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Espaço de publicação e discussão sobre oncologia. GBM IMMUNOTHERAPY ONCO-VIRUS ONCOLOGY CANCER CHEMOTHERAPY RADIOTHERAPY



Sexta-feira, 24.04.15

Post-chemo cognitive depreciation linked to brain activity changes

Post-chemo cognitive depreciation linked to brain activity changes

 

(HealthDay News) -- For patients undergoing chemotherapy for breast cancer, cognitive complaints after treatment may be associated with changes in brain activity, according to a study published online May 27 in the Journal of Clinical Oncology.

Sabine Deprez, Ph.D., from the Katholieke Universiteit Leuven in Belgium, and colleagues assessed whether cognitive complaints after breast cancer treatment correlate with detectable changes in brain activity during multitasking. A functional magnetic resonance imaging multitasking task was performed in the scanner by 18 patients before the start of chemotherapy treatment (t1) and four to six months after completing treatment (t2). The same task was performed at matched intervals by 16 patients who were not scheduled to receive chemotherapy and 17 matched healthy controls.

The researchers found that, in chemotherapy-treated patients, voxel-based paired t tests revealed significantly decreased activation from t1 to t2 in the multitasking network, but no changes were observed in the control groups. No differences were seen between the groups at baseline. The chemotherapy-treated patients, but not controls, reported a significant increase in cognitive complaints at t2. There were significant associations between these increases and the decrease in multitasking-linked brain activation. There was a significant group-by-time interaction, with chemotherapy-treated patients, but not healthy controls, showing decreased activation.

"These results suggest that changes in brain activity may underlie chemotherapy-induced cognitive complaints," the authors write. "To the best of our knowledge, this is the first longitudinal study providing evidence for a relationship between longitudinal changes in cognitive complaints and changes in brain activation after chemotherapy."

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por cyto às 17:24

Sexta-feira, 24.04.15

Novel T-Cell Therapy Effective for Epstein-Barr Virus-Associated Lymphoproliferative Disorder

Novel T-Cell Therapy Effective for Epstein-Barr Virus-Associated Lymphoproliferative Disorder

 
 
Abril 22, 2015
 

By Nancy A. Melville

PHILADELPHIA -- April 22, 2015 -- A novel T-cell-based immunotherapy shows efficacy as a potentially life-saving therapy for patients with Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) who have failed to respond to standard rituximab treatment, according to 2 studies presented here at the 2015 Annual Meeting of the American Association for Cancer Research (AACR).

“The overall survival in both studies far exceeded the survival reported for this patient population,” according to Richard J. O’Reilly, MD, Pediatric Bone Marrow Transplantation Service at Memorial Sloan Kettering Cancer Center, New York, New York. “EBV-specific cytotoxic T lymphocytes had a favourable safety profile and were well-tolerated.”

The promising findings have prompted the US Food and Drug Administration (FDA) to grant breakthrough therapy designation to the Memorial Sloan Kettering Cancer Center for the development of the treatment for EBV-LPD.

EBV-LPD is a complication of blood stem cell transplantation, which can otherwise be highly beneficial for patients with conditions including leukaemia and lymphoma.

While rituximab produces remissions in approximately 55% of patients who develop EBV-LPD, those who fail to respond to the therapy have very poor outcomes, with a median survival time of only 16 to 56 days.

In 2 ongoing clinical trials, Dr. O’Reilly and colleagues have been testing the efficacy of T-cells from normal-immune individuals that are stimulated to respond to proteins from the Epstein-Barr virus to treat patients with EBV-LPD.

In the first study, 26 patients with EBV-LPD were treated with the EBV-CTLs from blood from their transplant donor, while 13 patients received human leukocyte antigen (HLA)-matched T-cells from a blood bank of EBV-CTLs from healthy third party donors that the cancer centre has established. The patients had a median age of 21, and 28 had failed prior rituximab.

For both studies, patients were treated with up to 5 cycles of EBV-specific cytotoxic T lymphocytes (EBV-CTL) infusions consisting of 1 or 2×106 cells/kg weekly for 3 weeks.

In the first study of the combined group of 39 patients, as many as 23 had a complete response, 1 had a partial response, and 3 had stabilised disease at 1 year, for a response rate of 62% and a non-progression-rate of 69%.

In the second trial, 18 patients were treated only with the third-party cells from the blood bank, and among them 9 patients had a complete response, 3 had a partial response, and 1 had stable disease.

“Strikingly, the 1-year overall survival for rituximab-refractory patients in both studies was 50% and 49% for patients treated with third party and transplant donor-derived EBV-CTLs, respectively,” the authors wrote.

Toxicity related to EBV-CTLs was low. Among patients who did not respond to the therapy, 6 in the first study and 4 in the second died within 2 months of the EBV-CTL infusion due to progression of EBV-LPD, a relapse of the leukaemia or other causes; however, none of the deaths were related to the treatment.

Dr. O’Reilly noted that the use of the third-party cells can be particularly beneficial in individualising treatment.

“The bank of 3rd party EBV-CTLs permits selection of appropriate cell lines based on a human leukocyte antigen partial match at 2 alleles and desired HLA restriction for more than 98% of all hematopoietic cell transplantation recipients referred,” he said. “The bank also allows selection of secondary EBV-CTLs restricted by different shared HLA alleles for patients not responding to initial treatment.”

While the third-party cells may require more than 1 cycle of therapy to achieve maximal response, with achievement of a complete response, remission is durable, added Dr. O’Reilly. “[And] unlike the paradigm of chemotherapy, partial responses are durable.”

[Presentation title: Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes (EBV-CTLs) for Treatment of Rituximab-Refractory EBV-Associated Lymphoproliferative Disorder (EBV-LPD). Abstract 8841]

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por cyto às 17:21

Sexta-feira, 24.04.15

New Oral Drug Can Normalize Blood Potassium Levels

New Oral Drug Can Normalize Blood Potassium Levels

Recent randomized clinical trials conducted by researchers from the UT Health Science Center in San Antonio and in Australia revealed ZS-9 as a new oral drug that controls high potassium levels in the blood. ZS-9 is the lead experimental therapy being developed by Coppell, Texas-based ZS Pharma. The results were presented at the National Kidney Foundation Spring Clinical Meetings 2015, Dallas, and appeared in The New England Journal of Medicine on Jan 15, 2015 in a study entitled “Sodium Zirconium Cyclosilicate in Hyperkalemia.”

High potassium levels in the blood, known as hyperkalemia, are associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes.  Blood potassium, within certain values, is essential to control muscle contraction and required for normal heart electrical rhythm. Severe hyperkalemia (potassium levels above 7 mmol/L) is considered a medical emergency, due to the risk of arrhythmia.

One of the major causes of hyperkalemia is kidney dysfunction, as potassium is normally excreted by the kidneys. Chronic kidney disease affects more than 20 million people in the U.S. and the incidence increases in people over 70, particularly those with diabetes. Hyperkalemia associates with a higher risk of death from cardiac arrhythmias at end-stage renal disease.

 Medications used by these patients can also increase potassium levels. A significant percentage of patients, between 5-30%, develops hyperkalemia when treated with a class of medications called Renin Angiotensin Aldosterone System inhibitors (RAASI’s). Kidney dialysis removes the excess of potassium through urine production and is the ultimate treatment to reestablish normal potassium levels in these patients. These results showed the effectiveness and safety of ZS-9 by normalizing potassium levels in 10000 patients through selectively binding of potassium in the intestines. “Dialysis is logistically difficult for patients, requires a catheter and is expensive,” Wajeh Y Qunibi, professor of medicine in the School of Medicine at the Health Science Center said in a news release. “In our studies, patients took a dose by mouth three times daily with meals, and potassium normalized in 98 percent of them within 48 hours. This is a major change in the way to treat hyperkalemia,” he added.

 

Importantly, ZS-9 is an effective option to prevent kyperkalemia in patients under RAASI’s treatment as these drugs are also important to slow down the progression of chronic renal disease.

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por cyto às 17:11

Sexta-feira, 24.04.15

Therapeutic Potential of Cancer Immunotherapies

Immune Response Dynamics Can Enhance Therapeutic Potential of Cancer Immunotherapies

A study entitled “The future of immune checkpoint therapy” recently published in the renowned journal Science offers a review on the topic of cancer immunotherapy and the underlying immune responses to tumors. The review was performed by Dr. Padmanee Sharma and Dr. James P. Allison at The University of Texas M.D. Anderson Cancer Center.

Cancer immunotherapy is defined by the use of the body’s own immune system to help fight cancer. One immunotherapy strategy developed is based on immune checkpoint blockade, where regulatory pathways in T cells (a white blood cell type that plays a central role in immunity) are targeted to enhance anti-cancer immune responses. This therapeutic strategy has proven effective in a significant number of cancer patients, with durable clinical responses and long-term survival rates. However, in order to further explore and enhance the therapeutic potential of immune checkpoint blockade, it is necessary to better understand the patients’ immune response within the tumor microenvironment.

“Identifying in advance who will benefit from treatment and developing combination therapies to improve and expand on current results will require us to decipher the dynamics of human immune response to tumors and their surrounding microenvironment,” noted the study’s co-author Dr. Sharma in a news release.

Immune checkpoint blockade therapies do not directly target the tumor; instead they stimulate the immune system to identify and kill cells with recognized tumor antigens. Ipilimumab (Yervoy) is an example of a first checkpoint inhibitor that blocks a molecule on T cells named CTLA-4, which once activated down-regulates the immune system. T cells have another checkpoint known as PD-1, which also down-regulates the immune system by preventing the activation of T-cells. PD-1 can be triggered by a molecule called PD-L1 found on the surface of tumor cells. Two antibodies have been developed to block PD-1 activation in advanced melanoma — nivolumab (Opdivo) and pembrolizumab (Keytruda). Both antibody drugs are currently in clinical trial studies for treatment against a variety of cancers. 

 

“We know the constantly evolving nature of immune responses makes it highly unlikely that a single biomarker could predict a patient’s response to one of these drugs,” said the review’s co-author Dr. Allison. The authors believe that panels with multiple biomarkers should be developed and adapted according to alterations in the tumor microenvironment so that treatment outcomes can be improved. This would only be possible through a careful monitoring of biomarkers prior, during and after cancer treatment.

It has been suggested that PD-L1 expression in tumors could be used as a predictive biomarker for treatments that directly target PD-L1 or PD-1. A clinical trial in melanoma patients showed that 37% of the patients whose tumors expressed PD-L1 had a positive response to nivolumab treatment, while patients who did not express PD-L1 were non-responsive. Other clinical trials, however, showed that 43 to 46% of the patients expressing PD-L1 have higher response rates to nivolumab, while patients who do not express PD-L1 also exhibited significant responses to treatment (11 to 17%).

“On the basis of data reported so far, it seems fair to conclude that PD-L1 expression in tumor tissues shouldn’t be used as a predictive biomarker for selection or exclusion of patients for treatment with anti-PD-1 or anti-PD-L1 antibodies,” advisedthe study authors.

Tumor genetic analysis for mutations might also be an important approach, as it was previously shown that melanomas with a higher mutational load (higher number of mutations) are more susceptible to checkpoint blockade by ipilimumab and correlate with better clinical responses to the drug.

The ability of the immune system to trigger specific T cell attacks on cancer cells, to adapt the attack according to alterations in the tumor microenvironment and memorize all the target antigens, offers several components with potential therapeutic activity and “make it essential to expand our efforts to find rational combinations to unleash antitumor immune responses that will benefit cancer patients. Properly done, it seems likely that cures for many types of cancer will soon become a reality,” concluded the authors.

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por cyto às 17:10

Quinta-feira, 16.04.15

Early Detection And Screening Of Cancer Tests

Asuragen Joins UK Cancer Research Consortium To Develop Early Detection And Screening Of Cancer Tests

Austin-based molecular diagnosis company, Asuragen, Inc., was recently selected to work with the Early Diagnosis Consortium (EDC) — a collaboration between Abcodia, the Cancer Research UK and Cancer Research Technology. The Consortium’s goal is not only to discover but validate serum biomarkers that can be used in screening and in earlier detection of cancer.

Asuragen is focused on conducting improved patient management in the oncology field and in genetic disorders by using the best clinical testing solutions available. In order to discover, advance and commercialize their diagnostic products for both clinical laboratories and pharmaceutical partners, the company uses a wide range of technologies and expertise in the field of molecular diagnosis in order to improve health economics and clinical outcomes.

The company plans to use its small RNA sequencing technology and bioinformatics tools, which are now optimized for the identification of isomers, miRNA and other small ncRNA biomarkers collected from biofluids. This project will support the discovery of circulating miRNA biomarkers that can improve early detection of cancer such as lung, colorectal, pancreatic and esophageal cancers.

 

President and CEO of Asuragen, Matt McManus, said in a press release: “The promise of detecting cancer in its earliest phases with innovative diagnostic tests is very exciting. Our ability to take products from the research bench to the market, coupled with our unique capabilities around miRNAs, positions us to support the discovery and development of such innovative diagnostic tests and, ultimately, their global commercialization.”

 

The small RNA approach only addresses one part of the most difficult and challenging analytical issues regarding the microRNA biomarker discoveries to use in early-stage cancer detection: quantification of known and novel microRNAs; identification of isomers; and achievement of tighter data over a wider dynamic range than other current non-sequencing-based options.

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por cyto às 19:47

Quinta-feira, 16.04.15

Immune Response Dynamics Can Enhance Therapeutic Potential of Cancer Immunotherapies

Immune Response Dynamics Can Enhance Therapeutic Potential of Cancer Immunotherapies

A study entitled “The future of immune checkpoint therapy” recently published in the renowned journal Science offers a review on the topic of cancer immunotherapy and the underlying immune responses to tumors. The review was performed by Dr. Padmanee Sharma and Dr. James P. Allison at The University of Texas M.D. Anderson Cancer Center.

Cancer immunotherapy is defined by the use of the body’s own immune system to help fight cancer. One immunotherapy strategy developed is based on immune checkpoint blockade, where regulatory pathways in T cells (a white blood cell type that plays a central role in immunity) are targeted to enhance anti-cancer immune responses. This therapeutic strategy has proven effective in a significant number of cancer patients, with durable clinical responses and long-term survival rates. However, in order to further explore and enhance the therapeutic potential of immune checkpoint blockade, it is necessary to better understand the patients’ immune response within the tumor microenvironment.

“Identifying in advance who will benefit from treatment and developing combination therapies to improve and expand on current results will require us to decipher the dynamics of human immune response to tumors and their surrounding microenvironment,” noted the study’s co-author Dr. Sharma in a news release.

Immune checkpoint blockade therapies do not directly target the tumor; instead they stimulate the immune system to identify and kill cells with recognized tumor antigens. Ipilimumab (Yervoy) is an example of a first checkpoint inhibitor that blocks a molecule on T cells named CTLA-4, which once activated down-regulates the immune system. T cells have another checkpoint known as PD-1, which also down-regulates the immune system by preventing the activation of T-cells. PD-1 can be triggered by a molecule called PD-L1 found on the surface of tumor cells. Two antibodies have been developed to block PD-1 activation in advanced melanoma — nivolumab (Opdivo) and pembrolizumab (Keytruda). Both antibody drugs are currently in clinical trial studies for treatment against a variety of cancers.

 

 

“We know the constantly evolving nature of immune responses makes it highly unlikely that a single biomarker could predict a patient’s response to one of these drugs,” said the review’s co-author Dr. Allison. The authors believe that panels with multiple biomarkers should be developed and adapted according to alterations in the tumor microenvironment so that treatment outcomes can be improved. This would only be possible through a careful monitoring of biomarkers prior, during and after cancer treatment.

It has been suggested that PD-L1 expression in tumors could be used as a predictive biomarker for treatments that directly target PD-L1 or PD-1. A clinical trial in melanoma patients showed that 37% of the patients whose tumors expressed PD-L1 had a positive response to nivolumab treatment, while patients who did not express PD-L1 were non-responsive. Other clinical trials, however, showed that 43 to 46% of the patients expressing PD-L1 have higher response rates to nivolumab, while patients who do not express PD-L1 also exhibited significant responses to treatment (11 to 17%).

“On the basis of data reported so far, it seems fair to conclude that PD-L1 expression in tumor tissues shouldn’t be used as a predictive biomarker for selection or exclusion of patients for treatment with anti-PD-1 or anti-PD-L1 antibodies,” advised the study authors.

Tumor genetic analysis for mutations might also be an important approach, as it was previously shown that melanomas with a higher mutational load (higher number of mutations) are more susceptible to checkpoint blockade by ipilimumab and correlate with better clinical responses to the drug.

The ability of the immune system to trigger specific T cell attacks on cancer cells, to adapt the attack according to alterations in the tumor microenvironment and memorize all the target antigens, offers several components with potential therapeutic activity and “make it essential to expand our efforts to find rational combinations to unleash antitumor immune responses that will benefit cancer patients. Properly done, it seems likely that cures for many types of cancer will soon become a reality,” concluded the authors.

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por cyto às 19:42

Quinta-feira, 16.04.15

Science Fact or Science Fiction? – 9 Common Cancer Myths

Science Fact or Science Fiction? – 9 Common Cancer Myths

myths vs facts
March 31, 2015
· Amber Bauer, ASCO staff

Just doing a quick search for “cancer” online not only brings up a wealth of credible information about the disease and its treatment, but also pages spreading common myths and misconceptions. So how do we know what’s accurate when some of these myths can sound perfectly logical?

Today, we’ll help separate the science fact from the science fiction.

MYTH 1: Cancer thrives on sugar.

FACT: The Internet is awash with claims that sugar feeds cancer growth and that eliminating sugar from your diet will cure the disease. However, there is no conclusive evidence that proves eating sugar will make cancer grow and spread more quickly. All cells in the body, both healthy cells and cancer cells, depend on glucose, a type of sugar, to function. And the body breaks down all of the food you eat into glucose molecules. So, eating sugar won’t speed up the growth of cancer, just as cutting sugar out completely won’t slow down its growth.

This doesn’t mean you should eat a high-sugar diet, though. Consuming too many calories from sugary foods has been linked to weight gain, obesity, and diabetes, which increase the risk of developing cancer and other health problems.

MYTH 2: You won’t get cancer if no one in your family has had it.

FACT: Only 5% to 10% of cancers are passed down from parents to children. The majority of cancers are caused by genetic changes that occur throughout a person’s lifetime. These changes, or mutations, are usually triggered by lifestyle choices, such as using tobacco, not wearing sunscreen, or maintaining an unhealthy weight. Exposure to certain chemicals in our workplaces and/or homes can also cause mutations. However, sometimes there is no clear reason why these mutations occur.

A single mutation is unlikely to cause cancer by itself. However, these mutations build up throughout our lifetime. That is one reason why more than 60% of cancers in the United States occur in people who are 65 and older.

MYTH 3: Hair dyes and antiperspirants can cause cancer.

FACT: There is currently no conclusive scientific evidence that using hair dye and antiperspirants increases the risk of developing cancer. Some studies have suggested that the hair dyes used before 1980 could be linked to an increased risk of developing non-Hodgkin lymphoma, but the unsafe chemicals have since been removed from these products. There is limited and inconsistent evidence that hair dye can increase the risk of other types of cancer.

As for antiperspirants, there is some evidence that the skin may absorb the aluminum-based compounds that act as the active ingredient. These compounds are known to cause hormonal changes, which has led some to believe that antiperspirants could contribute to the development of breast cancer. However, there is no consistent evidence to support this claim.

MYTH 4: Cancer is extremely painful.

FACT: Pain is one of the most common symptoms of cancer and side effects of treatment. However, not all people with cancer experience pain. If pain does develop, it can be successfully treated with medications and other pain management techniques. To benefit from these pain-relief strategies, you must talk honestly about your pain with a member of your health care team. There is no reason to suffer in silence because there are lots of things your health care team can do to help. Learn more about talking with your doctor about pain management.

MYTH 5: Cancer spreads when exposed to air during surgery.

FACT: There is no scientific evidence that cancer spreads because it has been exposed to air, and cancer rarely spreads as a result of surgery. Surgery is actually the most effective treatment option for many types of cancer. Some people believe cancer spreads after “exposure to air” because they feel worse after surgery than they did before. However, it takes time to recover from any operation. Others believe this myth because sometimes doctors find more cancer during surgery than was shown on scans and other imaging tests. This doesn’t happen because the cancer spread during the surgery. The cancer was already there. It just didn’t show up on these tests.

MYTH 6: Everyone with cancer must start treatment immediately.

FACT: If a cancer is found at an early stage, is growing slowly, and your doctor feels treating the cancer would cause more discomfort than the disease, your doctor may recommend active surveillance or watchful waiting. During active surveillance, the cancer is monitored closely. Treatment generally begins if the cancer shows signs of growing or begins causing symptoms.

MYTH 7: You can be too old for cancer treatment.

FACT: There is no age limit for cancer treatment. Decisions about cancer treatment for older adults should take into consideration the same factors as for younger adults and should not focus on the person’s age alone. Many older patients benefit as much as younger patients from treatment. However, some older adults may have other illnesses that limit the use of specific treatments.

MYTH 8: People being treated for cancer are confined to the hospital.

FACT: Most people living with cancer are treated in their home community on an outpatient basis and will not have to stay at a hospital. They often continue with some or all of their day-to-day activities. Many people can work part-time or full-time, care for their children, and attend social activities while they are having cancer treatment.

MYTH 9: We’ve made no progress in treating cancer.

FACT: During the last 40 years, advances have been made in every area of cancer care—prevention, screening, and treatment. These advances have increased survival rates for most common types of cancer.

According to the National Cancer Institute’s Office of Cancer Survivorship, the number of people with a history of cancer in the United States has increased dramatically, from 3 million in 1971 to about 14.5 million today. About 64% of today’s cancer survivors were diagnosed with cancer five or more years ago. And, approximately 15% of all cancer survivors were diagnosed 20 or more years ago. Over the next decade, the number of people who have lived five years or more after a cancer diagnosis is expected to increase by approximately 37%.

At the same time, better ways of managing nausea, pain, and other side effects help people maintain their quality of life throughout treatment.

Get more myths and facts about cancer in this ASCO Answers fact sheet (PDF), available in English or Spanish.

Approved by the Cancer.Net Editorial Board, 03/2015

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por cyto às 19:37

Quinta-feira, 16.04.15

Evaluating Complementary and Alternative Therapies

Evaluating Complementary and Alternative Therapies

Approved by the Cancer.Net Editorial Board, 03/2015

Key Messages:

  • Ask specific questions to find out about the safety and effectiveness of complementary and alternative therapies.
  • Talk with your doctor before using any complementary therapies. Do not use any alternative therapies.

Many people with cancer have questions about the methods and products used as complementary therapies. However, before you begin any complementary therapy, discuss all treatment options with your doctor. It is important to make sure the complementary therapy works well with your cancer treatment plan.

Some complementary therapies have research supporting their safety and effectiveness when used with standard cancer treatment. Alternative therapies, on the other hand, do not work, are often costly, and may be harmful. How are some ways to know?

First, find out who is recommending this therapy. If there are only people's personal stories and no trustworthy research, the treatment probably does not treat cancer. If news or ads about a therapy appear in mass media, but not in scientific journals, it is unlikely to help treat cancer. Learn more about evaluating cancer information on the Internet. If a treatment promises to cure all cancers, the ad is a fraud. There are more than 100 different types of cancer. No one treatment will work for every person or for every type of cancer.

Other considerations:

  • The word "natural" does not mean "safe." For example, poisonous mushrooms are natural, but not safe. It is possible to have bad reactions to natural products, even those that are safe, particularly if a person takes large doses.
  • Many herbal therapies and dietary products often act like drugs in your body and cause side effects.
  • Before giving a dietary or herbal product to a child, talk with his or her pediatric oncologist. A child's body uses drugs and nutrients differently and needs different doses than an adult's body.

Specific questions

Use the questions below to help find out more about a complementary or alternative therapy.

  • What is the goal of this therapy? Does it work in combination with a standard therapy, or would it replace standard therapy?
  • If I use this therapy instead of a standard treatment or a clinical trial, will it delay standard treatment? Could this delay be harmful? Will this therapy affect the chances of receiving treatment later?
  • What research is available about this treatment’s safety and effectiveness?
  • Does the person offering this treatment have a license or credentials for their specialization?
  • Will this treatment work for the type of cancer I have? Has research supporting this treatment been published in peer-reviewed medical journals?
  • Is it possible to have a reaction to or side effects from this therapy?
  • Is there a clinical trial for this therapy that I can join?

Learn more about complementary therapies and clinical trials.

More Information

Dietary and Herbal Products

Types of Complementary Therapies

How to Protect Yourself from Cancer Treatment Fraud

Additional Resources

Federal Trade Commission: Cancer Treatment Scams

National Cancer Institute: Thinking About Complementary and Alternative Medicine

National Center for Complementary and Integrative Health (NCCIH): Are You Considering Complementary Medicine?

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por cyto às 19:36

Quarta-feira, 15.04.15

Personalized cancer vaccines may fight tumors

Personalized cancer vaccines may fight tumors
 
 
 
 By Jocelyn Kaiser 2 April 2015 Jocelyn is a staff writer for Sciencemagazine.

Cancer treatments that harness the body’s immune system to wipe out tumors have begun paying off for some patients for whom all other therapies have failed. Now, a small clinical study has found support for a newcomer on the cancer immunotherapy front. Injected with a vaccine designed to match specific mutations in their tumors, three patients with advanced melanoma had a strong immune response and in two their tumors shrunk or stabilized, at least temporarily. Although the study was mainly meant to test safety, the results suggest it holds promise for stopping tumors from growing.

“There’s a lot of excitement about this approach,” says oncologist and cancer immunologist Craig Slingluff of the University of Virginia in Charlottesville, who was not involved with the study.

Vaccines for infectious diseases typically deliver into the body bits of protein or other material from a virus or bacterium that trigger the immune system to defend against the invading pathogen. With cancer, the similar idea is to vaccinate a patient with immune-stimulating molecules, known as antigens, found only on tumor cells, so that the person’s immune system ends up attacking the tumor. But cancer vaccines have a poor record of success. That’s because most of the tumor antigens tested also appear in small amounts on healthy cells, and the immune system has mechanisms that make it tolerate, or ignore, these familiar antigens.

Scientists have their eye on a more promising kind of tumor antigen: those that result from the mutations that riddle a tumor’s DNA, thanks to the chaos cancer causes to a genome. Some of these mutations do not appear in genes that drive cancer growth, but instead code for novel peptides—short proteins—that may act as antigens on the surface of tumor cells. Because these so-called neoantigens are completely foreign to the body, they could in theory make a cancer vaccine.

Devising a neoantigen cancer vaccine requires sequencing a lot of tumor DNA, which wasn’t feasible or affordable until recently. But now that DNA sequencing costs have dropped and speeds increased, researchers at Washington University in St. Louis have begun exploring neoantigen cancer vaccines for melanoma, a tumor in which the sun’s ultraviolet light that sparks cancer-causing mutations also creates hundreds of additional mutations that are likely to include many coding for neoantigens.

Human immunologist Beatriz Carreno, trial leader Gerald Linette, and collaborators recently studied three melanoma patients who had surgery to remove their tumors, but who had cancer cells that had spread to their lymph nodes, making tumors likely to recur. The researchers sequenced the exome, or protein-coding DNA, of each patient’s original melanoma tumor and compared it with the exome of their other cells to identify dozens of mutations coding for newly created peptides that might act as neoantigens. (Not all peptides made by a cell get displayed on its surface.) They analyzed the possible neoantigens’ structures and did lab tests to predict which are actually made by the cell and get displayed on its surface, then homed in on those most likely to trigger an immune response. For each melanoma patient they chose seven neoantigens unique to that person’s tumor.

After taking blood from each patient and harvesting from it immune sentinels called dendritic cells, the researchers then mixed each patient’s set of neoantigens with these white blood cells so that they would display the peptides to other immune cells. The team used the neoantigen-coated dendritic cells to make personalized neoantigen vaccines that were infused into the patients three times over about 4 months.

Carreno and collaborators found that a key measure of vaccine response, the number of immune system T cells specific to the neoantigens in each patient, rose in the patients’ blood, along with an increase in the diversity of these T cells. These neoantigen-specific T cells could also kill cultured melanoma cells expressing the same neoantigens, the teamreports online today in Science.

In one patient, metastatic tumors in the woman’s lungs shrank, then regrew, but are now stable after 8 months; the second person’s tumor remnants have also been stable for 9 months. A third patient who had received an immunotherapy drug after surgery that put his cancer in remission remains cancer-free. However, the trial was designed primarily to confirm the safety of the vaccine and immune response, not to test its effectiveness, and because the patients received other treatments, it is not possible to say whether the vaccine helped: “I would be speculating if I said that the vaccine had any benefit to the patients,” Linette says.

But the fact that the study found “a pretty high magnitude of immune response,” combined with recent reports that a different neoantigen vaccine can fight cancer in mice, suggests the idea is “promising,” Slingluff says.

Such a vaccine, which should be less toxic than chemotherapy, might be used to prevent cancer from recurring after surgery. It might also be combined with other immunotherapy drugs known as checkpoint inhibitors that seem to work best for cancers such as lung and melanoma in which tumors have many mutations. “The high anticipation is whether the one-two punch with checkpoint inhibition would work,” says Roger Lo, a melanoma researcher at the University of California, Los Angeles.

 

Posted in Health

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por cyto às 13:35

Quarta-feira, 15.04.15

New HIV Antibody May Suppress Virus,

New HIV Antibody May Suppress Virus, Early Results Suggest

 
New HIV Antibody May Suppress Virus, Early Results Suggest 
New HIV Antibody May Suppress Virus, Early Results Suggest

HealthDay News — Therapy with a human antibody may reduce levels of HIV in the blood for at least a month, according to preliminary findings published in a research letter in Nature.

The antibody "might be able to intensify current treatment strategies," study coauthor Florian Klein, MD, an assistant professor of clinical investigation at Rockefeller University in New York City, toldHealthDay, especially since this new treatment appears to be more potent than previous attempts at HIV immunotherapy. The researchers acknowledged that this antibody treatment would have to be combined with HIV drugs or another antibody. And much more research is needed before this treatment could even be used as an add-on therapy.

In the new study, researchers turned to an antibody known as 3BNC117 that targets HIV. These types of antibodies are only produced naturally by about 10 to 30% of people with HIV, according to the researchers. They injected the immunotherapy into 12 people without HIV and 17 infected people. The participants were almost all men, were between 22 and 58 years old, and about half were black.

The researchers reported that the levels of virus in infected patients who got the highest doses were "significantly reduced" for 28 days. The treatment was "generally safe and well-tolerated" without serious side effects, according to the investigators.

Reference

  1. Caskey M et al. Nature. 2015; doi:10.1038/nature14411.
 

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por cyto às 13:27

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