Lecture 1: What is cancer? Flashcards
What is cancer ?
An abnormal growth of cells that proliferate and expand in an uncontrolled
manner and, in some cases, colonize
(metastatize to) distant organs.
Where/how appear cancer ?
In part sustained by genetic changes (=mutations) that have occurred in normal cells, which provide new capabilities through normal (but uncontrolled) molecular and cellular processes.
Link between tumors and darwin ?
Tumors are darwinian ecosystems, they are part of a process of selection.
Frequency of all sites cancer in male and female (birth to death) ?
male : 1 in 2.5
female : 1 in 3
Il y a un pic pour le nombre de cancer de la prostate en 1990, pourquoi ?
Un nouveau test a été développé, ce qui a permis un meilleur diagnostic.
Pourquoi est-ce que l’incidence des cancers des poumons a diminué, et pourquoi est-ce que la courbe de ce cancer chez les femmes croît plus lentement (USA) ?
Car il y a eu une très grande campagne contre la cigarette aux USA début des années 2000 et les femmes ont commencé à fumer après les hommes.
Percent surviving 5 years between 2007 and 2013 ? (cancer mortality)
67%
What happens in 1971 ?
President Nixon declares “war on cancer”, launches a $1.6 Billion dollar crusade.
Proliferation rate in gut and blood ?
Gut : 3-4 days
Blood : every day
Basal layers and superficial layers, signals
Basal layer : Mitogenic signals (positive signals) -> self-renewal/proliferation
Superficial layers : Differentiation/quiescence cues (negative signals)
homeostasis, regeneration and cancer
Tumors are like wounds that never heal.
(mutations in genes that control cell and tissue homeostasis)
Tumors are composed of …
Tumors arise in normal tissues and are composd of cancer cells and stroma (stromal cells + extracellular matrix)
How does an invasive mammary carcinoma look like ? (mammary gland)
abnormally large nuclei, no well-structured ducts, invasion of the stroma. (no gland anymore)
Tumor stage 0
– «Benign» tumors growing locally without invading adjacent tissues
– Most of the times are harmless, do not evolve
- cure rate is 100%
- carcinoma in situ (“cancer in place”)
Invasive growth (malignant), stages I-IV
– Tumors invade nearby tissues, and may produce distant growths (metastases)
– 90% of cancer-related deaths are caused by metastases
Tumor stage 1
The primary tumor is small but invasive into surrounding tissues and has not spread.
Tumor stage 2
The primary tumor is larger and has invaded the surrounding tissues but had not spread (bon pronostic)
Tumor stage 3
The tumor has spread to lymph glands (also called lymph nodes) in that region of the body (mauvais pronostic)
Tumor stage 4
The cancer has spread beyond the region where it initiated to a distant tissue or organ (mort)
Multistep tumor progression
- cells grow as a benign tumor in epithelium
- break through basal lamina
- invade capillary, travel through bloodstream (less than 1 in 1000 cells will survive to form metastases)
- adhere to blood vessel wall in liver
- escape from blood vessel (extravasation)
- proliferate to form metastasis in liver
Metastases, what is it
colonies of cancer cells, spread throughout the body
Tumor classification by grade (G1, G2, …), general definition
Independent of the stage (local vs invasive) but relates to the « atypia » of the cancer cells, i.e., the extent they differ from the normal cells they derive from.
G1, G2, G3, G4
- G1: Well differentiated (low grade)
- G2: Moderately differentiated (intermediate grade)
- G3: Poorly differentiated (high grade)
- G4: Undifferentiated (high grade)
(often, it correlates with stage)
Groups of human tumors
- Epithelial cells → carcinoma
- Support cells → sarcoma
- Hematopoietic cells
* In the bloodstream → leukemia
* In the lymphatic system and tissues → lymphoma - Cells of the nervous system →
neuroectodermal tumors - All the tumors that do not fit into 1-4
Majority of human tumors arise from…
epithelial tissues:
– Superficial, non-secretory epithelia (protective layer)
– Secretory epithelia (glands)
Responsible for more than 80% of cancer-related deaths in the Western world
Two major categories of carcinomas
- Squamous carcinoma
- Adeno-carcinoma
Non-secretory, protective epithelia is…
the source of squamous carcinomas: esophagus, skin.
-> squamous cells compose the most superficial layer of the epithelia, they are flat and scale-like.
Squamous carcinoma arise from…
…flat epithelial cells that serve largely to protect the organ from the external environment (protective epithelial cell layers).
Adeno-carnicoma arise from…
…epithelial cells specialized to secrete substances (glands), also called secretory epithelia (ex: gallbladder, mammary gland, pancreatic gland).
Sarcomas
Sarcomas derive from various connective tissues
(support tissues, all deriving from the mesoderm germ layer)
Only 1% of all tumors
Derive from different mesenchymal cell types: fibroblasts, adipocytes (fat), osteoblasts (bone), myocytes (muscle)
Connective tissues (examples and composition)
examples : adipose tissue, cartilage, bone, muscle,..
composition :
- Sparse cells, with support function (structural, metabolic, etc.), which are embedded in abundant extracellular matrix (ECM)
- ECM: mostly collagens, other fibrous proteins, glycoproteins
- Blood vessels, nerves, are also present
Liposarcoma
arises from adipocytes in deep soft tissues (red lipid droplets)
Osteosarcoma
arises from mesenchymal cells that exhibit osteoblastic differentiation.
(bone cancer more frequently in young people)
Hematopoietic malignancies (2 main types)
leukemia, lymphoma
leukemia
malignant derivatives of several of hematopoietic cell lineages that move freely through the circulation
lymphoma
- tumors of the lymphoid lineages (B and T lymphocytes) that form solid tumor masses
- usually found in the lymph nodes, but also infiltrate other organs
4 types of cells found in the blood
erythrocytes, granulocyte, monocyte, lymphocyte
CML =
chronic myelogenous leukemia
Neuroectodermal tumors
Tumors arise from cells of various components of the central and peripheral nervous system.
1.3% of all diagnosed cancers,
2.5% of cancer-related deaths
Gliomas, glioblastomas,
neuroblastomas, shwannomas,
medulloblastomas
Non-metastatic, but most often
lethal
Medulloblastomas
origin in cerebellum, formed by precurors of granular cells (neurons).
Retinoblastomas
arise from rods and cones (=photoreceptors) and other neuronal cell types.
often discovered on very little children when the flash is used for taking picures.
2 types of tumor do not fit into the major classifications :
melanomas, small-cell lung carcinomas
melanomas
Derive from melanocytes (cells that arise from the neural crest and colonise the skin to provide pigment)
small-cell lung carcinomas
Have many attributes of neuroscretory cells.
