Block 3 - Integrated

Front 1

Clonality

Back 1

the entire population of cells within a neoplasm arises from a single cell
- assessed by examining cells in women who are heterozygous for polymorphic X-linked markers (G6PDH)

Front 2

Choristoma (Heterotopia)

Back 2

an ectopic rest of normal tissue
ex. neural tissue in the scalp

Front 3

Hamartoma

Back 3

a mass of disorganized but mature specialized cells indigenous to a particular site
- developmental abnormalities but not neoplasms

Front 4

Benign Neoplasms

Back 4

() cohesive, expansile masses
() remain localized to site of origin
() well differentiated
() slow growth

Front 5

Malignant Neoplasms

Back 5

() invasive
() poorly differentiated or undifferentiated
() may grow rapidly
() 'cancer'

Front 6

Desmoplasia

Back 6

the formation of an abundant collagenous stroma in response to tumor growth and invasion

Front 7

Differentiation

Back 7

the extent to which neoplastic cells resemble comparable normal cells

Front 8

Anaplasia

Back 8

lack of differentiation

Front 9

Morphologic Features of Malignant Neoplasms

Back 9

() pleomorphism - variation in cell size and shape
() abnormal nuclear morphology - hyperchromasia and inc. nuclear size
() mitoses - b/c rapidly dividing
() loss of cell polarity
() tumor giant cells
() necrosis - b/c they outgrow their blood supply

Front 10

Dysplasia

Back 10

() disordered growth
() falls short of malignancy - no invasion
() loss of cell uniformity and architecture
() full-thickness dysplasia = carcinoma in-situ
() may progress to cancer

Front 11

Metastasis

Back 11

tumor implant that is discontinuous w/ the primary tumor

Front 12

Direct seeding

Back 12

penetration of tumor into a natural open space (peritoneal, pleural, pericardial cavities..)

Front 13

Lymphatic spread

Back 13

epithelial malignancies

Front 14

Hematogenous spread

Back 14

mesenchymal malignancies

Front 15

Adenoma

Back 15

benign epithelial neoplasm

Front 16

Carcinoma

Back 16

malignant epithelial neoplasm

Front 17

Mesenchymal neoplasms

Back 17

() Benign - end in -oma
() Malignant - end in -sarcoma

Front 18

Teratoma

Back 18

germ cell tumors

Front 19

-blastomas

Back 19

embryonal tumors
tumors of children, derived from immature cells

Front 20

Wilms tumor (kidney)
Ewing sarcoma (bone)

Back 20

Wilms tumor (kidney)
Ewing sarcoma (bone)

Front 21

Grade

Back 21

expression of the level of differentiation of a malignant neoplasm (G I-G IV)
the better differentiated the tumor (G I) the better the prognosis
grade correlates with the aggressiveness of the neoplasm

Front 22

Stage

Back 22

extent of size and spread of cancer within the patient.
the lower the stage, the better the prognosis
stage dictates therapy

Front 23

TNM system

Back 23

For staging:
T = primary tumor size and extent of invasion
N = regional lymph node involvement
M = metastases

looks at size, spread, and metastases

Front 24

Fine-needle aspiration (FNA)
*can't tell if lesion is invasive or not

Back 24

used most commonly for readily palpable lesions (thyroid, lymph nodes)

Front 25

Is the prognosis for a receptor-positive tumor better or worse?

Back 25

better prognosis

Front 26

How many mutations are usually needed for a cell to be transformed into a cancer cell?

Back 26

a minimum of 5 or 6

Front 27

7 Critical features common to different cancers

Back 27

() they stimulate their own growth
() they ignore growth-inhibiting signals
() they avoid death by apoptosis
() they develop a blood supply: angiogenesis
() they metastasize
() they replicate continuously
() they evade or outrun the immune response

Front 28

Tumor rejection Ag's

Back 28

specific to individual tumors and prevent infections transfer of tumors from one individual to another

Front 29

Tumor specific Ag's

Back 29

peptides from mutated cellular 'self' proteins, will then be recognized as being foreign rather than self

Front 30

Tumor associated Ag's

Back 30

arise by reactivation of embryonic genes or by overexpression of normal self proteins

Front 31

3 Mechanisms by which tumors escape immune recognition:

Back 31

1) low immunogenecity - no MHCs, adhesion molecules, or co-stimulatory molecules
2) antigenic modulation - immune selection of Ag-loss variants
3) tumor-induced immune suppression - factors secreted by the tumor (TGFb) inhibit T cells directly* (most effective)

Front 32

3 Mechanisms by which tumors escape immune recognition:

Back 32

1) LOW IMMUNOGENICITY - no MHCs, adhesion molecules, or co-stimulatory molecules
2) ANTIGENIC MODULATION - immune selection of Ag-loss variants
3) TUMOR-INDUCED IMMUNE SUPPRESSION - factors secreted by tumor cells (TGFb) inhibit T cells directly* (most effective)

Front 33

What percent of lung cancers are associated w/ smoking?

Back 33

90%
*smoking is associated w/ depression

Front 34

Common Serum Tumor Markers:

Back 34

() Prostate Specific Ag (PSA) - for prostate cancer
() Carcinoembryonic Ag (CEA) - for colorectal and pancreatic cancers
() Ca-125 - for ovarian cancer

Front 35

Neoplasm

Back 35

an abnormal tissue mass whose growth exceeds and is uncoordinated with that of adjacent normal tissue and persists after cessation of the stimuli that provoked it

Front 36

General progression of breast cancer:

Back 36

Normal breast --> Atypical hyperplasia (lobar or ductal) --> carcinoma in situ --> invasive breast cancer --> metastatic breast cancer

Front 37

Carcinoma in situ

Back 37

full-thickness dysplasia extending from the BM to the surface epithelium.
applicable only to epithelial neoplasms.
if entire lesion is CIS then risk of metastasis = 0 (b/c no blood vessels above the BM)

Front 38

Gross Features of Malignancy:

Back 38

() Irregular borders
() Necrosis
() Metastasis

Front 39

Disruption of what molecular structure serves as a hallmark for transformation?

Back 39

disruption of actin filaments
allows for tumor migration and metastasis

Front 40

What characteristic will be seen with hematogenous spread?

Back 40

venous invasion of a sarcoma following the venous drainage from the site of the tumor

Front 41

Where do each of the following cancers tend to spread? Breast, Prostate, Colon

Back 41

Breast --> lungs
Prostate --> bone
Colon --> liver and pancreas

Front 42

Where do most genetic changes happen in the development of cancer?

Back 42

@ the transition from a normal cell --> atypical hyperplasia
*very early

Front 43

Promotion of progression to invasive breast carcinoma:

Back 43

Survival when invasive cells separate from the tumor mass
Increased resistance to apoptosis or anoikis
Increased motility
Ability to form motility structures such as lamellipodia, filopodia, membrane ruffles
Ability to relax the constraints of the actin-based cytoskeleton
Ability to activate signals that regulate focal adhesion/contacts
Increased invasive potential
Ability to form podosomes or invadopodia
Upregulate activity of cell surface proteases
Activation of kinase signaling cascades
Receptor tyrosine kinases
ErbB2, EGFr
cMet
VEGFr family
Nonreceptor kinases
Fak
Src
PKC
Angiogenesis pathways
PI3K  Akt  Hif1  VEGF
Tumor Microenvironment Changes
Loss of cell-cell tumor suppressor signals
e.g., loss of TGF from the stroma

Front 44

Signaling Pathways promoting progression to invasive breast cancer:

Back 44

() MAP Kinase Cascade - increasing cell proliferation
() VEGF - increasing angiogenesis, proliferation, motility, and invasion
() Rac/Rho - increasing motility
() MMPs and cell surface proteases - increasing invasiveness

Front 45

Haploinsufficiency

Back 45

with tumor suppressor genes, one fxnal allele is not enough. two alleles are required for normal fxn, otherwise --> transformation

Front 46

RAS family of GTP binding proteins

Back 46

*most common known oncogene in human tumors
considered a signal-transducing oncoprotein
contains: KRAS, NRAS, HRAS

Front 47

GAP

Back 47

GTPase-activating proteins - inactivate RAS via GTP hydrolysis

Front 48

Neurofibromatosis 1

Back 48

() caused by a mutation in neurofibromin 1, a GAP

Front 49

Why are breast cancer death rates on the decline?

Back 49

earlier diagnosis

Front 50

What is key to making cancers hard to treat with pharmacotherapeutics?

Back 50

As cancers progress they become more heterogenous

Front 51

What type of growth fraction makes tumors generally more sensitive to anti-cancer drugs?

Back 51

High growth fractions

Front 52

When are tumors most sensitive to treatment?

Back 52

when they are small and more actively growing
*as a tumor gets larger, the percent of cell mass that is dividing decreases

Front 53

What is released in tumor lysis syndrome?

Back 53

IC CaPO4, K, and Urea --> renal failure and coagulopathies

Front 54

Myelosuppression is normally subject to..

Back 54

dose limiting toxicity

Front 55

How do some cancers regulate the MDR transporter?

Back 55

the MDR transporter is a PGp that normally pumps foreign particles or toxins back into the intestinal lumen for excretion. Some drugs cause the PGp to see them as toxins, upregulating the transporter and in turn making the host more resistant to these drugs.

Front 56

How do alkylating agents work?

Back 56

they cause a DNA strand break

Front 57

Chronic Myeloid Leukemia (CML):

Back 57

9:22 translocation --> oncogenic tyrosine kinase and uncontrolled cell proliferation

Front 58

Top 3 Cancer by incidence in men and women:

Back 58

Men = prostate, lung, colon

Women = breast, lung, coon

Front 59

Top 3 Cancers by death in men and women:

Back 59

Men = lung, prostate, colon

Women = lung, breast, colon

Front 60

What proportion of men will develop cancer at some point in their life?

Back 60

1/2

Front 61

What proportion of women will develop cancer at some point in their life?

Back 61

1/3

Front 62

What percent of cancer pts (all cancers) will live 5+ years?

Back 62

70%

Front 63

The decrease in mortality of breast cancer is due to:

Back 63

90% of pts w/ breast cancer reach 5+yrs. This is due in part from:
() better understanding
() early detection
() effective tx

Front 64

Genetic risk factors for cancer:

Back 64

() FHx of cancer
() Cancer appears earlier in life
() Multiple and bilateral tumors
() May include rare tumor types

Front 65

Known causes of cancer:

Back 65

() Occupational exposure - asbestosis, mesothelioma, benzene
() Lifestyle factors - smoking, diet (#2 cause of cancer), EtOH
() Biologic agents - infections (HPV, HIV, EBV, Hepatitis)
() Iatrogenic

Front 66

What is the worldwide #1 cause of cancer?

Back 66

Hepatitis

Front 67

Smoking-related cancers:

Back 67

Lung
Larynx
Oral cavity
Esophagus

Front 68

EtOH-related cancers:

Back 68

Esophagus
Head and neck
Large bowel
Liver
Pancreatic
Breast

Front 69

Ionizing radiation, an iatrogenic contributor to cancer, usually cause which types of cancer?

Back 69

Breast and Leukemia

Front 70

What factors are characteristic of cancer cells?

Back 70

() loss of contact inhibition
() increase in GF secretion
() increase in oncogene expression
() loss of tumor suppressor genes
() neovascularization

Front 71

Breast cancer screening recommendations:

Back 71

CBE
() 20-40 = every 3 years
() 40+ = every year

Mammography - 1st by age 40
() 40-49 = every 1-2 yrs
() 50+ every year

Front 72

Colon cancer screening recommendations:

Back 72

() yearly fecal occult blood test (FOBT)* or fecal immunochemical test (FIT)
() flexible sigmoidoscopy every 5 years
() yearly FOBT* or FIT plus flexible sigmoidoscopy every 5 years**
() double-contrast barium enema every 5 years
() colonoscopy every 10 years

Front 73

Cervical cancer screening recommendations:

Back 73

() All women should begin cervical cancer screening about 3 years after they start having vaginal intercourse, but no later than when they are 21 years old.

Front 74

Systemic cancer therapy:

Back 74

() Chemotherapy - cytotoxic agents
() Hormonal therapy - mainly for prostate and breast cancers
() Targeted Txs - not cytotoxic, herceptin (trastuzumab), Imatinib

Front 75

Most lymphomas are of what type?

Back 75

B cell lymphomas

Front 76

What lymphomas are TdT(+)/TdT(-)?

Back 76

TdT(+) = precursor lymphomas

TdT(-) = mature lymphomas

Front 77

Polyclonality

Back 77

Multiple cells divide, giving rise to a population of cells w/ phenotypic and/or molecular differences
*tend to be reactive

Front 78

Monoclonality

Back 78

Single cell gives rise to the cell population w/out phenotypic and/or molecular differences
*tend to be malignant

Front 79

Autonomy

Back 79

Growth and proliferation outside of the normal body regulatory pathways - independent or non-regulated growth

*Malignancy = Monoclonality + Autonomy

Front 80

Mantle Cell Lymphoma (MCL) translocation:

Back 80

11:14 --> overexpression of Cyclin D1 --> uncontrolled proliferation

Front 81

Follicular Lymphoma (FL) translocation:

Back 81

14:18 --> overexpression of BCL2 --> anti-apoptotic

Front 82

Burkitt Lymphoma (BL) translocation:

Back 82

8:14 --> overexpression of MYC --> uncontrolled proliferation

Front 83

Risk factors for B lineage lymphomas:

Back 83

() Primary Immunodeficiency Syndromes
() Autoimmune Disorders
() Acquired Immunodeficiency Syndromes

Front 84

Prolymphocytes and paraimmunoblasts:

Back 84

seen in lymph node proliferation

Front 85

What CDs are normally present on B cells?

Back 85

19,20,22

Front 86

Which has a better prognosis in CLL/SLL pts, those w/ a non-somatic mutation or a somatic mutation?

Back 86

Those w/ a somatic mutation have a much better survival (20yrs) than those with a non-somatic mutation.
This is b/c those w/ a non-somatic mutation will take their hit after the germinal center stage (bad).

Front 87

Richter Syndrome

Back 87

Seen in 2-8% of those with CLL/SLL, is a transformation to Diffuse Large Cell Lymphoma

Front 88

CD10

Back 88

acts as a follicular marker in Follicular Lymphoma

Front 89

Diffuse Large B cell Lymphomas:

Back 89

Can be
Primary - De novo
Secondary - as a result of a transformation

Front 90

What are the 3 flavors of Burkitt's Lymphoma?

Back 90

Sporadic
Endemic
Immunodeficiency Associated

Front 91

The epinym CRAB in plasma cell myeloma stands for:

Back 91

hyperCalcemia
Renal insufficiency/failure
Anemia
Bone lesions, multifocal osteolytic

Front 92

What Sx's are seen at diagnosis of T cell lymphomas?

Back 92

Cytokine related Sx's:
() hypercalcemia - osteoclast activating factor
() hemophagocytic syndromes - malignant T cells tell monocytes to eat 'self'

Front 93

Types of T cell Lymphomas:

Back 93

() Leukemic or Disseminated
() Cutaneous
() Nodal Based
() Extranodal Based

Front 94

What is the diagnostic triad for Sezary Syndrome and what separates it from advanced mycosis fungoides?

Back 94

Diagnostic Triad
() Erythroderma = Red Man
() Lymphadenopathy
() Circulating Tumor Cells in Blood

Sezary Syndrome develops the triad instantaneously while the triad is seen as acme of progression with Mycosis Fungoides

Front 95

What are the 4 clinical pictures of T cell lymphomas and their respective survival rates?

Back 95

() Acute - survival 2wks-1yr
() Lymphomatous - survival 2wks-1yr
() Chronic - >2yrs survival
() Smoldering - >2yr survival

Front 96

What end up causing the death of those w/ T cell leukemia/lymphoma?

Back 96

Opportunistic pathogens:
Pneumocystis carinii
Cryptococcal Meningitis
Herpes Zoster, Disseminated
Hypercalcemia

Front 97

Anaplastic Large Cell Lymphoma:

Back 97

ALK(+) as well as CD30(+)

Front 98

Reed Sternberg Cells

Back 98

A minority of the cells seen in Hodgkin Lymphomas that secrete chemokines and cytokines that attract the inflammatory cell background that makes up the majority of the tumor (but are non-neoplastic)

Front 99

What are the Hodgkin subtypes and how are they distinguished?

Back 99

() Nodular Lymphocyte Predominant Hodgkins - looks like Hodgkins under the microscope but show presence of B cell gene expression w/ immunophenotyping - presence of OCT2, BOB1, absence of CD15, CD30
() Classical Hodgkins - looks like Hodgkins under the microscope and lacks B cell gene expression w/ immunophenotyping (like the other B cell lymphomas)

Front 100

What 2 Lymphomas have a tendency to involve the EBV?

Back 100

Burkitts and Hodgkins Lymphoma

Front 101

What are the 4 subtypes of Classical Hodgkins Lymphoma?

Back 101

() Nodular Sclerosis - dense pink bands of fibrosis surrounding tumor nodule, usually mediastinal with lacunar variant RS cells
() Mixed Cellularity - NS - fibrosis, male predominance, high EBV rate
*background for both NS and MC contain a host of immune cells
() Lymphocyte Rich - male predominance, only lymphocytes in background
() Lymphocyte Depleted - male predominance, very high EBV and HIV rates, RS cell or variant fails to secrete chemokines/cytokines --> rather pure population and poor ability to address

Front 102

What are the B symptoms?

Back 102

() fever
() night sweats
() weight loss

Front 103

Auer rods

Back 103

characteristic in acute myeloid leukemia (AML)

Front 104

Oral targeted therapy works best for remission of what type of lymphoma?

Back 104

Chronic Myeloid Leukemia (CML)

Front 105

Imatinib

Back 105

a protein tyrosine kinase inhibitor used effectively when the philadelphia chromosome is present (t9:22) - CML

Front 106

What are the common Myeloproliferative neoplasms and what mutation is present?

Back 106

() Polycythemia vera
() Essential thrombocytosis
() myelofibrosis
*each has a point mutation leading to constitutively active JAK2 --> GF INDEPENDENT PROLIFERATION

Front 107

Myc Oncogene

Back 107

Normally, Myc acts as a TF that enables immediate, high rate proliferation. Continuous expression of Myc is seen in tumor cells, most notably Burkitt's Lymphoma (t8:14)

Front 108

Retinoblastoma

Back 108

() autosomal dominant trait
() Rb usually fxns as a regulator of cell cycle by binding to E2F. When phosphorylated by cyclin D/E/.., or neutralized in the case of HPV and similar viruses, E2F is free to activate transcription of S phase genes (cyclin E)

Front 109

Loss of heterozygosity

Back 109

refers to the loss of the second allele, normal allele --> the cell now being homozygous for the mutant allele --> cancer development

Front 110

quiescence vs senescence

Back 110

quiescence = TEMPORARY cell cycle arrest
senescence = PERMANENT cell cycle arrest

Front 111

Fxns of p53:

Back 111

() activating quiescence
() DNA repair - initiated by ATM, ATR. p53-dep transcription of p21 (inhibits cyclin-CDK complexes from phosph Rb). p53 upregulation of mdm2 --> cell cycle block released
() inducing senescence
() triggering apoptosis - if DNA repair fails, p53 induces pro-apoptotic genes BAX and PUMA
() TF --> Mir34 (binds and inhibits pro-proliferative genes like cyclins, and anti-apoptotic genes like BCL2, preventing translation)

Front 112

Li-Fraumeni syndrome

Back 112

autosomal dominant inherited gene defect in p53 --> sarcoma

Front 113

Familial Adenomatous Polyposis (FAP)

Back 113

mutation in Adenomatous Polyposis Coli (APC) gene, a tumor suppressor --> adenomatous polyps in the colon
*both copies of APC gene must be lost for tumor formation

Front 114

APC fxn

Back 114

() APC normally complexes with B-catenin --> ubiquitinization
() Wnt stimulation breaks up this complex, allowing B-catenin to translocate to the nucleus where it stimulates proliferation
*If APC is mutated or absent, destruction of B-catenin does not occur and cells proliferate as if they were under continuous Wnt signaling

Front 115

Contact inhibition and the normal response to cell injury

Back 115

Normally, B-catenin binds to the cell surface protein E-cadherin. Loss of cell-cell contact (injury) disrupts the interaction btw B-catenin and E-cadherin allowing B-catenin to translocate and stimulate proliferation.
*loss of contact inhibition is a key characteristic of carcinomas

Front 116

p16/INK4 and p14/ARF

Back 116

tumor suppressors that share a genetic locus (CDKN2A)
mutation at this locus affects both p53 and Rb
() p16/INK4 - blocks cyclinD/CDK2 phosph or Rb
() p14/ARF - binds and inhibits MDM2, preventing p53 destruction

Front 117

TGF-b and it's dual fxns:

Back 117

() tumor preventative - inhibits proliferation in normal cells by repressing cMyc or by activating Rb
() tumor promotion - promotes immune system suppression and angiogenesis
*net action depends on location of pathway interruption

Front 118

PTEN (phosphatase and tensin homologue)

Back 118

a tumor suppressor that downregulates pro-growth PI3K/Akt signaling

Front 119

Cowden syndrome

Back 119

an autosomal dominant mutation in PTEN --> uncontrolled PI3K/Akt pro-growth signaling
- benign tumors (hamartomas)
- malignant tumors
- macrocephaly
- mucocutaneous lesions = facial trichilemmomas, papillomatous papules, and mucosal lesions

Front 120

Tuberous Sclerosis

Back 120

Normally, Akt inactivates the tumor suppressors TSC1/TSC2 which are in place to inhibit the mTOR pathway which stimulates uptake of nutrients needed for growth.
Suppression of the tumor suppressors TSC1/TSC2 --> hamartomas and other tumors

Front 121

von Hippel-Lindau (VHL)

Back 121

A tumor suppressor that binds hydroxylated HIF1a (hypoxia inducible TF 1a) in oxygenated tissues --> ubiquitinization
In ischemic tissue, HIF1a is not hydroxylated and thus doesn't bind VHL, instead activating transcription of genes for angiogenesis (VEGF, PDGF)

Front 122

Wilms' tumor

Back 122

a pediatric kidney cancer associated with mutation in the tumor suppressor WT1
these children also at a higher risk for aniridia

Front 123

Gorlin syndrome

Back 123

basal cell carcinomas alongwith jaw keratocysts and distinct dysmorphic features and skeletal anomalies stemming from a mutation in the tumor suppressor PTCH which normally regulates TGF-b, PDGFRa, PDGFRb pathways

Front 124

Mechanisms for evasion of apoptosis:

Back 124

() loss of sensors of genomic integrity - p53
() overexpression of inhibitors - BCL2
() reduced level of component proteins - decreased CD95/Fas, increased FLIP (binds death-inducing signaling complex and prevents activation of caspase 8)

Front 125

What upregulated enzyme allows cancer cells to have limitless replicative potential?

Back 125

telomerase - normally absent in somatic cells
- shortened telomeres --> nonreplicative senescence

Front 126

Angiogenic switch

Back 126

Angiogenesis is needed for tumor growth and metastasis.
The increased production of angiogenic factors (VEGF, FGF) and/or the loss of angiogenic inhibitors (p53) --> angiogenesis.
This is normally stimulated by hypoxia through HIF1a which activates VEGF and FGF

Front 127

What goes on in the 2 major phases of invasion and metastasis?

Back 127

() invasion of ECM
() vascular dissemmination, homing of tumor cells, and colonization

Front 128

Hereditary Nonpolyposis Colon Cancer Syndrome (HNPCC)

Back 128

an inherited defect in the DNA mismatch repair genes (MLH1, MSH2)
*each individual inherits one defective copy and acquires the 2nd hit in colonic epithelial cells
() microsatellite instability - hallmark of HNPCC, variability in length of repeat regions caused by insufficient proofreading during replication

Front 129

Xeroderma Pigmentosum

Back 129

an inherited defect in the DNA nucleotide excision repair system --> increased risk for skin cancer
- UV light causes cross-linking in pyrimidine residues, preventing normal DNA replication

Front 130

The Warburg Effect:

Back 130

a metabolic shift in cancer cells to aerobic glycolysis that allows for visualization via PET scanning

Front 131

miRNAs

Back 131

small noncoding, single-stranded RNAs
silences mRNA which can down or upregulate tumorigenic factors

Front 132

Carcinogenic Initiators vs Promoters

Back 132

Initiators - cause rapid, irreversible DNA damage, not sufficient for tumor formation, may be direct acting or indirect acting (requiring metabolic conversion or not)
Promoters - changes are reversible and don't directly affect DNA, capable of inducing tumors in initiated cells but not by themselves

Front 133

Aflatoxin B1

Back 133

a food contaminant associated w/ hepatocellular carcinoma that produces a characteristic 'signature' mutation in p53

Front 134

HTLV1 (Human T cell Leukemia Virus Type 1)

Back 134

a T cell leukemia/lymphoma caused by HTLV1 integration into the T cell (CD4+) genome --> monoclonal neoplastic T cell population

Front 135

Epstein Barr Virus

Back 135

may induce B cell lymphomas (esp. Burkitt's lymphoma) by facilitating acquisition of t(8:14)
may also lead to self-limited polyclonal B cell proliferation - infectious mononucleosis

Front 136

Helicobacter pylori

Back 136

known to cause gastric B cell lymphomas - MALTomas, via stimulation of chronic inflammation and polyclonal B cell proliferation (at first T cell dependent)

Front 137

The presence of an Auer rod signify that it is what type of leukemia?

Back 137

myeloid

Front 138

What are the 2 major groups of AML?

Back 138

() Not Otherwise Specified
() Recurrent Cytogenic Abnormalities

Front 139

What type of cells stain (+) for MPO-SBB?

Back 139

neutrophils

Front 140

What type of cells stain (+) for NSE?

Back 140

monocytic cells

Front 141

M5a vs M5b

Back 141

M5a - monoblastic, effects young ppl
M5b - monocytic, effects adults (50yrs+)

Front 142

You get a call from a dentist who has a pt w/ swelling, bleeding gums. What leukemia do you suspect?

Back 142

AML class subtype M5a - monoblastic or M7 - megakaryoblastic

Front 143

M6a vs M6b

Back 143

M6a - Erythroleukemia, >50% erythroid cells, >20% of non-erythroid are myeloblasts, MPO(+), NSE(-)
M6b - Pure Erythroid, >80% erythroid, no myeloblast increase, MPO(-), NSE(-)

Front 144

Dry Taps may result in which leukemias?

Back 144

() Primary myelofibrosis
() Hairy Cell Leukemia
() AML-M7

Front 145

t(8:21) is associated with what AML subtype?

Back 145

M2

Front 146

t(15;17) is associated w/ what AML subtype?

Back 146

M3

Front 147

t(9;11) is associated w/ what AML subtype?

Back 147

M5

Front 148

inv(16) is associated w/ what AML subtype?

Back 148

M4

Front 149

A pt comes in and presents with DIC and a hypergranular cell that has many Auer rods. What is your diagnosis?

Back 149

The pt has Acute Promyelocytic Leukemia (M3). They will have the t(15;17) PML/RARa and 'Faggot' cells upon further testing.

Front 150

Myeloid vs Lymphoid Acute Leukemias

Back 150

Myeloid
most of the cases
usually children
auer rods
CD13, CD33, CD34
MPO, NSE
Lymphoid
usually children under 6yo
TdT(+)
CD19/22 (B cell)
CD3, CD2 (T cell)

Front 151

What is the main difference in presentation btw Precursor B and T Lymphoblastic Leukemia/Lymphoma?

Back 151

B = blood and bone marrow presentation
T = tissue base presentation

Front 152

A few common benign tumors:

Back 152

() Hemangiomas
() Lymphangiomas
() Fibrous tumors
() Teratomas

Front 153

Most common teratoma of childhood?

Back 153

Sacrococcygeal teratoma - usually benign
* more common in girls
* most benign teratomas seen in younger infants

Front 154

WAGR Syndrome

Back 154

WT1 defect
Aniridia
Genital anomlies
mental Retardation

Front 155

Beckwith-Wiedemann Syndrome

Back 155

() enlargement of body organs, macroglossia, hemihypertrophy, omphalocele, adrenal cytomegaly
() involves WT2 gene

Front 156

Denys-Drash Syndrome

Back 156

() gonadal dysgenesis and nephropathy
() germline abnormalities in WT1

Front 157

Asymptomatic pathogenic bacteria of the nasopharynx

Back 157

Strep pyogenes
Strep pneumoniae
Staph aureus

Front 158

Small round blue cell tumors:

Back 158

Neuroblastoma
Lymphoma
Rhabdomysarcoma
Ewing sarcome/PNET

Front 159

Clinical presentations of neuroblastoma w/ consideration to age

Back 159

children < 2yrs of age
Lg abdominal mass
Fever
Possible wt loss

Children > 2yrs of age
May present w/ metastatic disease : bone pain, resp sxs, GI complaints

Front 160

What prokaryote is unique in lacking a rigid layer of peptidoglycan and also has sterols?

Back 160

mycoplasma

Front 161

Pseudomembranous colitis

Back 161

caused by opportunistic pathogenesis of Clostridium difficile

Front 162

Lysozyme

Back 162

a component of tears, cleaves the glycan in gram (+) peptidoglycan cell walls

Front 163

Capsule

Back 163

() protects against phagocytosis - gives virulence
() protects against drying out

Front 164

Mycoplasmas vs Mycobacteria

Back 164

Mycoplasmas - don't have cell walls

Mycobacteria - thick, waxy cell walls; use acid-fast stain

Front 165

What enzymes are missing in obligate anaerobes?

Back 165

SOD* and catalase

Front 166

auxotrophs

Back 166

strains of bacteria that need an added growth factor

Front 167

prototroph

Back 167

can make everything it needs from glucose and inorganics (ex. E. coli)

Front 168

Virulence factors possessed by bacteria:

Back 168

() type III secretion effectors (molecular syringes) - mainly gram (-)
() hemolysin (esp. beta) - in group A strep
() secretory IgA proteases - in respiratory pathogens

Front 169

2^10 =

Back 169

~ 10^3

Front 170

Fluoroquinolone

Back 170

targets bacterial DNA gyrase, disabling its ability to put in negative supercoils to allow replication/transcription. This leads to double strand breaks --> killing

Front 171

How do bacteria prevent multiple initiations in their DNA replication?

Back 171

There is a delay in methylation of the new strand (by DAM) that allows the replication machinery (DNA pol III) to check the newly added base.

Front 172

What 2 enzymes are needed for a bacteria to grow on lactose?

Back 172

lactose permease (lacY)- transports lactose into the cell

b-galactosidase (lacZ)- cleaves lactose to a dissaccharide

Front 173

What are the components of the lac operon and how do they fxn?

Back 173

() structural genes (lacZ, lackY) - encode the enzyme to cleave lactos --> monosacchardes and a lactose transporter, respectively
() promoter - promotes transcription of the above structural genes
() operator - is activated by the promoter to do the work
() regulatory gene (lacl) = REPRESSOR - binds next to promoter to inhibit RNA pol from binding

Front 174

How do cAMP and glucose play in (+) feedback of the lac operon?

Back 174

*in the presence of glucose, very little cAMP is made, inhibiting the synthesis of b-galactosidase (not needed at the time)
w/ no glucose, cAMP levels increase, binding to CRP which helps the promoter and activates RNA pol so b-galactosidase is made = (+) FEEDBACK

Front 175

Describe the 2-component regulatory system:

Back 175

Component #1 - a membrane bound sensor binds to a signaling molecule, causing dimerization and activation of internal kinase --> self-phosphorylation

Component #2 - Response Regulator - is phosphorylated by cognate kinase to form a dimer active for DNA-binding. This activated dimer may now activate or repress the DNA.

*2 component systems are impt for virulence and usually signal arrival in a host or compartment in a host

Front 176

Attenuation

Back 176

control of transcription after initiation which responds to the level of Trp in the cell and is quieted by conditional termination

Front 177

What dictates the growth rate of bacteria?

Back 177

# of ribosomes

Front 178

S20 and translational repression:

Back 178

S20 is one of the proteins involved w/ forming the 30S ribosomal subunit.
When translated, it can either bind to rRNA (if present) of, if not present, bind to and repress it's own mRNA = autoregulation

Front 179

Silent, Missense, Nonsense, and Frameshift mutations:

Back 179

Silent = mutation in base doesn't change amino acid, due to redundancy of genetic code

Missense = mutation in base causes an amino acid substitution that is accepted and allows the protein to still fxn as well as wild type

Nonsense = a mutation in the base results in transcription of a STOP CODON, usually results in complete loss of gene fxn

Front 180

Auxotroph

Back 180

deals w/ nutrition
mutant that cannot make an essential small molecule and won't grow w/out it

contrasted w/ prototrophs which make all the basic 'building blocks'

Front 181

Complementation

Back 181

an extra copy of some bacterial DNA is carried on a plasmid (small, circular dsDNA molecule) which can make up if a mutation is present

This also is targeted in producing avirulent bacteria, where both virulent genes need to be destroyed

Front 182

The low rate of mutation in bacterial DNA is a result of:

Back 182

1) base complementarity - assessed during insertion of the base
2) proofreading or editing fxn of DNA pol III - occurs just after base is inserted
3) mismatch repair - a mismatch distorts the dbl helix and is recognized via methyl-directed mismatch repair and fixed w/ DNA pol III

*overall frequency of spontaneous mutation = 3(10^-3) = 10^-9/generation

Front 183

Reversion

Back 183

change in a phenotype from mutant back to wild type as a result of a mutation (auxotrophs undergoing a mutation that allows them to once again be prototrophs)

Front 184

Why are amino-penicillins considered broad spectrum? (ampicillin, amoxicillin)

Back 184

they possess amino groups that allow penetration of the outer membranes, making it useful against gram (-) bacteria as well as gram (+)

Front 185

Do penicillins work on dormant, static bacteria?

Back 185

No

Front 186

Antibiotic resistance

Back 186

diminishing efficacy caused by decreased microbial susceptibility to abx

Front 187

penicillin-binding proteins (PBPs)

Back 187

are transpeptidases
PBP1 - binds penicillins
PBP2a
PBP3 - binds cephalosporins

If an organism loses a PBP, then those drugs that would usually bind and interfere w/ the transpeptidase are ineffective

*if only PBP2a = MRSA

Front 188

penicillinase

Back 188

aka b-lactamase
possessed by bacteria resistant to the b-lactams (overcome by cephalosporins)

Front 189

MIC (minimum inhibitory concentration)

Back 189

the lowest concentration of an abx that causes a significant reduction in the growth of a pt derived strain of pathogen (static)

*MIC_90 is the increased MIC common to 90% of all pt isolates

Front 190

MBC (minimum bacteriocidal concentration)

Back 190

the lowest concentration of an abx that will inhibit growth of a clinical isolate, even after subculture (cidal)

*favored for tx of endocarditis, osteomylitis, and infections w/ underlying immunocompromised conditions

Front 191

Breakpoints S,I,R for an abx

Back 191

S = susceptible
I = intermediate
R = resistant

reflect
1) pharmacological properties of abx
2) the pts disease
3) the microbe and its properties

Front 192

AST

Back 192

antibody susceptibility test

Front 193

What is the classic example of "cidal-static" antagonism?

Back 193

penicillin (cidal) + tetracycline (static)

Front 194

Bacterial Transformation

Back 194

DNA from a bacterium, either chromosomal or plasmid, can present outside the cell (via lysis) and bind to specific surface proteins of another bacterium which incorporates it.
This occurs w/out cell-cell contact and is susceptible to DNase.

Front 195

What bacterial species are naturally transformable?

Back 195

() Neisseria
() Haemophilu
() S. pneumoniae
*all respiratory pathogens

Front 196

Broad host range plasmid

Back 196

plasmids (usually R plasmids) containing vectors for abx resistance which have an origin of replication that can fxn in many different bacterial species

Front 197

Bacterial Conjugation*

Back 197

the transfer of LINEAR plasmid DNA (F or R plasmid) btw bacteria using cell-cell contact (utilizing a pilus). The plasmid encodes the fxnal genes required for conjugation.

*main mechanism for spread of bacterial resistance

Front 198

How do R plasmids acquire resistance genes?

Back 198

Through the action of transposons.

Front 199

Bacterial Transduction

Back 199

transfer of DNA (usually for toxins) btw bacteria mediated by a bacterial virus (bacteriophage)

Front 200

Phages

Back 200

Phages - can be lytic (virulent) or lysogenic (temperate). this latter allows for the recipient bacteria to have the ability to express changed phenotype.

Front 201

Specialized vs Generalized transduction

Back 201

Specialized transduction - toxin gene is permanently assoc w/ the phage DNA

Generalized transduction - host DNA packaged into virus by mistake

Front 202

Transposable elements and transposons

Back 202

Transposable elements are DNA segments that can move. The simplest ones are called insertion sequences (IS) which consists of a gene for a transposase enzyme which catalyzes the transfer rxn and the flanking sites that mark the boundaries of the transferred DNA.

A transposon is one type of complex transposable elements which has 2 IS elements acting as one to move themselves plus the intervening DNA.

Front 203

Salmonella typhimurium - sophisticated pathogen

Back 203

• adsorbs to and travels through gut epithelium
• uses macrophages like taxis to travel in the body
• eventually grows in spleen and liver

• acquired by "horizontal transfer"
• Salmonella has 2 big ones:
SPI-1 required for growth in epithelial cells
SPI-2 required for growth in macrophages

Front 204

Knudson's "two-hit" hypothesis

Back 204

sporadic form - both mutations in Rb gene are acquired by the retinal cells after birth
familial form - all cell inherit 1 mutant Rb gene, the second mutation affects the Rb locus after birth