Biology of Cancer.ppt

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1、1,Biology of Cancer,Chapter 11,2,Cancer,Derived from Greek word for crab, karkinoma Malignant tumor Tumor Also referred to as a neoplasmnew growth,3,Benign vs. Malignant Tumors,4,Classification and Nomenclature,Benign tumors Named according to the tissues from which they arise, and include the suffi

2、x “oma” Lipoma Glioma Leiomyoma Chondroma,5,Classification and Nomenclature,Malignant tumors Named according to the tissues from which they arise Malignant epithelial tumors are referred to as carcinomas Adenocarcinoma and basal cell carcinoma Malignant connective tissue tumors are referred to as sa

3、rcomas Chondrosarcoma and osteosarcoma,6,Classification and Nomenclature,Cancers of lymphatic tissue are lymphomas Cancers of blood-forming cells are leukemias Carcinoma in situ (CIS) Pre-invasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement

4、 membrane or invaded the surrounding stroma,7,Classification and Nomenclature,8,Classification and Nomenclature,9,Cancer Cells,Transformation Cancer cells independence from normal cellular controls Anchorage independent Immortal Anaplasia Pleomorphic,10,Cancer Stem Cells,Stem cells self-renew Cell d

5、ivisions create new stem cells Stem cells are multipotent Ability to differentiate into multiple different cell types,11,Cancer Stem Cells,12,Cancer Stem Cells,13,Tumor Markers,Tumor cell markers (biological markers) are substances produced by cancer cells or that are found on plasma cell membranes,

6、 in the blood, CSF, or urine Hormones Enzymes Genes Antigens Antibodies,14,Tumor Markers,Tumor markers are used to: Screen and identify individuals at high risk for cancer Diagnose specific types of tumors Observe clinical course of cancer,15,Cancer-Causing Mutations,Cancer is predominantly a diseas

7、e of aging Clonal proliferation or expansion Due to a mutation, a cell acquires characteristics that allow it to have selective advantage over its neighbors Increased growth rate or decreased apoptosis Multiple mutations are required before cancer can develop,16,Cancer-Causing Mutations,17,Types of

8、Mutated Genes,Secretion of growth factors (autocrine stimulation) Increased growth factor receptors Signal from cell-surface receptor is mutated in the “on” position Mutation in the ras intracellular signaling protein Inactivation of Rb tumor suppressor Activation of protein kinases that drive the c

9、ell cycle Mutation in the p53 gene,18,Types of Mutated Genes,19,Angiogenesis,Growth of new vessels Advanced cancers can secrete angiogenic factors,20,Hallmarks of Cancer,21,Telomeres and Immorality,Body cells are not immortal and can only divide a limited number of times Telomeres are protective cap

10、s on each chromosome and are held in place by telomerase Telomeres become smaller and smaller with each cell division,22,Telomeres and Immorality,23,Oncogenes and Tumor-Suppressor Genes,Oncogenes Mutant genes that in their nonmutant state direct protein synthesis and cellular growth Tumor-suppressor

11、 genes Encode proteins that in their normal state negatively regulate proliferation Also referred to as anti-oncogenes Proto-oncogene A normal, nonmutant gene that codes for cellular growth,24,Mutation of Normal Genes,Point mutations Changes in one or a few nucleotide base pairs Chromosome transloca

12、tion A piece on one chromosome is transferred to another Gene amplification Duplication of a small piece of chromosome over and over Results in an increased expression of an oncogene,25,Mutation of Normal Genes,26,Mutation of Normal Genes,27,Mutation of Normal Genes,Mutation of tumor-suppressor gene

13、s Allows unregulated cellular growth Loss of heterozygosity Both chromosome copies of a gene are inactivated Gene silencing Whole regions of chromosomes are shut off while the same regions in other cells remain active,28,Mutation of Normal Genes,29,Mutation of Normal Genes,Caretaker genes Encode for

14、 proteins that are involved in repairing damaged DNA Chromosome instability Increased in malignant cells Results in chromosome loss, loss of heterozygosity, and chromosome amplification,30,Inflammation and Cancer,Chronic inflammation is an important factor in the development of cancer Cytokine relea

15、se from inflammatory cells Free radicals Mutation promotion Decreased response to DNA damage,31,Genetics and Cancer,Exposure to mutagens If the mutation occurs in somatic cells, it is not passed to progeny If the mutation occurs in germline cells, it can be passed to future generations,32,Viruses an

16、d Cancer,Implicated Hepatitis B and C viruses Epstein-Barr virus (EBV) Kaposi sarcoma herpesvirus (KSHV) Human papillomavirus (HPV) Human T cell leukemialymphoma virus (HTLV),33,Bacterial Cause of Cancer,Helicobacter pylori Chronic infections are associated with: Peptic ulcer disease Stomach carcino

17、ma Mucosa-associated lymphoid tissue lymphomas,34,Environmental Risk Factors,Tobacco Multipotent carcinogenic mixture Linked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia,35,Environmental Risk Factors,Ionizing radiation

18、Emission from x-rays, radioisotopes, and other radioactive sources Exposure causes cell death, gene mutations, and chromosome aberrations Bystander effects Poor gene repair Changes in gap junction intercellular communication,36,Ionizing Radiation,37,Environmental Risk Factors,Ultraviolet radiation C

19、auses basal cell carcinoma, squamous cell carcinoma, and melanoma Principal source is sunlight Ultraviolet A (UVA) and ultraviolet B (UVB) Promotes skin inflammation and release of free radicals,38,Environmental Risk Factors,Alcohol consumption Risk factor for oral cavity, pharynx, hypopharynx, lary

20、nx, esophagus, and liver cancers Cigarette/alcohol combination increases a persons risk,39,Environmental Risk Factors,Sexual reproductive behavior Carcinogenic types of human papillomavirus High-risk HPV Physical activity Reduces cancer risk Decreases insulin and insulin-like growth factors Decrease

21、s obesity Decreases inflammatory mediators and free radicals Increased gut motility,40,Environmental Risk Factors,Occupational hazards Substantial number of occupational carcinogenic agents Asbestos Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc. Radon,41,Environmen

22、tal Risk Factors,Electromagnetic fields Carcinogenic? Are they, or arent they?,42,Environmental Risk Factors,Diet Xenobiotics Toxic, mutagenic, and carcinogenic chemicals in food Activated by Phase I activation enzymes Defense mechanisms Phase II detoxification enzymes Examples Compounds produced in

23、 the cooking of fat, meat, or proteins Alkaloids or mold by-products,43,Environmental Risk Factors,Obesity Correlates with the body mass index (BMI) Adipose tissue is active endocrine and metabolic tissue In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids Increased free fatty acids gives rise to insulin resistance and causes chronic hyperinsulinemia Correlates with colon, breast, pancreatic, and endometrial cancers,