Standards of Cancer Biology and Therapy .

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Growth and Age. Bosom. Colon. ALL. Testicular. CNS. NCCC 1988 - 2004. Classification. Kind
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Standards of Cancer Biology and Therapy David Dingli, MD, PhD Hematology and Molecular Medicine Mayo Clinic Rochester

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Cancer and Age Breast Colon Testicular CNS ALL NCCC 1988 - 2004

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Nomenclature Benign " Polyp " Malignant Epithelial "Carcinoma" Mesenchyme "Sarcoma" Hematopoietic Leukemia, lymphoma, myeloma

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Etiology Nature Inherited disease disorders p53, BRCA1 and 2, MMR Immune lack disorders Inherited/Congenital or gained Nurture Radiation (inestimable, aftermath, radon) Chemotherapy (MDS) Viruses and microscopic organisms EBV, HTLV-I/II, H. pylori Repeated damage (Acid reflux, hepatitis)

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Cancer pathogenesis Oncogenes myc , ras , src, abl, bcl2 Tumor silencer qualities p53, Rb , APC, MEN1, NF1 MicroRNA Transcriptome control

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The way to disease Clonal multiplication Starts from a solitary cell Expansion in steps Pre-dangerous states Polyp, MDS, MGUS Serial collection of transformations Clonal development Resistance

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"Signs of malignancy" Self-adequacy in development signals Insensitivity to against development signals Evading apoptosis Limitless conceptive potential Sustained angiogenesis Tissue intrusion and metastases Genomic precariousness Hanahan & Weinberg, 2000

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"I generally believed that record would remain until it was broken." Yogi Berra

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Tissue and tumor engineering Dingli & Pacheco, 2008

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Cancer foundational microorganisms Present in most (all) tumors Small portion of populace No widespread marker Often impervious to treatment May be vital focus of treatment Cancer starting cells in mice

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Genomic insecurity Is it fundamental? Typical versus irregular transformation rate 2 current perspectives Chromosomal flimsiness Gross translocations, misfortune and pick up of chromosome parts Mutator phenotype Repair qualities Xeroderma pigmentosum MMR and so on

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Translocations Balanced Reciprocal Aneuploidy Pseudodiploid Hyperdiploid Complex Random misfortune or increase Cytogenetic variations from the norm

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Limitless regenerative potential Hayflick speculation Limited number of doublings Telomere support Telomerase Not all tumor cells have this potential Tumor undeveloped cells

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Self-adequacy in development signals Autocrine circles Over-articulation of Receptor is dependably "on" Downstream flags Scaltriti et al, 2006

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Insensitivity to antigrowth signals Hanahan & Weinberg, 2000

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Evading apoptosis External triggers Intracellular triggers Death receptors Caspases Sensors (8, 9) Executioners (3)

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Sustained angiogenesis VEGF FGF1/2 Thrombospondin Thalidomide Avastin

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Tissue intrusion and metastases

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Tumor load - Staging Tumor Size, container attack Nodes Involved, what number of? Metastases Present/truant "Obscure essential"

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Imaging CT filter PET/CT SPECT/CT MRI Staging Response

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Prognostic scoring frameworks Host versus Disease load Disease science Co-bleak conditions Performance status

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Therapy Surgery Radiation Chemotherapy Antibodies Small atoms Adjunctive

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Surgery Diagnosis Therapy Curative Palliative Debulking Symptoms control Prevent complexities

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Radiation External bar radiation Gamma photons Neutron shafts Radioimmunoconjugates Antibody focused on radiation Radioconjugates Isotope labeled to bone looking for material Free isotopes 131 I, Gallium

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Radiation targets DNA Water Free radical era Oxygen is required Anti-oxidants are not useful Direct and circuitous impacts Not all phones are made equivalent Geometry vital

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Radiation Consolidation "Mantle radiation" "Axillary radiation" Palliation Spinal line pressure Pain help

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Radio(immuno)conjugates  or -emitters

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Free isotopes

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Chemotherapy Antimetabolites Antifolates, Purine nucleosides, nucleoside blend inhibitors Alkylators Direct DNA harm (Many), platinum Spindle harms Vinca alkaloids, taxanes Topoisomerase inhibitors Anthracyclines, Etoposide

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Chemotherapy Often utilized as a part of mixes "Hack", "ABVD", "Air conditioning", "Taxol/Carbo" Minimizes resistance Reduces harmfulness Different reactions Can be healing in particular cases AML, ALL, HD, NHL, Testicular growth

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Antibodies Target particular antigen Specificity is relative Various instruments of activity Complement actuation ADCC Calcium passage May synergize with chemotherapy R-CHOP and CHOP Expected or startling toxicities

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Small particles Target oncogene item Bcr-Abl, PML-RARA , Inhibit motioning at key strides Safer than chemotherapy Specific reactions Specificity is frequently relative

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Small atoms

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Adjuncts Glucocorticosteroids Estrogens/against androgens/SERMs Bisphosphonates

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The objective Tumor cells don\'t live in detachment Stroma Adhesion resistance Blood vessels Angiogenesis inhibitors Antibodies (Avastin) Small atoms (Thalidomide, different IMiDs) Immune framework Transplantation Vaccines

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