2 PRE LECTURE QUIZ (True/false) Cancer is a disorder of altered cell differentiation and growth.Surgery, radiation, and chemotherapy are the only identified treatment modalities for cancer.The Papanicolaou test is a cytologic method used to detect cancer cells.Cell differentiation is the process whereby proliferating cells are transformed into different and more specialized cell types.Benign neoplasms are less differentiated tumors that grow in a crablike manner to invade surrounding tissues, have cells that break loose and travel to distant sites to form metastases, and inevitably cause suffering and death unless their growth can be controlled through treatment.
3 PRE LECTURE QUIZThe process of ______________ a tumor involves the microscopic examination of cancer cells to determine their level of differentiation and the number of mitoses.In general, benign tumors usually are named by adding the suffix __________ to the parenchymal tissue type from which the growth originated.The term ________________ is used to describe the development of a secondary tumor in a location distant from the primary tumor.________________ spread would involve metastasis that occurs by way of the blood vessels.________________ syndromes are defined as the production of signs and symptoms at sites that are not directly affected by the disease or cancer.gradingHematogenicMetastasis-omaParaneoplastic
4 NeoplasiaNeoplasms proliferate to form new tissueThey do not wait for signals from the body that the new tissue is neededThey ignore signals to stop dividingThey often do not mature normally (differentiate) to do the “job” the tissue is supposed to doThey do not die off (apoptosis) to keep the number of total cells constant
6 The Cell CycleNormally, the number of cells produced = the number of cells that dieThe total number of cells in the body remains constant
7 Growth FactorsCells divide only when they are told to do so by growth factorsThese cause stable cells to enter the cell cycle and divide
8 Growth Factors (cont.)Attach to receptor proteins Which often work by affecting G proteins Which turn on enzymes (proteins) Which make second messengers Which go down inside the cell and make it divide
9 Growth Factor Receptors Now this cell is ready to respond to growth factors from another cellThey bind to the receptors and stimulate cell division
10 The normal genes that code for normal proteins used in cell division Proto-oncogenesThe normal genes that code for normal proteins used in cell divisionGrowth factorsGrowth factor receptorsG proteinsEnzymes that produce second messengersGenes that turn the production of these proteins on and off
12 Oncogenes Oncogenes are mutated proto-oncogenes They still code for the proteins needed for cell divisionBut they might produceToo much of the proteinAn abnormal proteinProtein that turns on all by itselfProtein that is made when it is not neededProtein that cannot turn cell division offProtein that should be made by a different cell
13 QuestionTrue or False: Oncogenes code for normal proteins used in cell division.
14 AnswerFalse The statement describes proto-oncogenes. Oncogenes are mutated proto-oncogenes that code for abnormal proteins.
15 Checkpoints in Cell Division Permanent cellCyclin proteins measure whether the cell has grown large enough to divideCyclins make sure the cell has made the proteins needed to separate the chromosomesG0MG2MitosisInter-phaseG1Cyclins check that the DNA has been correctly duplicatedSR
16 Tumor-Suppressor Proteins The checkpoints usually stop the division of mutated cellsThey keep most mutations from developing into cancerSo the proteins that control the checkpoints are called tumor-suppressor proteinsCyclinsCyclin-dependent kinasesCyclin inhibitors (p53)If the genes for these proteins were mutated, you might get many more cancers
17 Cell Division Requires Duplicating the DNA Telomeres: DNA sequences at the ends of the chromosomesThe enzymes that duplicate DNA attach hereThe end of the telomere does not get duplicatedWhat will happen to the telomere as the cell continues dividing?A man has a mutation that causes some of his cells to rebuild their telomeres after every division. Is this a good thing or a bad thing? Why?
18 Oncogenesis Initiation: Initial mutation occurs Promotion: Mutated cells are stimulated to divideProgression: Tumor cells compete with one another and develop more mutations which make them more aggressive
19 Labile = Apt or likely to change Normal CellsLabile = Apt or likely to changeNormally, after a cell has divided, it becomes either a permanent cell or a stable cellThese cells stop reproducing and continue working for the bodyMPermanent cellG2G1G0SStable cell
20 Differentiation“Grown-up” cells are called differentiated because they look different from one anotherYou can tell a spleen cell from a skin cell
21 Cell MutationWhen differentiated, “working” cells mutate, they form differentiated “working” tumors— benign tumorsWhen undifferentiated, rapidly dividing cells mutate, they form rapidly dividing tumors—malignant tumors
22 QuestionWhen a well-differentiated cell mutates, is it more or less likely to become a malignant tumor?MoreLessDegree of differentiation has no bearing on whether a tumor is malignant or benign.
23 AnswerLessThe more differentiated a cell is when it mutates, the more likely it is to become a benign tumor. If poorly differentiated cells mutate, the tumor is more likely to become malignant.
24 Naming Tumors Benign tumors: tissue name + “-oma” Glioma - tumor of the brain composed of neuroglia.Malignant tumors (cancers)Epithelial tissue: tissue name + “carcinoma”Basal cell carcinomaMesenchymal tissue: tissue name + “sarcoma”Osteo sarcoma
25 Contain cells that look like normal tissue cells Benign TumorsContain cells that look like normal tissue cellsMay perform the normal function of the tissue (like secreting hormones)This may lead to oversecretionUsually have a capsule around themUsually do not invade neighboring tissuesBut they can damage nearby organs by compressing them
26 Malignant TumorsContain cells that do not look like normal adult cellsThese cells divide rapidly, so:Tumors grow quicklyCells mutate faster and can change typeThe tumor does not have clear boundaries and sends “legs” out into surrounding tissue (the word cancer means “crab” and is based on these crablike legs)Do not perform the normal functions of the organMay secrete hormones associated with other tissuesCan compress and/or destroy the surrounding tissues
29 QuestionWhat gross anatomic feature of the lung tumor you just saw makes it likely to be malignant?The tumor is growing quickly.The tumor has a poorly defined border.Cells do not look like normal cells.All of the aboveb and c
30 Answerb and cGross anatomy can be viewed with the naked eye. Although rapid growth is a characteristic feature of malignant tumors, this cannot be determined from the slide. However, the lack of a clear border, and the different appearance of the group of cancer cells can be clearly seen.
31 MetastasisCells in a primary tumor develop the ability to escape and travel in the bloodImagine you were a cancer cell. What abilities would you need to survive in the tumor?What abilities would you need to metastasize?
32 ScenarioMrs. T Has Liver CancerHer doctor did an initial molecular diagnosis and put her on targeted therapy; the tumor shrank by almost 75%Two years later the tumor was growing again, and this time it did not respond to the drugLast year she was diagnosed with metastases in her femur that has not responded to the drug eitherMrs. T wants to know why the cancer cells stopped responding. Are they not all the same cells?
33 Manifestations of Cancer Changes in organ function (organ damage, inflammation, and failure)Local effects of tumors (e.g., compression of nerves or veins, gastrointestinal obstruction)Ectopic hormones secreted by tumor cells (paraneoplastic disorders)Nonspecific signs of tissue breakdown (e.g., protein wasting, bone breakdown)
34 Changes in Organ Function Organ failureBenign tumors may cause overproduction of normal organ secretionsMalignant tumors may occasionally cause overproduction (as in thyroid cancer), but more commonly decrease production of normal organ secretions
35 QuestionWhy do malignant tumors usually cause a reduction in the amount of hormones the affected organ produces?Organ damageInflammation of the organOrgan failureAll of the abovea and c
36 AnswerAll of the aboveEffects of malignant tumors on the organ system include inflammation and damage, which ultimately lead to organ failure. In all cases the organ cannot function optimally, and is unable to secrete the normal/typical amount of hormones.
37 Local Effects of Tumor Growth BleedingCompression of blood vesselsSuperior vena cava syndromePortal hypertensionCompression of lymph vesselsEdema, ascites, effusionCompression of hollow organsCompression of nervesPain, paralysis
38 Paraneoplastic Syndromes Cancer cells produce hormones or hormone-like proteinsADHACTHPTH-related proteinCancer cells produce proteins that affect clottingParaneoplastic neurologic disorders
39 Clinical Manifestations of Cancer Cancer cachexia syndromeWeight lossMuscle wastingWeaknessAnorexiaAnemiaCachexia -Greek meaning Bad Condition