Timeline of Cancer 3000 BC - 1999 AD

3000 B.C. Signs of cancer: Signs of cancer are found on the bones of mummies from ancient Egypt and Peru dating back as far as 30000 BC. The Edwin Smith Papyrus, which is the oldest written description of cancer known to exist, describes eight cases of breast tumours or ulcers in Egypt that were treated with cauterization. However, the document also states that there is no treatmentfor cancer. The original document, written in 3000 BC, was acquired in 1862 by Edwin Smith at Luxor, Egypt.

400 B.C. Hippocrates: known today as the father of medicine, proposed the Humoral Theory of Medicine, which states that the body is composed of four fluids, or humors: blood, phlegm, yellow bile, and black bile. Any imbalance of these fluids was thought to cause disease. He attributed cancer to an excess of black bile. Hippocrates was the first to use the words "carcinos" and "carcinoma" to describe tumors, and hence the term "cancer" was coined. "Cancer" is derived from the Greek word "karkinos," or crab, which is thought to reference the appearance of blood vessels on tumors resembling a crab's claws reaching out. He believed that it was best to leave cancer alone because those who got treatment didn't survive as long.

168 B.C. Galen: a Roman physician, was also a believer in the Humoral Theory of Medicine. He believed cancer to be curable in early stages, and that advanced tumors should be operated upon either by cutting around the affected area or by cauterization. Galen thought that unhealthy diet and bad climate were directly connected to cancer.

657 A.D. Paul of Aegina: one of the most prominent Byzantine physicians wrote a seven volume Epitome of Medicine. In his opinion, cancer of the breast and uterus were the most common. In the sixth book of the Epitome, exclusively to do with surgery, he asserted that surgery on uterine cancer was useless. For breast cancer, he recommended removal as opposed to cauterization.

1190 Moses Maimonides: a prominent physician, scientist, and philosopher, wrote ten medical treatises. His fifth treatise contains surgical aphorisms, some of which pertain to his treatment of cancer. His treatment of large tumors, as he wrote, involves "excis[ing] the tumor and uproots the entire tumor and its surroundings up to the point of healthy tissue,

except if the tumor contains large vessels&[or] the tumor happens to be situated in close proximity to any major organ, excision is dangerous."

1713 Bernardino Ramazzini: noticed the virtual absence of cervical cancer among nuns, and the high incidence of breast cancer within the same population. He concluded that this difference must be due to their different lifestyle, namely their abstinence. This observation lead the way to discovering the importance of hormonal factors in cancer. His work is a very early example of an epidemiological study. He is also known as the 'father' of occupational health for authoring his most well-known work - De Morbis Artificum Diatriba (Diseases of Workers).

1750 John Hunter: was a supporter of Stahl and Hofman's lymph theory of cancer; cancer is composed of fermenting lymph of differing pH and density. He believed that cancers could be removed if they had not yet spread to nearby tissues.

1761 Giovanni Morgagni: began performing autopsies to relate illness to pathological findings,. This helped to set a foundation for the study of cancer. John Hill: was the first to recognize the dangers of tobacco use, published "Cautions against the Immoderate Use of Snuff."

1775 Percival Pott: showed that chimney sweeps had an occupation-related cancer risk. Soot that collected under their scrotum was associated with scrotal cancer. This discovery leads to additional studies which identified other occupational cancer risks. The identification of these risks allowed public health measures to be taken. 1779 First cancer hospital: founded in Reims, France. The hospital was moved away from the city due to a widespread fear at the time that cancer was contagious.

1829 Joseph Claude Anthelm Recamier: was the first to recognize cancer metastasis.

1838 Johannes Muller: a German pathologist, published ber den feineren Bau und die Formen der krankhaften Geschwlste (On the Nature and Structural Characteristics of Cancer, and of Those Morbid Growths Which May Be Confounded with It), which began to establish pathological histology as an independent branch of science. He demonstrated that cancer is made up of cells, although he thought that cancer cells arose from abnormal cells. He believed that cancer cells came from 'blastema' (the undifferentiated tissue from which it was believed that cells arose from) between normal tissues.

1863-1867 Virchow: a student of Muller'. He wrote several papers and a three volume work, Die krankhaften Geschwlste, on malignant tumors. He theorized that tumors were the result of chronic irritation and that cancer spread in a manner similar to liquid.

1878 Theodore Billroth: a German surgeon performed the first pyloric resection (surgical removal of all or part of the stomach) for carcinoma. He also was the first (in 1872) to perform an esophageal resection for carcinoma.

1889 Steven Paget: proposed his "seed and soil" theory of cancer. He analyzed over 1000 autopsy records of women who had breast cancer and found that the patterns of metastasis were not random. Thus, he proposed that tumor cells (the seeds) have a specific affinity for specific organs (the soil), and metastasis would only result if the seed and soil were compatible.

1890 William Stewart Halsted: who was the first Professor of Surgery at Johns Hopkins, Harvard, and Yale, performed the radical mastectomy (removal of the entire breast, the muscles in the front of the chest, and the lymphatic system of the breast) to treat breast cancer.

1895 Wilhelm Conrad Rontgen: discover Skin neoplasms (also known as "skin cancer") are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises. Skin cancer generally develops in the epidermis (the outermost layer of skin), so a tumor can usually be seen. This means that it is often possible to detect skin cancers at an early stage. Unlike many other cancers, including those originating in the lung, pancreas, and stomach, only a small minority of those affected will actually die of the disease,[1] though it can be disfiguring. Melanoma survival rates are poorer than for non-melanoma skin cancer, although when melanoma is diagnosed at an early stage, treatment is easier and more people survive. Skin cancer is the most commonly diagnosed type of cancer. Melanoma and non-melanoma skin cancers combined are more common than lung, breast, colorectal, and prostate cancer.[1] Melanoma is less common than both basal cell carcinoma and squamous cell carcinoma, but it is the most serious for example, in the UK there were over 11,700 new cases of melanoma in 2008, and over 2,000 deaths.It is the second most common cancer in young adults aged 1534 in the UK. Most cases are caused by over-exposure to UV rays from the sun or sunbeds. Non-melanoma skin cancers are the most common skin cancers. The majority of these are basal cell carcinomas. These are usually localized growths caused by excessive cumulative exposure to the sun and do not tend to spread.

ed X-rays, which made the detection of tumours in the body much easier and non-invasive. 1899 Tage Anton Ultimus Sjogren: was the first to successfully treat cancer with X-rays.

1910 Francis Peyton Rous: provided scientific backing to the Viral Theory of Cancer by injecting chickens with cell free liquids obtained from chicken sarcomas and observing the formation of sarcomas in the injected hens.

1914 Theodor Boveri: proposed the Somatic Mutation Theory of Cancer. He believed that cancer was caused by abnormal chromosomes.

1915 Cancer induced in lab animals: Cancer was induced in laboratory animals for the first time at Tokyo University, by applying coal tar onto the skin of rabbits, leading the way for current cancer research methods.

1926 Johannes Fibiger: The Nobel Prize was awarded to Johannes Andreas Grib Fibiger for his work that showed a type of worm (nematode) caused cancer in mice. His findings were unable to be replicated by other scientists and were later discredited.

1933 First successful pneumonectomy: (surgical removal of all or part of the lung) for carcinoma of the lung was performed by Evarts Ambrose Graham and Jacob Jesse Singer.

1939 Charles Brendon Huggins: discovered that hormones were necessary for the growth of certain cancers through his research on androgen levels and prostate cancer in dogs. This laid the groundwork for hormone therapy for certain cancers.

1946 Louis Goodman: who studied chemical warfare agents during WWII, discovered that nitrogen mustards could be used in the treatment of cancer. He published the first paper reporting the use of nitrogen mustards as the first chemotherapeutic agents against Hodgkin's Disease, lymphosarcoma, and leukemias.

1960 Howard Temin: proposed the DNA Provirus Hypothesis of cancer. This asserts that certain RNA viruses are capable of inserting their genetic material into the DNA of the host cells. These inactive proviruses can eventually be expressed and may contribute to the formation of cancer.

1976 Harold E. Varmus and J. Michael Bishop: discovered the first cellular oncogene, src. This is the same gene carried by the virus originally described by Peyton Rous.

1986 Stephen H. Friend et al.: isolated the first tumor suppressor gene, Rb (for retinoblastoma).This gene was also one of the first associated with an inherited (familial) form of cancer.

1995 First DNA microarray chip: was constructed and used to measure gene expression levels in plants. This technology has been advanced and is now used to study cancer in humans. Currently 'gene chips' are being investigated as tools in the development of individualized treatment plans.

1999 First successful creation of tumor cells: Human epithelial and fibroblast cells were transformed into tumor cells for the first time in a laboratory. This was accomplished by the co-expression of telomerase(hTERT), the simian virus 40 large-T oncoprotein, and an oncogenic allele of H-ras.
http://www.cancerquest.org/cancer-timeline-3000bc-present.html

What causes cancer?

Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer begins to form. Unlike regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal cells that grows out of control.

What are the symptoms of cancer?

Cancer symptoms are quite varied and depend on where the cancer is located, where it has spread, and how big the tumor is. Some cancers can be felt or seen through the skin - a lump on the breast or testicle can be an indicator of cancer in those locations. Skin cancer (melanoma) is often noted by a change in a wart or mole on the skin. Some oral cancers present white patches inside the mouth or white spots on the tongue. Other cancers have symptoms that are less physically apparent. Some brain tumors tend to present symptoms early in the disease as they affect important cognitive functions. Pancreas cancers are usually too small to cause symptoms until they cause pain by pushing against nearby nerves or interfere with liver function to cause a yellowing of the skin and eyes called jaundice. Symptoms also can be created as a tumor grows and pushes against organs and blood vessels. For example, colon cancers lead to symptoms such as constipation, diarrhea,

and changes in stool size. Bladder or prostate cancers cause changes in bladder function such as more frequent or infrequent urination. As cancer cells use the body's energy and interfere with normal hormone function, it is possible to present symptoms such as fever, fatigue, excessive sweating, anaemia, and unexplained weight loss. However, these symptoms are common in several other maladies as well. For example, coughing and hoarseness can point to lung or throat cancer as well as several other conditions. When cancer spreads, or metastasizes, additional symptoms can present themselves in the newly affected area. Swollen or enlarged lymph nodes are common and likely to be present early. If cancer spreads to the brain, patients may experience vertigo, headaches, or seizures. Spreading to the lungs may cause coughing and shortness of breath. In addition, the liver may become enlarged and cause jaundice and bones can become painful, brittle, and break easily. Symptoms of metastasis ultimately depend on the location to which the cancer has spread.

How is cancer classified?

There are five broad groups that are used to classify cancer.
1. Carcinomas are characterized by cells that cover internal and external parts of the body such as lung, breast, and colon cancer. 2. Sarcomas are characterized by cells that are located in bone, cartilage, fat, connective tissue, muscle, and other supportive tissues. 3. Lymphomas are cancers that begin in the lymph nodes and immune system tissues. 4. Leukemias are cancers that begin in the bone marrow and often accumulate in the bloodstream. 5. Adenomas are cancers that arise in the thyroid, the pituitary gland, the adrenal gland, and other glandular tissues.

Cancers are often referred to by terms that contain a prefix related to the cell type in which the cancer originated and a suffix such as -sarcoma, -carcinoma, or just -oma. Common prefixes include:

Adeno- = gland Chondro- = cartilage Erythro- = red blood cell Hemangio- = blood vessels Hepato- = liver Lipo- = fat Lympho- = white blood cell Melano- = pigment cell Myelo- = bone marrow Myo- = muscle Osteo- = bone Uro- = bladder Retino- = eye Neuro- = brain

How is cancer treated?

Cancer treatment depends on the type of cancer, the stage of the cancer (how much it has spread), age, health status, and additional personal characteristics. There is no single treatment for cancer, and patients often receive a combination of therapies and palliative care. Treatments usually fall into one of the following categories: surgery, radiation, chemotherapy, immunotherapy, hormone therapy, or gene therapy.

Surgery
Surgery is the oldest known treatment for cancer. If a cancer has not metastasized, it is possible to completely cure a patient by surgically removing the cancer from the body. This is often seen in the removal of the prostate or a breast or testicle. After the disease has spread, however, it is nearly impossible to remove all of the cancer cells. Surgery may also be instrumental in helping to control symptoms such as bowel obstruction or spinal cord compression.

Radiation

Radiation treatment, also known as radiotherapy, destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Early radiation treatments caused severe side-effects because the energy beams would damage normal, healthy tissue, but technologies have improved so that beams can be more accurately targeted. Radiotherapy is used as a standalone treatment to shrink a tumor or destroy cancer cells (including those associated with leukemia and lymphoma), and it is also used in combination with other cancer treatments.

Chemotherapy
Chemotherapy utilizes chemicals that interfere with the cell division process - damaging proteins or DNA - so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. It is a necessary treatment for some forms of leukemia and lymphoma.

Chemotherapy treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options.

Immunotherapy
Immunotherapy aims to get the body's immune system to fight the tumor. Local immunotherapy injects a treatment into an affected area, for example, to cause inflammation that causes a tumor to shrink. Systemic immunotherapy treats the whole body by administering an agent such as the protein interferon alpha that can shrink tumors. Immunotherapy can also be considered non-specific if it improves cancer-fighting abilities by stimulating the entire immune system, and it can be considered targeted if the treatment specifically tells the immune system to destroy cancer cells. These therapies are relatively young, but researchers have had success with treatments that introduce antibodies to the body that inhibit the growth of breast cancer cells. Bone marrow transplantation (hematopoetic stem cell transplantation) can also be considered immunotherapy because the donor's immune cells will often attack the tumor or cancer cells that are present in the host.

Hormone therapy
Several cancers have been linked to some types of hormones, most notably breast and prostate cancer. Hormone therapy is designed to alter hormone production in the body so that cancer cells stop growing or are killed completely. Breast cancer hormone therapies often focus on reducing estrogen levels (a common drug for this is tamoxifen) and prostate cancer hormone therapies often focus on reducing testosterone levels. In addition, some leukemia and lymphoma cases can be treated with the hormone cortisone.

Gene therapy
The goal of gene therapy is to replace damaged genes with ones that work to address a root cause of cancer: damage to DNA. For example, researchers are trying to replace the damaged gene that signals cells to stop dividing (the p53 gene) with a copy of a working gene. Other gene-based therapies focus on further damaging cancer cell DNA to the point where the cell commits suicide. Gene therapy is a very young field and has not yet resulted in any successful treatments.

How can cancer be prevented?

Cancers that are closely linked to certain behaviors are the easiest to prevent. For example, choosing not to smoke tobacco or drink alcohol significantly lower the risk of several types of cancer - most notably lung, throat, mouth, and liver cancer. Even if you are a current tobacco user, quitting can still greatly reduce your chances of getting cancer. Skin cancer can be prevented by staying in the shade, protecting yourself with a hat and shirt when in the sun, and using sunscreen. Diet is also an important part of cancer prevention since what we eat has been linked to the disease. Physicians recommend diets that are low in fat and rich in fresh fruits and vegetables and whole grains.

Certain vaccinations have been associated with the prevention of some cancers. For example, many women receive a vaccination for the human papillomavirus because of the virus's relationship with cervical cancer. Hepatitis B vaccines prevent the hepatitis B virus, which can cause liver cancer. Some cancer prevention is based on systematic screening in order to detect small irregularities or tumors as early as possible even if there are no clear symptoms present. Breast self-examination, mammograms, testicular self-examination, and Pap smears are common screening methods for various cancers. There are over 200 types of cancers; most can fit into the following categories according to the National Cancer Institute:

Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs

Sarcoma: Cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue Leukemia: Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood

Lymphoma and myeloma: Cancers that begin in the cells of the immune system

Hunting for Genetic Mutations and Cancer The current paradigm holds that the cause of most cancers is a genetic mutation. In fact, mutation hunting is big business. Just look at the NIH budget allocated to discoveries of genetic mutations1, 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 cancer is not a genetic mutation. 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 the protein is tightly regulated. A mutated 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, 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. 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 (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 paper published in the European Journal of Cancer (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 tumorsuppressor 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". The Discovery A virus is a collection of genes. To replicate, some viruses settle in the nucleus of the host cell and use the cell machinery to replicate. What is the effect of a viral gene on the production of cellular proteins? Think of a gene as an assembly line of a protein. Like all assembly lines, the gene has two parts, a conveyor (the gene coding section), and a control panel (the gene promoter/enhancer). Imagine a cellular shop that assembles a product called BRCA1. One of the many buttons on the control panel is called N-box. Pressing the button increases production. However, only a small number of operators (called transcription factors), those who pass a special certification (called the p300 test), have permission to press this button. What happens when a virus opens a shop across the street from the cellular shop (called latent

infection) to produce its viral products? The control panel in the viral shop also has an N-box button. To start production, the virus begins to hire away some of the certified operators. What is the effect of this "hiring away" on the number of available BRCA1 units? The number decreases. Moreover, the decrease becomes apparent even before the virus starts production (the "hiring away" is what creates the effect, not the viral proteins). The viral assembly line competes with the BRCA1 assembly line for the certified operators, and by hiring them away prevents the cellular shop from producing the optimum, or "healthy" number of BRCA1 units. The lower number of BRCA1 units leads to excessive cell replication and breast cancer. (See note 2 for a description of the same idea with more technical detail2. See also a description in a recent paper published in the European Journal of Cancer.) The infection with the latent virus causes abnormal production of other genes, and as a result, the development of other chronic diseases such as atherosclerosis, obesity, osteoarthritis, type II diabetes, alopecia (male pattern baldness), type I diabetes, multiple sclerosis, asthma, lupus, thyroiditis, inflammatory bowel disease, rheumatoid arthritis, psoriasis, atopic dermatitis, graft versus host disease, and other chronic diseases. This sequence of events easily explains why people who suffer from obesity are also more likely to suffer from diabetes, cancer, and heart disease, and why a recent large scale study found that a low-fat diet does not protect against breast cancer (see study 1 and related studies). It also explains another surprising observation that male pattern baldness is associated with heart disease and prostate cancer (see study 2 and study 3 on the surprising relation between male baldness and heart disease, and study 4 on the relation between male baldness and prostate cancer). In general, this sequence of events easily explains the numerous observations indicating a co-existence or co-morbidity of these chronic diseases. This discovery was first described by Dr. Hanan Polansky in his book, Microcompetition with Foreign DNA and the Origin of Chronic Disease, published by The Center for the Biology of Chronic Disease. In his European Journal of Cancer, Dr. Raxit J. Jariwalla reports an interesting observation on the microcompetition discovery: "The key point of the theory is that the competing DNA sequences do not bind each other but compete for binding to a limiting transcription complex. In the example cited, the viral DNA and BRCA1 do not bind each other but compete for binding to the limiting GABP*p300/cbp transcription complex. It is interesting that when explaining observations reported in the literature, biologist tend to rely on the traditional physicochemical philosophy which centers on binding/non-binding events, or physical contact between molecules. In contrast, microcompetition with foreign DNA, which in essence is a reallocation of a rare resource, seem to draw on economic rather than physicochemical principles." To summarize: the cause of cancer, and other chronic diseases, is not a genetic mutation, it is a reallocation of scarce genetic resources caused by the presence of latent viral DNA sequences (or other types of foreign DNA).

Reaction of the Scientific Community What is the scientific community saying about Dr. Polansky's discovery? Consider what the famous heart surgeon and "Living Legend," Michael E. DeBakey, said about the discovery, "The theory underlying the basic concept concerning the origin of chronic diseases presented by Dr. Polansky is most interesting, indeed fascinating Perhaps a symposium could be held to provide a forum for further discussions and critiques of this fascinating theory." Elena N. Naumova, PhD, Associate Professor, Department of Family Medicine and Community Health, Tufts University School of Medicine, said, "Dr. Polansky's work compellingly demonstrates a framework that could bring together researchers from different fields. His proposed theory will work its magic by clarifying ambiguous definitions, identifying similarities and differences in various biological processes, and discovering new pathways I believe that Dr. Polansky's book will catalyze the scientific learning process, promote interdisciplinary crossfertilization, stimulate development of treatment strategies and drug discovery, and leave the reader inspired." Sivasubramanian Baskar, PhD, Senior Scientist from the National Cancer Institute, NIH, said, "At first, I wish to congratulate Dr. Hanan Polansky for his scientific bravery to take such a unique, novel approach to further stimulate our understanding of the origin and establishment of chronic diseases. The philosophy underscored is an excellent one ... The amazing correlation between theoretical predictions and observed in vivo effects seems to bring us a step closer to a deeper understanding of such complex biologic processes." Marc Pouliot, PhD, Assistant Professor, Department of Anatomy and Physiology, Faculty of Medicine, Universit Laval, Canada, said, "The concept of microcompetition will change our approach in the study of chronic diseases and will furthermore give scientists a higher level of understanding in biology. Presentation of this concept undoubtedly provides a new set of opportunities for attacking chronic diseases They lead the way to new approaches in chronic disease treatment." Howard A. Young, PhD, Section Head, Cellular and Molecular Immunology Section, Laboratory of Experimental Immunology, National Cancer Institute, NIH, said, "In summary, Dr. Polansky is to be applauded for his attempt to provide a unifying basis for chronic diseases. His theories are stimulating and offer a basis for experimental testing and possible treatment." Michael J. Gonzalez, PhD, Professor, Medical Sciences, University of Puerto Rico, said, "I know this book will profoundly impact medical research, drug discovery, as well as natural therapies. I also believe it will benefit the scientific community and society in general by providing further means of treatment for conditions in which only palliative care is available." You can find more reactions and the biographies the scientists reacting to Dr. Polansky's discovery on the publisher's website.

Hope for Cure and Protection The significance of Dr. Polansky's discovery cannot be overstated. For the first time, we can start to feel a little better about these diseases. With his discovery, pharmaceutical and biotech companies can now start to design medications that will target the cause of the disease rather than its symptoms, and therefore, cure the sick and protect the healthy from these deadly diseases. 1. See for instance, the statement "all cancers are based on genetic mutations in body cells" published in 2000 by the National Human Genome Research Institute (NHGRI), an institute at the NIH. In 2005, the NHGRI spent more than $492 million on research, directed towards research based on this misconception. 2. The transcription factor GA Binding Protein, or GABP (also called Nuclear Respiratory Factor 2 (NRF-2), E4 Transcription factor 1 (E4TF1) and Enhancer Factor 1A (EF-1A)) binds the promoter and enhancers of many cellular genes, including BRCA1. The N-box, the DNA box which binds GABP, is the core binding sequence of many viral enhancers, such as Cytomegalovirus (CMV) (IE-1 enhancer/promoter region), Epstein-Barr virus (EBV) (20 copies of the N-box in the +7421/+8042 oriP/enhancer), Herpes Simplex Virus 1 (HSV-1) (in the promoter of the immediate early gene ICP4), the polyomavirus enhancer area 3 (PEA3), adenovirus E1A enhancer, Rous Sarcoma Virus (RSV) enhancer, Moloney Murine Leukemia Virus (Mo-MuLV) enhancer, Human Immunodeficiency Virus (HIV) (the two NF-kB binding motifs in the HIV LTR), and Human T-cell lymphotropic virus (HTLV). GABP binds the p300/cbp co-activator. Since p300/cbp is limiting, the transcription complex GABPp300/cbp is also limiting. Consider a persistent latent infection with a virus that binds GABPp300/cbp. BRCA1 binds GABPp300/cbp. Binding of GABPp300/cbp transactivates the gene and increases the concentration of the BRCA1 protein in the cell. GABPp300/cbp is limiting. By binding GABPp300/cbp, the virus decreases availability of the complex to the BRCA1 promoter, which decreases binding of GABPp300/cbp to the promoter. The result is a decrease in BRCA1 transcription.

SKIN CANCER:

Skin neoplasms (also known as "skin cancer") are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises. Skin cancer generally develops in the epidermis (the outermost layer of skin), so a tumor can usually be seen. This means that it is often possible to detect skin cancers at an early stage. Unlike many other cancers, including those originating in the lung, pancreas, and stomach, only a small minority of those affected will actually die of the disease,[1] though it can be disfiguring. Melanoma survival rates are poorer than for non-melanoma skin cancer, although when melanoma is diagnosed at an early stage, treatment is easier and more people survive.[2] Skin cancer is the most commonly diagnosed type of cancer. Melanoma and nonmelanoma skin cancers combined are more common than lung, breast, colorectal, and prostate cancer.[1] Melanoma is less common than both basal cell carcinoma and squamous cell carcinoma, but it is the most serious for example, in the UK there were over 11,700 new cases of melanoma in 2008, and over 2,000 deaths.[3] It is the second most common cancer in young adults aged 1534 in the UK.[4] Most cases are

caused by over-exposure to UV rays from the sun or sunbeds.[5] Non-melanoma skin cancers are the most common skin cancers. The majority of these are basal cell carcinomas. These are usually localized growths caused by excessive cumulative exposure to the sun and do not tend to spread.

Classification
There are three main types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma.
Cancer Description Illustration

Note the pearly translucency to fleshy color, tiny blood Basal cell vessels on the surface, and sometime ulceration which can carcinoma be characteristics. The key term is translucency.

Commonly presents as a red, crusted, or scaly patch or Squamous cell bump. Often a very rapid growing tumor, pain is a common carcinoma characteristic.

Malignant melanoma

The common appearance is an asymmetrical area, with an irregular border, color variation, and often greater than 6 mm diameter.[6]

Basal cell carcinomas are present on sun-exposed areas of the skin, especially the face. They rarely metastasize and rarely cause death. They are easily treated with surgery or radiation. Squamous cell carcinomas (SCC) are common, but much less common than basal cell cancers. They metastasize more frequently than BCCs. Even then, the metastasis rate is quite low, with the exception of SCCs of the lip, ear, and in immunosuppressed patients. Melanomas are the least frequent of the 3 common skin cancers. They frequently metastasize, and could potentially cause death once they spread.[citation needed] Less common skin cancers include: Dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi's sarcoma, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, Pagets's disease of the breast, atypical fibroxanthoma, leimyosarcoma, and angiosarcoma.

The BCC and the SCC often carry a UV-signature mutation indicating that these cancers are caused by UV-B radiation via the direct DNA damage. However the malignant melanoma is predominantly caused by UV-A radiation via the indirect DNA damage.[citation needed] The indirect DNA damage is caused by free radicals and reactive oxygen species. Research indicates that the absorption of three sunscreen ingredients into the skin, combined with a 60minute exposure to UV, leads to an increase of free radicals in the skin, if applied in too little quantities and too infrequently.[7] However, the researchers add that newer creams often do not contain these specific compounds, and that the combination of other ingredients tends to retain the compounds on the surface of the skin. They also add the frequent re-application reduces the risk of radical formation.

Signs and symptoms

There are a variety of different skin cancer symptoms. These include changes in the skin that do not heal, ulcering in the skin, discolored skin, and changes in existing moles, such as jagged edges to the mole and enlargement of the mole.
Basal cell carcinoma

Basal cell carcinoma usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders. Sometimes small blood vessels can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly and with proper treatment can be completely eliminated, often without scarring.
Squamous cell carcinoma

Squamous cell carcinoma is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma.
Melanoma

Most melanomas are brown to black looking lesions. Unfortunately, a few melanomas are pink, red or fleshy in color; these are called amelanotic melanomas. These tend to be more aggressive. Warning signs of malignant melanoma include change in the size, shape, color or elevation of a mole. Other signs are the appearance of a new mole during adulthood or new pain, itching, ulceration or bleeding. An often-used mnemonic is "ABCDE", where A= asymmetrical, B= "borders" (irregular= "Coast of Maine sign"), C= "color" (variegated), D= "diameter" (larger than 6 mmthe size of a pencil eraser) and E= "evolving."
Other

Merkel cell carcinomas are most often rapidly growing, non-tender red, purple or skin colored bumps that are not painful or itchy. They may be mistaken for a cyst or other type of cancer.

Causes
Ultraviolet radiation from sun exposure is the primary cause of skin cancer.Other factors that play a role include:

Smoking tobacco HPV infections increase the risk of squamous cell carcinoma. Some genetic syndromes including congenital melanocytic nevi syndrome which is characterized by the presence of nevi (birthmarks or moles) of varying size which are either present at birth, or appear within 6 months of birth. Nevi larger than 20 mm (3/4") in size are at higher risk for becoming cancerous. Chronic non-healing wounds. These are called Marjolin's ulcers based on their appearance, and can develop into squamous cell carcinoma. Ionizing radiation, environmental carcinogens, artificial UV radiation (e.g. tanning beds), aging, and light skin color.

Pathophysiology

Micrograph of melanoma. FNA specimen. Field stain.

Squamous cell carcinoma is a malignant epithelial tumor which originates in epidermis, squamous mucosa or areas of squamous metaplasia. Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders. Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis). In well differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus). Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre of the tumor masses. Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls". The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization.

Prevention
While sunscreen has been shown to protect against BCC and SCC it may not protect against malignant melanoma. When sunscreen penetrates into the skin it generates reactive

chemicals.The experimental and epidemiological evidence suggests that sunscreen use is correlated with malignant melanoma incidence.This gives rise to questions regarding the possibility that a sunscreen user's lifetime exposure to ultraviolet light may be higher than average. Alternatively, one might question whether sun screens are themselves tumor promoters or carcinogens. Arguably, sunscreen users are the ones most likely to be burned or have been burned by sun light. Similarly, most sunscreens primarily screen UVB, the primary cause of sunburn, while UVA is the primary cause of melanoma. Thus, by limiting the discomfort of sunburn, UVB screening may indirectly result in more UVA exposure. In any case, if some sunscreens promote skin cancer, physical light-scattering sunscreens based in zinc oxide, titanium dioxide or some other natural base are likely safer than chemical blockers such as benzones, etc., as they will be less chemically active. The risk of developing skin cancer can be reduced through a number of measures including:

Decreasing indoor tanning and mid day sun exposure and increasing the use of sunscreen Avoiding the use of tobacco products Reducing overexposure to ultraviolet (UV) radiation, especially in early years Wearing protective clothing (long sleeves and hats) when outdoors Broad-spectrum sunscreen that blocks both UVA and UVB radiation Reapplying sun block according to the manufacturer's directions

There is insufficient evidence to recommend for or against screening for skin cancer.Vitamins and antioxidants have not been found to have an effect in prevention.

Management
Treatment is dependent on type of cancer, location of the cancer, age of the patient, and whether the cancer is primary or a recurrence. Treatment is also determined by the specific type of cancer. For a small basal cell cancer in a young person, the treatment with the best cure rate (Mohs surgery or CCPDMA) might be indicated. In the case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal cell cancer of the nose might warrant radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal cell carcinoma or invasive squamous cell carcinoma.[citation needed]. In general, melanoma is poorly responsive to radiation or chemotherapy. For low-risk disease, radiation therapy (external beam radiotherapy or brachytherapy), topical chemotherapy (imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; both, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, topical chemotherapy, electrodesiccation and curettage can be found in the discussions of basal cell carcinoma and squamous cell carcinoma. Mohs' micrographic surgery (Mohs surgery) is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin is limited, such as the face. Cure rates are equivalent to wide excision. Special training is

required to perform this technique. An alternative method is CCPDMA and can be performed by a pathologist not familiar with Mohs surgery. In the case of disease that has spread (metastasized), further surgical procedures or chemotherapy may be required.
Reconstruction

Currently, surgical excision is the most common form of treatment for skin cancers. The goal of reconstructive surgery is restoration of normal appearance and function. The choice of technique in reconstruction is dictated by the size and location of the defect. Excision and reconstruction of facial skin cancers is generally more challenging due to presence of highly visible and functional anatomic structures in the face. When skin defects are small in size, most can be repaired with simple repair where skin edges are approximated and closed with sutures. This will result in a linear scar. If the repair is made along a natural skin fold or wrinkle line, the scar will be hardly visible. Larger defects may require repair with a skin graft, local skin flap, pedicle skin flap, or a micro vascular free flap. Skin grafts and local skin flaps are by far more common than the other listed choices. Skin grafting is patching of a defect with skin that is removed from another site in the body. The skin graft is sutured to the edges of the defect, and a bolster is placed atop the graft for seven to ten days, to immobilize the graft as it heals in place. There are two forms of skin grafting: split thickness and full thickness. In a split thickness skin graft, a shaver is used to shave a layer of skin from the abdomen or thigh. The donor site, regenerates skin and heals over a period of two weeks. In a full thickness skin graft, a segment of skin is totally removed and the donor site needs to be sutured closed. Split thickness grafts can be used to repair larger defects, but the grafts are inferior in their cosmetic appearance. Full thickness skin grafts are more acceptable cosmetically. However, full thickness grafts can only be used for small or moderate sized defects. Local skin flaps are a method of closing defects with tissue that closely matches the defect in color and quality. Skin from the periphery of the defect site is mobilized and repositioned to fill the deficit. Various forms of local flaps can be designed to minimize disruption to surrounding tissues and maximize cosmetic outcome of the reconstruction. Pedicled skin flaps are a method of transferring skin with an intact blood supply from a nearby region of the body. An example of such reconstruction is a pedicled forehead flap for repair of a large nasal skin defect. Once the flap develops a source of blood supply form its new bed, the vascular pedicle can be detached.

Prognosis
The mortality rate of basal cell and squamous cell carcinoma are around 0.3% causing 2000 deaths per year in the US. In comparison the mortality rate of melanoma is 15-20% and it causes 6500 deaths per year. Even though it is much less common, malignant melanoma is responsible for 75% of all skin cancer-related deaths.

[edit] Epidemiology

Age-standardized death from melanoma and other skin cancers per 100,000 inhabitants in 2004. no data <0.7 0.7-1.4 1.4-2.1 2.1-2.8 2.8-3.5 3.5-4.2 4.2-4.9 4.9-5.6 5.6-6.3 6.3-7 7-7.7 >7.7

A study of the incidence of non-melanoma skin cancer from 1992 to 2006 in the United States was performed by the dermatologist Howard Rogers, MD, PhD, and his colleagues based on the evaluation of Medicare databases. The results of their research showed that cases of non-melanoma skin cancer rose an average of 4.2% a year. More than 3.5 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. According to the Skin Cancer Foundation, one in five Americans will develop skin cancer at some point of their lives. The first most common form of skin cancer is basal cell carcinoma, followed by the squamous cell carcinoma. Although the incidence of many cancers in the United States is falling, the incidence of melanoma keeps growing, with approximately 68,729 melanomas diagnosed in 2004 according to reports of the National Cancer Institute. The survival rate for patients with melanoma depends upon when they start treatment. The cure rate is very high when melanoma is detected in early stages, when it can easily be removed surgically. The prognosis is less favorable if the melanoma has spread to other parts of the body. In the UK, 84,500 non-melanoma skin cancers were registered in 2007 although a study estimated that at least 100,000 cases are diagnosed each year. Most NMSCs were basal cell carcinomas or squamous cell carcinomas. In 2007, 10,672 cases of malignant melanoma were diagnosed. According to the British Association of Dermatologists children, from 0 to 14 years, and teenagers, from 15 to 19 years, exhibit the highest rates of skin cancers of any European

country. Furthermore, incidence of melanoma increased four times in UK teenagers from 1978 to 1997. Australia exhibits one of the highest rates of skin cancer incidence in the world, almost four times the rates registered in the United States, the UK and Canada. Around 434,000 people receive treatment for non-melanoma skin cancers and 10,300 are treated for melanoma. Melanoma is the common type of cancer in people between 1544 years in Australia.[33] This is largely due to the ozone hole located over East Australia, making prolonged unprotected outdoor sun exposure very dangerous.

TYPES OF CANCER: Anal Cancer Bladder Cancer Breast Cancer Cervical Cancer Colon Cancer Endometrial Cancer Esophageal Cancer Kidney Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Ovarian Cancer Pancreatic Cancer Penile Cancer Prostate Cancer Skin Cancer Stomach Cancer

FIRST DISCOVERY OF SKIN CANCER Skin cancer was first identified as a disease by the French physician, Ren Laennec who spoke to a conference in 1804. It is believed that the disease was named. Laennec findings were published in 1806. The first person has operated in a skin cancer lesion Scottish anatomist and surgeon John Hunter in 1787. Hunter did not know what it was, but said it appeared a "cancerous fungous excrescence" - translated to "cancerous fungus. Interestingly, this fabric is so well preserved, scientists were able to examine in 1968 and was confirmed as a melanoma. In 1840, Samuel Cooper reported that most of treating melanoma was during the late stage. This situation has remained more or less true today. How are diagnosed with skin cancer Once the suspicion of skin cancer has been raised, a biopsy is performed to confirm the diagnosis. In many cases, the patient who first notices changes in a mole or wart on the skin and brings it to your doctor or dermatologist to care. There are two types of incisional and excisional biopsies. The excisional biopsy removes the entire growth for its consideration. With incisional, the dermatologist is only part of the tissue to be examined for cancer cells. Treatment and Prevention of Skin Cancer While sun exposure is the major constraint in skin cancer prevention; it is difficult to limit exposure to the sun all at once. Use sunscreen with SPF 15 or higher is recommended to provide some level of protection. The use of hats and clothing limiting sun exposure is also good, especially if you are in when the sun is hotter. Between 10 AM and 3 PM are the hours when the sun is at its warmest and exposure should be limited wherever possible. The complete removal of the sunlight is not recommended as sunlight is the best source of vitamin D. It is best to reapply sunscreen every two hours as sweat will help reduce the cSkin Cancer Overview

Skin cancer is the most common of all human cancers. Some form of skin cancer is diagnosed in more than 1 million people in the United States each year. Cancer occurs when normal cells undergo a transformation during which they grow and multiply without normal controls.

As the cells multiply, they form a mass called a tumor. Tumors of the skin are often referred to as lesions. Tumors are cancerous only if they are malignant. This means that they encroach on and invade neighboring tissues because of their uncontrolled growth. Tumors may also travel to remote organs via the bloodstream or lymphatic system. This process of invading and spreading to other organs is called metastasis. Tumors overwhelm surrounding tissues by invading their space and taking the oxygen and nutrients they need to survive and function.

Skin cancers are of three major types: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

The vast majority of skin cancers are BCCs or SCCs. While malignant, these are unlikely to spread to other parts of the body. They may be locally disfiguring if not treated early. A small but significant number of skin cancers are malignant melanomas. Malignant melanoma is a highly aggressive cancer that tends to spread to other parts of the body. These cancers may be fatal if not treated early.

Like many cancers, skin cancers start as precancerous lesions. These precancerous lesions are changes in skin that are not cancer but could become cancer over time. Medical professionals often refer to these changes as dysplasia. Some specific dysplastic changes that occur in skin are as follows:

Actinic keratosis is a patch of red or brown, scaly, rough skin, which can develop into squamous cell carcinoma. A nevus is a mole, and dysplastic nevi are abnormal moles. These can develop into melanoma over time.

Moles (nevi) are simply growths on the skin. They are very common. Very few moles become cancer.

Most people have 10-40 moles on their body. Moles can be flat or raised; some begin as flat and become raised over time. The surface is usually smooth. Moles are round or oval and no larger than -inch across. Moles are usually pink, tan, brown, or the same color as the skin. Other colors are sometimes noted. An individual's moles usually look pretty much alike. A mole that looks different from the others should be examined by your health-care provider.

Dysplastic nevi are not cancer, but they can become cancer.

People with dysplastic nevi often have a lot of them, perhaps as many as 100 or more. People with many dysplastic nevi are more likely to develop melanoma, either within an existing nevus or on an area of normal skin. Dysplastic nevi are usually irregular in shape, with notched or fading borders. Dysplastic nevi may be flat or raised, and the surface may be smooth or rough ("pebbly"). Dysplastic nevi are often large, -inch across or even larger. Dysplastic nevi are typically of mixed color, including pink, red, tan, and brown.

Recent studies demonstrate that the number of skin cancer cases in the United States is growing at an alarming rate. Fortunately, increased awareness on the part of Americans and their health-care providers has resulted in earlier diagnosis and improved outcomes.

http://cancer-studies.blogspot.in/2009/08/when-was-skin-cancer-first-discovered.html

Skin Cancer Causes

Ultraviolet (UV) light exposure, most commonly from sunlight, is overwhelmingly the most frequent cause of skin cancer. Other important causes of skin cancer include the following:

Use of tanning booths Immunosuppression-impairment of the immune system, which protects the body from foreign entities, such as germs or substances that cause an allergic reaction. This may occur as a consequence of some diseases or can be due to medications prescribed to combat autoimmune diseases or prevent organ transplant rejection. Exposure to unusually high levels of x-rays Contact with certain chemicals-arsenic (miners, sheep shearers, and farmers), hydrocarbons in tar, oils, and soot (may cause squamous cell carcinoma)

The following people are at the greatest risk:

People with fair skin, especially types that freckle, sunburn easily, or become painful in the sun People with light (blond or red) hair and blue or green eyes Those with certain genetic disorders that deplete skin pigment such as albinism, xeroderma pigmentosum People who have already been treated for skin cancer People with numerous moles, unusual moles, or large moles that were present at birth People with close family members who have developed skin cancer People who had at least one severe sunburn early in life

Basal cell carcinomas and squamous cell carcinomas are more common in older people. Melanomas are more common in younger people. For example, melanoma is the most common cancer in people 25-29 years of age.

Images of skin cancer

MELANOMA: