Conventional treatments: chemotherapy--a medical 'solution'.
However we are supporting patients from a totally different philosophy and practice--one that is health based and health promoting rather than disease based, so it can be critical to know what effects the medical treatments are having on our clients. If we know the mechanisms and effects of these treatments we have a better chance of supporting the bodily systems of the patient, thereby reducing the side effects of the treatment, improving the patient's quality of life and hopefully assisting in reducing the risk of a recurrence of their disease. There is certainly research to support this (Prasad 1999).
[FIGURE 1 OMITTED]
This paper has researched the mechanisms of how chemotherapy works, potentially providing clues for the practitioner to support the person's health through supportive programs. This paper has also gathered information into some of the newer research into cancer therapies, some of which comes out of a thinking more aligned with our philosophy.
Cancer is a disease where regulation of the cell cycle goes awry and normal cell growth and behavior is lost. This paper therefore focuses on the role various therapies have on the cell cycle as this can provide a basic molecular explanation for both medical treatments and (increasingly for) herbal/nutritional support.
The cell cycle is an ordered series of events culminating in cell growth and division into two daughter cells. Non dividing cells are not considered to be in the cell cycle. When a cell is in any phase of the cell cycle other than mitosis, it is in interphase.
Briefly a cell cannot divide unless two processes alternate: the doubling of its genome (DNA) in the S phase (synthesis phase) of the cell cycle; and the halving of that genome during mitosis (the M phase) when the nuclear chromosomes separate and cytoplasmic division occurs. The period between M and S is called G.sub.1] (Gap 1); that between S and M is [G.sub.2] (Gap 2). The cell cycle consists of: [G.sub.1] = growth and preparation of the chromosomes for replication and S = synthesis of DNA when DNA replication occurs, [G.sub.2] = preparation for M = mitosis.
Regulation of the cell cycle
How cell division (and thus tissue growth) is controlled is a very complex process. The following are some of the important features in regulation and places where errors can lead to cancer. The passage of a cell through the cell cycle is controlled by proteins in the cytoplasm, the cyclins and cyclin dependent kinase, and their levels rise and fall through different stages in the cell cycle. CDK (cyclin dependent kinase) adds phosphate to a protein and along with cyclins, are major control switches for the cell cycle causing the cell to move from [G.sub.1] to S or [G.sub.2] to M. MPF (maturation promoting factor) includes the CDK and cyclins that trigger progression through the cell cycle.
Restriction point--p53 is a protein that functions to block the cell cycle if the DNA is damaged. The levels of p53 are increased in damaged cells. The p53 protein senses DNA damage and can halt progression of the cell cycle in both [G.sub.1] and [G.sub.2]. allowing time for the repair of DNA. The p53 protein is a key player in apoptosis, forcing severely damaged (or not reparable) cells to commit suicide. For example p53 has the ability to evaluate the extent of damage to DNA, particularly for damage by radiation. At low levels of radiation, producing damage that can be repaired, p53 triggers arrest of the cell cycle until the damage is repaired. At high levels of radiation, producing severely damaged DNA, p53 triggers apoptosis (assuming there are adequate functioning levels of p53).
Damage to DNA is itself not a mutagenic event, but if not repaired this can be converted to a mutagenic event during the process of DNA replication. DNA synthesis itself is a tightly controlled highly coordinated process and delays in progression through S phase as a consequence of DNA damage, or insufficient availability of p53 proteins can result in chromosomal abnormalities or mutations and cancer development. Therefore p53 qualifies as a tumor suppressor gene. More than half of all human cancers harbour p53 mutations and/or have no functioning p53 protein.
Cell cycle checkpoints (Bertram 2001)
There are several cell cycle checkpoints in human (and mammalian) cells.
1. A cell will enter and leave the cell cycle many times, temporarily or permanently. It mainly exits the cycle at [G.sub.1] and enters a stage called Go (G zero). At this point it is often called "quiescent", a misnomer as it is in fact busy carrying out its functions in the organism e.g. secretion, conducting nerve impulses or attacking pathogens. Often Go cells are terminally differentiated and will never reenter the cell cycle but instead will carry out their function in the organism until they die.
For other cells Go can be followed by re-entry into the cell cycle. Most of the lymphocytes in human blood are in Go, however with proper stimulation such as an appropriate antigen, they can be stimulated to re-enter the cell cycle (at GI) and proceed on to new rounds of alternating S phases and mitosis. Go represents not simply the absence of signals for mitosis but an active repression of the genes needed for mitosis. Cancer cells cannot enter Go and are destined to repeat the cell cycle indefinitely.
2. Cells have devised further elaborate checkpoints to prevent premature entry into the division cycle. The next most significant checkpoint occurs in late [G.sub.1], approximately four hours prior to the cell's entry into S phase. At this point cells possess multiple mechanisms to prevent inappropriate passage from [G.sub.1] into S phase of the cell cycle where DNA synthesis occurs--usually involving the cyclins and CDKs. The most dangerous DNA mutations occur in cells damaged in late [G.sub.1] and early S phase, after the p53 restriction point, increasing the chance of proliferation in carcinogenesis.
3. There are also other cell cycle checkpoints which can be activated in [G.sub.2] or M phase of cell cycle in response to DNA damage.
Cancer cells, through alterations in the cell cycle, have significantly greater turnover rates than normal cells. They have gained the ability to become 'immortal' through various mechanisms including evading apoptosis and reactivating telomerase, thereby developing a greater ability to proliferate. In these processes the cancer ceils develop the ability for angiogenesis (grow or parasitise their own blood supply), and by being able to evade the inhibition of surrounding tissue and becoming undifferentiated, metastasise to both neighbouring areas as well as distant sites in the body.
According to Bertram (2001) there are five major pathways that must be either activated or inactivated in the genesis of a cancer cell.
1. Development of independence in growth stimulatory signals.
2. Development of a refractory state to growth inhibitory signals.
3. Development of resistance to programmed cell death, i.e. apoptosis.
4. Development of an infinite proliferative capacity, i.e. overcoming cellular senescence.
5. Development of angiogenic potential, i.e. the capacity to form new blood vessels and capillaries for its food supply.
Knowing these pathways gives us an understanding of the processes we attempt to normalise.
Principles of chemotherapy
Cancer cells prefer an environment that is mild to moderately oxidative as this increases their chance of survival and ability to proliferate and spread. During oxidative stress the excessive production of ROS results in lipid peroxidation. Because the rate of DNA synthesis and the rate of cell proliferation of both cancer cells and normal cells are inversely related to the degree of lipid peroxidation, mild oxidative stress prolongs the [G.sub.1] phase or may result in cells entering the [G.sub.0]phase.
In terms of the cell cycle, chemotherapy works by massively increasing the oxidative stress to the point where it damages the DNA of the cell (generally while the cell is dividing) and forces growth arrest. Different chemotherapeutic drugs can affect different processes of the cell cycle by blocking the synthesis of DNA precursors, damaging the integrity of DNA, interfering with DNA replication (separation of the two double helixes after replication) or the function of the mitotic spindle. If the severely damaged cell cannot repair itself, cell death will occur. This can generate necrosis (death of cells and tissue) rather than increasing apoptosis. Increasing apoptosis (cell suicide), often by increasing p53 activity, normalises the cell.
Chemotherapy resistance can occur if the cell repairs its DNA after the cytotoxic effects of the DNA damaging agents (instead of cell death), so combining drugs (a common practice) that have different actions at the cellular level may help reduce the risk of the cancer developing resistance. This is an increasing problem and one area where using antioxidants and herbal medicines can be very useful, e.g. Centella asiatica can increase the effectiveness of vincristine (Huang 2004). There is evidence to suggest that a variety of herbs such as Curcuma longa, Camellia sinensis and the berberine containing herbs, may help to reduce chemotherapy resistance when taken in conjunction with the drugs (Yarnell 2002).
There are over 50 different chemicals used as chemotherapy and more are being produced very year. Chemotherapy is big business.
Effectiveness and side effects
The therapeutic index of a drug reflects the difference between its efficacy (ability to destroy turnout cells) and its toxicity to normal cells.
Chemotherapy works best on cancers having a high proportion of rapidly dividing cells, such as leukemias and lymphomas, but it is less effective on cancers characterised by a low proportion of dividing cells, such as solid tumours found in the colon, rectum, lung and breast. In these turnouts chemotherapy is used in conjunction with either radiation and/or surgery.
As tumours generally consist of rapidly dividing cells, these will therefore be more sensitive to chemotherapeutic drugs than the slower dividing normal cells. However as normal cells also have varying speeds at which they divide, toxicities that occur with chemotherapeutic drugs also damage the faster dividing normal cells, such as those found in hair follicles, the bone marrow or the lining of the gastrointestinal tract.
Treatment can therefore lead to side effects such as alopecia (hair loss), myelosuppression (bone marrow suppression) and gastrointestinal symptoms such as nausea, vomiting and diarrhoea. To minimise the occurrence of excess toxic side effects (as well as reduce chemotherapeutic resistance), two or more chemotherapeutic agents are often used in combination.
Side effects: iatrogenesis and cardiotoxicity
Chemotherapeutic agents cause damage to DNA leaving the patient with an increased risk of iatrogenic cancers. Of most concern are alkylating agents, eg cyclophosphamide and antibiotics, eg doxorubicin, as these induce such significant free radical damage to the genome of the DNA that they greatly increase the risk of iatrogenesis. The risk is proportional to the cumulative dose and time, for example leukemias are more likely to develop after 8 years, solid tumours are more likely to develop 10 years post therapy with increasing incidence with time. Because of the time factor younger patients are at more risk (and therefore most susceptible to iatrogenesis). There is considered to be less risk with radiotherapy despite the higher levels of oxidative damage (depending on the dose), as the treatment is more localised.
A major problem with several chemotherapeutic agents is the greatly increased risk of cardiotoxicity, for example with anthracyclines (doxorubicin) and herceptin (a monoclonal antibody). Doxorubicin induced cardiotoxicity occurs because of severe depletion of mitochondrial CoQ10 resulting from the inhibition of CoQ10 biosynthesis by doxorubicin. CoQ10 depletion, which disrupts electron transport and mitochondrial respiratory bioenergetics, may ultimately lead to loss of mitochondrial integrity and necrosis of cardiac myocytes.
Categories of chemotherapy
The first drugs developed for the treatment of cancer in the 1940s were DNA damaging agents (nitrogen mustards). These developed from the mustard gas experiments during World War II.
Alkylating agents are highly reactive chemicals that introduce alkyl radicals into DNA, working on it directly to prevent the cell from reproducing. As a class of drugs these agents are not phase specific (i.e. they work in all phases of the cell cycle) but are most active in the resting phase of the cell cycle ([G.sub.0]). They are mainly active against chronic leukemias, non Hodgkin lymphoma, Hodgkin disease, multiple myeloma and lung, breast and ovarian cancers.
Alkylating agents are the mustard gas derivatives such as Cyclophosphamide, and alkylsulfonates such as Busulfan. Metal salts (commonly the platinum based drugs) are also alkylating (Carboplatin, Cisplatin and Oxaliplatin).
Nitrosoureas act in a similar way to alkylating agents as they interfere with enzymes that help repair DNA. Nitrosoureas are unique because, unlike most types of chemotherapy treatments, they can cross the blood brain barrier so are often used to treat brain tumours. They may also be used to treat non Hodgkin lymphomas, multiple myeloma and malignant melanoma. Examples of nitrosureas are Carmustine, Lomustine and Streptozocin.
Antimetabolites are substances that are chemically very similar to the building blocks of DNA and RNA--purine and pyrimidine. By masquerading as these substances, antimetabolites inhibit DNA synthesis by being built into the DNA and disrupting the code. When incorporated into the cellular metabolism the cells are unable to divide. Antimetabolites are cell cycle specific and work during the S phase of the cell cycle. They are mainly used to treat leukemias, tumours of the breast, ovary and gastrointestinal tract.
Antimetabolites are classified according to the substances with which they interfere and include the folic acid antagonist Methotrexate, pyrimidine antagonists such as 5-Fluorouracil (5-FU), and purine antagonists such as 6-Mercaptopurine.
Antitumour antibiotics are chemotherapeutics made from products produced by a species of the soil fungus Streptomyces. These drugs act during multiple phases of the cell cycle but can also be considered cell cycle specific as they can interfere with the specific enzymes involved in DNA replication. There are several types of antitumour antibiotics which are widely used for a variety of cancers, however a major concern is the effect they can have on heart muscle, e.g. doxorubicin induces acute cardiotoxicity.
Commonly prescribed anthracyclines are Doxorubicin and Epirubicin. Other antibiotics such as chromomycins (Dactinomycin and Plicamycin) and a miscellaneous group Mitomycin and Bleomycin are also used.
Topoisomerase I or II inhibitors
Topoisomerases are a unique group of enzymes that untangle chromosomal DNA in the process of cell division, cut gaps in one strand of double stranded DNA, pass the other strand through the gap and subsequently reseal the break. Topoisomerase enzymes manipulate the structure of DNA necessary for replication and inhibit the cell cycle at [G.sub.1]. Inhibitors of the topoisomerase enzymes prevent the breaks formed from being resealed.
The inhibitors of these enzymes are used to treat certain leukemias and lung, ovarian, gastrointestinal and other cancers. Many of the antitumour antibiotics can work as topoisomerase inhibitors. Examples of topoisomerase I inhibitors are ironotecan and topotecan. Topoisomerase II inhibitors are Amsacrine and Etoposide.
Research suggests that both quercetin and genistein can inhibit topoisomerase H in cancer patients
There is increasing medical interest in developing cancer treatments from plants. Medical research has focused on the alkaloid components (when synthesised) as these lend themselves most effectively to pharmaceutical use (Cragg 2005). However from the perspective of a herbalist or naturopath, there are many useful components of plants that have the ability to improve human health, including flavonoids and antioxidants as well as the alkaloid components. Utilising the whole plant to improve the health of the patient may be a slower process but has far less (if any) side effects.
Plant alkaloid derivatives prevent cell division from occurring by inhibiting the synthesis of microtubules which function to separate chromosomes in cell division. Plant alkaloids are mitotic inhibitors as they can stop mitosis or inhibit enzymes for making proteins needed for reproduction of the cell. They are cell cycle specific and work mainly during the M phase of the cell cycle.
* The vinca alkaloids (vincristine, vinblastine) are derived from the periwinkle (Catharanthus rosea).
* The taxanes (paclitaxel and docetaxel) are derived from the bark of the Pacific yew tree (Taxus brevifolia).
* The podophyllotoxins (etoposide and tenisopide) are derived from the May apple plant (Podophyllum peltatum).
* Camptothecan analogs (irinotecan and topotecan) are derived from the Asian "happy tree" (Camptotheca acuminata).
* Podophyllotoxins and camptothecan analogs are also effective as Topoisomerase inhibitors.
The vinca alkaloids and taxanes are also known as antimicrotubule agents. During cell division microtubules provide the scaffold through which chromosomes are segregated into daughter cells and their integrity is critical for cell survival. Microtubules are also involved in processes such as membrane and intracellular scaffolding, transport secretion, cell adhesion and signalling.
There are different activities but generally these drugs stabilise the overall microtubule structure and resist the depolymerization that occurs during mitosis, so the cells remain frozen or arrested at this (M) phase of the cell cycle An example of an antimicrotubule drug is Estramustine.
Steroids are natural hormones and hormone like drugs that are useful in treating some types of cancer (lymphoma, leukemias and multiple myeloma) as well as other illnesses.
When these drugs are used specifically to kill cancer cells or slow their growth they are considered chemotherapy drugs. They are often combined with other types of chemotherapy drugs to increase their effectiveness (and to reduce inflammatory side effects of the treatment). Examples include prednisone and dexamethasone.
Hormones, or hormone like drugs, alter the action or production of female or male hormones. They have a different action from standard chemotherapy and slow the growth of breast, prostate and endometrial cancers which grow in response to abnormal hormone levels. Other cancers that may have estrogen receptors (and may therefore respond to hormonal therapy) are melanomas and some lung cancers.
Anti-estrogens such as Tamoxifen bind to estrogen receptor sites on cancer cells thus blocking estrogen from entering the cancer cell. This interferes with cell growth and eventually leads to cell death.
Anti-androgens such as Flutamide block the effects of testosterone. Cancer of the prostate depends on the male hormone testosterone (in its DHT form) for its growth. If the amount of DHT is reduced it is possible to slow down or shrink the cancer.
One of the problems with pharmaceutical anti-estrogens like Tamoxifen is that they also inhibit the production of the p53 tumour suppressor gene thus increasing the risk of cancer of the endometrium with long term use. Generally the drug is stopped after 5 years to prevent this.
Selective estrogen receptor modulators (SERMS)
SERMS act like estrogen in some organs and as an anti-estrogen in others. Raloxifene is an example that acts like estrogen to prevent bone loss and improve lipid profiles (decreases total and LDL cholesterol) but also has the potential to block some estrogen effects such as those that lead to breast cancer and uterine cancer. Despite the current debate about soy products, there is evidence that the isoflavone content can be protective in an otherwise healthy diet (Wang 2004). Research is also supporting the use of indoles (Hong 2002).
Natural hormone 'regulators' are soy or Kudzu (genistein, diadzein), cabbage, broccoli, brussels sprouts (indoles I3C or DIM and isothiocyanates), at the correct dose have few (if any) adverse side effects
Aromatase inhibitors block the enzyme aromatase (found in the body's muscle, skin, breast and fat), which is used to convert androgens produced by the adrenal gland into estrogen. In the absence of estrogen, tumours dependent on this hormone for growth will shrink. Examples of aromatase inhibitors are anastrazole, exemestane, letrozole.
Research shows safflower oil increases aromatase, omega 3 fatty acids decrease aromatase, showing that dietary fatty acids play a role in modifying steroid hormone action through modulating these steroid metabolising enzymes (Venkatrman 1996)
Some chemotherapy drugs act in slightly different ways and do not fit well into any of the other categories. Several useful types of chemotherapy drugs are unique. Examples of these are the enzymes asparaginase and pegaspargase; ribonucleotide reductase inhibitor hydroxyurea; retinoids bexarotene, isotretinoin and tretinoin.
Meta-analysis of Astragalus and chemotherapy (McCulloch 2006)
This paper reviewed a variety of studies:
* 34 randomised studies totalling 2,815 patients
* 12 studies reported reduced risk of death at 12 months
* 30 studies reported improved tumour response
* 2 studies reported reduced risk of death at 24 months
* 4 studies totalling 257 patients
The preparation of Panax ginseng, Astragalus membranaceous, Eleutherococcus Senticosus and Mylabirs cichoi stablised or improved patient performance. The study concluded
Astragalus based Chinese herbal medicines may increase effectiveness of platinum based chemotherapy when combined with chemotherapy
New research--targeted chemotherapies
Pharmaceutical companies today are spending millions of dollars to research chemotherapies and gene therapies that attack cancer cells more specifically. Research for the last 100 years has focused on killing rapidly dividing cells, but research today (such as targeted therapies) identifies other features of cancer cells. Scientists research specific differences in the cancer cells versus normal cells in an attempt to create a therapy that will target the cancer cells without damaging the normal cells, hopefully generating fewer side effects. Each type of targeted therapy works a little differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells.
Modern targeted therapy types include the use of monoclonal antibodies and anti-angiogenesis drugs. There is also research on signal transduction inhibitors, biologic response modifiers, proteasome inhibitors etc. Many attack cells with mutant versions of certain genes or cells that express too many copies of these genes.
Monoclonal antibodies are a new type of targeted cancer therapy. Normally the body creates antibodies in response to an antigen (a protein). The antibodies attach to the antigen in order to mark the antigen for destruction by the body's immune system.
Scientists are analysing specific antigens on the surface of cancer cells (target) to determine a protein that matches the antigen.
Using protein from animals and humans, a specific antibody is created that will attach to the target antigen allowing treatment to target specific cells, causing less toxicity to healthy cells. Monoclonal antibody therapy can be used only for cancers in which antigens (and the respective antibodies) have been identified. Converting these proteins (monoclonal antibodies) into effective drugs is a challenging new area of research.
The following are examples of monoclonal antibodies: alemtuzumab, gemtuzumab, ozogamicin, rituximab, trastuzumab (herceptin). One of these monoclonal antibodies has been in the news a lot lately, Herceptin, with conflicting reports of its efficacy in relation to its cost. Two articles that are well worth reading for more information on the debate are the editorial by Dent and Clemons (2005 BMJ 331:1202) and particularly Herceptin: more hype than hope (2006 WDDTY 17:5;6-9) which discusses the politics of the use of Herceptin and compares effectiveness with Iscador (an anthroposophical mistletoe compound).
Angiogenesis is the process by which new blood capillaries form by sprouting from an existing small vessel. Angiogenesis is important in tumour growth which is limited by its blood supply. If a tumour does not have a direct blood supply it must depend on the diffusion of nutrients from its surroundings and will have difficulty growing. It is essential for tumours to induce the formation of a capillary network so that nutrients can be supplied directly to the tumour. In this way tumour cells parasitise the blood vessels of normal cells
Inhibition of angiogenesis should therefore limit tumour growth and the search for anti-angiogenic drugs is an active area in cancer research. Two proteins, angiostatin and endostatin, have been shown to possess anti-angiogenic activity. A popular angiogenesis inhibitor is Thalidomide. There are various herbs and nutrients that may function as angiogenesis inhibitors (Yance 2006).
Natural anti-angiogenesis possibilities Cartilage derivatives--shark, bovine Glucosamine and chondroitin sulphate Plants--Allium sativum, Camellia sinensis, Isoflavones--genistein, diadzein, Grapeseed
Apoptosis, or programmed cell death, is the body's way of ridding itself of old or unnecessary cells (largely through p53 proteins). Normal cells undergo apoptosis regularly when the cells shrink and are absorbed by neighbouring cells (cell suicide). Research has shown that apoptosis is a fundamental property of all animal cells. Normally it occurs when the uterine lining is excreted during menstruation; apoptosis helps form fingers and toes in the foetus; tadpoles lose their tales in becoming frogs etc.
Unlike normal cells however, cancer cells do not undergo apoptosis but continue to grow unchecked. Drugs able to induce cell suicide, or proapoptotic compounds, would be a valuable addition to the arsenal of anticancer agents.
There are two possible ways that proapoptotic compounds induce cell death: by attacking the cell's main energy source, the mitochondria, or by destroying the cell's DNA. Researchers in Sweden have found that one of the most abundant proteins in human breast milk, a-lactalbumin, induces apoptosis in cancer cells (Mathiasen 1999).
Apoptosis including vitamin D research (Mathiasen 1999)
Natural substances that may induce apoptosis of abnormal cells include
* Allium sativum
* Curcuma longa--synergistic with genistein (soy, kudzu) and Camellia sinensis
* Isoflavones (soy, kudzu), Ganoderma lucidum (polysaccharides)
* Indoles, limonene, selenium and vitamin E,
* Vitamin D (sunshine)
Vitamin D induces apoptosis but not through p53, caspases or death receptors, so has potential use in therapies where the turnout is resistant to apoptosis inducing agents by mutations in p53 genes or death receptors.
Biologic Response Modifiers (BRMs) including colony-stimulating factors and tumour vaccines
Immunotherapies are treatments that mobilise the body's immune system to fight cancer. They are designed to stimulate the immune system. Biologic response modifiers are able to trigger the immune system to indirectly affect tumours by increasing cytokines such as interferons and interleukins. The treatment involves giving large amounts of these substances by injection or infusion in the hope of stimulating the cells of the immune system to act more effectively.
Natural immunotherapies include
* Allium family--garlic, onions
* Hyperthermia, sodium butyrate and interferon
* Polysaccharides (mushroom, Aloes etc)
* Lycium and Astragalus (polysaccharides) which increase interferon.
Colony stimulating factors
Cancer treatments such as chemotherapy and radiation therapy can affect the bone marrow cells which put a person at greater risk of developing infections, anaemia and bleeding problems. Colony stimulating factors are substances that stimulate the production of blood cells and promote their function. They do not directly affect tumours.
Colony stimulating factors are cytokines and are general mediators of the inflammatory response. They can act on target cells in either additive, synergistic, suppressive or a cascade fashion. The main cytokines produced are 1L-l, IL-6, TNF-[alpha]. Cytokines act on organs, tissues and cells in an endocrine, paracrine or autocrine fashion with systemic or local effects, i.e. hormonal type effects. Cytokines play a key role as communication signals during both normal immunological responses and in pathological conditions. They are regulators of infectious, inflammatory or neoplastic conditions.
Side effects of immunotherapies
Like other forms of cancer treatment, immunotherapies can cause a number of side effects. These can vary widely from patient to patient. Biologic response modifiers may cause flu like symptoms including fever, chills, nausea and appetite loss. Rashes or swelling may develop at the site where they are injected. Blood pressure may also be affected usually decreasing it. Fatigue is another common side effect of biologic response modifiers.
Side effects of colony stimulating factors may include bone pain, fatigue, fever and appetite loss
Researchers are developing vaccines that may encourage the patient's immune system to recognise (and destroy) cancer cells. These vaccines are currently used after someone has developed cancer and can be made in various ways, from cells extracted from the tumour, and from dendritic cells (from the patient).
IL-2 (interleukin-2) is often injected as it enhances T-cell immune response in cancer patients and therefore enhances the effectiveness of the vaccine. The vaccines could be given to prevent the cancer from returning or to get the body to reject tumours (Nelson 2004).
A research article showed that vaccination produced from the patient's dendritic cells induced a Th1 cytokine profile and increased T cell proliferation in men with prostate cancer thus evidencing an antitumour effect (Fong 2001).
Telomerase is an enzyme found in cells that allows them to keep growing indefinitely (it confers immortality on cells). Telomerase lies dormant in normal cells but is active in cancer cells. It functions to restore short sequences of DNA to the tips of the chromosomes. These short sequences, or telomeres, are required for DNA replication necessary for cell division and gradually shorten with multiple replications. Each time a cell divides its telomeres shorten. When telomeres get down to a minimum length the cell stops dividing and dies. By restoring the DNA, telomerase thus confers 'immortality' to the cell. The development of telomerase inhibitors (compounds that bind to telomerase and halt DNA replication and cell division) could be an effective treatment for cancer and could be used in conjunction with existing chemotherapies. High dose antioxidants (nutritional and herbal) may play a 'normalising' role here.
Chemotherapy protective agents Amifostine, Mesna, Dexrazoxane
Chemoprotective agents are drugs that are used with chemotherapy to minimise the side effects. Common chemoprotective agents include amifostine, dexrazoxane, and mesna. Amifostine helps reduce the level of renal injury in some cancer patients treated with chemotherapy. It was studied in WWII to protect soldiers against chemical warfare. Dexrazoxane use has resulted in a significant decrease in cardiac events in cancer patients undergoing certain chemotherapy treatments. Mesna is used to decrease bladder irritation (hemorrhagic cystitis) caused by specific high dose chemotherapy protocols. Note these drugs can also have significant side effects.
[FIGURE 2 OMITTED]
To return to our picture of the cell cycle, the following diagram shows where different chemotherapeutic drugs affect the cycle to trigger enough DNA damage to kill the (otherwise) potentially immortal cancer cells. A second picture shows where herbs and nutrients may also help.
Bertram J. 2001. The Molecular Biology of Cancer--Review Molecular Aspects Med 21; 147-223.
Cragg G et al. 2005. Plants as a source of anti-cancer agents J Ethnopharmacol 100;72-9.
Fong et al. 2001. Dendritic Cell-Based Xenoantigen Vaccination for Prostate Cancer Immunotherapy. J Immunol 167;7150-6.
Hong C et al. 2002.3,3'-Diindolylmethane (DIM) induces a G1 cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21 WAF1/CIP1 expression. Carcin 23;1297-1305.
Huang Y, Zhang S, Zhen R, Xu X, Zhen Y. 2004. Asiaticoside inducing apoptosis of tumor cells and enhancing anti-tumor activity of vincristine. Ai Zheng 12:1599-604.
McCulloch Met al. 2006. Astragalus-Based Chinese Herbs and Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Meta-Analysis of Randomized Trials. J Clin Oncol 24;3: 419-30.
Mathiasen I et al. 1999. Apoptosis Induced by Vitamin D compounds in Breast cancer cells is inhibited by Bel-2 but does not involve known caspases or p53. Cancer Res 59;4848-56.
[FIGURE 3 OMITTED]
Nelson B. 2004. IL-2, Regulatory T ceils & Tolerance J Immunol 172;3983-8.
Prasad KN, Kumar A, Kochupillai V, Cole WC. 1999. High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J Am Coil Nutr 18:13-25.
Venkatraman Jet al. 1996. Effect of dietary lipids on activities of hepatic steroid metabolising enzymes (5[alpha]reductase & aromatase) and composition of microsomes. Nut Res 16:10;1749-59.
Wang Xu et al. 2004. Soya food intake and risk of endometrial cancer among Chinese women in Shanhai: population based case-control study. BMJ Accessed 10 May.
Yance DR, Sagar SM. 2006. Targeting Angiogenesis with Integrative Cancer Therapies. Integ Cancer Ther 5:1;929.
Yarnell E et al. 2002. Can Botanicals Reduce Multidrug resistance in Cancer. Alt & Comp Ther 336-40.
Dr Karen E Bridgman MAppSci MSc(Hons) PhD ND DBM DipHom
Dr Karen Bridgman has been renowned in the field of natural therapies for the last 25 years. Coming from a nuclear medicine background (15 years), Karen has been working clinically as a Naturopath for over 20 years, for the last 14 years in a holistic medical practice (Gordon, Sydney) and a private pathology laboratory (Sydney). Academically she lectures at the University of Sydney in the Masters of Herbal Medicine. She is in demand as a speaker at conferences on many aspects of nutrition and herbs. Karen is currently the Vice President of the Natural Health Care Alliance and was on the Health Claims & Consumer Protection Advisory Committee for the NSW Department of Health. She is also on the National Scientific Advisory Committee for the Australian Centre for Complementary Medicine Education and Research and is currently studying for a Master's Higher Education.
|Printer friendly Cite/link Email Feedback|
|Author:||Bridgman, Karen E.|
|Publication:||Australian Journal of Medical Herbalism|
|Date:||Mar 22, 2007|
|Previous Article:||An insight into the Italian herbal system.|
|Next Article:||Ethical and professional issues in the practice of complementary medicine in retail pharmacies.|