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Flashcards in Cancer (S2 Bird) Deck (18):
1

Cancer

Cancer is a group of diseases characterised by uncontrolled growth and spread of abnormal cells.

Not a simple or single disease state, but a group of conditions which comes in many shapes and forms with varied properties and characteristics.

All cancers have the common property of uncontrolled growth.

Normally cell growth and division is carefully controlled, but cells begin to divide randomly with no stimulation to.

Cells break off as a primary tumour and colonise other tissues (secondary sites). This is known as metastasis.
-If the spread is not controlled, it can result in death.
-Death is most commonly due to metastasis, not the primary disease.

2

Incidence

Cancer is a common disease

1 in 3 can expect to contract cancer at some stage in their life (1 in 5 can expect to die from it)

Given what we know about the inherent instability and innate chemical reactivity of DNA, it is quite clear that cancer is a disease which results from mutations in the DNA. It is actually quite surprising it is not more common.

3

Why has cancer only attained prominence in more recent times?

Although cancer has been known since human societies began recording their activities (it was well known to the ancient Egyptians and to succeeding civilisations), it has only attained prominence in more recent times.

This is because most cancers manifest themselves later on in life, so that until the expectation of life began to increase significantly (from the middle of the 19th century onwards), the number of people surviving into the 'cancer age' was relatively small.

Increased health care and advances in medicine means that the major infectious diseases and diseases of childhood that were the major causes of death in the past are now much more controlled, and cancer is now a major problem for our ageing population

4

Cancer incidence and age

Although some cancers appear late in life, the incidence of some cancers peaks at a particular age and later become less prevalent.
-Testicular cancer peaks at age 35.
-Thyroid cancer peaks at age 60.
-Breast cancer peaks at age 80.

Some cancers show peak incidence early in life.
-Retinoblastoma (cancer of the eye) and Wilms tumour (a nephroblastoma, a cancer of the kidney) are predominantly childhood cancers and are associated with inherited gene defects (Rb in the case of retinoblastoma and WT1 and/or WTX in Wilms tumour).

5

Typical tissue structure

Each tissue has its own specific cells, usually several types, which make up the tissue structure.

However, the tissue structure follows a fairly standard and consistent pattern.

Different organs vary in the nature of the specific cells and in the arrangement and distribution of the supporting mesenchyme, but the basic pattern in maintained.

6

Tissue structure

A layer of epithelium (the tissue specific cells) is separated from the supporting mesenchyme by a basement membrane.
-In the epithelium, the top layer of cells is differentiated, the middle are developing and the bottom are stem cells.
-In some tissues, such as the skin or intestine, the epithelium may be several cells thick. It may form tubes as in the kidney or lungs, or solid cords as in the liver but the basic pattern remains the same.
-Cancers form in the epithelial level.

The support tissue (or stroma) is made up of connective tissue and fibroblasts and may be supported on a layer of muscle or bone depending on the organ.
-The mesenchyme also includes blood vessels, lymphatics.
-There is often a layer of muscle below.

7

Proliferation and cell death

During normal development and throughout adult life, proliferation and cell death are carefully regulated to ensure proper growth to adulthood and the maintenance of the adult state.
-Cell birth and death rates determine adult body size.

The cells of many adult tissues do not normally divide except during healing processes.

8

Adult tissues showing constant and continuous cell proliferation

Some adult tissues show constant and continuous cell proliferation as a constant tissue renewal strategy.

Intestinal epithelial cells for example, have a lifetime of just a few days before they die and are replaced.

Some of the white blood cells are replaced as rapidly.

Skin cells live for about 2 to 4 weeks before being shed.

9

Tumour development

Tumour cells and cancer cells divide inappropriately.

Carcinoma in situ is the first stages of cancer, when cells become uncontrollable in their division and a tumour starts to form.

Very early on, cells begin to grow in all directions in an uncontrollable manner.

Once they break into the mesenchyme, there is a good chance they can break off from the tumour, into the blood vessels and lymphatic system, allowing the colonisation of other organs. Here metastasis is possible.
-Means screening is a very important tool for detecting cancer.

10

Disease of DNA

Cancer is a disease of the DNA, successive mutations leading to uncontrolled growth. It is generally held in 5-8 critical mutations in important areas of the genome before a malignant tumour is produced.

This is believed to hold for all tumours

11

Each mutation creates a cell increasingly well adapted for autonomous growth.

Since the probability of a single cell simultaneously acquiring these mutations is vanishingly small, this sequential process of acquisition of mutations can only be achieved if cell bearing the initial mutation, the so-called initiated cells, clonally expand until the population increases to many millions.

A second mutation at a critical locus in one of these cells then occurs which gives this cell a growth advantage and a second clonal expansion of this cell bearing two mutations.

The repeated process of clonal expansion allows subsequent mutations to be amassed and cells become progressively better adapted to an independent life until a full blown malignant cell finally results.

12

Traditional view of cancer development

The cells of the tumour are considered to be heterogeneous, but most, if not all, can grow readily and give rise to new cancer tissue.

A mutation occurs, a daughter cell inherits that mutation and develops another mutation again, it is this accumulation of mutations causes the cancer.

13

Cancer stem cell theory

Here, the cancer cells are heterogeneous but only the stem cells, which typically are only 1-2% of the total tumour can proliferate extensively and give rise to new tumours.

These cell, like the stem cells in normal tissue, can both self renew and produce differentiated daughter cells.

There is increasing support for the 'cancer stem cell' view of tumour growth, but whether all tumours arise from a stem cell isn't certain. Nor is it clear yet if the cancer stem cell arises from malignant changes in a normal stem cell, or whether a differentiated cell within the tissue undergoes some degree of de-differentiation and adopts a 'stem cell like' phenotype, though currently the former view is considered more likely.

The notion that there is a stem cell population which sustains the tumour growth has started to modify thoughts of how cancer therapy should be approached.

14

Benign Tumours

Develop in any tissue

Grow locally
-Do not metastasise.

May cause problems by pressure (brain) or obstruction (colon)

Histologically resemble the tissue of origin, i.e. cytologically the specific tumour cells do not differ substantially in structure from the cells of the tissue of origin.
-Benign tumours of cartilage or bone may produce nodules indistinguishable histologically from normal tissue.
-Covering or lining tissues of skin, intestine, bladder etc may produce wart-like outgrowth containing all cell types closely packed to form a solid nodule.
-In other situations only one cell type may be present, and in this case these tumours may produce an excess of particular hormone produced by that cell type.

Benign doesn't necessarily mean completely harmless.

Do not spread to distant sites.

15

Benign tumours in the brain and colon

Brain tumours: usually of the support tissue, not the nerve cells themselves, cause damage because of physical constraints of the skull.

Colon: Tumours of the small intestine are relatively rare, despite the high rate of cell turnover in the villus. High proliferative rates are not necessarily linked to a high incidence of tumour formation.

16

In situ tumours

Carcinomas (first stage of development)

Usually develop in the epithelium

Usually small

Have altered histological appearance and show morphological characteristics of tumour cells to a greater or lesser degree.
-Changes include loss of any normal regular arrangement of the cells
-Variations in cell size and shape
-Increase in nuclear size and staining (reflecting increased DNA content)
-Increase in mitotic activity
-The presence of abnormal chromosomes.
-Ability to grow in an uncontrolled fashion/

Do not invade basement membrane and supporting mesenchyme.

Very treatable.

17

Cancerous tumours

Fully developed malignant tumours with the specific capacity to invade and destroy the underlying mesenchyme.

Ability to metastasise
-The tumour passes through the basement membrane and invades the underlying tissues and then invades the blood vessels allowing individual tumour cells, or small clumps of tumour cells, to escape from the original, primary tumour and make their way around the body via the blood stream.
-These cells may then escape from the blood stream and invade other organs giving rise to secondary tumours.

Stimulate angiogenesis and development of blood supply, by producing agents which stimulate the growth of new blood vessels, because they need a supply of nutrients and oxygen.
-The new blood vessels are easily damaged and may increase the possibility for the tumour to metastasise

Primary tumours which have not invaded the underlying tissues and have not metastasised are often treatable by surgery or by localised chemotherapy of radiotherapy, and there is a good chance of the patient surviving.

Tumours which metastasised are much more difficult to treat

18

Hallmarks of Cancers

Six different fundamental cellular properties may be altered to give rise to the complete, most aggressive and destructive cancer phenotype.
-Less dangerous tumours arise when only some of these changes occur.
-The ability to invade and metastasise defines the most aggressive types, but benign and in-situ tumours will have some level of manifestation of the other changes.

Self-sufficiency in growth signals
Insensitivity to antigrowth signals
Evasion of apoptosis
Sustained angiogenesis
Limitless replicative potential
Tissue invasion and metastasis