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Neoplasia, tumor suppressor gene, oncogenes, carcinogen(発癌物質), tumor…
Neoplasia
tumor suppressor gene
loss of function→↑cancer risk
both allele
NF2; merlin protein: neurofibromatosis type 2
WT1; transcription factor: Wilms tumor
TSC1: tuberous sclerosis
APC: colorectal cancer
DCC: colon cancer
MEN1; menin: MEN1
Rb; inhibit E2F(block G₁→S phage): retinoblastoma, osteosarcoma
VHL: von Hippel-Lindau disease
BRCA1/BRCA2; DNA repair protein: breast, ovarian, pancreatic cancer
PTEN: breast, prostate, endometrial cancer
NF1; neurofibromin: neurofibromatosis type 1
SMAD4: pancreatic cancer
TP53; p53, activate p21, block G₁→S phase: most human cancer
TSC2: tuberous sclerosis
CDKN2A: melanoma, pancreatic cancer
oncogenes
gain of function mutation converts proto-oncogene to oncogene→↑cancer risk
HER2; receptor thyrosine kinase: breast and gastric carcinoma
RET; receptor thyrosine kinase: MEN2A,2B, papillary thyroid carcinoma
MYCL1; transciption factor: lung tumor
ALK; receptor tyrosine kinase: lung adenocarcinoma
BCL-2; antiapoptotic molecule: large B cell lymphoma
c-KIT; cytokine receptor: GIST
KRAS: GTPase: colon cancer, lung cancer, pancreatic cancer
BCR-ABL;tyrosine kinase: CML,ALL
N-myc; transcription factor: neuroblastoma
c-MYC; transcription factor: Burkitt lymphoma
JAK2; tyrosine kinase: chronic myeloproliferative disorder
BRAF: serine/threonine kinase: melanoma, non-Hodgkin lymphoma, papillary thyroid carcinoma
one allele
carcinogen(発癌物質)
cigarette smoke: bladder, cervix, esophagus, kidney, larynx, lung, pancreas
vinyl chloride: liver
nitrosamines: stomach
aflatoxins(aspergillus): liver
aromatic amines: bladder
arsenic: liver, lung, skin
ionizing radiation: thyroid
alkylating agents: blood
radon: lung
asbestos: lung
ethanol: esophagus, liver
tumor marker
CA125: ovarian cancer
PSA: prostate cancer
chromogranin: neuroendocrine tumor
alkaline phosphatase: metastasis to bone and liver, paget disease of bone, seminoma
β-hCG: hydatidiform moles(胞状奇胎), choriocarcinoma, testicular cancer, mixed germ cell carcinoma
CEA: major; colorectal carcinoma, pancreatic cancer; minor; gastric, breast, medullary thyroid carcinoma
CA15-3/CA27-29: breast cancer
α-fetoprotein: hepatocellular carcinoma, endodermal sinus(卵黄嚢) tumor, mixed germ cell tumor, ataxia-telangiectasia(毛細血管拡張性運動失調症), neural tube defect
LDH: testicular germ cell tumor, ovarian dysgerminoma, other cancer
calcitonin: medullary thyroid carcinoma
CA19-9: pancreatic adenocarcinoma
immunohistochemical stain
GFAP: neuroglia
chromogranin and synaptophysin: neuroendocrine cell
PSA: prostatic epithelium
vimentin: mesenchymal tissue
desmin: muscle
neurofilament: neurons
cytokeratin: epithelial cell
S-100: neural crest cell (melanoma, schwannoma, Langerhans cell histiocytosis)
TRAP: tartrate-resistant acid phosphatase (hairy cell leukemia)
oncogenic microbes
H.pylori: gastric carcinoma, MALT lymphoma
schistosoma haematobium(住血吸虫症): bladder cancer
Liver fluke(肝吸虫): cholangiocarcinoma(胆管がん)
EBV: Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, 1°CNS lymphoma
HHV-8: Kaposi sarcoma
HPV: cervical, anal, penile carcinoma (type16,18), head and neck cancer
HTLV-1: adult T-cell leukemia/lymphoma
HBV,HCV: hepatocellular carcinoma
neoplasia
progression
carcinoma in situ/ preinvasive: irreversible dysplasia, not penetrate basement membrane
invasive carcinoma: using collagenase and hydrolase, cell-cell contact lost by inactivation of E-cadherin
dysplasia
metastasis: seed(tumor embolus) and soil(first encountered capillary bed)
normal cell
nomenclature(命名法)
benign: well differentiated, well demarcated, low mitotic activity, no metastasis, no necrosis
malignant: poor differentiated, erratic growth, local invasion, metastasis, ↓apotosis
carcinoma: epithelial origin
sarcoma: mesenchymal origin
non-neoplastic
choristoma(絨毛腫)
hamartoma(過誤腫)
grade, stage
grade: degree of celluler differentiation and mitotic activity on histology (more prognostic value)
stage: degree of localization/spread based on site and size of 1° lesion (T; tumor size and invasiveness, N; node involvement, M; metastases
anaplasia: complete lack of differentiation of cell
uncontrolled, clonal proliferation of cell
evasion of apotosis, growth signal self-insufficiency, anti-growth signal insensitivity, Warburg effect(好気的、嫌気的両方の環境で解糖によるATP↑↑), angiogenesis, limitless replicative potential, tissue invasion, metastasis
metastasis
bone
prostate, brast>kidney, thyroid, lung
metastasis>>1°
predilection for axial skeleton
brain
lung>breast>melanoma, colon, kidney
50% are metastasis, multiple well circumscribed tumors
liver
colon>>stomach>>pancreas
lymph
in general, sarcoma=hematogenously, carcinoma=lymphatics
hematogenously: follicular thyroid carcinoma, choriocarcinoma, renal cell carcinoma, hepatocellular carcinoma
paraneoplastic syndrome
neuromuscular
paraneoplastic cerebellar degeneration
paraneoplastic encephalomyelitis
opsoclonus-myoclonus ataxia syndrome
Lambert-Eaton myasthenic syndrome
anti-NMDA receptor encephalitis
myasthenia gravis
hematologic
good syndrome
Trousseau syndrome
pure red cell aplasia(赤芽球癆)
nonbacterial thrombotic endocarditis
polycythemia
endocrine
cushing syndrome: ↑ACTH: small cell lung cancer
hyponatremia: ↑ADH; small cell lung cancer
hypercalcemia: PTHrP
musculoskeletal and cutaneous
acanthosis nigricans(黒色表皮腫):gastric adenocarcinoma, etc
sign of leser-trelat: multiple seborrheric(脂漏性) keratoses: GI adenocarcinoma
dermatomyositis: proximal muscle weakness, Gottron papules, heliotrope rash: adenocarcinoma
hypertrophic osteoarthropathy: abnormal proliferation of skin and bone at distal extrimities: adenocarcinoma of lung
P-glycoprotein
multidrug resistance protein 1
pump out toxins
classically seen in adrenocortical carcinoma
psammoma body(砂粒体)
laminated(薄片化した)、concentric spherules(同心円状の小球) with distrophic calcification
seen in: papillary thyroid carcinoma, serous papillary cystadenocarcinoma of ovary, meningioma, malignant mesothelioma(悪性中皮腫)
cachexia(悪液質)
weight loss, muscle atrophy, fatigue
mediated by TNF, IFN-γ, IL-1, IL-6