volume 1 issue no. 1 ijop · salvestrol scientist receives cancer drug award mass spectrometry and...
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The Discovery of aUniversal CancerMarker
IJOPThe International Journal Of Phytotherapy
The Hidden Power of PlantsIt’s NOT a small world after all!
RSC Teamwork in Innovation 2011 WinnersSalvestrol scientist receives cancer drug award
VOLUME 1 ISSUE No. 1AUTUMN 2012
THIS ISSUE
The Discoveryof a Universal Cancer Marker
The Hidden Power of Plants
RSC Teamwork in Innovation 2011 WinnersProfessor Potter and his former team haverecently earned the Royal Society of Chemistry(RSC) “Teamwork in Innovation” award.
“Let food be thy medicine and medicine be thyfood”
― Hippocrates
COVER STORY
NEWS
UPFRONT
IJOPThe International Journal Of Phytotherapy
This months featured article is on the discoveryof a protein CYP1B1 (pronounced sip-one-be-one) which is a universal cancer marker. Thisdiscovery has important implications for thetreatment and diagnosis of cancer.
EDITORIAL
What is IJOP?
The International Journal of Phytotherapy(IJOP) was formed as a bridge betweenresearchers and practitioners inphytotherapy. The Journal will includethe full spectrum of phytotherapyincluding herbal medicine and the use ofplants and plant derived compounds inmedicine. This Journal was launched as achannel of information from cutting edgescientific research to practitioners ofphytotherapy to put this understandingon a firm scientific basis to be viewedmore as a logical approach and less as
“alternative” medicine.
Featured Herb:
Milk thistle (Silybum marianum) has beenused for over 2,000 years in herbalmedicine for a variety of ailments, and inparticular for liver and kidney problems.Milk thistle is well known as a liver tonicand several scientific studies show thatsubstances in milk thistle such as silymarinprotect the liver from toxins. This alsoincludes toxins from cheotherpay drugswhich can cause liver damage in highdoses. Silymarin has antioxidant and anti-inflammatory properties, and it may helpthe liver repair itself by growing new cells.A number of human studies demonstratethat milk thistle can be helpful inprotecting the liver.
The active ingredient is thought to besilymarin, a chemical extracted from the
Professor Gerry Potter completed his first degree in Organic Chemistry at theUniversity of Manchester Institute of Science and Technology (UMIST) andwent on to do his Ph.D. in Medicinal Chemistry at the Institute of CancerResearch (ICR) within the Royal Marsden Hospital in Sutton. Here he wascoached by some of the top experts in cancer research at that time. Afterfinishing his Ph.D. he continued his research into developing effective newagents for the treatment of cancer. During this time he developed the newagent Zytiga (Abiraterone Acetate) for treating advanced prostate cancer.Professor Potter has over 30 years experience of cancer research at theforefront of drug development.
About The Editor
seeds. Silymarin is actually a group offlavonoids (silybin, silydianin, andsilycristin) which are thought to helprepair damaged liver cells. It reducesinflammation which is why it is oftensuggested for people with liverinflammation or hepatitis.
Most milk thistle products arestandardized preparations made fromthe seeds of the plant that contain 70 -80% of silymarin. However by focusing inon a single active component we may bemissing out on the other beneficialmolecules which are present in the wholeplant.
Molecular structure of Silybin, one of theactive components of milk thistle.
Guidelines for Authors
Articles on all aspects of phytotherapy arewelcome for submission, ranging fromoriginal research articles through to casestudy articles from practitioners usingphytotherapy. Manuscripts for submissionshould be sent to [email protected]
Professor Dan Burke of Care Bio-technologies is awarding Professor GerryPotter in recognition of his work onAbiterone Acetate (trade name Zytiga).
IJOPThe International Journal Of Phytotherapy
www.IJOPT.org
NEWS
Catherine Dooner
In the early 1990s, cancer researcherProfessor Gerry Potter had a definingeureka moment. Just having finished hisPhD in Medicinal Chemistry, he wasworking at the Institute of CancerResearch at the University of London, UK,as part of a team researching a new drugfor prostate cancer.
The team’s approach was radicallydifferent as they were not targeting theprostate cancer cell directly. They hadidentified an enzyme, CYP17, thatappeared to be supplying the male sexhormone, androgen, to aid prostatetumour growth. The hope was thatinhibiting the synthesis of androgen wouldstop the nutrient flow to the tumour andend its growth.
The team started with an existing drugcalled ketoconazole, which inhibitedCYP17 and the production of androgen.The problem was that ketoconazole wasnot potent enough to significantly stoptumour growth, and was quickly brokendown and eliminated by the body.
As Professor Potter was the medicinalchemist on the team, he was tasked withdevising a drug that better inhibited CYP17.After a few weeks of research, ProfessorPotter designed a chemical calledAbiraterone (CB7598) which worked toblock CYP17 and the production ofandrogen anywhere in the body. Thischemical formed the basis of AbiteroneAcetate (CB7630), a medicine that thenwent through years of clinical trials.
In April 2011, the US Food and Drugadministration (FDA) approved the use ofAbiterone Acetate (trade name Zytiga) inmen with castration resistant prostatecancer. European approval followed fivemonths later. Trials of Abiterone Acetatehave shown it can shrink tumours by 80%with few side effects. It is 10,000 morepotent than ketoconazole.
Professor Potter and his former team haverecently earned the Royal Society ofChemistry (RSC) “Teamwork in Innovation”award for their role in the discovery anddevelopment of Abiraterone Acetate for
prostate cancer. This is the third timeProfessor Potter’s research has beenhonoured by the RSC.
For more information, please seewww.rsc.org
Salvestrol scientist receives cancer drug award
Mass Spectrometry and Proteomics inNutrition and Health
In cells, proteins interact with othermolecules either by directly binding or byreaction. In all cases, interactions areresulting, from protein topologicalfeatures that are themselves theproducts of selective adaptation. Thesemolecular interactions, proteinabundance levels and other factors suchas post-translational modification servein complex ways to regulate globalfunctional levels in cells. However,topological features of proteins and theirinteractions are ultimately at the origin ofall fundamental biological processes.Therefore, improved technologies thatcan help visualise topological features ofprotein interactions in cells will, in turn,increase our understanding of functionalnetworks and their relationships todisease and normal function. To this end,the secound Symposium on StructuralProteomics was attended by Mr AnthonyDaniels and Dr Robbie Wood on 25 May2012 as part of CARE Biotechnologiescontinued research and developmentproject. The conference was hosted byThe British Columbia Proteomics Networkin Vancouver BC and co-chaired byProfessors Christoph Borchers, EvgeniyPetrochencko and Juergen Kast.
As proteins and protein complexes arecritical to all biological processes it wasnecessary to gain an even greaterunderstanding of the molecularmechanisms for protein functionincluding the visualisation of individual3-D structure and assembly of the proteincomplex. Various papers were presentedand the latest methods of analysisexamined. For instance, instead of usingtraditional high-resolution structuralmethods to assess proteins severalauthors presented chemical cross-linkingmass spectrometry (CXMS) as anemerging structural technique using less
material with a high-throughput. Anotherpaper reported on 3-D proteomics usinga combination of chemical cross-linking,mass spectrometry and databasesearching to show the increased successin providing medium resolution data onstatic protein structures.
At the heart of A Systems Approach toHealth another paper placed proteomicsat its core to investigate and deploysystems technologies as a function of dietand lifestyle to address nutritionallyactionable health conditions.
Pomegranate Juice Slows PSA IncreaseA Phase 2 clinical study of pomegranatejuice (PJ) in men with early stage prostatecancer showed that the rate of increaseof PSA levels in these men decreasedmore than 3 fold from a doubling time of15 months without PJ, lengthening to 54months for those who drankPomegranate Juice.
The PSA test measures the levels ofprostate specific antigen and thiscorrelates with prostate cancerprogression. These results mean thatconsumption of pomegranate juice canslow the rate of development of prostatecancer.
BOOK CORNER
Your Life In Your Hands byProfessor Jane Plant
Having done everything her oncologisthad advised and having undergone all thetreatments prescribed, the return ofcancer for the fifth time was a cruel blowindeed for Professor Plant . This finalpresentation was as a large lump in herneck as metastatic involvement of herlymph nodes from her primary breastcancer. With the prognosis of only 3 to 6months to live Jane declined furthermedical involvement. After all, she hadalready endured a lumpectomy, amastectomy, two further operations,thirty five radiotherapy sessions and fivecourses of chemotherapy. This all lead toProfessor Plant 's own personal battle forsurvival. Her book is a testimonial to herown personal approach to breast cancer.She encourages her readers to take thelead in their own cancer treatment withparticular emphasis on lifestyle anddietary changes.Through her own endeavours andsupported by her scientific background asone of the world's leading geochemists,she is able to bring together a subjectivelink between diet and cancer.Although her theory remainscontroversial her book is well-recommended, not just to those whosuffer from cancer of the breast orprostate, but also to all cancer sufferersand those free from disease who wish topromote a healthier lifestyle. The reader-sufferer is encouraged to be empoweredby scientifically-based knowledge and toengage with their physician in thedecision making and treatment processes,whether that be chemotherapy oralternatively a change in diet and lifestyle.
Health Defence 2nd Edition by DrPaul Clayton
Health Defence is a digest of pharmaco-nutritional approaches to promote betterhealth and understanding of why we maydevelop illness and disease, particularlythose of the chronic degenerative kind.Few people, it seems, actually die of oldage, yet evidence from healthycentenarians and from certainpopulations shows that the risk tochronic diseases can be cut dramaticallythrough simple nutritional means whichcan offer not just a longer life, but alonger quality life. Dr Paul Clayton, aleading Medical Pharmacologist, hasspent years sifting through thousands ofstudies to identify the nutrients with themost proven role in long term health andhas resulted in this excellent book.The book itself is clear and is set out intofour core parts and each part is furthersubdivided into chapters. Each chapter isannotated down the side of each pagewith key points and addenda. The book isintended as a reference such that a topiccan be dipped into and read separately.The reader shouldn't be daunted by thelist of references cited at the end of thebook but rather encouraged to researchthe facts for themselves.Dr Clayton should be congratulated forthis work. In all, he has outlined nineseparate groups of protective nutrients.These, in his opinion, promise a morebroad protection against disease,without any significant change to one'sown everyday diet. His idea is to informand empower the consumer to aim forquality longevity by using nutrition toreduce the risk of developing chronicdegenerative diseases. Eating the rightfoodstuffs containing the right nutrientsis his recipe for a long and healthy life.Therefore, nutrition is key to a maximumhealthy lifespan.
Review of The Cancer Break-through by Dr.Steve Hickey and Dr.Hilary Roberts
More than 40 years have passed sinceAmerican President Richard Nixon de-clared war on cancer. The Cancer Break-through is a short, informative andcompact book which expresses a disap-pointment with the failure of modern con-ventional medicine to eradicate thisdisease.Drs.Hickey and Roberts, having reviewedthe scientific literature, come to the con-clusion that it may be possible to controlmany cancers by dietary means alone .They challenge established medical dog-ma and offer nutritional protocols to doc-tors and patients to prevent and treatcancer.The book is divided into small, bite-sizedchapters with a short summary at the endof each. There are descriptive sections onnormal cells, their change to becomingcancerous cells and the role of phytonutri-ents in the prevention and treatment oftumours. Their phytotherapy regimenplaces a lot of emphasis on vitamin C, aswell as the synergistic effects of vitamin Cwhen combined with alpha-lipoic acid orwith vitamin K3.The authors' open disparagement of thepharmaceutical industry is forthright andhonest. It is true that there is less profit tobe made from natural anti-cancer treat-ments compared to commercial pharma-ceuticals, and the exclusion of naturalfoods from clinical trials is therefore notscientifically-based but pecuniary-based.The book brings an awareness to the read-er of the benefits of a nutritional ap-proach to the prevention and treatmentof cancer. Having an antioxidant rich dietis to be lauded, however, more recentscientific evidence shows that antioxi-dants may be just part of the puzzle.
UPFRONT
identifying new pharmacologically activecompounds from plants as mentionedabove. However this approach disregardsthe “inactive” components which canlead to undetection of the most impor-tant component of all – the proactives.
Recent research has revealed that the “in-active” component contains a sub groupof proactive compounds. These proactivecompounds require human metabolismto activate them and so remain hidden inthe inactive component. These com-pounds are the hidden power of plants.The human enzymes that activate proac-tive compounds mainly belong to the CYPfamily of enzymes. These proactives arealso referred to as prodrugs. So the prod-rugs remain hidden in the inactive compo-nents of plants and it is only throughresearch on drug metabolism that theseagents have been brought to light.
In cancer research the important proac-tive component of plants are calledsalvestrols. These are first metabolised bya CYP enzyme in the liver and delivered tothe tumour. Once inside the tumour cellsthe salvestrols encounter another CYPenzyme called CYP1B1 and are metabo-lized to the active anticancer compoundwhich destroys the tumour cell. The firstmetabolic step of salvestrols by the liverinvolves the alpha salvestrols which areconverted to beta salvestrols by the en-zyme CYP1A2, which is acting as an alphasalvestrol activase. This process ensuresconversion of the alpha salvestrols intothe beta salvestrols ready for delivery tothe tumour. The enzyme CYP1A2 makesan absolutely perfect fit around the
salvestrol and has evolved over millions ofyears to do just this. It is interesting torealise that there is an enzyme in our liverthat is there solely for the purpose ofactivating plant compounds from our diet.The impact of this discovery has not yetbeen fully realised and the search for newproactive compounds from herbal medi-cines already investigated may reveal fur-ther proactive constituents.
Herbal extracts standardised for the ac-tive compound may be devoid of impor-tant proactive molecules. For example,milk thistle extracts standardised for sily-marin may be low in salvestrols. The ques-tion is now whether we standardiseherbal medicines to include the proactivecomponents. Supplements containingsalvestrols have been standardised basedon the proactive components and havehad considerable success to date in treat-ing cancer. Of particular note is the lack oftoxicity for salvestrols since they them-selves are inactive. This is the main advan-tage of using the proactive component isthat you would not anticipate any harm-ful side effects since the prodrug formitself is inactive. Medicine without sideeffects could be the future thanks to thehidden power of plants.
Professor Gerry Potter
The Hidden Power of Plants
Phytotherapy is the use of plants to treatmedical conditions. In its traditional senseit has the same meaning as herbal medi-cine, but in its wider sense it is the use ofplants and plant derived compounds toboth prevent and treat disorders.
Cancer phytotherapy is the use of plantderived compounds for the treatment ofcancer. It has long been known that plantscontain toxic compounds with the abilityto kill cancer cells and some of these areused in mainstream oncology. For exam-ple vincristine and vinblastine are toxicalkaloids from the Madagascan periwin-kle (vinca major) and are establishedchemotherapeutic agents acting as inhibi-tors of mitosis. Their current use has de-clined following the introduction of thetaxanes such as Paclitaxel and Docetaxelwhich are derived from extracts of taxolfrom the Yew tree and also act as inhibi-tors of mitosis. Paclitaxel and Docetaxelare now well established chemotherapyagents used in front line therapy in main-stream oncology. Other notable antican-cer agents from plant sources areTopotecan and Irinotecan derived fromCamptothesin from the Chinese happytree (camptothera), and Etoposide fromthe Flax plant. However, these active cyto-toxins are also toxic to normal cells andcause side effects such as immunosuppre-sion and liver toxicity.
Traditional phytotherapy research (phy-topharmacology) has sought to identifythe active components of medicinalplants and to disregard the inactive com-ponents. This is the obvious approach andhas had considerable success to date in
The Hidden Power of Plants
Milk Thistle
Periwinkle
Flax
Doctor Robbie Wood
Cytochrome P450 enzymes (abbreviatedas CYPs and pronounced 'sips') belong toa superfamily of proteins which containiron at their core and often referred to as'haemoproteins'. These CYPs are a largeand diverse group of enzymes that use avariety of large and small molecules assubstrates in enzymatic reactions. Beingenzymes they are natural biologicalenabling devices which change structuresof chemicals in the body withoutthemselves becoming changed. CYPenzymes have a long history andoriginated 3.5 billion years ago. Theirname is a composite one derived fromhaving a cellular location(cyto), aspectrophotometric characteristic(chrome) and a unique opticalabsorbance peak at or near 450nm.
CYP enzymes are ubiquitous and found inall life forms from animals, plants andfungi. More than 11,500 distinctCytochrome P450 enzymes are known toexist. In humans there are 57 differentCYP proteins wich are all bound tomembranes of the endoplasmicreticulum or to the inner membrane ofthe mitochondria and as such havedistinct cell-specific, tissue-specific anddevelopmental-stage-specificcharacteristics. The majority of CYPs areto be found in the liver, however,individual forms have been identified inextra-hepatic tissues such as lung, kidneyand intestines.
Humankind emerged about 1 millionyears ago. During human evolution thediet was mainly vegetarian and as suchwe ate many phytochemicals.Phytochemicals can be drugs or poisonsand so it is vital to be able to neutralisethem in the human body. Human CYPsevolved to process natural plantcompounds we ate in our diet butnowadays CYPs are also important forphamaceutical metabolism.
The principal function of CYPs is themono-oxygenation of various substratesthrough the incorporation of one atom ofmolecular oxygen. This is achievedthrough the presence of iron at their coreand a multi-component electron transferchain. For instance, this oxidation orhydroxylation action on drugs and toxinsrenders them water-soluble, which in
turn allows them to be excreted from thethe body. Historically, this may have hada survival value for all types of specieswhen dealing with potentially harmfuland noxious substances.
The Human Genome Project hasidentified 57 human genes coding for thevarious Cytochrome P450 enzymes and32 pseudogenes. The nomenclatureallows for the division into families ofCytochrome P450's, which are thenfurther subdivided into sub-families andthen again by polypeptides. For instance,Cytochrome P450 family 2, subfamily E,polypeptide 1 in humans is encoded bythe gene CYP2E1 (pronounced 'sip two eeone') which is one of the enzymesinvolved in paracetamol metabolism.Another Cyp enzyme which was notidentified until 1990 is CYP1B1(pronounced 'sip one bee one'). (Fig 1.)
CYP1B1In 1993, at the University of Aberdeen,Scotland, Professor Dan Burke's researchteam discovered something of significantimportance regarding the enzymeCYP1B1. They reported the presence of
CYP1B1 in soft tissue sarcomas. Aunique find. This discovery wasachieved using a technique calledimmunohistochemical staining.
Immunohistochemical staining is theprocess for detecting antigens (in thiscase CYP1B1 protein) in cells of atissue section by raising and utilisingantibodies which will bind to specificantigens. A human tissue sample isobtained either through biopsy or sur-gical removal of a tumour. The firststep is to fix this sample tissue in form-alin and then embed it in wax to cre-ate a solid sample. Once fixed, a verythin slice or microtome is producedand treated with a monoclonal anti-body against CYP1B1. The antibodywill adhere to CYP1B1 but will notadhere to cells that show no CYP1B1expression. A second antibody is thenprepared with a stain. This secondantibody is an antibody against thefirst antibody (the CYP1B1 antibody).The stained antibody adheres to theCYP1B1 antibody, which in turn is ad-hering to the CYP1B1 enzyme. In thistwo-step process the CYP1B1 en-
Fig 1
The Discovery of a UniversalCancer Marker
COVER STORY
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the totals it can be seen that from a totalof 127 cancer biopsies 122 (96%) ex-pressed CYP1B1 protein in contrast withthe 130 normal biopsies where noCYP1B1 protein was detected (0%).CYP1B1 was therefore highly overex-pressed in cancer cells whereas by con-trast the same protein was notdetectable in normal tissue biopsies tak-en from patients who had never beendiagnosed with cancer.
This same method allows for thedetermination and presence of theCYP1B1 enzyme in all stages of cancer andall types of cancer that have been testedto date, while not being present in healthytissue. As a result of many experimentslike this, by Professor Burke and others,they were able to come to this conclusion:
This enzyme has, therefore, enormouspotential for use in cancer research andcould be used as both a universal earlybiomarker for detecting cancer and as atarget for anticancer therapy. Below is alist of all cancers for which this has beenshown. In fact, every type of cancer exam-ined in this way has tested positive forCYP1B1 protein overexpression. (fig 4)
Saint or Sinner
In humans CYP1B1 is over expressed intumour cells. This has important implica-tions for tumour development and pro-gression. Compared with all otherCytochromes P450 CYP1B1 is not a majorplayer in the metabolism of pharmaceuti-cal drugs. In fact, of all pharmaceuticaldrugs metabolised by each form ofCytochrome P450 CYP1B1 activityaccounts for less than 0.1%. On the otherhand, cytotoxic drugs used inchemotherapy, for example Docetaxel,are metabolised by CYP1B1 and anti-cancer agents like Tamoxifen are
inactivated by CYP1B1. In order toovercome this latter issue CYP1B1inhibitors could be administered beforegiving those cytotoxic drugs.
CYP1B1 can metabolise a range of toxicand carcinogenic chemicals. For instance,procarcinogens in tobacco smoke can beconverted by CYP1B1 into carcinogens.However, it must be noted that tobaccosmoke contains, among other things, car-bon monoxide which is itself a CYP1B1inhibitor. Another area of research in-volves the conversion of Estradiol to 4-hydroxyestradiol by the catalytic action ofCYP1B1. It is worthy of note that CYP1B1is the most efficient estradiol 4-hydroxy-lase known. 4-hydroxyestradiol hasknown carcinogenic and mutagenic prop-erties and has lead some researchers toimplicate CYP1B1 as instrumental in thecause of certain cancers, like breast can-cer. It does seem hard to concur with abelief that CYP1B1, which can be tracedas far back as 150 million years in mam-mals, is fundamentally detrimental to life.
Resveratrol is known as a cancer preven-tative agent found in grapes and red wine.Piceatannol is a closely related stilbenewith known antileukaemic properties andis also a tyrosine kinase inhibitor. Resvera-trol is metabolised by CYP1B1 to producethe metabolite piceatannol. Although thisdemonstrates resveratrol to have cancerpreventative properties, research hasshown that resveratrol is self limiting. Invitro experiments with resveratrol on can-cer cell lines show the action of resvera-trol involves its metabolic action by theCYP1B1 isoform in cancer cells only at lowconcentrations but at higher concentra-tions CYP1B1 is down-regulated and itsbeneficial effect inhibited. In other words,the greater the dose, the less is the pre-ventative effect. However, it does pro-vide evidence to support the concept thatCYP1B1 in tumours may be functioning asa tumour growth suppressor enzyme or'rescue enzyme'.
CYP1B1 Regulation
Expression of CYP1B1 is upregulated earlyduring malignant transformation. Thereare many evidence-based theories to ex-plain overexpression of CYP1B1 but thewaters have been muddied with mistakenmeasurements for messenger RNA (mR-NA). Some researchers measured mRNAin both healthy and cancer cells believingthat wherever mRNA was found that
COVER STORYzymes are stained a particular colour (de-pending on the stain used). Themicrotome is then counterstained withHaematoxylin which dyes and highlightshealthy cells in purple for contrast.(Fig 2.)
In 1995 Professor Burke's team foundCYP1B1 in breast cancer tissue and by1997 had repeated the process for a totalof 14 different tissues, comparing normalwith malignant biopsies. An antibody wasraised against a peptide specific toCYP1B1. This antibody was found to recog-nise CYP1B1 but not to recognise otherforms of Cytochrome P450, particularlyCYP1A1 and CYP1A2. Using this antibody,the cellular distribution and localisationof CYP1B1 could be investigated immuno-histochemically for a range of malignanttumours and corresponding normal tis-sues. They looked at between 5 and 12biopsies for each,with each biopsy beingfrom a different patient. This enabledthem to report the presence or absenceof CYP1B1. CYP1B1 was found to be ex-pressed at a high frequency in a widerange of human cancers of different histo-genetic types including cancers of thebladder, brain, colon, oesophagus, kidney,lung, stomach and testis with no detect-able presence in normal healthy tissue.(Fig 3)
From the table above in Fig 3 it can beseen, for instance, that the analysis forbladder shows 8 biopsies of normal blad-der with no detection of CYP1B1 whereasthe 8 biopsies of bladder cancer showeda 100% positive response for CYP1B1. Re-viewing the whole table and in particular
Fig 3
CYP1B1 protein is highly over-expressed In all types of
malignant tumours, in theirmetastases and also in
precancerous cells.
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Fig 5
COVER STORY
This curve plots the total number of can-cerous cells from initiation to death alongone axis and against time along the other.Once cancer has been initiated there is along period of silent growth, during whichthere are no symptoms and no clinicaltests or screening that can detect thecancerous cells. It is in this period of theso-called 'latent period' that unfortunate-ly is a time most responsible for a largeproportion of the entire growth time. Bythe time a diagnosis has been made itonly has to grow a relative small amountbefore it is fatal. For most of us we neverknow if we are truly free from cancer as itcould be present in that undetectable 'la-tent period' of development.
The latent period of silent growth for lungcancer is typically around 20 years.
Another unpredictable period of silentgrowth is the recurrence of metastaticcancer in those who have been medicallycleared from previous cancer. Early detec-tion would be a huge leap forward incancer diagnosis and treatment as earlydiagnosis would significantly improve pa-tient outcomes.Unfortunately, patients, once diagnosedwith advanced cancer, have limited op-tions for treatment.
A revolutionary new blood test will soonbe available commercially relying on theprinciple of CYP1B1 being a Universal Tu-mour Biomarker. The test works by de-tecting CYP1B1 protein, in particular afragment of it, which is only produced bycancer cells. It is, therefore, a direct andaccurate measure of cancer in the bodyand that means it differs from all othertests currently available. This test hasbeen developed to detect any cancer,even at early stages. The test will be aninexpensive first stage indicator. A posi-tive test would suggest further investiga-tions like more extensive scanning andpossible biopsy.The test has been developed and perfect-ed to a stage of commercial deploymentby Care Biotechnologies. The protein isdetected and quantified in blood samplesusing state of the art research technology.Detection from the very early stages ofdysplasia to the final stages of tumourgrowth are anticipated.This new test could also be used to assessdisease progression and treatment effica-cy.Although CYP1B1 is an intracellular en-zyme, located on the endoplasmic reticu-lum, CYP1B1 peptide fragments appearon the cancer cell surface. Cancer cellswill release CYP1B1 peptide into the
CYP1B1 protein would be found also.So,in fact, when Professor Burke first pub-lished his discovery, he was soundly disbe-lieved. This was because mRNA wasfound to be as almost abundant in normalcells as it was in cancer cells. The reasonfor this has now become clearer thanks tothe independent research undertaken inJapan and Northern Ireland. A schematicrepresentation is shown in Fig 5.
In the cancer cell everything is as expect-ed. There is both messenger RNA (mRNA)and CYP1B1 protein. The CYP1B1 gene istranscribed and mRNA is translated intoprotein by the Ribosomes.However, in the normal cell, although theCYP1B1 gene is transcribed it is not trans-lated. Translation is blocked by interac-tions between uncoded regions on theCYP1B1 gene and the microRNA recogni-tion site. In other words, in cancer cellsboth CYP1B1 mRNA and CYP1B1 proteinare present and in normal cells CYP1B1mRNA is present but no CYP1B1 protein.
ProteomicsCYP1B1 is truly a unique cancer specificsignature enzyme occurring in every can-cer tested. As this protein is so highlyoverexpressed in cancer cells, whilst atthe same time being almost undetectablein normal cells (save for trace amounts innormal breast and uterine cells owing tothe upregulation of estrogen), CYP1B1expression can be said to be virtually ex-clusive to all types of cancer cells irrespec-tive of their histogenetic origin. Therefore,it follows that if CYP1B1 can be directlydetected and measured then an exclusivetest for cancer would exist.
The body is made up of 10 -10 cells –not counting bacteria. Current detection
and measurement techniques can onlydetect cancer once it has reached a cer-tain minimum size of between 10 and 10cells. A typical minimum detectable lumphas around 10 cancer cells, which isabout 1 cm in diameter. With the mostadvanced scanning and tumour markerblood test techniques the detection canbe brought down to around 10 whichequates to about 0.3cm in diameter.Once the cancer (including its metasta-ses) has grown to 10 , about 1 litre in size,then it is typically fatal to the patient.Depending on the type of cancer the timeelapsing between initiation to eventualclinical diagnosis could be around 15-20years. This can be represented schemati-cally as the pattern of growth for cancercan be described both mathematicallyand diagrammatically. Below is a dia-gram for cancer growth as representedby a 'Gompertz curve'. (Fig 6)
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COVER STORY
blood. It is, therefore, a direct measure-ment of cancer irrespective of cancertype and is therefore applicable to allcancers. The method involves an ultra-sensitive process using antibody-affinitycapture to detect the CYP1B1 peptide
CYP1B1 is detected and measured in theblood using an antibody to CYP1B1, infact, an antibody to a fragment of CYP1B1and covering all the polymorphs ofCYP1B1. Data produced allows calcula-tions to be made and applying these tothis new proteomic cancer test, an esti-mate can be made to suggest the numberof cancer cells present. This in turn can berepresented on the Gompertz curve. (Fig7)When applied to lung cancer, for instance,it can be seen that detection is muchearlier at 10 cells. This equates to diag-nosing lung cancer 5.7 years earlier thanany current detection system available.Therefore, as can be seen from the forgo-ing CYP1B1 protein is truly a unique andunequivocal Universal Cancer Biomarkerthat lends itself to being a target for anti-cancer therapeutics.
Key Points:
� CYP1B1 protein is highly over-expressed in all types of malignanttumours, in their metastases and alsoin precancerous cells� CYP1B1 is a rescue enzyme� It is necessary to understand the
concept of silent growth of cancer� CYP1B1 is a universal cancer marker
and can be detected in the blood atlow levels
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Dr. Wood originally graduated from theUniversity of Newcastle. Following juniorhouse officer posts in Oral surgery andPeriodontology, he took a junior post aslecturer in Anatomy, Oral Anatomy andOral Histology teaching undergraduatestudents at both the macroscopic and atthe microscopic level. As registrar inOrthodontics and later in Maxillo-FacialSurgery he gained surgical experience inOral Surgery and in the treatment of oro-facial cancers and the associateddisciplines of radiotherapy andchemotherapy. Dr. Wood maintain’s anactive professional and personal interestin cancer research to this day and plays anactive roll in the development of newtechnology for the early stage detectionof cancers.
About The Author
Dr Robbie Wood
References
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Cytochrome P450 expression is a commonmolecular event in soft tissue sarcomeres.Journal of Pathology 171: 49-52
3. Mc Fadyen, M.C., Breeman, S., Payne,S., et al (1999)
Immunohistochemical localisation ofCytochrome P450 CYP1B1 in breast cancerwith monoclonal antibodies specific forCYP1B1. J. Histochem. Cytochem. (1999) 47:1457-1464.
4. Murray, G.I., Taylor, M.C., Mc Fadyen,M.C., et al (1997)
Tumour-Specific expression of cytochromeP450 CYP1B1. Cancer Res. 1997., 57: 3026-3031.
5. Mc Fadyen, M.C.E., Murray, G.I. (2005)
Cytochrome P450 1B1 : A novel anticancertherapeutic target. Future Oncol. 1(2). 259-263
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12
CLINICAL CORRESPONDENCE
Case Study follow up: lung cancer.Brian Schaefer
In 2007 we were involved in a case studywith a 69 year-old man that was sufferingfrom stage 2-3 squamous-cell carcinomaof the lung. His prognosis was not good.No treatment was offered due to thelevel of disease progression and he wastold that he had a life expectancybetween eight and eighteen months. Heimmediately engaged in dietary changeand Salvestrol supplementation andmade a stunning recovery in a matter ofsix weeks. During this six weeks he wentfrom inoperable, to operable to remove alung, to operable to remove a lobe. Thisprogression of surgical suggestionsfollowed a rapid diminishment ofsymptoms (no long periods of coughingup blood), a biopsy and a follow up PETscan. Although all evidence pointed to adisease in rapid retreat, at the end of sixweeks he was taken in for surgery. Ratherthan removing a lobe of his lung theyremoved a small shrunken tumour and acouple of suspicious looking lymph nodes.The nodes were clear and the patient wasdeclared cancer free.
Cancer free status was an enormous relief,especially coming so quickly on advicethat he had a very short life expectancy.He continued with his dietary change andfinished off the supply of salvestrols thathe had and then stoppedsupplementation and returned to hisformer diet.
In the spring of 2012 he was diagnosedwith a recurrence of his lung cancer andis currently scheduled for radiationtreatment. This was a disease remissionthat lasted for 59 months which, giventhe 5-year survival statistics forsquamous-cell carcinoma of the lung isquite remarkable. From the vantage pointof survival statistics one might count thisas a very successful case. However, it is infact a very tragic case.
This individual was encouraged to changehis diet and supplement with Salvestrolsby a family member. He did not receivethis encouragement by the medicalpractitioners that were dealing with him.I am quite sure that no one explained tohim that ‘all clear’ really means that awell trained practitioner using the best
available tools for detection can nolonger see cancer. It does not mean thatcancer is necessarily absent (see Burke,MD. 2009. The silent growth of cancerand its implications for nutritionalprotection. British Naturopathic Journal,26:1, 15-18.).
This man has received some recentencouragement to return to dietarychange and Salvestrol supplementationby a family member but at time of writinghe is putting his faith in radiationtreatment. Given the rapid and dramaticrecovery from his first cancer it would bea reasonable assumption that he wouldagain benefit from dietary change andSalvestrol supplementation. However, inorder for him to pursue this approach Ibelieve that he would need the support ofhis practitioner and some furtherguidance to help him to understand hisrecovery from lung cancer. Had he beensupported in this way he may havecarried on with dietary change and alower dose of Salvestrol supplementationand perhaps avoided his currentrecurrence.
I am revisiting this case here toemphasise how important it is to educatepeople about the ‘silent growth of cancer’and the fallibility of current cancerdetection technologies. When anindividual has recovered from cancerthrough dietary change andsupplementation it is necessary toeducate them about the role that dietarychange and supplementation will play inensuring that they keep their cancer atbay.
Brief Phytotherapy News
Clinical Intelligence Corporation haslaunched a new book titled: Salvestrols –Nature’s Defence Against Cancer.The book is available fromwww.salvestrolbook.comand Amazon while the ebook versions areavailable from the following websiteswww.lulu.com, www.smashwords.com.
NHPRS
The Natural Health Product Society ofCanada (NHPRS) was formed in 2003. Itsaim was to facilitate and support rigorousscientific research and education in the
field of Natural Health Products (NHPs).Since that time the NHRPS has heldsuccessful annual conferences in majorcities throughout Canada. Theirconferences have attracted world classscientists from both academia andindustry alike. This year was no exception
when the 9th annual conference ofNHPRS was held in Kelowna, British
Columbia May 22nd -25th. Among thosepresenting this year was Professor DanBurke from England who gave the key-note address on May 23rd entitled
“Salvestrols and CYP1B1 – a Natural TeamCombating Cancer Naturally”
New Zealand leaping ahead aftervist from Dr. Robbie Wood andAnthony Daniels
In April Dr Robbie Wood and AnthonyDaniels launched the first of manyplanned lectures to the New Zealandbranch of The Australasian IntegrativeMedicine Association (AIMA) is anindependent not for profit organisation ofindividual medical practitioners seeking toprovide whole person medical care byintegrating evidence-basedcomplementary medicine intomainstream practice.
The presentation was attended byNutritionists, Naturopaths, Pharmacists,Oncologists, General Practitioners andNurses.
IJOPThe International Journal Of Phytotherapy
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Diabetes: A modern disease
Insulin is a hormone in the body that regulates blood sugar.Over time, raised blood sugar (hyperglycaemia) can lead toserious damage of the body’s systems, particularly theblood vessels and nerves.
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A unique enzyme called CYP1B1 that is produced bycancer cells. The importance of this enzyme has lead to arevolutionary new blood test that has been developed todetect any cancer at very early stages of its developmentif cancer is found early enough, simple changes to dietand lifestyle could be enough to prevent the progressionof the disease. This is a huge step forward in cancerdiagnosis and treatment. It is estimated that one third ofall cancers could be cured, using current conventionalmethods, if detected early and treated appropriately. Thiswould mean that this new cancer test could save millionsof lives worldwide every year.
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Our technology will identify the significant presence of cancer cells without the need for any apriori idea of where in the body the cancer is located. In so doing it provides a relativelyinexpensive first stage indicator as to which individuals should go for more expensive scanningand biopsy cancer tests, and it also enables clinicians to assess the progression of disease andprovide an indication of the success or otherwise of any selected management programme.
Significant investment and directed research has already taken place to establish thefoundations for this new patented technology and as a result we have identified a number ofdifferent approaches which have the potential to be executed using current commonly availableanalytical techniques used in commercial laboratories.
Our two lead researchers have a wealth of experience in cancer discovery behind them andthese advances represent a new approach to the conundrum of how to assess and evaluate thepresence of cancer in an individual. Our approach uses simple analytical assessments of bloodor urine specimens and in the future, possibly breath, without the need for invasive methods,biopsies or highly expensive and complex in-vivo monitoring devices.
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