cell kinetics – Flashcards
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| what are the main kinds of cells in the body in terms of growth? which are at most risk of becoming malignant? |
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| continously dividing cells (bone marrow, epithelial lining of skin, bronchus, endocrine ducts), latent cells (will regenerate if damaged; liver, renal, glandular epithelial, endothelial fibroblasts, lypmhoctes, chondrocytes, osteoblasts), and static cells (non-dividing such as neurons, skeletal/cardiac muscle). dividing and latent cells are most at risk for becoming malignant |
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| what is atrophy? does it mean cells are damaged? |
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| a decrease in tissue/cell size, which is typically part of normal profile maintenance and not indicative of damage (it is reversible) |
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| what is hypertrophy? what is it usually due to? |
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| hypertrophy is an increase in size of cells, usually due to an overload event where cells are struggling and start to produce more proteins |
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| what is hyperplasia? metaplasia? neoplasia? |
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| hyperplasia is increased cell #, which can put the system at risk for conversion to abnormal phenotype. metaplasia is conversion of one cell type to another, (eg. smoker's epithelial lung lining converts to squamous or barret's esophagus). neoplasia means new growth, it can be benign or malignant |
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| what are the post-menopausal endometrial state and alzheimer's disease examples of? |
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| atrophy |
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| what are common causes of atrophy? |
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| decreased function, ischemia, loss of hormonal stimulation, denervation, compression, occulsion of ducts serving secretory glands, and apoptosis (can be due to CA chemo, radiation, or immunologic injury) |
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| what are some examples of cells that might undergo hypertrophy? |
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| myocardial cells and glomerular cells |
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| what is dysplasia? |
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| a potentially reversible mild to moderate upregulation and distortion of cell signalling w/nuclear enlargement and cell proliferation. with dysplasia, a different ratio of nucleus to cytoplasm called a nuclear cytoplasm ratio differential occurs and cells start to grow on top of each other. |
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| what is desmoplasia? |
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| TGF activation adjacent to neoplam with collagen formation (hardness of tumors) |
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| what is metrorrhagia, what might this be seen with? |
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| endometrial hyperplasia |
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| what is the visible difference between hyperplasia and dysplasia? |
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| with dysplasia, you would see more abnormal nuclei |
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| what is barrett's esophagus? |
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| metaplasia where the distal esophagus is typically squamous and becomes columnar close to the stomach due to GERD |
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| what is the common timeline for cells progressing toward malignancy? |
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| normal epithelium -> hyperplasia -> squamous metaplasia -> dysplasia -> carcinoma in situ (cells look extremely abnormal, can have large, small or different shaped nuclei, can have a lot of mitotic figures) -> invasive carcinoma (invasion to the submucosal area, metastasis doesn't always occur). multiple gene changes are needed for a true carcinoma formation) |
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| how do dysplasias or disordered formations manifest themselves in development, cytogenetics, and neoplasias? |
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| developmentally, dysplasia describes developmental defects (fibrous dysplasia of bone, renal dysplasia). cyogenetically, dysplasia describes abnormal nuclear enlargement and increased nuclear/cytoplasmic ratios. in tems of neoplasias, dyplasia may describe intraepithelia precursor lesions in the later development of malignant neoplasia and is often renamed as an intraepithelial neoplasia named for place of origin, (CIN, VIN, VAIN, PIN, EIN, PAIN; ex. CIN = cervical intra-epithelial neoplasia) |
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| what is a benign neoplasia? |
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| a focal & confined new growth that is slow, uniformly proliferating, composed of mature cells, usually diploid (proper DNA amount) and generally no threat to the pt |
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| what is a malignant neoplasia? |
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| malignant neoplasias are characterized by rapid and disturbed proliferation of immature pleomorphic cells, usually aneuploid (improper DNA amount) which invade across tissue boundaries, metastasize and usually cause morbidity (significant signs/symptoms of disease) and sometimes mortality |
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| what are other neoplasm-like processes? |
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| hamartoma, choristoma, and tertoma |
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| what is a hamartoma? |
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| a developmental proliferation of cells native to an organ (eg. hemangiomas anywhere, chondroma in lung, angiomyolipoma of kidney) |
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| what is a choristoma? |
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| a developmental flaw; consisting of cellular proliferation @ ectopic sites (eg. pancreatic tissue in the stomach) |
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| what is a teratoma? |
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| a germ cell (ovary/testicle) aberration with development of ectoderm, mesoderm, and endoderm in varying stages of maturation. (teeth and hair are found in teratomas which can be found almost anywhere in the body) |
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| what are the 2 pathways that can result from cellular insults such as ionizing radiation, carcinogens, and mutagens? what mutations might affect this? |
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| cells will be pushed into a cell recovery/apoptotic pathway OR malignancy will develop. certain mutations in oncogenes or tumor suppressors however will lead to loss of cell cycle regulation and the repair/apoptotic pathway cannot occur |
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| how many doublings of a cell does it take to get to a palpable mass of cells? x ray visible? |
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| 30, which gives ~ 1 billion cells. 27 doublings will give a mass visible by x ray. 35 will give huge tumors |
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| when a tumor grows, does its diameter double? |
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| tumor volume doubles not diameter (1 cm nodule only increases 3 mm with doubling, 2m increases 5mm) |
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| at what point does a breast carcinoma have a 50% chance of metastasis? |
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| 3.6 cm |
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| how many cells does it take to get a 1 cm breast carcinoma? |
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| 10^9, which requires ~30 doublings, each doubling takes 100 days, so from start to finish a 1 cm mass would take 8 years to develop |
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| within categories of the same tumors are doubling times different for pts of different ages? |
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| yes, younger people will have faster doubling times than older people |
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| why are cancers with long doubling times (1000 days) missed more often? |
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| they take longer to become apparent |
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| why is understanding cancer growth rates important? |
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| understanding the natural hx, determination of reasonable screening/follow up intervals, designing therapeutic interventions, prognostication - predicting likelihood of metastasis, and avoiding malpractice |
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| what is the correlation between cancer growth rate (measured in doubling time) and survival rate? what are 2 slow growing cancers that a majority of the population has? what are some considerations for treating such slow growing cancers? |
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| pts with slow growing cancers have much higher survival rates, for example, a large amount of the population has prostate (males) and/or thyroid cancer diagnosed at autotopsy. a desicion has to be made as to whether the expense and side effects are worth treating cancers with effects that probably will never be felt (b/c something else will probably kill the pt first) |
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| what is a benefit of using colchicine to treat pts with hepatitis-related cirrhosis? |
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| colchicine is an is an anti-inflammatory agent that interacts with inflammatory cell microtubules, interferes mitosis and inhibits leukocyte adherence, motility and chemotaxis. pts treated with it are less likely to develop a hepatocellular carcinoma, and if they do it grows much slower |
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| what is ploidy? |
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| ploidy is the analysis of the DNA index, where a DNA index of 1 means diploid. any change from diploid is called aneuploidy and can be categorized as hyperdiploid, tetraploid, hypertetraploid |
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| how does aneupliody correlate with severity of neoplastic malignancy? |
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| adenocarcinomas which are benign have only 30% aneuploidy, while malignant carcinomas are 82% aneuploidy. essentially the more aneuploidy, the more damage has occurred. |
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| how does ploidy correlate with doubling time? |
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| tumors cells with a higher doubling time have more aneuploidy |
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| can benign cells still have aneuploidy? how is this possible? what are some examples of such? |
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| yes, often this is b/c they remain encapsulated, they don’t move from that organ site, and/or they are confined to that site. examples: follicular adenomas of the thyroid, benign hurthle cell tumors, thymomas, meningiomas, astrocytomas, nevi, and hepatic adenomas |
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| what are mitotic figures? what can be determined from observing them? |
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| mitotic figures are chromosomes lined up with microtubles in the middle of the cell (evidence the cell is undergoing mitosis). @ 0-3 mitotic figures pts still have a 60% survival rate, but with >20 mitotic figures, pts only have about a 20% survival rate |
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| can a tumor's level of malignancy change over time? |
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| yes, the level of malignancy can change over time for individual tumors |
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| what is the paradox of cell kenetics? what causes this? |
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| a high growth rate can lead to either rapid death or a rapid response to chemotherapy. this is due to the fact that chemotherapy exerts its cytotoxic effects largely during the S phase of the cell cycle and many cells in rapid growth tumors are actively synthesizing DNA, and will go to the apoptotic pathway with chemotherapy |
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| what would the chemotherapy approach be to slow-growing tumors? |
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| slow growing tumors are more differentiated and a more prolonged approach will work better |
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| what are determinants of tumor growth? |
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| generation time (time spent in cell cycle), growth fraction (% cells in cycle G0->G1), and cell loss through necrosis/apoptosis |
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| why would a tumor's center become necrotic? |
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| if it was not stimulating enough angiogenesis (which is usually needed for metastasis) and became ischemic |
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| why can't early diganosis and treatment of primary tumors always prevent metastasis? |
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| micrometastases; individual or a few cells that migrate from the tumor to other areas of the body can undetectably spread through the body |
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| are aggressive or indolent tumors noticable faster? |
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| aggressive |
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| what is the lead-time bias? |
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| slower growing tumors take longer to kill a pt from the point of diagnosis than aggressive tumors, but both pts may die at the same point - just the pt with the slow tumor had an earlier heads up. definition from wikipedia: "Lead time bias is the bias that occurs when two tests for a disease are compared, and one test (the new, experimental one) diagnoses the disease earlier, but there is no effect on the outcome of the disease-- it may appear that the test prolonged survival, when in fact it only resulted in earlier diagnosis when compared to traditional methods. |
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| how does age affect the desicion to treat prostate cancer? |
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| young men diagnosed with prostate cancer may be treated with sx, radiation, androgen deprivation, while older men may just be watched/waited b/c harms may outweight the costs, and something else might kill them first |
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| what are the chances of dying of prostate cancer? being clinically diagnosed with it? having a histologically detectable prostate cancer? |
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| the lifetime risk of a 50 year old man developing histologically detectable prostate cancer is about 42%, the life time risk of developing clinically detectable prostate cancer is 9.5% and the chances of dying of the disease is 2.9% |
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| what is the median age of death from prostate CA? |
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| 80 w/71% of those deaths being in men over 75 |
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| what is the recommendation for prostate cancer screening in differing ages of men? |
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| prostate cancer screening is recommended against in men over 75 and recommends screening in younger men for the most part |
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| what are the goals of cancer treatment? |
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| inhibition of cell proliferation, induction of apoptosis, and promotion of terminal differentiation of cells |
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| how can endometrial adenocarcinomas be treated? |
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| progesterone can help stimulate cell differentiation |
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| how does arsenic trioxide therapy for acute promyelocytic leukemia work? |
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| this disrupts the fusion protein RAR-a (which promotes abnormal growth) as well as induction of apoptosis with increased caspase expression |
