Lecture 34 Flashcards Preview

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Flashcards in Lecture 34 Deck (30)
1

What is cancer cachexia?

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.

2

ITS FIBRE

AND NOT FIBER, YOU YANKEEEEE

3

What percentage of cancer patients suffer from cachexia?

more than 80% of cancer patients.

4

What are the extremes of the spectrum of cancer cachexia?

Precachexia -> Cachexia -> refractory Cachexia

5

Which groups of cancer patients experience cancer cachexia?

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

6

When does cancer cachexia typically set in?

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

7

How common in cancer in Australia?

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

8

What are the consequences of cancer cachexia?

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.

9

What happens to cachexic patients undergoing chemotherapy?

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

10

How does cancer cachexia affect muscle size?

Muscle fibers are smaller in cachexic mice.

11

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

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

12

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

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

13

How did cancer cachexia affect diaphragm muscles?

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

14

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

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

15

What was seen in cadavers with cancer cachexia?

Reduced heart mass
Structural remodelling
Cardiac fibrosis.

*this same effect was seen in mice.

16

How is chemotherapy caused cardiotoxicity affected by cancer cachexia?

Cardiotoxicity caused by chemotherapy is exacerbated by cachexia.

17

How many cancer deaths are caused by cachexia?

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

18

What can muscle mass indicate about a cachectic patient?

The toxicity associated with chemotherapy

The chance of remaining failure free following chemotherapy

survival

19

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

15% decrease in muscle mass = reduced function.

25 - 30% decrease in muscle mass = death.

20

What are the steps for treatment of cancer cachexia?

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

21

What are the steps for treatment of cancer cachexia?

1) Understand the pathogenesis and identify pathogenic targets.

22

What is the effect of eating during cancer cachexic anorexia?

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

23

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

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.

24

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

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.

25

What is activin A?

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.

26

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

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.

27

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

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.

28

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

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.

29

What was the result of combination therapy on cachexic mice?

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

30

What was the effect of exercise on cachexic patients?

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