Lecture 1: What is cancer?

Question 1

What is cancer ?

Answer 1

An abnormal growth of cells that proliferate and expand in an uncontrolled
manner and, in some cases, colonize
(metastatize to) distant organs.

Question 2

Where/how appear cancer ?

Answer 2

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.

Question 3

Link between tumors and darwin ?

Answer 3

Tumors are darwinian ecosystems, they are part of a process of selection.

Question 4

Frequency of all sites cancer in male and female (birth to death) ?

Answer 4

male : 1 in 2.5
female : 1 in 3

Question 5

Il y a un pic pour le nombre de cancer de la prostate en 1990, pourquoi ?

Answer 5

Un nouveau test a été développé, ce qui a permis un meilleur diagnostic.

Question 6

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) ?

Answer 6

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.

Question 7

Percent surviving 5 years between 2007 and 2013 ? (cancer mortality)

Answer 7

67%

Question 8

What happens in 1971 ?

Answer 8

President Nixon declares “war on cancer”, launches a $1.6 Billion dollar crusade.

Question 9

Proliferation rate in gut and blood ?

Answer 9

Gut : 3-4 days
Blood : every day

Question 10

Basal layers and superficial layers, signals

Answer 10

Basal layer : Mitogenic signals (positive signals) -> self-renewal/proliferation
Superficial layers : Differentiation/quiescence cues (negative signals)

Question 11

homeostasis, regeneration and cancer

Answer 11

Tumors are like wounds that never heal.
(mutations in genes that control cell and tissue homeostasis)

Question 12

Tumors are composed of …

Answer 12

Tumors arise in normal tissues and are composd of cancer cells and stroma (stromal cells + extracellular matrix)

Question 13

How does an invasive mammary carcinoma look like ? (mammary gland)

Answer 13

abnormally large nuclei, no well-structured ducts, invasion of the stroma. (no gland anymore)

Question 14

Tumor stage 0

Answer 14

– «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”)

Question 15

Invasive growth (malignant), stages I-IV

Answer 15

– Tumors invade nearby tissues, and may produce distant growths (metastases)
– 90% of cancer-related deaths are caused by metastases

Question 16

Tumor stage 1

Answer 16

The primary tumor is small but invasive into surrounding tissues and has not spread.

Question 17

Tumor stage 2

Answer 17

The primary tumor is larger and has invaded the surrounding tissues but had not spread (bon pronostic)

Question 18

Tumor stage 3

Answer 18

The tumor has spread to lymph glands (also called lymph nodes) in that region of the body (mauvais pronostic)

Question 19

Tumor stage 4

Answer 19

The cancer has spread beyond the region where it initiated to a distant tissue or organ (mort)

Question 20

Multistep tumor progression

Answer 20

1. cells grow as a benign tumor in epithelium
2. break through basal lamina
3. invade capillary, travel through bloodstream (less than 1 in 1000 cells will survive to form metastases)
4. adhere to blood vessel wall in liver
5. escape from blood vessel (extravasation)
6. proliferate to form metastasis in liver

Question 21

Metastases, what is it

Answer 21

colonies of cancer cells, spread throughout the body

Question 22

Tumor classification by grade (G1, G2, …), general definition

Answer 22

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.

Question 23

G1, G2, G3, G4

Answer 23

• G1: Well differentiated (low grade)
• G2: Moderately differentiated (intermediate grade)
• G3: Poorly differentiated (high grade)
• G4: Undifferentiated (high grade)
  (often, it correlates with stage)

Question 24

Groups of human tumors

Answer 24

1. Epithelial cells → carcinoma
2. Support cells → sarcoma
3. Hematopoietic cells
   * In the bloodstream → leukemia
   * In the lymphatic system and tissues → lymphoma
4. Cells of the nervous system →
   neuroectodermal tumors
5. All the tumors that do not fit into 1-4

Question 25

Majority of human tumors arise from...

Answer 25

epithelial tissues: – Superficial, non-secretory epithelia (protective layer) – Secretory epithelia (glands) Responsible for more than 80% of cancer-related deaths in the Western world

Question 26

Two major categories of carcinomas

Answer 26

* Squamous carcinoma * Adeno-carcinoma

Question 27

Non-secretory, protective epithelia is...

Answer 27

the source of squamous carcinomas: esophagus, skin. -> squamous cells compose the most superficial layer of the epithelia, they are flat and scale-like.

Question 28

Squamous carcinoma arise from...

Answer 28

...flat epithelial cells that serve largely to protect the organ from the external environment (protective epithelial cell layers).

Question 29

Adeno-carnicoma arise from...

Answer 29

...epithelial cells specialized to secrete substances (glands), also called secretory epithelia (ex: gallbladder, mammary gland, pancreatic gland).

Question 30

Sarcomas

Answer 30

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)

Question 31

Connective tissues (examples and composition)

Answer 31

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

Question 32

Liposarcoma

Answer 32

arises from adipocytes in deep soft tissues (red lipid droplets)

Question 33

Osteosarcoma

Answer 33

arises from mesenchymal cells that exhibit osteoblastic differentiation. (bone cancer more frequently in young people)

Question 34

Hematopoietic malignancies (2 main types)

Answer 34

leukemia, lymphoma

Question 35

leukemia

Answer 35

malignant derivatives of several of hematopoietic cell lineages that move freely through the circulation

Question 36

lymphoma

Answer 36

* 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

Question 37

4 types of cells found in the blood

Answer 37

erythrocytes, granulocyte, monocyte, lymphocyte

Question 38

CML =

Answer 38

chronic myelogenous leukemia

Question 39

Neuroectodermal tumors

Answer 39

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

Question 40

Medulloblastomas

Answer 40

origin in cerebellum, formed by precurors of granular cells (neurons).

Question 41

Retinoblastomas

Answer 41

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.

Question 42

2 types of tumor do not fit into the major classifications :

Answer 42

melanomas, small-cell lung carcinomas

Question 43

melanomas

Answer 43

Derive from melanocytes (cells that arise from the neural crest and colonise the skin to provide pigment)

Question 44

small-cell lung carcinomas

Answer 44

Have many attributes of neuroscretory cells.