Day 832: Scrapieing the Bottom of the Barrel

If you've heard the wild stories about experimental mRNA vaccines causing cancer and prion disease but brushed them off because the mechanism by which they might have such outrageous effects is unclear, the bad cat has some bad news for you:

a nasty ringer is the emergence of the GGGG quadruplex (made easier by adding more G’s) which can cause neurological disease and bind to prions.

this may actually be quite a lot worse in that it appears that you do not even need a full quadruplex for this to happen. duplexes will do if the protein can fold in such a way as to generate what is effectively a quadruplex binding site and thus based on THIS study, all of these sites can play this role: (i) d(TGGGGT), (ii) r(GGAGGAGGAGGA) and (iii) d(GGAGGAGGAGGA) can serve as a quad.

this appears to facilitate the transition of PrPc into its pathologic isoform.

that’s bad.

If you don't recognize PrPSc in the above, just keep in mind that now is not the time to take up cannibalism. And in the future, avoid new technologies that have gone down in flaming failure with horrific side-effects in every previous trial, but are allegedly working perfectly this time.

Speaking of the trials, Steve Kirsch, not content with breaking the news of all-cause mortality being up for the vaccinated in Britain by their own numbers, has also publicized evidence of what the internet cats call pfraud in the latest data dump: Pfizer fraud? Or just great execution? He waffles on whether what happened in Argentina was actual fraud, but of course there were yet more side effects that never made it onto the label:

Neither Augusto’s pericardial effusion, nor another volunteer’s penile vein thrombosis, appear to have found their way into the reported side effects of this trial.

P.S. Massachusetts cases were up a third of a percentage point today.

DFTD2: The Sequel

Tasmanian devil disease recently got curiouser when a graduate student identified a second cell line:

In March 2014, Murchison’s colleague Ruth Pye, a graduate student at the University of Tasmania, noticed something weird about a facial tumor taken from a devil captured just north of Hobart. Physically, it looked like DFTD; genetically, it was clearly something different. For example, DFTD cells have lost their X and Y sex chromosomes, both of which were present in the new tumor. Pye reasoned that this particular devil had spontaneously developed its own type of facial tumor that looked like DFTD, but wasn’t. It was a one-off.
Except, a few months later, she found the same genetically distinct tumor in a second devil from the same area. In both cases, the tumors bore absolutely no genetic resemblance to either DFTD or their respective hosts. These devils had developed a second type of contagious cancer.

They've found a total of eight infected devils and published their results this January.

Cure Your Own Cancer

Via plime: the AP reports on a Duke University student working to find a cure for his own rare form of cancer:

Chordoma — the cancer Josh learns he has — is a one-in-a million disease. Just 300 people get the terrible news each year, not even one per day. It strikes all ages, at different spots along the spinal column. The tumors can be removed, but the cancer is relentless. Chemotherapy doesn’t work. Life expectancy is around seven years.
The MRI shows Josh’s tumor is in a tough spot, in a bone inside his skull. It extends onto his brain stem and wraps around several arteries. There are two surgeries, then weeks of recovery in the hospital. He and Simone pass the time reading whatever they can about the disease.
There isn’t much. The massive apparatus of medical research — pharmaceutical companies, foundations, universities, government agencies — is utilitarian. High-prevalence diseases are at the front of the line, rare ones like chordoma usually at the back.
But then, a stroke of good fortune. It turns out that the only researcher in the country with a grant to study chordoma happens to be at Duke, working in a VA lab across the street from campus.

Josh later cuts back on his research activities in favor of the Chordoma Foundation which he and his mother founded to better organize research into chordoma. The article also mentions a few other patient-researchers.

Acromegaly in the News

Via pilme: the Daily Mail reports on a chance meeting at a restaurant that led to a diagnosis of acromegaly, a rare condition that affects 3 people in a million.

The life-saving handshake happened on December 6, when lifelong friend Rob Thompson brought Dr Britt to an Italian restaurant Mr Gurrieri runs in Canary Wharf.
"I came out to meet them at the door. My friend, Rob, brought Chris along for the first time," he said.
"We shook hands and I sat them down at the table. He didn't say anything to me at the time but he turned to Rob as soon as he sat down and said 'I'm sure he has acromegaly, I can tell you. I'll stake my career on it.'
"Rob didn't tell me straight away. He came in two days later and was really nervous about telling me.
"I got straight on the internet. I read down the lines and saw the word 'tumour'. That word is frightening, especially when it has to do with the head.
"I went to my GP with everything I could print off from the internet and waved it under his nose.
"He looked it up and said he wasn't sure but would send me off for a blood test and MRI scan. They came back positive for acromegaly."
The condition, in which a tumour grows on the pituitary gland, causes an increase in growth hormones that can cause giantism in children.
In adults, it causes soft tissues to be deposited in the hands and growth of the skull bones.

Birthwort and Balkan Nephropathy

Via ProMED-mail: New Scientist reports on the likely solution to a longstanding mystery.

Since it was first formally recognised in 1956, the disease called endemic Balkan nephropathy has perplexed experts, who have considered various explanations, including groundwater contamination.
Unlike most patients with kidney failure, people with the Balkan illness often have healthy blood pressure. Nonetheless, as their kidneys begin to fail they require dialysis and about half of them eventually develop a rare cancer of the upper urinary tract.
Arthur Grollman, at the University at Stony Brook, New York, US, did not expect to discover birthwort as the cause of this kidney disease when he set out for the region a few years ago. Instead, he had hypothesised that herbal remedies were to blame for this nephropathy.
[... H]e surveyed patients in dialysis clinics in the region on whether they had taken any herbal medicines. But none reported taking such supplements.
Disappointed his theory had proved wrong, Grollman headed for home – but not before killing a final afternoon in a library in Zagreb, the Croatian capital.
There, he came across a striking description from the 1930s about how horses in the region had developed kidney failure after grazing on a plant known as Aristolochia clematis, also known as birthwort. Grollman immediately cancelled his flight and set off to meet Balkan farmers.
A survey of their fields and mills revealed that some of their wheat was indeed contaminated with Aristolochia clematis seed. Back in the lab, Grollman and his colleagues examined kidney samples from Croatian nephropathy patients. They found the same telltale signs of DNA damage linked to Aristolochia clematis as seen in animal studies.

PlagueBlog recommends weeding the wheat.

DCA Research Page

The University of Alberta now has a webpage of DCA Reseach Information, including plans for clinical trials:

Investigators at the University of Alberta have recently reported that a drug previously used in humans for the treatment of rare disorders of metabolism is also able to cause tumor regression in a number of human cancers growing in animals. This drug, dichloroacetate (DCA), appears to suppress the growth of cancer cells without affecting normal cells, suggesting that it might not have the dramatic side effects of standard chemotherapies.
At this point, the University of Alberta, the Alberta Cancer Board and Capital Health do not condone or advise the use of dichloroacetate (DCA) in human beings for the treatment of cancer since no human beings have gone through clinical trials using DCA to treat cancer. However, the University of Alberta and the Alberta Cancer Board are committed to performing clinical trials in the immediate future in consultation with regulatory agencies such as Health Canada.

A Cure for Cancer?

Via GeekPress: NewScientist.com reports on dichloroacetate (DCA), a cheap, unpatented potential cancer drug:

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.
DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

A Virus for Prostate Cancer

Via Gene Expression: An article in the March issue of PLoS Pathogens, "Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant", connects yet another cancer to a viral agent.

Prostate cancer is the most frequent cancer and the second leading cause of cancer deaths in US men over the age of 50. Several genetic factors have been proposed as potential risk factors for the development of prostate cancer, including a viral defense gene called RNASEL. A common genetic variant in this gene, R462Q, was recently implicated in up to 13% of prostate cancer cases. Given the antiviral role of RNASEL, the authors sought to examine if a virus might be present in prostate cancers associated with the R462Q variant. Using a DNA microarray designed to detect all known viral families, the authors identified a novel virus, named XMRV, in a subset of prostate tumor samples. Polymerase chain reaction testing of 86 prostate tumors for the presence of XMRV revealed a strong association between the presence of the virus and being homozygous for the R462Q variant. Cloning and sequencing of the virus showed that XMRV is a close relative of several known xenotropic murine leukemia viruses. This report presents the first documented cases of human infection with a xenotropic retrovirus. Future work will address the potential connection between XMRV infection and the increased prostate cancer risk in patients with the R462Q RNASEL variant.

Gene Expression also links a second article about Borna disease virus and neurological disease.

HPV Vaccine

MedBroadcast reports on the new vaccine against human papilloma virus, the STD responsible for most cases of cervical cancer.