2010 Genitourinary Cancers Symposium Mar 5-7; More positive evidence on XMRV

[Jimk]

Sure can find it in the right tissues

http://www.medpagetoday.com/MeetingCoverage/ASCOGU/18850

 

[leelaplay]

Novel Retrovirus Mimics HIV Transmission

(if: nice find jimk! The below is the beginning of the article)

Novel Retrovirus Mimics HIV Transmission

By Crystal Phend, Senior Staff Writer, MedPage Today
Published: March 06, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

Action Points

* Caution patients that it is not yet known how common this virus is in the general population nor have researchers proven whether the virus actually causes prostate cancer or other disease.

* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

SAN FRANCISCO -- A novel retrovirus implicated in prostate cancer appears to be transmitted much the way HIV is, researchers found.

The recently-discovered xenotropic murine leukemia related virus -- dubbed XMRV -- likely spreads through contact with blood and semen, Eric A. Klein, MD, of the Cleveland Clinic, and colleagues reported here at the Genitourinary Cancers Symposium.

Semen dramatically enhanced infectivity of the virus, allowing it to slip more easily into human cells, they found.

"It's behaving just like the two other retroviruses that cause disease in humans," Klein told MedPage Today.

Infectious disease experts, too, have likened their scramble to make sense of the virus to the early days of HIV research, but caution that there has yet to be any clear causal evidence showing that XMRV leads to disease.

 

[parvofighter]

More POSITIVE evidence on XMRV; 2010 Genitourinary Cancers Symposium Mar 5-7

More evidence from familiar researchers (Silverman, Hackett) that:

1. XMRV exists and is infective in primates (including humans)
2. XMRV viremia can be transmitted intravenously (eg. by IV injection)
3. Hormones (eg. androgen) stimulate XMRV transcription and replication
4. XMRV may be sexually transmitted
5. Concern about the blood supply is very real
   

From: The American Society of Clinical Oncology's 2010 Genitourinary Cancers Symposium: March 5-7, 2010, San Francisco

Characterization of XMRV in prostate cancer:
URL: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=73&abstractID=30543

Sub-category: Prostate Cancer: Early/Localized disease, Locally Advanced/Recurrent/Advanced disease, and Biology
Category: Prostate Cancer: Early/Localized disease, Locally Advanced/Recurrent/Advanced disease, and Biology
Meeting: 2010 Genitourinary Cancers Symposium
Session Type and Session Title: Reception and General Poster Session B: Prostate Cancer
Abstract No: 117
Author(s): E. A. Klein, F. Villinger, J. Das Gupta, C. Magi-Galluzzi, S. Hong, C. Nguyen, C. J. Weight, G. Schochetman, J. Hackett, R. Silverman; Cleveland Clinic Foundation, Cleveland, OH; Yerkes Primate Center, Atlanta, GA; Cleveland Clinic, Cleveland, OH; Abbott Diagnostics, Abbott Park, IL

Abstract:
Background: Xenotropic Murine Leukemia Related Virus (XMRV) is a novel gammaretrovirus discovered in prostate tissue of men genetically predisposed to prostate cancer (Note: Do they mean RNase-L?). A growing body of evidence suggests a potential causative role in prostate cancer. Methods: XMRV was isolated and cloned from prostate tissue of unselected men with prostate cancer who underwent radical prostatectomy, with initial identification accomplished by hybridization to a DNA microarray containing conserved sequences of known viruses. Live virus was injected intravenously into rhesus macaques for acute and chronic infection studies. Tissue distribution of XMRV was studied by immunohistochemistry (using a rhesus-derived monoclonal to ENV protein) and RT-PCR based assays. Effect of androgen on XMRV growth was assessed by infection of LnCap and DU145 cells using virus mutated in the androgen response element (ARE) promoter region as control. Chromosomal integration sites were mapped from human prostates using a PCR-based approached that produced biotinylated-ds DNA and isolated by binding to streptavidin-agarose Dynabeads. Expressed prostatic secretions (EPS) were obtained by milking radical prostatectomy specimens. The presence of XMRV in EPS was assessed by qRT-PCR. Results: 1)preliminary observations suggest that XMRV is detectable by immunohistochemistry in prostate epithelium; 2) XMRV preferentially integrates into host chromosomes at transcriptionally active sites (My note: In other words, you have to know where to look for it); 3) IV injection of XMRV produces viremia and persistent infection in rhesus macaques with a robust immune response; 4) the XMRV promoter contains a consensus ARE; 5) androgen stimulates transcription and replication of XMRV independent of cell growth; 6) XMRV is present in 15% of EPS from unselected cases of prostate cancer; 7) human semen and semen-derived enhancers substantially increase XMRV in both prostate stroma and epithelium. Conclusions: XMRV is infective in primates and produces an immune response. The presence of XMRV in EPS and effect of semen on infectivity suggest sexual transmission. The presence of an ARE (My note: ARE= Androgen Response Element) and the stimulatory effect of androgen suggests that XMRV integration into host DNA could impart androgen stimulation on cellular genes, serving as a potential oncogenic mechanism
​

Conference Program here: http://www.asco.org/ASCOv2/Meetings...osium/Program+&+Onsite+Details/Program+Agenda )

Questions? E-mail gusymposium@asco.org
​

Can I punt, and ask that someone else follow up @ the email above, and request any other info on XMRV and/or RNase-L (?posted videos, articles, etc.) Note that this abstract looks like a late addition - it was not on the formal program (see link). And note that the conference ends today. :Retro smile:[FONT=&quot]

A final note on The XMRV Scoreboard - from my comment on the Mayo Clinic thread:
Post #8 (for more rationale, see: http://forums.aboutmecfs.org/showthread.php?3497-MAYO-CLINIC-ON-XMRV-March-04th-Talk-in-Sacramento )
[/FONT]

Here's the scoreboard so far:

1. Is XMRV a real retrovirus? YES
2. Is XMRV found in humans? YES
3. Is XMRV found outside the US and Japan (i.e. in the UK)? YES
4. Is XMRV behavior consistent with what we know about ME/CFS? YES
5. Might XMRV cause some prostate cancers? INCREASING EVIDENCE for YES
   
6. Might XMRV cause ME/CFS? DEFINITELY PLAUSIBLE, BUT WE NEED TO WAIT FOR MORE VALIDATION/REPLICATION OF THE SCIENCE WORK.

Look at our progress: 5 months after the publication of the Science paper, it is reasonable to say that science has answered the first 4 questions (just look at the CROI retroviral conference thread). And keep in mind that early shoddy replication attempts challenged these 4 tenets too. Doesn't say much for their "science", does it, eh?:Retro smile:

Just stay focused, and digest all the forthcoming science - including that from WPI - with a critical eye. The good science will stand the test of scrutiny of cohort AND lab methods.

Parvo:Retro smile:

I am reminded of Mark Twain's famous quote (on seeing his "obituary" published in an errant New York journal), when I see postings filled with Schadenfreude (disingenuous "concern" for ME/CFS patients looking for a cure) at the "demise" of XMRV research:

"The reports of my death are greatly exaggerated"
​

 

[garcia]

Brilliant as always Parvo!!

 

[Jimk]

Ditto

Thanks to Parvo for that cogent summary. Also thanks for retitling my original post!
Finding stealth bugs requires looking in the right places, not just the right test.

 

[rebecca1995]

Thanks, Parvo! You sure have a nose for delicious tidbits. Fetch us some more, huh?

Even as Wessely and van Kuppeveld claim XMRV doesn't exist in their countries, real scientists are filling in the details about the virus' basic biology. Down the road those who published in haste will repent at leisure! (As my grandma always used to say.:Retro wink

 

[Otis]

A wildly speculative throught/question

In the interest of getting my testosterone levels up and hopefully providing me some energy, I started using Androgel a little more than a year ago. Very shortly thereafter I started getting low grade fevers. This is a CFS symptom I've never had before. There appeared to a benefit in terms of energy but I stopped testosterone to try to control the fevers. Stopping didn't help as the fevers hung around and all my other symtoms got worse until I had to leave work.

So does it make sense that the testosterone may have added fuel to an XMRV (I have not been tested) fire?

Otis

 

[gracenote]

Otis.

I don't think anyone knows yet, but I'll leave it to others to speculate with you.

I want to welcome you to the forums. I hope you find them useful and encouraging.

gracenote

 

[Otis]

Thank you gracenote

Otis.

I want to welcome you to the forums. I hope you find them useful and encouraging.

gracenote

I'm not smart enough to intelligently add to much of the scientific discussions , but I'll be hanging around trying to learn...

 

[leelaplay]

I'm not smart enough to intelligently add to much of the scientific discussions , but I'll be hanging around trying to learn...

hi Otis - and welcome

it looks like you have the emoticons down already - that alone took me over a month I think, so you're ahead of the game in my books.

enjoy!

 

[parvofighter]

Good question Otis! Here's another...

Hey Otis!

Further to your thoughtful and insightful question:

In the interest of getting my testosterone levels up and hopefully providing me some energy, I started using Androgel a little more than a year ago. Very shortly thereafter I started getting low grade fevers. This is a CFS symptom I've never had before...

...does it make sense that the testosterone may have added fuel to an XMRV fire?

Here are some more goodies that would suggest the answer is, "Yes, it does make sense that the testosterone may have added fuel to an XMRV fire". And these prostate cancer/XMRV research findings also potentially open the door for a treatment avenue - not only for XMRV-associated prostate cancers - but also potentially for ME/CFS (assuming XMRV will indeed be definitively linked with ME/CFS shortly).

More from the American Society of Clinical Oncology 2010 Genitourinary Conference:
http://www.medpagetoday.com/MeetingCoverage/ASCOGU/18850

Novel Retrovirus mimics HIV transmission
Human prostate cancer cells chronically infected with XMRV showed that exposure to androgens boosted replication of the virus whereas the anti-androgens bicalutamide (Casodex) and flutamide (Eulexin) suppressed viral growth. Human semen increased viral RNA levels in a largely dose-dependent manner, while the viral yield for a given "dose" of virus rose 1.71- to 4.9-fold in the presence of semen-derived substances.
In human prostate tissue samples, Klein's group also showed that the retrovirus "preferentially integrates into host chromosomes at transcriptionally active sites," they said in the presentation. These DNA sites included those in androgen receptor signaling pathways, hereditary prostate cancer genes, and others related to tumor progression, metastasis, and invasiveness. These results suggested that this integration of the virus into human DNA may "impart androgen stimulation on cellular genes, serving as a potential oncogenic mechanism," the investigators concluded in the presentation.
​

In other words - and recognizing that this is theoretical, as you have not been tested for XMRV - the potential combination of XMRV and Androgel might give a ME/CFS/XMRV patient a 1-2 punch:

1. The Androgel stimulates/activates XMRV, bringing on a CFS relapse
2. XMRV itself, when it integrates into the cell genes, somehow causes the cells (all cells, or just prostate ones??) to produce androgen hormones, further increasing the disease-causing impact of XMRV.

Which leads to the next question.

Have any of the credible ME/CFS researchers tried the anti-androgens bicalutamide (Casodex) and flutamide (Eulexin) to see what they do for us patients?

Would love the answer to that one too!
And welcome to the forums...:Retro smile:​

 

[Otis]

Fascinating question

Hey Otis!

...<snip>

1. The Androgel stimulates/activates XMRV, bringing on a CFS relapse
2. XMRV itself, when it integrates into the cell genes, somehow causes the cells (all cells, or just prostate ones??) to produce androgen hormones, further increasing the disease-causing impact of XMRV.

Which leads to the next question.

Have any of the credible ME/CFS researchers tried the anti-androgens bicalutamide (Casodex) and flutamide (Eulexin) to see what they do for us patients?

Would love the answer to that one too!
And welcome to the forums...:Retro smile:​

Wow, great question Parvo. I'll have to research these meds, not that I would throw another random trial into the stew at this point.

Here's one more interesting tidbit. Despite stopping the testosterone, my levels have stayed up which confused my doc and I. Perhaps these levels are indicative of the XMRV-produced androgens which means we started a cascade which seems to still be going. Not a pretty thought but it would explain a lot since I'm still at the bottom of my worst flare ever, more than a year later. I wish I could sell the greedy disability company on this theory.

I may have to get tested sooner rather than later...

Glad to be here. :Retro smile:
Otis

 

[Adam]

Scientifically Challenged

Another welcome - from a scientifically challenged phoenix forum member:innocent1: Must have been missing when we did chemistry and biology at school.

Stick around Otis and soak up the geek stuff. The Gerwyn/Kurt Tag Team are a must . Or just stick around.

cheers from the other side of the pond

 

[Otis]

I'm just a wanna-be geek

Another welcome - from a scientifically challenged phoenix forum member:innocent1: Must have been missing when we did chemistry and biology at school.

Stick around Otis and soak up the geek stuff. The Gerwyn/Kurt Tag Team are a must . Or just stick around.

cheers from the other side of the pond

Adam,

Thanks, but I'm no match for the major brains here but. I've seen some of hard-core stuff tossed around and I can't pretend to hang with that crowd.

My pure science is a distant memory. For that matter, where I put the milk (NOT the fridge) is too.

I hope to make it back to your side of the pond one day. I had the brutal experience of being paid to live in Bath for more than a month. Such hardship.

Otis

 

[bullybeef]

XMRV: Latest Research (transmission)

See: http://www.asco.org/ASCOv2/Meetings/...stractID=30543

Abstract:

Background: Xenotropic Murine Leukemia Related Virus (XMRV) is a novel gammaretrovirus discovered in prostate tissue of men genetically predisposed to prostate cancer. A growing body of evidence suggests a potential causative role in prostate cancer.

Methods: XMRV was isolated and cloned from prostate tissue of unselected men with prostate cancer who underwent radical prostatectomy, with initial identification accomplished by hybridization to a DNA microarray containing conserved sequences of known viruses. Live virus was injected intravenously into rhesus macaques for acute and chronic infection studies. Tissue distribution of XMRV was studied by immunohistochemistry (using a rhesus-derived monoclonal to ENV protein) and RT-PCR based assays. Effect of androgen on XMRV growth was assessed by infection of LnCap and DU145 cells using virus mutated in the androgen response element (ARE) promoter region as control. Chromosomal integration sites were mapped from human prostates using a PCR-based approached that produced biotinylated-ds DNA and isolated by binding to streptavidin-agarose Dynabeads. Expressed prostatic secretions (EPS) were obtained by milking radical prostatectomy specimens. The presence of XMRV in EPS was assessed by qRT-PCR. Results: 1) preliminary observations suggest that XMRV is detectable by immunohistochemistry in prostate epithelium; 2) XMRV preferentially integrates into host chromosomes at transcriptionally active sites; 3) IV injection of XMRV produces viremia and persistent infection in rhesus macaques with a robust immune response; 4) the XMRV promoter contains a consensus ARE; 5) androgen stimulates transcription and replication of XMRV independent of cell growth; 6) XMRV is present in 15% of EPS from unselected cases of prostate cancer; 7) human semen and semen-derived enhancers substantially increase XMRV in both prostate stroma and epithelium.

Conclusions: XMRV is infective in primates and produces an immune response. The presence of XMRV in EPS and effect of semen on infectivity suggest sexual transmission. The presence of an ARE and the stimulatory effect of androgen suggests that XMRV integration into host DNA could impart androgen stimulation on cellular genes, serving as a potential oncogenic mechanism.

 

[gracenote]

Thank you bullybeef. This looks great. I couldn't get your link to take me to the abstract.

Here is a another way to read the abstract posted above.

Background:

Xenotropic Murine Leukemia Related Virus (XMRV) is a novel gammaretrovirus discovered in prostate tissue of men genetically predisposed to prostate cancer. A growing body of evidence suggests a potential causative role in prostate cancer.

Methods:

XMRV was isolated and cloned from prostate tissue of unselected men with prostate cancer who underwent radical prostatectomy, with initial identification accomplished by hybridization to a DNA microarray containing conserved sequences of known viruses.

Live virus was injected intravenously into rhesus macaques for acute and chronic infection studies. Tissue distribution of XMRV was studied by immunohistochemistry (using a rhesus-derived monoclonal to ENV protein) and RT-PCR based assays. Effect of androgen on XMRV growth was assessed by infection of LnCap and DU145 cells using virus mutated in the androgen response element (ARE) promoter region as control.

Chromosomal integration sites were mapped from human prostates using a PCR-based approached that produced biotinylated-ds DNA and isolated by binding to streptavidin-agarose Dynabeads. Expressed prostatic secretions (EPS) were obtained by milking radical prostatectomy specimens. The presence of XMRV in EPS was assessed by qRT-PCR.

Results:

1) preliminary observations suggest that XMRV is detectable by immunohistochemistry in prostate epithelium;

2) XMRV preferentially integrates into host chromosomes at transcriptionally active sites;

3) IV injection of XMRV produces viremia and persistent infection in rhesus macaques with a robust immune response;

4) the XMRV promoter contains a consensus ARE;

5) androgen stimulates transcription and replication of XMRV independent of cell growth;

6) XMRV is present in 15% of EPS from unselected cases of prostate cancer;

7) human semen and semen-derived enhancers substantially increase XMRV in both prostate stroma and epithelium.

Conclusions:

XMRV is infective in primates and produces an immune response. The presence of XMRV in EPS and effect of semen on infectivity suggest sexual transmission. The presence of an ARE and the stimulatory effect of androgen suggests that XMRV integration into host DNA could impart androgen stimulation on cellular genes, serving as a potential oncogenic mechanism.

 

[_Kim_]

Thanks bullybeef. I found the correct URL for theabove abstract titled Characterization of XMRV in prostate cancer.

It seems that this abstract was accepted for a poster session at the 2010 Genitourinary Cancers Symposium and was presented by Eric A Klein, MD

Here are the list of author: E. A. Klein, F. Villinger, J. Das Gupta, C. Magi-Galluzzi, S. Hong, C. Nguyen, C. J. Weight, G. Schochetman, J. Hackett, R. Silverman; Cleveland Clinic Foundation, Cleveland, OH; Yerkes Primate Center, Atlanta, GA; Cleveland Clinic, Cleveland, OH; Abbott Diagnostics, Abbott Park, IL

This looks to be another report based on the same studies that Silverman and Abbott Diagnostics are doing at the Yerkes Primate center. We first saw this work presented at the Retrovirology conference last month.

 

[parvofighter]

More dialogue here

Thanks for posting bullybeef, gracenote, & Kim. Neat stuff, eh? :Retro smile:

There's some more discussion & analysis on this exciting XMRV paper, & its potential implications for XMRV/CFS on the discussion thread at

2010 Genitourinary Cancers Symposium Mrch 5-7; More positive evidence on XMRV: http://www.forums.aboutmecfs.org/sh...tive-evidence-on-XMRV&highlight=genitourinary​

I wonder if someone can combine these two threads?


Cheers, Parvo

 

[bullybeef]

Sorry guys, I should have done a search first.