XMRV Buzz (11/24) – The Singh XMRV Patent – The Next Cancer for XMRV? Prostate Cancer Results Validated….Progress on CFS

November 24, 2010

Posted by Cort Johnson

The Next Cancer for XMRV? – JMK on the MECFS Forums snuffed out Dr. Singh’s XMRV patent application and then XMRV Global Action highlighted the most relevant sections and here we are with what is easily the most exciting news for XMRV since the Science paper was published in October of last year. The patent application states Dr. Singh has found XMRV in 25% of 178 samples from patients with breast cancer – a finding that will surely send a shock through Cancer research community. Tellingly, XMRV was not found in the tissues just surrounding the cancer as originally appeared with prostate cancer – it was found smack dab in the middle of the malignant breast tissues.

Hormones plays a role in many cancers including prostate and some breast cancers…is XMRV, which we know has a hormonal connection, zeroing in on hormone related cancers? Studies change the course of research efforts not patent application but it’s a patent application from a respected and careful researcher and you can bet your boots several papers on their way….

Prostate Cancer Clarified – breast cancer wasn’t the only cancer to get a big hit. The XMRV prostate cancer connection has been questioned because of the inability, thus far, to find XMRV in the malignant tissues themselves – it’s always been found in the tissues just surrounding those tissues but no longer; the application, rather startling, stated that these new immunohistochemistry and antibody results indicate XMRV is overwhelmingly found in the malignant epithelial tissues in prostate cancer patients. If validated, this will, undoubtedly ramp up XMRV cancer research efforts.

Happily the antibody (30%) and immunohistochemistry (27%) results correlated very nicely – thus providing an important check on their validity. The immunohistochemistry staining also revealed a telling pattern of XMR positive cells clustered together – just as you would expect with a virus.

Still an Underestimate – interestingly Dr. Singh believes her tests still underestimate the prevalence of XMRV in prostate cancer because it’s found in such a small subset of cells and that a closer examination of the tissues. will most likely lead to increased prevalence rates. Viral load is believed to be very low, in fact, she believes it is “close to the detection limit of the qPCR’ assay.

She doesn’t appear to have much doubt about the potential virulence of the pathogen, though; her results showed that XMRV presence was a correlated with cancer severity; that is, the more severe the cancer the more likely it was that XMRV was found in it.

More Cancers?/More Tissues? - Findings of other cancers were not detailed but the application does appear to indicate (?) XMRV was found in immune cells in the lymph nodes, the bone marrow and peripheral blood from hematological malignancies as well as the testes. (This is in a section that lists ‘embodiments’ of the present methods). Hematological malignancies refers to cancers that affect blood, bone marrow and lymph nodes and include such cancers as leukemias and non-Hodgkin’s (and other) lymphomas. Non-Hodgkins Lymphomas are reportedly found in 5% percent of Dr. Peterson’s Nevada cohort. http://phoenixrising.me/Conf/IACFSME09WPI.aspx

It seems likely that these results could reflect the autopsy work Dr. Singh has been doing. On the other hand, the application did state that the only other tissue XMRV was found in the 8 prostate cancer patients she autopsied was the testes.

XMRV Clarified – Dr. Singh has gone a long way in refining her techniques to find the virus. First she generated a new infectious clone called pXMRV33 constructed from two overlapping clones. She transfected some cells with her clones and nine weeks later began to detect reverse transcriptase – an enzyme associated with retroviruses. She then took the supernatant (cell free material), dropped some cells in it and then was able to detect retroviral activity in cells – indicating she had an infectious retrovirus on her hands.

Electron Microscopy -looking through an electron microscope she was able to see abundant viral particles that resembled a murine retrovirus.

Antibodies – she was able to find antibodies specific to XMRV by affecting rabbits with it and then doing Western blot tests. She found that (except for the env proteins) the amino acids in the proteins associated with XMRV were very similar (90%) to those in the Moloney murine retrovirus she’s been studying for quite some time.

It appears that she has replicated several important aspects of the WPI study and in at least one way has added to it; she has demonstrated that she has an infectious virus, she has created PCR and antibody tests whose results, at least in prostate cancer tissues, correlate with each and her electron microscopy results suggest she has a MLV-like retrovirus. Plus her immunohistochemistry test provides a newway to validate her results.

XMRV In Fluids- Dr. Singh has also refined her testing protocols for many of the bodily fluids. The application states that her immunohistochemistry assay, in fact, can be used to detect XMRV in saliva, semen, peritoneal fluid, synovial fluid, prostatic or cervical secretions, blood and serum. It describes a specific method for finding XMR in cervical fluid – and notes that the potential for spread from mother to child via that means.

Semen Findings Validate WPI Findings for Healthy Controls – The XMRV in semen finding had important implications because XMRV showed up in the semen in exactly the same percentage (7%) of healthy controls as tested positive in the original Science study – a very nice validation of the WPI’s original findings. Dr. Mikovits long ago, if I remember correctly, stated XMRV was found in the semen but Dr. Singh is the first researcher, I believe to validate Dr. Mikovits statement. The semen, of course, have significant implications for the possibility of transmission.

Chronic Fatigue Syndrome - The juice seemed to run out a bit when it came to ME/CFS, however. She has definitely made progress; the application states 2 XMRV antibodies have been found in a CFS patient and that most of the ‘non-reactive’ samples came from the healthy controls. Dr Singh also knows which XMRV antibodies to test for (SU, p15E) and which ones not to test for (CA – found in healthy people as well). We can guess that XMRV showed up more consistently in CFS patients than in the healthy controls – a nice start! – but we don’t have any idea of what percentage of people with CFS she found it. It looks like we will have to wait for her paper for that.

5 comments

{ 4 comments… read them below or add one }

Marie November 24, 2010 at 2:54 pm

Dr. Singh mentioned cervical cancer in her patent, which I think is important. I have CFS and was treated surgically for cervical cancer four years ago. Also my cancer was ‘poorly differentiated’, which is the technical term for aggressive type cancer. I am interested to know if XMRV is interacting with HPV. I am HPV positive and we know HPV is a major factor in cervical cancer. It must be that XMRV combines with HPV, or acts as a catalyst to promte oncogenesis. It pains me to wait for Dr. Singh’s work on XMRV and cancer to be published. Of course, the first questions I will be looking for answers to is: am I at risk for other cancers and what factors determine my risk?

As an aisde, I wonder if anyone thought of starting up an online emotinal wellness program for patients who are shell-shocked by the as-it happen-news about XMRV and disease risk. I for one am numbed by the ME/CFS research and politics over the past year. The internet is a terrible place to find out the ins and outs of my diagnosis, especailly after being minimized by the medical community for so many years. I am concerned for the care and emotional well-being of all CFS/ME patients as news of their diagnosis unfolds. Together we have been through so much already.

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Cort November 24, 2010 at 4:23 pm

XMRV’s possibilities for harm certainly seem to have increased over the past couple of days – leaving many people, no doubt, with new concerns. The internet is the place to be for news on CFS – is it not? Not the doctor’s office – a very astute observation. As patient observers it is incumbent on all of us to be accurate and objective – that’s for sure.

Have you tried the Phoenix Rising forums? forums.aboutmecfs.org It is in part an online wellness site for people with ME/CFS and there may be people there interested in creating something more specific.

Good luck with everything.

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priscilla November 25, 2010 at 6:49 am

WPI control samples were not 7percent positive. I think it was 3.7.
Seems like we can expect a lot from the next few months! thanks for your reporting.

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Cort November 25, 2010 at 10:59 am

Right! About 4% thanks.

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