Stress and Cancer

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Stress and Cancer

This page is dedicated to discussing Stress and alternitively, Cancer. Sometimes discussed together, sometimes separately, one or both of these two medical maladies have affected every American at one point or another in their lives.

We start out with a brand new article (1/11) describing a new CANCER BLOOD TEST. Should be interesting. Let's see what it all about:


BOSTON, MA; Jan. 3, 2011: A blood test so sensitive that it can spot a single cancer cell lurking among a billion healthy ones is moving one step closer to being available at your doctor's office. Boston scientists who invented the test and health care giant Johnson & Johnsonwill announce Monday that they are joining forces to bring it to market. Four big cancer centers also will start studies using the experimental test this year.

Stressandcancer-1

Stray cancer cells in the blood mean that a tumor has spread or is likely to, many doctors believe. A test that can capture such cells has the potential to transform care for many types of cancer, especially breast, prostate, colon and lung.

"This is like a liquid biopsy" that avoids painful tissue sampling and may give a better way to monitor patients than periodic imaging scans, said Dr. Daniel Haber, chief of Massachusetts General Hospital's cancer center and one of the test's inventors. Ultimately, the test may offer a way to screen for cancer besides the mammograms, colonoscopies and other less-than-ideal methods used now.

"There's a lot of potential here, and that's why there's a lot of excitement," said Dr. Mark Kris, lung cancer chief at Memorial Sloan-Kettering Cancer Center in New York. He had no role in developing the test, but Sloan-Kettering is one of the sites that will study it this year. Many people have their cancers diagnosed through needle biopsies. These often do not provide enough of a sample to determine what genes or pathways control a tumor's growth. Or the sample may no longer be available by the time the patient gets sent to a specialist to decide what treatment to prescribe. Doctors typically give a drug or radiation treatment and then do a CT scan two months later to look for tumor shrinkage. Some patients only live long enough to try one or two treatments, so a test that can gauge success sooner, by looking at cancer cells in the blood, could give patients more options.

"If you could find out quickly, 'this drug is working, stay on it,' or 'this drug is not working, try something else,' that would be huge," Haber said.

The only test on the market now to find tumor cells in blood - CellSearch, made by J&J's Veridex unit - just gives a cell count. It doesn't capture whole cells that doctors can analyze to choose treatments. Interest in trying to collect these cells soared in 2007, after Haber and his colleagues published a study of Mass General's test. It is far more powerful than CellSearch and traps cells intact. It requires only a couple of teaspoons of blood and can be done repeatedly to monitor treatment or determine why a drug has stopped working and what to try next.

"That's what got the scientific community's interest," Kris said. Doctors can give a drug one day and sample blood the next day to see if the circulating tumor cells are gone, he explained.

The test uses a microchip that resembles a lab slide covered in 78,000 tiny posts, like bristles on a hairbrush. The posts are coated with antibodies that bind to tumor cells. When blood is forced across the chip, cells ping off the posts like balls in a pinball machine. The cancer cells stick, and stains make them glow so researchers can count and capture them for study. The test can find one cancer cell in a billion or more healthy cells, said Mehmet Toner, a Harvard University bioengineer who helped design it. Researchers know this because they spiked blood samples with cancer cells and then searched for them with the chip. Studies of the chip have been published in the journals Nature, the New England Journal of Medicine and Science Translational Medicine. It is the most promising of several dozen that companies and universities are rushing to develop to capture circulating tumor cells, said Bob McCormack, technology chief for Veridex.

The agreement announced Monday will have Veridex and J&J's Ortho Biotech Oncology unit work to improve the microchip, including trying a cheaper plastic to make it practical for mass production. No price goal has been set, a company official said, but the current CellSearch test costs several hundred dollars. The companies will start a research center at Mass General and will have rights to license the test from the hospital, which holds the patents.

In a separate effort, Mass General, Sloan-Kettering, University of Texas M.D. Anderson Cancer Center in Houston and Dana-Farber Cancer Institute in Boston will start using the test this year. They are one of the "dream teams" sharing a $15 million grant from the Stand Up to Cancer telethon, run by the American Association for Cancer Research. Already, scientists have been surprised to find that more cancer patients harbor these stray cells than has been believed.

In one study, the test was used on men thought to have cancer confined to the prostate, "but we found these cells in two-thirds of patients," Toner said.

This might mean that cancer cells enter the blood soon after a tumor starts, or that more cancers have already spread but are unseen by doctors. Or it could mean something else entirely, because researchers have much to learn about these cells, said Dr. Minetta Liu, a breast cancer specialist at Georgetown University's Lombardi Comprehensive Cancer Center. She led a session on them at the recent San Antonio Breast Cancer Symposium and has been a paid speaker for Veridex. She hopes the cells will someday aid cancer screening.

"The dream is, a woman comes in for her mammogram and gets a tube of blood drawn," so doctors can look for cancer cells in her blood as well as tumors on the imaging exam, she said.

That's still far off, but Mass General's test already is letting doctors monitor patients without painful biopsies. Like Greg Vrettos, who suffered a collapsed lung from a biopsy in 2004, when he was diagnosed with lung cancer.

"It had spread to both lungs and they couldn't operate," said Vrettos, 63, a nonsmoker and retired electrical engineer from Durham, N.H. Tests from the biopsy showed that he was a good candidate for the drug Iressa, which he has taken ever since. He goes to Boston every three months for CT scans and the blood test.

"They could look at the number of cancer cells and see that it dropped over time. It corresponded with what the scans were showing," Vrettos said of doctors looking at his blood tests.

The test also showed when he had a setback last January and needed to have his treatment adjusted.

"I think it's going to be revolutionary," he said of the test.  *Let's hope so (JH).


>The stress hormone epinephrine: Changes prostate and breast cancer cells in ways that may make them resistant to cell death. This means that emotional stress could both contribute to the development of cancer and reduce the effectiveness of cancer treatments.  Epinephrine levels increase sharply in response to stressful situations, and can remain continuously elevated during long periods of stress or depression.  When cancer cells are exposed to epinephrine, a protein called BAD, which causes cell death, becomes inactive. An earlier study found that men who take beta blockers, which block the effects of epinephrine, can have an 18 percent lower risk of prostate cancer.

Journal of Biological Chemistry March 12, 2007

>Which Came First: The chicken or the egg? The age old question. The answer is, the egg of course. . . . .

*"Up close and Personal: There never will be a 'cure for cancer.' But a multiplicity of new ideas promise treatments for the multiplicity of diseases that cancer actually is," The Economist, Oct. 16th - 22nd, 2004.

This great article articulates precisely the big issue with cancer: it is many diseases. The idea that there will be some kind of golden bullet that cures all cancer is a myth. Just crunching the numbers data, it appears mankind continues to loose the so called war on cancer. According to the World Health Organization (WHO), 10m people around the entire planet were diagnosed with cancer in 2000, and 6m died from it. Now consider the rapidly aging population, the fact that people live much longer than they used to, increased tobacco consumption and the spread of "western" style eating habits and it is easy to see why cancer is on the rise. By 2010, over 50% of the people alive today in the U.S. will be diagnosed with cancer. And all this despite the grand announcement made by President Richard Nixon in a speech in 1971, announcing the "War on Cancer." Americans have forked out $70 Billion (in actual, not inflation adjusted dollars) to the National Cancer Institute (NCI) over the years since 1971. Add to that the money spent by drug companies and charities to say nothing of the research money spent by other countries. And what do we have to show for all of the expensive "research?" The rate of death from cancer in the U.S. has increased from 163 per 100,000 in 1971 to 194 per 100,000 by 2001. To keep this in perspective, consider that mortality rates from heart disease and strokes have actually fallen over the years. We single out heart disease and strokes as being two other health issues often associated with affluent life styles.

So what's up with Cancer? Cancer is characterized by uncontrolled cell growth. Healthy cells regulate their division into daughter cells carefully suborning the own tendency to reproduce in favor of survival of the host body. It truly is a marvel of evolutionary editing that allowed for multicelled beings. However, with trillions of cells in each animal, inevitably mutations (mistakes) can and do occur. Thus, the regulatory genes that inhibit cell growth will occasionally loose out in the competition of cell growth to the unregulated cells. That's because unregulated cells multiply faster and win out. The result is Cancer.

Early drug therapy, aka Chemotherapy, killed cancer as well as healthy cells which resulted in a multitude of side effects, some worse than the cancer itself. More recently, new drugs are being marketed that attack only deranged cells. The best known of these is Glivec. Now, consider the strange case of Chronic Myeloid Leukemia (CML). This Cancer is characterized by the overproliferation of white, myeloid blood cells. CML is caused by the union of two chromosomes, numbers 9 and 22. When these chromosomes break and their parts then join to form a 9-22 hybrid chromosome, they also bring together two genes called BCR and ABL. The new protein made by the new gene is called BCR-ABL. This new protein, BCR-ABL is one of a class of enxymes known as tyrosine kinases, which are involved in signalling pathways inside cells. In the case of BCR-ABL, the signal generated tells the myeloid cells to proliferate continuously. Thus, it doesn NOT stop cell growth, which the original gene would have. Glivec supposedly blocks this enzyme by literally sitting on it, and thus, uncontrolled cell growth stops. At least, that's what is supposed to happen. Chicken or the egg indeed; as we can clearly see, "point mutation" can and does occur completely changing an organism, sometimes for the worse. It had to be the egg.

Researchers now realize that by the time Cancer has been diagnosed, more than one mutation has happened, probably around 5 mutations. It simply is not realistic to think one drug or one radiation will kill the cancer. Better to diagnose a patient early. Like all diseases, early detection and treatment is the key here. As for what the typical person can do, consider keeping your weight down, if you drink too much alcohol think about reducing that intake. If you are a smoker, stop. If you don't exercise, start by walking 4 times a week for a mile or two. Again, as always, we stress the "wholistic" approach to general good health practices. This approach is not guaranteed to keep you from getting cancer but it can help. Yearly physicals are a good idea too, especially after one turns 40. For men, as we have said elsewhere, Prostate checks including PSA inventories are a good idea over the age of 40.


>Psychological Stress and Cancer

The complex relationship between physical and psychological health is not well understood. Scientists know that many types of stress activate the body's endocrine (hormone) system, which in turn can cause changes in the immune system, the body's defense against infection and disease (including cancer). However, the immune system is a highly specialized network whose activity is affected not only by stress but by a number of other factors. It has not been shown that stress-induced changes in the immune system directly cause cancer.

Some studies have indicated an increased incidence of early death, including cancer death, among people who have experienced the recent loss of a spouse or other loved one. However, most cancers have been developing for many years and are diagnosed only after they have been growing in the body for a long time (from 2 to 30 years). This fact argues against an association between the death of a loved one and the triggering of cancer.

The relationship between breast cancer and stress has received particular attention. Some studies of women with breast cancer have shown significantly higher rates of this disease among those women who experienced traumatic life events and losses within several years before their diagnosis. Although studies have shown that stress factors (such as death of a spouse, social isolation, and medical school examinations) alter the way the immune system functions, they have not provided scientific evidence of a direct cause-and-effect relationship between these immune system changes and the development of cancer. One NCI-sponsored study suggests that there is no important association between stressful life events, such as the death of a loved one or divorce, and breast cancer risk.* However, more research to find if there is a relationship between psychological stress and the transformation of normal cells into cancerous cells is needed.

One area that is currently being studied is the effect of stress on women already diagnosed with breast cancer. These studies are looking at whether stress reduction can improve the immune response and possibly slow cancer progression. Researchers are doing this by determining whether women with breast cancer who are in support groups have better survival rates than those not in support groups.

Many factors come into play when determining the relationship between stress and cancer. At present, the relationship between psychological stress and cancer occurrence or progression has not been scientifically proven. However, stress reduction is of benefit for many other health reasons.

*"Self-Reported Stress and Risk of Breast Cancer," Felicia D. Roberts, Polly A. Newcomb, Amy Trentham-Dietz, and Barry E. Storer. Cancer, March 15, 1996.

"Stress and Immune Responses After Surgical Treatment for Regional Breast Cancer," Barbara L. Andersen, William B. Farrar, Deanna Golden-Kreutz, et al. Journal of the National Cancer Institute, January 7, 1998.

Sources of National Cancer Institute Information:

Cancer Information Service
    Toll-free: 1-800-4-CANCER (1-800-422-6237)
    TTY (for deaf and hard of hearing callers): 1-800-332-8615

NCI Online
    Internet
    Use
http://www.cancer.gov to reach NCI's Web site.

    LiveHelp
    Cancer Information Specialists offer online assistance through the LiveHelp link on the NCI's
    Web site.


 

Nomenclature: Terms used in the discussion of Cancer:

The following closely related terms may be used to designate abnormal growths:

Neoplasm: a scientific term which refers to an abnormal proliferation of genetically altered cells.
Malignant neoplasm: synonymous with cancer.
Tumor: broadly defined, can be any swelling or mass. However, the vast majority of entities referred to as 'tumors' in common usage are in fact neoplasms. Specifically, a tumor is a solid neoplasm; some neoplasms, such as cancers of the blood, are not solid.
Benign tumor: a tumor (solid neoplasm) that has self-limiting growth and does not invade other tissues nor metastasize. Usually not cancerous.
Pre-malignancy: A non-invasive neoplasm that may not form an obvious mass, but has the potential to progress to cancer if left untreated. Pre-malignant neoplasms may show distinctive microscopic changes such as dysplasia or atypia.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:

Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
Lymphoma and leukemia: Malignancies derived from hematopoetic (blood-forming) cells
Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
Blastic tumor: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.
Malignant tumors are usually named using the Latin or Greek root of the organ of origin as a prefix and the above category name as the suffix. For instance, a malignant tumor of the liver is called hepatocarcinoma; a malignant tumor of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid). However, some cancers also use this prefix for historical reasons, examples being melanoma and seminoma.


Adult cancers:
In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.[3] On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and will vary substantially in other countries. The table below shows us what are the most common cancers in descending order downward for males and females. Next to that list are the biggest causes of death in descending order downward:

Male

Women

Most Common

Cause of Death

Most Common

Cause of Death

prostate cancer (33%)

lung cancer (31%)

breast cancer (32%)

lung cancer (27%)

lung cancer (13%

prostate cancer (10%)

lung cancer (12%)

breast cancer (15%)

colorectal cancer (10%)

colorectal cancer (10%)

colorectal cancer (11%)

colorectal cancer (10%)

bladder cancer (7%)

pancreatic cancer (5%)

endometrial cancer (6%)

ovarian cancer (6%)

cutaneous melanoma (5%)

leukemia (4%)

non-Hodgkin lymphoma (4%)

pancreatic cancer (6%)




Childhood cancers:
Cancer can also occur in young children and adolescents, but it is rare. Some studies have concluded that pediatric cancers, especially leukemia, are on an upward trend.

The age of peak incidence of cancer in children occurs during the first year of life. Leukemia (usually ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma. Teratoma is the most common tumor in this age group, but most teratomas are surgically removed while still benign.

Female and male infants have essentially the same overall cancer incidence rates, but white infants have substantially higher cancer rates than black infants for most cancer types. Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.


Signs and symptoms:
Roughly, cancer symptoms can be divided into three groups:

1) Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice.
2) Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.
3) Systemic symptoms: weight loss, poor appetite and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.
Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.


Diagnosis:
Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist.


Investigation:
X-rays showing lung cancers and other types is not very sensitive. There needs to be around 55% bone destruction before tumors can even begin to be seen in plain films. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy. Bone Scans, on the other hand, are extremely sensitive only requiring about 1-2% bone destruction to show a tumor is present.


Biopsy:
A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

The tissue diagnosis indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and choose the best treatment. Cytogenetics and immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best treatment.


Hyperthermia and the treatment of Cancer: Manfred von Ardenne (1907-1997)-David Rorvik

The Alicia Patterson Foundation
1025 F St. N.W.
Suite 700
Washington, D.C. 20004

The "Unproven" Wonders of Hyperthermia (*see an actual picture of von Ardenne on our Fever/Immunity page)

Nothing truly promising, however, is ever too obscure or abstruse to escape detection and then calumny by the American Cancer Society. In 1971 ACS, apparently alarmed by news that MvA and associates were getting remarkable results with something called "hyperthermia," hurried into print one of its "unproven" diatribes, in which, as usual (see DMR-6 for documentation), the research was misrepresented, criticized without foundation and presented out-of-context. Today, hyperthermia, which is only a part of von Ardenne's therapy, is attracting wide attention in orthodox circles in the United States and has even been reported upon, glowingly, in the Journal of the American Medical Association. ACS is keeping its mouth shut for the time being.

Before I explain the von Ardenne approach I must acknowledge my debt to Mark McCarty, a medical student at the University of San Diego who has made an in-depth study of the East German research. His patience in explaining the work to me was considerable. He has himself written about MvA's work and, for those with a penchant for all the fine, technical details, copies of one of his papers may be obtained - at cost - by sending $3.00 directly to McCarty at 1515 Madison Ave., San Diego, CA 92116. Request the paper entitled "Implications of Tumor Vascularity and Substrate Availability for Cancer Therapy: A Review."

One of the more intriguing aspects of von Ardenne's work in cancer is that it bears some resemblance to his work on the atomic bomb. His attack on cancer brings into play a unique biological chain reaction which reminds one of the chain reaction so critical to the explosion of a nuclear device. And as in the detonation of a bomb, von Ardenne's biological bomb can also be triggered by a burst of X-radiation.

But let us start at the beginning: *Key Summary in the next  paragraph-

The German assault on cancer takes advantage of three ways in which solid tumors differ significantly from normal tissue: 1) Tumors have sluggish blood flow; 2) to make energy, they rely heavily upon "fermentation" rather than respiration; 3) they have elevated levels of an enzyme called beta-glucuronidase. These differences, respectively, make tumors selectively vulnerable to attack by heat therapy (hyperthermia) acidification an enzymatic destruction. In combination, these differences synergize that vulnerability in a most remarkable and explosive fashion.

1) Let's look first at the inhibited blood flow through tumors and understand how this chink in cancer's armor can be exploited without destructive side effects. Unlike normal tissues, cancers are supplied almost exclusively by capillaries, those tiny blood vessels that complement veins and arteries in healthy tissue. These small vessels, many of them only large enough to accommodate a parade of blood cells marching in single file, provide considerable resistance to the onrush of blood from outside the tumor. It has been reliably estimated that, generally, blood flow through tumors is only two to fifteen percent that of normal tissue. This is a significant difference - and one that has profound implications in terms of "substrate supply" to the tumor and heat dissipation within the tumor.

Here a slight digression is in order to explain, in part, why the standard, prevailing anti-cancer therapies so often fail. The capillary vascularization of the tumor mass has a lot to do with that failure - even as it contributes to the success of hyperthermia and the East German assault. Stagnant blood flow minimizes the amount of drugs that can penetrate the tumor and attack the cancer cells. But these chemotherapies, which are all cell poisons, have little difficulty in reaching the rest of the body, with its normal vascularization. It is true that they are designed, in a sense, to be selective. But the degree of selectivity is limited. Cells are most vulnerable to attack while undergoing division - and particularly certain stages of division. Cancer cells are rapidly dividing and so, theoretically, at least, provide a good target for cytotoxic drugs. Unfortunately, the precursors of the cells that are the frontline soldiers in our natural, immunological defense systems, are also rapidly dividing and provide equally good targets - better, in fact, because they are not shielded by poor vascularization. Chemotherapeutic agents reach them easily.

There are still other problems. Some tumor cells, because of sluggish blood flow, get so little oxygen and other necessary "substrate" supplies that they stop cycling and go, in effect, into a state of temporary suspension where they are largely immune to the anti-mitotic (cell-division) chemotherapies. They form a malignant core from which trouble can - and will - arise again. As for radiation, it, too, is very likely to be more destructive of the body's immune cells than of cancer. It is well established that cancers exhibit "hypoxic radioresistance":X-radiation needs oxygen to be optimally effective. So once again that poor vascularization serves cancer well. Even when radiation and chemotherapies succeed in dissolving some of the cancer mass, cancer antigens (those little proteins that tip off the body that a foreign invader is present) attached to the tumor debris flood through the body, including the lymph nodes (factories for the body's immune surveillance and attack systems). The immune factories then respond by producing (through cell division) massive numbers of defensive cells designed to inactivate the invaders. This mitotic response immediately puts the immune system in the same danger as the cancer cells: destruction by chemotherapies (and/or radiation) which singlemindedly take advantage of cell-cycle rate differences.

So all too often we gain an inch and lose a mile.

The same peculiarities of the body - and of cancer - that previously contributed to our defeat, however, may now be used to help us succeed. As McCarty comments: "Rather than basing therapeutic selectivity on cell-cycle rate differences, a promising alternative approach is to use stagnant tumor blood flow and depressed substrate levels as a point of therapeutic attack."

2) And so back to hyperthermia. Heat will kill tissue - both normal and cancerous, but it will kill those tissues in which there is stagnant blood flow first. The body, after all, is not so different from an engine, the various parts of which will not overheat and be destroyed so long as an ample flow of water or other coolant circulates through passages within the engine block, carrying off heat generated by the combustion of fuel within the cylinders. Tumors are engines with a coolant supply insufficient to cope with temperatures not too much above that which normally exist within the body, temperatures which, felicitously, leave normal tissues, with their more adequate coolant supply, largely unscathed. The safety margin is widened further by the fact that many cancers, independent of the vascularization issue, perish at temperatures lower than those necessary for the destruction of normal tissue; why this is, no one knows.

Hyperthermia in the U.S.: Remarkable Results

The American Cancer Society was already trying to discourage anyone from investigating hyperthermia (high-temperature therapy) several years ago, citing Manfred von Ardenne as the principal practitioner of this "unproven" idea. Fortunately, MvA paid the ACS no heed, and neither did several researchers in this country who have now come forward with extremely promising results. The field looks so promising in fact that the ACS was recently pressured, by some very orthodox individuals, I have learned, into removing from its "Unproven" list the so-called "Coley Toxins" developed by the late W. B. Coley, M.D. These toxins, consisting of various infectious agents, apparently brought about striking remissions in several advanced cancer patients. They constituted, many now believe, an early form of whole-body hyperthermia, which may have worked not so much by directly killing cancer cells through heat but by stimulating the body's overall immune-response systems. There is evidence that generalized (whole-body) hyperthermia can do that.

Indeed, there is fascinating speculation now that this sort of whole-body heat effect may be responsible, at least in part (dietary factors are certainly also important), for the lower incidence of cancers of the breast, penis, testis and skin in Japan. In a land essentially without central heating, the Japanese, over the centuries, have learned to love and rely upon daily - and sometimes twice daily - baths in special tubs that leave them immersed to the neck. These are extremely hot baths, meant to have a lingering effect, and they are indulged in for long periods of times. The water temperature is amazingly hot - 42-48 degrees C. or 110 to 120 degrees F. Investigators have found that such bathing often produces rectal temperatures of 104 degrees F.

Commenting on this phenomenon in an address delivered to the International Conference on Hyperthermia and Radiation in Washington D.C., not long ago, Helen Coley Nauts, daughter of the late Dr. Coley and executive director of the Cancer Research Institute in New York (the medical director of which is Dr. Lloyd Old, vice president of Sloan-Kettering), noted that "in Finland, where very hot sauna bathing is practiced, the incidence of testicular and breast cancer is also lower than in neighboring countries where the sauna is not used. The end results in Finland following lumpectomy and relatively low doses of irradiation for breast cancer are markedly better than in other countries using more radical surgery and radiation."

All of this, as I note, remains speculative. Controlled experiments in the United States, however, demonstrate that heat, quite clearly, can kill cancer while sparing normal tissue. Writing in the Journal of the American Medical Association (May 17, 1976), Harry H. LeVeen, M.D., and colleagues from the department of surgery, Veterans Administration Hospital, Downstate (NY) Medical Center and State University of New York, Brooklyn, reported on the response of 21 cancer patients to hyperthermia. In their article, called "Tumor Eradication by Radiofrequency Therapy," the New York researchers reported that they were able to shrink or completely eradicate a variety of tumors in most of the 21 patients after exposing their growths to heat-producing electromagnetic waves at a frequency of 13-56 megahertz (13-56 million cycles per second).

Electrodes are placed on either side of the tumor (e.g., on either side of the chest wall in the case of lung tumors) and energy pulsed between them. Only in the tumor itself, with its inefficient blood flow, do the temperatures reach significant, destructive levels. This sort of "local," as opposed to "whole-body," hyperthermia, is thus aimed directly at the tumor. So far it has been effective against solid tumors of a wide variety, including those of the lungs, kidneys, neck, head and intestines. It is not effective against leukemias and other widely disseminated cancers, although whole-body hyperthermia may be of some benefit even in those categories.

The number of heat treatments needed to destroy a tumor varies from patient to patient; each treatment usually lasts 30 to 45 minutes. In many cases, the heat treatment does not totally destroy the tumor but shrinks it sufficiently that it can be safely and effectively removed by surgery. It is not a cancer "cure" in and of itself because it does not, so far as anyone knows, correct the fundamental problems that gave rise to the cancer in the first place or allowed it to take hold. But since it is apparently devoid of serious side effects and since it does not suppress the body's immune-response systems (and, indeed, especially in the case of whole-body hyperthermia, may actually enhance them) it appears to be a very significant step forward and a substantial advance over radiation and chemotherapy.

Other researchers, at the Animal Resource Facility of the University of New Mexico School of Medicine, using what they call localized current field hyperthermy (emitting at 500 kHz), say they are effecting complete tumor eradication in about one-third of their cancerous test animals. Another third experience partial tumor regression; the final third evince no change. And another group in New Mexico, also affiliated with a VA hospital, has reported significant shrinkage of tumors in 14 of 20 advanced cancer patients brought about by a combination of hyperthermia and chemotherapy. In this instance, whole-body hyperthermia, was induced by wrapping patients in hot-water-heated blankets and by circulating hot gas through tubes inserted into the lungs. The results, the researchers conclude, were much better than could have been expected through the use of chemotherapy alone.

The Lysosomal Cytolytic Chain Reaction
(Delivering the Coup de Grace)

3) Apart from all the other beneficial effects of hyperthermia, there is yet another factor that it brings into play - one that is central to Manfred von Ardenne's unique approach to combating cancer. To understand this additional factor, let us move on to the second way in which cancerous tissues differ from normal tissues: they derive energy through the fermentation of glucose rather than through oxygen respiration. The end product of all this is lactic acid. As the lactate accumulates in the tumor, its pH falls, that is, it becomes acidified. Cancerous tissues are thus more acidic than normal tissues. Manfred von Ardenne recognized some years ago that tumor acidity might be used quite effectively to help destroy the tumor and he quickly devised ways of making tumors even more acidic than they normally are. One way to do this is to give the tumor all the glucose it wants in order to boost lactic acid production. This can be achieved by inducing hyperglycemia in cancer patients through glucose infusion which continues for many hours, during the course of treatment.

What does the acid do? Well, it happens that there are organelles, structures within the cells of the body, including all cancer cells, called lysosomes. These contain lysomal enzymes capable of lysing, destroying, cell membranes. McCarty calls them "the cells' suicide bags." Happily, nature has arranged things so that the conditions that could release great quantities of these self-destruct enzymes all at once seldom exist. It's equally fortunate, however, that conditions can be created so that massive lysosomal release occurs selectively in cancer cells. These enzymes are activated and potentiated by a btrung acidic milieu. There is evidence, additionally, that tumor acidification is enhanced by hyperthermia, which somehow further impairs the cancer cells' ability to utilize oxygen (and thus must rely ever more heavily on the energy-making process that produces lactic acid as an end-product). Hyperthermia, then, contributes to acidification, and acidification, when intense, makes cancer cells selectively vulnerable to lysosomal destruction. (The enzymes are not activated in presence of less acidic, normal cells.)

So, now it can be seen, all that needs to be done is to find some way to break open the lysosomes in the cancer cells, once the tumor has been hyperthermically primed and acidified. All it takes is a few lysosomes to get the chain-reaction started, and von Ardenne and his colleagues have found a number of ways of triggering this unique explosion. Bursts of local hyperthermia and very strong acidity will, themselves, labilize, break open, some of the lysosomes, releasing their enzymes and freeing them to attack acidified neighbor cells. With the ever-escalating intracellular release of activated cytotoxic lysosomal enzymes, the chain reaction builds, eventually engulfing the entire tumor mass, provided it has been thoroughly acidified. (The greater the acidity the greater the chances of wiping out the whole thing.) Other very effective triggering devices include small bursts of X-radiation and large doses of vitamin A.

To reiterate: once released, the first lysosomal enzymes, highly potentiated by the acidity and heat, kill the cells in which they originated and then attack neighbor cells. The lysosomal organelles in the neighbor cells are ruptured by the enzymes in the process and their own enzymes are released and, in turn, begin attacking other cells. The process expands, involving more and more of the tumor until there are no more cells left to attack. This is von Ardenne's lysosomal cytolytic chain reaction. Once the "explosion" is over, the Germans "mop up" with a combination of therapies, which may include more immunostimulating whole-body hyperthermia and the BCG vaccine, also a general immunostimulant. (BCG is Bacillus Calmette-Guerin, a living, but attenuated, strain of the bacterium that causes tuberculosis in cattle. It has been observed that TB victims have an unusually low incidence of cancer. The theory, borne out to some extent in animal and clinical testing, is that BCG is a "non-specific" immunological substance that stimulates the body to respond to a wide variety of foreign antigens, including cancer antigens. It is now attracting considerable attention around the world, as an anti-cancer substance.)

Preliminary von Ardenne Results

Concerning the early results of von Ardenne's work, McCarty has reported:

In vivo (living animal) trials of therapeutic strategies designed to achieve tumor-specific lysosomal enzyme release and activation have been conducted by the Forschungs-Institute Manfred von Ardenne in Dresden. Various combinations of a single 1000 rad [triggering] dose of radiation, a whole-body hyperthermy of several hours duration, and hyperglycemic tumor acidification, were tried on rat DS carcinosarcoma. Any of these modalities alone, or the combinations of radiation with hyperthermy or acidification with hyperthermy, produced no tumor regression or life prolongation as compared to controls. The combination of radiation with acidification produced slight but significant tumor regression in most animals. The concurrent use of all three modalities produced complete tumor regression in all animals with tumor mass less than five grams; comparable results were found with Ehrlich ascites carcinoma of the mouse.

And on preliminary human works, McCarty reports:

First results from clinical trials in East Germany involving mild 39 degree C. whole-body hyperthermia, simple hyperglycemic acidification, vitamin A injections and low triggering doses of radiation have been reported. Seven consecutive cases of inoperable cervical cancer were treated with one-fourth to one-third of the usual dose of radiation accompanied by hyperthermic acidification; complete tumor regression was achieved in all cases. A single dose or 500 rads reduced a 48 mm diameter breast tumor to 12 mm diameter; the lowest dose of radiation capable of inducing a comparable regression in mammary tumors at that clinic had been 6,000 rads. No significant toxicity from these methods was reported. Further trials will make use of additional local microwave hyperthermy of main tumor masses, a technique, which in itself is capable of inducing complete regression in many tumors. Supplementary techniques for enhancing hyperglycemic acidification, which might strongly enhance the therapeutic efficacy of these methods, have not yet been tried in humans.

The addition of local hyperthermy, McCarty indicates, will reduce even further the need for triggering X-radiation. And some new methods of enhancing tumor acidification worked out by von Ardenne, McCarty observes, have been so potent that complete tumor regressions have been achieved in some animal systems without adding hyperthermia, X-rays, vitamin A or any of the other modalities. In some of these tests, hyper-acidification alone completely obliterated tumor masses.

McCarty concludes one of his papers on von Ardenne with diplomatic understatement:

"Further research along these lines is urgently indicated. The optimization of tumor-specific lysosomal enzyme cytotoxicity by means of hyperthermic acidification techniques may prove to be the greatest advance in cancer therapy since the advent of chemotherapy."

And very likely, I will add, since before the advent of chemotherapy.

 

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