• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/39

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

39 Cards in this Set

  • Front
  • Back
A primary immune response to a previously seen antigen takes how many days to appear? How long does it take for a secondary exposure (re-exposure of same antigen)?
Primary response: 7-10 days (with lag period)

*Secondary response: 1-5 days (and is more vigorous)
What is the MHC?
It describes a region of genes located on chromosome 6 which encode proteins responsible for rejection of tissue between different species or members of the same species
When do T cells become activated?
When TCR (T-cell receptors) engages an antigen for which it is specific
What are signals 1, 2, and 3 for T cell activation?
Signal 1: TCR must see the antigen peptide presented in the groove of an MHC molecule on an antigen-presenting cell
Signal 2: Co-stimulation by proteins on APC that engage specific receptors on T-cell surface
Signal 3: Delivery of growth factors (IL-2 and IL-15) for initiating cell cycle
What represents the intracellular signaling event after lymphocyte detection of specific antigens?
Phosphorylation of the tyrosines in immunoreceptor tyrosine-based activation motifs (ITAMS). This leads to increased calcium levels which activate calcineurin, an enzyme which regulates activation of a family of transcription factors called NFATs (nuclear factor of activated T cells)
Generation of the most effective tumor immune response depends on what?
Activation of T cells that recognize tumor-associated antigens. Also important is the activation of cytokines (especially IFN-gamma)
Extracellular bacteria are killed by which mechanisms in the body?
Phagocytosis and complement activation (bacteria try to evade these by surrounding themselves with capsules and secreting exotoxins that impede host responses)
Toll-like receptors are triggers for a variety of host defense genes and are found in which cells?
Monocytes, macrophages, dendritic cells, mast cells, B cells and epithelial cells
How are DNA microarrays made?
You spot a sequence of nucleotides on a glass support that represent a particular gene (aka probe) to which a complementary sequence of nucleotides (aka target) will hybridize according to molecular attraction (A-T and G-C)
What are oncogenes and tumor suppressor genes?
Oncogenes are genes that promote cell growth- increased expression contributes to cancer.
Tumor suppressor genes inhibit growth and loss of expression causes cancer growth.
What is methylation and how does this relate to cancer?
Methylation is an alternative method of dysregulation and methylation of normally unmethylated genes can suppress gene expression and vice versa.
This is important since if a tumor suppressor gene is silenced by methylation, one could use demethylation to cause reexpression of the gene to treat cancer
What are three hereditary renal cancer genes?
VHL: Chromosome 3; clear cell RCC, retinal angiomas, pheos, hemangiomas of CNS, epididymal cystadenomas, pancreatic islet cell tumors
MET: Associated with hereditary papillary RCC (HPRCC)
FLCN: Birt-Hogg-Dube, chromosome 17, folliculin protein (FLCN)
What defines hereditary prostate cancer?
Cluster of 3 affected relatives within a nuclear family or occurrence of CaP in 3 generation or 2 affected relatives who both developed cancer <55yo
At least 7 loci associated with this- many candidate genes
Which genetic defect is attributed to familial upper tract TCC?
Hereditary nonpolyposis colorectal cancer (aka Lynch syndrome)
Caused by mismatch repair enzyme defects (6 different types based on which mismatches occur)
What % of Wilms’ tumors are hereditary? Which tumor syndromes predispose to Wilms?
Only 1% of Wilms’ tumors are herediatry
WT1 mutations (chr 11- transcriptional regulator)
Loss of imprinting at IGF2 locus
The gene most closely linked to Beckwith Wiedemann syndrome is…
Cell cycle regulator CDKN1C (decreased expression)
What are the two types of polymorphisms?
Microsatellite repeats
Single nucleotide polymorphisms
What are the two primary point of cell cycle controls?
G1S and G2M
What is the most commonly mutated gene in cancer, playing a prominent role in GU malignancies? What does the normal gene do?
TP53
Expression of TP53 results in cell cycle arrest and repair of DNA damage. If it cannot repair damage, TP53 stimulates apoptosis.
What is the function of cyclin-cyclin-dependent kinase complexes? What do cyclin-dependent kinase inhibitors do?
CCDK complexes activate the machinery that allows the cell to replicate its DNA
CDK inhibitors stop the cell from replicating its DNA response to a variety of signals (including DNA damage, cell-cell contact, cytokine release, and hypoxia)
What does RB do?
Key regulatory elements at the G1S checkpoint which is responsible for familial and sporadic retinoblastoma
How is ATM important in the cell cycle?
It plays a central role in sensing DNA damage, inducing S phase and G2M phase arrest and DNA repair
Its name stands for ataxis telangiectasis mutated (which is a human disease in which patients are 100x at increased risk for cancer)
Does DNA damage often lead to malignancy?
No- because the cell possesses multiple repair mechanisms. However, if there are defects in DNA repair, the cell will accumulate mutations critical for tumor formation and progression
What are the four types of DNA repair and what specific items do they repair?
Nucleotide excision repair: DNA damage from UV radiation & chemical exposure
Base excision repair: From spontaneous deamination of bases, radiation, oxidative stress, alkylating agents, and replication errors
Mismatch repair: Removes nucleotides mispaired by DNA polymerase
Double-stranded break repair: DNA damage from ionizing radiation, free radicals and chemicals
What is the classic inhibitor of the mitochondrial pathway of apoptosis?
BCL2 which is overexpressed in some GU malignancies (e.g. hormone-refractory prostate cancer, aggressive bladder cancers)
What is the importance of ceramide and clusterin in GU malignancies?
They are all alternative regulators of apoptosis
Clusterin (TRPM2- testosterone repressed prostate message-2) is upregulated in men w/ hormone-sensitive CaP
Ceramide: Key modulator of radiation-induced tissue damage & apoptosis, promotes apoptosis
What do telomeres do and how do they relate to cancer?
Each cycle of cellular division results in loss of a chromosomal end (telomere) which limits the number of cellular divisions a cell can undergo
Telomerase maintains chromosomal length by rebuilding the telomere so that the cell can undergo unlimited cellular divisions. Most GU malignanices (as well as other cancers) express high levels of telomerase
BUT the presence of telomerase itself does not cause cancer
What is the current thinking of stem cells and their relation to cancer?
Cancer is thought to be a stem cell disease in which a small population of stem cells maintains a larger tumor. Prostate cancer is believed to be a stem cell disease and these stem cells can be identified using the SCA-1 antigen. If we can target the particular stem cell, cancer can be eradicated.
Cells communicate via transmission of signals to each other through cell surface and generate a cascade of downstream events which are regulated. In cancer, the overexpression of which growth factor receptors is common in GU malignancy?
Overexpression or mutation of the EGFR and IGFR
What is the PTEN lipid and protein phosphatase and how does this relate to activation of cellular signaling in cancer?
It is a negative regulator of the PI3 kinase pathway that leads to constitutive activation of the Akt oncogene and is frequently mutated or lost in bladder and prostate cancers.
How are adhesion molecules and methods of cell signaling important in cancer progression?
Adhesion molecules like integrins and cadherins regular cellular attachment and motility and their abnormalities can lead to cancer metastasis. Membrane microdomains (e.g. cholesterol rafts and caveolae) serve as platforms of cell signaling to cause cancer progression.
The first oncogenes discovered were…
Viruses
E.g. human papillomavirus is a cause of cervical cancer
What are the major players in cancer neoangiogenesis?
VEGF (targeted by Avastin)
VHL tumor suppressor gene (basis for sunitinib, sorafenib, etc)
List the major angiogenesis activators and angiogenesis inhibitors.
Activators: FGF-2 and VEGF
Inhibitors: Chemotherapeutics (bleo, vincristine), abx (linomide, fumagillin), proteolytic products, endogenous inhibitors (interferons, thrombospondin), protease inhibitors (MMPs, plasmin), thalidomide, avastin, and small molecules (sutent, sorafenib, erlotinib)
What is PCA3?
It is a test developed out of the identification of a gene called DD3, which is differentially expressed in prostate cancer (present 10 to 100-fold higher in prostate cancer than normal) but does not correlate with stage or grade. An assay was made to look for prostate cells shed into the urine after prostate massage, converted to RNA and subjected to quantitative PCR for PSA and DD3 (now known as PCA3). Presence of PCA3 implies CaP.
What are proteomics and epitomics?
Proteomics is a field of microarray technology which compares patterns analyzed by mass spectrometry to known patterns to identify disease
Epitomics is an offshoot of proteomics- it takes advantage of the host’s B cell response to cancer epitopes to aid diagnosis. e.g. AMACR is pathognomonic for CaP. Detection of autoantibodies that recognize AMACR signals the presence of prostate cancer.
What happens when patients get lymphoma after transplant?
The risk of developing a non-Hodgkin's lymphoma is also markedly increased in patients who have received a solid organ transplant. The histologic appearance of these lymphomas is variable, but they frequently resemble aggressive lymphomas in nonimmunocompromised patients. Similar disorders can be seen in patients who are treated with methotrexate for autoimmune disorders and in recipients of allogeneic hematopoietic stem cell transplants, especially if the transplants are T-cell depleted. These post-transplantation lymphoproliferative disorders, which may develop within weeks after surgery, are more common in those patients who have received more aggressive immunosuppression after trans-plantation. Involvement of extranodal sites is common, and lymphoma frequently involves the transplanted organ.
The use of MESNA with cyclophosphamide or isofosfamide is it really beneficial? How do you give it?
*It is beneficial, both in the setting of giving it with each dose of cyclophosphamide or ifosfamide to prevent hematuria from developing, but it can also be given with subsequent doses of cyclo or isofosfamide to prevent worsening of the hematuria. This was shown in article '87 written by Andriole and Linehan here at the NIH, have saved on QUOSA.

You give it at the same time as the cyclophosphamide or isofosfamide as an iv infusion to prevent the urotoxic effects.
How does MESNA work?
Recently, mesna (2-mercaptoethane sodium sulfonate), a sulfhydryl compound, was shown to
be an effective uroprotective agent in patients receiving oxazaphosphorine therapy.4 Mesna is converted to inactive dimesna in serum, but is
reactivated in the kidney. Mesna is, in fact, almost
exclusively excreted by the kidney--a valuable property relevant to its uroprotective
effect. In the urine, mesna binds to acrolein, the
urotoxic substance produced by hydrolysis of the
4-hydroxy-metabolites of the administered oxazaphosphorine, and the resultant inert thioether is passed innocuously in the urine.5 Mesna also reacts with urinary 4-hydroxy-metabolites directly, and in doing so inhibits their breakdown and the consequent release of acrolein.