Physiopathology of cancer

Brain Cancer Cell

Dr. Julio Hilario Vargas Department of Physiology School of Medicine National University of Trujillo
Source: http://www.alternative-cancer.net/Cell_photos.htm

CANCER
Is a class of disease in which a group of cells display uncontrolled growth through division beyond normal limits, invasion that intrudes upon and destroys adjacent tissues, and sometimes metastasis, in which cancer cells spread to other locations in the body via lymph or blood. These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, and do not invade or metastasize.

Cancers classification
By the type of cell that the tumor resembles and is therefore presumed to be the origin of the tumor. These types include: Carcinoma: Cancer derived from epithelial cells. This group includes many of the most common cancers, including those of the breast, prostate, lung and colon. Sarcoma: Cancer derived from connective tissue, or mesenchymal cells. Lymphoma and leukemia: Cancer derived from hematopoietic (blood-forming) cells Germ cell tumor: Cancer derived from pluripotent cells. In adults these are most often found in the testicle and ovary, but are more common in babies and young children Blastoma: Cancer derived from immature "precursor" or embryonic tissue. These are also commonest in children

Tipos comunes de cncer

- American Cancer Society: Cancer Facts and Figures for Hispanics/Latinos 2006-2008. Atlanta, Ga: American Cancer Society, 2006. Disponible tambin en Internet. - Lipworth L, Tarone RE, McLaughlin JK: The epidemiology of renal cell carcinoma. Journal of Urology 176(6 pt 1):23532358, 2006

Genomic Instability
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional

Phenotypic Changes in the Progression of Neoplasia

Phenotypic Changes in the Progression of Neoplasia

Cancer Immunoediting: The New Surveillance Hypothesis

Zitvogel L et al., Nat. Rev. Immunol., 2006, 6:715.

Cancer Immunoediting: Three Es

Surveillance

At equilibrium immune selection develops leading to tumor escape

Dunn GP et al., Nat. Immunol., 2002, 3:991.

The three Es of cancer immunoediting: host protective versus tumor sculpting actions of immunity

Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004 Aug;21(2):137-48.

Genetic determinants of cancer metastasis

Don X. Nguyen & Joan Massagu. Nature Reviews Genetics 8, 341-352 (May 2007)

Cancers are primarily an environmental disease with 90-95% of cases due environmental factors such as lifestyle, and 5-10% directly due to heredity. Common environmental factors leading to cancer include: tobacco (25-30%), diet and obesity (30-35%), infections (15-20%), radiation, lack of physical activity, and environmental pollutants. Some viruses and bacteria are included too.

Oncogenic Human Viruses

HTLV: Human T-cell leukemia-lymphoma virus; HHV-8: Human herpesvirus-8; KSHV: Kaposis sarcoma herpesvirus

Proto-oncogene
Is a normal gene that can become an oncogene due to mutations or increased expression. The resultant protein may be termed an oncoprotein. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon activation, a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene. Examples of protooncogenes include RAS, WNT, MYC, ERK, and TRK

Src-induced signaling from membrane/adhesions that controls cell behaviour

Biochim Biophys Acta 1602(2), M. Frame, Src in Cancer, 114-130, 2002

Is a gene that has the potential to cause cancer

Representative Oncogenes Activated in Human Tumors

Representative Tumor Suppressor Genes Inactivated in Human Tumors or the Human Germline

Rescuing the function of mutant p53

Alex N. Bullock & Alan R. Fersht. Nature Reviews Cancer 1, 68-76 (October 2001)

Retinoblastoma : the tumor suppressor gene paradigm

DNA damage, repair mechanisms, and consequences

2001 Nature Publishing Group Hoeijmakers, J. H. J. Genome maintenance mechanisms for preventing cancer. Nature 411, 366374 (2001)

DNA repair mechanisms

Signs and symptoms

Local symptoms: Are restricted to the site of the primary cancer. They can include lumps or swelling (tumor), hemorrhage (bleeding from the skin, mouth or anus), ulceration and pain. Although local pain commonly occurs in advanced cancer, the initial swelling is often painless. Metastatic symptoms: are due to the spread of cancer to other locations in the body. They can include enlarged lymph nodes (which can be felt or sometimes seen under the skin), hepatomegaly (enlarged liver) or splenomegaly (enlarged spleen) which can be felt in the abdomen, pain or fracture of affected bones, and neurological symptoms. Systemic symptoms: occur due to distant effects of the cancer that are not related to direct or metastatic spread. Some of these effects can include weight loss (poor appetite and cachexia), fatigue, excessive sweating (especially night sweats), anemia (low blood count) and other specific conditions termed paraneoplastic phenomena. These may be mediated by immunological or hormonal signals from the cancer cells