Cancer Flashcards

Question

Normal vs. Cancer size

Answer 1

Normal cells -- usually larger (usually found in G0) Cancer cells -- Usullay smaller -- usually going through cell cyle = going through mitosis = smaller

Answer 2

Normal cells-- Lower nucleus to cytoplasm ration Cancer cells -- Higher nuclues to cytoplasm ratio

Answer 3

Normal cells -- Cytoskeleton is organized Cancer cells -- Cytoskeleton is less organized

Answer 4

Normal cells -- Exctensive ECM Cancer cells -- Low ECM (Have no firbrnotectin because it would make it get stuck and it wants to move)

Answer 5

Normal cells -- Grow in a single layer Cancer cells -- Grow in culture in multilayer (they have no contact inhibition = they don't stop dividing)

Answer 6

Because normal cells are characterized by contact inhibition -- once it is multilayer = the cells are in contact = they stop dividing

Answer 7

Normal cells -- No tumors in SCID mouse Cancer cells -- Generate tumors in SCID mouse --> used to test if you have cancer cells that generate a tumor

Answer 8

Normal cells -- serum dependent growth (need fetal calf serum) Cancer cells -- Don't always require serum (depends on the cancer cell) --> some cancer is very clever

Answer 9

Normal cells-- secrete few growth factors (unless they are designed to do that) Cancer cells -- Secrete their own Growth factors (Autocrine)

Answer 10

1. cancer cells 2. normal cells in the hypothalamus -- designed to secrete growth factors

Answer 11

Normal cells -- telemeres shortes every cell division Cancer cells -- telemeres never shorten (requirment for cancer)

Answer 12

Long telemers -- require that the telemeres never shorten

Answer 13

Somocent cells (few divisons = short telemers) --> Somatic cells (25-50 disvison -- depends on teh age of the donor) --> Adult Stem cells (100-200) --> Cancer cells (immortal)

Answer 14

Cancer cells = immortal even though on occasion a few will go through apoptosis

Answer 15

Normal cells -- few genetic defects Cancer cells -- Lots of mutations

Answer 16

Normal cells -- normal glycolysis Cancer cells -- warburg effect

Answer 17

Normal cells -- normal outter CM permeability Cancer cells -- higher permability of Cell memebrane (10X permeablity)

Answer 18

Normal cells -- don't secrete andorgenic factors Cancer cells -- Solid tumors (some cancers) secrete androgenic factors

Answer 19

Because they have few blood vessels

Answer 20

Normal cells -- normal apoptosis Cancer cells -- can resist apoptosis --> can happen in many ways (ex. Virus)

Answer 21

Normal cells -- RTKs -- receteprots that are stimulated by hormes/growth factors that cause cell to divise (normal = normal RTKs) Cancer cells -- defective RTKs (mutated) --> constitutive = not regulates (always turned on)

Answer 22

DATELINE -- FDA steps up to the plate - FDA = issued warning letters to 14 companies for marketing supplements that can cure cancer but do not have a proven + documentable outcome ***65 products total Suplement = not FDA apporved

Answer 23

Zebra fish -- used to study defective genes that cause melanoma

Answer 24

Ocular melanoma = 6/1 million BUT 4 friends in Auburn all have it ***Don't know why they all have it Example of time when there is a cluster of cancer --> more people have cancer than you would expect

Answer 25

1. Intitaion (mutation event in somatic cell) 2. Cancer progression (mutauin and genome detsabilization + dysregulation of growth control pathways) - Have proliferating cells (takes time to make a tumor) 3. Evasion of cancer elimination (Block apoptosis + blocj Killing by T-cells) --> Precacerous cells - Apoptosis normally occurs because of tumor supressor genes BUT in cancer progression the cancer blocks the apoptosis - Blocking T-cells = basis of immunotherapy --> because canver have receptors that say "don't kill me" = the T-cells can't kill it 4. Tumor growth + dispersion - Tumor can release factors to grow blood vessels - Have angiogenisis (grow blood vessles) + metastsasis

Answer 26

Colon polyp

Answer 27

First cancer vaccine -- now can be used for both boys and girls to prevent up to 90% HPV infections that can cause cervical and other cancers ***They wanted the HPV vaccine to be required for girls going into highschool -- very controvrsial Texas: Former Gov. Rick Perry ( US Energy Secretary 2017 - 2019) mandated vaccination in 2007 (Merck donated $$ to his campaign) for girls and then reversed position due to public opposition

Answer 28

MANY THINGS can cause cancer 1. Viruses 2. Radiation (UV light) 3. Chemical Mutangens 4. Blocking CDks/cylins 5. Defective tumor supressor genes 6. Defective DNA correction.DNA repair enzymes 7. Defects in apoptosis pathway 8. Defects on growth factor signalling path 9. Telemers 10. Cancer stem cells 11. Chromosmal translocation 12. DBA amplification 13. Overproducting and or mutating trasncription factors ***Once find out what causes cancer = can find treatments

Answer 29

1. Sacrcoma Virus 2. SV40 3. HPV 4. Epstein Barr Virus

Answer 30

Reserachers found that virus caused cancer in 1911 1911 -- reserachers = figured out that virsues can cause cancer using the Rous Sarcoma Virus (Rouse sarcoma = showed that viruses can cause cancer) 1970 -- they still thought the basis of cancer was virsuses --> could not sequence things

Answer 31

1. Found V-SRC -- Rouse Sarcoma Virus 2. Found V-SRC is similar to C-SRC - C-SRC = protooncogene (normal gene) - C-SRC is found in Us Virus = takes C-SRC and turns it into V-SRC --> turns it into a cancer gene

Answer 32

Virus that can cause cancer ***Has large T-antigen Once it gets into cells it knows it needs to take out tumor supressor genes

Answer 33

Has to sites Site #1 -- for p53 gene Site #2 -- for R3 gene Once it gets into cell it knows it needs to take out tumor supressor genes --> large T antigen takes out the tumor supressor genes

Answer 34

Human Pavlova Virus -- virus that can cause cancer ***Causes cirvical carcinoma (HeLa cells) - Gardasil = 1st cancer vaccine

Answer 35

Gardasil -- for HPV -> revolutionized how we think about treating cancer

Answer 36

Virus that causes cancer --> causing Hotchikning Lymphoma ***Causes translocation of chromsomes

Answer 37

Paradox = radiation causes skin cancer BUt radiation is a common way to treat tumors

Answer 38

Causes thiamine dimers --> usually you have repair enzymes that fix it

Answer 39

1. Direct 2. Indirect ***Most chemical mutagens = known

Answer 40

Type of chemical mutagen -- includes promoters + initiators ***Have both types of mutagens

Answer 41

Can block g1 by blocking cylcin + CDK ***Defective cyclins = often found in cancer ***Checkpoint doesn't work Example -- breast cancer -- many breast cancers = have defective cyclin D = p53 won't stop things ***p53 and other checkpint controls work by inhibiting cyclin-CDKs -- if p53 doesnt work than cancer can result

Answer 42

Example -- p53 --> we know that over 50% of cancer have defective p53 + defective RAS

Answer 43

We know that defective DNA correction/DNA repair enzymes cause many cancers Example cancer = Xeroderma Pigmentosa

Answer 44

Examples: 1. defective p53 --> because p53 causes apoptosis 2. Bcl2 --> if high Bcl2 = chemo and radaition won't work because Bcl2 is an anti-apoptic protein

Answer 45

Very variable Example: 1. RTK path -- because RTKs = signla cell to divide 2. TGF Beta --> affects growth receptors -- interacts with receptors and stops cell division = if it is defcetive them you get cell division

Answer 46

Have the fewest number of cell divsions in aging cells

Answer 47

Inability to shorten telemers = causes cancer Cancer = repairs telemers + keeps them long

Answer 48

May be the major of cancer --> they may give rise to mature cancer cells - They were orginally rejected --> made us rethink how we think of cancer developmnet - May be responsible for metastasis - Often reisistent to standrad chemo = they are a big challenge

Answer 49

There are very few of them --> less than 10% of tumor = they are hard to find

Answer 50

They are hard to find because there are so few BUT then we started cloning cells and found that one cancer stem cell acts different than the other clones

Answer 51

CD133 -- CD133 positive cells = likley a cancer stem cell ***You can use FACS and purify cancer stem cells using the surface marker CD133

Answer 52

Barkitts lymphoma

Answer 53

Amplifying genes for growth factors --> causes cancer

Answer 54

Example: 1. FOS --> early response gene 2. MYC --> Late response gene ***Both important in G1 cell cycle (both are early and late response genes in G1)

Answer 55

NY bill would require HPV vaccine for children to enter school, daycare. As of 5/21 - Only four jurisdictions currently require HPV vaccine for school entry: Rhode Island, Virginia, Puerto Rico, and the District of Columbia (DC). NY = trying to have law that you need HPV vaccine for preschoolers (vaccine = gardacil)

Answer 56

DNA damage --> ATM/R --> Phosphorylates p53 = p53 active --> p53 affects G1 CDKs

Answer 57

Chronic Myelogenous Luekemia -- they are rageting it with HDAC inhibitors Treatment -- Just Imatinib --> Use Imatinib kills tumor but when stop the tumor keeps growing -- keeps growing because cancer stem cells generate more tumor - means you need two drugs to also kill cancer stem cells in order to find cure Imatinib + HDAC --> using two drugs to kill cancer stem cells + the tumor cells

Answer 58

Kills tumor BUT not cancer stem cells ALSO used to block BCR -- made knowinh the substarte = blocks ability of chromosome to phosphorykate substrate = no cell division (Imatnib = binds to actuve site and inhibits subsrate binding)

Answer 59

Results in "philideplphia" Chrmosome ***In luekemia = have translocationon philedelphia chromsome --> have fusion of gene -- makes Bcr able to fuse genes --> protein phosphorylates substarte = cell survives = cell is a cancer cell Have translocation = fusion of genes = gets transcribed and makes the BCR-fusiogenic protein --> protein gets phosphorylated (protein = substarte) --> phosphorylation = canuses cell division = cell is cancer cell

Answer 60

V-SARC - oncogene

Answer 61

Focus = on oncogenes Experiment #1: Took DNA from human tumor --> isolated DNA --> Put DNA into 3T3 cells --> get cancer cell Result: get clones -- clones = cancer cells ***The clones were multilayer in contact with each other = know they are cancer cells Experiment #2: Realized that 1 oncogene doesn't necessarily transform all cells Part 1 -- Take 3T3 cells + DNA with oncogene (add haRAS oncogene) Result: Get cancer Part 2 -- Take REF cell (rat embryo fibroblast) --> Add DNA with oncogene (add haRAS oncogene) Result: No cancer BUT then took the trasnfected REF cell and but in a new microenvirnment (put in semi-solid media) Result: Got a cancer cell Experiment = suggested that can cells care about their microenvirnment + showed that 1 oncogene doesn't necessarily trasnform all cells

Answer 62

Worked on oncogenes ***Isolated the 1st tumor supressor gene Rb + showed oncogenes are not specifc specific ***Was one of the founders of the cancer institute at Harvard ***He started Vera Stem --> Biotech company for cancer -- focuses on his second discovery (RAS causing cancer)

Answer 63

1. Discovered the 1st tumor supressor gene --> found Rethoblastoma gene (Rb gene) 2. Discoveres RAS oncogene --> found RAS deviant that causes cancer

Answer 64

Causes cancer -- usually needs to have other oncogenes with it to be able to cause cancer

Answer 65

Normal gene that typically are related to cell division pathways

Answer 66

Cancer= age dependent -- we know that most but not all cancers take time to develop --> increase with age ***Older = more likley to get cancer

Answer 67

***Known for a while ***Typically need multiple oncogenes to cause cabcer 1. Know most but not all cancers take time to develope --> reason why cancer increases with age 2. Know most cancers = caused by epithelial cells

Answer 68

***Known for a while ***Typically need multiple oncogenes to cause cancer 1. Know most but not all cancers take time to develop --> reason why cancer increases with age 2. Know most cancers = caused by epithelial cells

Answer 69

Look at tumor incidince in 3 mice - Over time the percent of tumor free mice Use three transgenic mice: have mutations in genes that increase cancer 1. MYC mouse 2. RAS mouse 3. MYC + RAS Mouse Result: Over time the amount of tumor free mice decrease -- mice with most tumors = older mouse with mutations in both genes Shows cancer = increases over time + often need multiple oncogenes to cause cancer

Answer 70

Colon cancer

Answer 71

Colon cancer = very slow growing cancer --> easy to prevent - Have defects that occur sequentially until you get to a point of no return (once its metastisized you can't help) BUT it takes many yeats to get there = you can taje out the polyps before that happens and it won't metastisize = reason why get colonoscopy because you can take out the polyps (because it takes a while for the polyps to be able to metastisize) 50% of people have poplys -- precancerous Cancer = Can be prevented by having a colonoscopy

Answer 72

Answer: Comes from a single cell How do we know: Women = a mosaic of cells If look at tumors in women --> You always have the same X chromsome activated in teh tumor cells as the X chromsome activated in teh cell it orginated from Women = verified the fact that tumors come from one single cell

Answer 73

Women = mosiac of cells --> because the tissues in female only have one X chromsome that is activated

Answer 74

Many oncogenes aere associated with RTKs Example: Have HER2 receptor -- protooncogene + EGF recepor (EGF = inactive) THEN have single change in one Amino Acid HER2 --> NEU oncoprotein -- NOW always on OR have a delation EGF --> ERbB oncoprotein -- always on = constitutive

Answer 75

A few oncoproteins are chimeras Ex. Chimeric Trk oncoprotein -- C termical of Tropomysoin binds to Trk receptor = get cancer

Answer 76

Some oncogenes are due to interactions with Virus Glycoproteins -- SFFC (Spleen focus forming virus) = example --> results in excessive number RBCs How does it work: A 55,000 da glycoprotein from virus binds to Epo RTK = turns it on --> get RBCs (have hematoposis) Causes -- Eurothro Lukemia -- overproduction of RBCs

Answer 77

Rb - Retenoblastomal ***Discovered by Robert Weinburg

Answer 78

Tumor supresser gene Comes from nueronal stem cells ***Bilateral --> affects retina --> Kids can go blind 1/200,000 ***to treat = use enuculation --> take eye out

Answer 79

Can be inherited or sparatic - Inherited dfective gene -- inherit one loss of function alele (have normal cell because receisisve) BUT then have another loss of function mutations -- homozygous loss of function (because now both have loss of function allele) cell gives rise to tumors in retina - Sparatic -- have loss of functional gene -- need 2 sparatic mutations to occur = rare - Sparatic = inherit two healthy alleles --> have one loss of function mutaion THEN anoteh rloss of function mutation and teh homozygous loss of function gives rise to tumor ***can occur from missegragation during mitosis

Answer 80

1. P53 2. Rb 3. BRACA 1/2 4.

Answer 81

Misegrigation + recombination -- if have 1 defcetive allele through misegregation then have recombination

Answer 82

Results in Li Frimueni Syndrome --> have 25X higher chance of getting cancer

Answer 83

Tumor supressor gene -- normal function is repair DNA breaks Defective gene = increases breast cancer (60% chance of getting breastcancer VS normal chance without mutation is 2%) ***Some people with mutatations have masectamy before the cancer developes ***There was a law suit based on BRACA assay

Answer 84

There are 1300 gentic tests for human diseases including cancer suceptability such as BRACA ***There was a big lawsuit based on BRACA assay

Answer 85

Indirect --> the native form does not cause cancer BUT when they are processed by the liver Cytp450 takes the indirect and makes it into a carcinogen (because the cytp450 cant tell a difference between the indirect and not harmful things) Direct --> Does soemthing to DNA to a point where p53 can't correct it

Answer 86

1. Aflotoxin (peanut fungus that mutates p53) 2. Benzo pyerene

Answer 87

Tumor supressir genes look for and repair mistakes in DNA

Answer 88

We have DNA repair enzymes that fix defective genes

Answer 89

Inherited disease that is caused by probelms with DNA repair enzymes - Affects kids - Charcahterized by many skin lesions because of UV sensityity --> can't repair thiamine dimers ***Camp sundown = camo for kids with UV sensitivity disorder + midnight sun is a movie based on story of person with XP

Answer 90

Used to detect cancer -- we now have liquid biopsy that is a real way to detect cancer Galeri Test -- idetifies cancer by looking at cfDNA -- can idetify 50+ types of cancer - Many peolpe investing - Recomended for adults with risk of cancer -- not replacing other cancer screening methods

Answer 91

1. Radiation 2. Surgical Ablation (Resection) 3. Chemothearapy using non-biologics (drugs) 4. Biologics (mABs + conjugated antobodies) 5. Immunotherapy

Answer 92

1. Brachythearpy -- injecting radioisotope into tumor (radioactive seeds) --> localized -- good for solid tumors 2. EBRT (External Beam Radiation Thearapy) -- Cyberknife -- no seeds + focuses on tumor

Answer 93

Overall: Works by triggering checkpoint systems resulting in apoptosis ***Causes so many issues in target tissue then p53 will come in and cause apoptosis - Bad if p53 is defective -- then you are just making cancer

Answer 94

Robotic system for prostate cancer -- Surgical!!! Example of surgical ablation -- remove the cancer

Answer 95

1. Da vinci System (prostate cancer) 2. SCN PSN systems -- cryoablation Surgery = removing the cancer

Answer 96

Surgical option -- treats cancers with cryoablation - Uses slender catheter to then reach and kill cancer --> kill cancer with heat + cold ***Used for prostate cancer -- made a prostate cancer tissue to test it on using tissue engineering

Answer 97

Chemo Drug Targets the M phase -- promotes polymerizes = interferes with spindle

Answer 98

taxol = natural product Taxatrene = semi synthetic -- taxol is hard to harvest enough from trees = made synthetic product ***Both = target microtubulues ***Clinical name = pacitaxel

Answer 99

Looks at microtubulues --> sees if there are mistakes -- if there are mistakes then it triggers apoptosis Taxol = affects the spindle = affects the M phase checkpoint

Answer 100

Chemo drug -- Drug that looks like a DNA based but isn't --> Cell incorportaes it into DNA --> p53 sees it and can't fix the probelm so it makes teh cell go through apoptosis ***Triggers DNA damage ***Most common chemo drug ***Affects RNA + DNA

Answer 101

Chemo drug -- Inhibits the bcr-abl fusion protein ***Designed based on BCR able protein --> protein kinase -- inhibits BCR kinase = no phosphorylation = no cancer ***Needed to know molceular action in order to make drug

Answer 102

Chemo Drug -- Competative antagonist of estrogen receptor ***Used with women worried about breast cancer

Answer 103

Includes: 1. mAB 2. Conjugated antibodies -- synthetic bispecific AB ***Billion dollar industry

Answer 104

Has two different FaB regions = one binds to cancer cell and one binds to T-cell --> brings the two together = kill cancer cell Trifunctional Generated using quodroma cell lines -- two different FaB ends Ex. Catumaxomab

Answer 105

1. Herceptin 2. Kadcyla 3. L-DOS 47

Answer 106

mAB used for breast cancer - Used for HER2 positive breast cancer --> 1-2 million HER2 receptors How does it work: HER2 = RTK --> causes cell division BUT with teh AB the AB blocks dimerizations = can't bind HER2 to ligand = no cell division

Answer 107

Herceptin (1998)

Answer 108

Alone = not an oncoprotein BUT overproduction of HER2 (overexpression) = leads to cancer --> have more cell division

Answer 109

Conjugated mAB -- 2nd generation HER2 ***Has DM1 attatched --> DM1 affects microtubulues = triggers Mphase checkpoint How does it work: Cell endocytoses the DM1 + AB blocks HER2 receptor --> HAS TWO EFFECTS

Answer 110

Conjugated AB BUT has nothing bound to it INSTEAD it has Urease Urease -- binds to cell = changes teh pH (increase pH) around the cancer cell = kills it ***Changes the microenvirnment = kills cancer ***Acidic envirnment prevents T-cell attacks of tumor cells = it makes envirnment less acidic ***In clincal trials

Answer 111

Blocks angiogensis -- many solid tumors secrete angiogensis factors = blood vessls grow towards the tumor Avastin acts like sponge -- binds to VEGF surrounding the tumor

Answer 112

Used to treat macular degeneration

Answer 113

Overall: treating cancer = use many things in cocktail --> drugs are not used in isolation -- they are used in combination to target different forms of the cell R-CHOP -- mAB

Answer 114

Immune system = can recognize solid tumors and approach Issue: Tumor cells = have a don't kill me sign

Answer 115

Start = Dedreon --> They thought to built a better immune system to attack cancer cell better --> they took a dendritic cell and genetically modified it so that they are more robust so they could kill cancer Dedreon target = prostate cancer Results: It works --> gave people 4 more months to live but insurance companies did not want to help people pay for it = the company went out of buissness Begining of interest in immunotheraoy -- dedreaon treating prostate cancer

Answer 116

Treatment regime that directs an individual's immune system to fight cancer by either stimulating it to attcak cancer cells or by introducing manufactured immune system componenents top augment immune function KEY = T-cells recignize and eradicate cancer cells

Answer 117

T-cells with CAR modification --> Take out T cells and modify them so that they now express CAR receptor --> Now its AB like molecule --> CAR-T cells can bind to the target cancer lymphoma cells = can kill the cancer cells CAR = Chimeric Antigen receptor ***Genetically modified T cell

Answer 118

1. Stimulate iverall immune system response of patients 2. Introduce engineered T cells harvest from pateints with CAR modified T cells

Answer 119

Doesn't work in solid tumors -- works in liquid tumors

Answer 120

First used with Chronic Lymphatic Leukemia (CLL)

Answer 121

1. Tumor cells can express multiple inhibitory ligans to repress T-cell function and thereby evade being targeted by the immune system 2. Challenges is to design a CAR -T cell that targets only the target tumor and not similar surroudning tissue 3. Sever toxicty can occur leading to death 4. Not currentley applicable for solid non-blood tumors (like liver tumors)

Answer 122

Immunithearpy that blocks the "don't kill me signal" on tumor cells Anti-PDL -- ant-PD1 mABs FDA approved mAB -- blocks PD-L! Some blocks PD-L1 some blocks PD1

Answer 123

Wearable CTC Filter system Device = collects and counts CTCs -- monotiors tumor load = know if you need to go back/change chemo treatment ***Shows if chemo works Second thing = finding and understanding driver mutations --> make drugs

Answer 124

Selectively kill cancer cells

Cancer Flashcards

(150 cards)