TODAY

1
TODAY

• ?? -gt ?? -gt ??

2
??
3
??(tumor)? ??

• ????? ??? ??? ?? ????
• ??? ????? ??? ??? ???
• ???, ??? ?? ??? ?? ????
• ?? ??? ??? ?? ?? ?? ???

4
??? ??
?? ??
-oma -carcinoma
-sarcoma
Malignant -
?? ??
?? ??
Nevus Seminoma
melanoma
Immature teratoma
5
???

• Neoplasia (???)
• The process of tumor growth
• Cancer (?)
• malignant neoplasm

6
???

• Dysplasia
• The disordered development of cells
• resuling in an alteration in their size,
• shape and organization
• Metaplasia
• The change from one type of
• differentiated tissue to another

7

• ???? vs. ????

8
1. ?? ??? ?? ??/???
9
??? ??
10

• Lack of differentiation or anaplasia
• Pleomorphism
• Abnormal nuclear morphology
• Mitoses
• Loss of polarity
• Other changes

11
2. ?? ??? ?? ????
???
???
VS.
12

• Fig 7-12

13
3. ?? ??? ?? ?? ??

• ?? ?? ????

14
??? ??
15
Development of sustained angiogenesis
???
????
???
16
Tumor vessel? ??

• Tortuous
• Irregularly shaped
• Unstable and leaky

17
4. ?? ??? ?? ??

• ??? ??

18
?? ??
19
??? ??
20

1. Seeding of body cavities and surfaces
2. Lymphatic spread
3. Hematogenous spread

21
??
?? ??
??/??? ??? ?? ??? ???
???? ??? ???
???? ?? ??? ??? ?? ?? ??? ??
?? ?? ??
22
? ??? (??)
2002? ?????
23
? ??? (??)
2002? ?????
24
??? ???
???
???
??
??
25
?? ? ????
26
?? ?????? ??
????? ????
?????? ??
??????? ???
???? ????
????? ?????
??? ??
27
?? ???
????
DNA ??
????
????
???????????
????????
???????
??? ??
??? ?? ?? ????
28
1. ?? ??? (protooncogenes, oncogenes)

• Genes that promote autonomous cell
• growth in cancer cells are called oncogenes,
• and their normal cellular counterparts
• are called protooncogenes.

29
Fig 7-32
30

• ?????
• ???? ????
• ?? ??? ???
• ?? ?? ???
• ????? ?????? ?????

31
Growth factor Protooncogene Associated human tumor
PDGF-b chain SIS Astrocytoma Osteosarcoma
Fibroblast growth factors HST-1 INS-2 Stomach cancer Bladder cancer Breast cancer Melanoma
TGFa TGF-a Astrocytoma Hepatocellular carcinoma
HGF HGF Thyroid cancer
32
Growth factor receptors Protooncogene Associated human tumor
EGF-receptor family ERB-B1 ERB-B2 Squamous cell carcinoma of lung Breast and ovary cancer
CSF-1 receptor FMS Leukemia
Receptor for neurotrophic factors RET Multiple endocrine neoplasia
PDGF receptor PDGF-R Gliomas
Receptor for stem cell factor KIT GIST
33
2. ??????? (tumor suppressor genes)

• The physiologic function of the genes
• is to regulate cell growth,
• not to prevent tumor formation.

34
?? ???
????
DNA ??
????
????
???? ???????
????????
???????
??? ??
??? ?? ?? ????
35

• Fig 7-36

36
(No Transcript)
37

• Rb ??? ????? ??
• p53 ???? ??, ?????
• APC familial adenomatous polyposis
• NF-1 neufibromatosis
• DCC ??, ???
• WT-1 ??? ?? ??

38
3. ??? ?? (Apoptosis)

• ???????

39
?? ???
????
DNA ??
????
????
???????
???????????
????????
??? ??
??? ?? ?? ????
40
Normal cells
Cancer cells?
Normal p53
Defective p53
Cell death by apotosis
Mutation repaired cells
Tumor
41

• Colon cancer ????

42
??- ??? ??

• ????? ???
• ??????? ????
• ????? ??

43
???? ???
44
?? ?? ??

• ??? ??
• ??? ??

45
1. ??? ??- ??? ????

• ??? ???? ?? ??

46
???
??
??? ????
??
DNA? ??
????
???
?? DNA ?? ????
???? ??, ??
??
????
47
Tobacco
Lung
Bladder
Oral cavity
Larynx
Esophagus
48
2. ??? ??- ??? ????

• ???
• ???

49
UV
Squamous cell carcinoma
Malignant melanoma
Basal cell carcinoma
50
3. ??? ??- ?? ???? ? ???

• ??? DNA ????
• Human papilloma virus
• Epstein-Barr virus
• Hepatitis B virus
• ??? RNA ????
• ?? T-?? ??? ????
• ?????

51

• ??? ??? ?? ?????!
• 1980? ?? ???????
• ?? ?? ?? ??? ?? ??

52
Helicobacter pylori

• 1. ?? ??? ????? ? ? ???
• 2. ??? ??? ???
• ?? ??? ??? ??? ????
• ?? ??? 30? ??
• 3. ??? ???
• ??????? ??? ???????

53
Virus Tumor
Human T cell leukemia T cell leukemia
Human immunodeficiency AIDS-related lymphoma
Human papilloma virus Cervical cancer
Epstein Barr virus Burkitt lymphoma
Hepatitis B virus Hepatocellular carcinoma
54
?? ?? ??

• ??? ??
• ??? ??

55
??? ??- ???? ?? ??? ? ???
Familial retinoblastoma
Familial adenomatous polyposis
Hereditary non polyposis colon cancer
Multiple endocrine neoplasia syndrome
Neurofibromatosis type 1 and 2
Von Hippel-Lindau syndrome
56
??? ??
??? ??- ??? ??
Breast cancer
Ovarian cancer
Colon cancers other than familiar adenomatous polyps
57
DNA ?? ??? ???? ?? ???
Xeroderma pigmentosum
Ataxia-telangiectasia
Blooms syndrome
Fanconis anemia
58
??- ?? ??

• ??? ??
• ??? ????
• ??? ????
• ?? ???? ? ???
• ??? ??
• ???? ?? ??? ? ???
• ??? ??
• DNA ?? ??? ???? ?? ???

59
???? ???
60
??? ?? ??-??
61
????- ????

• ?????? ????? ????
• ????? ???? ??
• (CEA, AFP, CA19-9, CA125, MAGE)

62

1. Products of mutated oncogenes and tumor suppresor
   genes
2. Overexpressed or aberrantly expressed cellular
   proteins
3. Tumor antigens produced by oncogenic viruses
4. Oncofetal antigens
5. Altered cell-surface glycolipids and
   glycoproteins
6. Cell type specific differentiation antigens

63
?? ????-????
64
????- ??? ????

• CD8 ???? T???
• NK/T ??
• Macrophages
• Antibodies

65
??? ???
66

• Fig 7-53

67

1. Selective outgrowth of antigen-negative variants
2. Loss of reduced expression of MHC molecules
3. Lack of costimulation
4. Immunosuppression
5. Antigen masking
6. Apoptosis of cytotoxic T cells

68
??? ????
69
???? ?? ??

• ??
• ??
• ?? ??

70
???????

• ?? ??? ?? ?? ????
• ????? ??? ??

71
Paraneoplastic syndrome

• Cushing syndrome
• Hypercalcemia
• Hyperglycemia
• Polycythemia
• Dermatomyositis
• Venous thrombosis
• Anemia

72
? ???
73
Cachexia results from the action of soluble
factors such as cytokines produced by the tumor
and by the host in response to the tumor.
TNF IL-1 IFN-r PIF
?
cachexia
74
??

• ??? ?? ??
• ?? ???? ???
• ??? ??? ???
• ?? ??? ???? ??

75
??? ?? ? ?? ???
76
??
77
????
78
??
79

• ????
• ????

80
?? ??- ???, ??
81
??? ???
82

• ??? ???.
• ??? ?? ?? ?? ?? ???.
• ??? ???? ???? ?? ???
• ? ??? ?? ???

83
???? ?? ??
84

• ?? ?? ???? ??? ? ??? ??? ??
• ??? ??? ????? ???? ??? ??
• ?????. ? ??? ???? ?? ? ?.
• ????? ???.
• ?, ? ???? ? ???. ??? ??
• ?? ?? ??? (12? ?) ?? ????
• ??? ? ? ? ???.

85

• ?? ??? ??? ?? ??? ????
• ???. ?? ??? ??? ??? ??
• ?? ??? ?? ????? ?? ???
• ??? ???? ??? ??? ??? ??
• ??? ???? ??? ?????.
• ??? ???? ??? ???? ??? ??
• ?? ??? (.) ??? ??? ?? ??
• ? ?? John Berger

86
8? 4??

• ???? ??

87
91?/1000?

• 5? ??? ????
• ????? ???

88
?? ? ?? ??
?? ?? ??
??
? ??
??
89
??? (Marasmus) ??????? (Kwashiorkor)
???? ?? ???? ??
??? ?? ? ????? ?? ?? (? ??) ?? (??? ??)
??? ?? ??, ???
??? ?? ??? ???
90
??? ??
91
Vitamin A

• ???? ???? ??
• ?? ???? ????
• ??? ???
• ?????
• ???? ???

92

• Fig 9-23

93
Vitamin C

• Fig 9-30

94
Vitamin D
95
Fig 9-24
96
?? ??- ??

• BMI
• Skin fold measurements
• Various body circumferences

97
United States of America
25
98

• Leptin

99
??
100
??

• Pathogenicity
• The capacity of a particular micro-organism to
  cause disease
• Virulence
• The degree of pathogenicity of a microorganism
  measured by the severity of the ensuing infection

101

• Opportunitic infection
• infection by organisms of low pathogenicity,
  usually due to impaired immune responses

102
Bioterrorism

• Category A
• Highest risk agents and can be readily
• disseminated or transmitted from person to person
• Category B
• Moderately easy to disseminate,
• produce moderate morbidity but low mortality
• Category C
• Emerging infectious disease threats
• Potential for high morbidity and mortality

103
Category A

• Anthrax
• Botulism
• Plague
• Smallpox
• Tularemia
• Viral hemorrhagic fevers (Ebola)

104
Categories of infectious agents

• Prions
• Viruses
• Bacteriophages, Plasmids, Transposons
• Bacteria
• Chlamydiae, Rickettsiae, Mycoplasmas
• Fungi
• Protozoa
• Helminths
• Ectoparasites

105
Infectious agents? ??

• Skin
• Gastrointestinal tract
• Respiratory tract
• Urogenital tract

106
? Gastrointestinal tract

• Viscous mucous layer covering the gut
• Lytic pancreatic enzymes
• Mucosal antimicrobial peptides called defensins
• 4) Normal flora
• 5) Secreted IgA antibodies

107
Microoganisms? ??? ???.

• Host cell?? ??? cell death
• Toxin
• Induce host cellular responses

108
Virus???
Reduced host cell DNA, RNA, protein systhesis
Metabolic derangements
Viral inclusion
Viral proteins
Cell lysis or fusion
Viral asembly
Neoplastic transformation
Viral antigens
109
????? ???? ?? ??
Gram stain Most bacteria
Acid-fast stain Mycobacteria
Silver stains Fungi, legionellae
PAS Fungi, amebae
Mucicarmine Cryptococci
Giemsa Campylobacteria
Culture All classes
110
Virus
111

• Rhinovirus
• Influenza virus
• Measles
• Mumps
• EBV
• CMV
• ..

112
Virus type Example
DNA viruses Herpes simplex virus VZV Adenovirus Papillomavirus
RNA viruses Measles virus Mumps virus Rabies virus Poliovirus
Retroviruses HIV I and II HTLV I and II
113
1. Rhinovirus

• ??? 60

114
2. Influenze virus

• A, B or C
• Viral hemagglutinin and neuraminidase
• (H1 to H16 N1 to N9)
• Antigenic shift- new face
• Antigenic drift- mutations of the
• hemagglutinin and
• neuraminidase

115
?? ?? (Avian bird influenza)

• A? ????? H5N1

116
(No Transcript)
117
(No Transcript)
118
(No Transcript)
119
3. ??? (mumps)? ?? (measles)

• p123

120
4. Epstein-Barr virus
121
(No Transcript)
122
5. Cytomegalovirus

1. Transplacental transmission
2. Cervical or vaginal secretion
3. Saliva
4. Venereal route
5. Iatrogenic transmission

123
CMV- Congenital infection

• 95 ???
• Cytomegalic inclusion disease
• remebles erythroblastosis fetalis

124
(No Transcript)
125
CMV- Immunosuppressed individuals

• Solid organ transplants
• Allogeneic bone marrow
• transplants
• AIDS

Pneumonia, colitis, retinitis.
126
(No Transcript)
127
Bacteria
128

• ?? ?? ? (Gram positive bacteria)
• ?? ?? ? (Gram negative bacteria)

129
Gram-positive bacteria

• ???? ?? (Staphylococcus)
• ???? ?? (Streptococcus)

130
Clusters
Staphylococcus
Aerobic
Chains/paris
Streptococcus
Cocci
Anaerobic
Peptococcus
Gram positive
Sporing
Bacillus
Aerobic
Non-sporing
Listeria
bacilli
Sporing
Clostridium
Anaerobic
Non-sporing
Propionibacterium
131
Staphylococcus
Respiratory infection
Wound infection
Toxic shock syndrome
Staphylococcal infection
Food poisoning
Endocarditis
Focal skin infection
132
Streptococcus
133

• A? (S. pyogenes)
• ???, ???, ???, ?????,
• ?????
• B? (S. agalactiae)
• ??? ???, ?? ??
• D? (Enterococcus faecalis)
• ????, ?? ??

134
Post-Streptococcal syndrome

• ???? ? (Rheumatoid fever)
• ????? ??? ??
• (Post-streptococcal glomerulonephritis)
• 3) ???? (Erythema nodosum)

135
Gram-negative bacteria

• ??? ?? (Escherichia coli)
• ??? ?? (Pseudomonas)

136
??? ?? (Escherichia coli)
ETEC Cholera-like toxin, no invasion Watery diarrhea
EHEC Shiga-like toxin, No invasion Hemorrhagic colitis
EPEC No invasion Watery diarrhea
EIEC Invasion Fever, pain, diarrhea
137
??? ?? (Pseudomonas)

• ??

138
Mycobacterium
139

• ?? (Tuberculosis)
• ???, ?? (Leprosy)

140
???

• Temp 32 34C (Human skin)
• Tuberculoid leprosy vs. Lepromatous leprosy

141
(No Transcript)
142
(No Transcript)
143

• Tuberculoid leprosy
• Dry, caly skin lesions that lack sensation
• Lepromatous leprosy
• Symmetric skin thickening and nodules
• Damage to the nervous system

144
(No Transcript)
145
Fungi
146

• ???? (Candida)
• ??????? (Aspergillus)
• ?????? (Cryptococcosis)
• ????? (Mucormycois)
• ????? ?? (pneumocystis carinii)

147
Immunosuppressive patients
148
Candida
149
Aspergillus
150
Cryptococcus
151
Malaria
152
(No Transcript)
153
(No Transcript)
154
(No Transcript)
155
(No Transcript)
156
?????? ????
???????
157
(No Transcript)
158
??? ??(Suppurative polymorphonuclear inflammation

• ??? ????
• Pyogenic bacteria
• ex. Staphylococcus aureus,
• Streptococcus pyogenes

159
???? ??(Granulomatous inflammation)

• ????
• Epithelioid feature? macrophage? ??
• ex. M. tuberculosis, M. leprae

160
??? ??(Necrotizing inflammation)

• ??? ??
• Ex. Clostridia

161
???????.