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- <strong><strong>The Cancer Matrix</strong> </strong> It isn't hard to understand that
- in heart failure the heart is undergoing changes in a unitary way, with all parts of the organ
- affected, and that parallel changes are happening in the rest of the body, interacting with and contributing
- to the changes in the heart, so that heart failure is now considered to be a systemic disease. (Most doctors
- see the systemic nature of heart disease, at least to the extent of warning their patients to lower
- cholesterol and avoid thyroid hormone.) But if someone tells a cancer patient or an oncologist that cancer
- is a systemic disease, the thought will be flatly rejected as untrue. They have been taught that cancer is a
- disease of bad, mutated, cells, which have to be completely eradicated, and that the patient's general
- health is a separate issue.
- </p>
- <p>
- <span> The US government (NIH, CDC) provides a cancer curriculum to schools. For high school,
- grades 9-12, they explain that a series of gene mutations causes it. In grade school, the basic idea of
- the cancer curriculum is just to teach them to fear cancer and the sunlight which, according to the
- curriculum, seems to be a very important mutagen.</span>
- <span> The gene mutation theory of cancer is sustained by a broader mystique of "genetics" in
- our culture. Over 100 years ago, an ideology of chance and random changes in organisms was superimposed
- onto the theory of evolution. After 1944, when Avery, MacLeod and McCarty showed that strands of DNA
- carry hereditary information, the doctrine of random change took on a specific chemical meaning--changes
- in the sequence of bases in the DNA molecule. This made it easier to disregard the evidence of the
- inheritance of acquired changes, since chemical, even biochemical, reactions are usually interpreted
- statistically, with an assumption of randomness. If the changes in the DNA code are random, and not
- influenced by the organism's physiology and biochemistry, then the four nucleotides that make up DNA
- (abbreviated G, C, A, and T) should show a random composition, but in fact the ratio of GC pairs to AT
- pairs varies in different types of organism, and in mitochondrial DNA, the GC (guanine-cytosine) content
- corresponds closely to the rate of oxidative metabolism and longevity (Lehmann, et al.,
- 2008). </span>
- <span> The official (government and American Cancer Society) view of cancer is that a tumor
- consists of the descendants of a single mutated cell. A current "proof" of this is that in a given
- tumor, all of the X chromosomes which are active have the same genetic composition, while in the rest of
- the organism, the X chromosome which remains active is a matter of chance. That shows, they argue, that
- the tumor must have developed from a cell in which that chromosome was active, not from a group of
- cells. However, non-random inactivation of X chromosomes is now known to occur, and that it involves
- epigenetic imprinting processes, such as methylation (Falconer, et al., 1982; Heard, 2004). Mary Lyon,
- the person who discovered that females inactivate one of their X chromosomes, has recognized the
- complexity of the process (Lyon, 2004). In arguing against the idea that the development of cancer is an
- epigenetic process, the cancer-gene people have invoked a process that responds to epigenetic
- influences.</span>
- <span> The assumption of randomness, and the assertions of the cancer doctors who subscribe
- to the doctrine, have had terrible effects on biology and medicine. Following the doctrine, their
- treatments must concentrate on eliminating every single cell of the cancer clone. Since surgery can't
- eliminate defective cells that have entered the blood stream, radiation and chemical toxins are logical
- necessities. Since mutations are random events, the person's general health is of little importance to
- the oncologist. Typically, they will tell the patient that their diet doesn't matter, except that they
- should avoid antioxidants if they are going to have radiation therapy. </span>
- <span> For centuries, the definition of a malignant tumor has been that it's one which
- will return after it has been cut out. In recent years, the definition has been extended to those that
- return after the original tumor has been eliminated by radiation or chemotherapy. The idea of a "cancer
- stem cell," an especially tough type of cell from the mutated clone, has been invoked to explain the
- reason for the regrowth of a tumor in an area that was treated with intense radiation. However, it's now
- clear that normal cells are attracted to an irradiated area (Klopp, et al., 2007; Kidd, et al., 2009).
- The recognition of a "bystander effect," in which radiation (or other--Mothersill and Seymour, 2009)
- injury to one cell injures near-by cells by signals from the injured cell, has led to the recognition
- that ordinary stem cells or repair cells entering an area where a tumor has been destroyed will be
- modified by the residual damage of cells in the area. The ability to recruit normal cells into a damaged
- area, the "cancer field," the way normal organs do, shows that tumors can be thought of as organ-like
- structures, and that knowledge of the organizing principles of normal organs might improve our knowledge
- of tumors. The idea that cancer is primarily a problem of organization isn't new: Johannes Muller, in
- the 19th century, and J.W. Orr, and D.W. Smithers, in the 1940s and 1950s, and many others, have
- suggested that something outside of the individual cell could cause the
- disorganization. </span>
- <span> Once it is accepted that cancer is a systemic disease, and that a tumor, or the
- place in the body where a tumor has been removed, is something more than a collection of defective
- cells, very different therapeutic approaches can be considered. Looking at the events in a failing
- heart, we can see that the potential repair cells recruited by the stressed heart are diverted by the
- conditions that they encounter there, and either die or become connective tissue cells, secreting
- collagen, rather than becoming new muscle cells. </span>
- <span> Something that everyone knows about tumors is that they are harder than the normal
- tissues in which they appear--they can be identified as lumps. Like the failing heart, they become
- harder than normal, and like the failing heart, the hardening can proceed to calcification. There has
- been general recognition that inflammation has a role in both heart disease and cancer, but the fact
- that chronic inflammation leads to fibrosis, and that fibrosis often leads to calcification, is still
- usually considered not to be relevant to understanding and treating cancer. The tissue hardness that
- allows oncologists to diagnose cancer (Huang and Ingber, 2005) is ignored when choosing treatments,
- which isn't surprising, since treatments that destroy cancer cells increase the production of
- collagen.</span>
- <span> Aspirin is commonly recommended for preventing heart attacks, because it helps to
- prevent abnormal blood clots, but it has other effects that are beneficial in heart disease, for example
- reducing the generalized fibrosis of the heart that develops after a heart attack (Kalkman, et al.,
- 1995; Wu, et al., 2012). It also protects against fibrosis in other organs, by a variety of mechanisms,
- and this effect on the extracellular matrix seems to be one of ways in which it protects against cancer.
- DCA, dichloroacetate, the drug that has been in the news in recent years because it can stop cancer
- growth, by restoring the oxidation of glucose and stopping the aerobic production of lactic acid, has
- been found to reduce the fibrosis of a failing heart, by the same mechanism, restoring glucose
- oxidation. In general, substances that increase collagen production are promoters of cancer and
- contribute to the progression of heart failure, and other degenerative changes.</span>
- <span> The incidence of cancer increases exponentially with age, but when random mutations
- are seen as the cause of cancer, aging as an essential cause of cancer is disregarded. The total
- collagen content of the body increases with aging, and the stiffness of that collagen also increases.
- The total collagen content in cancer patients is higher than in people without cancer (Zimin, et al.,
- 2010). This suggests that the processes in the body that produce aging are acting more intensely in
- those who develop cancer. As the collagen accumulates in the extracellular matrix, the whole body
- becomes more favorable for the appearance of cancer. </span>
- <span> Plastic surgeons have promoted the idea of injecting collagen into tissues with the
- argument that they are "replacing collagen lost with aging," but in fact collagen accumulates with
- aging. It is the greater compactness and stiffness of collagen in old skin that produces noticeable
- changes such as wrinkling. The difference between calf skin leather, used for soft gloves and purses,
- and cow hide, used for shoe soles and boots, illustrates the changes that occur with aging. Supermarkets
- used to categorize chickens as fryers and stewers, or stewing hens. The difference was the age and
- toughness, very young chickens could be cooked quickly, old laying hens had accumulated more collagen,
- and especially the cross-linked hardened collagen, and required long cooking to reduce the toughness.
- Old beef animals are usually sold as cheaper stew meat or hamburger, because the age-hardened collagen
- can make a steak too rubbery to chew if it's quickly cooked. </span>
- <span> In a healthy young organism, tissue injuries are repaired by processes reminiscent
- of Metchnikov's experiment in which he put a thorn into a jelly fish, and found that wandering cells,
- phagocytes, converged on the foreign object, surrounding it. If they couldn't eat it, they caused it to
- be expelled. The importance of that experiment was that it showed that injured tissues emit signals that
- attract certain types of cell. The process of removing damaged tissues by phagocytosis guides the
- formation of new tissue, starting with the secretion of collagen, which guides the maturation of the new
- cells. </span>
- <span> Around the middle of the last century, Hans Selye experimented with the antiseptic
- implantation of a short piece of a narrow glass tube under the skin of rats. The irritation from the
- glass object caused a collagenous capsule to be formed around it, in the well known "foreign body
- reaction." He found that a filament of tissue formed in the center of the tube, connecting the two ends
- of the capsule. The isolated tissue of the filament quickly underwent the degenerative changes seen in
- aged connective tissues, but if he periodically removed the fluid around it, and allowed fresh lymph
- fluid to fill the capsule, the filament retained a youthful elasticity, even as the rat aged. Isolation
- from the organism caused age-like degeneration to develop rapidly. When the organism can't remove a
- foreign object, the collagenous capsule that encloses it has a high probability of forming a cancer.
- This "foreign body carcinogenesis" has been studied for many years. </span>
- <span> </span>
- <span> Foreign body carcinogenesis is closely related to chemical carcinogenesis, radiation
- carcinogenesis, and hormonal carcinogenesis. Chemical carcinogens such as methylcholanthrene are
- irritating when injected, and stimulate collagen production. Neither type of carcinogenesis is always
- effective, because this collagen reaction can be protective, by isolating the irritant toxin (Zhang, et
- al., 2013). Radiation stimulates the secretion of collagen, and causes cross-linking that makes it
- stiffer, and slows its removal, leading to its accumulation (Sassi, et al., 2001). Some types of
- cross-linking block the ability of macrophages to remove it, creating something like a diffuse foreign
- body reaction. Estrogen, for example in the process of causing breast cancer, causes increased collagen
- synthesis. This is widely recognized, in the association of "breast density" (a high collagen content)
- with the risk of cancer. Estrogen also causes the formation of the enzymes that cross-link and stiffen
- the collagen, lysyl oxidase and transglutaminase(Sanada, et al., 1978; Campisi, et al., 2008;
- Balestrieri, et al., 2012).</span>
- <span> Although ultraviolet and ionizing radiation can act directly on collagen, to stiffen
- it, the greatest effect of the radiation is probably by reaction with relatively unstable components of
- tissues, such as polyunsaturated fatty acids, which then react with the collagen, cross-linking it
- (Igarashi, et al., 1989). Even in the absence of radiation, a deficiency of vitamin E accelerates the
- spontaneous decomposition of the unsaturated fats, accelerating the aging of collagen (Sundholm and
- Visapää, 1978 ). Many observations suggest that all of the collagen-aging carcinogenic factors interact
- synergistically.</span>
- <span> When cells are placed on a glass slide coated with collagen, they move to parts of
- the collagen that have been cross-linked, and they move from slightly cross-linked collagen to stiffer,
- more thoroughly cross-linked areas (Vincent, et al., 2013). When they are on stiffer collagen, they pull
- themselves more tightly toward it, continuously expending energy in the process. The muscle-like
- contraction of the cell causes it to become more rigid (Huang and Ingber, 2005). The increased hardness
- of even small tumors makes it possible to identify lymph node metastases from a breast cancer by touch,
- without removing them (Miyaji, et al., 1997).</span>
- <span> The increased energy cost of this "isotonic contraction" of the cell filaments
- requires more energy to sustain, and will tend to create lactic acid, the way intense muscle contraction
- does, while consuming oxygen at a higher rate. The increased lactic acid and decreased oxygen
- availability stimulate the synthesis of more collagen, the growth of new blood vessels, expression of
- enzymes for increasing the stiffness of the collagen, and other processes associated with inflammation,
- aging, and cancer. Blocking even one of these processes, the lysyl oxidase cross-linking enzyme, can
- reduce the invasiveness of a cancer (Lee, et al., 2011). Some observations (Tan, et al., 2010) show that
- the circulating cells of metastatic cancer are more rigid than other cells, which would increase the
- likelihood that they will block capillaries, creating oxygen-deprived nests of collagen-secreting
- cells.</span>
- <span> One of the substances produced by stressed cells that's involved in tumor induction,
- growth, and metastasis (Tanaka, et al., 2003; Datta, et al., 2010; Was, et al., 2010) is the enzyme heme
- oxygenase, which breaks down the essential component of respiratory enzymes, heme, producing carbon
- monoxide as a product, which inhibits cell respiration, increasing reliance on the glycolysis which
- produces lactic acid. If metastatic cells continue to produce this enzyme, this is likely to contribute
- to reconstituting the "cancer field," with increased HIF, hypoxia inducible factor, and a variety of
- other regulatory agents, each of which has its protective functions elsewhere, but which in combination
- can worsen the tumor.</span>
- <span> Substances that inhibit inflammation are likely to also inhibit excessive collagen
- synthesis, serotonin secretion, and the formation of estrogen. Besides aspirin, some effective
- substances are apigenin and naringenin, found in oranges and guavas. These flavonoids also inhibit the
- formation of nitric oxide and prostaglandins, which are important for inflammation and carcinogenesis
- (Liang, et al., 1999). Increased CO2, which has a variety of anti-inflammatory effects, can decrease
- collagen formation and tissue collagen content significantly (Ryu, et al., 2010).</span>
- <span> Deprivation of glucose and oxygen, which can be the local result of a cellular
- environment of condensed, stiffened collagen and the cellular tension and activation produced in
- response, combined with systemic stress that causes free fatty acids to interfere with the oxidation of
- sugar, activates enzymes that can dissolve collagen (MMP-2 and MMP-9). These enzymes are involved in
- metastasis, allowing cells to escape from the condensed collagen, but although they are normally thought
- of as enzymes that act outside of cells, they can also enter the cell's nucleus, where they degrade the
- DNA, causing the mutations and chromosomal abnormalities that are so characteristic of cancer (Hill, et
- al., 2012). Like glucose deprivation, exposure to 2-deoxyglucose, often used in tumor imaging, promotes
- metastasis (Schlappack, et al., 1991).</span>
- <span> The fact that cancer cells are stressed and damaged, and accumulate DNA damage,
- means that in a typical tumor there is a high rate of cell death. The number of apoptotic
- (disintegrating) cells in a tumor corresponds to the aggressiveness of the tumor (Vakkala, et al, 1999).
- In the 1940s and 1950s, Polezhaev demonstrated that dying cells stimulate cell renewal, and this is true
- in young and healthy organs, as well as in tumors. </span>
- <span> In 36% of women who had had a breast removed, from 7 to 22 years previously,
- identifiable (by the same tests used to diagnose breast cancer) cancer cells could be found circulating
- in their blood stream (Meng, et al., 2004). Tissue biopsies would be able to find the sources of those
- circulating cells, nests of similar cells throughout the body, which were dying about as fast as they
- were replicating. In 1969, Harry Rubin described an autopsy study which found that everyone over the age
- of 50 had at least one diagnosable cancer in some tissue. "Occult microscopic cancers are exceedingly
- common in the general population and are held in a dormant state by a balance between cell proliferation
- and cell death and also an intact host immune surveillance"(Goldstein and Mascitelli, 2011). These
- authors observed that the stress of surgery stimulates tumor growth, by various mechanisms, and that
- surgery increases the risk of developing cancer in apparently cancer-free patients.</span>
- <span> In 1956, Hardin Jones wrote "If one has cancer and opts to do nothing at all, he
- will live longer and feel better than if he undergoes radiation, chemotherapy or surgery, other than
- when used in immediate life-threatening situations." In the 1990s, a group of cancer specialists were
- asked what they would do if they were diagnosed with prostate cancer, and most of them said they would
- do nothing. </span>
- <span> The radical mastectomy, which removed massive amounts of apparently normal tissue as
- well as the breast tumor, was practiced for hundreds of years, and was the standard treatment for breast
- cancer until the 1980s, after G.W. Crile, Jr., had publicized the evidence showing that simply removing
- the tumor lump itself didn't cause a higher mortality rate, and that the surgery produced much less
- disability. </span>
- <span> Although the lumpectomy was eventually accepted by the profession, the evidence that
- the long term survival rate was higher when the surgery was done during the luteal phase in
- premenopausal women has been generally ignored, because the cancer ideology maintains that the fate of
- the cancer is in the cells, rather than in the patient's hormone balance. </span>
- <span> Because of the continual indoctrination about the importance of "early diagnosis to
- increase the chance of a cure," and the widely publicized "cure rates," it's easy for doctors to rush
- people into treatment, before they have time to study the issue. Dean Burk, who was a collaborator of
- Otto Warburg's for many years, was quoted in regard to the claims of the American Cancer Society that
- "They lie like scoundrels."</span>
- <span> In the 1970s, I noticed that the definitions of the features of uterine cancer had
- been changed recently, including as "cancer" things that had previously been classified as merely
- abnormal or precancerous. Reading more about the grading of cancer, I saw that other cancers
- had been defined more inclusively since the 1940s. Things that had previously not been called cancer
- were now being counted among the cancers that were cured by the various treatments, so, necessarily, the
- rate of cure had increased. The true situation could be seen by the age-specific mortality rate for each
- type of cancer. During the period when the "cure rates" were increasing, the age-specific death rates
- had increased. I think that's the sort of thing that Dean Burk had in mind. </span>
- <span> Nearly all of the studies of "cure rates" are comparisons of one
- ideologically-based and lucrative treatment against another ideologically-based and more or less
- lucrative treatment. When the cure rate, for example for breast cancer surgery, varies with the amount
- of progesterone in the body, there is very little interest in investigating the processes involved,
- because lucrative products aren't involved.</span>
- <span> When abnormal "metastatic" cells circulate in the blood or lymph, most of them die
- spontaneously when they stick in a place that doesn't support their growth. Many of the nests of cells
- that have started to grow probably regress spontaneously when conditions in the body change. Even large,
- clearly diagnosed tumors occasionally regress spontaneously. Aging and sickness tend to support the
- vicious cycles that lead to the progressive deterioration of the collagenous matrix. Stress (even
- anxiety-induced hyperventilation) produces alkalosis, and alkalosis favors increased collagen synthesis,
- while lower pH inhibits it (Frick, et al., 1997). For example, within a minute or two of
- hyperventilating, platelets release serotonin, and serotonin is a major promoter of collagen synthesis
- and fibrosis. </span>
- <span> The vicious cycles that promote cancer can be interrupted to some extent simply by
- reducing exposure to things that promote stress and inflammation--endotoxin, polyunsaturated fats, amino
- acid imbalance, nutritional deficiencies, ionizing radiation, estrogens--and maintaining optimal levels
- of things that protect against those--carbon dioxide, vitamin E, progesterone, light, aspirin, sugars,
- and thyroid hormone, for example.</span>
- <span> </span>
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- </p>
-
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