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Epidemiologia e noes principais sobre a Natureza do Cancro
(Epidemiology and major concepts about the Nature of Cancer)
Oncobiologia 2012FML
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Lung; 1608055;
12%
Breast; 1384155;
11%
Colorectum;
1235108; 10%
Stomach; 988602;
8%
Prostate; 899102;
7%Liver; 749744; 6%
Cervix uteri;
530232; 4%
Oesophagus;481645; 4%
Bladder; 382660;
3%
Other; 4403251;
35%
World Incidence New cases - 2008
All cancers excl. non-melanoma skin cancer New cases 12 662 554
SOURCE: GLOBOCAN 2008IARC
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Lung; 1376579;
18%
Stomach; 737419;
10%
Liver; 695726; 9%
Colorectum;
609051; 8%Breast; 458503;
6%Oesophagus;
406533; 5%
Cervix uteri;
275008; 4%
Pancreas; 266669;
4%
Prostate; 258133;
3%
Other; 2481181;
33%
World Mortality - Deaths - 2008
All cancers excl. non-melanoma skin cancer - Deaths 7 564 802
SOURCE: GLOBOCAN 2008IARC
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223,2246,9
264,3 255,8
181,6
106,3117,3 114,7 111,1 106,1
0
50
100
150
200
250
300
PORTUGAL EUROPE EUROPEAN
UNION (EU-27)
MORE
DEVELOPED
REGIONS
WORLD
New cases Age-standardised rate (W)/105 Inhabitants
Deaths Age-standardised rate (W)/105 Inhabitants
2008
New cases Age-standardised rate (W) Deaths Age-standardised rate (W)
SOURCE: GLOBOCAN 2008IARC
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40,6
37,0
41,6 40,8 40,8 40,4
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
40,045,0
Colorectum Breast Prostate Lung Stomach All cancers excl.
non-melanoma
skin cancer
Portugal 2008-2030
Estimated number of new cancers (all ages)
Growing rate (%)
All ages Ages < 65 Ages >= 65
SOURCE: GLOBOCAN 2008IARC
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43284
44422
47185
50031
52981
55783
24302
25061
26830
28579
30616
32693
0 20000 40000 60000 80000
2008
2010
2015
2020
2025
2030
New cases Deaths
Portugal 2008 2030
Estimated number of new cancers
Estimated number of cancer deaths
Year
SOURCE: GLOBOCAN 2008IARC
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Colorectum;6952; 16%
Breast; 5333;
12%
Prostate;5140; 12%
Lung; 3288;
8%
Stomach;
2889; 7%
Other; 19682;
45%
2008
Colorectum;
9333; 17%
Breast; 6312;11%
Prostate; 7145;
13%
Lung; 4374; 8%Stomach; 3809;
7%
Other; 24810;44%
2030
SOURCE: GLOBOCAN 2008 -IARC
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10,4
15,8
14,6
15,2
13,5
13,7
16,4
31,4
50,1
60,0
0 10 20 30 40 50 60
Stomach
Lung
Colorectum
Prostate
Breast
Portugal 2008New cases Age-standardised rate (W)/105 Inhabitants
Deaths Age-standardised rate (W)/105 Inhabitants
Incidence ASR (W) Mortality ASR (W)
SOURCE: GLOBOCAN 2008IARC
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Ten Leading Cancer Types for the Estimated New Cancer Cases and Deaths By Sex,United States, 2011
CA CANCER J CLIN 2011;61:212236
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Ten Leading Cancer Types for the Estimated New Cancer Cases and Deaths By Sex,United States, 2011
CA CANCER J CLIN 2011;61:212236
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The Demographics and Epidemiology of Cancer
Populations in developed countries are aging rapidly.
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The Demographics and Epidemiology of Cancer
-the number of elderly has increased steadily over the past century
-the age-adjusted death rate of most cancers has been relatively constant
for many decades
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Luis Costa
The best kept secret today, is that cancers,as a group, are among the most curable ofchronic disease.
Vincent T. DeVita
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T.Murray, E. Ward et al., CA Cancer J. Clin. 55:10-30, 2005
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T.Murray, E. Ward et al., CA Cancer J. Clin. 55:10-30, 2005
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Burden of breast cancer
More than 1 million new cases diagnosed in 2000 worldwide1,2
Estimated global 5-year prevalence: 3.9 million1
1 in 8 lifetime risk in women3
Leading cause of cancer death in women worldwide2
1. Ferlay et al. GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide, version 1.0. Lyon,
IARCPress. 2001. 2. Shibuya et al. BMC Cancer2002; 2:37. 3. Ries et al. SEER Cancer Statistics Review,1975-2001. Available at: http://seer.cancer.gov/csr/1975_2001. 2004.
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BMJ, 2008
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Incidence and Mortality Rates of Female Breast Cancer by Age, United States,1975 to 2008
CA CANCER J CLIN 2011;61:409418
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Luis Costa
Geographic variation in cancer incidence and death rates
Which of the two alternatives heredity or environment is the
dominant determinant of the country-to-country variabilityof cancer incidence?
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Geographic variation in cancer incidence and death rates
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Country-to-country comparisions of cancer incidence
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The great majority of cancers are caused by factors or agentsthat are external to the body, enter into the bodyand corrupt its tissues.
Geographic variation in cancer incidence and death rates
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Proctor, Nat. Rev. Cancer1:82-86; 2001
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Conceptual model for understanding mechanisms of tobacco
carcinogenesis. PKA, protein kinase A.
DeVita, 2008
Tobacco and Lung Cancer
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The Nature of Cancer
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Proofs of tumor monoclonality: all of the cancer cells in a tumor arising in aG6DP heterozygous patient express either one or the other form of this enzyme
Open question?
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Tumors arise from normal tissues
Histopathology: tumors , like normal tissues, are composed of masses of cells
Cancer cells have a quite different and more focused agenda:Making more copies of themselves new colonies
Primary/ metastases
Liver metastasesfrom colon cancer
Brain metastasesfrom breast cancer
Hyperplastic Dysplastic Neoplastic
Metastatic
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Intraductal carcinoma(DCIS)
Invasive carcinoma
Pre-malignant Malignant phenotype
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Histopathology Principles
All tumors should, in principle, be traceable back to the specifictissue or organ site in which they first arose
Tumors are classificable
Carcinomas / sarcomas hematopoietic tumors
Correlate behavior with microscopic features
benign / malignant
What is going to happen with me?
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(> 80% of cancer-related deaths in western world)
Mesoderm origen
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Osteosarcoma Liposarcoma Leiomyosarcoma
Lung metastases(< 2 years)
Local relapse Lung metastases(Long time to relapse)
Chromossomal Translocations in Sarcomas
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Chromossomal Translocations in Sarcomas
V l f C i A l i i h T f
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Value of Cytogenetic Analysis in the Treatment ofDermatofibrosarcoma Protuberans
JCO, April 2008
Translocation t(17;22) was confirmed using caryotype showing asupernumerary ring chromosome (Fig 2, A).
Fluorescent in situ hybridization (FISH) analysis on interphase cell nucleishowing the merged green-red signals corresponding to collagen 1A1promoter (COL1A1)platelet-derived growth factor-B (PDGF) fusion gene(Fig 2, B),
V l f C t ti A l i i th T t t f
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Value of Cytogenetic Analysis in the Treatment ofDermatofibrosarcoma Protuberans
JCO, April 2008
Treatment response to Imatinib
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Small cell
carcinomas
Melanomas
Anaplastic
tumors
Carcinomas:
Adenocarcinoma
Squamous cell
Sarcomas
Neuroectodermal
Malignancies:
Glioblastoma
Retinoblastoma
Hematopoietic
malignancies
Histology
Clinical BehaviourTreatment specificity
Cancer Biology
Molecular MedicineIndividualized Therapy
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Cancer cellResistance toAnti proliferativesignals
Cell Imortalization
Inhibition ofapoptosis
Angiogenesis
Capacity to invadeand metastasize
Growth factors (oncoproteins)Transduction signaling alterations
Cancer: proliferation; dedifferentiation; invasiveness; metastases
What is common in Cancer Nature?
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Os cancros so devidos a
-Factores genticos ?-Factores do ambiente (carcinognios) ?
-Ambos ?
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Cancer is caused by mis-regulation of gene expression
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A limited number of acquired phenotypesin all cancers
Cancers generate their own mitogenic signals,Resist exogenous growth-inhibitory signals,
Evade apoptosis,Proliferate without limits,Acquire vasculatureInvade and metastasize
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Point mutations in the 12th 13th or 61st codon result in activated Ras protein
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Figure 4.10 The Biology of Cancer( Garland Science 2007)
Point mutations in the 12th, 13th, or 61st codon result in activated Ras protein(detected in more than one-fifth of all human cancers)
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A limited number of acquired phenotypesin all cancers
Cancers generate their own mitogenic signals,Resist exogenous growth-inhibitory signals,
Evade apoptosis,Proliferate without limits,Acquire vasculatureInvade and metastasize
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The absence of p53-triggered responses to geneticdamage will permit the survival of cells
that are accumulating mutationsat a greater-than-normal rate
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A limited number of acquired phenotypesin all cancers
Cancers generate their own mitogenic signals,Resist exogenous growth-inhibitory signals,
Evade apoptosis,Proliferate without limits,Acquire vasculatureInvade and metastasize
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Control of pRB function is perturbed in most if not allhuman cancers
Deregulation of the pRB pathway leads to unconstrainedproliferation
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Cancer cells need to become immortal
in order to form tumors
85 to 90% of human tumors are telomerase-positive
The remaining 10-15% have an alternative lengtheningof telomeres, ALT mechanism to construct and maintain
their telomeres
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How to make a human cancer cell?
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How to make a human cancer cell?
1. Express protein that inactivates pRB and p53
2. Activate telomerase expression
3. Express active ras
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The Biology of CancerFirst Edition
Robert A. Weinberg
Copyright Garland Science 2007
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Figure 5.1 The Biology of Cancer( Garland Science 2007)
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