Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

year 4 CDM 2 > Case 17: cancer basics > Flashcards

Case 17: cancer basics Flashcards

1
Q

Types of cellular communication

A
  • Endocrine
  • paracrine (adjacent target cells)
  • autocrine (target sites on same cell)
  • juxtacrine (contact dependent, including contact inhibition of further growth)
  • Errors in cell communication lead to cancer and autoimmunity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Mechanisms of signal transduction

A
  • Direct ligand gated channel
  • G protein coupled
  • tyrosine kinase linked
  • intracellular receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does signal transduction via direct ligand gated channels work

A
  • when a signal binds to the receptor, the gate allows specific ions through a channel
  • Example: nicotinic Ach receptors- GABA receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How does signal transduction via G protein couples receptors work:

A
  • hormone binds to inactive receptor which activates G alpha subunit
  • muscarinic Ach receptors- adrenergic receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Tyrosine kinase linked receptors work

A
  • signalling molecule binds causing dimerisation of the molecule, activating tyrosine kinase regions which then become phosphorylated and activate relay proteins
  • Example: binding of specific ligands (EGF and TGF-a) to EGFR activates the receptor and triggers signal transduction cascades that affect cell proliferation
  • Tyrosine kinase inhibitors e.g. gefitinib and erlotinib target signal transduction pathways: they bind to the intracellular tyrosine kinase domain which inhibits autophosphorylaltion and downstream intracellular signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Signal transduction via intracellular receptors

A
  • intracellular receptors are found in the cytosol of the nucleus of target cells small hydrophobic chemical messengers can cross the membrane and activate receptors
  • which drugs can target signal transduction pathways: - monoclonal antibodies. Tyrosine kinase inhibitors
  • Monoclonal antibodies e.g. trastuzumab and cetuximab target signal transduction pathways by binding to the extracellular domain of EGFR which blocks growth factor binding and signal transduction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

The 10 hallmarks of cancer

A
  • sustained proliferative signalling
  • evading growth suppressors
  • avoiding immune destruction
  • enabling replicative immortality
  • tumour promoting inflammation
  • activating invasion and metastasis
  • inducing angiogenesis
  • genome instability and mutation
  • resisting cell death
  • dysregulating cellular energetics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do cancer cells sustain proliferative signalling by

A
  • producing growth factor ligands
  • structurally altering receptor molecules via mutation
  • elevating levels of receptor proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Common cancer mutations

A
  • what growth factor receptor do many cancers express: EGFR/ HER (involved in cell proliferation)
  • what type of cancer is EGFR mutation commonly associated with: NSCLC
  • what type of cancer is high levels of HER2 associated with: breast cancer
  • what do growth suppressor programmes depend upon: tumour suppressor genes e.g. TP53 (codes for p53) and RB1 (codes for retinoblastoma protein)
  • function of retinoblastoma protein (pRb): gatekeeper of cell cycle progression
  • in what conditions is retinoblastoma protein (pRb) inactivated: - retinoblastoma. some SCLCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Immune system and cancer

A
  • What type of growth inhibition is lost in cancer cells: contact inhibition
  • How might cancer cells disable components of the immune system: they can recruit inflammatory cells that are immunosuppressive e.g. regulatory T cells and myeloid derived suppressor cells which can suppress CD8
  • How does immuno stimulation therapy help treat cancer: enhances immuno-surveillance to assist the immune system to recognise tumour cell antigens
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cancer cells and immortality

A
  • how do cancer cells have replicative immortality: they have high levels of telomerase which adds telomere repeat segments to the ends of telomeric DNA
  • how does telomestatin therapy work to treat cancer: telomestatin is a telomerase inhibitor in trial which causes telomere shortening and activation of proliferative barriers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do cancers progress

A
  • Neoplastic lesions contain immune cells: they supply growth factors, survival factors and angiogenic factors to the tumour microenvironment
  • Release of reactive oxygen species promotes cancer progression: mutogenic
  • Tumour associated inflammatory responses such as vasodilation and increased permeability of vessels
  • increased permeability allows migration of leukocytes from blood into tissues
    (extravasation) but also allows leakage of plasma proteins and fluid into tissues
    which causes swelling
  • The complement system is activated due to tumour promoted inflammation: coagulation and fibrinolytic systems
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Regulators and proteins in cancer

A
  • reduction in E-cadherin allows invasion of cancer
  • Angiogenesis is important in cancer: tumours require nutrients and
    oxygen as well as an ability to evacuate metabolic waste and carbon dioxide
  • what is the key mediator of angiogenesis in cancer: VEGF
  • what causes up regulation of VEGF: oncogene expression, growth factors and hypoxia
  • why do cancer cells have increased rates of mutation: they compromise the surveillance systems that normally monitor genomic integrity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Give example of cancers associated with DNA repair defects

A
  • Lynch syndrome
  • xeroderma pigmentosum
  • Bloom’s syndrome
  • Fanconi anaemia
  • hereditary breast/ ovarian cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Genes in cancer

A
  1. which gene is the central guardian of the genome: TP53 (codes for p53)
  2. role of BRCA1/2 and PALB2 in genomic integrity: repair of double stranded
    DNA
  3. role of PARP1 in genomic integrity: repairing single stranded breaks in DNA
  4. how do PARP inhibitors work: they prevent repair of cancer cells with damaged DNA, leading to death of these cells
  5. loss of function of p53 in cancer cells may allow them to resist cell death: causes apoptosis in damaged cells
  6. how might cancer cells dysregulate cellular energetics: they can up regulate glucose transporters (GLUT1) to increase glucose import into the cytoplasm and increase glycolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

TMN cancer staging system

A
  • what is Tx in cancer staging: primary tumour can’t be assessed
  • what is T0 in cancer staging: no evidence of primary tumour (cancer of unknown primary)
  • what is Tis in cancer staging: pre-invasive cancer (cancer in situ)
  • what is T1-3 in cancer staging: different degrees of local spread
  • what is T4 in cancer staging: invasion to adjacent organs
  • what is M0 in cancer staging: cancer has not spread to other parts of the body
  • what is M1 in cancer staging: cancer has spread to other parts of the body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What causes clinical manifestations of cancer

A
  • direct effects due to compression
  • obstruction of a conduit (airway, biliary tract, bowel, ureteric system)
  • ulceration of a serial or mucosal surface
  • metastases
  • paraneoplastic syndromes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How might obstruction of a conduit due to cancer present

A
  • jaundice due to biliary obstruction
  • stridor due to airway obstruction
  • DVT due to venous obstruction
  • facial congestion due to SVC obstruction
  • absence of stool/ flatus, anorexia and dehydration due to bowel obstruction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What causes paraneoplatic syndrome

A
  • production of substances from tumour
  • depletion of normal substances
  • immunological response to tumour
  • why does eradicating the cancer not always resolve the paraneoplastic
    syndrome: some are immunological so the antibody will still be present even if the
    cancer is gone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Examples of paraneoplastic syndrome

A
  • ACTH overproduction
  • SIADH
  • gonadotropins
  • hypercalcaemia due to PTH like peptide
  • neurological paraneoplastic syndromes
  • Lambert Eaton syndrome
  • dermtomyositis
  • acanthosis nigricans
  • haematological paraneoplastic syndromes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What cancers cause lymphadenopathy in different areas

A
  • lymphadenopathy in the face is suggestive of which types of cancer: ENT cancers
  • lymphadenopathy in the supraclavicular/ axillary nodes is suggestive of which types of cancer: cancers in the thorax: breast, lung, oesophagus, stomach
  • lymphadenopathy in the inguinal/ femoral nodes is suggestive of which
    types of cancer: gynae, pelvis, scortal or penile cancers
  • lymphadenopathy in the pelvic/ para-aortic nodes (not the inguinal nodes)
    is suggestive of which types of cancer: ovarian or testicular cancer
22
Q

Tumour markers

A
  • what are tumour markers: serum secreted proteins produced by cancers that
    are detectable in the serum
  • Tumour markers are generally used for: rarely diagnostic, more useful in monitoring and surveillance for early relapse
  • ideal sensitivity and specificity of tumour markers: - sensitivity above 50%, specificity above 95%
  • when useful tumour marks are often measured: - with each cycle of chemo to assess response. at clinical reviews as part of follow up
23
Q

Features of an ideal tumour marker

A
  • produced by malignant cells only
  • exclusive to a certain malignancy
  • detectable at all levels of disease
  • obtained in a non-invasive manner
  • levels should equate to disease burden
24
Q

hCG and AFP

A
  • what is hCG: a glycoprotein formed in the syncytotropioblast of the placenta
  • uses of hCG: to diagnose and monitor pregnancy, gestational trophoblastic disease and germ cell tumour
  • what is APF: serum protein synthesised by foetal yolk sac, liver and intestine acts as albumin like carrier protein in foetus
  • increased levels of APF are seen in which cancers: - HCC, germ cell tumours of testes, ovaries, mediastinum and pineal gland
25
Q

Placental ALP, CA19-9, inhibin

A
  • what is placental ALP: an isoenzyme of ALP
  • elevated placental ALP may be seen in which conditions: - testicular seminoma, ovarian dysgerminoma
  • main use of CA19-9: monitor response to treatment in gastric and pancreatic
    cancer
  • what is inhibin: protein secreted by granulosa cells including Sertoli cells that
    inhibits FSH
  • inhibin may be used to monitor which type of tumour: rare granulosa cell
    tumours of the ovary
26
Q

CEA, CA15-3

A
  • what is CEA: a glycoprotein
  • main use of CEA: monitor treatment in colorectal cancer
  • what is CA15-3: mucin like antigen
  • main use of CA15-3: elevated levels have been found in breast cancer. elevation increases with stage (highest levels seen in patients with liver or bone metates). rising level during follow up can detect relapse 2-9 months before clinical signs
    develop
27
Q

CA-125, PSA

A
  • CA125 is present at the surface of non-mutinous epithelial ovarian tumours
  • main use of CA125: monitoring response to chemo in ovarian cancer and detection of relapse
  • high levels of CA125 prior to surgery is associated with: worse prognosis
  • why is CA125 not useful for screening ovarian cancer: only elevated in 50%
    of patients with stage 1 disease
  • main use of squamous cell carcinoma associated antigen: monitor treatment of squamous cell cervical cancer and head and neck squamous carcinoma
  • PSA: protease produced by prostate epithelium. Elevated in prostate cancer, BPH
28
Q

Calcitonin, thyroglobulin, LDH, beta 2 microglobulin

A
  • which cancer may cause elevated calcitonin: medullary thyroid carcinoma
  • which cancers may cause elevated thyroglobulin: papillary and follicular
    thyroid carcinoma
  • main uses of LDH: - measure bulk of disease. can identify rapidly growing tumours and patients at risk of tumour lysis syndrome
  • which cancers may raise beta 2 microglobulin: myeloma, non Hodgkin’s lymphoma
  • main use of beta 2 microglobulin: prognostic
29
Q

Classification of cancer treatment intent

A
  • palliative, curative
  • Types of cancer treatments: - palliative, adjuvant, neoadjuvant, chemoprevention
30
Q

what needs to be assessed prior to giving chemoprevention:

A
  • survival benefit as many agents are carcinogenic
  • e.g. tamoxifen reduces breast cancer incidence but increases the risk of endometrial cancer and is also thromboembolic
31
Q

Timing of cancer treatment

A
  • within what time period should cancer patients start treatment: - within 31
    days of agreeing plan, within 62 days of 2ww referral
  • how long is one cycle of treatment usually: 21 days or 28 days
  • how many cycles are normally given in a course of treatment: up to 6
32
Q

Dosing approaches in cancer

A
  • Low dose therapy
  • high dose therapy
  • dense dose therapy
  • alternating therapy
33
Q

Low dose in chemotherapy

A
  • how is low dose therapy given: the next cycle is commenced once bone
    marrow function has recovered
  • what indicates bone marrow recovery following cancer treatment: -
    netrophils above 1, platelets above 100
  • what may be given if bone marrow recovery is delayed following cancer
    treatment: G-CSF
34
Q

Options to increase the rate of bone marrow recovery following high dose
therapy:

A

G-CSF. autologous stem cells can be harvested and re-adminstered to repopulate bone marrow faster (allows recovery within 16-21 days as opposed to 6-7 weeks)

35
Q

Sites of action of cytotoxic agents

A
  • purine and pyrimidine synthesis (antimetabolites)
  • DNA formation and replication (alkylating agents and intercalating agents)
  • microtubules (spindle poisons)
36
Q

How might existing cancer drugs be improved

A
  • improved tolerability (e.g. wrap doxorubicin in liposomal monolayer)
  • increased spectrum of activity
  • altered delivery e.g. continuous infusion
37
Q

Summary of how we measure response to cancer treatment

A
  • overall survival rate: % that are alive for a certain period of time after the diagnosis (usually 5 year survival rate)
  • remission rate: % that achieve a state where the cancer is no longer detectable and signs and symptoms have disappeared
  • disease free survival: length of time after treatment during which a
    patient survives with no signs or symptoms of the disease
  • residual disease: that left at completion of planned treatment and if presence indicates resistance to treatment (adverse prognostic factor). Detect with fine needle aspirate or biopsy of residual
    lesion
38
Q

Causes of cancer

A
  • single biggest preventable cause of cancer: tobacco
  • which infections may increase the risk of cancer: - HPV, H pylori, hep B/C
39
Q

What is cytology

A
  • examination of cells from sputum/ urine/ cervix/ pleural
    effusions/ ascites
  • cytological features of malignancy: - altered polarity, tumour cell enlargement, increased nuclear to cytoplasmic ratio, pleomorphism (variation in size and shape), clumping of chromatin, atypical or bizarre mitoses, mutlinucleated
40
Q

carcinogenesis

A
  • Process by which normal cells are transformed into
    cancer
  • how does carcinogenesis occur: 1. a single cell multiplies and acquires
    additional changes providing survival advantage. Altered cells are amplified to generate billions of cells that constitute cancer (this takes time, hence why age is a risk factor)
  • causes of carcinogenesis: - chemicals, radiation, occupational hazards, viruses, bacteria or parasites, drugs, hormones, lifestyle and genetics
41
Q

Describe how carcinogenesis due to chemicals leads to cancer

A
  • initiation (single exposure to carcinogen may be sufficient): failure to repair chemically
    induced DNA damage resulting in mutation
  • promotion (requires multiple exposures): produces selective growth advantage,
    usually without DNA mutation
  • progression: irreversible, multiple complex DNA changes
  • Chemicals including tobacco causes 80-90% of tumours
42
Q

Smoking can cause cancer in what organs and why

A
  • lungs due to bronchial inflammation
  • liver as transported through blood
  • kidney and bladder as filtered into urine
  • cervix and breast as compounds secreted by these organs
    also oropharynx, oesophagus, pancreas
43
Q

Germline and Somatic mutations

A
  • what are germline mutations: present at embryogenesis (present in all cells
    of the host) can be passed on
  • what are somatic mutations: acquired genetic changes that occur within the
    DNA of individual somatic cells (only affect cells in which they originally occurred and descendants of these) not inheritable
44
Q

Classes of genes implicated in carcinognesis

A
  • proto oncogenes: promote proliferation (mainly encode growth factors, growth factor receptors, signal transducers or transcription factors). Dominant mutations
  • tumour suppressor genes: inhibit proliferation. recessive inheritance (both functional gene copies have to be lost if sporadic)
  • care taker genes: repair DNA damage, recessive mutations
45
Q

Tumour growth terms

A
  • what is hypertrophy: increase in size due to increase in size of individual cells
  • what is hyperplasia: increase in number of cells
  • what is metaplasia: replacement of one fully differentiated tissue with another,
    usually in response to persistent injury
  • what is dysplasia: architectural and cytological changes
46
Q

How a diagnosis of cancer is made

A
  • Histological assessment of a biopsy or resected specimen
  • Gross features: Tumour size, lymph node size and number
  • Microscopic findings: tumour grade, margins, lymphovascular invasion, mitotic rate (Proliferation index Ki-67), Immunohistochemistry staining
47
Q

General histopathological features of cancer

A
  • Abnormal cellular morphology
  • Increased rate of mitosis
  • Multinucleated cells
  • Increased nuclear DNA and nuclear-cytoplasm ratio
  • Less organised tissue architecture
48
Q

Cancer staging: general

A
  • Invasive tumours: invade the basement membrane
  • In situ: non invasive but has all other features of cancer
49
Q

Oncology terms

A
  • -oma describes a benign tumour although some aren’t tumours i.e. granuloma
  • -carcinoma: malignant epithelial tumour
  • -sarcoma: malignant connective tissue tumour
  • Terato-: malignant germ cell
  • adeno-: glandular epithelium
  • Osteo-: bone
  • Lipo-: fat
  • Angio-: vascular
50
Q

More unusual cancer terminology

A
  • Can have more than one type of cancer tissue present within a single organ i.e. carcinosarcoma
  • The cancer tissue may not fit within a known classification and is termed carcinoma NOS (Not otherwise specified)

year 4 CDM 2 (39 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions