aula cancro

+

Hugo SousaBScH Microbiology| MSc Oncology | PhD Biomedical Sciences

MD Student @ FMUPhugomls@gmail.com

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…

+

Lung

Breast (women)

Colon

BladderProstate (men)

Common sarcomas:Fat

Bone

Muscle

Lymphomas:Lymph nodes

Leukemias:Bloodstream

Common carcinomas:

Cancro…

+

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

+

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)

+

CancroDesregulação•Proliferação aumentada

•Morte celular diminuída

+

CancroDesregulação•Proliferação aumentada

•Morte celular diminuída

+

+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

+

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

+

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

+

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

+

Hugo SousaBScH Microbiology| MSc Oncology | PhD Biomedical Sciences

MD Student @ FMUPhugomls@gmail.com

CANCRO…uma abordagem geral

_________________________________________Serviço Virologia – Lab Biologia MolecularGrupo Oncologia Molecular

NÚCLEO REGIONAL DO NORTE