Cancer and Tumors– Pathophysiology – Flashcards
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What is the second leading cause of death in the US
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Cancer
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Most common causes of cancer death in men
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Lung Cancer (28%), Prostate (10%) and Colon & Rectum (9%)
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Most common causes of cancer death in women
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Lung Cancer (26%), Breast Cancer (14%) and Colon & Rectum Cancer (9%)--- Lung cancer remains stable while other types of cancer are declining
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Definition of Cancer
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tissue overgrowth which is independent of the laws governing the remainder of the body. Independent and can't regulate the functions of proliferation and differentiation
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Neoplasm (Tumor)
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tumor or new growth that serves no useful purpose to the organism
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Malignant Tumor (Cancerous)
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- Rapid Growth (high mitotic index) -Loss of differentiation (anaplasia) -Lack of capsule -Invade surrounding tissue -Metastasis through blood vessels or lymph to other body parts
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Benign Tumor
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"-oma" lipomas or hypertrophy (accumulations of cells)
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Carcinomas
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benign tumors in epithelial tissue
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Adenocarcinomas
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benign tumors in ductal or glandular epithelium
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Sarcoma
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benign tumors in connective tissue
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Lymphomas
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benign tumors in the lymphatic tissue
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Leukemia
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benign tumors in blood forming cells
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Terato
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benign tumors in germ cells
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Carcinoma in Situ (CIS)
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pre-invasive epithelial tumors of glandular or squamous cell origin. They have not broken through the basement membrane of the epithelium. Cant be in the blood stream, can just remove
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Stages of Cancer Spread
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Stage 1: original site Stage 2: locally invasive Stage 3: regionally spread Stage 4: Distant spread
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Benign Tumors
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-Grow slowly -Have a well defined capsule -Are not invasive -Are well differentiated; look like tissue from which they arise -Have low mitotic index; dividing cells are rare -Do not metastasize
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Malignant Tumors
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-Grow rapidly -Are not encapsulated -Invade local structures and tissue -Are poorly differentiated; may not be able to find tissue origin -Have a high mitotic index -Can spread distantly, often through blood vessels and lymphatics
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Tumor Markers
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substances produced by both benign and malignant tumors that are either present in or on tumor cells or found in blood, spinal fluid, or urine
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Tumor Markers can be found in...
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hormones, enzymes, genes, antigens, and antibodies Liver and Germ Cells secrete protein AFP into blood Prostate Cells secrete PSA (Prostate Specific Antigen) into blood Ovarian Cancer secretes CA25
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True or False: Cancer is predominantly a disease of aging
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True
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What is the "Many-hits Theory"?
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Multiple mutations are required before cancer can develop (4-7 "hits")
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Characteristics of Cancer Cells
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-transformed cells= created from normal cells -lack contact inhibition, they continue to crowd -are anchorage independent, they don't attach they can float -immortal and seem to have an unlimited life span
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Clonal Proliferation or Expansion
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As a result of mutation, a cell acquires characteristics that allow it to have selective advantage over it's neighbors Ex. Increased growth rate or decreased apoptosis (programmed cell death)
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Driver Mutations
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Drive the progression of cancer
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Passenger Mutations
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Random mutations that don't contribute to cancer
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Oncogenes
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mutant genes that in their normal non-mutant state direct synthesis of proteins that positively regulate (accelerate) proliferation
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Tumor-suppressor Genes, "anti-oncogenes"
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encode proteins that are in their normal state negatively regulate (decelerate, halt) proliferation
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Proto-oncogene
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Normal genes that direct protein synthesis and cellular growth
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Point Mutations
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Changes in one or a few nucleotide base pairs, small changes in DNA, effects activity, RAS genes
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Chromosome Translocation
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a piece on one chromosome is transferred to another, changes code..large changes in chromosome structure, can activate oncogenes, can cause excess and inappropriate production of proliferation factor
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Gene Amplification (highlight a component--can activate oncogene)
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Duplication of a small piece of chromosome over and over (not just 2, 10s of 100s), results in increased expression of an oncogene and sometimes even drug resistant genes
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Tumor-suppressor genes
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Major function is to negatively regulate cell growth and prevent mutations. Mutation that allows unregulated cellular growth. RB GENE=strongly inhibits cell division cycle
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True or False: oncogenes are activated in cancers, tumor suppressors must be inactivated to allow cancer to occur
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True
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True or False: Tumor Suppressor genes are often inactivated by point mutations
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True
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Loss of Heterozygosity
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Both chromosome copies of a gene are inactivated (for loss of function to tumor supressor gene)
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Gene Silencing
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Whole regions of chromosomes are "shut off" while the same regions in other cells remain active. Caused by inheritance, histone modifications, DNA methylation
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Caretaker Genes
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Encode for proteins that are involved in repairing damaged DNA, New cancer treatment??, responsible for the maintenance of gnomic integrity. Loss of function leads to increased mutation rates
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True or False: If the mutation occurs in somatic cells, it is not passed to your offspring
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True
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True or False: If the mutation occurs in germline (reproductive) cells, it can be passed to future generations
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True
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Genes that can be transfer (usually in tumor suppressor gene)
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-Retinoblastoma (RB Gene) -Wilms Tumor (WT1 gene) -Neurofibromatosis (NF1 gene) -Breast Cancer (BRCA1 gene) -Polyposis coli/colon Cancer (APC)
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Types of Mutations
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-Secretion of Growth Factors (autocrine stimulation their own growth factors) -Increased growth factor receptors -Signal from cell surface receptor is mutated in the "on" position -Mutation is the RAS intracellular signaling protein -Inactivation of Rb tumor suppressor -Activation of protein kinases that drive the cell cycle -Apoptosis (programed cell death) in the p53 gene
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Angiogenesis
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Growth of new blood vessels to help bring nutrients to the cancer cells.
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Advanced cancers secrete angiogenic factors such as vascular endothelial growth factor (VEGF) to....
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recruit new vascular endothelial cells and initiate the proliferation of existing blood vessel cells, allowing small cancers to become large cancers
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True or False: Body cells are not immortal and can only divide a limited number of times
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True
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True or False: Telomeres are protective caps on each chromosome and are held in place by telomerase, they block cell division and prevent immortality
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True
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True or False: Telomeres become smaller and smaller with each cell division
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True
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True or False: Cancer cells can activate telomerase (enzyme rebuilds telomeres), unlimited division and proliferation
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True
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Cancer Metabolism
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-Parasitic extraction of nutrients from blood Divide even in hypoxic or acidic states -Use aerobic glycolysis so subsequent metabolites can be used for growth
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Cancer Stem Cells
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-Stem cells self-renew: Cell divisions create new stem cells -Stem cells are pluripotent: Ability to differentiate into multiple different cell types -Current cancer chemotherapy does not kill cancer stem cells
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Bacterial Cause of Cancer (Stomach Cancer)
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H. Pylori --> peptic ulcer disease --> gastric carcinoma
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Hepatitis B and C
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chronic inflammation predisposes to cancer development --> Liver Cancer, Cervix and hepatocellular carcinoma
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HPV and Genital Warts
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Viral DNA becomes integrated into cervical cell chromosome--> Cervical Cancer
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Epstein Barr
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infects B lymphocytes and stimulates proliferation--> B cell non-hodgkin lymphoma, nasopharyngeal carcinoma
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Kapsoi Sarcoma-associated herpes virus
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depressed immune system causes cancer
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Human T cell leukemia Virus
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lymphoma: oncogenic retrovirus
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Ulcerative colitis
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chronic inflammation that causes an increase in colon cancer risk (Khron's)
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Hepaptitis B or C
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chronic inflammation that causes an increase in liver cancer risk
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Environmental Risk Factors of Cancer: Carcinogens
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Enviormental agents that increase the risk of cancer
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Environmental Risk Factors of Cancer: Tobacco
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Major preventable cause of death (particularly lung cancer)
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Food items that decrease risk of cancer
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Fruits and Vegetables, Vitamin A,C,E; mineral selenium, Green tea
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Food items that increase risk of cancer
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Fat, Preservatives, Alcohol consumption, Grilled, Blackened, Fried Foods
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Environmental Risk Factors of Cancer: Obesity
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epidemic proportions in the US- the largest increases occurring in the 1990s among men and women
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Environmental Risk Factors of Cancer: Sexual and Reproductive Behavior
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can cause cervical cancer
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Environmental Risk Factors of Cancer: Air Pollution
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from industrial gases, passive smoke and radon emissions
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Metastasis
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the spread of cancer cells from the site of the original tumor to distant tissues and organs throughout the body -Direct or continuous extension -Penetration into lymphatics, blood vessels or body cavities -release into lymph or blood -transport to secondary sites -Entry and growth in secondary site
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Steps of Tumor Spread
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1) Cellular multiplication and Mechanical Invasion (pressure from mass can cause tissue death by blocking blood vessels) 2) Lytic Enzymes: Break down the surrounding tissue 3) Decreased Cell adhesion (tight gap junctions, cancer cells change polarity) 4) Increased Motility: detachment and infiltration of cells into adjacent tissue, into and out of vascular wall
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Tumor Staging
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involves size of tumor, local invasion, extent of metastases
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TNM System:
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T is tumor spread, N is node involvement, M is distant Metastasis
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T is Tumor, Levels of Tumor
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T0= no tumor Tis= Carcinoma in situ T1-4= Ascending degrees of increase in tumor size and involvement T1=Lesion <2 cm in size T2= Lesion 2-5 cm in size T3= Skin and chest wall involved in invasion
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N is nodes, Levels of Nodes involved
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N0= No nodes involved N 1-4= Ascending degrees of nodes involved N1=Mobile nodes involved N2= Fixed nodes involved
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M is Metastases
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M0= No metastases M1-4= Ascending Degrees of Metastatic Involvement, including distant modes M1= Demonstrable Metastases M2= Suspected Metastases
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Behaviors of Cancer: Pain
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Most feared of advanced cancer--In early cancer there is often little or no pain. Pain comes from pressure, obstruction, invasion of sensitive structure, stretching of visceral surfaces, tissue destruction, and inflammation
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Behaviors of Cancer: Fatigue
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Most frequently reported symptom of cancer. Caused by sleep disturbances, biochemical changes and lifestyle changes. Cancer may cause loss of muscle function
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Behaviors of Cancer: Cachexia
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Most severe form of malnutrition results in wasting emaciation and decreased quality of life
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Behaviors of Cancer: Anemia
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Hgb Below 9 g/dl due to chronic bleeding, severe malnutrition, medical therapies or malignancy in blood forming organs
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Behaviors of Cancer: Leukopenia (decreased WBC count) and Thrombocytopenia (decreased platelets)
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Invasion of bone marrow or from chemo or radiation of areas of bone marrow
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Behaviors of Cancer: Infection
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With decreased WBC count risk of infection increases (reduction of army)
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Behaviors of Cancer: Paraneoplastic Syndromes
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Symptom complexes that cannot be explained by the local or distant spread of the tumor or by the effects of hormones released by the tissue from which the tumor arose--- tumors can secrete hormones in substitute causing a hormone imbalance
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Seven Warning Signs of Cancer (CAUTION)
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C: Change in bowel or bladder habits A: A sore that doesn't heal U: Unusual bleeding or discharge from any body orifice T: Thickening of 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
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Tumor cell markers can
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monitor the course of cancer
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Telomeres:
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block unlimited cell division
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Metastasis is
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the ability to establish a secondary neoplasm at a new site
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Carcinoma in situ is
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preinvasive, a glandular and epithelial lesion
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Known routes od metastasis include:
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continuous extension, lymphatic spread, bloodstream dissemination
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Tumor Suppressor genes are:
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genes that produce proteins that inhibit cellular division
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In the current theory of carcinogenesis:
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several mutagenic hits are required, sequential genetic changes occur
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What is not involved in metastasis:
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interference
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Loss of E-cadherin:
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Causes cells to detach from their extracellular attachments
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The p53 gene:
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enables cells to cope with DNA damage, blocks the proliferation of cells that have suffered carcinogenic mutations, mutations disable an emergency brake on cell proliferation
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Local invasive factors include:
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lytic enzymes, mechanical pressure, cellular multiplication
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The sequence of carcinogenesis is:
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several mutagenic hits to DNA, reactivation of telomerase and development of immortal cells
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Adjuvant chemotherapy
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follows surgery to eliminate micrometastases
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Neoplasia
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abnormal, proliferating cells possessing a higher degree of autonomy than normal cells
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Anaplasia
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lack of cellular differentiation or specialization, primitive cells
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Autonomy
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cancer cells' independence from normal cellular controls
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Stage 3 Cancer
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cancer has spread to regional structures
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Tumor Markers:
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substances produced by cancer cells
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Loss of Heterozygosity:
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unmasks mutations in recessive genes
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Silencing
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methylation of DNA "shuts off" genes
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AFP
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hepatic, germ cells
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CEA
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GI, pancreas
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Urinary Bence- Jones Protein
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multiple myeloma
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PSA
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prostate gland
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Malignant Tumor
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-coma
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Benign Tumor:
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-oma
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True or False: Childhood cancers are more common than adult cancers
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False
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True or False: Childhood cancers have the strongest relationship to environmental agents
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False
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True or False: There is an association between the gene N-myc and neuroblastoma
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True
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True or False: Childhood cancers involve tissues more than organs
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True
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True or False: Childhood cancers involve epithelial cells more often than connective tissue cells
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False
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True or False: There is an association between the gene WTC and Wilms Tumor
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True
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True or False: There is an association between the gene ATM and leukemia
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True
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True or False: Among childhood cancers in caucasian children, lymphoma has the highest incidence
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False, Leukemia
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True or False: Childhood cancers have more long-term consequences than adult cancers
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True
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True or False: Childhood cancers have a better prognosis than adult cancers
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True
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Risk factor of Down Syndrome
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acute leukemia
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Risk factor of Wilms Tumor
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congenital absence of iris of the eye
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Risk factor of Retinoblastoma
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Rb1 gene
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Risk factor of Fanconi Anemia
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nonlymphocytic leukemia
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Risk factor of Vaginal adenocarcinoma
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DES
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True or False: Childhood cancers originate in the mesoderm
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True
