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Exercise Is Medicine > Cancer and Cachexia > Flashcards

Cancer and Cachexia Flashcards

1
Q

cancer epidemiology
1. age
2. sex based differences

A
  1. age assoc cancer risk increases with 19% decrease in 5 yr survival, with growing aging pop more Canadians getting cancer but early detection screening and medications improving
  2. traditionally rate of cancer higher for males than females but in recent years opp since improvements in incidence and mortality for males; in females highest incidence of breast and lung cancer with high risk 50+ for breast cancer due to aging, reproductive state, and poor lifestyle choices; in males prostate is most common followed by lung, with almost all men 50+ getting prostate cancer due to aging or racial/cultural background
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2
Q

overview pathophysiology of cancer

A
  1. normally cells grow old, die, and are replaced, but some risk factors (hereditary, UV rad, chem, virus, epigenetics, and mutations from cell div) cause genetic changes resulting in abnormal cells that don’t die and exp abnormal growth, cell div, and form tumors occurring in any tissue
  2. tumors can be malignant (migrate and invade other tissues) or benign (can still be dangerous if in wrong spot)
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3
Q

cancer as a genetic disease and identifying cancer cells

A
  1. dmg to DNA, causes genes regulating cell growth (oncogenes) to be altered, cannot be turned off, inactivate tumor suppressor genes thus causing uncontrolled growth
  2. canceer cells proliferate without signals, ignore apoptosis, reprogram BV to feed tumors, hide from immune sys, and alter metabolism
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4
Q

metastasis

A

cells break away from primary cancer and travel through blood or lymph circ to form new tumor in another area within body with the same type of cancer cells as primary area in new area (breast cancer cells in the lung)

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5
Q

therapeutic interventions for cancer
1. treatments
2. goal
3. side effects on muscle

A
  1. surgery, chemo, radiation, targeted biologic, hormonal, or immune therapy target different stages of the cell cycle and often use together
  2. complete remission (no evidence of disease signs or symptoms), continued monitoring for many years since cancer can stay dormant for while
  3. cancer specific and treatment related sequelae affect muscle function and different side effected depending on cancer and treatment; therapies also have off target effects thus kills some normal cells too
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6
Q

chemotherapy
1. overview
2. muscle and survivability

A
  1. adminster as infusion, injection, oral, or intrathecal, can be used before surgery or radiation to make tumor smaller, after surgery or radiation to get rid of remaining cells, stop or slow growth of cells by affecting fast growing cells such as cancer but can also affect other cells such as hair, intestines, skin, and bone marrow
  2. Chemo decrease SM area over 3 months by 6% and muscle loss more than 9% at 6 months greatly decrease survivability
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7
Q

radiation therapy

A
  1. radiation destroys tumor cells using high physical E to dmg DNA through direct beam to break DNA or indirectly create free radicals to break DNA; use external beam or internal therapy (liquid or solid put in body to emit rad)
  2. cancer cells more sensitive to DNA dmg than normal cells but can have negative ikmpact on satellite cells and cause muscle fibrosis (replacing muscle with fibrotic tissue)
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8
Q

cachexia
1. overview
2. primary characteristics
3. other diagnostic criteria

A
  1. key sign in 80% people with cancer, is complex multifactorial syndrome affecting many tissues, change metabolism, change basal E expenditure and resistant to coventional nutritional support, responsible for 40% of cancer assoc death and decreases QoL
  2. invol and progressive loss of lean and fat mass, is muscle wasting disease (5% total weight loss in previous 6 months)
  3. fatigue, anorexia, reduced strength, reduced FFM (usual muscle but can also be bone)
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9
Q

pathophysiology of cachexia on resting E expenditure

A
  1. increase resting E expenditure due to increase metabolism combined with decreased E intake
  2. increase immune response and inflammation
  3. tumor uses infficent but higher E stores (anabolic) and increased glycolysis increase lactate production for increased hepatic gluconeogenesis
  4. all cells decreased E efficiency leading to overwork and oxidative stress, exacerbating muscle loss for insulin res and decreased MPS and increased MPB
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10
Q

multisys pathophysiology of cachexia
1. muscle
2. hypothalamus
3. adipose tissue
4. liver

A

systemic inflammation induced by tumorkines from cancer and treatment:
1. direct catabolic effect on muscle resulting in greater fatigue and reduction in phys func, dyregulate satellite cells as they overwork from constant muscle repair and shift proteolysis balance for greater MPB driving by inactivity and nutritional deficit of PRO
2. hypothalamus decreases appetite and increases satiety, decrease in pro ingestion decrease MPS
3. adipose tissue increase breakdown of brown (thermogenesis) and white (inflammatory) decrease mass
4. liver try to repress cascade but changes increase toxity in liver

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11
Q

stages of cancer: stage 0-4 and restaging

A
  1. stage 0: carcinoma in situ
  2. stage 1-3 cancer is present increase with size and stage, 3 indicates spreading to nearby tissues
  3. stage 4 has metastasized to distant parts of the body
  4. restaging dependent on clinical outlook and depend on TMN ranking sys
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12
Q

stages of cancer: TMN ranking
1. tumor
2. lymph nodes
3. metastasis

A
  1. 1-4 rank based on size and if spreaded to nearby tissues
  2. N0 cancer has not spread to lymph nodes around organ; N1.2.3 cancer has spread to lymph nodes can be used to describe the number, size, and location
  3. M0 no metastasis, M1 has spread into blood or lymphatic sys
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13
Q

proposed mechanisms of exercise on cancer

A
  1. alteration of metabolic patheways and growth factors
  2. reduction in sex-steroid synth
  3. improve immune func
  4. reduce systemic inflammation and oxidative dmg
  5. interrupt angiogenesis in tumor via capilliarization, allowing for redistribution of blood away from tumor
  6. reduce metastasis since metastasis is responsible for 90% cancer-assoc mortaility
  7. may have protective effect through change in amount of AT and SM
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14
Q

5 stages of the metastatic process

A
  1. epithelial-mesenchymal transition (EMT) acquires invasive phenotype and becomes a cancer cell
  2. intravasation: local invasion into nearby stroma and pass through endothelial cells into blood supply (intravasation)
  3. circulating tumor cell survive and travel through circulation to favourable site that matches the characteristics of the cell
  4. extravasation out of circ and invade into parenchyma of foreign tissue
  5. seed and colonization: survive at secondary site by trick immune cells to leave them alone and bind to other cells to collect E, adaptation and proliferation to form new tumor (metastases)
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15
Q

how exercise reduces metastasis

A

regulates metastatic factors at each of the 5 stages:
1. reduces the invasion of tumour cells by stopping cells from communicating with each other and endothelial cells, since exercise stresses cells, enhancing only important communication lines, inhibiting EMT
2. reduces vascular permeability since endothelial closer with stronger inter-endothelial communication to suppress intravasation
3. reduce survival of CTC by increasing shear force, by increasing speed of BF, smash cancer and normal cells against BV walls, killing them and calling immune cells to site to repair dmg to BV and take care of leftover CTC
4. inhibits platelet aggregates with fibrinolysis to prevent tumour cells from adhering to endothelial cells, suppressing extravasation
5. anoikis: isolates cells, inducing apoptosis since cells need to attach and communicate to other cells to survive; and improves distal organ cells so that it becomes poor soil for tumor seed to prevent metatasis

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16
Q

psychosocial distress and barriers to exercise in cancer

A
  1. exercise reduces depression and anxiety to elevate mood
  2. psychosocial distress impact self-efficacy, confidence, motivation, and willingness to begin exercise and affect ability to stick with lifestyle over time therefore req additional support to improve adherence to program
  3. cancer has large influence on life, common to dev PTSD and feel isolation thus group exercise with other cancer survivors may be helpful and involving caregivers can improve connections and the caregiver’s own health and caregiving abiltities
17
Q

cancer treatment on exercise tolerance and capability

A
  1. can fluctuate with treatment cycles and with accumulation of treatment side effects like fatigue and pain
  2. during chemo be aware of changes in blood count (thrombocytopenia, anemia, and neutropenia, leukopenia) since therapy targets fast proliferating cells and dehydration and low intake
  3. ANS and metabolic disruption make resting and exercise HR and BP less reliable values so use RPE instead for intensity
  4. modify all exercises for safety
18
Q

late effects of cancer

A
  1. cancer diagnosed at later age have late effects acting synergistically with age-related decline and other comorbidities that affect exercise tolerance
  2. cancer surviviors are living longer after initial diagnosis, exp muscle wasting that linger long after treatment ends and should be screened before exercise for CV risk factors and osetoporosis since treatment can exacerbate issues
19
Q

CV and metabolic disease in cancer

A
  1. cancer treatment and the subsequent inactivity and muscle wasting can contribute to increased risk of CVD, metabolic syndrome, and T2DM and manifest several year after treatment
  2. obesity is both risk factor and consequence of cancer and fuel progression of conditions after treatment
20
Q

frailty and cancer
1. 5 frail criteria
2. cancer and bone loss

A
  1. unintentional weight loss, exhaustion, weakness, slow walking speed, low PA; older adults with at least three criteria at increased risk of worsening mobility, hospitalization, and death
  2. cancer treatment increases risk of frailty and places older cancer survivors at higher risk of poor health outcomes; cancer treatments can accelerate bone loss and increase risk of osteoporosis and subsequent fractures
21
Q

CAR-T therapy: mechanism

A
  1. blood drawn from patient
  2. T-cells are purified and reprogrammed with genetic sequence through a lentiral vector so that T-cells have new surface receptors becoming chimeric antigen receptor T cell
  3. recognize and attach to specific markers on cancer cells so that they can target and kill those only
  4. infused back into the patient
22
Q

exercise and NK cells

A
  1. NK cells are the first line against cancer and pathogens
  2. within minutes, exercise increases concentration of NK cells in the blood more than T and B cells

Exercise Is Medicine (8 decks)

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