MICR J210 1st Edition Lecture 23Outline of Last Lecture 1. Human Immunodeficiency Virus2. Hepatitis Virusesa. Hep Ab. Hep Ec. Hep Bd. Hep Ce. Hep DOutline of Current Lecture I. Neoplams and CancerII. Tumor VirusesIII. Slow Virusesa. Conventional Slowb. Unconventional SlowCurrent Lecture- Neoplasm and Cancero Neoplasm (tumor): An abnormal mass of tissue that results when cells divide more than they should or do not die when they shouldo Tumors benign (not cancerous) malignant (cancerous)- A tumor that invades surrounding tissues, is usually capable of producing metastases, may recur after attempted removal, and is likely to cause death unless adequately treated) o Neoplastic transformations (cancers): Result from mutations, or changes, in genes that control cell growth and behavior (eg. P53 gene).  Cell growth control genes normally restrict cell proliferation and direct the cell to repair DNA damage, or failing that, to self-destruct, a process called apoptosis, or programmed cell 'suicide.' These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute. The mutated genes free the cell from these controls, allowing it to divide continuously and to pass on the mutation(s) to its progeny.o What causes these mutations? Many factors come together to cause each type of cancer Induced genetic mistakes can be inherited or they can be acquired as a result of exposure to - Chemicals (carcinogens)- Radiation- viruseso Random mistakes also occur each day in the course of duplicating the three billion units in our DNA during cell division.o No one mutation is enough to make a cell cancerous. Multiple genetic changes, in specific classes of genes, are needed to transform a normal cell into a neoplastic cell that grows out of control.o A small percentage of people inherit a susceptibility for certain types of cancer, putting all their body's cells one step closer to the disease.- Tumor Viruseso Cell TRANSFORMATION BY A VIRUS:  Changes in the biological functions of a cell that result from regulation of the cell by viral genes and that confer on the infected cell certain properties characteristic of neoplasia These change often result from integration of the viral genome into the host cell genome. This integration may result in the host cell neoplasm by2 general mechanisms:- A viral genome that can cause a tumor is called an oncogene, is carried into a cell by the virus and cause the host cell to take on new properties such as immortalization and uncontrolled nonstop growth (i.e. HTLV I & II)- The integration of virus into the host cell genome may inactivate the regions of host cell genome that code for prevention of unwanted cell divisions (cell growth brake system, i.e. HPV)o With few exceptions, all DNA viruses are capable of causing tumors under optimal conditions. RNA viruses that go through a DNA intermediate stage, such as HIV, are also able to induce tumors Estimates range from 3 – 8 % of the human genome as being comprised of sections of viral DNA.  These and other parasitic, self-replicating pieces of nucleic acids have evolved with us over millions of years after being inserted into our DNA by the viruses that infected our ancestorso Tumor viruses: that cause human cancer: HUMAN PAPILLOMA VIRUSE (HPV): Cervical cancer- Warts : Skin, larynx, genitals (condyloma acuminata)- 95% of HPVs cause tumors that are benign (common and plantar warts), most can be frozen off with liquid N2 or surgically removed as an out-patient procedure. Generally no problem unless the warts begin to grow- There is a strong correlation between HPV and cervical carcinoma- 99% of all cervical carcinoma tissues are positive for HPVs. The other 1% may be positive but can not be detected as yet- About 1% of sexually active adults had visible genital warts, while 15% have a subclinical infection - PAP smear tests (developed in 1928 by Dr. George Papanicolaou)o Sexually active young women (after 1st intercourse) should get a pap test every year. (PAP smear=looking for precancerous cells)- HPV alone does not seem to be sufficient to cause cancer. Certain pre-disposing co-factors are also involved:o Smoking, Intercourse at a young age, multiple sex partners,long-term oral contraceptive use HBV, HCV: Liver cancer- Strong correlation with liver carcinoma- A vaccine is available for HBV which looks very good EPSTEIN-BARR VIRUS (EBV): Burkitt’s lymphoma- EBV causes Burkitt's lymphoma in the African population- Out of 42,000 infected people, 42 got Burkitt's lymphomao All were EBV antigen+, and all had antibody titers much higher than average o All had malaria which suppresses immunity, and that may be a co-factor- Similar correlation exists between EBV and nasopharyngeal carcinoma in the Chinese population. o All are EBV antigen+, and all have elevated antibody titers HUMAN T-CELL LYMPHOTROPIC VIRUS (HTLV) I & II : Leukemia- ss RNA-containing, enveloped retrovirus, a cousin of HIV-1- Causes adult T-cell leukemia, especially in the Japanese population- Rare disease but 100% correlation with HTLV-1- HUMAN HERPES VIRUS-8: Kaposi’s sarcoma in HIV patients- Slow Viruseso Cause of several chronic degenerative diseases All affect the CNS–spongiform encephalopathy All are rare and always lethalo 2 general categories Conventional slow viruses- Measles virus (Sub-acute sclerosing pan-encephalitis (SSPE) o A very rare, late-onset, neurological complication of natural measles infectiono 1 in 100,000 people infected with measles develop SSPEo It occurs anywhere from 2-10 years after contracting measleso Successful measles vaccination programs directly and indirectly protect the population against SSPE and have thepotential to eliminate SSPE through the elimination of measles- JC (John Cunningham) virus (Progressive multi-focal leukoencephalopathy: PML)o JC virus infects most healthy people (70-90%), but is associated with progressive multifocal leukoencephalopathy in the immunosuppressed. o PML is an opportunistic demyelinating disease caused by the usually non pathogenic JC Polyomavirus Unconventional slow growing agents (prions)- Kuru (shaking death)o Tribe in New Guinea islands off SE Asia - Cannibals - Consumed their dead relatives’ brains as a sign of respect. Only women and children handled the brain tissues and got infected. o Severe shaking and