APOPTOSIS

BCl protein family

- present in the cytosol in soluble inactive form (they need to be activated)
- regulated the intrinsic pathway
Constitutive Gene
- housekeeping genes, always expressend
Inducible Gene
- only expressed when certain factors are present
Tbid crosstalk between extrinsic and intrinsic pathway
Autophagy
Neoplasm and Cancer (Anatomy, Physiology and Genetic Basis)
Neoplasia new growth of tumor
Neurofibromatosis benign tumor
Oncology study of tumors or neoplasms
Cancer common term for malignant neoplasm
Neoplasm
Abnormal mass of tissue, the growth of which exceeds and in an
uncoordinated manner with that of a normal tissue emanating from one
cell
It persists in the same manner after the cessation of stimuli and causes a
lump or tumor
All tumors, benign or malignant have:
Proliferating neoplastic cells that constitute their parenchyma
Supporting stroma made up of tissue of connective tissues and blood
vessels (neovascularization or angiogenesis)
Benign Tumors
In general, benign tumors are designated by attaching the suffix -oma to
the cell origin
Tumors of mesenchymal cells generally follow this rule
Benign Epithelial Tumors
Nomenclature is more complex. They are classified based on:
1. Their cell of origin
2. On their microscopic architecture
3. Macroscopic pattern
Colonic Polyp
1. Benign glandular tumor (adenoma)
2. Projecting intro the colonic lumen
3. Attached to the mucosa by a distinct stalk
4. Can be classified into villous, tubular, tubulovillous and sessile adenoma
Malignant Mesenchymal Tumors
Malignant tumors arising in mesenchymal tissues are usually called
sarcomas
They have little connective tissue stroma and are fleshy or soft (e.g.,
fibrosarcoma, leimyosarcoma, rhabdomyosarcoma)
Malignant Epithelial Tumors
Malignant neoplasms of epithelial cells origin derived from three germ
layers

Malignant Mixed Tumor

Tumors of salivary glands
Teratoma
The great majority of malignant neoplasms, even mixed tumors, are
composed of cells representative of a single germ layer
Made up of variety of parenchymal cell types, representing one or more
germ layers
Choristoma
Benign, ectopic (located in an organs where it should not be present) crest
of normal tissue (should not be mistaked as a cancer transformation)
Hamartoma
Aberrant differentiation of cell producing a mass of disorganized but
mature specialized cells or tissues indigenous to a particular site
Cellular Anatomy
Anaplasia
Lack of cellular differentiation
Hallmark of malignant transformation
Pleiomorphism
o loss of normal size and shape of cell
o Abnormal cell size and shape
o Abnormal nuclear morphology
Hyperchromaticity (blue- acidic)
Increase nucleus:cytoplasm ratio (normal is 1:4)
Aneuploidy (increase in the number of chromosomes)
Increase of nucleoli
Atypical and bizarre mitotic figures
Loss of normal cell polarity
Presence of tumor giant cells
Local Invasion
Benign
Cohesive expansile mass
Encapsulated
Easily removes since they are encapsulated
Malignant
Infiltrative
Destruction of surrounding tissue
Metastasis
Most reliable feature which differentiates benign from malignant cancers
All cancers metastasize
Except:
1. Glioma
2. Basal Cell Carcinoma
Metastasis Pathways
Seeding of body cavities and surfaces
Lymphatic spread
Pattern of lymph node involvement and routes of lymphatic drainage
More common among carcinomas
Hematogenous spread

Bone, liver, brain, lungs

More common among sarcomas

Comparison of Benign and Malignant Cancers

Benign
Well differentiated
Slowly progressive
Cohesive and expansile
No metastasis
Malignant
Lack of differentiation with anaplasia
Erratic
Always metastatic
Physiological Changes
Increase rate of growth and metabolism
Doubling time of the tumor
Fractions of the tumor within the replicative pool
Rate at which cells are shed and lost in the growing tumor
Hallmarks of Cancer
Evading apoptosis
Self-sufficient in growth signals
Insensitivity to growth signals
Metastatic
Metastasis Initiation by Epithelial-Mesenchymal Transition
Cells acquire mobility to it can infiltrate other tissues
Angiogenesis
Loss of contact inhibition
Biochemical Features of Cancer
Increased uptake of glucose
Most of the glucose avidly taken in by cancer cells are used for increases
in glycolysis to produce lactate and increase the biosynthesis of
macromolecules needed for cancer cell growth and division
Less production of ATP through oxidative phosphorylation
Devotes more molecules for anabolic pathways for macromolecules for cell
division
The turnover of building blocks for biosynthesis is higher than degradation
of macromolecules
Anaerobic glycolysis
In human host with cancer
Cachexia or body wasting of patients with cancer
Increase glycogenolysis and gluconeogenesis
Increase lipolysis
Increase proteolysis
Increase ketogenesis
Decrease in general biosynthesis of macromolecules o produces necessary
glucose for the growth of the cancer cells or malignant tumor

The avid increase in the absorption of glucose by cancer cells and

decreasing the ATP production through oxidative phosphorylation even
when the oxygen is plentiful are toward cancer cell growth and is called
the Warburg Effect
This increase uptake of glucose allows for the detection of cancer, tis
progression and treatment response using PET Scan using FDG
(fluorodeoxyglucose)
Genetic Basis of Cancer
Major causes of carcinogenesis are linked to mutagenesis or alteration I
the DNA sequence or epigenetic changes (alteration in gene expression
not associated with changes in DNA sequences)
Chemical carcinogens
Radiation such as xray and UV radiation
Mutation in several groups of gene families such as
o Cell cycle and cyclin/cyclin dependent kinase genes
o Proto-oncogenes
o Tumor suppressor genes
o DNA repair genes
o Apoptotic genes
Several Mutations for Cancer Progression
Genetic Mosaicism
Heterogeneity in the genetic make-up of cancer cell population
Kras
Tumor suppressor gene
Genetic Basis which Gives rise to tumorigenesis
Initiation start of tumorigenesis of a single cell which is usually genetic in
nature
Promotion maintenance of growth factors