Neoplasia Flashcards
Chorisoma, hamartoma
Normal act topic tissue
Normal tissue location but poorly organized
Nomenclature
- Benign tumors typically end in “Oma”
- Epithelial malignancies; carcinomas
- Mesenchymal Malignancies; sarcoma
- Hematopoietic Malignancies; leukemia
- Lymphoid Malignancies; lymphoma
Grading versus staging
- Staging is based on how far the metastases travel
- Grading is how undifferentiated they are; a measure of Anaplasticity
MYC
- Amplification indicates a poor prognosis in many cancers
- This pathway emerges heavily with other intracellular pathways
VHL
- Associated with von Hippel-Lindau syndrome
- Clear-cell renal carcinoma And CNS malignancies
- degrades HIFIa In the presence of oxygen (Activates various growth factors)
- Hypoxia induces H1FIa To initiate Angiogenesis (VEGF/bEGF)
Imanitib
MAb TRK inhibitor
- bcr-abl: Philadelphia chromosome
Philadelphia chromosome
Merging of two proto-oncogenes chromosome locations Resulting in overexpression of Cell cycle advancing factors
RAS
One of the most commonly mutated proto-oncogenes
Rb
Ubiquitous tumor suppressor genes that inhibits E2F.
- E2F have initiates transcription of S-phase genes
- Mutation represents “first hit” in retinoblastoma development
- Is active in a hypophosphorylated state in quiescent cells
- Cyclin D/ CDK/6 Complex phosphorylates Causing it to become in active in replicating cells
ATM/ATR
Mediates damage repair
P53
One of the primary tumor suppressor genes
- p 53 activation is considered a primordial response To damage
- Can initiate quiescence (Temporary cycle arrest) senescence (permanent cell cycle arrest)or apoptosis
INK4/ARF
Blocks cyclin D/CDK 2 phosphorylation of RB protein
TGF-beta
Inhibition of proliferation
SMADs
- Mutation found in 100% of pancreatic cancers and 80% of colon cancers
PTEN
Inhibits mTOR via PI3K/AKT
Associated with Cowden syndrome
NF-1
Associated with neurofibromatosis via the RAS pathway
BCL-2
Anti-Apoptotic gene
Telomerase
Imparts cellular immortality by elongating telomeres and preventing degradation
Warburg effect
In the presence of an oxygen-rich environment metabolism shifts to anaerobic Glycolysis. Allows tumor cells to gain energy very quickly For rapid reproduction
Typical lymphoid mutations
Swapping translocations With proto-oncogenes, Resulting in overexpression
Typical hematopoiesis mutations
Formation of Chimeric proteins promoting growth and survival
- E.g. chronic myelogenous leukemia
Solid tumor mutations
Tend to be deletions
N-MYC
Proto-oncogene of which amplification is implicated in lots of tumors
- Increased amplification is associated with poor prognosis
Benzopyrine
Indirect carcinogen produced from the combination of heat and tobacco
P450 and cancers
Most known carcinogens are metabolized by P450
Oncofetal antigens
Expressed as glycoprotein markers cancers and developing fetuses
- AFP, CEA
Cancer markers (4)
PSA - Marker for prostate cancer but better marker for treatment efficacy
AFP/CEA-Marker for recurrence
CA-125-Ovarian cancer
Bence-Jones Immunoglobulins-Multiple myeloma
Typical tumor progression
Progression from one cell to 10^9 in about 30 doublings: Represents a tumor mass of about 1 g -> In 10 more doublings tumor mass typically is about 1 kg, Which usually is incompatible with life. Detection usually occurs in the last 10 doublings, Hence many have already metastasized
Progression to metastasis
TGIF
- Transformation
- Growth
- Invasion
- fucked (Metastases)
Invasion process
- Degradation of cell to cell junctions (E-cads)
- Mutations in catenin contribute to loosening of cells
- matrix metalloproteinases: Degrades type for collagen in basement membrane And allows for penetration
- Develops novel extracellular matrix attachments and uses it as Migration path
Lung and lymphatic metastases
Originate from the liver due to portal blood supply
FISH assay in prognosis: eg
Fish assay can determine overexpression of proto-oncogenes indicating favorable or unfavorable Prognosis
- HER-2 Amplification indicates susceptibility to trastuzumab
- N-MYC Amplification indicates poor prognosis in Neuroblastoma
MUC-1
Induces antibody/T-cell response in breast tissue
CD 20
B cell stimulation factor
- Target for Rituximab
Immune cells in cancer
Cytotoxic T lymphocytes are the Primary immune response In malignancy, But require sensitization
- Encase cells are secondary but do not require sensitization
- CD4 cells play a minor role
- Antibodies playing no immune function but can be used for identification
Immune avoidance mechanisms of neoplasms
- Antigen negative overgrowth
- Decreasing HLA 1 expression
- Immunosuppression via TGF-beta
- Decrease costimulation receptor B7
- Fas ligand apoptosis of CTLs
Cachexia Syndrome
- Often the first sign of occult Cancer
- MAWW: Malaise, Anorexia, Weakness, Wasting
Carcinoid syndrome
Inflammatory cytokines released causing flushing, cyanosis, G.I. symptoms, bronchoconstriction attacks
Acanthrosis Nigricans
Associated with up to 50% of neoplasms
Cancer trends in men versus women
Incidence in men: Prostate, lung, colon
Incidence in women: Breast, lung, colon
Mortality in men: Lung, prostate, colon
Mortality in women: Lung, breast, colon
Screening recommendations
Breast: Mammogram at 40; MRI if significant family history
Prostate: combo PSA and prostate exam at 50 (45 if black)
Colon: Colonoscope at 50 every 10 years
Cervix: Pap smear at 21 Q3 years, HPV only if abnormal. At 35 Pap smear HPV combo Q5 years
Cushing’s perineoplastic syndrome
Lung neoplasm constitutively releases glucocorticoids
Familial cancer syndromes (4)
Familial retinoblastoma: Rb
Familial Adenomatous polyposis: APC (FAPC)
Multiple endocrine neoplasia: RET mutation
Hereditary non-polyposis colorectal cancer: mismatch repair mutation
Carcinogens; initiators and promoters
- Initiators cause Irreversible DNA damage
- Promoters Do not directly damage the DNA
Complete carcinogens initiate and promote, Incomplete carcinogens initiate only
Carcinogens associated with specific conditions
Aromatic amines -> Bladder cancer
Aflatoxin b1 -> liver carcinoma
All other As -> lung skin
H pylori and neoplasms
Associated with inflammation from chronic gastritis
CAG Associated with higher incidence of malignancy
MALTomas
Germinal center neoplasm, Form in response to chronic inflammation and irritation.
Bacteria in malignancy
In both cases of H. pylori and MALToma’s removing the bacteria or stimulus takes away the cancer
- HPV
most strains associated with benign growths
- 6,11,16,18 (esp. 16 and 18)
- E6 protein: p53
- E7 protein: p53, p21, Rb
EBV
Associated with African Burkitt’s lymphoma
- LMP-1 Activates CD40 ligand initiating proliferation
- inhibits BCL-2 -> No apoptosis
Human T-cell leukemia virus type one
Associated with Japan the west Indies and the Pacific Islands
-TAX gene Initiates polyclonal T cell proliferation and NFKB (survival)
-
MAWW
Cachexia syndrome Malaise Anorexia Wasting Weakness