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UMass Amherst MICROBIO 160 - Typical Cancer Progression

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MICROBIO 160 1st Edition Lecture 7 Outline of Last LectureI. Evidence for Immune Reaction toTumorsII. How does Cancer Escape DetectionIII. Cancer VaccinesIV. Antibodies that Stimulate Cell KillingV. ConjugatedAntibodiesVI. Antibodies that Block ReceptorsOutline of Current LectureI. Typical Cancer ProgressionII.Primary and Secondary Cancer III.Cancer Spread and Mortality IV.How Cancer SpreadsV. The Metastatic ProcessVI.Vasculogenesis vs.AngiogenesisVII.Tumorsneed Blood Vessels to GrowVIII.Cancer Cells ProduceAngiogenesis-StimulatingMoleculesIX. Treating Cancer by Inhibition ofAngiogenesisX.TumorAngiogenesisCurrent LectureMutations can be activated by 3 gene families:•DNArepair genes•Tumor suppressors•Oncogenes•Hyperplasia: the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells (initial stage in the development of cancer) —cells begin to enlarge and less organized•Dysplasia: abnormality of development of growth anddifferentiation—cells grow on top of each other/ overlapping•Carcinoma in situ: cancer that has stayed in the place where it began and has not spread to neighboring tissues—still localized, hasn’t startedto invade•Once you collect enough genes, it leads to cancer and cancer invades(transformation)Primary and Secondary Cancer:•Metastasis is the main reason cancer can be difficult to cure-Inorder to spread, some cells fromthe primary cancer must break away, travel to another part of the body and start growing there—chances of survival are much better if you find it before it spreads•Primary tumor (the first tumor) may live in the liver and can metastasize to brain (second tumor: where the cancer spreads)•Cells that metastasize will be like the original tumor-Breast cancer tissues that grow in the brain will have breast tissues in the brain as well (the second tumor resembles the primary)•Tumor causes cells to stick together—cancer cells separate from the tumor then spread to other parts of the bodyCancer Spread and Mortality:•You have a tumor, hasn’t started to metastasize yet (small)— the cancer cells are sending chemical messages to different organs in the body to set up an area that it is as favorable asfavorable as possible for when it isgoing to metastasize-Stomach cancer likes to metastasize to bone, send out signals to the spine to take on characteristics that will make it more favorable—when cancer lands on the bone it makes it easier to metastasize•Metastasizes are so dangerous because they overwhelm the organ— they can grow quickly and cause the organ to shut down-Body starts off with one cell, it could take years for it to be detected— it eventually gets to the point where it’s big enough and recognized by the immune system— immune keeps it small and controls proliferation•90% of cancer deaths occur because of where cancer ends up, not where it begins-Most metastatic niches or landing pads, allow cancerous cells to colonize a secondary organ-When cancer cells travel to a vital organ, they often overwhelm the cells and cause the organ to shut downCancer Spreads•Local invasion•Blood: When cancer cells slip out of capillary into body tissue•LymphaticsSteps Involved in the Metastatic Process:•Cancer cells can sense from chemical messages when it has landed•The ability to invade differs among cancer cells and tumor-Extravasation:escaping the blood vessel-1/1000survive because theyare highly exposed— othercells cause them to getbombarded1.Cancer cells invade surrounding tissues and vessels-Theability to invade differs among cancer cells and tumors-Eachcancer has a preferred target tissue2.Cancer cells are transported by the circulatory system to distant sites-Relativelyfew cancer cells survive the voyage through the bloodstream3.Cancer cells reinvade and grow at new locationCancer cells are able to invade because:•Decreased adhesiveness: lose anchoring proteins•Activated motility: the ability to move randomly— gain ability to move past macrophages•Protease production (squiggly lines: protein fibers in tissues)—proteins get cut by the proteaseDetecting Metastasis: gold standard for looking at metastasis•PETscan: it is a way of looking at the body and different organs-In a PETscan, cancer gets highlighted in pink— pink resembles the abnormal lymph nodes•Metabolic rate in cancer is higher than normal cells (dividing and doing everything faster— glucose: provides the energy— sucks up the most)Vasculogenesis andAngiogenesis:•Vasculogenesis: the development of new blood vessels when there areno pre- existing ones-Undifferentiated cells that grow blood vessels on their own-Endothelial precursor cells (angioblasts) migrate and differentiate in response to local cues (such as growth factors) to form new blood vessels-Has immature cells (angioblasts) become angiogenesis•Angiogenesis: the development of new blood vessels from pre-existing on-Mature endothelial cells lining the blood vessels start to divide in response to local cues to form new blood vessels-Cells keep dividing— causing them to grow out towards the cancer-Has mature cellsTumors Need Blood Vessels to Grow:•Scientists have noticed thattumors only grow to a certainsize then start to die (they diefrom the inside out)-Nomatter how many nutrients they are given, they still dieExperiment:•Tumor cells were injected into anterior chamber of an eye (it has no blood supply and is unable to induce blood supply)•Tumor cells were implanted into the iris (blood supply easily induced)•RESULT:Anterior chamber tumor did not grow(signals couldn't travel to where they wanted to go), Iris tumor grew (doesn’t supply blood to the tumorCells ProduceAngiogenesis-Stimulating Molecules:1. Cancer cells surrounded by filter with tiny poresVasc2. Place chamber containing cancer cells beneath the animal’s skin3. Blood vessels growth (angiogenesis) occurs outside chamber•If you put a tumor with tissue (flow that carries the tumor)—near blood supply;blood vessels grow towards cancer cells1. Cancer cells produce VEGF (a signaling protein that promotes the growth of new blood vessels)— go towards Receptor2. Receptor produces a signal that is recognized by endothelial cells as starving tissue so it turns on genes and the genes get activated, proliferate, and migrate— this is in attempt to get blood vessels to


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UMass Amherst MICROBIO 160 - Typical Cancer Progression

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