Cancer Research Paper


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A research paper I read recently which seemed quite interesting !!!

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Cancer Research Paper

  2. 2. INTRODUCTION - Phaseolus vulgaris (common, dry beans) and mammary cancer -It is a well known staple food, widely available and affordable -Average consumption can reach 150- 200g/day, BUT, typical US consumptions are below recommended levels* This paper researches on the cancer risk associated with bean consumption and thus investigates specific Systemic factors known to contribute to the survival and proliferation of cancer cells. *Please see Notes below.Copyright 2008 | Redistribution Prohibited | Image © 2008 clix/ | This text section may be deletedfor presentation.
  3. 3. HYPOTHESIS - So its Man vs Food; Cancer vs Beans 1) Does consumption of beans, really help in reduction of cancer risk? 2) What systemic factors does it actually affect? 3) The signaling mechanism initiated by bean consumption is dose-dependent or even traces of it can activate the cascade?- Solving these issues would definitely bring to us a new solution to not treat mammary cancer (which is under the R&D world already) but will allow us to maintain our dietary structure to be ‘actually’ healthy.And we always thought, only running and gyming would keep us fit, healthy and disease free!!!!Copyright 2008 | Redistribution Prohibited | Image © 2008 clix/ | This text section may be deletedfor presentation.
  4. 4. OBJECTIVES OF THE STUDY-So to know the role of Beans in stimulating the health of ourbody; we need to study cancer progression focusing on:1) Systemic Factors(such as glucose-dependent pathways)2) Cell Autonomous Mechanisms(cellular energy and networking pathways)3) Signaling pathways(such as mTOR; this one is the main crux of beans and cancer risk) **Note
  5. 5. METHODS – A Detailed protocol (for all the curious heads   )Step I: Female Sprague-Dawley rats were obtained for thisexperiment; at 20 days of age(make a point of this) andmaintained at 22⁰C with 50% relative humidity and a 12hlight/dark cycleStep II: At 21 days of age(here we go), the rats were injectedwith 1-methyl-1-nitrosourea(Carcinogen; cancer causing agent)Step III: Seven days after the injection, all the rats wererandomized based on diet groups (so that we can finally testbeans against others). Bean was incorporated at 60% wt/wt andfor Dose-Response at 7.5%, 15%, 30% and 60% wt/wt. Fed till46 days post injectionStep IV: Following an overnight fast, rats were ‘euthanized’ overa 3 h time interval with Carbon monoxide. Blood wasobtained, plasma was isolated by centrifugation at 1000g for10mins.
  6. 6. Step V: Plasma Glucose, insulin, IGF-1, interleukin-6 and C-reactive protein (CRP) levels were measured using differentassays, such as ELISA for Insulin, IL-6 and CRP.Step VI: Cell proliferation and apoptosis was determined usingKi-67 immunohistochemical staining method for the mammarytissues isolated from the rats. Corresponding hematoxylin- andeosin-stained serial sections were acquired using Zeiss AxioskopII at 400x magnification.Step VII: Western Blotting of the carcinomas (homogenized inlysis buffer) was performed. 40 ug of protein lysate per samplewas subjected to 8-16% sodium dodecyl sulfate-PAGE gradientelectrophoresis. After electrophoresis, proteins were transferredto a nitrocellulos membrane. The levels of Cyclin D1, E2F-1, Rb, p21, p27, Bcl2, X-linked inhibitor of apoptosisproteins, Bax, AMPK, pACC, ACC, Akt, Raptor were determinedusing specific primary antibodies.Step VIII: Extraction of plasma metabolites using HPLC-Liquidchromatography and analysis of them using ANOVA was done.
  7. 7. RESULTSFig 1: Showing the difference in levels offactors after and before bean-treatmente.g: We see a decrease in the levels of Cyclin D1 implyingthe fact that ratio of hyperphosphrylated Rb to hypo-decreases in bean-fed rats compared to control ones.***Note
  8. 8. Cont……Figure 2: Dose-dependent effects of bean feeding onmTOR signaling components (as studied through theprevious data) – Western BlotsAs seen from the above data, at a higher dose there seemsto be a considerable increase in the levels of thesecomponents of the mTOR pathway. This is also confirmedfrom the next data.
  9. 9. Graph A gives a good summarized dose-dependentcurve showing the 60% wt/wt being the best forreduction of mammary cancer.****
  10. 10. mTOR is a conserved serine/threoninekinase that integrates external cellularstimuli with intracellular energy and nutrient-sensing pathways to regulate cellularmetabolism and growth. (presence of Aktpromotes mTOR’s cell growth activity)In this paper, two upstream regulators ofmTOR pathway were investigated. AMPK (anitrogen containing phytochemicalderivative; BTW Common bean is a richsource of small nitrogen containingcompounds , so here we go!) and Akt (adownstream effector of the insulin and IGF-1receptors and both plasma insulin and IGF-1were reduced dose-dependently withincreasing dietary bean consumption).mTOR affects lipid metabolism, lipid isrequired for cancer cell proliferation. SoAMPK affects mTOR which decreases thelipid available and thus reduced Cancer risk.
  11. 11. Important word – AMPK (as it affects mTOR for a better effect)Twist being: AMPK normally is activated under cellular stress andnutrient deprivation.. Hmm.. So that needs more study for theeffect of dietary bean on AMPK. I am presuming that AMPKactivation in our case in through LKB1 factor.
  12. 12. THUS,-Common bean consumption appears to reduce mammarycancer burden through inducing apoptosis (increasedBax/Bcl2 ratio, p27, p21 increased levels, etc) andmodifying key metabolic signaling networks linked to cellgrowth and survival (mTOR being the main one studied)-We need to know : a) How AMPK is actually affected? b) Does the mTOR pathway have a relation with otherfactors such as p27 and Bax/Bcl2? c) What component of Bean and why only this variety? d) Has study been done also in Asians, who have ahuge intake of dry beans in their regular diet? (Importantas even the environmental effects and bean quality mightdiffer and give varied results)Lets research more and make this world a better place toenjoy and diseases just a mere thought  THANK YOU!!!!