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What is metaplasia?
reversible replacement of one cell type with another (ie Barrett's esophagus)
What is dysplasia?
Disordered growth (still reversible). Includes:
  • loss in uniformity of cells
  • loss of architectural organization
  • large hyperchromatic nuclei
  • high nuclear/cytoplasmic ratio
What are the two basic tissue components of a neoplasm?
Parenchyma-- (proliferating neoplastic cells).
Stroma--connective tissue, blood vessels.  This is the place for a tumor to grow
Discuss cellular morphology, rate of growth, spread of tumor with regard to BENIGN tumors.
Cells are Well differentiated (they appear identical to normal tissue), but have encapsulation.

Most grow slowly. But some can grow rapidly.

Most are encapsulated, stay localized.
Discuss cellular morphology, rate of growth, spread of tumor with regard to MALIGNANT tumors.
Marked pleiomorphism, hyperchromatic, mitosis, anaplasia

Highly variable rate of growth.  **correlates with level of differentiation

ability to METASTASIZE
What are some benign and malignant examples of tumors originating from the mesechyma?
Benign--Fibroma, Lipoma
Malignant--Sarcoma (spreads in blood)
What are some benign and malignant examples of tumors originating from the epithelium?
Benign--adenoma, papilloma
Malignant--Carcinoma (spreads to lymph nodes then possibly blood)
What does carcinoma in situ mean?
indicates that it is NON invasive--has not yet crossed the basement membrane.
What is a mixed tumor?

What are some benign and malignant examples of mixed tumors?
2 histoloigc types of tissue from SAME CELL LAYER.  Parotid is most common.

Benign--pleomorphic adeoma of parotid gland, fibroadenoma of breast tissue.

Malignant--malignant mixed tumor, malignant cytosarcoma
Why did Larry spend 1200 at the strip club?
Who knows.
What tumor originates from totipotential cells and where do they usually present antomically?
Teratoma, midline.
Rhabdomyosarcoma, leiomyosarcoma, and liposarcoma are malignances of _________ tissue. 

What specific tissue for each?

Rhabdo--striated muscle
Leiomyosarcoma--smooth muscle
Name some major factors that correlate with incidence of any specific type of cancer
Geographic, environmental, occupational exposure, Age, genetics

The heritable condition Familial Adendomatous poylps of the colon has to do with the ____ gene which is a _________.  ____% of these people develop colon cancer.
APC, tumor suppressor, 100%
The heritable condition Familial Retinoblastoma has to do with the ___ gene, which is a _______
RB, tumor suppressor
What are the pathways of metastasis?
Lymphatics (carcinoma-epithelial)
Hematogenous (sarcoma-mesenchymal)
Direct seeding of body cavities or surfaces (rare)
True or False?  By the time tumors are clnically detected, they are often heterogenous (subclonal populations).
True.  While tumors start out as monoclonal, new mutations cause them to be heterogenous.
What is the growth fraction?
The percent of cells in the proliferative pool. 

At the time of clinical detection, the majority of cells have left the proliferative pool and will be LESS RESPONSIVE to chemo, so we use RADATION.
Fill in the missing steps of invasion:
2.  Attachment to matrix (up reg laminin receptors)
4.  Migration
1.  Deatachment of tumor cells from each other

3.  Degradation of the basement membrane (Type IV collagenase)
What is a proto-oncogene and give examples.
growth promoting gene.  RAS is an example (keeps GTP on)
What is a tumor suppressor gene and give examples.
growth inhibiting gene.  (RB gene, p53)
p53 upregulates ____ which is a(n) _____gene.

p53 inhibits _____, which is a(n) _______ gene.
BAX, apoptosis gene

BCL-2, anti-apoptosis gene
Two examples of Tumor Angiogenesis factors, which are important for establishing tumor stroma, are ____ and _____
Three main groups of environmental carcinogens are:
Chemical, Radiation, Viral-Oncogenic
Chemical carcinogenesis can be talked about as INITIATION and PROMOTION.  Explain.
Initiation results from exposure of cells to a sufficient dose of carcinogenic agent, but NOT ENOUGH for tumor formation.  It does cause permanent DNA damage.

Promoters can induce tumors in INITIATED cells, but they are non-tumorigenic by themselves.  They usually cause inc. proliferation, which increases likelihood of getting mutation.
Describe direct-acting carcinogenic agents and give examples.

Describe indiret-acting carcinogenic agents and give examples
Direct--require NO metabolic conversion to cause DNA damage.  Ex: alkylating/acylating agents like CYCLOPHOSPHAMIDE (chemo drug)

Indirect--require metabolic conversion to become active carcinogens.  ex: POLYCYLCLIC and HETEROCYCLIC AROMATIC HYDROCARBONS
Describe and give examples of promoters

Describe co-carcinogens
can increase proliferation rates, causing increased risk of mutation.  ALCOHOL and ESTROGEN.

Co-carcinogens act in concert with viruses or radiation to induce neoplasms.
Describe the idea of DOSE DEPENDENCE and the LATENT period with regard to carcinogens.
Larger dose= greater incidence

Latent period between exposure to carcinogens and neoplastic transformation
List 4 sources of radiation that are carcinogenic
Sunlight (UV rays)
Nuclear Fusion
List two syndomres that cause increased susceptibility to radiation via DEFECTS in DNA repair mechanisms.
Xeroderma pigmentosa--sunlight causes severe rash

Ataxia-telangiectasia-increased risk of leukemia and lymphoma.
RNA viruses have ______ which allows transcription of viral RNA into virus-specific DNA.
Name an associated cancer for each oncogenic virus:
  • Human T-cell leukemia virus
  • Infections hepatitis B virus
  • Epstien Barr virus
  • Herpes 2
  • Human Papilloma Virus (HPV)
  • T cell leukemia, lymphoma
  • hepatocellular carcinoma
  • Burkitt's lymphoma and nasopharyngeal carcinoma
  • Cervical carcinoma
  • Cervical carcinoma
What are Tumor Specific Antigens?  Give an example.
Specific tumor marker for the immune system to recognize and attack!
Ex: MAGE-1 (melanoma antigen 1)
What are Tumor Associated Antigens?
They are also present on NORMAL cells so the tumor evades the immune system.
These methods are describing what general concept of a tumor?
  • selective outgrowth of antigen-negative variants
  • loss or reduced expression of MHC molecules
  • lack of costimulation
  • immunosuppression
  • apoptosis of cytotoxic T cells
Immunosurveillance--how the tumor can evade the immune system!
How neoplasms might affect host:
  • local and hormonal effects
  • Cancer cachexia (weight loss)
  • Paraneoplastic syndomes
What are paraneoplastic syndomes?
tumors or cancers can produce specific secondary effects that manifest early in their progression. So identification can be key for early treatment!
What underlying cancer matches each of the Paraneoplastic syndomes?

Cushing Syndrome

  • small cell lung carcinoma (making ACTH)
  • Squamous cell carcinoma of the lung, other ones too (making PTH)
  • Ovarian cancer (immunologic)
Grading assesses __________.  Accounts for degree of differentiation, _________, mitotic index, and degree of loss of normal architecture.

Staging uses the TNM system.  What is TNM?
T is size (I remember this because Tamano is size in spanish) 1-4

N is extent of spread to lymph Nodes. N0-N3
M is presence or absence of Metastasis. M0 or M1

Carcinoembryonic antigen (CEA) and Alpha-fetoprotein (AFP) are only produced by SOME of the cancers listed, so they are only good for determining ______ rather than primary diagnosis
In the brain, the grade is the _____
non-neoplastic growth of tissue
Normal tissuw where it should NOT be
Vikram Goyal
Andrew Putnam
Malignant tumors have ______ nuclear/cytoplasmic ratio and ______ mitotic spindles
Increased, abnormal
Malignant tumors have upregulation of ________ activity
The second most important criterion for malignancy
The most common route of metastasis fo surface-derived ovarian cancers.
Most common site of bone metastasis
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