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Physiology > Lecture 8: Neoplasia II > Flashcards

Lecture 8: Neoplasia II Flashcards

1
Q

Examples of causes of cancer

A

Smoking

Diet, overweight and obesity

Lack of exercise

Viruses

Alcohol

UV and ionizing radiation

Occupational carcinogens

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2
Q

Smoking cessation and cancer progression

A

See figure

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3
Q

Example of cancer vaccine

A

HPV 6, 11, 16, and 18 associated with 70% of cervical cancers in women; also anal and mouth cancers

Nobel prize for zur Hausen in 2008

“Gardasil” is available for teen girls (prevention) but uptake is too low

Now including teen boys in Manitoba

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4
Q

Points for cancer control

A

Prevention

Early diagnosis

Therapies for primary tumor

Therapies for systemic disease (metastases)

Palliative care

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5
Q

Cancer diagnostic tests

A

Blood, urine, ascites fluid for biomarkers

Blood in urine / feces

Biopsy of tumor/lymphnodes (fine needles aspirates; multi-needle biopsy cores)

Cytology of cells scraped (eg.Papsmear)

Imaging (X-ray, MRI, PET, CT)

Palpation

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6
Q

Common tumour biomarkers

A

Ovarian cancer: CA-125

Prostate cancer: PSA

Colorectal cancer: CEA, K-ras

Breast cancer: ER, PR, HER2

Testicular cancer: AFP, hCG

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7
Q

How are tumour biomarkers used?

A

Diagnosis—to confirm the results of other tests and symptoms

Prognosis—to predict the cancer’s behavior, response to treatment, and chance of recovery

Monitor treatment—to determine how the cancer is responding to treatment

Surveillance—to determine whether the cancer has returned after treatment (relapse)

Screening—to find cancer in healthy or high-risk people before symptoms develop

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8
Q

What do tumour grading systems rely on?

A

pathologists’ assessment of:

cell differentiation

nuclear abnormality

size

shape

proportion of involvement

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9
Q

What is the TNM staging system?

A

uses information from biopsy, surgery, imaging to assign clinical stage based on usual clinical course (prognosis and therapy)

T [tumor] 1,2,3,or 4 - primary tumor site based on size,
number, location, vascular invasion

N [node] 0 or 1 - metastasis in regional lymph node

M [metastases] 0 or 1 - metastasis in distant organ / tissue

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10
Q

Growth factor receptors

A

All are cross-membrane proteins with an extracellular domain and their cytoplasmic tyrosine kinase domain in the cytosol

Cancers can overexposes these receptors and ligands

EGF receptor (cysteine rich domain)

IGF-1 receptor (has cysteine bonds in extracellular portion)

PDGF receptor

NGF receptor

FGF receptor

VEGF receptor (has Ig-like extracellular domain)

See figures

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11
Q

Example of nuclear hormone receptors

A

Half of breast cancers express Estrogen Receptor (ER)

Over 70% of prostate cancers express Androgen Receptor (AR)

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12
Q

Receptor antagonists in ER positive breast cancers

A

ER positive breast cancers can be treated with receptor antagonists (such as tamoxifen) or aromatase inhibitors (block estrogen production)

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13
Q

Receptor antagonists in AR positive prostate cancers

A

AR positive prostate cancers can be treated with receptor antagonists (such as flutamide) or GnRH agonists (block androgen production)

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14
Q

Bcr-Abl fusion

A

Philadelphia

Occurs in leukaemia cells

Part of Bcr gene from chr 22 is translocated to All gene on chr 9

creates fused Bcr/Abl gene, which is transcripts into mRNA, which is translated into protein

See figure

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15
Q

Example of tumour grading and staging

A

Gleason grade in prostate cancer is most aggressive form

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16
Q

Gleevac

A

Novel treatment

Normally, the Bcr-Abl protein requires ATP to phosphorylate its substrate protein. This phosphorylation leads to cell survival and proliferation, which leads to leukaemia.

When Gleevec is present, it binds to the ATP binding site on Bcr-Abl. The substrate protein cannot become phosphorylated.

See figure

17
Q

Tumor microenvironment

A

Important

Can turn off immune cells, which means they cannot target the cancer cells (suppression of recognition)

See figure

18
Q

Characteristics of cancer cells - signals that regulate cell proliferation

A

Disregard the external and internal signals that regulate cell proliferation.

19
Q

Characteristics of cancer cells - apoptosis and proliferation

A

Avoid suicide by apoptosis (enhanced survival)

Circumvent programmed limitations to proliferation, escaping senescence and avoiding terminal differentiation.

20
Q

Characteristics of cancer cells - genetic stability

A

Genetically unstable.

21
Q

Characteristics of cancer cells - tissue homeostasis

A

Disregard signals for tissue homeostasis and become locally invasive
(proteolysis).

22
Q

Characteristics of cancer cells - movement

A

Survive and proliferate in foreign sites (metastasis)

23
Q

Characteristics of cancer cells - drugs

A

May develop capacity to pump out drugs (MDR1).

Ideally, use multiple drugs to cure cancer

See figure

24
Q

Death rates for different cancers in females

A

Uterine cancer: has decreased in part due to PAP testes and precancerous tissue removal

Breast cancer: slight decline

Stomach cancer: decreasing, people used to eat out of cans

Lung cancer: after the war, lung cancer is up

Colorectal cancer: decreasing due to early ID and treatments

See figure

25
Q

Death rates for different cancers in males

A

See figure

26
Q

What is the most common type of lung cancer? How do lung cancers present?

A

Adenocarinomas

Present as cough, chest pain, weight loss (like pneumonia / bronchitis)

27
Q

What is necessary for treatment of lung cancer?

A

TNM staging necessary for treatment decisions (resection, imaging, nodes)

28
Q

How are breast cancers detected?

A

Detection by screening mammography or palpation

29
Q

How are breast cancers treated?

A

Tumor resection and local lymph nodes assessed for ER, PR, HER2

Treatment plan patient-specific

30
Q

How can long term survival be increased for patient with breast cancer?

A

by use of anti-ER (tamoxifen) and anti-HER2 (trastuzumab) when indicated

31
Q

What is the most common cancer in men?

A

Prostate

32
Q

How is prostate cancer diagnosed?

A

Digital rectal exam (DGE), PSA level high and increasing

Biopsies to assign Gleason score

33
Q

Symptoms of prostate cancer

A

Often no symptoms, may not affect urinary tract

Benign prostatic hyperplasia (BPH) is not a precursor

Frequent urination occurs when there is BPH

34
Q

How to stop advanced disease?

A

Surgery, radiation androgen ablation for advanced disease

35
Q

How does colorectal cancer occur?

A

Polyps process to adenocarcinoma

36
Q

How does colorectal cancer present?

A

Bloody stool

Altered bowel habits

37
Q

What happens after colorectal cancer is diagnosed?

A

Colonoscopy and CT scan for spread

Surgical resection followed by chemo if stage III (CEA biomarker)

Novel anti-EGFR agents effective when indicated

38
Q

How does cancer affect the host?

A

Tumor displaces/replaces/invades normal tissue (impingement, loss of function, bleeding, spinal cord compression, superior vena cava obstruction)

Ectopic production of hormones, cytokines, growth factors

Tumor creates ionic imbalances; cachexia (weight loss, muscle atrophy, lipolysis, loss of appetite)

Tumor necrosis, fever, pain

39
Q

How cancer treatment affects the host?

A

Radiation - damage to adjacent normal tissue

Chemotherapy - damage to systemic normal tissue (hair loss, tumor lysis, nausea, peripheral neuropathy, cardiovascular damage)

Physiology (19 decks)

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