Shock- is a life-threatening condition which happens when the body isn’t getting enough flow of blood.

Cancer Society

Invasion and metastasis

The hallmark of a malignant tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process called metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood.

Mutation.

Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation.

Carcinomas, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke. Tuna and Amos have summarized the mutation frequencies per megabase (Mb) in some carcinomas, as shown in the table (along with the indicated frequencies of mutations per genome).

The high mutation frequencies in carcinomas reflect the genome instability characteristic of cancers. Cause of mutations

The likely major underlying cause of mutations in carcinomas is DNA damage. For example, in the case of lung cancer, DNA damage is caused by agents inexogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). Endogenous (metabolically-caused) DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells (also see DNA damage (naturally occurring)). Externally and endogenously caused damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair (e.g. By non-homologous end joining).

High frequency

The high frequency of mutations in the total genome within carcinomas suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. For instance, mutation rates substantially increase (sometimes by 100-fold) in cells defective in DNA mismatch repair[14]

A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epigenetic alterations or epimutations. While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may be carried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects (causing a very high mutation rate), likely give rise to the high frequency of total genome mutations seen in carcinomas.

DNA repair

In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal carcinomas, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these cancers had reduced MGMT protein expression due to methylation of the promoter region

Shock- is a life-threatening condition which happens when the body isn’t getting enough flow of blood.

Management of shock

If they are showing signs of shock:

• Lay them down with their head low and legs raised and supported, to increase the flow of blood to their head.

• Call 03 or 112 for medical help and say you think they are in shock, and explain what you think caused it.

• Loosen any tight clothing around the neck, chest and waist to make sure it doesn’t constrict their blood flow

• Fear and pain can make shock worse, by increasing the body’s demand for oxygen, so while you wait for help to arrive, it’s important to keep them comfortable, warm and calm. Do this by covering them with a coat or blanket and comforting and reassuring them

• Keep checking their breathing, pulse and level of response.

• If they lose consciousness at any point, open their airway, check their breathing, and prepare to treat someone who has become unconscious.

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