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The memory of things gone is important to a jazz musician. Things like old folks singing in the moonlight in the back yard on a hot night or something said long ago.
- Louis Armstrong

Combinatorial Therapy Allows Viruses to Destroy Tumors

Brain Tumor Treatment, Research No Comments »

Web address:
     http://www.sciencedaily.com/releases/2010/04/
     100401173713.htm
 

Combinatorial Therapy Allows Viruses to Destroy Tumors

ScienceDaily (Apr. 1, 2010) — For several years, researchers have been developing a new approach to treating cancer that uses viruses to infect and kill cancer cells while leaving normal cells unharmed. Recent data have indicated that this approach, which is known as oncolytic virotherapy, has potential.

Now, Richard Vile and colleagues, at the Mayo Clinic, Rochester, have found that this approach can be combined with a standard clinical therapy to provide substantial regression and cure of tumors in mice, leading them to suggest that this combinatorial approach could be of tremendous benefit in the clinic.

Tumors that grow to a certain size need to form new blood vessels if they are to continuing growing and spread to other sites. One of the molecules that controls this new blood vessel growth, VEGF, is the target of drugs used to treat several forms of cancer. In this study, the authors found that modulating VEGF signaling, for example by transiently stopping anti-VEGF therapy in mice harboring cancer cells expressing high levels of VEGF, allowed the cells that line tumor blood vessels to be targeted and killed by viruses.

Importantly, as this approach targets the cells lining tumor blood vessels, rather than specific types of tumor cells, the authors suggest that this combinatorial approach to therapy could be used to treat a wide range of cancers.

The research appears in the Journal of Clinical Investigation.

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Targeted Agent Blocked Growth of Deadly Brain Cancer in Preclinical Studies

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Web address:
     http://www.sciencedaily.com/releases/2010/03/
     100330142426.htm
 

Targeted Agent Blocked Growth of Deadly Brain Cancer in Preclinical Studies

ScienceDaily (Mar. 31, 2010) — A drug already in clinical trials to treat a variety of tumors shows a remarkable ability to shut down growth of glioblastoma in both laboratory cells and in animals, say researchers from Georgetown Lombardi Comprehensive Cancer Center and the University of California, San Francisco (UCSF). In their experiments, the agent put a brake on growth of laboratory cancer cell lines, and no mice with glioblastoma in their brain died as a result of their tumor while on therapy.

They say their findings, reported in the April 15 issue of Cancer Research, provides hope that the drug, PD-0332991, could offer a new treatment option for glioblastoma, which is the most common as well as the deadliest form of brain cancer. A clinical trial testing the therapy in patients with recurrent brain cancer is under development.

“We have had just amazing results in these preclinical studies,” says Todd Waldman, MD, PhD, an associate professor of oncology at Lombardi. “We are hopeful it will prove to be effective in brain cancer patients for which there is little effective therapy.”

Waldman is the study’s co-lead investigator, along with C. David James, PhD, professor of neurological surgery at UCSF. “What is especially encouraging about this agent is that we found it can easily pass through the blood-brain barrier and access glioblastoma, and that there is already a simple test available for screening glioblastoma patients in advance to see whether or not they should be responsive to this therapy,” James says.

Given the molecular data from a recently published study by The Cancer Genome Atlas Research Network, about 90 percent of glioblastoma patients have a molecular profile that would make them candidates for the drug, the researchers say.

The drug is currently being tested in clinical trials for otherwise untreatable teratomas, as well as multiple myeloma and breast cancer. It is designed to shut down the activity of molecules, cyclin-dependent kinases 4 and 6 (cdk4/6), that drive cell division. “In normal cells, these kinases are kept under exquisite control by a gene known as p16,” says Waldman. “But in glioblastoma, and other cancers, p16 is frequently deleted, and these two kinases are uncontrollably activated, which drives the cell to divide and form cancer.”

The agent, however, does not work if the cancer is missing expression of a tumor suppressor protein known as retinoblastoma (Rb) because Rb is needed to control growth in these cells even if cdk4/6 are inhibited. A test to determine if RB is present is already being used to screen patients for use of PD-0332991 in the ongoing clinical trials.

A research team at Georgetown led by Waldman, conducted laboratory studies on 21 different cell lines derived from the tumors of patients with glioblastoma. They tested PD-0332991 at various concentrations to see if it could stop growth of the cancer cells, and found it to be effective in all 16 cell lines with a functioning Rb gene, but it did not work in 5 cell lines missing Rb. “The agent was very potent in stopping cancer growth, but it was also quite clean in that it only seemed to inhibit the two molecules it targeted, and no other,” says Waldman. “Most drugs are dirtier than that — they hit multiple unintended targets.”

What intrigues Waldman, he says, is that no one has discovered what the “normal” function for cdk4/6 is. “Mice lacking either cdk4 or cdk6 grow up to be relatively healthy, so it may be that these kinases are really only important for cancer growth,” Waldman says. “That would be an exciting development, if true, but no one knows yet.”

James led a team of scientists at UCSF that implanted three different kinds of human glioblastoma directly into the brains of mice, and then they treated them with PD-0332991. They discovered first that the agent effectively reached intracranial tumors — “and it wasn’t known beforehand that it would, so this was very good news,” says James — and that the cancer did not grow as long as the mice continued on the drug, but that they quickly died from the cancer when the agent was withdrawn.

Because PD-0332991 itself does not kill cancer cells — just arrests their growth — the researchers then combined the agent with radiation and found that outcomes were superior to use of PD-0332991 alone. They further successfully tested the agent in mice in which glioblastoma had come back after treatment with temozolomide, a chemotherapy that is the standard-of-care for many patients.

“We don’t know how well this agent will perform in patients with glioblastoma, but in the mice we studied, we saw very impressive, durable effect that was sustained as long as therapy was administered,” says James.

The study was funded in part by grants from the National Institutes of Health and the American Cancer Society. Pfizer Global Research and Development supplied PD-0332991, and a researcher from that company also participated in the study.

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Mobile Access

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I’ve quietly been upgrading the blog software behind-the-scenes. I am now beginning to add more functionality such as making the blog accessible from blackberries and iPhones as well as adding small improvements such as threaded commenting and the ability to share posts through more of the social  networking sites.

As for the mobile application, as with many it’s a scaled-down version of the blog. I can post to it from anywhere and readers can read the posts, comment on a post and use the contact form to contact me.  All of my research is also there.

Here is a look at a few of the blog screens on an iPhone:

This SimpleViewer gallery requires Macromedia Flash. Please open this post in your browser or get Macromedia Flash here.
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Is There A Brain Tumor Virus?

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Interesting story from Newsweek.  I donated tissue for research by Charles Cobbs as part of my last surgery.

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Drug Slows Brain Cancer, Calgary Researchers Say

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This is the very type of research and discovery that we all want to see – that makes us hold on, push our lives out as far as we can.  Yes, we who have GBMs have the odds stacked against us but there are a lot of advances being made so it’s important to hang in there. 

I hope everyone is ready / enjoying the Holiday Season…

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CBS News: What’s Behind the Mystery Cancer Cluster?

Research 12 Comments »

As we all know, there is very little information with regard to the genesis of primary brain tumors / brain cancer.  Unlike most cancers, there are no genetic or environmental correlations that can be easily made to explain why we have been diagnosed with our disease.  Suffice it to say, short of blowing asbestos through a hose in attics as a career, you’re hard-pressed to find an answer.  And, as difficult as that may be to not have an “answer”,  it is comforting to know that there isn’t a lot of evidence to suggest your children will be subject to a brain tumor.  For a group of residents in a small community in Northern Illinois, they may very well have an answer for the cause of their brain cancer which leads me to a blog comment I received late this afternoon…

Someone at the “CBS Evening News with Katie Couric” left a comment and brought my attention to an exclusive they were airing tonight on the CBS Evening News about a brain cancer “cluster” they discovered in the small community of McCullom Lake Village in Illinois.  More than a dozen cases of primary brain tumors, some on the same street – adjoining neighbors – across the street neighbors.  Unbelievable.  Well, when I read her comment I certainly became more interested, particularly considering there is no solid science behind the cause of brain tumors.

First off, at a high level, I went out to the National Cancer Institute into their analytics database – I was simply curious about the national incidence rate of brain cancer.  One would think that it might step in line with the most populous states, yes?  It doesn’t.  Now, as a GBM survivor with the “you don’t have many years left” (yeah right) statements being thrown at me, I really don’t want to spend my time researching this, but I do find it interesting at some level that some of the Northeast and Midwest states have the highest incident rates.  It’s off the beaten path but take a look at this – it’s pretty interesting just to study for a moment:

12-15-2008-8-02-26-pm.jpg

The CBS story is taking this map and putting a pin in the upper right corner of Illinois – McCullom Lake Village.  There is no reason to paraphrase the story.  NOTE:  I had a link here but the story is now a VIDEO ONLY.  I am using CBS’s embedding code to embed the report below:


Watch CBS Videos Online

From my standpoint, this could very well be a case where you can tie brain tumor cause and effect together.  As the story indicates, you have scientists in the same hall all suffering from primary brain tumors.  You have residents on the same street suffering.  I volunteer through the NBTS and get emails from the newly diagnosed who are sometimes in other states – just looking for support.  These folks have a support group just among themselves.  Let’s also keep in mind – only 20,000 primary brain tumors are diagnosed annually – slice that up between Glioblastomas, Oligoastrocytomas and other types and this is not a coincidence – at all.  This is obviously my own, personal opinion.

This is not a “Love Canal” situation but in my opinion it’s close.  The fact is you have chemicals running under ground (the Love Canal involved some 10K+ tons of  toxic waste buried underground) and this was within striking distance of water supplies and a lake around this community.

The bottom line?  Who are any of us to think that anything around us may or may not cause various types of cancer.  We always hear reports about what to do and what not to do.  One day a glass of cab is great for your heart, the next day it’s the worst thing you can do!  It’s great to avoid what you can control – and we all should.  However, when you have a town of innocent, unsuspecting people who are just living their lives and a cluster of them are diagnosed with primary brain tumors, you have to stop and look at the environment.  For me, this is clear cut but unfortunately it’s going to take a lot of money, court battling and jousting and will drag some very wonderful people through some hard trials.

I applaud CBS for they have accomplished here.  In my view, the environment ties into this but I can only say this based on the circumstances.  Science needs to take over and prove this out but I think given the right authority to do so, this will come out right.

Lastly but absolutely the most important, I pray for each and every one of the brain tumor survivors in that community, that they obtain the care they need and that the courts prevail upon the appropriate parties to resolve this issue.  I pray that their families find comfort in the light CBS is shedding on the issue and that they feel that they aren’t fighting this battle alone.

If I can say anything to them?  You aren’t alone – I think you all know that.  I know it must be even more difficult to believe your brain tumor was caused by your environment but like all of us, we have today – it’s the day we were given so we all need to be grateful for what we have – a gift.

Mark

Remember the film Erin Brokovich?

I’d like to thank Kelly Rippin again for pointing this out to me.  Great story.

Updated:  

This is a picture of the Santa Ana River Jetties in Huntington Beach/Newport Beach, California that relates to several of the comments submitted.  You’ll have to read the comments.  I don’t know anyone else in my position however except for Michael.

jetties.jpg

Best…

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Research Mode

Research 3 Comments »

Rachael and I are going to meet with my Neurosurgeon tomorrow at around Noon.  The meeting was set up on fairly quick notice but mostly because I’m pressing.  The vaccine work appears to be tracking in the background although as I have said before, this is a grade 4 tumor.  There is no single solution, vaccine or not.  If there is one premise that can be learned about high grade gliomas it is this – you have to keep them guessing. 

Our meeting tomorrow is going to be one of strategy.  My doctors have been looking far and wide at many different types of treatment – to potentially augment our vaccine treatment if it is not performing to our success criteria and b) as follow through after the vaccine.  A lot of dialogue has taken place between the institute here and UCSF as I understand it but of course I will find out a lot more tomorrow.  Well, make that today – it’s 1:15am!  Which brings me to my research.

I’m not ususally a night owl at ALL.  In fact, I’m in bed at 9 or 10pm.  There are times though that I think I just need to put some hard work in and this happens to be one of them.  Before my first, I spent so much time researching, amassed the research library you’ll find under the Library Tab above but most importantly, armed Rachael and I with information we needed to make intelligent, well-informed decisions about my care (i.e. second opinion re watch and wait vs have surgery).  So tonight is no different.  I may not sleep – I do have a lot on my mind tonight.  We talk about comment about staying in today.  I am squarely in today – believe me.  And today is about focusing on my treatment options, my health, working with the doctors and Rachael and ensuring that I have the latest “refreshed” information I can.

There are a number of treatments out there that will likely come up.  One is something called CDX-110 which I have heard of.  I really don’t know if this is feasible or not.   With CDX-110, the vaccine targets an abnormal form of a growth-promoting hormone and the vaccine is thought to boost the immune system’s ability to fight any residual cancer.   Another is a treatment at UCLA.  It’s different than the DCVax-Brain.    There will be countless others and some criteria by which to select, prioritize and implement a treatment based on where I am in my recovery process.  However, it’s clear that the DCVax-Brain is the treatment out of the gate that is being pursued.

If I didn’t mention it, I have placed a number of docs in the library tonight should you be interested:

That’s all for now.  I am going to try to get some sleep before the whole night is gone!  But this was time well spent.  Between the time and research I have already put into this and tonight’s work, I think we’ll have a productive discussion.

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Brain Tumor Resource Library

Research No Comments »

For quite some time now I have wanted to organize my research and documentation in such a way that I could share it online. I have come up with a tool that allows me to do that but I am still working out the bugs. So, this is what I will call a “beta release”. You’ll find the library by clicking on the “Library” tab at the top of the site. Once you access this page, you’ll find a listing of publications, research articles, documents pertaining to diet, nutrition, etc. and templates I have created that have helped me with my treatment and have helped to educate me through this journey. My hope is that you will benefit from the research that I have done. It is my way of giving back.

I had to look all over the place to get my hands on this information. My thinking is if you can find a lot of what I had to find in what seemed like hundreds of locations on the internet, than I have met my objective. Couple that with hopefully speeding you along in getting you up-to-speed with what you are facing, then I have hopefully helped you and have given back. That’s my goal. For me, that was one of the most intimidating aspects of the beginning moments of this journey – information overload. What information do I really need. So, I went out and sorted through a ton of information and was able to get what I felt was the information I needed.

For now, there is certainly plenty there to keep anyone busy – particularly if you are on the front end of this journey. Feel free to download the docs. Keep in mind that some of this information is copy-written as noted in the documents. Therefore, this is meant for personal use only. There are plenty of other docs that I put together based purely out of research and pulling all of that together and aggregating it in a single document. The point? Don’t mass produce this stuff and be a tool! Use it to help yourself and to help you be your own advocate in your recovery and treatment.

I will be adding to the library when I have time. Also, if you have any issues with the library just know that it’s an initial release here and I’m still working out some issues with the downloading function and some other aspects of how the system is working.

I hope you find value in this!

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