viagra vs cancer

[Guest guest]

from Bio-Medicine:

Sildenafil and other " impotence drugs " that boost the production of a

gassy chemical messenger to dilate blood vessels and produce an

erection now also show promise in unmasking// cancer cells so that

the immune system can recognize and attack them, say scientists at

the s Hopkins Kimmel Cancer Center.

Tests at Hopkins on mice with implanted colon and breast tumors

showed that tumor size decreased two- and threefold in

sildenafil-treated animals, compared to mice that did not get the

drug. In mice engineered to lack an immune system, tumors were

unaffected, proof of principle, the scientists say, that the drug is

abetting the immune system's own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of

Experimental Medicine, the Hopkins team says boosted levels of the

chemical messenger nitric oxide appear to dampen the effects of a

specialized cell that diverts the immune system away from tumors,

allowing swarms of cancer-attacking T-cells to migrate to tumor sites

in the rodents.

Lab-grown cancer cells treated with sildenafil showed similar

results, as did tissue samples taken from 14 head and neck cancer and

multiple myeloma patients.

Sildenafil, marketed under the trade name Viagra, is one of a class

of drugs used to treat erectile dysfunction in millions of men, and

in recent years, its ability to stimulate the production of NO has

been investigated by experts in diseases linked to the activity of

blood vessels and blood components.

The new Hopkins study homes in on a tactic used by cancers to avoid

detection by the immune system by turning elements of that system to

its own advantage, says Ivan Borrello, M.D., assistant professor at

the s Hopkins Kimmel Cancer Center.

Borrello and his colleagues found that tumors exploit nitric

oxide-producing immune cells to create a sort of " fog " that keeps

them hidden from white blood cells (T-cells) that mount attacks on tumors.

These NO-producing cells, a.k.a. myeloid-derived suppressor cells

(MDSCs), normally use nitric oxide to help bring the immune system

back down to surveillance levels after an " attack mode " response to

foreign material.

The impotence drugs seem to reverse this process, stopping the

production of nitric oxide by MDSCs thereby allowing other immune

cells to " see " the cancer and attack it, says Paolo Serafini, Ph.D.,

a research fellow in Borrello's laboratory and lead author on the paper.

Nitric oxide is infamous among city dwellers as a component of

air-polluting smog, but is gaining importance in medical research for

its cell-signaling duties and its ability to divert soldiering

T-cells that patrol and protect.

The Hopkins team also analyzed gene expression patterns of the

myeloid-derived suppressor cells and found that sildenafil blocked

two genes regulating enzymes -- arginase and nitric oxide synthase --

which are key to triggering immune suppression via MDSCs. Borrello's

team found that the arginase enzyme, which metabolizes a dietary

supplement called L-arginine, also contributes to dampening the

immune system through MDSCs much like nitric oxide, and its

production can be reversed by sildenafil.

" Impotence drugs won't cure cancer, " Borello cautioned, " but could be

used in addition to standard chemotherapy or immunotherapy treatments. "

The investigators are planning human studies to begin in the next year.

J Exp Med. 2006 Nov 27;203(12):2691-702. Epub 2006 Nov 13.inks

Phosphodiesterase-5 inhibition augments endogenous antitumor immunity

by reducing myeloid-derived suppressor cell function.

<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Serafini%\

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_RVAbstractPlusDrugs1>Serafini

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K,

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L,

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V,

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_RVAbstractPlusDrugs1>Borrello

I.

Sidney Kimmel Comprehensive Cancer Center, Department of

Otolaryngology-Head and Neck Surgery, s Hopkins University,

Baltimore, MD 21231, USA.

Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, and

vardenafil) are agents currently in clinical use for nonmalignant

conditions. We report the use of PDE5 inhibitors as modulators of the

antitumor immune response. In several mouse tumor models, PDE5

inhibition reverses tumor-induced immunosuppressive mechanisms and

enables a measurable antitumor immune response to be generated that

substantially delays tumor progression. In particular, sildenafil,

down-regulates arginase 1 and nitric oxide synthase-2 expression,

thereby reducing the suppressive machinery of CD11b+/Gr-1+

myeloid-derived suppressor cells (MDSCs) recruited by growing tumors.

By removing these tumor escape mechanisms, sildenafil enhances

intratumoral T cell infiltration and activation, reduces tumor

outgrowth, and improves the antitumor efficacy of adoptive T cell

therapy. Sildenafil also restores in vitro T cell proliferation of

peripheral blood mononuclear cells from multiple myeloma and head and

neck cancer patients. In light of the recent data that enzymes

mediating MDSC-dependent immunosuppression in mice are active also in

humans, these findings demonstrate a potentially novel use of PDE5

inhibitors as adjuncts to tumor-specific immune therapy.

PMID: 17101732 [PubMed - indexed for MEDLINE]

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Comment from VG:

Cialis is much longer acting than viagra and there is no good reason

to believe that PDE5 inhibition won't also help women in immune

strategies vs cancer. This is just another tool to be considered

with cell-mediated immune strategies. Other examples include using a

single dose of very small amount of cyclophosphamide about 3-4 days

prior to using a subunit cancer vaccine, another is injecting

intradermally at multiple inguinal sites, another is the use of Th-1

directing adjuvants, and another is the reduction of omega-6 oils in

the diet. What is often ignored is the importance of optimizing five

trace elements: zinc, selenium, cobalt, copper and iodine. I do have

discourses on these and many other immune strategies in my seminars,

but I won't be passing out Viagra or Cialis. They are

non-prescription in Mexico though.