Neofuckingplasia - Putthoff Flashcards by Jes Testa

Q

Cancer by incidence in US

A

Breast/prostate
Lung
Colorectal

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Q

Cancer by mortality in US

A

Lung
Breast/prostate
Colorectal

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Q

Should you smoke cigarettes? Why or why not?

A

Nope.
Cause it will fucking kill ya.
Very painfully

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Q

3 things that define neoplasia

A

Uncontrolled
Irreversible
Monoclonal

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Q

What is the proof for monoclonality?

A

G6PD enzyme isoforms

–it has multiple isoforms, one inherited from each parent, only one present in ALL tumor cells

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Q

Metaplasia

A

One mature cell into another
Reversible
Can progress to CA if stress not removed

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Q

Dysplasia

A

Ugly, but NOT cancer
Loss of cell shape, size, orientation
Reversible

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Q

Anaplasia

A

CANCER - the big dog

Irreversible

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Q

How does cancer look (in general) histologically?

A

Many mitotic figures - dividing
High nuclear to cytoplasmic ratio
Prominent nucleoli

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Q

3 characteristics of benign tumors

A

Well differentiated
Slow with low mitotic activity
Well demarcated borders, can be encapsulated

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Q

4 characteristics of malignant tumors

A

Poorly/undifferentiated
Erratic growth with many mitotic figures
Locally invasive
Possibly metastasis

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Q

-oma generally means

A

Benign

NOT always - melanoma, lymphoma

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Q

What is a malignancy of epithelial tissue?

A

Carcinomas

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Q

3 types of carcinoma

A

Squamous
Adeno - glands
Transitional - aka urothelial

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Q

Where do carcinomas metastasize to?

A

Lymph nodes

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Q

4 exceptions to the carcinomas metastasize to LN rule?

A

Renal cell carcinoma
Hepatocellular carcinoma
Follicular carcinoma of the thyroid
Choriocarcinoma
They like to go blood

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Q

What type of malignancy comes from mesenchymal tissue?

A

Sarcomas

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Q

What are some examples of where sarcomas occur?

A

Muscle, fat, bone, CT, blood vessels

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Q

Where do sarcomas metastasize to?

A

Hematogenously

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Q

Leukemia

A

Malignancy of stem cells in the bone marrow

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Q

Lymphoma

A

Malignancy of the lymph nodes

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Q

If you see a keratin pearl what type of cancer do you have?

A

Squamous cell carcinoma

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Q

What is the max number of cell layers you should have in urothelial lining?

A

6

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Q

Respiratory passages
Tissue of origin?
Benign name?
Malignant name?

A

Epithelial
B - bronchial adenoma
M - bronchogenic carcinoma

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Renal epithelium Tissue of origin? Benign name? Malignant name?

Epithelial B - renal tubular adenoma M - renal cell carcinoma

Liver Tissue of origin? Benign name? Malignant name?

Epithelial B - Hepatic adenoma M - hepatocellular carcinoma

Connective Tissue Tissue of origin? Benign name? Malignant name?

Mesenchymal B - fibroma, lipoma, chondroma, osteoma M - fibrosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma

Blood vessels Tissue of origin? Benign name? Malignant name?

Mesenchymal B - Hemangioma M - angiosarcoma

Lymph vessels Tissue of origin? Benign name? Malignant name?

Mesenchymal B - lymphangioma M - lymphangiosarcoma

Urinary tract Tissue of origin? Benign name? Malignant name?

Epithelial B - transitional cell papilloma M - transitional cell (urothelial) carcinoma

Placental Tissue of origin? Benign name? Malignant name?

Epithelial B - hydatidiform mole M - choriocarcinoma

Mesothelium Tissue of origin? Benign name? Malignant name?

Mesenchymal B - ----- M - mesothelioma

Testicular Tissue of origin? Benign name? Malignant name?

Epithelial B - ----- M - seminoma, embryonal carcinoma

Brain coverings Tissue of origin? Benign name? Malignant name?

Mesenchymal B - meningioma M - invasive meningioma - very rare

Melanocytes Tissue of origin? Benign name? Malignant name?

Epithelial B - nevus M - melanoma

Smooth muscle Tissue of origin? Benign name? Malignant name?

Mesenchymal B - Leiomyoma M - Leiomyosarcoma

Striated muscle Tissue of origin? Benign name? Malignant name?

Mesenchymal B - rhabdomyoma M - rhabdomyosarcoma

Salivary glands Tissue of origin? Benign name? Malignant name?

Mixed tumor B - pleomorphic adenoma M - malignant mixed tumor of salivary gland origin

Hematopoietic stem cells Tissue of origin? Benign name? Malignant name?

Mesenchymal B - ---- M - Leukemia

Lymphoid tissue Tissue of origin? Benign name? Malignant name?

Mesenchymal B - --- M - Lymphoma

Mixed tumor of the kidney Benign name? Malignant name?

B - ----- | M - Wilm's Tumor

Teratoma Benign name? Malignant name?

From totipotent cells in gonad B - mature teratoma, dermoid cyst M - immature teratoma, teratocarcinoma

How many times do cells need to divide before they are detectable?

10^9 | ~ 30 doublings

Carcinogen

Agent that damages dna

Sequence of events in carginogenesis

Initiation - mutation Promotion - multiple copies of mutations made Progression

4 things that are disrupted by the accumulation of DNA mutations

Proto-oncogenes Tumor suppressor genes Apoptotic genes DNA repair genes

CA epigenetics

Alterations to histones that indirectly affect DNA | ie. methylation of tumor --> turns off gene --> unregulated cell growth

8 Hallmarks of CA

``` Cell division without growth signals Growth in spite of growth inhibitory factors Immortality by self renewal Angiogenesis Invasion and metastasis Evasion of apoptosis Evasion of host defense Inflammation ```

How does cancer invade and metastasize

Loss of cell to cell by loss of E-cadherin function ECM broken down by proteolytic enzymes Proteolytic enzymes responsible for chemotactic and angiogenic factors

Dormancy

Tumor cells can go to sleep and appear if they have been eradicated

3 ways for metastasis

Lymphatic spread - carcinomas Hematogenous spread - sarcomas Seeding into body cavities

How does cancer evade apoptosis in follicular lymphoma

t(14;18) moves Bcl2 from 18 to Ig heavy chain locus on 14 that is always on = increase in Bcl2 = no apoptosis of B cells that would normally and leads to lymphoma

What do tumor antigens do? Few examples?

with T cells they kill tumor cells Ex: mutated proto-oncogenes, tumor suppressor genes, aberrant proteins, oncofetal antigens, altered glycolipids and glycoproteins

4 Ways tumors evade the immune system?

Failure to produce tumor antigen Mutation in MHC genes Apoptosis of T-cells (by FasL) Production of immunosuppressive cytokines or expression of inhibitory cell surface proteins

Cancer and inflammation

Stimulated by the same physiological processes Anemia - iron sequestration and down regulation of EPO Fatigue Cachexia

What cytokine is implicated in cachexia

TNF-a

Proto-oncogenes

Normal genes that regulate cell growth and proliferation

Oncogenes

Gas pedal | Mutated proto-oncogene --> gain of function --> abnormal growth and proliferation

How many alleles do oncogenes need mutated or knocked out?

ONE

Tumor suppressor genes

aka anti-oncogenes Traffic cop of the cell cycle Stop to repair stuff

How many alleles need to be knocked out for tumor suppressor genes?

TWO

What are the two ways tumor suppressors can be KO?

Sporadic - acquire mutations | Familial - inherit one copy

Function of normal Rb gene?

Governor of cell cycle Holds E2F (necessary to progress from G1 to S) E2F released when RB is phosphorylated --> goes through cell cycle

What happens to mutated Rb?

Free E2F --> cell cycle continues

Rb and 2 Hit hypothesis

Both genes must be knocked out

Rb and sporadic mutations

Both hits are somatic | Leads to unilateral retinoblastoma

Rb and familial mutations

One hit inherited, one somatic | Leads to bilateral retinoblastoma and osteosarcoma

Tp53

Guardian of the genome | Most frequently mutated gene in cancer

4 functions of Tp53

Regulates cell cycle progression Regulates DNA repair Regulates cell senescence Regulates apoptosis

APC gene and colon cancer - 3 steps

1. APC mutations increase risk for polyp formation 2. KRAS mutation leads to formation of polyp 3. p53 mutation + increased expression COX progresses to carcinoma

Von Hippel Lindau - 4 cancers associated with it

Hemangioblastoma of the cerebellum Retinal hemangioblastoma Pheochromocytoma Bilateral renal cell carcinoma

Characteristics of Von Hippel Lindau

``` VHL - tumor suppressor Autosomal dominant Chr 3 Angiogenesis stimulator Think blood vessels ```

Chronic Myelogenous Leukemia

(CML) t(9;22) "philadelphia chromosome" Fusion of BCR-ABL genes

MCY oncogene

Transcription factor --> roles in cell cycle progression and apoptosis c-MYC N-MYC L-MYC

Burkitt's Lymphoma

EBV translocation of chr 8 & 14 c-MYC

N-MYC

Neuroblastoma

L-MYC

Lung carcinoma - small cell

2 Steps of chemical carcinogens

Initiation - carcinogen exposure --> permanent dna damage --> capable of tumor formation Promotion - can induce tumor formation but only AFTER initiation

Direct acting carcinogens

Require NO metabolic conversion to become carcinogenic | Ex. alkylating agents like chemo

Indirect acting carcinogens

Require metabolic conversion to become carcinogenic Ex. polycyclic hydrocarbons in grilled meat MOST chemical carcinogens

Polycyclic hydrocarbons

In cigarette smoke

Azo dyes in dye factories

Bladder CA

Betel nut

Oropharyngeal CA

Aflatoxins from aspergillus

Hepatocellular carcinoma

Pickled fish and veggies

Throat and esophageal CA

Vinyl chloride

Angiosarcoma of the liver

Reading Big Robbins

Not 100% sure, but I think it is a cystosarcoadenocarinomasarcoma AND it is deadly

Chromium salts

Lung CA

Nickel salts

Lung and upper airway CA

Asbestos

Lung CA and mesothelioma

Arsenic

Squamous cell skin CA, lung CA, angiosarcoma

Anabolic steroids

Hepatocellular carcinoma

Iron overload - free radical damage

Hepatocellular carcinoma

Nitrosamines (smoked foods)

Stomach CA

Radium and uranium

Leukemia

Radium painters

Osteosarcomas

Ionizing radiation

ie. Hiroshima --> DNA mutations | AML, CML, Papillary carcinoma of the thyroid

Non-ionizing radiation

ie. UVB sunlight --> pyrimidine dimers | Basal cell skin CA, squamous cell skin CA, melanoma

Thorotrast (injected dye)

Liver CA

EBV

Burkitt's lymphoma, nasopharyngeal carcinoma, CNS lymphoma in AIDS

HPV

Cancer of the cervix, vulva, anus, vagina, penis

HHV-8

Kaposi's sarcoma in AIDS pt

HBV and HCV

Hepatocellular carcinoma

HTLV-1

Adult T-cell leukemia/lymphoma

Merkel cell polyomavirus

Merkel cell melanoma

Only bacteria associated with development of CA?

Helicobacter pylori | --stomach adenocarcinoma

Tumor Grading

The degree of cellular differentiation and mitotic activity | How does it look?

Low grade CA

Well differentiated, low mitotic activity

High grade CA

Poorly differentiated, anapestic, high mitotic activity

Tumor staging - 3 components

TMN Staging system T - tumor size N - node involvement M - metastases

IgG

Plasma cell myeloma

CEA

Carcinoembryonic antigen | Colorectal and pancreatic carcinomas

AFP

Alpha-fetoprotein | -yolk sac tumors, hepatocellular carcinoma, testicular CA

hCG

Germ cell cancer, hydatidiform moles

Calcitonin

Medullary thyroid carcinoma

CA-125

Ovarian CA

CA-19-9

Pancreatic adenocarcinoma

Acanthosis nigricans

Visceral malignancy - esp stomach CA

Cushing's

Small cell lung carcinoma

SIADH (low serum sodium)

Small cell lung carcinoma, intracranial neoplasms

Lambert-Eaton

Small cell lung carcinoma

Hypercalcemia

Squamous cell lung carcinoma, renal cell carcinoma, breast CA

Fever, night sweats from cytokines

Lymphomas, Hodgkin and non-Hodgkin's

Low blood glucose

Insulinoma (pancreatic)

Erythrocytosis/polycythemia

``` Renal cell carcinoma Hepatocellular carcinoma Pheochromocytoma Hemangioblastoma Thymoma ```

Who is gonna kick ass on this test?

WE ARE!!!!

Why are we gonna kick ass on this test?

Cause we are not gonna fucking remediate!! :)))