[A] 1.74 The tumor-organism relationship (tumor progression, heterogeneity, metabolism of tumor cells, cancer anorexia-cachexia syndrome, paraneoplasia, tumor immunity)

Question 1

Tumour progression

Answer 1

“Increase of the tumour’s malignant potential”

• Neoplastic transformation (neoplastic stem cell)
• Invasion ability
• Metastasis
• Generalisation

Question 2

Tumour heterogeneity: Hypothesis

Answer 2

• The mutation of 1 cell is in the background
• The tumour is monoclonal

Question 3

Tumour heterogeneity

Answer 3

1. Genetic damage in tissue stem cells → Immortalise
2. Monoclonal tumour cells mutate further → Genetic heterogeneity

Can lead to tumour subclones

Question 4

Define: Heterogeneity

Answer 4

Being diverse in quality or character

Question 5

Tumour heterogeneity: Positive selection with…

Answer 5

• Less antigenic tumour
• Fast-growing
• Ability to metastasise
• Low need of GF
• Resistance against cytostatic agents

Question 6

Tumour heterogeneity: Result

Answer 6

Dominant, resistant tumour subpopulations

Question 7

Relationship between tumour and the host?

Answer 7

• Competitive, disharmonic relationship with the host
• Autonomous growth
• Loss of BW; asthenia; immunosuppression; recurring infections; metabolic crisis

Question 8

Metabolism of tumour cells

Answer 8

• Constant glucose supply in the body
• Genetic instability
• Adhesion and proliferation in hypoxic environment
• Non-oxidative processes
• Decreased FA and Aa synthesis
• Increased proliferation rate:
  
  • Undifferentiated, low functioning cells

Question 9

Metabolism of tumour cells: Genetic instability

Answer 9

• Increased proliferation rate
• Change of metabolism
• Increased need of RNA & DNA

Question 10

Metabolism of tumour cells: Non-oxidative processes

Answer 10

Activated intracellularly

Question 11

Cancer anorexia-cachexia syndrome

Answer 11

• Frequent in case of carcinomas
• Multifactorial
• Cachectic mediators
  
  • Tumour-derived factors
  • Host’s humoral factors

Question 12

Cancer anorexia-cachexia syndrome: Clinical turnout

Answer 12

• Anorexia
• Early satiety
• Emaciation
• Anaemia
• Asthenia, weakness

Question 13

Cancer cachexia

Answer 13

1. Host’s macrophages/lymphocytes → Activated → Cytokines
2. TNF and IL-1 induce leptin expression
3. Hypothalamus → CRF
4. CRF is norexigenic → Animal will feel full

Question 14

Cancer cachexia: Processes that follow

Answer 14

• Tumour cells → Proteolysis-inducing factor (PIF)
• Increased metabolism in muscle & adipose

Muscle atrophy; Hormonal changes; Glucose intolerance; Insulin resistance

Question 15

Paraneoplasia

Answer 15

Often follows neoplasia

• Humoral symptoms
• Biologically active compounds produced by bacteria

Question 16

Paraneoplastic changes

Answer 16

1. Tumour cachexia
2. Hormonal symptoms
3. Paraneoplastic skin lesions
4. Hematologic symptoms
5. Hemostatic changes (thrombophilia, DIC)
6. Musculoskeletal symptoms
7. Amyloidosis
8. Pyrexia
9. Nephropathies

Question 17

Paraneoplastic changes: Hormonal symptoms

Answer 17

Ectopic hormone production

• Not normal in tissue of origin
• E.g Dog: Mediastinal lymphoma → Parathormone-like peptide → Hypercalcalcaemia

Question 18

Paraneoplastic changes: Feminisation syndrome

Answer 18

In case of oestrogen-producing testicular tumours

• Bilateral symmetric alopecia
• Gynecomastia
• Myelosuppression
• Changes in behaviour

Question 19

Anti-tumour effector cells

Answer 19

• Cytotoxic T-cell → Antigen recognition
• NK cells → Direct lysis
• Macrophages - TNFα, ROS
  
  • Increase apoptosis
  • Inhibition of angiogenesis
• Humoral processes - Complement system activation

Question 20

Tumour specific antigens (TSA)

Answer 20

• Only on tumour cells
• Increased expression in case of E.g seminoma/melanoma
• Increased lymphocytic infiltration means usually a better prognosis

Question 21

Tumour immunity: Causes

Answer 21

• Anti-tumour effector cells
• Tumour specific antigens (TSA)
• Tumour-associated antigens (TAA)
• Microevolutionary causes

Question 22

Tumour-associated antigens (TAA)

Answer 22

• Next to tumour cells
• Some normal cells can also express these

Question 23

Tumour immunity: Race between neoplasia and the immune system

Answer 23

• The selective proliferation of non-antigenic tumour cells
• Modulation or losing of tumour antigens
• Antigens binding to normal cells nearby (False target)
• Antigen covering by the fibrin network
• Losing of proteins aiding tumour recognition
• Lymphocytes can increase angiogenesis
• Immunosuppression