Melanoma_Missionary: Sounding the Danger Signal through chemotherapy to Cause Cancer Cell Death..Melanoma ..Jim Breitfeller

Thursday, March 17, 2011

Sounding the Danger Signal through chemotherapy to Cause Cancer Cell Death..Melanoma ..Jim Breitfeller

Sounding the Danger Signal through chemotherapy to Cause Cancer Cell Death

“Schedule and Dose for Combination Therapy,”
2011 Scientific Colloquium of the Cancer Immunotherapy Consortium

Thursday, March 17, 2011 7:00 AM - Saturday, March 19, 2011 1:30 PM
Eastern Time

Dr. Hy Levitsky is introducing Dr. Laurence Zitvogel from Institut Gustave Roussy, a leader in cell biology in cancer.

New Speaker: Laurence Zitvogel, Ph.D.

Institut GustaveRoussy, Villejuif, France

"Dr. Zitvogel graduated in medical oncology from the School of Medicine of the University of Paris in 1992. She started her scientific career when she was at the University of Pittsburgh in Michael Lotze’s laboratory. She became research director at Institut National de la Santé et Recherche Médicale in a laboratory located at Institut Gustave Roussy, a large cancer center in Villejuif, France, and the head of the Center for Clinical Investigations for vaccine developments at Villejuif. Dr. Zitvogel has been actively contributing to the field of cancer immunology and immunotherapy, bringing together basic and translational research, including the design of cancer therapies through combined animal studies and phase I patient trials. Her expertise is mainly dendritic cell and innate effector biology and relevance during tumor development, as well as exosome-based vaccine designs."

Zitvogel: chemotherapy may work because cancer cell death is immunogenic and triggers anti-cancer immunity

Zitvogel: Chemo causes cancer to express "eat me" or "come and get me" signals to the immune system. Nice way to phrase it!

Jimmy B: See Graph Below

Autophagy Defintion: The process of self-digestion by a cell through the action of enzymes originating within the same cell.

Zitvogel: "autophagy" is important to death of cancer cells. It breaks down in cancer growth. Chemo re-starts the autophagy process.

Zitvogel: some types of chemo are better at inducing immunogenic cell death than others. Cisplatin and taxols aren't strong in this.

Zitvogel: new tests can show how a drug falls short in triggering immunogenic cancer death -- and how to compensate for that.

Zitvogel: Giving thapsigarin can improve cisplatin's ability to trigger immunogenic cancer cell death.

Jimmy B: Thapsigargin sensitizes human melanoma cells to TRAIL-induced apoptosis

Zitvogel: "drug repositioning" is the process of combining drugs to compensate for where one falls short in immunogenic cell death.

Zitvogel: combining immunogenic chemotherapies with immunomodulators or other immunotherapy is a very promising strategy.

Source: Cancer Research on Twitter

http://twitter.com/#!/search?q=%23cic11

“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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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

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!!!

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!!!

Sincerely,

Jimmy Breitfeller

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

Melanoma_Missionary

Thursday, March 17, 2011

Sounding the Danger Signal through chemotherapy to Cause Cancer Cell Death..Melanoma ..Jim Breitfeller

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Melanoma and the “Magic Bullet” (Monoclonal Antibodies)

Public Service Announcement

Join the Relay for Life!!!

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

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Call For Melanoma Patients!!!!

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