Lecture 34

Question 1

What is cancer cachexia?

Answer 1

Cancer cachexia is the multifactorial syndrome that causes an ongoing loss of skeletal muscle mass with or without loss of fat mass that leads to functional impairment.

Question 2

ITS FIBRE

Answer 2

AND NOT FIBER, YOU YANKEEEEE

Question 3

What percentage of cancer patients suffer from cachexia?

Answer 3

more than 80% of cancer patients.

Question 4

What are the extremes of the spectrum of cancer cachexia?

Answer 4

Precachexia -> Cachexia -> refractory Cachexia

Question 5

Which groups of cancer patients experience cancer cachexia?

Answer 5

Cancer cachexia is more common in elderly and children cancer patients.

Question 6

When does cancer cachexia typically set in?

Answer 6

Cancer cachexia is usually present upon diagnosis (85% of patients. This means it’s an early onset condition associated with cancer.

Question 7

How common in cancer in Australia?

Answer 7

more than 115k new diagnoses of cancer occur and more than 43k will die from cancer.

Question 8

What are the consequences of cancer cachexia?

Answer 8

Enhanced fatigue in patients of cancer cachexia and they move around a lot less with 40% less activity levels.

Muscle function is reduced

Reduced independence

Increased incidence of metabolic diseases

Increased risk of complications during surgery.

Impaired response to chemo and radio therapy

An overall reduction in quality of life.

Respiratory and cardiac failure can result.

Question 9

What happens to cachexic patients undergoing chemotherapy?

Answer 9

Cachexia decreases chance of recovering with the help of chemotherapy. Many patients don’t even survive through chemotherapy.

Question 10

How does cancer cachexia affect muscle size?

Answer 10

Muscle fibers are smaller in cachexic mice.

Question 11

Why are mice an ideal specimen for symptoms of cancer cachexia?

Answer 11

The mild and severe stages of cachexia mimic the human spectrum of cachexia.

Question 12

What happened when chemotherapy was introduced to 2 mice; 1 with mild cachexia and 1 with severe cachexia?

Answer 12

The more severe cachexia that mice had the less the tumour shrunk with chemo

Question 13

How did cancer cachexia affect diaphragm muscles?

Answer 13

Severely cachectic mice have very weak respiratory muscles compared to less severely cachectic mice.

Question 14

What happened to cachectic mice’s tidal volume and cardiac activity?

Answer 14

Tidal volume and cardiac activity were greatly reduced in mice with cachexia.

Question 15

What was seen in cadavers with cancer cachexia?

Answer 15

Reduced heart mass
Structural remodelling
Cardiac fibrosis.

*this same effect was seen in mice.

Question 16

How is chemotherapy caused cardiotoxicity affected by cancer cachexia?

Answer 16

Cardiotoxicity caused by chemotherapy is exacerbated by cachexia.

Question 17

How many cancer deaths are caused by cachexia?

Answer 17

Cachexia is responsible for 20 - 30% of all cancer related deaths

Question 18

What can muscle mass indicate about a cachectic patient?

Answer 18

The toxicity associated with chemotherapy

The chance of remaining failure free following chemotherapy

survival

Question 19

What are the indicators of reduced function and death in cachectic patients?

Answer 19

15% decrease in muscle mass = reduced function.

25 - 30% decrease in muscle mass = death.

Question 20

What are the steps for treatment of cancer cachexia?

Answer 20

1) Understand the pathogenesis and identify pathogenic targets.
2) Develop suitable preclinical models and clinically relevant tests.
3) Test efficacy of therapies in preclinical models
4) Test efficacy of therapies in clinical trials

Question 21

What are the steps for treatment of cancer cachexia?

Answer 21

1) Understand the pathogenesis and identify pathogenic targets.

Question 22

What is the effect of eating during cancer cachexic anorexia?

Answer 22

Counteracting anorexia with more food does not result in preservation of muscle mass.

Question 23

What is the problem with using anti-inflammatory drugs in treating cancer cachexia?

Answer 23

Anti inflammatory drugs have often been associated with adverse side effects.

Another limitation is that they usually only target one cytokine.

New drugs are being produced to target several cytokines simultaneously which is showing promising prospects.

Question 24

What is myostatin? What is the effect of myostatin inhibition?

Answer 24

Myostatin is a negative regulator of muscle mass. If it is inhibited it results in large muscle mass. Using this treatment in mice caused small but significant improvements in cachexic mice.

Question 25

What is activin A?

Answer 25

Myostatin is one type of TGF-alpha protein another example of this family of proteins is activin A which has a similar effect to myostatin. It has a greater effect in causing atrophy.

Question 26

What is the result of injection of inhibitory activin receptors in achexic mice?

Answer 26

Mice were injected with activin receptors which prevents binding of activin and myostatin with the activin receptor. This resulted in a decrease in atrophy in mice and prolonged survival in mice with cancer cachexia.

Question 27

What does the Renin-angiotensin system do in cachexic mice? How did ACE inhibitors fair in treatment of cancer cachexia?

Answer 27

Renin-angiotensin system causes muscle wasting in muscles. Inhibiting this pathway did not improve body mass or muscle mass but caused large improvements in muscle function and fatigue.

Question 28

What is the function of the TWEAK pathway? How did inhibiting it affect cachexic mice?

Answer 28

TWEAK Fn14 pathway is a pathway that results in muscle wasting. Fn14 and TWEAK were inhibited by antibodies and this improved survival, prevented loss of body mass and muscle mass and increased muscle strength in mice with cancer cachexia.

Question 29

What was the result of combination therapy on cachexic mice?

Answer 29

A combination of treatments were used and this resulted in the most improvement in patients with cancer cachexia.

Question 30

What was the effect of exercise on cachexic patients?

Answer 30

Exercise has negative effects on cachexic patients due to the anaemic aspect of it, however results were not conclusive.