Firstranker's choice NEOPLASIA
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Tumorigenesis
Benign
HPV
Malignant
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Cancer
6 16
18
11
Characteristic-
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1) Rate of growth - Monoclonal
Hamartoma - Benign tumor
Choriostoma - non-neoplastic
-clonal inactivation
Polyclonal
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[abnormal tissue in
ectopic Rests of
anatomical site]
normal tissue.
2] Metastasis - Sure Sign of malignancy
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exception
BCC
Glioma
Metastasis
Pheochromocytoma Promotes
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Carcinoma
pituitary...
Adenoma
Routes.
Parathyroid
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Lymphatic
Hematogenous
epithelial tumors...
Sarcoma
*Alveolar Rhabdomyosarcoma Osteogenic Sarcoma
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except-
RCC>HCC
Rhabdomyosarcoma Pleoma
Angioinvasive
*Synovial Sarcoma
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Alveolar
FirstRanker.com Tumor Progression Severity of tumor
Metaplasia
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Dysplasia
Reversible
Partially
Completely
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Reversible.
Irreversible
Nuclear/ Ratio N/C Ratio- altered. N/C Ratio 1
cytoplasmic
cell polarity-
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Lost-cell
Anaplasia
Complete Loss
(rearrangement)
polarity
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of differentiation
over BINT)
Ca-insitu-
-Hallmark of
malignancy
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N/C = 1/4 to 6 times
Basement membrane
mets << Anaplasia
Intact
Hallmark features of Cancer cells (*)
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1) Proto-oncogene mutations Oncogene
1) Self Sufficiency [donot-require growth factor].
2) Resistant to growth inhibitory Signals (Tumor Suppressors)
3) Invasion from apoptosis [Tec/2 antiapoptic expression]
4) Limitless Replicative potential (Telomerase)
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5) Angiogenesis (m/c Cause - Hypoxia) - HIF I gene VEGF,
without angiogenesis limit of growth 1-2mm
BFGF
disorganized B.V
6) Metastasis-m/essential factor Angiogenesis
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Balance Metastatic gene Anti-metastatic gene
b/w
E-zoin (RNTS)
1) NM-123.
(first to discover)
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mir-lob
2) mir-226, 335
3) KAI-1-prostate Ca
Snail, Twist Breast Calloburation 4) Kiss - melanoma
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EMT - Epithelial mesenchymal Transition
-also associated with wound Healing & Repair.
organfibrosis...
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e-cadherin [B/wnormal/tumor cells]
epithelial downregulation (e-cadherin)
Tumor cells
1) Detachment.
Proteases
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2) Degradation of ECM. By.
- i) plasmin
mmp
MTMP
mmpa Better.
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Detachment
Breaker &
Degradation
attachment
3) Attachment with ECM synthesize BV
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Integrin + Synthesis of ECM
protein
mesenchymal upregulation
[Collagen, Laminin, Vitronectin, Fibronectin]
4) Tumor emboli. in BV mostly associated.
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T cell + platelet
5) Organ
FirstRanker.com System
Firstranker's choice
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Antitumor cells
CDs, NK cells, N
1) Ag -ve Tumor cells
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i) glycocalyx coating,
ii) Ca cell express FAS/FASL sundugo
apoptosis
iii) Ca-metabolism - Aerobic glycolysis (warburg effect)
Warburg 1921, Basis of PET Scan
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Nobel price - 1931
Gene Repair Defect- Chromosomal instability Syndrome.
Big) - Bloom Syndrome
Homologous DNA
Fanconi
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defect disorden.
A Ataxia Telangiectasia
AR
X - Xeroderma pigmentosa (nucleotide excision Repair
Defect)
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Lynch Syndrome AD.
ov light
Skin
Pyrimidine Repaired accumulated in Xp
Dimeus
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by excision
Skinla
Firstranker's choice - DNA mismatch Repair gene defect
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(Spell checker)
Stomach
microsatellite Instability
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Colon.
Chromothripsis - Dramatic Chromosomal
Catastrophy
Random damage of chromosome
- activation of oncogenes
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- inhibition of tumor Suppressor
eg: Osteosarcoma, Glioma.
Proto-oncogenes: Helps in normal proliferation & differentiation
1) growth factor...
2) GF-R
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Signal Transduction protein
Nuclear Transcription
Cyclin & Cyclin Dependent kinase
Cell Cycle Go G1 S G2 M
Any Proto-oncogene-oncogene-affect Cell cycle
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Tumorigenesis
Firstranker's choice
i) PDGF
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ii) FGF
iii) HGF
iv) TGIF-2 (TGIF-B-tumor suppressor gene)
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2) Growth factor Receptor group
i) ERBB-1: Adenocarcinoma of lung
ii) ERBB-2 [Her-2/neu] - Breast Ca
iii) RET-Proto-oncogene - medullary Ca of thyroid
iv) C-KIT/- GIST, melanoma, Seminoma, myeloid Cancers
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CD-117
3) Signal Transduction Protein-
a) RAS - m/c oncogene mutation in Human Cancer
P53>50% Human Ca 53%
RAS-20-30%
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P53>RAS
Ca. Pancreas - m/c mutation. KRAS(60-70%) << p-16 (95%)
m/concogene mutation - KRAS.
4) ABL
BCR-ABL
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CML
ALL
(good)
(poor)
>60/ Skin Ca BRAF
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5) BRAF -> 60% Skin Ca (melanoma)
>90% Human Ca BRAF
Firstranker's choice
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Langerhan Cell Histiocytosis (monoclonal)
4) JAK-2 - Polycythemia vera
NOTCH - T cell leukemia
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4) Nuclear Transcription Factor-
Myc; Fos; Jun
n-myc amplification
neuroblastoma (Bad)
medulloblastoma
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C-myc - Burkitt's lymphoma
Translocation
5) Cyclin & Cyclin Dependent kinase-
Cyclin
D1
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D2 (Bcl-2)
Bcl-1
mantle cell lymphoma.
follicular
lymphoma
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CDK4 mutation
fibroblastoma
melanoma
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Firstranker's choice
Cyclin
A
B
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+
+
+
+
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CDK
4
2
2
1
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[OFF] Rb + EF-2 (inactive) [EF-elongation factor
D+4 02 phosphorylation
ATP
Rb allows
Rb
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EF
G1 S
molecular-ON-OFF
Switch
Governor of cell Rb
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Removal elongation factor. Progression of cell cycle
Cyc D +4
Cyc E +2
A+2
B+1
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G0 G1 S G2 M
mid Go phase-Cyclin - Synthesis
Check point- G1 S
G2M
error before DNA
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after DNA
replication
replication occurs.
Cyclin A << Cyclin B
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Firstranker's choice Cell cycle inhibitors
P16 INK 49
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Cip kip family
(cap-way)
-Specific inhibitors
Cyclin D + K4
- Non specific inhibitor
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K6
P21, P27, P57
P4
P6
P53 induce P21
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P18
indirect
G1-S >> G2-M
P19
cell cycle
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inhibitor
Tumor Suppressor Gene
BRCA-1: ch-17.
BRCA-2 ch-13
male Breast Ca (BRCA 2 BRCA1
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Ovarian tumor
BRCA-Imedullary Breast Ca
Triple negative [ER-ve, PR-ve, Her-ve].
BRCA-2= ER+, PR +ve Her-2-ve
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Firstranker's choice molecular weight - 53 kDalton
Ch-
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Li- Fraumeni Syndrome multiple ca.
guardian of genome
molecular policeman
Tissue injury P53
GADD-45
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Induce P21.
BAX/BAK
(growth courest DNA
Inhibit cell cycle at G1 S > G2M.
Puma
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damage)
Apoptosis
DNA Repair
P53
Silencing
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MIRNA
Linc-RNA
(mi-329/c]
-ve
-ve
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Cell cycle
Antiapoptic gene. BCL-2
arrest (romitasis)
Carcinogenesis
1) Chemical Carcinogenesis- Benzopyrene
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Tissue damage
Somatic
mutation.
P53
DNA Repair
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Liver.
nucleophitic.
C-P-450
Carbonium ion
Benzopyrene
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Epoxide
FirstRanker.com checked by - AMES assay
Leaginec
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Salmonella typhimurium
Chemical + (normal Histidine negative)
Histidine +ve
Histidine -ve
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Que-tomulation
non mutagenic
Inference mutagenic
chemical
chemical
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Radiation Carcinogenesis
Ionising
Non Ionising
UV
2. 3, x. Ray.
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Pyrimidine dimes
m/c
Skin Ca.
Blood Ca papillary Ca
of thyroid
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intermittent Sunlight exposure
Blood Ca-ANTL
melanoma
ALL.
CTL
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CLL is not associated with
radiation
Firstranker's choice
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Microbe ist established th pylori gastric adeno Ca NHL
m/c NHC lymphoma of stomach - DLBL > malforma
NTALT -m/c site ileum (Peyer's pather)
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NTALToma-m/c site - stomach
HPV
-6,11-Papilloma
16,18-Carcinoma
E6 inactivate P53
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E7 inactivate Rogene
HPV
episomal
Integrated
Precancuous lesion
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Carcinogenic
Benign papilloma
no Risk-in non. endemic
HPV Risk for esophageal Scc-only in endemic regions
Sofidendysis Bullosa - Risk of esophageal Scc
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Vit-A. Zn, Se-pastedive
HBV
HCV 21-30yes
HCC
DNA.
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HBV > HCV
Nuclear
damage
layaw.
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Firstranker's choice can alter.cause HCC directly even without
undergoing Cirrhosis
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But HCV-donot cause direct HCC
HBV
HCV
Cirrhosis
No direct
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Causation.
Carrier-HBC
HCC
Cirrhosis HCV
Transfusion Hepatitis HBV > HCV
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EBV
HL
NHL
Nasopharyngeal Ca[m/c aw EBV]
m/c malignancy with EBV - Gastric adeno Ca
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Tumor diagnosis approach-
1) Tumor markers - Never confirm diagnosis
Moes-prognosis,
Response to R
may correlate to size of tumor.
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egf- L-HCG-notamaku.
FSH/LH/TSH
B-HCG Chorio Carcinoma.
FirstRanker.com Hepatoblastoma (790)
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Firstranker's choice
variant
Fibro lamellar variant-N-AFP, Neurtension marker
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2-pp- Non Seminomatous; max elevation yolk Sac tumorfended
Seminomatous - LDH, PLAP 15./-ause from Syncytiabudhat
15.1-B-HCG
Yolk Sac tumor - AFP, 2-1 antiTaufprin.
CD 30+ve, C-KIT-Ve: embryonal Ca
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Melanoma - m/Sensitive - S-100; m/Specific HNTB-45
Vimentin
milf-1 (micro-fhithalmia Transition factor-)
Choroidal melanoma
Cytokeratin - for epithelial cancer
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Ca15 Breast Ca
Ca19.9 pancreas, Colon'!! - ustained startforum!
Ca1215 - Ovarian tumor (not used for Screening)
Sonly for prognosis.
FNAC : Size: 226-2761
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1) Patient's consent
2) Bleeding Diathesis
3) H/o anaphylaxis
4) Testicular malignancy
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Firstranker's choice
7 NAC can be done
Tosule out infertility
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Follicular adenoma vs Follicular Carcinoma - 7 NAC
Confirm - only by tissue Biobay
not useful
Immunophenotyping Study of Dmasters
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Flow cytometry-ideal for lymphocytasis
simultaneous provide immunophenoty
IOC CLL, ANTL.
Flow cytometer
Cell density
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Side Scatter vacuoles,
granularity, membrane
Size
Light
Forward Scatter.
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-cell size.
Immunohistochemistry -IHC
Artificial (doured Ab
Tumor Ag-complex under
microscope.
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Basis - Intermediate filament
1) Cytokeratin (epithelial tumors)
Carcinoma (any Carcinoma
2) Vimentin - Connective tissue
melanoma, Seminoma
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This download link is referred from the post: Medical PG Handwritten Notes 1st Year, 2nd Year, 3rd Year and 4th Year (Study Material)
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