Term
| How are acute and chronic inflammation involved in the foreign body response? |
|
Definition
Similar cells and chemical mediators are employed in both inflammation and FBR.
These include cytokines, PMN, macrophages, lymphocytes, and fibroblasts |
|
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Term
| What are the molecular modifiers of the foreign response? |
|
Definition
Growth factors such as PDGF, FGF, TGFβ > proliferation of fibroblasts, endothelial
cells, and specialized fibrogenic cells
Cytokines such as TNF, IL-1, IL-4, IL-13 > increased collagen synthesis > fibrosis |
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Term
| Give an overview of the sequence of the inflammatory response |
|
Definition
1. vasoconstriction
2. vasodilation (histamine, NO)
3. increased permeability
4. edema
5. decreased blood flow (hypotension)
6. neutrophils (roling, adhesion, transmigration, chemotaxis)
7. phagocytosis
3 outcomes
1. chronic inflammation (angiogenesis, mononuclear cell infiltrate, scar)
2. resolution (resolvin, etc)
3. Scarring |
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Term
| What are the roles of serotonin, prostaglandins, and Leukotrienes in Inflammation? |
|
Definition
serotonin comes from platelets, and does vasodilation and increased permeability.
prostaglandins, from mast and leukocytes do vasodilation, pain and fever
leukotrienes come from mast and leukocytes and do chemotaxis, increased permeability, leukocyte adhesion and activation |
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Term
|
Definition
| natural or synthetic materials introduced into body as part of medical device |
|
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Term
| What is the foreign body response? |
|
Definition
body's reaction to introduction or presence of external object/ device
1. non-specific protein deposition in surface
2. recruitment/ interaction of inflammatory cells w/ coated surface
3. repair-like processes
4. foreign body giant cells (multinucleated macrophages fuse)
5. matrix production and encapsulation |
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Term
| What are similarities and differences between wound healing and the foreign body response? |
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Definition
Similarity-- beginning steps similar - recruit platelets, neutrophils, fibroblasts, macrophages
Differences:
1. depostion of DENSE collagen in FBR (only some collagen syn in wound healing)
2. healing restores normal tissue arch. and vasculature- FBR collagen in parallel, fibrosis, avascular |
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Term
| What are the pathways of the receptors w/ intrinsic tyrosine kinase activity? |
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Definition
| PI3 kinase pathway, MAP-kinase pathway, IP3 pathway > Ca2+ release |
|
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Term
| What are the pathways of the G-protein coupled receptors? |
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Definition
|
|
Term
| What are the pathways of the receptors w/o intrinsic tyrosine kinase activity? |
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Definition
| JAK/STAT > STATs direct binding to DNA |
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Term
| What are the differences between autocrine, paracrine and endocrine signaling? |
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Definition
autocrine- cell responds to signals they secrete themselves
paracrine- cells in close proximity signal to neighboring cells
endocrine- synthesized by cells of endocrine organs- target cells distant (blood steam) |
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Term
| What are the 2 main signal effects of growth factors (within the cell)? |
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Definition
1. stimulate transcription of many genes that were silent in resting cells
2. regulate entry into cell cycle |
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Term
| What are stem cells? (name the liver, skin and skeletal stem cells) |
|
Definition
cells that self renew and differentiate
(asymmetric or symmetric)
Liver= Oval
Skin= Bulge
Skeletal= satallite, satallite glial cells in PNS |
|
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Term
| What is the difference between labile, quiescent and non-dividing? |
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Definition
labile = continuously divide eg. surface epithelia
quiescent= low replication rate, rapid w/ stimulus (eg. liver, kidney, pancreas)
Nondividing= senescence (eg. neuron, skeletal and cardiac muscle) |
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Term
| Define regeneration and healing |
|
Definition
regeneration= growth of cells to replace lost structures
healing= regeneration and laying down of fibrous tissue (scar formation)
-after MI can lead to constrictive pericarditis :(
(usually in response 3 injury- 1.wound, 2. inflammation, 3. necrosis) |
|
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Term
| What is the difference between regeneration and healing? |
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Definition
| regneration restores normal tissue structure while in healing there is a loss of ECM > involves fibrosis and scar formation |
|
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Term
| What are growth factor functions? |
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Definition
| proliferation, cell survival, locomotion, contractility, differentiation, angiogenesis |
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Term
| Describe the unique angiogenic and fibrogenic response elicited by foreign bodies |
|
Definition
Unique angiogenic response: vessels are pushed away from the encapsulated foreign
body (instead of penetrating the site as during normal inflammation)
b. Unique fibrogenic response: thick and tightly packed collagen network formed around the foreign body (see above for more details) |
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Term
| What is the overlap between granulomas and the foreign body response? |
|
Definition
In both granuloma formation and FBR, inflammatory cells accumulate at the site of foreign object, and fibrosis is initiated to wall off the object. The term granuloma is
commonly used to denote the encapsulation of a pathogen (bacteria or parasites),
whereas the term FBR is used to denote the reaction against artificially introduced devices/materials. |
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Term
|
Definition
| New growth (cells growing autonomously, escaping normal feedback mechanisms, and the growth exceeds and is uncoordinated with that of the normal tissues). The growth continues after cessation of the stimuli |
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Term
| What are the two basic components of both benign and malignant tumors? |
|
Definition
1. clonal neoplastic cells (parenchyma)
2. reactive stroma of connective tissue, blood vessels, macrophages and lymphocytes |
|
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Term
| How are hyperplasia, metaplasia and dysplasia different from neoplasia? |
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Definition
Hyperplasia may still be regulated by growth factors
Metaplasia is replacement of one type of cell with another type (usually there is still orderly growth and it can be reversible or self-limiting
dyplasia is simply disordered growth (loss of uniformity of individual cells and loss of architectural orientation)
neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue and persists in the absence of stimulus. |
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Term
| How do we name benign mesenchymal tumors (suffix?) |
|
Definition
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|
Term
| How do we name benign epithelial tumors (examples)? |
|
Definition
adenoma - glandular tissue
papilloma- finger like projections
cytoadenomas- form cysts
polyp- projection above mucosal surface into lumen (eg. GI) |
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Term
| How do we name malignant mesenchymal tumors? |
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Definition
| Sacroma (eg. fibrosarcoma) |
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Term
| How do we name malignant epithelial tumors? |
|
Definition
| carcinoma (eg. adenocarcinoma) |
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Term
| Compare benign and malignant tumors on differentiation, rate of growth, local invasion and metastasis |
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Definition
Begnin- well differentiated, progressive/slow, do not invade or metastasize
Malignant- range of differentation (some lack = anaplasia), erratic rates (slow to rapid), locally invasive, frequently metastasize |
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|
Term
|
Definition
|
|
Term
| How do we characterize tumors? |
|
Definition
| classification, grading, and staging |
|
|
Term
| What is classification of tumors? |
|
Definition
| Classifying type of cell that the tumor resembles (presumed origin of tumor) |
|
|
Term
| What is grading of tumors? |
|
Definition
| The degree of differentiation (1-5) with 1 being very differentated |
|
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Term
| What is staging of tumors? |
|
Definition
| Based on the size of tumor (T), extent of spread to regional lymphnodes (N), presence or absence of metastasizes (M) |
|
|
Term
| What are some techniques for diagnosing cancer? |
|
Definition
excision/ biopsy
fine needle aspiration
pap smear
immunohistochemistry
flow cytommetry
molecular diagnosis |
|
|
Term
| What determines the rate of growth of tumors? |
|
Definition
| doubling time of tumor cells, fraction of tumor cells in the replication pool, rate at which cells shed or die |
|
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Term
| What are some of the clinical manifestations of neoplasia? |
|
Definition
paraneoplastic syndromes (unexplained system complexes
tumor endocrine production
anemia
jaundice
ischemia
fever
masculinization
leucocytosis (increased number of WBC)
leucopenia (decreased number of WBC)
episodic flushing (caused by serotonin and bradykinin)
infection
hemorrhage
obstruction
pain
fracture
Death |
|
|
Term
| What are some serologic markers of tumors? |
|
Definition
tumor associated enzymes
hormones (eg. Hcg, calcitonin)
specific proteins (immunoglobulins)
antigens
molecular markers (p53, RAS) |
|
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Term
| Name two important oncogenes and explain their mechanism |
|
Definition
RAS- G protein that when mutated is continuously in the active state, binding GTP. This leads to continued cell proliferation (via stimulation of regulators or proliferation like MAP kinase pathway)
MYC- controls transcription, mutation leads to increased histone acetylation and reduced cell adhesion, increased protein synthesis, and other changes that induce high rate of cell division. |
|
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Term
| Name specific tumors in which MYC oncogene is involved |
|
Definition
Burkitt's lymphoma (B cell tumor)
Breast, colon, lung cancer |
|
|
Term
| Name specific tumors in which RAS oncogene is involved |
|
Definition
pancreatic and lung adenocarcinomas
colon and thyroid cancer
myeloid leukemias |
|
|
Term
| Name two important tumor suppresor genes and their mechanism |
|
Definition
RB gene- (retinal blastoma) enforces the G1 phase which once crossed leads to obligatory mitosis
p53 gene- prevents propagation of genetically damaged cells, guards the G1-S phase transition, involved in activating DNA repair pathways |
|
|
Term
| Name specific tumors in which RB tumor suppressor gene is involved |
|
Definition
retinoblastoma
glioblastomas
osteosarcomas
breast, bladder cancer |
|
|
Term
| Name specific tumors in which p53 tumor suppressor gene is involved |
|
Definition
|
|
Term
| Name 2 apoptosis regulating genes |
|
Definition
|
|
Term
|
Definition
BRCA1
BRCA2
--these are the DNA damage response network that repair intra and interstrand DNA crosslinks
--these are important in breast and ovary carcinoma |
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Term
| Name the 7 physiologic activities required for malignancy |
|
Definition
self-sufficiency in growth signals
insensitivity to growth inhibition
evasion of apoptosis
limitless proliferative potential
sustained angiogenesis
defects in DNA repair
ability to invade and metastasize |
|
|
Term
| How do tumors gain self-sufficiency in growth signals? |
|
Definition
Through activation of oncogenes, which produce oncoproteins that are devoid of important regulatory elements
Additionally they do not depend on external signals of GFs |
|
|
Term
| How are tumor cells able to evade apoptosis? |
|
Definition
Inactivate p53, activate antiapoptotic genes, reduce levels of FAS/CD95 receptors or have high levels of FLIP, which prevents activation of caspase 8.
The best established is to use BCL2 to prevent apoptosis |
|
|
Term
| How does a metastatic tumor invade the ECM? |
|
Definition
1. Alterations in intercellular adhesion molecules.
2. Local degradation of the basement membrane and interstitial connective
tissue. (proteolytic enzymes secreted by themselves or induce stromal cells to elaborate proteases.
3. Changes in attachment of tumor cells to ECM proteins.
4. Locomotion |
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|
Term
| Why is genomic instability considered the enabler of malignancy? |
|
Definition
Basically lack of DNA repair leads to genomic instability, and defects in DNA repair contribute to most cancer!
(both copies of the DNA repair gene are lost usually but there is evidence that there is a subset of genes that can promote cancer in a haploinsufficient manner) |
|
|
Term
| What are the categories of genetic change that can activate oncogene or inactivate tumor suppressor genes? |
|
Definition
| Mutations, translocations, amplification, deletions, epigenetic regulation. |
|
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Term
| Describe the rationale for activity of at least 2 molecularly targeted cancer drugs |
|
Definition
Herceptin- monoclonal antibody that binds HER2 to block the signaling of the growth factor receptor
Gleevac- used in CML, tyrosine kinase inhibitor for the BCR/ABL tyrosine kinase which is constitutively on in CML. |
|
|
Term
| What is the Philidelphia chromosome? |
|
Definition
| Fused BCR/ ABL translocation, chimeric gene encodes a constitutively active oncogenic BCR/ABL tyrosine kinase! Leads to CML. |
|
|
Term
| Describe the concept of premalignancy |
|
Definition
Premalignancy is a state in which the tissue is at risk of tumorgenesis due to genetic mutations, yet there is no cancer specific phenotypes (example: leukoplakia)
In FAP Familial Adenomatous Polyposis, the APC gene is mutated |
|
|
Term
| What are some agents that can cause cancer |
|
Definition
Physical like UVB light, ionizing radiation
Chemical like carcinogens
Infectious agents, like HPV, Hep B |
|
|
Term
| What are some conditions that can lead to cancer |
|
Definition
| Chronic inflammatory conditions, genetic predisposition, tumorimmunoediting (changes in tumor surveillance), genetic diseases |
|
|
Term
| Compare and contrast acquired vs. germline cancer causing genetic mutations |
|
Definition
They both can lead to tumorgenesis
Germline mutations put people one step ahead compared to acquired mutations, like shortened time |
|
|
Term
| Describe carcinogenesis in terms of initiation and progression |
|
Definition
Initiation occurs when a chemical irreversibly damages DNA and the damage is non lethal, but these cells DO NOT progress to tumors
Progession is the next step that is needed to stimulate proliferaiton of mutant cells. These promoting agents are not tumorgenic by themselves |
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Term
| What is a cancer stem cell? |
|
Definition
| A group of self-renewing cells that possess tumorogenic mutations |
|
|
Term
|
Definition
| Reversible heritable changes in gene expression that occur without mutation, for example histone acetylation and DNA methylation |
|
|
Term
| Describe how we use epigenetics for cancer diagnosis and therapies. |
|
Definition
Cancer cells have abnormal epigenetic signatures
Theraputic targets include having inhibitors of DNA methylation and histone acetylation. |
|
|
Term
| Mechanisms that regulate tumor migration, invasion and metastasis! |
|
Definition
Adhesion (cell-cell, cell-matrix)
Proteolysis (proteases and their inhibitors)
Migration (Roles of adhesion and proteolysis)
Tumor cell-endothelial cell interation
Angiogenesis |
|
|
Term
| What are the 5 categories of congenital anomalies? |
|
Definition
| malformation, disruption, deformation, sequences, syndromes |
|
|
Term
|
Definition
| Results from intrinsically abnormal developmental process (eg. anencaphaly) |
|
|
Term
|
Definition
| Results form extrinsic interference on previously normal development (eg. amnionic band can wrap around limbs and impair growth) |
|
|
Term
|
Definition
| Localized or generalized compression of the growing fetus by abnormal biochemical forces leading to structural abnormalities (eg. clubbed feet resulting from decreased amnionic fluid and pressure from the uterine wall) |
|
|
Term
|
Definition
| Its a cascade of anomalies triggered by one initiating aberration (any of the other congenital anomalies) |
|
|
Term
|
Definition
| Multiple congenital anomalies believed to be pathologically related and explained by a single localized initiating defect |
|
|
Term
|
Definition
| Gestational age less than 37 weeks |
|
|
Term
| What are the causes of prematurity? |
|
Definition
1. preterm premature ruption of placental membranes (PPROM) usually caused by infection
2. Intrauterine infection
3. Uterine, cerviccal and placental structural abnormalities
4. Multiple gestation (twins!) |
|
|
Term
| What are the consequences of prematurity? |
|
Definition
1. Hyaline membrane disease
2. Necrotizing enterocolitis
3. Sepsis
4. Intraventricular hemorrhage
5. Develpmental delay |
|
|
Term
| What is hyaline membrane disease? |
|
Definition
| reduced surfactant at premature birth > increased alveolar surface tension > hypoxemia and CO2 retention > accidosis > pulmonary vasoconstriction > pulmonary hypoperfusion > edothelial damage and pithelial damage > plasma leak into alveoli ? fibrin and necrotic cells (hyaline membrane) |
|
|
Term
| What is intraventricular hemorrhage |
|
Definition
| Loss of autoregulation of cerebral blood flow leads to hemorrhage into the ventricles |
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