2023 Student Biology of Cancer (1) PDF

 15 top causes of death in MN http://www.worldlifeexpectancy.com/top-15- causes-of-death-minnesota  CDC MN Data  http://www.cdc.gov/nchs/fastats/leading-cau ses-of-death.htm  http://www.cdc.gov/nchs/nvss/mortality/lcw k9.htm  Also known as neoplasm (new growth) or...

 15 top causes of death in MN http://www.worldlifeexpectancy.com/top-15- causes-of-death-minnesota  CDC MN Data  http://www.cdc.gov/nchs/fastats/leading-cau ses-of-death.htm  http://www.cdc.gov/nchs/nvss/mortality/lcw k9.htm  Also known as neoplasm (new growth) or neoplasia  Loss of Differentiation (anaplasia) ◦ haphazard arrangement ◦ no relation to normal structure ◦ Cells that look and act like the parent cell are called well-differentiated. (non malignant) ◦ Cells that bear little or no resemblance to the tissue of origin are called poorly differentiated or undifferentiated. (malignant)  Benign Malignant  Grow slowly  Grow rapidly  Encapsulated  Not encapsulated  Not invasive  Invasive  Poorly  Well differentiated  Low mitotic index differentiated  High mitotic index  Do not metastasize  Can spread distantly (metastasize)  Stages of cancer development ◦ Tumor initiation ◦ Tumor promotion ◦ Tumor progression  Cancer is caused by genetic mutations ◦ Mutation of genes which alters the function of the proteins ◦ Epigenetic mechanisms  Multiple mutations are required before cancer can develop ◦ Driver mutations “drive” progression of cancer ◦ After critical number of driver mutations, cell becomes cancerous  Clonal proliferation or expansion ◦ Mutations cause cell to acquire characteristics that give it selective advantage over its neighbors  Increased growth rate or decreased apoptosis  Transformation of normal cells ◦ Decreased need for growth factors to multiply ◦ Lack contact inhibition ◦ Anchorage independence ◦ Immortality Figure 11.6: Clonal Proliferation Model of neoplastic progression in the colon  Proto-oncogene (anti-oncogene): genes that encode for pathways that regulate normal cell proliferation ◦ Cancer cells express mutated or overexpressed proto-oncogenes, called oncogenes  Oncogenes act independently of normal regulatory mechanisms, causing abnormal proliferation and growth  Primarily genomic alterations ◦ Sustained proliferative signaling ◦ Evading growth suppression ◦ Genomic instability ◦ Replicative immortality  Secondary to genomic change ◦ Angiogenesis ◦ Reprogramming energy metabolism  Tumor resistance to destruction ◦ Resistance to apoptotic cell death ◦ Tumor-promoting inflammation ◦ Avoiding immune destruction  Culmination of other hallmarks ◦ Activating invasion and metastasis  Discuss the role genetics plays in the development of cancer.  What are the genetic changes that occur?  Why would cancer be considered a disease of aging?  What is the difference between an oncogene and anti oncogene?  How can epigenetic changes lead to cancer?  Can a mutagen exposure in your somatic cells lead to transmission of an increased cancer risk in your children?  How do cancer cells develop replicative immortality?  Growth of new vessels Angiogenesis ◦ Essential in tissue undergoing repair ◦ Essential to growth and spread of cancer  Cancerous tumors ◦ Maintain secretion of angiogenic factors (VEGF) ◦ Suppress angiogenesis inhibitors  How do cancer cells create their own blood supply (angiogenesis)?  Chronic inflammation is an important factor in the development of cancer ◦ Some organs more susceptible to oncogenic effects of inflammation ◦ Successful tumors can alter inflammation to benefit tumor growth  Helicobacter pylori ◦ Chronic inflammation associated with:  Peptic ulcer disease  Stomach carcinoma  Mucosa-associated lymphoid tissue lymphomas  Tumor-associated macrophage (TAM) ◦ Key cells that promote tumor survival ◦ Presence frequently correlates with a worse prognosis ◦ Mimic M2 phenotype ◦ Have diminished cytotoxic response ◦ Develop the capacity to block T-cytotoxic cell and NK cell functions and produce cytokines that are advantageous for tumor growth and spread  Normal immune system protects against cancer  Tumor-associated antigens ◦ Immune surveillance hypothesis—predicts developing malignancies are suppressed by efficient immune response ◦ Immunotherapy—products immune system could be used to target these antigens and destroy tumors  Tumor-infiltrating lymphocytes ◦ Cancers actively recruit immune response  Remodel tissues  Form new blood vessels  Promote metastasis  Microscopic analysis for staging—based on presence of metastasis ◦ Stage I: No metastasis ◦ Stage II: Local invasion ◦ Stage III: Spread to regional structures ◦ Stage IV: Distant metastasis  World Health Organization’s TNM system: ◦ T for tumor spread ◦ N for node involvement ◦ M for the presence of distant metastasis  Tumor markers are used to: ◦ Screen and identify individuals at high risk for cancer. Example – Prostate specific antigen (PSA). ◦ Diagnose specific types of tumors ◦ Observe clinical course of cancer  Problem: false positives and negatives  Biochemical markers  Substances produced by cancer cells that are found on or in tumor cells, in the blood, CSF, or urine ◦ Hormones ◦ Enzymes ◦ Genes ◦ Antigens ◦ Antibodies  Invasion ◦ Local spread ◦ Prerequisite for metastasis ◦ Recruitment of TAMs is critical  Metastasis ◦ Spread of cancer from a primary site of origin to a distant site ◦ Changes in tumor microenvironment initiate metastasis and cause cancer cells to evolve  Epithelial-mesenchymal transition  Model for transition to metastatic cancer cells  Epithelial characteristics lost ◦ Increased migratory capacity ◦ Increased resistance to apoptosis ◦ Dedifferentiated stem cell–like state  Growth favored in foreign microenvironments  Lytic enzymes: break down surrounding tissue  Decreased cell adhesion: abnormal fibronectin or fibronectin broken down. Anchors cells in place  Increased motility: detachment and infiltration of cells into adjacent tissue, into and out of vascular wall Invasion or Local Spread: First Step in Metastatic Process  Cellular multiplication: cell generation time, number of cells dividing and degree of cell loss  Mechanical Invasion: pressure from mass can cause tissue death by blocking blood vessels Spread of Tumor cells from primary site of origin to Distant Site. Five steps: 1. Direct or continuous extension 2. Penetration into lymphatics, blood vessels or body cavities 3. Release into lymph or blood 4. Transport to secondary sites 5. Entry and growth in secondary sites  Metastasis often occurs in the first capillary bed encountered by circulating cells  Organ tropism ◦ Preferential growth of cancerous cells in certain organs  Growth factors, chemokines, hormones, tissue-selective homing receptors, and chemotactic factors  What are the clinical manifestations of cancer?  What symptom do you think is the most distressing to the family?  What symptom do you think is most distressing to health professionals?  Pain ◦ Little or no pain is associated with early stages of malignancy ◦ Influenced by fear, anxiety, sleep loss, fatigue, and overall physical deterioration ◦ Mechanisms:  Pressure  Obstruction  Invasion of sensitive structures  Stretching of visceral surfaces  Tissue destruction  Inflammation/Infection  Fatigue ◦ Most frequently reported symptom ◦ Subjective clinical manifestation ◦ Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression, sleepiness, boredom, and lack of motivation ◦ Suggested causes:  Sleep disturbance  Biochemical changes secondary to disease and treatment  Psychosocial factors  Level of activity  Nutritional status  Environmental factors  Cachexia ◦ Multiorgan, energy wasting syndrome ◦ Most severe form of malnutrition ◦ Muscle weakness and fatigue ◦ Altered protein, lipid, and carbohydrate metabolism ◦ Loss of white adipose tissue ◦ Appetite-stimulating and appetite-suppressing pathways altered Cachexia. https://www.oncologynurseadvisor.com/home/hot-topics/side- effect-management/cachexia-not-improved-with-celecoxib- plus-megestrol-vs-megestrol-alone/  Paraneoplastic syndromes ◦ Symptom complexes triggered by cancer ◦ Causes  Biologic substances from tumor  Immune response to tumor  Not caused by direct local effects of tumor ◦ Can be earliest symptoms of unknown cancer  Gastrointestinal manifestations ◦ Oral ulcers caused by decreased cell turnover from chemotherapy and radiation ◦ Malabsorption ◦ Diarrhea ◦ Therapy-induced nausea  Hair and skin manifestations ◦ Alopecia from chemotherapy  Usually temporary ◦ Skin breakdown and dryness  Anemia: Hgb below 9 g/dl. ◦ Due to chronic bleeding, severe malnutrition, medical therapies or malignancy in blood forming organs  Leukopenia (decreased WBC count) and Thrombocytopenia (decreased platelets) ◦ Invasion of bone marrow or from chemo or radiation of areas of bone marrow.  Infection ◦ With decreased WBC count risk of infection rises.  C – Change in bowel or bladder habits A – A sore that does not heal U – Unusual bleeding or discharge from any body orifice T – Thickening or a lump in the breast or elsewhere I – Indigestion or difficulty swallowing O – Obvious change in a wart of mole N –Nagging cough or hoarseness  Environmental-lifestyle factors and genetic factors cause cancer  Patterns of cancer are influenced by environmental and lifestyle, factors ◦ Genetic and epigenetic alterations and abnormalities drive cancer at the cell level ◦ Factors influenced by the external environment  Stromal tissue immune cells promote chronic inflammation ◦ Can precede and initiate cancer changes  Bacterial ◦ Helicobacter pylori  Viral ◦ Hepatitis B and C: chronic inflammation predisposes to cancer development ◦ Human papilloma virus (HPV) Genital warts. Viral DNA becomes integrated into cervical cell chromosome ◦ Epstein Barr: infects B lymphocytes and stimulates proliferation ◦ Kaposi sarcoma-associated herpes virus ◦ Human T cell leukemia-lymphoma: oncogenic retrovirus  Chronic inflammation ◦ Ulcerative colitis → ↑’ed colon cancer risk ◦ Hepatitis B or C → ↑’ed risk of liver cancer  Carcinogens Environmental agents that increase the risk of cancer  Environmental Risk Factors ◦ Tobacco: major preventable cause of death. Cancers – lung, bladder, pancreas, kidney, pharynx, larynx, esophagus ◦ Diet: Decrease risk – Fruits and vegetables, dietary fiber, Vit. A, C, E and mineral selenium, green tea. Increase risk – Fat, preservatives, alcohol, grilled, blackened, fried foods Obesity – epidemic proportions in the US. Higher risk of breast, endometrium, colorectum, esophagus, gall bladder, kidney cancers  Sexual and reproductive behavior: ◦ HPV associated with cervical cancer, increased risk with multiple partners  Air pollution: Industrial, passive smoke, radon (radioactive gas from decay of uranium)  Occupational Hazards: Metalworking fluids, asbestos  Radiation: UV light, natural and artificial light. Ionizing radiation, atomic bomb, x-ray  Oral contraceptives ◦ increased risk of breast cancer in some users. Not a significant risk of breast cancer  Estrogens ◦ Women’s Health Initiative: 26% increased risk of breast cancer with Hormone Replacement Therapy. Decreased risk for colorectal cancers.  Most originate from the mesodermal germ layer ◦ Layer gives rise to connective tissue, bone, cartilage, muscle, blood, blood vessels, gonads, kidneys, and the lymphatic system  Often diagnosed during peak growth periods under age 6, and again during adolescence  Fast growing and without early signs  Most common childhood cancers are leukemias, sarcomas, lymphomas, and embryonal tumors  Embryonal tumors ◦ Originate during intrauterine life ◦ Immature embryonic tissue unable to mature or differentiate into fully developed cells ◦ Diagnosed early in life ◦ Name includes root term “blast”  Neuroblastoma, retinoblastoma  Mutations in oncogenes and tumor- suppressor genes  Chromosome abnormalities ◦ Abnormalities in number or structure ◦ Congenital syndromes and cancers occur together  Down syndrome and leukemia  Prenatal exposure ◦ Drugs ◦ Ionizing radiation  Childhood exposure ◦ Ionizing radiation, drugs, electromagnetic fields, and viruses associated with higher risk of cancer ◦ Infections ◦ May help “prime” immune system, providing protective effect ◦ Epstein-Barr virus and AIDS have strong associations with cancer development  What environmental factors are you and your family exposed to?  Which factors are you most concerned about?