Module 8b 0 Immune System Flashcards

Question

What is the cause of tumor development?

Answer 1

• DNA abnormalities- lead to abnormal protein production • Mutations caused by exogenous and endogenous stimuli • Epigenetic changes- nongenetic influences on gene expression • A genetic change in the DNA leads to tumor growth development • Can be internal, external (viral), or inherited

Answer 2

Carcinoma • Refer to cancers that originate from epithelial tissue or cells that line glands • Skin/Epidermis, Glands, Intestines, Bronchus, Breast, Prostate, Pancreas, Thyroid, Kidney, Testis, Ovary, Adrenals, Liver, Cervix • 1. Adenocarcinomas • Form from glands (breast, prostate, ovary, colon, pancreas) • 2. Squamous Cell Carcinoma • Form epithelial tissue Lymphomas • Refer to cancers that originate from lymph tissue or blood cells • Lymphoma Cancers (lymph tissue) • Hodgkin Lymphoma • Non-Hodgkin Lymphoma • Leukemia Cancers (blood cells) • Acute myeloid (or myelogenous) leukemia (AML) • Chronic myeloid (or myelogenous) leukemia (CML) • Acute lymphocytic (or lymphoblastic) leukemia (ALL) • Chronic lymphocytic leukemia (CLL) Sarcoma • Refer to cancers that originate from connective tissue • Osteosarcoma (bone) • Chondrosarcoma (cartilage) • Synovial cell sarcoma (joint) • Liposarcoma (fat) • Angiosarcoma (blood vessel) • Rhabdomyosarcoma (skeletal muscle)

Answer 3

Hallmark Characteristics of Cancer • 1. Self-sufficiency in growth signals • 2. Insensitivity to growth-inhibitory signals • 3. Altered cellular metabolism • 4. Evasion of apoptosis • 5. Limitless replicative potential (immortality) • 6. Sustained angiogenesis • 7. Invasion and metastasis • 8. Evasion of immune surveillance

Answer 4

• Weight loss without lifestyle changes • Pain that doesn’t resolve with OTC • Pain at night • Fatigue • Changes in other physiological processes (GI, bowel movements, urination) • Depend on organ/area involved

Answer 5

D. Pain that is relieved with pain medications

Answer 6

D. Adenocarcinoma

Answer 7

Neoplasm (Tumor) • Abnormal growth of tissue in which the proliferation of cells is uncontrolled and progressive • Can be benign or malignant

Answer 8

• Benign (not cancer) • Malignant (cancer)

Answer 9

• A classification of malignant tumors that are caused by an uncontrolled division of abnormal cells in a part of the body that have the potential to invade or spread to other areas of the body

Answer 10

• Benign Tumors Appearance • NOT CLASSIFIED AS CANCEROUS • Encapsulated* • Does not invade surrounding tissues and structures • Cells still resemble normal cells form and function • Do not metastasize • Are not life threatening unless pressing upon an organ structure

Answer 11

• Malignant Tumors Appearance • CLASSIFIED AS CANCEROUS • Non-encapsulated • Invade surrounding tissues and structures • Cells do not resemble normal cells form and function • Metastasize to other areas of the body • Life threatening

Answer 12

• 1. Differentiation and anaplasia • 2. Rate of growth • 3. Local invasion • 4. Metastasis

Answer 13

• Functional tissue of an organ as distinguished from the connective and supporting tissue

Answer 14

• Supportive tissue of an organ consisting of connective tissues and blood vessels

Answer 15

• Seen only in the parenchymal cells • Differentiation refers to the extent to which they resemble their normal anatomy and physiology status Benign • Composed of well-differentiated cells Malignant • Characterized by a wide range of parenchymal cell differentiation, from well that closely resemble their normal differentiated to completely undifferentiated counterparts • Malignant neoplasms that are composed of undifferentiated cells are said to be anaplastic • Lack of differentiation, or anaplasia, is considered a hallmark of malignancy • The term anaplasia literally means “backward formation”—implying dedifferentiation, or loss of the structural and functional differentiation of normal cells

Answer 16

• Pleomorphism • Variation in size and shape • Nuclei are extremely hyperchromatic (dark-staining), large, variable and bizarre in size and shape • Fail to develop recognizable patterns of orientation to one another • The more rapidly growing and the more anaplastic a tumor, the less likely it is to have specialized functional activity

Answer 17

• Alteration in size, shape, and organization of adult cells

Answer 18

• Loss of differentiation of cells and of their orientation to one another • An extremely advance form of dysplasia

Answer 19

• There are always exceptions, but in general benign tumors grow slowly and malignant tumors grow rapidly • Malignant tumors are immortal and have limitless proliferative capacity, indicating that like normal tissues, they also must contain cells with “stemlike” properties • Henrietta Lacks Benign • Commonly grow slowly • Grow slowly over a period of months to years Malignant • Commonly grow fast, invade local tissue, and can even metastasize • Rate is correlated inversely with their level of differentiation • Poorly differentiated tumors grow much faster than well differentiated cells

Answer 20

• In general, benign tumors remain localized while malignant tumors can metastasize to other areas of the body Benign • Remains localized at site of origin • Commonly are encapsulated • Does not have the capability to infiltrate, invade, or metastasize Malignant • Grow by progressive infiltration, invasion, destruction, and penetration of surrounding tissue • Do not develop well defined capsules • Surgical pathologists carefully examine the margins of resected tumors to ensure that they are devoid of cancer cells (clean margins) • Next to the development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumors

Answer 21

• Secondary implants of a tumor that are discontinuous with the primary tumor and located in remote tissues • Only malignant tumors can undergo metastasis Benign • Do not undergo metastasis Malignant • More than any other attribute, the property of metastasis identifies a neoplasm as malignant • Not all cancers have equivalent ability to metastasize • Some hardly metastasis and other metastasis right away during growth • The more anaplastic and larger the primary neoplasm, the more likely is metastatic spread

Answer 22

• B. Malignant tumors are encapsulated

Answer 23

D. All the options are true

Answer 24

The study (scientific, systematic, and data-driven) of the distribution (frequency, pattern) and determinants (causes, risk factors) of health-related states and events (not just diseases) in specified populations (neighborhood, school, city, state, country, global).

Answer 25

Geographic differences in death rates from specific forms of cancer • Death rates from breast cancer are about four to five times higher in the United States and Europe than in Japan • Conversely, the death rate for stomach carcinoma in men and women is about seven times higher in Japan than in the United States

Answer 26

• Environmental factors are the predominant cause of the most common sporadic cancers • Infectious agents, smoking, alcohol consumption, diet, obesity, reproductive history, environmental carcinogens • Infectious Agents • Cause of about 15% of cancers worldwide • Human papillomavirus (HPV) • A lot of other virus have correlations with specific cancers • Enough with your crap, viruses! • Smoking • Single most important environmental factor contributing to premature death in the United States • Smoking, particularly of cigarettes, is implicated in cancer of the mouth, pharynx, larynx, esophagus, pancreas, and bladder and, most significantly, in about 90% of lung cancers • Alcohol Consumption • Increases the risk of carcinoma of the oropharynx, larynx, and esophagus and, by the development of alcoholic cirrhosis, hepatocellular carcinoma • Diet • Precise dietary factors that affect cancer risk remain a matter of debate, there are a lot of correlations of diet and specific cancers • Obesity • In the U.S. population have 52% (men) to 62% (women) higher death rates from cancer compared to individuals who are not categorized as overweight or obese • Reproductive History • Lifelong cumulative exposure to estrogen stimulation, particularly if unopposed by progesterone, increases the risk of cancers of the breast and endometrium, tissues that are responsive to these hormones • Carcinogens • Any substance capable of causing cancer in living tissue • Don’t freak out- but there are carcinogens all around you • Home, Occupation, water, sun

Answer 27

• Most carcinomas occur in adults older than 55 years of age • Cancer is the leading cause of death among women aged 40 to 79 and among men aged 60 to 79 • Decline in cancer deaths after age 80 is due to the lower number of individuals who reach this age • Cancer causes slightly more than 10% of all deaths among children younger than 15 years

Answer 28

• Most cancers have environmental and genetic etiology • Hereditary forms of cancer can be divided into three categories based on their pattern of inheritance: 1. Autosomal Dominant Cancer • Inheritance of a single mutant gene greatly increases the risk of developing a tumor 2. Autosomal Recessive Syndromes of Defective DNA Repair • Predisposition to these tumors shows an autosomal recessive pattern of inheritance 3. Familial Cancers of Uncertain Inheritance • Features that characterize familial cancers include early age at onset, tumors arising in two or more close relatives of the index case, and sometimes multiple or bilateral tumors

Answer 29

• Precancerous Conditions • Referred to as preneoplastic lesions or precancer • Condition or lesion that involves abnormal cells which have an associated risk with developing cancer Examples • Squamous metaplasia and dysplasia of the bronchial mucosa • Seen in habitual smokers—a risk factor for lung cancer • Endometrial hyperplasia and dysplasia • Seen in women with unopposed estrogenic stimulation—a risk factor for endometrial carcinoma

Answer 30

A. Carcinogens only pertain to environmental toxins

Answer 31

1. Genes that promote cell growth ( Proto-Oncogenes) 2. Genes that inhibit growth ( Tumor Suppressor Genes) 3. Genes that regulate apoptosis 4. Genes that regulate DNA Repair

Answer 32

Mutations of proto-oncogenes

Answer 33

Proto-Oncogenes: Growth Promoting • Group of genes that produce proteins that regulate cell growth, division, differentiation • Ras, HER2, Cyclin D • Mutations of proto-oncogenes are referred to as: ONCOGENES Tumor Suppressor Genes: Growth Inhibiting • Group of genes that slow down cell division allow for DNA repair • p53, Rb, p21, and BRCA1/BRCA2 • Mutated p53 genes have been identified in more than one-half of all human tumor cells

Answer 34

Proto-Oncogenes: Growth Promoting Tumor Suppressor Genes: Growth Inhibiting

Answer 35

• Changes in the way genes are switched on and off without changing the actual DNA sequence • No mutations • Two types: DNA Methylation and Histone Modifications • These changes can affect a person’s risk of disease and may be passed from parents to their children • How is this important?

Answer 36

The role of G1, G2, and metaphase checkpoints is a stopping point to assure everything looks good. Without those checkpoints you lose the capability of actually checking to see if the DNA was replicated correctly. Need cyclin proteins present to proceed with cell cycle steps • Inhibit proteins that block DNA synthesis or replication from occurring • Promote the production of proteins that are needed for mitosis G1 Checkpoint • Are internal/external factors good for replication • CDK4-Cyclin D activates the Rb (retinoblastoma) protein • When Rb is activated, it CANNOT inhibit DNA replication G2 Checkpoint • Was replication completed? • Check for DNA damage Metaphase Checkpoint • Chromosomal attachment to spindles?

Answer 37

Cyclin Dependent Kinases (CDKs) • Always present in an inactive form • Need to be activated by a specific cyclin Cyclin • Proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes These two bind together to form CDK-Cyclin molecules • Become activated to regulate cell cycle steps

Answer 38

Tumor Heterogeneity • Tumor cells are actually very diverse • Once tumor cells start to replicate, they undergo Darwinian selection Tumor Progression • Over a period of time tumors can become more aggressive and acquire greater malignant potential • Basically, tumor cells evolve as they grow by immune and nonimmune selection pressures Genetic evolution and selection can explain two of the most main properties of cancers: • 1. Become more aggressive • 2. Less responsive to therapy over time

Answer 39

B. Proto-oncogenes are mutated oncogenes that can lead to cancer

Answer 40

• Any cancer-producing substance; often a distinction is made between epigenetic and genotoxic carcinogens

Answer 41

• Altering the activity of DNA gene expression without changing the DNA sequence

Answer 42

• Damage to the DNA changing the DNA sequence

Answer 43

• Chemicals • Radiant energy • Microbial agent

Answer 44

Direct-Acting Agents • Require no metabolic conversion to become carcinogenic • Can be chemotherapeutic drugs Indirect-Acting Agents • Chemicals that require metabolic conversion to become a carcinogen

Answer 45

Radiant energy is high intensity energy transferred by electromagnetic radiation Source of Energy • Ultraviolet Radiation • X-Rays • Nuclear Fission • Radiation Therapy Leads to severe DNA damage and mutations

Answer 46

• Oncogenic DNA Viruses (Four Main Types) • Human papillomavirus (HPV) • Epstein-Barr virus (EBV) • Kaposi sarcoma herpesvirus (KSHV) • Hepatitis B virus (HBV) • Epstein-Barr Virus (EBV) • The first virus linked to a human tumor: Burkitt lymphoma • Discovered with the cells of a surprisingly diverse list of cancers including various lymphomas (Hodgkin lymphoma), nasopharyngeal carcinoma, gastric carcinomas • Causes infectious mononucleosis (mono) • Spreads through direct contact from an infected person (bodily fluids) Kaposi Sarcoma Herpesvirus (KSHV) • Also known as human herpesvirus 8 (HHV8) • Causes Kaposi sarcoma — Cancer of the soft tissues of connective tissues — Associated with what condition?

Answer 47

Human Papillomavirus (HPV) • Numerous strains of this virus- each having different effects on body — Benign and Malignant tumors • Some cause benign squamous papillomas (warts) tumors • Others cause several cancers — Squamous cell carcinoma of the cervix and anogenital region • Sexual and physical contact is an ability to contract it

Answer 48

Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) • Epidemiologic evidence linking chronic HBV and HCV infection with hepatocellular carcinoma is strong — Estimated that 70% to 85% of hepatocellular carcinomas worldwide are due to infection with HBV or HCV • Hepatitis B virus contraction occurs when blood, semen, or other body fluid infected with the hepatitis B virus enters the body of someone who is not infected — Even a toothbrush- gross, don’t share your toothbrush • Hepatitis C virus contraction occurs with contact of infected blood

Answer 49

E. All of the options are a possible source of a carcinogen

Answer 50

B. Hepatitis viruses

Answer 51

1. Self-sufficiency in growth signals 2. Insensitivity to growth-inhibitory signals 3. Altered cellular metabolism 4. Evasion of apoptosis 5. Limitless replicative potential (immortality) 6. Sustained angiogenesis 7. Invasion and metastasis 8. Evasion of immune surveillance

Answer 52

• Starts with the development of genetic and epigenetic alterations These hallmarks can be accelerated by • 1. Cancer Promoting Inflammation • 2. Genomic Instability Considered enabling characteristics • Promote cellular transformation and subsequent tumor progression

Answer 53

CANCER PROMOTING INFLAMMATION • Cancer cells hijack inflammatory mechanisms to promote their own growth and survival • Form an Inflammatory Tumor Microenvironment (TME) — Initiates carcinogenesis and involved with the hallmarks of cancer

Answer 54

Inflammatory Tumor Microenvironment (TME) Leads To: • Release of factors that promote proliferation • Removal of growth suppressors • Enhanced resistance to cell death • Angiogenesis

Answer 55

B. Increases growth suppressor molecules

Answer 56

Self-sufficiency in growth that characterizes cancer cells generally stems from mutations that convert proto-oncogenes to oncogenes • Oncogenes encode proteins called oncoproteins • Promote cell growth, even in the absence of normal growth-promoting signals Normal cells require stimulation by growth factors to undergo proliferation • Various factors that can be altered that lead to cancer cells to become self-sufficient with growth 1. Growth Factors • A) Acquire the ability to synthesize own growth factors • B) Acquire the ability to stimulate the ECM to produce growth factors 2. Growth Factor Receptors • A) Up-regulation of growth factor receptors 3. Downstream Signal-Transducing Proteins • A) Mutations can lead to overactivation of secondary messenger system to stimulate growth

Answer 57

Oncogenes encode proteins

Answer 58

Oncogenes encode proteins

Answer 59

• Mutated RAS leads to a continuous signal to the nucleus for cell proliferation — Despite external signals or stimuli

Answer 60

ABL • Forms the BRC-ABL protein that activates all of the signals that are downstream of RAS • Potent stimulator of cell growth • Associated with Leukemia formation (NBCE loves this)

Answer 61

• Mutations in genes regulating these checkpoints allow cells with damaged DNA to divide, producing daughter cells carrying mutations

Answer 62

• Tumor suppressor genes apply brakes to cell proliferation Tumor Suppressor Genes create antigrowth signals can • Prevent cell proliferation by several complementary mechanisms

Answer 63

Two Major Tumor Suppressor Genes • RB (Retinoblastoma) Gene: Governor of the Cell Cycle • Produces Rb protein • TP53 Gene: Guardian of the Galaxy Genome • Produces the p53 protein Two Other Well Known Tumor Suppressor Genes • BRCA 1 (BReast CAncer gene 1) • BRCA 2 (BReast CAncer gene 2) • These genes help keep breast, ovarian, and other types of cells from growing and dividing too rapidly or in an uncontrolled way

Answer 64

• RB (Retinoblastoma) Gene: Governor of the Cell Cycle • Produces Rb protein • TP53 Gene: Guardian of the Galaxy Genome • Produces the p53 protein

Answer 65

• Mutations of RB gene is found in breast cancer, small cell cancer of the lung, and bladder cancer • Regulation of the G 1/S checkpoint- cells must pass before DNA replication commences — Reviews external “cues” • Inactive form prevents cell growth by inhibiting cell cycle progression until a cell is ready to divide • Rb active form: hyperphosphorylated state and allows cell cycle progress

Answer 66

• Abnormal Rb protein- always in activated state • ALWAYS ALLOWS CELL TO PROGRESS THROUGH THE G1/S checkpoint — Increase of cyclin-CDK complexes — Loss of CDKIs • HPV binds to the hyperphosphorylated state of Rb — Preventing it it from inhibiting the E2F transcription factors

Answer 67

The p53 protein prevents neoplastic transformation by three interlocking mechanisms: • Activation of temporary cell cycle arrest (termed quiescence) • Induction of permanent cell cycle arrest (termed senescence) • Triggering of programmed cell death (termed apoptosis) • Activates DNA repair • Arrest growth by holding the cell cycle at the G1/S regulation point on DNA damage recognition — Gives cell time to repair itself • Initiate apoptosis — Irreversible DNA damage • Initiate senescence — Short telomeres, morphological changes

Answer 68

B. Stimulates downstream signaling to stimulate the nucleus to proceed with cell proliferation

Answer 69

A. It could allow the cell to progress through cell proliferation with DNA damage

Answer 70

C. Focuses strictly on level of cellular differentiation

Answer 71

C. Commonly associated with bone cancers