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Fas
Fas-ligand (pro-apoptotic extrinsic factor) binds Fas receptor/ TNF-1 receptor (CD95)
- -> activates FADD (death domain)
- -> cytosolic caspases activated
- -> cellular breakdown
Granzyme
Extrinsic apoptic factor from Killer T cells
- Release granzyme B and perforin
- -> hole in membrane
Bax
pro-apoptotic factor–> increased mitochondrial permeability
- -> cytochrome C released
- -> mitochondrial Ca+2 released
- -> cytosolic caspases released
- -> cellular breakdown
** in balance of Bcl-2= anti-apoptotic factor (mutations promoting Bcl-2–> cancer)
E-selectin/P-selectin
Rolling neutrophils bind to E/P selectin on vasculature/stroma via Sialyl-Lewis(x) group)
- Sialyl Lewis group missing in Leukocyte Adhesion Deficiency Type II
ICAM-1
Intracellular adhesion molecule-1
Leukocyte binds LFA-1 (integrin) on its surface to ICAM-1 (tight binding) on blood vessel wall
PECAM-1
Platelet endothelial cell adhesion molecule
Diapedesis: leukocyte binds PECAM-1 and migrates between endothelial cells–> exits into interstitium
C5a, IL-8, LTB4, Kallikreain
Bacterial products that attract leukocyte (chemotactic signals)–> phagocytosis of bacteria
Granulomatous disease
Th1 cells secrete gamma-IFN–> macrophage activation
Macrophages secrete TNF-alpha= induces and maintains granuloma
Decreased ESR
Sickle cell (altered shape)
Polycythemia (too many RBCs)
CHF (unknown)
AL amyloidosis
Primary amyloidosis
IgLight chains
- Due to plasma cell disorder, multiple myeloma
- -> multi organ system impact (renal, cardiac, hematologic, hepatic, neuropathy)
AA amyloidosis
Secondary to chronic disease: RA, IBD, spondyloarthropathy, chronic infections
- Fibrils= serum Amyloid A (AA)
- Multisystem
beta-2 microglobulin fibrils
Seen in dialysis-related amyloidosis
–> carpal tunnel syndrome, joint issues
ATTR amyloidosis
Heritable
- Neurologic/cardiac amyloidosis d/t transthyretic (TTR or prealbumin) gene mutation
Anaplasia
Abnormal cells lacking differentiation: ressemble primitive cells of same tissue
- Little or no resemblance to tissue of origin
Irreversible change (like neoplasia)
Desmoplasia
Fibrous tissue formation in response to neoplasm
Irreversible change (like neoplasia)
Tumor stage
TNM:
Tumor size (perforate out of capsule?)
Node involvement
Metastases (perforate vessels, lymph? important prognostic factor)
** Staging has more prognostic value than grade
Cachexia
Mediated by TNF-alpha (cachectin), IFN-gamma, IL-6
- Macrophages–> TNF-alpha, IL-6 (pyrogenic)
Weight loss, atrophy, fatique d/t chronic disease
Tuberous sclerosis
Facial angiofibroma, seizures, mental retardation
Associated neoplasms:
- Giant cell astrocytoma
- Renal angiomylolipoma
- Cardiac rhabdomyoma
Plummer-Vinson syndrome
Esophageal webs, dysphagia, iron-deficiency anemia
Associated neoplasm: squamous cell carcinoma of esophagus
abl
Oncogene encoding Tyrosine kinase
- Associated with CML (t(9;22)–> bcr-abl fusion protein)
c-myc
Transcription factor oncogene
- Associated with Burkitt’s lymphoma= t(8;14)–> CD10, BCL-6
HER2/neu (c-erbB2)
Tyrosine kinase
- Associated with breast, ovarian, gastric carcinomas
ras
GTPase: GTP bound–> activated–> MAPKinase system–> nucleus
- Colon carcinoma
ret
Tyrosine kinase
- MEN 2A, 2B
c-kit
Cytokine receptor
- Gastrointestinal stromal tumor (GIST)
p16
Tumor suppressor gene
- LOF seen in melanoma, along with BRAF
Rb
Chromosome 13: RB1
Inhibits E2F (transcription factor)
Blocks G1–> S phase
- Associated with Retinoblastoma, osteosarcoma
2 hit hypothesis: lose heterogeneity (after already having one defective gene)
p53
Transcription factor for p21
Blocks G1–> S phase
Seen in most human cancers, Li-Fraumeni syndrome
CEA
CarcinoEmbryonic Antigen
- Seen in colorectal, pancreatic cancer
- Also gastric, breast, medullary thyroid cancer
CA-125
Ovarian cancer marker
S-100
Neural-crest derived tumors:
- Melanoma, neural tumor, schwannomas
Alkaline Phosphatase
Elevated in Bone, liver mets
Seen in Paget’s disease of bone
Bombesin
Marker of neuroblastoma, lung, gastric cancer
CA-19-9
Pancreatic adenocarcinoma marker
Vinyl chloride
Exposure related to angiosarcoma of liver
Arsenic
SCC of skin
Angiosarcoma of liver
Iron poisoning
Peroxidation of membrane lipids
- Acute= gastric bleeding
- Chronic= metabolic acidosis, scarring–> GI obstruction
N-myc
Transcription factor
- See in neuoroblastoma
WT1
Wilm’s tumor
- Chromosome 11
NF1
Neurofibromatosis 1
- NF-1 gene codes for neurofibromin= suppressor of Ras
- RAS GTPase activation protein (RAS-GAP)
- Chrom 17
NF2
Neurofibromatosis 2
- Merlin (schwannomin protein)
- Chrom 22
