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Understanding Cancer



          Heri Fadjari

          Hematology – Medical Oncology Division
          Dept. of Internal Medicine


          Hasan Sadikin General Hospital
          Bandung
What Is Cancer?
Different Kinds of Cancer


                             Leukemias:
Some common
                             Bloodstream
  carcinomas:
         Lung                Lymphomas:
                             Lymph nodes
Breast (women)




        Colon                Some common
                             sarcomas:
      Bladder
                             Fat
Prostate (men)
                             Bone

                             Muscle
Naming Cancers

Cancer Prefixes Point to Location
Prefix     Meaning
adeno-     gland
chondro-   cartilage
erythro-   red blood cell
hemangio- blood vessels
hepato-    liver
lipo-      fat
lympho-    lymphocyte
melano-    pigment cell
myelo-     bone marrow
myo-       muscle
osteo-     bone
Loss of Normal Growth Control

     Normal
cell division


                                                              Cell Suicide or Apoptosis

                                      Cell damage—
                                        no repair


     Cancer
cell division




                 First     Second        Third      Fourth or
                mutation   mutation     mutation later mutation
                                                                  Uncontrolled growth
Example of Normal Growth


  Dead cells
  shed from
outer surface


   Epidermis
                         Cell migration


Dividing cells
in basal layer
                         Dermis
The Beginning of Cancerous Growth




                       Underlying tissue
Tumors (Neoplasms)




               Underlying tissue
Invasion and Metastasis




            1
            Cancer cells invade
            surrounding tissues
            and blood vessels
                 2
                 Cancer cells are
                 transported by the
                 circulatory system
                 to distant sites
                       3
                       Cancer cells
                       reinvade and grow
                       at new location
Malignant versus Benign Tumors
       Benign (not cancer)       Malignant (cancer)
       tumor cells grow          cells invade
       only locally and cannot   neighboring tissues,
       spread by invasion or     enter blood vessels,
       metastasis                and metastasize to
                                 different sites




Time
Why Cancer Is Potentially Dangerous

           Brain



                        Melanoma
                        cells travel
                        through
                        bloodstream

            Liver


       Melanoma
   (initial tumor)
Cancer Detection and Diagnosis
Early Cancer May Not Have Any Symptoms
Cervical Cancer Screening


                       Normal
                       Pap smear




                       Abnormal
                       Pap smear
Breast Cancer Screening
Prostate and Ovarian Cancer Screening
Colon Cancer Screening
Biopsy




                      Pathology




                   Proteomic profile




    Patient’s
tissue sample or   Genomic profile
  blood sample
Microscopic Appearance of Cancer Cells
Hyperplasia




Normal                 Hyperplasia
Dysplasia




Normal    Hyperplasia   Mild dysplasia
Carcinoma in Situ




Normal   Hyperplasia     Mild      Carcinoma in
                       dysplasia    situ (severe
                                     dysplasia)      Cancer
                                                   (invasive)
Tumor Grading

           General Relationship Between
            Tumor Grade and Prognosis
  100%


                                              Low grade

 Patient
Survival
   Rate
                                              High grade




              1      2           3   4    5
                         Years
Tumor Staging
          Five-Year Survival Rates for
       Patients with Melanoma (by stage)
100%




50%




           I            II            III
         Stage at Time of Initial Diagnosis
What Causes Cancer?
           Some viruses or bacteria




Some chemicals                    Radiation


                   Heredity
                     Diet
                  Hormones
Population-Based Studies
             Regions of Highest Incidence
U.K.:
Lung
cancer



                          JAPAN:
                          Stomach
                          cancer             CANADA:
                                             Leukemia

                                    U.S.:
           CHINA:                   Colon
           Liver                    cancer
           cancer
                                             BRAZIL:
                                             Cervical
                AUSTRALIA:                   cancer
                Skin
                cancer
Heredity? Behaviors? Other Factors?

          Colon Cancer                     Stomach Cancer
         (Number of new cases              (Number of new cases
           per 100,000 people)               per 100,000 people)
100                                100

                                   70

50



                                    7
 5
 0                                  0
      Japan Japanese        U.S.         Japan Japanese        U.S.
             families                           families
              in U.S.                            in U.S.
Tobacco Use and Cancer
Some Cancer-Causing Chemicals in Tobacco Smoke
Low-Strength Radiation

    High


                                         Dallas


     Skin
   Cancer
Incidence
                          Pittsburgh
             Detroit


     Low
            Least                           Most
                       Annual Sunshine
                        (UV radiation)
High-Strength Radiation

    High




Leukemia
Incidence




     Low
            Least                        Most
                        X-ray Dose
                    (atomic radiation)
Lag Time

                 20-Year Lag Time Between
                 Smoking and Lung Cancer
                     Cigarette
                     consumption
                     (men)
              4000

                                   Lung
                                            150
 Cigarettes   3000                 cancer
   Smoked                                         Lung Cancer
                                   (men)
per Person                                  100   Deaths (per
   per Year                                       100,000 people)
              2000
                                            50
              1000

                1900 1920 1940 1960 1980
                          Year
Viruses




                      Virus inserts
                      and changes
                      genes for
                      cell growth
Cancer-linked virus
Examples of Human Cancer Viruses


    Some Viruses Associated with Human Cancers
AIDS and Kaposi’s Sarcoma


   Without
   disease


HIV infection
                  Depressed
                   immune
                    system

                KSHV infection
                                 Kaposi’s
                                 sarcoma
Bacteria and Stomach Cancer




         Patient’s    H. pylori
      tissue sample
Heredity and Cancer

                  All Breast Cancer Patients




Inherited factor(s)
Other factor(s)
Heredity Can Affect Many Types of Cancer


     Inherited Conditions That Increase Risk for Cancer
Genetic Testing
Cancer Risk and Aging

                       Cancer Risk and Aging
            400
                                                     Colon

            300
                                                     Breast
   Number of
Cancer Cases 200
 (per 100,000
      people)
            100



                   0     20     40       60     80
                       Age of Person (in years)
Genes and Cancer
            Viruses

Chemicals             Radiation




      Heredity




                                  Chromosomes
                                  are DNA
                                  molecules
DNA Structure




                Chemical
                bases


                A
                    T
                C
                    G

DNA molecule
DNA Mutation
         CA AG C T A A C T
DNA

                Normal gene


         CA AG C G A A C T


                Single base change


         CA A G G CG C T A A C T


                Additions
                            C
                             T
         CA A G A A C T


                Deletions
Oncogenes


Normal cell                         Normal
                                     genes
                                      regulate
                                        cell growth




                                    Oncogenes
Cancer cell                         accelerate
                                     cell growth
                                      and division




         Mutated/damaged oncogene
Proto-Oncogenes and Normal Cell Growth
                  Normal Growth-Control Pathway

  Growth factor

      Receptor
                             Signaling enzymes

                                        Transcription
                                        factors

                                             DNA
   Cell nucleus




                               Cell proliferation
Oncogenes are
   Mutant Forms of Proto-Oncogenes
        Inactive growth factor receptor         Inactive intracellular
                                                signaling protein

Signaling protein from active oncogene


                                              Activated gene
                                              regulatory protein




                                                  Transcription




                                       Cell proliferation driven by
                                      internal oncogene signaling
Tumor Suppressor Genes


  Normal cell                            Normal
                                         genes
                                          prevent
                                            cancer



Remove or inactivate
tumor suppressor genes




  Cancer cell                            Damage to
                                         both genes
                                          leads to
                                            cancer


                  Mutated/inactivated
                tumor suppressor genes
Tumor Suppressor Genes
           Act Like a Brake Pedal
                      Tumor Suppressor
                        Gene Proteins
Growth factor

    Receptor


                Signaling
                enzymes                Transcription
                                       factors
 Cell nucleus                             DNA




                            Cell proliferation
p53 Tumor Suppressor Protein
       Triggers Cell Suicide

              p53 protein




Normal cell   Excessive DNA damage   Cell suicide
                                     (Apoptosis)
DNA Repair Genes



            Normal DNA repair
                 T C GA C
Base pair
mismatch                        No cancer
 TC TAC

                 AG C T G

                 TCTAC          TCT AC

 AG C T G
                                            Cancer

                 AG   TG        AG A T G
                      No DNA repair
Cancer Tends to Involve Multiple Mutations
        Benign tumor cells         Malignant cells invade
        grow only locally and      neighboring tissues, enter
        cannot spread by           blood vessels, and
        invasion or metastasis     metastasize to different sites




 Time
 Mutation    Cells          Mutations    Proto-oncogenes     More mutations,
 inactivates proliferate    inactivate   mutate to           more genetic
 suppressor                 DNA repair   oncogenes           instability,
 gene                       genes                            metastatic
                                                             disease
Mutations and Cancer

   Genes Implicated in Cancer
Cancer Tends to
Corrupt Surrounding Environment
Growth factors = proliferation
                                 Invasive




Matrix

                                   Proteases
  Fibroblasts,
  adipocytes                                      Cytokines
                                   Blood vessel




Cytokines, proteases = migration & invasion
Cancer Prevention

                  Carcinogenic
                   chemicals
   Carcinogenic
     radiation


Cancer viruses
  or bacteria
Avoid Tobacco

                   Lung Cancer Risk Increases
                   with Cigarette Consumption
         15x



         10x
 Lung
Cancer
  Risk
         5x




               0                  15              30
         Non-smoker
                      Cigarettes Smoked per Day
Protect Yourself From Excessive Sunlight
Limit Alcohol and Tobacco
    Combination of Alcohol and Cigarettes
 Increases Risk for Cancer of the Esophagus
              40x


              30x
       Risk
   Increase
              20x


              10x



   Alcoholic Drinks
   Consumed per Day
                         AND
   Packs of Cigarettes
   Consumed per Day
Diet: Limit Fats and Calories
             Correlation Between Meat Consumption and
              Colon Cancer Rates in Different Countries

                  40


                  30
Number of Cases
   (per 100,000
        people)
                  20


                  10



                       0    80    100    200     300
                           Grams (per person per day)
Diet: Consume Fruits and Vegetables
Avoid Cancer Viruses

              HPV Infection Increases
      High
              Risk for Cervical Cancer




Cervical
 Cancer
   Risk




       Low
             Noninfected     Women
               women         infected
                             with HPV
Avoid Carcinogens at Work

   Some Carcinogens in the Workplace
Industrial Pollution




 Incidence of
Most Cancers




            1930     1950          1970   1990
                            Year
Is There a Cancer "Epidemic"?
We would like to hear a questions from you . . .
.
Breast implant




Breast augmentation
A good result, but note
   the excessive gap
    between breasts,
       common in
 transsexual women.
Saline filled implants
Augmentation                    3-Year Risk Rate
  Complications            By Patient       By Implant
                            N=1264           N=2528
Wrinkling                      21%            20%
Reoperation                    13%            10%
Loss of Nipple Sensation       10%             8%
Capsular Contracture             9%            7%
Implant Remova                 l8%             6%
Asymmetry                        7%            5%
Intense Nipple Sensation         5%            4%
Breast Pain                      5%            4%
Leakage/Deflation                3%            2%
Implant Palpability              2%            2%
Infection                        2%            1%
Breast Sagging                   2%            1%
Scarring Complications           2%            2%
Wrinkling   Capsular contracture
Understanding cancer
Understanding cancer
Understanding cancer
Understanding cancer
Understanding cancer
Understanding cancer
Understanding cancer
Understanding cancer

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Understanding cancer

  • 1. Understanding Cancer Heri Fadjari Hematology – Medical Oncology Division Dept. of Internal Medicine Hasan Sadikin General Hospital Bandung
  • 3. Different Kinds of Cancer Leukemias: Some common Bloodstream carcinomas: Lung Lymphomas: Lymph nodes Breast (women) Colon Some common sarcomas: Bladder Fat Prostate (men) Bone Muscle
  • 4. Naming Cancers Cancer Prefixes Point to Location Prefix Meaning adeno- gland chondro- cartilage erythro- red blood cell hemangio- blood vessels hepato- liver lipo- fat lympho- lymphocyte melano- pigment cell myelo- bone marrow myo- muscle osteo- bone
  • 5. Loss of Normal Growth Control Normal cell division Cell Suicide or Apoptosis Cell damage— no repair Cancer cell division First Second Third Fourth or mutation mutation mutation later mutation Uncontrolled growth
  • 6. Example of Normal Growth Dead cells shed from outer surface Epidermis Cell migration Dividing cells in basal layer Dermis
  • 7. The Beginning of Cancerous Growth Underlying tissue
  • 8. Tumors (Neoplasms) Underlying tissue
  • 9. Invasion and Metastasis 1 Cancer cells invade surrounding tissues and blood vessels 2 Cancer cells are transported by the circulatory system to distant sites 3 Cancer cells reinvade and grow at new location
  • 10. Malignant versus Benign Tumors Benign (not cancer) Malignant (cancer) tumor cells grow cells invade only locally and cannot neighboring tissues, spread by invasion or enter blood vessels, metastasis and metastasize to different sites Time
  • 11. Why Cancer Is Potentially Dangerous Brain Melanoma cells travel through bloodstream Liver Melanoma (initial tumor)
  • 12. Cancer Detection and Diagnosis
  • 13. Early Cancer May Not Have Any Symptoms
  • 14. Cervical Cancer Screening Normal Pap smear Abnormal Pap smear
  • 16. Prostate and Ovarian Cancer Screening
  • 18. Biopsy Pathology Proteomic profile Patient’s tissue sample or Genomic profile blood sample
  • 20. Hyperplasia Normal Hyperplasia
  • 21. Dysplasia Normal Hyperplasia Mild dysplasia
  • 22. Carcinoma in Situ Normal Hyperplasia Mild Carcinoma in dysplasia situ (severe dysplasia) Cancer (invasive)
  • 23. Tumor Grading General Relationship Between Tumor Grade and Prognosis 100% Low grade Patient Survival Rate High grade 1 2 3 4 5 Years
  • 24. Tumor Staging Five-Year Survival Rates for Patients with Melanoma (by stage) 100% 50% I II III Stage at Time of Initial Diagnosis
  • 25. What Causes Cancer? Some viruses or bacteria Some chemicals Radiation Heredity Diet Hormones
  • 26. Population-Based Studies Regions of Highest Incidence U.K.: Lung cancer JAPAN: Stomach cancer CANADA: Leukemia U.S.: CHINA: Colon Liver cancer cancer BRAZIL: Cervical AUSTRALIA: cancer Skin cancer
  • 27. Heredity? Behaviors? Other Factors? Colon Cancer Stomach Cancer (Number of new cases (Number of new cases per 100,000 people) per 100,000 people) 100 100 70 50 7 5 0 0 Japan Japanese U.S. Japan Japanese U.S. families families in U.S. in U.S.
  • 28. Tobacco Use and Cancer Some Cancer-Causing Chemicals in Tobacco Smoke
  • 29. Low-Strength Radiation High Dallas Skin Cancer Incidence Pittsburgh Detroit Low Least Most Annual Sunshine (UV radiation)
  • 30. High-Strength Radiation High Leukemia Incidence Low Least Most X-ray Dose (atomic radiation)
  • 31. Lag Time 20-Year Lag Time Between Smoking and Lung Cancer Cigarette consumption (men) 4000 Lung 150 Cigarettes 3000 cancer Smoked Lung Cancer (men) per Person 100 Deaths (per per Year 100,000 people) 2000 50 1000 1900 1920 1940 1960 1980 Year
  • 32. Viruses Virus inserts and changes genes for cell growth Cancer-linked virus
  • 33. Examples of Human Cancer Viruses Some Viruses Associated with Human Cancers
  • 34. AIDS and Kaposi’s Sarcoma Without disease HIV infection Depressed immune system KSHV infection Kaposi’s sarcoma
  • 35. Bacteria and Stomach Cancer Patient’s H. pylori tissue sample
  • 36. Heredity and Cancer All Breast Cancer Patients Inherited factor(s) Other factor(s)
  • 37. Heredity Can Affect Many Types of Cancer Inherited Conditions That Increase Risk for Cancer
  • 39. Cancer Risk and Aging Cancer Risk and Aging 400 Colon 300 Breast Number of Cancer Cases 200 (per 100,000 people) 100 0 20 40 60 80 Age of Person (in years)
  • 40. Genes and Cancer Viruses Chemicals Radiation Heredity Chromosomes are DNA molecules
  • 41. DNA Structure Chemical bases A T C G DNA molecule
  • 42. DNA Mutation CA AG C T A A C T DNA Normal gene CA AG C G A A C T Single base change CA A G G CG C T A A C T Additions C T CA A G A A C T Deletions
  • 43. Oncogenes Normal cell Normal genes regulate cell growth Oncogenes Cancer cell accelerate cell growth and division Mutated/damaged oncogene
  • 44. Proto-Oncogenes and Normal Cell Growth Normal Growth-Control Pathway Growth factor Receptor Signaling enzymes Transcription factors DNA Cell nucleus Cell proliferation
  • 45. Oncogenes are Mutant Forms of Proto-Oncogenes Inactive growth factor receptor Inactive intracellular signaling protein Signaling protein from active oncogene Activated gene regulatory protein Transcription Cell proliferation driven by internal oncogene signaling
  • 46. Tumor Suppressor Genes Normal cell Normal genes prevent cancer Remove or inactivate tumor suppressor genes Cancer cell Damage to both genes leads to cancer Mutated/inactivated tumor suppressor genes
  • 47. Tumor Suppressor Genes Act Like a Brake Pedal Tumor Suppressor Gene Proteins Growth factor Receptor Signaling enzymes Transcription factors Cell nucleus DNA Cell proliferation
  • 48. p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage Cell suicide (Apoptosis)
  • 49. DNA Repair Genes Normal DNA repair T C GA C Base pair mismatch No cancer TC TAC AG C T G TCTAC TCT AC AG C T G Cancer AG TG AG A T G No DNA repair
  • 50. Cancer Tends to Involve Multiple Mutations Benign tumor cells Malignant cells invade grow only locally and neighboring tissues, enter cannot spread by blood vessels, and invasion or metastasis metastasize to different sites Time Mutation Cells Mutations Proto-oncogenes More mutations, inactivates proliferate inactivate mutate to more genetic suppressor DNA repair oncogenes instability, gene genes metastatic disease
  • 51. Mutations and Cancer Genes Implicated in Cancer
  • 52. Cancer Tends to Corrupt Surrounding Environment Growth factors = proliferation Invasive Matrix Proteases Fibroblasts, adipocytes Cytokines Blood vessel Cytokines, proteases = migration & invasion
  • 53. Cancer Prevention Carcinogenic chemicals Carcinogenic radiation Cancer viruses or bacteria
  • 54. Avoid Tobacco Lung Cancer Risk Increases with Cigarette Consumption 15x 10x Lung Cancer Risk 5x 0 15 30 Non-smoker Cigarettes Smoked per Day
  • 55. Protect Yourself From Excessive Sunlight
  • 56. Limit Alcohol and Tobacco Combination of Alcohol and Cigarettes Increases Risk for Cancer of the Esophagus 40x 30x Risk Increase 20x 10x Alcoholic Drinks Consumed per Day AND Packs of Cigarettes Consumed per Day
  • 57. Diet: Limit Fats and Calories Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries 40 30 Number of Cases (per 100,000 people) 20 10 0 80 100 200 300 Grams (per person per day)
  • 58. Diet: Consume Fruits and Vegetables
  • 59. Avoid Cancer Viruses HPV Infection Increases High Risk for Cervical Cancer Cervical Cancer Risk Low Noninfected Women women infected with HPV
  • 60. Avoid Carcinogens at Work Some Carcinogens in the Workplace
  • 61. Industrial Pollution Incidence of Most Cancers 1930 1950 1970 1990 Year
  • 62. Is There a Cancer "Epidemic"?
  • 63. We would like to hear a questions from you . . . .
  • 65. A good result, but note the excessive gap between breasts, common in transsexual women.
  • 66.
  • 67.
  • 69. Augmentation 3-Year Risk Rate Complications By Patient By Implant N=1264 N=2528 Wrinkling 21% 20% Reoperation 13% 10% Loss of Nipple Sensation 10% 8% Capsular Contracture 9% 7% Implant Remova l8% 6% Asymmetry 7% 5% Intense Nipple Sensation 5% 4% Breast Pain 5% 4% Leakage/Deflation 3% 2% Implant Palpability 2% 2% Infection 2% 1% Breast Sagging 2% 1% Scarring Complications 2% 2%
  • 70. Wrinkling Capsular contracture