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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:Here's the scoreboard so far:
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:
- Is XMRV a real retrovirus? YES
- Is XMRV found in humans? YES
- Is XMRV found outside the US and Japan (i.e. in the UK)? YES
- Is XMRV behavior consistent with what we know about ME/CFS? YES
- Might XMRV cause some prostate cancers? INCREASING EVIDENCE for YES
- Might XMRV cause ME/CFS? DEFINITELY PLAUSIBLE, BUT WE NEED TO WAIT FOR MORE VALIDATION/REPLICATION OF THE SCIENCE WORK.
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:
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...
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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).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?
Hey Otis!
...<snip>
Which leads to the next question.
- The Androgel stimulates/activates XMRV, bringing on a CFS relapse
- 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.
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:
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
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.
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.