RE: metal pots/qing hao, iron and malaria

[Guest guest]

Sammy,

 

Thanks for the lead. I am amazed (and humbled) at what I found. I guess the

more I learn, the more I realize how little I know. Read the article that

follows:

 

 

ARTEMISININ

Artemisinin is a compound extracted from the plant Artemesia annua L. (sweet

wormwood,.also known as the Chinese herbal Qinghao). Artemisinin is a

sesquiterpene lactone (emperical formula C15H22O5.) Its derivatives, such as

artemether, artesunate, arteether, and artelinate, which are quickly converted

to their active plasma metabolite, dihydroartemisinin (DHA). Artesunate and

artelinate are water-soluble, the others are oil (fat)-soluble.

According to a WHO research report (No. 36 Malaria, encouraging results from

studies to improve the safety and efficacy of natural drug compounds), extracts

from the herb Artemeisa annua have been used in China since AD 341 to treat

febrile illness. In 1971, the active component, qinghaosu (now know as

artemisinin) was identified and shown to be effective against malaria, including

chloroquine-resistant parasites. It has generally proven safe and free of toxic

side effects from widespread experience with dosages designed to treat Malaria.

WHO has recommended artemisinin-based anti-malaria drugs.

 

 

More recently, research done by scientists, like Dr. Henry Lai and Dr. N.P.

Singh of the University of Washington, Seattle, WA, USA, has shown in both in

vitro and in vivo tests that artemisinin is selectively toxic to cancer cells.

Consequently, many cancer patients around the world have been taking artemisinin

or its derivatives as an alternative cancer treatment, mostly under the

supervision of physicians. Many encouraging results, though mostly anecdotal,

have been reported from these patients.

 

These clinical applications of artemisinin, in the treatment of malaria and

cancer, could be one of the most important discoveries in the 21st century.

Further research could lead to an effective, affordable, non-surgery and

non-toxic treatment for cancer, malaria and other deadly diseases.

 

Artemisia annua L

 

 

 

Drug of Choice

 

 

 

How does Artemisinin work?

 

The artemisinin, a sesquiterpene lactone peroxide contains two oxygen atoms

hooked together in what is termed an endoperoxide bridge, which is essential for

its anti-malarial and anti-cancer activity.

 

 

All cancer cells sequester iron. Artemisinin reacts with free iron atoms in

cells. In the presence of free iron, the endoperoxide bridge breaks down,

forming very reactive free radicals that cause rapid and extensive damage and

death to cancer cells. Similarly, the anti-malaria action of artemisinin is due

to its reaction with intraparasitic heme iron, which generates free radicals,

leading to damage to the parasite.

 

Dr. Henry Lai and Dr. NP Singh of University of Washington, School of Medicine

has collected more than 300 peer reviewed publications or Dr. Singh Presentation

and summarized by Dr. Wayne Li of Holley Pharmaceuticals listed as follows for

your source of further research.

 

This serves as a primary source of information and references for scientists and

health professionals. Readers should refer to the original articles for details.

This does not constitute a suggestion or an imply to take artemisinin for any

diseases. Only qualified healthcare professionals can give you medical advices.

 

Artemisinin

 

Artemisinin is a compound extracted from the plant Artemesia annua L. (sweet

wormwood, also known as the Chinese herbal Qinghao). Artemisinin (C15H22O5 ) is

a sesquiterpene lactone. Artemesia annua has been used in China since AD 341 to

treat febrile illness. In 1971, the active ingredient, artemisininin, was

identified and isolated. (PM O’Neill, Univ. of Liverpool, WHO Report, No. 36,

Malaria, Encouraging Results from Studies to Improve the Safety and Efficacy of

Natural Drug Compounds. 2001)

 

Derivatives of artemisinin have been synthesized. These include:

dihydroartemisinin (DHA), artemether, artesunate, arteether, and artelinic acid.

These compounds have been packaged in different forms: tablets, capsules,

suppositories and injectibles. DHA, artesuante and artelinate are relatively

water-soluble, whereas the others are oil (fat) – soluble. (Artemisinin Research

Foundation website, 2002)

 

Mechanism of Action

 

The artemisinin molecule contains two oxygen atoms linked together in what is

known as an ‘endoperoxide bridge’, which could react with an iron atom to form

free radicals. Artemisinin is toxic to malaria parasites because the parasite

contains a high amount iron in the form of heme molecules. (Zhang F., Gosser DK

Jr. et al, Hemin-catalyzed decomposition of artemisinin (qinghao). Biochem

Pharmacol 1992; 43: 1805-9.)

 

Free radicals cause to macromolecular damages and kill the parasites.

Artemisinin has been used as an antimalaria in more than two millions patients.

(Anderson KM et al, Free radicals and reactive oxygen species in programmed cell

death. Med Hypotheses, 1999; 52: 451-63.)

 

Compared to normal cells, cancer cells sequester relatively large amount of iron

mainly in the form of holotransferrin. Artemisinin has been shown to cause

rapid and extensive damage and death in cancer cells and have relatively low

toxicity to normal cells. (Artemisinin FAQ, Dr. H. Lai and Dr. NP Singh, Dept.

of Bioengineering, School of Medicine, University of Washington, 2002.)

 

Toxicity

 

Large Animals. When artemisinin was tested with monkeys, they showed no toxicity

after they received up to 292 mg/kg of artemether over 1 to 3 months. High doses

of artemisinin can produce neurotoxicity such as gait disturbances, loss of

spinal and pain response, respiratory depression, and ultimately cardiopulmonary

arrest in large animals. (Journal of Traditional 2(1): 31-36,

1982.)

 

Healthy Volunteers. 250-mg artemisinin and artesunate were used in a

pharmacokinetic studies. Both pharmaceutical forms were well-tolerated and no

undesirable side effects were observed. (Benakis et al. Pharmacokinetics of

artemisinin and artesunate after oral administrationi in healthy volunteers.

American Journal of Tropical Medicine Hyg, Jan;56(1):17-23,1997.)

 

Mice. Artemisininin is virtually non-toxic (LD50 = 4228 mg/kg orally

administered to mice) and without carcinogenicity. (Jung, Mankil and Schinazi,

Raymond, Bioorganic & Medicinal Chemistry Letters, Vol. 4, No. 7; 931-934,

1994.)

 

Pharmacokinetics.

 

The healthy human voluntarily oral administrated 250 mg tablets of artemisinin

and artesunate. For Artemisinin, the mean maximum drug concentration Cmax = 0.36

microgram/ml, appearance half life T1/2 = 0.62 hr, distribution half life t1/2

á = 2.61 hr, decline half-life t1/2 â = 4.34 hr, total area under the

concentration-time curve (AUC) = 1.19 microgram.hg/ml, its main metabolite,

dihydroartemisinin was measurable in the plasma. For artesunate, half lives were

much shorter. (Benakis, et al, Dept. of Pharmacology, Geneva U. Swiss, Am J Trop

Med Hyg, Jan;56(1): 17-23, 1997.)

 

Malaria, Cancer, Parasites

 

A Cancer Treatment Method of inhibiting or killing cancer cells has been

disclosed wherein compounds having an endoperoxide moiety that is reactive with

iron are administered under conditions which enhance intracellullar iron

concentrations. Representative endoperoxide compounds are artemisinin and its

analogs. (US Patent Document 5,578,637, University of Washington, Inventors Dr.

H. Lai and Dr. NP Singh, November 26, 1996.)

 

Cell of a human Leukemia cell line (Molt-4) were exposed to holotransferrin and

dihydroartemisinin and a rapid cell death, as evidenced by a decrease in cell

counts, was observed. (H. Lai and NP Singh, Selective Cancer Cell Cytotoxicity

from Exposure to Dihydroartemisinin and Holotransferrin, Cancer Letters,

91:41-46, 1995.)

 

Artemisinin had been analyzed for its activity against 55 cancer cell lines. It

was most active against leukemia and colon cancer cell lines and active for

melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines.

Importantly, a comparison of artemisinin’s cytotoxicity with those of other

standard cytostatic drugs showed that it was active in molar ranges comparable

to those of established anti-tumor drugs. These results and known low toxicity

of artemisinin and its derivatives make them a promising novel candidate for

cancer chemotherapy. (Efferth et al, Anti-Malaria Drug is Also Active against

Cancer, Int’l Journal of Oncology, 18; 767-773, 2001.)

 

Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx

is high in cancer cells, artemisinin and its analogs selective kill cancer cells

under conditions that increase intracellular iron concentrations. Artemisinin

analog effectively killed radiation-resistant human breast cancer cells in

vitro. The same treatment had considerably less effect on normal human breast

cells. Administration of artemisinin like drugs may be a simple, effective, and

economical treatment for cancer. (NP Singh and H Lai, Selective toxicity of

dihydroartemisinin and holotransferrin toward human breast cancer cells, Life

Sciences, 70:49-56,2001.)

 

Small-cell Lung Carcinoma Cells (SCLC). Artemisinin was tested for the effects

on drug-sensitive (H69) and multi-drug resistant (H69VP) SCLC cells, pretreated

with transferrin to increase the intracellular iron level. Low doses of

artemisinin were cytotoxic to SCLC cells. The cytotoxicity of artemisinin for

H69VP cells was ten-fold lower than for H69 cells, indicating that artemisinin

is part of the drug resistance phenotype. Pretreatment of H69 did not alter the

IC50 for artemisinin, however, in the artemisinin-resistant H69VP cells,

pretreatment with transferrin lowered the artemisinin IC50 to near

drug-sensitive levels. Desferrioxamine inhibited the effect of transferrin on

the IC50 for artemisinin in drug-resistant cells but did not have an effect on

artemisinin cytotoxicity in drug-sensitive cells. These data indicate the

potential use of artemisinin and transferrin in drug-resistant SCLC. (Sadava, D

et al. Transferrin overcomes drug resistance to artemisinin in human small-cell

lung carcinoma cells, Cancer Letter, 179, 151- 156, 2002.)

 

Combined with Chemotherapy Drugs. This article reported experiemnts to study the

activity of 22 drugs on leukemia CCRF-CEM cells lines, artemisinin, artesuante,

baicalein, baicalin, berberine, bufalin, cantharidin, cephalotaxine, curcumin,

daidzein, daidzin, diallyl disulfide, ginsenoside Rh2, glycirrhizic acid,

isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin, quercetin,

tannic acid, and tetrahydronardosinon, carried out independently in Germany and

Australia. As shown by flow cytometry, artesunate significantly increased

daunorubicin accumulation in CEM/E1000 cells. As artesunate and bufalin showed

both anti-leukemic activity if applied alone and modulation activity in

combination with daunorubicin in multidrug-resistant (MDR) cells, these two

drugs may be suitable for novel combination treatment regimens to improve

leukemia cell killing. (Efferth et al. Blood Cells, Molecules, and Diseases

28(2) Mar/Apr; 160-168, 2002.)

 

Modulation of Multidrug Resisitance for Chemotherapy. Artemisinin and its

derivatives have been found to inhibit the proliferation of cancer cells and

increased cytotoxicity of perarubicin and doxorubicin in

P-glycoprotein-overexpressing, and in MRP1-overexpressing, but not in their

corresponding drug-sensitive cell lines. (Reungpatthanaphong, P et al

Modulation of MDR by Artemisinin, artesunate and DHA in K562, GLC4 Resistant

Cell Lines, Biology Pharmocology Bull. 25 (12) 1555-1561,2002.)

 

A triterpene and a sesquiterpene were isolated from separation of Artemisia

stolonifera. These two aromatic compounds showed in vitro cytotoxicity against

non-small cell lung adenocarcinoma, ovarian, skin melanoma, CNS and colon.

(Kwon, Phytochemical constiuents of Artemisia stolonifera, Arch. Pharm. Research

24(4):312-315, 2001.

 

9 C-10 non-acetal derivatives of the natural trioxane artemisinin were prepared

as dimers using some novel chemistry. All compounds showed good to excellent

anti-malarial and antiproliferative activities in vitro. Dimers 8, 10, and 12

were especially potent and selective at inhibiting growth of some human cancer

cell lines in the NCI in vitro 60-cell line assay. (Posner, GH et al,

Antimalarial, antiproliferative, and antitumor activities of Artemisinin Derived

Dimers, J Medicinal Chemistry, 42(21),178-181, Oct. 1999.)

 

Leukemia and Non Small-Cell Lung Carcinoma Cell Lines. Modification of

artemisinin structure led to discovery of a novel class of antitumor compounds.

The artemisinin derivatives containing cyano and aryl groups showed potent

antiproliferative effect in vitro against leukemia and human lung carcinoma cell

lines. (Li, Ying, et al. Novel antitumor artemisinin derivatives targeting G1

phase of the cell cycle. Bioorganic & Medicinal Chemistry Letters 11:5-8,2001.)

 

A series of artemisinin-related endoperoxides was tested for cytotoxicity to

Ehrlich ascites tumor cells (EAT). Artemisinin showed cytotoxicity to the EAT

cells and its derivatives exhibited a somewhat more potent cytotoxicity.

Artemisinin and its derivatives showed cytotoxicity to EAT cells at higher

concentrations than those needed for in vitro anti-malaria activity.

(Woerdenbag, HJ et al. Cytotoxicity of artemisinin-related endoperoxides to EAT

cells, J. Natural Products 56:(6),849-856, 1993.)

 

Blood-Brain Barrier & Alzheimer’s disease (AD). A methanolic extract from

Artemisia showed the highest inhibitory effect on acetylcholinesterase in vitro.

The study demonstrated that an alkaloid of Artemisia asiatica, metabolized to

small molecule in digestive tract and passed through the BBB, be an

acetylcholinesterase inhibitor with a blocker of neurotoxicity induced by a beta

in human brain causing AD. Heo et al. Inhibitory effect of Artemisia asiatica

alkaloids on acetylcholinesterase activity from PC12 cells, Molecule Cells, Jun

30;10(3):253-262.)

 

AIDS and HIV. A series of artemisinin (qinghaosu) related trioxanes has been

prepared and assayed in vitro for anti-HIV activity. One of these compounds,

12-n-butyldeoxoartemisinin shows a good antiviral activity against HIV-1. (Jung,

M et al. Synthesis and In Vitro Anti-Human Immunodeficienvy Virus Activity of

Artemisinin (Qinghaosu) Related Trioxanes, Bioorganic & Medicinal Chemistry

Letters, Vol. 4, No. 7, 931-934; 1994.)

 

Hepatitis B and Lyme Disease 320 cases of chronic Hepatitis B were treated with

artemisinin derivatives resulted in the recovery of liver function. Herbmed

website, Zhang, et al, 1993

 

This publication describes the treatment of a laryngeal squamous cell carcinoma

case with the water-soluble artemisinin analog, artesunate. Artemisinin is a

novel anti-cancer drug with demonstrated results in killing cancer cells.

Artesunate injections and tablets were administered to the patient over a period

of nine months. The tumor was significantly reduced (by approximately 70%)

after two months of treatment. Overall, the artesunate treatment of the patient

was beneficial in prolonging and improving the quality of life. Artemisinin and

its analogs offer promise for cancer therapy. (Singh and Verma, Case report of

a laryngeal squamous cell carcinoma treated with artesunate, Archive of

Oncology, Vol. 10(4), 279-80, 2002.)

 

A protocol clinic trials for 50 canines diagnosed with metastatic osteosarcoma

to the lungs is being considered following in vitro testing at Georgetown

University and Washington Cancer Institute. Toxicity data do not suggest that

systemic toxicity occurs at therapeutic dosages. It is believed that the use of

oral artemisinin protocol will produce clinically measurable cytotoxic effects

in the tumor cells of canines with metastatic disease. (Dr. Krutz, D. Hartmann,

P. Wodajo & K.Graney, A Letter to FDA, Treatment of Metastasic Canine Cancer

with Artemisinin, Dec. 2002.)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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[Guest guest]

I've added Qing hao to a cancer formula and have gotten some very

encouraging results with my cancer patients. All have shown

significant improvement. One woman who has 30 tumor sites dropped

her markers in half. But since I'm also doing acupuncture on all of

them, it's difficult to say what percent is atrributable to the

herbs alone.

 

 

Jim Ramholz

 

 

 

 

 

 

, @j... wrote:

> Thanks for the lead. I am amazed (and humbled) at what I found.

I guess the more I learn, the more I realize how little I

know. Read the article that follows:

>

>

> ARTEMISININ

> Artemisinin is a compound extracted from the plant Artemesia annua

L. (sweet wormwood,.also known as the Chinese herbal Qinghao).

Artemisinin is a sesquiterpene lactone (emperical formula C15H22O5.)

Its derivatives, such as artemether, artesunate, arteether, and

artelinate, which are quickly converted to their active plasma

metabolite, dihydroartemisinin (DHA). Artesunate and artelinate are

water-soluble, the others are oil (fat)-soluble.

> According to a WHO research report (No. 36 Malaria, encouraging

results from studies to improve the safety and efficacy of natural

drug compounds), extracts from the herb Artemeisa annua have been

used in China since AD 341 to treat febrile illness. In 1971, the

active component, qinghaosu (now know as artemisinin) was identified

and shown to be effective against malaria, including chloroquine-

resistant parasites. It has generally proven safe and free of toxic

side effects from widespread experience with dosages designed to

treat Malaria. WHO has recommended artemisinin-based anti-malaria

drugs.

>

>

> More recently, research done by scientists, like Dr. Henry Lai and

Dr. N.P. Singh of the University of Washington, Seattle, WA, USA,

has shown in both in vitro and in vivo tests that artemisinin is

selectively toxic to cancer cells. Consequently, many cancer

patients around the world have been taking artemisinin or its

derivatives as an alternative cancer treatment, mostly under the

supervision of physicians. Many encouraging results, though mostly

anecdotal, have been reported from these patients.

>

> These clinical applications of artemisinin, in the treatment of

malaria and cancer, could be one of the most important discoveries

in the 21st century. Further research could lead to an effective,

affordable, non-surgery and non-toxic treatment for cancer, malaria

and other deadly diseases.

>

> Artemisia annua L

>

>

>

> Drug of Choice

>

>

>

> How does Artemisinin work?

>

> The artemisinin, a sesquiterpene lactone peroxide contains two

oxygen atoms hooked together in what is termed an endoperoxide

bridge, which is essential for its anti-malarial and anti-cancer

activity.

>

>

> All cancer cells sequester iron. Artemisinin reacts with free iron

atoms in cells. In the presence of free iron, the endoperoxide

bridge breaks down, forming very reactive free radicals that cause

rapid and extensive damage and death to cancer cells. Similarly, the

anti-malaria action of artemisinin is due to its reaction with

intraparasitic heme iron, which generates free radicals, leading to

damage to the parasite.

>

> Dr. Henry Lai and Dr. NP Singh of University of Washington, School

of Medicine has collected more than 300 peer reviewed publications

or Dr. Singh Presentation and summarized by Dr. Wayne Li of Holley

Pharmaceuticals listed as follows for your source of further

research.

>

> This serves as a primary source of information and references for

scientists and health professionals. Readers should refer to the

original articles for details. This does not constitute a suggestion

or an imply to take artemisinin for any diseases. Only qualified

healthcare professionals can give you medical advices.

>

> Artemisinin

>

> Artemisinin is a compound extracted from the plant Artemesia annua

L. (sweet wormwood, also known as the Chinese herbal Qinghao).

Artemisinin (C15H22O5 ) is a sesquiterpene lactone. Artemesia annua

has been used in China since AD 341 to treat febrile illness. In

1971, the active ingredient, artemisininin, was identified and

isolated. (PM O'Neill, Univ. of Liverpool, WHO Report, No. 36,

Malaria, Encouraging Results from Studies to Improve the Safety and

Efficacy of Natural Drug Compounds. 2001)

>

> Derivatives of artemisinin have been synthesized. These include:

dihydroartemisinin (DHA), artemether, artesunate, arteether, and

artelinic acid. These compounds have been packaged in different

forms: tablets, capsules, suppositories and injectibles. DHA,

artesuante and artelinate are relatively water-soluble, whereas the

others are oil (fat) – soluble. (Artemisinin Research Foundation

website, 2002)

>

> Mechanism of Action

>

> The artemisinin molecule contains two oxygen atoms linked together

in what is known as an `endoperoxide bridge', which could react with

an iron atom to form free radicals. Artemisinin is toxic to malaria

parasites because the parasite contains a high amount iron in the

form of heme molecules. (Zhang F., Gosser DK Jr. et al, Hemin-

catalyzed decomposition of artemisinin (qinghao). Biochem Pharmacol

1992; 43: 1805-9.)

>

> Free radicals cause to macromolecular damages and kill the

parasites. Artemisinin has been used as an antimalaria in more than

two millions patients. (Anderson KM et al, Free radicals and

reactive oxygen species in programmed cell death. Med Hypotheses,

1999; 52: 451-63.)

>

> Compared to normal cells, cancer cells sequester relatively large

amount of iron mainly in the form of holotransferrin. Artemisinin

has been shown to cause rapid and extensive damage and death in

cancer cells and have relatively low toxicity to normal cells.

(Artemisinin FAQ, Dr. H. Lai and Dr. NP Singh, Dept. of

Bioengineering, School of Medicine, University of Washington, 2002.)

>

> Toxicity

>

> Large Animals. When artemisinin was tested with monkeys, they

showed no toxicity after they received up to 292 mg/kg of artemether

over 1 to 3 months. High doses of artemisinin can produce

neurotoxicity such as gait disturbances, loss of spinal and pain

response, respiratory depression, and ultimately cardiopulmonary

arrest in large animals. (Journal of Traditional 2

(1): 31-36, 1982.)

>

> Healthy Volunteers. 250-mg artemisinin and artesunate were used

in a pharmacokinetic studies. Both pharmaceutical forms were well-

tolerated and no undesirable side effects were observed. (Benakis et

al. Pharmacokinetics of artemisinin and artesunate after oral

administrationi in healthy volunteers. American Journal of Tropical

Medicine Hyg, Jan;56(1):17-23,1997.)

>

> Mice. Artemisininin is virtually non-toxic (LD50 = 4228 mg/kg

orally administered to mice) and without carcinogenicity. (Jung,

Mankil and Schinazi, Raymond, Bioorganic & Medicinal Chemistry

Letters, Vol. 4, No. 7; 931-934, 1994.)

>

> Pharmacokinetics.

>

> The healthy human voluntarily oral administrated 250 mg tablets of

artemisinin and artesunate. For Artemisinin, the mean maximum drug

concentration Cmax = 0.36 microgram/ml, appearance half life T1/2

= 0.62 hr, distribution half life t1/2 á = 2.61 hr, decline half-

life t1/2 â = 4.34 hr, total area under the concentration-time curve

(AUC) = 1.19 microgram.hg/ml, its main metabolite,

dihydroartemisinin was measurable in the plasma. For artesunate,

half lives were much shorter. (Benakis, et al, Dept. of

Pharmacology, Geneva U. Swiss, Am J Trop Med Hyg, Jan;56(1): 17-23,

1997.)

>

> Malaria, Cancer, Parasites

>

> A Cancer Treatment Method of inhibiting or killing cancer cells

has been disclosed wherein compounds having an endoperoxide moiety

that is reactive with iron are administered under conditions which

enhance intracellullar iron concentrations. Representative

endoperoxide compounds are artemisinin and its analogs. (US Patent

Document 5,578,637, University of Washington, Inventors Dr. H. Lai

and Dr. NP Singh, November 26, 1996.)

>

> Cell of a human Leukemia cell line (Molt-4) were exposed to

holotransferrin and dihydroartemisinin and a rapid cell death, as

evidenced by a decrease in cell counts, was observed. (H. Lai and NP

Singh, Selective Cancer Cell Cytotoxicity from Exposure to

Dihydroartemisinin and Holotransferrin, Cancer Letters, 91:41-46,

1995.)

>

> Artemisinin had been analyzed for its activity against 55 cancer

cell lines. It was most active against leukemia and colon cancer

cell lines and active for melanomas, breast, ovarian, prostate, CNS,

and renal cancer cell lines. Importantly, a comparison of

artemisinin's cytotoxicity with those of other standard cytostatic

drugs showed that it was active in molar ranges comparable to those

of established anti-tumor drugs. These results and known low

toxicity of artemisinin and its derivatives make them a promising

novel candidate for cancer chemotherapy. (Efferth et al, Anti-

Malaria Drug is Also Active against Cancer, Int'l Journal of

Oncology, 18; 767-773, 2001.)

>

> Artemisinin becomes cytotoxic in the presence of ferrous iron.

Since iron influx is high in cancer cells, artemisinin and its

analogs selective kill cancer cells under conditions that increase

intracellular iron concentrations. Artemisinin analog effectively

killed radiation-resistant human breast cancer cells in vitro. The

same treatment had considerably less effect on normal human breast

cells. Administration of artemisinin like drugs may be a simple,

effective, and economical treatment for cancer. (NP Singh and H Lai,

Selective toxicity of dihydroartemisinin and holotransferrin toward

human breast cancer cells, Life Sciences, 70:49-56,2001.)

>

> Small-cell Lung Carcinoma Cells (SCLC). Artemisinin was tested for

the effects on drug-sensitive (H69) and multi-drug resistant (H69VP)

SCLC cells, pretreated with transferrin to increase the

intracellular iron level. Low doses of artemisinin were cytotoxic to

SCLC cells. The cytotoxicity of artemisinin for H69VP cells was ten-

fold lower than for H69 cells, indicating that artemisinin is part

of the drug resistance phenotype. Pretreatment of H69 did not alter

the IC50 for artemisinin, however, in the artemisinin-resistant

H69VP cells, pretreatment with transferrin lowered the artemisinin

IC50 to near drug-sensitive levels. Desferrioxamine inhibited the

effect of transferrin on the IC50 for artemisinin in drug-resistant

cells but did not have an effect on artemisinin cytotoxicity in drug-

sensitive cells. These data indicate the potential use of

artemisinin and transferrin in drug-resistant SCLC. (Sadava, D et

al. Transferrin overcomes drug resistance to artemisinin in human

small-cell lung carcinoma cells, Cancer Letter, 179, 151- 156, 2002.)

>

> Combined with Chemotherapy Drugs. This article reported

experiemnts to study the activity of 22 drugs on leukemia CCRF-CEM

cells lines, artemisinin, artesuante, baicalein, baicalin,

berberine, bufalin, cantharidin, cephalotaxine, curcumin, daidzein,

daidzin, diallyl disulfide, ginsenoside Rh2, glycirrhizic acid,

isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin,

quercetin, tannic acid, and tetrahydronardosinon, carried out

independently in Germany and Australia. As shown by flow cytometry,

artesunate significantly increased daunorubicin accumulation in

CEM/E1000 cells. As artesunate and bufalin showed both anti-leukemic

activity if applied alone and modulation activity in combination

with daunorubicin in multidrug-resistant (MDR) cells, these two

drugs may be suitable for novel combination treatment regimens to

improve leukemia cell killing. (Efferth et al. Blood Cells,

Molecules, and Diseases 28(2) Mar/Apr; 160-168, 2002.)

>

> Modulation of Multidrug Resisitance for Chemotherapy. Artemisinin

and its derivatives have been found to inhibit the proliferation of

cancer cells and increased cytotoxicity of perarubicin and

doxorubicin in P-glycoprotein-overexpressing, and in MRP1-

overexpressing, but not in their corresponding drug-sensitive cell

lines. (Reungpatthanaphong, P et al Modulation of MDR by

Artemisinin, artesunate and DHA in K562, GLC4 Resistant Cell Lines,

Biology Pharmocology Bull. 25 (12) 1555-1561,2002.)

>

> A triterpene and a sesquiterpene were isolated from separation of

Artemisia stolonifera. These two aromatic compounds showed in vitro

cytotoxicity against non-small cell lung adenocarcinoma, ovarian,

skin melanoma, CNS and colon. (Kwon, Phytochemical constiuents of

Artemisia stolonifera, Arch. Pharm. Research 24(4):312-315, 2001.

>

> 9 C-10 non-acetal derivatives of the natural trioxane artemisinin

were prepared as dimers using some novel chemistry. All compounds

showed good to excellent anti-malarial and antiproliferative

activities in vitro. Dimers 8, 10, and 12 were especially potent and

selective at inhibiting growth of some human cancer cell lines in

the NCI in vitro 60-cell line assay. (Posner, GH et al,

Antimalarial, antiproliferative, and antitumor activities of

Artemisinin Derived Dimers, J Medicinal Chemistry, 42(21),178-181,

Oct. 1999.)

>

> Leukemia and Non Small-Cell Lung Carcinoma Cell Lines.

Modification of artemisinin structure led to discovery of a novel

class of antitumor compounds. The artemisinin derivatives containing

cyano and aryl groups showed potent antiproliferative effect in

vitro against leukemia and human lung carcinoma cell lines. (Li,

Ying, et al. Novel antitumor artemisinin derivatives targeting G1

phase of the cell cycle. Bioorganic & Medicinal Chemistry Letters

11:5-8,2001.)

>

> A series of artemisinin-related endoperoxides was tested for

cytotoxicity to Ehrlich ascites tumor cells (EAT). Artemisinin

showed cytotoxicity to the EAT cells and its derivatives exhibited a

somewhat more potent cytotoxicity. Artemisinin and its derivatives

showed cytotoxicity to EAT cells at higher concentrations than those

needed for in vitro anti-malaria activity. (Woerdenbag, HJ et al.

Cytotoxicity of artemisinin-related endoperoxides to EAT cells, J.

Natural Products 56:(6),849-856, 1993.)

>

> Blood-Brain Barrier & Alzheimer's disease (AD). A methanolic

extract from Artemisia showed the highest inhibitory effect on

acetylcholinesterase in vitro. The study demonstrated that an

alkaloid of Artemisia asiatica, metabolized to small molecule in

digestive tract and passed through the BBB, be an

acetylcholinesterase inhibitor with a blocker of neurotoxicity

induced by a beta in human brain causing AD. Heo et al. Inhibitory

effect of Artemisia asiatica alkaloids on acetylcholinesterase

activity from PC12 cells, Molecule Cells, Jun 30;10(3):253-262.)

>

> AIDS and HIV. A series of artemisinin (qinghaosu) related

trioxanes has been prepared and assayed in vitro for anti-HIV

activity. One of these compounds, 12-n-butyldeoxoartemisinin shows a

good antiviral activity against HIV-1. (Jung, M et al. Synthesis and

In Vitro Anti-Human Immunodeficienvy Virus Activity of Artemisinin

(Qinghaosu) Related Trioxanes, Bioorganic & Medicinal Chemistry

Letters, Vol. 4, No. 7, 931-934; 1994.)

>

> Hepatitis B and Lyme Disease 320 cases of chronic Hepatitis B were

treated with artemisinin derivatives resulted in the recovery of

liver function. Herbmed website, Zhang, et al, 1993

>

> This publication describes the treatment of a laryngeal squamous

cell carcinoma case with the water-soluble artemisinin analog,

artesunate. Artemisinin is a novel anti-cancer drug with

demonstrated results in killing cancer cells. Artesunate injections

and tablets were administered to the patient over a period of nine

months. The tumor was significantly reduced (by approximately 70%)

after two months of treatment. Overall, the artesunate treatment of

the patient was beneficial in prolonging and improving the quality

of life. Artemisinin and its analogs offer promise for cancer

therapy. (Singh and Verma, Case report of a laryngeal squamous cell

carcinoma treated with artesunate, Archive of Oncology, Vol. 10(4),

279-80, 2002.)

>

> A protocol clinic trials for 50 canines diagnosed with metastatic

osteosarcoma to the lungs is being considered following in vitro

testing at Georgetown University and Washington Cancer Institute.

Toxicity data do not suggest that systemic toxicity occurs at

therapeutic dosages. It is believed that the use of oral artemisinin

protocol will produce clinically measurable cytotoxic effects in the

tumor cells of canines with metastatic disease. (Dr. Krutz, D.

Hartmann, P. Wodajo & K.Graney, A Letter to FDA, Treatment of

Metastasic Canine Cancer with Artemisinin, Dec. 2002.)

>

>

>

>

>

>

>

>

______________

> The best thing to hit the internet in years - Juno SpeedBand!

> Surf the web up to FIVE TIMES FASTER!

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[Guest guest]

Michael Broffman has picked up on the use of artemesin, an extract of

qing hao, for cancer patients, based on positive studies in mainland

China.

 

 

On Friday, October 10, 2003, at 02:21 PM, James Ramholz wrote:

 

> I've added Qing hao to a cancer formula and have gotten some very

> encouraging results with my cancer patients. All have shown

> significant improvement. One woman who has 30 tumor sites dropped

> her markers in half. But since I'm also doing acupuncture on all of

> them, it's difficult to say what percent is atrributable to the

> herbs alone.

>

>

> Jim Ramholz

, @j... wrote:

>> Thanks for the lead. I am amazed (and humbled) at what I found.

> I guess the more I learn, the more I realize how little I

> know. Read the article that follows:

>>

>>

>> ARTEMISININ

>> Artemisinin is a compound extracted from the plant Artemesia annua

> L. (sweet wormwood,.also known as the Chinese herbal Qinghao).

> Artemisinin is a sesquiterpene lactone (emperical formula C15H22O5.)

> Its derivatives, such as artemether, artesunate, arteether, and

> artelinate, which are quickly converted to their active plasma

> metabolite, dihydroartemisinin (DHA). Artesunate and artelinate are

> water-soluble, the others are oil (fat)-soluble.

>> According to a WHO research report (No. 36 Malaria, encouraging

> results from studies to improve the safety and efficacy of natural

> drug compounds), extracts from the herb Artemeisa annua have been

> used in China since AD 341 to treat febrile illness. In 1971, the

> active component, qinghaosu (now know as artemisinin) was identified

> and shown to be effective against malaria, including chloroquine-

> resistant parasites. It has generally proven safe and free of toxic

> side effects from widespread experience with dosages designed to

> treat Malaria. WHO has recommended artemisinin-based anti-malaria

> drugs.

>>

>>

>> More recently, research done by scientists, like Dr. Henry Lai and

> Dr. N.P. Singh of the University of Washington, Seattle, WA, USA,

> has shown in both in vitro and in vivo tests that artemisinin is

> selectively toxic to cancer cells. Consequently, many cancer

> patients around the world have been taking artemisinin or its

> derivatives as an alternative cancer treatment, mostly under the

> supervision of physicians. Many encouraging results, though mostly

> anecdotal, have been reported from these patients.

>>

>> These clinical applications of artemisinin, in the treatment of

> malaria and cancer, could be one of the most important discoveries

> in the 21st century. Further research could lead to an effective,

> affordable, non-surgery and non-toxic treatment for cancer, malaria

> and other deadly diseases.

>>

>> Artemisia annua L

>>

>>

>>

>> Drug of Choice

>>

>>

>>

>> How does Artemisinin work?

>>

>> The artemisinin, a sesquiterpene lactone peroxide contains two

> oxygen atoms hooked together in what is termed an endoperoxide

> bridge, which is essential for its anti-malarial and anti-cancer

> activity.

>>

>>

>> All cancer cells sequester iron. Artemisinin reacts with free iron

> atoms in cells. In the presence of free iron, the endoperoxide

> bridge breaks down, forming very reactive free radicals that cause

> rapid and extensive damage and death to cancer cells. Similarly, the

> anti-malaria action of artemisinin is due to its reaction with

> intraparasitic heme iron, which generates free radicals, leading to

> damage to the parasite.

>>

>> Dr. Henry Lai and Dr. NP Singh of University of Washington, School

> of Medicine has collected more than 300 peer reviewed publications

> or Dr. Singh Presentation and summarized by Dr. Wayne Li of Holley

> Pharmaceuticals listed as follows for your source of further

> research.

>>

>> This serves as a primary source of information and references for

> scientists and health professionals. Readers should refer to the

> original articles for details. This does not constitute a suggestion

> or an imply to take artemisinin for any diseases. Only qualified

> healthcare professionals can give you medical advices.

>>

>> Artemisinin

>>

>> Artemisinin is a compound extracted from the plant Artemesia annua

> L. (sweet wormwood, also known as the Chinese herbal Qinghao).

> Artemisinin (C15H22O5 ) is a sesquiterpene lactone. Artemesia annua

> has been used in China since AD 341 to treat febrile illness. In

> 1971, the active ingredient, artemisininin, was identified and

> isolated. (PM O'Neill, Univ. of Liverpool, WHO Report, No. 36,

> Malaria, Encouraging Results from Studies to Improve the Safety and

> Efficacy of Natural Drug Compounds. 2001)

>>

>> Derivatives of artemisinin have been synthesized. These include:

> dihydroartemisinin (DHA), artemether, artesunate, arteether, and

> artelinic acid. These compounds have been packaged in different

> forms: tablets, capsules, suppositories and injectibles. DHA,

> artesuante and artelinate are relatively water-soluble, whereas the

> others are oil (fat) – soluble. (Artemisinin Research Foundation

> website, 2002)

>>

>> Mechanism of Action

>>

>> The artemisinin molecule contains two oxygen atoms linked together

> in what is known as an `endoperoxide bridge', which could react with

> an iron atom to form free radicals. Artemisinin is toxic to malaria

> parasites because the parasite contains a high amount iron in the

> form of heme molecules. (Zhang F., Gosser DK Jr. et al, Hemin-

> catalyzed decomposition of artemisinin (qinghao). Biochem Pharmacol

> 1992; 43: 1805-9.)

>>

>> Free radicals cause to macromolecular damages and kill the

> parasites. Artemisinin has been used as an antimalaria in more than

> two millions patients. (Anderson KM et al, Free radicals and

> reactive oxygen species in programmed cell death. Med Hypotheses,

> 1999; 52: 451-63.)

>>

>> Compared to normal cells, cancer cells sequester relatively large

> amount of iron mainly in the form of holotransferrin. Artemisinin

> has been shown to cause rapid and extensive damage and death in

> cancer cells and have relatively low toxicity to normal cells.

> (Artemisinin FAQ, Dr. H. Lai and Dr. NP Singh, Dept. of

> Bioengineering, School of Medicine, University of Washington, 2002.)

>>

>> Toxicity

>>

>> Large Animals. When artemisinin was tested with monkeys, they

> showed no toxicity after they received up to 292 mg/kg of artemether

> over 1 to 3 months. High doses of artemisinin can produce

> neurotoxicity such as gait disturbances, loss of spinal and pain

> response, respiratory depression, and ultimately cardiopulmonary

> arrest in large animals. (Journal of Traditional 2

> (1): 31-36, 1982.)

>>

>> Healthy Volunteers. 250-mg artemisinin and artesunate were used

> in a pharmacokinetic studies. Both pharmaceutical forms were well-

> tolerated and no undesirable side effects were observed. (Benakis et

> al. Pharmacokinetics of artemisinin and artesunate after oral

> administrationi in healthy volunteers. American Journal of Tropical

> Medicine Hyg, Jan;56(1):17-23,1997.)

>>

>> Mice. Artemisininin is virtually non-toxic (LD50 = 4228 mg/kg

> orally administered to mice) and without carcinogenicity. (Jung,

> Mankil and Schinazi, Raymond, Bioorganic & Medicinal Chemistry

> Letters, Vol. 4, No. 7; 931-934, 1994.)

>>

>> Pharmacokinetics.

>>

>> The healthy human voluntarily oral administrated 250 mg tablets of

> artemisinin and artesunate. For Artemisinin, the mean maximum drug

> concentration Cmax = 0.36 microgram/ml, appearance half life T1/2

> = 0.62 hr, distribution half life t1/2 á = 2.61 hr, decline half-

> life t1/2 â = 4.34 hr, total area under the concentration-time curve

> (AUC) = 1.19 microgram.hg/ml, its main metabolite,

> dihydroartemisinin was measurable in the plasma. For artesunate,

> half lives were much shorter. (Benakis, et al, Dept. of

> Pharmacology, Geneva U. Swiss, Am J Trop Med Hyg, Jan;56(1): 17-23,

> 1997.)

>>

>> Malaria, Cancer, Parasites

>>

>> A Cancer Treatment Method of inhibiting or killing cancer cells

> has been disclosed wherein compounds having an endoperoxide moiety

> that is reactive with iron are administered under conditions which

> enhance intracellullar iron concentrations. Representative

> endoperoxide compounds are artemisinin and its analogs. (US Patent

> Document 5,578,637, University of Washington, Inventors Dr. H. Lai

> and Dr. NP Singh, November 26, 1996.)

>>

>> Cell of a human Leukemia cell line (Molt-4) were exposed to

> holotransferrin and dihydroartemisinin and a rapid cell death, as

> evidenced by a decrease in cell counts, was observed. (H. Lai and NP

> Singh, Selective Cancer Cell Cytotoxicity from Exposure to

> Dihydroartemisinin and Holotransferrin, Cancer Letters, 91:41-46,

> 1995.)

>>

>> Artemisinin had been analyzed for its activity against 55 cancer

> cell lines. It was most active against leukemia and colon cancer

> cell lines and active for melanomas, breast, ovarian, prostate, CNS,

> and renal cancer cell lines. Importantly, a comparison of

> artemisinin's cytotoxicity with those of other standard cytostatic

> drugs showed that it was active in molar ranges comparable to those

> of established anti-tumor drugs. These results and known low

> toxicity of artemisinin and its derivatives make them a promising

> novel candidate for cancer chemotherapy. (Efferth et al, Anti-

> Malaria Drug is Also Active against Cancer, Int'l Journal of

> Oncology, 18; 767-773, 2001.)

>>

>> Artemisinin becomes cytotoxic in the presence of ferrous iron.

> Since iron influx is high in cancer cells, artemisinin and its

> analogs selective kill cancer cells under conditions that increase

> intracellular iron concentrations. Artemisinin analog effectively

> killed radiation-resistant human breast cancer cells in vitro. The

> same treatment had considerably less effect on normal human breast

> cells. Administration of artemisinin like drugs may be a simple,

> effective, and economical treatment for cancer. (NP Singh and H Lai,

> Selective toxicity of dihydroartemisinin and holotransferrin toward

> human breast cancer cells, Life Sciences, 70:49-56,2001.)

>>

>> Small-cell Lung Carcinoma Cells (SCLC). Artemisinin was tested for

> the effects on drug-sensitive (H69) and multi-drug resistant (H69VP)

> SCLC cells, pretreated with transferrin to increase the

> intracellular iron level. Low doses of artemisinin were cytotoxic to

> SCLC cells. The cytotoxicity of artemisinin for H69VP cells was ten-

> fold lower than for H69 cells, indicating that artemisinin is part

> of the drug resistance phenotype. Pretreatment of H69 did not alter

> the IC50 for artemisinin, however, in the artemisinin-resistant

> H69VP cells, pretreatment with transferrin lowered the artemisinin

> IC50 to near drug-sensitive levels. Desferrioxamine inhibited the

> effect of transferrin on the IC50 for artemisinin in drug-resistant

> cells but did not have an effect on artemisinin cytotoxicity in drug-

> sensitive cells. These data indicate the potential use of

> artemisinin and transferrin in drug-resistant SCLC. (Sadava, D et

> al. Transferrin overcomes drug resistance to artemisinin in human

> small-cell lung carcinoma cells, Cancer Letter, 179, 151- 156, 2002.)

>>

>> Combined with Chemotherapy Drugs. This article reported

> experiemnts to study the activity of 22 drugs on leukemia CCRF-CEM

> cells lines, artemisinin, artesuante, baicalein, baicalin,

> berberine, bufalin, cantharidin, cephalotaxine, curcumin, daidzein,

> daidzin, diallyl disulfide, ginsenoside Rh2, glycirrhizic acid,

> isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin,

> quercetin, tannic acid, and tetrahydronardosinon, carried out

> independently in Germany and Australia. As shown by flow cytometry,

> artesunate significantly increased daunorubicin accumulation in

> CEM/E1000 cells. As artesunate and bufalin showed both anti-leukemic

> activity if applied alone and modulation activity in combination

> with daunorubicin in multidrug-resistant (MDR) cells, these two

> drugs may be suitable for novel combination treatment regimens to

> improve leukemia cell killing. (Efferth et al. Blood Cells,

> Molecules, and Diseases 28(2) Mar/Apr; 160-168, 2002.)

>>

>> Modulation of Multidrug Resisitance for Chemotherapy. Artemisinin

> and its derivatives have been found to inhibit the proliferation of

> cancer cells and increased cytotoxicity of perarubicin and

> doxorubicin in P-glycoprotein-overexpressing, and in MRP1-

> overexpressing, but not in their corresponding drug-sensitive cell

> lines. (Reungpatthanaphong, P et al Modulation of MDR by

> Artemisinin, artesunate and DHA in K562, GLC4 Resistant Cell Lines,

> Biology Pharmocology Bull. 25 (12) 1555-1561,2002.)

>>

>> A triterpene and a sesquiterpene were isolated from separation of

> Artemisia stolonifera. These two aromatic compounds showed in vitro

> cytotoxicity against non-small cell lung adenocarcinoma, ovarian,

> skin melanoma, CNS and colon. (Kwon, Phytochemical constiuents of

> Artemisia stolonifera, Arch. Pharm. Research 24(4):312-315, 2001.

>>

>> 9 C-10 non-acetal derivatives of the natural trioxane artemisinin

> were prepared as dimers using some novel chemistry. All compounds

> showed good to excellent anti-malarial and antiproliferative

> activities in vitro. Dimers 8, 10, and 12 were especially potent and

> selective at inhibiting growth of some human cancer cell lines in

> the NCI in vitro 60-cell line assay. (Posner, GH et al,

> Antimalarial, antiproliferative, and antitumor activities of

> Artemisinin Derived Dimers, J Medicinal Chemistry, 42(21),178-181,

> Oct. 1999.)

>>

>> Leukemia and Non Small-Cell Lung Carcinoma Cell Lines.

> Modification of artemisinin structure led to discovery of a novel

> class of antitumor compounds. The artemisinin derivatives containing

> cyano and aryl groups showed potent antiproliferative effect in

> vitro against leukemia and human lung carcinoma cell lines. (Li,

> Ying, et al. Novel antitumor artemisinin derivatives targeting G1

> phase of the cell cycle. Bioorganic & Medicinal Chemistry Letters

> 11:5-8,2001.)

>>

>> A series of artemisinin-related endoperoxides was tested for

> cytotoxicity to Ehrlich ascites tumor cells (EAT). Artemisinin

> showed cytotoxicity to the EAT cells and its derivatives exhibited a

> somewhat more potent cytotoxicity. Artemisinin and its derivatives

> showed cytotoxicity to EAT cells at higher concentrations than those

> needed for in vitro anti-malaria activity. (Woerdenbag, HJ et al.

> Cytotoxicity of artemisinin-related endoperoxides to EAT cells, J.

> Natural Products 56:(6),849-856, 1993.)

>>

>> Blood-Brain Barrier & Alzheimer's disease (AD). A methanolic

> extract from Artemisia showed the highest inhibitory effect on

> acetylcholinesterase in vitro. The study demonstrated that an

> alkaloid of Artemisia asiatica, metabolized to small molecule in

> digestive tract and passed through the BBB, be an

> acetylcholinesterase inhibitor with a blocker of neurotoxicity

> induced by a beta in human brain causing AD. Heo et al. Inhibitory

> effect of Artemisia asiatica alkaloids on acetylcholinesterase

> activity from PC12 cells, Molecule Cells, Jun 30;10(3):253-262.)

>>

>> AIDS and HIV. A series of artemisinin (qinghaosu) related

> trioxanes has been prepared and assayed in vitro for anti-HIV

> activity. One of these compounds, 12-n-butyldeoxoartemisinin shows a

> good antiviral activity against HIV-1. (Jung, M et al. Synthesis and

> In Vitro Anti-Human Immunodeficienvy Virus Activity of Artemisinin

> (Qinghaosu) Related Trioxanes, Bioorganic & Medicinal Chemistry

> Letters, Vol. 4, No. 7, 931-934; 1994.)

>>

>> Hepatitis B and Lyme Disease 320 cases of chronic Hepatitis B were

> treated with artemisinin derivatives resulted in the recovery of

> liver function. Herbmed website, Zhang, et al, 1993

>>

>> This publication describes the treatment of a laryngeal squamous

> cell carcinoma case with the water-soluble artemisinin analog,

> artesunate. Artemisinin is a novel anti-cancer drug with

> demonstrated results in killing cancer cells. Artesunate injections

> and tablets were administered to the patient over a period of nine

> months. The tumor was significantly reduced (by approximately 70%)

> after two months of treatment. Overall, the artesunate treatment of

> the patient was beneficial in prolonging and improving the quality

> of life. Artemisinin and its analogs offer promise for cancer

> therapy. (Singh and Verma, Case report of a laryngeal squamous cell

> carcinoma treated with artesunate, Archive of Oncology, Vol. 10(4),

> 279-80, 2002.)

>>

>> A protocol clinic trials for 50 canines diagnosed with metastatic

> osteosarcoma to the lungs is being considered following in vitro

> testing at Georgetown University and Washington Cancer Institute.

> Toxicity data do not suggest that systemic toxicity occurs at

> therapeutic dosages. It is believed that the use of oral artemisinin

> protocol will produce clinically measurable cytotoxic effects in the

> tumor cells of canines with metastatic disease. (Dr. Krutz, D.

> Hartmann, P. Wodajo & K.Graney, A Letter to FDA, Treatment of

> Metastasic Canine Cancer with Artemisinin, Dec. 2002.)

>>

>>

>>

>>

>>

>>

>>

>>

>>

>>

>>

>>

>>

>>

>> ______________

>> The best thing to hit the internet in years - Juno SpeedBand!

>> Surf the web up to FIVE TIMES FASTER!

>> Only $14.95/ month - visit www.juno.com to sign up today!

>

>

>