Non-Toxic Treatment (NTT) of Cancer
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1 Non-Toxic Treatment (NTT) of Cancer Combining Dihydroartemisinin, Lactoferrin and Alpha-Lipoic Acid Claus J. Timmermans MD, PhD. A B S T R A C T Background: A new method for the treatment of malignant processes is presented by Artemisinin. It is an extract of the plant Artemisia annua, currently in use for the treatment of malaria. There are different derivatives, of which Dihydroartemisinin demonstrates the most effective anticancer properties. The addition of a small amount of Alpha-Lipoic Acid will enlarge the effect. Cancer cells acquirer large amounts of iron. In a recent pilot study ( ) the Non-T oxic Treatment (NTT) is introduced, using Lactoferrin as a further additive. It demonstrates the optimal transportation of Dihydroartemisinin into the cancer cell. All kinds of cancer and their metastases will be eliminated by damaging the mitochondria of the cancer cell by fragmentation. Using NTT in cases of high tumour load, the result will be a targeted carcinolysis. It will become necessary to remove fluidised necrotic tumour substances by aspiration, followe d by a haemodialysis and /or a peritoneal dialysis. Interpretation: Dihydroartemisinin has cancer killing properties and is well tolerated. Introduction Life expectancy is correlated to the continuous renewing of tissues by apoptosis (programmed cell death). Old cells disappear when replaced by new cells. This process is controlled by the gene p53. When this gene is damaged, an uncontrolled replication of cells will appear and cancer will be the result (1). When a malignant tumour is diagnosed, treatment will follow. Today s standards are surgical procedures and / or chemotherapy and radiation. In addition a lot of attention is focused on immunotherapy, using a combination of Ipilimumab and Nivolumab. It works life extending, but it is not curative. One of the side effects of today s treatment is the destruction of the body s own defence system. Protection of the gene p53 will help to prevent the onset of cancer (2, 3). Antioxidant activity will prevent damage of the gene (4, 5, 6). A new method for the treatment of malignant processes is presented by Artemisinin. It
2 is an extract of the plant Artemisia annua, currently in use for the treatment of malaria. There are different derivatives, of which Dihydroartemisinin demonstrates the most effective anticancer properties (7). The addition of a small amount of Alpha-Lipoic Acid will enlarge the effect (8, 9). Cancer cells acquirer large amounts of iron, sometimes up to a 1,000 times more than healthy cells. Given this fact, a combination of Dihydroartemisinin and Holotransferrin, a protein, containing a large amount of iron, will demonstrate destruction of cancer cells (7, 10). In a recent pilot study ( ) the Non-Toxic Treatment (NTT) is introduced. Holotransferrin is replaced by Lactoferrin, a product of mother s milk. It demonstrates the optimal transportation of Dihydroartemisinin into the cancer cell (11,12). All kinds of cancer and their metastases will be eliminated by damaging the mitochondria of the cancer cell. A study of the BioQuant Centre of the of has proved the fragmentation of cancer-cell mitochondria using Artemisinin derivatives (13), confirmed by a clinical study of St. Gorges University, (14).UniversityHeidelberg Diagnosis and Treatment Using the NTT approach for the elimination of a malignant process, diagnosis, treatment and follow-up control will be different from today s standards. When a primary tumour is diagnosed in an early stage, there is no need to search for metastases. This will simplify diagnostic procedures. During the pilot study in , an experimental medication Canceron C (125 mg Dihydroartemisinin + 25 mg Alpha-Lipoic acid) has been used in combination with Lactoferrin 150 mg twice a day. Before starting a treatment, it is important to know, whether we have to treat an early stage of cancer with a low tumour load, or a late stage with a high tumour load, spread th rough large parts of the patient s body. 1. An early stage (low tumour load) NTT results in tumour necrosis and fibrosis. Apoptosis will not appear. Waste products will be eliminated by diuresis of the kidneys. A proper diuresis, producing of urine a day, will remove all toxic substances from the circulating blood. 1.5 litre In a late stage (high tumour load), often with a reduced kidney function, caused by chemotherapy, large amounts of necrotic tumour (carcinolysis) will be observed. It is the result of aggressive growing of cancer cells. The tumour is no longer in the position to
3 grow the needed vascularisation. 1. Using NTT in cases of high tumour load, the result will be a targeted carcinolysis. After the third week of NTT it will become necessary to remove fluidised necrotic tumour substances from body s cavities by aspiration and washing out, using Ringer solution, followed by a haemodialysis and /or a peritoneal dialysis. Peritoneal dialysis is easy to perform, using a DUAN pigtail catheter (COOK Medical). Th e introduction of the catheter will be realised by the radiologist, under echo control. As values of control there are tumour markers, such as CEA (Carcino Embryonic Antigen) and LDH (Lacto De Hydrogenases). These values will present some information of the growing activity of a mitotic process and also about the degree of destruction of cancer tissue. In prostate cancer PSA (Prostate Specific Antigen) will be an important indicator. Protocol Breast Cancer During a physical examination, feeling a hard swelling in the mammalian structure, suspicion for cancer will exist. Using mammographic pictures the suspicion may be confirmed. Needle biopsies and investigation of the tissue by the pathologist will inform about the type of cancer. Following to the diagnosis malignancy, an NTT- treatment needs to be started. This will be an adjuvant treatment, as introduction to a surgical procedure. It is proved, that a treatment using 250 mg Dihydroartemisinin and additives a day, in 3 weeks time will destroy 40% of the present carcinoma. Partly necrosis and partly fibrosis will be formed. An NTT- treatment of about 9 weeks will probably remove the malignancy completely. After 9 weeks, the surgeon will perform a breast-saving procedure. The tumour will then demonstrate a smaller and harder structure, as result of the formation of connective tissue. The pathologist will find mostly connective tissue. In case of remaining cancer cells, the NTT-treatment needs to be continued.
4 Prostate Cancer The first difficulties manifest a reduction of normal urination. Physical examination and rectal touché will demonstrate an enlargement. When the tissue is soft, a benign hypertrophy will be the expectation. A 6 weeks treatment, using for example Avodart (Dutasteride) will improve the urination. When a hard structure is found, a carcinoma will be the expectation. When an elevated PSA (Prostate Specific Antigen) is found, the diagnosis is confirmed. An MRI-investigation and needle biopsies to estimate Gleason values are not needed. When the prostate cancer is diagnosed, NTT- treatment is indicated for about 3 months. In case of strongly elevated PSA, a progressing of the cancer will be eliminated using temporal depot injections of Zoladex ( Goseriline), Lucrine (Leuproreline-acetate) or Calutol (Bicalutamide) tablets. Other medications and treatments are not necessary. Follow-up is performed by regular control of the PSA value. In the beginning every month, later every six months. Lung Cancer Lung cancers will often be found at a relatively late stage. Patients will consult their doctor when they have difficulties. Generally, there will already be a stage III or IV lung carcinoma. Anamnesis and physical examination may confirm the suspicion of a lung cancer. An X- ray of the thorax will make the suspicion visible. Resampling of cancer tissue will be possible, using a direct needle biopsy or a bronchoscopy for the biopsy. The pathologist will confirm the diagnosis. It always concerns epithelial types of cancer. It can be a small cell lung cancer or a nonsmall cell lung cancer, with or without metastases. It can be cured by an NTT - treatment of about 9 weeks, no additive investigation is needed. Also, it is not of importance which type of cancer has been found. After the third week of NTT - treatment it will be necessary to remove fluidised necrotic tumour substances from the body. If needed by aspiration and washing of the pleura, followed by a haemodialysis and / or a peritoneal dialysis. Colon Cancer
5 In an early stage, diagnosis can be achieved by control of an occult loss of blood, using the IFOBT (immunological faecal occult blood test). Loss of blood by the rectum, if caused by a tumour, will always be located in the rectum or sigmoid. When the diagnosis colon cancer (with or without metastases) is confirmed, an NTTtreatment will follow. Probably as a pre-treatment to a surgical resection of the involved part of the bowel. This adjuvant pre-treatment will last about 9 weeks. During this period the tumour, for example a tumour of the sigmoid, will mostly disappear. Partly it will be replaced by fibrous tissue. The tumour will get smaller and harder. In colon carcinoma with high tumour load and extended metastases, in mesentery and retroperitoneal structures, we can expect ascites and large amounts of necrotic, fluidised tumour necrosis. The CEA and other tumour markers will be raised and will continue raising during the treatment. As a result of an accumulation of fluid, the abdomen will swell. In addition, a displacement of the diaphragm will occur. A heavy and difficult breathing will result. In this situation, an urgent indication exists for aspiration and washing of the bowels, using a Ringer-solution until the returning solution is clear. In the circulating blood, a high load of toxic substance as result of tumour necrosis (carcinolysis) will appear. In this situation, a haemodialysis and / or a peritoneal dialysis is urgently needed. References 1. Ventura A. et alt., Restoration of p53 function leads to tumour regression in vivo, Nature 445, (2007). 1. De Rosa S.C., Zaretsky M.D. et alt., N-acetylcysteine replenishes glutathion in HIV infection, Eur.J. Clin. Inves, 30, (2000). 1. Peristeris P., Clark B.D. et alt. N-acetylcysteine and glutathion as inhibitors of tumor necrosis factor production, Cell Immunology 140, (1992). 1. Harman D. Free radical theory of aging. In Free Radicals and Aging. Emerit I and Chance B (eds.), Birkhauser Verlag, Basel, 1992.
6 1. Senthilmohan S.T., Zhang J. and Stanley R.A., Effects of flavonoid extract Enzogenol with vitamin C on protein oxidation and DNA damage in older human subjects. Nutrition Research. 23, (2003). 1. Senti T. Senthilmohon, Jingli Zhang, Roger A. Stanley, Effects of flavonoid extract Enzogenol with vitamin C on protein oxidation and DNA damage in older Human subjects. Nutrition Research 23, (2003). 1. Singh NP, Lai HC. Artesiminin induces apoptosis in human cancer cells. Anticancer Res. 24(4) : (2004). 1. Wenzel U, Nickel A, Daniel H. alpha-lipoic acid induces apoptosis in human colon cancer cells by increasing mitochobndrial respiration with a concomitant O2-*- generation, Apoptosis, 10 (2) : (2005). 1. Michikoshi H, Nakamuri T, Sakai T et alt., a-lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells. Cancer Lett (2) : (2013). 1. Lai H, Sasaki T, Singh NP, Messy A, Effects of artemisinin-tagged holotransferin on cancer cells. Life Sciences (2005). 1. Kanwa JR, Palmano KP, Sun X et alt. Iron-saturated lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy. Immunol. Cell Biol. 86(3), (2008) 1. Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, Azuma I, Bovine lactoferrin and lacoferricin inhibit tumor metastasis in mice. Jpn. J. Cancer Res. 88(20), (1997). 1. Hamacher-Brady A, et alt. Artesunate activates mitochondrial apoptosis in breast cancer cells via ironcatalyszed lysosomal reactive oxygen species production. J. Biol. Chem. 286(8) : (2011}. 1. Sanjeev Krishna, Senthil Ganapathi, et alt. A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. EBioMedicine (2015).
7 Dr. Claus J. Timmermans This paper has been presented at the congress of BioMah, (BIOMATERIALS FOR HEALTHCARE), Rome, Italy, October
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