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Posts Tagged ‘Prostate Cancer’

As with many scientific discoveries, there is an interesting back story here.

The story begins with a biologist, Robert Silverman of the Cleveland Clinic Foundation in Ohio, investigating if prostate cancer is caused by a virus.

Actually, the story begins a bit earlier than that. Scientists have known that viruses can cause cancer since the early 20th century.

In 1909 Peyton Rous discovered that a virus could cause sarcomas in chickens. For discovering the Rous Sarcoma Virus, Dr. Rous was awarded the Nobel Prize in 1966. This discovery led directly to the discovery of cellular oncogenes (genes that cause cancer) by Bishop and Varmus, which also was rewarded with a Nobel Prize.

Subsequently, numerous other human cancers have been associated with viral infections. The most important of these is Burkitt’s lymphoma. Burkitt’s lymphoma comes in three varieties: one form is endemic to sub-Saharan Africa and is most likely caused in large part by infection with a virus called Epstein-Barr Virus (EBV, which also causes mono), one form is sporadic (as opposed to endemic), and one form is associated with immunodeficiencies such as AIDS. The endemic form of Burkitt’s lymphoma typically causes a large, painful jaw mass, while the sporadic form more commonly involved the intestines. Interestingly, another name for EBV is Human Herpesvirus-4 (HHV-4). EBV, or HHV-4, also causes nasopharyngeal carcinoma in southeast Asia (and elsewhere). It is clear that there is a real connection between viruses and cancer.

Now back to Robert Silverman, who discovered a new retrovirus called XMRV.

The retrovirus was very similar to MLV, a group of viruses that can cause cancer and neurological and immunological diseases in mice. Silverman found XMRV in a subset of prostate tumours, and more recent research found a stronger correlation between XMRV and aggressive prostate tumours.

We should pause for a moment and explain the difference between a virus and a retrovirus. A virus is a very simple organism – basically a protein shell containing a little DNA. Viruses need to find hosts because they lack the tools to multiply on their own.

Cells also contain DNA, but cells (especially those of complex organisms such as humans) have ridiculous amounts of DNA. Most of the instructions in DNA used by cells on a daily basis are for creating proteins. Since mistakes are most likely to occur proportionally to how often DNA is copied, a system using RNA minimizes copying by only duplicating the specific section of DNA needed to build a specific protein. RNA is slightly different than DNA on a molecular level, so cellular machinery can respond to it but not to DNA. A cell which needs a particular protein manufactured goes through the following (simplified) steps:

  1. A portion of DNA is translated into RNA.
  2. RNA is sent to the endoplasmic reticulum.
  3. The specified protein is built.

A standard virus hijacks the cell’s machinery by inserting DNA, which gets translated into RNA, which is then made into the specified protein; only in that case the protein is the virus.

Retroviruses are more insidious. They contain RNA rather than DNA. When a retrovirus attacks a cell, the RNA gets translated into DNA, which then gets incorporated into the cell’s own genome. Rather than hijacking the cellular machinery for their own nefarious plans, they Borg the cell. From then on, every time the cell multiplies it is bringing the virus along with it. Our genome is littered with scars from ancient battles with retroviruses which may have fundamentally shaped us into what we are today.

Alright, enough with the interruptions already.

Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, asked Silverman to see if there was a connection to chronic fatigue syndrome.

Mikovits asked Silverman to analyze the blood samples of 101 CFS patients and 218 healthy controls. The authors detected XMRV DNA in the immune cells of 67% of the CFS patients but in only 3.7% of healthy controls. The authors also showed that the virus was able to spread from infected immune cells to cultured prostate cancer cells and that the virus’s DNA sequence was more than 99% similar to the sequence of the virus associated with prostate cancer. The findings were published in Science.

So far, although the results are encouraging, there has only been one pilot study completed. The magic which makes science work is verification and duplication of results.

William Reeves, principal investigator for the Centers for Disease Control and Prevention (CDC)’s CFS public health research programme, says the findings are “unexpected and surprising” and that it is “almost unheard of to find an association of this magnitude between an infectious agent and a well-defined chronic disease, much less an illness like CFS”.

But Reeves is cautious. “Until the work is independently verified, the report represents a single pilot study,” he says. According to Reeves, the CDC is already trying to replicate these findings. He also notes that CFS is a heterogeneous disease and likely arises from a combination of many factors.

The Wall Street Journal has a heartbreaking example of the suffering caused by CFS:

Ms. Whittemore-Goad says she was a regular school girl, playing sports and involved in school activities, until the age of 10, when she became ill with a monolike virus that she couldn’t shake. She said doctors first told her parents that the illness was psychological, that she had school phobia and was under stress from her parents. “We kept searching for an answer,” says Ms. Whittemore-Goad, who says lymph nodes in her groin were so painful that her brothers and sisters used to have to carry her upstairs. She was diagnosed at age 12 with chronic-fatigue syndrome.

Over the years, doctors have treated her symptoms, like intense headaches and severe pain, but the illness persists. She has had her gallbladder, spleen, and appendix removed because they became infected. She tried an experimental drug that she says gave her relief for years, but she then started experiencing side effects and had to stop taking it. Recently the illness has become worse; she began suffering seizures and can no longer drive.

Go read the whole thing.

If this virus is the cause of CFS, diagnosis and detection can be done with a simple blood test. Antiretroviral therapies designed in the fight against HIV are under investigation as a potential cure. The story is not yet over but we remain hopeful that this breakthrough represents the real deal for sufferers of CFS.

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This is still early stage news, so don’t get too excited. For example, the study itself had some slight flaws.

“Unfortunately, this trial was not a randomized trial, which would have been needed to be more sure that the observed changes were truly attributable to the green tea components and not to some other lifestyle change (better diet, taking vitamins, etc.) men undertook in preparation for surgery,” added Nelson, who is also a senior editor for Cancer Prevention Research. However, “this trial is provocative enough to consider a more substantial randomized trial.”

The men chosen for the study did not sit around drinking tea all day. They received measured doses of one particular compound found in green tea.

The study included 26 men, aged 41 to 72 years, diagnosed with prostate cancer and scheduled for radical prostatectomy. Patients consumed four capsules containing Polyphenon E until the day before surgery — four capsules are equivalent to about 12 cups of normally brewed concentrated green tea, according to Cardelli.

The exciting part is the actual results which were obtained.

Findings showed a significant reduction in serum levels of HGF, VEGF and PSA after treatment, with some patients demonstrating reductions in levels of greater than 30 percent, according to the researchers.

There is still much work to be done, and this seems like a good step in the right direction.

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Dr. Gary D. Kao, at a V.A. hospital in Philadelphia, was supposed to implant radioactive seeds into a patient’s prostate, to eliminate a tumor. However, most ended up in the patient’s bladder instead. With the blessings of his higher ups, he rewrote the surgical plan to cover up the mistake.

Unfortunately for many other patients, 92 out of 116 cancer treatments over the course of 6 years were botched at this V.A. hospital. Many people knew, and had no problem keeping it quiet.

Not because hospitals are above covering up malpractice, or because doctors don’t protect other doctors, but because any private hospital would have been terrified of getting sued.  The VA is very hard to sue because of sovereign immunity.

Something to keep in mind, as certain groups are aggressively pushing for government to take over healthcare in the United States.

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There are two general types of prostate cancer, and one of them is very aggressive. Unfortunately for some men, that means surgery is no longer an option by the time it gets noticed. Fortunately, some great forward strides have been made on this front at the Mayo Clinic to give these men a fighting chance.

Dr. Kwon called Dr. Allison and designed the trial together. The idea: use androgen ablation or hormone therapy to ignite an immune approach — a pilot light — and then, after a short interval of hormone therapy, introduce an anti-CTLA-4 antibody that acts like gasoline to this pilot light and overwhelms the cancer cells. MDX-010 (now called Ipilimumab) is the clinical antibody being tested in the Mayo trial.

This has been tested on two patients so far, with very good results, but some caution is in order.

Both investigators are quick to point out that the outcomes in these two patients need to be validated in further studies. Plans are already underway for extended trials at Mayo Clinic to determine the dosage to optimize this therapy and explain how this combined treatment actually works.

“It’s important for us to understand the mechanism of favorable response in these patients,” says Dr. Blute. “This could have significant implications for other forms of cancer, including hormone-sensitive forms, such as breast and ovarian cancer.

Go read the source material for a detailed account of the patients experiences, and to learn a little more about the treatment.

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