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CRNA -Cancer

Tumor Invasion and Metastasis

QuestionAnswer
This is a direct invasion of contiguous organs known as local spread
This defines the spreading to cancer cells to distant organs by way of lymphatics and veins (lymph and blood) Metastasis
This describes the spreading of tumor cells to different sites Seeding
The 5 things spreading of tumor depends on its 1) rate of growth, 2) degree of differentiation, 3) anatomic presence, 4) absence of barriers, 5) other biologic factors.
The four phases of tumor Progression Transformation, Growth, Invasion, Metastasis
This occur when there is malignant change in the initiating cell Transformation
The amount of original cell transformation doublings it takes to produce a tumor weighting about 1g which is the smallest clinically detectable tumor 30
This is a major cause of poor clinical outcome of individuals with cancer Metastasis
The cause of invasion of cancer cell Detached or lose cell-to-cell adhesion from the primary tumor and invade surrounding interstitial spaces.
Local tumor invasion mechanisms depends on what 5 things Cellular multiplication, Mechanical pressure, Release of lytic enzymes, Decreased cell-to-cell adhesion, Increased motility of individual tumor cells
Cellular multiplication involved Mitotic rate vs. cellular death. Degree of cell loss from the tumor (how many cells are dividing vs. how many tumor cells are dying) = ratio living/dying tumor cells
This is the number of cells dividing at one time Growth fraction
The pressure on normal tissue causes cell death and abnormal tissue fills in Mechanical pressure
The Pressure from the growing mass blocks local blood vessels can lead to… Local tissue death and a reduction in mechanical resistance, allows tumor to spread easier
Release of lytic enzymes from cancer cells causes…. Destruction normal tissue, allowing for space for cancer cells to grow
It is believed that this molecule helps cancer cells slip between healthy cells during tumor invasion Fibronectin
This molecule alters cell-to-cell adhesion - potentiating cell-matrix interactions that helping cancer cells survive, expand, and disseminate. E-cadherin
The movement of tumor cells into blood vessels Intravasation
The movement of tumor cells into other tissues/secondary site Extravasation
T/F Tumor cells become more mobile as a result of hepatocyte growth factor and epidermal growth factor and tumor-secreted or autocrine motility factor. True
T/F Cell migration is often initiated in response to chemotactic stimulus. True
Encapsulated tumors are more contained and less likely to spread related to … The containment by physiologic barrier. Ex. Bowman’s capsule: kidney
The 3 Step Theory of Invasion 1) Tumor cell attachment 2) Degradation of the matrix 3) Locomotion into the matrix
Membrane vesicles on cell surface of tumor cells are rich in >>this <<enable cancer cells to attach to basement membrane. Laminin receptors
T/F Once anchored, tumor cells secrete proteolytic enzymes or induce host cells to produce them, which causes degradation of the cellular matrix. True
These are finger-like projections that extend from the tumor cell, facilitate movement by attaching to blood vessel walls that cross the basement membrane. Invadopodia (pseudopodia). Tumor cells then extravasate from the vasculature into the interstitial stroma. Direction of locomotion seems to be influenced by chemotactic factors.
This is the spread of cancer cells from a primary site of origin to a distant site, is the life-threatening characteristic of malignancy. METASTASIS
The 5 Steps of metastasis 1) Direct or continuous extension of local invasion of tumor cells into surrounding tissue 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
Define how cancerous tumors may extend into several areas without breaking away from the parent tumor: including tissue spaces, lymph vessels, blood vessels, body cavities (serosal seeding), and cerebrospinal spaces. Continuous extension
This is initiated by loss of intracellular adhesion, movement of cells through tissue barriers is further influenced by proteases and paracrine and autocrine motality factors. Direct Tumor Extension
These offer malignant cells direct access into circulation Blood vessels within tumors offer malignant cells direct access into circulation
These have a good chance of spreading compared to single cells Clumps of tumor cells
This is when tumor cells invade serous surface, implant and become distant metastases. Seeding
Most common route for distant metastasis through lymphatics. Lymph channels occur at the periphery of the tumor, not within the tumor mass. Tumor cells are then carried to regional lymph nodes.
For many types of cancer, the first sign of distant spread is… presence of tumor cells in the lymph nodes (esp. breast CA). Initially lymph nodes attempt to wall off tumor, preventing spread into lymphatic system, (where host defenses like tumor necrosis factor and macrophages attempt to eliminate tumor cells/kill
T/F When tumor cells get lodged in lymph node, tumor cell death does not occur from inflammatory reaction False, death does result from inflammatory reaction
T/F When tumor cells get lodged in lymph node, death because of incompatible local environment for unknown reasons, and there may be a growth into a discernible lump True
T/F When tumor cells get lodged in lymph node, sustained dormancy for unknown reasons True
To establish metastasis, tumor cells must escape Host defenses and lodge in vascular bed of target organ. Growth in target organ requires vascular network (angiogenesis) and the host defenses be ineffective.
Most attach directly to preexisting regions of the… Endothelial surface or to preexisting regions of exposed subendothelial basement membrane. Emboli or tumor cells that contain leukocytes, fibrin, or platelets can cause direct emoblization in precapillary venules. Once lodged in vascular wall and interst
Growth of cancerous colonies depends on… An adequate blood supply
Tumors will be unable to enlarge without vascularization because Hypoxia causes apoptosis.
The activator and effects of P53 gene causes apoptosis (programmed cell death). Stimulated by hypoxia and causes apoptosis (programmed cell death)
This proangiogenic factors promote angiogenesis Vascular endothelial growth factor (VEGF)
T/FAngiogenesis inhibitors: platelet factor-4, angiostatin, endostatin, canstatin, tumstatin, thrombospondin, and interferon alph/beta. True
This is produced by tumor cells and has been implicated in regulating the angiogenic switch that regulates the balance of positive and negative angiogenic factors. Tissue factor (TF)
Cancer cells that stop producing this protein that inhibits the growth of new blood vessels. Thrombospondin: Normal cells prevent the development of new blood vessels by producing thrombospondin
This is the process of developing new blood vessels Angiogenesis
3 Conditions that must be met for a tumor to grow 1) developed vascular network, 2) host defenses are evaded, 3) a compatible environment is available (“the soil”).
Mutations in the p53 gene may prevent the body’s “emergency brake” causing uncontrolled growth. The affected cells no longer go through apoptosis, but continue to live and proliferate and may become much more aggressive/stronger tumor cells. These cells may produce larger tumors which may overwhelm host defenses
This defines when some cancers show preferential growth in certain organs Organ Tropism. Ex. Lung cancer often metastasizes to the brain and liver. Organ tropism may be the result of: growth factors, chemokines, or hormones present in the target organ and the presence of chemotactic factors that diffuse from the target organ a
This is the preferential adherence to the surface of certain target organs tissue-selective homing receptors
This Stage is when cancer confined to the organ of origin Stage I
This Stage is when cancer that is locally invasive Stage II
This stage is when cancer that has spread to regional structures such as lymph nodes Stage III
This stage is when the cancer that has spread to distant sites, such as a liver cancer spreading to the lungs, or a prostate cancer spreading to bone. Stage IV
*The TNM system is used to … standardize staging.Used by the WHO
T/F The TNM stands for tumor location, nodal involvement, and metastasis False, stand for Tumor Spread, Nodal Involvement, and metastasis
T/F Per Textbook, early stages of cancer are usually accompanied by little or no pain. True
Pain does occur in 10% of people who are terminally ill with cancer False, textbook states 70-80%
This is strongly associated by fear, anxiety, sleep loss, fatigue, and overall physical deterioration, as well as it occurs through an interaction with psychogenic, cultural, and physiologic components Pain. Mechanisms may be mediated by cytokines acting on the peripheral and central nervous systems, pressure, obstruction, invasion of a sensitive structure, stretching of visceral surfaces, tissue destruction, and inflammation.
Pain may be a direct result of >this< but may be the result of other problems. i.e. infection, bone metastasis and back pain (caused by periosteal irritation, medullary pressure, or pathologic fractures). Malignancy
Abdominal pain caused by severe (blank) from tumor invasion of hollow viscus. Stretching. Another example,hepatic malignancy can cause stretch the liver, resulting in a dull pain or a feeling of fullness over the right upper abdominal quadrant.
Tumor compression of nerve endings against a firm surface can lead to this manifastation pain
The way a person perceives pain can vary according to… to their ethnocultural background.
The 3 Treatment Goals for Pain Control: 1) Control pain rapidly and completely as judged by person. 2) Prevent recurrence. 3) continued evaluation.
This the most frequently reported symptom of cancer and cancer treatment FATIGUE. Suggested causes: sleep disturbance, various biochemical changes, including cytokines and neurotransmitters, secondary to disease and treatment, numerous psychosocial factors, level of activity, nutritional status, and other environmental factor
T/F S/S of Fatigue include tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression, sleepiness, boredom, and lack of motivation. True. Proposed physiological cause: probably decreased muscle contractility, muscle function consequences from metabolic products of cancer treatment and associated muscles loss from circulating cytokines, tumor necrosis factor (TNF), and interleukin-1
This definition includes anorexia; early satiety (filling); weight loss; anemia; asthenia (marked weakness); taste alterations; and altered protein, lipid, and carbohydrate metabolism. Cachexia **Very severe form of malnutrition associated with cancer and results in wasting: extensive loss of adipose tissue, emaciation, and decreased quality of life.This appears to be due to increase in catabolism of triglycerides, rather than decrease
The most significant cytokine because of its role in cachexia syndrome. cachectin (activated macrophage-produced TNF-α) Important roles in normal cells: 1) in the defense against viral, bacterial, and parasitic infections; 2) in autoimmune responses; 3) in the selective destruction of malignant cells.
Anorexia may be caused by alterations in … taste
This is malnutrition that evolves from protein-deficient diet, in which calories primarily come form carbohydrates. kwashiorkor. Serum proteins will be decreased (transferring, albumin)-results in edema
This is a form of malnutrition resulting from a decreased intake of calories and proteins. Marasmus . Characterized by decreased anthropometric measurements caused by prolonged and gradual wasting of muscle mass and normal serum albumin.
T/F Metabolic rates in people with cancer are low leading progressive weight loss False, metabolic rates are high in the person with cancer can occur despite normal or increased food intake. Hyperinsulinemia is present, and many individuals show insulin resistance, hyperglycemia, and an abnormal glucose tolerance test results.
A frustrating sense of fullness only after mouthfuls of food. **early satiety
The result of chronic bleeding, severe malnutrition, medical therapies (chemotherapy and radiation), malignancy in blood-forming organs. ANEMIA. Several of the aforementioned causes can cause the suppression of the action of erythropoietin on the bone marrow, presumably by the release of cytokines. Erythropoietin produced in the kidney and acts on the bone marrow to stimulate the release
This can correct anemias caused by cancer Erythropoietin, drug name of Epogen/Procrit
Anemia can also lead to iron deficiency.
This is a decreased white blood cell count (leukocyte count) Leukopeni
This is a decreased platelet count Thrombocytopeni
Radiation and Chemotherapeutic agents are toxic to bone marrow and therefore can lead to 2 things granulocytopenia and thrombocytopenia.
Major cause of hemorrhage in cancer due to… chemotherapy and bone marrow involvement by malignancy.
This accompanies DIC that occurs in patients with acute promyelocytic leukemia and prostate cancer. Thrombocytopenia
Most significant cause of complications and death in persons with cancer INFECTION. Most at risk when absolute granulocyte or lymphocyte count falls, the risk of infection, increases and persons with cancer have reduced immunologic functions, debility with advanced disease, and immune-suppression from radiation and chemo.
This can increase infection risks due to the removal of large amounts of tissue: create favorable sites for infection when combined with hemorrhage, dead spaces, ad poor tissue perfusion. Surgery
This results from bone marrow radiation dramatically increases infection risk. Leukopenia.
Mucous membranes and other rapidly dividing cells are prone to irritation and ulceration from … Radiation. Radiation can cause bladder, cervix and GI fistulas.
These are 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. PARANEOPLASTIC SYNDROME
T/F PARANEOPLASTIC SYNDROME affects approximately 75% of patients with cancer. False, only 10%
This may be the earliest symptom of an unknown cancer PARANEOPLASTIC SYNDROME
T/F PARANEOPLASTIC SYNDROME affected individuals they may represent serious and life-threatening problems, and may mimic progression and therefore interfere with appropriate treatment. True. Ex. Cushing syndrome, SIADH, Hypercalcemia, Hypoglycemia, Carcinoid syndrome, Polycythemia, Myasthenia etc.
This denotes the use of relatively nonselective cytotoxic drugs that target vital cellular machinery or metabolic pathways critical to both malignant and normal cell growth and replication. Chemotherapy
To be curative, chemotherapy must eradicate enough tumor cells so that the rest can eradicate by body’s own defenses
This are agents known to have significant early response rates but the duration of response was short lived. Single Agent Chemotherapy
This is a synergistic use of several agents, each of which individually has an effect against certain cancer. Combination Chemotherapy ***The point is to avoid single-agent drug resistance which may be present even in previously untreated tumors. It also may prevent acquired drug.
A benefit of ssing small doses of multiple chemotherapy drugs can diminish negative effects of chemo agent on healthy tissue
This implies a direct correlation between dose of chemo agent and killing tumor cells. Logarithmic fashion. Small dose increases can significantly increase antitumor effects. Principle Dose Intensity
This is relative effective dose needed to kill cancer cells as compared to the dose that would be harmful to normal cells, is generally quite low and is one of the limiting factors in the escalation of chemotherapy use. Therapeutic index
This is done after local treatment or removal of the primary tumor. Used in patients who have minimal or no residual disease but who are at high risk for metastasis. Prevents micrometastatic deposits, decreasing reoccurrence. Adjuvant chemotherapy
There are early use of agents before definitive local control surgery or irradiation to decrease tumor size. May allow for less extensive local control measures as well as early treatment opportunities. Primary, neoadjuvant, chemotherapy. Chemotherapy agent effectiveness dependent on the cell cycle.
Created by: honeybeeforeman on 2008-09-15



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