Neoplasia Flashcards
Describe the Warburg effect?
Excessive glycolysis in the presence of oxygen
What are agonists of HER1/2?
EGF - epidermal growth factor
TGFα - transforming growth factor
Do carcinomas have mesenchymal or epithelial origin?
Epithelial
What are the pathways of spread for metastasis?
Direct seeding of body cavities/surfaces
Lymphatic system
Vascular system
Src signaling regulates what?
Cytoskeleton
Cell migration
Adhesion
Invasion
What underlying cancers can cause hypoglycemia as a paraneoplastic syndrome. Why?
Ovarian carcinoma
Fibrosarcoma
Mesenchymal sarcomas
Produce insulin or insulin-like substance; induces glucose uptake
What is the function of p53?
Inhibit cell cycle progression to allow DNA repair
What type of gene promotes proliferation and inhibit cell death?
Oncogenes
Describe the TNM system.
Numbers are assigned to each characteristic based on a scale for individual cancers
T = tumor size
N = lymph node metastases
M = other metastases

In the epithelium, when dysplasia breaches the basement membrane it is considered ____.
Invasive
Metaplasia refers to ____.
Replacement of one cell type to another; associated with tissue damage, repair, and regeneration
Ex: Barrett’s Esophagus

What are some of the local effects of a cancerous tumor?
Affect function of vital tissue by pressure, obstruction, or infection
Solid tumors cannot be more than ______ in diameter without angiogenesis, as it is the diffusion limit
1-2 mm
Where are you most likely to see metastasis via direct seeding?
Peritoneal
Any spaces (including joints and subarachnoid)
A sarcoma has _____ stroma and is considered _____.
little
“fleshy”
Grading of a tumor is determined by?
Cytology
Ex: Pap Smear

The transition between what two phases of the cell cycle is disrupted in most cancers?
G1 to S phase
Under hypoxic conditions, Src signaling promotes what?
Angiogenesis
(VEGF, MMPs, IL8)
Myc controls _____% of all mammalian genes.
10-15%
Does grading or staging have greater clinical value?
Staging
What is a teratoma?
Tumor derived from totipotent cells; mixture of adult tissue types
What are the ways cancer cells evade the immune system?
Antigen loss
HLA mutations (histone compatibility)
Produce immune inhibitors

Stroma refers to what in cancer.
Supportive tissue
ex: connective tissue, blood vessels, lymphatics
Mutations in BRCA1/2 are associated with?
Inherited breast cancer susceptibility
What is a leiomyoma? Is it highly differentiated or does it lack differentiation?
Benign smooth muscle tumor of the uterine wall
Highly differentiated

Does parenchyma or stroma determine tumor behavior?
Parenchyma
What cancer is associated with overactivation of HER1/2?
Breast cancer
Is a papilloma mesenchymal or epithelial in origin?
Epithelial
Is a fibroma mesenchymal or epithelial in origin?
Mesenchymal
Is a leiomyoma mesenchymal or epithelial in origin?
Mesenchymal
The likelihood of metastasis increases due to what cellular factors?
Lack of differentiation
Aggressive local invasion
Rapid growth
Large size
What extracellular stimuli activate Myc?
Growth factors
Cytokines
Cell adhesion
What enzymes does Rb interact with?
Chromatin remodeling enzymes; has significant impact on global gene expression
Does stroma affect parenchymal behavior or does parenchymal affect stroma behavior?
Stroma affects parenchymal behavior
HIF1α induces VEGF, which leads to?
Angiogenesis
The following are all characteristics of what class of tumor?
Pleomorphism
Abnormal nuclear morphology
Irregular and increased mitoses
Loss of polarity
Central ischemic necrosis
Anaplastic
What glycolytic enzyme is activated by HIF1α?
Hexokinase 2 (HK2)
Responsible for initiating glycolysis by phosphorylating glucose into glucose-6-phosphate
Pleomorphism refers to _____?
Variations in size and shape of cells
Ex: tumor giant cells in a Rhabdomyosarcoma (malignant tumor of skeletal muscle)

Pathological staging of a tumor is determined by?
Biopsies
Clinical staging information
Do carcinomas originate from endoderm, mesoderm, or ectoderm?
Any of them
What is the function of cyclins?
Activate cyclin-depending kinases (Cdks) at specific points in the cell cycle
What cancer is linked to exposure to Aflatoxin B1?
Hepatocellular carcinoma
What is the normal function of BRCA1/2?
Act as mediators of double-stranded break (DSB) repair
Replication fork collapse recovery

Is a cystadenoma mesenchymal or epithelial in origin?
Epithelial
What is are paraneoplastic syndromes?
Cancer patients that have symptoms unrelated to an existing tumor that cannot be explained by new pathology and is not due to systemic effects of hormones or inflammation
What is the hallmark characteristic of a papilloma?
Fingerlike projections, either micro or macroscopic
What are the potential fates of double-stranded DNA repair? (4)
Repaired directly
p53-mediated pathways
Apoptosis
Senesce
Mesenchymal tumors are derived from?
Mesoderm
What is the most common pathway for spread of carcinomas?
lymphatic system
Are veins or arteries more likely to be penetrated by a metastasis?
Veins
Clinical staging of a tumor is determined by?
Physical exam
Imaging
Lab tests
How is Rb regulated in the cell?
Inhibited by hyperphosphorylation by cyclin/CDK complexes; allows for cell cycle progression

How does p53 activate?
Complexes with PIDD to form PIDDosome

Glycolytic enzymes are expressed at ____ rates in cancer cells.
Higher
What are the three main stages of carcinogenesis?
- Initiation/priming
- Permanent DNA damage
- Additional promoter mutations

What is the consequence of acute exposure to Aflatoxin B1 at high levels or exposure in children?
Hepatic necrosis
Anaplasia refers to ____.
Lack of differentiation
Is a chondroma mesenchymal or epithelial in origin?
Mesenchymal
Breast cancer can be induced by what hormone?
Estrogen
How does merlin act on the cell membrane and the nucleus?
Membrane: inhibits RTKs and integrins
Nucleus: inhibits E3 ubiquitin ligase

What extracellular stimuli inhibit Myc?
Contact-inhibition
TGFβ
Differentiation
How does Aflatoxin B1 act on a cell?
Causes characteristic mutation on Ser249 of p53
Parenchyma refers to ____ in cancer.
The cancer cells themselves
What must occur in order for Myc to bind to DNA?
It must complex with another protein (Max)
Anaplasia is a hallmark of ____.
Malignancy
When a tumor is more differentiated, does that generally indicate a better or worse prognosis?
Better prognosis
An adenoma is a tumor of?
Glands
What does cyclin D1 mediate?
G1 to S phase transition
What kind of gene inhibits proliferation and promotes cell death?
Tumor suppressor genes
Mutations in cyclin D1 can result in what?
Inappropriate entry into S phase
What is the function of Rb?
Inhibits cell cycle progression and differentiation by interacting with transcription factors
BRCA2 acts in?
Homologous recombination
HIF1α counteracts the activity of what protein? How?
Myc
Blocks or displaces it due to overlapping recognition sequences
What are the three types of staging of a tumor?
Clinical
Pathological
Restaging
Staging of a tumor is based on?
Location of primary tumor
Tumor size
Lymph node spread (local v. regional)
Distant metastases
What is Max?
Myc-associated protein X
FOrms a heterodimer with Myc so it can bind to DNA
Is a polyp mesenchymal or epithelial in origin?
epithelial
Staging of a tumor can be determined by?
Surgery or imaging
What is Aflatoxic B1?
Carcinogen produced by Aspergillus (mold that grows on nuts)
What is VHL? Function?
Von Hippel Lindau protein
Ubiquitin ligase that targets HIF1α for destruction
What type of abnormal nuclear morphology would you expect to see in an anaplastic tumor?
Unusually large for the cell with variable and irregular shape
Coarse, clumped chromatin that may be hyperchromatic
Abnormally large nucleoli

Prostate cancer is dependent on what hormones?
Androgens
What is Myc?
An oncogenic transcription factor that serves as an intracellular sensor and transducer of extracellular stimuli
Are adenomas mesenchymal or epithelial in origin?
Epithelial
Does Ras signaling promote proliferation or inhibit proliferation?
Promotes proliferation
In the epithelium, when dysplasia is contained by the basement membrane, it is referred to as ______.
Carcinoma In situ

What is the consequence of chronic low level exposure to Aflatoxin B1?
Hepatocellular carcinoma
HER1/2 genes code for what protein?
Epidermal growth factor receptor (EGFR)
What are some of the normal functions of Myc?
Cell survival
Cell cycle progression
Cell adhesion
Energy production
Protein biosynthesis
Nucleotide and Amino acid metabolism
What causes p53 to activate?
Genotoxic stress due to double-stranded DNA breaks
Do sarcomas have a mesenchymal or epithelial origin?
Mesenchymal
What is the protein product of the NF2 gene? What is its function?
Merlin
Inhibits proliferation and survival
What type of receptor is EGFR?
Receptor tyrosine kinase

What is a mixed tumor?
Divergent differentiation of a neoplastic clone of the SAME germ layer
Ex: mixed tumor of the salivary gland can have epithelial components in the stroma as well as islands of cartilage or bone
What is the most common pathway for spread of sarcomas?
Vascular system
What is HIF1α? Function?
Hypoxia-inducible factor
Dimerizes with HIF1β and acts as a transcription factor for survival proteins; especially glycolytic proteins
Dysplasia refers to _____.
Disordered growth; loss of cellular uniformity and normal organization of tissue
What protein is mutated in pheochromocytomas (tumor of the adrenal glands)
Max
Grading of a tumor assumes that what two aspects of it are related?
Behavior and differentiation
What is cachexia? Symptoms?
Progressive loss of both fat and lean tissue, typically from cancer
Profound weakness, anorexia, anemia
Dysplasia is a precursor to ____.
Malignancy, but does not always lead to cancer.
BRCA1 acts in?
Checkpoint activation and DNA repair
What enzyme of the citric acid cycle is activated by HIF1α?
Pyruvate dehydrogenase kinase