Post on 12-May-2015
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Biology, Clinical Manifestations, and Treatment of Cancer
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Cancer
Derived from Greek word for crab, karkinoma
Malignant tumor Tumor
Also referred to as a neoplasm—new growth Let’s review the two different types:
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Benign vs. Malignant Tumors
Benign MalignantGrow slowly Grow rapidly
Well-defined capsule Not encapsulated
Not invasive Invasive
Well differentiated Poorly differentiated
Low mitotic index High mitotic index
Do not metastasize Can spread distantly (metastasis)
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Classification and Nomenclature
Benign tumors Named according to the tissues from which
they arise and include the suffix “-oma”• Lipoma• Glioma• Leiomyoma• Chondroma
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Classification and Nomenclature (cont’d)
Malignant tumors Named according to the tissues from
which they arise• Malignant epithelial tumors are referred to
as carcinomas Adenocarcinoma
• Malignant connective tissue tumors are referred to as sarcomas
Rhabdomyosarcomas
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Classification and Nomenclature (cont’d)
Cancers of lymphatic tissue are lymphomas
Cancers of blood-forming cells are leukemias
Carcinoma in situ (CIS) Preinvasive epithelial malignant tumors of
glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma
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Histology and Genetics
Tumors are classified based on immunohistochemical analysis of genetic alterations for improved treatment Determine specific genetic mutation Identify multiple subdivision
• Breast cancer—six different types
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Tumor Markers
Tumor cell markers (biologic markers) are substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine Hormones Enzymes Genes Antigens Antibodies
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Tumor Markers (cont’d)
Tumor markers are used to: Screen and identify individuals at high risk for
cancer Diagnose specific types of tumors Observe clinical course of cancer Problem: false positives and negatives
What tumor markers can you state? What are the values?
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Cancer Stem CellsNew Research
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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Inflammation and Cancer
Chronic inflammation is an important factor in the development of cancer Cytokine release from inflammatory cells Free radicals Mutation promotion Decreased response to DNA damage Examples: ulcerative colitis, chronic viral
hepatitis
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Immune System and Cancer
Normal immune system protects against cancer
Immunosuppression fosters cancer Non-Hodgkin lymphoma (10X) Kaposi sarcoma (1000X)
In some cases cancer promotes secretion of cytokines that foster cancer
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Viruses and Cancer
Implicated Hepatitis B and C viruses Epstein-Barr virus (EBV) Kaposi sarcoma herpesvirus (KSHV) Human papillomavirus (HPV) Human T cell leukemia–lymphoma virus
(HTLV)
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Bacterial Cause of Cancer
Helicobacter pylori Chronic infections are associated with:
• Peptic ulcer disease • Stomach carcinoma• Mucosa-associated lymphoid tissue lymphomas
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Three-Step Theory of Invasion
Tumor cell attachment Fibronectin and laminin
Degradation or dissolution of the matrix Enzymes
Locomotion into the matrix Invadopodia (pseudopodia)
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Sequential Process of Metastasis
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Clinical Manifestations
Many Different clinical manifestations occur:
Syndrome of cachexia Most severe form of malnutrition Present in 80% of cancer patients at death Includes anorexia, early satiety, weight loss,
anemia, asthenia, taste alterations, and altered protein, lipid, and carbohydrate metabolism
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Cachexia
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Clinical Manifestations
Anemia A decrease of hemoglobin in the blood Mechanisms:
• Chronic bleeding resulting in iron deficiency• Severe malnutrition• Medical therapies• Malignancy in blood-forming organs
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Clinical Manifestations (cont’d)
Leukopenia and thrombocytopenia Direct tumor invasion to the bone marrow causes
leukopenia and thrombocytopenia Chemotherapy drugs are toxic to the bone marrow
Infection Risk increases when the absolute neutrophil and
lymphocyte counts fall
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Clinical Manifestations (cont’d)
Paraneoplastic syndromes 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
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Environmental Risk Factors
Tobacco Multipotent carcinogenic mixture Linked to cancers of the lung, lower urinary tract,
upper aerodigestive tract, liver, kidney, pancreas, cervix uterus
Linked to myeloid leukemia Secondhand smoke (ETS) contains many toxic
chemicals Cigar and pipe smoking equally harmful
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Environmental Risk Factors
Diet May account for 30% of the overall risk factors for
cancer Xenobiotics
• Hydrocarbons and amines produced during cooking of meat protein
• Toxic, mutagenic, and carcinogenic chemicals in food• Examples:
– Compounds produced in the cooking of fat, meat, or proteins
– Alkaloids or mold by-products• May influence epigenetics
Research ongoing regarding vitamin influe
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Cancer in Children
Incidence Rare but is leading cause of death from disease in
children In 2004, mortality rate was 2.4 per 100,000 cases Survival rates have dramatically improved over
past 30 years
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Cancer in Children
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
Most sarcomas vs. carcinomas in adults Diagnosed during vs. peak growth periods Fast growing and without early signs
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Etiology with Children
Most do not demonstrate predisposing environmental factors
Genetic factors: Chromosome abnormalities
• Aneuploidy, amplifications, deletions, translocations, and fragility
• Certain congenital syndromes and cancers occur together
Wilms tumor and urogenital abnormalities Down syndrome and leukemia
Oncogenes and tumor-suppressor genes• Fanconi anemia, Bloom syndrome
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Prognosis
More than 70% of children cured Survival rates higher in children under 15
years Younger are more likely to be enrolled in
clinical trials Survivors have increased risk of cancer later
in life Residual and long-term effects of treatment Psychologic sequelae
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Components of the hematologic system
Chief functions: Delivery of substances needed for cellular
metabolism Removal of wastes Defense against microorganisms and injury Maintenance of acid-base balance
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Components of the hematologic system
As a review remember what the following functions are:
Bone Marrow Lymphoid Organs Platelets RBC WBC
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Erythropoiesis
Erythrocytes are derived from erythroblasts (normoblasts)
Maturation is stimulated by erythropoietin Erythropoietin causes an increase in red cell
production and release from bone marrow
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Regulation
Numbers of circulating red cells in healthy individuals remain constant
The peritubular cells of the kidney produce erythropoietin
Hypoxia stimulates the production and release of erythropoietin
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Erythropoiesis
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Evaluation of the Hematologic System
Tests of bone marrow function:Bone marrow aspiration
Bone marrow biopsyMeasurement of bone marrow iron stores
Differential cell countBlood tests
Large variety of tests
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Pediatrics and the Hematologic System
Blood cell counts increase above adult levels at birth
Trauma of birth and cutting the umbilical cord
The hypoxic intrauterine environment stimulates erythropoietin production
Results in polycythemia
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Aging and the Hematologic System
Erythrocyte life span is normal but erythrocytes are replaced more slowly
Possible causes:
Iron depletionDecreased total serum iron, iron-binding capacity, and intestinal iron absorption
Lymphocyte function decreases with ageThe humoral immune system is less responsive
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Multiple Myeloma (MM)
Malignant proliferation of plasma cells Infiltrate bone marrow and aggregate into
tumor masses in skeletal system M-proteins Bence Jones protein Hypercalcemia, renal failure, bone lesions
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Multiple Myeloma