of NOVAGEN). ( resistance in drugs used in chemotherapies- especially in platinum compounds ) We defined the DNA methyl transferase which is a target of the alkylating factors (products of platinum, cyclophosphamide and the products of it ) We defined the mrna of the thymidylate synthetase ( TS ) and the DHFR. (sensitivity in 5-FU, capecitabine and methotrexate ) We defined the mrna of the reductase of 5-CMP (sensitivity in gemcitabine) We defined the receptors of the MMP and the receptors of laminin (invasive ability of the tumor ) We defined the expression of protein p27 that is responsible for cell arrest in G stage. We defined the VEGF ( neoangiogenetic factor ) and the induction of the apoptotic pathway using ONCOGENE kit from NOVAGEN. We defined the ability of acting of the nucleus protein kinases which are a target of the carbazine compounds. We defined the overexpression of TGFa and TGFb factors as targets for suramin sulfate. We defined the overexpression of somatostatin receptor (SS-R), of COX-2 and 5-LOX, of c-erb-b2 (Her/Neu2), c-erb-b1, and androgen estrogen and progesterone receptors.

10 The above conclusions were also confirmed by the cell cultures of the tumor and in the diagrams there is a development curve for each category of cytostatics cisplatin carboplatin cyclophosfamide ifosfamide dacarbazine oxaliplatin mitomycin melphalan treosulfan temozolomide procarbazine BCNU ACNU CCNU Bleomycin Trofosfamide Estramustine *Bendamustin doxorubicin liposomal doxorubicin epirubicin daunorubicin dactinomycin CPT11 topotecan idarubicin 1 Paclitaxel Docetaxel Vincristin Vinblastin Vinorelbin MDR1 MRP LRP GST

11 FU MTX Gemcitabine capecitabine etoposide mitoxandrone FUdR UFT raltitrexed pemetrexed NAME RELATED RESULTS CES1 &2 (carboxyesterase) Resist to camptothecin Normal E2F1 Transcr. Fact of TS & topoi Normal p1 Tyrosin kinase growth f. Normal p27 Cell arrest (G ) 45% over control DPD Resist to 5FU Normal UP Resist to 5FU Normal NP Resist to pyrim. antagonist Normal TP Resist to 5FU Normal Gamma GC Resist to alkylating drug Normal p53 Cell cycle regulator 65% over control p16 Apoptosis 5% over control VEGF Angiogenesis % over control FGF Angiogenesis 5% over control PDGF Angiogenesis 65% over control COX2 Tumour Growth Normal 5-LOX Tumour Growth Normal MMP Metastases 55% over control TS Rapid cell cycle (THFA) Normal DHFR Rapid cell cycle (THFA) Normal SHMT Rapid cell cycle (THFA) Normal GARFT Rapid cell cycle(thfa) Normal NFκB Transcription fact 35% over control IκB (a,d,e) Inhibitor of NFκB 15% below control Ribonucleoside reductase DNA synthesis Normal DNA methyltransferase I DNA methylation Normal DNA demethylase DNA methylation Normal O6-methylguanine-DNA-tran. DNA methylation Normal TGF-b Tumor Growth 25% over control EGF Tumor Growth % over control IGF Tumor Growth Normal CypB1 Xenobiotic metabolism Normal Histone deacylase -dipeptide DNA coiling(nucleosome) Normal c-erb-b2 Her/neu2 Normal c-erb-b1 Her1 Normal Bcr-abl Resist phenotype Normal h-tert (Human telomerase) M2 crisis-aggressive phen. 25% over control From the investigation above we concluded to the following : 1. From the whole neoplasmic population we have an expression of MDR1 in a percentage of 65% over control.( positive in the check of resistance ) 2. The activity of GST is stable in the low limits (no resistance to platinum compounds ) 3. The activity of gammagc is stable in the low limits (no resistance to platinum compounds ) 4. The activity of CES1 and CES2 is normal range (no resistance to camptothecin compounds ) 5. The concentration of p1 is in normal range 6. Increased activity of the laminin and the MMP ( increased invasive ability )

12 7. There is great sensitivity in taxanes (especially in docetaxel) and great sensitivity noticed in alkaloids of Vinca (especially in vinorelbine). 8. Minimal sensitivity noticed in 5FC, in 5-FU, in UFT, in FUdR in capecitabine, in raltitrexed, in methotrexate and in pemetrexed but there is great sensitivity in gemcitabine. 9. Decreased sensitivity in alkylating factors. 1. There is great overexpression of TGF b (25% over control), of NFkBeta (35% over control) and EGF-r (%,<7%) growth factors and suppression of expression of isoforms of IκB (a, d, e) (15% below control). 11. It appears to have no sensitivity in the inhibitors of topoisomerase II a and II b. 12. There is great sensitivity in the inhibitors of topoisomerase I (especially in topotecan). 13.There is no overexpression of SS-r receptor and there is no overexpression of 5-LOX mrna, of COX-2, of c-erb-b2, of c-erb-b1, of estrogen receptor mrna and progesterone receptor mrna. 14. We notice great neoangiogenetic ability (overexpression of VEGF-R % over control ). 15. Finally, there is no sensitivity in dacarbazine. 16. We notice that taurolidin cannot induce the apoptosis to the malignant cells (in IV route dosage). 17. We notice that taurolidin can induce the apoptosis to the malignant cells (in intraperitoneal route dosage) 18.We notice down-regulation of HSP 27 (Heat shock proteins) (3% below control), HSP 9 (5% below control) and HSP 72 (% below control). Conclusion : The specific tumor appears to have resisting populations because of the MDR1 overexpression that can be reversed by the use of verapamil combined with disulfiram. The neoplasmatic cells have the greatest sensitivity in the inhibitor of tubulin dimmer polymerization vinorelbine, in the nucleus spindle stabilizer docetaxel in the antagonist gemcitabine, and in the inhibitor of topoisomerase I topotecan. Also you can use: cetuximab (C225) as inhibitor of EGF-r, bortezomib as inhibitor of proteasome over-activity and indirectly the transcriptional activity of NFκB and bevacizumab as inhibitor of angiogenesis. Regardly, Dr Papasotiriou Ioannis MD Head of molecular medicine dpt of R.G.C.C.-RESEARCH GENETIC CANCER CENTRE INDEX: M : Abnormal p16, normal p53 and htert, M1: Normal htert, abnormal p53, p16, M2 crisis : over-expression of htert, p53, p16 6 th Sample viability : <% greater sensitivity, 65%-% partial sensitivty, >65% no sensitivity *This test and the recommendations are not designed to replace traditional oncological treatment and or care. It is only intended to support the immune system & nutritional needs during standard traditional oncological care and treatment. These statements and recommendations have not been evaluated by the FDA. These recommendations are not intended to diagnose, treat, cure, or prevent any disease. ATMC

13 CHEMO/FOOD/NUTRIENT/HERB INTERACTIONS {REVISED } NAME: DATE: CANCER: Breast Cancer AVOID THE FOLLOWING FOODS, HERBS AND/OR NUTRIENTS IF YOU ARE TAKING THE FOLLOWING CHEMO-DRUGS AND OR MODIFIERS LISTED BELOW. YOUR ONCOLOGIST AND MEDICAL PHYSICIAN WILL MONITOR ANY DRUG TO DRUG INTERACTIONS. PLEASE LET ME KNOW OF ANY CHANGES IN YOUR PRESCRIPTIONS SO WE CAN CHECK FOR COMPATIBILITY. CHEMO DRUGS RECOMMENDED: DOCETAXEL (TAXOTERE) AVOID ALCOHOL, ST. JOHNS WORT ( DOCETAXEL LEVELS) SUBSTRATE CYP3A4 (MAJOR); INHIBITS CYP34A (MINOR). APP BREAST GEMCITABINE (GEMZAR) AVOID ALCOHOL (GI UPSET). APP BREAST TOPOTECAN (HYCAMTIN) AVOID ALCOHOL (GI UPSET). NOT APP BREAST VINORELBINE (NAVELBINE) AVOID ST. JOHNS WORT ( DRUG LEVELS). SUBSTRATE CYP2D6 (MINOR), 3A4 (MAJOR); INHIBITS CYP2D6 (WEAK), 34A (WEAK). APP BREAST MODIFIERS & SENSITIZING AGENTS {REVISED } BEVACIZUMAB (AVASTIN) NK REACTIONS (C/M) BORTEZOMIB (VELCADE) AVOID ST. JOHN S WORT AND GREEN TEA AND THEIR EXTRACTS MAY DRUG LEVELS; AVOID GRAPEFRUIT JUICE MAY DRUG LEVELS (C/M) CETUXIMAB 225 (ERBITUX) NO KNOWN NUTRIENT (C/M) DISULFIRAM (ANTABUSE) AVOID ALL FORMS OF ALCOHOL INGESTION, CIDERS, VINEGARS, FLAVOR EXTRACTS, ANY FOOD OR LIQUID CONTAINING ALCOHOL. (M) VERAPAMIL (CA ++ CHANNEL BLOCKER) NO ALCOHOL AND NO GRAPEFRUIT PRODUCTS ( DRUG LEVEL), ST. JOHN S WORT ( DRUG LEVEL) DON QUAI ( ESTROG. EFFECT), EPHEDRA, YOHIMBE, GINSENG ( BP & ARRHYTHMIA), GARLIC ( ANTIHYPER. EFFECT). (M) *WE STRONGLY RECOMMEND THAT YOU FOLLOW THE RE-CHECK CELL COUNT SCHEDULE EVERY 3 MONTHS SO WE CAN MONITOR YOUR IMPROVEMENT. OUR GOAL IS TO GET ALL CD MARKERS TO NEGATIVE AND A TOTAL CELL COUNT TO ZERO. ONCE WE HAVE DONE THIS THEN WE WILL RE-CHECK THE CELL COUNT IN 6 MONTHS THEN AGAIN IN ONE YEAR AS LONG AS WE CONTINUE TO GET ALL NEGATIVES AND ZEROS. SINCE CANCER IS A SYSTEMIC DISEASE, NOT A LOCAL DISEASE, WE STRONGLY RECOMMEND THE CELL CHECK ONCE A YEAR FROM NOW ON. *This test and the recommendations are not designed to replace traditional oncological treatment and or care. It is only intended to support the immune system & nutritional needs during standard traditional oncological care and treatment. These statements and recommendations have not been evaluated by the FDA. These recommendations are not intended to diagnose, treat, cure, or prevent any disease. ATMC *PART OF OUR SUPPORT PROTOCOL REQUIRES THAT WE HAVE UP TO DATE MINIMAL BLOOD WORK ON FILE IN OUR OFFICE. THIS MEANS BLOOD WORK NOT OLDER THAN 4-6 WEEKS. THIS CAN BE BROUGHT TO US FROM EITHER YOUR ONCOLOGIST OR PRIMARY CARE PHYSICIAN. IF YOU DO NOT HAVE YOUR BLOOD KEPT UP TO DATE WE WILL DRAW THE BLOOD HERE AND YOU WILL BE CHARGED OUR USUAL FEES FOR THIS SERVICE. EACH PATIENT WILL REQUIRE DIFFERENT BLOOD WORK THAT IS NECESSARY FOR THEIR CONDITION. Please Initial