An article appeared in Self October 2008 issue. Here is the excerpt:
Slash your cancer risk in minutes a day
Little lifestyle changes can lower your odds of hearing the dreaded diagnosis. Slip them into your routine and sleep better tonight.
By Aviva Patz
From the October 2008 Issue
Slash your cancer risk in minutes a day
More from this package
Stay weight wise
Excess pounds boost cancer risk, a study in The Lancet shows. Build an exercise habit now to head off trouble: The American Cancer Society (ACS) recommends aiming for 30 minutes of activity five days a week. When you hit your 45th birthday, make sure you're also doing 45 minutes of strength training twice weekly to minimize metabolic slowdown. "Beginning in our mid-40s, we lose up to a third of a pound of muscle a year and gain it back as fat, and fat burns fewer calories than muscle," says Miriam Nelson, Ph.D., director of Tufts University John Hancock Center for Physical Activity and Nutrition in Boston.
Practice peace
Say ahhh! High levels of the stress hormone cortisol may inhibit a key gene from suppressing tumor growth, findings in the journal Genes, Chromosomes & Cancer suggest. Tame tension with this formula from the University of Pittsburgh Medical Center Healthy Lifestyle Program: 1. Take deep belly breaths. You slow and elongate brain waves, bringing on calm. 2. Watch your favorite comedy. Enjoying a good laugh activates the areas of the brain that govern humor, in turn suppressing the brain's stress regions. 3. Adopt an uplifting mantra. Try "I love my life!" and repeat it when you're happy. You will train your mind to associate the phrase with being content. Then when you're on edge, chant your mantra and you'll immediately feel at ease.
Bake, don't burn
Grilling beef, poultry and fish until it's charred to a crisp can turn amino acids and other substances in the meat into heterocyclic amines (HCAs), compounds that have been linked to cancer. "HCAs are 10 times more potent than most other environmental carcinogens," says Kenneth Turteltaub, Ph.D., a toxicologist at Lawrence Livermore National Laboratory in California. Try these cookin'-good tips!
Marinate meat before grilling. Soaking chicken breasts in a mixture of cider vinegar, olive oil, lemon juice and spices reduced HCA formation by 92 to 99 percent, notes a study published in Food and Chemical Toxicology. "Marinating creates a barrier between the hot surface and meat, enough to lower the temperature and prevent HCAs from forming," Turteltaub says.
Keep the grill temp below 325 degrees, the point at which HCAs begin to form.
Grill meat or fish in punctured aluminum foil to protect against flare-ups. When fat drips on the hot coals, it forms HCAs, plus other carcinogens called polycyclic aromatic hydrocarbons that rise with the smoke.
Microwave beef burgers for one to three minutes before browning; doing so reduces HCA production by 95 percent, according to a study in Food and Chemical Toxicology. Prior to grilling, discard the juices, which contain the building blocks of HCAs.
Flip burgers often—about once a minute. This action keeps meat juices from getting too hot and activating HCA formation.
Thursday, October 30, 2008
Monday, October 27, 2008
Friday, October 24, 2008
Cancer Alternative Medicine(CAM)
I have subscribed to one mailing list, that is cancercaregiversareus is a yahoo mailing group. While reading the list I suddenly had this urge to write this article.
In the mailing group there are real people with real experience with life and cancer. Most people suffer uncannily from the cancer treatment alone. Be that chemotherapy, radiation, monoclonal antibody therapy or anything modern medicine can offer. Some of them incapacitates people for the rest of their lives and the quality of life is suddenly snatched away from them. I was wondering can we not try an alternative approach than going straight to our oncologists who have no idea about nutrition and healthy life style? I have read most of the stories where the doctors prescribe people to have some energy drinks that are available in stores. They have no clue that those drinks are full of preservatives, sugar and other unwanted stuff..
There are numerous examples where people have cured their own cancer by sheer will to survive and taking their treatment to their own hands. One such example is in Oprah show where Randy Pausch and an aspiring model Kris were featured together - both had cancer[ A link here]. Where she is stable with her vegetable juices, Randy passed away with all the great treatments he received. The point I am trying to make here is to create some kind of awareness among people to eat right, change life style to keep cancer at bay. Even those that are not having cancer need to adopt a healthy life style that will give them immunity from cancer.
Here are a few points I would like to suggest people with or without cancer:
1. Avoid Sugar completely.Cancer is known to feed on sugar.
2. Avoid trans fat - instead eat good fat(uncooked olive oil, flax seed oil, pumpkin seed, sunflower seed etc.)
3. If you can grow wheat grass and barley grass at home. Consume at least 1 ounce juice every morning.
4. Eat raw or half cooked vegetable that are highly pigmented.
5. Do regular exercise - atleast 5 times a week for at least 30 minutes.
6. Do yoga to relieve stress - atleast 3 times a week.
7. Try sweating everyday.
8. Try avoiding meat in all forms if possible stop eating dairy and wheat.
9. Drink plenty of water.
10. Avoid drinking, smoking.
11. If you can buy Essiac tea. They are very good for your immunity.
12. Avoid caffeine.
13. NO canned food, No packed food.
14. Resort to freshly cooked meal. Don't have those energy drinks, or drinks that are readily available in stores.
15. Stop eating outside: The food cooked outside have the least food value.
16. STOP SODA ALTOGETHER.
17. NO ICE CREAMS.
18. Try eating 3-4 colorful fruits a day.
19. Eat wild rice and vegetables regularly.
20. Meditate if you can.
These are surely going to reduce your cancer risks as well as help you get rid of your cancer if you already have it.
I was very happy to know that NIH is now funding CAM(Cancer alternative medicine)
Here is the announcement:
NEW COMPLEMENTARY AND ALTERNATIVE MEDICINE RESEARCH CENTERS TARGET
STRESS-RELATED ILLNESSES, OBESITY, CANCER, AND OTHER CONDITIONS
The National Institutes of Health's National Center for Complementary
and Alternative Medicine (NCCAM) has added four new Centers of
Excellence for Research on Complementary and Alternative Medicine
(CERCs) to its research centers program. The new centers will add to
knowledge about complementary and alternative medicine (CAM) approaches
and their potential in treating and preventing diseases and conditions
that are common among Americans.
In NCCAM's CERC program, highly accomplished researchers across a
variety of disciplines apply cutting-edge technology to projects in CAM.
The new centers and their projects are as follows.
WISCONSIN CENTER FOR THE NEUROSCIENCE AND PSYCHOPHYSIOLOGY OF MEDITATION
Principal Investigator: Richard J. Davidson, Ph.D.
Institution: University of Wisconsin, Madison
Dr. Davidson's team will examine the impact of two forms of meditation
-- loving-kindness/compassion meditation and mindfulness meditation --
on the brain and body, focusing on the regulation of emotion and on
emotional reactivity. Potential applications in health include
biological and behavioral processes linked with emotions and/or stress,
such as recurrent depression.
METABOLIC AND IMMUNOLOGIC EFFECTS OF MEDITATION
Principal Investigator: Frederick M. Hecht, M.D.
Institution: University of California, San Francisco
Dr. Hecht and his colleagues will study a program combining mindfulness
meditation, mindful eating (the practice of awareness and attentiveness
in the present moment while eating), and a diet and exercise program,
for use in obesity and metabolic syndrome. They will test whether this
program helps alter participants' hormonal responses to stress and helps
enhance and maintain weight loss. Metabolic syndrome involves a cluster
of abnormalities--including increased cholesterol, high blood pressure,
and insulin resistance--that increases one's risk for developing
diabetes and cardiovascular diseases.
CAM AS COUNTERMEASURES AGAINST INFECTIOUS AND INFLAMMATORY DISEASE
Principal Investigator: Mark A. Jutila, Ph.D.
Institution: Montana State University, Bozeman
This center will study biologically based CAM therapies and their
effects on immune system function in infectious and inflammatory
diseases. One project focuses on effects of botanical extracts--from
apple polyphenols, which are concentrated in apple skins, and from
yamoa, which comes from the bark of an African gum tree -- on white
blood cells, using models of infection and inflammation of the
intestinal mucosa. A second project examines two compounds in licorice
root -- glycyrrhizin and 18-glyrrhetinic acid--for their potential
antiviral effects in models of influenza and stomach virus. A third
project will focus on bacterial products to see how they treat
autoimmune diseases, like arthritis, which may also help build
understanding of probiotics' action.
CENTER FOR HERBAL RESEARCH ON COLORECTAL CANCER
Principal Investigator: Chun-Su Yuan, M.D., Ph.D.
Institution: University of Chicago
Colorectal cancer is the third most common cancer and the third leading
cause of cancer-related death. Dr. Yuan and his colleagues will examine
the anti-tumor effects of different preparations of the herbs American
ginseng (Panax quinquefolius) and notoginseng (Panax notoginseng). They
will seek to learn more, through laboratory and animal studies, about
how these herbs act upon cellular and molecular pathways of the
mechanisms of cancer inhibition.
"The new CERCs, all based on strong preliminary work, apply
natural-product and mind-body CAM approaches across a range of health
conditions that affect the American public," said Josephine P. Briggs,
M.D., NCCAM director. "Their multidisciplinary, collaborative structure
increases opportunities for improving health and discovering insights
into important aspects of human biology."
The grants provide five years of support and bring the total number of
CERCs to 11. To learn more about NCCAM's research centers, go to
The National Center for Complementary and Alternative Medicine's mission
is to explore complementary and alternative medical practices in the
context of rigorous science, train CAM researchers, and disseminate
authoritative information to the public and professionals. For
additional information, call NCCAM's Clearinghouse toll free at
1-888-644-6226, or visit the NCCAM Web site at.
The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and
its programs, visit.
CONTACT: NCCAM Press Office, 301-496-7790
In the mailing group there are real people with real experience with life and cancer. Most people suffer uncannily from the cancer treatment alone. Be that chemotherapy, radiation, monoclonal antibody therapy or anything modern medicine can offer. Some of them incapacitates people for the rest of their lives and the quality of life is suddenly snatched away from them. I was wondering can we not try an alternative approach than going straight to our oncologists who have no idea about nutrition and healthy life style? I have read most of the stories where the doctors prescribe people to have some energy drinks that are available in stores. They have no clue that those drinks are full of preservatives, sugar and other unwanted stuff..
There are numerous examples where people have cured their own cancer by sheer will to survive and taking their treatment to their own hands. One such example is in Oprah show where Randy Pausch and an aspiring model Kris were featured together - both had cancer[ A link here]. Where she is stable with her vegetable juices, Randy passed away with all the great treatments he received. The point I am trying to make here is to create some kind of awareness among people to eat right, change life style to keep cancer at bay. Even those that are not having cancer need to adopt a healthy life style that will give them immunity from cancer.
Here are a few points I would like to suggest people with or without cancer:
1. Avoid Sugar completely.Cancer is known to feed on sugar.
2. Avoid trans fat - instead eat good fat(uncooked olive oil, flax seed oil, pumpkin seed, sunflower seed etc.)
3. If you can grow wheat grass and barley grass at home. Consume at least 1 ounce juice every morning.
4. Eat raw or half cooked vegetable that are highly pigmented.
5. Do regular exercise - atleast 5 times a week for at least 30 minutes.
6. Do yoga to relieve stress - atleast 3 times a week.
7. Try sweating everyday.
8. Try avoiding meat in all forms if possible stop eating dairy and wheat.
9. Drink plenty of water.
10. Avoid drinking, smoking.
11. If you can buy Essiac tea. They are very good for your immunity.
12. Avoid caffeine.
13. NO canned food, No packed food.
14. Resort to freshly cooked meal. Don't have those energy drinks, or drinks that are readily available in stores.
15. Stop eating outside: The food cooked outside have the least food value.
16. STOP SODA ALTOGETHER.
17. NO ICE CREAMS.
18. Try eating 3-4 colorful fruits a day.
19. Eat wild rice and vegetables regularly.
20. Meditate if you can.
These are surely going to reduce your cancer risks as well as help you get rid of your cancer if you already have it.
I was very happy to know that NIH is now funding CAM(Cancer alternative medicine)
Here is the announcement:
NEW COMPLEMENTARY AND ALTERNATIVE MEDICINE RESEARCH CENTERS TARGET
STRESS-RELATED ILLNESSES, OBESITY, CANCER, AND OTHER CONDITIONS
The National Institutes of Health's National Center for Complementary
and Alternative Medicine (NCCAM) has added four new Centers of
Excellence for Research on Complementary and Alternative Medicine
(CERCs) to its research centers program. The new centers will add to
knowledge about complementary and alternative medicine (CAM) approaches
and their potential in treating and preventing diseases and conditions
that are common among Americans.
In NCCAM's CERC program, highly accomplished researchers across a
variety of disciplines apply cutting-edge technology to projects in CAM.
The new centers and their projects are as follows.
WISCONSIN CENTER FOR THE NEUROSCIENCE AND PSYCHOPHYSIOLOGY OF MEDITATION
Principal Investigator: Richard J. Davidson, Ph.D.
Institution: University of Wisconsin, Madison
Dr. Davidson's team will examine the impact of two forms of meditation
-- loving-kindness/compassion meditation and mindfulness meditation --
on the brain and body, focusing on the regulation of emotion and on
emotional reactivity. Potential applications in health include
biological and behavioral processes linked with emotions and/or stress,
such as recurrent depression.
METABOLIC AND IMMUNOLOGIC EFFECTS OF MEDITATION
Principal Investigator: Frederick M. Hecht, M.D.
Institution: University of California, San Francisco
Dr. Hecht and his colleagues will study a program combining mindfulness
meditation, mindful eating (the practice of awareness and attentiveness
in the present moment while eating), and a diet and exercise program,
for use in obesity and metabolic syndrome. They will test whether this
program helps alter participants' hormonal responses to stress and helps
enhance and maintain weight loss. Metabolic syndrome involves a cluster
of abnormalities--including increased cholesterol, high blood pressure,
and insulin resistance--that increases one's risk for developing
diabetes and cardiovascular diseases.
CAM AS COUNTERMEASURES AGAINST INFECTIOUS AND INFLAMMATORY DISEASE
Principal Investigator: Mark A. Jutila, Ph.D.
Institution: Montana State University, Bozeman
This center will study biologically based CAM therapies and their
effects on immune system function in infectious and inflammatory
diseases. One project focuses on effects of botanical extracts--from
apple polyphenols, which are concentrated in apple skins, and from
yamoa, which comes from the bark of an African gum tree -- on white
blood cells, using models of infection and inflammation of the
intestinal mucosa. A second project examines two compounds in licorice
root -- glycyrrhizin and 18-glyrrhetinic acid--for their potential
antiviral effects in models of influenza and stomach virus. A third
project will focus on bacterial products to see how they treat
autoimmune diseases, like arthritis, which may also help build
understanding of probiotics' action.
CENTER FOR HERBAL RESEARCH ON COLORECTAL CANCER
Principal Investigator: Chun-Su Yuan, M.D., Ph.D.
Institution: University of Chicago
Colorectal cancer is the third most common cancer and the third leading
cause of cancer-related death. Dr. Yuan and his colleagues will examine
the anti-tumor effects of different preparations of the herbs American
ginseng (Panax quinquefolius) and notoginseng (Panax notoginseng). They
will seek to learn more, through laboratory and animal studies, about
how these herbs act upon cellular and molecular pathways of the
mechanisms of cancer inhibition.
"The new CERCs, all based on strong preliminary work, apply
natural-product and mind-body CAM approaches across a range of health
conditions that affect the American public," said Josephine P. Briggs,
M.D., NCCAM director. "Their multidisciplinary, collaborative structure
increases opportunities for improving health and discovering insights
into important aspects of human biology."
The grants provide five years of support and bring the total number of
CERCs to 11. To learn more about NCCAM's research centers, go to
The National Center for Complementary and Alternative Medicine's mission
is to explore complementary and alternative medical practices in the
context of rigorous science, train CAM researchers, and disseminate
authoritative information to the public and professionals. For
additional information, call NCCAM's Clearinghouse toll free at
1-888-644-6226, or visit the NCCAM Web site at
The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and
its programs, visit
CONTACT: NCCAM Press Office, 301-496-7790
Wednesday, October 22, 2008
Give your immune system a chance..
I wrote this article for an annual newsletter for a small community of non-scientists. I thought it will be useful to post it on my blog as well. Here is the article.
Give your immune system a chance
If we don’t use a particular instrument for sometime, then it gathers junk. If we don’t use our brain often, then brain cells degenerate. Similarly, if we don’t use our immune system for sometime, then immune system starts corroding. What an amazing fact it is!! Yes, this is true… It is said that “If you take medicine, then cold goes away in just a week and if you don’t, then cold gets away in 7 long days”. The reason I chose to write this article is to introduce our amazing immune system in over simplified terms that we have little or no knowledge about.
Humans are highly evolved organisms belonging to class vertebrata that have a very well defined vertebral column. Almost all life forms have immune system. But this immune system has continuously improved to reach its highest state in jawed vertebrates. Humans are the highest life forms having the most sophisticated immune system. During evolution, immune system has been continuously undergoing modifications to help us fight elimination by natural selection.
Our Immune System:
Our immune system is broadly classified into two groups;
1. Innate immunity 2. Acquired immunity.
Innate Immunity is what we are born with and acquired immunity is what we acquire during our life time against certain types of response. The response could be infection, toxins, our own cells gone bad etc. Innate immunity comes to play as an immediate response to a threat to our body from an external agent – be it bacteria, virus, toxins, proteins etc. When innate immunity realizes that its resources are not adequate enough to fight against the disease causing agent, it passes the responsibility to the more sophisticated acquired immunity. Acquired immunity uses all its inbuilt tricks to fight against the attacker until it wins. Once the battle is won by the acquired immune system, the cells remember that. So, in future if there is an attack from a similar organism then the immune system reacts immediately, effortlessly. That is why we acquire life long immunity against a particular type of disease we already had.
Typically our immune system comprises of fighter cells and fighter molecules. The fighter cells are often known as B cells(Produced by Bone marrow) or T cells(Produced by Thymus) and the fighter molecules or antibodies are produced by these fighter cells. The fighter T cells often roam around within our system through our vascular system (blood/lymph network ) and clean it up when they see any foreign particle floating around. They do this by phagocytosis(Phago -> to eat; cytosis -> cellular process [Fig 1] ). It is interesting how they recognize the foreign elements. They generally have an antenna type of molecule on the top of their cell membranes that act as a sensor. The B cells are the factories that produce the sensor molecules. Through out our life time, our immune system builds its memory to identify good and bad elements. This system is highly efficient in humans and it not only eliminates our attackers but also cleans our own dead cells, cancerous cells and any other cell that has gone wrong by a process called as apoptosis. Typically if there is a new attack on our body, generally the memory forming cells try to look at its existing database and determine if the response is already preserved in cellular memory. If it finds out that it is not listed, then it goes back to its expression system, where it creates new fighter molecules that will be a fitting reply to the attacker.
Genetics of Immunity:
The attackers to our system produce a molecule (usually a protein) called ‘antigen’ and our body’s antidote for that is ‘antibody’. Often antibody binds and incapacitates the antigen and makes it inactive[Fig – 2]. Antibodies are highly specific and can identify millions of different antigens – in other words we are capable of producing millions of specific antibodies. As per the famous one gene one enzyme hypothesis (Beadle and Tatum's 1941 Breakthrough), we should have several million of genes to produce several million of antibodies, but we have in total only 30,000 or so genes in our body, and our immune related genes are not even more than a thousand.In that case how we are capable of producing millions of proteins from just thousand genes?
Structurally antibodies are comprised of 4 polypeptide(=proteins) - 2 heavy chains and 2 light chains. Each of these 4 polypeptides have a variable region and a constant region[fig-3]. The constant region forms the structural unit of the antibody while the variable region forms the functional unit. The variable parts are the ones that make the antibody so specific. Often the variable parts are the products of alternative splicing. So, now what is this ‘alternative splicing’? In order to understand the splicing event, we need to know little bit about the structure of our genes. Our genes have coding(useful) and non-coding(not so useful) regions. The coding parts are called as exons and the non-coding parts are called as introns. In a typical human gene, the exons and introns alternate with each other. Before a gene is expressed all the exons are joined together, that is translated to form a valid protein. In alternative splicing event all the exons don’t join together in the same order or same number. They join in different permutations and combinations. For instance if a gene has 4 exons, then it may join them to form > 4 products[Fig – 4].Here, we can’t speak strictly in mathematical terms because there are a certain sets of rules in splicing, that makes the straight forward calculation very complicated. This procedure of creating a specific product against a antigen can be compared to finding a drug target for a particular disease – only it takes place at a cellular level and it happens very quickly! The moment it finds the molecule that can fight against the attacker, it remembers that and starts producing them at a very higher number. The war takes place and generates heat. That is why often we develop fever against a certain infection. Once the fight is over, the product is remembered in our cellular memory. So, when there is another attack by same organism, we already have immunity against it. This is the same principle how the vaccination works. Vaccines are often the dead bacteria or viruses that cause a disease. Once injected into the body it elicits the immune response and it stays there for the entire life time. So, the individual gets immunity against that disease for the whole life.
Sometimes, the immune system can’t fight that well especially when our immune system is week or under utilized, it generally looses the disease fighting abilities. So, it is essential in that case to have medical intervention. In order to remain healthy we need to exercise our immune system as well and strengthen it.
Immune boosters:
Healthy habits are great immune boosters. The best food for healthy immune system is colorful fruits and vegetables. Apart from food, regular exercise, adequate sleep, drinking enough clean water, vitamins(mostly from natural plant sources – they get absorbed well), reducing stress helps improve our compromised immune system. So, the bottom line here is to increase our cellular memory so that it is capable of identifying a myriad of infectious particles and fight against it without much trouble.
Certain food are know to weaken our immune system are coffee, sugar, soda, alcohol, preserved food(mostly canned food). So to conclude: stay healthy, eat healthy and do regular exercise to minimize doctor visits.
Fig – 1: Phagocytosis
Fig – 2 : Antigen – Antibody binding
Fig – 3 : Structure of a immunoglobulin
Fig – 4 : Gene Structure and alternative splicing
Give your immune system a chance
If we don’t use a particular instrument for sometime, then it gathers junk. If we don’t use our brain often, then brain cells degenerate. Similarly, if we don’t use our immune system for sometime, then immune system starts corroding. What an amazing fact it is!! Yes, this is true… It is said that “If you take medicine, then cold goes away in just a week and if you don’t, then cold gets away in 7 long days”. The reason I chose to write this article is to introduce our amazing immune system in over simplified terms that we have little or no knowledge about.
Humans are highly evolved organisms belonging to class vertebrata that have a very well defined vertebral column. Almost all life forms have immune system. But this immune system has continuously improved to reach its highest state in jawed vertebrates. Humans are the highest life forms having the most sophisticated immune system. During evolution, immune system has been continuously undergoing modifications to help us fight elimination by natural selection.
Our Immune System:
Our immune system is broadly classified into two groups;
1. Innate immunity 2. Acquired immunity.
Innate Immunity is what we are born with and acquired immunity is what we acquire during our life time against certain types of response. The response could be infection, toxins, our own cells gone bad etc. Innate immunity comes to play as an immediate response to a threat to our body from an external agent – be it bacteria, virus, toxins, proteins etc. When innate immunity realizes that its resources are not adequate enough to fight against the disease causing agent, it passes the responsibility to the more sophisticated acquired immunity. Acquired immunity uses all its inbuilt tricks to fight against the attacker until it wins. Once the battle is won by the acquired immune system, the cells remember that. So, in future if there is an attack from a similar organism then the immune system reacts immediately, effortlessly. That is why we acquire life long immunity against a particular type of disease we already had.
Typically our immune system comprises of fighter cells and fighter molecules. The fighter cells are often known as B cells(Produced by Bone marrow) or T cells(Produced by Thymus) and the fighter molecules or antibodies are produced by these fighter cells. The fighter T cells often roam around within our system through our vascular system (blood/lymph network ) and clean it up when they see any foreign particle floating around. They do this by phagocytosis(Phago -> to eat; cytosis -> cellular process [Fig 1] ). It is interesting how they recognize the foreign elements. They generally have an antenna type of molecule on the top of their cell membranes that act as a sensor. The B cells are the factories that produce the sensor molecules. Through out our life time, our immune system builds its memory to identify good and bad elements. This system is highly efficient in humans and it not only eliminates our attackers but also cleans our own dead cells, cancerous cells and any other cell that has gone wrong by a process called as apoptosis. Typically if there is a new attack on our body, generally the memory forming cells try to look at its existing database and determine if the response is already preserved in cellular memory. If it finds out that it is not listed, then it goes back to its expression system, where it creates new fighter molecules that will be a fitting reply to the attacker.
Genetics of Immunity:
The attackers to our system produce a molecule (usually a protein) called ‘antigen’ and our body’s antidote for that is ‘antibody’. Often antibody binds and incapacitates the antigen and makes it inactive[Fig – 2]. Antibodies are highly specific and can identify millions of different antigens – in other words we are capable of producing millions of specific antibodies. As per the famous one gene one enzyme hypothesis (Beadle and Tatum's 1941 Breakthrough), we should have several million of genes to produce several million of antibodies, but we have in total only 30,000 or so genes in our body, and our immune related genes are not even more than a thousand.In that case how we are capable of producing millions of proteins from just thousand genes?
Structurally antibodies are comprised of 4 polypeptide(=proteins) - 2 heavy chains and 2 light chains. Each of these 4 polypeptides have a variable region and a constant region[fig-3]. The constant region forms the structural unit of the antibody while the variable region forms the functional unit. The variable parts are the ones that make the antibody so specific. Often the variable parts are the products of alternative splicing. So, now what is this ‘alternative splicing’? In order to understand the splicing event, we need to know little bit about the structure of our genes. Our genes have coding(useful) and non-coding(not so useful) regions. The coding parts are called as exons and the non-coding parts are called as introns. In a typical human gene, the exons and introns alternate with each other. Before a gene is expressed all the exons are joined together, that is translated to form a valid protein. In alternative splicing event all the exons don’t join together in the same order or same number. They join in different permutations and combinations. For instance if a gene has 4 exons, then it may join them to form > 4 products[Fig – 4].Here, we can’t speak strictly in mathematical terms because there are a certain sets of rules in splicing, that makes the straight forward calculation very complicated. This procedure of creating a specific product against a antigen can be compared to finding a drug target for a particular disease – only it takes place at a cellular level and it happens very quickly! The moment it finds the molecule that can fight against the attacker, it remembers that and starts producing them at a very higher number. The war takes place and generates heat. That is why often we develop fever against a certain infection. Once the fight is over, the product is remembered in our cellular memory. So, when there is another attack by same organism, we already have immunity against it. This is the same principle how the vaccination works. Vaccines are often the dead bacteria or viruses that cause a disease. Once injected into the body it elicits the immune response and it stays there for the entire life time. So, the individual gets immunity against that disease for the whole life.
Sometimes, the immune system can’t fight that well especially when our immune system is week or under utilized, it generally looses the disease fighting abilities. So, it is essential in that case to have medical intervention. In order to remain healthy we need to exercise our immune system as well and strengthen it.
Immune boosters:
Healthy habits are great immune boosters. The best food for healthy immune system is colorful fruits and vegetables. Apart from food, regular exercise, adequate sleep, drinking enough clean water, vitamins(mostly from natural plant sources – they get absorbed well), reducing stress helps improve our compromised immune system. So, the bottom line here is to increase our cellular memory so that it is capable of identifying a myriad of infectious particles and fight against it without much trouble.
Certain food are know to weaken our immune system are coffee, sugar, soda, alcohol, preserved food(mostly canned food). So to conclude: stay healthy, eat healthy and do regular exercise to minimize doctor visits.
Fig – 1: Phagocytosis
Fig – 2 : Antigen – Antibody binding
Fig – 3 : Structure of a immunoglobulin
Fig – 4 : Gene Structure and alternative splicing
Thursday, October 16, 2008
BMC cancer journals
BMC has a special cancer issue. The link is here
Once you get to the site, you will see a large number of other cancer related journals on the menu bar. They are all free!!
BMC Cancer
BMC Medical Genomics
Breast Cancer Research
Cancer Cell International
Current Oncology Reports
Current Treatment Options in Oncology
Genome Medicine
Head & Neck Oncology
Infectious Agents and Cancer
International Seminars in Surgical Oncology
Journal of Biology
Journal of Carcinogenesis
Journal of Experimental & Clinical Cancer Research
Journal of Hematology & Oncology
Molecular Cancer
Radiation Oncology
UroOncology
World Journal of Surgical Oncology
Once you get to the site, you will see a large number of other cancer related journals on the menu bar. They are all free!!
BMC Cancer
BMC Medical Genomics
Breast Cancer Research
Cancer Cell International
Current Oncology Reports
Current Treatment Options in Oncology
Genome Medicine
Head & Neck Oncology
Infectious Agents and Cancer
International Seminars in Surgical Oncology
Journal of Biology
Journal of Carcinogenesis
Journal of Experimental & Clinical Cancer Research
Journal of Hematology & Oncology
Molecular Cancer
Radiation Oncology
UroOncology
World Journal of Surgical Oncology
Wednesday, October 1, 2008
Cancer alternative treatment
This has been my favorite topic for the last 3 years. Having said that does not mean I completely shun traditional treatment. I strongly believe there is always a non-invasive alternative way to deal with this. I have been looking for research as well as other articles published online on this subject and collected quite a few.
The other day I happened to see Oprah's page on "confronting death". Following is the uplifting excerpt of the show:
In 2003, Kris was a model and aspiring actress. Then she received devastating news—she had a rare form of cancer that was in its most serious stage. Kris immediately set to figuring out what to do about the cancer…and picked up a camera to record the process.
After getting prescribed drastic treatments—including a recommendation for a triple organ transplant—Kris searched for other opinions and explored alternative options like health food and yoga. Her journey was made into the documentary Crazy Sexy Cancer, which aired on TLC, and the book Crazy Sexy Cancer Tips. "A lot of people look at me like I have 10 heads when I say it, but cancer's been my guru, it's my teacher," Kris says in the film. "It teaches me every day the hard things and the beautiful things."
Years later, Kris says the tumors on her liver and lungs are completely stable. "I'm happy and, I think, healthier than I was before I was diagnosed," she says.
In her kitchen, Kris whipped up a special health cocktail for Dr. Oz using cucumber, celery, sprouts and kale. "It's green," she says. "Whatever is in the refrigerator that's green, it's in my juice."
"And it tastes good," Dr. Oz says.
Kris says this healthy lifestyle is far removed from her old self. "I did martinis before, now I do green drinks," she says. "I knew when I was diagnosed with cancer the only thing I could control was what I ate, what I drank and what I would think. I thought the best place to start was with what I put in my mouth. It's one of the many reasons I think I feel better."
The biggest change Kris says she made in her fight with cancer was in her mind. "I think that life is just too sweet to be bitter," she says. "Once I was able to change my focus, desperation led to inspiration. Once I was able to do that, I looked around me. I made so many changes and I thought, 'This is an awesome life. I mean, honestly, I don't think anybody has a better life than me.'"
Instead of focusing on cancer and death, Kris says she focuses on staying in the moment of living. "How do you live your life with the knowledge of cancer?" she says "I might not ever be able to get rid of it, but I can't let that ruin my life."
link here
The other day I happened to see Oprah's page on "confronting death". Following is the uplifting excerpt of the show:
In 2003, Kris was a model and aspiring actress. Then she received devastating news—she had a rare form of cancer that was in its most serious stage. Kris immediately set to figuring out what to do about the cancer…and picked up a camera to record the process.
After getting prescribed drastic treatments—including a recommendation for a triple organ transplant—Kris searched for other opinions and explored alternative options like health food and yoga. Her journey was made into the documentary Crazy Sexy Cancer, which aired on TLC, and the book Crazy Sexy Cancer Tips. "A lot of people look at me like I have 10 heads when I say it, but cancer's been my guru, it's my teacher," Kris says in the film. "It teaches me every day the hard things and the beautiful things."
Years later, Kris says the tumors on her liver and lungs are completely stable. "I'm happy and, I think, healthier than I was before I was diagnosed," she says.
In her kitchen, Kris whipped up a special health cocktail for Dr. Oz using cucumber, celery, sprouts and kale. "It's green," she says. "Whatever is in the refrigerator that's green, it's in my juice."
"And it tastes good," Dr. Oz says.
Kris says this healthy lifestyle is far removed from her old self. "I did martinis before, now I do green drinks," she says. "I knew when I was diagnosed with cancer the only thing I could control was what I ate, what I drank and what I would think. I thought the best place to start was with what I put in my mouth. It's one of the many reasons I think I feel better."
The biggest change Kris says she made in her fight with cancer was in her mind. "I think that life is just too sweet to be bitter," she says. "Once I was able to change my focus, desperation led to inspiration. Once I was able to do that, I looked around me. I made so many changes and I thought, 'This is an awesome life. I mean, honestly, I don't think anybody has a better life than me.'"
Instead of focusing on cancer and death, Kris says she focuses on staying in the moment of living. "How do you live your life with the knowledge of cancer?" she says "I might not ever be able to get rid of it, but I can't let that ruin my life."
link here
Tuesday, September 23, 2008
Growing wheat grass
Recently I have become a wheat grass freak. After hearing the uncountable number of benefits the freshly squeezed juice has, I have taken up this hubby of growing these on my trays. Initially I was following all the protocols published in the internet, but later it proved to be kind of difficult to follow with the involvement of soil, insects etc. Not to mention the dirt. So, I toyed with the idea of growing them soil less. Wheat like many other seeds have storage products that breaks down during germination of seeds to provide necessary nutrients for the seeds to sprout and grow till they start photosynthesizing. I was also looking for the wheat grass kits that are available that does not need soil. To my surprise, they were so much over priced!! I am hoping these tips will be beneficial for those who don't own a large backyard - yet want to be able to produce decent amount of grass for daily consumption.
Ingredients:
5 shallow trays of the dimension of 2 ft tall X 1 ft wide. If that is not available, then have smaller trays that are available in any garden store. If they have no holes, just poke holes in them, so that water gets drained easily.[Fig - 1]
Spread kitchen paper or any other thicker blotting paper on the tray. Soak around 1/2 cup of wheat seeds for about 24 hours(till you see the germ tubes). Spread the pre-soaked wheat seeds on the paper evenly[Fig - 2]. Put another layer of kitchen paper on the top of the seeds without exposing any area to light[Fig - 4]. Now moisten the papers and let them drain thoroughly. Always try to keep the paper wet. In another 48 hours you will notice the upper layer of paper has been lifted a nit. this is an indication that the wheat seeds have germinated and the fine root hair is adding to the volume. After about 3-4 of sowing you can see the epicotyls(the part of the seedling upper to the root looks green. At that point you can take off the upper paper. Again continue spraying water 2-3 times a day. In about 10 days you will have wheat grass about 3-4 inch in length ready for harvest[fig - 5]. You can either juice with a manual juicer or a mixie[Fig - 6].
Essence of wheat grass
I have been drawn to wheat grass after reading a number of articles that are going round in internet. To find the validity, I looked for the original wheat grass article on wikipedia. The first research on wheat grass dates back to 1930s when an agricultural chemist Charles F. Schnabel fed his sick poultry stock with dried wheat grass. He found not only the poultry revived but also they produced more good quality eggs than the control group. In rural India, the infertile cows are left in wheat field to restore their fertility. Although the claim that 1 oz of wheat grass juice has enough nutrients as 1 KG of vegetable does not sound right. I just saw some data and it may be as good as 1 oz of broccoli, spinach, carrot and some other vegetables together. Still exciting... When we eat vegetables in different forms we have almost lost a lots of nutritional values altogether. Another great thing I read about wheat grass is the readiness with which the componenets are absorbed by our system. That may make it a superfood.
Although specific research on this is lacking, I would not doubt the beneficial effects of wheat grass for the fact that "there are many well known facts that are yet to be proved by scientific research". For this I looked at pubmed and selected the limit as 'alternative medicine' + wheat grass. There was a total of 331 articles showed up as of today and here are just a few of research articles I pulled out.
1) Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study
2) Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer patients: a pilot study
3) Wheat grass juice appeared effective and safe as a single or adjuvant treatment of active distal UC.
4)Adjuvant fermented wheat germ extract (Avemar) nutraceutical improves survival of high-risk skin melanoma patients: a randomized, pilot, phase II clinical study with a 7-year follow-up
5)Avemar, a nontoxic fermented wheat germ extract, induces apoptosis and inhibits ribonucleotide reductase in human HL-60 promyelocytic leukemia cells.
6) The formulation of WIT-NP, in which WGA(wheat germ aglutinins) is conjugated to the surface of paclitaxel and IPM-loaded PLGA nanoparticles, significantly potentiates the anticancer activity of paclitaxel
7) Fermented wheat germ extract (Avemar) in the treatment of cancer and autoimmune diseases: Avemar, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, Avemar can inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of Avemar treatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune conditions. This document reviews the clinical and experimental results obtained with this extract so far. Special references are made for its safety, including its coadministration with anticancer drugs, as well as for its immunomodulatory activity, its molecular targets, and its use in cancer clinical trials.
The list goes on and on. So, the properties of wheat grass is definitely something that needs further attention. The studies have been done with respect to wheat grass and auto immune disorders, ulcerative colitis, cancer etc. I think this can further be expanded to studies on endometriosis, female, male fertility, anti aging, diabetes and so on and so forth.
There are often mention of macronutrients in wheat grass, but there are lots of micronutrients that need be studied in great detail. A study need to be conducted to profile the nutritional property of this wonder grass vs other formulated vitamins.
Although specific research on this is lacking, I would not doubt the beneficial effects of wheat grass for the fact that "there are many well known facts that are yet to be proved by scientific research". For this I looked at pubmed and selected the limit as 'alternative medicine' + wheat grass. There was a total of 331 articles showed up as of today and here are just a few of research articles I pulled out.
1) Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study
2) Wheat grass juice may improve hematological toxicity related to chemotherapy in breast cancer patients: a pilot study
3) Wheat grass juice appeared effective and safe as a single or adjuvant treatment of active distal UC.
4)Adjuvant fermented wheat germ extract (Avemar) nutraceutical improves survival of high-risk skin melanoma patients: a randomized, pilot, phase II clinical study with a 7-year follow-up
5)Avemar, a nontoxic fermented wheat germ extract, induces apoptosis and inhibits ribonucleotide reductase in human HL-60 promyelocytic leukemia cells.
6) The formulation of WIT-NP, in which WGA(wheat germ aglutinins) is conjugated to the surface of paclitaxel and IPM-loaded PLGA nanoparticles, significantly potentiates the anticancer activity of paclitaxel
7) Fermented wheat germ extract (Avemar) in the treatment of cancer and autoimmune diseases: Avemar, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, Avemar can inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of Avemar treatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune conditions. This document reviews the clinical and experimental results obtained with this extract so far. Special references are made for its safety, including its coadministration with anticancer drugs, as well as for its immunomodulatory activity, its molecular targets, and its use in cancer clinical trials.
The list goes on and on. So, the properties of wheat grass is definitely something that needs further attention. The studies have been done with respect to wheat grass and auto immune disorders, ulcerative colitis, cancer etc. I think this can further be expanded to studies on endometriosis, female, male fertility, anti aging, diabetes and so on and so forth.
There are often mention of macronutrients in wheat grass, but there are lots of micronutrients that need be studied in great detail. A study need to be conducted to profile the nutritional property of this wonder grass vs other formulated vitamins.
Tuesday, September 16, 2008
Cancer's Sweet Tooth
I am a firm believer of natural healing and I strongly believe that systemic diseases like cancer develop over a period of time. When the body is no longer able to fight malignant cells that are produced on a day to day basis, the malignant cells win and almost take over our body. That is why in younger people where the immune system is strong, cancer growth are rare. Recently, I came across this very well written article about the relationship between cancer and Sugar. Although this is a very well established fact, very few doctors seem to be aware of it. The health drinks often they prescribe to patients is so full of sugar. Here is the summary of this article:
by Patrick Quillin, PHD, RD, CNS
From The April 2000 Issue of Nutrition Science News
During the last 10 years I have worked with more than 500 cancer patients as director of nutrition for Cancer Treatment Centers of America in Tulsa, Okla. It puzzles me why the simple concept "sugar feeds cancer" can be so dramatically overlooked as part of a comprehensive cancer treatment plan.
Of the 4 million cancer patients being treated in America today, hardly any are offered any scientifically guided nutrition therapy beyond being told to "just eat good foods." Most patients I work with arrive with a complete lack of nutritional advice. I believe many cancer patients would have a major improvement in their outcome if they controlled the supply of cancer's preferred fuel, glucose. By slowing the cancer's growth, patients allow their immune systems and medical debulking therapies -- chemotherapy, radiation and surgery to reduce the bulk of the tumor mass -- to catch up to the disease. Controlling one's blood-glucose levels through diet, supplements, exercise, meditation and prescription drugs when necessary can be one of the most crucial components to a cancer recovery program. The sound bite -- sugar feeds cancer -- is simple. The explanation is a little more complex.
The 1931 Nobel laureate in medicine, German Otto Warburg, Ph.D., first discovered that cancer cells have a fundamentally different energy metabolism compared to healthy cells. The crux of his Nobel thesis was that malignant tumors frequently exhibit an increase in anaerobic glycolysis -- a process whereby glucose is used as a fuel by cancer cells with lactic acid as an anaerobic byproduct -- compared to normal tissues.1 The large amount of lactic acid produced by this fermentation of glucose from cancer cells is then transported to the liver. This conversion of glucose to lactate generates a lower, more acidic pH in cancerous tissues as well as overall physical fatigue from lactic acid buildup.2,3 Thus, larger tumors tend to exhibit a more acidic pH.4
This inefficient pathway for energy metabolism yields only 2 moles of adenosine triphosphate (ATP) energy per mole of glucose, compared to 38 moles of ATP in the complete aerobic oxidation of glucose. By extracting only about 5 percent (2 vs. 38 moles of ATP) of the available energy in the food supply and the body's calorie stores, the cancer is "wasting" energy, and the patient becomes tired and undernourished. This vicious cycle increases body wasting.5 It is one reason why 40 percent of cancer patients die from malnutrition, or cachexia.6
Hence, cancer therapies should encompass regulating blood-glucose levels via diet, supplements, non-oral solutions for cachectic patients who lose their appetite, medication, exercise, gradual weight loss and stress reduction. Professional guidance and patient self-discipline are crucial at this point in the cancer process. The quest is not to eliminate sugars or carbohydrates from the diet but rather to control blood glucose within a narrow range to help starve the cancer and bolster immune function.
The glycemic index is a measure of how a given food affects blood-glucose levels, with each food assigned a numbered rating. The lower the rating, the slower the digestion and absorption process, which provides a healthier, more gradual infusion of sugars into the bloodstream. Conversely, a high rating means blood-glucose levels are increased quickly, which stimulates the pancreas to secrete insulin to drop blood-sugar levels. This rapid fluctuation of blood-sugar levels is unhealthy because of the stress it places on the body (see glycemic index chart, p. 166).
Sugar in the Body and Diet
Sugar is a generic term used to identify simple carbohydrates, which includes monosaccharides such as fructose, glucose and galactose; and disaccharides such as maltose and sucrose (white table sugar). Think of these sugars as different-shaped bricks in a wall. When fructose is the primary monosaccharide brick in the wall, the glycemic index registers as healthier, since this simple sugar is slowly absorbed in the gut, then converted to glucose in the liver. This makes for "time-release foods," which offer a more gradual rise and fall in blood-glucose levels. If glucose is the primary monosaccharide brick in the wall, the glycemic index will be higher and less healthy for the individual. As the brick wall is torn apart in digestion, the glucose is pumped across the intestinal wall directly into the bloodstream, rapidly raising blood-glucose levels. In other words, there is a "window of efficacy" for glucose in the blood: levels too low make one feel lethargic and can create clinical hypoglycemia; levels too high start creating the rippling effect of diabetic health problems.
The 1997 American Diabetes Association blood-glucose standards consider 126 mg glucose/dL blood or greater to be diabetic; 126 mg/dL is impaired glucose tolerance and less than 110 mg/dL is considered normal. Meanwhile, the Paleolithic diet of our ancestors, which consisted of lean meats, vegetables and small amounts of whole grains, nuts, seeds and fruits, is estimated to have generated blood glucose levels between 60 and 90 mg/dL.7 Obviously, today's high-sugar diets are having unhealthy effects as far as blood-sugar is concerned. Excess blood glucose may initiate yeast overgrowth, blood vessel deterioration, heart disease and other health conditions.8
Understanding and using the glycemic index is an important aspect of diet modification for cancer patients. However, there is also evidence that sugars may feed cancer more efficiently than starches (comprised of long chains of simple sugars), making the index slightly misleading. A study of rats fed diets with equal calories from sugars and starches, for example, found the animals on the high-sugar diet developed more cases of breast cancer.9 The glycemic index is a useful tool in guiding the cancer patient toward a healthier diet, but it is not infallible. By using the glycemic index alone, one could be led to thinking a cup of white sugar is healthier than a baked potato. This is because the glycemic index rating of a sugary food may be lower than that of a starchy food. To be safe, I recommend less fruit, more vegetables, and little to no refined sugars in the diet of cancer patients.
What the Literature Says
A mouse model of human breast cancer demonstrated that tumors are sensitive to blood-glucose levels. Sixty-eight mice were injected with an aggressive strain of breast cancer, then fed diets to induce either high blood-sugar (hyperglycemia), normoglycemia or low blood-sugar (hypoglycemia). There was a dose-dependent response in which the lower the blood glucose, the greater the survival rate. After 70 days, 8 of 24 hyperglycemic mice survived compared to 16 of 24 normoglycemic and 19 of 20 hypoglycemic.10 This suggests that regulating sugar intake is key to slowing breast tumor growth (see chart, p. 164).
In a human study, 10 healthy people were assessed for fasting blood-glucose levels and the phagocytic index of neutrophils, which measures immune-cell ability to envelop and destroy invaders such as cancer. Eating 100 g carbohydrates from glucose, sucrose, honey and orange juice all significantly decreased the capacity of neutrophils to engulf bacteria. Starch did not have this effect.11
A four-year study at the National Institute of Public Health and Environmental Protection in the Netherlands compared 111 biliary tract cancer patients with 480 controls. Cancer risk associated with the intake of sugars, independent of other energy sources, more than doubled for the cancer patients.12 Furthermore, an epidemiological study in 21 modern countries that keep track of morbidity and mortality (Europe, North America, Japan and others) revealed that sugar intake is a strong risk factor that contributes to higher breast cancer rates, particularly in older women.13
Limiting sugar consumption may not be the only line of defense. In fact, an interesting botanical extract from the avocado plant (Persea americana) is showing promise as a new cancer adjunct. When a purified avocado extract called mannoheptulose was added to a number of tumor cell lines tested in vitro by researchers in the Department of Biochemistry at Oxford University in Britain, they found it inhibited tumor cell glucose uptake by 25 to 75 percent, and it inhibited the enzyme glucokinase responsible for glycolysis. It also inhibited the growth rate of the cultured tumor cell lines. The same researchers gave lab animals a 1.7 mg/g body weight dose of mannoheptulose for five days; it reduced tumors by 65 to 79 percent.14 Based on these studies, there is good reason to believe that avocado extract could help cancer patients by limiting glucose to the tumor cells.
Since cancer cells derive most of their energy from anaerobic glycolysis, Joseph Gold, M.D., director of the Syracuse (N.Y.) Cancer Research Institute and former U.S. Air Force research physician, surmised that a chemical called hydrazine sulfate, used in rocket fuel, could inhibit the excessive gluconeogenesis (making sugar from amino acids) that occurs in cachectic cancer patients. Gold's work demonstrated hydrazine sulfate's ability to slow and reverse cachexia in advanced cancer patients. A placebo-controlled trial followed 101 cancer patients taking either 6 mg hydrazine sulfate three times/day or placebo. After one month, 83 percent of hydrazine sulfate patients increased their weight, compared to 53 percent on placebo.15 A similar study by the same principal researchers, partly funded by the National Cancer Institute in Bethesda, Md., followed 65 patients. Those who took hydrazine sulfate and were in good physical condition before the study began lived an average of 17 weeks longer.16
In 1990, I called the major cancer hospitals in the country looking for some information on the crucial role of total parenteral nutrition (TPN) in cancer patients. Some 40 percent of cancer patients die from cachexia.5 Yet many starving cancer patients are offered either no nutritional support or the standard TPN solution developed for intensive care units. The solution provides 70 percent of the calories going into the bloodstream in the form of glucose. All too often, I believe, these high-glucose solutions for cachectic cancer patients do not help as much as would TPN solutions with lower levels of glucose and higher levels of amino acids and lipids. These solutions would allow the patient to build strength and would not feed the tumor.17
The medical establishment may be missing the connection between sugar and its role in tumorigenesis. Consider the million-dollar positive emission tomography device, or PET scan, regarded as one of the ultimate cancer-detection tools. PET scans use radioactively labeled glucose to detect sugar-hungry tumor cells. PET scans are used to plot the progress of cancer patients and to assess whether present protocols are effective.18
In Europe, the "sugar feeds cancer" concept is so well accepted that oncologists, or cancer doctors, use the Systemic Cancer Multistep Therapy (SCMT) protocol. Conceived by Manfred von Ardenne in Germany in 1965, SCMT entails injecting patients with glucose to increase blood-glucose concentrations. This lowers pH values in cancer tissues via lactic acid formation. In turn, this intensifies the thermal sensitivity of the malignant tumors and also induces rapid growth of the cancer. Patients are then given whole-body hyperthermia (42 C core temperature) to further stress the cancer cells, followed by chemotherapy or radiation.19 SCMT was tested on 103 patients with metastasized cancer or recurrent primary tumors in a clinical phase-I study at the Von Ardenne Institute of Applied Medical Research in Dresden, Germany. Five-year survival rates in SCMT-treated patients increased by 25 to 50 percent, and the complete rate of tumor regression increased by 30 to 50 percent.20 The protocol induces rapid growth of the cancer, then treats the tumor with toxic therapies for a dramatic improvement in outcome.
The irrefutable role of glucose in the growth and metastasis of cancer cells can enhance many therapies. Some of these include diets designed with the glycemic index in mind to regulate increases in blood glucose, hence selectively starving the cancer cells; low-glucose TPN solutions; avocado extract to inhibit glucose uptake in cancer cells; hydrazine sulfate to inhibit gluconeogenesis in cancer cells; and SCMT.
A female patient in her 50s, with lung cancer, came to our clinic, having been given a death sentence by her Florida oncologist. She was cooperative and understood the connection between nutrition and cancer. She changed her diet considerably, leaving out 90 percent of the sugar she used to eat. She found that wheat bread and oat cereal now had their own wild sweetness, even without added sugar. With appropriately restrained medical therapy -- including high-dose radiation targeted to tumor sites and fractionated chemotherapy, a technique that distributes the normal one large weekly chemo dose into a 60-hour infusion lasting days -- a good attitude and an optimal nutrition program, she beat her terminal lung cancer. I saw her the other day, five years later and still disease-free, probably looking better than the doctor who told her there was no hope.
Patrick Quillin, Ph.D., R.D., C.N.S., is director of nutrition for Cancer Treatment Centers of America in Tulsa, Okla., and author of Beating Cancer With Nutrition (Nutrition Times Press, 1998).
References
1. Warburg O. On the origin of cancer cells. Science 1956 Feb;123:309-14.
2. Volk T, et al. pH in human tumor xenografts: effect of intravenous administration of glucose. Br J Cancer 1993 Sep;68(3):492-500.
3.Digirolamo M. Diet and cancer: markers, prevention and treatment. New York: Plenum Press; 1994. p 203.
4. Leeper DB, et al. Effect of i.v. glucose versus combined i.v. plus oral glucose on human tumor extracellular pH for potential sensitization to thermoradiotherapy. Int J Hyperthermia 1998 May-Jun;14(3):257-69.
5. Rossi-Fanelli F, et al. Abnormal substrate metabolism and nutritional strategies in cancer management. JPEN J Parenter Enteral Nutr 1991 Nov-Dec;15(6):680-3.
6. Grant JP. Proper use and recognized role of TPN in the cancer patient. Nutrition 1990 Jul-Aug;6(4 Suppl):6S-7S, 10S.
7. Brand-Miller J, et al. The glucose revolution. Newport (RI) Marlowe and Co.; 1999.
8. Mooradian AD, et al. Glucotoxicity: potential mechanisms. Clin Geriatr Med 1999 May;15(2):255.
9. Hoehn, SK, et al. Complex versus simple carbohydrates and mammary tumors in mice. Nutr Cancer 1979;1(3):27.
10. Santisteban GA, et al. Glycemic modulation of tumor tolerance in a mouse model of breast cancer. Biochem Biophys Res Commun 1985 Nov 15;132(3):1174-9.
11. Sanchez A, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr 1973 Nov;26(11):1180-4.
12. Moerman CJ, et al. Dietary sugar intake in the aetiology of biliary tract cancer. Int J Epidemiol 1993 Apr;22(2):207-14.
13. Seeley S. Diet and breast cancer: the possible connection with sugar consumption. Med Hypotheses 1983 Jul;11(3):319-27.
14. Board M, et al. High Km glucose-phosphorylating (glucokinase) activities in a range of tumor cell lines and inhibition of rates of tumor growth by the specific enzyme inhibitor mannoheptulose. Cancer Res 1995 Aug 1;55(15):3278-85.
15. Chlebowski RT, et al. Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 1987 Feb 1;59(3):406-10.
16. Chlebowski RT, et al. Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol 1990 Jan;8(1):9-15.
17. American College of Physicians. Parenteral nutrition in patients receiving cancer chemotherapy. Ann Intern Med 1989 May;110(9):734.
18. Gatenby RA. Potential role of FDG-PET imaging in understanding tumor-host interaction. J Nucl Med 1995 May;36(5):893-9.
19. von Ardenne M. Principles and concept 1993 of the Systemic Cancer Multistep Therapy (SCMT). Extreme whole-body hyperthermia using the infrared-A technique IRATHERM 2000 -- selective thermosensitisation by hyperglycemia -- circulatory back-up by adapted hyperoxemia. Strahlenther Onkol 1994 Oct;170(10):581-9.
20. Steinhausen D, et al. Evaluation of systemic tolerance of 42.0 degrees C infrared-A whole-body hyperthermia in combination with hyperglycemia and hyperoxemia. A Phase-I study. Strahlenther Onkol 1994 Jun;170(6):322-34.
POSTED BY
Dr. Mercola
by Patrick Quillin, PHD, RD, CNS
From The April 2000 Issue of Nutrition Science News
During the last 10 years I have worked with more than 500 cancer patients as director of nutrition for Cancer Treatment Centers of America in Tulsa, Okla. It puzzles me why the simple concept "sugar feeds cancer" can be so dramatically overlooked as part of a comprehensive cancer treatment plan.
Of the 4 million cancer patients being treated in America today, hardly any are offered any scientifically guided nutrition therapy beyond being told to "just eat good foods." Most patients I work with arrive with a complete lack of nutritional advice. I believe many cancer patients would have a major improvement in their outcome if they controlled the supply of cancer's preferred fuel, glucose. By slowing the cancer's growth, patients allow their immune systems and medical debulking therapies -- chemotherapy, radiation and surgery to reduce the bulk of the tumor mass -- to catch up to the disease. Controlling one's blood-glucose levels through diet, supplements, exercise, meditation and prescription drugs when necessary can be one of the most crucial components to a cancer recovery program. The sound bite -- sugar feeds cancer -- is simple. The explanation is a little more complex.
The 1931 Nobel laureate in medicine, German Otto Warburg, Ph.D., first discovered that cancer cells have a fundamentally different energy metabolism compared to healthy cells. The crux of his Nobel thesis was that malignant tumors frequently exhibit an increase in anaerobic glycolysis -- a process whereby glucose is used as a fuel by cancer cells with lactic acid as an anaerobic byproduct -- compared to normal tissues.1 The large amount of lactic acid produced by this fermentation of glucose from cancer cells is then transported to the liver. This conversion of glucose to lactate generates a lower, more acidic pH in cancerous tissues as well as overall physical fatigue from lactic acid buildup.2,3 Thus, larger tumors tend to exhibit a more acidic pH.4
This inefficient pathway for energy metabolism yields only 2 moles of adenosine triphosphate (ATP) energy per mole of glucose, compared to 38 moles of ATP in the complete aerobic oxidation of glucose. By extracting only about 5 percent (2 vs. 38 moles of ATP) of the available energy in the food supply and the body's calorie stores, the cancer is "wasting" energy, and the patient becomes tired and undernourished. This vicious cycle increases body wasting.5 It is one reason why 40 percent of cancer patients die from malnutrition, or cachexia.6
Hence, cancer therapies should encompass regulating blood-glucose levels via diet, supplements, non-oral solutions for cachectic patients who lose their appetite, medication, exercise, gradual weight loss and stress reduction. Professional guidance and patient self-discipline are crucial at this point in the cancer process. The quest is not to eliminate sugars or carbohydrates from the diet but rather to control blood glucose within a narrow range to help starve the cancer and bolster immune function.
The glycemic index is a measure of how a given food affects blood-glucose levels, with each food assigned a numbered rating. The lower the rating, the slower the digestion and absorption process, which provides a healthier, more gradual infusion of sugars into the bloodstream. Conversely, a high rating means blood-glucose levels are increased quickly, which stimulates the pancreas to secrete insulin to drop blood-sugar levels. This rapid fluctuation of blood-sugar levels is unhealthy because of the stress it places on the body (see glycemic index chart, p. 166).
Sugar in the Body and Diet
Sugar is a generic term used to identify simple carbohydrates, which includes monosaccharides such as fructose, glucose and galactose; and disaccharides such as maltose and sucrose (white table sugar). Think of these sugars as different-shaped bricks in a wall. When fructose is the primary monosaccharide brick in the wall, the glycemic index registers as healthier, since this simple sugar is slowly absorbed in the gut, then converted to glucose in the liver. This makes for "time-release foods," which offer a more gradual rise and fall in blood-glucose levels. If glucose is the primary monosaccharide brick in the wall, the glycemic index will be higher and less healthy for the individual. As the brick wall is torn apart in digestion, the glucose is pumped across the intestinal wall directly into the bloodstream, rapidly raising blood-glucose levels. In other words, there is a "window of efficacy" for glucose in the blood: levels too low make one feel lethargic and can create clinical hypoglycemia; levels too high start creating the rippling effect of diabetic health problems.
The 1997 American Diabetes Association blood-glucose standards consider 126 mg glucose/dL blood or greater to be diabetic; 126 mg/dL is impaired glucose tolerance and less than 110 mg/dL is considered normal. Meanwhile, the Paleolithic diet of our ancestors, which consisted of lean meats, vegetables and small amounts of whole grains, nuts, seeds and fruits, is estimated to have generated blood glucose levels between 60 and 90 mg/dL.7 Obviously, today's high-sugar diets are having unhealthy effects as far as blood-sugar is concerned. Excess blood glucose may initiate yeast overgrowth, blood vessel deterioration, heart disease and other health conditions.8
Understanding and using the glycemic index is an important aspect of diet modification for cancer patients. However, there is also evidence that sugars may feed cancer more efficiently than starches (comprised of long chains of simple sugars), making the index slightly misleading. A study of rats fed diets with equal calories from sugars and starches, for example, found the animals on the high-sugar diet developed more cases of breast cancer.9 The glycemic index is a useful tool in guiding the cancer patient toward a healthier diet, but it is not infallible. By using the glycemic index alone, one could be led to thinking a cup of white sugar is healthier than a baked potato. This is because the glycemic index rating of a sugary food may be lower than that of a starchy food. To be safe, I recommend less fruit, more vegetables, and little to no refined sugars in the diet of cancer patients.
What the Literature Says
A mouse model of human breast cancer demonstrated that tumors are sensitive to blood-glucose levels. Sixty-eight mice were injected with an aggressive strain of breast cancer, then fed diets to induce either high blood-sugar (hyperglycemia), normoglycemia or low blood-sugar (hypoglycemia). There was a dose-dependent response in which the lower the blood glucose, the greater the survival rate. After 70 days, 8 of 24 hyperglycemic mice survived compared to 16 of 24 normoglycemic and 19 of 20 hypoglycemic.10 This suggests that regulating sugar intake is key to slowing breast tumor growth (see chart, p. 164).
In a human study, 10 healthy people were assessed for fasting blood-glucose levels and the phagocytic index of neutrophils, which measures immune-cell ability to envelop and destroy invaders such as cancer. Eating 100 g carbohydrates from glucose, sucrose, honey and orange juice all significantly decreased the capacity of neutrophils to engulf bacteria. Starch did not have this effect.11
A four-year study at the National Institute of Public Health and Environmental Protection in the Netherlands compared 111 biliary tract cancer patients with 480 controls. Cancer risk associated with the intake of sugars, independent of other energy sources, more than doubled for the cancer patients.12 Furthermore, an epidemiological study in 21 modern countries that keep track of morbidity and mortality (Europe, North America, Japan and others) revealed that sugar intake is a strong risk factor that contributes to higher breast cancer rates, particularly in older women.13
Limiting sugar consumption may not be the only line of defense. In fact, an interesting botanical extract from the avocado plant (Persea americana) is showing promise as a new cancer adjunct. When a purified avocado extract called mannoheptulose was added to a number of tumor cell lines tested in vitro by researchers in the Department of Biochemistry at Oxford University in Britain, they found it inhibited tumor cell glucose uptake by 25 to 75 percent, and it inhibited the enzyme glucokinase responsible for glycolysis. It also inhibited the growth rate of the cultured tumor cell lines. The same researchers gave lab animals a 1.7 mg/g body weight dose of mannoheptulose for five days; it reduced tumors by 65 to 79 percent.14 Based on these studies, there is good reason to believe that avocado extract could help cancer patients by limiting glucose to the tumor cells.
Since cancer cells derive most of their energy from anaerobic glycolysis, Joseph Gold, M.D., director of the Syracuse (N.Y.) Cancer Research Institute and former U.S. Air Force research physician, surmised that a chemical called hydrazine sulfate, used in rocket fuel, could inhibit the excessive gluconeogenesis (making sugar from amino acids) that occurs in cachectic cancer patients. Gold's work demonstrated hydrazine sulfate's ability to slow and reverse cachexia in advanced cancer patients. A placebo-controlled trial followed 101 cancer patients taking either 6 mg hydrazine sulfate three times/day or placebo. After one month, 83 percent of hydrazine sulfate patients increased their weight, compared to 53 percent on placebo.15 A similar study by the same principal researchers, partly funded by the National Cancer Institute in Bethesda, Md., followed 65 patients. Those who took hydrazine sulfate and were in good physical condition before the study began lived an average of 17 weeks longer.16
In 1990, I called the major cancer hospitals in the country looking for some information on the crucial role of total parenteral nutrition (TPN) in cancer patients. Some 40 percent of cancer patients die from cachexia.5 Yet many starving cancer patients are offered either no nutritional support or the standard TPN solution developed for intensive care units. The solution provides 70 percent of the calories going into the bloodstream in the form of glucose. All too often, I believe, these high-glucose solutions for cachectic cancer patients do not help as much as would TPN solutions with lower levels of glucose and higher levels of amino acids and lipids. These solutions would allow the patient to build strength and would not feed the tumor.17
The medical establishment may be missing the connection between sugar and its role in tumorigenesis. Consider the million-dollar positive emission tomography device, or PET scan, regarded as one of the ultimate cancer-detection tools. PET scans use radioactively labeled glucose to detect sugar-hungry tumor cells. PET scans are used to plot the progress of cancer patients and to assess whether present protocols are effective.18
In Europe, the "sugar feeds cancer" concept is so well accepted that oncologists, or cancer doctors, use the Systemic Cancer Multistep Therapy (SCMT) protocol. Conceived by Manfred von Ardenne in Germany in 1965, SCMT entails injecting patients with glucose to increase blood-glucose concentrations. This lowers pH values in cancer tissues via lactic acid formation. In turn, this intensifies the thermal sensitivity of the malignant tumors and also induces rapid growth of the cancer. Patients are then given whole-body hyperthermia (42 C core temperature) to further stress the cancer cells, followed by chemotherapy or radiation.19 SCMT was tested on 103 patients with metastasized cancer or recurrent primary tumors in a clinical phase-I study at the Von Ardenne Institute of Applied Medical Research in Dresden, Germany. Five-year survival rates in SCMT-treated patients increased by 25 to 50 percent, and the complete rate of tumor regression increased by 30 to 50 percent.20 The protocol induces rapid growth of the cancer, then treats the tumor with toxic therapies for a dramatic improvement in outcome.
The irrefutable role of glucose in the growth and metastasis of cancer cells can enhance many therapies. Some of these include diets designed with the glycemic index in mind to regulate increases in blood glucose, hence selectively starving the cancer cells; low-glucose TPN solutions; avocado extract to inhibit glucose uptake in cancer cells; hydrazine sulfate to inhibit gluconeogenesis in cancer cells; and SCMT.
A female patient in her 50s, with lung cancer, came to our clinic, having been given a death sentence by her Florida oncologist. She was cooperative and understood the connection between nutrition and cancer. She changed her diet considerably, leaving out 90 percent of the sugar she used to eat. She found that wheat bread and oat cereal now had their own wild sweetness, even without added sugar. With appropriately restrained medical therapy -- including high-dose radiation targeted to tumor sites and fractionated chemotherapy, a technique that distributes the normal one large weekly chemo dose into a 60-hour infusion lasting days -- a good attitude and an optimal nutrition program, she beat her terminal lung cancer. I saw her the other day, five years later and still disease-free, probably looking better than the doctor who told her there was no hope.
Patrick Quillin, Ph.D., R.D., C.N.S., is director of nutrition for Cancer Treatment Centers of America in Tulsa, Okla., and author of Beating Cancer With Nutrition (Nutrition Times Press, 1998).
References
1. Warburg O. On the origin of cancer cells. Science 1956 Feb;123:309-14.
2. Volk T, et al. pH in human tumor xenografts: effect of intravenous administration of glucose. Br J Cancer 1993 Sep;68(3):492-500.
3.Digirolamo M. Diet and cancer: markers, prevention and treatment. New York: Plenum Press; 1994. p 203.
4. Leeper DB, et al. Effect of i.v. glucose versus combined i.v. plus oral glucose on human tumor extracellular pH for potential sensitization to thermoradiotherapy. Int J Hyperthermia 1998 May-Jun;14(3):257-69.
5. Rossi-Fanelli F, et al. Abnormal substrate metabolism and nutritional strategies in cancer management. JPEN J Parenter Enteral Nutr 1991 Nov-Dec;15(6):680-3.
6. Grant JP. Proper use and recognized role of TPN in the cancer patient. Nutrition 1990 Jul-Aug;6(4 Suppl):6S-7S, 10S.
7. Brand-Miller J, et al. The glucose revolution. Newport (RI) Marlowe and Co.; 1999.
8. Mooradian AD, et al. Glucotoxicity: potential mechanisms. Clin Geriatr Med 1999 May;15(2):255.
9. Hoehn, SK, et al. Complex versus simple carbohydrates and mammary tumors in mice. Nutr Cancer 1979;1(3):27.
10. Santisteban GA, et al. Glycemic modulation of tumor tolerance in a mouse model of breast cancer. Biochem Biophys Res Commun 1985 Nov 15;132(3):1174-9.
11. Sanchez A, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr 1973 Nov;26(11):1180-4.
12. Moerman CJ, et al. Dietary sugar intake in the aetiology of biliary tract cancer. Int J Epidemiol 1993 Apr;22(2):207-14.
13. Seeley S. Diet and breast cancer: the possible connection with sugar consumption. Med Hypotheses 1983 Jul;11(3):319-27.
14. Board M, et al. High Km glucose-phosphorylating (glucokinase) activities in a range of tumor cell lines and inhibition of rates of tumor growth by the specific enzyme inhibitor mannoheptulose. Cancer Res 1995 Aug 1;55(15):3278-85.
15. Chlebowski RT, et al. Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 1987 Feb 1;59(3):406-10.
16. Chlebowski RT, et al. Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol 1990 Jan;8(1):9-15.
17. American College of Physicians. Parenteral nutrition in patients receiving cancer chemotherapy. Ann Intern Med 1989 May;110(9):734.
18. Gatenby RA. Potential role of FDG-PET imaging in understanding tumor-host interaction. J Nucl Med 1995 May;36(5):893-9.
19. von Ardenne M. Principles and concept 1993 of the Systemic Cancer Multistep Therapy (SCMT). Extreme whole-body hyperthermia using the infrared-A technique IRATHERM 2000 -- selective thermosensitisation by hyperglycemia -- circulatory back-up by adapted hyperoxemia. Strahlenther Onkol 1994 Oct;170(10):581-9.
20. Steinhausen D, et al. Evaluation of systemic tolerance of 42.0 degrees C infrared-A whole-body hyperthermia in combination with hyperglycemia and hyperoxemia. A Phase-I study. Strahlenther Onkol 1994 Jun;170(6):322-34.
POSTED BY
Dr. Mercola
Sunday, September 7, 2008
Cancer Cell metabolism: Warburg and beyond
Recently an essay appeared in Cell on "Cancer Cell Metabolism: Warburg and Beyond". It tries to establish a framework for understanding on the altered metabolism of cancer cells.In 1920 Warburg found that even in presence of ample oxygen cancer cells metabolize sugar through glycolysis. Glycolysis is an anerobic process and is less efficient in producing ATP molecules than its aerobic metabolism counterpart.
Why it happens? Lets discuss in little more detail in simpler language. As an early tumor grows, it outgrows the diffusion limit that blood vessels can supply. Thus, it causes hypoxia(Oxygen deficiency) in the surrounding cells. Hypoxia leads to decreased dependency on aerobic respiration leading to glycolysis.
It has also been shown that prevention of glycolysis leads to attenuated tumor growth and possible reversal of tumor cells into normal cells. Inhibition of lactate dehydrogenase LDH A forces cancer cells to oxidative phosphorylation in order to reoxidize NADH and produce ATP (Shim et al., 1997
,Fantin et al., 2006
)
Its also known that the altered biochemical pathways in tumor cells leads to changed programmed cell death(Apoptosis). Overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents caspase-independent cell death, presumably by stimulating glycolysis, increasing cellular ATP levels, and promoting autophagy (Colell et al., 2007). Whether or not GAPDH plays a physiological role in the regulation of cell death remains to be determined.
Although altered metabolism confers several advantages on the cancer cell, it does not come without disadvantages. As a consequence of a deranged or simply overactive metabolism, cancer cells may be burdened with toxic byproducts that require disposal. So far, there is relatively little evidence for this hypothesis in the existing literature, but a few examples do suggest that cancer cells require detoxification mechanisms to maintain survival. Although there are enzymes that detoxify exogenous toxins, several “house-cleaning” enzymes, a term coined from studies in bacteria, deal with endogenous toxic metabolites (reviewed in Galperin et al., 2006). The best example of “house-cleaning” enzymes are the NUDIX (noncanonical nucleoside diphosphate linked to some other moiety X) hydrolases, a family of enzymes that act on the nucleotide pool and remove noncanonical nucleoside triphosphates. When incorporated into the DNA, these aberrant nucleotides can lead to mismatches, mutations, and eventually cell death. The dUTP pyrophosphatase (DUT), which hydrolyzes dUTP to dUMP and prevents the incorporation of uracils into DNA, may play a role in resistance to thymidylate synthase inhibitors. Suppression of DUT sensitizes some cancer cells to pyrimidine antimetabolites, suggesting that inhibition of these cellular house-cleaning enzymes may be an effective adjunct chemotherapeutic strategy (Koehler et al., 2004).
The lactate production associated with the shift to a glycolytic metabolism is thought to contribute to the acidification of the microenvironment. Able to adapt to and even benefit from an acidic environment, cancer cells have been shown to upregulate vacuolar H+-ATPases, Na+-H+ antiporters, and H+-linked monocarboxylate transporters (reviewed in Gatenby et al., 2004). Inhibition of these adaptive mechanisms can lead to decreased viability of cancer cells and increased sensitivity to chemotherapeutic agents (reviewed in Fais et al., 2007, Fang et al., 2006).
Many mysteries remain unsolved in our understanding of even normal human metabolism, let alone that of cancer cells. The metabolic pathways of the mammalian cell and their many interconnections are incomplete, as many enzymes remain unannotated in the human genome. Although we have guesses by homology, the identities of the human enzymes that catalyze reactions we know must occur are still elusive. In addition to annotating all human metabolic genes, the “ins” and the “outs” (i.e., the metabolites that enter and exit cells) should be measured and cataloged. It is also entirely unclear what percentage of the cellular fuel is normally used for ATP generation, biosynthesis, or other processes. And with few exceptions surprisingly little is known about intercellular metabolism. Much of our understanding of metabolism has been inherited from work in simple organisms; the compartmental nature of human metabolism is an exciting area of potential exploration.
Although aerobic glycolysis is the most characterized, although still puzzling, metabolic phenomenon in cancer, many other aspects of cancer metabolism are likely to be derangements of normal metabolism and ought to be elucidated. The nutrient conditions of the tumor microenvironment have not yet been carefully examined. Cancer cells, despite engaging in energy-costly processes, must still be able to maintain ATP levels, by either relying on increased flux through glycolysis or utilizing a diversity of fuel sources. Several hypotheses exist as to why a fraction of tumors are refractory to imaging by FDG-PET. One possibility is that certain cancer cells may not be primarily glucose-metabolizers but may rely on alternative fuel sources, the detailed characterization of which may lead to the detection and treatment of “PET-negative” tumors. Furthermore, there are more complex questions to be answered: Is it possible that cancer cells exhibit “metabolite addiction”? Are there unique cancer-specific metabolic pathways, or combinations of pathways, utilized by the cancer cell but not by normal cells? Are different stages of metabolic adaptations required for the cancer cell to progress from the primary tumor stage to invasion to metastasis? How malleable is cancer metabolism?
From a therapeutic perspective, knowledge of the causes, benefits, and vulnerabilities of cancer cell metabolism will enable the identification of new drug targets and will facilitate the design of metabolite mimetics that are uniquely taken up by cancer cells or converted into the active form by enzymes upregulated in tumors. Profiling of either metabolites or enzymatic activities may allow us to develop diagnostic tests of cancer, and metabolite derivatives can be used for the molecular imaging of cancer, as exemplified by FDG-PET. We find the possibility of a new class of cancer therapeutics and diagnostic tools especially exciting. Therefore, we emphasize the need to explore beyond a glucose and energy-centric driven model of cancer metabolism to a broader one that encompasses all of the metabolic needs of a cancer cell. Perhaps it is time to step out from under Warburg's shadow.
Why it happens? Lets discuss in little more detail in simpler language. As an early tumor grows, it outgrows the diffusion limit that blood vessels can supply. Thus, it causes hypoxia(Oxygen deficiency) in the surrounding cells. Hypoxia leads to decreased dependency on aerobic respiration leading to glycolysis.
It has also been shown that prevention of glycolysis leads to attenuated tumor growth and possible reversal of tumor cells into normal cells. Inhibition of lactate dehydrogenase LDH A forces cancer cells to oxidative phosphorylation in order to reoxidize NADH and produce ATP (Shim et al., 1997
,Fantin et al., 2006
)
Its also known that the altered biochemical pathways in tumor cells leads to changed programmed cell death(Apoptosis). Overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents caspase-independent cell death, presumably by stimulating glycolysis, increasing cellular ATP levels, and promoting autophagy (Colell et al., 2007). Whether or not GAPDH plays a physiological role in the regulation of cell death remains to be determined.
Although altered metabolism confers several advantages on the cancer cell, it does not come without disadvantages. As a consequence of a deranged or simply overactive metabolism, cancer cells may be burdened with toxic byproducts that require disposal. So far, there is relatively little evidence for this hypothesis in the existing literature, but a few examples do suggest that cancer cells require detoxification mechanisms to maintain survival. Although there are enzymes that detoxify exogenous toxins, several “house-cleaning” enzymes, a term coined from studies in bacteria, deal with endogenous toxic metabolites (reviewed in Galperin et al., 2006). The best example of “house-cleaning” enzymes are the NUDIX (noncanonical nucleoside diphosphate linked to some other moiety X) hydrolases, a family of enzymes that act on the nucleotide pool and remove noncanonical nucleoside triphosphates. When incorporated into the DNA, these aberrant nucleotides can lead to mismatches, mutations, and eventually cell death. The dUTP pyrophosphatase (DUT), which hydrolyzes dUTP to dUMP and prevents the incorporation of uracils into DNA, may play a role in resistance to thymidylate synthase inhibitors. Suppression of DUT sensitizes some cancer cells to pyrimidine antimetabolites, suggesting that inhibition of these cellular house-cleaning enzymes may be an effective adjunct chemotherapeutic strategy (Koehler et al., 2004).
The lactate production associated with the shift to a glycolytic metabolism is thought to contribute to the acidification of the microenvironment. Able to adapt to and even benefit from an acidic environment, cancer cells have been shown to upregulate vacuolar H+-ATPases, Na+-H+ antiporters, and H+-linked monocarboxylate transporters (reviewed in Gatenby et al., 2004). Inhibition of these adaptive mechanisms can lead to decreased viability of cancer cells and increased sensitivity to chemotherapeutic agents (reviewed in Fais et al., 2007, Fang et al., 2006).
Many mysteries remain unsolved in our understanding of even normal human metabolism, let alone that of cancer cells. The metabolic pathways of the mammalian cell and their many interconnections are incomplete, as many enzymes remain unannotated in the human genome. Although we have guesses by homology, the identities of the human enzymes that catalyze reactions we know must occur are still elusive. In addition to annotating all human metabolic genes, the “ins” and the “outs” (i.e., the metabolites that enter and exit cells) should be measured and cataloged. It is also entirely unclear what percentage of the cellular fuel is normally used for ATP generation, biosynthesis, or other processes. And with few exceptions surprisingly little is known about intercellular metabolism. Much of our understanding of metabolism has been inherited from work in simple organisms; the compartmental nature of human metabolism is an exciting area of potential exploration.
Although aerobic glycolysis is the most characterized, although still puzzling, metabolic phenomenon in cancer, many other aspects of cancer metabolism are likely to be derangements of normal metabolism and ought to be elucidated. The nutrient conditions of the tumor microenvironment have not yet been carefully examined. Cancer cells, despite engaging in energy-costly processes, must still be able to maintain ATP levels, by either relying on increased flux through glycolysis or utilizing a diversity of fuel sources. Several hypotheses exist as to why a fraction of tumors are refractory to imaging by FDG-PET. One possibility is that certain cancer cells may not be primarily glucose-metabolizers but may rely on alternative fuel sources, the detailed characterization of which may lead to the detection and treatment of “PET-negative” tumors. Furthermore, there are more complex questions to be answered: Is it possible that cancer cells exhibit “metabolite addiction”? Are there unique cancer-specific metabolic pathways, or combinations of pathways, utilized by the cancer cell but not by normal cells? Are different stages of metabolic adaptations required for the cancer cell to progress from the primary tumor stage to invasion to metastasis? How malleable is cancer metabolism?
From a therapeutic perspective, knowledge of the causes, benefits, and vulnerabilities of cancer cell metabolism will enable the identification of new drug targets and will facilitate the design of metabolite mimetics that are uniquely taken up by cancer cells or converted into the active form by enzymes upregulated in tumors. Profiling of either metabolites or enzymatic activities may allow us to develop diagnostic tests of cancer, and metabolite derivatives can be used for the molecular imaging of cancer, as exemplified by FDG-PET. We find the possibility of a new class of cancer therapeutics and diagnostic tools especially exciting. Therefore, we emphasize the need to explore beyond a glucose and energy-centric driven model of cancer metabolism to a broader one that encompasses all of the metabolic needs of a cancer cell. Perhaps it is time to step out from under Warburg's shadow.
Wednesday, August 27, 2008
Randy Pausch
Dr. Randy Pausch, A professor in computer science at the coveted CMU(Carnegie Mellon Institute) passed away on July 25th 2008. When he was still fighting I got to know about his best seller 'The last Lecture'. I saw the entire lecture on his web page and was quite taken aback by his zest for life. Since then I have been a regular visitor to his daily update page to check how he is doing and whether he has any positive improvement. But sadly enough after his June 24th post, no post came forward. although I kept him in may daily prayers, I did not see any new post on his health until July 24th. Then finally on 25th July 2008 he passed away. He was suffering from terminal pancreatic cancer which was diagnosed in Summer of 2006. His prognosis was not good and cancer recurred in August 2007 only leaving him 3-6 months of healthy living. Although he has outlived the time line, but his health continued to decline. Then finally the inevitable happened on 25th July 2008. This paragraph is a tribute to a great life...
Here are some reminiscence of his "Last lecture".
Achieving your childhood dreams – by Randy Pausch
* "Really Achieving Your Childhood Dreams"
* Randy Pausch's "final" lecture was given on 18 September 2007, as part of a series at Carnegie Mellon University. A full transcript is carried at www.randypausch.com. Here are some highlights.
* "It's wonderful to be here. What they didn't tell you is that this lecture series used to be called 'The Last Lecture'. If you had one last lecture to give before you died, what would it be? I thought, damn, I finally nailed the venue and they renamed it."
* "We cannot change the cards we are dealt, just how we play the hand. If I don't seem as depressed as I should be, sorry to disappoint you. I assure you I am not in denial. It's not like I'm not aware of what's going on... The other thing is that I am in phenomenally good health right now. I mean, it's the greatest thing of cognitive dissonance you will ever see: the fact that I am in really good shape. In fact, I am in better shape than most of you. [Pausch starts doing push-ups.] So anybody who wants to cry or pity me can get down and do a few of those."
* "How do you get people to help you? By telling the truth. Being earnest. I'll take an earnest person over a hip person every day, because hip is short-term."
* "Apologise when you screw up and focus on other people, not on yourself. How do I make a concrete example of that? See, yesterday was my wife's birthday. If there was ever a time I might be entitled to have the focus on me, it might be the last lecture. But no, I feel very badly that my wife didn't really get a proper birthday, and I thought it would be very nice if 500 people... [a birthday cake is wheeled on to the stage]."
* "Remember, brick walls let us show our dedication. They are there to separate us from the people who don't really want to achieve their dreams. Don't bail. The best of the gold's at the bottom of barrels of crap."
* "Show gratitude. When I got tenure I took all of my research team down to Disney World for a week. And one of the other professors said, 'How can you do that?' I said: 'These people just busted their ass and got me the best job in the world for life. How could I not do that?'"
* "Don't complain. Just work harder [shows slide of Jackie Robinson, the first black major league baseball player]. It was in his contract not to complain, even when fans spit on him."
* "Work hard. I got tenure a year early. Junior faculty members used to say to me, 'What's your secret?' I said, 'It's pretty simple: call me any Friday night in my office at ten o'clock and I'll tell you.'"
* "Find the best in everybody. You might have to wait a long time, but people will show you their good side. Just keep waiting, it will come out. And be prepared. Luck is truly where preparation meets opportunity."
Here are some reminiscence of his "Last lecture".
Achieving your childhood dreams – by Randy Pausch
* "Really Achieving Your Childhood Dreams"
* Randy Pausch's "final" lecture was given on 18 September 2007, as part of a series at Carnegie Mellon University. A full transcript is carried at www.randypausch.com. Here are some highlights.
* "It's wonderful to be here. What they didn't tell you is that this lecture series used to be called 'The Last Lecture'. If you had one last lecture to give before you died, what would it be? I thought, damn, I finally nailed the venue and they renamed it."
* "We cannot change the cards we are dealt, just how we play the hand. If I don't seem as depressed as I should be, sorry to disappoint you. I assure you I am not in denial. It's not like I'm not aware of what's going on... The other thing is that I am in phenomenally good health right now. I mean, it's the greatest thing of cognitive dissonance you will ever see: the fact that I am in really good shape. In fact, I am in better shape than most of you. [Pausch starts doing push-ups.] So anybody who wants to cry or pity me can get down and do a few of those."
* "How do you get people to help you? By telling the truth. Being earnest. I'll take an earnest person over a hip person every day, because hip is short-term."
* "Apologise when you screw up and focus on other people, not on yourself. How do I make a concrete example of that? See, yesterday was my wife's birthday. If there was ever a time I might be entitled to have the focus on me, it might be the last lecture. But no, I feel very badly that my wife didn't really get a proper birthday, and I thought it would be very nice if 500 people... [a birthday cake is wheeled on to the stage]."
* "Remember, brick walls let us show our dedication. They are there to separate us from the people who don't really want to achieve their dreams. Don't bail. The best of the gold's at the bottom of barrels of crap."
* "Show gratitude. When I got tenure I took all of my research team down to Disney World for a week. And one of the other professors said, 'How can you do that?' I said: 'These people just busted their ass and got me the best job in the world for life. How could I not do that?'"
* "Don't complain. Just work harder [shows slide of Jackie Robinson, the first black major league baseball player]. It was in his contract not to complain, even when fans spit on him."
* "Work hard. I got tenure a year early. Junior faculty members used to say to me, 'What's your secret?' I said, 'It's pretty simple: call me any Friday night in my office at ten o'clock and I'll tell you.'"
* "Find the best in everybody. You might have to wait a long time, but people will show you their good side. Just keep waiting, it will come out. And be prepared. Luck is truly where preparation meets opportunity."
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