Main Category: Melanoma / Skin Cancer
Article Date: 31 Jan 2009 - 6:00 PST
http://www.medicalnewstoday.com/articles/137383.php?nfid=76490
Stress May Hasten Growth Of Melanoma Tumors
For patients with a particularly aggressive form of skin cancer malignant melanoma stress, including that which comes from simply hearing that diagnosis, might amplify the progression of their disease.
But the same new research that infers this also suggests that the use of commonly prescribed blood pressure medicines might slow the development of those tumors and therefore improve these patients' quality of life.
The study, the third by Ohio State University scientists in the last two years that looked for links between stress hormones and diseases like cancer, is published in the February 2009 issue of the journal Brain, Behavior and Immunity.
Eric V. Yang, a research scientist at the Institute for Behavioral Medicine Research (IBMR), exposed samples of three melanoma cell lines to the compound norepinephrine, a naturally occurring catecholamine that functions as a stress hormone. In times of increased stress, levels of norepinephrine increase in the bloodstream.
Yang and colleague Ronald Glaser were looking for changes in the levels of three proteins released by the cells. Glaser is a professor of molecular virology, immunology and medical genetics, member of the university's Comprehensive Cancer Center and director of the IBMR.
One of the proteins vascular endothelial growth factor, or VEGF plays a key role in stimulating the growth of new blood vessels needed to feed a growing tumor, a process called angiogenesis. The other two proteins, Interleukin-6 and Interleukin-8, are both involved in fostering tumor growth.
All three of the cell lines were grown from tissues taken from secondary tumors that had metastasized from a primary site and they signify aggressive forms of cancer. But one of them C8161 - represented the most aggressive and advanced form of melanoma.
"We noticed that all three of these proteins increased in response to the norepinephrine," Yang explained, adding that in the C8161 cells, "we got a 2,000 percent increase in IL-6. In untreated samples from this cell line, you normally can't detect any IL-6 at all.
"What this tells us is that stress might have a worse effect on melanoma that is in a very aggressive or advanced stage, and that one marker for that might be increased levels of IL-6," he said.
The researchers ruled out cell proliferation - an increase in the number of cells present - as a reason for the increase in all three proteins. That meant that the only other answer was that the cells were increasing their expression of the genes responsible for producing these compounds.
The researchers showed that the norepinephrine molecule binds to receptors on the surface of cancer cells and once this linkage occurs, it stimulates the release of the proteins that support angiogenesis and tumor growth.
Yang and Glaser first confirmed that the receptors were present on cells in all three cell lines and then tested what would happen when the receptors were blocked by common blood pressure medicine - the so-called "beta-blockers."
When the beta-blockers did bind to the receptors, the production of the three proteins reduced significantly, suggesting that in patients with melanoma, using these types of medications might be used to slow the progression of the disease in patients.
While the study was restricted to tumor cell lines, rather than using animal models or human patients, the findings are still exciting. The researchers found strong evidence that the same receptors are expressed on the surface of tumor cells from biopsies that were taken from melanoma patients. That supports the clinical importance of the results.
Two earlier studies on different tumor cell lines - one prepared from a multiple myeloma and the other from a nasopharyngeal carcinoma - also showed that exposure to norepinephrine increased the levels of proteins responsible for accelerating tumor growth.
The research is showing not only that different forms of cancer react differently to stress hormones but also that those reactions can vary within a specific form of the disease, with the possibility of a more aggressive form of the disease reacting more strongly to the stressors.
For melanoma patients, that can be very important since these tumors are able to metastasize, or spread, when they are much smaller than most other solid cancers. The American Cancer Society estimates that nearly 48,000 cases of melanoma are diagnosed each year and nearly 8,000 people are killed each year by the disease.
This research was supported in part by the National Cancer Institute. Other collaborators in the study included Sanford Barsky, professor and chair of pathology; and IBMR members Elise Donovan, Min Chen, Amy Gross, Jeanette Webster Marketon and Seung-jae Kim.
Ohio State University
1125 Kinnear Rd.
Columbus
OH 43212-1153
United States
http:// www.osu.edu
I believe that I saw it in the way my tumors were growing. I was under a lot of fiancial stress, My daughter was just starting College. I believe that stress can play an important role in your therapy. You need to reduce it as much as possible. That is done by reading and research and medication. The fear of the UNKNOWN may kill you. By gaining knowledge on the subject matter, the unknown barrier is broken down and stress is relieved.
Jimmy B
This is Jim Breitfeller's journey into the Maze of Melanoma. Jim Breitfeller has gathered medical information for the patient and the caregiver. As Lance Armstrong would say "Lets stand Up to Cancer" Jim's Battle with the Beast July 2005 to present.
Tuesday, February 3, 2009
Stress May Hasten Growth Of Melanoma Tumors!! Jim Breitfeller
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Brain tumors,
Dr. Yang,
IL-6,
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Ohio State University,
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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.
Jimmy and Dee
Carepage: Jimmybreitfeller
Jimmy Breitfeller
It was he, who showed me How to live and give back. He was wise beyond his years.
Jimmy and Dee
Carepage: Jimmybreitfeller
Jimmy Breitfeller
My Profile as of 2009
- jimmy_B
- 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)"
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)
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
"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
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer
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
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
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- Did you have your Blueberries Today??Melanoma ..Ji...
- Cancer Miracles !!!!!!! Melanoma Jim Breitfeller
- Hand and Hand Tumor Rejection ..Melanoma ..Jim Bre...
- Jay Tenenbaum Urges Collaboration To Treat the Lon...
- Fewer, Smaller Skin Cancer Tumors After Blocking P...
- In Loving Memory ..Melanoma.. Jim Breitfeller
- IL-2 Regulates Perforin and Granzyme Gene Expressi...
- I AM STUCK AT BASE CAMP 2!!! Melanoma Jim Breitfeller
- Are You Going to Finish Strong? Melanoma Jim Breit...
- Patient knowledge of health information influences...
- Failure at the effector phase: immune barriers at ...
- Here Goes!!! I am going to Spill the Beans!!!!!! M...
- Next Slide Please!!!!!!! Melanoma Jim Breitfeller
- Natural Killer T-cells!!!!! Melanoma Jim Breitfeller
- We are all in it together!!!!!! And the Beat goes...
- Patty Luker, This for you!!! Melanoma..Jim Breitfe...
- I believe I am Half way There!!!!!!!! Melanoma Jim...
- CTLA-4 Therapy--Permission to used Diagrams..Melan...
- Helpful hint of the day!!!!!!!! Melanoma.. Jim Bre...
- Dr. Polly Matzinger Danger!! Danger!! Melanoma..Ji...
- Genomics: The convoluted promise of our generation...
- Figure 1. T-cell Mobilized!!! Melanoma..Jim Breitf...
- If you are wondering where I am!!!!! Melanoma .. J...
- A Conversation with Dr. Natalie Ahn ..Melanoma..Ji...
- A Stage IV Malignant Melanoma Drug That Increases ...
- Micro RNA Plays A Key Role In Melanoma Metastasis....
- Did the clinical trials on CTLA-4 Therapy Sell us ...
- Remember I said HOMEWORK..HOMEWORK..HOMEWORK!!!!! ...
- Clinical Care Options!!! Melanoma Jim Breitfeller
- Delayed Melanoma Response Could Impact Clinical De...
- Brenda Schmall Thanks for Sharing!! Melanoma Jim B...
- Melanoma – A Look Down The Road Ahead!! Jim Breitf...
- Cancer Care Costs Squeeze Millions of Americans.. ...
- Researchers Uncover Gene for Melanoma of the Eye J...
- Are The Europeans ahead of us in the War Against M...
- Genomic and Molecular Profiling Predicts Response ...
- 'Targeted Chemo' Safely Shrinks Liver Tumors ..Mel...
- Targeted Therapy ...Ocular/unveal Melanoma ..Jim ...
- I am back from my Punch Biopsy !!!! Melanoma .. Ji...
- Cambridge University Research Group Employs Fluidi...
- Stress May Hasten Growth Of Melanoma Tumors!! Jim ...
- You heard it here first..“Personalized medicine is...
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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)
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.
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