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Cancer Adjuvant Therapy

Women with polymorphisms (genetic variations) of the vitamin D receptor gene may be less able to benefit from the nutrient. There is some evidence that vitamin D receptor gene polymorphisms play a role in the breast cancer (Bretherton-Watt et al. 2001); however, recent studies do not support this evidence (Buyru et al. 2003).
Identifying the at-risk groups, through the assessment of genetic variations in the vitamin D receptor, appears to be a forthcoming tool for planning intervention strategies.

Human leukemia cells cultured in the presence of vitamin D exhibited a reduced rate of tumor growth when injected into mice. Cells grown in vitamin D3 failed to form detectable tumors in 11 of 12 inoculated mice (Wang et al. 1997). The anticarcinogenic properties of vitamin D, confronts multiple stages of cancer development, including apoptosis, differentiation, angiogenesis, and metastasis, as well as regulating the cell growth cycle (van den Bemd et al. 2002).

Since vitamin D can cause calcium to be released from bones (a condition referred to as hypercalcemia), large doses of vitamin D cannot be used in patients whose medical history or genetics puts them at increased risk. Using a combination of Vitamin D3 and vanadium (a metallic element) enables vitamin D to retain its anticancer activity and vanadium addresses the problem of hypercalcemia (Basak et al. 2000).

Rats were supplemented with vanadium or vitamin D3 or both vanadium and D3 four weeks prior to induced liver cancer and continued thereafter until the 20th week. After 20 weeks of supplementation, the vitamin D3-vanadium combination had significantly reduced the number and size of abnormal hepatic nodules. The combination also showed an additive effect, reducing the number and size of hyperplastic nodes from 83.3% to 37.5%. In addition, vanadium effectively blocked the entry of calcium into cells.

A modified form of vitamin D (referred to as a deltanoid) delays the onset and reduces the number of skin cancers in laboratory mice. The microscopically altered structure of vitamin D produced a potentially effective cancer therapeutic. The vitamin D analog retains its anticancer profile but diminishes the threat of hypercalcemia. The most effective of four analogs tested was a doubly modified hybrid compound containing fluorine (Posner 2000).

During one study, mice painted with a chemical substance, inducing cancerous tumors were concurrently the animals were given the deltanoid. After 20 weeks, the fluorine-containing analog had reduced the incidence of tumors more than 28%, while the actual number fell 63% (Kensler et al. 2000). Deltanoids are in the early stages of development and, unfortunately, it may take 10 years before they become available (Guyton et al 2003). It is possible that deltanoids could lessen the need for hormone treatments or aggressive chemotherapy. Patients could theoretically stay on the treatment for the remainder of their life to keep the cancer from advancing.

Studies indicate that moderate or severe hypovitaminosis D was present in 66% of patients taking daily vitamin D in amounts less than the recommended dosage for their age. Adults may need a minimum of 5 times the 200-IU RDA, (or 1000 IU daily), to protect against cancer (Vieth 1999). Therapeutic dosages of vitamin D typically range from 800-4000 IU a day. Monthly kidney function blood tests (creatine, BUN, etc.) should be performed if daily vitamin D intake exceeds 1400 IU. These tests are included in most standard blood chemistry tests that cancer patients regularly perform to guard against anemia and overt immunosuppression.

Food sources of vitamin D include egg yolks, organ meats, fortified dairy products, butter, cod liver oil, and cold-water fish, such as salmon, herring, and mackerel. Vitamin D enhancers are vitamins A and C, calcium, magnesium, phosphorus, and choline. Antagonists are mineral oil, phenobarbital, and laxatives.

Vitamin E--is an antioxidant that can protect smokers, reduces radiation damage, potentiates chemotherapy, and inhibits many types of cancers
The inhibitory role of vitamin E in the growth of a number of human tumor cells, as well as its defensive functions in overcoming treatment-induced toxicity have been examined. The impact of vitamin E (perhaps acting through its antioxidant strengths) is significant, as evidenced by the following studies:

• After examining 29,000 male smokers in Finland, researchers found that high blood levels of alpha-tocopherol reduced the incidence of lung cancer by approximately 19%. The relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development (Woodson et al. 1999).
• A combination of vitamin E and pentoxifylline (PTX), a drug that inhibits abnormal platelet aggregation, allowing more blood to reach irradiated areas, resulted in a 50% regression of superficial radiation-induced fibrosis (the proliferation of fibrous connective tissue) in half of the patients studied (Gottlober et al. 1996; Delanian 1998). A suggested dosage is 800 mg a day of PTX and 1000 IU per day of vitamin E.
• An anti-melanoma effect obtained from vitamin E succinate in vivo has been reported (Malafa et al. 2002).
• Gamma-tocopherol inhibits COX-2 activity, demonstrating anti-inflammatory properties (Jiang et al. 2001; Life Extension Magazine 2002).
• The use of vitamin E, in combination with vitamins A and C, led to a four-fold reduction in p53 mutations (Brotzman et al. 1999). This is an extremely important finding because p53 mutations indicate a more malignant, aggressive form of cancer.
• Men with a high intake of vitamin E are 65% less likely to develop colorectal adenomas (precursors to colon cancer) compared to men with low vitamin E intake (Tseng et al. 1996).
• Lower morbidity and mortality from prostate cancer in men taking 50 mg of synthetic alpha-tocopherol daily. Subsequent testing determined gamma-tocopherol to be superior, however, to alpha-tocopherol in terms of tumor cell inhibition (Moyad et al. 1999). Men in the highest fifth of the distribution for gamma-tocopherol had a five-fold reduction in the risk of developing prostate cancer compared to those in the lowest fifth. In addition, statistically significant protection from high levels of selenium and alpha-tocopherol occurred only when gamma-tocopherol concentrations were also high (Helzlsourer et al. 2000).
• Vitamin E's mode of efficacy in regard to prostate protection: Vitamin E interferes with two proteins (the receptor for testosterone and prostate-specific antigen [PSA]). The fewer androgen receptors there are on a prostate cancer cell, the less capable the remaining receptors are of turning on genes that stimulate prostate cancer growth and progression. PSA serves as a good marker molecule for androgen receptor activity (Mercola 2002b).
• Tocotrienols, quite similar to a tocopherol (but for the addition of an unsaturated tail in its chemical structure), accumulate in adipose tissues, including mammary glands. If a cell becomes diseased, the tocotrienol is prepared for action, ready to inhibit growth and regulate aberrant cellular activity at onset. Curiously, the more cancerous the cell, the more susceptible it is to tocotrienols. Scientists apparently have been focusing upon the wrong form of vitamin E (the tocopherols), which show little protection against breast cancer. Tocotrienols appear to inhibit proliferation of human breast cancer cells by as much as 50% (Nesaretnam et al. 1998). Results suggest that tocotrienols are effective inhibitors of both estrogen receptor-negative and estrogen receptor-positive cells and that combination with tamoxifen should be considered as a possible improvement in breast cancer therapy. This strategy could significantly reduce the amount of tamoxifen required to affect the cancer (Guthrie et al. 1997).
• Cortisol (associated with poorer survival) and IL-6 (a negative marker for various cancers) were significantly lower in laboratory animals that received alpha-tocopherol before a cortisol-IL-6 challenge (Webel et al. 1998).

A suggested vitamin E dosage is from 400-1200 IU a day of alpha-tocopherol together with gamma E tocopherol. For optimal results, use 80% alpha-tocopherol and 20% gamma-tocopherol. A tocotrienol dosage is 240 mg each day. Good food sources of vitamin E are cold-pressed vegetable oils, wheat germ, eggs, dark green vegetables, nuts, brown rice, and butter.

Vitamin K--is a growth regulator, promotes apoptosis, and decreases pro-inflammatory cytokines
A novel form of vitamin K that appears extremely promising in the treatment of primary liver cancer, a type notoriously resistant to chemotherapy has been discovered by scientists at the University of Pittsburgh Cancer Institute (UPCI). The research published in the Journal of Biological Chemistry described an innovative approach to treat, and possibly prevent, cancer by triggering apoptosis (Ni et al.1998).

The UPCI team found that a vitamin K analog, Compound 5 (CPD5), causes an imbalance in the normal activity of enzymes that controls the addition or removal of small molecules (phosphate groups) from proteins inside cells. Specifically, CPD5 blocks the activity of enzymes (protein-tyrosine phosphatases) that normally remove phosphate groups from selected proteins inside liver cancer cells. CPD5, however, does not interfere with another group of enzymes called protein tyrosine-kinases, which add phosphate groups to the same proteins. The result is an excess of tyrosine-phosphorylated proteins, which triggers a variety of activities within cells, including the shutting down and subsequent death of the cell.

It may be possible to remove some individuals from liver transplant waiting lists if CPD5 is as effective in humans as it is experimentally. However, the vitamin K compound is not limited to killing liver cancer; in tissue culture the compound was also effective against melanoma and breast cancers. Although the new vitamin K is not in clinical testing at this time, clients and physicians may contact the UPCI's Cancer Information and Referral Service at (800) 237-4PCI (4724) or (412) 624-1115 for periodic updates regarding the treatment. Inquirers can also visit the university's website at http://www.upci.upmc.edu.

Vitamin K compounds inhibited IL-6 production by lipopolysaccharide-stimulated fibroblasts, which are recognized as rich sources of cytokines (Reddi et al. 1995). This finding has significant anticancer implications because over-expression of IL-6 is intricately involved in the inflammatory process, bone resorption, the activation of telomerase, and cancer proliferation. A suggested vitamin K dosage is 10 mg a day. Interesting research relating to the use of vitamin K concurrent with anticoagulant therapy (not usually a recommended practice) appears in the protocol Cardiovascular Disease: Comprehensive Analysis in the section dedicated to vitamin K.

OTHER FACTORS AFFECTING PATIENT OUTCOME

• What Should Cancer Patients Eat?
• Cholesterol

What Should Cancer Patients Eat?
For a cancer patient who appreciates the importance of a properly planned diet, the task is daunting. The diversity of the population minimizes the likelihood of a universal diet; nonetheless, most diets are hyped as being nutritionally correct for everyone. This section explores dietary variables, conceding that many generalities exist, that is, eat organic when available and eat on schedule to avoid blood glucose swings. Select foods characterized by color and texture. Avoid synthetic and refined foods: white flour products and sugar as well as trans fats (those fats altered by overheating, hydrogenation, and refining). Avoiding well-done meats and exposure to heterocyclic amines (formed during high temperature cooking) eliminates another significant cancer source (Zheng et al. 1998).

Tumors are primarily obligate glucose metabolizers, meaning they require sugar for survival. Even though the brain normally uses high amounts of glucose, hepatomas (a tumor of the liver) and fibrosarcomas (a sarcoma that contains fibrous connective tissue) consume roughly as much glucose as the brain. Some Americans continuously satisfy cancer's appetite, ingesting as much as 295 pounds of sugar a year.

Nobel laureate Otto Warburg, Ph.D., discovered in 1955 that cancer cells use glucose for fuel. But glucose accomplishes another strategic maneuver that strongly favors the cancer: it immobilizes internal defenses, the actions of the immune system. A study involving 10 healthy human volunteers assessed fasting blood glucose levels and the phagocytic index of neutrophils, a type of white blood cell. Glucose, fructose, sucrose, honey, and orange juice all significantly decreased the capacity of neutrophils to engulf bacteria. A diet structured away from sugars deprives cancer of its energy and increases the reliability of the immune response.

Dr. Jeff Bland advises selecting foodstuffs low on the glycemic index to avoid gratifying the tumor's appetite. The glycemic index lists the relative speed at which different foods are digested and raise blood sugar levels. Each food is compared to the effect of the same amount of pure glucose on the body's blood sugar curve. Glucose itself has a glycemic index rating of 100. Foods that are broken down and raise blood glucose levels quickly have higher ratings. The closer to 100, the more the food resembles glucose. The lower the rating, the more gradually that food affects blood sugar levels.

Common foods have the following glycemic ratings: baked potatoes, 95; white bread, 95; mashed potatoes, 90; chocolate candy bar, 70; corn, 70; boiled potatoes, 70; bananas, 60; white pasta, 55; peas, 50; unsweetened fruit juice, 40; rye bread, 40; lentils, 30; soy, 15; green vegetables; and tomatoes, < 15.

Note: The glycemic index should not be relied upon without factoring in the glycemic load, which is the glycemic index of a food times its carbohydrate content in grams, a concept developed at Harvard School of Public Health in 1997. Carrots, for instance, have a high glycemic index, but a very low glycemic load. This means that carrots consumed in moderation usually do not present a problem. Refer to the Obesity protocol for complete information about the glycemic index load.

An admonition, based more on folk medicine than scientific certainty, to avoid the white foods (all sugar-containing foods, as well as rice, and white flour and flour-based products) appears to have validity when applied to the glycemic index. A diet structured principally around carbohydrates that promotes hyperglycemia (high blood sugar level) and hyperinsulinemia (high blood insulin level) provides an environment that feeds the fire of cancer. High blood insulin levels drive protein tyrosine kinase (leading to cell division) and high blood glucose metabolically feeds cancer cells. On the other hand, a diet centered on fiber-, vitamin-, and mineral-rich foods that cause no blood glucose rise or insulin rush is an excellent target for healthy eating.

The diseases such as obesity and diabetes mellitus (often characterized by hyperinsulinemia) are associated with an increased risk of endometrial, colorectal, and breast cancers. The mechanisms underlying insulin-mediated neoplasias appear to include enhanced DNA synthesis (with the resultant tumor cell growth), inhibited apoptosis, and an altered sex hormone milieu. The reduced insulin levels seen with physical activity, weight loss, and a high fiber diet may in fact account for the decreased cancer incidence observed in individuals who maintain normal glucose and insulin levels (Gupta et al. 2002). Comment: Reducing blood insulin levels may result in remarkable improvements in men with prostate disease, with a concurrent drop in PSA levels (Hsing et al 2001).

Unfortunately, glucose modulation is an under-utilized component of cancer treatment. Some aspects of traditional treatments actually contribute to higher blood levels of glucose. For example, consider hospital meals, often favoring sugar-based foodstuffs. In addition, if the patient is on an IV solution, the infusion is largely dextrose based, feeding the cancer and perpetuating its growth.

The American Cancer Society believes that 30% of all cancer is due to inadequate consumption of vegetables and fruits. About 91% of Americans fail to achieve target recommendations, that is, 5 vegetable servings a day or 2-3 pounds a week. Asians who consume from 15-20 servings of fruits and vegetables a day have a much lower incidence of some cancers.

Vegetables of the cruciferous family isolate the anticarcinogenic constituents of Brassica plants. Glucosinolates (appearing in cruciferous vegetables) can inhibit, retard, or even reverse experimental multistage carcinogenesis (Fimognari et al. 2002). As enzymatic processes hydrolyze glucosinolates, isothiocyanates are released, including sulphoraphane. Sulphoraphane wields a strong arm against cancer, promoting apoptosis, inducing Phase II detoxification enzymes, increasing p53 and participating in the regulatory mechanisms of the cell's growth cycle. Necrosis (localized death of diseased tissues) is typically observed after prolonged exposure to elevated doses of sulphoraphane.