aula cancro
TRANSCRIPT
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Hugo SousaBScH Microbiology| MSc Oncology | PhD Biomedical Sciences
MD Student @ [email protected]
CANCRO…uma abordagem geral
_________________________________________Serviço Virologia – Lab Biologia MolecularGrupo Oncologia Molecular
NÚCLEO REGIONAL DO NORTE
+Verdade ou Mentira…
O Cancro é uma doença GENETICA
O Cancro é uma doença INFECCIOSA
O Cancro é uma doença ADQUIRIDA
O Cancro é uma doença SEXUALMENTE TRANSMITIDA
O Cancro é uma doença PREVENÍVEL
O Cancro é uma doença HEREDITÀRIA
+Cancro…Breve introdução
+Cancro...
+Cancro…
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Lung
Breast (women)
Colon
BladderProstate (men)
Common sarcomas:Fat
Bone
Muscle
Lymphomas:Lymph nodes
Leukemias:Bloodstream
Common carcinomas:
Cancro…
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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
Cancro…
+Cancro…Epidemiologia
+Cancro...Grave problema de saúde pública…
+Cancro…
+Cancro…Homem
+Cancro…Mulher
+Cancro…Epidemiologia
+Cancro…Epidemiologia
CANADA:
Leukemia
BRAZIL:
Cervical cancer
U.S.:
Colon cancer
AUSTRALIA:
Skin cancer
CHINA:
Liver cancer
U.K.:
Lung cancer
JAPAN:
Stomach
cancer
+Cancro…Etiologia
+Cancro...Etiologia
Doesyour cancer share similar mutations?
Cancer genome
Gene mutations
Gene mutations
Kidney Cancer: A Sporadic CaseKidney Cancer in FamilyCancer
cells
Cancergenome
+Cancro...Etiologia
+Cancro...Etiologia hereditária
Inherited factor(s)
All Breast Cancer Patients
Other factor(s) ~15% Hereditário
+Cancro...Etiologia multifactorial
Agentes Biológicos
Hospedeiro
AmbienteHábitos
Agentes FísicosAgentes Químicos
- Vírus- Bactérias
- Radiações
The role of these factors has been demonstrated consistently in modern populations, but the epidemiology of cancer has changed over human history as the environmental conditions and the genetic characteristics of human populations have changed (Vogelstein B and Kinzler KW 2001; Capasso LL 2005)
ExposiçãoAmbiental
CargaGenética
Interacção
+Cancro...Etiologia multifactorial
Age
Obesity
Weak immune system
AlcoholDietSmoking
Cancer
AlcoholDietSmokingCarcinogensViruses
HormonesDiet
Age Age
Cancer
Time
+Cancro…Exposição Ambiental
= cancer
+Cancro…Exposição Ambiental
+Cancro…Exposição Ambiental
+Cancro…Exposição Ambiental
Metal Cancers Present in Human Carcinogen?
Arsenic Skin, lung, bladder, Wood preservatives, Yeskidney, liver glass, pesticides
Beryllium Lung Nuclear weapons, Yesrocket fuel, ceramics, glass, plastic,fiberoptic products
Cadmium Lung Metal coatings, Yesplastic products,batteries, fungicides
Chromium Lung Automotive parts, Yes floor covering, paper, cement, asphalt roofing; anti-corrosive metal plating
Lead Kidney, brain Cotton dyes, metal Probable carcinogencoating, drier in paints, varnishes and pigment inks, certain plastics, specialty glass
Nickel Nasal cavity, lung Steel, dental fillings, Nickel metal: copper and brass, Probable carcinogenpermanent magnets, storage batteries, Nickel compounds:glazes Yes
+Cancro…Tabaco
aminostilbene arsenic benz[a]anthracene benz[a]pyrene benzene benzo[b]fluoranthenebenzo[c]phenanthrene benzo[f]fluoranthene cadmium chrysene dibenz[a c]anthracene
dibenzo[a e]fluoranthene dibenz[a h]acridine dibenz[a j]acridine dibenzo[c g]carbazoneN-dibutylnitrosamine 2,3-dimethylchrysene indeno[1,2,3-c d]pyrene S-methylchryseneS-methylfluoranthene alpha-naphthylamine nickel compounds N-nitrosodimethylamine
N-nitrosomethylethylamine N-nitrosodiethylamine N-nitrosonornicotine N-nitrosoanabasineN-nitrosopiperidine polonium-210
Non-smoker
Lung
Can
cer
Ris
k
5x
10x
15x
3015
Cigarettes Smoked per Day
0
+Cancro...Vírus
1908 – Leucemia Aviária (Agente transmissível um Vírus);
1911 – Chicken Sarcoma (Rous Sarcoma Virus – RSV);
1964 – Linfoma de Burkitt (Epstein-Barr Virus – EBV);
1980 – Leucemia Células T (Human T-cell Leukemia Virus – HTLV-1)
Nos anos 90 a OMS reconheceu a associação entre Vírus e Cancro HPV e Cancro do Colo do Útero HBV e Hepatocarcinoma EBV e Linfoma de Burkitt
+Cancro...Vírus
Repr
esen
tam
cer
ca d
e 15
% d
e Re
pres
enta
m c
erca
de
15%
de
todo
s os
cas
os d
e ca
ncro
todo
s os
cas
os d
e ca
ncro
+Cancro...Etiologia
Proportion of Cancer Deaths Linked to
Avoidable Risk Factors
Tobacco 29–31 percent
Diet 20–50 percent
Infections:
bacteria, viruses 10–20 percent
Ionizing and UV light 5–7 percent
Occupation 2–4 percent
Pollution:
air, water, food 1–5 percent
Source: Doll R. (UK data) Recent Results in
Cancer Research 1998; 154:3-21.
+Cancro...Interacção hospedeiro-ambiente
+Cancro...Interacção hospedeiro-ambiente
Mutated susceptibility genes
Weak immune system
Mutated detox enzymes
Mutated repair genes
Change in hormone levels
Cancer patient
+Cancro...Interacção hospedeiro-ambiente
Water-soluble carcinogen
Carcinogen
Hyperactive detox proteins
Slow detox proteins
Water-soluble carcinogen
Carcinogen
+Cancro…Carcinogénese
+Cancro...Carcinogénese
Diabetic islet cell
Normal islet cellNormal lung cell
Lung cancer cell
Many years later
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CancroDesregulação•Proliferação aumentada
•Morte celular diminuída
+Cancro...Carcinogénese
Cell Suicide or Apoptosis
Normal cell
division
Químicos
Vírus
Físicos
+Cancro...
Iniciação Alterações genéticas
Promoção Adopção de novo fenótipo
Transformação Re-organização das células
Progressão Selecção clonal das células e proliferação
Metastização Disseminação à distância
Carcinogénese
+Cancro...Carcinogénese
Malignant cells
Normalcell
Fourth orlater mutation
Thirdmutation
Secondmutation
Firstmutation
M (mitosis)
DNA repair genes
Oncogenes
Tumor suppressor
genesG2
G1 (cell growth)
S (synthesis)
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CancroDesregulação•Proliferação aumentada
•Morte celular diminuída
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CancroDesregulação•Proliferação aumentada
•Morte celular diminuída
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+Cancro...Carcinogénese
Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
Time
Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis
+Cancro...Carcinogénese
TimeMore mutations, more genetic instability, metastatic disease
Proto-oncogenes mutate to oncogenes
Mutations inactivate DNA repair genes
Cellproliferataion
Mutation inactivates suppressor gene
Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis
+Cancro...Carcinogénese
+Cancro...Carcinogénese
+Cancro...Carcinogénese
Growth factors = proliferation
Blood vessel
Proteases
Cytokines
Matrix
Fibroblasts, adipocytes
Invasive
Cytokines, proteases = migration & invasion
+Cancro...Carcinogénese
+Cancro...Carcinogénese
Melanoma cells travel through bloodstream
Melanoma(initial tumor)
Brain
Liver
+Cancro...Carcinogénese
+Cancro…Carcinogénese - exemplos
+CancerMultistep & multifactorial disease
Normal
Pre neoplastic lesion
Grade I
Ca In Situ Invasive Ca
infection iniciation
transformation progression invasion
Abolishment of Immune Response
Abolishment of Cell Cycle
regulation
Abolishment of Apoptosis
Activation of Invasion Pathways
Susceptibility to Viral Infection
Pre neoplastic lesion
Grade II
Pre neoplastic lesion
Grade III
+CancerMultistep & multifactorial disease
+CancerMultistep & multifactorial disease
+CancerMultistep & multifactorial disease
+Cancro…Rastreio e Diagnóstico Precoce
Cancer Screening for Early Detection
Normal Pap smear
Abnormal Pap smear
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Abnormal Pap smear
Normal Pap smear
Cancro…Cervical Cancer Screening
+Cancro…Breast Cancer Screening
+Cancro…Prostate and Ovarian Cancer Screening
+CancroColon Cancer Screening
+Cancro…Rastreios vs Guidelines…
+Cancro…Estadiamento
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Grade 1 (of 4) Renal Carcinoma Grade 3 (of 4) Renal Carcinoma
Cancro…Estadiamento
+Cancro…
Sistema desenvolvido para ajudar os clínicos
Forma uniforme de falar dos casos e de agrupar se acordo com tipos de tratamento e prognóstico
TNM T = Tumor (tamanho, extensão…) N = Nodes (gânglios linfáticos locais/distantes) M = Metastasis (metastização)
Estadio Integração dos dados do TNM
Estadiamento
+Cancro…
T refers to the extent of the primary tumor Tx - cannot assess T0 indicates no evidence of primary tumor Tis is carcinoma in situ T1, T2, T3 and T4
Estadiamento TNM
+Cancro…
N to the extent of regional lymph node metastases Nx - cannot assess N0 - no regional node metastases N1, N2, N3 indicate increasing involvement of regional lymph nodes
Examples… Breast
1 of 15 axillary LNs + (breast) = N1 Cervix
1 + pelvic node = N1
Estadiamento TNM
+Cancro…
M to absence or presence of distant metastases... Mx - cannot assess M0 is no distant metastases M1 indicates distant metastases
Estadiamento TNM
+Cancro…
Referência global (varia de acordo com o tumor) Tis = Stage 0 Stage I Stage II Stage III Stage IV
Estadiamento TNM
Group Stage Examples (Breast)Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIA T0 N1 M0
~~~~~ ~~~~~ ~~~~ ~~~
Stage IIIB T4 N0 M0
Stage IIIC Any T N3 M0
Stage IV Any T Any N M1
+Cancro…
Referência global (varia de acordo com o tumor) Tis = Stage 0 Stage I Stage II Stage III Stage IV
Estadiamento TNM
Group Stage Examples (Cervix)Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIA T2a N0 M0
~~~~~ ~~~~~ ~~~~ ~~~
Stage IIIB T1 N1 M0
T2 N1 M0
Stage IV Any T Any N M1
+Cancro…Estadiamento TNM
Five-Year Survival Rates forPatients with Melanoma (by stage)
Stage at Time of Initial Diagnosis
100%
50%
I II III
+Cancro…Prevenção
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Cancer viruses or bacteria
Carcinogenic radiation
Carcinogenic chemicals
Cancro…Prevenção
+Cancro…Prevenção
+Cancro…Prevenção
15x
10x
5x
Non-smoker Cigarettes Smoked per Day
Lung Cancer Risk Increases with
Cigarette Consumption
Lung
Can
cer
Ris
k
0 15 30
40x
30x
20x
10x
Alcoholic Drinks Consumed per Day
Packs of Cigarettes Consumed per Day
Combination of Alcohol and Cigarettes Increases Risk for Cancer of the Esophagus
Ris
k In
crea
se
AND
+Cancro…Prevenção
0
Num
ber
of C
ases
(p
er 1
00,0
00 p
eop
le)
Grams (per person per day)
Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries
40
30
20
10
30020010080
+Cancro…Prevenção
Noninfected women
HPV Infection Increases Risk for Cervical Cancer
Cer
vica
l Can
cer
Ris
k
Low
High
Women infected with HPV
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Hugo SousaBScH Microbiology| MSc Oncology | PhD Biomedical Sciences
MD Student @ [email protected]
CANCRO…uma abordagem geral
_________________________________________Serviço Virologia – Lab Biologia MolecularGrupo Oncologia Molecular
NÚCLEO REGIONAL DO NORTE