Sunday, April 29, 2012

Giving Thanks… Five Years Later..Melanoma..Jim Breitfeller

Giving Thanks… Five Years Later

Back in July of 2005 I was diagnosed with Melanoma Cancer. It has turned my life inside out and upside down. Here is a note that I sent to my colleagues at Eastman Kodak.


Dear Friends and Family,


I wanted to take a moment to let you know that I’ll be leaving my position at Eastman Kodak Company as of March 9, 2007. I will be starting a new phase of my life trying to win this battle of cancer. My short term disability ends and the long term starts.


I have enjoyed my 25 years there and I appreciate having had the opportunity to work with each and every one of you. Thank you for the support, guidance, and encouragement you have provided me during my time at Kodak. Even though I will miss my colleagues and the company, I am looking forward to this new challenge and to starting a new phase of my life. Even though the paths are many, I must go down each one to find the “Yellow Brick Road.” With your support and encouragement we can beat this disease together.

Please keep in touch,


Jimmy B


It has been five years now and I believe I accomplished what I had set out to do, that was to beat this disease melanoma. With the help of family, carepage friends and researchers, oncologists, we have come a long way. I have spent most of my waking hours researching and helping fellow melanoma comrades traverse the canyons of this disease. Along the way I have met and lost so many friends to this disease and only wish that they could be here today to celebrate with me.



Without you, I would not have been so focused on finding a cure. So today , I just want to say thanks for everything. Thanks for keeping me on the right path and believing in me. We are making great inroads in understanding the immune system and how it can be trained to eradicate Cancer. We are in the emergence of the renaissance (A rebirth) of Immunology and Combinatorial Therapy. I believe whole heartedly that we will see a Cure for cancer in my lifetime.

We must keep on persevering to obtain that goal.


Jimmy B


“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B

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Friday, April 27, 2012

Macrophage Activation… The Missing Link to Activation an immune response to Melanoma..Jim Breitfeller


"The development of Th1 cells producing high levels of IFN-gamma could not be induced with dendritic cells alone but required the addition of appropriately activated macrophages." Et al A. O'Gara March 23, 1993 "Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from αβ TCR transgenic mice: IL-12 substitution f.or macrophages to stimulate IFN-γ production is IFN-γ-dependent"
Local IL-12 therapy stimulates Th cells to secrete Th1 cytokines. Exogenous IL-12 application creates an environment rich in IL-12 around the cancer site. In such a local environment, newly activated Th cells, responding to the presence of cancer, exit the blood and are influenced to become Th1 cells and secrete more Th1 cytokines and activate macrophages and NK cells. Activated macrophages will produce more IL-12 and via positive feedback, cell-mediated immunity can be promoted to battle the cancer thereby leading to the prevention of reoccurrence. As you can see, the activated macrophage secretes IL-12, IL-1a, IL-1b, and IL-6 along with a Chemoattractant, IP-10. Without macrophage activation, the immune response does not take place and the patient will relapse.(see graphic below)
With IL-1b and IL-6 missing, the T-Regulatory Cells (Tregs) rule the Tumor's Microenviroment. IL-6 controls Th17 immunity by inhibiting the conversion of naive CD4+ T cells into Foxp3+ regulatory T cells. IL-1β–Mediated Signals Preferentially Drive Conversion of Regulatory T Cells but Not Conventional T Cells into IL-17–Producing Cells (Danger Signal).So if the IL-1b signaling is missing,conversion of the Tregs never take place along with no Danger Signals.
Dr. Steven Rosenberg is using engineered T-cells that secrete IL-12 to stimulate Th cells to secrete Th1 cytokines. This sets in motion the positive feed back loop needed to initiate an immune response. His therapy is show great promise. “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.” ~Charles Darwin~ Take Care, Jimmy B
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Thursday, April 26, 2012

Wednesday, April 25, 2012

Interview with Dr. Jim Allison. ..The making of Yervoy..Melanoma..Jim Breitfeller

To Cure cancer, your immune system  must make memory cells that can distingush Melanoma cancer when and if you relapse. This done in at initial stage of T-cell Differentation and propagation. You must have the right Melieu (An environment or a setting) in place. This can be done with Systematic Combinatorial Therapy.
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.” ~Charles Darwin~ Take Care, Jimmy B Photobucket

Sunday, April 22, 2012

Thinking outside the Box for the Elderly Melanoma Cancer Patients..Jim Breitfeller

Immunotherapy and Cancer - KTVN Channel 2 - Reno Tahoe News Weather, Video -
New rules of engagement for older patients The body’s immune system does weaken with age, but it also changes, and that changes the rules for fighting disease within the body. Dr. Curiel’s group started by examining an immune therapy that they previously had shown to work in younger hosts, including cancer patients. It’s designed to eliminate regulatory T cells (called Tregs), which are cells that turn off immune responses, allowing cancer to progress. Tregs increase in cancer. In young hosts, the drug turns off Treg activity, allowing the immune system to function better. In older hosts, even though the drug turns off the Tregs, it has no clinical benefit. Dr. Curiel asked the question why, and in this paper his team explains the answer. In older mice, when the drug turned off the Tregs, the researchers found that another type of immune suppressor cell (a myeloid-derived suppressor cell or MDSC) exploded in number to take the Tregs’ place, hampering clinical efficacy. That did not happen in young mice. The team added a second drug that targets the MDSC, and found that with those tools to help immunity, the older hosts can combat cancer just as well as the younger hosts. Adding the second drug afforded no clinical benefit to young hosts, as their MDSC numbers had not increased. “We’ve shown that an aged immune system can combat cancer just as well as a young one if you remove the impediments to successful immunity, which are different than those in younger hosts,” Dr. Curiel said. “We’ve shown that if you test all your immune therapy just in young mice and young people, you’ll never learn how it works in older patients — the ones most at risk for cancer. You might conclude that drugs don’t work in aged hosts, when they do. But they have to be combined with some help.” Human trials on the horizon The next step is to test these concepts in an immune therapy clinical trial for elderly patients, which the research team plans to do, Dr. Curiel said. The drug that is added is anti–Gr-1 antibody and would have to get approval from the FDA, meaning Clinical Trial. With that said, What if we added 5-Fluorouracil to immunotherapy like Yervoy and or Anti-PD1. 5FU immunogenic effects are primarily attributable to MDSC depletion. 5-Fluorouracil selectively kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity. This would be the one, two punch for elderly cancer patients. Let's Think outside the box. Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells with the ability to suppress T-cell activation in humans and mice. These cells accumulate in the blood, lymph nodes, bone marrow, and at tumor sites in many human cancers and animal tumor models, and inhibit both adaptive and innate immunit. They notably have the capacity to inhibit CD8+ T cell antigen-specific reactivity by different mechanisms, mainly through their capacities to produce nitric oxide and radical oxygen species.




“It is not the strongest of the species that survives, nor most intelligent, but the one most responsive to change.” ~Charles Darwin~ Take Care, Jimmy B Photobucket

Friday, April 13, 2012

I finally have some good news to report!..Julie..Melanoma ..Jim Breitfeller

I finally have some good news to report!

Quick review: Dx Feb 2011 WLE SNLB positive microscopic 1 node. Complete rt groin dissection- rest of nodes negative. Did high dose interferon May 2011, 1 high dose injection then stopped. Surgery July 1 for recurrence at bottom of lymph node scar. Did 4 rounds biochemo- July , august, sep, oct. Recurrence again in same area surgery end November. Started Yervoy end dec had 2 rounds then did radiation to right leg 20 treatments. Finished 4th Yervoy on 2/15/2012.

First PET/CT post Yervoy 02/28/2012 showed "Extensive progression of malignant disease with development of multiple, hepatic, osseous and pulmonary metastatic lesions."

Labs were also awful- LDH got up to 414. Liver enzymes markedly elevated alk phosphatase 374, ast 499, alt 1106.

Labs yesterday-LDH 152 normal!!. Liver enzymes alk phosphotase 142, ast 81, alt, 111 these are still a little high, but markedly improved.
PET/CT: " Very pronounced improvement in metastatic disease. Most of the pulmonary modules noted previously are no longer visible. A few small punctate nodules remain. Only one has identifiable activity on PET portion with < 1 SUV. It measures only a few millimeters. Hepatic metastatic disease has significantly improved. Very significant improvement in skeletal metastatic disease. Many lesions are no longer visible."

Hallelujah!!!!!!!!
Can't stop doing the happy dance.

I'm praying for all to see some improvement in their disease and even a cure.
Hope this post gives some hope to others. I really wonder if the biochemo with IL2 followed by Yervoy along with some radiation is the key to my body finally getting the message.

Julie in Las Vegas

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Julie, Congrats!!!!!

"I really wonder if the biochemo with IL2 followed by Yervoy along with some radiation is the key to my body finally getting the message .".."

You are right on target. The biochem with IL-2 primed your Immune system, while Yervoy deactivated the T-Regs cell suppression of your T-cells. Radiation added the tumor cell debris that is needed to be presented on the Dendritic Cells which are acting as the Antigen Presenting Cells (APCs). The process can be presented in this Diagram.




Remember the this blog. It will lead to a CURE!!! Combinatorial Therapy


“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


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Greetings to One and All

This Blog is dedicated My Brother Kenny B. who passed away in the late 1970's with Cancer before the Internet.

It was he, who showed me How to live and give back. He was wise beyond his years.



Kenny B




Jimmy and Dee

Carepage: Jimmybreitfeller
Jimmy Breitfeller


My Profile as of 2009

My photo
Last July (2005)I was riding my bicycle to work at the Eastman Kodak Research Labs about 3 miles from home. I was wearing a knapsack to carry my things to and from the labs. I started noticing an ache on my back. So I decide to go to the dermatologist. To make the long story short, it was cancer. I knew from my research that I would be needing adjuvant therapy. So I started communicating with Sloan Kettering, University of Pittsburgh Cancer Center, and a couple of others including the Wilmot Cancer Center at Strong. I realized that by telling my story, I might help someone else out there in a similar situation. So to all who are linked by diagnosis or by relation to someone with melanoma, I wish you well. Stay positive, read as much as you can (information helps to eliminate the fear associated with the unknown), and live for today, as no one can predict what tomorrow may bring. Jimmy B. posted 12/15/08

Disclaimer

The information contained within this Blog is not meant to replace the examination or advice of your Oncologist or Medical Team. The educational material that is covered here or Linked to, does not cover every detail of each disorder discussed.

Only your physician/Oncologist can make medical decisions and treatment plans that are appropriate for you. But, An Educated Consumer is a Smart consumer.

As Dr. Casey Culberson Said:

"The BEST melanoma patient is an ACTIVE PARTICIPANT in his or her treatment
(not a PASSIVE RECIPIENT)"

Melanoma and the “Magic Bullet” (Monoclonal Antibodies)

Just to let you know I posted the first draft of the Melanoma and the “Magic Bullet” (Monoclonal Antibodies). on Melanoma Missionary In the Shared File Section. you can download it for 19.95 (Only kidding) it is Free for the taking.


It is 33 pages long and may help you in your quest for the Yellow Brick Broad. Just to let you know it is only the first draft. Revisions are sure to come. I wanted to get it to the people that need it the most, the Melanoma Patients.

Preview:

So, where does Interluekin-2 (IL-2) come into play? According to Byung-Scok et al and recent reports, IL-2 is not needed for developmental CD4+ CD25+ Treg cells in the thymus but does play an important role in the maintenance and function in the peripheral.18 Peripheral is defines as secondary system outside the bone marrow and thymus. It entails the site of antigen, immune system interaction. IL-2 is required for the peripheral generation of Tregs based Abbas’s and colleagues research.19

IL-2 prevents the spontaneous apoptosis of the CD4+ CD25+ Treg cells. It has been reported that patients with multiple advance-stage tumors have elevated levels of Tregs within the tumor microenviroment.20 Interluekin-2 is the survival factor for CD4+ CD25+ Treg cells.21 If the addition of IL-2 is on or before the maximum propagation of the CD4+ T cells, the Tregs population can increase 5-fold in a 96 hour period based on certain growth mediums.

By controlling the addition of the endogenous IL-2, one has a knob to turn and can lead to the control of the expansion of the Tregs. When you combined this control with the anti-CTLA-4 blockage, you can shift the balance of the immune response.

Now here is the catch. The maintenance and function of the CD8+ T-cells require CD4+ cells which secrete IL-2. So we don’t want to deplete the CD4+ cells, we want to control the expansion of the Tregs which are a subset of the CD4+ cells. It has been postulated by some researchers that the Anti-CTLA-4 blockage also suppresses the Treg function in a different mechanism. By using IL-2 as the rate limiting factor, we can suppress the CD4+ CD25+ Treg cell expansion by controlling the concentration and timing of the Inerluekin-2 at the tumor microenvironment.


The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+ T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. As stated previously, CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or more perforin molecules insert themselves into the plasma membrane of target cells forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end for the cancer cells. The tumors begin to shrink and the rest is history,



On the other hand, prolong therapy with Il-2 can result in causing apoptotic death of the tumor- specific CD8+ T-cells.23

Clearly in a clinical setting, timing, dose, and exposure to these drugs play a major roll in the immunotherapy, and can have dramatic effects on the outcome.

All it takes is that one magic bullet to start the immune reaction..

https://app.box.com/shared/kjgr6dkztj

Melanoma And The Magic Bullet (Monoclonal Antibodies)

Public Service Announcement

A call for Melanoma Patients by Dr. Steven A Rosenberg

"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.

"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."

If you would like to apply for his trials, here is the website and information.

Dr. Rosenberg's information


Dr. Rosenberg's Clinical Trials


For the Warriors




The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen’s public service announcement inspired by Danny Federici. Danny was the E Street Band’s organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.


http://www.melanomaresearchalliance.org/news/PSA/

Source Fastcures blog



Join the Relay for Life!!!

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Dear Family and Friends,

I’ve decided to take a stand and fight back against cancer by participating in the American Cancer Society Relay For Life® event right here in my community! Please support me in this important cause by making a secure, tax-deductible donation online using the link below.

To donate on line now, click here to visit my personal page.
Jimmy B AKA Melanoma_Missionary

Relay For Life® is a life-changing event that brings together more than 3.5 million people worldwide to:

CELEBRATE the lives of those who have battled cancer. The strength of survivors inspires others to continue to fight.

REMEMBER loved ones lost to the disease. At Relay, people who have walked alongside people battling cancer can grieve and find healing.

FIGHT BACK. We Relay because we have been touched by cancer and desperately want to put an end to the disease.

Whatever you can give will help - it all adds up! I greatly appreciate your support and will keep you posted on my progress.

Keep the Fire Burning!!!

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Sincerely,

Jimmy Breitfeller
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer

How Skin Cancer Develops by "About.com : Dermatology"

Call for Patients with Unresectable Liver Metastases Due to Melanoma



Delcath Systems Granted Orphan-Drug Designations for Cutaneous and Ocular Melanoma


Delcath is actively enrolling patients in a Phase III clinical trial testing its proprietary drug delivery system, known as Percutaneous Hepatic Perfusion (“PHP”), with melphalan for the treatment of ocular and cutaneous melanoma metastatic to the liver.

This NCI-led trial is enrolling patients at leading cancer centers throughout the United States. Commenting on these orphan-drug designations, Richard L. Taney, President and CEO of Delcath, stated, “These favorable designations are important steps in our efforts to secure Delcath’s commercial position upon conclusion of our pivotal Phase III trial for metastatic melanoma. We remain steadfast in our commitment to become the leader in the regional treatment of liver cancers and we continue to enroll patients in this study, and advance our technology and the promise that it offers to patients with these deadly forms of melanoma and other cancers of the liver, all with limited treatment options.”

Orphan drug designation, when granted by the FDA’s Office of Orphan Products Development, allows for up to seven years of market exclusivity upon FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.


Current Trial Centers


Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using
Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies



James F. Pingpank, Jr., MD, FACS
Associate Professor of Surgery
Division of Surgical Oncology
Suite 406, UPMC Cancer Pavillion
5150 Centre Avenue
Pittsburgh, PA 15232
412-692-2852 (Office)
412-692-2520 (Fax)
PingpankJF@UPMC.edu


Blog Archive

Call For Melanoma Patients!!!!

Call For Melanoma Patients!!!!

Dr. Rosenberg Has a New Clinical Trial.

Our latest treatment has a 72% objective response rate with 36% complete responses.

We are currently recruiting patients for our latest trial.

Is there some way to post this “Call for Patients” on the web site?

Steve Rosenberg

Dr. Rosenberg's Clinical Trials



(For a copy of the research paper.. see My Shared files)

The news headlines shown above for Melanoma / Skin Cancer are provided courtesy of Medical News Today.