Chapter 7 Neoplasia 1 Introduction a Neo new Plasia growth b Tumor i Any abnormal cell growth ii Malignant cancer altered cellular gene expression iii Benign 2 Benign vs Malignant Tumors a Malignant i Possibly fatal if untreated because of the actual tumor ii iii Anaplasia lacks differentiation it doesn t look like normal cells Invasion dissemination metastases anymore iv Rapid growth angiogenesis necrotic dysfunctional tissue v Carcinoma epithelial vi Sarcoma mesenchymal vii Leukemia WBC b Benign room i Life threatening if compressive or obstructive if it takes up too much ii Local noninvasive encapsulated iii Well differentiated doesn t invade adjacent tissue iv Slow growth v oma 3 Cancer Cell Characteristics Insensitive to growth inhibitory signals evade apoptosis a Autonomous proliferate without growth signals independent of everything b c Unlimited replication d Genetically unstable rapid accumulation of mutations too rapid too many replications e Lose differentiated features lose tissue function f g Angiogenesis 4 Cancer Epidemiology Invade local tissue malignant cells migrate and metastasize a Cancer is the 2nd leading cause of death in the U S i 25 of general population ii 77 of population over 55 years iii Risk men 1 2 women 1 3 b 66 5 year survival rate 5 Cancer Epidemiology CDC 6 Cancer Risk Factors a Lifestyle factors 40 50 of deaths of cancer due to lifestyle choices preventable and avoidable cancers i Contribute 1 3 of cancer related deaths ii Tobacco iii Nutrition high fat low fiber high alcohol low antioxidants iv Obesity v Sun exposure vi HPV STD normal contact with a patient can spread to health care workers it does not have to always be sexually HPV can cross condoms so abstinence is the only way to 100 prevent contracting HPV One type of strain causes cauliflower type of looking warts that protrude out of the vagina for females and out of the anus for males A different strain can cause cancers cervical pharyngeal oral sex and penile 1 HIV does not always cross condoms so it is considered condom safe but should be discussed and agreed upon with your partner b Early screening early detection 7 Genetic Mechanisms of Cancer a Carcinogens potential cancer causing agents i carcin o cancer ii gens creating b Proto oncogene gain of function mutation normal genes physiological code for signals factors we need them They contribute for cellular growth If they are overexpressed it means they have gain too much expression and hyperactivate These become oncogenes which are abnormal and cause cancer i Oncogenes overactive proto oncogene mutations of proto 1 Retrovirus HIV c Tumor suppressor gene loss of function mutation initiate apoptosis the genes must be there for it to occur if not there than apoptosis cant occur and cells will accumulate So they are normally suppose to be there if not then they are deficient or defective 8 Genetic Mechanisms of Cancer a Proto oncogenes i Normal genes that are transformed into oncogenes by activating mutations ii Proto oncogenes normally code for growth factors mitogens growth factor receptors cytoplasmic signaling pathways nuclear transcription factors 9 Genetic Mechanisms of Cancer a Oncogenes i Mutations alter proto oncogene activity by abnormally enhancing proliferation promoting signals forming activated oncogenes ii 4 paths of activation Intracellular proto oncogene suffers mutagenic event 1 Oncogenes introduced into host by retrovirus 2 3 Abnormal proto oncogene activation via DNA loss damage 4 Chromosome replication errors form extra copies of proto oncogenes amplification produce more and wont stop b Tumor suppressor genes i Contribute to physiological inhibitory pathways ii Cancer develops when both maternal and paternal copies are defective chromosomal deletions point mutations chromosomal nondisjunction iii Rb gene p53 BRCA 1 BRCA 2 1 Rb Gene causes retinal blastoma tumor in the retina of the eye 2 P53 breast colon cancers a BRCA 1 2 breast cancer affect both male and female being more severe in males Also causes ovarian cancer in females too which can lead to both a hysterectomy and a mastectomy in that affected female 10 Multistep Nature of Carcinogenesis a Initiation start of production of dysplastic or anaplastic cells i Initiating events inappropriately activate proto oncogenes and inactivate tumor suppressor genes ii Carcinogens complete partial 1 Partial needs to be combined with some other factor tendency to be combined with tumor genetic suppressor gene or environment a Ex You have the partial gene and add in a bad lifestyle diet cancer 2 Complete inherit the right mutation to form cancer a Inherit colon cancer b Promotion actual growth of the tumor growing a clump of cancerous cells replicating No signs or symptoms in the body yet i Mutant cell proliferation ii Proliferation essential for cancer development iii Results from activation of other oncogenes inactivation of tumor suppressor genes iv Promoters nutritional factors infections hormones c Progression start seeing cancer in the body Signs and symptoms weight loss fatigue pain cough phenotype i Proliferating mutant cells begin to exhibit malignant behavior ii Cells whose phenotype gives them a growth advantage proliferate more readily iii Most malignant cells synthesize telomerase to repair chromosomal telomere thereby achieving immortality 11 Metastasis not just to adjacent tissues but to distant tissues too a Process whereby cancer cells migrate from tissue of origin to form new malignant cell colonies in distant sites b Enzymes digest basement membranes to allow movement through the membranes c Ex Lung cancer growth the in the lung is the primary tumor growth if dislodged into the bloodstream or lymph it can travel to spleen liver vertebral column etc and cause secondary tumor 12 Metastasis Patterns of Spread a Cancer cell dissemination via blood lymph i Not all cells survive migration due to immune response b Tumor markers tags labels States where the cancer originated from Each cancer has their own marker As the cancer grows tumor marker grows i Enzymes proteins specific to a certain cell type ii Help identify tissue type of primary tumor for diagnostic purposes and to iii Rely on the fact that metastasized tissue retain some characteristics of track tumor activity primary tumor iv Released into circulation or used for biopsies v TAGS TO KNOW 1 CEA Tag tumor marker specific to colon cancer 2 AFP liver cancer 3 CA 125 ovarian cancer 13 Angiogenesis in