Lectures 12-17 Flashcards
characteristics of benign tumors
usually resemble normal tissue, slow growth rate
cell of origin: adeno-
epithelial; glandular
cell of origin: lipo-
mesenchymal; fat
cell of origin: fibro-
mesenchymal; connective tissue-making
cell of origin: leio
mesenchymal; smooth muscle
cell of origin: rhabdomyo-
mesenchymal; skeletal muscle
cell of origin: osteo-
mesenchymal; bone
cell of origin: chondro-
mesenchymal; cartilage
cell of origin: angio-
mesenchymal; blood vessel
what are mixed tumors?
tumors with epithelial and mesenchymal compartments
what are teratomas?
tumors composed of tissue derived from multiple germ layers; predominantly benign
what are hamartomas?
mass of disorganized, mature tissue, not necessarily neoplastic conditions
what are choriostomas?
ectopic tissue in a foreign location, an anomaly of development (not tumor)
cell of origin: carcino-
epithelial
cell of origin: sarcoma
mesenchymal
define “well-differentiated”
resembles normal tissue
carcinoma in situ
malignant cells do not penetrate beyond basement membrane
define dysplasia
disordered growth of epithelium
characteristics of dysplasia (4)
loss of polarity, loss of maturation, loss of organization, abnormally located mitoses
malignant tumors that don’t metastasize (2)
basal cell carcinoma, gliomas (brain tumors)
most common pathway for sarcoma spread
hematogenous
most common pathway for carcinoma spread
lymphatics
seeding of peritoneal cavity is a frequent finding of what cancers?
ovarian and peripheral lung cancers
TNM staging system
T=tumor size; N=nodal involvement; M=metastasis
histologic examination: process
portions of tissue are sectioned into cassettes, fixed in formalin and embedded in paraffin overnight, cut into thin sections and H&E stained the next day
indications for frozen tissues
surgical margin assessment and sentinel lymph node involvement
karyotype analysis: process
dependent on isolation of chromosomes in metaphase, following stimulation with a mitogen, chromosomes are stained and arranged in pairs
describe the exogenous pathway of tumor antigen processing
APCs capture tumor proteins from the microenvironment, process them, and present them on class II MHCs for CD4 T cells
describe the endogenous pathway of tumor antigen processing
tumor cells process cytoplasmic proteins into peptides and present them on MHC class I for CD8 T cells
tumor-infiltrating lymphocytes (TILs): mechanism
lymphocytes are cultured from tumors removed by surgery, expanded, then given back to patients
chimeric antigen receptors (CARs): what are they
fuse antibody/binding portion of BCRs to internal portion of TCR which contains T cell signaling motifs
chimeric antigen receptors (CARs): process
extract total white cells from patient, extract T cells, activate with cytokines, expand, transduce with CAR, return to patient
allogeneic T cells as cancer immunotherapy: mechanism
donor T cells become activated to host alloantigens, can eliminate residual host cancer cells that express the alloantigens
only one mutant allele required
oncogene (gain of function gene)
ERB B2 gene (Her-2-Neu): mechanism, what type of gene is this
ERB B2 gene (Her-2-Neu) is a growth factor receptor that is amplified in breast cancer; protooncogene
role of RAS in oncogenesis
Ras proteins are GTP-binding proteins and point mutations cause reduced GTPase activity –> continuous ON signal
role of ABL in oncogenesis
ABL is normally a transient tyrosine kinase; t(9;22) Philadelphia Chromosome creates a BCR-ABL fusion product –> constitutive activity –> CML and ALL
role of MYC in oncogenesis
normally MYC expression is increased following signal to replicate; mutated form leads to overexpression or amplification
Burkitt lymphoma: mechanism
increased c-MYC expression via t(8;14), myc is placed under the control of Ig heavy chain locus –> B cell cancer
n-MYC: clinical relevance
amplified in neuroblastoma; amplification is associated with poor prognosis; amplifies within chromosome or as little pieces of DNA
role of cyclin D1 in oncogenesis
mantle cell lymphoma: t(11;14), cyclin D1-IgH fusion leading to overexpression of cyclin D1 –> CDK4 constitutively activated
mantle cell lymphoma: two genes responsible
cyclin D1 and IgH
increased c-MYC expression
Burkitt lymphoma
what is the model for the two-hit hypothesis?
retinoblastoma (familial and sporadic forms)
role of RB in oncogenesis
RB gene encodes for a tumor suppressor protein, mutations cause a failure of E2F regulation, allowing for uncontrolled E2F activation and unregulated cell growth –> retinoblastoma
retinoblastoma: mechanism
mutations in RB cause a failure of E2F regulation allowing for uncontrolled E2F activation and unregulated cell growth
role of APC in oncogenesis
APC gene encodes for a tumor suppressor that downregulates beta-catenin; mutations in APC cause beta-catenin accumulation and beta-catenin can complex with a transcription factor that stimulates the transcription of other growth factors –> hundreds of adenomas
familial adenomatous polyposis (FAP): mechanism
mutations in APC cause beta-catenin accumulation and beta-catenin can complex with a transcription factor that stimulates the transcription of other growth factors –> hundreds of mucosal polyps carpet the colon of adolescents; need prophylactic colectomy
hundreds of mucosal polyps carpet the colon of adolescents: what disease, mechanism
familial adenomatous polyposis (FAP); mutations in APC cause beta-catenin accumulation and beta-catenin can complex with a transcription factor that stimulates the transcription of other growth factors
Li-Fraumeni syndrome: mechanism
inheritance of a mutated p53 allele, second mutation acquired later in life
role of BCL-2 in oncogenesis
BCL-2 is an antiapoptotic protein, overexpressed in many lymphomas; t(14;18) causes IgH-bcl-2 fusion –> overexpression of BCL-2 –> follicular lymphoma
follicular lymphoma: mechanism
t(14;18) causes IgH-bcl-2 fusion –> overexpression of BCL-2 (antiapoptotic protein)
initiator and promoter chemical carcinogens
initiator: cause permanent DNA damage; promoter: enhances proliferation of mutated cells (Ex: hormones)
role of EBV in oncogenesis
infected B cells in lymphoid tissue of oropharynx –> in immunocompromised patients, B cells are not checked by T cells so the infected B cells continue to grow and accumulate more mutations –> Burkitt lymphoma
what kind of tumors are more likely to form in immunocompromised patients?
EBV-driven B cell tumors
role of Hepatitis viruses in oncogenesis
chronic liver injury leads to regeneration, which leads to increased potential for genetic abnormalities; HBx (a viral protein from Hepatitis B) activates growth genes and inhibits p53
role of Helicobacter pylori in oncogenesis
host inflammatory response leads to carcinogenesis; regeneration, metaplasia, dysplasia –> adenocarcinoma; treatment with eradication of H. pylori
a constant dose of drug kills a constant ??? of tumor cells
fraction
tumor size predicts what component of therapy?
duration
to be a curative, a chemotherapy regimen must have a ??? efficiency and be repeated for ??? cycles
2-4 log-kill; 4-12 cycles
cell cycle-specific, phase nonspecific drugs (3)
cyclophosphamide, cisplatin, doxorubicin
