Monday, January 18, 2010

Eureka!!!!!! A possible cure for Melanoma, the Deadly Skin Cancer..Jim Breitfeller

Eureka!!!!!! A possible cure for Melanoma, the Deadly Skin Cancer.
Jim Breitfeller, a patient/survivor/researcher of Matastatic Melanoma has so far beaten the odds of survival. After years of researching his own treatment, he has scientifically figured out why his treatment has worked. Jim explains it like this:

“You need the tumor specific antigens, (The Keys), you need the (Spark Plug) Anti-CTLA-4 and you need the (Gas) IL-2. Without these three key components your car won’t run.”

CTLA4 Role in Immune Function
Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA4) is a protein involved in T-cell expansion or replication and activation in response to an immune event. Following T-cell stimulation, T-cell proliferation is up-regulated. Following successful response, CLTA4 is also up-regulated, which then sends an inhibitory signal to down-regulate or decrease T-cell proliferation and IL-2 production. This is one of the brakes associated with immune system so it won’t go into overdrive and create a possible autoimmune event.
In the presence of the tumor’s microenvironment, the CTLA4 molecule is upregulated on the T-Cells with the help of TGF-beta, a suppressive Cytokine secreted by the tumor cells. TGF-beta requires CTLA-4 early after T-Cell Activation to Induce FoxP3 and generates adaptive CD4+CD25+ Regulatory Cells. et al Song Guo Zheng and colleagues.

If you add the combination of IL-2 and TGF- beta at the beginning of the treatment, it induces naive or total CD4+CD25– cells to develop strong suppressive effects both in vitro and in vivo according to Horwitz et al 2001. The T-Cell differentiation is pushed towards developing Treg suppressive immune cells.

Anti-CTLA4 monoclonal antibodies block the ability of CTLA4 molecule to down-regulate T cell proliferation. The theory behind this therapy is that by decreasing the inhibitory signal, there will be a subsequent increase in the number of activated T-cells available, to improve the ability of the T-cells to recognize melanoma cells as non-self.
Tregs show remarkably suppressive activities on different components of the immune system, including T lymphocytes and dendritic cells, suggesting they act both at the initiation phase (DC) and at the effector phase (activated T cells) of the immune response. Interestingly, temporal depletion of Treg has been shown to enhance anti-tumor immune responses and in case of prolonged absence of Treg even autoimmunity.

The green boxes show possible Therapeutic Intervention,

By blocking the CTLA-4 receptor, you keep the T-cell activated, you push the T-cell differentiation towards the TH17 cells and you now have that the Third signal, (The inflammatory signal) that is needed to induce an Immune response. et al Ribas

By adding the HD IL-2 after the expansion of the T-cells, IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of tumor-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells. et al Wherry

CTLA-4 blockade in cancer immunotherapy.

Dendritic cells can sample tumor antigens and present them to T cells. (A) Although activation of dendritic cells may result in upregulation of B7.1/B7.2, the potentially responsive T cells expressing reactive TCR may be inhibited from effector function by inhibitory signaling via CTLA-4 and PD-1.

Blockade of CTLA-4 signaling may allow unopposed CD28 costimulation, resulting in recruitment of these T cells as antitumor effectors, either directly or as helpers of CD8-mediated T cells responses. Activated cytotoxic T cells can then affect antitumor responses. CTLA-4 expressing regulatory T cell populations may still be locally active in suppressing antitumor responses. Their activity could also be directly downregulated by CTLA-4 blockade, although the relative importance of CTLA-4 expression to their function remains controversial.

Recent research by Probst et al reveal that resting dendritic cells induce peripheral CD8+ T-cell tolerance through the PD-1 and the CTLA-4 molecule/surface receptor. Blocking the costimulatory molecule CTLA-4 resulted in breaking the tolerance.

When you put the Melanoma Puzzle together, this is what you get,

A well Orchestrated Event, your immune system in action.

The Perfect Storm, the Orchestration of an Immune Response Unrehearsed

• Early after the CD4+ T-cells are activated, the CTLA-4 receptors are upregulated according to the research.

• TGF- beta requires CTLA-4 upregulation early after T Cell Activation to Induce FoxP3 and generate adaptive CD4+CD25+ Regulatory Cells. Song Guo Zheng et al and colleagues.

• By blocking the CTLA-4 receptor, you keep the T-cell activated, you push the T-cell differentiation towards the TH17 cells and you now have that the Third signal, (The inflammatory signal) that is needed to induce an Immune response. Ribas et al

• If you add the combination of IL-2 and TGF- beta at the beginning of the treatment,it induces naive or total CD4+CD25– cells to develop strong suppressive effects both in vitro and in vivo according to Horwitz et al in 2001.

• By adding the The HD IL-2 after the expansion of the T-cells, IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of tumor-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells. Wherry et al

Here are some other papers I have written that puts the Melanoma Therapy into perspective.

Melanoma and the Magic Bullet [Monoclonal Antibodies]

The Making of an Immune Response by Combinatorial Therapy using Anti-CTLA-4 Blockade and Interluekin-2

Déjà vu Blame it on the tregs]

The Missing Link in T-cell Activation

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


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

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.


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..

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.

Source Fastcures blog

Join the Relay for Life!!!


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!!!



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

How Skin Cancer Develops by " : 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)

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.