THE MOSS REPORTS Newsletter (12/26/04)

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THE MOSS REPORTS Newsletter (12/26/04)

 

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #164 12/26/04

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THE MOSS REPORTS

 

 

Last week I began a two-part discussion of new developments in the

field of photodynamic therapy (PDT). The discussion concludes, with

references and resources, this week.

 

At present, PDT is FDA-approved for use in the treatment of a few,

mainly early stage, cancers. However, as research progresses and

more and

more ingenious methods of selectively targeting cancer tissue are

developed, it is to be hoped that this minimally invasive treatment

technique will come to occupy a more prominent place in the treatment of

cancers of many kinds.

 

For thirty years I have been writing about cancer research and

treatment. The fruit of my long career in this field is The Moss

Reports, a

comprehensive library of more than two hundred individual reports on

specific cancer diagnoses. For a cancer patient, a Moss Report

represents

an invaluable guide and handbook for the journey ahead.

 

If you would like to order a Moss Report for yourself or someone you

love, you can do so from our website, www.cancerdecisions.com, or by

calling Diane at 1-800-980-1234 (814-238-3367 from outside the US).

 

We look forward to helping you.

 

 

 

SOME PROMISING NEW DEVELOPMENTS IN PDT, PART II

 

 

 

Most current methods of PDT work by generating highly energized oxygen

molecules (called 'singlet oxygen') when the photosensitizer is

activated by the light source. However, a team led by Dr. Karen

Brewer of

Virginia Tech University has developed a series of photosensitizing

agents

that are oxygen independent. Dr. Brewer's team is working with cell

cultures to compare the effectiveness of the agents in the dark and in

visible light. The team presented its findings at the 228th American

Chemical Society National Meeting in Philadelphia in late August, 2004.

 

" Another improvement for our systems is that the agents are activated

by visible light, as opposed to UV (ultraviolet) light, " said Brewer,

associate professor of chemistry. " Using only visible light is a

safeguard against inadvertent damage of tissue. "

 

The researchers have obtained results in three separate areas that,

when used together, may provide more effective, less invasive, and more

specific treatments for cancer and other diseases. In particular, they

have developed some new tri-metallic 'supra-molecules' that can be

introduced not just into cancer tissue in general, but into specific

parts –

called 'organelles' - of cancer cells themselves. The supra-molecules

can then be activated by a specific wavelength of light that propagates

efficiently through tissue. Only when the light hits these

supra-molecules do they become toxic to the cancer cells.

 

The new system " allows much lower dosages of light to be effective, so

we can use agents that are more aggressive and not get the side effects

of chemotherapy, " Prof. Brewer said. Researchers in her laboratory

developed the new mixed-metal supra-molecular complexes that she and a

colleague, Prof. Brenda Winkel, have proven are capable of breaking up

DNA

when activated by light (a process called 'photocleaving'). The

researchers can also alter the wavelength of light that is used. " We

can fine

tune the compound for light-absorbing characteristics, " said Prof.

Brewer. " By using a lower energy [i.e., a higher wavelength of light,

ed.]

we can better penetrate the body. "

 

Prof. Brian Storrie and Dr. Maria Teresa Tarrago-Trani of Virginia

Tech's biochemistry department have developed what they call a 'rocket'

mechanism, by which to deliver the cancer-killing agents to particular

organelles. " We have used a polypeptide that binds to a cell surface

receptor, and that molecule is over-expressed for certain cancers. We can

deliver photosensitizers accurately to the cancer, " Storrie said.

 

The delivery vehicle is actually the B-fragment of the shiga toxin,

which is produced by the microbe that causes a form of dysentery

(Shigella

dysenteriae) as well as by certain disease-causing strains of E. coli.

This may sound dangerous. However, while the shiga A-fragment is toxic,

the B-fragment is not, and B-fragment therefore makes a harmless

delivery system.

 

Professor Storrie developed the technique of using the B-fragment to

deliver the photodynamic agents developed by Brewer directly into the

cells (Harris 2002). This allowed the researchers to target particular

cancer cells that have receptors for the B-fragment and to deliver the

agent to the exact spot in the cell that enables the supra-molecule to

attack it, thereby opening the way for the selective destruction of many

crucial parts within cancerous cells.

 

" We can attach the delivery vehicles, change the light we need, change

the biological target in the cells, and design a molecule that reacts

with that part, " said Prof. Brewer. She hopes that someday this system

will be the basis for important strides in the treatment of cancer and

other diseases.

 

 

Some Practical Applications

 

 

Photodynamic therapy is a highly promising treatment modality that has

so far remained very much at the fringes of cancer treatment,

overshadowed by the prevailing preference for chemotherapy. Because of

this

'poor relation' status, research into PDT has historically been

plagued by

many obstacles and false starts. However, it now appears to be getting

some of the serious scientific consideration that it deserves.

 

PDT has great potential as a way of killing cancer cells with less

damage to normal tissues. For skin and superficial tumors, PDT can be

administered using an external light source such as a laser attuned to

the

absorbency peak of the corresponding photosensitizer and delivered in a

highly targeted way. In the case of deep-seated tumors, however, the

light source generally must be applied (1) endoscopically (i.e., by

inserting a tube into a hollow organ such as the esophagus) or

intra-arterially, by way of a catheter threaded through the blood

vessels to a

target organ; (2) interstitially (i.e., by inserting a probe directly

into a

solid tissue, such as the liver); or (3) intraoperatively (i.e., in the

course of surgery).

 

In such ways, PDT may be used in the treatment of larger internal

areas, including the pleura (lining of the chest cavity) and peritoneum

(lining of the abdominal cavity). Logically, it could be eventually be

used

in the treatment of many, if not most, kinds of cancer.

 

But caution is advised. PDT is certainly no cure-all. It has not been

demonstrated, for instance, that PDT can be used with any external light

source to treat advanced, systemic disease (Moss 2003). PDT may also be

accompanied by more adverse effects than one might suppose by reading

enthusiastic reports in the media or even in the scientific literature.

 

Because of this, readers who are interested in receiving PDT are urged

to concentrate exclusively on those programs that use FDA or

EU-approved agents, or that enroll patients in carefully designed

clinical trials

under institutional review board (IRB) supervision. This is important

in order to safeguard the interests and rights of patients undergoing

treatment with what remains a largely experimental treatment modality.

 

 

 

DEPARTMENT OF CORRECTIONS

 

 

In last week's newsletter I mistakenly referred to the metal rhodium as

being liquid at room temperature, like mercury. This is incorrect.

Rhodium is solid at room temperature. I apologize for this error.

 

 

 

 

--Ralph W. Moss, PhD

 

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Resources:

 

Here is contact information on some prominent centers using PDT:

 

Photodynamic Therapy Center

Roswell Park Cancer Institute

Elm & Carlton Streets

Buffalo, NY 14263 USA

1-800-ROSWELLPDT Nurse = (716) 845-4427

email: pdtctr

http://www.roswellpark.org/document_187_620.html

 

Photodynamic Therapy Center

Department of Radiation Oncology

The Brody School of Medicine at East Carolina University

Greenville, NC 27858

Phone 1-800-223-9328 (252) 744-2900 / Fax (252) 744-2812

http://www.ecu.edu/radiationoncology/PDT/default.htm

 

Mr. Colin Hopper

Eastman Dental Institute for Oral Health Care Sciences

University College London

256 Gray's Inn Road,

London WC1X 8LD, UK

Fax: +44 (0) 20 7915 1056

Email: c.hopper

 

PDT Treatment in China: http://www.pdt-med.com/en/treatment.htm

 

Prof. Morrison: http://www.chem.purdue.edu/morrison/

Karen Brewer 540-231-6579, kbrewer,

Brian Storrie 540-231-6434, storrie,

Ken Meissner 540-231-2512, cmeissne

Sally Harris 540-231-6759 slharris

 

Prof. Avigdor Scherz, MD, PhD

Head-Minerva-Avron Center for Photosynthesis

Department of Plant Sciences

Weizmann Institute of Science, Rehovot, 76100

e-mail: Avigdor.Scherz

Tel(O): +972-8-9344309

Tel(H): +972-8-9473943

Fax: +972-8-9344181

 

 

References:

 

 

[Anonymous]. Light turns on anticancer agents. Cancerfacts.com. August

29, 2004. Retrieved September 1, 2004 from:

http://www.cancerfacts.com/Home_News.asp?NewsId=1717 & CB=14 & CancerTypeId=4

 

Boutin, Chad. Bright idea could doom cancer and viruses, say Purdue

scientists. August 23, 2004. Purdue University Press Release. Retrieved

September 1, 2004 from:

http://www.chem.purdue.edu/NewsFeed/newsstory.asp?itemID=121

 

Harris, Sally. Researchers develop exciting new arsenal in war against

cancer. December 11, 2002. Retrieved September 1, 2004 from:

http://www.technews.vt.edu/Archives/2002/Dec/02211.htm

 

Holder AA, Swavey S, Brewer KJ. Design aspects for the development of

mixed-metal supramolecular complexes capable of visible light induced

photocleavage of DNA. Inorg. Chem. 2004;43:303-308.

 

Menon EL, Perera R, Navarro M, Kuhn RJ, Morrison H. Phototoxicity

against tumor cells and Sindbis virus by an octahedral rhodium

bisbipyridyl

complex and evidence for the genome as a target in viral

photoinactivation. Inorg. Chem. 2004;43:5373-81.

 

Moss, RW. Moss RW. Patient responses to Cytoluminescent Therapy for

cancer: an investigative report of early experiences and adverse effects

of an unconventional form of photodynamic therapy. Integr Cancer Ther.

2003;2:371-89.

 

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