Neoplasia (M) Flashcards
What is the nationality and profession of Willis?
He is a British oncologist
As defined by Willis, what is neoplasia?
It is an abnormal mass of tissue the growth of w/c exceeds and is uncoordinated w/ that of normal tissue and persists in the same excessive manner after cessation of stimuli w/c evoked the change
What are the phases of cell cycle?
1) G0
2) G1 - presynthetic
3) S - synthetic
4) G2 - premitotic
5) M - mitotic
What are the grps of cells accdg to proliferative potentials?
1) Labile cells
2) Stable cells
3) Permanent cells
What are labile cells?
These are cells that are continuously dividing
What are stable cells?
These are also called as quiescent cells
What are permanent cells?
These are nondividing cells
Cell proliferation can be stimulated by what?
1) Injury
2) Cell death
3) Mechanical deformation of tissues
How can growth be accomplished?
It can be accomplished by shortening the cell cycle
What are the most impt factors in relation to growth?
Those that recruit resting or quiescent cells into the cycle
What are the fxns of molecular controls and what is its result?
Regulate and orchestrate events leading to cell division
What is involved in cascade of protein phosphorylation?
Cyclins
What are the fxns of set of checkpoints (present in the cell cycle)?
1) These monitor molecular events
2) These may delay the progression to the next phase of the cell cycle
What are the fxns of checkpoints?
1) These provides surveillance mechanisms
2) These causes cell cycle arrests
What is the purpose of providing surveillance mechanisms done by checkpoints?
For ensuring that critical transitions occur in the correct order w/ fidelity in their completion
How does checkpoints cause cell cycle arrests?
By promoting inhibitory pathways or inhibiting activation pathways
Why is p53 activated and what is its result?
In response to DNA damage w/c in turn activates p21
*What is p21?
It is a CDK inhibitor
What is the fxn of CDK1B complex?
It controls transition from G2 - M
*The fxn of CDK1B complex is done after what?
After completion degraded by ubiquitin-proteosome pathway
What is the action of CDK1B complex?
It may bind w/ CDK inhibitors
What is the definition of new growth?
Neoplasm
What is the definition of “onco”?
Tumor
What is cancer?
It is a malignant neoplasm
What is carcinoma?
It is a malignant epithelial tumor
What is sarcoma?
It is a malignant mesenchymal tumor
What is the meaning of salise?
To circumvent
What are the 6 fundamental physiological changes in the neoplastic cell?
SALISE
1) Self sufficiency in growth signals
2) Ability to invade and metastasize
3) Limitless replicative potential
4) Insensitivity to growth-inhibitory signals
5) Sustained angiogenesis
6) Evasion of apoptosis
*What are the danger signals of neoplasm (/ its clinical manifestation)?
CAUTION US
1) Change in bowel or bladder habits
2) A sore that does not heal
3) Unusual bleeding or discharge
4) Thickening or lump (breast or elsewhere)
5) Indigestion or difficulty of swallowing
6) Obvious change in a mole or a wart
7) Nagging cough or hoarseness
8) Unexplained anemia
9) Sudden unexplained weight loss
How can tumors be classified?
1) Based on biologic behavior
2) Based on tissue of origin
What are the classifications of tumors based on biologic behavior?
1) Benign
2) Malignant
What are the classifications of tumors based on tissue of origin?
1) Epithelial
2) Mesenchymal
3) Mixed
4) Teratoma
Where does the biologic behavior of tumors depend?
1) Degree of differentiation
2) Rate of growth
3) Local invasion
4) Presence / absence of metastasis
What is the hallmark of malignancy?
Metastasis
What are the characteristics of a benign neoplasm?
1) It is well-circumscribed
2) It is encapsulated
3) It is well-differentiated
4) It pushes margins
5) There is no metastasis
What are the characteristics of a malignant neoplasm?
1) It is ill-defined
* 2) Irregular margins are present
3) It is anaplastic
4) There is invasion / metastasis
What are the 2 principles present in benign neoplasms?
1) Encapsulation
2) Differentiation
*What are the types of differentiation for malignant neoplasms?
1) Well-differentiated
2) Moderately differentiated
3) Poorly differentiated
4) Undifferentiated / anaplastic
What is the principle of differentiation?
The extent to w/c parenchymal cells resemble comparable normal cells, both morphologically and fxnally
What is dysplasia?
1) Disordered growth
2) Disordered maturation
What is anaplasia?
There is lack of differentiation
What is present in well-differentiated squamous cell CA?
Keratin pearls
What are the characteristics of anaplasia?
1) Pleomorphism
2) Hyperchromasia
3) Increased nucleo-cytoplasmic ratio
4) Abnormal (atypical) mitotic figures
5) Loss of polarity (loss of orientation)
6) Presence of multiple or enlarged nucleoli
7) Formation of tumor giant cells
How long does it take to produce a clinically overt tumor mass?
The original transformed cell (approx 10 um in diameter) must undergo at least 30 population doublings to produce 10^9 cells (weighing approx 1 g)
What is the smallest clinically detectable mass?
A transformed cell that weighs approx 1 g
What are the 3 factors that determines the rate of growth of a tumor?
1) The doubling time of tumor cells
2) The fraction of tumor cells that are in replicative pool
3) The rate at w/c cells are shed or die
*What are the 2 principles under biology of tumor growth?
1) Tumor angiogenesis
2) Tumor progression and heterogeneity
*What are the factors present / involved in tumor angiogenesis?
1) Vascular endothelial growth factor
2) Basic fibroblast growth factor
3) Anti-angiogenic factors
*What are the events present under tumor progression and heterogeneity?
1) Increased aggressiveness
2) Genetic instability / random mutations
3) Loss of p53, DNA repair genes
*What are the 2 types of local invasion?
1) In-situ
2) Invasive
What is the principle of local invasion that is in-situ?
Malignant cells confined to epithelial lining, limited by the basement membrane
*What are the 2 types of local invasion in-situ?
1) Intraepithelial
2) Intramucosal
What is the principle of local invasion that is invasive?
Malignant cells have breached basement membrane and are in the subepithelial stroma, lamina propia, or submucosa
Local invasion can be thru what?
1) Invasion thru basement membrane
2) Invasion thru lamina propia
3) Invasion thru muscularis mucosa
What is metastasis?
It is the contiguous invasion to adjacent organ
What can happen in metastasis?
Seeding of body cavities / surfaces
What are the 2 types of spread (in relation to metastasis)?
1) Lymphatic spread
2) Hematogenous spread
What are the sequence of events in invasion and metastasis?
1) Detachment of tumor cells
2) Attachment to matrix components
3) Degradation of extracellular matrix
4) Migration of tumor cells
5) Vascular / lymphatic drainage
6) Microenvironment
What is responsible for detachment of tumor cells?
E-cadherins
What are responsible for attachment to matrix components?
1) Laminin
2) Fibronectins
What are responsible for degradation of extracellular matrix?
1) Collagenase
2) Cathepsin D
What are the sequence of events present in the metastatic cascade?
1) Clonal expansion, growth, diversification, and angiogenesis
2) Metastatic subclone
3) Adhesion to and invasion of basement membrane
4) Passage through extracellular matrix
5) Intravasation
6) Interaction w/ host lymphoid cells
7) Tumor cell embolus
8) Adhesion to basement membrane
9) Extravasation
10) Metastatic deposit
11) Angiogenesis
12) Growth
What are the simplified sequence of events present in metastatic cascade?
1) Loosening of intercellular junctions
2) Attachment
3) Degradation
4) Migration
What are the concepts related to biology of CA?
1) Clonality
2) Progression
3) Proto-oncogenes
What are the principles (/ principles related to clonality) of clonality?
1) Neoplastic cell arise from a single cell
2) 30 population doubling time produce 10^9 cells = 1 gram
What is the principle of progression?
Acquisition of permanent, irreversible qualitative changes in 1 or more characteristics of a neoplasm
What are the principles (/ principles related to proto-oncogenes) of proto-oncogenes?
1) Cellular genes that can become activated to become CA causing oncogenes
2) Encode proteins involved in normal differentiation / proliferation
How does CA develop (/ also called as carcinogenesis)?
Gene damage -> clonal proliferation
What are the concepts related to development of CA?
1) Point mutation
2) Chromosomal translocation
3) Chromosome deletion
4) Gene amplification
What are the principles related to gene amplification (/ what are the events that occur in gene amplification?)
1) DNA-binding protein proto-oncogenes
2) myc family, present in all eukaryotes, bind to protein products are intranuclear and bind to DNA itself. They enable DNA synthesis
3) myc activation is usually by amplification (excess copies of a gene) and/or translocation rather than by mutation
What are the characteristics of myc family?
1) Present in all eukaryotes
2) Its protein products are intranuclear
3) Its protein products bind to DNA itself
What are the ways of how myc activation is done?
1) Via / by amplification (usual)
2) Translocation
What are the targets of genetic damage?
1) Growth-promoting proto-oncogenes
2) Growth-inhibiting cancer suppressor genes
3) Apoptosis-regulating genes
Provide an ex relating to the principle of growth-promoting proto-oncogenes as a target of genetic damage
The related neu (once erb2, now HER2) is amplified in many carcinomas, notably adenocarcinomas, especially of the breast, and the degree of amplification strongly correlates w/ bad outcome
What is the characteristic of neoplasia?
It is a multi-step process
What is the process related to neoplasia being a multi-step process?
Tumor progression
What is the molecular biology of malignant transformation (accdg to Volgenstein’s Multistep Adenoma-Carcinoma Sequence)?
Normal Epithelium -> Hyperplastic Epithelium (Early Adenoma) -> Adenoma (Intermediate Adenoma) -> CANCER
Note: Early Adenoma -> Intermediate Adenoma
What are the concepts present in normal epithelium?
1) Chromosome: 5q
2) Alteration: M / L
3) Gene: APC; MCC
Note:
Legend: M - mutation
L - loss
What are the concepts present in the transition from hyperplastic epithelium to adenoma?
1) Chromosome: 12p
2) Alteration: M
3) Gene: ϰ-RAS
Note:
Legend: M - mutation
L - loss
What are the concepts present in adenoma?
1) Chromosome: 18q
2) Alteration: L
3) Gene: DCC
Note:
Legend: M - mutation
L - loss
What are the concepts present in the transition between adenoma to CA?
1) Chromosome: 17q
2) Alteration: L
3) Gene: p53
Note:
Legend: M - mutation
L - loss
What are the mechanisms related to activation of proto-oncogenes?
1) Point mutation
2) Chromosome rearrangements
3) Gene amplification
What are oncogenes?
These are DNA sequences within eukaryotic cells that seem to be involved in the development and maintenance of tumors
What is the action of oncogenes?
These genes direct the synthesis of proteins that under some conditions transform a benign host cell into a CA cell
What is the action of tumor suppressor genes?
These encode proteins that normally inhibit cell proliferation
What are the proteins related to tumor suppressor genes?
1) Cell surface protein
2) Signal transduction protein
Provide an ex of cell surface protein
DCC
What is the action of DCC?
Cell adhesion
Provide an ex of signal transduction protein
NF - 1
What is the action of NF - 1?
GTPase activator
What is the characteristic of most oncogenic ras?
Most oncogenic ras are mutations w/ a single base pair change that alters an AA at position 12, 13, or 61 in the protein product
What is the action of oncogenic ras?
It destroys GTP-ase activity but retains GTP-binding activity, and current thinking is that these stay locked “on”, telling the transformed cell, “Keep dividing!”
What are the proteins that regulate transcription (in relation w/ tumor suppressor genes)?
1) p53
2) pRb
What is apoptosis?
It is the programmed cell death
Provide a gene that is involved in apoptosis
Bcl-2
What is the action of Bcl-2?
It is an inhibitor of apoptosis
What is the action of tumor suppressor genes?
These keep cells benign, even when the oncogenes are activated
What should be done to lose the anti-CA effect of tumor suppressor genes?
Both copies must be altered
What is viral oncogene?
It is a proto-oncogene minus its regulatory sequences, or w/ a characteristic mutation, or in an excessive # of copies (“amplification”)
What is the action of viral oncogene?
They are capable of causing CA by themselves, and hence are very different from their normal counterparts (i.e., have been damaged several times)
What virus (/ viral oncogene) causes squamous cell carcinoma of the cervix?
Human papilloma virus (HPV | types 16 / 18)
What is the virus (/ viral oncogene) that causes genital warts?
HPV (types 6 / 11)
What is the virus (/ viral oncogene) that causes Burkitt’s lymphoma?
Epstein-barr virus (EBV | t [or types] [8;14])
What is the virus (/ viral oncogene) that causes nasopharyngeal carcinoma and lymphoma in AIDS?
EBV
What is the virus (/ viral oncogene) that causes hepatocellular carcinoma?
Hepatitis B virus (HBV)
What is the principle of immune surveillance?
Recognition and destruction of NON-SELF tumor cells upon their appearance
What are the cells / mechanisms related to immune surveillance?
1) CD8+ cytotoxic T cells (CTLs)
2) Natural killer (NK) cells
3) Macrophages
4) Humoral mechanism
What are the mechanisms of how immunosurveillance tumor cells escape?
1) Selective outgrowth of Ag negative variants
2) Loss / reduced expression of HLA Ags
3) Tumor-induced immunosuppression
4) No co-stimulation / no sensitization
5) Apoptosis of cytotoxic T-cells
What are the mechanisms of the role of p53 in maintaining the integrity of the genome?
1) The p53 gene product is a sequence-specific binder to DNA that prevents mitosis during times of cell injury, so that there will be more time for DNA repair
2) Sometimes (gamete, lymphocyte, chemotherapy) p53 even tells an injured cell to undergo apoptosis
How is nomenclature for benign tumors of mesenchymal origin done?
Root word + “oma”
Provide exs of nomenclature for benign tumors of mesenchymal origin
1) Fat = lipoma
2) Blood vessel = hemangioma
3) Smooth muscle = leiomyoma
4) Skeletal muscle = rhabdomyoma
5) Fibrous tissue = fibroma
6) Cartilage = chondroma
7) Bone = osteoma
How is nomenclature done for benign tumors of epithelial origin w/ glandular pattern?
Adenoma
How is nomenclature done for benign tumors of epithelial origin w/ finger-like projections?
Papilloma
How is nomenclature done for benign tumors of epithelial origin w/ large cystic masses?
Cystadenoma
How is nomenclature done for benign tumors epithelial origin visible projection above a mucosal surface?
Polyp
How is nomenclature for malignant tumors of mesenchymal origin done?
Root word + “sarcoma”
Provide exs of malignant tumors for mesenchymal origin
1) Fat = liposarcoma
2) Blood vessel = hemangiosarcoma
3) Smooth muscle = leiomyosarcoma
4) Skeletal muscle = rhabdomyosarcoma
5) Fibrous tissue = fibrosarcoma
6) Cartilage = chondrosarcoma
7) Bone = osteosarcoma
Provide an ex of nomenclature for malignant tumors of epithelial origin w/ glandular microscopic pattern done?
Adenocarcinoma
Provide an ex of nomenclature for malignant tumors of epithelial origin w/ squamous cells arising in any epithelium done
Squamous cell carcinoma
What are the types of tumors based on tumor composition?
1) Simple tumors
2) Mixed tumors
3) Compound tumors
What are simple tumors?
1 parenchymal cell type
What are mixed tumors?
1 > neoplastic cell type usually from 1 germ layer
What are compound tumors?
1 > neoplastic cell type from 1 > germ layer
What are the exs of tumors of mesenchymal origin?
1) Connective tissues and derivatives
2) Endothelial and related tissues
3) Blood cells and related cells
4) Muscle
5) Bone
6) Cartilage
What are the exs of tumors of epithelial origin?
1) Stratified squamous
2) Basal cells of the skin
3) Epithelial lining (gland or ducts)
4) Respiratory epithelium
5) Neuroectoderm
6) Renal epithelium
7) Liver cell
8) Urinary tract epithelium
9) Placental epithelium
10) Testicular epithelium
What are the 10 leading CA sites (for males and females) accdg to Philippine Cancer Figures (2018)?
1) Breast
2) Lung
3) Colorectal
4) Liver
5) Prostate
6) Cervix uteri
7) Thyroid
8) Leukemia
9) Ovary
10) Corpus uteri
What are the 10 leading CA sites in males?
1) Lung
2) Liver
3) Colorectal
4) Prostate
5) Stomach
6) Leukemia
7) Nasopharynx
8) Thyroid
9) Lymphomas
10) Oral cavity
What are the 10 leading CA sites in females?
1) Breast
2) Cervix
3) Lung
4) Colorectal
5) Ovary
6) Liver
7) Thyroid
8) Uterus
9) Stomach
10) Leukemia
What are the 6 leading CA sites in children?
1) Leukemia
2) Brain and spinal cord
3) Retinoblastoma
4) Lymphoma
5) Bone and soft tissues
6) Gonadal / germ cell site
What are the 2 concepts related to neoplasia?
1) Grading
2) Staging
What is the characteristic of grading?
It depends on the differentiation of tumor
How is grading done?
1) Well differentiated
2) Moderately differentiated
3) Poorly differentiated
What are the concepts related to staging?
1) Tumor size
2) Node involvement
3) Presence or absence of metastasis
TNM system
What is the characteristic of TNM system (/ staging)?
It is a better method for prognostication
