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Cancer Biology 1

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19 views27 pages

Cancer Biology 1

.

Uploaded by

sbijlani
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Neoplasia

•“New growth”
•Cancer, malignancy
•Genetic disorder
•Cell cycle normally tightly controlled
•Signals →growth/cell divisions
•Signals →prevention of growth/cell
division
•Mutations →uncontrolled growth
Clonality
• Single cell develops mutation
• Gives rise to daughter cells (clones)
• All clones carry same mutation
Tumor Locations
•Rapidly dividing cells
•Stop/start for cell division
•Lots of DNA replication
•Many chances for mutation
•Increased likelihood of cancer
•GI epithelium: common site of cancer
•Myocardium: very rare sight of cancer
Tumor Progression
•Change in tumor over time
•Become more aggressive
•Accumulate more mutations
•Less responsive to chemotherapy
•Large tumors often heterogenous
Warburg Effect

• Glucose metabolized to lactate for ATP


• “Aerobic glycolysis”
• Less ATP than oxidative phosphorylation
• Occurs even in presence of oxygen
• Result: High glucose uptake
• Basis for PET scanning
• Radiolabeled glucose scan
PET Scan
Dysplasia

• Description of tissue morphology


• Disordered but non-neoplastic growth
• Precedes neoplasia
• Progresses to cancer
• Described in epithelial tissues
• Carcinoma in situ
• Dysplasia of entire epithelial layer
• No invasion of basement membrane (contained)
Anaplasia

• Undifferentiated cell growth


• Cells do not look like cells of origin
• Metabolic activity to growth
• Little/no other functions
• Seen in malignant, aggressive tumors
• Usually poor prognosis
• Well-differentiated tumors: resemble tissue or origin
• Anaplastic tumors: lack of distinguishing features
Cancer Progression
Hallmarks of Malignant Cells
• Autonomous growth
• Not sensitive to growth factors/inhibitors
• Evasion of cell death
• Do not undergo apoptosis
• Evade the immune system
• Unlimited ability to replicate (“immortal”)
• Normal cells become “senescent” after XX replications
• Angiogenesis
• New blood vessels to fuel growth
• Ability to invade tissues and spread
Telomerase
•Normal cells capable of 60-70 divisions only
•Thereafter become senescent
•Caused by shortening of telomeres
•Telomeres: nucleotides at end of chromosomes
•Telomerase: avoids loss of genes with duplication
•Active in stem cells
•Little activity in other cells
•Telomerase upregulation in almost all cancers
Grade
•Degree of differentiation
•Determined by pathologist
•Requires biopsyfor microscopic tissue analysis
•Grades I, II, III, IV
•Well-differentiated: low grade
•Anaplastic/undifferentiated: high grade
Stage

• Degree of tumor extension/spread


• Local, lymph nodes, metastasis
• Usually done by radiology/imaging
• Early stage: localized growth
• Advanced stage: spread, metastasis
TNM Staging System
• T: primary tumor size
• T1, T2, T3, T4
• N: degree of regional lymph node spread
• N0, N1, N2, N3
• M: metastases
• M0=no mets; M1 = mets
Nomenclature
• Benign
• Likely to remain localized without spread
• Amenable to surgical removal
• May still cause problems (e.g., compression)
• Well-differentiated
• Low mitotic activity
• Malignant
• Invades and spreads
• May cause death
Non-neoplastic Growths

• Hamartoma
• Mass of mature but disorganized cells
• Example: lung hamartoma contains disorganized lung tissue
• Developmental anomalies
• Choristoma
• Mature, well-differentiated tissue in the wrong place
• Example: Meckel’s diverticulum (gastric tissue in ileum)
• Both are benign (i.e., do not invade/metastasize)
Tumor Naming.
Benign Tumors

• Naming: cell/tissue type of origin plus –oma


• Fibroma: benign fibrous tumor
• Chondroma: benign cartilage tumor
• Adenoma
• Benign epithelial tumors
• Often forming gland structures
• Papilloma
• Benign epithelial tumors on surfaces with “finger-like” projections
Tumor Naming
Malignant Tumors

• Mesenchymal tissues
• Connective tissue, bones, blood, lymph
• Solid tumor: sarcoma (e.g., osteosarcoma)
• Blood/lymph: leukemia or lymphoma
• Epithelial cells: carcinoma
• Glandular tumors: adenocarcinoma
• Colon adenocarcinoma, lung adenocarcinoma
• Skin: squamous cell carcinoma
Tumor Spread
• Sarcoma: spread via blood (hematogenous)
• Arteries (thick walls) difficult to penetrate
• Veins (thin walls): easily penetrated
• Liver and lungs most common sites of hematogenous spread
• Carcinoma: usually spread via lymphatics
• Key exceptions:
• Four carcinomas spread via bloodstream
• Choriocarcinoma (“Early hematogenous spread”)
• Renal cell carcinoma (renal vein)
• Hepatocellular carcinoma (portal vein)
• Follicular thyroid carcinoma
Teratoma
• Cells from multiple germ layers
• Ectoderm (skin, hair follicles)
• Endoderm (lung, GI)
• Mesoderm (muscle, cartilage)
• Arise from germ cells in ovaries and testes
• Cells of origin capable of forming multiple germ layers
Epidemiology
• Cancer is 2ndleading cause of death
• Heart disease #1
• Respiratory disease #3 (e.g., COPD)
• Accidents/trauma #4•New cases (incidence)
• Breast/prostate →lung →colorectal
• Mortality (death rate)•Lung →breast/prostate →colorectal
• Lung cancer mortality declining in men
• But not in women
Epidemiology
Children
• Causes of death
• Accidents →cancer →congenital disorders
• Incidence/mortality
• Leukemia →CNS tumors →neuroblastoma
Carcinogenesis
• Nonlethal DNA damage →cancer
• Mutations in two types of genes lead to cancer
• Tumor suppressor genes
• Oncogenes
Tumor Suppressor Genes

• Limit cell growth


• Classic examples:
• P53 gene: blocks progression through cell cycle
• Retinoblastoma gene: inhibits transcription factors
• Need mutations in both alleles to shut down activity
Germline Mutations

• One gene mutated in all cells at birth


• Occurs in some tumor suppressor genes
• Leads to increased cancer risk at early age
• BRCA1/BRCA2 (breast cancer)
• Hereditary retinoblastoma
• HNPCC (Lynch syndrome)
• Familial Adenomatous Polyposis (FAP)
• Li-Fraumeni syndrome
Oncogenes
• Promote uncontrolled cell growth
• Proto-oncogenes: normal cellular genes
• Growth factors, growth factor receptors, signal transducers
• Proto-oncogene mutation →oncogene →cancer
• Single gene mutation →malignancy
Carcinogens
• Substances that cause cancer
• Chemicals
• Asbestos →mesothelioma
• Viruses
• HPV →cervical cancer
• Radiation
• Sunlight →skin cancer

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