Brain Tumour Survivor

A site dedicated to leading edge treatment for brain tumours
It is currently Wed Nov 21, 2018 12:30 am

All times are UTC + 10 hours




Post new topic Reply to topic  [ 304 posts ]  Go to page Previous  1, 2, 3, 4, 5, 6, 7, 8 ... 21  Next
Author Message
 Post subject:
PostPosted: Fri Mar 18, 2011 1:09 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Personlized Dendritic Cell Vaccine Increases Survival in Patients With Deadly Brain Cancer

ScienceDaily (Mar. 16, 2011) — A dendritic cell vaccine personalized for each individual based on the patient's own tumor may increase median survival time in those with a deadly form of brain cancer called glioblastoma, an early phase study at UCLA's Jonsson Comprehensive Cancer Center has found.

Published in the peer-reviewed journal Clinical Cancer Research, the study also identified a subset of patients more likely to respond to the vaccine, those with a subtype of glioblastoma known as mesenchymal, which accounts for about one-third of all cases. This is the first time in brain cancer that a subset of patients more likely to respond to an immunotherapy has been identified, said Dr. Linda Liau, a Jonsson Cancer Center researcher, professor of neurosurgery and senior author of the study.

The study found that the vaccine, administered after the conventional treatments of surgery and radio-chemotherapy, was associated with a median survival of 31.4 months, double the 15 months of historical controls in the published literature. In all, 23 patients were enrolled in the Phase I study that was launched in 2003. Of those, about one third of participants are still alive, some more than eight years after their diagnosis.

The study also found that the vaccine was safe and that side effects were minimal, limited mostly to flu-like symptoms and rashes near the vaccine injection site.

"This is quite an encouraging result, especially in an early phase study like this," Liau said. "It's promising to see patients with this type of brain cancer experience such long survivals."

However, Liau cautioned that the findings need to be confirmed in larger, randomized studies. She currently is leading a Phase II, randomized study at UCLA testing the vaccine in newly diagnosed glioblastoma patients. The patients will receive either the standard of care (surgery, radiation and chemotherapy) or the standard of care plus the vaccine. The study is a multi-center trial, and UCLA is the only site offering it in California.

It has recently been discovered that there are at least three subtypes of glioblastoma: proneural, proliferative and mesenchymal. During the course of her study, Liau and her colleagues saw that one group of patients seemed to be responding very well to the vaccine and examined their tumors using a microarray analysis of their DNA. They found that those with a gene expression profile identifying their cancers as mesenchymal responded better to the vaccine.

The finding was surprising, Liau said, because patients with the mesenchymal subtype generally have more aggressive disease and shorter survival than those with the other subtypes. In patients with this type of glioblastoma, several genes that modulate the immune system are dysregulated, meaning they don't work properly. Liau speculates that the vaccine helped replenish the immune system, allowing that subset of patients to more easily fight the brain cancer.

"Glioblastoma remains one of the diseases for which there is no curative therapy … and the prognosis for patients with primary malignant brain tumors remains dismal," the study states. "Our results suggest that the mesenchymal gene expression profile may identify an immunogenic sub-group of glioblastoma that may be more responsive to immune-based therapies."

Brad Silver, 41, who grew up in Southern California and now lives in a Cleveland suburb, was diagnosed with glioblastoma in 2003 and was told that he had, at best, two months to live. He was stunned.

"I was 33 years and my wife was seven months pregnant with my son," said Silver, a college water polo instructor. 'I didn't think I was going to live to see my son born, let alone grow up."

Silver sought a second opinion at UCLA and the golf-ball sized tumor in his left lateral lobe was removed. He underwent radiation and chemotherapy and enrolled in the vaccine clinical trial. Today, eight years later, he remains cancer free. His son, named Brad Silver II and a miniature version of his dad, will celebrate his eighth birthday in April.

"If I had listened to that first doctor, I would not be here today. If not for Dr. Liau, I would not be here today," Silver said. "I'm 100 percent back to being me because of this vaccine and that clinical trial. It's almost unbelievable."

The vaccine preparation is personalized for each individual. After the tumor is removed, Liau and her team extract the proteins, which provide the antigens for the vaccine to target. After radiation and chemotherapy, the white blood cells are taken from the patient and grown into dendritic cells, a type of white blood cell that is an antigen-presenting cell. The vaccine preparation from this point takes about two weeks, as the dendritic cells are grown together with the patient's own tumor antigens. The tumor-pulsed dendritic cells are then injected back in to the body, prompting the T cells to go after the tumor proteins and fight the malignant cells.

"The body may have trouble fighting cancer because the immune system doesn't recognize it as a foreign invader," Liau said. "The dendritic cells activate the patient's T cells to attack the tumor, basically teaching the immune system to respond to the tumor."

The individualized vaccine is injected into the patient in three shots given every two weeks for a total of six weeks. Booster shots are given once every three months until the cancer recurs. Patients are scanned every two months to monitor for disease recurrence, Liau said.

http://www.sciencedaily.com/releases/20 ... 093111.htm


Top
 Profile  
 
 Post subject:
PostPosted: Sun Mar 20, 2011 8:46 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
How fever can cure cancer

(NaturalNews) Artificially induced fever has been successfully used for the treatment of cancer, especially in Germany. One must first understand the importance of fever for healing. Fever is not a symptom that we must eliminate with toxic pharmaceuticals as prescribed by mainstream medicine. Fever is nature's way of healing and eliminating pathogens. (Natural News "Do Not Kill a Fever; Fever Kills Viruses" source below).

French microbiologist Dr. Andre Lwoff has scientifically demonstrated that fever cures even incurable diseases. Leading European cancer specialist, Dr. Josef Issels, wrote on this topic: "Artificially induced fever has the greatest potential in the treatment of many diseases, including cancer." Oxford professor Dr. David Mychles and his research team have recently confirmed the effectiveness of induced fever for treating disease, including cancer.

An Incident of Fever Removal's Aftermath

A leading practitioner of hyperthermia for cancer, Dr. Werner Zabel, tells this true tale to illustrate fever's cancer preventative and curing capability. A swamp area outside of Rome was a breeding ground for malaria infecting mosquitoes. The government decided to drain the swamps. The incidents of malaria went way down, but the cancer rate, which had been significantly below normal, almost immediately went up to the normal cancer rate in Italy.

It was deduced that malaria induced fevers had helped prevent cancer in that segment of the population. European and Scandinavian nations have historically used various forms of heating the body for health purposes. Steam baths, hot springs, and saunas have been used for decades. So revving up the body's temperature for health isn't new to Europe.

But inducing fevers for cancer is not a casual do it yourself therapy. It demands skillful attention from health practitioners.

Hyperthermia (Thermotherapy) Methods

The oldest method, the Schlenz bath, has been around in Europe for a century. Before hyperthermia caught on for cancer, it had been used for a variety of illnesses. It involves being immersed in water with only the mouth and nose protruding for breath. The water temperature is around 102. After a half hour, the body temperature begins to match the water temperature. This technique is monitored to ensure pulse rates don't exceed 140.

Amazingly, around 1976 a unique method of localized hyperthermia, heating cancer tumors with ultra-sonic waves, was reported in the USA as a possible fourth approach for mainstream cancer treatments. Not surprisingly, even after several successful clinical trials this approach did not see widespread use in the USA.

But it was picked up in Germany and China, where it and other hyperthermia or thermotherapy applications have become common. Unfortunately, the scant American use of localized ultra-sonic or radio wave hyperthermia is relegated to supporting roles for softening tumors, making toxic interventions easier. So although discovered first in America, Germany and Europe are the hot spots for treating cancer with hyperthermia.

The Best Approach

Instead of integrative medicine using hyperthermia as an adjunct for toxic orthodox treatments, hyperthermia should be used as an adjunct to other alternative non-toxic, inexpensive cancer treatments. There are several alternative cancer therapies that could be integrated successfully with hyperthermia/thermotherapy.

For example, the Budwig Center in Spain offers a Far Infrared sauna as its form of hyperthermia along with the Budwig Diet and other therapies. Speaking of diets, a cancer diet should be part of any cancer therapy. Since cancer cells thrive on fermenting glucose, cancer diets shun all forms of sugar. Alcohol, processed foods and usually meats are avoided. The focus is on organic veggies, fruits, and whole grains.

Meanwhile, saunas and steam baths could be used by anyone for better health and disease prevention.

http://www.naturalnews.com/031751_fever_cancer.html

[comment - I'll be asking whether heat is an option in my next operation. Rather than radio or chemo, I'd prefer that heat was used to mop up stray cells. It is well documented that cancer cells have a lower temperature tolerance than normal cells]


Top
 Profile  
 
 Post subject:
PostPosted: Tue Mar 22, 2011 3:25 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Personalized vaccine doubles survival time in patients with deadly brain cancer

A dendritic cell vaccine personalized for each individual based on the patient's own tumor may increase median survival time in those with a deadly form of brain cancer called glioblastoma, an early-phase study at UCLA's Jonsson Comprehensive Cancer Center has found.

Published last week in the peer-reviewed journal Clinical Cancer Research, the study also identified a subset of patients more likely to respond to the vaccine — those with a subtype of glioblastoma known as mesenchymal, which accounts for about one-third of all cases. This is the first time in brain cancer research that a subset of patients more likely to respond to an immunotherapy has been identified, said the study's senior author, Dr. Linda Liau, a Jonsson Cancer Center researcher and a professor of neurosurgery.

The study found that the vaccine, administered after conventional surgery and radio-chemotherapy, was associated with a median survival of 31.4 months, double the 15 months of historical controls in the published literature. In all, 23 patients were enrolled in the Phase I study, which was launched in 2003. Of those, about one-third are still alive, some more than eight years after their diagnosis.

The study also found that the vaccine was safe and that side effects were minimal, limited mostly to flu-like symptoms and rashes near the vaccine injection site.

"This is quite an encouraging result, especially in an early-phase study like this," Liau said. "It's promising to see patients with this type of brain cancer experience such long survivals."

However, Liau cautioned that the findings need to be confirmed in larger, randomized studies. She currently is leading a Phase II, randomized study at UCLA testing the vaccine in newly diagnosed glioblastoma patients. The patients will receive either the standard of care (surgery, radiation and chemotherapy) or the standard of care plus the vaccine. The study is a multi-center trial, and UCLA is the only site in California.

How the vaccine works

The vaccine preparation is personalized for each individual. After the tumor is removed, Liau and her team extract the proteins, which provide the antigens for the vaccine to target. After radiation and chemotherapy, the white blood cells are taken from the patient and grown into dendritic cells, a type of white blood cell that is an antigen-presenting cell.

The vaccine preparation from this point takes about two weeks, as the dendritic cells are grown together with the patient's own tumor antigens. The tumor-pulsed dendritic cells are then injected back in to the body, prompting the T cells to go after the tumor proteins and fight the malignant cells.

"The body may have trouble fighting cancer because the immune system doesn't recognize it as a foreign invader," Liau said. "The dendritic cells activate the patient's T cells to attack the tumor, basically teaching the immune system to respond to the tumor."

The individualized vaccine is injected into the patient in three shots given every two weeks for a total of six weeks. Booster shots are given once every three months until the cancer recurs. Patients are scanned every two months to monitor for disease recurrence, Liau said.

Success with mesenchymal glioblastoma

It has recently been discovered that there are at least three subtypes of glioblastoma: proneural, proliferative and mesenchymal. During the course of her study, Liau and her colleagues saw that one group of patients seemed to be responding very well to the vaccine. The researchers examined their tumors using a microarray analysis of their DNA and found that those with a gene expression profile identifying their cancers as mesenchymal responded better to the vaccine.

The finding was surprising, Liau said, because patients with the mesenchymal subtype generally have more aggressive disease and shorter survival times than those with the other subtypes. In patients with this type of glioblastoma, several genes that modulate the immune system are dysregulated, meaning they don't work properly. Liau speculates that the vaccine helped replenish the immune system, allowing that subset of patients to more easily fight the brain cancer.

"Glioblastoma remains one of the diseases for which there is no curative therapy ... and the prognosis for patients with primary malignant brain tumors remains dismal," the study states. "Our results suggest that the mesenchymal gene expression profile may identify an immunogenic sub-group of glioblastoma that may be more responsive to immune-based therapies."

Eight years of survival

Brad Silver, 41, who grew up in Southern California and now lives in a Cleveland suburb, was diagnosed with glioblastoma in 2003 and was told that he had, at best, two months to live. He was stunned.

"I was 33 years old, and my wife was seven months pregnant with my son," said Silver, a college water polo instructor. "I didn't think I was going to live to see my son born, let alone grow up."

Silver sought a second opinion at UCLA, and the golf-ball sized tumor in his left lateral lobe was removed. He underwent radiation and chemotherapy and enrolled in the vaccine clinical trial. Today, eight years later, he remains cancer free. His son, named Brad Silver II, will celebrate his eighth birthday in April.

"If I had listened to that first doctor, I would not be here today. If not for Dr. Liau, I would not be here today," Silver said. "I'm 100 percent back to being me because of this vaccine and that clinical trial. It's almost unbelievable."

http://newsroom.ucla.edu/portal/ucla/pe ... 99138.aspx


Top
 Profile  
 
 Post subject:
PostPosted: Wed Mar 30, 2011 4:00 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Catching Cancer With Carbon Nanotubes: New Device to Test Blood Can Spot Cancer Cells, HIV on the Fly

ScienceDaily (Mar. 30, 2011) — A Harvard bioengineer and an MIT aeronautical engineer have created a new device that can detect single cancer cells in a blood sample, potentially allowing doctors to quickly determine whether cancer has spread from its original site.

The microfluidic device, described in the March 17 online edition of the journal Small, is about the size of a dime, and could also detect viruses such as HIV. It could eventually be developed into low-cost tests for doctors to use in developing countries where expensive diagnostic equipment is hard to come by, says Mehmet Toner, professor of biomedical engineering at Harvard Medical School and a member of the Harvard-MIT Division of Health Sciences and Technology.

Toner built an earlier version of the device four years ago. In that original version, blood taken from a patient flows past tens of thousands of tiny silicon posts coated with antibodies that stick to tumor cells. Any cancer cells that touch the posts become trapped. However, some cells might never encounter the posts at all.

Toner thought if the posts were porous instead of solid, cells could flow right through them, making it more likely they would stick. To achieve that, he enlisted the help of Brian Wardle, an MIT associate professor of aeronautics and astronautics, and an expert in designing nano-engineered advanced composite materials to make stronger aircraft parts.

Out of that collaboration came the new microfluidic device, studded with carbon nanotubes, that collects cancer cells eight times better than the original version.

Captured by nanotubes

Circulating tumor cells (cancer cells that have broken free from the original tumor) are normally very hard to detect, because there are so few of them -- usually only several cells per 1-milliliter sample of blood, which can contain tens of billions of normal blood cells. However, detecting these breakaway cells is an important way to determine whether a cancer has metastasized.

"Of all deaths from cancer, 90 percent are not the result of cancer at the primary site. They're from tumors that spread from the original site," Wardle says.

When designing advanced materials, Wardle often uses carbon nanotubes -- tiny, hollow cylinders whose walls are lattices of carbon atoms. Assemblies of the tubes are highly porous: A forest of carbon nanotubes, which contains 10 billion to 100 billion carbon nanotubes per square centimeter, is less than 1 percent carbon and 99 percent air. This leaves plenty of space for fluid to flow through.

The MIT/Harvard team placed various geometries of carbon nanotube forest into the microfluidic device. As in the original device, the surface of each tube can be decorated with antibodies specific to cancer cells. However, because the fluid can go through the forest geometries as well as around them, there is much greater opportunity for the target cells or particles to get caught.

The researchers can customize the device by attaching different antibodies to the nanotubes' surfaces. Changing the spacing between the nanotube geometric features also allows them to capture different sized objects -- from tumor cells, about a micron in diameter, down to viruses, which are only 40 nm.

The researchers are now beginning to work on tailoring the device for HIV diagnosis. Toner's original cancer-cell-detecting device is now being tested in several hospitals and may be commercially available within the next few years.

Rashid Bashir, director of the Micro and Nanotechnology Laboratory at the University of Illinois at Urbana-Champaign, says that the ability to filter specific particles, cells or viruses from a blood sample so they can be analyzed is a critical step towards creating handheld diagnostic devices.

"Anything you can do to improve capture efficiency, or anything novel you can do to get the particles to interact with a surface more effectively, will help with sample preparation," says Bashir, who was not part of the research team.

http://www.sciencedaily.com/releases/20 ... 134134.htm


Top
 Profile  
 
 Post subject:
PostPosted: Wed Mar 30, 2011 4:04 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Targeting Way to Stop Brain Tumor Cell Invasion

ScienceDaily (Mar. 29, 2011) — Gliomas are brain invaders. A kind of malignant tumor cell, gliomas branch out like tendrils from a central tumor source, spreading cancer throughout the brain. Traditional therapies, such as cutting out the tumor surgically, can be ineffective if the cells have already spread. Researchers at the University of Alabama at Birmingham may have come upon a way to stop a glioma invasion in its tracks, using a drug already approved for use in Europe.

Much like early explorers of the Old West followed rivers and streams, depending on them to provide drinking water and food, gliomas spread through the brain by following the path of blood vessels, tapping into those vessels for the nutrients they need to survive. Cut that glioma off from the blood supply, and it starves.

"An explorer lost in the wilderness without food and water soon succumbs and dies," said Harald Sontheimer, Ph.D., director of the UAB Center for Glial Biology in Medicine and senior author on the paper. "A glioma that can't find and tap into a blood vessel will also die."

In a paper published March 30, 2011 in the Journal of Neuroscience, Sontheimer and co-author Vedrana Montana, Ph.D., discovered that bradykinin, a peptide that increases the size of blood vessels, is the mechanism glioma cells use to find blood vessels. Glioma cells carry a receptor for bradykinin, called the B2R receptor. Using that receptor to attract bradykinin gives the cell a navigator to lead it to blood vessels. Block the receptor from interacting with bradykinin and the cell will end up lost in the wilderness.

The researchers introduced a B2R inhibitor known as HOE 140, a laboratory version of a drug approved for use in Europe for hereditary angioedema called Icatibant. HOE 140 bound to the B2R receptor on glioma cells, interfering with the receptor's opportunity to bind to bradykinin. The results were impressive.

"We found that 77 percent of glioma cells with bradykinin were able to locate a blood vessel and tap into its nutrients," said Montana. "However, when we blocked the B2R receptors from interacting with bradykinin, only 19 percent of glioma cells were able to find a blood vessel."

The researchers used human glioma cells transplanted into a mouse model and, using time-lapse techniques on a laser-scanning microscope, tracked the ability of the cells to navigate to blood vessels by means of fluorescent markers attached to the cells.

"Targeting the B2R receptors is an elegant and so far unexplored approach to treat gliomas, one of the most devastating types of brain tumor," said Sontheimer. "Icatibant, which is already in use in Europe, and its ability to block B2R receptors may prove to be very promising target for further investigation."

http://www.sciencedaily.com/releases/20 ... 172249.htm


Top
 Profile  
 
 Post subject:
PostPosted: Thu Mar 31, 2011 3:45 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
A Rare Happy Outcome for Glioblastoma Diagnosis

Newswise — MAYWOOD, Ill. -- John Moran was 27 years old when he underwent a longshot brain surgery for what appeared to be malignant tumor that would almost certainly be fatal.

But Loyola University Medical Center neurosurgeon Dr. Douglas Anderson thought it was worth trying to save the life of the young father of three. And against all expectations, the growth turned out to be a benign abscess, not cancer. Anderson removed the abscess, and Moran made a complete recovery.

That was 24 years ago. Moran, 51, went on to have a long and rewarding career as a FBI Special Agent. He and his wife, Deborah, now have nine children and four grandchildren.

Through the years, Moran has thought frequently about his remarkable surgery. So he decided recently to email Anderson a heartfelt note, thanking the surgeon once again for saving his life.

"Your efforts have never been forgotten," Moran wrote. "Because of you we have celebrated 28 years of marriage and have been blessed with a wonderful life."

Anderson said it was "gratifying and humbling" to receive Moran's note. "It is a wonderful reminder that we are part of a larger story," he said.

Moran recalled that before his surgery, he suffered terrible, pounding headaches on the left side of his head. In between the headaches, he experienced partial seizures that caused strange, troubling sensations. He would smell things that weren't there. And in social gatherings, other people did not seem real. He suffered a terrible sensation of being alone.

Moran recalls looking at his wife and saying, "I don't know who you are." She thought he was losing his mind.

A brain scan revealed a growth, larger than a golf ball, that looked like a glioblastoma -- an aggressive, fast-growing brain tumor that is almost always fatal. The first neurosurgeon Moran saw said an operation would not alter the eventual outcome.

Moran came to Anderson for a second opinion. Anderson said the only way to confirm the diagnosis would be to perform an open biopsy.

"Since Mr. Moran was young and otherwise healthy, I suggested that it was too early to give up," Anderson said. "If the other physicians were wrong -- while unlikely -- we might be able to remove the lesion without damage to his intellectual function. I'm thankful that we maintained a sense of hope."

Moran underwent surgery in January, 1987. The lesion turned out to be an abscess (bag of fluid) caused by an infection in the brain. Left untreated, it would be fatal in a month or two. Either the abscess would rupture and Moran would die suddenly, or it would continue growing, obstructing brain vessels and compressing the brain stem.

Fortunately, Anderson was able to completely remove the abscess. "We woke him up and told him, 'It's all gone,'" Anderson said.

Moran, who had been preparing to die, was dumbfounded. "It was miraculous," he said. "I went from a very dark night to a very bright morning."

The near-death experience had a profound effect on Moran's faith. Before the surgery, he said, he was a "mediocre" Catholic. Afterward, he became much more devout. Every day, he attends mass, says the rosary, studies church teachings and gets on his knees to pray.

"My faith is everything," he said. "And everything stems from my faith."

Through the years, Moran has thought often about the surgeon who saved his life. "Dr. Anderson is part of my life," he said. "I'm very thankful for the work that he does."

http://www.newswise.com/articles/a-rare ... -diagnosis

[comment - I was also told I had a GBM, but surgery revealed a 2/3 mixed glioma. So this man was fortunate and the moral is never to rely on scans alone]


Top
 Profile  
 
 Post subject:
PostPosted: Sat Apr 09, 2011 8:00 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Bevacizumab for recurrent glioblastoma multiforme: a meta-analysis

Abstract

The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose-response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5-74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9-10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%-57%) and 76% (95% CI, 69%-84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2-8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%-9%), 49% partial response (95% CI, 37%-61%), and 29% stable disease (95% CI, 20%-38%). No difference was seen in bevacizumab dose-response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose-response effect would require confirmation in a prospectively conducted clinical trial.

http://virtualtrials.com/newsarticle.cfm?item=5015


Top
 Profile  
 
 Post subject:
PostPosted: Sat Apr 09, 2011 8:02 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Benefits of interferon-β and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter: A multicenter study

Abstract

BACKGROUND: The aim of the current study was to catalog genomic and epigenomic abnormalities in newly diagnosed glioblastoma patients and determine the correlation among clinical, genetic, and epigenetic profiles and clinical outcome.

METHODS: This study retrospectively included 68 consecutive patients who underwent surgical treatment and received standard radiotherapy with temozolomide (TMZ)-based chemotherapy. Of a total of 68 patients, 39 patients (57.4%) received interferon (IFN)-β in combination of TMZ.

RESULTS: The genetic and epigenetic alterations frequently observed were EGFR amplification (51.5%), TP53 mutation (33.8%), CDKN2A loss (32.4%), TP53 loss (16.2%), methylation of the MGMT promoter (33.8%) and IDH1 mutation (5.9%). Multivariate analysis revealed that methylated MGMT promoter and the combination of TMZ and IFN-β were independent prognostic factors associated with survival. The median survival time (MST) of the patients who received the combination of IFN-β and TMZ was significantly greater with 19.9 months as compared to the TMZ alone group (12.7 months). Notably, in even patients whose tumors had unmethylated MGMT promoter, the MST prolonged to 17.2 months when receiving TMZ with IFN-β, compared to 12.5 months in those receiving TMZ without IFN-β.

CONCLUSIONS: Taken together, addition of IFN-β for newly diagnosed primary GBM achieved a favorable outcome, particularly in patients with unmethylated MGMT promoter. Cancer 2011. © 2010 American Cancer Society.

http://virtualtrials.com/newsarticle.cfm?item=5016


Top
 Profile  
 
 Post subject:
PostPosted: Sat Apr 16, 2011 8:27 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
FDA clears first-of-a-kind device for brain cancer

WASHINGTON (AP) — Device maker Novocure said Friday that the Food and Drug Administration approved its first-of-a-kind treatment that fights cancerous brain tumors using electrical energy fields.

The FDA approved the device for patients with aggressive brain tumors that have returned after treatment with chemotherapy and other interventions. Patients with recurring brain cancer usually live only a few months.

Studies showed that people using the device lived about as long as those taking chemotherapy, roughly six months. However, patients using the device had significantly fewer side effects.

For decades, doctors have treated cancer with three methods: drugs, radiation or surgery. Novocure's NovoTTF device represents a fourth approach.

The portable device uses electric fields to disrupt the division of cancer cells that allows tumors to grow and spread. The electric fields have little effect on healthy cells because they divide at a much slower rate, if at all, compared with cancer cells.

"The reason why this is so exciting is that we now have FDA approval of a totally new type of treatment for cancer," said Dr. Herb Engelhard, an associate professor of neurosurgery at the University of Illinois in Chicago. Engelhard helped conduct the study of NovoTTF but received no compensation from the company.

"All of us as investigators were skeptical at first, but I have seen the scans and I believe this is killing cancer cells in patients," Engelhard said.

The NovoTTF is a six-pound device that patients carry with them in a small bag. The electrical current is sent from the device to four electrodes which are attached to the patient's shaved head.

A panel of outside advisers to the FDA narrowly voted 7-6 in favor of the effectiveness of the device last month. The FDA is not required to follow such recommendations, though it often does.

A 237-patient study failed to show a survival benefit for patients using the device, compared with those taking chemotherapy. Patients in both groups lived just over six months, on average. However, those in the device group reported higher quality of life and did not have the side effects of chemotherapy, such as nausea, diarrhea and infection.

"This is as effective, or better, than anything that's ever been tried after standard treatment has failed. And while you're on it, you don't have any side effects from the treatment." said Al Musella, founder of the Musella Foundation for Brain Tumor Research and Information in Hewlett, N.Y. Musella's father and sister-in-law died of brain cancer.

The FDA approved the device specifically for a tumor type known as glioblastoma, the most aggressive form of brain cancer. Five-year survival for the disease is just 2 percent for patients over 45 years old, according to American Cancer Society. About 19,000 people in the U.S. are diagnosed with brain cancer each year, according to the National Cancer Institute.

Standard treatment is six weeks of high-dose radiation along with a chemotherapy pill, and then additional chemotherapy for at least six months or until the tumor stops responding.

Novocure is a privately held company based in Portsmouth, N.H., and Haifa, Israel, where the NovoTTF device was invented. The company is testing its device in other types of cancer, including non-small cell lung cancer.

WFD Ventures, Pfizer Inc. and Johnson & Johnson are among the investors in the company.

http://www.google.com/hostednews/ap/art ... d44302d9f0


Top
 Profile  
 
 Post subject:
PostPosted: Tue Apr 19, 2011 4:19 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Pro-inflammatory gene expression in solid glioblastoma microenvironment and in hypoxic stem cells from human glioblastoma

Adaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM).

The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs), hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype.

Methods: From each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB).

GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior.

Results: A panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3) were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry) were excluded.

Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas), less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues.

Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells.

Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells.

Conclusions: In human solid glioblastoma we have observed a coordinated overexpression of a panel of pro-inflammatory genes as compared to host normal tissue. We have also evidenced a similar pattern of overexpressed genes in GBM-SCs after hypoxic treatment, showing also a gain of invasive and migratory function that was lost when these stem cells differentiated.

We suggest that, as has been previously described for prostatic and mammary carcinoma, in human glioblastoma acquisition of a proinflammatory phenotype may be relevant for malignant progression.

http://7thspace.com/headlines/378965/pr ... stoma.html


Top
 Profile  
 
 Post subject:
PostPosted: Sat Apr 23, 2011 7:27 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Managing Chemoradiation Side Effects May Prolong Survival

FRIDAY, April 22 (HealthDay News) -- Brain cancer patients live longer if neurological side effects from chemoradiation can be minimized, a new study says.

U.S. researchers analyzed the records of 2,761 patients with high-grade gliomas -- the most common primary brain tumor -- who were enrolled in 14 Radiation Therapy Oncology Group studies between 1983 and 2003.

Patients who didn't experience neurological side effects, such as fatigue and memory loss, during chemoradiation lived an average of four months longer than those who had such effects, said the team at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia.

Chemoradiation involves giving patients chemotherapy and radiation treatments together.

Side effects were most likely to occur in patients who were older, frailer, had more symptoms and were receiving radiation twice a day.

The researchers said their findings suggest that damage to normal tissue during chemoradiation plays an important role in determining long-term survival and that minimizing side effects could benefit patients.

"Our results support the personalized approach to brain tumor management . . . and emphasize the importance of minimizing side effects," Yaacov Richard Lawrence, an assistant professor in the radiation oncology department at Thomas Jefferson University and director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel, said in a university news release.

The study is published in the April issue of the British Journal of Cancer.

http://health.usnews.com/health-news/ma ... g-survival


Top
 Profile  
 
 Post subject:
PostPosted: Sun Apr 24, 2011 8:24 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
Researchers discover new way to force cancer cells to self-destruct

Researchers at The Wistar Institute have found a new way to force cancer cells to self-destruct. Low doses of one anti-cancer drug currently in development, called Gamitrinib, sensitize tumor cells to a second drug, called TRAIL, also currently in clinical development as part of an anticancer regimen.

Their findings, published in the April issue of the Journal for Clinical Investigation, show how this combination approach kills tumor cells in both mouse models of glioblastoma and human glioblastoma cells. Glioblastomas are the most common and aggressive form of malignant brain cancer, affecting roughly 6 out of every 100,000 people. There is currently no effective treatment for glioblastoma, and patients rarely survive more than a year after diagnosis.

"We found that a low dose of Gamitrinib makes cancer cells susceptible to TRAIL, bypassing many of the mechanisms tumors use to survive," said senior author Dario Altieri, M.D., the Robert and Penny Fox Distinguished Professor at Wistar and director of The Wistar Institute Cancer Center. "Here we have found a new way to combine cancer therapies, one that could be applied to treating many types of cancer because both of these drugs target different mechanisms of tumor cell survival that revolve around mitochondria."

As commonly depicted in high school biology texts, mitochondria are the "powerhouses" of the cells, organelles whose main function is to turn sugar into useable energy. What is less commonly known is the role of mitochondria in programmed cell death, or apoptosis, the self-destruct system hardwired into every cell. Apoptosis evolved, in part, as a way for the body to react to extreme stress, a means to sacrifice damaged cells for the greater good of the organism. Cancer cells rely on the mitochondria to provide the energy rapidly-growing tumors need to survive, but find ways to block the signaling pathways that trigger apoptosis. Many researchers, including Altieri, have looked for ways to force tumor cells to hit this self-destruct switch.

Gamitrinib is a chemical inhibitor first developed by Altieri and his colleagues in 2009 at the University of Massachusetts. The drug binds to and inhibits Hsp90-Heat Shock Protein-90-a so-called chaperone protein that is highly active in mitochondria and other cellular organelles where it helps regulate and "rescue" other proteins, particularly in times of stress. Their previous studies have shown that Gamitrinib is effective in damaging tumor cell mitochondria, which can lead to cell death.

"When tumor cells are confronted with lower concentrations of Gamitrinib, they mount a stress-related defensive system, essentially eating damaged mitochondria and altering how genes are turned on and off to compensate for induced defects in the mitochondria," Altieri said. "This process naturally suppresses Nuclear Factor-kappa Beta, a protein that prevents apoptosis from happening. Ironically, it's this very defensive measure that we can exploit in killing tumor cells."

http://www.news-medical.net/news/201104 ... truct.aspx


Top
 Profile  
 
 Post subject:
PostPosted: Tue May 03, 2011 4:29 pm 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
New Protein Regulates Water in the Brain to Control Inflammation

ScienceDaily (May 2, 2011) — A new protein, called aquaporin-4, is making waves and found to play a key role in brain inflammation, or encephalitis. This discovery is important as the first to identify a role for this protein in inflammation, opening doors for the development of new drugs that treat brain inflammation and other conditions at the cellular level rather than just treating the symptoms.

The discovery was published in the May 2011 issue of The FASEB Journal.

"Our study establishes a novel role for a water channel, aquaporin-4, in neuroinflammation, as well as a cell-level mechanism," said Alan S. Verkman, M.D., Ph.D., a senior researcher involved in the work from the Department of Medicine and the Department of Physiology at the University of California, San Francisco. "Our data suggest that inhibition or down-regulation of aquaporin-4 expression in brain and spinal cord may offer a new therapeutic option in diseases such as multiple sclerosis, neuromyelitis optica and other conditions associated with neuroinflammation."

Scientists compared normal mice and mice without genes for producing aquaporin-4 using a model of brain inflammation. These experiments showed significantly reduced brain inflammation in the mice that did not produce aquaporin-4. Researchers then systematically investigated the various possible causes of this reduced neuroinflammation and surprisingly found that aquaporin-4 deletion causes the brain to be less susceptible to inflammation, involving differences in astrocyte reaction to stress. The involvement of aquaporin-4 in brain inflammation provides a new determinant and better understanding of how the brain responses to inflammatory stresses. This suggests that using drugs or other agents that target this protein may be effective for treating a variety of conditions associated with brain or spinal cord inflammation.

"This a new lead in our efforts to stem inflammation in the brain," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The importance of water movement in and out of cells cannot be understated, and this paper helps to clarify what has otherwise been a muddy view of aquaporins."

http://www.sciencedaily.com/releases/20 ... 141620.htm


Top
 Profile  
 
 Post subject:
PostPosted: Sat May 07, 2011 8:23 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
ImmunoCellular reports updated ICT-107 Phase I trial data in glioblastoma multiforme

ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular" or the "Company") (OTCBB:IMUC.OB), a biotechnology company focused on the development of novel immune-based cancer therapies, today announced updated long-term data from a Phase I clinical trial of ICT-107, the Company's lead cancer vaccine candidate for the treatment of glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. The data show 6 out of 16 (37.6%) newly diagnosed patients who received ICT-107 continue to show no tumor recurrence, with 3 of these patients (18.8%) remaining disease -free for almost four years while the other 3 patients have gone more than two and a half years disease-free. No new patients have shown disease recurrence since the last report of data in September, 2010. No treatment-related serious adverse events have been observed to date.

"The additional long-term data demonstrate that ICT-107 provides clinical benefit far beyond the standard of care to patients with glioblastoma multiforme, and support the Phase II trial of ICT-107," said Manish Singh, Ph.D. president and CEO of ImmunoCellular Therapeutics. "We are very encouraged that the additional time spent following the patients further supports the outcomes previously reported in our Phase I study."

The Phase I clinical study was conducted in 16 newly diagnosed glioblastoma patients, who received three injections of ICT-107 in addition to standard treatment with surgery, radiation and chemotherapy. The company has reported two year median survival rate of 80.2% in study patients, which compares favorably to the historic median two-year survival rate of 26.5% with standard of care alone. The study's median progression free (PFS) survival of 16.9 months compared especially favorably to the historic median PFS of 6.9 months. 10 of the 16 patients continue to survive. No serious adverse events have been reported and minor side effects have been limited to fatigue, skin rash and pruritis.

http://www.news-medical.net/news/201105 ... forme.aspx


Top
 Profile  
 
 Post subject:
PostPosted: Sun May 08, 2011 7:05 am 
Offline
Registered User
User avatar

Joined: Mon Mar 10, 2008 4:03 pm
Posts: 18130
Location: Australia
How Shifts in Temperature Prime Immune Response

ScienceDaily (May 7, 2011) — Researchers at The Scripps Research Institute have found a temperature-sensing protein within immune cells that, when tripped, allows calcium to pour in and activate an immune response. This process can occur as temperature rises, such as during a fever, or when it falls -- such as when immune cells are "called" from the body's warm interior to a site of injury on cooler skin.

The study, recently published online ahead of print by Nature Chemical Biology, is the first to find such a sensor in immune cells -- specifically, in the T lymphocytes that play a central role in activation of killer immune cells. The protein, STIM1, previously known as an endoplasmic reticulum (ER) calcium sensor, had been thought to be important in immune function, and now the scientists show it is also a temperature sensor.

"Temperature has a profound effect on all biological processes including immune responses, but surprisingly little is known about molecules in immune cells that sense temperature sifts," said the study's principal investigator, Scripps Research Professor Ardem Patapoutian. "Here we show that STIM1 senses temperature and has a profound impact on immune cells."

This is the second family of thermosensation molecules that the Patapoutian laboratory has uncovered. The team has isolated and characterized three of six members of the transient receptor potential (TRP) family of ion channels -- the so-called thermoTRPs. "These proteins translate temperature, which is a physical stimulus, into a chemical signal -- ions flowing into cells," said Patapoutian.

"ThermoTRPs mainly function in specialized sensory neurons that relay environmental temperature information to the brain."

In this study, the researchers turned to immune cells to look for temperature sensors. "Immune cells can experience dramatic temperature changes under either normal or pathophysiological conditions," said first author Bailong Xiao, a research associate in the Patapoutian laboratory. "The temperature drops significantly when, say, immune cells move from the 37 degree Celsius temperature of the spleen to skin, where it is normally 33 degrees. During fever, core body temperature can rise to 41 degrees." Scientists have discussed for decades whether fever is beneficial to the immune system. The researchers believe that identification of a molecular sensor of temperature within immune cells provides a novel avenue to address such questions mechanistically.

The research team, which included Bertrand Coste and Jayanti Mathur, also of the Patapoutian lab, found that STIM1 can be activated by heat with a high degree of temperature sensitivity. Both STIM1 and a plasma membrane pore-forming protein known as Orai1 have recently been identified as essential components of the so-called the calcium release activated calcium (CRAC) channel. But STIM1 had not been known to be heat sensitive until this research, according to Xiao.

The process goes like this: STIM1 proteins are located on the ER, which is the organelle that stores calcium inside the cell. When a sudden change in temperature occurs, STIM1 proteins cluster together and translocate close to the plasma membrane. There, these clusters then can activate Orai1, which leads to the opening of the channel pore and an influx of calcium to activate the cell. Calcium is essential for a number of cellular functions, and, in immune cells, a sustained influx of calcium into these cells activates gene expression and cell proliferation. It turns the immune cell "on," Xiao said.

The function of STIM1 and Orai1 had already been known to be critical to immune function, Xiao said. Mutations in genes encoding either of the proteins lead to development of severe combined immunodeficiency (SCID), the so-called "bubble boy" disease characterized by a complete absence of immunity.

Given the relatively wide expression pattern of STIM1, the researchers suggest that STIM1 may also function as a temperature sensor in other tissues in addition to immune system, including skin, brain, skeletal muscle, and even in blood platelets, all of which could experience moderate but significant temperature changes. For example, temperature-induced STIM1-mediated calcium influx may help muscle cells remodel after exercise, Xiao explained. "We know that calcium is very important for skeletal muscle physiology and remodeling. Temperature can rise in skeletal muscles when they are exercised."

The same principle may be working in blood platelets, where STIM1 is also found and plays important roles, he said. When platelets move to the skin surface to repair a cut, the change in temperature may activate STIM1, which can contribute to platelet activation, resulting in formation of a clot, Xiao said.

While sensing temperature is essential for survival and efficient metabolism, it is not clear yet if and how these findings can be clinically translated, said Patapoutian. "It is too early to make predictions on the implications of these findings, but STIM1 and Orai1 are of interest to the pharmaceutical industry given their role in immunodeficiency."

http://www.sciencedaily.com/releases/20 ... 165306.htm

[comment - I am at loss as to why heat isn't a standard treatment for all cancers, including brain]


Top
 Profile  
 
Display posts from previous:  Sort by  
Post new topic Reply to topic  [ 304 posts ]  Go to page Previous  1, 2, 3, 4, 5, 6, 7, 8 ... 21  Next

All times are UTC + 10 hours


Who is online

Users browsing this forum: No registered users and 2 guests


You cannot post new topics in this forum
You cannot reply to topics in this forum
You cannot edit your posts in this forum
You cannot delete your posts in this forum
You cannot post attachments in this forum

Search for:
Jump to:  
cron
Powered by phpBB® Forum Software © phpBB Group
[ Time : 0.077s | 13 Queries | GZIP : Off ]