This page is about TELOMERASE AND CANCER, AND IT EMBRYONIC NATURE.  IT IS VERY LONG, YOU WILL HAVE TO SCROLL DOWN SEVERAL TIMES TO READ IT ALL.

 

If a drug can’t be patented, no drug company will spend the $50 to $200 million dollars required to fulfill FDA clinical trial requirements.  There are many such compounds on this page. 

 

 

Telomerase Blog Site discussing which of these compounds should be in a trial.  Link to this sites Blog

 

 

USC DECLARES CANCER IS CAUSED BY REACTIVATION OF IMMATURE EMBRYONIC STEM CELLS.  The debate is over

Fund the science.

 

Cancer : Study supports a stem cell origin of cancer

 Researchers at the University of Southern California
 (USC) recently made significant strides toward
 settling a decades-old debate centering on the role
 played by stem cells in cancer development.
 According to the study's findings, which appear in
 an upcoming issue of Nature Genetics and now
 available online, genes that are reversibly
 repressed in embryonic stem cells are
 over-represented among genes that are permanently
 silenced in cancers; this link lends support to the
 increasingly discussed theory that cancer is rooted
 in small populations of stem cells.

 USC researchers uncovered this link after observing
 that of 177 genes repressed by Polycomb group (PcG)
 proteins, fully 77 showed evidence of
 cancer-associated enzymatic modification of DNA
 (known as methylation). "Finding that a Polycomb
 target in an embryonic stem cell is 12 times more
 likely to become abnormally methylated in cancer is
 highly significant," says Peter Laird, Ph.D., one of
 the lead researchers and associate professor of
 surgery, biochemistry and molecular biology, and
 director of basic research for surgery at the Keck
 School of Medicine of USC.

 Laird and his colleagues discovered that some genes
 repressed by Polycomb in embryonic stem cells are
 essentially pre-marked to become permanently
 silenced by DNA methylation. "This permanent
 silencing," Laird explains, "prevents embryonic stem
 cells from differentiating, and they thus become the
 seeds of cancer development later in life." USC
 researchers made these observations in relation to
 breast, colorectal, lung, and ovarian cancer.

 Not only does the USC study provide empirical
 evidence for a stem cell origin of cancer, but,
 according to Laird, "It also supports a very early
 involvement of epigenetics in cancer. We found that
 cancer arises in cells that have already undergone
 epigenetic alterations," he adds, "which points to
 epigenetic events preceding genetic events in cancer
 development." Laird notes that this theory, while
 relatively new, is gaining support among scientists.

 Findings from the USC study also can be applied to
 stem cell research funded by the California
 Institute for Regenerative Medicine (CIRM), which
 was created through passage of California
 Proposition 71 in 2004. "One of CIRM's aims," says
 Laird, "is to culture and differentiate embryonic
 stems cells – cells that would then be placed into
 patients. Since our research shows that cancer is
 rooted in stem cells, it would be very important to
 screen for the epigenetic abnormalities that we
 uncovered, so as to prevent people from receiving
 potentially cancer-prone cells."

 Looking ahead, Laird and his USC colleagues would
 next like to focus on what causes some genes to
 transition from temporary repression to permanent
 silencing. "Once we determine that," Laird explains,
 "we can turn to the fundamental question: How can we
 prevent this transition?"
***********************************

Telomerase activation , by any number of things, is probably one of the epigenetic events that awakens these immature embryonic stem cells in an adult body, they try to make the cell types they were originally programmed to make.  We call this cancer.

 

DOES TELOMERASE RE-AWAKEN THE SILENCED GENES?  TELOMERASE ACTIVATION UPREGULATES 70 GENES KNOWN OR SUSPECTED IN CANCER (BLACKBURN)

 

The plastics and hazardous chemicals in our air and water contribute to estrogen in the body, either directly, or by causing aromatase to convert male hormone into estrogen.  Some cause the body to produce estrogen.  Is estrogen responsible for the industrialized worlds cancer epidemic? Is an overabundance of estrogen the thing that wakes up that sleeping embryonic stem cell and causes it to go back to its original job, to make a new organ?  Is it Dr. Lairds “ epigenetic effect ”? that awakens the silenced cell?  Here are the results of a Google search for the phrase “estrogen activates telomerase” ::::::

http://www.google.com/search?hl=en&q=%22estrogen+activates+telomerase%22

 

 

This page is long with many links to telomerase inhibitors, scroll down to see more.

 

 

WARNING:: Don’t inhibit telomerase if you are pregnant or may become pregnant.(UNLESS YOUR DOCTOR SPECIFIES IT)  Fetal stem cells rely

upon telomerase, it’s a good thing in a fetus. Do lookup the paper by E.V. Gostjeva et al (MIT) imaged colon cancer cells in adults and compared them

with fetal stem cells trying to make a colon.  They were identical in appearance, and were producing  very similar cell types. This adds to the evidence for unrestricted research on embryonic stem cells that are being thrown away by the hundreds of thousands per year in fertility clinics all over the world.  They have a limited shelf life even when frozen.  Waste them or use them to treat, cure, and understand the leading killers of mankind.  The church never objected to the throwing away of these cells prior to scientific advances in stem cell research that indicated the study and therapeutic use of  such cells could cure and/or treat the worst diseases afflicting humanity.  I propose that the church has a GREATER interest in keeping us in fear of an earlier death and fiery hell, than in stopping human suffering and extending the human lifespan.  I clearly see now why the founding fathers wrote of the need for a wall between church and state. There is at least one study that shows a higher rate of AML and CLL in children in Japan from quercetin and genistien.  A lot of soy and other TOPO2 poisons should probably not be in the diet of children or pregnant women.  On the other hand, they appear to work the opposite way in adults.

NEWSFLASH !!!!!  Elizabeth Blackburn (UCSF) and others have shown that telomerase activates glycolysis in cancer cells, yet another stunning finding.  Telomerase activation gives cancer cells long life, and upregulates 70 cancer genes.  See story on melanoma toward bottom of this page.  Natural or other glycolysis inhibitors could aide in the fight, with telomerase inhibitors also inhibiting glycolysis.

 Glycolysis is the process by which cancer cells become able to more quickly use sugar to facilitate their rapid growth.

Note:  This year Dr. Blackburn shared the Lasker Prize for the discovery of telomerase, and also won the Gruber Genetics Prize for same. 

 

Notes

List of compounds covered:

                                                                                                        

EGCG from green tea ……………………..direct inhibitor

Curcumin from the spice Turmeric telomerase inhbitor     

Artemisinin …..kills cells with high iron demand, like cancer cells

Genistein from Soy………inhibitor of telomerase

Melatonin……..some inhibition of telomerase

All Trans Retinoic Acid (ATRA)………inhibits telomerase

Silibinin from Milk Thistle……inhibits telomerase

Mistletoe Lectin……inhibits telomerase

Olive Oil (the Oleic Acid)……inhibits telomerase

AZT at 1/100^th the dose for HIV……inhibits telomerase NEW            

Rapamycin an immune system modulator……..inhibits telomerase

An siRNA……2 different researchers including Elizabeth Blackburns Group

A Chinese Evergreen……..inhibits telomerase

EPA/DHA…….inhibits telomerase, fish oil

Gleevek (Imatinib)……..new work, inhibits telomerase

Dichloroacetate..also called DCA, an approved drug, shown to cause cancer to regress by normalizing the function of the mitochondria, story on U of Alberta research is below.  It shuts down glycolysis in cancer cells, doesn’t affect normal cells.  Who will have the courage to give it to cancer patients against the FDA, against the drug companies too. Where is the government?  Why aren’t they funding it NOW!!!!!!!!!!!!!!!!!!

3-Bromopyruvate, CHEAP, INTRA-ARTERIAL ADMINISTRATION ONLY(NEXT TO TUMOR), STOPS CANCERS ENERGY SUPPLY, CURED ALL THE RATS, ALL OF THEM!!!! IS SIMILAR TO SODIUM DICHLOROACETATE IN ACTION, MAYBE BETTER, NEW STUDY!!

 

 

I’ve been looking at telomerase inhibitors for cancer prevention and treatment for some years now.  ALL human cancers are critically dependent on telomerase for their survival and replication. There is a list of inhibitors below with research links.  All of these substances are approved or don’t require approval from FDA.  Each link goes to legitimate medical research that shows ability to inhibit telomerase.  Nobody has ever done a multi agent trial.  Telomerase is the primary promoter of metastasis and inhibiting it downregulates 70 known or suspected cancer genes (Dr. Elizabeth Blackburn co-discoverer of telomerase).  Inhibiting telomerase also allows P53 to be expressed and or act per papers I’ve read.   Cell death happens in most cases before the telomeres become critically short, or at least when the shortest telomere becomes critically short and actual DNA is lost in the next cell division.  Surviving cells might become senescent, or at least cease to be cancer stem cells while telomerase is being inhibited.

Please give this a read as I believe it may be beneficial:

 

Telomerase is an enzyme that is overproduced in cancer cells, over 90% of cancers depend on it for rapid growth and metastasis.  A telomere is a protective cap at the end of your DNA, like the plastic protective tip at the end of your shoelace.    Most cells die after 25 to 200 cell divisions, but in cancer cells, telomerase is turned on and it grants the cancer cell what is called replicative immortality.  It does so by keeping the telomeres from getting fatally short, it makes them longer, or at least refreshes their length to keep from becoming critically short.

 In a normal cell, when the chromosomes tear apart during the process of making a new cell, the ends of the DNA are ravaged and lost.  Fortunately, the ends are made of meaningless repeats that don’t contain genetic information.  But when a normal cell divides enough times, these protective ends get so short that during a cell division, actual genetic information is lost.  The cell dies.  In a cancer cell, telomerase keeps making the telomeres longer, granting the cancer cell immortality from the wear and tear and eventual death that a normal cell would experience with many replications.  Here is a good site that shows how telomerase increases telomere length.   Demonstration graphic on how telomerase works:  http://faculty.plattsburgh.edu/donald.slish/Telomerase.html

Learn more about telomerase here:  http://www.swmed.edu/home_pages/cellbio/shay-wright/intro/facts/sw_facts.html

 

3-Bromopyruvate

THIS AMAZING, CHEAP, HAS TOXICITY, FOR INTRARTERIAL USE ONLY NEXT TO TUMOR. COMPOUND HAS BEEN STUCK IN NOWHERE FOR YEARS, PATIENTS BEING DENIED IT, BECAUSE, ITS TOO CHEAP.  IT CURED , YES CURED RATS WITH CANCER:  LINK TO 3-Bromopyruvate STUDY RESULTS

 

AZT::: yup, AZT inhibits telomerase.

 

******NEWS******* Ohio State University researchers discover that minute amounts of AZT shows synergy with cisplatin in inhibiting telomerase, dual method of action:: http://researchnews.osu.edu/archive/canazt.htm

 

RAPAMYCIN:

 

Rapamycin Inhibits Telomerase

http://mct.aacrjournals.org/cgi/content/full/2/8/789

 

ASTOUNDING NEW STUDY ON RAPAMYCIN:

LINK TO RAPAMYCIN TRIAL RESULTS STORY

 

 

EGCG FROM GREEN TEA:

 

EGCG from green tea, strongly and directly binds to telomerase.    Multiple studies ongoing worldwide,,,this might be more acceptable to the patient without the tannins, which can cause constipation. You would need 12 or more cups a day , better to use several of these compounds than to try to do it with just one. 

The most conclusive work on dietary polyphenols, EGCG, telomerase, and cancer, is here:  Thanks to Dr. Imad Naasani   BESTEGCGSTUDY.PDF

 

Transdermal EGCG increases serum levels without G.I. concerns? (Rutgers)

Transdermal EGCG with no G.I. issues??

 

In MCF7 breast cancer cells:

http://147.52.72.117/IJO/2004/volume24/number3/703.pdf

 

In digestive tract carcinomas:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16157026&query_hl=6

 

green tea for CLL ……….  http://www.dehavilland.co.uk/webhost.asp?wci=default&wcp=NationalNewsStoryPage&ItemID=15114293&ServiceID=8&filterid=10&searchid=8

 

*************

CURCUMIN FROM THE SPICE TURMERIC:

Curcumin, from the spice turmeric, directly inhibits telomerase and has been
shown to inhibit 93% of telomerase in culture, and in rats, prevented
metastatic spread of disease.  No toxicity at 8 grams per day, absorption is
low, bioprene increases absorption quite a bit but don’t exceed 15 mg of bioprene per day.    Many trials worldwide, Indian researchers are increasing absorption by incorporating into a hard candy to dissolve in the mouth throughout the day, spacing out the dosage for better absorption. 

Bioprene also increases absorption, HOWEVER, IF YOU ARE ON CHEMOTHERAPY, YOU MUST NOTIFY YOUR DOCTOR THAT YOU ARE TAKING BIOPRENE, AND THAT IT MAY INCREASE THE BLOOD LEVELS OF CHEMO IN YOUR BODY!!!  Your doctor may want to monitor the blood levels of chemo more closely during and after chemotherapy sessions, or during the course of oral medications. He may tell you to stop taking bioprene with your curcumin, listen to him!! Please don’t forget this.  Too high of a blood level of chemo can hurt you or worse, and bioprene can increase the amount of chemo in your blood!!!  Never take more than 15 mg of bioprene per day even if healthy.  You can increase abosorption without bioprene by spreading the dosage throughout the day.  More research is needed!  Curcumin thins the blood, be sure to consult with your doctor if you are already on aspirin or blood thinners, make sure your doctor closely  monitors you blood for this consideration.

 

One option would be to buy curcumin without bioprene, and spread your dosage throughout the day, also making it into a hard candy would increase absorption of curcumin without needing bioprene.  

 

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12104041&dopt=Abstract

 

Curcumin and Green tea demonstrate synergy against cancer cells http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9525275&dopt=Citation

 

halts spread of  breast cancer in mice:

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16243823&dopt=Citation

 

again, breast cancer in mice:

http://www.brightsurf.com/news/headlines/view.article.php?ArticleID=21422

 

in lung cancer cells:  http://carcin.oxfordjournals.org/cgi/content/abstract/24/7/1269

 

New Study shows that Curcumin and Quercetin destroy colon polyps::

 

Combination Treatment With Curcumin and Quercetin of

Adenomas in Familial Adenomatous Polyposis

MARCIA CRUZ–CORREA,*,‡ DANIEL A. SHOSKES,§ PATRICIA SANCHEZ,* RHONGUA ZHAO,*

LINDA M. HYLIND,‡ STEVEN D. WEXNER,_ and FRANCIS M. GIARDIELLO‡,¶,#

Departments of *Medicine, §Kidney Transplant, and _Surgery, Cleveland Clinic, Weston, Florida; ‡Department of Medicine, ¶Oncology Center,

and #Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Background & Aims: Familial adenomatous polyposis

(FAP) is an autosomal-dominant disorder characterized by

the development of hundreds of colorectal adenomas and

eventual colorectal cancer. Regression of adenomas in this

syndrome occurs with the administration of nonsteroidal

anti-inflammatory drugs and cyclooxygenase-2 inhibitors,

but these compounds can have considerable side effects.

We evaluated the efficacy of the combination of dietderived

nonprescription supplements curcumin and quercetin

to regress adenomas in patients with FAP. Methods:

Five FAP patients with prior colectomy (4 with retained

rectum and 1 with an ileal anal pouch) received curcumin

480 mg and quercetin 20 mg orally 3 times a day. The

number and size of polyps were assessed at baseline and

after therapy. The Wilcoxon signed-rank test was used to

determine differences in the number and size of polyps.

Treatment side effects and medication compliance also

were evaluated. Results: All 5 patients had a decreased

polyp number and size from baseline after a mean of 6

months of treatment with curcumin and quercetin. The

mean percent decrease in the number and size of polyps

from baseline was 60.4% (P < .05) and 50.9% (P < .05),

respectively. Minimal adverse side effects and no laboratory

abnormalities were noted. Conclusions: The combination

of curcumin and quercetin appears to reduce the

number and size of ileal and rectal adenomas in patients

with FAP without appreciable toxicity. Randomized controlled

trials are needed to validate these findings.

Familial adenomatous polyposis (FAP) is an autosomaldominant

form of hereditary colorectal cancer caused by

germline mutation of the Adenomatous Polyposis Coli gene

located on chromosome 5q21.1 FAP is characterized by the

development of hundreds of colorectal adenomas in adolescence.

2 Nearly all affected individuals will develop colorectal

cancer by the 6th decade of life if prophylactic colectomy

is not performed.2

Regression of adenomatous polyps in FAP was first noted

in a case series by Waddell et al3 in 1983. These investigators

described decrease in adenomas with sulindac, a

nonsteroidal anti-inflammatory drug. Subsequently, this

observation was confirmed by randomized controlled studies

with sulindac4 and with celecoxib, a selective inhibitor

of cyclooxygenase 2.5 Although effective in adenoma regression,

cyclooxygenase 1 and 2 inhibitors possess side effects

that limit the use of these drugs as true chemopreventive

agents.

Curcumin is the major yellow pigment extracted from

turmeric, the powdered root of the herb Curcuma longa.

Curcumin long has been used as a spice in Asia and is

considered a safe food additive.6 In murine models, this

agent shows preventive activity in the initiation and progression

stages of colorectal carcinogenesis.6 Also, several

reports using this compound in patients with colorectal

cancer, and high risk for premalignant conditions, have

stimulated interest in curcumin as a chemopreventive

agent.7,8 In patients with advanced colorectal malignancy

refractory to standard chemotherapy, 5 of 15 individuals

given daily oral curcumin had stable disease at 4 months of

follow-up evaluation.8 Also, histologic improvement of precancerous

lesions in patients taking this agent was noted in

1 of 2 patients with resected bladder cancer, 2 of 7 with oral

leukoplakia, 1 of 6 with gastric intestinal metaplasia, and 2

of 6 with Bowen’s disease.

Quercetin belongs to a group of plant-derived polyphenolic

substances known as flavonoids, recognized for their

antioxidant properties. Rich sources of quercetin include

onions, red wine, green tea, and St. John’s wort. Quercetin

appears to inhibit cell growth of human colon cancer cell

lines9 and colorectal neoplasia development in murine models.

10,11

Because cell culture and animal evidence of chemopreventive

activity exists against colorectal neoplasia for both

curcumin and quercetin, each with potentially different

mechanisms of action, these compounds were used together.

Therefore, we evaluated the effectiveness and toxicity of the

Abbreviation used in this paper: FAP, familial adenomatous polyposis

© 2006 by the American Gastroenterological Association Institute

1542-3565/06/$32.00

doi:10.1016/j.cgh.2006.03.020

Quercetin as a single agent might well have to much plant estrogen which promotes cancer growth. But it appears to be working quite well in the above small trial when used with curcumin.

*******************************************************************

GLEEVEK::

 

Br J Cancer. 2005 May 23;92(10):1881-91.

Related Articles, Links

 
Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits proliferation in telomerase-expressing cell lines.

Uziel O, Fenig E, Nordenberg J, Beery E, Reshef H, Sandbank J, Birenbaum M, Bakhanashvili M, Yerushalmi R, Luria D, Lahav M.

Felsenstein Medical Research Center, Beilinson Campus, Sackler School of Medicine, Tel Aviv University, Petah-Tikva, Israel.

Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits phosphorylation of downstream proteins involved in BCR-ABL signal transduction. It has proved beneficial in treating patients with chronic myeloid leukaemia (CML). In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. In the light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on telomerase activity (TA) and regulation in various malignant cell lines. Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK-MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No apoptosis was observed. Inhibition of TA was caused mainly by post-translational modifications: dephosphorylation of AKT and, to a smaller extent, by early downregulation of hTERT (the catalytic subunit of the enzyme) transcription. Other steps of telomerase regulation were not affected by IM. This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation.

GENISTEIN:

Genistein, from the soy plant has been shown to inhibit telomerase. Consider that plant estrogens could promote cancer.  Inhibition might need to be complete enough to counteract the plant estrogens.  Excess estrogen activates telomerase in cells.  http://147.52.72.117/IJMM/2003/volume12/number1/29.pdf

 

MELATONIN:

Melatonin, some inhibition of telomerase.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12932205&dopt=Abstract

 

All Trans Retinoic Acid:

All Trans Retinoic Acid and similar compounds also inhibit telomerase, and
activate the suppressed immune cells around tumors per one oncologist drug developer.  I have no link for his claim.  Still inhibits telomerase.

http://www.ingentaconnect.com/content/bsc/bjd/2005/00000152/00000003/art00006

 

SILIBININ:

 

Silibinin from Milk Thistle inhibits telomerase 

http://www.jurology.com/article/PIIS0022534705622847/abstract

 

 

MISTLETOE LECTIN:

 

Mistletoe Lectin inhibits telomerase:::::

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=14969342&dopt=Abstract

*************************************************************

 

Telomerase Inhibition by siRNA Link

 

 

 

 IF YOU HAVE INFORMATION on Costunolide, PLEASE EMAIL IT TO ME. Prime3end@yahoo.com

 

Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells.

Choi SH, Im E, Kang HK, Lee JH, Kwak HS, Bae YT, Park HJ, Kim ND.

Department of Pharmacy, College of Pharmacy, and Research Institute for Drug Development, Pusan National University, Busan 609-735, South Korea.

Costunolide, a natural sesquiterpene compound, has been known having cytotoxic and chemopreventive effects on various human cancer cells. In the present study, we examined the effects of costunolide on telomerase activity and on the components of telomerase in MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) cells. We found that costunolide inhibited the growth and telomerase activity of MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner. The expression of hTERT mRNA was also inhibited but hTR mRNA was not. In addition, the bindings of transcription factors in hTERT promoters were significantly decreased in both cells by the treatment of costunolide. These results suggest that costunolide inhibited the growth of both MCF-7 and MDA-MB-231 cells and this effect was mediated at least in part by a significant reduction in telomerase activity.

PMID: 16112418 [PubMed - indexed for MEDLINE

 

 

*************************************

 

 

ARTEMISININ:

 

Artemisinin should be included in the trial.

 

If compatible, a good trial could include artemisinin, an extract of the wormwood bush, which the U of Washington is calling a magic bullet against cancer.  They are working to attach it to transferrin outside the body, increasing its selectivity from 100 to 1.  cancer cells to healthy cells killed, to 32,000 to one bad cells to good cells killed.   It works by getting into cells with a high iron demand, by attaching to transferrin, entering the cell, and causing a free radical buildup which results in cell death.   Dosage should be over the course of the day, without overdosing.   Reports of liver damage when using megadoses, otherwise safe compared to many chemo agents.

 

http://www.medicalnewstoday.com/medicalnews.php?newsid=19788

 

VITAMIN K3, ANOTHER APPROACH:

Another therapy that is not a telomerase inhibitor, at least directly, is Vitamin C and Vitamin K3  (Menadione), in a 100 to one dosage kills cancer cells. Vitamin K is found in green leafy vegetables or in supplement form.  K2 is formed from K by bacterial action in the gut. K3 can results in a new kind of cancer cell death, different from necrosis and apoptosis.  They call the new kind of cell death, autoschizis.  Here are a couple of links to research done with NCI funds.   K1 is converted to K2 in the gut.  K3 is manmade. 

 In Bladder Cancer Cells:::

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14698046&dopt=Abstract

 

In Prostate Cancer Patients

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12665684&dopt=Abstract

 In Ovarian cancer cells::::  http://www.scanning.org/scanabstracts/SCANNING03/25137.html

 

Large paper on autoschizis::

  http://www.md.ucl.ac.be/pharma/Full-texts-FARM/Jamison-2002-1.pdf

 

*******Risks and benefits of Vitamin K1 and K3:::::::: making anti clotting meds less effective, danger of anemia, etc., must read before taking K.

http://www.umm.edu/altmed/ConsSupplements/VitaminKcs.html

 

List of works on various Vitamin K forms re: cancers:::

 

Nouso K, Uematsu S, Shiraga K, et al.

Regression of hepatocellular carcinoma during vitamin K administration.  World J Gastroenterol. 2005 Nov 14;11(42):6722-4.

 

Yoshiji H, Kuriyama S, Noguchi R, et al.

Amerlioration of carcinogenicses and tumor growth in the rat liver by combination of Vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncol Rep. 2006 Jan;15(1):155-9

 

Kuriyama S, Hitomi M, Yoshiiji H, et al.  Vitamins K2, K3 and K5 exert in vivo Antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules. Int J Oncol. 2005 Aug;27(2):505-11.

 

Enokimura N, Shiraki K, Kawakita T, et al.

Vitamin K analog (compound 5) induces apoptosis in human hepatocellular carcinoma independent of the capase pathway.  Anticancer Drugs. 2005 Sept;16:(8):837-44.

 

Hitomi M, Yokoyama F, Kita Y, et al.

Antitumore effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo.  Int J Oncol. 2005 Mar;26(3):713-20

 

Lin C, Kang J, Zheng R.

Vitamin K3 triggers human leukemia cell death through hydrogen peroxide generation and histone hyperacetylation. Pharmazie. 2005 Oct;60(10):765-71

 

Yokoyama T, Miyazawa K, Yoshida T, Ohyashiki K

 Combination of vitamin K2 plus imatinib mesylate enhances induction of apoptosis in small cell lung cancer cell lines. Int J Oncol. 2005 Jan;26(1):33-40

 

Gad A, Tanaka E, Matsumoto A, et al. 

Assessment of KL-6 as a tumor marker in patients with hepatoellular carcinoma.  World J Gastroenterol. 2005 Nov 14;11(42):6607-12

 

Iso Y, Sawada T, Shimoda M, et al.

Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis. Hepatogastroenterology. 2005 Nov;52 (66):1930-2

 

Vitamin K3 and C
PMID: 15630164 [PubMed - indexed for MEDLINE]

 

The citations above are from Life Extension Foundation April 2006 magazine, haven’t read the citations yet.  Vitamin K2 is made in the gut by friendly bacteria.

Vitamin K and K3 are available it seems, from www.lef.org .  I would absolutely rely on a doctor who is familiar with K and knows about the

 

BACK TO TELOMERASE

 

By the way, if you do a search on Google, using the phrase, “cisplatin inhibits telomerase” you will get hits.  I wonder how many

Other toxic chemotherapies act directly or indirectly to inhibit telomerase.  Problem is, you cant take them long enough to suppress the cancer in many cases.  The long term battle in the body against cancer must be fought with compounds that do not poison healthy cells. The same goes for prevention.  The toxics are okay to use for short term, but I would use the natural extracts and foods also, for they are the long term cure.

Prime3end

You probably already know all of this but here it is:

 

 Telomerase imaging markers and detection kits are now available and are
 being used to predict (in studies) the likelihood of patient mortality and metastasis.

 
 Telomerase allows cancer cells to overcome the Hayflick limit, to divide a
 thousand times or more without dying or going into replicative senescence.
 Normal cells divide about 25 to 200 times before they die.  Telomerase is
 suspected of causing very rapid growth, and the level of telomerase is
 directly linked to patient survival and increased likelihood of metastasis.

 

 Dr. Blackburn claims that new research by her group shows that when

 telomerase is turned on in a cancer cell (cancer stem cell) , 70 genes that

 are known or suspected in cancers inception and growth are up regulated. 

 Conversely, when telomerase is inhibited, those same 70 genes are down regulated.

 The P53 gene is allowed to kill the cell, some research says. Dr. Blackburn claims that there is

 far more to telomerase  than simply making telomeres longer.  Down regulating 70 bad genes

is certainly beneficial and should add to the forces that kill cancer cells.
 
 Telomerase works by extending the telomere tails at the end of chromosomes.
 This is how it overcomes the Hayflick limit.  The tails usually
 get incrementally ripped off when a cell divides, but in cancer cells,
 telomerase is constantly making the tails longer by adding tail segments, which
 as you know are meaningless repeats of TTAGGG.  They are eroded with each
 cell division.   Telomerase in normal cells is limited to the nucleus.  In
 cancer cells it is throughout the cytoplasm and is externally expressed on
 the surface of the cell so a vaccine is a good idea.  Anyway, the good
 part is that even for the telomerase inhibitor drug (GRN163L), which does
 penetrate the nucleus and directly bind to the telomerase,,, reasonably short
 periods of inhibition are not expected to result in toxicity for normal
 cells(Dr. Jerry Shay). 

The telomerase in a normal cell is only transiently expressed, and otherwise

kept in a tiny sack and isn't thought to be bound by the telomerase inhibitor GRN163L, except during

transient expressions in germ and other cells.   

Of course the food-based inhibitors listed here have thousands of years of toxicity testing in humans. 

Because they are concentrates however, a multi- agent trial is needed on:
 

                           
 1.  an aggressive cancer cell line in culture
 2.  same in animal model
 3.  in humans.

Not necessarily in that order. 

 

RESEARCH GOALS:  HIGH OR COMPLETE DEGREE OF INHIBITION OF TELOMERASE.

               MEASUREMENT OF SELECTIVE CANCER CELL DEATH.

               ESTABLISH DOSAGE IN MULTI-AGENT TRIALS FOR PREVENTION AND CONTROL OF CANCER.

               MEASURE EXTRA CANCER CELL DEATH WITH T INHIBITORS AND ARTEMISININ.

 

  If synergy is attainable in regular chemotherapy, I see no reason why we couldn’t expect to see synergy in extracts of natural compounds that target various parts of the telomerase biology.  If some of the agents conflict with one another, that would be apparent too.  Establishing effective dosages would be of tremendous importance.  The one study I found from 1998 combined green tea and curcumin, and they were able to make the doses of both much smaller to achieve the same impact on the cancer cells.  This represents synergy, using only two agents, imagine what 4 agents might do, or five, or six.
 
**********************************************************************************************************

DRUG COMPANY WORKING ON TWO TELOMERASE THERAPIES:

 

 

Geron Corp, has a telomerase inhibitor (GRN163L (non toxic till 8 x MTD in mice through monkeys) in trials at 2 N.Y. hospitals for CLL, and a telomerase targeting vaccine in trials at Duke for prostate cancer (TVAX no toxicity observed) as telomerase expresses into the cytoplasm and onto the surface of cancer cells. 

 

Geron has seen synergy with various chemotherapies in animal models using GRN163L, including complete responses, so synergy could apply to natural compounds as well.  Geron tried to boost the vaccine, TVAX’s response, with Ontak, but simply giving another booster shot did a better job of increasing T cells.    Telomerase represents a pan cancer approach, expected to work on all cancers without toxicity.   Geron has presented at several AACR’s and other conferences.  Merck just bought into their vaccine target.  It created the strongest immune system reaction against cancer that has ever been seen in a cancer vaccine, including both CD4’s and 8’s (Dr. Yohannes Vieweg, Duke U).  TVAX could well be a miracle in cancer treatment.

The current CLL trials at 3 N.Y. hospitals ,  should cause a convincing inhibition of telomerase and sick people getting well.  The vaccine, TVAX eliminated circulating cancer cells from the blood with only 6 weekly shots, with PSA going statistical flat line,, from previously doubling every 2.9 months. 

I mentioned Geron to show that the concept is legitimate and help me make the point that targeting telomerase has some very good likelihood of saving and prolonging life.   www.geron.com  I do own some of their stock, a minor shareholder.  Here is a link to their presentation at the S.G. Cowen Conference, amazing stuff in both cancer and stem cells  SGCOWEN

 

In the meantime, the compounds listed above may provide some help, but they are non-patentable, so nobody has done a multi-agent trial using them.  The treatment would have to be continued beyond the chemo program to keep down metastasis and keep cancer stem cells from left over from re-emerging as a problem.  Some of the agents, like curcumin, might have to be discontinued if there is a conflict with a particular chemo agent, or a blood thinner based on warfarin  .  A goal of the trial would be to note if apoptosis occurs before the cancer cell should die from lack of telomere maintenance.  Progress could be monitored by testing for cancer cells in the blood, and measuring their telomeres.  Measuring the 70 genes Dr. Blackburn speaks of might be a bit on the expensive side, I don’t know.  Reduction in solid tumor mass could be measured.  PSA is an easy and inexpensive measure, as is measuring circulating tumor cells, so a prostate cancer trial would be a good choice.

 

Late breaking, two studies, one by Dr. Blackburn and another study as well have determined that stress may indeed be a cause of cancer.  Stress, shortens telomeres, pushing cells into telomeric crisis, making them more likely to turn cancerous. 

 

And get yourself a pet of some kind.  Enjoy life, but if you have to wear a backpack to keep your supplements, do it.  Have fun, laugh, play.  To quote the Blues Brothers, “Everybody, Needs Somebody, To Love” it’s a great, great tune.

 

 

Feel free to email. Feel free to pass this on to Researchers and Doctors who might be interested.

 

 

My feelings on clinical trials, interrogate them, find out how it went in the phase 1 and what will be better or different in the phase 2 or 3.  Consider a multi agent trial.  Multi agent therapies for cancer are showing much better results than most mono therapy treatments.  Take more than one thing at a time.  If your oncologist says not to take supplements, ask him to show you the research that shows that the supplement will interfere with the therapy.  If he doesn’t have the research, do an internet search and look for yourself.  Ask your doctor why, if you are given the different chemotherapies “one at a time”, if they are compatible, you are better off getting some new targeted therapies simultaneously.  Don’t wait till you are so sick you can’t care for yourself or get on an airplane.  Act fast, get more than one therapy at a time.  I’ve never been a patient, but I’ve known a few.  This advice is based on their successes and their unfortunate choices.   Act fast and don’t accept delays.  Get help with meditation or prayer, stress is no good for you.  Cut out sugar entirely, cancer loves glucose.   Chemo-preventive foods like green tea, curcumin, ATRA, Genistein and Silibinin should be part of the diet of people with risk factors for cancer.  Risk factors include many things, but most all of us have them now.  Our food is full of pesticide, plastics are in our air, food, homes, smoking is a big one, coal emissions from power plants, truck and car exhaust, wood burning, asbestos, solvents, etc.   There are a ton of risk factors that justify prevention, these are but a few.  There are sweeteners that don’t offer cancer the boost it gets from sugar.   

 

 

VITAMIN D IS CRITICAL TO CANCER PREVENTION, AND PREVENTING MANY DISEASES:

 

Forbes

WEDNESDAY, Dec. 28 (HealthDay News) -- Forget the fiber. You may be able to fend off colon, breast or ovarian cancer by simply getting enough vitamin D, a new analysis of previous research suggests.

But if you're overweight, black, older or live in the Northeast, there's a good chance you're not getting enough vitamin D in your diet, said study co-author Cedric F. Garland, a professor of medicine at the University of California, San Diego.

And that could put you at risk, he added.

Garland and his colleagues examined 63 previous studies that looked at possible links between several types of cancer and vitamin D deficiency. Their study appears in the current online edition of the American Journal of Public Health, and will appear in the February 2006 print edition.

According to the researchers, the studies -- from 1966 to 2004 -- suggest that vitamin D can reduce the risk of colon, breast and ovarian cancers, among others, by as much as 50 percent.

However, the debate over the value of vitamin D isn't over, said Lona Sandon, a spokeswoman for the American Dietetic Association.

The new research suggests a link between too little vitamin D and cancer, but doesn't confirm it, she said.

Why might vitamin D have a protective effect in the first place?

"Vitamin D's main role is to keep the balance of calcium and phosphorous in the blood, which helps keep bones strong," Sandon said. "However, a lesser-known role is how it regulates cell growth and determines what a cell becomes. A vitamin D deficiency may allow cells to become cancerous rather than becoming healthy cells."

The study authors found that several groups of people had low levels of vitamin D. Residents of the Northeast made up one group, perhaps because they miss out on vitamin D that's absorbed during exposure to the sun, Garland said. The obese had low levels, too, perhaps because they have trouble metabolizing vitamin D through their fatty tissues.

Other groups with low vitamin D levels include blacks -- they're five times more likely to be deficient than whites -- and the elderly, the researchers found.

"As we age, we lose the ability to convert vitamin D into its usable form, so elderly people are at greater risk," Sandon said.

And the increased skin pigmentation of blacks reduces their ability to synthesize vitamin D, the researchers said.

So what to do? The experts are divided on that answer.

Garland urges everyone to consume 1,000 International Units (IUs) a day of the active form of Vitamin D -- also known by its human form, Vitamin D3 -- which comes in yogurt, cheese, orange juice, fatty fish and milk.

By contrast, Sandon said adults aged 19 to 50 should get 200 IUs a day, equivalent to two glasses of fortified milk. People aged 50 to 70 should get 400 IUs, she said, while those 71 and older should get 700. But she acknowledged that "it is difficult to get this much vitamin D from food alone.

She recommends that people take brief walks during lunch to get exposure to vitamin D from the sun.

But what about seniors or those who refuse to change their diets or their habits? "A supplement of the active form of vitamin D would be the next option for those who just will not make even small changes, and likely to be a must in people over 50," Sandon said.

More information

To learn more about vitamin D, visit the National Institutes of Health.

********************************************************************o

BEST COLLECTION OF CURCUMIN INFORMATION IN AN ARTICLE !!!!!:::

http://www.latimes.com/features/health/la-he-turmeric6feb06,0,2713647.story?coll=la-home-health

From the Los Angeles Times

Out of the spice box, into the lab

Turmeric, an Indian staple, has long had medicinal uses. Now the West is taking notice.

By Hilary E. MacGregor
Times Staff Writer

February 6, 2006

The goddess of turmeric brings color in life

It is the ornament of married woman

And any woman who puts turmeric in her purse,

Her purse will never be empty



An old Indian folk song praises turmeric, the golden spice from the East, for its power to bring beauty, good health and good luck to those who use and carry it.

But in Indian medical lore, the pungent, woody-tasting powder is more precious still.

Modern medicine is starting to sit up and pay attention. Scientists are taking a closer look at this Asian wonder spice, teasing out active ingredients and testing its age-old cultural and medicinal uses in 21st century laboratories. The National Institutes of Health has funded at least eight studies investigating turmeric. The spice and a chemical it contains — curcumin — are being probed for their potential to prevent and treat a broad range of diseases: cancer, cystic fibrosis, Alzheimer's and arthritis.

The uses of turmeric, some described in ancient Indian medical texts, are indeed numerous. Indians put the spice on their Band-Aids as a disinfectant (Johnson & Johnson even makes turmeric Band-Aids for the Indian market) and sprinkle the powder on wounds to help them heal faster. People gargle with turmeric when they have laryngitis and rub it on the skin to cure cuts and psoriasis. They swallow it to treat bronchitis and chronic diseases such as diabetes.

Indian brides and grooms apply turmeric and milk to their skin before marriage, to look more beautiful.

And as anyone who has ever prepared a curry knows, turmeric is an essential cooking ingredient, used to flavor, color and preserve.

"You will find no house in India without turmeric. It is our daily spice, our daily life," said Vasant Lad, an Indian-trained practitioner who is chairman of the Ayurvedic Institute in Albuquerque.

Most of the studies so far have been on animals. But a growing number of mainstream researchers see turmeric and curcumin as possible aids in preventing and fighting disease in humans.



A powerful antioxidant

A relative of ginger, turmeric is a powder ground from the root of a large-leafed Asian plant. Researchers believe the curcumin it contains fights disease partly by shutting down a powerful protein that promotes an abnormal inflammatory response in the body. The spice also has potent antioxidant properties (and may even lower cholesterol).

Curcumin is medically promising because inflammation and oxidative damage are contributors to so many diseases, such as Alzheimer's, Parkinson's, arthritis and various cancers, said Gregory Cole, a professor of medicine and neurology at the David Geffen School of Medicine at UCLA who has conducted numerous studies on the spice.

And, he said, there's a need for better, safer drugs to treat these conditions.

"If it is not curcumin, we need something a lot like curcumin — something cheap and safe with a long history of use, and no side effects," Cole said.

Some clues as to turmeric's clout come from observing patterns of illness among people.

For example, scientists have long noted that Indians have much lower rates of certain cancers than their American counterparts. That led researchers to wonder whether diet plays a role — and, more specifically, the turmeric.

Mouse studies at the University of Texas M.D. Anderson Cancer Center have shown that the spice blocks growth of a skin cancer, melanoma, and inhibits the spread of breast cancer into the lungs.

One 2004 study with mice showed that adding curcumin to Taxol, or paclitaxel, a commonly prescribed chemotherapy for breast cancer, enhances the drug's effect, making the therapy less toxic and just as powerful.

Such studies have triggered two human clinical trials. One is testing the ability of curcumin tablets to help patients with pancreatic cancer, which kills 30,000 people a year. (Only 50% of patients with pancreatic cancer will live longer than six months.) Fifty patients will receive eight grams of curcumin daily, and researchers will evaluate their six-month survival rate.

A second, more preliminary clinical trial is examining a safe and active dose of curcumin in patients with multiple myeloma, a rare cancer of the bone marrow. If the trials pan out, curcumin may have an added advantage: Unlike most cancer therapies, it appears to have no toxic side effects.

The active component of turmeric turns out to be the best blocker yet of a natural chemical called TNF, or tumor necrosis factor, which contributes to cancers and arthritis and is resistant to chemotherapy drugs, said Bharat B. Aggarwal, professor of cancer medicine in the Department of Experimental Therapeutics at the University of Texas M.D. Anderson Cancer Center, who has studied the spice for a decade.

"You don't even need tens of thousands of dollars of TNF blockers," Aggarwal said. "Turmeric does exactly the same thing."

Turmeric is also being studied for its ability to help treat Alzheimer's disease. The prevalence of Alzheimer's among adults in India aged 70 to 79 is among the world's lowest. It is 4.4 times less than the rate in the United States.

A 2004 study with mice published in the Journal of Biological Chemistry suggested that curcumin might be of help for Alzheimer's patients.

The study, conducted by UCLA and Veterans Affairs scientists, showed that a rodent chow laced with curcumin slowed the accumulation in mouse brains of protein fragments known as beta amyloids. They are considered key to the development of Alzheimer's.

Curcumin did this more powerfully than many other drugs being tested as Alzheimer's treatments, said Cole, the study's principal investigator.

Scientists at UCLA are now conducting the first-ever clinical trials of curcumin on humans with Alzheimer's. In this pilot study of 36 patients, researchers will examine how well people tolerate high doses of curcumin and how well it is absorbed into the body. During the 48-week study, researchers will also test whether the spice affects chemicals in the blood and cerebrospinal fluid that indicate Alzheimer's disease activity, said Dr. John Ringman, assistant professor of neurology at the UCLA Alzheimer's Disease Center.

Meanwhile, researchers at the University of Washington and Johns Hopkins are conducting early human trials looking at whether curcumin can be used as a potential therapy for cystic fibrosis. This is the most common fatal genetic disease in whites, creating a salt imbalance that leads to thick, sticky mucus in the lungs and early death.

A study published in 2004 in the journal Science reported that curcumin corrected the genetic defect in mice with a cystic fibrosis-like condition. The human trial will give nine cystic fibrosis patients curcumin for two weeks to see if large doses of the spice are safe and well tolerated and if they efficiently enter the blood.

The researchers will also look at how much chloride they find in the sweat of the cystic fibrosis patients taking curcumin: A reduction would tell them that the chemical was helping to correct the disease.

If curcumin is useful, a slightly altered curcumin may be even more so. With that in mind, a team at Emory University has patented a synthetic variation of curcumin that stays in the bloodstream longer than the real thing. A North Carolina biotech company, Curry Pharmaceuticals, has licensed that compound: Scientists there are developing drugs for cancer, inflammatory diseases and possibly psoriasis, says company chief executive Dennis Schafer.

While intriguing, experts caution that all these results are still preliminary. No one yet knows if turmeric will end up another herbal fad or make a lasting contribution to Western medicine.

Dr. David Knopman, an Alzheimer's researcher at the Mayo Clinic in Rochester Minn., said many ideas in his field come from animal work, and the potential of turmeric seems biologically plausible. But until these compounds are tested in people there is no way to know their full potential, he added.

"We know turmeric has been used for hundreds of years, if not thousands, in China and Indonesia and is very valuable to these people," added James Adams, a professor at the USC School of Pharmacy. "It is clearly a very useful plant that we need to know more about. Basically we are waiting for more studies."

But some are not waiting for more science. In the health food stores, turmeric supplements are selling like hot samosas. And some doctors have brought the spice into their clinics.

Dr. Madalene Heng, a Ventura County-based dermatologist, is already marketing a curcumin-based product. She has developed Psoria-Gold, a topical ointment that she says will treat psoriasis, acne and rosacea. A 6-ounce vial costs $89.95, but Heng says the cream is so potent even in small doses that it will last six months. One treatment for psoriasis will make the skin disease disappear, Heng claims.

And, she says, it will even smooth away wrinkles.

 

 

 

**********************************************************************

Metastasis and Scout Cells:

 

Secret of cancer’s spread
by: sscottsups
Long-Term Sentiment: Strong Buy 12/26/05 12:15 am
Msg: 294004 of 294022
Metastasis isn’t from tumor pieces breaking off; instead, tiny ‘scout’ cells and proteins seek fertile sites, study finds

Why cancers possess a wanderlust, spreading from one site to another, has been one of the most confounding questions in medicine, and now New York scientists have unmasked the role of infinitesimal "scouts," cells and proteins that coalesce to seek out fertile ground for a tumor's spread.

The finding turns a corner in the history of cancer research, experts say, demonstrating that a series of ominous events lead these scouts -- dispatched by the tumor itself -- to find fresh ground and lay a foundation for a new cancer. In some cases, the foundation can be laid years before seeds of the new tumor arrive.

"For many years it was thought that cancer was happening in one way: A tumor developed, a piece of it broke off and traveled through the bloodstream and planted somewhere else. Even though people forever and a day thought that this was the case, we now realize that there is more to it than that," said Dr. Rosandra Reich Kaplan, a pediatric oncologist who holds joint appointments with Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center in Manhattan.

She said the finding opens a new window on understanding cancer, and could soon lead to new diagnostic targets and more treatments. "We're hoping to conduct a very large trial with patients in about a year or two," Kaplan said.

Dr. Goarav Gupta, a cancer researcher at Memorial Sloan-Kettering, who was not involved in the research, broached a similar possibility earlier this year when he described how his studies eavesdropped on the "crosstalk" between the initial tumor and the spot to which it spread. Kaplan and her colleagues delineated the multiple steps in this network.

"This is the first time that anyone has described the events that occur before you get metastasis," said Dr. David Lyden, co-director of the Children's Blood Foundation Laboratory at New York-Presbyterian Hospital/Weill Cornell Medical Center in Manhattan.

"Metastasis is the area of medicine in which we have not been very successful," said Lyden, who with Kaplan and Dr. Shahin Rafii, a professor of genetic medicine at Weill Cornell Medical College, published a report on their studies in a recent issue of the journal Nature. "Once the cancer metastasizes, there is not much that we can do."

As lead investigator of the research project, Lyden emphasized yesterday that it is rarely the initial tumor that proves deadly, but rather its lethal offshoots -- the metastatic disease.

In addition, snippets of the tumor itself don't break away to spur new cancers elsewhere; instead, tiny protein growth factors from the tumor stimulate and coalesce with bone marrow stem cells. These aggregates mobilize in the bloodstream to seek fertile ground. Once at the new site, the clusters prepare the tissue for a new cancer. Because the clusters can be identified in the blood, it is possible to interfere with their activity, Lyden said.

Kaplan said tumors seek fertile ground in specific sites. Breast cancers usually spread first to adjacent lymph nodes before going elsewhere. Gastrointestinal cancers spread first to the liver. It is therefore possible to detect clusters en route to their sites as well as those that already have laid a foundation but have yet to receive a new tumor.

"We identified patients with breast cancer who have ... [the growth factors] forming in the actual primary tumor, and have even more in the adjacent lymph nodes," Kaplan said. "This is a new way of thinking about cancer and definitely a paradigm shift in how metastasis occurs."

***************************

EPA and DHA , FISH OIL:

 

 

EPA and DHA inhibit telomerase, eat fish oil, etc.

 

PMID: 15870711 [PubMed - indexed for MEDLINE]

Public release date: 10-Jul-2006
[ | E-mail Article ]

Contact: Nancy Chan
nchan@pubaff.ucsf.edu
415-885-7277
University of California - San Francisco

UCSF study shows suppression of telomerase enzyme can inhibit spread of melanoma

UCSF researchers have found that the spread of melanoma can be inhibited by suppressing telomerase, the enzyme active in cancer cell growth.

Findings reported in the July 5 Proceedings of the National Academy of Sciences show for the first time a link between telomerase and glycolysis, the metabolic pathway used to consume glucose and produce lactic acid within the body.

"Identification of this relationship has great significance in understanding the role of telomerase and glycolysis together," said Mohammed Kashani-Sabet, MD, UCSF associate professor of dermatology and lead author of the study. "These results support the rationale for blocking telomerase in cancer therapy."

In the study, researchers found through gene expression profiling in mice that eight genes involved in glucose metabolism were lowered when telomerase was suppressed in skin cancer cells. The result was a return of pigmentation, frequently absent in advanced melanomas, and of cancer cells losing their metastatic potential.

"We introduced a telomerase inhibitor into melanoma cells and found that by suppressing telomerase, melanoma cells start to change," said Kashani-Sabet. "In some melanomas, pigmentation is lost. We found that when we are able to shut down telomerase, the cells regain functions previously lost, such as the ability to make pigment."

"As the cells become too acidic from the buildup of lactic acid, the proteins that control pigment production can be turned off, suggesting that glucose metabolism plays a key role when combined with telomerase in metastasis."

The ribonucleoprotein enzyme, telomerase, was discovered by study co-investigator Elizabeth Blackburn, PhD, Morris Herzstein Professor of Biology and Physiology in the UCSF Department of Biochemistry and Biophysics. Telomerase is well-documented as an instigator of cancer cell proliferation, but according to the researchers, its impact on tumor invasion and metastasis has been less studied.

In normal cells, the telomere is a strand of DNA that exists at the end of each chromosome and shortens with each cell division until it stops dividing, signaling the end of the cell life. Telomerase is activated in abnormal cells such as cancer cells, restoring the telomeres, and allowing them to divide and grow. As such, telomerase has been found to be over-expressed in 90 percent of human cancers.

Researchers were also able to ascertain for the first time how the use of a glucose compound injected into the body for positron emission topography (PET) scans was effective in diagnosing cancer. Use of the PET scan is now a regularly used method to diagnose and effectively pinpoint the source of cancer in an individual by utilizing radiation emitted from a patient to develop images. A radioactive substance is made up of glucose, a naturally occurring sugar, combined with a radioactive fluoride atom. The metabolism of glucose can be seen through gamma radiation produced from the positron-emitting fluoride that is detected by the PET scanner.

"Now for the first time, we understand why melanomas have high glucose uptake," Kashani-Sabet said. "We knew that use of PET scanning was effective in detecting melanoma metastasis, but we really didn't know why. Through this study, we found that telomerase is responsible for activation of glycolysis in melanoma cells."

Connecting telomerase and glucose metabolism together has implications for further therapeutic study. "By manipulating telomerase in cancer cells and suppressing glycolysis, it is possible to inhibit both melanoma invasion and metastasis."

###

The study was funded by the Zackheim Endowment Fund, American Cancer Society, Damon Runyon Postdoctoral Fellowship program, Steven and Michelle Kirsch Foundation and the U.S. Public Health Service grants.

Co-authors from UCSF were Sepideh Bagheri and Mehdi Nosrati, Comprehensive Cancer Center and Department of Dermatology; Shang Li and Elizabeth H. Blackburn, Department of Biochemistry and Biophysics; Sima Torabian, Javier Rangel, and Dan H. Moore, Department of Epidemiology and Biostatistics; Scot Federman, Rebecca R. LaPosa, Frederick L. Baehner, Richard W. Sagebiel, James E. Cleaver, and Christopher Haqq, Department of Medicine and Comprehensive Cancer Center. Co-authors from California Pacific Medical Research Institute, San Francisco, were Sylvia Fong and Robert J. Debs.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.

 

DCA is Huge NEWS!! Small molecule offers big hope against cancer.  See the news report on Canada T.V.:: http://www.depmed.ualberta.ca/dca/

 

Here is the story, but the video linked to above is amazing, click the link above to go to U of Alberta’s website to see it.

The study  paper is available there too, it was published in Cancer Cell .

 

DCA story:::::::::::::::::::::

DCA is an odourless, colourless, inexpensive, relatively non-toxic, small molecule. And researchers at the University of Alberta believe it may soon be used as an effective treatment for many forms of cancer.

Dr. Evangelos Michelakis, a professor at the U of A Department of Medicine, has shown that dichloroacetate (DCA) causes regression in several cancers, including lung, breast, and brain tumors.

Michelakis and his colleagues, including post-doctoral fellow Dr. Sebastian Bonnet, have published the results of their research in the journal Cancer Cell.

Scientists and doctors have used DCA for decades to treat children with inborn errors of metabolism due to mitochondrial diseases. Mitochondria, the energy producing units in cells, have been connected with cancer since the 1930s, when researchers first noticed that these organelles dysfunction when cancer is present.

Until recently, researchers believed that cancer-affected mitochondria are permanently damaged and that this damage is the result, not the cause, of the cancer. But Michelakis questioned this belief and began testing DCA, which activates a critical mitochondrial enzyme, as a way to "revive" cancer-affected mitochondria.

The results astounded him.

Michelakis and his colleagues found that DCA normalized the mitochondrial function in many cancers, showing that their function was actively suppressed by the cancer but was not permanently damaged by it.

More importantly, they found that the normalization of mitochondrial function resulted in a significant decrease in tumor growth both in test tubes and in animal models. Also, they noted that DCA, unlike most currently used chemotherapies, did not have any effects on normal, non-cancerous tissues.

"I think DCA can be selective for cancer because it attacks a fundamental process in cancer development that is unique to cancer cells," Michelakis said. "Cancer cells actively suppress their mitochondria, which alters their metabolism, and this appears to offer cancer cells a significant advantage in growth compared to normal cells, as well as protection from many standard chemotherapies. Because mitochondria regulate cell death--or apoptosis--cancer cells can thus achieve resistance to apoptosis, and this appears to be reversed by DCA."

"One of the really exciting things about this compound is that it might be able to treat many different forms of cancer, because all forms of cancer suppress mitochondrial function; in fact, this is why most cancers can be detected by tests like PET (positron emission tomography), which detects the unique metabolic profile of cancer compared to normal cells," added Michelakis, the Canada Research Chair in Pulmonary Hypertension.

 

Another encouraging thing about DCA is that, being so small, it is easily absorbed in the body, and, after oral intake, it can reach areas in the body that other drugs cannot, making it possible to treat brain cancers, for example.

 

Also, because DCA has been used in both healthy people and sick patients with mitochondrial diseases, researchers already know that it is a relatively non-toxic molecule that can be immediately tested in patients with cancer.

 

Furthermore, the DCA compound is not patented and not owned by any pharmaceutical company, and, therefore, would likely be an inexpensive drug to administer, Michelakis added.

 

However, as DCA is not patented, Michelakis is concerned that it may be difficult to find funding from private investors to test DCA in clinical trials. He is grateful for the support he has already received from publicly funded agencies, such as the Canadian Institutes for Health Research (CIHR), and he is hopeful such support will continue and allow him to conduct clinical trials of DCA on cancer patients.

 

"This preliminary research is encouraging and offers hope to thousands of Canadians and all those around the world who are afflicted by cancer, as it accelerates our understanding of and action around targeted cancer treatments," said Dr. Philip Branton, Scientic Director of the CIHR Institute of Cancer.

 

Source: University of Alberta 

 

 

 

 

 

This news is brought to you by PhysOrg.com

 

Don’t’ forget rosemary, ginger, broccoli, cooked tomatoes, blueberries and cauliflower in your diet.  Don’t take extracts in pill or capsule form when you can help it.  Add them to foods, teas, or other beverages.  Some of them can cause G.I. issues like constipation, upset stomach, etc. when taken in capsule/pill form.  Curcumin is great on broccoli. It doesn’t mix well with water based drinks but mixes well with olive oil and is great on broccoli with olive oil and other spices.  For tea, to get a large enough effect from it, I put two tea bags in the cup and empty 2 capsules of green tea extract into the tea, sweeten with stevia or a sweetener that doesn’t support tumor growth.  You need a ten cup equivalent of green tea to get good effect, you can take less tea if doing enough curcumin.  Spread your curcumin throughout the day to increase absorption.  Quercetin from apples is great stuff.  Watercress especially, and broccoli remove pollutants from the polluted air.

 

Germanium:::::::::::::::::::::::::::

This from a good friend.  Thank You Sandra:::::