JirotheHero

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-	[[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]]	+	[[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually looks like]] [[Image:JirotheHero.jpg|thumb|This is what JirotheHero actually 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Template:Otheruses Template:Infobox Disease Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). Cancer may affect people at all ages, but risk tends to increase with age. It is one of the principal causes of death in developed countries.

There are many types of cancer. Severity of symptoms depends on the site and character of the malignancy and whether there is metastasis. A definitive diagnosis usually requires the histologic examination of tissue by a pathologist. This tissue is obtained by biopsy or surgery. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for the type of cancer pathology. Drugs that target specific cancers already exist for several cancers. If untreated, cancers may eventually cause illness and death, though this is not always the case.

The unregulated growth that characterizes cancer is caused by damage to DNA, resulting in mutations to genes that encode for proteins controlling cell division. Many mutation events may be required to transform a normal cell into a malignant cell. These mutations can be caused by radiation, chemicals or physical agents that cause cancer, which are called carcinogens, or by certain viruses that can insert their DNA into the human genome. Mutations occur spontaneously, and may be passed down from one cell generation to the next as a result of mutations within germ lines. However, some carcinogens also appear to work through non-mutagenic pathways that affect the level of transcription of certain genes without causing genetic mutation.

Many forms of cancer are associated with exposure to environmental factors such as tobacco smoke, radiation, alcohol, and certain viruses. Some risk factors can be avoided or reduced.

History

Today, the Greek term carcinoma is the medical term for a malignant tumor derived from epithelial cells. It is Celsus who translated carcinos into the Latin cancer, also meaning crab. Galen used "oncos" to describe all tumours, the root for the modern word oncology.<ref name="Moss-Galen">Ralph W. Moss, Ph.D Galen on Cancer - How Ancient Physicians Viewed Malignant Disease 1989 Speech</ref>

Hippocrates described several kinds of cancers. He called benign tumours oncos, Greek for swelling, and malignant tumours carcinos, Greek for crab or crayfish. This name probably comes from the appearance of the cut surface of a solid malignant tumour, with a roundish hard center surrounded by pointy projections, vaguely resembling the shape of a crab (see photo). He later added the suffix -oma, Greek for swelling, giving the name carcinoma. Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. Treatment was based on the humor theory of four bodily fluids (black and yellow bile, blood, and phlegm). According to the patient's humor, treatment consisted of diet, blood-letting, and/or laxatives. Through the centuries it was discovered that cancer could occur anywhere in the body, but humor-theory based treatment remained popular until the 19th century with the discovery of cells.

Though treatment remained the same, in the 16th and 17th centuries it became more acceptable for doctors to dissect bodies to discover the cause of death. The German professor Wilhelm Fabry believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor Francois de la Boe Sylvius, a follower of Descartes, believed that all disease was the outcome of chemical processes, and that acidic lymph fluid was the cause of cancer. His contemporary Nicolaes Tulp believed that cancer was a poison that slowly spreads, and concluded that it was contagious.<ref name="Marilyn Yalom"> Marilyn Yalom "A history of the breast" 1997 Publisher: New York : Alfred A. Knopf ISBN 0-679-43459-3</ref>

With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("metastasis"). The use of surgery to treat cancer had poor results due to problems with hygiene. The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, asepsis improved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late 1800s felt that the rate of cure after surgery had been higher before asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor. During the same period, the idea that the body was made up of various tissues, that in turn were made up of millions of cells, laid rest the humor-theories about chemical imbalances in the body. The age of cellular pathology was born.

When Marie Curie and Pierre Curie discovered radiation at the end of the 19th century, they stumbled upon the first effective non-surgical cancer treatment. With radiation came also the first signs of multi-disciplinary approaches to cancer treatment. The surgeon was no longer operating in isolation, but worked together with hospital radiologists to help patients. The complications in communication this brought, along with the necessity of the patient's treatment in a hospital facility rather than at home, also created a parallel process of compiling patient data into hospital files, which in turn led to the first statistical patient studies.

Cancer patient treatment and studies were restricted to individual physicians' practices until World War II, when medical research centers discovered that there were large international differences in disease incidence. This insight drove national public health bodies to make it possible to compile health data across practises and hospitals, a process that many countries do today. The Japanese medical community observed that the bone marrow of bomb victims in Hiroshima and Nagasaki was completely destroyed. They concluded that diseased bone marrow could also be destroyed with radiation, and this led to the discovery of bone marrow transplants for leukemia. Since WWII, trends in cancer treatment are to improve on a micro-level the existing treatment methods, standardize them, and globalize them as a way to find cures through epidemiology and international partnerships.

Nomenclature and classification

The following closely related terms may be used to designate abnormal growths:

• Neoplasia and neoplasm are the scientific designations for cancerous diseases. This group contains a large number of different diseases. Neoplasms can be benign or malignant.
• Cancer is a widely used word that is usually understood as synonymous with malignant neoplasm. It is occasionally used instead of carcinoma, a sub-group of malignant neoplasms. Because of its overwhelming popularity relative to 'neoplasia', it is used frequently instead of 'neoplasia', even by scientists and physicians, especially when discussing neoplastic diseases as a group.
• Tumor in medical language simply means swelling or lump, either neoplastic, inflammatory or other. In common language, however, it is synonymous with 'neoplasm', either benign or malignant. This is inaccurate since some neoplasms usually do not form tumors, for example leukemia or carcinoma in situ.
• Paraneoplasia is a disturbance associated with a neoplasm but not related to the invasion of the primary or a secondary (metastatic) tumour. Disturbances can be hormonal, neurological, hematological, biochemical or otherwise clinical.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. The following general categories are usually accepted:

• Carcinoma: malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
• Lymphoma and Leukemia: malignant tumors derived from blood and bone marrow cells
• Sarcoma: malignant tumors derived from connective tissue, or mesenchymal cells
• Mesothelioma: tumors derived from the mesothelial cells lining the peritoneum and the pleura.
• Glioma: tumors derived from glia, the most common type of brain cell
• Germinoma: tumors derived from germ cells, normally found in the testicle and ovary
• Choriocarcinoma: malignant tumors derived from the placenta

Malignant tumors are usually named using the Latin or Greek root of the organ as a prefix and the above category name as the suffix. For instance, a malignant tumor of liver cells is called hepatocarcinoma; a malignant tumor of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumor is fibroid).

Adult cancers

In the USA and other developed countries, cancer is presently responsible for about 25% of all deaths.<ref name="CACancerJClin2005-Jemal"> Template:Cite journal</ref> On a yearly basis, 0.5% of the population is diagnosed with cancer.

The statistics below are for adults in the United States, and will vary substantially in other countries:

Male			Female
most common	cause of death<ref name="CACancerJClin2005-Jemal" />		most common	cause of death<ref name="CACancerJClin2005-Jemal" />
prostate cancer (33%)	lung cancer (31%)		breast cancer (32%)	lung cancer (27%)
lung cancer (13%)	prostate cancer (10%)		lung cancer (12%)	breast cancer (15%)
colorectal cancer (10%)	colorectal cancer (10%)		colorectal cancer (11%)	colorectal cancer (10%)
bladder cancer (7%)	pancreatic cancer (5%)		endometrial cancer (6%)	ovarian cancer (6%)
cutaneous melanoma (5%)	leukemia (4%)		non-Hodgkin lymphoma (4%)	pancreatic cancer (6%)

Childhood cancers

Cancer can also occur in young children and adolescents, but it is rare. Some studies have concluded that pediatric cancers, especially leukemia, are on an upward trend.<ref name="Haematologica2005-Dalmasso"> Template:Cite journal</ref><ref name="IntJCancer2005-Agha">Template:Cite journal</ref>

The age of peak incidence of cancer in children occurs during the first year of life. Leukemia (usually ALL) is the most common infant malignancy (30%), followed by the central nervous system cancers and neuroblastoma. The remainder consists of Wilms' tumor, lymphomas, rhabdomyosarcoma (arising from muscle), retinoblastoma, osteosarcoma and Ewing's sarcoma.<ref name="CACancerJClin2005-Jemal" />

Female and male infants have essentially the same overall cancer incidence rates, but white infants have substantially higher cancer rates than black infants for most cancer types. Relative survival for infants is very good for neuroblastoma, Wilms' tumor and retinoblastoma, and fairly good (80%) for leukemia, but not for most other types of cancer.

Causes and pathophysiology

Template:Main

Origins of cancer

Cell division or cell proliferation is a physiological process that occurs in almost all tissues and under many circumstances. Normally the balance between proliferation and programmed cell death is tightly regulated to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer disrupt these orderly processes.

The uncontrolled and often rapid proliferation of cells can lead to either a benign tumor or a malignant tumor (cancer). Benign tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they extrinsically compress vital structures. Malignant tumors can invade other organs, spread to distant locations (metastasize) and become life-threatening.

A few types of cancer in non-humans have been found to be contagious ("parasitic cancer"), such as Sticker's sarcoma, which affects dogs. The closest known analog to this in humans is individuals who have "caught cancer" from tumors hiding inside organ transplants.<ref>Template:Cite web</ref>

Molecular biology

Carcinogenesis, which means the initiation or generation of cancer, is the process of derangement of the rate of cell division due to damage to DNA. Cancer is, ultimately, a disease of genes. In order for cells to start dividing uncontrollably, genes which regulate cell growth must be damaged. Proto-oncogenes are genes which promote cell growth and mitosis, a process of cell division, and tumor suppressor genes discourage cell growth, or temporarily halt cell division in order to carry out DNA repair. Typically, a series of several mutations to these genes are required before a normal cell transforms into a cancer cell.

Proto-oncogenes promote cell growth through a variety of ways. Many can produce hormones, a "chemical messenger" between cells which encourage mitosis, the effect of which depends on the signal transduction of the receiving tissue or cells. Some are responsible for the signal transduction system and signal receptors in cells and tissues themselves, thus controlling the sensitivity to such hormones. They often produce mitogens, or are involved in transcription of DNA in protein synthesis, which creates the proteins and enzymes responsible for producing the products and biochemicals cells use and interact with.

Mutations in proto-oncogenes can modify their expression and function, increasing the amount or activity of the product protein. When this happens, they become oncogenes, and thus cells have a higher chance to divide excessively and uncontrollably. The chance of cancer cannot be reduced by removing proto-oncogenes from the genome as they are critical for growth, repair and homeostasis of the body. It is only when they become mutated that the signals for growth become excessive.

Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth. Generally tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Often DNA damage will cause the presence of free-floating genetic material as well as other signs, and will trigger enzymes and pathways which lead to the activation of tumor suppressor genes. The functions of such genes is to arrest the progression of cell cycle in order to carry out DNA repair, preventing mutations from being passed on to daughter cells. Canonical tumor suppressors include the p53 protein, which is a transcription factor activated by many cellular stressors including hypoxia and ultraviolet radiation damage.

Despite nearly half of all cancers possibly involving alterations in p53, its tumor suppressor function is poorly understood. It is clear it has two functions: one a nuclear role as a transcription factor, and the other a cytoplasmic role in cell cycle and division regulation and apoptosis.

The Warburg effect is the preferential use of glycolysis for energy to sustain cancer growth. p53 has been shown to regulate the shift from the respiratory to the glycolytic pathway. Synthesis of Cytochrome c Oxidase 2 (SCO2) has been recognized as the downstream mediator of this effect. SCO2 is critical for regulating the cytochrome c oxidase complex within the mitochondria, and p53 can disrupt the SCO2 gene. P53 regulation of SCO2 and mitochondrial respiration may provide a possible explanation for the Warburg effect.<ref name="Mantoba-Warburg">Template:Cite journal</ref>

However, a mutation can damage the tumor suppressor gene itself, or the signal pathway which activates it, "switching it off". The invariable consequence of this is that DNA repair is hindered or inhibited: DNA damage accumulates without repair, inevitably leading to cancer.

In general, mutations in both types of genes are required for cancer to occur. For example, a mutation limited to one oncogene would be suppressed by normal mitosis control and tumor suppressor genes, which was first hypothesised as the Knudson hypothesis. A mutation to only one tumor suppressor gene would not cause cancer either, due to the presence of many "backup" genes that duplicate its functions. It is only when enough proto-oncogenes have mutated into oncogenes, and enough tumor suppressor genes deactivated or damaged, that the signals for cell growth overwhelm the signals to regulate it, that cell growth quickly spirals out of control. Often, because these genes regulate the processes that prevent most damage to genes themselves, the rate of mutations increase as one gets older, because DNA damage forms a feedback loop. Knudson’s two hit model has recently been challenged by several investigators. Inactivation of one allele of some tumor suppressor genes is sufficient to cause tumors. This phenomenon is called haploinsufficiency and has been demonstrated by a number of experimental approaches. Tumors caused by haploinsufficiency usually have a later age of onset when compared with those by a two hit process.<ref name="Fodde-Haploinsufficiency">Template:Cite journal</ref>

Usually, oncogenes are dominant, as they contain gain-of-function mutations, while mutated tumor suppressors are recessive, as they contain loss-of-function mutations. Each cell has two copies of the same gene, one from each parent, and under most cases gain of function mutation in one copy of a particular proto-oncogene is enough to make that gene a true oncogene, while usually loss of function mutation needs to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one loss of function copy of a tumor suppressor gene can render the other copy non-functional. This phenomenon is called the dominant negative effect and is observed in many p53 mutations.

Mutation of tumor suppressor genes that are passed on to the next generation of not merely cells, but their offspring can cause increased likelihoods for cancers to be inherited. Members of these families have increased incidence and decreased latency of multiple tumors. The mode of inheritance of mutant tumor suppressors is that an affected member inherits a defective copy from one parent, and a normal copy from the other. Because mutations in tumor suppressor genes act in a recessive manner (although there are exceptions), the loss of the normal copy creates the cancer phenotype. For instance, individuals who are heterozygous for p53 mutations are often victims of Li-Fraumeni syndrome, and those who are heterozygous for Rb mutations develop retinoblastoma. Similarly, mutations in the APC gene are linked to adenopolyposis colon cancer, with thousands of polyps in colon while young, while mutations in BRCA1 and BRCA2 lead to early onset of breast cancer.

Cancer pathology is ultimately due to the accumulation of DNA mutations that negatively effect expression of tumour suppressor proteins or positively effect the expression of proteins that drive the cell cycle. Substances that cause these mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. Tobacco smoking is associated with lung cancer. Prolonged exposure to radiation, particularly ultraviolet radiation from the sun, leads to melanoma and other skin malignancies. Breathing asbestos fibers is associated with mesothelioma. In more general terms, chemicals called mutagens and free radicals are known to cause mutations. Other types of mutations can be caused by chronic inflammation, as neutrophil granulocytes secrete free radicals that damage DNA. Chromoo_ol translocations, such as the Philadelphia chromosome, are a special type of mutation that involve exchanges between different chromosomes.

Many mutagens are also carcinogens, but some carcinogens are not mutagens. Examples of carcinogens that are not mutagens include alcohol and estrogen. These are thought to promote cancers through their stimulating effect on the rate of cell mitosis. Faster rates of mitosis increasingly leave less opportunities for repair enzymes to repair damaged DNA during DNA replication, increasing the likelihood of a genetic mistake. A mistake made during mitosis can lead to the daughter cells receiving the wrong number of chromosomes, which leads to aneuploidy and may lead to cancer.

Furthermore, many cancers originate from a viral infection; this is especially true in animals such as birds, but also in humans, as viruses are responsible for 15% of human cancers worldwide. The main viruses associated with human cancers are human papillomavirus, hepatitis B virus, Epsto_on-Barr virus, and human T-lymphotropic virus. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage.<ref name="zur Hausen-viruses">Template:Cite journal</ref> The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, the virus genome is inserted, especially as viral genome insertion is an obligatory part of retroviruses, near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-oncogene is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming viruses, which already carry the viral-oncogene.

It is impossible to tell the initial cause for any specific cancer. However, with the help of molecular biological techniques, it is possible to characterize the mutations or chromoo_ol aberrations within a tumor, and rapid progress is being made in the field of predicting prognosis based on the spectrum of mutations in some cases. For example, some tumors have a defective p53 gene. This mutation is associated with poor prognosis, since those tumor cells are less likely to go into apoptosis or programmed cell death when damaged by therapy. Telomerase mutations remove additional barriers, extending the number of times a cell can divide. Other mutations enable the tumor to grow new blood vessels to provide more nutrients, or to metastasize, spreading to other parts of the body.

Malignant tumor cells have distinct properties:

• evading apoptosis
• unlimited growth potential (immortalitization) due to overabundance of telomerase
• self-sufficiency of growth factors
• insensitivity to anti-growth factors
• increased cell division rate
• altered ability to differentiate
• no ability for contact inhibition
• ability to invade neighbouring tissues
• ability to build metastases at distant sites
• ability to promote blood vessel growth (angiogenesis)

A cell that degenerates into a tumor cell does not usually acquire all these properties at once, but its descendant cells are selected to build them. This process is called clonal evolution. A first step in the development of a tumor cell is usually a small change in the DNA, often a point mutation, which leads to a genetic instability of the cell. The instability can increase to a point where the cell loses whole chromosomes, or has multiple copies of several. Also, the DNA methylation pattern of the cell changes, activating and deactivating genes without the usual regulation. Cells that divide at a high rate, such as epithelials, show a higher risk of becoming tumor cells than those which divide less, for example neurons.

Morphology

Cancer tissue has a distinctive appearance under the microscope. Among the distinguishing traits are a large number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, loss of normal tissue organization, and a poorly defined tumor boundary. Immunohistochemistry and other molecular methods may characterise specific markers on tumor cells, which may aid in diagnosis and prognosis.

Biopsy and microscopical examination can also distinguish between malignancy and hyperplasia, which refers to tissue growth based on an excessive rate of cell division, leading to a larger than usual number of cells but with a normal orderly arrangement of cells within the tissue. This process is considered reversible. Hyperplasia can be a normal tissue response to an irritating stimulus, for example callus.

Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure. Often such cells revert to normal behavior, but occasionally, they gradually become malignant.

The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and shows no propensity to invade other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.

Heredity

Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component, often a defective tumor suppressor allele. Examples are:

• certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer
• tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)
• Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft-tissue sarcoma, brain tumors) due to mutations of p53
• Turcot syndrome (brain tumors and colonic polyposis)
• Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
• Retinoblastoma in young children is an inherited cancer

Lifestyle factors

The most consistent finding, over decades of research, is the strong association between tobacco use and cancers of many sites. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men. Lifestyle choices cause cancer: tobacco, diet, exercise, alcohol, tanning choices, and certain o_oually transmitted diseases are the major risks. "Most cancers are related to known lifestyle factors."<ref>Update: Is There a Cancer Epidemic in the United States? American Council on Science and Health, 1995.</ref>

There is also a growing body of research that correlates cancer incidence with the lower levels of melatonin produced in the body when people spend more time in bright-light conditionsTemplate:Fact, as happens typically in the well-lit nighttime environments of the more developed countries. This effect is compounded in people who sleep fewer hours and in people who work at night, two groups that are knownTemplate:Fact to have higher cancer rates.

Epidemiology

Cancer epidemiology is the study of the incidence of cancer as a way to infer possible trends and causes. The first such cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that cancer of the scrotum was a common disease among chimney sweeps. The work of other individual physicians led to various insights, but when physicians started working together they could make firmer conclusions.

A founding paper of this discipline was the work of Janet Lane-Claypon, who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health. Her ground-breaking work on cancer epidemiology was carried on by Richard Doll and Austin Bradford Hill, who published "Lung Cancer and Other Causes of Death In Relation to Smoking. A Second Report on the Mortality of British Doctors" followed in 1956 (otherwise known as the British doctors study). Richard Doll left the London Medical Research Center (MRC), to start the Oxford unit for Cancer epidemiology in 1968. With the use of computers, the unit was the first to compile large amounts of cancer data. Modern epidemiological methods are closely linked to current concepts of disease and public health policy. Over the past 50 years, great efforts have been spent on gathering data across medical practise, hospital, provincial, state, and even country boundaries, as a way to study the interdependence of environmental and cultural factors on cancer incidence.

The biggest problem facing cancer epidemiology today is the changing concept of 'cancer incidence'. For example, a breast cancer tumor with a very slow growth rate may be found with a mammogram at 50 years, while the same tumor may have been found as a noteworthy 'lump' at 70 years, depending on the specific growth factors affecting that particular patient's case. As diagnostic tools improve, this has a direct impact on the epidemiological data.

In some Western countries, such as the USA,<ref name="CACancerJClin2005-Jemal" /> and the UK<ref name="BBC2000-news"> Cancer: Number one killer (9 November 2000). BBC News online. Retrieved 2005-01-29.</ref> cancer is overtaking cardiovascular disease as the leading cause of death. In many Third World countries cancer incidence (insofar as this can be measured) appears much lower, most likely because of the higher death rates due to infectious disease or injury. With the increased control over malaria and tuberculosis in some Third World countries, incidence of cancer is expected to rise; this is termed the epidemiologic transition in epidemiological terminology.

Cancer epidemiology closely mirrors risk factor spread in various countries. Hepatocellular carcinoma (liver cancer) is rare in the West but is the main cancer in China and neighboring countries, most likely due to the endemic presence of hepatitis B and aflatoxin in that population. Similarly, with tobacco smoking becoming more common in various Third World countries, lung cancer incidence has increased in a parallel fashion.

Prevention

Cancer prevention is defined as active measures to decrease the incidence of cancer. This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of pre-malignant lesions).

Much of the promise for cancer prevention comes from observational epidemiologic studies that show associations between modifiable life style factors or environmental exposures and specific cancers. Evidence is now emerging from randomized controlled trials designed to test whether interventions suggested by the epidemiologic studies, as well as leads based on laboratory research, actually result in reduced cancer incidence and mortality.

Examples of modifiable cancer risk include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men<ref>Template:Cite web</ref>), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption, being physically active, and maintaining recommended body weight may all contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain o_oually transmitted diseases, the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, certain occupational and chemical exposures, and infectious agents.

See alcohol and cancer for more on that topic.

Diet and cancer

The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States). Studies have shown that immigrants develop the risk of their new country, suggesting a link between diet and cancer rather than a genetic basis. Template:Fact

Despite frequent reports of particular substances (including foods) having a beneficial or detrimental effect on cancer risk, few of these have an established link to cancer. These reports are often based on studies in cultured cell media or animals. Public health recommendations cannot be made on the basis of these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.

The case of beta-carotene provides an example of the necessity of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in lung cancer. This hypothesis led to a series of large randomized trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but not significantly, increased by beta-carotene, leading to an early termination of the study.<ref name="CancerTopics-Bcarotene">National Cancer Institute Questions and Answers About Beta Carotene Chemoprevention Trials U.S. National Institutes of Health</ref>

Other chemoprevention agents

Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile. <ref>Template:Cite journal</ref>

Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumors. <ref>Template:Cite journal</ref> The effect of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients <ref>Template:Cite journal</ref> and in the general population. <ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity.

Genetic testing

Genetic testing for high-risk individuals is already available for certain cancer-related genetic mutations. Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance, chemoprevention, or risk-reducing surgery.

Gene	Cancer types	Availability
BRCA1, BRCA2	Breast, ovarian, pancreatic	Commercially available for clinical specimens
MLH1, MSH2, MSH6, PMS, PMS2	Colon, uterine, small bowel, stomach, urinary tract	Commercially available for clinical specimens

Diagnosing cancer

Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist.

Signs and symptoms

Roughly, cancer symptoms can be divided into three groups:

• Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice.
• Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.
• Systemic symptoms: weight loss, poor appetite and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every single item in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

Biopsy

A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

The tissue diagnosis indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and choose the best treatment. Cytogenetics and immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best treatment.

Screening

Cancer screening is an attempt to detect unsuspected cancers in the population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.

Screening for cancer can lead to earlier diagnosis. Early diagnosis may lead to extended life. A number of different screening tests have been developed. Breast cancer screening can be done by breast self-examination. Screening by regular mammograms detects tumors even earlier than self-examination, and many countries use it to systematically screen all middle-aged women. Colorectal cancer can be detected through fecal occult blood testing and colonoscopy, which reduces both colon cancer incidence and mortality, presumably through the detection and removal of pre-malignant polyps. Similarly, cervical cytology testing (using the Pap smear) leads to the identification and excision of precancerous lesions. Over time, such testing has been followed by a dramatic reduction of cervical cancer incidence and mortality. Testicular self-examination is recommended for men beginning at the age of 15 years to detect testicular cancer. Prostate cancer can be screened for by a digital rectal exam along with prostate specific antigen (PSA) blood testing.

Screening for cancer is controversial in cases when it is not yet known if the test actually saves lives. The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments. For example: when screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to treatment. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation. Follow up procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). Similarly, for breast cancer, there have recently been criticisms that breast screening programs in some countries cause more problems than they solve. This is because screening of women in the general population will result in a large number of women with false positive results which require extensive follow-up investigations to exclude cancer, leading to having a high number-to-treat (or number-to-screen) to prevent or catch a single case of breast cancer early.

Cervical cancer screening via the Pap smear has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being a cancer, it has clear risk factors (o_oual contact), and the natural progression of cervical cancer is that it normally spreads slowly over a number of years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.

For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake cancer screening.

Use of medical imaging to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an incidentaloma - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations.

Canine cancer detection has shown promise, but is still in the early stages of research.

Treatment of cancer

Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). A number of experimental cancer treatments are also under development.

Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.

Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.

Surgery

In theory, cancers can be cured if entirely removed by surgery, but this is not always possible. When the cancer has metastasized to other sites in the body prior to surgery, complete surgical excision is usually impossible.

Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy.

Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Chemotherapy

Template:Main Template:See also

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. It interferes with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous transplantation. Alternatively, bone marrow may be transplanted from a matched unrelated donor (MUD).

Monoclonal antibody therapy

Template:Main Immunotherapy is the use of immune mechanisms against tumors. These are used in various forms of cancer, such as breast cancer (trastuzumab/Herceptin®) and leukemia (gemtuzumab ozogamicin/Mylotarg®). The agents are monoclonal antibodies directed against proteins that are characteristic to the cells of the cancer in question, or cytokines that modulate the immune system's response.

Immunotherapy

Template:Main Other, more contemporary methods for generating non-specific immune response against tumours include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferon and interleukin. Vaccines to generate non-specific immune responses are the subject of intensive research for a number of tumours, notably malignant melanoma and renal cell carcinoma.

Radiation therapy

Template:Main Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Radiation therapy can be administered externally via external beam radiotherapy (EBRT) or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.

Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Hormonal suppression

The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Removing or blocking estrogen or testosterone is often an important additional treatment.

Symptom control

Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. Although all practicing doctors have the therapeutic skills to control pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of palliative care has arisen specifically in response to the symptom control needs of this group of patients.

Pain medication, such as morphine and oxycodone, and antiemetics, drugs to suppress nausea and vomiting, are very commonly used in patients with cancer-related symptoms.

Chronic pain due to cancer is almost always associated with continuing tissue damage due to the disease process or the treatment (i.e. surgery, radiation, chemotherapy). Although there is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, these are not usually the predominant etiologic factors in patients with cancer pain. Furthermore, many patients with severe pain associated with cancer are nearing the end of their lives and palliative therapies are required. Issues such as social stigma of using opioids, work and functional status, and health care consumption are not likely to be important in the overall case management. Hence, the typical strategy for cancer pain management is to get the patient as comfortable as possible using opioids and other medications, surgery, and physical measures.

Treatment trials

Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Patients who take part may be helped personally by the treatment(s) they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. Of course, there is no guarantee that a new treatment being tested or a standard treatment will produce good results. New treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit.

Cancer vaccines

Considerable research effort is now devoted to the development of vaccines (to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific epitopes) and to potential venues for gene therapy for individuals with genetic mutations or polymorphisms that put them at high risk of cancer.

As of October 2005, researchers found that an experimental vaccine for HPV types 16 and 18 was 100% successful at preventing infection with these types of HPV and, thus, are able to prevent the majority of cervical cancer cases.<ref name="Lancet2004-Harper"> Template:Cite journal</ref>

Complementary and alternative medicine

Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine. Oncology, the study of human cancer, has a long history of incorporating unconventional or botanical treatments into mainstream cancer therapy. Some examples of this phenomenon include the chemotherapy agent paclitaxel, which is derived from the bark of the Pacific Yew tree, and ATRA, all-trans retinoic acid, a derivative of Vitamin A that induces cures in an aggressive leukemia known as acute promyelocytic leukemia. Many "complementary" and "alternative" medicines for cancer have not been studied using the scientific method, such as in well-designed clinical trials, or they have only been studied in preclinical (animal or in-vitro) laboratory studies. Many times, "complementary" and "alternative" medicines are supported by marketing materials and "testimonials" from users of the substances.

Complementary and alternative medicines are not regulated by any government agency, so manufacturers are not under any guidelines about standardized doses from lot to lot of medication, or other substances present in the pills. An example of this problem was PC-SPES, marketed as an alternative treatment for prostate cancer. This medication was tested using sophisticated spectrometry techniques and found to have warfarin, the estrogenic compound DES, and other non-naturally occurring substances in the pills, along with tens of other compounds. As a result, the FDA banned PC-SPES from the United States marketplace in 2002. PC-SPES was effective treatment for prostate cancer in clinical trials, and efforts have been made to identify which of its many ingredients were responsible for the improved results. <ref>[1] Interesting information about PC-SPES</ref>

"Complementary medicine" refers to substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. A study of CAM use in patients with cancer in the July 2000 issue of the Journal of Clinical Oncology found that 69 percent of 453 cancer patients had used at least one CAM therapy as part of their cancer treatment.<ref>Template:Cite web</ref>

Some complementary measures include botanical medicine, such as an NIH trial currently underway testing mistletoe extract combined with chemotherapy for the treatment of solid tumors, acupuncture for managing chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery, prayer, psychological approaches such as "imaging" or meditation to aid in pain relief or improve mood.<ref>Template:Cite web</ref>

A wide range of alternative treatments have been offered for cancer over the last century. The appeal of alternative cures arises from the daunting risks, costs, or potential side effects of many conventional treatments, or in the limited prospect for cure. No alternative therapies have been shown in randomized controlled trials to effectively cure cancer by themselves, although the Journal of Urology published a study in 2005 <ref name="Ornish">Template:Cite journal</ref> demonstrating that a consuming plant based diet and making other lifestyle changes was able to reduce cancer markers in a group of men with prostate cancer using no conventional treatments. Other (unproven) anti-cancer diets include the grape diet and the cabbage diet.

Quackery in the treatment of cancer

Template:POV

Many substances and techniques proposed for cancer treatment are quackery. Some of the more well-known examples of these ineffectual and potentially dangerous treatments for cancer include megavitamin therapy, electromagnetic therapy with electrical devices (e.g., "rhumart", "zappers"), laetrile, and homeopathic remedies, unconventional use of conventional drugs (e.g., insulin), purges or enemas, physical manipulations of the body, and herbal preparations such as essiac. While patient stories attesting to the efficacy of these treatments sometimes exist, the treatments share a common thread in that there is no evidence that they accomplish the goal intended in a measurable fashion. Cancer patients are particularly vulnerable to quackery, since they may turn to any available treatment out of desperation for a better outcome, or for simple survival. Quacks can take advantage of this desperation, and without scientific assessment of efficacy, there is no way to determine which treatment is valid and which is quackery. <ref>[2] Some of the harms quacks can precipitate upon cancer patients, their families, and society</ref>

Coping with cancer

Many local organizations offer a variety of practical and support services to people with cancer. Support can take the form of support groups, counseling, advice, financial assistance, transportation to and from treatment, films or information about cancer. Neighborhood organizations, local health care providers, or area hospitals may have resources or services available.

While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and o_ouality.

Many governmental and charitable organizations have been established to help patients cope with cancer. These organizations often are involved in cancer prevention, cancer treatment, and cancer research. Examples include: American Cancer Society, Lance Armstrong Foundation, BC Cancer Agency, Macmillan Cancer Relief , the Terry Fox Foundation, Cancer Research UK, Cancer Research Foundation, Canadian Cancer Society, International Agency for Research on Cancer, The Cancer Council Australia and the National Cancer Institute (US).

Social impact

Cancer has a reputation for being a deadly disease. While this certainly applies to certain particular types, the truths behind the historical connotations of cancer are increasingly being overturned by advances in medical care. Some types of cancer have a prognosis that is substantially better than nonmalignant diseases such as heart failure and stroke.

Progressive and disseminated malignant disease has a substantial impact on a cancer patient's quality of life, and many cancer treatments (such as chemotherapy) may have severe side-effects. In the advanced stages of cancer, many patients need extensive care, affecting family members and friends. Palliative care solutions may include permanent or "respite" hospice nursing.

Cancer research

Template:Main

Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. Although understanding of cancer has greatly increased since the last decades of the 20th century, few radically new therapies have been discovered.

Targeted therapy which first became available in the late 1990s has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecules (such as the tyrosine kinase inhibitors imatinib and gefitinib) and monoclonal antibodies have proven to be a major step in oncological treatment. Targeted therapy can also involve small peptidic structures as ´homing device´ which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to this peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell (vide supra Radiation therapy). Especially oligo- or multimeris of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.

See also

Template:Wiktionary Template:Commons

• American Cancer Society
• Alcohol and cancer
• Oncology
• List of oncology-related terms
• American Association for Cancer Research
• European Organisation for Research and Treatment of Cancer (EORTC)
• Antibiotic Resistance in Cancer Patients

References

External links

Professional and research

• American Cancer Society Homepage
• American Cancer Society resources on clinical trials What to look for in clinical trials and how to find open trials.
• / The Leukemia and Lymphoma Society
• American Cancer Society Treatment Decision Tools – Trusted tools for helping patients make informed decisions
• American Association for Cancer Research A non-profit organization supporting advances in the knowledge of causes, diagnosis, treatment and prevention of cancer.
• The World Health Organisation's cancer site A review of worldwide strategies for the prevention and treatment of cancer.
• World Health Organization's fact sheet on cancer
• National Cancer Institute US Government agency responsible for conducting and supporting research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.
• National Comprehensive Cancer Network - Free guidelines for professionals and many pages of quality information for patients with all types of cancers
• The Institute of Cancer Research One of the world’s foremost independent cancer research organisations, based in the United Kingdom.
• EORTC European Organization for Research and Treatment of Cancer. A European non-profit organization that sets up and executes clinical trials.
• International Society for Biological Therapy of Cancer Society of medical professionals committed to investigating, developing and utilizing biologicals and biological therapy for the treatment of malignant disease.
• National Cancer Institute of Canada Longest-standing Canadian research organization devoted to advancing cancer control.
• Cancer Facts & Figures 2005 - 2005 United States Cancer Statistics
• Canadian Cancer Statistics 2006 - This publication reports cancer incidence and mortality in Canada, analyzed by gender, age and province/territory.
• Cancer Medicine, 6th Edition Textbook
• Template:Cite web
• Diet, Nutrition and the prevention of chronic diseases (including cancer) by a Joint WHO/FAO Expert consultation (2003). Summary by GreenFacts.
• Virtual Cancer Centre - information resource with the latest cancerous diseases news by professionals of Oncology, Haematology, Radiation Oncology and Palliative Care.

Support and advocacy

• American Cancer Society Patient advocate group
• Action Cancer Northern Ireland Cancer Charity providing screening and support
• Canadian Cancer Society Information on all types of cancer, ways to reduce your risk. Support for people living with cancer. Advocating for healthy public policy.
• American Association for Cancer Research Survivor and Patient Advocacy
• Cancer from MedlinePlus - provides links to news, general sites, diagnosis, treatment and alternative therapies, clinical trials, research, related issues, organizations, other MedlinePlus Cancers Topics and Living with Cancer, and more. Also, links to pre-formulated searches of the MEDLINE/PubMed database for recent research articles.
• Cancer Research UK - Cancer Resources - In-depth, up-to-date information for people with a professional or general interest in cancer and health.
• Cancer Council of Australia - Australia's national non-government cancer control organisation, involved in research, information, prevention, patient treatment and support.
• Sydney Children's Hospital: Centre for Cancer and Blood Disorders - Offers information on childhood cancer, treatment options, and support. [Australia].
• ACOR - Association of Cancer Online Resources ACOR is a unique collection of online communities designed to provide timely and accurate information in a supportive environment. ACOR offers access to mailing lists that provide support, information, and community to everyone affected by cancer and related disorders.
• Inside Cancer Multimedia guide to cancer biology from Cold Spring Harbor Laboratory

Template:TumorsTemplate:Link FA Template:Link FA Template:Link FA

ar:مرض السرطان zh-min-nan:Gâm bs:Rak (bolest) bg:Рак (болест) ca:Càncer cs:Rakovina da:Kræft de:Krebs (Medizin) el:Καρκίνος es:Cáncer eo:Kancero (medicino) eu:Minbizi fa:سرطان fr:Cancer gd:Aillse ko:암 hr:Rak (bolest) id:Kanker is:Krabbamein it:Cancro (medicina) he:סרטן (מחלה) la:Cancer (morbus) lt:Vėžys (liga) hu:Rák (betegség) mk:Рак (болест) ms:Penyakit Barah nl:Kanker ja:悪性腫瘍 no:Kreft pl:Rak (choroba) pt:Cancro (tumor) ro:Cancer ru:Карцинома sq:Kanceri simple:Cancer sl:Rak (bolezen) sr:Рак (болест) sh:Rak (bolest) fi:Syöpä sv:Cancer ta:நண்டு th:มะเร็ง vi:Ung thư tr:Kanser wa:Magnant må yi:קענסער zh-yue:癌 zh:癌症

Template:Otheruses Blood is a highly specialized circulating tissue consisting of several types of cells suspended in a fluid medium known as plasma. The cellular constituents are: red blood cells, which carry respiratory gases and give it its red color because they contain haemoglobin (an iron-containing protein that binds oxygen in the lungs and transports it to tissues in the body), white blood cells (leukocytes), which fight disease, and platelets, cell fragments which play an important part in the clotting of the blood.

Medical terms related to blood often begin with hemo- or hemato- (BE: haemo- and haemato-) from the Greek word "haima" for "blood." Anatomically, blood is considered a connective tissue from both its origin in the bones and its function.

Functions

• Supply of oxygen to tissues (bound to hemoglobin which is carried in red cells)
• Supply of nutrients such as glucose, amino acids and fatty acids (dissolved in the blood or bound to plasma proteins)
• Removal of waste such as carbon dioxide, urea and lactic acid
• Immunological functions, including circulation of white cells, and detection of foreign material by antibodies
• Coagulation, which is one part of the body's self-repair mechanism
• Messenger functions, including the transport of hormones and the signalling of tissue damage
• Regulation of body pH
• Regulation of core body temperature
• Hydraulic functions, including erection (see also jumping spider)

Problems with blood composition or circulation can lead to downstream tissue dysfunction. The term ischaemia refers to tissue which is inadequately perfused with blood.

The blood is circulated around the lungs and body by the pumping action of the heart. Additional return pressure may be generated by gravity and the actions of skeletal muscles. In mammals, blood is in equilibrium with lymph, which is continuously formed from blood (by capillary ultrafiltration) and returned to the blood (via the thoracic duct). The lymphatic circulation may be thought of as the "second circulation".

Anatomy of mammalian blood

Blood is composed of several kinds of cells (occasionally called corpuscles); these formed elements of the blood constitute about 45% of whole blood by volume, mostly red blood cells. The other 55% is blood plasma, a fluid that is the blood's liquid medium, appearing yellow in color. The proportion of blood occupied by red blood cells is referred to as the hematocrit.

The normal pH of human arterial blood is approximately 7.40 (normal range is 7.35-7.45), a weak alkaline solution. Blood that has a pH below 7.35 is acidic, while blood pH above 7.45 is alkaline. Blood pH along with arterial carbon dioxide tension (PaCO₂) and HCO₃ readings are helpful in determining the acid-base balance of the body. The respiratory system and urinary system normally control the acid-base balance of blood as part of homeostasis. Blood is about 7% of the human body weight,<ref>Bloodcenters.org</ref> so the average adult has a blood volume of about 5 litres, of which 2.7-3 litres is plasma. Human blood density is around 1060 kg/m³.<ref>Template:Cite web</ref> The combined surface area of all the red cells in the human body would be roughly 2,000 times as great as the body's exterior surface.Template:Fact

The cells are:

Red blood cells or erythrocytes (96%) 

In mammals, mature red blood cells lack a nucleus and organelles. They contain the blood's haemoglobin and distribute oxygen. The red blood cells (together with endothelial vessel cells and some other cells) are also marked by glycoproteins that define the different blood types.

White blood cells or leukocytes (3.0%) 

White blood cells are part of the immune system; they destroy infectious agents, pathogens.

Platelets or thrombocytes (1.0%) 

Platelets are responsible for blood clotting (coagulation). They change fibrinogen into fibrin. This fibrin creates a mesh onto which red blood cells collect and clot. This clot stops more blood from leaving the body and also helps to prevent bacteria from entering the body.

Blood plasma is essentially an aqueous solution containing 92% water, 8% blood plasma proteins, and trace amounts of other materials. Some components are:

• Serum albumin
• Blood clotting factors (to facilitate coagulation)
• Immunoglobulins (antibodies)
• Hormones
• Carbon dioxide
• Various other proteins
• Various electrolytes (mainly sodium and chlorine)

Together, plasma and cells form a non-Newtonian fluid whose flow properties are uniquely adapted to the architecture of the blood vessels.

The term serum refers to plasma from which the clotting proteins have been removed. Most of the protein remaining is albumin and immunoglobulins.

Physiology of blood

Production and degradation

Blood cells are produced in the bone marrow, this process is termed hematopoiesis. The proteinaceous component (including clotting proteins) is produced overwhelmingly in the liver, while hormones are produced by the endocrine glands and the watery fraction is regulated by the hypothalamus and maintained by the kidney and indirectly by the gut.

Blood cells are degraded by the spleen and the Kupffer cells in the liver. The liver also clears some proteins, lipids and amino acids. The kidney actively secretes waste products into the urine. Erythrocytes usually live up to 120 days before they are systematically replaced by new erythrocytes created by the process of hematopoiesis.

Transport of oxygen

Template:See

Blood oxygenation is measured in several ways, but the most important measure is the hemoglobin (Hb) saturation percentage. This is a non-linear (sigmoidal) function of the partial pressure of oxygen. About 98.5% of the oxygen in a sample of arterial blood in a healthy human breathing air at normal pressure is chemically combined with the Hb. Only 1.5% is physically dissolved in the other blood liquids and not connected to Hb. The hemoglobin molecule is the primary transporter of oxygen in mammals and many other species (for exceptions, see below).

With the exception of pulmonary and umbilical arteries and their corresponding veins, arteries carry oxygenated blood away from the heart and deliver it to the body via arterioles and capillaries, where the oxygen is consumed; afterwards, venules and veins carry deoxygenated blood back to the heart.

Differences in infrared absorption between oxygenated and deoxygenated blood form the basis for realtime oxygen saturation measurement in hospitals and ambulances.

Under normal conditions in humans at rest, haemoglobin in blood leaving the lungs is about 98-99% saturated with oxygen. In a healthy adult at rest, deoxygenated blood returning to the lungs is still approximately 75% saturated.<ref>Ventilation and Endurance Performance</ref><ref>Transplant Support- Lung, Heart/Lung, Heart MSN groups</ref> Increased oxygen consumption during sustained exercise reduces the oxygen saturation of venous blood, which can reach less than 15% in a trained athlete; although breathing rate and blood flow increase to compensate, oxygen saturation in arterial blood can drop to 95% or less under these conditions.<ref>J Physiol. 2005 July 1</ref> Oxygen saturation this low is considered dangerous in an individual at rest (for instance, during surgery under anesthesia): "As a general rule, any condition which leads to a sustained mixed venous saturation of less than 50% will be poorly tolerated and a mixed venous saturation of less than 30% should be viewed as a medical emergency."<ref>The 'St George' Guide To Pulmonary Artery Catheterisation</ref>

A fetus, receiving oxygen via the placenta, is exposed to much lower oxygen pressures (about 20% of the level found in an adult's lungs) and so fetuses produce another form of hemoglobin with a much higher affinity for oxygen (hemoglobin F) in order to extract as much oxygen as possible from this sparse supply.<ref>Oxygen Carriage in Blood - High Altitude</ref>

Substances other than oxygen can bind to the hemoglobin; in some cases this can cause irreversible damage to the body. Carbon monoxide for example is extremely dangerous when absorbed into the blood. When combined with the hemoglobin, it irreversibly makes carboxyhemoglobin which reduces the volume of oxygen that can be carried in the blood. This can very quickly cause suffocation, as oxygen is vital to many organisms (including humans). This damage can occur when smoking a cigarette (or similar item) or in event of a fire. Thus carbon monoxide is considered far more dangerous than the actual fire itself because it reduces the oxygen carrying content of the blood.

Insects

In insects, the blood (more properly called hemolymph) is not involved in the transport of oxygen. (Openings called tracheae allow oxygen from the air to diffuse directly to the tissues). Insect blood moves nutrients to the tissues and removes waste products in an open system.

Small invertebrates

In some small invertebrates like insects, oxygen is simply dissolved in the plasma. Larger animals use respiratory proteins to increase the oxygen carrying capacity. Hemoglobin is the most common respiratory protein found in nature. Hemocyanin (blue) contains copper and is found in crustaceans and mollusks. It is thought that tunicates (sea squirts) might use vanabins (proteins containing vanadium) for respiratory pigment (bright green, blue, or orange).

In many invertebrates, these oxygen-carrying proteins are freely soluble in the blood; in vertebrates they are contained in specialized red blood cells, allowing for a higher concentration of respiratory pigments without increasing viscosity or damaging blood filtering organs like the kidneys.

Deep sea invertebrates

Giant tube worms have extraordinary hemoglobins that allow them to live in extraordinary environments. These hemoglobins also carry sulfides normally fatal in other animals.

Transport of carbon dioxide

When systemic arterial blood flows through capillaries, carbon dioxide diffuses from the tissues into the blood. Some carbon dioxide is dissolved in the blood. Some carbon dioxide reacts with hemoglobin and other proteins to form carbamino compounds. The remaining carbon dioxide is converted to bicarbonate and hydrogen ions through the action of RBC carbonic anhydrase. Most carbon dioxide is transported through the blood in the form of bicarbonate ions.

Transport of hydrogen ions

Some oxyhemoglobin loses oxygen and becomes deoxyhemoglobin. Deoxyhemoglobin has a much greater affinity for H+ than does oxyhemoglobin so it binds most of the hydrogen ions.

Color

In humans and other hemoglobin-using creatures, oxygenated blood is bright red. This is due to oxygenated iron in the red blood cells. Deoxygenated blood is a darker shade of red, which can be seen during blood donation and when venous blood samples are taken. However, due to an optical effect caused by the way in which light penetrates through the skin, veins typically appear blue in colour. This has led to a common misconception that venous blood is blue before it is exposed to air. Another reason for this misconception is that medical charts always show venous blood as blue in order to distinguish it from arterial blood which is depicted as red on the same chart.

The blood of horseshoe crabs is blue, which is a result of its high content in copper-based hemocyanin instead of the iron-based hemoglobin found, for example, in humans.

Provision of force

In mammals the restriction of blood flow is commonly used as a temporary provision of force, as in an erection.

Health and disease

Ancient Medicine

Hippocratic medicine considered blood one of the four humors (together with phlegm, yellow bile and black bile). As many diseases were thought to be due to an excess of blood, bloodletting and leeching were a common intervention until the 19th century (it is still used for some rare blood disorders).

In classical Greek medicine, blood was associated with air, springtime, and with a merry and gluttonous (sanguine) personality. It was also believed to be produced exclusively by the liver.

Diagnosis

Blood pressure and blood tests are amongst the most commonly performed diagnostic investigations that directly concern the blood.

Pathology

Template:Seealso

Problems with blood circulation and composition play a role in many diseases.

• Wounds can cause major blood loss (see bleeding). The thrombocytes cause the blood to coagulate, blocking relatively minor wounds, but larger ones must be repaired at speed to prevent exsanguination. Damage to the internal organs can cause severe internal bleeding, or hemorrhage.
• Circulation blockage can also create many medical conditions from ischemia in the short term to tissue necrosis and gangrene in the long term.
• Hemophilia is a genetic illness that causes dysfunction in one of the blood's clotting mechanisms. This can allow otherwise inconsequential wounds to be life-threatening, but more commonly results in hemarthrosis, or bleeding into joint spaces, which can be crippling.
• Leukemia is a group of cancers of the blood-forming tissues.
• Major blood loss, whether traumatic or not (e.g. during surgery), as well as certain blood diseases like anemia and thalassemia, can require blood transfusion. Several countries have blood banks to fill the demand for transfusable blood. A person receiving a blood transfusion must have a blood type compatible with that of the donor.
• Blood is an important vector of infection. HIV, the virus which causes AIDS, is transmitted through contact between blood, semen, or the bodily secretions of an infected person. Hepatitis B and C are transmitted primarily through blood contact. Owing to blood-borne infections, bloodstained objects are treated as a biohazard.
• Bacterial infection of the blood is bacteremia or sepsis. Viral Infection is viremia. Malaria and trypanosomiasis are blood-borne parasitic infections.

Treatment

Blood transfusion is the most direct therapeutic use of blood. It is obtained from human donors by blood donation. As there are different blood types, and transfusion of the incorrect blood may cause severe complications, crossmatching is done to ascertain the correct type is transfused.

Other blood products administered intravenously are platelets, blood plasma, cryoprecipitate and specific coagulation factor concentrates.

Many forms of medication (from antibiotics to chemotherapy) are administered intravenously, as they are not readily or adequately absorbed by the digestive tract.

As stated above, some diseases are still treated by removing blood from the circulation.

It is the fluid part of the blood that saves lives where severe blood loss occurs, other preparations can be given such as ringers atopical plasma volume expander as a non-blood alternative, and these alternatives where used are rivalling blood use when used.

Mythology and religion

Due to its importance to life, blood is associated with a large number of beliefs. One of the most basic is the use of blood as a symbol for family relationships; to be "related by blood" is to be related by ancestry or descendance, rather than marriage. This bears closely to bloodlines, and sayings such as "blood is thicker than water" and "bad blood", as well as "Blood brother". Blood is given particular emphasis in the Jewish and Christian religions because (Leviticus 17:11) says "the life of a creature is in the blood."

Indigenous Australians

In many indigenous Australian Aboriginal peoples' traditions ochre (particularly red) and blood, both high in iron content and considered Maban, are applied to the bodies of dancers for ritual. As Lawlor states:

In many Aboriginal rituals and ceremonies, red ochre is rubbed all over the naked bodies of the dancers. In secret, sacred male ceremonies, blood extracted from the veins of the participant's arms is exchanged and rubbed on their bodies. Red ochre is used in similar ways in less secret ceremonies. Blood is also used to fasten the feathers of birds onto people's bodies. Bird feathers contain a protein that is highly magnetically sensitive. <ref>Lawlor, Robert (1991). Voices Of The First Day: Awakening in the Aboriginal dreamtime. Page 102-3. Rochester, Vermont: Inner Traditions International, Ltd. ISBN 0-89281-355-5</ref>

Lawlor comments that blood employed in this fashion is held by these peoples to attune the dancers to the invisible energetic realm of the Dreamtime. Lawlor then draws information from different disciplines charting a relationship between these invisible energetic realms and magnetic fields. Iron and magnetism having a marked relationship.

Indo-European paganism

Among the Germanic tribes (such as the Anglo-Saxons and the Norsemen), blood was used during the sacrifices, the Blóts. The blood was considered to have the power of its originator and after the butchering the blood was sprinkled on the walls, on the statues of the gods and on the participants themselves. This act of sprinkling blood was called bleodsian in Old English and the terminology was borrowed by the Roman Catholic Church becoming to bless and blessing. The Hittite word for blood, ishar was a cognate to words for "oath" and "bond", see Ishara. The Ancient Greeks believed that the blood of the Gods, ichor, was a mineral that was poisonous to mortals.

Judaism

In Judaism, blood cannot be consumed even in the smallest quantity (Leviticus 3:17 and elsewhere); this is reflected in Jewish dietary laws (Kashrut). Blood is purged from meat by salting and soaking in water.

Other rituals involving blood are the covering of the blood of fowl and game after slaughtering (Leviticus 17:13); the reason given by the Torah is: "Because the life of every animal is [in] his blood" (ibid 17:14), although from its context in Leviticus 3:17 it would appear that blood cannot be consumed because it is to be used in the sacrificial service (known as the korbanot), in the Temple in Jerusalem. Blood (the blood of a lamb) was also the means for atonement of sins for the Jews.

Christianity

Template:Main Some Christian churches, including Roman Catholicism, Eastern Orthodoxy, branches of Anglicanism, and the Moravian Church, teach that when consecrated the Eucharist wine becomes the material Blood of Jesus. Thus in the consecrated wine (now the Most Precious Blood of Christ), Jesus becomes spiritually and physically present. This teaching is rooted in the Last Supper as written in the four gospels of the Bible, in which Jesus stated to his disciples that the bread which they ate was his body, and the wine was his blood. "This cup is the new testament in my blood, which is shed for you." (Template:Sourcetext). Various forms of Protestantism, especially those of a Wesleyan or Presbyterian lineage, teach that the wine is no more than a symbol of the blood of Christ, who is not physically but spiritually present. Blood (the blood of Jesus Christ) is also seen as the means for atonement for sins for Christians. Lutheran theology teaches that the body and blood is present together "in, with, and under" the bread and wine of the eucharist feast. Mormons believe that before Adam and Eve ate the forbidden fruit, blood was not present in their bodies. It is said to have formed after the Fall when they became mortal.

Islam

Consumption of food containing blood is forbidden by Islamic dietary laws.

Jehovah's Witnesses

Template:Main

Jehovah's Witnesses do not eat blood or accept tranfusions of whole blood or its four major components namely, red blood cells, white blood cells, platelets (thrombocytes), and whole plasma. Members are instructed to personally decide whether or not to accept fractions, and medical procedures that involve their own blood.

Vampire legends

Vampires are mythological beings which live forever by drinking the blood of the living. Stories of creatures of this kind are known all over the world. European versions of this myth are mostly inspired by folklore based on the stories regarding Vlad Dracula.Template:Fact

Chinese and Japanese culture

In Chinese culture, it is often said that if a man's nose produces a small flow of blood, this signifies that he is experiencing o_oual desire. This often appears in Chinese-language and Hong Kong films. This is also evident in Japanese culture and is parodied in anime and manga. Male characters will often be shown with a nosebleed if they have just seen a female nude or in little clothing, or if they have had an erotic thought or fantasy.Template:Fact

Blood libel

Template:Main Various religious and other groups have been falsely accused of using human blood in rituals; such accusations are known as blood libel. The most common form of this is blood libel against Jews. Although there is no ritual involving human blood in Jewish law or custom, fabrications of this nature (often involving the murder of children) were widely used during the Middle Ages to justify anti-Semitic persecution and some have persisted into the 21st century.

Art

Blood is one of the body fluids that has been used in art.<ref>"Nostalgia" Artwork in blood</ref> In particular, the performances of Viennese Actionist Hermann Nitsch, Franko B, Lennie Lee, Ron Athey, Yang Zhichao and Kira O' Reilly along with the photography of Andres Serrano, have incorporated blood as a prominent visual element. Marc Quinn has made sculptures using frozen blood, including a cast of his own head made using his own blood.

See also

• Artificial blood
• List of human blood components
• Blood as food: see black pudding and tiết canh
• Blood and video game censorship
• Taboo food and drink#Blood

Notes

External links

Template:Wiktionary Template:Commonscat

• Blood Online, a journal published by the American Society of Hematology

Template:Blood Template:Cardiovascular system Template:Transfusion medicineTemplate:Link FA

ar:دم bs:Krv bg:Кръв ca:Sang cs:Krev cy:Gwaed da:Blod de:Blut arc:ܕܡܐ es:Sangre eo:Sango eu:Odol fa:خون fr:Sang gd:Fuil gl:Sangue ko:혈액 id:Darah ia:Sanguine is:Blóð it:Sangue he:דם ka:სისხლი ku:Xwîn la:Sanguis lb:Blutt lt:Kraujas ln:Makilá hu:Vér mk:Крв mt:Demm ms:Darah nl:Bloed ja:血液 no:Blod nn:Blod oc:Sang pam:Daya ps:وينه nds:Blood pl:Krew pt:Sangue ro:Sânge qu:Yawar ru:Кровь sq:Gjaku simple:Blood sk:Krv sl:Kri sr:Крв sh:Krv su:Getih fi:Veri sv:Blod ta:குருதி vi:Máu tr:Kan Doku uk:Кров yi:בלוט bat-smg:Kraus zh:血液

Is an accomplished musician

Discography

This page lists Pink Floyd albums and singles, both official and unofficial, as well as various awards. For individual songs, see the category listing.

Studio albums

PinkFloyd-album-piperatthegatesofdawn.jpg 1. The Piper at the Gates of Dawn <center>(1967) <center>#6 UK; #131 US	PinkFloyd-album-saucerfulofsecrets.jpg 2. A Saucerful of Secrets <center>(1968) <center>#9 UK; didn't chart in the US	MoreCover.jpg 3. Music from the Film More <center>(1969) <center>#9 UK; #153 US	PinkFloyd-album-ummagummastudio.jpg 4. Ummagumma <center>(1969) (Double album) <center>#5 UK; #74 US Platinum
AtomHeartMotherCover.jpeg 5. Atom Heart Mother <center>(1970) <center>#1 UK; #55 US Gold	MeddleCover.jpeg 6. Meddle <center>(1971) <center>#3 UK; #70 US 2x Platinum	Obs.jpg 7. Obscured by Clouds <center>(1972) <center>#6 UK; #46 US Gold	Dsotm.jpg 8. The Dark Side of the Moon <center>(1973) <center>#2 UK; #1 US (1 week) 15x Platinum(Diamond)
WishYouWereHere.jpg 9. Wish You Were Here <center>(1975) <center> #1 UK; #1 US (2 Weeks) 8x Platinum	Pink Floyd-Animals-Frontal.jpg 10. Animals <center>(1977) <center>#2 UK; #3 US 4x Platinum	PinkfloydThewallcover.jpg 11. The Wall <center>(1979) <center>(Double album) <center>#3 UK; #1 US (15 weeks) 23x Platinum (Diamond)	Thefinalcutcover.jpg 12. The Final Cut <center>(1983) #1 UK; #6 US 2x Platinum
Lapse-l.jpg 13. A Momentary Lapse of Reason <center>(1987) <center>#3 UK; #3 US 4x Platinum	Pink floyd the division bell front.jpg 14. The Division Bell <center>(1994) <center> #1 UK; #1 US (4 weeks) 3x Platinum

Live albums

Dsothunder.jpg Delicate Sound of Thunder (1988) (live) #11 UK; #11 US Platinum

Pulse.jpg P*U*L*S*E (1995) (2CD, live) #1 UK; #1 US 8X Platinum

Itaot cd.jpg Is There Anybody Out There? (2000) (live) #15 UK; #19 US Platinum

Major compilations

Pink Floyd Relics 1996.jpg Relics (1971) (A-sides, B-sides, album tracks 1967-69) #34 UK; #152 US	PinkFloyd ANicePair.jpg A Nice Pair (1973) #36 US -The Piper at the Gates of Dawn - A Saucerful Of Secrets (album)Gold	Collection.jpg A Collection of Great Dance Songs (1981) (compilation) #37 UK; #31 US 2X Platinum	PinkFloyd-album-works.jpg Works (1983) (compilation) #68 US
Shineoncover.jpg Shine On (1992) (boxed set) Platinum	Pink Floyd Echoes.jpg Echoes: The Best Of Pink Floyd (2001) #2 UK; #2 US 3X Platinum

Vinyl singles (1960s)

• 1967 (March 11th): "Arnold Layne" / "Candy and a Currant Bun" (#20 UK)
• 1967 (June 16th): "See Emily Play" / "The Scarecrow" (#6 UK, #134 U.S.)
• 1967 (November 18th): "Apples and Oranges" / "Paint Box"
• 1968 (April 12th): "It Would Be So Nice" / "Julia Dream"
• 1968 (December 17th): "Point Me at the Sky" / "Careful with That Axe, Eugene"

Other

• Tonite Let's All Make Love in London (1967 documentary film soundtrack, featuring 2 tracks)
• "Give Birth to a Smile" (song featuring (uncredited) all four members from Roger Waters and Ron Geesin's Music from "The Body", 1969)
• The Man and the Journey (1969 aborted live concept album)
• Zabriskie Point (1970)
• Masters of Rock (1974)
• London '66-'67 (1995)
• 1967: The First Three Singles (1997)
• The Committee (1968) (Unreleased soundtrack from the film, The Committee)
• The Early Singles (Distributed with the Shine On box set)

Bootlegs

Also see: List of Pink Floyd ROIOs

Pink Floyd are one of the heaviest-bootlegged bands in history, with bootleg recordings of the band numbering at least in the hundreds. Collectors of these bootlegs often call them RoIOs, or Recordings of Indeterminate/Illegitimate Origin. The vast majority of these are audience recordings of their various concerts, as only a few studio outtakes and soundboard recordings have leaked to bootleggers. The most popular exceptions are the unreleased Syd Barrett songs "Scream Thy Last Scream" and "Vegetable Man", but there are others as well, such as "Lucy Leave" and a cover of Slim Harpo's "I'm a King Bee" both from the first incarnation of the band. Many bootlegs before the 1990s featured singles such as "Candy and a Currant Bun" that had not been released on compilation discs, but these disappeared when the The Early Singles disc in the Shine On box set was released. Collecting bootlegs is usually easy, as the internet has made bootleg sales for profit largely pointless. Organizations such as Harvested have made a hobby of cleaning up and remastering bootleg recordings and issuing them to traders for free.

The hundreds of audience recordings vary in quality from excellent (concerts in 1994 and 1988) to abysmal (the era between 1967 and 1971). Audience noise is often absent, because audiences of the band in their early days were very quiet. There are sometimes recordings of standout quality in a period of otherwise low-quality recordings; an example is the Electric Factory show in late 1970, which was nearly soundboard-quality during a period when most other recordings were extremely poor. (Audience recordings would not regularly be as good as the Electric Factory show until 1988). Other standouts include the "Fireman" source of the Hollywood Bowl concert in 1972, in which a complete rendition of the pre-release "prototype" Dark Side of the Moon suite was played; the 9 May 1977 show in Oakland from the same source, which includes the last performance of "Careful with That Axe, Eugene" to date; and an excellent recording of the 24 April 1975 show in Los Angeles, taped by the legendary taper Mike Millard, containing the best-existing versions of Dick Parry performing a saxophone solo in "Echoes" and the prototype "Raving and Drooling" and "You've Gotta Be Crazy", which would eventually become "Sheep" and "Dogs" respectively.

The 6 July 1977 show in Montreal is widely traded, the occasion of Roger Waters infamously luring a fan onstage and then spitting on them; his self-disgust after the event inspired the idea of building a wall between the band and the audience. While lower quality than the previously mentioned shows, this concert is extremely popular due to the ability to hear this historic event happen at the end of "Pigs (Three Different Ones)".

One of the most widely traded bootlegs online is A Tree Full of Secrets, a massive 18-disc collection of Pink Floyd material which ignores live recordings but includes all material released on albums outside the Pink Floyd discography such as movie soundtracks, radio advertisements, television performances, studio outtakes, rehearsals and alternative mono/stereo remixes. It also features considerable rare solo material from all of Pink Floyd's members except Syd Barrett. It is the definitive collection of all Floyd rarities, and even includes materials suspected of being fake for the sake of completeness and allowing the listener to decide.

Syd Barrett's solo rarities are collected on the "sister set" Have You Got It Yet?, an equally large set which is also widely traded. In addition to studio rarities from both his Pink Floyd days (many of which are on both sets) and solo era, it also includes well over a hundred covers of Syd Barrett and Barrett-era Pink Floyd songs by major and minor artists.

Awards list

Pink Floyd have received several awards during their career.

Silver Clef

Pink Floyd was awarded a Silver Clef for their charity work for The Nordoff-Robbins Music Center in 1980

Grammys

Pink Floyd have been nominated for several Grammy Awards:

• 1973 nomination for Album of the Year
  • "Dark Side of the Moon" -- lost to Stevie Wonder's "Innervisions"
• 1980 nomination for Album of the Year
  • "The Wall" -- lost to Christopher Cross' Christopher Cross
• 1980 nomination for Best Rock Performance by Duo or Group
  • "Another Brick in the Wall (Part 2)" -- lost to Bob Seger's "Against the Wind"
• 1994 nomination for Best Rock Instrumental Performance
  • "Marooned" from The Division Bell -- won

American Music Awards

Pink Floyd have been nominated for an American Music Award

• 1995 nomination for Best Pop/Rock Duo or Group -- lost to Ace of Base

RIAA gold certifications

• Atom Heart Mother
• Obscured by Clouds
• A Nice Pair

RIAA platinum certifications

• Ummagumma (1,000,000+)
• Meddle - 2x (2,000,000+)
• Dark Side of the Moon - 15x (15,000,000+)
• Dark Side of the Moon DVD - 2x (100,000+)
• Live at Pompei VHS/DVD - 2x (100,000+)
• Wish You Were Here - 6x (6,000,000+)
• Animals - 4x (4,000,000+)
• The Wall - 23x (11,500,000+)
• A Collection of Great Dance Songs - 2x (2,000,000+)
• The Final Cut - 3x (3,000,000+)
• A Momentary Lapse of Reason - 4x (4,000,000+)
• Delicate Sound of Thunder - 3x (3,000,000+)
• Shine On - (9-CD boxed set) (1,000,000+)
• The Division Bell - 3x (3,000,000+)
• Pulse - 2x (2,000,000+)
• Pulse VHS/DVD - 8x (400,000+)
• Is There Anybody Out There? The Wall Live (1,000,000+)
• Echoes: The Best of Pink Floyd 3x (3,000,000+)

Both Dark Side of The Moon, and The Wall are Diamond records, for selling over 10 million copies.

Total US Sales According to RIAA 73,500,000+

(see RIAA)

Rock And Roll Hall of Fame

Pink Floyd were inducted into the Rock and Roll Hall of Fame in 1996, and the UK Music Hall of Fame in 2005. Barrett did not attend any of the inductions, due to his constant illness. Waters did not attend the 1996 induction, citing sickness, but did accept his 2005 induction via camera. Gilmour and Mason attended both events, but Wright could not make the 2005 induction due to eye surgery.

Miscellaneous

In 2002 Q magazine named Pink Floyd as one of the "50 Bands To See Before You Die". Two years later, the same magazine would place Pink Floyd as the biggest band of all time, above the Beatles, the Rolling Stones and Led Zeppelin, according to a complex system for comparing bands which included album sales, charts performance and concert attendance.

Singles

Year	Song	Chart positions				Album
		US Singles Chart	US Mainstream Rock	US Modern Rock	UK Singles Chart
1967	"Arnold Layne"	-	-	-	#20	single only
1967	"Flaming"	-	-	-	-	The Piper at the Gates of Dawn
1967	"See Emily Play"	#134	-	-	#6	single only
1967	"Apples and Oranges"	-	-	-	-	single only
1968	"It Would Be So Nice"	-	-	-	-	single only
1968	"Let There Be More Light"	-	-	-	-	A Saucerful of Secrets
1968	"Point Me at the Sky"	-	-	-	-	single only
1969	"The Nile Song"	-	-	-	-	Music from the Film More
1971	"One of These Days"	-	-	-	-	Meddle
1971	"Fearless"	-	-	-	-	Meddle
1972	"Free Four"	#46	-	-	-	Obscured by Clouds
1973	"Money"	#13	#37	-	-	The Dark Side of the Moon
1973	"Us and Them"/"Time (edited version)"	#101	-	-	-	The Dark Side of the Moon
1975	"Wish You Were Here"	-	-	-	-	Wish You Were Here
1975	"Have a Cigar"	-	-	-	-	Wish You Were Here
1979	"Another Brick in the Wall, Part II"	#1	#1	-	#1	The Wall
1980	"Comfortably Numb"	-	#1	-	-	The Wall
1980	"Hey You"	-	#1	-	-	The Wall
1980	"Young Lust"	-	#6	-	-	The Wall
1980	"Run Like Hell"	#53	-	-	-	The Wall
1982	"When the Tigers Broke Free"	-	-	-	#39	The Wall soundtrack
1983	"Not Now John"	-	#7	-	#30	The Final Cut
1983	"Your Possible Pasts"	-	#8	-	-	The Final Cut
1983	"The Fletcher Memorial Home"	-	-	-	-	The Final Cut
1983	"The Hero's Return"	-	#31	-	-	The Final Cut
1987	"Learning To Fly"	#70	#1	-	-	A Momentary Lapse of Reason
1987	"On the Turning Away"	-	#1	-	#55	A Momentary Lapse of Reason
1988	"The Dogs of War"	-	#30	-	-	A Momentary Lapse of Reason
1988	"One Slip"	-	#5	-	#50	A Momentary Lapse of Reason
1988	"Sorrow"	-	#36	-	-	A Momentary Lapse of Reason
1988	"Time (Live)"	-	#34	-	-	Delicate Sound of Thunder
1988	"Comfortably Numb (Live)"	-	#24	-	-	Delicate Sound of Thunder
1994	"Keep Talking"	-	#1	-	#26	The Division Bell
1994	"Take It Back"	#73	#4	-	#23	The Division Bell
1994	"High Hopes"	-	#7	-	#26	The Division Bell
1994	"What Do You Want from Me"	-	#16	-	-	The Division Bell
1995	"Lost for Words"	-	#21	-	-	The Division Bell
1995	"What Do You Want from Me (Live)"	-	#13	-	-	P*U*L*S*E
1995	"Wish You Were Here (Live)"	-	-	-	-	P*U*L*S*E
2000	"Young Lust (Live)"	-	#15	-	-	Is There Anybody Out There? The Wall Live 1980-81

External links

• Pink Floyd Lyrics

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