PHS 3300 final exam

neoplasia

the new and abnormal development of cells that may be benign or malignant

cancer

any malignant growth or tumor caused by abnormal and uncontrolled cell division

no need for stimuli

altered morphology

malignant

encompasses multiple diseases:

escape the point of orgin, invasion of local tissue

epithelial cells and cancer

skin cells that cover the external body surface and line the internal surfaces of organs

house 90% of cancers

adenocarcinoma

cancer of secretory epithelia, long colon breast pancrease

squamous cell carcinoma

cancer of the protective cell layers, skin nasal cavity oropharynx

osteosarcoma

malignant tumor of the bone

liposarcoma

malignant tumor of fat

leiomyosarcoma

malignant tumor of smooth muscle

rhabdomyosarcoma

malignant tumor of skeletal muscle

Neuroectodermal tumors

Derive from nervous system; responsible for ~2.5% of cancer related death but only 1% of cancers

Leukemia

cancer of white blood cells

lymphoma

malignant tumor of lymph nodes and lymph tissue

lymphocytic leukemias

involve immature lymphocytes and their progenitors that originate in the bone marrow but infiltrate the spleen, lymph nodes, CNS, and other tissues

myelogenous leukemia

affects the myeloid cells, which form red blood cells, white blood cells, and platelets

chronic leukemia (example)

slow gradual disease progression arise from mature cells (myeloid or lymphocytic)

e.g. chronic myelogenous leukemia

typically granulocytic leukemia containing the philadelphia gene (fusion of BCR and ABL)

BCR-ABL

BCR: multifunctional gene

ABL: tyrosine Kinase

their fusion forms a novel powerful onconogene with kinase activity (philadeplphia gene, high expression)

causes chronic myelogenous leukemia

treatement of chronic myelogenous leukemia

target kinase activity with imatanib (targeted therapy)

bone marrow transplant

limit standard chemotherapy

acute leukemia

arises from early immature cells

mostly myeloid leukemias

M0

Undifferentiated acute myeloblastic leukemia

M1

granulocytic differentiation

M2/M3

promyelocyte

treat with retinoic acid

reduce cancer by forcing differentiation

Chronic Lymphoid Leukemia (CLL)

most are B-cell leukemias

slow progression

eventually lymphandenopathy (swollen lymph)

acute lymphoblastic leukemia (ALL)

This is the overproduction of immature lymphocytes. The lymphocytes divide rapidly but fail to mature.

The most common leukemia of childhood

good prognosis w treatment

Most are B cells

Hodgkin's lymphoma

A malignancy of the lymphatic system

characterized by reed sternberg cells (from B cells)

metastasizes along lymph node (usually firstly evident in cervical lymph nodes)

treatment of hodgkins lymphoma

radiation, chemotherapy, surgery

non-hodgkins lymphomas

includes B cell, T cell Nk cell lymphomas

adult onset

environmental and lifestyle for cancers

tobacco

diet (atherogenic, high nitrates, salt)

diet (high fat, low fiber, broiled/fried food)

alcohol

proliferation

rapid increase in numbers

building blocks of DNA: pyrimidine

cytosine and thymine

building bocks of DNA: purine bases

adenine and guanine

mutations

Random errors in gene replication that lead to a change in the sequence of nucleotides

can lead to cancer

how do mutations happen

base deamination (point mutation)

reactive oxygen species

UV irridation

carcinogens

types of mutations

point (single base)

insertion

deletion

frameshift mutation

mutation that shifts the "reading" frame of the genetic message by inserting or deleting a nucleotide (insertion or deletion)

transolocation

rearrangement resulting from chromosome breakage where a chromosome fragment reunites with another non-homologous chromosome

types of translocation

nonreciprocal intrachromosomal

nonreciprocal interchromosomal

reciprocal interchromosomal

genomic instability

an increased tendency of the genome to acquire mutations when various processes involved in maintaining and replicating the genome are dysfunctional

gene amplifications

Increase in copy number results in too much protein

Many human cancers are associated with amplification of particular proto-oncogenes

genes involved in cancer development

tumor supressor gene

oncogenes

Tumor Supressor Genes (TSGs)

genes that prohibit over proliferation of cells and regulate apoptosis

Oncogenes

genes that cause cancer by blocking the normal controls on cell reproduction

p53

This tumor suppressor gene causes cell cycle arrest in G1, providing time for DNA repair. If repair is successful, cells re-enter the cycle. If unsuccessful, apoptosis

is mutated in many cancers

BRCA1 and BRCA2

tumor supressors proteins parts of DNA repair complex (caretaker function)

act in S phase

genetic mutations associated with increased risk for breast cancer

G1

Cell growth

tumor supressor genes can functions a gate keepers to prevent entry into the cell cycle or induce cell death

S phase

DNA replication (2n->4n)

tumor supressor genes act as caretakes which try to maintain the DNA

make sure genome is intact

retinoblastoma

tumor arising from a developing retinal cell

retina: light sensitive tissue at the back of the eyes that detects light and color

Non-Hereditary Retinoblastoma

unilateral as mutation of both wild type alleles in both eyes is very uncommon

somatic mutations

2 hits

hereditary retinoblastoma

- as a child it presents

primary hit is germline mutation

seconary hit is a somatic mutation

more common to lose both (tumor supressor is already inactive)

why does human papillomavirus cause cervical cancer

a protein made by the virus causes destruction of p53 in a infected cell therfore making the cell more likely to become cancerous

oncogenes typically include

growth factor receptors and proteins that help growth factors receptor to function (proliferate) (HER2/neu, Ras)

protein involved in the transcription of genes involved in cell proliferation (myc)

p53 cell cycle arrest methods

senescence, autophagy, ferroptosis, dna repair, apoptosis, necrosis, necroptosis, dormancy, metabolic switch

prooncogenes

normal proteins when overexpressed are cancerous

(MAS)

oncogene examples

ras, c-myc, Bcl-2 (pro survival protein), Mas

how do oncogenes function

pushing the cell to enter into the cell cycle at G1

how does Ras work

oncogene:

bad inhibition of apoptosis

cell growth

protein synthesis

transcription

cell movemtn

metastasis

HER2/neu

growth factor gene highly activated in cells of certain types of breast cancer

herceptin

antibody used to target and kill cells epression HER 2 on the surface

TNM scale

T: extent of the tumor

N: extent spread to lymph

M: presence of metastasis

stage 0 cancer

carcinoma in situ, only present in the layer of cells in which it began (not invasive yet)

stage I/II/III

higher #s indicate more extensive disease

stage IV cancer

the cancer has spread to another organ (clear distant metastasis

cadherins

proteins that attach cells to other cells

steps of cancer

loosening of intercellular junctions

attachment

degradation: protease activation (produces enzymes that break down the BM)

Migration (escape normal tissue position)

fibronectin

A glycoprotein that helps animal cells attach to the extracellular matrix.

carcinoma in situ

cancer in the early stage before invading surrounding tissue

dysplasia

abnormal development or growth of cells, tissues, or organs

hyperplasia

increase in cell number with abnormal growth

CIS/DCIS

forms of carcinoma in situ

CIN/PIN

forms of intraepithelial neoplasia

adenoma

pre-malignant cancer

atypical hyperplasia

benign (noncancerous) condition in which cells have abnormal features and are increased in number

initiator (cancer)

mutagenic carcinogen

ras mutation 1

causes papilloma

Promoter (cancer)

mitogenic proliferation inducer

ras mutation 2

causes carcinoma

papilloma

a benign, superficial wart-like growth on the epithelial tissue or elsewhere in the body, such as in the bladder

tumor promoters

agents that do not directly damage DNA, but act to promote tumor formation

(factors in the body can act as)

breast cancer tumor promoter

estrogen: causes cell division

(hormone replacement therapy contributes to breast cancer and late menopause)

treatment of breast cancer

tamoxifen

blocks estrogen receptor

breast cancer subtypes

estrogen receptor/progesterone

HER2/neu

triple negative (cant treat with herceptin, must be chemo)

metastatic spread

early adenoma

late adenoma

carcinoma

metastasis

cancer scans

Ct scans

Pet scan

MRI (cancer uses glucose, brain always uses glucose)

mammography

colonoscopy

prostate exams

skin exams

tumor invasion cycle

primary tumor formation

localized invasion

intravasation

transport through circulation

arrest in microvessels or various organs

extravasation

formation of micrometasis

colonization form of macrometasis

tumor stroma

makes factors that lock immune system, helping the tumor grow (evade immune recognition)

how does aging lead to cancer

inflammation

Renal blood flow

1200 ml/min

Kidneys receive ______ of CO

25%

in the kidneys the blood goes

1-2% to medulla

90% to cortex

How much of blood is excreted from the kidney

1% (1-1.8L)

constriction of afferent arteriole causes

decreased capillary hydrostatic pressure and decreased filtration (DECREASE GFR)

Dilation of afferent arteriole

increases GFR

Constricting efferent arteriole

increases GFR

Dilation of efferent arteriole

decrease pressure, decrease GFR

Where does the final urine concentration is determined

Distal convoluted tubule

Where is gfr determined

Th glomerulus

Podocytes

cells in the Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus

Final layer of filtration

Foot like processes

Fewer glomeruli leads to

Harder work for those functioning and easier damage, higher pressure

Glomerular basement membrane

The membrane that separates the glomerulus from the Bowman's capsule

mesengial cells

smooth muscle cells in the glomerulus

Pull capillary bed and change size (contract and relax)

Fenestrations

Large pores in endothelial cells allowing rapid exchange between blood vessels and tissue.

Increase the flow rate

Glomerular filtration rate

Rate at which plasma moves through glomerular capillaries in ml/min

Females 85-125

Males 97-140

Children's rate matured by 2 years