All lecturer of cancer dr faten zahran


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All lecturer of cancer dr faten zahran

  1. 1. 1. What is the cancer?2. How would you define cancer?3. Multiple changes lead to cancer.4. Loss of normal growth control.5. Naming cancers.6. Characters of cancer cells.7. Malignant Versus benign Tumors.8. Why cancer is potentially dangerous?9. Metastasis.10.Quiz.
  2. 2. To understand the origin of cancer and what ismeaning.
  3. 3. Cancer is a disease that begins when asingle cell escapes from the regulation of itsown division.
  4. 4. How would you define cancer? •A collection of different diseases •Cancers display uncontrolled growth •Metastasis=Migration from the site of originCancer=malignant growthMalignant=ability of growth to migrate and invade surrounding tissuesNeoplasm=new growthTumor=benign (harmless) and malignant growths
  5. 5. Multiple changes lead to cancer 1. Requires multiple exposures to chemicals or radiation, leading to changes in DNA 2. Cell cant repair some damage 3. Cell can commit suicide (programmed cell death) if badly damaged 4. Cancers except leukemia associated with age
  6. 6. Cancer can originate almost anywhere in thebody:Carcinomas, the most common types of cancer, arise from the cells that coverexternal and internal body surfaces. Lung, breast, and colon are the most frequentcancers of this type in the United States.Sarcomas are cancers arising from cells found in the supporting tissues of the bodysuch as bone, cartilage, fat, connective tissue, and muscle.Lymphomas are cancers that arise in the lymph nodes and tissues of the body’simmune system.Leukemias are cancers of the immature blood cells that grow in the bone marrowand tend to accumulate in large numbers in the bloodstream.
  7. 7. Leukemias: Some common carcinomas: Bloodstream Lung Lymphomas: Lymph nodesBreast (women) Colon Some common Bladder sarcomas: Prostate (men) Fat Bone Muscle
  8. 8. Loss of Normal Growth ControlCancer arises from a loss of normal growth control. Innormal tissues, the rates of new cell growth and old celldeath are kept in balance. In cancer, this balance isdisrupted. This disruption can result from uncontrolledcell growth or loss of a cell’s ability to undergo cellsuicide by a process called “apoptosis.” Apoptosis, or“cell suicide,” is the mechanism by which old or damagedcells normally self-destruct.
  9. 9. Normalcell division Cell Suicide or Apoptosis Cell damage— no repair Cancercell division First Second Third Fourth or mutation mutation mutation later mutation Uncontrolled growth
  10. 10. Naming CancersScientists use a variety of technical names to distinguish the manydifferent types of carcinomas, sarcomas, lymphomas, and leukemias.In general, these names are created by using different Latin prefixesthat stand for the location where the cancer began its uncheckedgrowth. For example, the prefix “osteo” means bone, so a cancerarising in bone is called an osteosarcoma. Similarly, the prefix“adeno” means gland, so a cancer of gland cells is calledadenocarcinoma--for example, a breast adenocarcinoma.
  11. 11. Cancer Prefixes Point to LocationPrefix Meaningadeno- glandchondro- cartilageerythro- red blood cellhemangio- blood vesselshepato- liverlipo- fatlympho- lymphocytemelano- pigment cellmyelo- bone marrowmyo- muscleosteo- bone
  12. 12. Characters of Cancer Cells:1. divide when they shouldn’t2. don’t cooperate3. don’t respond to normal signals4. don’t do their specialized job5. migrate away from their original site6. enter the blood stream7. move to other parts of the body
  13. 13. Growth of a tumor depends on: 1.Nutrients 2. Blood supplySurvival of cancer cells depends on: 1. Escaping detection 2. Finding fertile ground to migrate to
  14. 14. Malignant versus Benign TumorsDepending on whether or not they can spread by invasion andmetastasis, tumors are classified as being either benign ormalignant. Benign tumors are tumors that cannot spread by invasionor metastasis; hence, they only grow locally. Malignant tumors aretumors that are capable of spreading by invasion and metastasis. Bydefinition, the term “cancer” applies only to malignant tumors.
  15. 15. Benign (not cancer) tumor Malignant (cancer) cells cells grow invade neighboring only locally and cannot tissues, enter blood spread by invasion or vessels, and metastasize metastasis to different sitesTime
  16. 16. Why Cancer Is Potentially Dangerous?A malignant tumor, a “cancer,” is a more serious health problem thana benign tumor because cancer cells can spread to distant parts of thebody. For example, a melanoma (a cancer of pigmented cells) arisingin the skin can have cells that enter the bloodstream and spread todistant organs such as the liver or brain. Cancer cells in the liverwould be called metastatic melanoma, not liver cancer. Metastasesshare the name of the original (“primary”) tumor. Melanoma cellsgrowing in the brain or liver can disrupt the functions of these vitalorgans and so are potentially life threatening.
  17. 17. Brain Melanoma cells travel through bloodstream Liver Melanoma(initial tumor)
  18. 18. MetastasisCells from the original tumor can break away and startnew cancers at distant locations, a process calledmetastasis
  19. 19. Cancer cells can travel virtually anywhere in the body viathe lymphatic and circulatory systems. The lymphaticsystem collects fluids lost from microscopic blood vesselscalled capillaries. Some blood is lost from the thin wallsof the capillaries; the lymphatic system collects the lostfluids (called lymph) and returns them to the blood. Lymphnodes are small ducts that filter the lymph.
  20. 20.  1. Cancer display controlled growth.2. Malignant ability of growth to migrate and invade surrounding tissues.3. All types of cancer associated with age.4. Loss of cell suicide ability related to cancer progression.5. Myocarcinoma related to liver cancer.6. survival of cancer cells depends on blood supply.7. Cancer cells can travel any where in the body via circulatory and excretory systems.
  21. 21. 1. Plasma Membrane2. Nucleus3. Cytoplasm4. Mitochondria5. Cytoskeleton6. Extracellular matrix/cell junctions
  22. 22. To understand what goes wrong in a cancer cell, weneed to know more about the structure and functionof normal cells. In todays class we will reviewsome basic cell biology and point out some ofchanges that occur in cancer cells.
  23. 23. Plasma membrane
  24. 24. 1. forms boundary of cell 2. critical for receiving signals from outside cell and deciding what enters cell. 3. phospholipid bilayer 4. contains embedded proteins, such as receptors Normal cell Cancer cellLet nutrients and oxygen in, Same as normal cellwastes outReceive/send signals to other cells Incorrectly process signals/send wrong signals
  25. 25. Nucleus
  26. 26. Nucleus = membrane bound organelle that contains thegenetic material. Changes in appearance when celldivides. Normal cell Cancer cellNucleus contains genes Some of the genes are "mutated"Nucleus directs cell to make Mutated genes in the nucleusproteins direct synthesis of alteredDNARNA protein proteinsNucleus receives chemical signals Cancer cell nucleus receives thefrom cytoplasm that alter gene wrong signals; tell cell to divideexpression or to turn on inappropriate genes
  27. 27. CytoplasmConsists of fluid (cytosol), proteins, ribosomes (sites ofprotein synthesis), and membrane bound organellesOrganelles include•Mitochondria: Energy metabolism•Endoplasmic reticulum and Golgi body: Proteinprocessing•Lysosomes: Degration of organelles and proteins
  28. 28. Mitochondria
  29. 29. Mitochondria = organelles involved in energy metabolism and cell death Normal cell Cancer cellEfficiently make ATP, the energy Hog ATP and starve out normalstoring molecule cellsOld cells receive a signal to die Old cells not told to die; get tooso they are replaced by new cells many cells cancer
  30. 30. Cytoskeleton:
  31. 31. cytoskeleton=Network of fibers throughout the cytoplasmMade of filamentous proteins: tubulin, actin, keratin1. Provide structural support2. Determine cell shape3. Involved in cell movement4. Anchor cell-cell connections5. Move organelles around6. Move chromosomes during cell division
  32. 32. Normal cell Cancer cellPredetermined cell shape Become metastatic, able to change shape and migrate from original siteDivide in response to Cell division not regulatednormal signals
  33. 33. Extracellular matrix/cell junctionsECM=material outside cell that holds cell in place yet allows formovement of nutrients, oxygen, and signaling molecules.Includes a lot of "sticky proteins" (collagen, proteoglycan,fibronectin). Normal cell Cancer cellCells stay put Cells migrate awayCells anchored to ECM Secrete enzymes that break down ECM
  34. 34. Intercellular junctions1. Hold cells together2. Some allow communication between cells3. Some prevent fluid from seeping into tissues4. Most common in epithelia Normal cell Cancer cellCells attached to each other Cells lose their attachmentsCell communication good Cell communication reduced
  35. 35. 1. ……………….…………..……... directs cell to make proteins.2. ……………….……….Let nutrients and oxygen in, wastes out.3. …......… genes in the nucleus direct synthesis of altered proteins.4. …..………...efficiently make ATP, the energy storing molecule.5. Cytoskeleton Made of filamentous proteins: ……….., …..….., ………….…
  36. 36. 1. Cancer detection and diagnosis.2. Early cancer may not have any symptoms.3. Biopsy.4. Microscopic appearance of cancer cells.5. Cancer classification.6. Tumor grading.7. Tumor staging.
  37. 37. Cancer Detection and DiagnosisDetecting cancer early can affect the outcome of the disease for somecancers. When cancer is found, a doctor will determine what type it isand how fast it is growing. He or she will also determine whethercancer cells have invaded nearby healthy tissue or spread(metastasized) to other parts of the body. In some cases, findingcancer early may decrease a person’s risk of dying from the cancer.For this reason, improving our methods for early detection iscurrently a high priority for cancer researchers.
  38. 38. Early Cancer May Not Have Any SymptomsSome people visit the doctor only when they feelpain or when they notice changes like a lump inthe breast or unusual bleeding or discharge. Butdon’t wait until then to be checked because earlycancer may not have any symptoms. That is whyscreening for some cancers is important,particularly as you get older. Screening methodsare designed to check for cancer in people withno symptoms.
  39. 39. BiopsyTo diagnose the presence of cancer, a doctor must look at a sample of the affectedtissue under the microscope. Hence, when preliminary symptoms, Pap test,mammogram, PSA test, FOBT, or colonoscopy indicate the possible existence ofcancer, a doctor must then perform a biopsy, which is the surgical removal of asmall piece of tissue for microscopic examination. (For leukemias, a small bloodsample serves the same purpose.) This microscopic examination will tell the doctorwhether a tumor is actually present and, if so, whether it is malignant (i.e., cancer)or benign. In addition, microarrays may be used to determine which genes areturned on or off in the sample, or proteomic profiles may be collected for ananalysis of protein activity. This information will help doctors to make a moreaccurate diagnosis and may even help to inform treatment planning.
  40. 40. Pathology Proteomic profile Patient’stissue sample or blood sample Genomic profile
  41. 41. Microscopic Appearance of Cancer CellsCancer tissue has a distinctive appearance under themicroscope. Among the traits the doctor looks for are alarge number of irregularly shaped dividing cells, variationin nuclear size and shape, variation in cell size and shape,loss of specialized cell features, loss of normal tissueorganization, and a poorly defined tumor boundary.
  42. 42. Cancer classification1. There are >100 different types of cancers.2. Arise from abnormalities in cell growth and division.3. Originate from different types of normal cells.4. Vary in rates of growth and ability to spread.
  43. 43. Classification of cancers based on cell/tissue originCarcinomas: cancers of epithelial cells.•Epithelia: cell that cover surfaces, for example skin, lining of digestive tract.• Glands also are epithelia.•Make up 90% of human cancers.Sarcomas: tumors of connective tissues. •Connective tissues lie below epithelia and hold things together or support the body. • Some examples are muscle and bone. •Cancers are rare, because these cells do not reproduce very often.
  44. 44. Leukemias and Lymphomas: Cancers of blood cells.1. Leukemias are cancers of circulating blood cells or stem cells of the bone marrow.2. Lymphomas are usually solid tumors in lymphatic organs (system that cleanses the blood).3. Comprise 8% of all human cancers.
  45. 45. Further classification of cancers site of origin: lung, breast carcinomas. cell type: squamous cell carcinoma: cancer of flat epithelial cell. Cancers of glands: prefix adeno- Example adenocarcinoma Cancers of embryonic tissues: suffix -blastoma Neuroblastoma: Childhood cancer of neurons. Retinoblastoma: Childhood eye cancer.
  46. 46. HyperplasiaInstead of finding a benign or malignant tumor, microscopicexamination of a biopsy specimen will sometimes detect a conditioncalled “hyperplasia.” Hyperplasia refers to tissue growth based on anexcessive rate of cell division, leading to a larger than usual numberof cells. Nonetheless, cell structure and the orderly arrangement ofcells within the tissue remain normal, and the process of hyperplasiais potentially reversible. Hyperplasia can be a normal tissue responseto an irritating stimulus.
  47. 47. Normal Hyperplasia
  48. 48. DysplasiaIn addition to hyperplasia, microscopic examination of a biopsyspecimen can detect another type of noncancerous condition called“dysplasia.” Dysplasia is an abnormal type of excessive cellproliferation characterized by loss of normal tissue arrangement andcell structure. Often such cells revert back to normal behavior, butoccasionally they gradually become malignant. Because of theirpotential for becoming malignant, areas of dysplasia should beclosely monitored by a health professional. Sometimes they needtreatment.
  49. 49. Normal Hyperplasia Mild dysplasia
  50. 50. Carcinoma in SituThe most severe cases of dysplasia are sometimesreferred to as “carcinoma in situ.” In Latin, the term “insitu” means “in place,” so carcinoma in situ refers to anuncontrolled growth of cells that remains in the originallocation. However, carcinoma in situ may develop into aninvasive, metastatic malignancy and, therefore, is usuallyremoved surgically, if possible.
  51. 51. Normal Hyperplasia Mild Carcinoma in situ dysplasia (severe dysplasia) Cancer (invasive)
  52. 52. Tumor GradingMicroscopic examination also provides information regarding thelikely behavior of a tumor and its responsiveness to treatment.Cancers with highly abnormal cell appearance and large numbers ofdividing cells tend to grow more quickly, spread to other organsmore frequently, and be less responsive to therapy than cancerswhose cells have a more normal appearance. Based on thesedifferences in microscopic appearance, doctors assign a numerical“grade” to most cancers. In this grading system, a low number grade(grade I or II) refers to cancers with fewer cell abnormalities thanthose with higher numbers (grade III, IV).
  53. 53. General Relationship Between Tumor Grade and Prognosis 100% Low grade PatientSurvival Rate High grade 1 2 3 4 5 Years
  54. 54. Tumor StagingAfter cancer has been diagnosed, doctors ask the following threequestions to determine how far the disease has progressed:1. How large is the tumor, and how deeply has it invaded surroundingtissues?2. Have cancer cells spread to regional lymph nodes?3. Has the cancer spread (metastasized) to other regions of the body?Based on the answers to these questions, the cancer is assigned a“stage.” A patient’s chances for survival are better when cancer isdetected at a lower stage.
  55. 55. Five-Year Survival Rates for Patients with Melanoma (by stage)100%50% I II III Stage at Time of Initial Diagnosis
  56. 56. Clinical staging of cancerStaging specific to particular types of cancer,1. prostate cancer—Gleason system2. lung cancer—Stages I-IV, now correlated with TNM stagingUniversal system: "TNM system"•Developed by US and International committees•Based on 3 considerations T = condition of primary tumor (values usually T1-T4) N = extent of lymph node involvement (values N0-N2) M = extent of distant metastasis (values M0 or M1)
  57. 57. 25
  58. 58. Grade of tumor:Refers to the degree of abnormality of cancercells compared with normal cells.Based on microscopic examination of cancercells. 26
  59. 59. Grades:• Grade I: 75 : 100 % differentiation• Grade II: 50 : 75 % differentiation• Grade III: 25 : 50 % differentiation• Grade IV: 0 : 25 % differentiation 27
  60. 60. Stage of tumor:Is a descriptor of how much the cancer hasspread.It takes into:1. The size of tumor.2. How deep it has penetrated3. How many lymph nodes it has metastasized 28
  61. 61. Stages:Stage 0: carcinoma in situ.Stage I: usually means a cancer is small and containedwith in the organ it started in.Stage II: usually means the cancer is localized.Stage III: usually means the cancer is larger and theircells in the lymph nodes in the area.Stage IV: means that the cancer has spread from whereit started to another body organ. 29
  62. 62. TNM stagingTNM Staging is used for solid tumorsis an acronym for the words Tumor,Nodes, and Metastases • Tumor (T) refers to the primary tumor and carries a number of 0 to 4. • N represents regional lymph node involvement and can also be ranked from 0 to 4. • Metastasis is represented by the letter M, and is 0 if no metastasis has occurred or 1 if metastases are present. 30
  63. 63. Example: TNM staging of colon cancer Stage Survival rate (5 yr)T1N0M0 ~90%T2N0M0T3N0M0 ~80%T4N0M0 ~60-70%T3N1M0 ~50%T4N1M0 ~40% For early stage: surgery usually leads to cure For T3, T4, N1 or N2: radiation and/or chemotherapy useful in addition to surgery M1 stage: No longer curable; treatments can prolong life
  64. 64.  1) Detecting Cancer early can affect the outcome of the disease forall cancers.2) Carcinomas are cancers of epithelial cells.3) Hyperplasia is an excessive rate of cell division leading to alarger than usual number of cells.4) Carcinoma in situ refers to a controlled growth of cells thatremains in the original location.5) Grade III refers to Cells with fewer abnormalities than grade I.
  65. 65. 1. What Causes of Cancer ?2. Population based studies.3. Heredity? Behavior? Other factors.4. Tobacco use and cancer.5. Low strength radiation.6. High strength radiation.7. Lag time.8. Viruses.9. Bacteria and stomach cancer.10. Heredity and Cancer .11. Genetic testing.12. Cancer risk and aging.
  66. 66. What Causes Cancer?Some chemicals Radiation Heredity Diet Hormones
  67. 67. Cancer is often perceived as a disease that strikes for noapparent reason. While scientists don’t yet know all thereasons, many of the causes of cancer have already beenidentified. Besides intrinsic factors such as heredity, diet,and hormones, scientific studies point to key extrinsicfactors that contribute to the cancer’s development:chemicals (e.g., smoking), radiation, and viruses orbacteria.
  68. 68. Population-Based StudiesOne way of identifying the various causes of cancer is by studyingpopulations and behaviors. This approach compares cancer ratesamong various groups of people exposed to different factors orexhibiting different behaviors. A striking finding to emerge frompopulation studies is that cancers arise with different frequencies indifferent areas of the world. For example, stomach cancer isespecially frequent in Japan, colon cancer is prominent in the UnitedStates, and skin cancer is common in Australia. What is the reasonfor the high rates of specific kinds of cancer in certain countries?
  69. 69. Regions of Highest IncidenceU.K.:Lungcancer JAPAN: Stomach cancer CANADA: Leukemia U.S.: CHINA: Colon Liver cancer cancer BRAZIL: Cervical AUSTRALIA: cancer Skin cancer
  70. 70. Heredity? Behaviors? Other Factors?In theory, differences in heredity or environmental risk factors might beresponsible for the different cancer rates observed in different countries.Studies on people who have moved from one country to another suggestthat exposure to risk factors for cancer varies by geographic location. Forexample, in Japan, the rate of colon cancer is lower, and the rate ofstomach cancer is higher, than in the United States. But this difference hasbeen found to gradually disappear in Japanese families that have moved tothe United States. This suggests that the risk of developing the two kindsof cancer is not determined primarily by heredity. The change in risk forcancer for Japanese families could involve cultural, behavioral, orenvironmental factors predominant in one location and not in the other.
  71. 71. Colon Cancer Stomach Cancer (Number of new cases (Number of new cases per 100,000 people) per 100,000 people)100 100 7050 5 7 0 0 Japan Japanese U.S. Japan Japanese U.S. families families in U.S. in U.S.
  72. 72. Tobacco Use and CancerSome Cancer-Causing Chemicals in Tobacco Smoke
  73. 73. Among the various factors that can cause cancer, tobacco smoking isthe greatest public health hazard. Cigarette smoke contains morethan two dozen different chemicals capable of causing cancer.Cigarette smoking is the main cause of lung cancer and contributesto many other kinds of cancer as well, including cancer of themouth, larynx, esophagus, stomach, pancreas, kidney, and bladder.Current estimates suggest that smoking cigarettes is responsible forat least one out of every three cancer deaths, making it the largestsingle cause of death from cancer. Other forms of tobacco use alsocan cause cancer. For example, cigars, pipe smoke, and smokelesstobacco can cause cancers of the mouth.
  74. 74. Low-Strength RadiationSome atoms give off radiation, which is energy that travels throughspace. Prolonged or repeated exposure to certain types of radiationcan cause cancer. Cancer caused by the sun’s ultraviolet radiation ismost common in people who spend long hours in strong sunlight.Ultraviolet radiation from sunlight is a low-strength type ofradiation. Effective ways to protect against ultraviolet radiation andto prevent skin cancer are to avoid going into strong, direct sunlightand to wear protective clothing. Sunscreen lotions reduce the risk ofsome forms of skin cancers.
  75. 75. High Dallas Skin CancerIncidence Pittsburgh Detroit Low Least Most Annual Sunshine (UV radiation)
  76. 76. High-Strength RadiationIncreased rates of cancer also have been detected in people exposedto high-strength forms of radiation such as X-rays or radiationemitted from unstable atoms called radioisotopes. Because these twotypes of radiation are stronger than ultraviolet radiation, they canpenetrate through clothing and skin into the body. Therefore, high-strength radiation can cause cancers of internal body tissues.Examples include cancer caused by nuclear fallout from atomicexplosions and cancers caused by excessive exposure to radioactivechemicals.
  77. 77. HighLow Least Most X-ray Dose (atomic radiation)
  78. 78. Lag TimeChemicals and radiation that are capable of triggering thedevelopment of cancer are called “carcinogens.” Carcinogens actthrough a multistep process that initiates a series of geneticalterations (“mutations”) and stimulates cells to proliferate. Aprolonged period of time is usually required for these multiple steps.There can be a delay of several decades between exposure to acarcinogen and the onset of cancer. For example, young peopleexposed to carcinogens from smoking cigarettes generally do notdevelop cancer for 20 to 30 years. This period between exposure andonset of disease is the lag time.
  79. 79. 20-Year Lag Time Between Smoking and Lung Cancer Cigarette consumption (men) 4000 150 LungCigarettes 3000 cancer Smoked (men) Lung Cancerper Person 100 Deaths (per per Year 2000 100,000 people) 50 1000 1900 1920 1940 1960 1980 Year
  80. 80. VirusesIn addition to chemicals and radiation, a few viruses also can triggerthe development of cancer. In general, viruses are small infectiousagents that cannot reproduce on their own, but instead enter intoliving cells and cause the infected cell to produce more copies of thevirus. Like cells, viruses store their genetic instructions in largemolecules called nucleic acids. In the case of cancer viruses, some ofthe viral genetic information carried in these nucleic acids is insertedinto the chromosomes of the infected cell, and this causes the cell tobecome malignant.
  81. 81. Virus inserts and changes genes for cell growthCancer-linked virus
  82. 82. Examples of Human Cancer VirusesOnly a few viruses that infect human cells actually cause cancer.Included in this category are viruses implicated in cervical cancer,liver cancer, and certain lymphomas, leukemias, and sarcomas.Susceptibility to these cancers can sometimes be spread from personto person by infectious viruses, although such events account foronly a very small fraction of human cancers. For example, the risk ofcervical cancer is increased in women with multiple sexual partnersand is especially high in women who marry men whose previouswives had this disease. Transmission of the human papillomavirus(HPV) during sexual relations appears to be involved.
  83. 83. Bacteria and Stomach CancerViruses are not the only infectious agents that have beenimplicated in human cancer. The bacterium Helicobacterpylori, which can cause stomach ulcers, has beenassociated with the development of cancer, so peopleinfected with H. pylori are at increased risk for stomachcancer. Research is under way to define the geneticinteractions between this infectious agent and its hosttissues that may explain why cancer develops.
  84. 84. Patient’s tissue H. pylori sample
  85. 85. Heredity and CancerCancer is not considered an inherited illness because most cases ofcancer, perhaps 80 to 90 percent, occur in people with no familyhistory of the disease. However, a person’s chances of developingcancer can be influenced by the inheritance of certain kinds ofgenetic alterations. These alterations tend to increase an individual’ssusceptibility to developing cancer in the future. For example, about5 percent of breast cancers are thought to be due to inheritance ofparticular form(s) of a “breast cancer susceptibility gene.”
  86. 86. All Breast Cancer PatientsInherited factor(s)Other factor(s)
  87. 87. Heredity Can Affect Many Types of CancerInherited mutations can influence a person’s risk ofdeveloping many types of cancer in addition to breastcancer. For example, certain inherited mutations havebeen described that increase a person’s risk ofdeveloping colon, kidney, bone, skin or other specificforms of cancer. But these hereditary conditions arethought to be involved in only 10 percent or fewer ofall cancer cases.
  88. 88. Genetic TestingLaboratory tests can determine whether a person carries some of thegenetic alterations that can increase the risk of developing certaincancers. For example, women who inherit certain forms of a genecalled BRCA1 or BRCA2 have an elevated risk of developing breastcancer. For women with a family history of breast cancer, takingsuch a test may relieve uncertainty about their future risk. However,the information obtained from genetic tests is often complex anddifficult to interpret. The decision to undergo genetic testing shouldtherefore be a personal, voluntary one and should only be made inconjunction with appropriate genetic counseling.
  89. 89. Cancer Risk and AgingBecause a number of mutations usually must occur for cancer toarise, the chances of developing cancer increase as a person getsolder because more time has been available for mutations toaccumulate. For example, a 75-year-old person is a hundred timesmore likely to develop colon cancer than a 25-year-old. Becausepeople are living longer today than they did 50 or 100 years ago,they have a longer exposure time to factors that may promote genechanges linked to cancer.
  90. 90. Cancer Risk and Aging 400 Colon 300 Breast Number ofCancer Cases 200(per 100,000 people) 100 0 20 40 60 80 Age of Person (in years)
  91. 91.  1) Cigarette smoking is the main cause of only lung cancer.2) UV. Radiation from sun light is a high strength type of radiation.3) Lag time is the period between exposure and onset of disease.4) Viruses are the only infections agents that have been implicatedin human cancer.5) Developing of cancer related to accumulated further mutations
  92. 92. 1. Cell Cycle2. Cancer as error in controlling cell cycle3. Growth of normal cells vs. cancer cells4. Cell death pathways
  93. 93. What are the normal constraints on cell growth? Some cells divide continuously •hematopoietic (blood-forming) cells •intestinal epithelia •skin cells Some cells divide often •Epithelia of various types •Some connective tissue cells Some cells never divide in adults •Nerve cells •Cardiac muscle
  94. 94. Cell CycleWhat happens when cells divide? Interphase: Preparation for next cell division. G1 Gap 1 can vary for different cells, cell growth occurs S Synthesis phase DNA replication occurs G2 Gap 2 cell growth occurs Mitosis: Cell division of somatic (body) cells.  Replicated chromosomes are equally distributed among two daughter cells.
  95. 95. Checkpoints Before proceeding around the cell cycle, the cell checks its stateG1/G0 checkpoint: Assess whether nutrients and growth factors are available for growth Rb (retinoblastoma) protein and its metabolic state is involved in decision: Acts like a molecular switch to decide whether the cell proceeds through the cell cycle. If Rb has a phosphate group added to it, the cell cycle can move forward. If Rb has the phosphate group removed, the cell stalls in G0 of the cell cycle
  96. 96. G2/M checkpoint Is all DNA replicated? Is environment good? Are conditions in the cell favorable? p53 plays a critical role in checking for DNA damageMitotic metaphase checkpoint Are chromosomes correctly aligned in center of the cell for cell division?
  97. 97. Cancer as a defect in cell cycle controlMany tumor suppressor genes and oncogenes encodeproteins important for controlling the cell cycle.The following examples show that.
  98. 98. Component Role in cell cycle Defect in cancerPDGF (platelet derived Regulates cell growth Signal cell to reentergrowth factor, encoded by cell cycle when celloncogene c-sis) should be quiescentRb (retinoblastoma, tumor Needed for quiescence Cell can proceedsuppressor protein) through cell cyclep53 (tumor suppressor Surveys for DNA damage, Allows cell division toprotein) triggers cell death if needed proceed, often leading to abnormal chromosomesCyclin D (cyclins are Helps cell proceed through Unregulated cell growthunstable proteins involved cell cyclein the cell cycle)
  99. 99. Growth of cells in culture as model for cancer.
  100. 100. "Normal cells" Tumor cells After several cell divisions, cells become Cells continue to divide quiescent Require growth factors to grow Reduced need for growth factors Require surface to grow Become anchorage independent Die after 50-100 divisions Cells become immortalized Chromosome # mostly stable Chromosome # may vary--unstableOther differences between normal cells and cancer cells observedin animal studies of cancer (in vivo): Observation* Normal cells Cancer cells (in vivo) Protease secretion Low High Secretion of angiogenic Low High factors Can terminally Able Unable differentiate Able to undergo Able Unable programmed cell death
  101. 101. is genetically programmed cell death, which leads tobreakdown and disposal of cellsMorphologically, apoptosis is characterized by changesin the cell membrane (with the formation of small bodiesknown as “apoptotic bodies”), shrinking of the nucleus,chromatin condensation, and fragmentation of DNA.Macrophages other phagocytic cells recognize apoptoticcells and remove them by phagocytosis withoutinflammatory phenomena developing. 16
  102. 102. all rights preserved (C) Abou-Mesalam2008 17
  103. 103. Systems initiate apoptosis process  Tumer necrosis Fas system  P53 factor-α (TNF-α ) 18
  104. 104. all rights preserved (C) Abou-Mesalam2008 19
  105. 105.  1) Cardiac muscle cells divide continuously.2) During Gap2 phase , cell growth occurs.3) If Rb protien has a Phosphate group add to it , the cell cycle canmove forward.4) P53 protein is the product of Rb gene during translation.5) Protease secretion is low by cancer cells in vivo.
  106. 106. 1.Genes and Cancer.2.DNA structure.3.DNA mutations.4.Oncogenes.5.Tumor suppressor genes.6.DNA repair genes.7.Mutations and cancer.
  107. 107. Genes and CancerChemicals (e.g., from smoking), radiation, viruses, and heredity allcontribute to the development of cancer by triggering changes in acell’s genes. Chemicals and radiation act by damaging genes,viruses introduce their own genes into cells, and heredity passes onalterations in genes that make a person more susceptible to cancer.Genes are inherited instructions that reside within a person’schromosomes. Each gene instructs a cell how to build a specificproduct--in most cases, a particular kind of protein. Genes arealtered, or “mutated,” in various ways as part of the mechanism bywhich cancer arises.
  108. 108. VirusesChemicals Radiation Heredity Chromosomes are DNA molecules
  109. 109. DNA StructureGenes reside within chromosomes, the large DNA molecules, whichare composed of two chemical strands twisted around each other toform a “double helix.” Each strand is constructed from millions ofchemical building blocks called “bases.” DNA contains only fourdifferent bases: adenine, thymine, cytosine, and guanine (abbreviatedA, T, G, and C), but they can be arranged in any sequence. Thesequential order of the bases in any given gene determines themessage the gene contains, just as the letters of the alphabet can becombined in different ways to form distinct words and sentences.
  110. 110. Chemical bases A T C GDNA molecule
  111. 111. DNA MutationGenes can be mutated in several different ways. Thesimplest type of mutation involves a change in a singlebase along the base sequence of a particular gene--muchlike a typographical error in a word that has beenmisspelled. In other cases, one or more bases may be addedor deleted. And sometimes, large segments of a DNAmolecule are accidentally repeated, deleted, or moved.
  112. 112. CA AG C T A A C TDNA Normal gene CA AG C G AAC T Single base change CA AG GCG C T A A C T Additions C T CA A G A A C T Deletions
  113. 113. OncogenesOne group of genes implicated in the development ofcancer are damaged genes, called “oncogenes.” Oncogenesare genes whose PRESENCE in certain forms and/oroveractivity can stimulate the development of cancer.When oncogenes arise in normal cells, they can contributeto the development of cancer by instructing cells to makeproteins that stimulate excessive cell growth and division.
  114. 114. Normal cell Normal genes regulate cell growth OncogenesCancer cell accelerate cell growth and division Mutated/damaged oncogene
  115. 115. Proto-Oncogenes and Normal Cell GrowthOncogenes are related to normal genes called proto-oncogenes thatencode components of the cell’s normal growth-control pathway.Some of these components are growth factors, receptors, signalingenzymes, and transcription factors. Growth factors bind to receptorson the cell surface, which activate signaling enzymes inside the cellthat, in turn, activate special proteins called transcription factorsinside the cell’s nucleus. The activated transcription factors “turnon” the genes required for cell growth and proliferation.
  116. 116. Normal Growth-Control PathwayGrowth factor Receptor Signaling enzymes Transcription factors DNA Cell nucleus Cell proliferation
  117. 117. Oncogenes are Mutant Forms of Proto-OncogenesOncogenes arise from the mutation of proto-oncogenes. They resemble proto-oncogenes inthat they code for the production of proteins involved in growth control. However,oncogenes code for an altered version (or excessive quantities) of these growth-controlproteins, thereby disrupting a cell’s growth-signaling pathway.By producing abnormal versions or quantities of cellular growth-control proteins, oncogenescause a cell’s growth-signaling pathway to become hyperactive. To use a simple metaphor,the growth-control pathway is like the gas pedal of an automobile. The more active thepathway, the faster cells grow and divide. The presence of an oncogene is like having a gaspedal that is stuck to the floorboard, causing the cell to continually grow and divide. Acancer cell may contain one or more oncogenes, which means that one or more componentsin this pathway will be abnormal.
  118. 118. Inactive growth factor receptor Inactive intracellular signaling protein Activated gene regulatory protein Transcription Cell proliferation driven by internal oncogene signaling
  119. 119. Tumor Suppressor GenesA second group of genes implicated in cancer are the “tumor suppressor genes.”Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer. Inother words, if a pair of tumor suppressor genes are either lost from a cell orinactivated by mutation, their functional absence might allow cancer to develop.Individuals who inherit an increased risk of developing cancer often are born withone defective copy of a tumor suppressor gene. Because genes come in pairs (oneinherited from each parent), an inherited defect in one copy will not lead to cancerbecause the other normal copy is still functional. But if the second copy undergoesmutation, the person then may develop cancer because there no longer is anyfunctional copy of the gene.
  120. 120. Normal cell Normal genes prevent cancerRemove or inactivate tumorsuppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes
  121. 121. Tumor Suppressor Genes Act Like a Brake PedalTumor suppressor genes are a family of normal genes that instructcells to produce proteins that restrain cell growth and division. Sincetumor suppressor genes code for proteins that slow down cell growthand division, the loss of such proteins allows a cell to grow and dividein an uncontrolled fashion. Tumor suppressor genes are like the brakepedal of an automobile. The loss of a tumor suppressor gene functionis like having a brake pedal that does not function properly, therebyallowing the cell to grow and divide continually.
  122. 122. Tumor Suppressor Gene ProteinsGrowth factor Receptor Signaling enzymes Transcription factorsCell nucleus DNA Cell proliferation
  123. 123. p53 Tumor Suppressor Protein Triggers Cell SuicideOne particular tumor suppressor gene codes for a proteincalled “p53” that can trigger cell suicide (apoptosis). Incells that have undergone DNA damage, the p53 proteinacts like a brake pedal to halt cell growth and division. Ifthe damage cannot be repaired, the p53 protein eventuallyinitiates cell suicide, thereby preventing the geneticallydamaged cell from growing out of control.
  124. 124. p53 proteinNormal cell Excessive DNA damage Cell suicide (Apoptosis)
  125. 125. DNA Repair GenesA third type of genes implicated in cancer are called “DNA repair genes.”DNA repair genes code for proteins whose normal function is to correcterrors that arise when cells duplicate their DNA prior to cell division.Mutations in DNA repair genes can lead to a failure in repair, which in turnallows subsequent mutations to accumulate. People with a condition calledxeroderma pigmentosum have an inherited defect in a DNA repair gene. Asa result, they cannot effectively repair the DNA damage that normallyoccurs when skin cells are exposed to sunlight, and so they exhibit anabnormally high incidence of skin cancer. Certain forms of hereditarycolon cancer also involve defects in DNA repair.
  126. 126. Normal DNA repair TC GACBase pairmismatch No cancerTC T AC AG C T G TC TAC TC T ACAG C T G Cancer AG TG AG A T G No DNA repair
  127. 127. Cancer Tends to Involve Multiple MutationsCancer may begin because of the accumulation of mutations involvingoncogenes, tumor suppressor genes, and DNA repair genes. For example,colon cancer can begin with a defect in a tumor suppressor gene thatallows excessive cell proliferation. The proliferating cells then tend toacquire additional mutations involving DNA repair genes, other tumorsuppressor genes, and many other growth-related genes. Over time, theaccumulated damage can yield a highly malignant, metastatic tumor. Inother words, creating a cancer cell requires that the brakes on cell growth(tumor suppressor genes) be released at the same time that the acceleratorsfor cell growth (oncogenes) are being activated.
  128. 128. Benign tumor cells Malignant cells invade neighboring grow only locally and tissues, enter blood vessels, and cannot spread by invasion metastasize to different sites or metastasisTime Mutation Cells Mutations Proto-oncogenes More mutations, inactivates proliferate inactivate mutate to oncogenes more genetic suppressor DNA repair instability, gene genes metastatic disease
  129. 129. Mutations and CancerWhile the prime suspects for cancer-linked mutations are theoncogenes, tumor suppressor genes, and DNA repair genes, cancerconspires even beyond these. Mutations also are seen in the genesthat activate and deactivate carcinogens, and in those that governthe cell cycle, cell senescence (or “aging”), cell suicide (apoptosis),cell signaling, and cell differentiation. And still other mutationsdevelop that enable cancer to invade and metastasize to other partsof the body.
  130. 130. Cancer Tends to Corrupt Surrounding EnvironmentIn addition to all the molecular changes that occur within a cancercell, the environment around the tumor changes dramatically as well.The cancer cell loses receptors that would normally respond toneighboring cells that call for growth to stop. Instead, tumors amplifytheir own supply of growth signals. They also flood their neighborswith other signals called cytokines and enzymes called proteases.This action destroys both the basement membrane and surroundingmatrix, which lies between the tumor and its path to metastasis--ablood vessel or duct of the lymphatic system.
  131. 131. Growth factors = proliferation InvasiveMatrix Proteases Fibroblasts, adipocytes Cytokines Blood vesselCytokines, proteases = migration & invasion
  132. 132.  1) Viruses damage genes by introduce their own genes to cells.2) Mutations occurred only by additions of single bases.3) Over activity of Oncogenes may stimulate the development ofcancer.4) Tumor suppressor genes are normal genes whose absence canlead to cancer.5) P53 is oncogene can trigger cell suicide.
  133. 133. 1. Cancer prevention.2. Avoid Tobacco.3. Protection from sun light.4. Diet.5. Avoiding cancer viruses.6. Avoiding carcinogens.7. Industrial pollution.8. Is there a cancer “epidemic” ?
  134. 134. Cancer PreventionSince exposure to carcinogens (cancer-causing agents) isresponsible for triggering most human cancers, people canreduce their cancer risk by taking steps to avoid suchagents. Hence the first step in cancer prevention is toidentify the behaviors or exposures to particular kinds ofcarcinogens and viruses that represent the greatest cancerhazards.
  135. 135. Carcinogenic chemicals Carcinogenic radiationCancer viruses or bacteria
  136. 136. Avoid TobaccoAs the single largest cause of cancer death, the use of tobaccoproducts is implicated in roughly one out of every three cancerdeaths. Cigarette smoking is responsible for nearly all cases of lungcancer, and has also been implicated in cancer of the mouth, larynx,esophagus, stomach, pancreas, kidney, and bladder. Pipe smoke,cigars, and smokeless tobacco are risky as well. Avoiding tobacco istherefore the single most effective lifestyle decision any person canmake in attempting to prevent cancer.
  137. 137. Lung Cancer Risk Increases with Cigarette Consumption15x10x 5x 0 15 30Non-smoker Cigarettes Smoked per Day
  138. 138. Protect Yourself From Excessive SunlightWhile some sunlight is good for health, skin cancer caused byexcessive exposure to sunlight is not among the sun’s benefits.Because some types of skin cancer are easy to cure, the danger posedby too much sunlight is perhaps not taken seriously enough. It isimportant to remember that a more serious form of skin cancer,called melanoma, is also associated with excessive sun exposure.Melanomas are potentially lethal tumors. Risk of melanoma andother forms of skin cancer can be significantly reduced by avoidingexcessive exposure to the sun, using sunscreen lotions, and wearingprotective clothing to shield the skin from ultraviolet radiation.
  139. 139. Limit Alcohol and TobaccoDrinking excessive amounts of alcohol is linked to an increased riskfor several kinds of cancer, especially those of the mouth, throat, andesophagus. The combination of alcohol and tobacco appears to beespecially dangerous. For example, in heavy smokers or heavydrinkers, the risk of developing cancer of the esophagus is roughly 6times greater than that for nonsmokers/nondrinkers. But in peoplewho both smoke and drink, the cancer risk is more than 40 timesgreater than that for nonsmokers/nondrinkers. Clearly thecombination of alcohol and tobacco is riskier than would be expectedby just adding the effects of the two together.
  140. 140. Combination of Alcohol and Cigarettes Increases Risk for Cancer of the Esophagus 40x 30xRisk Increase 20x 10x Alcoholic Drinks Consumed per Day AND Packs of Cigarettes Consumed per Day
  141. 141. Diet: Limit Fats and CaloriesStudies suggest that differences in diet may also play a role indetermining cancer risk. Unlike clear-cut cancer risk factors such astobacco, sunlight, and alcohol, dietary components that influencecancer risk have been difficult to determine. Limiting fatconsumption and calorie intake appears to be one possible strategyto decrease risk for some cancers, because people who consumelarge amounts of meat, which is rich in fat, and large numbers ofcalories exhibit an increased cancer risk, especially for coloncancer.
  142. 142. Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries 40 30Number of Cases (per 100,000 people) 20 10 0 80 100 200 300 Grams (per person per day)
  143. 143. Diet: Consume Fruits and VegetablesIn contrast to factors such as fat and calories, which appear toincrease cancer risk, other dietary components may decrease cancerrisk. The most compelling evidence has been obtained for fruits andvegetables, whose consumption has been strongly correlated with areduction in cancer risk. Although the exact chemical components inthese foods that are responsible for a protective effect are yet to beidentified, eating five to nine servings of fruits and vegetables eachday is recommended by many groups.
  144. 144. Avoid Cancer VirusesActions can also be taken to avoid exposure to the small number ofviruses that have been implicated in human cancers. A goodexample is the human papillomavirus (HPV). Of the more than 100types of HPVs, over 30 types can be passed from one person toanother through sexual contact. Among these, there are 13 high-risktypes recognized as the major cause of cervical cancer. Havingmany sexual partners is a risk factor for infection with these high-risk HPVs, which can, in turn, increase the chance that mild cervicalabnormalities will progress to more severe ones or to cervicalcancer.
  145. 145. HPV Infection Increases Risk for Cervical Cancer HighCervical Cancer Risk Low Noninfected women Women infected with HPV
  146. 146. Avoid Carcinogens at WorkBecause people spend so much time at work, potentialcarcinogens in the work environment are studied carefully.Some occupational carcinogens have been identifiedbecause coworkers exposed to the same substances havedeveloped a particular kind of cancer at increasedfrequency. For example, cancer rates in constructionworkers who handle asbestos have been found to be 10times higher than normal.
  147. 147. Avoid Carcinogens at Work
  148. 148. Industrial PollutionThe fact that several environmental chemicals can cause cancer hasfostered the idea that industrial pollution is a frequent cause ofcancer. However, the frequency of most human cancers (adjusted forage) has remained relatively constant over the past half-century, inspite of increasing industrial pollution.So, in spite of evidence that industrial chemicals can cause cancer inpeople who work with them or in people who live nearby, industrialpollution does not appear to be a major cause of most cancers in thepopulation at large.
  149. 149. Incidence ofMost Cancers 1930 1950 1970 1990 Year
  150. 150. Is There a Cancer "Epidemic"?A common misconception arises from news stories suggesting we areexperiencing a cancer “epidemic.” This only appears to be the case because thenumber of new cancer cases reported is rising as the population as a whole isaging, and older people are more likely to develop cancer. However, this trend isoffset by the number of new births, which is also increasing, and cancer is rareamong the young. So as more and more members of a 75-million-strong “baby-boomer” cohort begin shifting en masse to older, more cancer-prone ages, thenumber of new cancer cases is expected to increase in the next several decades.But since the birth rate is also expected to increase, the cancer rate may eitherstay the same or, perhaps, decline.
  151. 151. 1. Progression toward metastatic cancer2. Role of the circulatory system3. Soil and seed hypothesis4. Angiogenesis
  152. 152. Although tumors in situ are usually easily treated withsurgery, Cancer in its metastatic form is often lethal. Inmetastasis, cells from the primary tumor break off andtravel to distant parts of the body, including lymph nodesand other body organs, such as the lung, liver, bone orbrain. In today’s lecture we will discuss mechanismstumors use to grow larger and metastasize.
  153. 153. Progression toward metastatic cancerloosening of intracellular connectionsCell-Cell adhesion mediated by interactions at the surfaces ofcells.Protein receptors on the surface that interact with similar (homotypic)or different (heterotypic) receptors on the surface of other cells orthat interact with the extracellular matrix. Act as tumor suppressors •Integrins •Cadherins •Selectins •Immunoglobulin family
  154. 154. Example:that mediates communication between a celladhesion protein (E-cadherin) and the cytoskeletonis important for hereditary colon cancer(adenomatous polyposis coli). May also be atranscription factor.
  155. 155. Secretion of proteasesProteases—Enzymes that break down other proteins.Proteases released by the cell break down proteins that attach cellstogether on the outside and on basement membranes, to free cells oftheir normal constraints.Some cells secrete inhibitors (TIMPs=tissue inhibitors ofmetalloproteinases); these bind to metalloproteinases and areassociated with decreased metastatic potential.
  156. 156. Intravasion=Process of invading blood vessels. Involves attachmentof cancer cells to blood vessel basement membrane, proteasedigestion of basement membrane, and migration of cells into bloodstream.Extravasion=Escape of cancer cells from the blood vessel.Involves attachment to the endothelial lining,cancer cellattachment to and destruction of the basement membrane,migration into the tissue (often referred to as stroma).
  157. 157. Migration of cancer cells to new siteRequires 1.proteases to digest matrix 2.alternate attachment/detachment of cell 3.signaling from cell surface to trigger changes in the cytoskeleton 4.“motility factors”
  158. 158. Angiogenesis Growth and development of blood vessels Cancer cells need blood vessels in the area or they will starve when the tumor gets large. Cancers >1 mm in diameter need blood vessels. Cancer cells secrete growth factors that attract blood vessels.+ growth factors for angiogenesis (these help - growth factors for angiogenesisblood vessels form in tumors) (these might serve as anti-tumor drugs)PDGF thrombospondin (p53 regulates)VEGF (vascular endothelial growth factor) angiostatinFGF (fibroblast growth factor) endostatinTGF  and  (transforming growth factor) interferonsangiogenin TIMPs (inhibitors of metalloproteases)
  159. 159. Genetic instabilityCan include: Loss of chromosomes: visible under microscope Deletion: loss of some part of a chromosome Duplications: extra copy of part of the chromosome Rearrangements and translocations: segments of chromosomes get moved to another place. Gene amplification: many copies are made of one region of the chromosome.
  160. 160. Role of the circulatory system in cancerCirculatory system is a network of blood vessels and the heart,which acts as pump.Serves as way of carrying nutrients to all parts of the body andremoving wastes.Tumors develop blood vessels to provide them with nutrients.Tumor cells escape their normal tissues and can move in the bodythrough the blood vessels.
  161. 161. The trip through the circulatory system puts cancer cells in closerange of the immune system; only 1 in 10,000 cells complete the trip.Secondary tumors often form in the lung or the liver, sites of capillarybeds (small blood vessels). The cancer cells may get stuck in the bloodvessels or may move from the capillaries to surrounding tissues andstart a new growth.The lymphatic system, which filters the blood, is also often a site ofmetastasis as cancer cells can get trapped in the dense lymph nodes
  162. 162. Soil and seed hypothesisSome primary tumors metastasize often to particular sites.For example, prostate cancer often metastasizes to bone.To explain the link between the sites, there is the "soil and seed"hypothesis. The idea is that the distant site has a receptor or binding site for a protein on the surface of the tumor cell. To put it another way, the distant site provides fertile soil for the growth of the cancer "seed".. The tumor cell binds to the distant site and begins to grow and reproduce into a secondary tumor
  163. 163. To further explore this idea, Ruoslahti and others are trying toidentify proteins on the surfaces of cells that specify their "molecularaddress", the place in the body they are destined for. Until this isunderstood for normal cells, it will be difficult to determine whetherthe "soil and seed" hypothesis is a reasonable idea to explain thebehavior of cancer cells.
  164. 164. Process of angiogenesis (blood vessel development)
  165. 165.  1) Proteases enzymes breaks proteins .2) Angiogenesis is growth and development of blood vesselsspecific for cancer cells only.3) VEGF is a growth factor stimulate angiogenesis.4) Tumors develop blood vessels to provide them with nutrients.5) Soil and seed hypothesis isnt able to explain behavior of cancercells
  166. 166. 1.Cancer treatments.2.Surgery.3.Chemotherapy.4.Radiotherapy.
  167. 167. Cancer can be treated by surgery, chemotherapy,radiation therapy, immunotherapy, monoclonalantibody therapy or other methods.The choice of therapy depends upon1. the location2. grade of the tumor and the stage of the disease3. the general state of the patient (performance status). 4
  168. 168. • Surgery.Traditional • Chemotherapy. • Radiation therapyTherapies • Immune therapy. New • Gene therapy. • Stem cell therapy.Therapies • Nanotechnology tumor therapy. 5
  169. 169. 6
  170. 170. Aims Of Surgery Treatments Prevention Diagnosis
  171. 171. What is chemotherapy?Chemotherapy (also called chemo) is a typeof cancer treatment that uses drugs to destroycancer cells.
  172. 172. Antineoplastic CancerChemotherapy Cytotoxic 11
  173. 173. How does chemotherapy work?Chemotherapy works by stopping or slowing the growthof cancer cells, which grow and divide quickly. But it canalso harm healthy cells that divide quickly, such as thosethat line your mouth and intestines or cause your hair togrow. Damage to healthy cells may cause side effects.Often, side effects get better or go away afterchemotherapy is over.
  174. 174. What does chemotherapy do?Depending on your type of cancer and how advanced itis, chemotherapy can: Cure cancer - when chemotherapy destroys cancer cells to the point that your doctor can no longer detect them in your body and they will not grow back. Control cancer - when chemotherapy keeps cancer from spreading, slows its growth, or destroys cancer cells that have spread to other parts of your body. Ease cancer symptoms (also called palliative care) - when chemotherapy shrinks tumors that are causing pain or pressure.
  175. 175. How is chemotherapy used?Sometimes, chemotherapy is used as the only cancer treatment. But more often,you will get chemotherapy along with surgery, radiation therapy, or biologicaltherapy. Chemotherapy can: 1. Make a tumor smaller before surgery or radiation therapy. This is called neo- adjuvant chemotherapy. 2. Destroy cancer cells that may remain after surgery or radiation therapy. This is called adjuvant chemotherapy. 3. Help radiation therapy and biological therapy work better. 4. Destroy cancer cells that have come back (recurrent cancer) or spread to other parts of your body (metastatic cancer).
  176. 176. How is chemotherapy given?Chemotherapy may be given in many ways:Injection. The chemotherapy is given by a shot in amuscle in your arm, thigh, or hip or right under the skin inthe fatty part of your arm, leg, or belly.
  177. 177. Intra-arterial (IA). The chemotherapy goes directly into the artery that is feeding the cancer. Intravenous (IV). The chemotherapy goes directly into a vein.Intraperitoneal (IP). The chemotherapy goes directly into theperitoneal cavity (the area that contains organs such as yourintestines, stomach, liver, and ovaries).
  178. 178. Topically. The chemotherapy comes in a cream that you rub ontoyour skin. Orally. The chemotherapy comes in pills, capsules, or liquids that you swallow.
  179. 179. What are side effects?Side effects are problems caused by cancertreatment. Some common side effects fromchemotherapy are fatigue, nausea, vomiting,decreased blood cell counts, hair loss, mouthsores, and pain.
  180. 180. What causes side effects?Chemotherapy is designed to kill fast-growing cancercells. But it can also affect healthy cells that growquickly. These include cells that line your mouth andintestines, cells in your bone marrow that make bloodcells, and cells that make your hair grow. Chemotherapycauses side effects when it harms these healthy cells.
  181. 181. Side Effects1. Anemia 9. Infertility2. Appetite changes 10. Mouth and throat changes3. Bleeding 11. Nausea and vomiting4. Constipation 12. Nervous system changes5. Diarrhea 13. Pain6. Fatigue 14. Sexual changes7. Hair loss 15. Skin and nail changes8. Infection 16. Urinary, kidney, and bladder changes
  182. 182. Chemotherapeutic Drugs Groups
  183. 183. Alkylating Agents: Nitrosoureasm AntimetabolitesAnthracyclines and Related Drugs Topoisomerase Inhibitors Mitotic InhibitorsMiscellaneous Chemotherapy Drugs
  184. 184. •Radiation uses high energy x-rays, electronbeams or radioactive isotopes for damaging ordestroying malignant cancer cells.•The main objective is destroying cancer cellswith minimum injury to normal tissue andorgan.
  185. 185. •There are two types of radio therapy: Internal External
  186. 186. Internal radiation therapy (also calledbrachytherapy) uses radiation that is placed very close to or inside the tumor. The radiation source is usually sealed in a small holder called an implant. Implants may be in the form of thin wires, plastic tubes called catheters, ribbons, capsules, or seeds. The implant is put directly into the body. Internal radiation therapy may require a hospital stay.
  187. 187. External radiation therapyusually is given on an outpatient basis; most patients donot need to stay in the hospital. External radiation therapyis used to treat most types of cancer, including cancer ofthe bladder, brain, breast, cervix, larynx, lung, prostate,and vagina. In addition, external radiation may be used torelieve pain or ease other problems when cancer spreadsto other parts of the body from the primary site
  188. 188. What are the sources of energy for externalradiation therapy? X-rays or gamma rays, which are both forms of electromagnetic radiation. Although they are produced in different ways, both use photons (packets of energy). Particle beams use fast-moving subatomic particles instead of photons. This type of radiation may be called particle beam radiation therapy or particulate radiation.
  189. 189. Types of Radiation Used to Treat Cancer
  190. 190. Ionizing radiation used in two majortypes: X-rays Gamma rays Electrons Protons Neutrons Alpha and Beta Particles
  191. 191. The most common types of radiation Used in cancer treatments:
  192. 192. NecrosisApoptosis Terminal differentiation
  193. 193.  1) Location isnt play role in determination of treatment of cancer2) Surgery used in prevention and diagnosis of cancer besidetreatment.3) Cytotoxic chemotherapeutic drugs used in killing cancer cells.4) There isnt any effect on blood from chemotherapy.5) Radiation cause necrosis of cancer cell.