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Anti-Cancer Activity of Cow Urine: Current Status and Future Directions

Article · January 2005

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Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 1 © 2005,Cow Therapy Society, Pantnagar, India.0973-2241/05/$5.0 International JournalofCowScience Division of Avian Diseases, ANTI-CANCER ACTIVITY OFCOWURINE:CURRENTSTATUS curing cancers,andthusinspire confidenceinthepublicaboutits goodvirtues. side effects, asgenerallyobservedwithchemotherapyand radiationtherapybeingfollowedfor of thescientists, researchersandclinicianstostrengthenthis alternatelowcosttherapyhavingno cow urinetherapyneedsimmediateattention,promotion, andwidepopularitypropersupport promoting its vital medicinalpotentialandprospectivesforthebenefitofmankindwithview that and popularity. This reviewhighlights theanti-canceractivityofcowurineandstrategiesfor extensively. However, scientificvalidationofcowurinetherapyisrequiredforitsworldwideacceptance even thecancer, theuseofGomutra(cowurine)indigenousbreedscattleshouldbepromoted cows ismosteffective. Seeingthepotentialuseof indigenous cowurineinseveralailments including therapy. Experimentally ithasbeenprovedthatamongallsorts ofurines,theurineIndian and helps themtosurvive;andefficiently repairs thedamagedDNA,thusiseffective forthecancer prevent thefreeradicalsformationandactasanti-aging factor;reducesapoptosisinlymphocytes of cancer. Cowurineenhancestheimmunocompetenceandimprovesgeneral healthofanindividual; reflected byseveralcasereports, successstoriesandpracticalfeedbackofpatients forthetreatment pollutants, occupational healthhazards etc. Anti-cancer potentialofcowurinetherapyhasbeen predisposing factorsofcarcinogenssuchastobaccochewing,smoking,alcoholintake, environmental increasing inthecurrentscenarioofchangedlifestyleandfoodhabbits alongwithexposureto cancer, adeadlymaladywhichisbeingfacedbythemankindandincidencesofareever few yearscowurinetherapyhasprovidedpromisingandauthenticresults forthetreatmentof cancers andthatcowurineenhancestheefficacy andpotencyoftherapeuticdrugs.Duringthepast milestone the uptake ofdrugsincombinationtherapyandreducethedosedurationtreatment. These fungal andanti-cancerdrugs. Thus itcanpromoteandaugmentthebioactivityorbioavailability as ‘ark’,hasbeenidentifiedabioenhanceroftheactivitiescommonlyusedantibiotics,anti- against cancers. Through extensive researchstudiesacowurinedistillatefraction,popularlyknown properties, particularly forits usealongwithantibioticsforthecontrolofbacterialinfectionandfight Recently thecowurinehasbeengrantedU.S.Patents (No.6896907and6,410,059) forits medicinal aging, chemicalintoxicationetc.Cowurinecankillthenumberofdrugresistant bacteriaandviruses. tuberculosis, chickenpox,hepatitis, leucorrhoea,leprosy, ulcer, heartdisease, asthma,skininfections, reported withthosesuffering fromflu,allergies,colds,rheumatoidarthritis,bacterial/viralinfections, the medicinesmadefromitareusedtocureseveraldiseases.Improvements havebeenshownor diabetes. Practitionersof Ayurvedic medicinefromIndiaroutinelyusecowurineasaremedyand or ‘cowpathy’, hasbeenreportedtobebeneficialevenfordreadeddiseaseslikecancer, AIDS and curable byallopathic treatments. This kindofalternativetreatment, termedas‘panchgavya therapy’ are usedsinglyorincombinationwithsomeotherherbsagainstmanydiseases,eventhosenot ghee, curdanddung),obtained fromcow. All thefiveproducts possessmedicinalproperties,and important ingredientofpanchgavya, atermusedtodescribefivemajorsubstances (urine,milk, nector oftheGod.InIndia,drinkingcowurinehasbeenpracticedforthousandsyears.Itisan therapeutic values.Ithasbeenrecognizedaswateroflifeor“Amrita” (beverages ofimmotality), the ‘Ashtanga Sangraha’ tobethemosteffective substance/secretion ofanimaloriginwithinnumerable Cow urinehasauniqueplacein Ayurveda andhasbeendescribedin‘Sushrita Samhita’ and Key words:

achievements highlightthebeneficialroleofcowurineintreatingbacterialinfectionsand Indian Veterinary ResearchInstitute,Izatnagar(U.P.)- 243122,INDIA 2 Centre for Animal DiseaseResearchand Diagnosis(CADRAD), K. DHAMA Cowurine,cancer, tumor, cowpathy, panchgavya, treatment AND FUTUREDIRECTIONS , 1 1 (2): 1-25 , R.S.CHAUHAN Abstract 2 AND LOKESH SINGHAL 2 REVIEW ARTICLE www.ijcs.coz.in www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 Chauhan, 2005). fight diseasessuchascancer (GargandChauhan,2003; infections, savemankind from different ailments and the alternativetherapeutic approachestocontrolthe circumstances mentioned above onehastothinkover and evensomeofthetumors areincurable.Inallthese physical andmental agonyofthepatientandarecostly, therapies produceseveresideeffects addingtothe particularly withmalignanttumors,andmoreover, these for treatingthecancer, butthesuccessrateislow chemotherapy, radiotherapyandsurgeryareavailable health hazardsetc. The methodologieslike alcohol intake, environmental pollutants, occupational carcinogen intheformoftobaccochewing,smoking, lifestyle andfoodhabbits alongwithdangersof ever increasinginthecurrentscenarioofchanged of humansufferings fromcancer, adeadlymalady, are almost ineffective bytheyear2020. Also theincidences drugs “antibiotics”willnotremainusefulandbecome individual. As perWHO,thetwentiethcenturywonder infections, and/ordecreasedimmunestatus ofan development ofresistance inbacteria,recurrent chain. This hasleadtotheinefficacy ofantibioticdrugs, pesticides, heavymetals,fungaltoxinsetc.inthefood use ofagrochemicalsinagricultureandpresence drastically asaresultoftheenvironmental pollution, autoimmune disordersinhumans.Immunityisreducing residues infoodchainand/orassociatedallergiesand resistance inmicroorganisms,presenceofantibiotic treatments duetothedevelopmentof multiple drug clinicians arefacingprobleminmodernallopathic of chemicalfertilizersandpesticides.Scientists / 2005). These canprovidefoodfreefromhealthhazards al., and Chauhan,2003a,b; Achliya et al., Chauhan, 2000,2001,2002a,b,2004a,b,2005;Fulzele Samhita, 1981,Susruta Samhita,1985; Tietze, 1996; resources (biogas,fuelandelectricity)(Charaka- fertilizer, pestrepellants andasalternateenergy as goodqualitynaturalmanureandbiopesticides,bio- beneficial implicationsinagriculture,organicfarming Apart fromhighmedicinalvalues,panchgavya hasmany panchgavya inthetreatmentofvarioushumandiseases. Ayurveda, hasdetail mentionsofimportance of and bio-diversity. The ancientIndiansystemofmedicine, significant roleinruraleconomy, representcattlewealth “Gaumata, hashighsocio-culturalvalues,plays distinct species,popularlyknownas“Kamdhenu”and dung, gheeandcurd.Indiancowbreedsareunique Dhamaetal. INTRODUCTION 2 2004,SinghandChauhan,Dhama “Panchagavya” isacombinationofcowurine,milk, 2001,2003;Joshi,2002;Nautiyal,Garg et al., 2004;Saxena et al., et scientists, researchersandclinicians soastostrengthen promotional campaigns andjudicious support ofthe good virtuesofcowurine needproperattentionand cancer, themostdreadedandincurable malady. Manya safer, cheaperandwithoutanysideeffects forfighting alternate prophylactic/therapeutic approach,whichis popularizing “CowUrine Therapy /Chikitsa” asan compiled thisinformationwithultimategoal of patients treatedwithcowurinetherapy. The authorshave and casereports, successstoriesandfeedbackofcancer of cowurine,wellsupportedbytheknownscientificfacts of it. The presentreviewfocusestheanti-cancer activity scientific validation,peopleareusingandgettingbenefits optimal powerfortheserviceofmankind.Regardless of in termsofmedicinalapplicationssoastoexploit its is requiredforits worldwideacceptance andpopularity infections etc.However, scientificvalidationofcowurine infections, hepatitis, leucorrhoea,leprosy, asthma, skin allergies, colds,rheumatoidarthritis,bacterial/viral successful inrelievinghumansufferings fromflu, panchgavya, andthecowurine therapyhasbeen diseases. Cowurineisanimportant elementof benefited bythepanchgavya products forseveral of allopathy arenowusingcowpathy drugsandbeing panchgavya products(Chauhan,2005). the medicinalpropertiesofcowurineandother of M.Sc.,M.V.Sc., M.D.and/orPh.D. areworkingon urine andotherpanchgavya products.Severalstudents are workingondifferent medicinalpropertiesof cow Government Organizations(NGOs)andotherInstitutes Indian Veterinary ResearchInstitute(IVRI),besidesNon- University of Agriculture and Technology, Pantnagar, and Institute ofMedicalSciences(AIIMS),G.B. Pant of ScientificandIndustrialResearch(CSIR), All India Several scientists fromdifferent laboratoriesofCouncil of resistance inmicroorganismsagainsttheantibiotics. with theantibioticscanalsopreventdevelopment opening anewerainmedicalscience.Cowurinealong its useintuberculouspatients andfightcancers,thus establishing thebioenhancingpropertiesofcowurine, patents havebeengrantedtoIndianscientists on recently hasreceivedworldwideattention. Two US like cancer, AIDS anddiabetes.Ofthese,thecowurine been reportedtobebeneficialevenfordreadeddiseases the infections. This kindofalternativetreatmenthas enhance thebody’s immunityandresistance tofight be beneficialincuringseveralhumanailments and naturopathy. Panchgavyaproducts havebeenfoundto panchgavya therapyor milk, ghee,curdanddung,thekindoftreatmentiscalled The peoplefrustratedfromtheheavymedication Utilizing thebeneficialpropertiesofcow’s urine, cowpathy , asystemof www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 and formaneverincreasingmassoftissue. irrespective ofanystructuralorfunctionalrequirements growth, andits cellscontinuetomultiplyindefinitely does notobeythelawsofhealingornormaltissue useful functionandnoclearetiology. A neoplasticgrowth embryonic cells,nostructural/orderlyarrangement, by keyfeaturesofcontinuousgrowth,resemblanceto purpose lessproliferationofcells of abnormal,excessive,uncoordinated,autonomousand It canbedefinedas“ formations ornewgrowth”(Neo=new, plasm=growth). been derivedfromGreeklanguagemeans“New cancerous ornon-cancerous. The wordneoplasmhas 2004; MerckSource.htm). (Oncos=tumour, logos=study)(Ezra,2002;Stephen, science whichdealswiththestudyoftumours cessation ofthestimuli/etiology. Oncologyisbranchof growth oftumourpersists inthesameexcessevenafter can spread(metastasize) throughoutthebody. The failure. Cancerouscellsfromtheprimary(initial)site normal functionofvitalorgansandcancauseorgan at theexpenseofhealthytissues. This growth prevents Tumors generallyprovidenousefulfunctionandgrow which invadesanddestroysadjacenthealthytissue. they formamassofcanceroustissue,calledtumor, within anyorgan. As cancerouscellsgrow andmultiply, Cancerous (malignant)cellscandevelopfromanytissue mechanisms andthushasunregulatedgrowth. derived fromasinglecell,thathaslostits normalcontrol as neoplasmortumorItisagroupofcells,usually changed, ormutated, fromnormalcells,itisalsoknown uncontrolled growthofabnormalcellsthathave Chondroma, Adenoma, Papilloma. Chondroma, Adenoma, addition ofasuffix-oma tothecelltype.e.g.Fibroma, can beremovedbysurgery. They areclassifiedwith membrane. They remainlocalized, encapsulated and expansion anddonotinvadebelowbasement These neoplamsarewelldifferentiated, growslowly by in nature. harmless dependingonthelocation.Itisnon-cancerous malignant. deadly diseaseslikecancercouldbetreated. confidence inthephysiciansaswellpublicthat the miraculouscowurinetherapywhichcaninspire Neoplasm isageneraltermfortumor, whether Cancer isthetermusedtodescribe CANCER Benign: Tumors areclassifiedaseither benignor CLASSIFICATION

In Benigntumours,thecellsareofadulttype. These areslow-growingandoften A massoftissueformedasaresult ” andischaracterized niCne ciiyo o rn 3 Anti-Cancer activityofcowurine or toperform new functions.Cellsthatare damagedor regulated. Newcellsarecreated toreplaceolderones division ofcellsinthebody isstrictlycontrolledand abnormal regulationofcell division. Typically, the chromosome 15occursto12. lymphocytes) inwhichtranslocationofsegments of translocations. e.g. karyotype intheformofchromosomalbreaks or diploid numberofchromosomes. This givesapathologic usually aneuploidi.e.cellshavingmoreorlessthan cytoskeleton. chromosome movements causeabnormalityin in thegrowth/spreadoftumours. helps ininvasionandmetastasis. neighbouring cellsduetodecreasedadhesiveness.It undifferentiated neoplasm. malignant tumours”. undifferentiated theyarereferredas“undifferentiated Squamous cellcarcinoma.Sometumorsarehighly Sarcoma. e.g.Lymphosarcoma, Adenocarcinoma, Ectodermal origin-Carcinoma,Mesodermal classified withsuffix ascarcinomaorsarcoma. crab”. They canadheretoanypart ofbody. They are tissue. They arealsocalledascancermeaning“like and invadetheadjacenttissuesdestroynormal Thus, theneoplasticcellsareanaplastic,metastasize figures, hyperchromasiaandembryonictypefeatures. enlargement ofnucleolus,increasenumbermitotic nucleus, multiplenuclei,(tumourgiantcells), malignant cellscharacteristicallyshowenlargementof will dependonthedegreeofanaplasiainwhich we seeinatumourmoremalignancywillbethere.It is alsoknownasanaplasia. more primitiveorembryonicandlessdifferentiated type of embryonicstages. This reversiontowardscellstoa malignant tumorsthecellsarehavingcharacteristics spread toacompletelynewlocationbymetaplasia. In surrounding tissueaffects its spread.Cancerouscells The invasivecapacity ofacancertoinfiltrateanddestroy to otherparts ofthebodyandcausesevereproblems. cancer. In general,tumorsappear tobecausedby ETIOLOGY AND RISKFACTORS Chromosomal defects: Abnormal cytoskeletonofcells: Neoplastic celllackcontact inhibition: Loss ofcontact: Anaplasia: NEOPLASTIC CELLSTRUCTURE Malignant:

These arefaster-growingandlikelytospread Malignanttumorsarewhatwecall More anaplasiarepresents more . Plasmacytoma (tumourofB- Neoplastic cellslosscontact with

The moreanaplasticcells Malignant cellsare Its unstable It helps www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 common infemales. the body’s immunesystem. Tumors ofgenital tractare prolonged exposuretocarcinogensandweakeningof rate isprobablyduetoacombinationofincreasedand are morecommoninolderpeople. The increasedcancer among childrenortheelderly. However, mostcancers in onesexthantheother, somearemorecommon hereford cattle. is common.Squamouscellcarcinomacommonin cancer development.InwhitehorsesMelanosarcoma are resistant forleucosis.Pigmentation alsoeffects the Some chickenaresusceptibleforleucosiswhileothers abnormal chromosomemayincreasetheriskofcancer. History ofgeneticabnormalitiesandanextraor Hormones (Estrogen), Drugs(Phenobarbital), Artificial (Aldrin, Dieldrin,Chlordane). Metals (Nickel,Lead,Cobalt,Chromium),Insecticides (Tobacco, Smoke,Pollutants), Benzanthracene, Arsenic, Nitrosourea), Polycyclic aromatichydrocarbons (Cyclophosphamide, agents Mitomycin, Alkylating so. cause cancerandmanyothersaresuspectedofdoing Ionizing radiationisparticularlycarcinogenic. radiation primarilyfromsunlight,causesskincancer. ultraviolet radiation(UV-rays), X-rays,radium,ionizing tumors. detects andblocksaberrantgrowth,canalsoleadto Abnormalities oftheimmunesystem,whichusually Dhamaetal. deaths fromcancerthananyotherenvironmental agent. obesity andsedentarylifestyle. Tobacco causesmore radiation, excessivesunlightexposure,alcoholism, years. Otherfactorsincludegeneticabnormalities, chemicals anddevelopmentofthecancermaybemany aflatoxins etc. The timebetweenexposuretothe nuts, tobacco,certain viruses,poisonousmushrooms, inhibitors, diethylstilbestrol,radiationtherapy),betel agents, chemotherapydrugssuchastopoisomerase exhaust), medicinal/therapeuticagents(alkylating chromates, nickel,vinylchloride,mineraloil,diesel (arsenic, asbestos,aromaticamines,benzene, that causescancerandincludesmanychemicals is disturbed,atumormayform.Carcinogenanagent replacements. Ifthebalanceofcelldivisionanddeath no longerneededdietomakeroomforhealthy 4 Initiators: Sex and Age: Family HistoryandGenetic/Heredityfactors: Instrinsic orPredisposingFactors Chemical factors: Physical factors: Extrinsic Factors Coal-tar, Aflatoxins, Actinomycin D, Coal-tar,Actinomycin Aflatoxins, Sometumorsaremorecommon Many chemicalsareknownto Extended exposureto Promoters: Phenols, (iii) themalfunction ofatumorsupressor gene. transformation ofanormal geneintoanoncogeneand impairment ofaDNA repair pathway (ii)the mechanisms forthecancers developmentare(i) develop amalignantgrowth. The predominant promoting factorshaveto add upbeforeapersonwill predisposition, orboth.Usually, severalcancer- factor (e.g.tobaccosmoke)orbecauseofagenetic cancer, beitthroughexposuretosome environmental in oneormoreofthenodesthisnetworkcantrigger should happenandhowerrorscanbefixed.Mutations together tosaywhenacellcandivide,howoften it constraint, involvinganetworkofsignalsthatwork control. Usually, thetimingofcelldivisionisunderstrict SPREAD DEVELOPMENT AND chronically irritating thebladder. Schistosoma (Bilharzia) result incoloncancer. Infectionwiththeparasite meats increasestheriskofdevelopingstomachcancer. diet highinsmokedandpickledfoodsorbarbecued at muchhigherriskofdevelopingesophagealcancer. A cancer. Peoplewhodrinklargeamounts ofalcoholare increased riskofcolon,breast,andpossiblyprostate diet andenvironment. risk isprobablymultifactorial:acombinationofgenetics, Retrovirus andHerpesvirus. (Hepatitis Bvirus–hepatocellular carcinoma), Polyoma virus, Adeno virus,Poxvirus,Hepdnavirus lymphoma. Othervirusescausingcancersinclude of thebloodsystem.Epstein-Barr viruscausesBurkitt’s human retrovirusescauselymphomasandothercancers women. Hepatitis Bviruscancauselivercancer. Some causes genital warts) isonecauseofcervicalcancerin suspected ofcausingcancer. The papillomavirus (which cause cancerinhumans,andseveralothersare and bladder. of developingcancersthelung,mouth,larynx,kidney, produces carcinogensthatsubstantially increasetherisk exposure maycauselungcancer. Smokingcigarettes increase thecancerrisk.Forexample,asbestos whether fromindustrialwastesorcigarettesmoke,can preservatives. sweetners (saccharine,colouring/flavouringagents and Cancer occurswhencelldivisiongets outof Inflammatory Diseases: Diet: Geography: Other factors Viral Infections: Environmental Factors: A diethighinfathasbeenlinkedtoan The geographicvariationincancer Severalvirusesareknownto maycausebladdercancerby Ulcerativecolitiscan Pollutionintheair, www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 mechanism) favourproliferationoverdifferentiation. normal genesexpressedatabnormallevel(epigenetic presence ofabnormalgenes(geneticmechanisms)or characters areactivated.Inneoplasticcells,the switched off andgenesformoredifferentiated so thatthegenescontrolembryoniccharactersare controlled byspecificgene.Cellsbecomedifferentiated from lessspecializedcells(embryoniccells)are ionizing radiation, usedinX-raysand producedin cancer withouttheneedfor promotion.Forexample, carcinogens aresufficiently powerfultobeablecause carcinogen, areneeded tocausecancer. Some often thecombinationofa susceptiblecellanda has noeffect onnon-initiatedcells. Thus, severalfactors, undergone initiationtobecomecancerous.Promotion themselves. Instead,promotersallowacellthathas Unlike carcinogens,promotersdonotcausecancer by environment orevensomedrugs(suchasbarbiturates). are calledpromoters,whichmaybesubstancesinthe cancer iscalledpromotion. Agents thatcausepromotion carcinogens. The secondstepinthedevelopmentof physical irritation maymakeacellmoresusceptibleto in acellmaymakeitmoresusceptible.Evenchronic are equallysusceptibletocarcinogens. A geneticflaw that causescancer(acarcinogen).However, notallcells may occurspontaneously orbebroughtonbyanagent cancerous. This changeinthecell’s geneticmaterial chromosome structure,primesthecelltobecome genetic material,intheDNAandsometimes process isinitiation,inwhichachangethecell’s process calledtransformation. The firststepinthe Cancerous cellsdevelopfromhealthyinacomplex to respondnormalsignalsfordifferentiation. tumour. Neoplasticcellsdonot“dedifferentiate” butfail cells (pluripotential)mustbepresentforthegrowthof such asneuronsorkeratinizedepithelialcells,butstem Tumors donotarisefromcompletelydifferentiated cells through neutralizingnormalgrowthcontrollinggene. of viralgenestohostDNAthatinducescellproliferation direct chemicalorradiationdamagethereisinsertion for proliferation.ChangesoccurinDNAasaresultof mRNA translatedtoprotein(enzymes)whichdirectcells rearrangement occurslikeDNAtranscribetomRNAand which isresponsibleforabnormalgrowthofcells. cancer cellbuttranscriptionandtranslationisabnormal population ofcells. nucleic acidoccurstoprovideastable andmonoclonal Genetic mechanisms: Cell differentiation: Neoplastic cellgenesis(Carcinogenesis) In mosttumorsgeneticmutation orgenetic Epigenetic mechanism: Specialized cellsderived Mutation inasomaticcell Genome isnormalin niCne ciiyo o rn 5 Anti-Cancer activityofcowurine raf, myc via DNA damagingreagents or ionizingradiation. telomeres orlossofcapping cansensitizecellstodeath cells areconvertedintocancer cells.Inducingshort within multiplegrowthcontrol pathways beforenormal humans isgrowingolder. Geneticalterations mustoccur progression. The greatestriskfactorforcancer in to playcriticalrolesinagingaswellcancer tumorigenesis. Telomere dysfunction has beenproposed involved ingrowthcontrol,ultimatelyresulting in in mostcancersandleadstomis-regulationofgenes one oftheearliestneoplasticchangesknowntooccur telomeres mightleadtocancer. Genomicinstabilityis preimmortal cellsduetodysfunctionaloruncapped mechanisms, thegenomicinstability encounteredin instability. Inconjunction withotherpredisposing undergoing senescence,apoptosis,orgenomic that cellrespondstodysfunctionaltelomeresby recognized asdouble-strandedbreaks.Itissuggested chromosome end-to-endfusionsand/orendsbeing the disruptionoftelomeremaintenanceresultin maintaining genomicintegrity. Alterations thatleadto telomere-associated proteins,whichareessentialfor structures thatcontain noncoding TTAGGG repeats and inactivation ofantioncogene. as aresultofactivationoncogeneordueto cellular proliferation.Soneoplasticgrowthoccurseither and ( leucosis virus), (Rous sarcomaVirus), control. Someoftheviraloncogenes(v-oncs)are: adjacent geneactivatedforgrowthofthecellwithout integration ofviralDNAintohostcellcauses integration ofviralDNA intohost cell DNA. The inappropriate expressionofproto-oncogenesand of pointmutation, translocation,geneamplification, converted intoactiveoncogenesthroughmechanisms of cellsthroughproteinproduct.Proto-oncogenesare range ofcellsandhasaphysiologicalroleproliferation oncs) orproto-oncogenes,whicharepresentinawide in normalcellsthatareknownascellularoncogenes(c- get transformedtomultiply. Whensuchgenesarepresent when theyareincorporatedincellsculture,the man. Itisalsopresentincertain viruses.Experimentally, forming genespresentinmosttumorcellsofanimaland leukemia, thyroidcancerandbreastcancer. cause avarietyofcancers,particularly sarcomas, nuclear powerplants andatomicbombexplosionscan Reticuloendotheliosis), fes, fms Telomeres: Antioncogenes Viral Oncogenesis: (Papillomavirus), (Felinesarcomavirus). pim - These areuniqueDNA-protein 1 , myc are genesthatsuppressesthe myc yes, ros (FelineleukemiaVirus) Oncogenes arethetrans- , hap myb, erb-B,erb-A (Avian sarcomavirus) (Hepadna virus), (Avian , src, src rel www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 as theirgrowthincreases. infiltrate inneighbouringtissue.However, theyexpand surrounded byfibroustissueandhencetheydonot abnormal enzymesoncellsurface. phosphorous duetohighrateof ATP hydrolysisand DNA ofmoitochondria,overproductioninorganic increased glycolysisduetodamageinselfreplicating molecules andglycoproteinsonneoplasticcells; sodium pump(ATPase) duetoabnormalreceptor synthesis tomeettherequirements ofmitosis;defective and mRNAtranslationisbeingdirectedtowardspurine synthesis islostinneoplasticcells.Geneexpression cells arelodged insubcapsular sinusoflymph node lymphatic permeationand formtumoremboli. These cells invadethewalloflymphatics whichisknownas carcinomas spreadthrough lymphaticroute.Cancer complement. enzymes, roleofchemotactic factorsandactivationof inhibition, motilityofmalignantcells,secretionlytic invasion aregrowthofnewcells,lackcontact the surroundingtissue.Various factorsresponsiblefor are asunder: subsequent proliferation. (invasion), separation, dissemination,establishment and of metastasis includes5steps viz.penetration system andbasalcellcarcinomaofskin. The process metastasize exceptmalignanttumorofcentralnervous the bloodstream.Mostofmalignanttumors extensively throughoutthebody. Sarcomasspreadvia first tothenearbylymphnodesandthenitspreadsmore system. Forexample,breastcancerusuallyspreads Carcinomas typicallyspreadthroughthelymphatic or undetectable, intheformofmicrometastasis. spread maybeovert,intheformofvisiblemetastases, the abilitytoinvadebloodandlymphvessels.Such throughout thebodyshortlyafter thetumorcellsdevelop to tissuesororgans,nearbydistant. Cancerspreads They cangrowdirectlyintosurroundingtissueorspread mass mayformsecondarytumoratthesiteoflodgment. tumors byinvasioninsuchawaythatdetached tumor bloodstream orthelymphsystem.Itisspreadof or tissuetoanother. Cancercellsusuallyspreadviathe movement orspreadingofcancercellsfromoneorgan Dhamaetal. 6 Distant spread/metastasis: Expansion: Spread ofNeoplasms Normal regulationofprogrammedprotein Neoplastic CellMetabolism Lymphatic spread: Infiltration: There areseveralmethodsofmetastasis, which Benign tumorsareencapsulated and Neoplastic cellsinfiltrateorinvade Epithelial tumorslike Metastasis isthe system’s protectivesurveillance. functioning normally, cancercanescapetheimmune However, evenwhenaperson’s immunesystemis immune systemworkslesswellthaninyoungerpeople. autoimmune diseases,andolderpeople,inwhomthe receiving immunosuppressivedrugs,thosewithcertain acquired immunodeficiencysyndrome(AIDS),those immune systemisalteredorimpaired, asinpeoplewith body; Canceroflowerlipmaymetastasize toupperlip. may transfertumorcellsfromonetoanotherplacein site inadvertently, e.g.Surgeon’s scalpel,needle,sutures of tumors.Inthisthetumorcellsareimplantedatanother central nervoussystemthroughCSF. the detached tumorcellsmetastasize atothersitesin of meningesmayspreadthroughcerebrospinalfluidas to alveoli. endometrium, andspreadoftumorthroughbronchus of tumorthroughfallopiantubefromovariesto basement membranewithoutdamagingit,e.g. neoplasms ofepitheliumspreadalongtheline colon cancause weightloss,diarrhea,constipation and shortness ofbreath,orchest pain whiletumorsofthe For example,lungtumors cancausecoughing, specific tothetypeofcancer andwhereitisgrowing. occur withmanyoralmost allcancers,andothersare on thetypeandlocationof thetumor. Somesymptoms some tumorsproducenosymptom.Symptomsdepend cavity- carcinomaofstomach/ovary. tumor cellsimplantatanotherplace,e.g.Peritoneal serosal wallandentersincoelomiccavitythen scattered intheorgan. metastasis appearasmultipleandroundednodules the wallofcapillariestoformtumoremboli.Bloodborne liver, lungs,kidneys,brainandbones.Cancercellinvade blood. Commonsitesoflodgmenttumorcellsare mammary gland,thyroid,kidney)mayspreadthrough (connective tissuetumors).Somecarcinomas(lung, blood iscommonrouteformostofthesarcomas flow andisresponsibleformetastasis atunusualsites. lymphatics bytumorcellsalsodisturbsthelymphatic environment forgrowthoftumorcells.Obstruction filter andkillthetumorcellsbutlateritprovidesfertile and maygrow. Nearestlymphnodeinitiallyactasbarrier Cancer ismorelikelytoprogressinpeoplewhose Implantation: Spread viacerebrospinalfluid(CSF): Cancer canproducemanydifferent symptomsbut SIGNS SYMPTOMS AND Spread alongepitheliallinedsurfaces: Transcoelomic spread: Hematogenous spread: It isaveryraremethodofspread The tumorcellsinvade Metastasis through s Tumor pread The www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 that theyfeel very tiredorbecomeshort ofbreathwhen People withadvancedstage cancerareoftenmayfind headaches, nausea,changes invision,andseizures. hard topinpointbutcaninclude confusion,dizziness, When acancergrowsinthe brain,symptomsmaybe or pneumoniaandtheinability tocoughupsecretions. as theairwaysinlungs,causingshortnessofbreath rubbery. Cancercancompressorblockstructures,such which becomeswollenandmaybefeltashard or to spread,itmayfirstspreadnearbylymphnodes, be massiveandevenlifethreatening. As acancerbegins Particularly withadvancedcancer, thebleedingmay and undetectable ordetectable only withtesting. vessel, causingbleeding. The bleedingmaybeslight surrounding tissues,itmaygrowintoanearbyblood weakness. As thecancerenlargesandinvades sensations (suchastinglingsensations)ormuscle and muscularsymptoms,includingachangein other structures. This maycauseseveralneurological from thecancercompressingorerodingintonerves severe pain asthecancerenlarges. The pain mayresult discomfort, whichmaysteadilyworsenintoincreasingly as theygrow, thefirstsymptomisoften amild heal, enlargedlymphnodesetc. color ofamoleorchangesinskinulcerthatdoesnot by specialtests), chroniccough,changesinthesizeor diarrhea), bloodinurine/stool(eithervisibleordetectable a recentchangeinbowelhabits (constipation or appetite, suddendepression,fatigue,malaise,vomiting, persistent pain, recurrentnausea,weightloss,lossof include: fevers,recurrentfever, chills,nightsweating, often accompany tumors(warningsignsofcancer) in theearlydetectionofcancer. General symptomsthat after thecancerprogressesandarethereforenothelpful be evaluatedbyadoctor. Othersymptomsdeveloponly and arethereforeimportantwarningsignsthatshould Some symptomsdevelopearlyinthecourseofcancer as itspreads(metastasizes) tootherparts ofthebody. as itgrowsinits initialsiteandcausedifferent symptoms other bodilyfunctions.Itmaycauseonesetofsymptoms and usingenergynutrients normallyavailablefor pressure onothertissues,producingtoxicsubstances, into andthusirritating ordestroyingothertissues,putting relatively small.Cancersproducesymptomsbygrowing may causesymptoms(suchashoarseness)whenitis in amorerestrictedspace, suchasonavocalcord, until itbecomesquitelarge.Incontrast,acancergrowing of thelargeintestine,itmaynotcauseanysymptoms grows inanareawithalotofspace, suchasinthewall cells, producesnosymptomswhatsoever. Whencancer blood inthestool. At first,cancer, asatinymassof Cancersaretypicallypainless atfirst.However, niCne ciiyo o rn 7 Anti-Cancer activityofcowurine secreted by tumor cellsorbyaltered macrophages suppression ofappetite centre inbrain.Cytokines humoral factorisreleased bytumourcellsthatcauses occurs duetodepression of appetitecentreinbrain. A leading tolossofweight and letharginess. Anorexia of malignanttumors.Inlater stages, anorexiaoccurs in death. in urinarytractorobstructionbileducts mayleadto obstruction inpharynx. Tumors whichcauseobstruction respiratory tractcausesdyspnoeaandhypoxiadue to outside tumors. e.g.squamouscellcarcinomaof The lumenofducts areobstructedduetopressurefrom oedema andlymphaticblockadeinsurroundingtissue. on surroundingtissue. The tumorcausespain,ischemia, and systemiceffects. through manyeffects whicharecategorizedintolocal appearance ofcellsvaryondegreemalignancy. resembles thetypeoftissue/organinvolved. The Microscopically, thetumouriscomposed ofcells,which and denseorsclerotic.Braintumorsaremostlysoft. bone ishardwhileconnectivetissuetumorsarefirm depends onthetypeoftissueinvolved. The tumourof milligram toseveralkg. The consistencyofatumour tumors etc. The weightoftumoralsovariesfromfew tumors havemanycentimeterdiametersuchasuterine papilloma overskinhavesmallersizewhilecertain several centimeterdiameter. The common warts/ feelings ofanger, fear, anddepression. a patient’s capabilities. These effects often leadto quality oflife,interferingwithdailyactivitiesandlimiting bone, whichinturnhasadetrimental affect onapatient’s first indicationthatthetumorhasmetastasized to the kidneys, andcentralnervoussystem.Painisoften the and maycausedysfunctionofthegastrointestinaltract, to paralysis ordeath.Hypercalcemiaispotentiallylethal spinal cordcompression.Cordcompressioncanlead fractures duetoreducedload-bearingcapabilities, and mobility, symptomsofhypercalcemia,pathologic considerable morbidity, includingseverepain,impaired indirect effects onbonehealth.Bonemetastases cause of independence.Cancerproducesbothdirectand the symptomsofillness,afeardying,andloss sleep manyhoursaday. Depressioncanberelatedto exerting themselves,fatiguedandlooseweight. They Cachexia: Systemic effects Local effects: Malignant neoplasticcellskillhumansandanimals NEOPLASMS CLINICOPATHOLOGICAL EFFECTS OF The sizeofatumourvariesfromonemmto

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Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 Dhamaetal. Hepatocytes becomeatrophied. skeletal muscles, liver, pancreas andotherorgans. out theessentialaminoacidsleadingtoregressionof Neoplastic cellsactasaminoacidtrapandthus,drain lipogenic enzymesresponsibleforfatdeposition. which causessuppressionofgenethatproduces (affected byneoplasticcell)areknownascachectin 8 episodes ofcollapse andseizures. characterized byrestlessness,weakness,tremors, tumors ofpancreas andotherepithelialtumors.Itis there issuppressionoferythropoitinbykidneys. Autoimmune anemiaoccursinlymphoidneoplasmsand or dividingcellsofbonemarrowleadingtoanemia. regeneration ofstemcells.Itcausesdeathcells to anemia.Dueanticancertherapythereisnon circulation. Irondeficiencyduetotumormayalsolead spleenomegaly duetoexcessiveremovalofRBCfrom chances ofanemia.Inhyperspleenism,thereis though tumors.Inhighlyvasculartumor, therearemore erythrocyte fragmentation asmanyblood vessels pass to invasionoftumourcellsinbonemarrow, increased invasion bycancercells,decreasederythropoiesisdue metastatic tumors. It iscausedbyhaemorrhagethrough thrombi formation. which areresponsibleforintravascularcoagulationand in dogs. leukemia, plateletsurvivalrateisreducedfrom40-80% thrombocyte productionisreduced.e.g.inviral characteristic feature. nature. Inlatestage ofmetastatic tumors feverisa increases bodytemperature whichisantineoplasticin diarrhoea leadingtodeath oftheaffected individual. cell secretesvasoactiveintestinalpeptidesthatcause and nonassociatedwithmicroorganisms.Neoplastic malignant neoplasmswhichisunresponsivetotherapy horses. and adenocarcinomaindogsgastriccarcinoma in mammary glandcancer, fibrosarcoma,lymphosarcoma in blood.Pseudohyperpara-thyroidism isassociatedwith parathyroid hormoneleadingtoincreaseincalciumlevel release. Tumour cellalsosecreteproteinsthatincreases excessive boneresorptionoccursleadingtocalcium mechanism. Insolidtumorsduetoosteolyticmetastasis neoplasms, hypercalcemiaoccursthroughtwo Hypoglycemia: Anemia: Thrombocytopenia: Hypercalcemia Thrombosis: Fever: Diarrhoea: Sometumorcellsrelease pyrogensthat

Anemia isacommonfeatureinall

Tumor cellsproduceprocoagulants Prolonged diarrhoeaoccursin Itischaracteristicfeatureof : In mostofthemalignant Intumorpatients in speaking,dizziness,and doublevision,whichmay in walking,incoordinationof thearmsandlegs,difficulty destroys thecerebellum.Symptoms areunsteadiness breast orovariancancer, duetoanautoantibody that Subacute cerebellardegeneration occursinwomenwith sensation, reducedreflexesandincoordination. peripheral nerves,resultinginweakness,loss of seizures. Polyneuropathy occursasadysfunctionof abnormal sensations,weakness,nausea,vomiting,and sedation, agitation, headaches,abnormalvision, different symptomscanoccur, including confusion, metastasis fromacancerelsewhereinthebody. Many either asabraincancerormorecommonly a abnormally asaresultofcancergrowingwithin it, resulting inpain andlossoffunction. compresses thespinalcordornerves, Spinal cordcompressionoccurswhencancer swelling oftheface,neck,andupperpart ofthechest. upper part ofthechestandnecktoswell,resultingin blocks thesuperiorvenacavacausingveinsin syndrome occurswhencancerpartiallyorcompletely causing shortnessofbreath.Superiorvenacava when fluidaccumulatesinthepleuralsacoflungs, breast cancer, andlymphoma.Pleuraleffusion occurs pump blood. This canbeobservedwithlungcancer, pressure ontheheartandinterfereswithits abilityto invades thepericardiumandirritates itand whichputs heart (pericardium,orpericardialsac),whenacancer accumulates inthebaglikestructuresurrounding result. Cardiactemponadeoccurswhenfluid low bloodsugar, diarrhea,andhighbloodpressurecan organs oractuallydestroytissues.Symptomssuchas Others directlyinterferewiththefunctionofdifferent organs ortissuesbycausinganautoimmunereaction. other tissuesandorgans.Somesubstances damage the body. These substancescanaffect thefunctionof of protein),orotherproteinsandthusspreadthroughout in thebloodstream,suchashormones,cytokines(atype cancer producesoneormoresubstances thatcirculate treatment. Paraneoplasticsyndromesoccurwhena complications canbeseriousandrequireemergency and canaffect one’s entirelife.Someofthese The diagnosisofcanceroften causesalotofanxiety which atumorgrowsandspreadsi.e.its aggressiveness. complications canresult,dependingonthedegreeto and spreadsthroughoutthebody, anumberof of thenormalorgan.Whenamalignanttumorgrows region ofthebodywhereitcompromisesfunction TUMOR COMPLICATIONS Brain dysfunctionoccurswhenthebrainfunctions Complications canoccurifatumorislocatedin www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 biopsy (mostoften for lymphomaorleukemia), blood chemistries,biopsy ofthetumor, bonemarrow tomography (PET)scan,complete bloodcount(CBC), magnetic resonanceimaging (MRI),positronemission the tests include:Computed tomography(CT)scan, to determinewhetherthecancer hasspreadinthebody examination. Fordiagnosingandstaging cancers encompasses screening,testing,andaphysical warning signsofcancershouldnotbeignored.Diagnosis conditions. Nonetheless,thedevelopmentofany symptoms areusuallycausedbyfarlessserious person toseekmedicalcare.Fortunately, mostofthe early warningofcancerandshould,therefore,trigger a based ontheirsiteandtype.Somesymptomsmaygive technologies. The symptomsandsignsof tumorsvary examination) andemployingrecentdiagnostictools and grossmicroscopicfeatures(histopathological effects, immunologicalmethodsbyusingtumormarkers the basisofsymptomsandlesions,clinicopathological ingestion, tolerance,andutilization. Malignancy canadverselyaffect foodandnutrient also beduetoapsychological responsetothedisease. is probablytheresultofphysiologicalchangesbutmay adipose tissue(fat)stores.Cancer-associatedanorexia changes contributetothelossofskeletal muscleand carbohydrate, protein,andfatmetabolism. These appetite. There arealsoindividualalterationsin status byalteringmetabolism andcausinglossof therapy. Malignanciesdirectlycompromisenutritional treatments suchassurgery, chemotherapy, andradiation cancer itself, orthesideeffects ofcommoncancer deficiencies. The deficienciesmaybethe resultofthe People withcancerareatriskfordevelopingnutritional changes, includingdarkeningoftheskininarmpits. excess ofthyroidhormone(hyperthyroidism),andskin include breastenlargementinmen(gynecomastia),an can progresstocomaandevendeath.Otherproblems thereby releasingcalciumintothebloodstream,which also betheresultifcancerdirectlyinvadesbone, levels intheblood(hypercalcemicsyndrome). This may hormone likesubstance thatleadstoveryhighcalcium long bones.Squamouscellcarcinomamaysecretea fingers andtoescauseschangesattheendsof in peoplewithlungcancer, inwhichtheshapeof blastoma. Hypertrophicosteoarthropathy canalsooccur movements canoccurinsomechildrenwithneuro- of theeyeandmuscleslackcoordination is detectedandoften resultinseveredisability. Spasms appear weeks,months,orevenyearsbeforethecancer Diagnosis ofcancer/neoplasmscanbedoneon DIAGNOSIS niCne ciiyo o rn 9 Anti-Cancer activityofcowurine

and levels arehigh inmenwithprostate cancer, butlevels of prostate-specific antigen(PSA)in the blood.PSA common screeningtestinvolves measuringthelevel and mammographytodetect breastcancer. Inmen,a are thePapanicolaou (Pap)testtodetectcervicalcancer In women,twoofthemost widelyusedscreeningtests sometimes havepsychologic orphysicalrepercussions. tests canhelpsavelives,theybecostlyand with furtherexaminationsandtests. Although screening are notdefinitive;results areconfirmedordisproved critical thatcancerbediscoveredearly. These usually cancer ismorelikelytobecurediftreatedearly, itis them attheirearliestandmosttreatable stages. Because Screening forcancerscanhelppreventtumorsordetect that acancerispresentbeforesymptomsoccur. diagnosis ofcancerandservetodetectthepossibility identified. radiation emission(possiblecancerlesions)canbe with agammacounter, andanyareasoflocalized low-intensity radionuclides. The patient isthen“scanned” antigens canbeuseddiagnosticallywhenlinkedwith antibodies, whichcanselectivelybindtouniquetumor processes withinit.Monoclonal(one-celltype) used tovisualizetumors,bymeasuringbiochemical and spinalcord.Morerecently, PET scanshavebeen particular valueindetectingcancersofthebrain,bone detailed anatomicimagesareobtained. MRI is of powerful magneticfieldgeneratesandexquisitely location ofthetumorandits extent.InMRI,avery tumors undergoCTscansorMRItodeterminetheexact mammography forbreastcancer. Mostpatients with test forcervicalcancer, physicalexaminationand cancer, pelvicexamination and Papanicolaou (Pap) for occultblood,rectal examinationforrectal andcolon photography isdoneforskincancer, stoolexamination sample oftissue.Physicalexaminationandwhole-body Sometimes, however, surgeryisneededtoobtain a be performedwithaneedleanddonotrequiresurgery. an imagingtestiscancer. Manykindsofbiopsies can needed tobesurethatanabnormalitydiscoveredon procedure oraseriousoperation.Biopsies areoften the locationoftumor, thebiopsy maybeasimple important inbothdiagnosisandstaging. Dependingon determine ifthetumorisbenignormalignant,which body. Whenatumorisfound,biopsy isperformedto These testsvarywiththelocationoftumorin examination andtestingfortumormarkers/antigens. radioisotope scan,exploratorysurgery, bariumenema blood tests forliverenzymes, sputumcytology, chest X-ray, mammogram,bonescans,ultrasound, endoscopy usuallyguidedbyaCT scan,bariumX-ray, Screening programsallowearlydetectionand www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 helping todetermineprognosis. determine themostappropriatetreatmentaswell to otherparts ofthebody. Staging allowsdoctorsto Dhamaetal. location, size,growthintonearbystructures,andspread determine howadvancedthecancerisintermsofits detect mouthcancerinanearlystage. Periodically checkingthemouthforsorescanhelp forms ofcancer, especiallywhendiagnosedearly. men detecttesticularcancer, oneofthemostcurable breast cancer. Periodicallyexaminingthetestescanhelp self-examinations arevaluableinhelpingwomendetect tests canbedoneathome.Forexample,monthlybreast amounts ofbloodtoleakintothestool.Somescreening although manyotherdisorderscanalsocausesmall wrong inthecolon. The problemmaybecancer, stool inolderpeopleisanindicationthatsomething enlargement oftheprostate. Findingoccultbloodinthe are alsoelevatedinmenwithnoncancerous(benign) 10 marker increasesifthecancer recurs. cancer hasprobablyreturned i.e.thelevelofatumor disappears after treatmentthenlaterreappears,the probably beensuccessful.Ifthetumormarker a bloodsampleafter treatment,thetreatmenthas was presentbeforetreatmentbutnolongerappears in possible recurrenceofthecancer. Ifthetumormarker monitor theeffectiveness oftreatmentandtodetect who dohavecancer, tumormarkerscanbeusedto necessarily meanapersonhascancer. But,inpeople not havecancer. Thus, findingatumor markerdoesnot sometimes arepresentinthebloodofpeoplewhodo symptoms ofcancer. However, tumormarkers used asscreeningtests inpeoplewhohaveno Measurements ofsomethetumormarkerscanbe to evaluatetheperson’s responsetotreatment. Sometimes theseareusedfordiagnosisandsometimes (osteosarcoma), andsomecancersofthedigestivetract. including malignantmelanoma,bonecancer antigens havebeenidentifiedinseveraltypesofcancer, or viralantigensoncellsurface.,e.g. normally. Itisadifferentiation antigenasinnormalcells by livercellsbutafter birthit’s productionisstopped fetoproteins producedbyembryoniccells.Itis blood tests. These arefetal antigensandalpha bloodstream bycertain tumorsandcanbedetectedwith also beraised inpeoplewhoareheavy cigarette breast, pancreas, bladder, ovary, orcervix.Levelsmay raised inthebloodofpeople withcancerofthecolon, Tumor When cancerisdiagnosed,staging tests help Carcinoembryonic antigen (CEA): Tumor markersaresubstances secretedintothe

Markers/Antigens : . Retrovirus. Tumor Levelsare of neoplastic cells orvirusinfectedcells. lymphocytes whichbearsFc receptorthatcauseslysis act astumorpromoter. neutrophils “respiratoryburst” aremutagenicandmay On thecontraryreactive oxygenmetabolites of them susceptibletooxidativeinjurybymacrophages. decreased catalase andglutathione contents makes leading todeathofcell.Becauseincancercell lysosomal enzymesintothecytoplasmofcancercell cytoplasmic processesintothetumorcellsandtransfer cells andmacrophages.Oncontact, macrophagesinsert tumor cellsarephagocytosedbypolymorphonuclear neoplastic cells. functions inthebodywhichworkstogethertofightwith to 1yearcausedeath. There aremanysystems/ malignant tumorisclinicallymanifestedittakes 6month slow andtheindividualmaysurviveseveralyears.When fast thatleadstoearlydeath.Inothers,tumorgrowthis testicular cancer, melanomas,andlymphomas. for avarietyofreasons,andparticularly inpeoplewith leukemia, andinmanyformsoflymphoma. people withmultiplemyeloma,chroniclymphocytic particularly pancreaticcancer. are raisedinpeoplewithcancersofthedigestivetract, are raisedinpeoplewithbreastcancer. including cancer. raised inwomenwithavarietyofovariandiseases, prostate cancer. of theprostate andareconsiderablyhigherinmenwith raised inmenwithnoncancerous(benign)enlargement cancer. placenta andinmenwithvarioustypesoftesticular occurs inwomenwhohaveacanceroriginatingthe This hormoneisproducedduringpregnancybutalso children andyoungadultswithpinealglandtumors. people withcertain cancersoftheovaryortestisandin liver cancer(hepatoma). AFP isoften alsofoundin fetal livercells, AFP isfoundinthebloodofpeoplewith ulcerative colitis. smokers andinthosewhohavecirrhosisoftheliveror Natural killercell: Nonspecific lysisandphagocytosis: In someindividualsthegrowthofneoplasmisvery IMMUNE MECHANISMS: Lactate dehydrogenase: Beta Carbohydrate antigen19-9(CA19-9): Carbohydrate antigen15-3(CA15-3): Carbohydrate antigen125(CA-125): Prostate-specific antigen(PSA): Beta-human chorionicgonadotropin(ß-HCG): Alpha-fetoprotein (AFP): 2 (ß 2 )-microglobulin: Itisapopulationofimmature Levelscanberaised Normallyproducedby Levelsareraisedin

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Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 aspects ofmedical care.Successfultreatment ofcancer immune response. immunocytes thatleadstosuppressionofspecific recognition oftumorantigensonneoplasticcellsbythe general, causesimmunosuppressioninbody. that leadstoimmunetolerance. antigenic determinants ontheneoplasticcellsurface escape thecellfromimmuneresponse. antigenic determinants overneoplasticcellsurfacemay surface causingdelayedimmuneresponse. antigens appearlateontheanaplastic/neoplasticcell tumor. ve bacteria.Itaffects subcutaneous transplantation of cells. Itneedstobeactivatedby necrosis factor(TNF)whichcausesoftumor that arehavinganti-tumouractivities,suchastumour e.g. macrophagesalsoreleasecertain soluble factors excrete someproducts thatinhibits themacrophages, growth by71%.Inearlytumorgrowth,cells cell carcinoma,intratumorinjectionofBCGreduces remove itthroughphagocytosis.e.g.inocularsquamous Macrophages attractandattach ontumorgrowthand stimulate thereticulo-endothelialsystemagainsttumors. BCG andfilterateofG-ve Propionibacterium acnes(Corynebacteriumparvum), cancer cells,theprognosisisconsideredasgood. biopsy material,ifonefindslymphocytesalongwith cells. Duringcytologicalorhistologicalexaminationof selective CMIresponsewhichdestroysthemalignant inhibit thetumourcellgrowth. Tumour antigensinduced by humoralorcellmediatedmechanismwhichmay These antigensmayevokeimmuneresponseinbody differentiating betweenneoplasticorpreneoplasticcell. that makesthe“tumour”antigens”. These areusefulin biochemical alterationsontheirsurface(proteinchange) also restrainthegrowthoftumor. neoplastic actionbyanother source. antigens andblocksthe effect ofmorepotentanti- Antibodies: Treating cancerisoneofthe most complex TREATMENT: Humoral antibodies: Specific immunodeficiency: General immunodeficiency Antigenic overload: Antigenic modulation: Delayed immunostimulation: destruction Escape ofneoplasticcellsfromimmunological Tumour antigens: Antibodies againsttumorantigens

Tumour cellsdevelopcertain bacterial culturesareusedto Antibodies bindswithtumor There aretoomany P. acnes Frequent changein There islackof Neoplasia, in niCne ciiyo o rn 11 Anti-Cancer activityofcowurine or LPSofG- The tumor Patients with distant metastases arenotcurable lymph nodesonly, sometimescanalsoberemoved. metastases arepresent,isgood.Ifithasspreadtolocal removed, thechanceofcuring mosttumortypes,ifno and asmallmarginofsurrounding healthytissueare the lesionissmallandhasnot metastasized. Ifthe lesion to onelocation.Cancerismostcurablesurgicallywhen patients withlocalizedtumorsi.e.thecancerconfined primary methodforcuringaboutone-thirdofcancer available techniquefortreatingcancer. Itstillisthe radiotherapy andchemotherapy, surgerywastheonly with thefewestsideeffects (Groenwald be ensuredthatpeoplereceivethemosteffective care the risksinvolvedwithtreatment. Therefore itshould radiation therapyoranti-cancerdrugsmustunderstand therapy). However, peoplewhoarecandidatesfor improves thequalityandlengthoflife(palliative the cancercanoften berelievedwithtreatmentthat when acureisimpossible,symptomsresultingfrom longest survivalwiththehighestqualityoflife.Even cancer treatmenthopeforthebestoutcomeand the chanceofspread(metastases). Peopleundergoing symptoms, thesideeffects oftreatment,andreduce cure isnotpossible,theeffect oftreatmenton including thelikelihoodofcureorprolonginglifewhen Treatment decisionstake intoaccountmanyfactors, physiotherapists, socialworkers,andpharmacists). other typesofhealthcareworkers(forexample,nurses, surgeons, radiotherapists, andpathologists) andmany primary caredoctors,gynecologists, oncologists, many typesofdoctorsworkingtogether(forexample, chemotherapy. require acombinationofsurgery, radiationand radiation andchemotherapy, orboth.Somepatients removed withsurgery, theoptionsfortreatmentinclude response modifiers.Ifallofthecancercannotbe hormone therapy, andimmunotherapyusingbiologic application ofsurgery, radiation,chemotherapy, that hasspreadbeyondtheregionalplacelike reasons. A varietyofapproachesareusedtotreatcancer Sometimes benigntumorsmayberemovedforcosmetic of theorgan,sometimesnotreatmentisneeded. will notcausesymptomsordisturbtheproperfunctioning tumor isbenignandlocatedina“safe”areawhereit whether itisbenignormalignant,andits location.Ifthe Treatment also variesbasedonthetypeoftumor, result thatthespecificcancerwillnotgrowback. metastatic tootherregionsofthebody, andwiththe primary site,extendedtolocal-regionalareas,or requires eliminationofallcancercells,whetheratthe Surgery: Cancer therapyinvolvesateamthatencompasses Historically, until theadventof et al. , 1997). www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 which maybe placeddirectlyintothecancer. A linear in treatmentofthyroidcancer, orradioactiveimplants, cancer, forexampleradioactive iodine,whichisused substance may be injectedintoaveintotravelthe is alsoenhancedbysupervoltage radiation. A radioactive from adeviceoutsidethebody. The accuracyofdelivery or withinthetarget tissue. Teletherapy deliversradiation brachytherapy, theradiationsourceisplacedcloseto delivery areused:brachytherapyandteletherapy.With Sievert (SV). Two generaltechniques ofradiation DNA. Otherunits ofradiationarethegray(Gy)and generation ofoxygenfreeradicals,whichdegradetumor the ( Gold ( ( Commonly usedradioactivesubstances areCesium energy focusedonacertain areaororganofthebody. DNA withinthecancercells.Itinvolvesafieldofintense stop thegrowthofmalignantlesionsbydamaging be effectively treated.Radiationtherapyisthoughtto by radiation,someareveryresistant andthuscannot further. Cancercellsdiffer inhoweasilytheyarekilled reproduce andthusprevents thetumorfromgrowing prevents thecancerouscellsfromcontinuingto than mostnormalcellstobekilledbyradiation.Radiation other cellsinthebodyandthereforearemorelikely divide rapidly. Cancercellsusuallymultiplyfasterthan cancer cells.Radiationpreferentiallykillscellsthat uses radiation(x-raysorrelatedradiation)todestroy disseminated cancer(Sabiston,1991). and thyroidtumors.Surgeryisnevercurativein (cancer oftheconnectivetissue),somebraintumors cancers, renal(kidney)cancer, salivarygland, sarcomas melanomas, manyheadandneckcancers,mostskin Dhamaetal. the uterus),eye,genitalia,cervix,ovary, larynx,lung, gallbladder, bone,breast, endometrium(theliningof gastrointestinal tractandaccessorystructures, is usedinthecancerssuchasallof treatment isdictated bythestage ofdisease.Surgery disease andovariancancer, whereintheextentof used fordiagnosisand/orstaging, asinHodgkin’s some tumors,suchasovariancancer. Surgeryisalso the responsetochemotherapyand/orradiotherapyin Decreasing thetumormass(debulking)mayincrease to reducethetumorburdenand/orrelievesymptoms. treated. Surgerymaybeperformedforpalliative reasons tend toprogressmalignantlesions,ifnotproperly lesions canalsobecuredbysurgicalremoval. These indicated. Premalignant,alsocalledprecancerous, surgically, althoughpalliative resectionissometimes 12 103 137 Pa). The units ofmeasurement forradiationinclude Cs), Cobalt( roentgen, radiationabsorbeddose(rad), Radiotherapy: 198 Au), Iridium( 60 Co), Iodine( It isatreatmentapproachthat 192 Ir), Yttrium ( Ir), Yttrium 131 I), Phosphorus( 90 Y), Palladium 32 the P), effectively treatcertain tumorsinareaswhere damage radiation therapy, suchasproton radiation,can back. Newtechniquesof intense andhighlyfocused surgery itisusedtoprevent thecancerfromcoming possible beforesurgeryto removethecancer. After or brain.Often it isusedtoshrinkthetumorasmuch to relievesymptomscausedbyspreadofcancerbone stomach cancers.Itcanbegivenaspalliativetherapy and advancedlung,esophageal,headneck, cannot beremovedwithsurgeryasinmultiplemyeloma advanced cancer, ortotreatmalignancies(cancers)that to providetemporaryreliefofsymptomsparticularly in therapy isthetreatmentofchoice.Itmayalsobeused treated withsurgeryandchemotherapy, theradiation radiate suchlargeareas.Lymphoma isusually not metastases, becauseonewouldnotbeabletosafely could noteffectively controlnumeroussitesof medulloblastoma (abrainorspinalcordtumor).One cancer, early-stage breastcancer, lungcancer, and breast, larynx,seminoma(atesticularcancer),prostate and neck,canceroftheskin,cervix,endometrium, Hodgkin’s disease,squamouscellcancerofthehead many cancersparticularlylocalizedtumors,including lethal dose.Radiationtherapyplaysakeyroleincuring between normaltissuetolerancedoseandthetumor and 4)therapeuticratio(TR)-definedastherelationship debilitated patient maybeapoorriskforradiotherapy, tumor istoolargeorwidespread,3)patienthealth-a tumor- benefitfromradiotherapymaybelimitedifa sensitive toradiation(eg,spinalcord),2)extentofthe located onornearavital organthatisparticularly location -radiationmayposeproblemsifatumoris the treatmentofcancerwithradiotherapy:1)tumor Milenic andBrechbiel,2004). being exposedtoradiation(DowandHilderley, 1992; have thecapacity torepair themselvesquicklyafter compromising anti-tumorefficacy. Also normalcells on normalcells,thusreducingtheacutetoxicitywithout cells, whiledecreasingthetoxiceffects oftheradiation increases thelethaleffects oftheradiationontumor beam paths overaprolongedperiodoftime,which doses withmoderateofradiotherapyormultiple Therefore, radiationtherapyisdividedintoaseriesof radiation dosesmaydamageadjacentnormaltissue. sufficiently highdosage,bekilled.However, high more resistant totheeffects ofradiation, butcan,with electron beamisused.Cellswithlowsensitivityare normal cells.Fortreatingsuperficialskinlesions,the tries toaccuratelytarget theradiationtherapytoprotect normal tissueisshieldedasmuchpossible. A doctor accelerator directs theradiationtotumor, while Physiciansevaluatefour

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Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 disease, certain leukemias, diffuse non-Hodgkin’s the tumor. Forexample,testicularcancer, Hodgkin’s or palliativeintent,depending onthetypeandstage of 2005). combined withradiationtherapy andsurgery(Crowell, Chemotherapy maybeusedasthesoletreatment or drugs areused,inwhatcombination,andatdose. to chemotherapy. The typeofcancerdetermineswhich may beadministeredislimited.Notallcancersrespond agents canbequitetoxicandthenumberofcyclesthat cells. Classicchemotherapeuticdrugssuchasalkylating efficacy (tumorcellkilling)versusits toxicitytonormal index ofadrugreflects thedifference betweenits not belinkedtospecificcellcycleevents. Therapeutic involves multipleintracellularsitesofactionandmay material. Inmanycases,itislikelythatdrugcytotoxicity deoxyribonucleic acid(DNA),thecellulargenetic Most chemotherapeuticagents actbydamaging bone marrowortheliningofgastrointestinaltract. harm dividingnormalcells,suchasthosefoundinthe with chemotherapeuticdrugtreatment,whichtendto injured orkilledbychemotherapy. Thus toxicitiesoccur cells sharesomeofthesepathways, andthusarealso parts ofthecellgrowthcycle.However, normalhealthy arrests thegrowthofcancercellsbytargeting specific few suchdrugsexist.Cancerchemotherapykillsor would destroycancercellswithoutharmingnormalcells, normal cells. Although anidealchemotherapydrug are moresensitivetoanticancerdrugsthannon-dividing, consists ofrapidlydividingcancercellsandthese Effectiveness ofchemotherapydependsonthatatumor may becuredbychemotherapyinmanycases. acute leukemia,germcellcancer, andseveralothers) that arethemostrapidlygrowing(Burkitt’s lymphoma, followed forcancersofsystemicsites. Those cancers rapidly growingcells,todestroycancercells.Itis involves theuseofdrugs(chemicalagents), thatkill of soft-tissue sarcomas. led tosignificantimprovementinlocalcontrolandcure operatively todestroyresidualcells. This approachhas operatively toreducethetumormass,orpost- many headandneckcancers,radiotherapyisusedpre- or theoverallcurerate.Inthisrespect,asincaseof when itcanimprovethelocalandregionalcontrolrate In conjunctionwithsurgery, radiationshouldbeused inaccessibility oftheselesionstosurgicalprocedures. of choiceformosttumorstheCNS,because are high-risksurgicalcandidates.Itisalsothetreatment spinal cord.Radiationmaybepreferredinpatients who to normaltissueisaworry, suchastheeye,brain,or Chemotherapy maybeadministered withcurative Chemotherapy ordrugtherapy: Chemotherapy niCne ciiyo o rn 13 Anti-Cancer activityofcowurine treatment based on“individualized”therapy. These new cancer. These insightswillusherinanew ageofcancer pathways andsystems aredysregulatedineachtypeof the knowledgecontinue to beexploredthatwhich development oftargeted therapieswillbeacheived as blood vesselformation (angiogenesis).Further leukemia (CML)andbevacizumab,whichinhibits tumor remarkable activitysuchasGleevecforchronicmyeloid Some ofthesenewtargeted drugshaveshown receptors innonsmallcelllungcancerandcoloncancer. the digestivetract.Othersuchdrugstarget cellsurface in chronicmyelocyticleukemiaandcertaintumors of energy siteinthemalignantcellandishighlyeffective toxicity. Imatinibsome,thefirstsuchdrug,alters defective, andtheydie,whileavoidingundesirable information flowinthecell,andthusrendercells (malignant) cellsandinterruptimportant pathways of “molecularly targeted” drugscanentercancerous be moreeffective whilealsobeinglesstoxic. These pathways thatareonlyfoundincancercellsandmay pathways. These aremorespecificallytargeted atgrowth to inhibitspecificcellularproteinsandsignaltransduction of cancercellbiology, newagents arebeingdesigned Vuillemin identification ofmoleculartargeted therapies(Thiery- promising newareaofcancerdrugdevelopmentisthe normal cellsintheprocess. An excitingandvery that areeffective atkillingtumorcellswhilesparing and returnedtothepersonafter chemotherapy. marrow cellsareharvestedbeforethechemotherapy combined withbonemarrowrescuestrategies,inwhich injury tothebonemarrow. Therefore, itiscommonly person’s survival.However, itcancauselife-threatening dose tokillmorecancercellsandthusprolongthe drugs. The strategyistomarkedlyincreasethedrug person hadagoodresponsewhenfirsttreatedwith and leukemia)thathaverecurredeventhoughthe cancer (includingsometypesofmyeloma,lymphoma, drugs areused. This therapyisusedforafewtypesof but riskyapproachinwhichespeciallyhighdosesof such resistance. Dose-intensitychemotherapyisanew (combination chemotherapy)isonewaytominimize 2005). Usingseveraldrugsatthesametime resistant tochemotherapeuticagents (GattiandZunino, resistance toantibiotics,cancercellsmaybecome effective palliation. Justasbacteriamaydevelop (including hormonaltherapy)mayprovideyearsof (eg. disseminatedbreastcancer),chemotherapy patients withothertypesofadvancedincurablediseases now curablewithchemotherapyalone.However, in lymphomas, Ewing’s sarcoma, andWilms’ tumorare Goal ofcancerdrugdevelopmentistofindagents et al. , 2003).Drivenbyincreasedknowledge www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 blockage ofenzymescalledtopoisomerases. Dhamaetal. Irinotecan :PreventDNA synthesisandrepair through Block divisionofcancercells. synthesis ofDNA. Fludarabine, 6-Mercaptopurine,5-Fluorouracil:Block of DNA. DNA, causingbreaksinDNAanderrorsreplication Chlorambucil, Melphalan:Formschemicalbondwith traditional, cytotoxicchemotherapy. but areoften moreeffective whencombinedwith molecules haveanticanceractivitywhenusedalone, 14 become established. However, evenafullyfunctioning often abletodestroycancerouscellsbeforethey can the cancerouscellsby immunemechanismandis antigens asforeignandmay beabletocontain ordestroy antigens). The immunesystemmayregardthese new the immunesystem,appear onthecell’s surface(tumor a cellbecomescancerous,newantigens,unfamiliar to for antibody-directedorcell-mediatedimmunity. When distinct surfaceproteinantigensthatarepotentialtargets lymphocytes). Its basisisthatcancercellspossess production ofantibodiesorimmunecells (T antigens derivedfromtumorcellstoboostthebody’s of humancancer. Useofvaccinesiscomposed being developedtoutilizebiotherapyinthetreatment biotherapy). Thus, anumberofdifferent approachesare cultured forenhancedantitumoreffects injection ofthepatient’s owncytotoxiclymphocytes levamisole, orthe restoration ofimmunefunction,aswithinterferon, tumors; 2)general(nonspecific)stimulationor cell fragments to“immunize”patients againsttheirown include: 1)theuseofvaccinesdevelopedfromtumor system torecognizeandattack tumorcells. These Several approachesareusedtostimulatetheimmune is tostimulatethebody’s immunesystemagainstcancer. replicates orspreads.So,thepurposeofimmunotherapy recognize itasabnormalanddestroybefore cancerous, theimmunesystemisthoughttobeable vaccines (Rieger, 1995;Rosenberg,1997). enhance endogenousimmunecellkillingandtumor and biologicresponsemodifier(BRM)therapyto Form bondswithDNAcausingbreaks. Alkylating agents: Chemotherapy Drugs Platinum derivatives: Topoisomerase inhibitors: Antimitotics: Antimetabolites: Immunotherapy: Biotherapy: Biotherapy includesimmunotherapy Vincristine, Paclitaxel,Vinorelbine: Mycobacterium Evenwhenacellbecomes Methotrexate,Cytarabine, Cisplatin,Carboplatin: Cyclophosphamide, BCG; and3)the in vitro Doxorubicin, (adoptive on thecellsurface, and3)generalimmune stimulation regulation ofthemajorhistocompatibility complex (MHC) effects), 2)enhancedantigenicity oftumorsbyup- inhibition ofproteinsynthesis (oneofits mainantiviral produces antitumoreffects byseveralmechanisms:1) α Two of themostfrequentlyusedbiotherapyagents are leukemia, renalcellcarcinomaandmalignantmelanoma. people withKaposi’s sarcoma, chronicmyelocytic interferons measurableresponseshaveoccurred in be madeartificiallyusingrecombinanttechnology. With human cellsproduceinterferonnaturally, butitcanalso most widelyusedbiologicresponsemodifier. Almost all (of whichthereareseveraltypes)isthebest-knownand produce chemicalmessengers(mediators). cancer cells,suchasbystimulatingnormalcells to improve theimmunesystem’s abilitytofindanddestroy and Herrmann,2005). responses (Reiche advanced cancer, whichhavedepressedimmune immune responseisoften usedinpatients with “HAMA” reactions). Approaches forstimulatingthehost effects (i.e.,fewerhuman anti-mouseantibodyor antibodies, whichhavemuchlowersensitizingside with theemergingavailabilityofnon-rodent(humanized) This areaofresearchiscertain toexpand, especially be usedtodeliverradiationdirectlythecancercells. bullets. Antibodies linkedtoaradioactiveisotope can the cancerdrugortoxintotumor, calledthemagic antibody bindstothecancercell,selectivelydelivering radionuclides orpotentplanttoxins,suchasricin. The therapeutically whenlinkedtocancerdrugs,therapeutic The monoclonalantibodies(MoAbs)canbeused the cancerpatient inanattempttodestroytumortissue. proteins onthecellsurface. These areadministeredto of experimentally producedantibodiestospecific of cancer. Monoclonalantibodytherapyinvolvestheuse other vaccineshavenotprovenusefulinthetreatment which avaccineisavailabletocontrolcancer. To date, malignant lymphomainpoultry, istheonlyvirusfor by aHerpesvirus,whichcausespolyneuritisand to bladdercancers.Marek’s diseasevirus(MDV),caused response, havebeensuccessfulwhenappliedlocally bacteria, whichareknowntoboosttheimmune Substances suchasextracts ofweakenedtuberculosis but areusuallynotpowerfulenoughtocontrolthecancer. antibodies againstthetumorantigenscanbeproduced, system ishighlyunlikelytobeabledestroyit. Thus, mass ofcancerouscells(tumor),thebody’s immune cells. And, oncecancerouscellsreproduceandforma immune systemcannotalwaysdestroyallcancerous -IFN (alfainterferon)and interleukin-2 (IL-2). Biologic responsemodifiers: et al., 2004;Li et al These areusedto ., 2005;Stern Interferon α

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Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 response rates arelow. Hormone-responsivetumors are although completeresponses arerareandoverall tumors havebeenshownto beresponsivetobiotherapy, castration) withouttheneed forsurgery. A numberof prostate gland ofitsandrogenstimulation(amedical of sexhormones,FSHand LH. This deprivesthe (GnRH) whichactatthepituitary toreduce therelease several analogsofgonadotropinreleasinghormone endogenous peptidehormones.Forexample,thereare hormonal agents aresyntheticpeptideswhichmimic agents maybenaturalorsynthetic.Severalofthenewer now beingassessedfordiseaseprevention.Hormonal disease asadjuvantandpreoperative endocrine therapyiswidely hormonal therapy. Because tumor often maybe“turnedoff” formanymonthsby can belonglasting. The growthofahormone-sensitive eradication ofdisease.Nonethelesstheseresponses symptoms (palliation), butnotcompleteshrinkageor (prednisone), Imatinibetc. These agents tendtoreduce estrogens (diethylstilbestrol),glucocorticosteroids tamoxifen. Otheragents arelikeprogestins(megestrol), likelihood ofrespondingtoanti-estrogentherapywith cancers withhighestrogenreceptorcontenthavea that hormoneinthetumortissue.Forexample,breast to ahormonedependsonthepresenceofreceptorsfor by blockingitsreceptor. Whetheratumorwillrespond reducing localandsystemichormone therapy deprivesthetumour sensitivity, evenafter malignantchanges.Endocrine prostate, endometriumandliver)retain this tissues sensitivetohormonalgrowthcontrol(eg.breast, hormonal therapyisthatsomecancersarisefrom adoptive nonspecificbiotherapy. into thepatient, aprocesscalled“adoptivetransfer”or LAK cellformation. These cellscanthenbereinfused own lymphocytes,IL-2hasbeenusedasastimulantof tumor-lytic activity. Whencultured found withintumormasses. This cellhasevengreater cell isthetumor-infiltratinglymphocyteor TIL, whichis to thetarget tumorcell. A morespecializedtypeofLAK mediate directtumorcelllysisbyreleasingtoxinsnext called lymphokineactivatedkiller(LAK)cells. These cells numbers andactivityofspecializedcytotoxic T-cells cancer therapy, IL-2hasbeen showntoincreasethe following antigenpresentation on amacrophage.In lymphocytes, Its normalfunctionistoincrease T cells weekly. IL-2 administered subcutaneousinjection, usuallythreetimes T-lymphocytes (CTL). to increasetheactivityofeffector cellssuchascytotoxic Hormonal/Endocrine Therapy:

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therapy, andis withapatient’s niCne ciiyo o rn 15 Anti-Cancer activityofcowurine than byanyone ofthesemethodsalone. cancers aremoreeffectively treatedbycombinations combinations ofthesemethods areusedbecausesome agents inanattempttodestroytumortissue. Frequently, help thebodyfightcanceror toadministerbiotherapeutic biotherapy isusedtomanipulate theimmunesystemto can beusedtocureorcontrolmetastatic malignancies; sometimes avoidingdeformingsurgery;chemotherapy control orcurecertain cancersconfinedtoalimitedarea, from surroundingnormaltissues;radiationtherapycan can controlorcuretumorsthatbeentirelyremoved value inthetreatmentofcancer. Forexample, surgery into clinicaltrials(Gilley will benecessarytoseetheirpositivepotentialtranslated catastrophe ofapoptosisorterminalgrowtharrest.It unstable cancercellscantriggertheultimatemitotic additional DNAdamagesignalsinthemitotically or uncappedtelomerestoberecognizedasDNAbreaks, cancer treatmentregimen.Byallowingcriticallyshort prevent tumorre-populationmightprovetobeauseful conventional cancertherapiesorusinginhibitorsto therapies. Combiningtelomeraseinhibitorswith identify high-riskgroups forpreventative cancer Thus, itmightbepossibletousetelomerelengths in screeningpatients fortelomeraseinhibitortherapies. Ascertaining thetelomerelengthstatus maybeuseful to beapotentialcancerpredispositionfactor. blocked. Shorttelomereshavebeenrecentlysuggested the limitlessproliferativepotentialofcancercouldbe telomerase apotentialcancertherapeutictarget. Thus division incancercells,maketheinhibitionof length, coupledwiththemuchmorerapidrateofcell the growthofcancercells. The differences intelomerase window ofopportunitytospecificallytarget andinhibit mode oftherapy. This mightprovideamechanismor thus theimmortal phenotypeofcancermightbeauseful such asviatelomeraseinhibitionorlossoft-loop,and Therefore, preventingthemaintenanceoftelomeres, and increasedsensitivitytoothercancertherapeutics. lead tocatastrophic events includingrapidcelldeath dysfunction incancercellsbyinhibitingtelomerasecan maintenance mechanismsandinducingtelomere proliferation ofcancersandthattargeting telomere maintenance, whichcontributestowardstheindefinite and viabilityisdependentuponpropertelomere cryotherapy andheat. endometrium andlivercancers. tumors, lymphocyticleukemiaandlymphomas, breast cancer, prostratecancer, neuroendocrinegut Each treatmentmethodhasauniqueplaceand Recent evidencehasshowncancercellgrowth Thermotherapy: et al. It utilizestheprinciplesof , 2005). www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 metastases (spread). A partial responseisa >50% after treatment,eitherintheprimarylocationoras recurrence ofcancer, wherethecancerouscells return neoplastic cellsthatwill, intime,causerelapse or may appeartobecured butmaystillhaveviable after treatmentistermedasremission.Suchpatients evident disease. Absence ofallevidenceacancer be achieved,whichrequiresdisappearanceofclinically cure, acompleteremissionorresponsemust clarified byobservingthesuccessofcure.Forapotential cancer. pancreatic cancer, melanoma,and nonsmallcelllung cancer, ovariancancer, headandneck cancer, with breastcancer, osteogenic sarcoma,largebowel irradiation oftheprimarytumor. Itispractisedinpatients micrometastases thatremainafter surgeryand/or therapy. Itisdesignedtoeradicatedisseminated following orinconjunctionwithsomeotherprimary response modifiers). Adjuvant chemotherapyisused the body’s immunesystemagainstcancer(biologic be combinedwithantibodiesordrugsthatstimulate intolerable sideeffects. Drugsthatkilltumorcells may each drugcanbeusedatits optimaldose,helpingavoid the likelihoodthatmorecancercellswillbekilled.Here parts ofthecancercell’s lifecycle,therebyincreasing chemotherapy), soastousedrugsthatworkondifferent several chemotherapydrugsarecombined(combination esophageal cancer, orbladder cancer. Commonly for example,thosewithnonsmallcelllungcancer, that arenotsuitable forirradiationorsurgicaltreatment, life. This canbeusefulforpeoplewithadvancedcancers used nottocurebutreducesymptomsandprolong and surgery. Sometimescombination chemotherapy is usually treatedwithchemotherapy, radiationtherapy, risk ofrecurrence.Locallyadvancedbreastcanceris Dhamaetal. treatments, dependingonthesizeoftumorand radiation therapy, chemotherapy, orwithallthree be treatedwithsurgeryaloneorcombined needed. Forexample,early-stage breastcancermay determines whethersingletherapyoracombinationis remaining cancercells. The stage ofthecanceroften surgery morelikely, orafter surgerytodestroyany thereby makingthecompleteremovaloftumorusing chemotherapy isgivenbeforesurgerytoshrinkatumor, cells thatmayhavespread.Sometimesradiationor confined locally, whilechemotherapyalsokillscancer Surgery orradiationtherapytreats cancerthatis combination ofsurgery, radiation,andchemotherapy. treatment. Forsomecancers,thebestapproachisa therapy combinestheassets ofvariousmodescancer 16 Combined-Modality Therapy: The goalsandprogressofcancertherapycanbe Multimodality swallowing, erythema, edema,desquamation (shedding Others arelowbloodcounts, difficult orpainful libido, hairloss,mucositis,and bonemarrowdepression. complaints arefatigue,malaise,anorexia,decreased redness, andpossiblyhair loss. The mostcommon radiation treatment,resulting inskinlesions,burning, testes. Skinandhairaremostnoticeablyaffected by intestines. Radiationcanalsodamagetheovaries or follicles, andtheliningofmouth,esophagus, divide rapidlysuchasskin,thebonemarrow, hair to thetumor, especially tissuesinwhichcellsnormally sensitive tissues.Itcandamagenormaltissuesadjacent proximityto and schedulegiven,thetumor’s irradiated, howlargeanareaisbeingtreated,thedose reactions, whichdependonthepartofbodybeing is alsoassociatedwithasignificantnumberofadverse to lossofbonemineraldensity(BMD).Radiationtherapy which leadstoestrogendeprivation,inturn premature ovarianfailureinpatients withbreastcancer, bone cells(primarilyosteoblasts) andcaninduce chemotherapy hasanindependentlynegativeeffect on lining ofstomachanddecreasedfertility. damage, hearingloss,bonemarrowsuppression,injure also cancausenervedysfunction,heartandkidney of thetoxiceffect ofdrugsonbonemarrow. These drugs or platelets (thrombocytopenia),candevelop because (anemia), whitebloodcells(neutropeniaorleukopenia), blood celllikeabnormallylownumbersofredcells hair. Cytopenia,adeficiencyofoneormoretypes to anemiaandriskofinfections.Peopleoften losetheir weight loss,fatigue,andlowbloodcellcountsthatlead causes nausea,vomiting,lossofappetite(anorexia), according tothetypeofdrug.Chemotherapycommonly affect normalcells and causesideeffects, varying most likelytobedamaged. All chemotherapydrugs gastrointestinal tractarealsorapidlydividing,and including bloodcells,hair, andcellsliningthe marrow andintestinalmucosa.Somenormalcells, side effects onrapidlydividinghosttissuessuchasbone cytotoxic agents becausetheykillcells,producetoxic treatment. Chemotherapeuticagents, sometimescalled treatment andtheareaofbodyundergoing experiences sideeffects, whichvaryaccordingtothe or disease-freesurvival. of cancerandrelapse istermedthedisease-freeinterval have noresponse. The intervalbetweendisappearance life, buttumorregrowthisinevitable. A patient mayalso may leadtosignificantpalliation andprolongationof reduction inthesizeofatumormassormasses,which Almost everyonewhoreceivescancertreatment Side Effects ofCancerTherapy:

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Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 induced menopause byoophorectomywill decline reduced functionandnumber ofosteoblasts). Surgically radiation therapytobone (causing osteonecrosisand ablation orsuppression(ovarian andtesticular), (CTIBL). Soitcanbecaused by osteoporosis orcancer-treatment–induced boneloss depletion. This is referredtoastreatment-related hormonal therapyleadingtoestrogenorandrogen therapy directedtowardthetumororbysurgical or after eating.Bonelossalsocanbecausedbycytotoxic there canberapidpulseandcoldsweats immediately symptoms includefeelingwarm,dizzy, andfaint fullness, nauseaandcrampyabdominalpain. Other undigested foodinthejejunumleadstoabdominal minutes afterbeingswallowedandthepresence of is “dumped”intothejejunum(smallintestine)10or15 cancer treatments cause“dumpingsyndrome”i.e.food also causelactoseintoleranceandmouthulcers.Some to renalorcardiacinsufficiency. Cancertherapycan along withsignificantfluidaccumulation,whichcanlead of IL-2aremoreseriousandincludeaflu-likesyndrome myalgia andbonemarrowsuppression. The toxicities syndrome (headache,fever, chills,respiratorydistress, also showtoxicity, alpha-IFNproducesaflu-like cause allergicreaction.Biologicresponsemodifierscan increases riskforfracture.Monoclonalantibodiescan deprivation therapymaycausehypogonadism,which premenopausal womenwithbreastcancer. Androgen inhibitors havebeenshowntocausebonelossin replacement modulators(SERMs)andaromatase retention. These therapies,suchasselective estrogen (impotence), abnormalliverfunctiontestandfluid cancer, bloodclots, hotflashes,erectiledysfunction generally respondtotreatment. usually spontaneously reversibleandtheydonot secondary neoplasms.Latecomplicationsarenot tissue, likefistulas,fibrosis,necrosis,edema,and are usuallycausedbydamagetovascularorconnective after therapy, dependingonthetotal radiationdose,and Late adversereactionsappearmonthsorevenyears months after radiotherapy, liketheradiationpneumonitis. Subacute adversereactionsdevelopwithinweeksto6 doses ortheconcomitant useofchemotherapy. a fewweeks. These effects aremoreseverewithhigher within thefirstfewweeksoftreatmentandsubsideafter susceptibility toinfection. Acute adversereactions occur damage (inapregnantwoman)andincreased nausea, vomiting,gastritis/enteritis,diarrhea.fetal (pruritus), skinpain, changesintaste,lackofappetite, skin pigment(hyperpigmentation), atrophy, skinitching or sloughing-off oftheouterlayerskin),increased Hormonal therapiescancauseendometrial

glucocorticoids, gonadal niCne ciiyo o rn 17 Anti-Cancer activityofcowurine medicine may betoxic,mayinteract withstandard cancer. Itisgenerallybelievedthattheuse of alternative the effectiveness ofalternativemedicine intreating to carefulscientificstudies. Very littleisknownabout types ofalternativemedicine havenotbeensubjected or inadditiontostandard treatment.However, most certain medicinalherbstotreattheircancer, insteadof Some peopleturntoalternativemedicineincluding CAM therapiesintotheirconventionalcancercare. medicine (CAM)grows,patients areincorporatingmore healthy weightaregoodpreventivesmeasures. vegetables, beingphysicallyactiveandmaintaining a example, asbestos),increasingintake offruits and colon cancer. Avoiding occupational carcinogens(for anti-inflammatory drugs(NSAIDs)reducestheriskof and coloncancer. Useofaspirinandothernon-steroidal sources, inthedietappearstodecreaseriskofbreast cancer. A reducedintake offat, particularly fromanimal against ultravioletlightalsohelps reducetheriskofskin sunscreen lotionwithahighsunprotectionfactor(SPF) the riskofskincancer. Coveringexposed skinandusing (especially duringthemiddleofday)canreduce the mouthandtongue. Avoiding sunexposure tobacco (snuff, chew)decreasestheriskofcancer head andneckcancer. Avoiding theuseofsmokeless can greatlyreducetheriskoflung,kidney, bladder, and Not smokingandavoidingexposuretotobaccosmoke can bepreventedbyavoidingthingsthatcausecancer. to radiationandtoxicchemicals. The idea is thattumors exposure ifyouburneasily, andminimizingexposure regularly, maintaining ahealthyweight,reducingsun alcohol consumption,eatingahealthydiet,exercising by notsmokingorchewingtobacco,avoidingheavy changes. The riskofmalignanttumorscanbereduced possible throughcertain dietaryandotherlifestyle can assistinnutritionalplanningforpeoplewithcancer. is atrainedhealthprofessionalintheareaofnutrition, for someofthesideeffects. A registereddietitian,which part oftreatment.Symptomatictreatmentcanbegiven hospital settings.Relievingsideeffects isanimportant treatment modalitiesarerequiredinwellmonitored be followedincancertreatment.Carefuldosesof therapies, preventiveandcorrectivemeasuresshould estrogen levelsandproducenegativebonehealth. As thepopularityofcomplementary/alternative (CAM) COMPLEMENTARY / ALTERNATIVE MEDICINE Reducing therisksofcertain cancersmaybe PREVENTIVE MEASURES Seeing theseveralsideeffects ofcancer www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 Cytokines and aminoacidsmightplaya roleinimmune the powertodestroydiseases andactasanantidote. cytokine andlactoseetc.(Bhadauria, 2002).Copperhas potassium, urea,uricacid, aminoacids,enzymes, ammonia, manganese,iron, sulphur, phosphates, calcium, phosphorus,carbonic acid,potash,nitrogen, salt, hormones,andenzymes-2.5%.Itcontains iron, Its maincontentsarewater95%,urea2.5%, minerals, Chauhan, 2003a).Cowurinecontains 24 typesofsalts. the body(Bartnett,1988;Chauhan capable ofremovingalltheilleffects, imbalances in properties, potentialitiesandconstituents thatare animals onHPLCanalysis “Rasayan” whichhasbeenfoundabsentinurineofother indigenous cowurineisduetothepresenceof a buffaloes. The immunomodulatory propertyof present intheurineofcrossbred,exoticcowsand properties withregardstoimmunomodulationare effective andinterestinglyalmostnilorfewmedicinal sorts ofurines,theurine theIndiancowsismost It hasalsobeenexperimentally provedthatamongall immune response(Kumar, 2001;Chauhan reported thatitenhancesbothcellularandhumoral for its immunomodulatorypropertiesandhavebeen panchgavya, whichhasbeentestedbyvariousworkers for thousandsofyears.Itisanimportant ingredientof Asia. InIndia,drinkingofcowurinehasbeenpracticed Hindu writing,whichissaidtobetheoldestbooksin immotality), thenector oftheGodinVedas, sacred recognized as‘wateroflife’ or“Amrita” (beveragesof drugs. Cowurinetherapyhasalonghistory. Itis is beingusedtoproduceawholerangeof Ayurvedic general health.Exploringits antimicrobialactivities,it unique placein Ayurveda andissuggestedforimproving in measuredquantities,cowurineorgaumutrahasa from cowurineareusedtocureseveraldiseases. Taken innumerable therapeuticvalues. The medicinesmade effective substance/secretionofanimaloriginwith Samhita’ and‘Ashtanga Sangraha’ tobethemost 8Dhamaetal. be discussedindetails (Treasure, 2005). the nextsectionofthisreview, cowurinetherapywill therapy cansharethehighstandards ofmedicine.In medicine, herbalproducts, homeopathy andcowurine practical implications/clinicaltrials.Ofthese Ayurvedic points havetobeclarifiedviascientificbasisand ability toafford standard treatment. Therefore these chemotherapy, itmaybecostly, reducingtheperson’s treatment, thusreducingtheeffectiveness of 18 Cow urinesingularlyhasgotallsuchchemical Cow urinehasbeendescribedin‘Sushrita COW URINETHERAPY et al., et al., 2001; 2004). like cancer, AIDS anddiabetes. has beenreportedtobebeneficialfordreadeddiseases drug resistant bacteriaand viruses.Eventhistherapy is non-toxicinnature.Cowurinecankillthenumberof are curedbyits regularusewithoutanysideeffects. It increase ofcoughandurinaryirregularitiesinhumans diseases menstruationdisorders,asthma,giddiness, material. Hencediseaseslikefever, mouthandskin cleans theintestinesandremovesdeposited leucorrhoea andevenleprosy. The urineofthecow etc. Itisprovedasauniversalcurerofblooddisorders, baldness, headaches,fever, chemicalintoxication, aging of chronicmalaria,enteritis,constipation, edema, It isalsousedasadiuretic,laxativeandfortreatment eczema, tetanus, morningsickness,fever, obesity, etc. depression, hypertension,fatigue,burns,skininfections, hepatitis, leprosy, asthma,gastriculcer, heartdisease, bacterial/viral infections,tuberculosis,chickenpox, sinus, allergies,colds,earinfection,rheumatoidarthritis, been shownorreportedwiththosesuffering fromflu, vapours termedas‘ark’ (distillate).Improvements have medicines aremadebydistillingurineandcollecting could betreatedbycowurinetherapy. Mostofthe routinely useurineasaremedy. A numberof ailments atmosphere. disinfectant andprophylacticagentthuspurifies after secretionandhasantisepticeffect. Itacts likea from allsorts ofimpurities.Cowurineisentirelysterile strength aswell.Itincreaseslifespan andpurifiesblood power ofwisdomman,andincreasestheirphysical smoothens andnourishestheheartaddsto urine ofthecowworksasbestappetizer. It the mostincurablediseases. There isevidencethatthe unique qualityoftheurine,whichhelps incuringeven reduces theincreasedelements inthebody. Itisthe medicine thatfulfillsthedeficiencyofelements and beneficial elements init,henceit is naturalanduniversal enhancement. Sincetheurineofcowcontains all lymphocyte proliferation activity(Prabhakar to developingchicksmarginally upregulatedthe production andeggquality. protection alongwithvaccination andincreasesegg immunocompetence of birds andprovidebetter poultry, cowurinehasbeenreportedtoenhance the engulfment poweraswellbactericidalactivity. In activating themacrophagesandaugmentingtheir enhances theimmunestatusofanindividualthrough and animals.Recentresearchesshowedthatcowurine Practitioners of Ayurvedic medicine(fromIndia) Cow’s urinehasimmunostimulantactivityinplants Cow UrineasImmunostimulant In-vivo cowurinetreatment et. al., www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 observed with otherdrugsviz. Ampicillin, Isoniazid, negative bacteria.Bioenhancement hasalsobeen membrane intheanimalcells, grampositiveand helps intheabsorptionofantibioticsacross thecell against infectiousagents. The moleculeofinvention bioenhancer andincreases theefficacy oftheantibiotics has nowbeenfoundthatcowurinealsoacts asa have beenearlierisolatedonlyfromplantsources. It of drugsincombinationtherapy. Suchbioenhancers augment thebioactivityorbioavailabilityuptake not possessdrugactivityoftheirownbutpromoteand 4 July, 2002).Bioenhancers aresubstances,whichdo bacteria (TheHindu,4July, 2002; The IndianExpress, against used againsttuberculosis,increasesbyabout5-7folds activity ofRifampicin,afront-lineanti-tuberculardrug of bacterialinfectionandfightagainstcancers. The particularly forits use along withantibioticsforthecontrol (No. 6896907and6410059)forits medicinalproperties, Recently thecowurinehasbeengrantedU.S.Patents used antibiotics,anti-fungalandanti-cancerdrugs. identified asabioenhanceroftheactivitiescommonly get goodqualityeggsandimmune-enhancer. can beusedasafeedadditiveforlayerbirdsinorderto reported. Garg gain andhaematologicalprofileshavealsobeen as antimicrobialagent,positiveeffect onbodyweight calcium andcholesteroloflayingbirds.Itsusefulness biochemical profile(total serumprotein,glucose, (2004) reportedbeneficialeffects ofcowurineonserum the positivedirectiontoanoptimumlevel.Garg maintains theimmunityofbodybutalsomodulateitin adjunct tovaccination. Thus thecowurinenotonly experimental trailsforspecificuseofcowurineasan apoptosis andsuggestedtheexploitation through protective effect onlymphocytesofbirdsundergoing Prabhakar (2004)reportedthatthecowurinehad significantly by14.75and33.6%,respectively. respectively andinrats theselevelswereincreased IL-1 and2inmicegotincreasedby30.911.0%, secretion ofinterleukin-1and2also. The levelofboth Chauhan increases thetitrelevelofIgG, IgA andIgMantibodies. enhances both T andBcellproliferationalso immunity inmice.Itwasobservedthatcowurine which increasesbothhumoralandcellmediated distillate) tobeapotentandsafeimmunomodulator, reported thecowurine(Kamdhenuark’/ 2004). Chauhan A cowurinedistillatefraction(ark)hasbeen Cow urineasBioenhancer E. coli et al. and3-11 foldsagainstGram-positive (2004)observedthatitincreasesthe et al. et al. (2004)suggestedthatcowurine (2001)andKumar niCne ciiyo o rn 19 Anti-Cancer activityofcowurine et al. (2004) et al. and potency of thechemotherapydrugs, andreduce of cancerousdrugs,thus could enhancetheefficacy augment thebioactivityor bioavailabilityortheuptake have beenreportedtocause cancer. reduce theincidencesofcancer sincemanyaviruses number ofdrugresistant bacteriaandviruses, thuscan the followingproperties– possess potentanti-cancerabilitiesbythevirtues of radicals formation. one cangetthecharmofayouthasitprevents thefree ageing processofaperson.Byregularusecowurine producing achainreactionofdestructionleadingtothe disrupting normalcellactivitiesormembranes, various tissuesandattackenzymes,fatproteins cow urinetherapy. These radicalscausedamageto prevention ofpathogenic effect offreeradicalsthrough suicide (apoptosis).Kumar urine helps thelymphocytestosurviveandnotcommit by mitocycininhumanleukocyte(Datta, 2001).Cow (Ambwani, 2004).Itprotects chromosomalaberrations rapidly asobservedafter damagedue topesticides of DNA.Distilledcowurineprotects DNA andrepairs it lymphocytes ofbloodandtissuesthroughfragmentation at verylowdosescauseapoptosis(cellsuicide)in Ujala, July, 19,2005). 6896907) inthefieldoftreatmentcancers(Amar has beenvalidatedbythegrantofU.S.Patent(No. anti-cancer drugs.Recently, thissignificantachievement that cowurineenhancestheefficacy andpotencyof highlight theroleofcowurineincuringcancersand Nagpur confirmedthismilestoneachievement.Studies collaboration withGo-Vigyan Anusandhan Kendra, Plants (CIMAP),CSIRCenteratLucknow, alongwith Scientists ofCentralInstituteMedicinaland Aromatic urine therapyagainstfightingcancercarriedoutby treatment ofcancers.Furtherextensiveresearchoncow revealed thebeneficialpropertiesofcowurinein Kendra (CowScienceResearchCenter)atNagpur Research workscarriedoutbyGo-Vigyan Anusandhan immune systemandactasbioenhancer. “Rasayan” tatva, whichisresponsibletomodulate (Joshi, 2002). The Indigenouscowurinecontains per dayanddurationoftreatmentintuberculosispatients activity hasbeenfoundtoreducetheantibioticdose Clotrimazole, Cyanocobalamineetc.Bioenhancer Bioenhancing property: Antimicrobial capability: Thus, thecowurinetherapyissuggestedto Scientists haveprovedthatthepesticides even Cow urinepossessesanti-cancerproperties. ANTI-CANCER PROPERTIESOFCOW-URINE et al. Cowurinecankillthe Itcanpromoteand (2004) reportedthe www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 studied. Cow urinewasdistillatedaround 40-50°Cto fraction (GM-IV)obtained fromcowurinedistillate was (‘Taxol’- Peclitaxel) andacowurine distillateoradried composition comprisingof at leastoneanticanceragent and ofthedriedfraction (GM-IV). A pharmaceutical Anusandhan Kendra,Nagpur, Indiaandstudiedits effect the ‘Kamadhenu Arka’ (CUD)fromGo-Vigyan (Khanuja applicantstherapies. The effectively reducedthedosageofdrugneededfor cancer drugs.Itwasfoundthattheurinedistillate bioactive moleculessuchasanti-infectiveandanti- an activationenhancerandavailabilityfacilitatorfor invention relatestoanabsolutelynoveluseofCUD as additive wastestedandappliedforaUSpatent. The distillate (CUD)asapharmaceuticallyacceptable effective amountofbioactivefractionfrom cowurine Recently apharmaceuticalcompositioncomprisingan and survivabability. abilities ofthelymphoctyesattheiroptimumactivity survive, thusthebodycanavailtumorfighting reduce apoptosisinlymphocytesandhelps themto tumors. reduce thespreadofmalignantcancersandhelpfighting for thecancerpreventionandtherapy, andcanalso repairs thedamagedDNA,thuscanbeveryeffective cancer increasesastheoneprogressestowardsoldage. could helppreventingcancersastheincidencesof factor, sinceprevents thefreeradicalsformation,which the lymphocytes. the bodyandcytotoxicactivitiesoftumorkillingcells, the recognitionoftumorcellsbyimmune cytokines (IL-1,Il-2)playssignificantrolebyenhancing Dhamaetal. production andincreasedsynthesissecretionof increased macrophageactivity, higherantibody lymphocyte proliferationandstimulationactivity, several mechanisms,ofwhichtheupregulation parameter topreventthedevelopmentofcancersby immunocompetece ofanindividualisaveryessential the humoralandcellularmediatedimmunity. Increased (both T andBcells),hasbeenreportedtoincrease enhance theactivityofmacrophagesandlymphocytes general healthofanindividual.Ithasvital potentialto enhances theimmunocompetenceandimproves efficiently. So incombinationtherapycowurinecanbeused help reducethecostandsideeffects ofchemotherapy. their doseanddurationoftreatment,whichcouldalso 20 US PatentforCowurineinthefieldofcancer: Apoptosis inhibitor: DNA repairing potential: Anti-aging factor: Immunomodulating activity: Itisanefficient anti-aging Cowurinecantremendously Cowurineefficiently et al., 2002) obtained Cowurine ao nta ir ia ir Finaltitreof titre Final titre Initial ( Taxol chewing, smoking, alcoholintake, environmental predisposing factorsofcarcinogens suchastobacco lifestyle andfoodhabbits alongwithexposureto ever increasinginthecurrent scenarioofchanged faced bythemankindand theincidencesofwhichare treatment ofcancer, adeadlymaladywhichisbeing provided promisingandauthenticresults forthe have astrongscientificbase. the traditionalpracticesfromIndiansystemsofmedicine Scientists onCowurinetherapyalsomaderealizethat attracted globalattention.USPatents honoredtoIndian radiation treatments. The abovetwoU.S.Patents have it mayverywellreducetheharmfulsideeffects of therapy isencouragingespeciallyincancertherapy, and as abio-enhancer. Therefore, thefutureofcowurine in reducingtheeffective doseofdrugsas wellasacting therapy. The findingshavereflectedadirectimplication urine treatmentfortheantibioticsaswellcancer the costoftreatment. ark canbehelpful incuringcancer, whichcanreduce (nano tomicromolarlevels),thusaverylowdoseof of the‘Arka’isachievableinverylowconcentration finding thattheenhancementactionandeffectiveness 0.01 0.005 0.001 used obtained bylyophilization. The cowurinedistillatewas obtain thedistillateandconcentrate activation enhancerof‘Taxol’ Table showingtheeffect ofCowurinedistillateas cell linein get increaseagainstMCF-7,ahumanbreastcancer Thus thepotencyof‘Taxol’ (paclitaxel) wasobservedto considered astheadvancedproductofinvention. and devoidofunpleasantsmellurine andhence effect at0.001-10 10-20 grams/100mlofthedistillateshowedsame folds. The GM-IVwhichwasobtained intherangeof breast cancercellline,MCF-7(NCCS,Pune)by2-20 the celldivisioninhibitoryactivityofdrug‘Taxol’ in andata concentration1 ml, µ µ µ µ µ /l of g/ml)

During thepast fewyears cowurinetherapyhas Thus encouragingresults wereobservedwithcow The mostimportant featureofthisinventionisthe in aconcentrationrangeof0.001 in-vitro cells 0.9x10 0.9x10 0.9x10 cancer of cancer viable cancer viable ofcancer cancer µ assays. g/ml andwasfoundtobemorestable 6 6 6 0.036 x10 0.042 x10 0.059 x10 ao Taxol andCow cellswith Taxol cells with µ l/ml wasfoundtoenhance 6 6 6 µ 0.012 x10 0.032 x10 0.039 x10 urine distillate l/ml to100 6 6 6 µ l/ www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 IV highly sensitivetoradiations,itisunablecurethe radiotherapy. Eventhoughthecarcinomaoftonsilis cell carcinomaoftonsil,andwastreatedwith Sciences, Kasragod,Kerala,withstage IVsquamous was presentedtoKasargodInstituteofMedical from KasargoddistrictofKeralastate inNovember2003 Carcinoma- A CaseReport: size oftumor, clinical andbiochemicalpicture ofthe the absenceofcancerous cells/tissue, decreaseinthe was successfulinfighting thecancerasreflectedby of ‘Ark’,ithasbeenobserved thatcowurinetherapy treated forcancerusingprocessed cowurineintheform other casereports andfeed backobtainedfrompersons response. both ofwhichactedtogethertoelicitafavorable properties ofvitamins A, E,Candthevolatile cow urinemaypossiblybeduetotheantioxidant the cancertonormalcy. The antineoplasticeffects of the dramaticrecoveryofpatient from stage IV of as aneffective antineoplasticdrug,clearlyevincedby points tothepossibilityof theroleof‘AmruthaSara’ the antineoplasticeffects ofcowurinedistillate. This malignancy disappearedcompletelywhichsuggested and showednoevidenceoftumorgrowth. The tonsillar surface ofthetosillarfossaandfaucesweresmooth lesions inlymphglandswereeffectively controlled. The glands. The malignantlesionsintonsilsandsecondary oropharyngeal lesionsandnocervicalpalpable lymph therapy, thephysicalexaminationrevealednovisible completely curedofthedisease. After thecowurine period of10monthswithwhichthepatient was feeding tube. The sametherapywascontinuedfora take smallquantitiesofliquidfoodwithoutthehelp shown improvementinthesymptomsandwasableto follow up.Onthefirstupvisitpatient had a dayandwasaskedtocomeafter 2weeksforthe take 15mlof‘AmruthaSara’ (cowurinedistillate)twice suggesting apoorprognosis.Shewaslateradvicedto appearance andtheseverityofsymptoms to thetonsilarneoplasiaasevincedbycachetic blood attimes. The patient wassupposedtosuccumb regurgitation, dysphagia,dyspnoeaandwasspitting back ofpatients forthetreatmentofcancer. several casereports,successstoriesandpracticalfeed potential ofcowurinetherapyhasbeenreflectedby pollutants, occupationalhealthhazardsetc. Anti-cancer th stage. The presentedpatient showednasal Cow UrineCancerCure:Oro-Pharyngeal STORIES CASE REPORTS,FEEDBACK AND SUCCESS Other CaseReports And SuccessStories: A patient (63oldwomen) niCne ciiyo o rn 21 Anti-Cancer activityofcowurine

fatty acids, In STRATEGIES TO PROMOTECOW-URINE THERAPY in thepublicaboutitsgoodvirtues. curing cancers,andthusconfidencecanalsobeinspired chemotherapy andradiationtherapybeingfollowedfor having nosideeffects, generallyobservedwith can furtherstrengthenthisalternatelowcosttherapy field oftreatmentcancerscanbegenerated,which and practicalimplicationsofcowurinetherapyinthe physicians isneededbywhichauthenticresearchdata support ofthescientists, researchersandclinicians/ mankind shouldbeplannedappropriately. Forthisproper medicinal potentialandperspectivesforthebenefitof attention andthestrategiesforpromotingits vital anti-cancer activityofcowurineneedsimmediate its worldwideacceptance andpopularity. The unique in theabovepracticalcasesandreports, isrequiredfor for thepreventionandtreatmentofcancer, asreflected improvement withthecowurinetherapy. multiple myelomaandseverewaistpain showed Mr. NanakBhosrayDhingra,apatient suffering from in thefunctioningofkidneysandrelievingcancer. to 5.3and63,respectivelywithadrasticimprovement his serumcreatinineandurealevelsweredroppeddown twice aweek. After cowurinetherapy(Kamdhenu Ark) 10.4 and107,respectively, andwaskeptondialysis renal failure,withserumcreatinineandurealevelbeing Rungta, gotaffected withcancersuffered fromchronic brest cancerbytaking kamdhenuark.Mr. Babulal of Jainagar(northBihar),wascompletelycuredfrom after cowurinetherapy. Smt.SeemaVerma ,resident north bihargot80%improvementinthethroatcancer his cancer. Mr. RamSagarSingh,anativeofBegusaray, physicians, Nagpur, 98%improvementwasreportedin the useof‘Kamdhenu Ark’ prescribedbytheCowpathy therapies, therewasnoimprovementinhishealth. After functional andinspiteofdifferent knowncancer- kidney duetowhichhisbecamenearlynon- Dist. Narsinghpur(MP)suffered fromacancernearthe patient. MrKamleshkumar Agarwal, anativeofKareli l l However, scientificvalidationofcowurinetherapy by organizing conferences,seminars, field ofmedicinethroughinformation sharing research andapplicationsof cowurineinthe be madeforpromotingscientific outlook, Integrated andcoordinated approachshould scientifically. significance shouldbeevaluated reference totheirmedicinalandnutritional indigenous cattlebreedswithspecial immunological analysisofurinevarious Comparative chemical,microbiologicaland www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 2Dhamaetal. 22 l l l l l l l l cow urinedistillate orarkinbulkquantities Subsidies shouldbegiven forproductionof directions. health needstobeexplored intheright urine inenhancingtheimmunity andgeneral livestock/poultry populations. The role ofcow protection againstseveraldiseasesinthe urine andpanchgavya therapyforinducing Proper attentionshouldbegivenoncow methodologies. help ingeneratingalternativetreatment grant ofU.S.Patents, andwhichmayalso Lucknow andothercenters,whichledtothe Anusandan Kendra,NagpurandCSIRat therapy suchasthatdonebytheGovigyan should begiventoresearchincowurine Encouragements, rewardsandhonors cancer. in thefieldofutilitycowurinetreating recognized forpromotionoftheinnovations therapy. Centersshouldbeestablished and several diseasesandasapotentanti-cancer on theimplicationsofcowurinefortreating popular articles,andlaunchingweb-site(s) needed bypublishingliterature,research/ Wide publicitybymasscommunicationis standardized. production andqualitymaybesuitably in Indianpharmacopiasothattheir thorough examination,includesuchproducts The drugcontrolauthoritiesshould,after time-bound projectsoncowurine. institutions toundertake result-orientedand encourage bothpublicandprivatesector Special R&Dfundshouldbecreatedto government organizations(NGOs). national institutions,universitiesandnon- undertaken, encouragedandsupportedin Hospitals. Researchprogrammesshouldbe Research Institutes,Universitiesand in clinicaltrialsVeterinary Colleges, Applications ofcowurineneedtobetestified related tomedicinalpropertiesofcowpathy. medicinal claimsmadeinancientliterature be adrivefortheverificationofclinicaland incurable diseaseslike AIDS. There should cancer andotherdiseasesincludingthe evaluation ofcowurineinthetreatment should bedevelopedforfurtherscientific A sounddata-base ordata-collection system programmes. workshops, exhibitionsandorientation stamp ofapproval forIndianSystemsof Medicineand of U.S.Patents tocowurine hasgiventheultimate may bemanymorepatents areawaitingahead.Grant research oncowurineand other panchgavya elements, widely promoted.Modulating intotherightchannels approaches andtheirpotential applicationsshouldbe anti-cancer andbio-enhancingproperties. These resulted inUSpatents forthecowurineinpossessing science, spiritualityandwisdom.Suchablendinghas based onresearch.Itisthereforenecessarytoblend adventures. Nowpeopleneedinformationanddata therapy arerejectedasmythormythological Most ofthetestedpracticescowpathy orcowurine many butscientificvalidationofthoseclaimsisrequired. cow urinetherapy. Though, theenduser claimsare made forpublicawarenessaboutthevital virtuesof not beenexploitedtotheextremes.Efforts need tobe tremendous potentialinthefieldofmedicineandhas therapy forcancer. The areaofcowurinetherapyhas stories ofthepatients treatedbythisnovelalternate years bythecasereports, feedbacksandsuccess in curingcancerhasalsobeensupportedthelastfew anti-cancer drugs. The hypothesisofcow urine therapy treatment byitsvirtuesofbioenhancingtheactivity recently bythegrantofUSpatent inthefieldofcancer possess anti-cancerpropertiesandhasbeensupported cancer. Cowurinetherapyhasalsobeenclaimedto claimed tobehelpful inthepreventionand controlof homeopathy andayurvedicmedicineshavealsobeen be treated. Alternate therapiesincludingofherbs, well knownsideeffects puts burdenonthepatients to therapy modalitiesisnotveryhighandmoreover, their of genetherapy, butthesuccessrateandcostofthese immunotherapy alongwithrecentmolecularapproaches procedures ofsurgery, chemotherapy, radiotherapyand though canbetreatedbyfollowingvarioustherapy CONCLUSION companies. shoulders withtheallopathy andmulti-nationaldrug curing cancers,thisalternativecancomeouttoshare scientific data forthesupportofcowurinetherapyin sements, massmediaawareness)andgenerating needful promotionalcampaigns ofpublicity (adverti- Cancer isadreadedmaladytothemankind,which By providingproperfunds,infrastructureand l wealth shouldbepromotedinthecountry. along withagriculturalbenefits, thecattle mechanical, thermal,andelectricalenergy As sourceofmedicinalbenefits apart from and strengthened. and its wideavailabilityshouldbefacilitated www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 Achliya, GirishS.,SudhirG, Wadodkar and Avinash KDorle REFERENCES feed-backs frompatients tocompilethisarticle. providing clinicalcasehistories,successstoriesand Director, Go-Vigyan Anusandhan Kendra,Nagpurfor ACKNOWLEDGEMENT and shouldbepassed ontothemasses. ‘Kamdhenu Ark’ aretobebroughtmedical attention involving thesuccessfuluseof‘Go-muthra Ark’ or alternative withoutsideeffects. Furthercasestudies attention astheycanserveareliabletreatment The roleofcowurineincuringthecancerneedsfurther and otherdeadlymaladiescanbetreatedsuccessfully. far awaywhentheincurablediseaseslikecancer, AIDS the beneficialpropertiesofcowurine,daymaynotbe by followingthedesiredpromotionalstrategies.Utilizing definitely apromisingformulationintheyearstocome Cowpathy, anewversionof ancientscience,whichis highly valuablevirtuesandwideapplicationsof an integratedapproachisnecessarytopromotethe but alsoinhighlyeducatedandscientificsocieties. Thus should gainpopularitynotonlyintraditionalfamilies domestication ofindigenouscow. The cowurinetherapy It isnon-toxicandcanbeobtained freeofcosttrough therapy formankindincuringvarioussorts ofdisorders. Cow urineisauniversalmedicineandcanbethebest would provideagreatrelieftothehumansufferings. alternate therapyinfightingagainstthecancer, which can strengthenandpromotethisuniquenatural scientists andresearchersshouldbegivenpriority, which in thetreatmentofcancerbyphysicians,clinicians, authentic dataforthesupportandofcowurinetherapy this medicinalutilityofcowurineandgeneration Establishment ofresearchanddevelopmentcentersin modern scientifictestifyingmethodologies. since theyhavepassedthroughthehighstandards of the panchgavya products, particularly thecowurine, Bhadauria, H.(2002).Gomutra-Ek Chamatkari Aushadhi Bartnett, B.(1988): The miraclesofUrine Therapy. Water Ambwani S.2004.Molecularstudiesonapoptosisinavian officinalis Gaerth Panchagavya formulationcontaining (2004). Neuropharmacologicalactionsof Authors arethankfultoSriSuneelMansinhka, Patrika, (Cow urine–A Magical Therapy). Vishwa Ayurveda of LifeInstitute,Hollywood, Florida. GBPUA&T, Pantnagar, India lymphocytes inducedbypesticides.PhDthesis, 2004, pp.499-503. Indian JournalofExperimental Biology Vol. 42,May 5 : 71-74. and Glycyrrhiza glabraLinn niCne ciiyo o rn 23 Anti-Cancer activityofcowurine Emblica inmice. Chauhan, R.S.,SinghD.D.,Singhal,L.K.andKumar, R. Chauhan, R.S.(2005).Cowpathy: Anew versionof Ancient Chauhan, R.S.(2004b).Panchgavyatherapy(Cowpathy): Chauhan, R.S.(2004a).GovanshEvamManav Chauhan, R.S.(2003c).Neoplasms,inIllustratedSpecial Chauhan, R.S.(2003b).Panchgavyaserogpratirodhi Chauhan, R.S.(2003a).Gomutrasesarirkirogpratirodhi Chauhan, R.S.(2002b).Medicalimportance ofPanchgavya Chauhan R.S.andSharma,R.(2002).Desigayokiupyogita Chauhan R.S.(2002a).Panchgavya:desigayseprapta Chauhan R.S.(2000).Panchgavyadwaraprakritikchikitsa. Chauhan,. R.S.(2003).Immunomodulation: pesticidesand Chauhan, R.S.,Singh,B.P., Singhal, L.K., Agrawal, D.K. Chauhan, R.S.,Singh,B.P. andSinghal,L.K.(2001) Chauhan R.S.andSingh,B.P. (2001).Panchgavyadwara Caraka-Samhita, Editor-Translator P. Sharma, Journal ofImmunologyandImmunopathology (2004): Effect ofcowurineontheinterlukin-1 and2. July, 2005,pp1-2. Science. EmploymentNews,Vol. xxx,No.15,9-15 July-September Issue Current status andfuturedirections. Shwashthya. CowtherapySociety, Pantnagar. 1-67. Publishing Division,Lucknow, India.Chapter1, Veterinary Pathology, RSChauhan(Editor),IBDCO chamta mevridhi.Prakritismarika at IVRI,Izatnagar(U.P.). Singh Endowment Trust, Bareilly, Feb. 27-28,2003, Ministry ofHRD,Delhi;IVRI,Izatnagar&Dr. C.M. by CommissionforScientific& Technical Terminology, Sciences–Research DirectionsintheNextDecade chamta mevridhi.NationalSeminaronVeterinary Period). IVRI,Izatnagar, April 16-17, 2002. Husbandry in Ancient India,Vedic and Ashokan Overview onVeterinary Sciencesand Animal (Cow therapy).In:NationalSymposiumonHistorical tulna. Pashupalan, May2002,31-33. thatha unkisankarevamvideshinaslkigayonse ek adbhutaushadhipashudhan, Kheti sansar, environmental institute, Nagpur April, 28-29,2003. ayurveda andagricultural systemnational panchgavya. National conferenceonpanchgavya, November 8-10,2001. Improve HealthandProduction, Pantnagar. Symposium on Animal Structural Dynamics to XVI Annual ConventionofIAVA andNational activity ofleucocytesinmicewithKamdhenuark.In: and Singh, A.K. (2001).Enhancement ofphagocytic 77. Journal ofImmunologyandImmunopathology Immunomodulation withKamdhenu Ark inmice. (1):38-39. prakritik chikitsa. Asian kisansansar, 1981, p.213 Chaukhambha Orientalia, Varanasi, India,Volume 1, 3: 21-23.

1: 3-7 17 (3): pp The IndianCow. 2 (3) 9. 5-7. : 29-31. , 3: 74- Pp: , 6 www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 Groenwald SL,FroggeMH, GoodmanMand Yarbro CH. Gopalan, C.,Rama Sastri,B.V. andBalasubramaniumS.C. Gilley D, Tanaka HandHerbertBS.2005. Telomere Gatti L andZuninoF. 2005.Overviewoftumorcell Garg, Nidhi,Kumar, Ashok, Chauhan,R.S.,Sinhgal,L.K. Garg, Nidhi,Kumar, Ashok andChauhan, R.S. (2004a): Garg, NidhiandChauhan,R.S.(2004):DraughtPower: Garg, NidhiandChauhan,R.S.(2003b).Kamdhenuark Garg, NidhiandChauhan,R.S.(2003a).Cowtherapyas Garg, NidhiandChauhan,R.S.(2002).Roleofcowinthe Fulzele, S.V., Satturwar, P.M., Joshi,S.B.and Dorle, A.K. Fulzele, S.V., Satturwar, P.M. andDorle, A.K. (2001). 4Dhamaetal. Finley RS.2003.Overviewoftargeted therapiesforcancer. Ezra CohenEW. 2002. Tumor Review. Online Dow KMandHilderleyLJ.1992.NursingCareinRadiation Datta, D.(2001).Effect ofKamdhenuark,anantioxidant Crowell JA.2005. The chemopreventiveagentdevelopment 24 Institute ofNutrition,ICMR, Hyderabad. (1993). NutritiveValue ofIndianFoods.National Biol dysfunction inagingandcancer. chemoresistance mechanisms. Indian Co.July-SeptemberIssue production andqualitytraits ofEggsin Layers. and Lohani,M.(2004b):Effect ofcowurineonthe Oct-Dec Issue parameters ofwhiteleghornlayers. Assessing theeffect ofcowurineonbiochemical Dec Issue Back boneofIndianEconomy. Graduate Update,January18,2003,Gwalior. Symposium onMolecularBiologyinIndia-APost changes humoralimmunityinrat.National 3-7 January, 2003,Bangalore. an alternativetoantibiotics.IndianScienceCongress, December 2002,Pantnagar. Security andLivelihoodsinMountains Areas; 30-31, Livestock ProductionSystemsforSustainable Food life ofhumanbeing.InternationalSymposiumon Pharmacology, Haridradi ghrita (2003). Study oftheimmunomodulatoryactivity Immunology andImmunopathology Immunostimulant activityofcow’s ghee. 111 Am JHealthSystPharm Network. Chicago. ReviewprovidedbyVeriMed Healthcare Department ofMedicine, The UniversityofChicago, AllRefer.com, EzraEWCohen(Reviewer), Oncology University, Gwalior(M.P.). on chromosomalaberration.M.Sc. Thesis, Jiwaji J Cancer of theUSNationalCancerInstitute:anoverview. research programintheDivisionofCancerPrevention :127-148. . 37 (5):1000-1013. . .

Philadelphia, WBSaunders,USA. 41 2: 11-22. (13):1889-1910.

2: 35 38-41. : 51-54. inrats. IndianJournalof . 60 (24 Suppl9):S4-10. The IndianCow. Oct- Methods MolMed

Int JBiochemCell 1 TheIndianCow. :12-15. , 3(2): Journalof 87-88. The Eur . Saxena, Sumit,Garg,Virendra andChauhan, R.S.(2004): Sabiston DCJr. 1991. Rosenberg SA.1997.Principlesofcancermanagement in Rieger PT. 1995. Reiche EM,NunesSOandMorimotoHK.2004.Stress, Prabhakar Kumar, Singh,G.K., Chauhan,R.S.andSingh, Prabhakar Kumar(2004).Structural dynamicsofapoptosis Parihar, G.S., Rajput,M.K.S.,Upadhyay, A.K. andMahesh Nautiyal, C.S.(2002).Cow’smilkanovalsourceofmicrobial Li CY, HuangQandKungHF. 2005.Cytokineandimmuno- Kumar, R.,Chauhan,R.S.,Singhal,L.K.,Singh, A.K. and Kumar Atul, Kumar, P. Singh,L.K.and Agrawal, D.K. Joshi, M.M.(2002):Cowtherapy(Panchgavya)andcattle Gupta, Amita (2003).Effect ofcow’surineonhealthrats. Milenic DEandBrechbielMW. 2004. Targeting ofradio- Maheshwari, A.K., Gupta. A.K. and Das, A.K. (2004): Effect (2004): Das, A.K. and Gupta. A.K. Maheshwari, A.K., WB SaundersCo. Basis ofModernSurgicalPractice. 373. eds), Oncology biologic therapy. In: Bartlett. Oncol depression, theimmunesystem,andcancer. Cow. Oct-DecIssue proliferation indevelopingstages ofchicks. D.D. (2004):Effect ofcowurineonlymphocyte Agric. and Tech. Pantnagar. College ofVeterinary Sciences.,G.B. PantUniv. of in avianlymphocytes.M.V.Sc. Thesis submittedto Indian Cow. July-SeptemberIssue of crossbred,sahiwalandnon-descriptivecattle. Kumar (2004):Comparison ofmineralprofileinurine New Delhi.pp.86-98 wealth. In:GayKaDudh Amrit Hai..Love4cow Trust, gene therapyforsolidtumors. and Immunopathology, Vasant Kusumakarinmice.JournalofImmunology immunostimulatory effects ofKamdhenu Ark and Singh, D.D.(2004b). A comparative studyon Dec Issue prevention throughcowpathy. (2004a): Pathogeniceffect offreeradicalsandtheir Ayurvedas Sammelanon7.9.2002.IIT, NewDelhi. based economy. InauguralspeechinVishva Technology, Kanpur(U.P.). (Mathura) ,CSA Universityof Agriculture and M.V.Sc. Thesis, CollegeofVeterinary Science ed. Boston,MA:JonesandBartlett. 1997. 3 isotopes forcancertherapy. September Issue of CowUrineonWounds. :81-91. (4):361-70.

5th ed.Philadelphia,PA: Lippincott-Raven :349– . Cancer NursingPrinciplesandPractice. 5 (10):617-625. (DeVita VT Jr, HellmanS,RosenbergSA,

2: 27-34. Biotherapy. Textbook ofSurgery:TheBiological

1: 19-24. Cancer: Principles&Practiceof

2: 3-5 4 :104-106. Boston, MA:Jonesand The IndianCow. July- Cell MolImmunol The IndianCow. Oct- Cancer BiolTher

Philadelphia, PA: 1 : 8-11 The Indian Lancet . The 2 4th (2) . www.IndianJournals.com Members Copy, Not for Commercial Sale

Downloaded From IP - 14.139.62.136 on dated 28-Aug-2012 The Hindu,4July, 2002.UnitedStates Patentand Trade The Hindu,July3,2002,Pre-digestedorganicwastesfor Treasure J.2005.Herbalmedicineandcancer:an Tietze H.W. (1996).Urinetheholywater, PhreeBooks, Thiery-Vuillemin A, Nguyen T, PivotX,Spano JP, Dufresnne Susruta Samhita - The MedicalScienceofthe Ancient Stern MandHerrmannR.2005.Overviewofmonoclonal Stephen G. 2004. Tumor. ReviewedbyStephen G, George Singh, D.D.,Kumar, P andChauhan,R.S.(2004): Singh, B.P. andChauhan,R.S.(2004):CowDahi(curd)or Singh, Atul and Agarwal, D.K.(2004):Qualitymilkfrom make antibiotics,anti-fungalagents andalsoanti- innovation whichhasprovedthatcow’s urinecan Office hadgrantedPatentNo6410059toan“Indian high qualityvermi-compost Year. 2):S3-8. introductory overview. PO Box34,BermaguiSouth,2546, Australia. interventions. their promiseascancerchemopreventive A andSoriaJC.2003.Molecularlytargeted agents: Calcutta. 1885. Aryans’, Tr. andEd. A.C. Bandopadhyaya, 2nded. Crit RevOncolHematol antibodies incancertherapy:presentandpromise. Network. New Britain. ReviewprovidedbyVeriMed Healthcare Bray CancerCenteratNewBritain GeneralHospital, The IndianCow. July-SeptemberIssue Comparative ProfilesofIndigenous andexoticcows. diseases. Matha (ButterMilk): As probiotictocontrolanimal 1: Indian Cows. 1: ailments. Cow Urine Therapy: PromisingCureforhuman 25-30. 39-49 TheIndianCow. July-SeptemberIssue TheIndianCow. Oct-DecIssue The IndianCow. July-SeptemberIssue Eur JCancer Semin Hematol . 54 . (1):11-29. 41 (13):2003-2015. niCne ciiyo o rn 25 Anti-Cancer activityofcowurine .

1: 42

56-60 2: (3 Suppl 6-10. . Times NewsNetwork,Friday, January24,200301:19:13 Times NewsNetwork,January02,200301:09:18 AM. Cow The HINDU-Thursday, Sep19,2002. The IndianExpress4July2002,CentralInstituteof www.cancer.gov National seminaroncowandbio-diversityorganizedbylove MerckSource.htm. Merck ManualHomeEdition.htm.2003.CancerSection, http://www.iscowp.org (TheInternationalSocietyforCow http://www.cowindia.org http://www.cowurine.com http://www.love4cow.com http://www.cowindia.org/dung&urine.htm http://govigyan.com/institution.htm http://dahd.nic.in/ch2/chap8.htm#1#1: The http://www.pavapuri.com/gaumata.html Amar Ujala,19 Am: dung agoodnuclearshield? of theantibiotic”. can helpkillmorebacteriathanasingleapplication the commonlyusedanti-tuberculosisdrugrifampicin, when usedincombinationwithcertain antibioticslike established that“Certain compoundsincowurine, Medicinal and Aromatic Plants atLucknow cancer drugsmoreeffective”. 2001. Lodi Estate, NewDelhi-110003 on30thNovember, 4 cowtrustheldatIndiaInternationalCentre(IIC), Merck andCo.,Inc. Protection) Cattle Recommendations oftheNationalCommissionon American patient toIndia. Cow’ th s milkap July, 2005.Gomutrasecancerkaelaj- anacea.