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Cancer / Neoplasia
From Damjanov Pathology for the health professions
| Question | Answer |
|---|---|
| neoplasia | uncontrolled growth of cells whose proliferation cannot be adequately controlled through regulatory mechanisms operating in normal tissues |
| the proliferation of normal cells is regulated internally by... | 1. the genetic program of the cell |
| The proliferaction of normal cells is regulated internally by.... | 1. the genetic program of each cell 2. signals transmitted from one cell to another through direct contact and 3. various soluble substances that have growth-promoting or growth inhibiting effects |
| differentiation | selective activation of genes which causes cells to assume specialized functions once they stop proliferating |
| Proliferation of neoplastic cells can be described as... | Autonomous, Excessive, Disorganized |
| Tumor | Masses formed from the proliferation of neoplastic cells |
| Oncology | Scientific discipline concerned with cancer |
| True of fase? All neoplasms form tumors | False. ex, Leukemia is a malignant disease of the bone marrow, but the malignant cells do not form distinct masses |
| Two most important classifications of tumors: | Clinical classification & Histologic classification |
| Clinical classification | Takes into account the clinical presentation and outcome of neoplastic diseases |
| Histologic classification | Based on histologic classification of tumors. From these, one can determine if the tumor is epithelial, mesenchymal, lymphoid, etc... |
| Benign tumors | Limited growth potential; good outcome |
| Malignant tumors | Grow uncontrollably and eventually kill the host |
| Macroscopic features | B: tumors are sharply demacrated from normal tissue and are often encapulated. M: tumors lack capsules, invade surounding tissue by infiltrating normal tissue like tree roots, lack borders |
| Microscopic features | B: cells resemble the tissue from which they originate. M: undifferentiated and don't resemble cells from tissue of origin |
| Anaplasia | Describes cells that exhibit new features not inherent to the tissue tissue of their origin |
| Cellular features | B: cells of same population have approx. same features, regular shaped nuclei, which have an even distribution of chromatin. M: cells are of variable shape, high nuclear to cytoplasmic ratio, more cells undergoing mitosis at once. |
| Chromosomal features | B: normal # of chromosomes. M:do not have a normal # of chromosomes, or may be structurally abnormal |
| Pleomorphism | Variability in the shape of cells |
| Biologic features | B: cells may retain some complex functions. M: cells have no specialized functions, all metabolism is geared towards growth and replication |
| Metastasis | Process in which cells move from one site to another in the body. Only malignant cells have the capacity to metastasize |
| Metastasis occurs through the following pathways... | 1. Lymphatics 2. Blood (aka hematogenous spread) 3. seeding of the surface body cavities. |
| Steps of the metastatic cascade | 1. Primary tumor develops 2. metastatic clone develops. 3. Proliferation of the clone and invasion of vessel. 4. Transport by circulation. 5. Emboloization. 6. Invasion. 7. New tumor formation at site of metastasis |
| Cells can only metastasize when... | the primary tumor begins CLONAL expansion |
| Angiogenesis | New blood vessel formation which malignant tumor elicit to survive at new sites |
| Immune cells that attack malignan cells | T lymphocytes, natural killer cells, macrophages |
| Mesenchymal (connective) malignancy | Sarcoma |
| Fat cell | Lipoma/Liposarcoma |
| Blood vessels | Hemangioma/Angiosarcoma |
| Smooth muscle cells | Leiomyoma/Leiomyosarcoma |
| Fibroblast | Fibroma/Fibrosarcoma |
| Striated Muscle cells | Rhabdomyoma/Rhabdomyosarcoma |
| Cartilage | Chondroma/Chondrosarcoma |
| Bone cell | Osteoma/Osteosarcoma |
| Epithelial Malignancy | Carcinoma |
| Squamous epithelium | Epithelioma (papilloma)/Squamous cell carcinoma |
| Transitional epithelium | Transitional cell papilloma/transitional cell carcinoma |
| Glandular epithelium | Adenoma/Adenocarcinoma |
| Neuroendocrine cells | Carcinoid/Oat cell carcinoma |
| Liver cell | liver cell adenoma/liver cell carcinoma |
| Kidney cells | Renal cell adenoma/Renal cell carcinoma |
| White blood stem cells | Leukemia |
| Lymphoid cells | Lymphoma |
| Plasma cells | Multiple myeloma |
| Neuroblast cells | Glioma (malignant) |
| Meningeal cells | Meningioma (B) |
| Schwann cells | Schwannoma/Malignant schwannoma |
| Embryonic (germ) cells | Teratoma/Teratocarcinoma |
| Mixed tumors | Tumors which typically involve the salivary glands and uterus |
| Staging of tumors is done through... | Clinical examination, x-ray studies, biopsy or surgical examination. |
| TNM stands for... | T: tumor size, N: lymph node involvement, M: distant metastases |
| Tumor stage is expressed on a scale of... | I-IV or A-D |
| Grading of tumors is based on... | histologic examination of tumors |
| Grade 1 tumors are... | well differentiated |
| Grade 2 lesions are... | moderately well differentiated |
| Grade 3 lesions are... | undifferentiated |
| Tumor outcome is generally based on... | Tumor staging and grading |
| True of false? Staging has more predictive value than grading | True. |
| True of false? there are no definitive of absolute biochemical differences normal and neoplastic cells. | True |
| True or false? Biochemical tests can tell whether a cell is benign or malignant | False. There are no biochemical tests at present to tell whether a cell is benign or malignant |
| Malignant cells need less _____ and therefore have fewer ______ | Oxygen; mitochondria |
| Rough ER is _____ (more/less) prominent in tumor cells. | Less. Tumor cells do not synthesize all the proteins that are made by normal cells |
| Glucose is procesed less effeciently in _______ cells | Tumor |
| A loss of highly specialized functions in tumor cells can be attributed to... | simplified metabolism |
| Tumor cells require less oxygen and are able to metabolize glucose ______ | anaerobically |
| Due to anaerobic metabolism, tumor cells produce ______ more readily than normal cells | Lactic acid |
| Alpha-feto-protein (AFP) | A major secretory product of fetal liver cells that is not synthesized by normal adult cells, but is secreted by liver cancer cells |
| True or false: Tumor cells may "regress" to assume fetal features | True |
| Carcinoembryonic antigen (CEA) | A glycoprotein normaly found only in embryonic intestinal cells, produced by intestinal carcinoma cells |
| True or false: malignant cells can survive in vitro under simple growth media, but they can only undergo mitosis a limited number of times after whichthey die | false. although cancer cells require a very simple groth media, they can survive indefinately, replicating an indefinate number of times |
| Contact inhibition | Phenomenon of cells discontinuing cell division in vitro once the bottom of the culture dish in ocmpletely covered; not presesnt in cancer cells |
| Cancer cells lack this property which contributes to their mobility in the body | adhesiveness |
| Many tumor cells secrete their own growth factors. this is called... | Autocrine stimulation |
| The growth of tumor cells is excessive and unregulated because.... | neoplastic cells do not respond to the normal inhibitory influences of adjacent cells |
| Carcinogen | any substance or agent that tends to produce a cancer |
| It is convenient to divide the causes of cancer into these two groups: | Exogenous and Endogenous |
| Exogenous causes can be further divided into these three groups: | chemical, physical agents, and viruses |
| This type of cause of cancer resides in the genome and is heritable | endogenous causes |
| Oncogenes | Human cancer genes; identical to exogenous viral genes |
| Transfection | the process by which cellular oncogenes are isolated and used like viruses to infect normal cells. Reuslts in malignant transformation |
| Clinical studies | include data gathered by physicians observing pts. also, clinical trials |
| Epidemiologic studies | concentrate on identifying the exogenous cause of cancer in in a population |
| Experimental studies | can be performed on animals or cells and tissues. can be performed in vitro. |
| The search for a cause of a particular cancer usually begin with... | clinical observation |
| Any clues about the causation of cancer based on clnical observation must be validated with... | Epidemiologic studies |
| The suspected causative agent must be identified... | biochemically |
| The definitive proof of a caricongen's ability is when... | the cancer can be reproduced in animals injected with the carcinogen. |
| Incidence | the number of newly diagnosed cases of a disease in a given time period, usually a year |
| Industrial carcinogens | exposure to cancer-causing agents in the workplace. ex, asbestos, naphthylamine, nickel, arsenic |
| Drugs as carcinogens | many drugs used in cancer Tx are carcinogenic. ex, nitrogen mustard, cyclophosphamide |
| Chemical carcinogens can be classified according to... | origin, chemical composition, or their mode of action |
| polycyclic aromatic hydrocarbons | a group of carcinogens, may be natural or human-made |
| Aflatoxin B1 | a veru potent natural liver carcinogen produced by the fungus Asperggillus flavus |
| True or false: Some sex hormones have a polycyclic structure | true. thus, they may induce tumors in sensitive tissues. |
| chemical carcimogens may act in 4 ways. these are: | Locally (contact), at the site of digestion in the intestines, at the site of metabolic activation in the liver, and at he site of excretion in urine |
| procarcinogen | a potentially harmful subtance that gets converted into a carcinogen by locally active enzymes in the exposed cells or in the liver. |
| Outline the process of carcinogenesis | Ingestion of carcinogen; metabolic action by the liver; action on susceptible tissue (lg. intestine); initiation;promotion;conversion;progression;clonal expansion; (liver) metastases |
| Initiation | an induction of irreversibe genetic changes in exposed cells |
| Promotion | initiated cells are stimulated to proliforate by promoters |
| Conversion | Cells acquire an ability to proliforate on their own (w/o promoter) and are able to convert a new cells type |
| Progression | acquisition of new genetic features and expansion of cell clones that do not regress after the carcinogen or promoter has been removed |
| Clones | Cells given rise by cancer cells; identical daughter cells. Can be invasive, metastatic, dormant, or differentiated |
| Selection | the process by which the most vital clones that are best able to survive in adverse conditions are chosen |
| Radiation originates from these sources: | UV light, radiation, X-rays, Radioactive isotopes, and Atomic bombs |
| UV light | a potent skin carcinogen, long term exposure from which may cause basal cell carcinoma, squamous cell carcinoma, and melanoma. Damages the DNA of the skin thus causing mutations. |
| Xeroderma pigmentosum | a genetic defect in which people lack enzyme that repair DNA damaged by UV light. prone to skin cancer and lesions |
| X-rays | used in Tx of malignant tumors. Benefits outweigh the risks |
| True or false: parasites are not involved in carcinogenesis | false. Parasites such as Schistosoma haematobium or Opistorchis sinensis are associated with increased incedences of cancer |
| Reverse transcriptase | an enzyme found in RNA viruses. used to synthesize fragments of dna which are incorporated into cellular DNA |
| Transduction | Formation of a cellular oncogene that is an exact replica of the viral oncogene |
| The transformation of an infected normal cell occurs only if... | the insertional mutagenesis occurs at a locus that activates an oncogene capable of transforming the cell |
| Human papillomaviruses (HPVs) | linked to common and genital warts, dysplasia of human epithelium, etc. lesion types 16, 18, 33 have a propensity of progressing to cancer |
| Epstein-Barr virus (EBV) | has a predilection for B lymphucytes. causes mononucleosis, prevalent with Burkitt's lymphoma, nasopharyngeal carcinoma |
| Hepatitis B virus (HBV) | transmitted via blood. Integrated into DNA of neoplastic cells. |
| Human T-cell lymphoma/ leukemia virus 1 (HTLV-1) | RNA virus in the same family as HIV |
| proto-oncogenes | encode for proteins important for basic cell functions |
| Proto-concogenes can be transformed into oncogenes by these mechanisms: | Point mutation, gene amplification, chromosomal rearrangement, insertion of viral genome |
| Point mutation | includes a single base substitution in the DNA chain resulting in a microcoded protein that has an amino acid sustituted for another amino acid |
| gene amplification | cell acquires an increased number of copies of the proto-oncogene |
| chromosomal rearrangements | translocation of one chromosomal fragment onto another, or deletion of a fragment of a chromosome |
| Insertion of viral genome | an insertional mutagenesis which results in the disruption of normal chromosomal architetcure and genetic dysregulation |
| Tumor suppressor genes | Genes that do not permit the development of neoplasia. Mutation or loss of tumor suppressor genes may lead to tumor formation. Best known are Rb-1 and p53 |
| Osteosarcoma | a malignant bone-forming tumor composed of neoplastic osteoblasts |
| Neurofibromatosis type 1 | most common autosomal dominant disease in humans. presents with numerous subcutaneous neural sheath tumors called neurofibromas. Linked to tumor suppressor gene NF-1 |
| Hereditary polyposis coli | colon maintains numerous polyps, many of which undergo malignant transformation. Linked to tumor suppressor gene APC |
| Wilm's tumor (nephroblastoma) | a renal malignant tumor of infancy and childhood. Linked to tumor suppressor gene WT-1 |
| Tumor antigens | are perceived as foreign to the body, thus will induce antibody production and a cell-mediated immune response. This response can limit the growth of the tumor |
| Bacille Calmette Guerin (BCG) | a tuberculosis bacillus, which when injected into pts with bladder cancer evokes a nonspecific stimulus from which there is an i nflux of magrophages which destroy tumor cells. |
| Seven warning signs of cancer | CAUTION- Change in bowel or bladder habits, A sore that doesn't heal, Unusual bleeding or discharge, Thickening or lump, Indigestion or difficulty swallowing, Obvious change in war of mole, Nagging cough of hoarseness |
| Clinical features of tumors depend on... | Type, location, histologic grade, clinical stage of tumor, immune status of host, sensitivity to therapy. |
| Cachexia | a systemic symptom of tumors which is characterized by generalized weakness, weight loss, anorexia, and paraneoplastic syndromes |
| Paraneoplastic syndromes | Caused by various substances secreted by tumor cells. cause endocrine, hematologic, neuromuscular, and CV changes.(Hypercalcemia, Cushing's syndrome, venous thrombosis, myasthenia gravis...) |
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