James (lung cancer) LO's Flashcards
1
Q
Phases of cell cycle
A
- G1 (Gap/growth 1)
- S (synthesis)
- G2 (Gap/growth 2)
- Mitosis
2
Q
Cyclin
A
- family of proteins that control the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes
- act as a signal to the cell to pass to the next cell cycle phase
- Cyclin eventually degrades deactivating cdk, signalling exit from that phase
3
Q
CDK
A
- cyclin dependent kinase (protein kinases)
- form complexes with cyclins
- coordinate cell cycle progression through phosphorylation
4
Q
Categories of lung cancer
A
- small cell lung cancer
- non-small cell lung cancer
5
Q
Incidence of lung cancer
A
- second most common after breast and prostate
- leading cause of cancer death worldwide
6
Q
Epidemiology
A
- males more than females except adenocarcinoma
- declining incidence in men but not women
- Mortality rates in men and women are converging
Age: 65-75 years peak
7
Q
Causes of lung cancer
A
- tobacco smoking (90% of lung cancers except weaker association with adenocarcinoma)
- passive smoking
- Radon (2nd leading cause)
- Uranium decays into radon
- Asbestos
- Occupational carcinogens (arsenic, chromium, nickel, beryllium, silica)
- Environmental air pollution
- Family Hx (genetic predisposition)
- Pulmonary scarring, previous radiation, pulmonary fibrosis, chronic infections (TB,HIV)
8
Q
Non small cell lung cancer types
A
- lung adenocarcinoma
- lung squamous cell carcinoma (SCC)
- Large cell carcinoma
9
Q
Lung neuroendocrine tumor types
A
- small cell lung cancer (SCLC)
- Large cell neuroendocrine carcinoma
- bronchial carcinoid tumor
10
Q
Lung adenocarcinoma
A
- NSCLC
- Peripheral
- most common type of primary lung cancer
- more common in women and nonsmokers
- Associated with mutations in EGFR, ALK, KRAS genes
- digital clubbing
- most common type that originates in pulmonary scars
- Better prognosis than other types
- Glandular tumour
- Mucin producing cells
- Lepidic adenocarcinoma
(alveolar thickening)
11
Q
EGFR
A
Epidermal growth factor receptor
12
Q
ALK
A
Anaplastic lymphoma kinase translocation
13
Q
Lung squamous cell carcinoma
A
- NSCLC
- Central
- Strong association with smoking
- Cavitary lesions arising from a hilar bronchus
- PTHrP: hypercalcemia
- Solid epithelial tumor
- Intercellular bridges
- Keratin pearls
14
Q
Large cell carcinoma
A
- NSCLC
- peripheral
- strong association with smoking
- poor response to chemotherapy
- early metastases
- poor prognosis
- Undifferentiated tumor
- Large tumor cells
15
Q
Small cell lung cancer (SCLC)
A
- central
- strong association with smoking (extremely rare in nonsmokers)
- associated with several paraneoplastic syndromes
- undifferentiated and very aggressive with early metastases
- associated mutations: L-myc oncogene
- Neuroendocrine kulchitsky cells
- Rapid growth pattern
- Expressed tumor markers: chromogranin A, synaptophysin neuron specific and enolase
16
Q
Tumor markers SCLC
A
chromogranin A, synaptophysin neuron specific and enolase
17
Q
Large cell neuroendocrine carcinoma
A
- peripheral
- generally high grade tumors
- poor clinical prognosis
- same histology as SCLC
18
Q
Bronchial carcinoid tumor
A
- central/peripheral
- accounts for 1-2% of all lung cancers but are the most common primary lung cancer in children and adolescents
- Good prognosis
- Metastases are rare
- Carcinoid syndrome eg flushing, diarrhea is rare
- Mass effect of tumor eg wheezing
- Same histology as SCLC
19
Q
Carcinoid syndrome
A
Carcinoid syndrome – characterized by diarrhea, flushing, dyspnea, and wheezing – may occur if a serotonin-producing tumor has metastasized to the liver, bypassing first-pass metabolism.
20
Q
Central vs peripheral tumor
A
- central occurs near entrance of lungs, common in smokers
- fine bronchi and ai sacs, smokers and non-smokers
21
Q
Clinical features
A
- often only symptomatic in late stages–> poor prognosis
- cough, hemoptysis, progressive dyspnea, wheezing, chest pain
- weight loss, fever, weakness
- hoarseness: paralysis of recurrent laryngeal nerve (poor outcome)
- Dyspnea and diaphragmatic elevation: paralysis of phrenic nerve
- Dullness on percussion, reduced breath sounds: malignant pleural effusion on affected side
- postobstructive pneumonia
- Dysphagia : oesophageal compression
- Superior vena cava syndrome: compression of vena cava impairs the venous backflow to the right atrium, resulting in venous congestion in the head, neck and upper extremities
22
Q
Spread of lung cancer
A
BLAB
- Bones (bone pain, elevated serum alkaline phosphatase and calcium
- liver: typically asymptomatic but may manifest with nausea, jaundice, ascites
- adrenal: typically asymptomatic
- brain: headaches, focal motor deficits, behavioral changes
23
Q
Mode of spread of lung cancer
A
BLAB (brain, liver, adrenal, bones)
- cancer leaves original tumor site and attach and degrade proteins of ECM and cancer cells can escape
- direct spread (local invasion)
- lymphatic spread: follows natural route of drainage –> hilar, mediastinal and supraclavicular regions
- Haemtogenous spread`; bones, liver, adrenal and brain, arteries penetrated les regularly than veins
- Transcoelomic spread: spread of malignancy into body cavities can occur via seeding the surface of pleural space , lung CA can spread through pleural cavity, oftn causes pleural effusion
24
Q
Bronchoscopy and radiology in investigation of lung cancer
A
- chest xray
- CT chest
- PET/CT
- bronchoscopy
25
XRAY and lung cancer
- less sensitive than CT but may have indirect signs of malignancy
- postobstructive pneumonia, pleural effusion, mediastinal widening, cavitary lesions, atelectasis
- adenocarcinoma: hazt infiltrates as seen in pneumonia
- SCC may manifest as a cavitating lesion with air fluid levels
26
Define pleural effusion
- collection of fluid that accumulates in the pleural cavity and impairs expansion of lungs (exudative or transudative)
27
Pathophysiology pulmonary collapse
- loss of lung volume due to inadequate expansion of airspaces
- reduced ventilation or a blockage --> obstruction of passage of air to and from alveoli--> trapped alveolar air absorbed into bloodstream but air outside cannot replace--> affected portion of alveoli becomes airless--> alveolar collapse
28
Clinical findings of pulmonary collapse
- small numbers of alveoli affected --> minimal symptoms or asymptomatic
- large number of affected alveoli or rapid onset--> acute dyspnea, chest pain, tachypnea, tachycardia and cyanosis
- dull percussion note, diminished breath sounds and decreased fremitus over affected lung
- possible tracheal deviation towards side of lesion
29
Differential diagnosis of haemoptysis
- acute respiratory tract infections eg pneumonia, bronchitis
- asthma
- bronchiectasis
- COPD
- TB
- malignancy
- pulmonary embolism
- blood thinners
- coughing
- cystic fibrosis
30
Liver function tests
- AST: aspartate transaminase
- ALT: alanine transaminase
- ALP: alkaline phosphatase
- GGT: gamma glutamyl-transferase
- LDH: lactate dehydrogenasee
- Albumin and total protein
- Bilirubin
- Prothrombin time
31
Tissue biopsy lung cancer
- bronchoscopy with transbronchial biopsy: central
| - CT guided transthoracic biopsy: peripheral nodules
32
Types of bronchoscope
- Bronchoscopes are inserted through nose or mouth and moved down throat and trachea into airways
- rigid bronchoscope: straight tube to view larger airways
- flexible/fibrooptic: flexible bronchoscope, can be moved into bronchioles
33
ALT
Alanine transaminase
- only occurs in liver disease
- enzyme used to metabolize alanine, only found in liver
34
AST
Aspartate transaminase
- mitochondrial enzyme
- aspartate to glutamate
- liver, heart, muscle, brain, kidney
- increased may indicate liver disease
35
ALP
- Alkaline phosphatase
- enzyme in liver, bile ducts, bone
- increased may indicate liver damage/disease such as blocked bile duct or bone disease
- GGT increased also, presumed to be liver problem
36
GGT
Gamma glutamyl-transferase
- increased may indicate liver damage
- increased in response to alcohol consumption and fatty liver disease
37
LDH
Lactate dehydrogenase
- enzyme found in liver
- increase may indicate liver disease
38
Albumin and total protein
- albumin made in liver
| - decreased may indicate liver disease
39
Bilirubin
produced from red blood cell breakdown, normally unconjugated, increase liver disease
40
Prothrombin time
time for blood to clot, increase may indicate liver disease
41
Prothrombin time
time for blood to clot, increase may indicate liver damage
42
Pathophysiology of exudative pleural effusion
-
43
Pathophysiology of exudative pleural effusion
- increased capillary permeability due to inflammation
| - proteins leak out of tissues into pleural space
44
Pathophysiology of transudative pleural effusion
- increased capillary hydrrostatic pressure
- deecreaseed capillarry oncotic pressure
- usually ultrafiltrates of plasma squeezed out og
45
Pathophysiology of transudative pleural effusion
- increased capillary hydrostatic pressure
- decreased capillary oncotic pressure
- usually ultrafiltrates of plasma squeezed out of pleura as a result of these imbalances and fluid moves into pleural space
46
Pathophysiology of exudative pleural effusion
- increased capillary permeability due to inflammation
- proteins leak out of tissues into pleural space
- Pneumonia, TB, lung cancer, RA
47
Paraneoplastic features of lung cancer
- hypercalcemia (SCC)
- Gynecomastia due to production of hCG (large cell carcinoma and poorly differentiated adenocarcinoma)
- cushing syndrome (SCLC_
- LOOK UP
48
Transudate vs exudate
- Transudates: ultrafiltrate of plasma due to increased hydrostatic pressure with normal vascular permeability, non-inflammatory
- < 3g/l of protein, clear or serous, no bacteria
- Exudates: increased vascular permeability in inflammatory processes
- > 3g/l of protein, purulent or hemorrhagic, bacteria
49
Investigations for pleural effusion
- chest xray: blunting of costophrenic angle
- fluid in lung fissures
- large effusions`--> meniscus
- tracheal and medistinal deviation
- sample of pleural fluid (analyze for protein, acidity, glucose , LDH, microbiology)
50
Transudate vs exudate
- Transudates: ultrafiltrate of plasma due to increased hydrostatic pressure with normal vascular permeability, non-inflammatory, low LDH, low protein, low cell count
- < 3g/l of protein, clear or serous, no bacteria, does not froth or form clots, more glucose
- Exudates: increased vascular permeability in inflammatory processes /fluid pushed out of blood vessels into nearby tissues
- > 3g/l of protein, cloudy or straw coloured sometimes hemorrhagic, bacteria, high LDH, high cell count, neutrophils in acute and lymphocytes in chronic, froths when shaken and clots when left standing, less glucose as bacteria metabolize
51
Somatic mutation theory
most significant risk factor for cancer is ageing as incidence increases with age
- ageing = accumulation of mutations in genetic material of somatic cells a a function of time results in a decrease in cellular function
- telomeres determine lifespan of cell, become shorter each time cell divide , eventually cell cannot divide without losing important parts of DNA
52
Hyperplasia
- Increase in number of cells in organ or tissue
- Can be physiological due to a normal stressor eg increase in size of breasts during pregnancy, increase in thickness of endometrium during menstrual cycle and liver growth after partial resection OR
- Pathological due to an abnormal stressor such as proliferation of endometrium due to prolonged oestrogen stimulus
- Only cells that divide can undergo hyperplasia so it is impossible to have hyperplasia in myocytes in heart or neurons in brain
- Slight cancer risk
53
Hypertrophy
-Increase in size of cells
Physiological- normal stressor eg enlargement of skeletal muscle with exercise
-Pathologic- abnormal stressor eg cardiac hypertrophy where heart muscle is thickened, decreasing size of chambers of heart and a reduced capacity of the heart to pump blood to the tissues and organs around body
- not usually cancer risk
54
Metaplasia
- Reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type
- Barrett oesophagus: acid reflux, esophageal squamous to glandular columnar
55
Neoplasia
abnormal and excessive growth of tissue. Can be benign or malignant.
56
benign vs malignant factors
- degree of differentiation
- Rate of growth
- local invasion
- metastasis
57
Malignant
Poorly or completely undifferentiated ( do not look like non-cancerous cells in region) anaplasia
Fast growing (can be erratic slow to fast)
Poorly circumscribed and invade surrounding tissue
Locally invasive and potentially metastasis to distant sites
58
Benign
Resemble tissue of origin (well differentiated)
Slow growing
Well circumcised and have a capsule (seperated from host tissue)
Localised to site of origin (no metastasis)
59
Dysplasia
- presence of abnormal cells within a tissue or organ
60
Anaplasia
cells that are poorly differentiated
61
morphological differences between benign and malignant tumours
- degree of differentiation
- rate of growth
- local invasion
- metastasis
62
Benign tumors morphology
- Resemble tissue of origin (well differentiated)
- Slow growing
- Well circumcised and have a capsule (seperated from host tissue)
- Localised to site of origin (no metastasis)
63
Malignant tumors morphology
- Poorly or completely undifferentiated ( do not look like non-cancerous cells in region) anaplasia
- Fast growing (can be erratic slow to fast)
- Poorly circumscribed and invade surrounding tissue
- Locally invasive and potentially metastasis to distant sites
64
Staging
-extent or progression of a neoplasm
T: primary tumor (T0-T4)
N: lymph nodes (N0-N3)
M: metastasis (M0/M1)
65
Grading
- differentiation of a neoplastic cell
| - G1-G4
66
Breslow thickness
- measure from granular layer of the epidermis down to deepest point that tumour has invaded tissues
- mm
67
Clarke level
anatomical level of invasion
68
G1 phase
- Synthesis of RNA, proteins, and cell organelles
- Occurs after mitosis
- There is one chromatid present per chromosome.
- The cell grows during this phase
- Nucleotide excision repair takes place.
- G1 checkpoint before entering S phase
69
S phase
- DNA replication results in two sister chromatids per chromosome.
- Synthesis of proteins required for DNA packaging (especially histones)
- Most mismatch repair takes place during the S phase.
- Once the S phase is initiated, the cell cycle must be completed.
70
G2 phase
- Further synthesis of proteins required for mitosis
- Repair of DNA replication errors
- G2 checkpoint before entering mitosis
71
G0 phase
- a resting phase which a cell enters after exiting the cell cycle from the G1 phase
72
M phase
- the process of cell division from the distribution of DNA to the budding of a cellular
73
Mitosis
- Prophase
- Metaphase
- Anaphase
- Telophase
74
Cyclin-CDK complex
-A type of protein complex with an enzymatic function that phosphorylates other proteins to regulate the progression of the cell cycle
75
Tumor suppressors
- A group of proteins that arrest and modulate (e.g., repair or induce apoptosis) the cell cycle of cells with an abnormal genome
- DNA mutations can lead to defective tumor suppressor genes allowing cells to divide uncontrollably.
76
cell cycle checkpoint
-specific point in time that marks the transition from one cell cycle phase to another during which the current condition of a cell is revised (i.e., if all requirements for the transition to the next phase are met)
77
G1 checkpoint
- a cell division checkpoint during the G1 phase that restricts entry into the S phase
- Cyclin D/Cdk4 complex
- p53
78
Cyclin D/Cdk4
- G1 checkpoint
- Cyclin D/Cdk4 complex phosphorylates pRb--> pRb inactivation--> release of previously bound transcription factor E2F--> transcription of genes needed for DNA replication
79
p53
- G1 checkpoint
- A protein that inhibits DNA replication by activating pRb and initiates apoptosis of the cells with irreparable DNA damage
- DNA damage → activation of protein kinases → phosphorylation of p53 → activation of p21 → inhibition of Cdks → inhibition of Cdk-mediated phosphorylation of pRb → pRb activation and binding of transcription factor E2F → cell arrest in the G1 phase (no entry into the S phase)
80
G2 checkpoint
- Checks for DNA damage and completeness of DNA replication
| - Cdk1 and cyclin B
81
M checkpoint
a checkpoint between metaphase and anaphase in mitosis
82
Labile cells
- rapidly dividing
- Short G1, never enter G0
- epithelial cells
83
Quiescent (stable) cells
- can enter G1 phase from G0 phase when stimulated
| - hepatocytes
84
Permanent cells
- remain in G0
- skeletal and cardiac cells
- neurons
85
Properties of malignant cells
- sustained proliferative signalling due to mutations of genes regulating cell division and growth
- Evade growth suppressors
- Genome instability and mutations
- Resist cell death, mutations in apoptosis regulatory genes
- enable replicative immortality, reactivation of telomeres
- induce angiogenesis
- Activate invasion and metastasis
- Avoid immune detection, decrease MHC I expression on malignant cells
86
oncogene
the product of a gain-of-function mutation in a proto-oncogene which leads to overexpression of signaling proteins and growth factors, and thus, uncontrolled cellular proliferation (e.g., dysplasia, neoplasia)
Only one allele of the proto-oncogene requires damage to form an oncogene.
87
Proto-oncogene
Proto-oncogene: Genes that encode proteins that are important in normal cell division and cell differentiation.
