Lecture 10 Flashcards
Mechanisms of control for cell growth
Constant renewal (Hair follicles, gut lining), Stable, but can renew when stimulated (T-cells), Permanent, therefore, no renewal (cardiac muscle)
How is cancer developed?
Loss of control of cell division/ mutation of a gene
Characterization of Cancer tumours
Benign vs. Malignant
Solid vs. Invasive
In situ vs. Infiltrating
Benign Tumor characteristics (Growth rate, Character of growth, Tumor spread, Cell differentiation)
Growth rate: Slow
Character of growth: Expansion
Tumor spread: Localized (Brain tumors can do damage while being benign)
Cell differentiation: Well differentiated
Malignant Tumor characteristics (Growth rate, Character of growth, Tumor spread, Cell differentiation)
Growth rate: Fast
Character of growth: Infiltration
Tumor spread: Metastasis by bloodstream and lymphatics (establish secondary sites)
Cell differentiation: Poorly differentiated
Benign tumor classification
The cell of origin (Prefix-) and -oma (suffix)
Malignant tumor classification
3 groups (carcinoma, sarcoma, leukemia/lymphoma)
Carcinoma cancer
Most common (85% of tumors); Epithelial tissue (arises from the surface, glandular or parenchymal epithelium) and spreads through lymph nodes
Adenocarcinoma
Subtype of carcinoma cancer (ex. pancreas - glandular/ secretory cells)
Squamous cell carcinoma
Subtype of carcinoma cancer found on skin
Sarcoma cancer
Less common; Arise from connective tissue, endothelium, and mesothelium and spreads rapidly through the bloodstream
Fibrosarcoma
A subtype of sarcoma cancer affects fibroblasts
Myosarcoma
A subtype of sarcoma cancer affects muscles
Leukemia
Neoplasm of blood cells; non-solid tumors and overgrows and crowds out normal blood-forming cells
What happens if neoplasm cells populate LN and spleen
Lymphoma (T cell/ B cell)
Neoplasm development
A stepwise process that involves ongoing series of genetic changes over time (activation of oncogenes, loss of function of one or more tumor suppressor genes, and additional random genetic changes)
What does cancer in stem cells cause?
A tumor with a high degree of heterogeneity
True or False: Fast-growing neoplasms may outgrow the blood supply
True, this can be used as a therapeutic target
True or False: Tumors have their own blood supply
False, tumors derive blood supply from tissues they invade
Angiogenesis
Malignant tumors frequently induce new blood vessels to proliferate in adjacent normal tissues to supply the demands of the growing tumor
Necrosis in parts of malignant tumors
When the tumor outgrows its blood supply part with the poorest blood supply undergoes necrosis
The blood supply in tumors in the lung
Blood supply is best at the periphery of the tumor and poorest at the center (central necrosis)
The blood supply in tumors growing outward from an epithelial surface (ex. colon)
The best blood supply is at the base and the poorest at the surface (peripheral necrosis)
How can genetic change occur in cancer-causing genes?
Radiation, carcinogens, viruses – failure of DNA repair/fidelity mechanisms, Failure of Immune defences, over time these can accumulate (age-dependent), can also be inherited susceptibilities to developing cancer
Proto-oncogene
Philadelphia chromosome – seen in chronic granulocytic leukemia (translocation of pieces of chromosome 9 and 22); a very aggressive cancer
Loss of apoptotic control leads to…
Uncontrolled cell growth and cells eventually form a tumor
Tumor-suppressor genes
Genes (expressed in pair of homologous chromosomes) that inhibit/control cellular division/proliferation; prevent DNA replication (ex. APC, DCC, p53)
What virus causes leukemia and lymphoma?
T cell leukemia–lymphoma virus (HTLV-1) that is related to the AIDS virus (tax onocogene)
What virus causes Kaposi sarcoma?
Human herpesvirus 8 (HHV-8)
What virus causes Condylomas (warts)
Papilloma virus (HPV); predisposes to cervical carcinoma
What virus causes Chronic viral hepatitis
Hepatitis B and C viruses (chronic inflammation/repair)
What virus causes Nasopharyngeal carcinoma
Epstein-Barr virus also causes infectious mononucleosis
Which immune cells detect and destroy cancerous cells?
CD8 T-cells and NK cells
Which cancers do those with severe immunodeficiency have an increased risk of?
Blood and skin cancers
True or False: All mutations that cause cancers are directly related
False, Most mutations that cause cancer are not directly inherited (it can influence it, ex. only 10% of breast cancer cases linked to genetic mutations)
Which abnormal gene causes an 80% risk of breast cancer by age 90
BRCA1/2 DNA repair genes
Neurofibromatosis
increased production of benign tumours of the nerves that have an increased risk of malignancy (autosomal dominant)
Actinic keratoses
Small, crusted, scaly patches that develop on sun-exposed skin; may develop into cancer if untreated
Lentigo maligna
The freckle-like proliferation of melanin-producing cells that may develop on sun-exposed skin; may transform into melanoma
Leukoplakia
Thick white patches in the mucous membranes of the mouth from exposure to tobacco tars from pipe or cigar smoking or smokeless tobacco (may give rise to squamous cell cancers of the oral cavity)
Diagnosis of Tumors
Recognize early warning signs and symptoms, Complete medical history and physical examination, screening early (need to consider invasiveness/severity, cost/benefits), Surface – Visual, Orifice (opening) – Endoscopy, Internal – CT scan/MRI, Lab procedures
Cytologic diagnosis
Fine needle aspiration, biopsy (many organs – precise location of tumor by CT, Xray or US)
Histology
Frozen section Slides prepared and stained – rapid histological diagnosis in minutes
Abnormal smear
Slides of abnormal cells shed from surface of tumors
Tumor-associated antigen tests
Some cancers secrete substances that can be detected in the blood by lab tests (Carcinonembryoic antigen, Alpha-fetoprotein, Human chorionic gonadotropin, Acid phosphatase)
Carcinoembryonic antigen (CEA)
Produced by most malignant tumors of the GI tract, pancreas, breast
Alpha-fetoprotein
Normally produced by fetal tissues in the placenta but not adult cells
Human chorionic gonadotropin
Normally produced by the placenta in pregnancy
(PSA test) Acid phosphatase
Normally produced by prostate epithelial cells
Treatments of tumor
Surgery, TNM Classification, Staging I-IV, Radiotherapy, Hormones (Corticosteroids), Chemotherapy (anti-cancer drugs), Adjuvant chemotherapy,
TNM Classification
T- size 1-4, N spread to regional LN 1-3, M distant metastasis 0-2
Staging I-IV
Early, localized, regional spread, distant spread
Chemotherapy
Lasts 3-6 months (4-8 cycles of 3-4 weeks), 3 stages: Induction (1 month intensive) /Consolidation (few months) / Maintenance (2-3 years); Normal cells recover quickly, side effects disappear gradually (prognosis of the patient depends on their overall health and the type of anticancer drugs used)
Alkylating agents
Inhibit DNA synthesis, structure or function (DNA replication)
Side effects of chemotherapy
Anemia, Constipation, Depression, Diarrhea, Hair loss (alopecia), Infection, Loss of appetite (anorexia), nausea and vomiting, Mouth, gum, and throat problems; sores, and sexual problems
External Radiation Therapy
Damages DNA to disrupt growth of cancer, targeted external bean for 15 min 5x/week for 3-9 weeks
Internal Radiation Therapy
Tablet, liquid (IV) or brachytherapy (implant to deliver radioactive dose directly to tumor); fewer side effects compared to external
Considerations for Surgery (PROO)
Patient health/survivability (risks)
Resectability of tumor
Operability of tumor
Other treatment options
Immune system cancer control (CNMA)
CD8 (Cytotoxic) T cells destroy cancer antigens presented by MHC I
NK cells can destroy cells expressing stress signals, deficient MHC I expression
Macrophages can destroy tumor cells by phagocytosis
Antibodies to tumor antigens can tag tumor cells for destruction by Macrophages/ complement
Immunotherapy (Non-specific or Specific types)
Stimulating the body’s immune response to attack cancer
Nonspecific: Cytokines
Specific: Tumor-infiltrating lymphocyte therapy, Tumor vaccines, Tumor antibody therapy
IFN alpha
Has general antiviral effects, inhibition of tumor growth, useful in leukemia, multiple myeloma
IL-2
Stimulates NK cells and Cytotoxic CD8 T cells
and used in metastatic melanoma, renal cell carcinoma
CAR-T therapy
Specific Immunotherapy; Genetic TCR alteration
Dendritic cell therapy
Activation of dendritic cells in presence of tumor antigens
Anti-tumor vaccines
Tumor antigens from patient used to immunize patient against recurring disease after resection
Anti-tumor antibodies
Specific antibodies directed against tumor, sometimes linked with antitumor drug (chemo) or toxin (radioactive)
Drugs to remove blockades that are inhibiting immune function
Prevents tumor immune suppression functions (CTLA-, PD1, PD-L1)
Oncolytic viruses (Vaccinia, Vesicular stomatitis virus)
Infects and kills cancer cells, stimulate anti-tumor immunity - Attenuation
Thyroid cancer survival rate
95% (5-year rate)
Pancreatic cancer survival rate
4% (5-year rate)
Most common cancers in males and females
Lung cancer (males) and Breast cancer (females)
