Re: Potential Treatment - continued/BE VERY CAREFUL...Not everything is what it seems...Dr.B.

[Guest guest]

This smacks too much of a PR for a pharmaceutical company...most of

those

on this list are against this type of questionable bioengineering since

the long

term risks are unknown...many cancers are known to be induced by

virally-manufactured

products such as the HEP vaccine series, polio vaccine, influenza

vaccines...

I'd be very wary of this type of thing...putting foreign proteins that

have been

manipulated into a very vulnerable population is the worst kind of

experimentation

in my view...

Dr.Bormann

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

reovirusmike wrote:

> Generally what I have found in all my research and reading and what I

>

> have come to understand while learning all of this, is that usually

> the more agressive a cancer is, the more likely that it has an

> activated RAS pathway. If you do much reading into the biology of

> cancer, you will find a multitude of articles on RAS and its role or

> suspected role in the progression of cancer.

>

> >From what I have read is mutated or activated RAS doesn't necessarily

>

> cause cancer, however it seems to cause cancer to transform into more

> agressive and resistant to thearapy states.

>

> There is much information to read on websites, here are some links to

> the clinical information that talks more in depth of what I am

> talking about.

>

> EFFICACY AND SAFETY EVALUATION OF HUMAN REOVIRUS TYPE 3 IN A

> IMMUNOCOMPETENT RACINE GLIOMA MODEL

> http://www.oncolyticsbiotech.com/022801p4.html

>

> Reovirus as an Oncolytic Agent Against Experimental Human Malignant

> Gliomas

> Journal of the National Cancer Institute, Vol. 93, No. 12, 903-912,

> June 20, 2001

> http://jncicancerspectrum.oupjournals.org/cgi/content/abstract/jnci;93

>

> /12/903?

> maxtoshow= & HITS= & hits= & RESULTFORMAT= & fulltext=reovirus & searchid=102299

>

> 3142942_6875 & stored_search= & FIRSTINDEX=70 & sortspec=date & resourcetype=1

>

> MEMORANDUM FOR: Science Writers and Editors on the Journal Press List

> Reovirus Shows Promise Against Brain Tumors

> Journal of the National Cancer Institute, Vol. 93, No. 12, 887, June

> 20, 2001

> http://jncicancerspectrum.oupjournals.org/cgi/content/full/jnci;93/12/

>

> 887-a?

> maxtoshow= & HITS= & hits= & RESULTFORMAT= & fulltext=reovirus & searchid=102299

>

> 3142942_6875 & stored_search= & FIRSTINDEX=70 & sortspec=date & resourcetype=1

>

> Reovirus oncolysis in medulloblastoma is effective in vivo and safe

> in rodents and primates

> A Forsyth, Wen Qing Yang, Donna Senger, Huong Muzik, Zhong Q

> Shi, Penny Brasher, Dyck, Univ of Calgary & Tom Baker Cancer

> Ctr, Calgary, AB, Canada.

> http://www.asco.org/cgi-bin/prof/abst.pl?

> absno=289 & div=0011 & year=02abstracts

>

> Human reovirus acts as a novel therapeutic against medulloblastoma

> Wenqing Yang, Donna L. Senger, Huong Muzik, Zhongqiao Shi, Penny Ma

> Brasher, Wk Lee, Randy N. ston, A. Forsyth,

> University of Calgary, Calgary, AB, Canada.

> http://aacr02.agora.com/planner/displayabstract.asp?

> presentationid=3303

>

> Reovirus Therapy of Tumors with Activated Ras Pathway. Science 282:

> 1332-1334, Nov. 13, 1998.

> http://www.asco.org/prof/oc/html/m_coffey0799.htm

> http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?

> uid=9812900 & form=6 & db=m & Dopt=b

>

> A phase I clinical trial evaluating intralesional Reolysin (reovirus)

> in histologically confirmed malignancies.

> Don G , A Forsyth, H Paterson, Fonseca,

> M Difrancesco, Brad G , C Coffey, Tom Baker

> Cancer Center, Calgary, AB, Canada; Oncolytics Biotech Inc, Calgary,

> AB, Canada.

> http://www.asco.org/cgi-bin/prof/abst.pl?

> absno=92 & div=0044 & year=02abstracts

>

> NOVEL VIRAL ONCOLYTIC THERAPY OF SUPERFICIAL BLADDER CANCER IN AN

> ANIMAL MODEL: A COMPARITIVE STUDY TO BCG.

> http://www.oncolyticsbiotech.com/scientific_01.html

>

> Reovirus as a novel oncolytic agent

> http://www.jci.org/cgi/content/full/105/8/1035

>

> EVALUATION OF REOVIRUS THERAPY FOR SPONTANEOUSLY OCCURRING CANINE

> TUMORS

> http://www.oncolyticsbiotech.com/scientific_02.html

>

> REOVIRUS PROLONGS SURVIVAL IN INTRACEREBRAL MODELS OF GLIOMAS

> http://www.oncolyticsbiotech.com/REOVIRUS11082000.html

>

> The molecular basis of viral oncolysis: usurpation of the Ras

> signaling pathway by reovirus

> The EMBO Journal Vol. 17,pp. 3351-3362, 1998

> http://emboj.oupjournals.org/cgi/content/full/17/12/3351?

> maxtoshow= & HITS= & hits= & RESULTFORMAT= & author1=coffey & fulltext=reovirus &

>

> searchid=1022993666248_1493 & stored_search= & FIRSTINDEX=0 & resourcetype=1

>

> & journalcode=emboj

>

> IN VITRO AND IN VIVO RESPONSE OF MALIGNANT NON-HODGKIN'S LYMPHOMAS TO

> REOVIRUS

> http://www.oncolyticsbiotech.com/022801p3.html

>

> REOVIRUS INDUCES APOPTOSIS IN BREAST AND PROSTATE CELL LINES AND

> ACTIVATES NF-êB IN THE NUCLEUS:IMPLICATIONS FOR A PROGNOSTIC FACTOR

> IN SUCCESSFUL REOVIRUS THERAPY

> http://www.oncolyticsbiotech.com/022801p2.html

>

> REOVIRUS THERAPY OF METASTATIC CANCER MODELS IN IMMUNE-COMPETENT MICE

> http://www.oncolyticsbiotech.com/022801p1.html

>

> Oncolytic Reovirus against Ovarian and Colon Cancer1

> Cancer Research 62, 1696-1701, March 15, 2002

> http://cancerres.aacrjournals.org/cgi/content/abstract/62/6/1696?

> maxtoshow= & HITS= & hits= & RESULTFORMAT= & fulltext=reovirus & searchid=102299

>

> 2920109_6822 & stored_search= & FIRSTINDEX=20 & sortspec=date & resourcetype=1

>

> Reovirus Therapy of Tumors with Activated Ras Pathway

> Science, Nov 1998; 282: 1332 - 1334

> http://www.sciencemag.org/cgi/content/abstract/282/5392/1332?

> maxtoshow= & HITS= & hits= & RESULTFORMAT= & author1=forsyth & fulltext=reovirus

>

> & searchid=1022993507787_6934 & stored_search= & FIRSTINDEX=0 & resourcetype=

>

> 1

>

> Effective systematic reovirus therapy of metastatic cancer in immune-

> competent mice

> Kensuke Hirasawa, G. Nishikawa, Kara L. Norman, W. K.

> Lee, University of Calgary, Calgary, AB, Canada

> http://aacr02.agora.com/planner/displayabstract.asp?

> presentationid=7322

>

> The molecular basis of Ras-dependent reovirus oncolysisKara L.

> Norman, An-Dao Yang, Kensuke Hirasawa, W. K. Lee, University

> of Calgary, Calgary, Canada.

> http://aacr02.agora.com/planner/displayabstract.asp?

> presentationid=2755

>

> Reovirus Therapy of Metastatic Cancer Models in Immune-Competent Mice

> Kensuke Hirasawa, Chang-Soon Yoon, G. Nishikawa, M.

> Waisman, WK Lee, University of Calgary, Calgary, AB, Canada.

> http://aacr01.agora.com/planner/displayabstract.asp?

> presentationid=13225

>

> Reovirus Induces Apoptosis in Breast and Prostate Cell Lines and

> Activates Nf-kB in the Nucleus:Implications for a Prognostic Factor

> in Successful Reovirus Therapy

> Chandini M. Thirukkumaran, Joanne Luider, Mchael Nodwell,

> Lee, , Tom Baker Cancer Centre, Calgary, AB, Canada.

> http://aacr01.agora.com/planner/displayabstract.asp?

> presentationid=13236

>

>

>

>

>

[Guest guest]

Dr. Bormann,

First of all I am not advocating people use it, it is a drug under

development which has completed a Phase 1 trial and is currently in a

Phase 2 trial for prostate cancer and is being injected into patients

brains in a Phase 1/2 Glioma trial.

The second comment I would like to make is relative to your comment

on bioengineering. Had you read the information provided you would

see that they are using type 3 Dearing Reovirus, a naturally occuring

virus that is NOT engineered.

The reason I put it up here is the fact that it is not bioengineered

nor genetically engineered, it seems to go with the theme of this

forum, the fact that it only replicates in RAS activated cancer cells

adds to that.

Ultimately on trials will dictate both safety and efficacy.

They are not introducing a new virus to the human population, most

people reading this if they have reached maturity will have had prior

exposure to the virus known through the presence of viral antibodies

and will not have ever known they have been exposed to it.

http://www.jci.org/cgi/content/full/105/8/1035

" Reovirus as a novel oncolytic agent

Kara L. Norman and W.K. Lee

Department of Microbiology and Infectious Diseases, University of

Calgary, Calgary, Canada

Address correspondence to: W.K. Lee, Department of

Microbiology and Infectious Diseases, Room B855, Health Sciences

Building, University of Calgary, 3330 Hospital Drive NW, Calgary,

Alberta T2N 2N1, Canada. Phone: (403) 220-7548; Fax: (403) 270-8520;

E-mail: plee@....

Reovirus is a double-stranded RNA-containing virus that possesses the

distinctive ability to replicate in transformed cells while sparing

normal cells, both in vitro and in vivo, in rodent models of cancer.

The discovery of this property only arose through years of basic

research on the biology of reovirus infection. Upon elucidation of

the intracellular factors that govern cellular susceptibility, it

became clear that reovirus Type 3 Dearing was capable of replicating

in cells with an activated Ras signaling pathway, whereas normal,

untransformed cells were unable to support reovirus infection (1).

Because normal cells are resistant to reovirus, it is not surprising

that reovirus infection in humans is usually subclinical (2, 3).

Altogether, the potential impact of such findings is impressive when

one considers that activating mutations in the ras genes alone

contribute to more than 30% of all human cancers and that many other

mutations in elements of the Ras pathway can also contribute to

oncogenesis (4, 5). Recently, research using murine cancer models has

revealed that this genetically unmodified laboratory strain of

reovirus can indeed selectively destroy tumor cells, with no

manifestations of animal morbidity or mortality (6). This has led the

way to investigation into its therapeutic potential in human cancer.

Background

Reovirus belongs to the Reoviridae family, which includes viruses of

a variety of tropisms (with examples of animal-, plant-, and insect-

pathogenic viruses) and, most notably, the major human pathogen,

rotavirus (7). Unlike the clinically significant rotavirus, reovirus

is relatively nonpathogenic in humans. In 1959, Sabin coined the name

reovirus as a descriptive acronym signifying its nonpathogenicity

(8). This acronym refers to the fact that although reovirus can be

isolated from the respiratory and enteric tracts, there is a lack of

association of infection with clinical symptoms and it is, hence, an

orphan virus. There are three serotypes of reovirus, based on their

hemagglutination-inhibition activity. Prototypical laboratory strains

of each serotype were isolated from children's respiratory and

enteric tracts and are designated Type 1 Lang, Type 2 , Type 3

Abney, and Type 3 Dearing.

All three serotypes of reovirus are found ubiquitously in the

environment, including such sources as water and sewage. This,

combined with the fact that reovirus possesses a highly stable

unenveloped icosahedral capsid, explains why as many as 50% of adults

aged 20–30 years have been exposed to reovirus over the course of

their lives and thus carry antibodies against the virus (9).

Seropositivity has been documented to be as high as 70–100% of

subjects in some studies (10, 11), despite the fact that most

reovirus infections go unnoticed. In 1963, volunteers from a

correctional institution demonstrated the nonpathogenic nature of

reovirus; upon intranasal inoculation by serotypes 1, 2, or 3, only

nine of 27 subjects developed symptoms (3). Symptoms were uniformly

mild and ranged from sneezing to pharyngitis. Moreover, serologic and

virologic tests indicated that not all that fell ill were

productively infected with reovirus but that some subjects with no

symptoms were seropositive, confirming that infection leading to

immunity is often benign. "

,

> This smacks too much of a PR for a pharmaceutical company...most of

> those

> on this list are against this type of questionable bioengineering

since

> the long

> term risks are unknown...many cancers are known to be induced by

> virally-manufactured

> products such as the HEP vaccine series, polio vaccine, influenza

> vaccines...

>

> I'd be very wary of this type of thing...putting foreign proteins

that

> have been

> manipulated into a very vulnerable population is the worst kind of

> experimentation

> in my view...

>

> Dr.Bormann

> *****************