cancer
TRANSCRIPT
General concepts of cancerGeneral concepts of cancer
Relevance of oncology:One-third of all individuals in the U.S.A.
Will develop some type of cancer during their lives.
Is the second cause of death in U.S.A.
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CANCERCANCER
NEOPLASM: SIR RUPERT WILLIS
ABNORMAL MASS OF TISSUE, THE GROWTH OF WHICH EXCEEDS AND IS UNCOORDINATED WITH THAT OF THE NORMAL TISSUES AND PERSISTS IN THE SAME MANNER AFTER CESSATION OF THE STIMULUS WHICH EVOKED THE CHANGE.
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CANCER IN U.S.A.CANCER IN U.S.A.
YEAR 20001.22 MILLION NEW CASES OF
INVASIVE CANCER WERE DIAGNOSED
552,000 PEOPLE DIED FOR CANCERCAUSE 23% OF ALL DEATHS (only cardiovascular disease cause more
deaths)
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CANCERCANCER
Gains in the treatment of nonresectable cancer have been gradual and have beeen focused on those malignancies characterized by unusual sensitivity to radiation and chemotherapy.
Survival rate at 5 years have been increased close to 50% as a result of progress in the early diagnosis and the therapy.
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CANCERCANCER
The three most common cancers are:
LUNGBREASTCOLON/RECTUM
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CANCERCANCER
ECONOMIC BURDEN: More than 10 billion dlls./year
SOCIAL IMPACT: The number of cases are increasing and are affecting young people every year.
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THE NORMAL CELL CYCLETHE NORMAL CELL CYCLE
MITOSIS:Chromatin aligns itself and formed two identical daugther cells
G1:DNA synthesis ceases (rest period)
S phase:Unknown signal/ increase of DNA and RNA synthesis
G2: DNA synthesis stop
GO: Aditional resting period
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CANCERCANCER
The relevance of knowing the “cell Cycle” is for a better understanding
of the mechanism of action of cancer chemotherapy drugs.
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CANCERCANCER
Is a Disorder of cellular homeostasis in which there is lost of the normal growth controlling mechanisms.
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The characteristics of cancer The characteristics of cancer cells are:cells are:
Clonality: Originates from a SINGLE STEM CELL that change in it`s behavior
Autonomy: The growth rate is unrestrictedAnaplasia: Lack of normal, coordinated
cellular differentiation.Metastasis: Dissemination to other parts of
the body.
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Abnormalities of cancer cellsAbnormalities of cancer cells
– Abnormal DNA synthesis– Membrane cells alterations– Cytoplasmic alterations– Increase ATP asa activity (Anaerobic shift)– Increase levels of proteolytic enzymes– Angiogenesis factor synthesis
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ONCOLOGY DEFINITIONSONCOLOGY DEFINITIONS
DIFFERENTIATION: Degree of morphologic and functional resemblance to comparable normal cell.
ANAPLASIA: Lack of “differentiation”, is a cancer marker.
ENCAPSULATION: Induction of peripheral fibrosis, characteristic of
“benign” neoplasm www.freelivedoctor.com
ONCOLOGY DEFINITIONSONCOLOGY DEFINITIONS
INVASION/INFILTRATION: Unrestricted permeation into contiguous structures, characteristic of “malignant” neoplasms.
METASTASES: Remote distant tumor implants from the primary neoplasm.
LOSS OF GROWTH CONTACT INHIBITION RATE.
DOUBLING TIME: Time required by the tumor to double in size.
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CANCERCANCER
Oncogenesis:Are those changes induced by oncogenic
factors in the normal cellular behavior which lead to the development of malignant/ cancer behavior of cells
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CANCERCANCER
ETIOLOGY: Cancer incidence vay with age, sex, race and geographic location. Hereditary traits have been obseved, also variations in diet and exposure to chemical and physical agents in the external environment contribute to the development of neoplasia.
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Differences between benign Differences between benign and malignant tumor cellsand malignant tumor cells
Characteristics Benign Malignant
Growth Expansile(Capsule)
Infiltrative (notencapsulated)
Vascularity Slight Increased(Angiogenesisfactor?)
Metastases None Present (loss ofcohesiveness)
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Differences between benign and Differences between benign and malignant tumor cellsmalignant tumor cells
Characteristics Benign MalignantUlceration Unusual CommonCytologic
Ultrastructure
Normalnuclear tocytoplasmicratio. Fewmitoses.Normal
Increasednuclear tocytoplasmicratio.>Mitoses.<Mitocondriaand <endoplasmicreticulum
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ETIOLOGIC MECHANISMETIOLOGIC MECHANISM
GENETIC FACTORS
VIRUS DNA -RNA
CHEMICAL CARCINOGENS
PHYSICAL CARCINOGENS
OTHERS
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GENETIC FACTORSGENETIC FACTORS
Proposed mechanism are: I-Genes which are deregulated and excessively
expressed, displaying dominant genetic activity. II-Genes which are supressors of tumorigenic
genetic activities and are recessive in that both alleles must be lacking for malignacy occur.
The inheritane patterns are generally autosomal dominant, with varying penetrance.
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CHEMICAL CARCINOGENSCHEMICAL CARCINOGENS
Tobacco smoke: (Tar)Polycyclic hydrocarbonsNitrosamines
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CHEMICAL CARCINOGENSCHEMICAL CARCINOGENS
DiethylstilbestrolEstrogensAlkylating agentsAzathyoprineMethrotexateMany others
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CHEMICAL CARCINOGENSCHEMICAL CARCINOGENS
DIRECT-ACTING
ALKYLATINGAGENTS (H2N)SODIUMARSENITE
SKINCANCERSGICANCERS
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CHEMICAL CARCINOGENSCHEMICAL CARCINOGENS
ACTIVATEDMETABOLITES
*AROMATICHYDROCARBONS*DYES*COAL TARPRODUCTS
LUNGBLADDERSKINGI Ca.
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CHEMICAL CARCINOGENSCHEMICAL CARCINOGENS
METALS
MOLDPRODUCTS
CHROMIUMNICKELASBESTOS
AFLATOXINBRACKENFERN,CYCAD NUT
LUNG Ca.
MESOTHELIOMAGI Ca.
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PHYSICAL CARCINOGENSPHYSICAL CARCINOGENS
ULTRAVIOLET LIGHT
IONIZING RADIATION
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ONCOGENIC VIRUSESONCOGENIC VIRUSES
Viruses have been implicated as the direct cause of only one human cancer.
The HTLV-I (human T-lymphotrophic virus can lead to adult T-cell leukemia.
Several others are closely associated but have to be taken only as cofactors in oncogenesis.
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ONCOGENIC VIRUSESONCOGENIC VIRUSES DNA VIRUS: PAPILOMA VIRUS (WARTS, C.U. Ca.,
Anogenital cancer)
HERPES SIMPLEX (C.U. Carcinoma)
EPSTEIN-BARR (Burkitt`s Lymphoma, Nasopharyngeal carcinoma)
Hepatitis B (Hepatocellular carcinoma)
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ONCOGENIC VIRUSESONCOGENIC VIRUSES
RNA virus: Mainly transcriptase reverse virus
AIDS virus (Kaposy`s sarcoma, primary C.N.S. Lymphoma)
HTLV-I and II (T leukemia)
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GENERAL AND LOCAL GENERAL AND LOCAL EFFECTS OF CANCEREFFECTS OF CANCER
Cancer can kill the patien by:
Local effectsSystemic effects
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LOCAL EFFECTS OF LOCAL EFFECTS OF CANCER ON HOSTCANCER ON HOST
OcclusionDestruction of critical structuresUlcerationTumor infarctionAbscess formation
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LOCAL EFFECTSLOCAL EFFECTS
Occlusion at the level of: Airways Gastrointestinal tract Blood vessels Lymphatic channels Urinary tract Biliary tract Heart (valves/pericardium) Cerebro-spinal fluid system
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LOCAL EFFECTSLOCAL EFFECTS
DESTRUCTION OF CRITICAL STRUCTURES:
Large blood vessels (aorta, carotid, etc.)Pituitary glandC.N.S.SkullBones
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SYSTEMIC EFFECTS OF SYSTEMIC EFFECTS OF CANCER ON HOSTCANCER ON HOST
Cachexia
Hormone and hormone-like production
Paraneoplastic syndromes
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PARANEOPLASTIC PARANEOPLASTIC SYNDROMESSYNDROMES
Paraneoplastic syndromes are related to “remote” effects of cancer cells on the host, whic are not attributable to functions of the original normal tissue
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PARANEOPLASTIC PARANEOPLASTIC SYNDROMESSYNDROMES
Paraneoplastic syndromes resembles other clinical endocrine, neurologic and coagulation clinical syndromes, but, by definition the clinical abnormalities are due to systemic effects produced by the cancer cells.
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PARANEOPLASTIC PARANEOPLASTIC SYNDROMESSYNDROMES
Relevance of paraneoplastic syndromes remains on two facts:
1.- As explained before, these syndromes have a different etiology and sometimes different mechanisms of production, by then, treatment of the clinical abnormalities have to be different also.
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PARANEOPLASTIC PARANEOPLASTIC SYNDROMESSYNDROMES
2.- Some paraneoplastic syndromes dissapear completely after removal of the cancer, while some of the resembled clinical syndromes have not cure. This fact, makes more important the differential diagnosis between them.
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PATHOPHYSIOLOGYPATHOPHYSIOLOGY
The pathophysiology of paraneoplastic syndromes remains unclear, but some proposed mechanisms are:
1.- Hormone & hormone “like” synthesis 2.- Synthesis of identifiable chemical mediators 3.- Production of auto-inmune responses 4.- Activation of factors of the coagulation system
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1.- HORMONE & HORMONE 1.- HORMONE & HORMONE “LIKE” SYNTHESIS( ectopic “LIKE” SYNTHESIS( ectopic
hormone secretion)hormone secretion)
Gene derepression
Cellular dedifferentiation
Cellular arrested differentiation
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2.- SYNTHESIS OF 2.- SYNTHESIS OF IDENTIFIABLE CHEMICAL IDENTIFIABLE CHEMICAL
MEDIATORSMEDIATORS
ProstaglandinsInterleukinsTumor necrosis factorNeurotransmitters / Neurohormones
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3.-PRODUCTION OF 3.-PRODUCTION OF AUTOIMMUNE RESPONSESAUTOIMMUNE RESPONSES
Auto-antibodies
Cross reactions
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4.- ACTIVATION OF 4.- ACTIVATION OF COAGULATION SYSTEM COAGULATION SYSTEM
FACTORSFACTORS
Increased Coagulation
Increased Fibrinolysis
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ECTOPIC HORMONE ECTOPIC HORMONE SYNDROMES IN NON-SYNDROMES IN NON-ENDOCRINE TUMORSENDOCRINE TUMORS
Hypercortisolism (Cushing`s sd.) A.C.T.H. Synthesis C.R.H. Synthesis Etiology: Lung cancer (small cell type) 50%
Carcinoid tumorThymomaBronchial adenoma (Benign neoplasia)Medullary thyroid carcinoma
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HypercalcemiaHypercalcemia
Without bone metastasis:
Prostaglandin synthesis (PGE2)
Interleukin 2-Osteoclast activating factor
P.T.H. secretion
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HYPERCALCEMIA HYPERCALCEMIA ETIOLOGYETIOLOGY
Multiple myelomaSolitary plasmocytomaLung cancerLeukemiaLymphoma (Hodgkin and Non-hodgkin)Breast cancerRenal carcinoma
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INAPPROPIATE SECRETION OF INAPPROPIATE SECRETION OF ANTIDIURETIC HORMONEANTIDIURETIC HORMONE
This particular syndrome “could be”associated with neoplasias and some pulmonary infections.
Etiology:Small cell carcinoma of the lungCarcinoid tumorPulmonary tuberculosisPneumonia ( Bacterial and viral)
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HypoglicemiaHypoglicemia
Ectopic insulin production Insulin “like” hormone production
(somatomedins). Etiology: Gastric carcinoma Uterine fibroma Uterine fibrosarcoma Retroperitoneal fibrosarcoma Neuroma
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SECRETION OF CHORIONIC SECRETION OF CHORIONIC GONADOTROPINGONADOTROPIN
Clinical features:Male: Female:
– Gynecomastia *Amenorrhea– Infertility *Menstrual disorders– Impotence (hyper-hypo)– False (+) pregnancy test *Infertility
*False (+)
pregnancy test
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SECRETION OF CHORIONIC SECRETION OF CHORIONIC GONADOTROPINGONADOTROPIN
Etiology:Lung carcinomaGastric carcinomaOvarian carcinomaPancreatic carcinomaHepatoma
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OTHER HORMONE OTHER HORMONE RELATED SYNDROMESRELATED SYNDROMES
T.S.H. Production Prolactin Growth hormone V.I.P. (Vasoactive intestinal polipeptide) Gastrin Bombesin Glucagon Erythropoietin
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NEUROMUSCULAR NEUROMUSCULAR PARANEOPLASTIC SYNDROMESPARANEOPLASTIC SYNDROMES
Myasthenia gravis: Thymoma
Mechanism: Auto-antibodies against the acetilcholine receptor at the “motor end” plate.
Myasthenic syndrome (Lambert eaton syndrome) Etiology: Small cell carcinoma of the lung Mechanism: Auto-antibodies against the calcium
channels on the motor nerve terminals, which interfere with the Ach release.
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CANCER ASSOCIATED CANCER ASSOCIATED RETINOPATHYRETINOPATHY
Etiology: Small cell carcinoma of the lung
Mechanism: Immunoglobulins against several polypeptide or protein antigens in the retinal and tumor cells. (Cross reaction)
Clinical picture: Proggressive loss of visual acuity
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CEREBELLAR CEREBELLAR DEGENERATIONDEGENERATION
Etiology: Small cell carcinoma of the lung• Ovarian cancer
• Mechanism: • 1.-Immunoglobulins that react
selectively with cerebellar purkinje cells.• 2.-Associated viral c.n.s. Infections• 3.-Side effects of chemotherapy
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PERIPHERAL NEUROPATHYPERIPHERAL NEUROPATHY
( 15% of all cancer patients) Sensory neuropathy
Motor neuropathy
Mixed
MECHANISM:
*Unknown
*Auto-antibodies against axonal components
*Side effects of chemotherapy
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HEMATOLOGIC PARANEOPLASTIC HEMATOLOGIC PARANEOPLASTIC SYNDROMESSYNDROMES
PolycytemiaHemolytic anemiaThrombocytopenic purpuraCoagulopathy
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POLYCYTEMIA POLYCYTEMIA ( ERYTHROCYTOSIS)( ERYTHROCYTOSIS)
Etiology: Cerebellar hemangioblastoma Uterine benign fibroma Pheochromocytoma Adrenocortical carcinoma Hepatoma / carcinoma Ovarian cancer Mechanism: Ectopic production of erythropoietin
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HEMOLYTIC ANEMIAHEMOLYTIC ANEMIA
Etiology:Lymphoid malignanciesLung carcinomaBreast cancerG.I. CarcinomaMechanism: Immune mediated hemolysis
(cross-reaction)
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PARANEOPLASTIC PARANEOPLASTIC COAGULOPATHIESCOAGULOPATHIES
Hypercoagulability (thrombosis Prone)
Etiology: Pancreatic carcinoma
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DISSEMINATED INTRAVASCULAR DISSEMINATED INTRAVASCULAR COAGULATION (D.I.C.)COAGULATION (D.I.C.)
Mucin producing adenocarcinomas (G.I. Tract)
Prostatic carcinomaAcute myeloblastic leukemia type IV
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BLEEDING TENDENCY (CLOTTING BLEEDING TENDENCY (CLOTTING FACTOR DEFFICIENCIES)FACTOR DEFFICIENCIES)
Lymphomas : Antibodies against clotting factors
Amiloid deposit: Factor “X” defficiency
Hepatic carcinoma : Deffective fibrinogen
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CAQUEXIA / MALNUTRITIONCAQUEXIA / MALNUTRITION
There are several mechanism proposed to explain the severe emaciation of patients with cancer.
Direct effect at G.I. Tract Obstruction of the lumen (dysphagia) <Gastric emptying with a fullness sensation <Gastric secretion /digestion <Small intestine digestion /absorption Increase Motility / secretion (GIP-VIP) Parasitic effect of the tumor
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ANOREXIA OF CANCER PATIENTSANOREXIA OF CANCER PATIENTS
Proposed mechanism are alterations in:Smell and taste, by altered glucose & A.A.
MetabolismSecretion of inhibitory peptidesCachectin substanceCancer treatment: Chemotherapy-
Radiotherapy-Surgery-Morphine
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FUNCTIONAL BEHAVIOR OF FUNCTIONAL BEHAVIOR OF NEOPLASMNEOPLASM
Functional tumors
Ectopic hormone syndromes
Paraneoplastic syndromes
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HORMONE AND HORMONE-LIKE HORMONE AND HORMONE-LIKE PRODUCTIONPRODUCTION
Thyroid Ca. Hypo /hyperthyroidismAdrenal Ca. Hypo/HypercortisolismPituitary tumors Prolactin, growth h.Pancreatic Ca. Insulinoma,
Gastrinoma VIPomaOvarian Ca. Hypo/Hyperestrogen. Testicular cancer Hyperandrogenism,
Precocious puberty
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