Exam January 2018, questions PDF

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Given in Workshop 8...

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306BMSCancerBi ol ogy–Wor kshop8.

Exam Revi si on I nt hi s Wor k shop y ou hav et he c hanc et ot es ty our knowl edge and under s t andi ngofc anc erhal l mar k s.Li s t edbel ow ar eex am ques t i onss etf or t hi sex er c i s e,t hes eques t i onsi l l ust r at et oy oubot ht hes t y l eofques t i onand c ont entas ses s ed.Youshoul ds pendt i mepr i ort ot hes es s i ons t udy i ngt he ques t i onsandr ev i si ngi nasui t abl emanner . Youshoul dc omepr epar edt o answert wooft heques t i onsbel ow.Youwi l l t hengett hechancet ogai ns ome f eedbac kony ourans wer .Remembert hatt hi si spr epar at i onf orafi naly ear ex am,t ogai nany t hi ngf r om t hes es s i ony oumus tc omepr epar edandwi l l i ng t ot es ty our s el f .

Exam quest i ons–AR

1.Genomi ci nst abi l i t yi si nher entt omostcancer sandi scr uci alf or t umour pr ogr essi on. Usi ng PARP i nhi bi t or s as an exampl e di scuss how our under st andi ng of mol ecul ar event s t hat cont r i but et ot hi skeycancerf eat ur ehasl edt onovelt her apeut i c st r at egi es. Genomei ns t abi l i t yal l owst heac c umul at i onofmut at i onsi nc anc erc el l , enabl i ng t umourpr ogr es s i on,r es i s t ance t ot her apy and met as t as i s . Al mos tal lc anc er s have s t r i k i ng genome i ns t abi l i t y ,mak i ng i tan i mpor t anthal l mar kf orc ancerpr ogr es s i on.Under s t andi ng mol ecul ar ev ent st hatcont r i but et o genome i ns t abi l i t ycr eat est he pot ent i alf or dr ugt ar get sf ort her apeut i cs t r at egi es . PARPi sanenz y mei nvol v edi ns i ngl enuc l eot i des t r andbr eakr epai rby r ec r ui t i ngot herDNA r epai renz y mes ,ei t herc aus edbyenv i r onment al f ac t or sorPARPi nhi bi t or s .I nanor malcel l ,homol ogousr ec ombi nat i on l eadst oc el ls ur v i v al .Howev er ,cel l swi t haBRCAmut at i on,ar eunabl e t or epai rt hr ough homol ogous r ec ombi nat i on. Tumour s uppr ess or BRCA genesar ek eymol ec ul esi nhomol ogousr ec ombi nat i on.PARP

i nhi bi t or sar eus edt ot r eatBRCA1andBRCA2mut at edc ancer s .PARP i nhi bi t i onl eadst odoubl es t r andbr eak si nDNA,whi c hcel l swi t hBRCA defic i enc yc annotr epai r .Thi si sbec aus et womut at edgenesocc ur r i ng si mul t aneous l y caus es s ynt het i c l et hal i t y bet ween PARP and homol ogousr epai rwi t hi nt hec el l ,l eadi ngt oapopt osi s .Under s t andi ng BRCAgenesandPARP’ sr ol ei nDNAr epai r ,al l owsust ot ar getPARP and i nhi bi ti t s ac t i on i n BRCA mut at ed genes ,f or ci ng c el l si nt o pr ogr ammedcel l deat hi nt het r eat mentofbr eas tc anc er s .

Exam quest i ons–CM

2. “ Met ast asi si s a mul t i st ep pr ocess whi ch l eads t ot he mi gr at i on of t umourcel l sf r om apr i mar yt oasecondar ysi t e.Di scussi ndet ai l ,usi ng di agr amswher enecessar y ,t hepr ot ei nsandpr ocessesi nvol vedi nt he l oss of cel ladhesi on t hati ni t i at es mi gr at i on and how t hese cel l s subsequent l ypasst hr ought heECM sot heycanul t i mat el ygai naccess t ot heci r cul at or ysyst em”-nope

3. “ Bl oodvessel sdel i veroxygenandnut r i ent st oever ypar toft hebody , butal so nour i sh di seases such as cancer .Usi ng di agr ams wher e necessar y di scusst hemol ecul armechani sms ofangi ogenesi s( bl ood vesselgr owt h)andhow under st andi ngt hesepr ocesseshasl edt oant i angi ogeni ct her api est ocombatcancer ” Exam quest i ons–KH

4. Ther ei sst r ongevi dencet hatt hei mmunesyst em canr ecogni seand ki l lcel l s wi t h ear l y neopl ast i c changes.However ,t her ei s st i l lhi gh i nci denceofcancer .Di scusst hemechani smsbywhi cht umourcel l sar e abl et o evade i mmune dest r uct i on and how t hi s has l ed t ot he devel opmentofspeci fici mmunot her api es.

I mmunoedi t i ngconsi st sof3st ageswhi chl eadt ocancerdevel opment i nvol vi ng t he i mmune syst em. I mmunosur vei l l ance at fir st al l ows dest r uct i onoft r ansf or medcel l sbef or et umourdevel opmenti nt hefir st st age,el i mi nat i on.The 2nd st age consi st s ofequi l i br i um,wher et he i mmune syst em can cont ai n butnotel i mi nat et he t umour .Event ual l y , t r ansf or medcel l swhi char enol ongerr est r i ct edbyt hei mmunesyst em and f r eel y pr ol i f er at et of or m at umouras t hey escape t he i mmune syst em.Thi s coul d be due t o a var i et y of r easons whi ch i ncl ude r ecogni t i onofcancercel l smaybedel ayed ast hephenot ypechanges ar esl ow,ort heymaybet oosmal lt ober ecogni sed.Cancercel l smay i ni t i at e an i mmune r esponse,r el easi ng HI F1 and ROS,whi ch i n hi gh doses damages genes and pr omot es f ur t heri nvasi on.Tumour s may al so evade t he i mmune syst em, by downr egul at i on MHC cl ass I r ecept or sr esul t i ngi nf ai l ur eofant i genpr esent at i on,t hecyt ol yt i cTcel l nornat ur alki l l ercel l scannotr ecogni seandr ecr ui tCTKsnorNKcel l st o ki l lt he i nf ect ed t umour .Thi st ype ofevasi on i s usual l y due t o an i nt r acel l ul arpat hogeni nf ect i ngt hecel l ,suppr essi ngpr ot ei nsynt hesi s ofMHC I .Tar getandi ncr easeMHCIexpr essi onf ori mmunesyst em t o r ecogni se t umourand dest r oy i t sel f .Regul at or y T cel l s mai nt ai nt he bal ance ofsel f t ol er ance and assi st si nt he mai nt enance ofi mmune t ol er ance.I ncancer ,r educt i onofTr egsmaybr eaki mmunet ol er ancet o cancercel l s,whi ch consi st s oft he bodys abi l i t y oft he l ack ofan i mmuner esponseagai nstsel fcel l s.TCR wi t hl ow affini t yf orMHC and sel fpept i dedevel opi nt oi mmat ur eTcel l st hatr eadsel fcel l sl eadi ngt o sur vi valandmat ur at i onofcel l s.Al t er i ngt heTCRr ecept ormayal l ow t he i mmunesyst em t opr oducecel l swhi chr ecogni sesel fcel l sagai nstnon sel f ,i ni t i at i ng an i mmune r esponse t o dest r oy cancer cel l s or by i nt r oduci ngant i bodyl i ker ecogni t i oni nant i genr ecept or sf ort hecancer t ype.Modi fied ant i bodi es coul d al so be used t o pr eventi nhi bi t i on of CTLs and enabl i ng ki l l i ng cancer cel l s.Dur i ng i nflammat i on,pr oi nflammat or ycyt oki neTNFi sr el eased.TNFandi t sr ecept orTNFR ar e l i nked t ot heext r i nsi cpat hwa yofapopt osi s,act i vat i ng caspase8and

10,al l owi ng f ort he conver si on ofe xecut i onerpr ocaspase 9 and 3, i ni t i at i ng deat h subst r at es t o cause apopt osi s.Thi sf ur t herampl i fies compensat or y pr ol i f er at i on pr omot i ng mor e mut at i ons t o accumul at e andi ncr easet hepr ogr essi onofcar ci nogenesi s.

5.I nt he1800sVi r chow fir sti dent i fied anassoci at i on bet ween t umour devel opmentand si t es ofchr oni ci nflammat i on.Di scuss t he cur r ent under st andi ng of i nflammat or y pr ocesses cont r i but i ng t o cancer devel opmentandhow t hi scanbet ar get edt her apeut i cal l y . Chr oni ci nflammat i onl eadi ngt ocanceri smost l yi nducedbyi nf ect i ous agent s. I t has been f ound t hough sense and ant i sense cDNA t r ansf ect i on exper i ment s,t het hymosi n bet a4gene,whi ch cr eat esan act i nr egul at i ng pr ot ei n and f unct i ons i n angi ogenesi s and woul d heal i ngwasf oundt obehi ghi nal lar i si ngt umourcel l s,suggest i ngi ti s r esponsi bl ef ort umourf or mi ngandmet ast asi st hr oughr egul at i ngcel l mot i l i t y. E1AF ,amemberofet concogeni cf act orwasi ncr easedi nar i si ngt umour l i nes.E1AFr egul at est umourcel lmot i l i t yandi nvasi veact i vi t i est hr ough i nduct i on ofmembr ane t ype1mat r i x met al l opr ot ei nase ( MT1MMP) , whi chconver t sl at entf or m ofmat r i xmet al l opr ot ei nase2( MMP2)i nt oi t s act i vef or m,al l owi ngt umourcel l st obecomei nvasi ve. Neut r ophi l s,fir str esponsemonocyt esi ni nflammat i on,wer ef oundt obe mai ncomponent sofi nflammat i onassoci at edt umourdevel opmentand pr ogr essi on,butcapabi l i t y ofneut r ophi l st o accel er at et umourcel l mal i gnancy var i ed dependi ng on act i ve phase. Onl y i nfil t r at ed neut r ophi l s conver t ed r egr essi vecel l si nt o mal i gnantones.Wi l dt ype der i ved phagocyt es i ncr eased f r equenci es of t umour devel opment . Tar get one of t hese. Neut r ophi l s r el ease l ar ge amount s of NO, accompani edbyROS,l eadi ngt ocel ldest r uct i on,andf ur t herpr omot i ng t umour pr ogr essi on. Admi ni st r at i on of ami noguani di ne, a br oad i nhi bi t orofi nduci bl e ni t r i c oxi de synt hase,par t i al l y butsi gni ficant l y suppr essedconver si oni nani malmodel s,sol i di f yi ngt het heor yt hatNO

i si nvol ved i nt he pr ocess.ROS and NO der i ved f r om f or ei gn bodi es i nduced i nflammat or ycel l sar ean i nt r i nsi cf act ori nt heconver si onof r egr essi vecel l st omor emal i gnantones,cont i nuousgener at i onofROS andNO causecompensat or ycel lpr ol i f er at i on,whi chhel psaccumul at e DNA damages/ genemut at i onsand effect i vel yi ncor por at ei nt er naland ext er nalcar ci nogeni cf act or si nt o gr owt h ofnor malst i mul at ed cel l s. MnSOD i nduced at i nflammat i on si t e was effect i ve i n suppr essi ng i nflammat i on r el at ed car ci nogenesi s. An effect i ve pr event i on of i nflammat i on r el at ed car ci nogenesi s coul d be by t ar get i ng ROS pr oduct i on of i nflammat or y cel l s or by bl ocki ng i nfil t r at i on of i nflammat or y cel l si nt ot he i nflamed si t e.I nflammat or y envi r onment s accel er at e epi genet i c al t er at i ons and t hose al t er at i ons coul d cause i nflammat i on

r el at ed

car ci nogenesi s, suggest i ng

i nflammat or y

envi r onmenti sani chei ncar ci nogenesi s.

Exam Quest i ons–EG

6.How doesourunder st andi ngoft heWar bur geffecti ncancercel l sai d i nei t hercancerdi agnosi sort her apy?nope...