Handout Neoplasia Two Flashcards
Cachexia
catabolic state of severe wasting mediated by TNF
Paraneoplastic Syndrome
Symptoms not attributable to direct effects of tumor (or hormones native to the primary tumor organ)
Tumor grade
qualitative microscopic assessment of the differentiation of a tumor
Tumor stage
anatomic extent of tumor, including primary tumor size, extent of lymph node and distant metastases
Biopsy
tissue sample obtained by surgical or endoscopic forceps, incision, or excision
Cytology
sample of cells exfoliated or aspirated from the body
Follicular B-cell lymphomas have what type of translocation?
t(14;18) trnaslocation that fuses the BCL2 gene from chromosome 18 with the active IgH locus on chromosome 14 resulting in overproduction of anti-apoptotic BCL2.
lymphocytes are subjected to apoptosis at a slow rate –> slow accumulation of excess lymphocytes
How do follicular lymphoma patients present?
painless, generalized, very slowly progressive enlargement of lymph nodes at an average age of 60.
equally common in men and women, but twice as common in whites as blacks and asians
What is required for tumors to grow over 2mm?
Growth of new blood vessels
What is angiogenesis normally inhibited by?
Thrombospondin-1 (induced by p53) and destruction of HIF-1a (by VHL).
What happens with tumoral hypoxia
calls off VHL, so that HIF-1a starts VEGF production and growth of irregular leaky blood vessels –> ANGIOGENIC SWITCH
What is the angiogenic switch mediated by?
HIF-1a, basic FGF, loss of p53, decreased TSP-1, and overcoming anti-angiogenic factors (angiostatin, endostatin, vasculostatin)
Does inhibiting sustained angiogenesis have efficacy in controlling cancer?
NO!
What are the four steps involved in local invasion by malignant tumors?
1) detachment of tumor cells from e/o
2) degradation of BM and ECM
3) attachment of tumor cells to BM
4) migration of the escaped malignant cells through the interstitium
Detachment of tumor cells from each other is mediated by…
downregulation of E-cadherin or mutated B-catenin
What is involved in the degradation of the BM and ECM?
BM is composed of type IV collagen
Degradation is by matrix metalloproteinases (especially MMP-9)
Attachment of tumor cells to exposed BM is mediated by…
laminin and fibronectin receptors
Migration through BM and ECM is mediated by…
binding to various factors such as autocrine motility factor
Characteristic Patterns of Metastasis
Colon cancer –> local lymph nodes and then liver
Prostate and Breast –> local lymph nodes then bone
Organ Tropism
the mechanisms of metastatic organ tropism include differential concentration of endothelial cell ligands for adhesion molecules in different organs and chemokines such as CXCR4 and CCR7 receptors in the case of breast cancer
Tumor Embolus
Tumor cells that invade veins generally pass through the right heart and go to the lungs, where they stop and elicit formation of blood clot around them. Fibroblasts organize the blood clot part of this. The obstruction of small pulmonary blood vessels can eventually lead to pulmonary HTN and right heart failure
Chemicals that cause cancer can be categorized as…
1) Initiators: cause mutations, which become irreversible in the progeny of the mutated cell, if not reversed in it
2) Promoters: cause reversible proliferation of initiated cells
3) Direct: reactive electrophiles
4) Indirect: require metabolic activation of procarcinogens commonly by CYP450
Name the 3 most common and important carcinogens
estrogen
alcohol
anti-cancer chemotherapy agents
Radiation Carcinogenesis
The cancer-causing effect of radiation has a long latent period (years-decades). UV light cases skin cancer. Radiation therapy causes sarcomas. Nuclear power plant leaks cause thyroid cancer.
