Proliferation, transformation, microenvironment, immunity

unlimited, stimuli, apoptosis

neoplastic cells have _______ proliferative potential that is independent of _______ or inhibitors.

These cells are also less susceptible to ___________

false; not technically, because irregular cycles and occasional death (cycle arrest)

true/false: growth of neoplastic cells is truly exponential

quiescence, G1/S checkpoint, G2/M checkpoint

unlimited proliferative cells will not enter the ________ phase of the cell cycle, and will bypass which two checkpoints?

mitotic count

_________: tell us the average mitotic figures per standardized field

malignant potential

Active division can increase the concern for _____________ even though some cells never complete the division process

senescence

_____________________: permenant arrest in G1 phase for neoplastic cells

DNA damage, oxidative stress, telomere shortening

telomerase

Cells get trapped in senescence (in G1) due to _________, ___________ or _________, but some neoplastic cells can reexpress __________ to lead to the expansion of telomeres and the escape of senescence

p53 inactivation

Some proliferative cells escape apoptosis by _______ inactivation

latency

_______: time before a tumor is clinically detectable

slow, fast

as a general rule, benign tumors are _____ moving and malignant are _______

cumulative

• cell proliferation

• DNA repair

• angiogenesis

• invasiveness

genetic and epigenetic changes in the neoplasm have a _________ effect overtime.

list a couple of the things that this can affect (4)

true

true/false: gradual change = stepwise motion = multistage carcinogenesis

This applies to many neoplasms but not all of them

(sorry, I didnt know how else to write this)

initiation, promotion, progression

what are the three general phases of a neoplastic timeline?

irreversible genetic damage

_______________________________ must occur for the development of a neoplasm to happen. (initiation)

mutagen

chemical, physical, or viral agents

Initiation stems from a genetic change that is introduced by an initiator/______________________ that can be _______, _______ or ________ agents that damage DNA

promoters, benign tumors

initiated cells can stay quiescent for years, but eventually they will encounter ________ that make the environment better for proliferation. They then begin outgrowth and give rise to ________________

false; they are NOT mutagenic (yes reversible)

true/false: the promotors that push initiated cells into the promotion phase are introducing mutagenic (irreversible) change

progression, malignant, subclones

When cells enter ________ the final stage, they have entered a _________ transformation and this is irreversible.

The increasing complexity and genetic instability means that growth is rapid and ________ can stem from heterogenous copies of tumor cells

BAD, they can help the tumor evolve and adapt

are subclones good or bad?

increase proliferation, immune system evasion, independent blood supply

what three things are necessary for neoplastic success in the progression phase?

neoplastic cells

the tumor parenchyma includes what?

extracellular matrix, blood vessels, fibroblasts, inflammatory/immune cells

what does the tumor stroma include?

growth factors, cytokines, hormones, inflammatory mediators

tumor-stromal interactions include the use of molecules like that? (4)

scirrhous

__________ = desmoplastic reaction with features of a carcinoma invasion; hyjacking the old host environment to degrade and rebuild new tissue

scirrhous reaction, pre-existing collagen, new collagen

What type of reaction is this?

What is the pink material around the outside?

What is the purple material surrounding the tumor islets??

angiogenesis

__________________: the formation of new blood vessels; pivotal for tumor growth and progression

Vascular endothelial growth factor (VEGF), Fibroblastic growth factor (FGFs)

______________________ stimulates endothelial cells to multiply and restore endothelial lining

_____________________ stimulates keratinocyte migration, angiogenesis, wound contraction

Both are necessary for angiogensis

lymphangiogenesis

_____________________: formation of new lymphatics; requires VEGF and is essential for lymph node metastasis

chemokines, cytokine

mixed

prostaglandins, leukotrienes, & ROS

inflammation around the tumor is attracted by ________ and _______ secreted by tumor cells

It is classified as ___________ and is a source of _______, ________ and ________

immunosurveilance

____________________: identification and targeting of infected or foreign cells

true

true/false: failure of antitumor response can allow neoplasms, so those who are immunosupressed can have increased tumor susceptibility

tumor antigens

_______________: proteins expressed on surface of neoplastic cells (includes neoantigens and tumor associated antigens)

tumor specific antigen, unique, unfamilliar

a tumor neoantigen is also called a _____________________________

These are ________ mutations in a transformed cell that lead to proteins that are ________ to T cells

Great therapy! for INDIVIDUALS. Can't really mass produce them

Because they are so unique to a specific tumor, these neoantigens should be really easy to target for therapy! SO! We cured cancer!!! Right?

tumor-associated antigen

_______________________ are expressed in both normal and neoplastic cells. but are way OVER produced or produced in the wrong location in tumor cells

study, identify, large scale therapies

tumor-associated antigen is easier to _______ and _______ than other markers and is far more convenient for _____________

NK cells, macrophages

what are the innate antitumor effector mechanisms?

dendritic cells presenting tumor antigens, cell mediated (CD8+, CD4+), humoral immunity

what are some of the adaptive antitumor effector mechanisms?

cell mediated

what is the most effective adaptive antitumor effector mechanism?

antigen masking, immunosuppression,

What are two ways that tumor cells evade the immune system?

antigen masking

___________: selection of clones lacking tumor antigen expression OR integration with glycocalyx molecules, fibrin and antibodies

PD-L1, TGF-a, Fas ligand

Neoplastic cells can express _________ which inhibits T cell killing; _________ which inhibits lymphocyte and macrophage function and secretion or _______ which binds to T cells and causes LYMPHOCYTE apoptosis

rapidly dividing cells

Chemotherapy targets _______ which means both host and tumor cells

antitumor effector, antitumor immune resposne

INSTEAD of chemo,

yuo can provide increased _____________ cells or antibodies which is a passive process, or you can stimulate _________ which is an active process

monoclonal antibodies, tumor antigens, fast, short-lived

passive immunotherapy includes giving the patient __________.

These target ____________ and provide a therapy that is [fast/slow], [long/short lived] and can also deliver therapeutic agents

vaccination, cytokine, proinflammatory

active immunotherapy includes __________ with tumor cells or antigens, ________ administration or ______________ compounds being stimulated or given to the patient

melanoma vaccine

___________: Tumor vaccine in dogs made from human DNA which aims to delay metastasis. The human DNA is seen as foreign and triggers the immune system

protein tyrosinase

melanoma vaccines target _________ which is overexpressed in melanomas