Hunting for Genetic Mutations and Cancer
A little background:

1. What is a gene? A gene is an assembly line that produces a protein. A gene is made out of DNA.
2. What are proteins? Proteins are the major building blocks of cells.
3. What is a mutated gene? A mutated gene is a modified assembly line. A modification can take many forms, such as removing an essential part of the assembly line, replacing an important part with junk, etc. Very rarely a mutation is beneficial to the organism (X-Men, Evolution, Lance Armstrong?). In all other cases, a mutated gene is considered damaged DNA.

Current belief:

What is the cause of cancer? The word cause has two meanings. The first refers to the elements in the environment which impact our body, for instance, tobacco, x-ray radiation, asbestos, other chemicals, etc. These elements are usually called carcinogens. Today, hundreds of substances and mixtures are classified as carcinogens. The other meaning of the word cause refers to the internal element of the body which is the first to collapse under the attack of the carcinogens. Let us call this element our “Achilles heel.”

The current belief in medical research holds that most cancers are caused by exposure to carcinogens, and that carcinogens cause cancer by mutating genes. In other words, according to the current belief, the structural integrity of our genes is our Achilles heel, and therefore, the first internal element to collapse under the attack of the carcinogens. This belief is so ingrained that the National Human Genome Research Institute (NHGRI), an institute at the NIH, recently stated that “all cancers are based on genetic mutations in body cells.” Moreover, a search on PubMed, the search engine for scientific papers in life science, with the keywords “Mutation” AND “cancer” produced 86,490 papers and 12,238 reviews. Mutation hunting is also a big business. Look at the NIH budget allocated to discoveries of genetic mutations, the number of biotech companies chasing genetic mutations, the magnitude of the licensing agreements between biotech and pharmaceutical companies aimed to utilize newly discovered genetic mutations, and the number of stories in the media on genetic mutations and their so-called “link” to disease. However, this huge effort and billions of dollars has produced few discoveries and little benefits to the public. The reason for this limited success is simple. The cause of most cancers is not a genetic mutation. Our Achilles heel is not the structural integrity of our genes.

The story of the BRCA1 gene is a typical example of mutation hunting.

The Mystery of BRCA1
Genes, in general, produce proteins, which are the building blocks of cells. The concentration of proteins is tightly regulated. A mutated or physically altered gene produces an abnormal concentration of its protein, which may lead to disease. In 1994, Mark Skolnick, PhD, discovered the BRCA1 gene (BRCA1 is short for BReast CAncer 1). Following the discovery, scientists observed an abnormally low level of the BRCA1 protein in breast cancer tissues. The BRCA1 protein is a cell cycle suppressor, which means that the protein prevents cell replication. This observation created a lot of excitement. At the time, scientists believed that they were on the verge of finding the cause of breast cancer. The reasoning was that breast cancer patients must have a mutated BRCA1 gene, that is, a defected BRCA1 assembly line, which would explain the decreased production of the protein, and the excessive replication of breast cancer cells in tumors.

In the United States, 180,000 cases of breast cancer are diagnosed each year. However, the BRCA1 gene is mutated in less than 5% of these cases. In more than 95% of breast cancer patients the gene is not mutated, the assembly line is not defected.

So here is the mystery. If the gene is not mutated in the great majority of the breast cancer patients, why are the tumors showing low levels of the BRCA1 protein? Today, this is one of the biggest mysteries in cancer research.

The BRCA1 gene is not unique. Many normal (perfect shape, non-mutated) genes exhibit a mysterious abnormal (increased or decreased) production of proteins in cancer. Moreover, studies also report abnormal gene expression of normal genes in other diseases, such as atherosclerosis, obesity, osteoarthritis, type II diabetes, alopecia, type I diabetes, multiple sclerosis, asthma, lupus, thyroiditis, inflammatory bowel disease, rheumatoid arthritis, psoriasis, atopic dermatitis, and graft versus host disease.

According to Dr. Raxit J. Jariwalla in his European Journal of Cancer paper: (Jariwalla RJ. Microcompetition and the origin of cancer. Eur J Cancer. 2005 Jan;41(1):15-9): “The prevalent view of the nature of cancer holds that it is a complex genetic process resulting from the progressive accumulation of mutations in specific cellular genes, such as proto-oncogenes or tumor-suppressor genes, leading to perturbations in processes involving signal transduction, cell cycle regulation, and/or apoptosis. Genetic instability in tumors has been known for decades, however, the role of genomic instability in causing and promoting tumor growth remains controversial. Furthermore, although many studies report abnormal gene expression in cancer cells, often, no mutations or chemical modifications are observed around the locus of the dysregulated gene(s), suggesting that a genetic alteration is not the initiating event of cancer.”

So what is the cause of most cancers, and how do carcinogens cause cancer? You can find the answer to these questions at causeofcancer.org/

John S. Boyd, Ph.D.
The Center for the Biology of Chronic Disease (see cbcd.net/ cbcd.net/), and causeofcancer.org (see causeofcancer.org/ causeofcancer.org/), Rochester, NY

We are a 501(c)3 not-for-profit organization that specializes in researching the biology of chronic disease. By “the biology of chronic disease” we mean the original disruption that causes the disease, and the sequence of events that lead from the original disruption to the development of clinical symptoms. We hope that once the biology is clear, pharmaceutical and biotech companies will be able to formulate drugs that reverse the effects of the disruption, and therefore cure the disease, or even block the original disruption, and therefore prevent the disease from developing in healthy individuals.

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Tags: breast cancer, cancer patient, oncogenes

Colon cancer, although non-infectious, has been sometimes called the plague of our time due to the increasing number of lives it has ended or debilitated. Cancer is genetic; therefore, if your parents had it or your uncle had it, chances are you will have it too. If you can’t run from it, you will have to face it and fight. Your best weapons will be screening, early detection and possible prevention. Prevention is key for everyone whether or not they have a history of cancer. Plus, it is easy to do. Since the disease presents itself in the large intestines, which is part of the digestive system, the prevention is closely related to diet. One thing you should keep in mind is “Keep it Natural”.

Remember your mother saying “Eat your vegetables”? She was absolutely right. Eat your fruits too. What’s cooler is that they are color-coded so it is easy to follow. The red, yellow, orange and green fruits and vegetables are rich in Antioxidants. Some of these are oranges, strawberries, peppers and carrots. Cruciferous vegetables such as broccoli, cabbage and Brussels sprouts are also very rich in these natural cancer fighting chemicals. Generous amounts of unprocessed grains help a lot too. The “bad food” you would want to avoid as much as possible is saturated fat. The problem nowadays is that there are so many products on the market that contain saturated fat. Meat has saturated fat so eat only your recommended daily allowance. Many non-animal foods have high fat content such as your favorite cakes, pastries, ice cream and cookies. Make sure you read the food labels to see how much fat you’re getting. Food such as these increase your risk of colon cancer because when these fats are broken down by the digestive juices and bile, the by-products are known to cause neoplastic growths in the colon where they get dumped. Increasing fiber in your diet helps flush out these toxins and clean your colon.

It would surprise many but increasing your intake of calcium might help lower your risks of colon cancer. Calcium is one of the basic minerals in the body and is necessary for bone strength and the regulation of many chemical processes of the body. However, studies on animals have found that a lack of calcium has led to excessive cell growth in the colon. Although it is not clear if it would have the same effect on humans, calcium is still important in so many other ways that you should still get enough of it. All adults must have 1000mg of calcium per day. Women, especially during pregnancy and after menopause have a greater risk for osteoporosis and should have 1500mg of calcium per day. Adequate calcium can be given by drinking a quart of milk per day. If you can’t drink this much milk, try mixing it in your food or eat other dairy products such as cheese and yogurt. Also rich in calcium are seafood and shellfish and many green leafy vegetables. If still not enough, your physician may recommend calcium supplements for you.

Michael Russell
Your Independent guide to colon-cancer-guide.com/ Colon Cancer

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Tags: colon cancer, natural cancer

The aim of treatment in patients with cancer is either kill cancer cells or modify their growth. The selectivity of antitumour drugs is marginal at best. Many cancers are characterized by localized tumour masses but surgery or radiotherapy often fail to eradicate it which can become widespread.

Treatment for malignant diseases with drugs started after 1940 when nitrogen mustard was used. From then very rapid progress has been made in new drug discovery for cancer, new effective combination of drugs and pathobiology of the disease.

Drugs used to treat cancer inhibit cell proliferation by inhibiting certain mechanisms of cell proliferation. Therefore they are toxic to both tumour and other normal proliferating cells present in bone marrow, gastrointestinal epithelium and hair follicles. The malignant tumours have a higher proportion of cells undergoing division than in normal proliferating cells in the body. So, the selectivity of cytotoxic drugs occurs.

In addition to leukemias and lymphomas, drugs, are also used in conjunction with surgery, radiotherapy and immunotherapy in a combined approach for many solid tumours, like metastatic. The anticancer drugs are used with the aim of:

1. Cure or prologed remission: This is now possible in cancers like

Acute leukemias

Choriocarcinoma

Wilmis tumour

Hodgkin’s disease

Ewing’s sarcoma

and Mycosis fungoides

2. Palliation: In this gratifying results are obtained and life is prolonged. This is used in the following cases,

Breast cancer

Chronic lymphatic leukemia

Ovarian carcinoma

Chronic myeloid Leukemia

Prostatic carcinoma

Non Hodgkin lymphomas

Lung (small cell) cancer

Head and neck cancers

Many other malignant tumours are less sensitive to drugs - life may or not be prolonged by chemotherapy. Tumours that are largely refractory to presently available drugs are:

Colorectal carcinoma

Malignant melanomas

Carcinoma pancreas

Bronchogenic carcinoma (non small cell)

3. Adjuvant chemotherapy: Not all radiotherapy and surgery eradicate the cancer cells completely. So adjuvant chemotherapy is used to mop up any residual cancer cells. This is routinely employed now.

(c) 2006 by A.K. Dinesh kumar is a Pharmacist and writer of articles on health and drugs. Now anybody can take advantage of the comprehensive drug and disease information site pharma-encyclopedia.com pharma-encyclopedia.com

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Tags: breast cancer, chemotherapy, leukemia, lymphoma, melanoma

Various anticancer drugs are used nowadays to treat breast cancer.

Antimetabolites are drugs that act as “dummy” building blocks and are incorporated into the cells’ DNA. When cells get ready to divide, a defect occurs in the process and causes them to die. Examples of this class of drugs used for breast cancer treatment are 5 fluorouracfil (5-FU) and methotrexate. 5-FU is a “false” building block for nucleic acids that are part of the genetic structure in the nucleus of the cell. 5-FU is a fluoropyrimidine carbamate class of drug. A new fluoropyrimidine drug has recently been developed known as capecitabine (brand name: Xeloda). This drug can be administered orally and requires an intracellular enzyme to convert it to its active form. Breast cancer cells contain an abundant amount of this enzyme than normal cells, giving capecitabine a selective advantage in destroying cancer cells over normal cells. Capecitabine is presently going through testing process and is not used in the adjuvant setting at present but may be available in the future. The other drug, methotrexate acts by inhibiting an enzyme that is important in providing a building block for DNA. The vitamin folic acid can antagonize this drug action, so this vitamin should while a cancer patient is on methotrexate.

Alkylating agents affect cancer cells in the same manner as radiation. Cyclophosphamide (Cytoxan) is the most commonly used drug of this class. It is usually administered intravenously but can also be given orally on a daily basis. The intravenous form of the drug does not usually cause hair loss (alopecia), but the oral form may. This drug is very effective and is part of most regimens used for cancer adjuvant chemotherapy.

Antineoplastic antibiotics are different from antibiotics used to treat infection in the sense that they are potent inhibitors of DNA replication. The most commonly used drug of this class in breast cancer therapy is doxorubicin (Adriamycin). Adriamycin is extremely active with breast cancer. A related drug, known as metoxantrone (Novantrone) is less frequently. Mitomycin, another drug in this class, is active with breast cancer but is not usually used in adjuvant regimens.

Cisplatin is a heavy metal also used to kill cancer cells. Its efficacy as an anticancer agent was discovered in the late 1970s when scientists were trying to pass electrical currents though Petri dishes of bacterial colonies to determine if the electronic activity inhibited bacterial growth. Interestingly, the bacteria around the platinum electrode died instantly. From this discovery, it was found that platinum leaked into the tissue media and was responsible for killing the bacteria. This observation made way to further investigations that demonstrated that platinum as a potent inhibitor of cell division and an excellent anticancer agent. Most recently, it has been used in ovary and breast cancer treatment with similar results. It has good anticancer activity and can be used in high doses with moderate adverse events.

During cell division, the chromosome line up and migrate to opposite poles on the nucleus of the cell. The apparatus for this process is called the mitotic spindle. Certain drugs block this process in cell division and cause the inability of cells to migrate. Vincistine is an example of this drug, as is a new drug called vinorelbine.

Antimicrotubule agents are unique agents that originated from the Pacific yaw tree. Examples of this class are paclitaxel and docetaxel. They are very potent in killing cancer cells. In a span of a few years, these drugs went from discovery to rapid testing in several cancer types, including breast cancer. Because of their impressive ability to kill cancer cells and a relatively acceptable degree of toxicity to normal cells, they are now part of many regimens for women who have a significant risk of metastatic breast cancer.

Michael Russell
Your Independent guide to breast-cancer.treatment-and-guides.com/ Breast Cancer

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Tags: breast cancer, cancer patient, cancer treatment, chemotherapy