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

even mixed tumors. 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 .Malignant Mixed Tumor  Tumors of salivary glands Teratoma  The great majority of malignant neoplasms. 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. 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.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.

  Bone. 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 . liver.

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 . 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.