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Chelidonium majus L. (greater celandine)
1: Arch Pharm Res 2002 Apr;25(2):158-64
Immunomodulatory activity of protein-bound polysaccharide extracted from Chelidonium majus.
Song JY, Yang HO, Pyo SN, Jung IS, Yi SY, Yun YS.
Laboratory of Immunology, Korea Cancer Center Hospital KAERI, Seoul.
In the course of searching immunomodulators from natural sources, the protein-bound polysaccharide, CM-Ala, has been isolated from the water extract of Chelidonium majus L. (Papaveraceae). The immunostimulatory characteristics have been investigated in several experiments such as generation of activated killer (AK) cells, proliferation of splenocytes, activation of macrophages and granulocyte macrophage-colony forming cell (GM-CFC) assay. Of the fractions obtained using Sephacryl S200 column chromatography, CM-Ala was the most effective fraction that augmented the cytotoxicity against Yac-1 tumor cells from 0.88% to 34.18% by culturing with splenocytes for 5 days. CM-Ala also enhanced nitric oxide production by two fold in peritoneal macrophages and exhibited antitumor activity. It showed mitogenic activity on both spleen cells and bone marrow cells. CM-Ala induced proliferation of splenocytes by 84 fold and increased GM-CFC numbers by 1.48 fold over than the non-treated. On the contrary, CM-Ala had cytotoxic activity to a diverse group of tumor cells. From the above results, we proposed that CM-Ala has a possibility of an effective antitumor immunostimulator.
PMID: 12009029 [PubMed - in process]
2: BMC Complement Altern Med 2002 Apr 10;2(1):4
Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice.
Biswas S, Khuda-Bukhsh A.
Cytogenetics Laboratory, Department of Zoology, University of Kalyani, Kalyani-741 235, W,B, India. arkb@klyuniv.ernet.in
BACKGROUND: Crude extracts of Chelidonium majus, and also purified compounds derived from crude extracts of this plant, have been reported to exhibit anti-viral, anti-inflammatory, anti-tumor and anti-microbial properties both in vitro and in vivo. Chelidonium is a homeopathic drug routinely used against various liver disorders including cancer in humans. Two potencies of Chelidonium (Ch-30, Ch-200) have been tested for their possible anti-tumor and enzyme modulating activities in liver and anti-clastogenic effects during p-DAB-induced hepatocarcinogenesis in mice compared to suitable controls. METHODS: Several cytogenetic and enzymatic protocols were used at three fixation intervals; at 60 days, 90 days and 120 days of treatment. Different sets of healthy mice were fed: i) hepatocarcinogen, p-DAB plus phenobarbital (PB), ii) only PB, iii) neither p-DAB nor PB (normal control). One set of mice fed with p-DAB plus PB was also fed Ch-30 (iv) and another set Ch-200 (v). All standard currently used methods were adopted for cytogenetical preparations and for the enzyme assays. fixation intervals, while none of group (ii) and (iii) mice developed any tumors. About 40% mice in group (iv) and group (v) did not show tumor nodules in their liver. Feeding of Chelidonium to group (iv) and (v) mice reduced genotoxic effects to a significant extent (p < 0.05 to p < 0.001). CONCLUSION: The homeopathic drug Chelidonium exhibited anti-tumor and anti-genotoxic activities and also favorably modulated activities of some marker enzymes. Microdoses of Chelidonium may be effectively used in combating liver cancer.
PMID: 11943072 [PubMed - as supplied by publisher]
3: Langenbecks Arch Surg 2002 Mar;386(8):570-4
NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial.
Gansauge F, Ramadani M, Pressmar J, Gansauge S, Muehling B, Stecker K, Cammerer G, Leder G, Beger HG.
Department of General Surgery, University of Ulm, Germany.
BACKGROUND: NSC-631570 (Ukrain) is a semisynthetic compound of thiophosphoric acid and the alkaloid chelidonine from the plant Chelidonium majus. It has been used in complementary herbal medicine for more than 20 years for the treatment of benign and malignant tumors. PATIENTS/METHODS: Between August 1999 and June 2001, 90 patients with histologically proven unresectable pancreatic cancer were randomized in a monocentric, controlled, randomized study. Patients in arm A received 1000 mg gemcitabine/m2, those in arm B received 20 mg NSC-631570, and those in arm C received 1000 mg gemcitabine/m2 followed by 20 mg NSC-631570 weekly. End point of the study was overall survival. RESULTS: In all three arms moderate. At the first re-evaluation in arm A 32%, in arm B 75%, and in arm C 82% showed no change or partial remission according to WHO criteria (arm A versus arm B: P<0.01, arm A versus arm C: P<0.001). Median survival according to Kaplan-Meier analysis was in arm A 5.2 months, in arm B 7.9 months, and in arm C 10.4 months (arm A versus arm B: P<0.01, arm A versus arm C: P<0.01). Actuarial survival rates after 6 months were 26%, 65% and 74% in arms A B and C, respectively (arm A versus arm B: P<0.05, arm A versus arm C P<0.01). CONCLUSION: We could show that in unresectable advanced pancreatic cancer, NSC-631570 alone and in combination survival times in patients suffering from advanced pancreatic cancer.
Publication Types: Clinical Trial Clinical Trial, Phase II Randomized Controlled Trial
PMID: 11914932 [PubMed - indexed for MEDLINE]
4: Tsitologiia 2001;43(11):1046-50
[The inhibition enzymatic hydrolysis of acetylthiocholine by acetylcholinesterase using principal alkaloids isolated from celandine and macleya and their derivatives]
[Article in Russian]
Kuznetsova LP, Nikol'skaia EB, Sochilina EE, Faddeeva MD.
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg.
A study was made of a possible inhibitory action on the enzymatic hydrolysis of acetylthiocholine by human erythrocyte acetylcholinesterase of principal alkaloids isolated from Chelidonium majus L. and Macleaya (Bocconia) cordata and microcarpa (namely sanguinarine, chelidonine, berberine), and of drugs "Ukrain" (thiophosphoric acid derivative of a sum of the alkaloids isolated from Chelidonium majus L.) and "Sanguirythrine" (a mixture of unseparated closely related to benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine, isolated from Chelidonium majus L. and other plants of Papaveraceae family). All agents under study have been shown to be reversible inhibitors of the enzymatic hydrolysis of acetylthiocholine. On the basis of the kinetic data it has been determined that chelidonine belonged to reversible inhibitors of a competitive type. All other examined agents have been demonstrated to be inhibitors of a mixed competitive-noncompetitive type, and a greater contribution to the inhibition was made by the competitive constituent. Among all examined agents berberine, sanguinarine and "Sanguirythrine" were the strongest inhibitors of this reaction (the values of generalized inhibitory constants being 0.23, 0.23 and 0.29 microM, respectively) and cheliodonine and "Ukrain" were much weaker (2.0 and 2.5 microM, respectively). Judging from the data obtained, sanguinarine and chelerythrine exert similar inhibitory effects on the reaction of enzymatic hydrolysis of acetylthiocholine, since sanguinarine and "Sanguirythrine" have nearly equal generalized inhibitory constants.
PMID: 11840780 [PubMed - indexed for MEDLINE]
5: Ned Tijdschr Geneeskd 2002 Jan 19;146(3):124-8
Comment in: Ned Tijdschr Geneeskd. 2002 Jan 19;146(3):100-2.
[Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus)]
[Article in Dutch]
Crijns AP, de Smet PA, van den Heuvel M, Schot BW, Haagsma EB.
Afd. Maag-, Darm- en Leverziekten, Academisch Ziekenhuis, Hanzeplein 1, Postbus 30.001, 9700 RB Groningen.
A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal within 2 months. The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view of the increasing popularity of herbal remedies, greater awareness of side effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations carry the risk of liver damage. The supposed clinical effectiveness of herbal remedies does not seem to always outweigh the potential risks. In the event of non-clarified liver function disturbances the ingestion of supposedly harmless, but potentially hepatotoxic, herbal products should be considered.
PMID: 11826672 [PubMed - indexed for MEDLINE]
6: Ned Tijdschr Geneeskd 2002 Jan 19;146(3):100-2
Comment on: Ned Tijdschr Geneeskd. 2002 Jan 19;146(3):124-8.
["Dosis solum facit venenum" also for herbal products]
[Article in Dutch]
van Noordwijk J.
jnoordwi@wxs.nl
A report of severe hepatitis due to the use of material from the plant Chelidonium majus, reminds us that herbal products can be much more life-threatening than many people realise. The widespread use of plants for food has reinforced the idea that eating plants promotes health. With the development of organic chemistry in the 19th century it became possible for the first time to purify and identify pharmacologically active plant constituents and later on to synthesize related compounds with an even stronger activity. The development of the antimalarial artemotil from Artemisia plants is a recent example. The activity, safety and composition of such compounds can be controlled in just the same manner as purely synthetic compounds. However, some people still believe that traditional plants are much safer and better than modern synthetic pharmaceuticals. The qualitative and quantitative composition of such herbal medicines from alternative medical sources, are not covered by public health legislation. Whereas phytotherapists consider plants to be a source of useful drugs, regular physicians maintain that the composition of a preparation and not the provenance, determines its effects.
Publication Types: Comment Review Review, Tutorial
PMID: 11826667 [PubMed - indexed for MEDLINE]
7: Int J Radiat Biol 2002 Jan;78(1):17-27
Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation.
Cordes N, Plasswilm L, Bamberg M, Rodemann HP.
Section of Radiobiology and Molecular Environmental Research, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany.
PURPOSE: Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. MATERIALS AND METHODS: Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 microg ml(-1) for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 microg ml(-1) Ukrain for 24h plus 2-8 Gy. RESULTS: Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without affecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. CONCLUSIONS: Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical radiochemotherapy.
PMID: 11747550 [PubMed - indexed for MEDLINE]
8: Folia Histochem Cytobiol 2001;39(2):215-6
Effect of lectin from Chelidonium majus L. on normal and cancer cells in culture.
Fik E, Wolun-Cholewa M, Kistowska M, Warchol JB, Gozdzicka-Jozefiak A.
Department of Molecular Virology, University of Poznan, Poland.
Lectin from Chelidonium majus L. (CML) significantly stimulates the proliferation of human lymphocytes and has hemagglutination activity towards group B human erythrocytes and potent antimicrobial properties against multiresistant enterococci and staphylococci. In the present work we describe the effect of lectin from Chelidonium majus L on normal and cancercells in culture in vitro. The studies were performed on three types of cells: CHO, R2C and on normal mouse fibroblasts. Effects on the cultures were examined 24 h after addition of CML. Exposure to CML resulted in growth inhibition of CHO and R2C cells but not of fibroblasts. Moreover, evident apoptotic lesions were observed in CHO cells and less well marked apoptotic lesions in R2C cells. In contrast, only insignificant numbers of fibroblasts reacted to the applied lectin.
PMID: 11374832 [PubMed - indexed for MEDLINE]
9: Drugs Exp Clin Res 2000;26(5-6):341-56
Ukrain: a novel antitumor drug.
Uglyanitsa KN, Nefyodov LI, Doroshenko YM, Nowicky JW, Volchek IV, Brzosko WJ, Hodysh YJ.
Medical Institute of Grodno, ul Gorkogo 80, 230015 Grodno, Belarus.
A review of the recent literature on the new anticancer drug Ukrain is provided herein. We review Ukrain, a thiophosphate derivative of alkaloids from Chelidonium majus L., its capacity to exert selective cytotoxic and cytostatic effects on tumor cells, simultaneously acting as an immune response modifier, its good tolerance and lack of side effects even after long-term application, perspectives of the application of this drug in oncology.
Publication Types: Review Review, Academic
PMID: 11345050 [PubMed - indexed for MEDLINE] Presented by THE ROBERT CATHEY RESEARCH SOURCE http://www.navi.net/~rsc -------------------------------------------------------------------------------- ------------------- Cancer of the Liver(E.G.Jones, M.D.)
Symptoms. The sallow appearance of the face will be noticeable in this disease, also marked emaciation [cachexia, rc], the *weak hurried* pulse of cancer, the pearly tint to the white of the eye, tongue coated a dirty yellow and underneath the coating the *dark red* color of advanced cancer are all indications of this disease. There will be an enlargening of the liver. It may reach below the false ribs, even to the brim of the pelvis. By pressing the fingers down upon the liver it is felt to be irregular and knobby to the hand. [don't do this, rc]. There is pain and fullness in the right hypochondrium [below the lowest rib], the pain is of a *burning boring* nature; the patient will tell you that the jolting of a carriage in riding hurts his side, that he experiences the same trouble in walking. He is constantly *pressing* his hand over the *region* of the liver to *support* it as he walks. I regard this as a pretty reliable symptom of this disease. There is gastric disturbance, symptoms of indigestion and vomiting. Treatment. For the pain of this disease we may give tincture echinacea -3ss.(half ounce), Aqua -3vi. Mix. Sig. One teaspoonful every hour. When there is perpendicular enlargement of the liver, a dusky hue to the face, constipation, indigestion, strong urinous odor to the urine, Tr.[tincture, rc] chelidonium [Garden Celandine..Chelidonium Majus. A fluid extract of flowering herb is advised by Parke, Davis 1909, cautiously: 1/2 to 1 fluidrachm; rc] is the remedy. Dose, five drops three times a day. If the pulse shows a *weak*, discouraged feeling I like sulph. strychnine[ strychnine sulphate] one-thirtieth grain before each meal and at bedtime. For the symptoms of indi Page 211 [these links will be helpful in any research you may wish to do on this:
When the disease seems to affect the *left* lobe of the liver, that portion that lies between the liver and the pancreas, iodoform third decimal is the remedy. The two remedies, iodoform third decimal and cholestrinum third decimal, may be alternated each once in four hours. In February, 1891, a man came to consult me for a liver trouble. I made a thorough examination of the liver and found it quite an enlargement of that organ. The surface of the liver felt *nodulated*. He complained of a burning pain in the region of the liver and was obliged to hold his hand over his right side when he walked. His face ad the cancer cachexia, there was a weak rapid pulse, yellow conjunctiva, a dirty yellow tongue. My diagnosis was cancer of the liver. For the vomiting of sour fluid I gave him nux vomica sixth decimal, three tablets once in three hours. To act upon the diseased organ I gave him cholestrinum third decimal, six grains three times a day. A second examination of his liver in a month's time revealed the fact that the size of the organ had been much reduced. The treatment was continued until the liver had resumed its normal size and Page 212 In June, 1896, a patient came under my treatment who had been the rounds of the doctors but none of them could give a clear diagnosis of his case. He complained of a *boring* pain in the region of the liver. His face had a sallow look and he had a very poor appetite. There were symptoms of indigestion, spitting up his food, much gas in the stomach, and vomiting of sour fluids quite often. I found his liver enlarged, perpendicularly, nearly to the right nipple. My diagnosis was cancer of the liver. I gave him tincture chelidonium, ten drop three times a day, nux vomica second decimal three tablets once in three hours. For the constipation ten tablets of Kali mur [another I don't know, kali is Latin and German for "potash", it may be an East Indian plant? Again, probably known by homeopathic physicians] sixth decimal at bedtime. In a week his condition was improved; he had better digestion, no vomiting, bowels had begun to act more natural. In a month I examined the liver and found it *not* quite so much enlarged; from month to month it seemed to be growing smaller until it had regained its normal size." End of selection on liver cancer from:
Homeopathic Educational Services
Summary Ukrain is a semi-synthetic compound formed by the complex binding of Chelidonium majus L alkaloids and thiophosphoric acid (thio TEPA) derivative. Ukrain® is almost a new chemical entity for the treatment of a various cancers. Ukrain® has proved to be extremely effective in numerous in vitro models to kill tumor cells from different origin directly. This effect was much more pronounced than with standard chemotherapeutics. In clear contrast to all available chemotherapeutic compounds Ukrain® shows several immune system stimulating effects. Thus it helps to activate autologous (self) immune mechanisms to attack the cancer from within your own body. Ukrain® inhibits the formation of tumor blood vessels (Antiangiogenesis effect), with the result of tumor necrosis and the prevention of a local and distant spread - metastasis. In 14 clinical studies of Ukrain® it proved to be effective in tumor control in 40 % of patients suffering from advanced late stage cancer without any other therapeutic alternative. In lung cancer, the clinical response is strongly correlated with a prolongation of survival time. In colorectal carcinoma, the 21 month survival rate with Ukrain is 78. 6 % compared to 33 % with traditional chemotherapeutics. In one of our pancreatic cancer patients, tumor markers went down 50% with one course of treatment. In clear contrast to all available chemotherapeutic compounds, Ukrain® has a very low toxicity and, for sure, quality of life is greatly improved. Description: Active substance: Chelidonium majus L. alkaloid-thiophosphoric acid derivative Form of medication: Solution Manufacturer: Nowicky Pharma, A-1040, Vienna, Austria. The name is given by the developer from where he came from, ie. Ukrain, Russia. Composition: It is marketed by the above company in ampoules, each contains 5 mg Chelidonium majus L. alkaloid-thiophosphoric acid derivative in 5 ml bidistilled water for injection, with a pH range of 3.5 to 5.5. UKRAIN is a combination of various alkaloids (allocryptopine, berberine, chelamine, chelidonine, chelerythine, coptisine, magnoflorine, protopine, sanguinarine, sparteine and others) from the plant Chelidonium majus L. The roots of this plant also contain choline, histamine, tyramine, saponins, chelidoniol, chelidonic acid, vitamin C, yellow latex with carotenoid latex. Many scientific tests have demonstrated that the preparation destroys cancer cells through apoptosis (programmed cell death) at the same time preserving the healthy cells, and the therapeutic dose has hardly any side effects. Its anti-tumour effect is the result of the interplay of the properties of several substances. Besides killing cancer cells, UKRAIN activates a whole series of highly effective immune system mechanisms in the patient so that the body’s own defenses act on the cancers. UKRAIN inhibits the formation of new blood vessels, which is very important for the growth and spread of cancers. Without the nutrition and proper oxygen supply, the new tumor cells will not multiply and spread to the distant parts of the body (metastasis). Importance of UKRAIN for cancer therapy is based on 149 scientists from 16 countries in 47 universities and research institutes that have carried out detailed tests on UKRAIN and published their results in more than 120 scientific papers. Inspite of all these studiues for more than 15 years, it is marketed only in Austria. It is not marketed or distributed in the US. Present options in the treatment of solid tumor malignancies Cancer still represents the second common cause of death in Europe and the United States with no end in sight about its treatment. In spite of all the research advances made during the last decade the general progress in terms of clinical efficacy is still negligible: The following table represents a list of the most important available tools of systemically applied anticancer strategies and a short and extremely simplified overview of their main direct or indirect biological activities against tumor cells (not considering specific subclasses of pharmaceutical compounds). The treatment of cancers falls into 6 main catogories besides surgery: 1 Chemotherapeutics 2. Immunotherapeutics 3. Antihormones therapy 4. Radiation 5. Intracellular hyperthermia therapy (Intra Cellular Hyperthermia) 6. Gene therapy It is very important to stress that most of the antineoplastic compounds just demonstrate one specific biological activity. Therefore the various treatment strategies being applied in cancer treatment have to consider a combination of different compounds in order to evoke synergistic antitumor efficacy. We know that in the course of tumor progression the biological capacity of the immune system deteroriates and the addition of chemotherapeutic agents will enhance this effect. Therefore many of these patients have to receive immunostimulating compounds. Active immunological stimulation also prevents opportunistic infections. Unfortunately, there is no antincancer compound available on market, which can kill tumor cells and enhance immunostimulating effect with the excaption of Ukrain. Characteristics of Ukrain® Ukrain® represents a semi-synthetic compound formed by purified alkaloids of the Chelidonium majus with thiophosphoric acid derivatives, triethylene-thiophosphoric acid triamide (Thio-TEPA). Three moles of Chelidonium majus alkaloids bind with one mole of Thio-TEPA. The final product contains at least 90 % Chelidonium majus alkaloid-thiophosphoric acid derivative and a maximum of 10 % of free Chelidonium majus alkaloids, while Thio-TEPA or free Aziridine ring components cannot be detected. Pharmacodynamics The antincancer properties of Chelidonium majus extract on various histologies of skin cancer have been described in folk medicine for many years. In order to increase the affinity of Chelidonium majus alkaloids to the tumor tissue the herbal alkaloids were bound to Thio-TEPA (1). Due to the high cell-cleavage turnover (proliferation rate) of tumor cells and therefore a tremendous need of energy input, it was suggested that a phosphoric acid containing compound being complex-bound to the Chelidonium alkaloids might enhance the affinity of the compound to the tumor cells. Moreover it was suggested that this new complex molecule would not only lead to an improved therapeutic activity but also to a significant reduction of systemic side effects being the result of the affection of non-malignant cells apart from the tumor. Safety of Ukrain has been tested in various animals. . In mice and rats the Ukrain® dosage at which 50 % of the treated animals died (LD50) was determined at approximately 280 mg /kg body weight while the relevant therapeutic dosage of Ukrain® in humans is 20 mg per application at a maximum which is lower by the factor of 100 compared to the toxic dosage in animals. Thus the Ukrain is very safe to use in humans. Direct antineoplastic activities Ukrain® has antitumor activity by inhibition of DNA-RNA and protein synthesis in tumor cells. The National Cancer Institute in Bethesda (USA) investigated the antineoplastic effect of Ukrain® on 60 different human cancer cell lines of the 8 most common types of solid human tumors. Surprisingly almost all cell lines demonstrate a growth inhibition between 50 % and 100 % which, at higher concentrations, even turned into a cytolytic effect with a reduction of cell mass. The highest sensitivity towards Ukrain® was found in the following cell lines: Small cell lung cancer and non-small cell lung cancer, malignant melanoma, ovarian cancer, hypernephroma, and various brain tumors. On the other hand, 5-Fluorouracil (5-FU) which was investigated under identical conditions, a reduction of cell mass could never be detected and only in a few cell lines under extremely high dosages a complete growth inhibition could be achieved In a tumor xenograft animal test, a significant antitumor effect could be demonstrated with colorectal tumors, gastric tumors, large cell lung cancer, breast cancer and malignant melanoma. Ukrain® was even able to demonstrate significant antitumor efficacy even though the breast cancer cells proved to be cisplatin resistant. The cytological pattern of Ukrain® induced tumor cell destruction is akin to programmed cell death by apoptosis. Normal human cells were not affected even at the concentration of 100-fold. Interestingly, the Ukrain® irreversibly reduced the oxygen consumption down to zero on Ehrlich’s ascites tumor cells while in normal cells, turned to normal within minutes. Immunostimulating activities Ukrain® demonstrates several immunological activities predominantly regarding cell mediated immunity. Ukrain® does not modulate that much the humoral components of the immune system. In the peripheral blood of tumor patients Ukrain® usually enhances the number of monocytes,T-helper cells and NK-cells and reduces the number of T-suppressor cells. As a result of this, the T-helper/T-suppressor ratio is increased. Interestingly these parameters could not be modulated significantly by Ukrain® in healthy individuals. Even after chemotherapy or radiotherapy the rosette forming ability of the T-lymphocytes remains in a normal range. In several immunological target-effector cell systems it could be demonstrated that Ukrain® significantly enhances the malignotoxic activity of macrophages, lymphocytes and NK-cells towards different tumor cells. For these reasons Ukrain® has also be defined as a potent ‘biological response modifier. When administered to tumor patients, Ukrain® usually hardens the consistency of the tumor and demarcates it from the surrounding tissue with a yellow-orange coloration that can last up to 19 days after one single injection in the animal experiments. (Autofluorescence under UV-light which allows the physician to monitor the accumulation of Ukrain® in the tumor tissue after local or intravenous injection) Surprisingly in cases where this phenomenon could not be observed a concentration of Ukrain® at the site of the tumor and a reduction of the tumor volume could not be achieved. Under histological studies show that the tumor responding are infiltrated with mononuclear cells, B-lymphocytes and cytotoxic T-cells, tumor cells are ecrotic, degenerated with vacuolated cytoplasm. Activities on tumorangiogenesis Beside its various direct (antiproliferative) and indirect (immunological) effects on malignant cells, it also acts by inhibiting the formation of new blood vessels to supply the tumors (antiangiogenisis). Recently in an in vitro model it could be demonstrated that even very low concentrations of Ukrain® could effectively inhibit the formation of capillary structures mediated directly or indirectly via a Ukrain® induced release of anti-angiogenetic cytokines. It is known biological function of the cytokine TNF is induction of tumor necrosis via the destruction of tumor-nutrifying blood vessels and inhibition of the formation of new blood vessels. Thus Ukraine may have TNF-concentrating properties. It has also been observed that Ukrain® treated tumor patients with signs of clinical response at the site of the primary tumor usually never develop additional metastases. Clinical efficacy To this date a total of 701 people (662 patients and 39 healthy volunteers, 5 different tumor types which were the most common among all 701 patients colorectal carcinoma, lung cancer, breast cancer, cervical and ovarian cancer) have been recruited into 15 clinical studies utilizing Ukrain® with “Good” Clinical results. Just the extract of the plant have been used for years as spasmolytic, cholagogue, bitter, alterative, diuretic, laxative, anodyne, purgative, caustic, anti-inflammatory, abortifacient. It has been indicated specifically indicated for cholycystitis and gallstones. Topically, the juice has been used in eczema, verrucae and malignant tumours of the skin. Safety Long term studies for up to 3 years in doses between 5 and 50 mg per application without any evidence of toxic or cumulative effect. Study reports registered the ages of patients being treated with Ukrain from 6 to 85 years. The observed side effects of UKRAIN therapy were local pains with intramuscular injection, and with rapid intravenous injection of larger doses (over 20 mg per minute). In addition hot flushes, vertigo, unstable circulation in cases of hypotonia, thirst and polyuria as well as occasional headaches during the first 30 minutes after administration were observed. Reported rare side effects were, in two cases, short-lasting spastic, gastro-intestinal pains and dyspepsia after administration. In a few cases, fever of up to 38°C - possibly due to tumor breakdown. None of the side effects required any treatment. According to current clinical experience at a clinical dosage range from 5 - 25 mg per application, UKRAIN demonstrates no acute toxicity. According to long-term observations, with therapy of up to 3 years and a total administration of 3500 mg, no cumulative effects or organ burden were observed. The side effects of therapy, which just appeared in individual cases, were always of low intensity and required no additional therapeutic measures. Allergic or anaphylactic reactions were not observed. Cost: We use 10 injections of 10-20 mg intravenously using two-cycle IPT. The money has to be wired to Austria to the company’s bank account. Once they receive the bank transfe, we will fax the prescription, and the company from Autstria (Nowicky Pharma) will ship it the proper address. The total cost of medication itself is approximately $3500.00. This includes shipping, handling, bank transfer and prescription. If a patient desires to receive Ukrain therapy, they need to pay $3500.00 dollars over and above the standard protocol.cost. Research publications about Chelidonium majus L. INTRIGUING NEW ANTICANCER COMPOUND FROM EAST EUROPE Immunomodulatory activity of protein-bound polysaccharide extracted from Chelidonium majus. Song JY, Yang HO, Pyo SN, Jung IS, Yi SY, Yun YS. Laboratory of Immunology, Korea Cancer Center Hospital KAERI, Seoul. In the course of searching immunomodulators from natural sources, the protein-bound polysaccharide, CM-Ala, has been isolated from the water extract of Chelidonium majus L. (Papaveraceae). The immunostimulatory characteristics have been investigated in several experiments such as generation of activated killer (AK) cells, proliferation of splenocytes, activation of macrophages and granulocyte macrophage-colony forming cell (GM-CFC) assay. Of the fractions obtained using Sephacryl S200 column chromatography, CM-Ala was the most effective fraction that augmented the cytotoxicity against Yac-1 tumor cells from 0.88% to 34.18% by culturing with splenocytes for 5 days. CM-Ala also enhanced nitric oxide production by two fold in peritoneal macrophages and exhibited antitumor activity. It showed mitogenic activity on both spleen cells and bone marrow cells. CM-Ala induced proliferation of splenocytes by 84 fold and increased GM-CFC numbers by 1.48 fold over than the non-treated. On the contrary, CM-Ala had cytotoxic activity to a diverse group of tumor cells. From the above results, we proposed that CM-Ala has a possibility of an effective antitumor immunostimulator. PMID: 12009029 [PubMed - in process] 2: BMC Complement Altern Med 2002 Apr 10;2(1):4 Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice. Biswas S, Khuda-Bukhsh A. Cytogenetics Laboratory, Department of Zoology, University of Kalyani, Kalyani-741 235, W,B, India. arkb@klyuniv.ernet.in BACKGROUND: Crude extracts of Chelidonium majus, and also purified compounds derived from crude extracts of this plant, have been reported to exhibit anti-viral, anti-inflammatory, anti-tumor and anti-microbial properties both in vitro and in vivo. Chelidonium is a homeopathic drug routinely used against various liver disorders including cancer in humans. Two potencies of Chelidonium (Ch-30, Ch-200) have been tested for their possible anti-tumor and enzyme modulating activities in liver and anti-clastogenic effects during p-DAB-induced hepatocarcinogenesis in mice compared to suitable controls. METHODS: Several cytogenetic and enzymatic protocols were used at three fixation intervals; at 60 days, 90 days and 120 days of treatment. Different sets of healthy mice were fed: i) hepatocarcinogen, p-DAB plus phenobarbital (PB), ii) only PB, iii) neither p-DAB nor PB (normal control). One set of mice fed with p-DAB plus PB was also fed Ch-30 (iv) and another set Ch-200 (v). All standard currently used methods were adopted for cytogenetical preparations and for the enzyme assays. fixation intervals, while none of group (ii) and (iii) mice developed any tumors. About 40% mice in group (iv) and group (v) did not show tumor nodules in their liver. Feeding of Chelidonium to group (iv) and (v) mice reduced genotoxic effects to a significant extent (p < 0.05 to p < 0.001). CONCLUSION: The homeopathic drug Chelidonium exhibited anti-tumor and anti-genotoxic activities and also favorably modulated activities of some marker enzymes. Microdoses of Chelidonium may be effectively used in combating liver cancer. PMID: 11943072 [PubMed - as supplied by publisher] 3: Langenbecks Arch Surg 2002 Mar;386(8):570-4 NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. Gansauge F, Ramadani M, Pressmar J, Gansauge S, Muehling B, Stecker K, Cammerer G, Leder G, Beger HG. Department of General Surgery, University of Ulm, Germany. BACKGROUND: NSC-631570 (Ukrain) is a semisynthetic compound of thiophosphoric acid and the alkaloid chelidonine from the plant Chelidonium majus. It has been used in complementary herbal medicine for more than 20 years for the treatment of benign and malignant tumors. PATIENTS/METHODS: Between August 1999 and June 2001, 90 patients with histologically proven unresectable pancreatic cancer were randomized in a monocentric, controlled, randomized study. Patients in arm A received 1000 mg gemcitabine/m2, those in arm B received 20 mg NSC-631570, and those in arm C received 1000 mg gemcitabine/m2 followed by 20 mg NSC-631570 weekly. End point of the study was overall survival. RESULTS: In all three arms moderate. At the first re-evaluation in arm A 32%, in arm B 75%, and in arm C 82% showed no change or partial remission according to WHO criteria (arm A versus arm B: P<0.01, arm A versus arm C: P<0.001). Median survival according to Kaplan-Meier analysis was in arm A 5.2 months, in arm B 7.9 months, and in arm C 10.4 months (arm A versus arm B: P<0.01, arm A versus arm C: P<0.01). Actuarial survival rates after 6 months were 26%, 65% and 74% in arms A B and C, respectively (arm A versus arm B: P<0.05, arm A versus arm C P<0.01). CONCLUSION: We could show that in unresectable advanced pancreatic cancer, NSC-631570 alone and in combination survival times in patients suffering from advanced pancreatic cancer. Publication Types: PMID: 11914932 [PubMed - indexed for MEDLINE] 4: Tsitologiia 2001;43(11):1046-50 [The inhibition enzymatic hydrolysis of acetylthiocholine by acetylcholinesterase using principal alkaloids isolated from celandine and macleya and their derivatives] [Article in Russian] Kuznetsova LP, Nikol'skaia EB, Sochilina EE, Faddeeva MD. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg. A study was made of a possible inhibitory action on the enzymatic hydrolysis of acetylthiocholine by human erythrocyte acetylcholinesterase of principal alkaloids isolated from Chelidonium majus L. and Macleaya (Bocconia) cordata and microcarpa (namely sanguinarine, chelidonine, berberine), and of drugs "Ukrain" (thiophosphoric acid derivative of a sum of the alkaloids isolated from Chelidonium majus L.) and "Sanguirythrine" (a mixture of unseparated closely related to benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine, isolated from Chelidonium majus L. and other plants of Papaveraceae family). All agents under study have been shown to be reversible inhibitors of the enzymatic hydrolysis of acetylthiocholine. On the basis of the kinetic data it has been determined that chelidonine belonged to reversible inhibitors of a competitive type. All other examined agents have been demonstrated to be inhibitors of a mixed competitive-noncompetitive type, and a greater contribution to the inhibition was made by the competitive constituent. Among all examined agents berberine, sanguinarine and "Sanguirythrine" were the strongest inhibitors of this reaction (the values of generalized inhibitory constants being 0.23, 0.23 and 0.29 microM, respectively) and cheliodonine and "Ukrain" were much weaker (2.0 and 2.5 microM, respectively). Judging from the data obtained, sanguinarine and chelerythrine exert similar inhibitory effects on the reaction of enzymatic hydrolysis of acetylthiocholine, since sanguinarine and "Sanguirythrine" have nearly equal generalized inhibitory constants. PMID: 11840780 [PubMed - indexed for MEDLINE] 5: Ned Tijdschr Geneeskd 2002 Jan 19;146(3):124-8 Comment in: [Acute hepatitis after use of a herbal preparation with greater celandine (Chelidonium majus)] [Article in Dutch] Crijns AP, de Smet PA, van den Heuvel M, Schot BW, Haagsma EB. Afd. Maag-, Darm- en Leverziekten, Academisch Ziekenhuis, Hanzeplein 1, Postbus 30.001, 9700 RB Groningen. A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal within 2 months. The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view of the increasing popularity of herbal remedies, greater awareness of side effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations carry the risk of liver damage. The supposed clinical effectiveness of herbal remedies does not seem to always outweigh the potential risks. In the event of non-clarified liver function disturbances the ingestion of supposedly harmless, but potentially hepatotoxic, herbal products should be considered. PMID: 11826672 [PubMed - indexed for MEDLINE] 6: Ned Tijdschr Geneeskd 2002 Jan 19;146(3):100-2 Comment on: ["Dosis solum facit venenum" also for herbal products] [Article in Dutch] van Noordwijk J. jnoordwi@wxs.nl A report of severe hepatitis due to the use of material from the plant Chelidonium majus, reminds us that herbal products can be much more life-threatening than many people realise. The widespread use of plants for food has reinforced the idea that eating plants promotes health. With the development of organic chemistry in the 19th century it became possible for the first time to purify and identify pharmacologically active plant constituents and later on to synthesize related compounds with an even stronger activity. The development of the antimalarial artemotil from Artemisia plants is a recent example. The activity, safety and composition of such compounds can be controlled in just the same manner as purely synthetic compounds. However, some people still believe that traditional plants are much safer and better than modern synthetic pharmaceuticals. The qualitative and quantitative composition of such herbal medicines from alternative medical sources, are not covered by public health legislation. Whereas phytotherapists consider plants to be a source of useful drugs, regular physicians maintain that the composition of a preparation and not the provenance, determines its effects. Publication Types: PMID: 11826667 [PubMed - indexed for MEDLINE] 7: Int J Radiat Biol 2002 Jan;78(1):17-27 Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation. Cordes N, Plasswilm L, Bamberg M, Rodemann HP. Section of Radiobiology and Molecular Environmental Research, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany. PURPOSE: Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. MATERIALS AND METHODS: Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 microg ml(-1) for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 microg ml(-1) Ukrain for 24h plus 2-8 Gy. RESULTS: Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without affecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. CONCLUSIONS: Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical radiochemotherapy. PMID: 11747550 [PubMed - indexed for MEDLINE] 8: Folia Histochem Cytobiol 2001;39(2):215-6 Effect of lectin from Chelidonium majus L. on normal and cancer cells in culture. Fik E, Wolun-Cholewa M, Kistowska M, Warchol JB, Gozdzicka-Jozefiak A. Department of Molecular Virology, University of Poznan, Poland. Lectin from Chelidonium majus L. (CML) significantly stimulates the proliferation of human lymphocytes and has hemagglutination activity towards group B human erythrocytes and potent antimicrobial properties against multiresistant enterococci and staphylococci. In the present work we describe the effect of lectin from Chelidonium majus L on normal and cancercells in culture in vitro. The studies were performed on three types of cells: CHO, R2C and on normal mouse fibroblasts. Effects on the cultures were examined 24 h after addition of CML. Exposure to CML resulted in growth inhibition of CHO and R2C cells but not of fibroblasts. Moreover, evident apoptotic lesions were observed in CHO cells and less well marked apoptotic lesions in R2C cells. In contrast, only insignificant numbers of fibroblasts reacted to the applied lectin. PMID: 11374832 [PubMed - indexed for MEDLINE] Ukrain: a novel antitumor drug. Uglyanitsa KN, Nefyodov LI, Doroshenko YM, Nowicky JW, Volchek IV, Brzosko WJ, Hodysh YJ. Medical Institute of Grodno, ul Gorkogo 80, 230015 Grodno, Belarus. A review of the recent literature on the new anticancer drug Ukrain is
provided herein. We review Ukrain, a thiophosphate derivative of alkaloids
from Chelidonium majus L., its capacity to exert selective cytotoxic and
cytostatic Publication Types: PMID: 11345050 [PubMed - indexed for MEDLINE] Active constituents: Greater celandine, like other members of the Papaveraceae (poppy) family, contains alkaloids as its major constituents. These include chelidoxanthine, chelidonine, and coptisine. Greater celandine extracts have been shown to stimulate production of bile and pancreatic digestive enzymes in human studies.5 Animal and test tube studies have shown that the alkaloids and whole plant extract can relieve gallbladder spasms and stimulate an under-active gallbladder.6 7 Test tube and animal studies have also shown celandine extracts and purified alkaloids to have anti-inflammatory, anti-cancer and antimicrobial properties.8 9 10 They have also shown greater celandine’s ability to protect animal livers from toxic substances.11 12 A double-blind trial found that a standardized extract of greater celandine could relieve symptoms of indigestion (such as abdominal cramping, sensation of fullness, and nausea) significantly better than a placebo.13 The trial used an extract standardized to 4 mg of chelidonine per capsule and gave 1–2 tablets three times daily for six weeks. An earlier, preliminary trial also found the same extract reduced symptoms in people with indigestion.14 Preliminary reports from Russia and China have reported that a tincture of greater celandine applied topically was useful for warts.15 However, these results have not yet been confirmed by double-blind clinical trials. Several reports describe Eastern European clinical trials using semi-synthetic derivatives of greater celandine alkaloids for people with cancer.16 This injectable product goes by the name Ukrain®. The findings on this drug cannot be applied to greater celandine because the alkaloids have been modified from their original form. How much is usually taken? One explanation for the variable results obtained from using greater celandine is improperly prepared, dried extracts.17 Drying extracts quickly at high temperature is necessary to preserve the alkaloids.18 Extracts standardized to a content of 4 mg chelidonine per capsule are recommended to be taken three times per day.19 Alternatively, one may mix 1–3 ml tincture into water and sip slowly 10–30 minutes before eating. Topical applications should consist of either concentrated tinctures or the fresh yellow latex. Herbalists and doctors recommend applying fresh latex once per day to warts and allowing it to dry in place.20 Are there any side effects or interactions? Use of fresh plant products
may cause stomach upset.21 Topical use has been associated with intense
itching and a rash in one case.22 Greater celandine should be avoided
during pregnancy and in children under age 12.23 A recent report of ten
women in Germany suffering from acute hepatitis following supplementation
with a standardized extract of greater celandine (dosage was not given)
suggest this herb should be avoided by people with hepatitis or impaired
liver function. Greater celandine should be used cautiously and under
the supervision of a healthcare professional until more is understood
about its potential liver toxicity.24
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| Cancer cells hide after Chemotherapy
and Radiation After the initial doses of radiation and/or chemotherapy, cancer cells start hiding. " They develop a slime coating, and they become like Stealth bombers, and they can hide from future doses of radiation and chemotherapy. This is why repeated dose of radiation and chemotherapy become less effective".Dr. John Maras, Nu-Gen Educational Library. " The way to get rid of this "slime coating" is to use large doses of plant and animal enzymes- especially bromelain and pancreatin. This allows an 'access point' for the immune system to attack the cancer cells".....Dr. John Maras, Nu-Gen Educational Library What doctors say about Chemo Therapy ? |
"The world is a dangerous
place to live; not because of the people who are evil, but because of
the people who don't do anything about it." Albert Einstein A Sad day for Alternative healing  |
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NOTICE: Due to FDA TGA MOH (plus other institutions with a vestige interest) regulations and various state laws, no medical claims can be made for alternative therapys and technology. All of the information expressed herein must be considered theoretical and unproven and for experimental research only | |
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