Neoplasia 3 Flashcards
The _____ family of regulators is involved with blocking apoptosis.
BCL
What is the “prototypic anti-apoptosis gene?”
BCL2
How is BCL2 activated?
by TRANSLOCATION from chromosome 18 to the Ig heavy locus of chromosome 14
BCL is activated by translocation from chromosome 18 to the _______ locus on chromosome 14.
Ig heavy chain
What is the problem with over-expression of BCL2 protein?
cells are protected from apoptosis and are able to survive for prolonged periods
Over-expression of BCL2 results in the steady _______ of cells that is often seen in “low-grade” ______.
accumulation
lymphomas
_______ to a tumor is critical for sustained growth.
blood supply
Tumors cannot grow larger than ______ in diameter unless they are vascularized (nutrients and oxygen)
1 to 2 mm
______ facilitates metastases by providing access to the vasculature.
angiogenesis
True or False: Anti-angiogenesis treatment is sufficient in controlling tumors.
False: it is not sufficient on its own
What are the two characteristics most often associated with malignancy?
invasion
metastasis
Only certain _____ may be capable of metastasizing.
subclones
The complex process of invasion/metastasis involves what two major phases?
- invasion of the ECM
2. vascular dissemination and adhesion/homing of tumor cells
Describe the process for invasion of the ECM.
- tumor cells detach from each other
- attach to ECM components (basement membrane and CT) : collagens, glycoproteins, and proteoglycans
- degradation of matrix components
- migration
To which ECM components do tumor cells attach to?
collagen
glycoprotein
proteoglycan
______ is considered the hallmark of malignancy although not all tumors will have this characteristic. What is always characteristic of malignancy?
Metastasis
always = invasion
Tumor metastasis is usually a function of what two cellular traits?
- function of the site
2. vascular/lymphatic drainage
What is “organ tropism” associated with cancer?
the tendancy of metastasis to occur at specific sites due to possible chemoattraction or receptors
ex: skeletal muscle cancer is rare (possibly fewer receptors on skeletal muscle)
Humans are constantly exposed to _______ such as ionizing radiation, sunlight, and dietary agents.
environmental carcinogens
Errors in DNA replication occur naturally, so why isn’t cancer more common?
DNA repair genes!
Hereditary Nonpolyposis Colon Cancer Syndrome and Xeroderma Pigmentosum are two examples of conditions with ______ ____.
Unstable DNA
What is Hereditary Nonpolyposis Colon Cancer Syndrome?
mismatch repair defect (microsatellite instability)
______ ______ is an inability to repair UV damage that commonly results in skin cancers.
xeroderma pigmentosum
Which proteins are associated with familial breast cancers?
BRCA1 and BRCA2
DNA control and tumor suppression
True or False: A single mutation could result in cancer.
False, cancers exhibit multiple genetic alterations
Cancers exhibit multiple genetic alterations including activation of several _______ and two or more ____ ____ _____.
oncogenes
cancer suppressor genes
As DNA damage goes un-repaired, the risk for mutations increases dramatically once reaching the _____ ______ stage.
clonal expansion
True or False: Over time, many tumors become more aggressive locally and have greater metastatic potential.
True
Why do many tumors become more aggressive locally?
due to the acquisition of multiple mutations during tumor growth, resulting in numerous “subclones” with different characteristics
How do “subclones” survive?
they develop different characteristics that are survival selective such as drug resistance, resistance to hypoxia, etc.
What is the most common karyotypic change seen in tumors?
Balanced Translocations (for example: 22 and 9 in Philidelphia chromosome)
What are the three types of karyotypic changes seen in tumors?
- Balanced translocations
- Deletions
- Gene amplifications
Retinoblastoma is associated with which type of karyotypic change?
Deletion (Rb)
Neuroblastoma and breast cancers are associated with which karyotypic change?
gene amplification
Chronic Myelogenous Leukemia is associated with the Philidelphia chromosome which involves chromosomes ____ and ____. This results in what kind of mutation?
22 and 9
Tyrosine Kinase Mutation
N-MYC is associated with _______.
neuroblastoma
What are “double minutes?”
chromosomes that enter circulation in the cytoplasm and can be transcribed when the re-enter the nucleus later
What are the three major classes of carcinogenic agents (factors associated with genetic damage)?
- Radiant Energy
- Chemicals
- Oncogenic Viruses
Over 200 years ago, Sir Percival Pott linked soot exposure to ______ cancer in chimney sweeps.
scrotal skin
Chemical carcinogens can be of what two types?
natural
synthetic
True or False: Chemical carcinogens are synthetically produced to kill cancer cells.
True, some are produced for that reason
True or False: Direct-reacting carcinogens require chemical transformation.
False, they require no transformation
Most cancer-causing chemical are _______ carcinogens.
indirect
What is an “indirect” carcinogen?
they become active only after metabolic conversion
Indirect carcinogens are _________
pro-carcinogens
What are the “true” carcinogens?
Active metabolites (ultimate carcinogens)
All chemical carcinogens are highly reactive ______.
Electrophiles
True or False: Chemical carcinogens affect anything with a positive charge.
False, NEGATIVE charge (such as DNA, RNA, proteins)
How can chemical carcinogens be enhanced?
by other chemicals called “promoters” that drive cells to divide and thus immortalize DNA alterations
True or False: Promoters are carcinogens.
False, not in-and-of themselves. They have LITTLE mutagenicity on their own
What are examples of radiation carcinogens?
- UV light
- X-rays
- Radionuclides
- Gamma Radiation from nuclear fission
True or False: Early dental practitioners developed squamous cell carcinomas from x-radiation.
True
What is an example of radionuclide carcinogenesis?
miners of radioactive elements (uranium) and the development of lung cancer
Why did atomic bomb survivors develope leukemia/cancer 8-12 years after the explosion?
gamma radiation is hematopoetic and can go latent for decades
Human T-cell Leukemia Virus Type I is an example of an ___ ____ virus.
RNA Oncogenic
Where is Human T-cell Leukemia most prevalent?
parts of Japan and Caribbean basin
HPV with Cervical/Oropharyngeal Cancer, or EBV with Burkitt’s lymphoma are two examples of what type of carcinogenesis?
DNA oncogenic Viruses
HHV8 is associated with what type of cancer?
Kaposi’s Sarcoma
What are four important anti-tumor mechanisms?
cytotoxic T-cells (CD8+)
natural killer cells
macrophages
humoral factors
What is “immunosurveillance?”
increased frequency of cancer observed in immunocompromised
What is PSA?
Prostate Specific Antigen (it is used to monitor current or past disease)
A tumor is exposed to the immune system which will exert local controls. What is an example of cell alteration that could be a potential avenue for melanoma therapy?
Dendritic Cell alterations
How does a tumor evade the immune system?
- selects for antigen-negative variants
- reduces expression of HLA antigens
- lacks T-cell co-stimulation (requires 2nd signal)
- immunosuppression
What are four clinical features of neoplasia?
- Location
- Functional Activity
- Ulceration
- Cachexia
True or False: A benign tumor can be lethal.
True, if its in the wrong place (i.e: blocking a major artery)
What is cachexia?
progressive wasting state (mediated by IL-1 and TNFalpha)
10-15% of cancer patients develop ______ syndromes due to hormone and peptide alterations.
paraneoplastic
Why would Cushing’s syndrome or hypercalcemia develop secondarily to cancer?
they are paraneoplastic syndromes associated with an alteration in the body’s ability to mobilize calcium
What are the two steps in evaluating cancer?
- Grading
2. Staging
What is “grading” in regards to evaluation of a neoplasm?
grading is an estimate of the aggressiveness of a cancer based on the MICROSCOPIC appearance
What is “staging” of a neoplasm?
staging describes the cancer EXTENT (size, node involvement, spread) as estimated by CLINICAL EXAM and IMAGING
True or False: Staging involves the use of microscopy.
False, “look and see”
True or False: Grading is an estimation of aggressiveness.
True, based on microscope analysis
Biopsy can be _____ or _____.
incisional
excisional
Why is “frozen section biopsy” sometimes a difficult method to rely on?
artifacts can form due to crystal formation
True or False: Fine-needle aspiration biopsy is actually better termed “cytology”
True
What is a common example of a “cytology?”
Pap Smear (tissue cells)
Which laboratory diagnosis is used to evaluate a blood malignancy?
Flow Cytometry
What is the difference between incisional and excisional biopsy?
incisional is a “small part”
excisional is “the entire thing”
When evaluating a pap smear, what do you want to see?
almost all cytoplasm, if the cells are hyperchromatic and have a high ratio of nucleus to cytoplasm that is indication of cancer
Prostate Specific Antigen (PSA), Carcinoembryonic Antigen (CEA), and alpha-fetoprotein are examples of ________.
biochemical assays for diagnosing cancer
ISH, FISH, and PCR are _______ diagnosis methods for cancer.
molecular
