CANCER

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CANCER
Dr. Juan Carlos VeraDepartamento de
FisiopatologíaFacultad de Ciencias
BiológicasUniversidad de Conceción
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CARCINÓGENOS
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• PROTO-ONCOGENES Y ONCOGENES
• Proto-oncogenes.
• Genes expresados en las celulas normales cuyos
  productos regulan procesos de proliferacion
  celular.
• Su actividad es regulada espacial y
  temporalmente.
• -Factores de crecimiento.
• Receptores para factores de crecimiento.
• Proteinas de transduccion de senales.
• Factores de transcripcion nuclear.

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• PROTO-ONCOGENES Y ONCOGENES
• Oncogenes
• Genes expresados en celulas tumorales y sus
  productos se encuentran activados
  constitutivamente (ganancia de funcion).
• Mecanismos de alteracion
• Alteracion de la estructura del gen.
• Translocacion cromosomica.
• Amplificacion genica.
• Efectos
• -Factores de crecimiento alterados.
• Receptores para factores de crecimiento
  alterados.
• Proteinas de transduccion de senales alteradas.
• Factores de transcripcion nuclear alterados.

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Circuitos regulatoorios en cancer
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CARCINÓGENOS
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CARCINÓGENOS
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SUPERPOSICION ENTRE LAS LONGITUDES DE LA LUZ
ULTRAVIOLETA QUE LLEGA ALA SUPERFICIE DE LA
TIERRA Y EL ESPECTRO DE ABSORBANCIA DEL ADN
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Circuitos regulatoorios en cancer
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Progresion tumoral
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Complejidad del microambiente tumoral
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Complejidad del microambiente tumoral
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Microambiente tumoral y metastasis
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Celulas madres tumorales
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microRNAs y cancer
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Uso de xenografts
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Agentes antitumorales de nueva generacion
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TUMOR FORMATION
Neoplastic Transformation
Proliferation
Tumor stem-cell
Cell Death
Differentiation
Death
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TUMOR CELL HETEROGENEITY
Tumor stem-cell
Autocrine Growth-loop
Metastatic
Non-proliferative
Growth Factor Independent
Non-antigenic
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TUMOR FORMATION
Neoplastic Transformation
Proliferation
Tumor stem-cell
Cell Death
Differentiation
Death
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Interaccion celula tumoral-estroma en metastasis
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Complejidad del microambiente tumoral
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Metastasis is Organ Specific
It has long been observed that certain cancers
prefer certain organ sites of metastasis.
Cancer
Preferred Metastatic Site(s)
Prostate
Bone
Breast
Bone (liver, brain, lung)
Colon
Liver
Lung
Brain
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The Debate of Organ Specificity
1889 Stephen Pagets Seed and Soil Hypothesis.
The seed (cancer cell) will grow only if it
falls on congenial soil (factors in the organ
environment). Certain organs are better for
certain cancer cells. Versus 1920s James Ewing
challenged that its the anatomic circulatory
patters between the tumor and the metastatic site.
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Why is Metastasis Bad?
Once a tumor metastasizes, it is difficult to
cure by surgery. Metastatic cancer cells forming
tumors in other organs can impede the function of
that organ. Growing metastases may destroy the
organ they inhabit. Prostate bone metastases
change bone structure and bone marrow function.
Causes pain and blood production problems.
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Why No Cure? Three Major Reasons
Every tumor is different from patient to
patient. Cancer cells are very
adaptable. Cancer arises from our own tissue.
How do you kill self cells?
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Every Tumor is Different
There is no single cancer gene. There are many
different combinations of gene mutations that can
give rise to cancer. The current list of cancer
genes includes about 85 oncogenes and 25 tumor
suppressor genes. Challenge every patient has a
unique set of genes that have been changed to
derive their cancer.
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What Are The Chances?
The lifetime probability of developing some form
of cancer
Men 1 in 2
Women 1 in 3
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Major Forms of CancerDiagnosed Cases of Cancer
in U.S. in 2005

• Women
• (662,870 cases)
• Breast - 32
• Lung - 12
• Colon - 11
• Uterine - 6
• Ovary - 3
• Other 35

• Men
• (710,040 cases)
• Prostate - 33
• Lung - 13
• Colon - 11
• Bladder - 6
• Skin - 5
• Other 32

Excludes basal and squamous cell skin cancers
and in situ carcinomas except urinary
bladder. Source American Cancer Society, 2005.
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Major Forms of CancerDiagnosed Cases of Cancer
in U.S. in 2005

• Women
• (662,870 cases)
• Breast - 32
• Lung - 12
• Colon - 11
• Uterine - 6
• Ovary - 3
• Other 35

• Men
• (710,040 cases)
• Prostate - 33
• Lung - 13
• Colon - 11
• Bladder - 6
• Skin - 5
• Other 32

Excludes basal and squamous cell skin cancers
and in situ carcinomas except urinary
bladder. Source American Cancer Society, 2005.
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Cancer Death Rates for Men (US, 1930-2000)
Lung
Rate Per 100,000
Prostate
Colon
Pancreas
Leukemia
Source US Mortality Public Use Data Tapes
1960-2000, US Mortality Volumes 1930-1959,
National Center for Health Statistics, Centers
for Disease Control and Prevention, 2003.
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Cancer Deaths in 2004

• Men
• (290,890 deaths)
• Lung - 32
• Colon - 10
• Prostate - 10
• Pancreas - 5
• Leukemia 5
• Other 38

• Women
• (272,810 deaths)
• Lung - 25
• Breast - 15
• Colon 10
• Ovary - 6
• Pancreas - 6
• Other 38

Source American Cancer Society, 2004 estimates.
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