(Source: http://www.drmirkin.com/men/9431.html)
An article in the British medical journal, Lancet, offers evidence that lack of vitamin D causes prostate cancer.
Most men meet their needs for vitamin D through exposure to sunlight because they do not get enough from their diet. Men who live in colder climates have a higher incidence of prostate cancer because they get less sunlight. Studies from Harvard School of public Health show that men who drink more than four glasses of milk a day have low blood levels of vitamin D and are at increased risk for prostate cancer. Calcium uses up vitamin D and not enough vitamin D is added to milk to cover the extra calcium used.
This study shows that prostate cancer is associated with not exposing skin to sunlight and not going on holidays to beach resorts. Susceptibility to prostate cancer was not found to be associated with vasectomy, benign prostatic enlargement or eating any particular food.
Visualizzazione post con etichetta cancer. Mostra tutti i post
Visualizzazione post con etichetta cancer. Mostra tutti i post
mercoledì 27 aprile 2016
High Blood Sugar Linked to Prostate Enlargement, Low Testosterone and Prostate Cancer
(Source: http://www.drmirkin.com/men/high-blood-sugar-linked-to-prostate-enlargement-low-testosterone-and-prostate-cancer.html)
Metabolic syndrome and type II diabetes are characterized by high blood sugar, insulin, and triglycerides, low HDL and a fatty liver and obesity. Of 490 male adults, average age 58 years old, 37 percent with lower urinary tract obstruction (LUTS) had metabolic syndrome (Adv Urol, published online Jan 23, 2014). Of those with:
• mild LUTS, 37.4 percent had metabolic syndrome,
• moderate LUTS , 46.5 percent had metabolic syndrome and
• severe LUTS, 54.1 percent had metabolic syndrome.
The patients with metabolic syndrome had much larger prostates than those who did not have that syndrome. Obese men and those with higher levels of the bad LDL cholesterol also had larger prostates.
Low Testosterone and Prostate Cancer Linked to Metabolic Syndrome
Of 1,150 men aged 30 years or older, the lower the testosterone, the more likely a man is to have metabolic syndrome. (Urology, published online October 08, 2013). The researchers defined Metabolic Syndrome as a waist circumference of 85 cm or more plus any two of the following: triglyceride 150 mg/dl or higher, good HDL cholesterol level below 40 mg/dL, taking statins, systolic blood pressure of 130 mm Hg or higher, diastolic blood pressure of 85 mm Hg or higher, taking high blood pressure medications, fasting blood sugar 110 mg/dL or higher, or use of a drug to lower high blood sugar.
Men who had any three of the risk factors for metabolic syndrome are one and a half times more likely to develop prostate cancer than those who do not have metabolic syndrome (European Urology, published online February 24, 2014).
Metabolic Syndrome and Diabetes
Metabolic syndrome means you are on your way to becoming diabetic. Diabetes is a disease in which high blood sugar levels damage every cell in your body. When blood sugar levels rise too high (high blood sugar), the pancreas releases large amounts of insulin (high insulin), which converts sugar to a type of fat called triglycerides (high triglycerides). Then your body uses up its good HDL cholesterol to carry triglycerides from the bloodstream to the liver (low HDL). Next, the extra triglycerides carried to the liver are stored in the liver to form a fatty liver. The triglycerides are also stored in your body to make you fat (overweight). These are the components of both metabolic syndrome and Type II diabetes.
Metabolic syndrome and type II diabetes are characterized by high blood sugar, insulin, and triglycerides, low HDL and a fatty liver and obesity. Of 490 male adults, average age 58 years old, 37 percent with lower urinary tract obstruction (LUTS) had metabolic syndrome (Adv Urol, published online Jan 23, 2014). Of those with:
• mild LUTS, 37.4 percent had metabolic syndrome,
• moderate LUTS , 46.5 percent had metabolic syndrome and
• severe LUTS, 54.1 percent had metabolic syndrome.
The patients with metabolic syndrome had much larger prostates than those who did not have that syndrome. Obese men and those with higher levels of the bad LDL cholesterol also had larger prostates.
Low Testosterone and Prostate Cancer Linked to Metabolic Syndrome
Of 1,150 men aged 30 years or older, the lower the testosterone, the more likely a man is to have metabolic syndrome. (Urology, published online October 08, 2013). The researchers defined Metabolic Syndrome as a waist circumference of 85 cm or more plus any two of the following: triglyceride 150 mg/dl or higher, good HDL cholesterol level below 40 mg/dL, taking statins, systolic blood pressure of 130 mm Hg or higher, diastolic blood pressure of 85 mm Hg or higher, taking high blood pressure medications, fasting blood sugar 110 mg/dL or higher, or use of a drug to lower high blood sugar.
Men who had any three of the risk factors for metabolic syndrome are one and a half times more likely to develop prostate cancer than those who do not have metabolic syndrome (European Urology, published online February 24, 2014).
Metabolic Syndrome and Diabetes
Metabolic syndrome means you are on your way to becoming diabetic. Diabetes is a disease in which high blood sugar levels damage every cell in your body. When blood sugar levels rise too high (high blood sugar), the pancreas releases large amounts of insulin (high insulin), which converts sugar to a type of fat called triglycerides (high triglycerides). Then your body uses up its good HDL cholesterol to carry triglycerides from the bloodstream to the liver (low HDL). Next, the extra triglycerides carried to the liver are stored in the liver to form a fatty liver. The triglycerides are also stored in your body to make you fat (overweight). These are the components of both metabolic syndrome and Type II diabetes.
Study: Antioxidant Pills Can Cause Cancer to Spread
(Source: http://www.drmirkin.com/morehealth/antioxidant-pills-can-cause-cancer-to-spread.html)
A study from China shows that antioxidant pills caused mice with liver cancer or colon cancer to have their cancers spread rapidly though their bodies. The study used saxagliptin, sitagliptin, and a-lipoic acid, three powerful antioxidant drugs used to treat diabetes. The antioxidants protected the cancer cells from harm, rather than protecting the mice from spread of their cancers. These antioxidants activated NRF2 antioxidant signaling pathway that protected the cancer cells instead of protecting the mice.
The authors then tested antioxidant pills on cells taken from patients with malignant cancers and grown in test tubes. The antioxidants caused the human cancer cells to grow faster and spread through the cultures. Overall, the conclusion from this and several other cancer studies is that antioxidants can help healthy cells to be protected from free radicals in the body, but they can cause already-developed cancer cells to grow and spread. The researchers cautioned that more studies are needed to evaluate the safety of antioxidant-containing medications for diabetic patients with cancer. They want to confirm their findings in human cancer patients before any definitive clinical recommendations can be made.
Radiation and chemotherapy, the most common cancer treatments used today, are both based on generating oxidants that help to keep cancer from spreading. Ionizing radiation kills cancer cells by generating oxidants. Chemotherapy drugs such as paclitaxel kill cancer cells by generating very powerful oxidants — superoxide, hydrogen and hydrogen peroxide.
What Are Antioxidants?
Every chemical reaction in your body works by transferring electrons from one molecule to another. During a chemical reaction, molecules and atoms called free radicals are formed and contain an unpaired electron that has an electrical charge that can destroy tissue and damage DNA. Antioxidants are molecules that donate an electron to the free radical, thus neutralizing the electrical charge and stabilizing it. Without antioxidants, the electrical charge of free radicals causes oxidative stress that is associated with aging, heart failure, cancer, Alzheimer’s, and just about every disease.
There are thousands of antioxidants, including vitamins A, C and E, minerals such as selenium and zinc, and enzymes that cause chemical reactions to proceed in your body. Foods containing antioxidants include fruits, vegetables, grains, tea, chocolate, red wine and many others, but no good studies have shown that antioxidants in foods are harmful. The many studies showing harm from antioxidants have used pills containing single antioxidants or combinations of antioxidants that have been removed from foods or manufactured in laboratories. We do not know why antioxidants in foods are different, but it may be be that antioxidants in foods are affected by other chemicals found in the same foods. For example, “chocolate has more than 20 antioxidant flavonoids. One is converted into a free radical and becomes reactive, but less reactive [than the first]. It then reacts with another, and that one is less reactive and so on and so forth, and all of them react with each other, decreasing the damage that would be happening to our lipids, or proteins or DNA” .
How Antioxidants Can Harm You
After an antioxidant donates an electron to a free radical, it becomes charged and can damage your cells. Foods contain many different antioxidants, so an antioxidant in a food has many other antioxidants readily available to neutralize the charge it picks up. However, in a pill, the antioxidant stands alone or has only one or a few other antioxidants to protect it. Antioxidants taken in pills can carry and retain electrical charges that damage your cells, which can cause aging and diseases including cancer.
Your cells are supposed to protect you from free radicals by producing their own antioxidants. Since exercise produces huge amounts of oxidants, exercise causes a natural production of antioxidants by your own body, and therefore exercise helps to protect you from free radicals, aging, cancer and disease. When you take antioxidant pills, you markedly reduce the amount of antioxidants that your own body produces. Antioxidant supplements also prevent growth of new mitochondria in exercisers. See my report on Antioxidant Pills May Reduce Gains from Exercise
Other Studies Showing That Antioxidant Pills May Cause Cancers to Spread
This new study from China is just the latest of many studies showing that antioxidant pills may cause an existing cancer to spread. A study from Notre Dame showed that antioxidant pills may cause an existing breast cancer to spread through the body. Research from the University of Gothenburg in Sweden showed that people who take antioxidant vitamin pills suffer twice as much melanoma metastasis. Another study from Gothenburg’s Sahlgrenska Academy showed that antioxidants accelerate lung cancer progression in mice. The authors of this study state, “Our current research combined with information from large clinical trials with antioxidants suggests that people who have been recently diagnosed with cancer should avoid such supplements.” They also note that skin lotions and suntan lotions often contain large amounts of antioxidants such as vitamin E and beta carotene.
Antioxidant Pills Are Everywhere
Antioxidant supplements are widely available in stores and online, and they are often promoted with claims that they can help to prevent and cure cancer. A 2011 report from the National Center for Health Statistics estimated that 53 percent of American adults take supplements and spent $28 billion on them in 2010 alone. Research at Sahlgrenska Academy has shown that cancer patients are particularly prone to taking supplements containing antioxidants.
My Recommendations
• There is no credible evidence that antioxidant pills, such as vitamins A, C, and E or minerals such as selenium, are effective in preventing cancer, heart attacks or diabetes.
• A multibillion dollar industry is based on the unproven concept that antioxidants promote health.
• There is evidence that antioxidant pills may spread existing cancers.
• Some data show that antioxidant pills may increase risk for cancer and reduce benefits of chemotherapy.
• Instead of taking antioxidant pills or any other supplements, I recommend that you eat a varied diet that contains plenty of plants.
A study from China shows that antioxidant pills caused mice with liver cancer or colon cancer to have their cancers spread rapidly though their bodies. The study used saxagliptin, sitagliptin, and a-lipoic acid, three powerful antioxidant drugs used to treat diabetes. The antioxidants protected the cancer cells from harm, rather than protecting the mice from spread of their cancers. These antioxidants activated NRF2 antioxidant signaling pathway that protected the cancer cells instead of protecting the mice.
The authors then tested antioxidant pills on cells taken from patients with malignant cancers and grown in test tubes. The antioxidants caused the human cancer cells to grow faster and spread through the cultures. Overall, the conclusion from this and several other cancer studies is that antioxidants can help healthy cells to be protected from free radicals in the body, but they can cause already-developed cancer cells to grow and spread. The researchers cautioned that more studies are needed to evaluate the safety of antioxidant-containing medications for diabetic patients with cancer. They want to confirm their findings in human cancer patients before any definitive clinical recommendations can be made.
Radiation and chemotherapy, the most common cancer treatments used today, are both based on generating oxidants that help to keep cancer from spreading. Ionizing radiation kills cancer cells by generating oxidants. Chemotherapy drugs such as paclitaxel kill cancer cells by generating very powerful oxidants — superoxide, hydrogen and hydrogen peroxide.
What Are Antioxidants?
Every chemical reaction in your body works by transferring electrons from one molecule to another. During a chemical reaction, molecules and atoms called free radicals are formed and contain an unpaired electron that has an electrical charge that can destroy tissue and damage DNA. Antioxidants are molecules that donate an electron to the free radical, thus neutralizing the electrical charge and stabilizing it. Without antioxidants, the electrical charge of free radicals causes oxidative stress that is associated with aging, heart failure, cancer, Alzheimer’s, and just about every disease.
There are thousands of antioxidants, including vitamins A, C and E, minerals such as selenium and zinc, and enzymes that cause chemical reactions to proceed in your body. Foods containing antioxidants include fruits, vegetables, grains, tea, chocolate, red wine and many others, but no good studies have shown that antioxidants in foods are harmful. The many studies showing harm from antioxidants have used pills containing single antioxidants or combinations of antioxidants that have been removed from foods or manufactured in laboratories. We do not know why antioxidants in foods are different, but it may be be that antioxidants in foods are affected by other chemicals found in the same foods. For example, “chocolate has more than 20 antioxidant flavonoids. One is converted into a free radical and becomes reactive, but less reactive [than the first]. It then reacts with another, and that one is less reactive and so on and so forth, and all of them react with each other, decreasing the damage that would be happening to our lipids, or proteins or DNA” .
How Antioxidants Can Harm You
After an antioxidant donates an electron to a free radical, it becomes charged and can damage your cells. Foods contain many different antioxidants, so an antioxidant in a food has many other antioxidants readily available to neutralize the charge it picks up. However, in a pill, the antioxidant stands alone or has only one or a few other antioxidants to protect it. Antioxidants taken in pills can carry and retain electrical charges that damage your cells, which can cause aging and diseases including cancer.
Your cells are supposed to protect you from free radicals by producing their own antioxidants. Since exercise produces huge amounts of oxidants, exercise causes a natural production of antioxidants by your own body, and therefore exercise helps to protect you from free radicals, aging, cancer and disease. When you take antioxidant pills, you markedly reduce the amount of antioxidants that your own body produces. Antioxidant supplements also prevent growth of new mitochondria in exercisers. See my report on Antioxidant Pills May Reduce Gains from Exercise
Other Studies Showing That Antioxidant Pills May Cause Cancers to Spread
This new study from China is just the latest of many studies showing that antioxidant pills may cause an existing cancer to spread. A study from Notre Dame showed that antioxidant pills may cause an existing breast cancer to spread through the body. Research from the University of Gothenburg in Sweden showed that people who take antioxidant vitamin pills suffer twice as much melanoma metastasis. Another study from Gothenburg’s Sahlgrenska Academy showed that antioxidants accelerate lung cancer progression in mice. The authors of this study state, “Our current research combined with information from large clinical trials with antioxidants suggests that people who have been recently diagnosed with cancer should avoid such supplements.” They also note that skin lotions and suntan lotions often contain large amounts of antioxidants such as vitamin E and beta carotene.
Antioxidant Pills Are Everywhere
Antioxidant supplements are widely available in stores and online, and they are often promoted with claims that they can help to prevent and cure cancer. A 2011 report from the National Center for Health Statistics estimated that 53 percent of American adults take supplements and spent $28 billion on them in 2010 alone. Research at Sahlgrenska Academy has shown that cancer patients are particularly prone to taking supplements containing antioxidants.
My Recommendations
• There is no credible evidence that antioxidant pills, such as vitamins A, C, and E or minerals such as selenium, are effective in preventing cancer, heart attacks or diabetes.
• A multibillion dollar industry is based on the unproven concept that antioxidants promote health.
• There is evidence that antioxidant pills may spread existing cancers.
• Some data show that antioxidant pills may increase risk for cancer and reduce benefits of chemotherapy.
• Instead of taking antioxidant pills or any other supplements, I recommend that you eat a varied diet that contains plenty of plants.
sabato 7 giugno 2014
Prostate cancer biomarkers identified in seminal fluid
From ScienceDaily website (see original article)
Improved diagnosis and management of one of the most common cancers in men -- prostate cancer -- could result from research at the University of Adelaide, which has discovered that seminal fluid (semen) contains biomarkers for the disease.
Results of a study now published in the journal Endocrine-Related Cancer have shown that the presence of certain molecules in seminal fluid indicates not only whether a man has prostate cancer, but also the severity of the cancer.
Speaking in the lead-up to Men's Health Week (9-15 June), University of Adelaide research fellow and lead author Dr Luke Selth says the commonly used PSA (prostate specific antigen) test is by itself not ideal to test for the cancer.
"While the PSA test is very sensitive, it is not highly specific for prostate cancer," Dr Selth says. "This results in many unnecessary biopsies of non-malignant disease.
More problematically, PSA testing has resulted in substantial over-diagnosis and over-treatment of slow growing, non-lethal prostate cancers that could have been safely left alone.
"Biomarkers that can accurately detect prostate cancer at an early stage and identify aggressive tumors are urgently needed to improve patient care.
Identification of such biomarkers is a major focus of our research," he says.
Dr Selth, a Young Investigator of the Prostate Cancer Foundation (USA), is a member of the Freemasons Foundation Centre for Men's Health at the University of Adelaide and is based in the University's Dame Roma Mitchell Cancer Research Laboratories.
Using samples from 60 men, Dr Selth and colleagues discovered a number of small ribonucleic acid (RNA) molecules called microRNAs in seminal fluid that are known to be increased in prostate tumors.
The study showed that some of these microRNAs were surprisingly accurate in detecting cancer.
"The presence of these microRNAs enabled us to more accurately discriminate between patients who had cancer and those who didn't, compared with a standard PSA test," Dr Selth says.
"We also found that the one specific microRNA, miR-200b, could distinguish between men with low grade and higher grade tumors.
This is important because, as a potential prognostic tool, it will help to indicate the urgency and type of treatment required."
This research builds on previous work by Dr Selth's team, published in the British Journal of Cancer, which demonstrated that microRNAs in the blood can predict men who are likely to relapse after surgical removal of their prostate cancer.
"We are excited by the potential clinical application of microRNAs in a range of body fluids," he says.
Improved diagnosis and management of one of the most common cancers in men -- prostate cancer -- could result from research at the University of Adelaide, which has discovered that seminal fluid (semen) contains biomarkers for the disease.
Results of a study now published in the journal Endocrine-Related Cancer have shown that the presence of certain molecules in seminal fluid indicates not only whether a man has prostate cancer, but also the severity of the cancer.
Speaking in the lead-up to Men's Health Week (9-15 June), University of Adelaide research fellow and lead author Dr Luke Selth says the commonly used PSA (prostate specific antigen) test is by itself not ideal to test for the cancer.
"While the PSA test is very sensitive, it is not highly specific for prostate cancer," Dr Selth says. "This results in many unnecessary biopsies of non-malignant disease.
More problematically, PSA testing has resulted in substantial over-diagnosis and over-treatment of slow growing, non-lethal prostate cancers that could have been safely left alone.
"Biomarkers that can accurately detect prostate cancer at an early stage and identify aggressive tumors are urgently needed to improve patient care.
Identification of such biomarkers is a major focus of our research," he says.
Dr Selth, a Young Investigator of the Prostate Cancer Foundation (USA), is a member of the Freemasons Foundation Centre for Men's Health at the University of Adelaide and is based in the University's Dame Roma Mitchell Cancer Research Laboratories.
Using samples from 60 men, Dr Selth and colleagues discovered a number of small ribonucleic acid (RNA) molecules called microRNAs in seminal fluid that are known to be increased in prostate tumors.
The study showed that some of these microRNAs were surprisingly accurate in detecting cancer.
"The presence of these microRNAs enabled us to more accurately discriminate between patients who had cancer and those who didn't, compared with a standard PSA test," Dr Selth says.
"We also found that the one specific microRNA, miR-200b, could distinguish between men with low grade and higher grade tumors.
This is important because, as a potential prognostic tool, it will help to indicate the urgency and type of treatment required."
This research builds on previous work by Dr Selth's team, published in the British Journal of Cancer, which demonstrated that microRNAs in the blood can predict men who are likely to relapse after surgical removal of their prostate cancer.
"We are excited by the potential clinical application of microRNAs in a range of body fluids," he says.
venerdì 29 marzo 2013
Fish Peptide May Inhibit Cancer Metastasis
From Science Daily website (see original article).
Mar. 19, 2013 — Researchers at the University of Maryland School of Medicine have identified a peptide, or protein, derived from Pacific cod that may inhibit prostate cancer and possibly other cancers from spreading, according to preclinical research published online in the Proceedings of the National Academy of Sciences (PNAS).
"The use of natural dietary products with anti-tumor activity is an important and emerging field of research," says senior author Hafiz Ahmed, Ph.D., assistant professor of biochemistry and molecular biology at the University of Maryland School of Medicine and scientist at the Institute for Marine and Environmental Technology (IMET).
"Understanding how these products work could allow us to develop foods that also act as cancer therapeutics and agents for immunotherapy."
Most people who succumb to cancer die because tumor cells invade the surrounding tissue and migrate into the nearby blood and lymph vessels, a process known as metastasis.
For example, prostate cancer typically spreads to the bones, lungs and liver. Cancer cells that metastasize to other parts of the body grow new blood supplies and eventually overcome the person's organ systems.
"This study is among the first to explore the therapeutic utility of a bioactive cod TFD-containing glycopeptide to inhibit prostate cancer from progressing," says Dr. Ahmed, who also is affiliated with the University of Maryland Marlene and Stewart Greenebaum Cancer Center.
The TFD (Thomsen-Friedenreich disaccharide) antigen in the fish protein is hidden in normal human cells but is exposed on the surface of cancer cells and is believed to play a key role in how cancer spreads.
Polar fish, such as northern cod, express glycoproteins that are rich in the TFD antigen, which protect them from freezing.
The research team developed a special form of TFD, called TFD100, purified from Pacific cod.
Using animal models, the researchers found that TFD100 binds to galectin-3, a protein that is overexpressed in prostate cancer cells, and blocks its interaction with the TFD antigen found on the surface of the cells.
Galectin-3 (gal3) enables cancer cells to adhere to the walls of blood vessels and also kills activated T-cells, a type of white blood cell, which helps the cancer cells to spread throughout the body and evade the immune system.
The researchers observed that TFD100 prevents cancer cells from attaching to the vessel walls, suppresses T-cell death and boosts the immune response.
"Because the gal3-TFD interaction is a key factor driving metastasis in most epithelial cancers, this high-affinity TFD100 should be a promising anti-metastatic agent for the treatment of various cancers, including prostate adenocarcinoma," the researchers conclude in the study, which was published online March 11 in PNAS' Early Edition.
"This research breaks new ground in our ongoing quest to discover new ways to prevent cancers from metastasizing to distant parts of the body," says E. Albert Reece, M.D., Ph.D., M.B.A., Vice President for Medical Affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine.
"If we could one day offer patients a natural dietary supplement, derived from fish proteins, which could help to block that process, we could have a significant impact on improving patients' outcomes and survival."
Co-investigator Dhan V. Kalvakolanu, Ph.D., a professor of microbiology and immunology at the School of Medicine, notes that additional research is needed to develop a dietary supplement from the cod peptide that could complement chemotherapy and other standard treatments.
"No single drug on its own is going to offer protection against advanced cancers. We need a multi-pronged approach to successfully treat this disease," he adds.
The study was conducted by researchers from Dr. Ahmed's laboratory, in collaboration with Dr. Kalvakolanu and other investigators at the University of Maryland Greenebaum Cancer Center and the IMET. Prasun Guha, Ph.D., a postdoctoral fellow in Dr. Ahmed's laboratory, was the study's lead author.
domenica 3 marzo 2013
Tumors Deliberately Create Conditions That Inhibit Body's Best Immune Response
From Science Daily website (see original article).
Mar. 1, 2013 — New research in the Journal of Clinical Investigation reveals that tumours in melanoma patients deliberately create conditions that knock out the body's 'premier' immune defence and instead attract a weaker immune response unable to kill off the tumour's cancerous cells.
The study also highlights a potential antibody biomarker that could help predict prognosis and identify which patients are most likely to respond to specific treatments.
The research, led by Dr Sophia Karagiannis and Professor Frank Nestle at King's College London, UK, was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London.
Karagiannis and colleagues have previously shown that, in patients with melanoma, antibodies are produced that can attack tumour cells.
Despite this, the patient's immune system is often ineffective in preventing the cancer from progressing.
The body's B cells (part of the immune system) produce a total of 5 different antibody classes. The most common, IgG, comprises 4 types (or subclasses) of which the researchers have shown that IgG1 subclass antibodies are the most effective at activating immune cells, while antibodies of the IgG4 subclass are thought to be the least efficient.
In this new research, the authors analysed tumour tissue and blood donated by 80 patients from the melanoma clinic of St John's Institute of Dermatology at Guy's and St Thomas', as well as tissue and blood from healthy volunteers.
By analysing the lesions found in melanoma, the authors show that melanoma tumours not only create conditions that attract IgG4, the weakest possible response, but also that IgG4 antibodies interfere with the action of any IgG1 antibodies circulating.
"We were able to mimic the conditions created by melanoma tumours and showed that B cells can be polarised to produce IgG4 antibodies in the presence of cancer cells," says Dr Karagiannis.
In the presence of healthy cells, the body's immune response functions normally, and IgG1 are the main antibodies circulating.
To better understand the functional implications of IgG4 subclass antibodies in cancer, the authors engineered these two antibodies (IgG1, IgG4) against a tumour antigen and demonstrated that unlike IgG1, the IgG4 antibody was ineffective in triggering immune cells to kill cancer cells.
Importantly, IgG4 also blocked the tumour cell killing actions of IgG1, thus preventing this antibody from activating immune cells to destroy tumours.
Additionally, using samples from 33 patients, the authors found that patients with higher IgG4 levels in their blood are more likely to have a less favourable prognosis compared to those whose blood levels of IgG4 are closer to normal levels.
This suggests that IgG4 may help assist in predicting disease progression.
"This work bears important implications for future therapies since not only are IgG4 antibodies ineffective in activating immune cells to kill tumours but they also work by blocking antibodies from killing tumour cells," says Dr Karagiannis.
"The latter means that IgG4 not only prevents the patient's more powerful antibodies from eradicating cancer, but could also explain why treatments may be hindered by those native IgG4 antibodies found in patients, making therapeutic antibodies less effective."
"Now, with the help of our NIHR Biomedical Research Centre, more work needs to be done on developing IgG4 as a potential clinical and prognostic biomarker which can improve patient care by informing clinical decisions and helping to identify patients most likely to respond to treatments," concludes Professor Nestle.
Therefore, these findings are expected to inform the design and help improve the potency and efficacy of future therapies for cancer.
"This study can also inform the rational design of novel strategies to counteract IgG4 actions."
The authors are now broadening the study by examining larger groups of patients.
The team is analysing blood and sera from patients with melanoma and from patients with other cancers to determine whether the presence of IgG4 could inform patient outcomes or predict responses to therapy.
They are also analysing the mechanisms of IgG4 blockade of new and existing therapeutic antibody candidates, and developing new antibody candidates which may be less prone to IgG4 blockade.
Mar. 1, 2013 — New research in the Journal of Clinical Investigation reveals that tumours in melanoma patients deliberately create conditions that knock out the body's 'premier' immune defence and instead attract a weaker immune response unable to kill off the tumour's cancerous cells.
The study also highlights a potential antibody biomarker that could help predict prognosis and identify which patients are most likely to respond to specific treatments.
The research, led by Dr Sophia Karagiannis and Professor Frank Nestle at King's College London, UK, was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London.
Karagiannis and colleagues have previously shown that, in patients with melanoma, antibodies are produced that can attack tumour cells.
Despite this, the patient's immune system is often ineffective in preventing the cancer from progressing.
The body's B cells (part of the immune system) produce a total of 5 different antibody classes. The most common, IgG, comprises 4 types (or subclasses) of which the researchers have shown that IgG1 subclass antibodies are the most effective at activating immune cells, while antibodies of the IgG4 subclass are thought to be the least efficient.
In this new research, the authors analysed tumour tissue and blood donated by 80 patients from the melanoma clinic of St John's Institute of Dermatology at Guy's and St Thomas', as well as tissue and blood from healthy volunteers.
By analysing the lesions found in melanoma, the authors show that melanoma tumours not only create conditions that attract IgG4, the weakest possible response, but also that IgG4 antibodies interfere with the action of any IgG1 antibodies circulating.
"We were able to mimic the conditions created by melanoma tumours and showed that B cells can be polarised to produce IgG4 antibodies in the presence of cancer cells," says Dr Karagiannis.
In the presence of healthy cells, the body's immune response functions normally, and IgG1 are the main antibodies circulating.
To better understand the functional implications of IgG4 subclass antibodies in cancer, the authors engineered these two antibodies (IgG1, IgG4) against a tumour antigen and demonstrated that unlike IgG1, the IgG4 antibody was ineffective in triggering immune cells to kill cancer cells.
Importantly, IgG4 also blocked the tumour cell killing actions of IgG1, thus preventing this antibody from activating immune cells to destroy tumours.
Additionally, using samples from 33 patients, the authors found that patients with higher IgG4 levels in their blood are more likely to have a less favourable prognosis compared to those whose blood levels of IgG4 are closer to normal levels.
This suggests that IgG4 may help assist in predicting disease progression.
"This work bears important implications for future therapies since not only are IgG4 antibodies ineffective in activating immune cells to kill tumours but they also work by blocking antibodies from killing tumour cells," says Dr Karagiannis.
"The latter means that IgG4 not only prevents the patient's more powerful antibodies from eradicating cancer, but could also explain why treatments may be hindered by those native IgG4 antibodies found in patients, making therapeutic antibodies less effective."
"Now, with the help of our NIHR Biomedical Research Centre, more work needs to be done on developing IgG4 as a potential clinical and prognostic biomarker which can improve patient care by informing clinical decisions and helping to identify patients most likely to respond to treatments," concludes Professor Nestle.
Therefore, these findings are expected to inform the design and help improve the potency and efficacy of future therapies for cancer.
"This study can also inform the rational design of novel strategies to counteract IgG4 actions."
The authors are now broadening the study by examining larger groups of patients.
The team is analysing blood and sera from patients with melanoma and from patients with other cancers to determine whether the presence of IgG4 could inform patient outcomes or predict responses to therapy.
They are also analysing the mechanisms of IgG4 blockade of new and existing therapeutic antibody candidates, and developing new antibody candidates which may be less prone to IgG4 blockade.
venerdì 8 febbraio 2013
Excess Sugar Linked to Cancer
From Science Daily website (see original article).
Feb. 1, 2013 — Sugars are needed to provide us with energy and in moderate amounts contribute to our well-being. Sustained high levels of sugars, as is found in diabetics, damages our cells and now is shown that can also increase our chance to get cancer: "The dose makes the poison" as Paracelsus said.
It is well known that obesity is a leading cause of diabetes, a disease where the body fails to control blood sugar levels.
High blood sugar levels are characteristic in obesity and diabetes.
What is less well known is that diabetes and obesity are also linked to an increase in cancer risk.
That is, the diabetic population has up to double chances to suffer pancreatic or colon cancer among others, according to well sustained epidemiological studies.
With obesity in British and Spanish children reaching 16%, the highest in Europe, this epidemic has major health implications.
How obesity or diabetes increase cancer risk has been a major health issue.
Scientists led by Dr. Custodia Garcia-Jimenez at the University Rey Juan Carlos in Madrid have uncovered a key mechanism that links obesity and diabetes with cancer: high sugar levels, which increase activity of a gene widely implicated in cancer progression.
Dr Garcia Jimenez's laboratory was studying how cells in the intestine respond to sugars and signal to the pancreas to release insulin, the key hormone that controls blood sugar levels.
Sugars in the intestine trigger cells to release a hormone called GIP that enhances insulin release by the pancreas.
In a study published in Molecular Cell, Dr Garcia Jimenez's team showed that the ability of the intestinal cells to secrete GIP is controlled by a protein called β-catenin, and that the activity of β-catenin is strictly dependent on sugar levels.
Increased activity of β-catenin is known to be a major factor in the development of many cancers and can make normal cells immortal, a key step in early stages of cancer progression.
The study demonstrates that high (but not normal) sugar levels induce nuclear accumulation of β-catenin and leads to cell proliferation.
The changes induced on β-catenin, the molecules involved and the diversity of cancer cells susceptible to these changes are identified.
Dr. Custodia García said "We were surprised to realize that changes in our metabolism caused by dietary sugar impact on our cancer risk.
We are now investigating what other dietary components may influence our cancer risk. Changing diet is one of easiest prevention strategies that can potentially save a lot of suffering and money."
Colin Goding, Professor of Oncology at the University of Oxford, UK said 'Previously we were unsure about how increased blood sugar found in diabetes and obesity could increase cancer risk.
This study identifies a key molecular mechanism through which high blood glucose would predispose to cancer.
It opens the way for potential novel therapies aimed at reducing cancer risk in the obese and diabetic populations.'
Estimations published by the World Health Organisation (WHO): Obesity predisposes to diabetes and its prevalence is doubling every 20 years worldwide.
More than 1 in 10 adults worldwide (12%) are obese (BMI>30).
1 in 6 children in UK and Spain suffer obesity.
Diabetes caused 4.6 million deaths in 2011, more than 2 deaths per hour in Spain, more in USA. Worldwide, 1 in 10 adults (10%) suffered from diabetes in 2010 and more than one-third of individuals with diabetes are unaware they suffer from the disease.
The national cost of diabetes or cancer is in the order of billions of pounds or euros in Spain or England.
More than half (63%) of premature deaths worldwide are due to non communicable diseases (NCD) of which cancer and diabetes are among the 4 causes more frequent.
At least 1 in 3 of the main cancers (27-39%) can be prevented by improving diet, physical activity and body composition.
Feb. 1, 2013 — Sugars are needed to provide us with energy and in moderate amounts contribute to our well-being. Sustained high levels of sugars, as is found in diabetics, damages our cells and now is shown that can also increase our chance to get cancer: "The dose makes the poison" as Paracelsus said.
It is well known that obesity is a leading cause of diabetes, a disease where the body fails to control blood sugar levels.
High blood sugar levels are characteristic in obesity and diabetes.
What is less well known is that diabetes and obesity are also linked to an increase in cancer risk.
That is, the diabetic population has up to double chances to suffer pancreatic or colon cancer among others, according to well sustained epidemiological studies.
With obesity in British and Spanish children reaching 16%, the highest in Europe, this epidemic has major health implications.
How obesity or diabetes increase cancer risk has been a major health issue.
Scientists led by Dr. Custodia Garcia-Jimenez at the University Rey Juan Carlos in Madrid have uncovered a key mechanism that links obesity and diabetes with cancer: high sugar levels, which increase activity of a gene widely implicated in cancer progression.
Dr Garcia Jimenez's laboratory was studying how cells in the intestine respond to sugars and signal to the pancreas to release insulin, the key hormone that controls blood sugar levels.
Sugars in the intestine trigger cells to release a hormone called GIP that enhances insulin release by the pancreas.
In a study published in Molecular Cell, Dr Garcia Jimenez's team showed that the ability of the intestinal cells to secrete GIP is controlled by a protein called β-catenin, and that the activity of β-catenin is strictly dependent on sugar levels.
Increased activity of β-catenin is known to be a major factor in the development of many cancers and can make normal cells immortal, a key step in early stages of cancer progression.
The study demonstrates that high (but not normal) sugar levels induce nuclear accumulation of β-catenin and leads to cell proliferation.
The changes induced on β-catenin, the molecules involved and the diversity of cancer cells susceptible to these changes are identified.
Dr. Custodia García said "We were surprised to realize that changes in our metabolism caused by dietary sugar impact on our cancer risk.
We are now investigating what other dietary components may influence our cancer risk. Changing diet is one of easiest prevention strategies that can potentially save a lot of suffering and money."
Colin Goding, Professor of Oncology at the University of Oxford, UK said 'Previously we were unsure about how increased blood sugar found in diabetes and obesity could increase cancer risk.
This study identifies a key molecular mechanism through which high blood glucose would predispose to cancer.
It opens the way for potential novel therapies aimed at reducing cancer risk in the obese and diabetic populations.'
Estimations published by the World Health Organisation (WHO): Obesity predisposes to diabetes and its prevalence is doubling every 20 years worldwide.
More than 1 in 10 adults worldwide (12%) are obese (BMI>30).
1 in 6 children in UK and Spain suffer obesity.
Diabetes caused 4.6 million deaths in 2011, more than 2 deaths per hour in Spain, more in USA. Worldwide, 1 in 10 adults (10%) suffered from diabetes in 2010 and more than one-third of individuals with diabetes are unaware they suffer from the disease.
The national cost of diabetes or cancer is in the order of billions of pounds or euros in Spain or England.
More than half (63%) of premature deaths worldwide are due to non communicable diseases (NCD) of which cancer and diabetes are among the 4 causes more frequent.
At least 1 in 3 of the main cancers (27-39%) can be prevented by improving diet, physical activity and body composition.
Eating Deep-Fried Food Linked to Increased Risk of Prostate Cancer
From Science Daily website (see original article).
Jan. 28, 2013 — Regular consumption of deep-fried foods such as French fries, fried chicken and doughnuts is associated with an increased risk of prostate cancer, and the effect appears to be slightly stronger with regard to more aggressive forms of the disease, according to a study by investigators at Fred Hutchinson Cancer Research Center.
Corresponding author Janet L. Stanford, Ph.D., and colleagues Marni Stott-Miller, Ph.D., a postdoctoral research fellow and Marian Neuhouser, Ph.D., all of the Hutchinson Center's Public Health Sciences Division, have published their findings online in The Prostate.
While previous studies have suggested that eating foods made with high-heat cooking methods, such as grilled meats, may increase the risk of prostate cancer, this is the first study to examine the addition of deep frying to the equation.
From French fries to doughnuts: Eating more than once a week may raise risk.
Specifically, Stanford, co-director of the Hutchinson Center's Program in Prostate Cancer Research, and colleagues found that men who reported eating French fries, fried chicken, fried fish and/or doughnuts at least once a week were at an increased risk of prostate cancer as compared to men who said they ate such foods less than once a month.
In particular, men who ate one or more of these foods at least weekly had an increased risk of prostate cancer that ranged from 30 to 37 percent.
Weekly consumption of these foods was associated also with a slightly greater risk of more aggressive prostate cancer.
The researchers controlled for factors such as age, race, family history of prostate cancer, body-mass index and PSA screening history when calculating the association between eating deep-fried foods and prostate cancer risk.
"The link between prostate cancer and select deep-fried foods appeared to be limited to the highest level of consumption -- defined in our study as more than once a week -- which suggests that regular consumption of deep-fried foods confers particular risk for developing prostate cancer," Stanford said.
Deep frying may trigger formation of carcinogens in food.
Possible mechanisms behind the increased cancer risk, Stanford hypothesizes, include the fact that when oil is heated to temperatures suitable for deep frying, potentially carcinogenic compounds can form in the fried food.
They include acrylamide (found in carbohydrate-rich foods such as French fries), heterocyclic amines and polycyclic aromatic hydrocarbons (chemicals formed when meat is cooked at high temperatures), aldehyde (an organic compound found in perfume) and acrolein (a chemical found in herbicides).
These toxic compounds are increased with re-use of oil and increased length of frying time.
Foods cooked with high heat also contain high levels of advanced glycation endproducts, or AGEs, which have been associated with chronic inflammation and oxidative stress.
Deep-fried foods are among the highest in AGE content.
A chicken breast deep fried for 20 minutes contains more than nine times the amount of AGEs as a chicken breast boiled for an hour, for example.
For the study, Stanford and colleagues analyzed data from two prior population-based case-control studies involving a total of 1,549 men diagnosed with prostate cancer and 1,492 age-matched healthy controls.
The men were Caucasian and African-American Seattle-area residents and ranged in age from 35 to 74 years.
Participants were asked to fill out a dietary questionnaire about their usual food intake, including specific deep-fried foods.
The first study of its kind "To the best of our knowledge, this is the first study to look at the association between intake of deep-fried food and risk of prostate cancer," Stanford said.
However, deep-fried foods have previously been linked to cancers of the breast, lung, pancreas, head and neck, and esophagus.
Because deep-fried foods are primarily eaten outside the home, it is possible that the link between these foods and prostate cancer risk may be a sign of high consumption of fast foods in general, the authors wrote, citing the dramatic increase in fast-food restaurants and fast-food consumption in the U.S. in the past several decades.
Jan. 28, 2013 — Regular consumption of deep-fried foods such as French fries, fried chicken and doughnuts is associated with an increased risk of prostate cancer, and the effect appears to be slightly stronger with regard to more aggressive forms of the disease, according to a study by investigators at Fred Hutchinson Cancer Research Center.
Corresponding author Janet L. Stanford, Ph.D., and colleagues Marni Stott-Miller, Ph.D., a postdoctoral research fellow and Marian Neuhouser, Ph.D., all of the Hutchinson Center's Public Health Sciences Division, have published their findings online in The Prostate.
While previous studies have suggested that eating foods made with high-heat cooking methods, such as grilled meats, may increase the risk of prostate cancer, this is the first study to examine the addition of deep frying to the equation.
From French fries to doughnuts: Eating more than once a week may raise risk.
Specifically, Stanford, co-director of the Hutchinson Center's Program in Prostate Cancer Research, and colleagues found that men who reported eating French fries, fried chicken, fried fish and/or doughnuts at least once a week were at an increased risk of prostate cancer as compared to men who said they ate such foods less than once a month.
In particular, men who ate one or more of these foods at least weekly had an increased risk of prostate cancer that ranged from 30 to 37 percent.
Weekly consumption of these foods was associated also with a slightly greater risk of more aggressive prostate cancer.
The researchers controlled for factors such as age, race, family history of prostate cancer, body-mass index and PSA screening history when calculating the association between eating deep-fried foods and prostate cancer risk.
"The link between prostate cancer and select deep-fried foods appeared to be limited to the highest level of consumption -- defined in our study as more than once a week -- which suggests that regular consumption of deep-fried foods confers particular risk for developing prostate cancer," Stanford said.
Deep frying may trigger formation of carcinogens in food.
Possible mechanisms behind the increased cancer risk, Stanford hypothesizes, include the fact that when oil is heated to temperatures suitable for deep frying, potentially carcinogenic compounds can form in the fried food.
They include acrylamide (found in carbohydrate-rich foods such as French fries), heterocyclic amines and polycyclic aromatic hydrocarbons (chemicals formed when meat is cooked at high temperatures), aldehyde (an organic compound found in perfume) and acrolein (a chemical found in herbicides).
These toxic compounds are increased with re-use of oil and increased length of frying time.
Foods cooked with high heat also contain high levels of advanced glycation endproducts, or AGEs, which have been associated with chronic inflammation and oxidative stress.
Deep-fried foods are among the highest in AGE content.
A chicken breast deep fried for 20 minutes contains more than nine times the amount of AGEs as a chicken breast boiled for an hour, for example.
For the study, Stanford and colleagues analyzed data from two prior population-based case-control studies involving a total of 1,549 men diagnosed with prostate cancer and 1,492 age-matched healthy controls.
The men were Caucasian and African-American Seattle-area residents and ranged in age from 35 to 74 years.
Participants were asked to fill out a dietary questionnaire about their usual food intake, including specific deep-fried foods.
The first study of its kind "To the best of our knowledge, this is the first study to look at the association between intake of deep-fried food and risk of prostate cancer," Stanford said.
However, deep-fried foods have previously been linked to cancers of the breast, lung, pancreas, head and neck, and esophagus.
Because deep-fried foods are primarily eaten outside the home, it is possible that the link between these foods and prostate cancer risk may be a sign of high consumption of fast foods in general, the authors wrote, citing the dramatic increase in fast-food restaurants and fast-food consumption in the U.S. in the past several decades.
Loneliness, Like Chronic Stress, Taxes the Immune System, Researchers Find
From Science Daily website (see original article).
Jan. 19, 2013 — New research links loneliness to a number of dysfunctional immune responses, suggesting that being lonely has the potential to harm overall health.
Researchers found that people who were more lonely showed signs of elevated latent herpes virus reactivation and produced more inflammation-related proteins in response to acute stress than did people who felt more socially connected.
These proteins signal the presence of inflammation, and chronic inflammation is linked to numerous conditions, including coronary heart disease, Type 2 diabetes, arthritis and Alzheimer's disease, as well as the frailty and functional decline that can accompany aging.
Reactivation of a latent herpes virus is known to be associated with stress, suggesting that loneliness functions as a chronic stressor that triggers a poorly controlled immune response.
"It is clear from previous research that poor-quality relationships are linked to a number of health problems, including premature mortality and all sorts of other very serious health conditions.
And people who are lonely clearly feel like they are in poor-quality relationships," said Lisa Jaremka, a postdoctoral fellow at the Institute for Behavioral Medicine Research at Ohio State University and lead author of the research.
"One reason this type of research is important is to understand how loneliness and relationships broadly affect health.
The more we understand about the process, the more potential there is to counter those negative effects -- to perhaps intervene.
If we don't know the physiological processes, what are we going to do to change them?"
The results are based on a series of studies conducted with two populations: a healthy group of overweight middle-aged adults and a group of breast cancer survivors.
The researchers measured loneliness in all studies using the UCLA Loneliness Scale, a questionnaire that assesses perceptions of social isolation and loneliness.
Jaremka will present the research January 19 at the Society for Personality and Social Psychology annual meeting in New Orleans.
The researchers first sought to obtain a snapshot of immune system behavior related to loneliness by gauging levels of antibodies in the blood that are produced when herpes viruses are reactivated.
Participants were 200 breast cancer survivors who were between two months and three years past completion of cancer treatment with an average age of 51 years.
Their blood was analyzed for the presence of antibodies against Epstein-Barr virus and cytomegalovirus.
Both are herpes viruses that infect a majority of Americans.
About half of infections do not produce illness, but once a person is infected, the viruses remain dormant in the body and can be reactivated, resulting in elevated antibody levels, or titers -- again, often producing no symptoms but hinting at regulatory problems in the cellular immune system.
Lonelier participants had higher levels of antibodies against cytomegalovirus than did less lonely participants, and those higher antibody levels were related to more pain, depression and fatigue symptoms.
No difference was seen in Epstein-Barr virus antibody levels, possibly because this reactivation is linked to age and many of these participants were somewhat older, meaning reactivation related to loneliness would be difficult to detect, Jaremka said.
Previous research has suggested that stress can promote reactivation of these viruses, also resulting in elevated antibody titers.
"The same processes involved in stress and reactivation of these viruses is probably also relevant to the loneliness findings," Jaremka said. "Loneliness has been thought of in many ways as a chronic stressor -- a socially painful situation that can last for quite a long time."
In an additional set of studies, the scientists sought to determine how loneliness affected the production of proinflammatory proteins, or cytokines, in response to stress.
These studies were conducted with 144 women from the same group of breast cancer survivors and a group of 134 overweight middle-aged and older adults with no major health problems.
Baseline blood samples were taken from all participants, who were then subjected to stress -- they were asked to deliver an impromptu five-minute speech and perform a mental arithmetic task in front of a video camera and three panelists.
Researchers followed by stimulating the participants' immune systems with lipopolysaccharide, a compound found on bacterial cell walls that is known to trigger an immune response.
In both populations, those who were lonelier produced significantly higher levels of a cytokine called interleukin-6, or IL-6, in response to acute stress than did participants who were more socially connected.
Levels of another cytokine, tumor necrosis factor-alpha, also rose more dramatically in lonelier participants than in less lonely participants, but the findings were significant by statistical standards in only one study group, the healthy adults.
In the study with breast cancer survivors, researchers also tested for levels of the cytokine interleukin 1-beta, which was produced at higher levels in lonelier participants.
When the scientists controlled for a number of factors, including sleep quality, age and general health measures, the results were the same.
"We saw consistency in the sense that more lonely people in both studies had more inflammation than less lonely people," Jaremka said.
"It's also important to remember the flip side, which is that people who feel very socially connected are experiencing more positive outcomes," she said.
Jan. 19, 2013 — New research links loneliness to a number of dysfunctional immune responses, suggesting that being lonely has the potential to harm overall health.
Researchers found that people who were more lonely showed signs of elevated latent herpes virus reactivation and produced more inflammation-related proteins in response to acute stress than did people who felt more socially connected.
These proteins signal the presence of inflammation, and chronic inflammation is linked to numerous conditions, including coronary heart disease, Type 2 diabetes, arthritis and Alzheimer's disease, as well as the frailty and functional decline that can accompany aging.
Reactivation of a latent herpes virus is known to be associated with stress, suggesting that loneliness functions as a chronic stressor that triggers a poorly controlled immune response.
"It is clear from previous research that poor-quality relationships are linked to a number of health problems, including premature mortality and all sorts of other very serious health conditions.
And people who are lonely clearly feel like they are in poor-quality relationships," said Lisa Jaremka, a postdoctoral fellow at the Institute for Behavioral Medicine Research at Ohio State University and lead author of the research.
"One reason this type of research is important is to understand how loneliness and relationships broadly affect health.
The more we understand about the process, the more potential there is to counter those negative effects -- to perhaps intervene.
If we don't know the physiological processes, what are we going to do to change them?"
The results are based on a series of studies conducted with two populations: a healthy group of overweight middle-aged adults and a group of breast cancer survivors.
The researchers measured loneliness in all studies using the UCLA Loneliness Scale, a questionnaire that assesses perceptions of social isolation and loneliness.
Jaremka will present the research January 19 at the Society for Personality and Social Psychology annual meeting in New Orleans.
The researchers first sought to obtain a snapshot of immune system behavior related to loneliness by gauging levels of antibodies in the blood that are produced when herpes viruses are reactivated.
Participants were 200 breast cancer survivors who were between two months and three years past completion of cancer treatment with an average age of 51 years.
Their blood was analyzed for the presence of antibodies against Epstein-Barr virus and cytomegalovirus.
Both are herpes viruses that infect a majority of Americans.
About half of infections do not produce illness, but once a person is infected, the viruses remain dormant in the body and can be reactivated, resulting in elevated antibody levels, or titers -- again, often producing no symptoms but hinting at regulatory problems in the cellular immune system.
Lonelier participants had higher levels of antibodies against cytomegalovirus than did less lonely participants, and those higher antibody levels were related to more pain, depression and fatigue symptoms.
No difference was seen in Epstein-Barr virus antibody levels, possibly because this reactivation is linked to age and many of these participants were somewhat older, meaning reactivation related to loneliness would be difficult to detect, Jaremka said.
Previous research has suggested that stress can promote reactivation of these viruses, also resulting in elevated antibody titers.
"The same processes involved in stress and reactivation of these viruses is probably also relevant to the loneliness findings," Jaremka said. "Loneliness has been thought of in many ways as a chronic stressor -- a socially painful situation that can last for quite a long time."
In an additional set of studies, the scientists sought to determine how loneliness affected the production of proinflammatory proteins, or cytokines, in response to stress.
These studies were conducted with 144 women from the same group of breast cancer survivors and a group of 134 overweight middle-aged and older adults with no major health problems.
Baseline blood samples were taken from all participants, who were then subjected to stress -- they were asked to deliver an impromptu five-minute speech and perform a mental arithmetic task in front of a video camera and three panelists.
Researchers followed by stimulating the participants' immune systems with lipopolysaccharide, a compound found on bacterial cell walls that is known to trigger an immune response.
In both populations, those who were lonelier produced significantly higher levels of a cytokine called interleukin-6, or IL-6, in response to acute stress than did participants who were more socially connected.
Levels of another cytokine, tumor necrosis factor-alpha, also rose more dramatically in lonelier participants than in less lonely participants, but the findings were significant by statistical standards in only one study group, the healthy adults.
In the study with breast cancer survivors, researchers also tested for levels of the cytokine interleukin 1-beta, which was produced at higher levels in lonelier participants.
When the scientists controlled for a number of factors, including sleep quality, age and general health measures, the results were the same.
"We saw consistency in the sense that more lonely people in both studies had more inflammation than less lonely people," Jaremka said.
"It's also important to remember the flip side, which is that people who feel very socially connected are experiencing more positive outcomes," she said.
lunedì 28 gennaio 2013
Tumor Cells Engineer Acidity to Drive Cell Invasion
From Science Daily website (see original article).
Jan. 25, 2013 — Researchers at Moffitt Cancer Center and colleagues at Wayne State University School of Medicine investigated the acidity in solid tumors to determine if pH levels play a role in cancer cell invasion in surrounding tissues. They found that an acidic microenvironment can drive cancer cells to spread and propose that neutralizing pH would inhibit further invasion, providing a therapeutic opportunity to slow the progression of cancers.
Their study appeared in the Jan. 3 online release of Cancer Research, a publication of the American Association for Cancer Research.
According to the study's corresponding author, Robert J. Gillies, Ph.D., chair of the Department of Cancer Imaging & Metabolism at Moffitt, acidity in solid tumors is the result of an increased fermentative metabolism combined with poor delivery of blood to tissues.
In this study, tumor invasion and pH were monitored in immunodeficient laboratory mice hosting a variety of tumors. "We monitored the test animals over time using microscopy and found that the highest regions of tumor invasion corresponded to areas with the lowest pH," Gillies explained. "Tumor invasion did not occur in regions with normal or near normal pH levels. Furthermore, when we neutralized the acidity with oral sodium bicarbonate, the invasion was halted."
Researchers proposed that the acidic pH of the tumor microenvironment represents a "niche engineering" strategy on the part of tumor cells, promoting invasion and growth of malignant tumors into surrounding tissue. Niche engineering is a concept in ecology describes how plants and animals alter their environment to in ways that promote their own growth and survival over their competitors. "We have long regarded cancers cells as an invading species," said study co-author Robert Gatenby, M.D., chair of the Diagnostic Imaging Services and Integrated Mathematical Oncology departments at Moffitt.
A key to this process of adaptation and invasion is increased glucose metabolism in the tumor. "The vast majority of malignant tumors metabolize glucose at high rates," Gillies said. "We have proposed that there is a direct, causative link between increased glucose metabolism and the ability of cancer cells to invade and metastasize."
According to the research, elevated glucose metabolism is the cause of increased acidity in the tumor microenvironment. Most tumors develop an abnormal vascular network that tends to be poorly organized and leaky, disrupting blood flow and hampering the delivery of oxygen.
"This poorly organized vascular system has a two-fold effect on tumor acidity," explained Gatenby. "First, it subjects tumor regions to poor perfusion, which restricts oxygen and increases the rate of glucose fermentation. Second, the poor perfusion hampers the ability to eliminate the resulting acids, resulting in very low pH in surrounding tissues."
As tumor cells adapt to increasing acidity, niche engineering through normal cell death and new blood vessel formation occurs in the tumor and the immune response is suppressed.
"Tumor cells perform niche engineering by creating an acidic environment that is not toxic to the malignant cells but, through its negative effects on normal cells and tissues, promotes local invasion of malignant cells," Gatenby said.
The researchers suggested that targeting this activity with buffers and other mechanisms aimed at increasing pH levels will likely provide a valuable alternative to traditional therapies focused entirely on killing tumor cells.
Jan. 25, 2013 — Researchers at Moffitt Cancer Center and colleagues at Wayne State University School of Medicine investigated the acidity in solid tumors to determine if pH levels play a role in cancer cell invasion in surrounding tissues. They found that an acidic microenvironment can drive cancer cells to spread and propose that neutralizing pH would inhibit further invasion, providing a therapeutic opportunity to slow the progression of cancers.
Their study appeared in the Jan. 3 online release of Cancer Research, a publication of the American Association for Cancer Research.
According to the study's corresponding author, Robert J. Gillies, Ph.D., chair of the Department of Cancer Imaging & Metabolism at Moffitt, acidity in solid tumors is the result of an increased fermentative metabolism combined with poor delivery of blood to tissues.
In this study, tumor invasion and pH were monitored in immunodeficient laboratory mice hosting a variety of tumors. "We monitored the test animals over time using microscopy and found that the highest regions of tumor invasion corresponded to areas with the lowest pH," Gillies explained. "Tumor invasion did not occur in regions with normal or near normal pH levels. Furthermore, when we neutralized the acidity with oral sodium bicarbonate, the invasion was halted."
Researchers proposed that the acidic pH of the tumor microenvironment represents a "niche engineering" strategy on the part of tumor cells, promoting invasion and growth of malignant tumors into surrounding tissue. Niche engineering is a concept in ecology describes how plants and animals alter their environment to in ways that promote their own growth and survival over their competitors. "We have long regarded cancers cells as an invading species," said study co-author Robert Gatenby, M.D., chair of the Diagnostic Imaging Services and Integrated Mathematical Oncology departments at Moffitt.
A key to this process of adaptation and invasion is increased glucose metabolism in the tumor. "The vast majority of malignant tumors metabolize glucose at high rates," Gillies said. "We have proposed that there is a direct, causative link between increased glucose metabolism and the ability of cancer cells to invade and metastasize."
According to the research, elevated glucose metabolism is the cause of increased acidity in the tumor microenvironment. Most tumors develop an abnormal vascular network that tends to be poorly organized and leaky, disrupting blood flow and hampering the delivery of oxygen.
"This poorly organized vascular system has a two-fold effect on tumor acidity," explained Gatenby. "First, it subjects tumor regions to poor perfusion, which restricts oxygen and increases the rate of glucose fermentation. Second, the poor perfusion hampers the ability to eliminate the resulting acids, resulting in very low pH in surrounding tissues."
As tumor cells adapt to increasing acidity, niche engineering through normal cell death and new blood vessel formation occurs in the tumor and the immune response is suppressed.
"Tumor cells perform niche engineering by creating an acidic environment that is not toxic to the malignant cells but, through its negative effects on normal cells and tissues, promotes local invasion of malignant cells," Gatenby said.
The researchers suggested that targeting this activity with buffers and other mechanisms aimed at increasing pH levels will likely provide a valuable alternative to traditional therapies focused entirely on killing tumor cells.
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