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The State Education Institution of Higher Professional Training
The First Sechenov Moscow State Medical University
under Ministry of Health of the Russian Federation
Department of Pathophysiology
Disorders of tissue growth.
Tumors.
Lecture presentation
Professor Pirozhkov S.V.
2014-2015 education year
TYPICAL FORMS OF DISORDERS OF
TISSUE GROWTH
● Pathologic hypertrophy
● Pathologic hypotrophy
● Pathologic hyperplasia
● Pathologic hypoplasia
● Pathologic metaplasia
● Pathologic regeneration
● Sclerosis, fibrosis
● Dysplasia
● Tumors
DIFFERENCES BETWEEN BENIGN AND MALIGNANT
TUMORS
Benign
Malignant
■ typically well differentiated
► typically poorly
differentiated
■ grow slowly
► grow rapidly
■ grow as cohesive
expansile masses
► infiltrate the
surrounding tissue
■ typically form a fibrous
capsule
► do not form a
capsule
■ compress the surrounding
tissue
► invade and destruct
the surrounding tissue
■ do not or rarely
metastasize
► typically metastasize
■ rarely recidivate
► recidivation is typical
■ do not cause cachexia
► cause cachexia
THE PRINCIPAL TARGETS OF GENETIC
DAMAGE DURING NEOPLASTIC
TRANSFORMATION OF A CELL
► the growth-promoting
protooncogenes
► the growth-inhibiting cancersuppressor genes (antioncogenes)
► genes that regulate programmed cell
death (apoptosis)
► genes that regulate repair of
damaged DNA
Pathways of transformation of
normal cell into neoplastic
involving protooncogenes:
► Transformation of normal
protooncogene to oncogene
► Overexpression of protooncogene
► Formation of chimeric oncogene
Mechanisms of neoplastic transformation
associated with inactivation of
antioncogenes, genes regulating apoptosis,
or DNA repair genes:
● Deletion of gene (e.g., Rb)
● Point mutation of gene (e.g. p53)
THREE MAIN CONCEPTS OF
CARCINOGENESIS
► Chemical carcinogenesis
► Viral carcinogenesis
► Radiation carcinogenesis
CHEMICALS INITIATING CARCINIGENESIS
1. Direct-acting compounds (do not require
chemical transformation for their
carcinogenicity)
● alkylating and acylating agents
(e.g., alkylating anticancer drugs –
cyclophasphamide, nitrosoureas;
acetylating - 1-acetyl-imidazole etc.)
2. Indirect-acting compounds, or
procarcinogens (require metabolic
conversion in vivo to produce ultimate
carcinogens)
Two stages of chemical
carcinogenesis:
► Initiation
► Promotion
Radiation carcinogenesis
1. Ultraviolet rays
UVA – 320-400 nm
UVB – 280-320 nm
UVC - 200-280 nm
cutaneous cancer
filtered by the ozone shield
2. Ionizing radiation
electromagnetic – X-rays, γ-rays
particulate - α-particles, β-particles, protons,
neutrons
TUMOR PROGRESSION: generation of heterogeneity and selection of clones
Normal cell
Transformation events
Tumor cell
Tumor cell
variants
Death
Clonal expansion
of surviving cell
variants
Nonantigenic
Invasive
Metastatic
Human solid
malignancy
Requiring fewer
growth factors
ANTINEOPLASTIC MECHANISMS
1.
Anticarcinogenic (neutralization of carcinogen)
●
●
●
●
2.
metabolism by cytochrome P-450
conjugation with glutathione
scavenging of the active free radicals by antioxidants
recognition and elimination of oncogenic viruses
Antitransformational (refers to DNA repair)
● activity of the mismatch repair genes
● activity of the nucleotide excision repair system
3.
Anticellular (elimination of the transformed cell)
●
●
●
●
●
cytotoxic T-lymphocytes
antibodies
NK-cells
activated macrophages
humoral mechanisms (activation of complement,
antibody-dependent cellular cytotoxicity)