Standards of Cancer Biology and Therapy David Dingli, MD, PhD Hematology and Molecular Medicine Mayo Clinic RochesterSlide 2
Cancer and Age Breast Colon Testicular CNS ALL NCCC 1988 - 2004Slide 3
Nomenclature Benign " Polyp " Malignant Epithelial "Carcinoma" Mesenchyme "Sarcoma" Hematopoietic Leukemia, lymphoma, myelomaSlide 6
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)Slide 7
Cancer pathogenesis Oncogenes myc , ras , src, abl, bcl2 Tumor silencer qualities p53, Rb , APC, MEN1, NF1 MicroRNA Transcriptome controlSlide 8
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 ResistanceSlide 9
"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, 2000Slide 10
"I generally believed that record would remain until it was broken." Yogi BerraSlide 11
Tissue and tumor engineering Dingli & Pacheco, 2008Slide 12
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 miceSlide 13
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 onSlide 14
Translocations Balanced Reciprocal Aneuploidy Pseudodiploid Hyperdiploid Complex Random misfortune or increase Cytogenetic variations from the normSlide 15
Limitless regenerative potential Hayflick speculation Limited number of doublings Telomere support Telomerase Not all tumor cells have this potential Tumor undeveloped cellsSlide 16
Self-adequacy in development signals Autocrine circles Over-articulation of Receptor is dependably "on" Downstream flags Scaltriti et al, 2006Slide 17
Insensitivity to antigrowth signals Hanahan & Weinberg, 2000Slide 18
Evading apoptosis External triggers Intracellular triggers Death receptors Caspases Sensors (8, 9) Executioners (3)Slide 19
Sustained angiogenesis VEGF FGF1/2 Thrombospondin Thalidomide AvastinSlide 20
Tissue intrusion and metastasesSlide 21
Tumor load - Staging Tumor Size, container attack Nodes Involved, what number of? Metastases Present/truant "Obscure essential"Slide 22
Imaging CT filter PET/CT SPECT/CT MRI Staging ResponseSlide 23
Prognostic scoring frameworks Host versus Disease load Disease science Co-bleak conditions Performance statusSlide 24
Therapy Surgery Radiation Chemotherapy Antibodies Small atoms AdjunctiveSlide 25
Surgery Diagnosis Therapy Curative Palliative Debulking Symptoms control Prevent complexitiesSlide 26
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, GalliumSlide 27
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 vitalSlide 28
Radiation Consolidation "Mantle radiation" "Axillary radiation" Palliation Spinal line pressure Pain helpSlide 29
Radio(immuno)conjugates or -emittersSlide 30
Free isotopesSlide 31
Chemotherapy Antimetabolites Antifolates, Purine nucleosides, nucleoside blend inhibitors Alkylators Direct DNA harm (Many), platinum Spindle harms Vinca alkaloids, taxanes Topoisomerase inhibitors Anthracyclines, EtoposideSlide 32
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 growthSlide 33
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 toxicitiesSlide 34
Small particles Target oncogene item Bcr-Abl, PML-RARA , Inhibit motioning at key strides Safer than chemotherapy Specific reactions Specificity is frequently relativeSlide 36
Small atomsSlide 38
Adjuncts Glucocorticosteroids Estrogens/against androgens/SERMs BisphosphonatesSlide 39
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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