News Article | April 13, 2016
MitoSOX Red mitochondrial superoxide indicator was from Life Technologies. MitoTEMPO, N-acetylcysteine (NAC), Nocodazole, DHEA and DCA were from Sigma. The IDH1 inhibitor 321 and control compound 990 were from GlaxoSmithKline12. Cell lines were identified using DNA fingerprinting and confirmed to be mycoplasma free. H460, A549, HBEC30 and HCC4017 cells were provided by J. D. Minna, UT Southwestern. MCF7 cells were provided by David A. Boothman, UT Southwestern. HT-29 cells were provided by Jared Rutter, University of Utah. H460 and A549 cells were cultured in RPMI supplemented with penicillin/streptomycin, 5% fetal bovine serum (FBS), l-glutamine (4 mM) and 1 mM HEPES. HT-29 and MCF7 were cultured in DMEM supplemented with penicillin/streptomycin, 10% fetal bovine serum (FBS), l-glutamine (4 mM) and 1 mM HEPES. HBEC30 and HCC4017 cells were cultured in defined medium5. Dishes with an Ultra-Low Attachment surface were used for suspension and spheroid culture. Identical culture medium was used for monolayer and spheroid culture. For spheroids, 2 × 105 H460 cells were plated in a 10 cm Ultra-Low Attachment dish. The medium was changed on days 4, 6 and 7 of culture, by centrifuging at 50g for 3 min, then gently resuspending in fresh medium. For labelling assays, the spheroids were resuspended in medium containing 13C-labelled nutrients, and the time of resuspension was considered time 0 of the labelling period. IDH1, IDH2, IDH3 and SLC25A1-deficient H460 cell lines were generated using the CRISPR/Cas9 system21. Wild type clones were selected from both the control vector (Vector) and targeting vector transfections (WT). In order to control for variations among individual clones, 4 to 5 clones were pooled together, and different pools for each targeted gene were used for further experiments. Cell proliferation was measured by counting cells after trypsinization. DNA content was also used to monitor monolayer cell growth, as previously described22. Spheroid size was determined by measuring the maximum cross-sectional area of individual spheroids using ImageJ software. Glucose, lactate, glutamine and glutamate were measured in culture medium using an automated electrochemical analyser (BioProfile Basic-4 analyser, NOVA). Ammonia was measured using an enzymatic assay (Megazyme). Nutrients labelled with 13C, 2H or 15N were purchased from Cambridge Isotope Laboratories. Stable isotope tracing experiments to determine isotopologue distributions in soluble metabolites and fatty acids were performed as described previously22, 23. For deuterium tracing, H460 clones were engineered to express the IDH2-R172K mutant (mtIDH2) under control of doxycycline16. Clones lacking wild-type IDH1 or IDH2, or containing both, were generated. Spheroids were cultivated for 7 days, then doxycycline (0.2 μg ml−1) was added for 24 h to induce mtIDH2. On day 8, spheroids were cultured in RPMI containing 10 mM [3-2H]glucose and unlabelled glutamine for 6 h. Mitochondria were prepared with the Qproteome Mitochondria Isolation Kit (Qiagen). Isotope tracing was modified from a previously described procedure22. Mitochondrial pellets were reconstituted in assay buffer (125 mM KCl, 10 mM Tris/MOPS, 0.1 mM EGTA/Tris, 1 mM P , pH 7.4) supplied with indicated nutrients and tracer. For glutamine tracing, 40 μM [U-13C]glutamine and 40 μM unlabelled pyruvate were added to the assay buffer. For citrate tracing, 40 μM [U-13C]citrate with or without 40μM unlabelled glutamine and 40μM unlabelled pyruvate were added to the assay buffer. Mitochondria were incubated in the tracing buffer for 10 min, at 30 °C with 500 r.p.m. agitation in a heat block. Steady state metabolic fluxes were calculated by combining extracellular flux rates (glucose/glutamine utilization, lactate/alanine/glutamate secretion) and 13C mass isotopologue distributions (MIDs) for citrate, glutamate, fumarate, malate, aspartate and palmitate, using the INCA software package24, which applies an elementary metabolite unit framework to efficiently simulate MIDs25, 26. We developed reaction networks describing the stoichiometry and carbon transitions of central carbon metabolism (Supplementary Table 2), with assumptions as previously described4 and summarized below. Parallel labelling data from cultures fed [1-13C]glutamine, [5-13C]glutamine, [U-13C]glutamine or [U-13C]glucose were used to simultaneously fit the same network model to estimate intracellular fluxes. Data used in metabolic flux analysis for monolayer and spheroid cultures are reported in Supplementary Table 3. To ensure that a global minimum of fluxes was identified, flux estimations were initiated from random values and repeated a minimum of 50 times. A chi-square test was applied to test goodness-of-fit, and accurate 95% confidence intervals were calculated by assessing the sensitivity of the sum of squared residuals to flux parameter variations. Extended Data Table 1 contains the degrees of freedom and sum-of-squared residuals (SSR) for the best fit model and the lower and upper bounds of 95% confidence intervals for all fluxes. Whole cells/spheroids or mitochondrial lysates were prepared in RIPA buffer and quantified using the BCA Protein Assay (Thermo Scientific). Proteins were separated on 4–20% SDS–PAGE gels, transferred to PVDF membranes, and probed with antibodies against IDH1 (ab94571), IDH2 (ab55271), IDH3 (ab58641) from Abcam, PDHα (#459400, Thermo), PDHα-pSer293 (AP1062), GAPDH (AB2302) from Millipore, PDK1 (#3820), Hif1α (#3716) from Cell Signaling, CTP (sc-86392), AIF (sc-13116) from Santa Cruz Biotechnology and Actin (A3853, Sigma). Day 7 H460 spheroids were cultured under normoxia (21% oxygen) or hypoxia (1% oxygen) for 16 h. The spheroids were then treated with 100 μM EF5 compound for 3 h, fixed in 4% paraformaldehyde, and embedded in OCT for frozen sectioning. 10 μm spheroid sections were stained with EF5 antibody as previously described27. Cytosolic and mitochondrial ROS levels were measured with the organelle-specific HyPer system as previously described15, 28. Briefly, trypsinized H460 cells were transfected with HyPer-cyto or HyPer-mito vectors. Half of the transfected cells were allowed to attach as a monolayer, and the other half were cultured in suspension using Ultra-Low Attachment dishes. Images were acquired 48 h after transfection, and ROS levels were calculated as the ratio of fluorescence at 488 nm and 405 nm. For monolayer respiration assays, H460 cells were plated in growth media at 3 × 104 cells per well in XF24 microplates (Seahorse Bioscience; Billerica, MA) 24 h before the assay following manufacturer’s recommendations for cell seeding. Growth media was changed to XF assay media and the plates were incubated at 37 °C in a non-CO incubator for 45 min before starting the assay. To normalize the data, the cells were trypsinized and counted by haemocytometer or ViCELL automated cell counter (Beckman Coulter). To measure respiration in spheroids, H460 Spheroids were grown for 3 days in 96-well Ultra-Low Attachment round bottom plates (Sigma; Cat# CLS7007) starting with 2 × 103 cells per well, resulting in an average spheroid diameter of 401 ± 13 μm. For the respiration assay, spheroids were transferred to a Poly-d-lysine-treated XFe96 Spheroid Microplate (Seahorse Bioscience cat# 102959-100) containing 37 °C XF assay media at pH 7.4. Following each assay, the spheroid diameter was measured using images acquired on a Cytation 3 Cell Imaging Reader (BioTek; Winooski, VT). Volume was then calculated using the equation v = 4/ πr3. To normalize the data, the cell number of each spheroid was calculated by dividing the spheroid volume by the single-cell volume (average diameter of H460 cells = 14 μm). This method of calculating spheroid cell number was independently validated in parallel cultures by digesting spheroids with trypsin and manually counting the cells with a haemocytometer. IDH1 was generated as previously described29. IDH2 was expressed in Sf 9 cells by baculovirus infection. Cells were lysed in lysis buffer (50 mM Tris, pH 7.5, 300 mM NaCl, 10% glycerol, 1% Triton) by Avestin emulsiflex C50. The supernatants were mixed with anti-Flag resin at 4 °C overnight and then eluted with addition of 100 μg ml−1 Flag peptide in lysis buffer (without Triton). The eluate was concentrated and loaded onto a Superdex 200 size exclusion column and eluted with sizing buffer (25 mM Tris, 100 mM NaCl, 1 mM DTT, pH 7.5). Fractions containing dimer were pooled and concentrated for use in kinetics. IDH activity was assessed by measuring the evolution of NADPH abundance using a coupled diaphorase/resazurin fluorescence assay30. Reactions were conducted at room temperature in 384-well Greiner black microtitre plates in a total volume of 10 μl of assay buffer. Final compound concentrations were typically varied from 5 to 100,000 nM; the isocitrate concentration was fixed at 10 μM, the NADP+ concentration was fixed at 5 μM, and IDH was fixed at 0.1 nM. Reactions were conducted in quadruplicate and run kinetically. After each addition, plates were centrifuged for 60 s to ensure complete mixing of reagents. Data were fit to the following equation to determine the IC : where y is the % of normalized enzyme activity, x is the concentration of inhibitor, and s is the Hill slope factor. No statistical methods were used to predetermine sample size. The experiments were not randomized, and the investigators were not blinded to allocation during experiments and outcome assessment. Experiments in Figs 2a, 2b, 4f, and Extended Data Figs 5d, 7d and 8e were performed twice, and all other experiments were performed 3 times or more. Variation is always indicated using standard deviation. To assess the significance of differences among cultures and conditions, a two-tailed Welch’s unequal variances t-test was used to assess the significance between two groups. For three or more groups, a one-way ANOVA followed by Dunnett’s multiple comparisons test was performed. Before applying ANOVA, we first tested whether there was homogeneity of variation among the groups (as required for ANOVA) using the Brown–Forsythe test. Where the assumption of equal variance was violated, a log transformation was applied to the data before analysis. In a few cases, when significant differences in variation among groups persisted after transformation, we used Welch’s unequal variances t-test followed by multiple-comparison correction.
Antunes H.S.,Instituto Nacional Of Cancer Inca |
Herchenhorn D.,INCA |
Small I.A.,Instituto Nacional Of Cancer Inca |
Araujo C.M.M.,INCA |
And 7 more authors.
Radiotherapy and Oncology | Year: 2013
Background Oral mucositis (OM) is a complication of chemoradiotherapy treatment of head and neck squamous cell carcinoma (HNSCC) patients with no effective therapy. This study was designed to assess the efficacy of preventive low-level laser therapy (LLLT) in reducing the incidence of grade 3-4 OM. Material and methods From June 2007 to December 2010, 94 HNSCC patients entered a prospective, randomized, double-blind, placebo-controlled phase III trial. Chemoradiotherapy consisted of conventional radiotherapy plus concurrent cisplatin every 3 weeks. A diode InGaAlP (660 nm-100 mW-1 J-4 J/cm2) was used. OM evaluation was performed by WHO and OMAS scales and quality of life by EORTC questionnaires (QLQ). Results A six-fold decrease in the incidence of grades 3-4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%). LLLT impacted the incidence of grades 3-4 OM to a relative risk ratio of 0.158 (CI 95% 0.050-0.498). After treatment QLQ-C30 showed, differences favoring LLLT in physical, emotional functioning, fatigue, and pain; while the QLQ-H&N35 showed improvements in LLLT arm for pain, swallowing, and trouble with social eating. Conclusion Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective tool for reducing the incidence of grade 3-4 OM. Efficacy data were corroborated by improvements seen in quality of life. © 2013 Elsevier Ireland Ltd. All rights reserved.
Correa S.,Laboratorio Celula Tronco CEMO |
Binato R.,Laboratorio Celula Tronco CEMO |
Du Rocher B.,Laboratorio Celula Tronco CEMO |
Ferreira G.,Laboratorio Celula Tronco CEMO |
And 5 more authors.
Epigenetics | Year: 2014
One of the potential mechanisms of imatinib mesylate (IM) resistance in chronic myeloid leukemia (CML) is increased level of P-glycoprotein (Pgp). Pgp is an efflux pump capable of activating the multidrug resistance (MDR) phenotype. The gene encoding Pgp (ABCB1) has several binding sites in its promoter region, along with CpG islands and GC boxes, involved in its epigenetic control. In our previous work, we performed a proteomic study to identify proteins involved in IM cross-resistance. Among these proteins, we identified LRPPRC as a potential regulator of ABCB1 transcription, in acute leukemia, via an invMED1 binding site in ABCB1. Interestingly, this invMED1 binding site overlaps with the GC -100 box. In this work, we investigated the potential role of LRPPRC in the regulation of ABCB1 transcriptional activity in CML resistance. In addition, we evaluated the potential connection between this regulation and the methylation status of the ABCB1 promoter in its GC -100 box. Our results show that LRPPRC binds prominently to the ABCB1 promoter in Lucena cells, an IM-resistant cell line. Luciferase assays showed that ABCB1 transcription is positively regulated by LRPPRC upon its knockdown. Pyrosequencing analysis showed that the ABCB1 promoter is differentially methylated at its GC -100 box in K562 cells compared with Lucena cells, and in CML patients with different response to IM. Chromatin immunoprecipitation and Pgp expression after DNA demethylation treatment showed that LRPPRC binding is affected by the methylation status of ABCB1 GC -100 box. Taken together, our findings indicate that LRPPRC is a transcription factor related to ABCB1 expression and highlight the importance of epigenetic regulation in CML resistance. © 2014 Landes Bioscience.
News Article | October 28, 2016
Microplastics are increasingly seen as an environmental problem of global proportions. While the focus to date has been on microplastics in the ocean and their effects on marine life, microplastics in soils have largely been overlooked. Researchers are concerned about the lack of knowledge regarding potential consequences of microplastics in agricultural landscapes from application of sewage sludge. Sewage sludge is in principle waste, but it can also represent a resource in agriculture and horticulture. Fertilizer based on sludge contains valuable nutrients, but sustainable use requires that the levels of undesirable substances in the sludge is kept under control. Waste water treatment plants receive large amounts of microplastics emitted from households, industry and surface run-off in urban areas. Most of these microplastics accumulate in the sewage sludge. Today, sludge from municipal sewage treatment plants is applied to agricultural areas as a supplement to traditional fertilizers. These applications are generally well regulated as sludge might contain hazardous substances of different sorts. Microplastics are however not currently on the regulatory agenda for the use of sludge in agriculture. The potential consequences for sustainability and food security have not been adequately analyzed. These concerns have been expressed in an article recently published in the journal Environmental Science & Technology. The researchers behind the article are Luca Nizzetto and Sindre Langaas from the Norwegian Institute for Water Research (NIVA) and Martyn Futter from the Swedish University of Agricultural Sciences (SLU) in Uppsala. "We have found figures from the Nordic countries suggesting that a large fraction of all the microplastics generated in Western societies tend to end up in the sludge in wastewater treatment plants," says Nizzetto. Via the sludge the particles are transferred to agricultural soils. The amount of sewage sludge used as fertilizer varies greatly from country to country. In Europe and North America approximately 50 % of this sludge is reused as fertilizer on average. According to Statistics Norway, about two thirds of the sludge is reused in this manner. Nizzetto et al estimates that between 110,000 and 730,000 tons of microplastics are transferred every year to agricultural soils in Europe and North America, comprehensively. This is more than the estimated total burden of microplastics currently present in ocean water. These figures are of concern since the effects of microplastics accumulating in agricultural soils are unknown. "We have very little knowledge on the effect of microplastics on soil organisms, and their impact on farm productivity and food safety is unknown." The first simulation of microplastic fate on land and rivers In an earlier study from the same authors, and researchers of Oxford University, the first mathematical model describing the dynamics of microplastics' fate in terrestrial environments and rivers was presented. Due to a lack of empirical data on microplastics emissions and concentrations in soils and the stream system, this study was conceived to provide a purely theoretical, nevertheless rigorous, assessment of microplastics circulation. The model is called INCA Microplastics, and simulations have showed a strong influence of meteorological conditions and river characteristics and flows in controlling the export of microplastics from agricultural soils and their transport to the ocean. Application of sewage sludge to soils likely represent a considerable source of microplastics to the coastal and ocean environments. Similar predictions for the transport of microplastics in rivers were independently confirmed by a follow-up study by Besseling et al. INCA Microplastics is an important tool for risk assessment and evaluating sludge management scenarios. It is the first model able to simulate microplastic applications to land, and the consequent fate of these materials in soils and surface waters. The consequences of transfers of microplastics from urban waste water to agricultural soil barely have been considered by researchers and authorities, particularly in lieu of the extended attention directed at microplastics in the ocean. "Clearly further research is needed to get an overview of the problem -- and to find solutions -- so that the growing need in the community for recycling and so-called circular economy can be safeguarded," Luca Nizzetto says.
News Article | December 21, 2016
VANCOUVER, Dec. 21, 2016 /PRNewswire/ - INCA ONE GOLD CORP. (TSX.V: IO) ("Inca One" or the "Company") is pleased to provide the following update on the Company's operations from its wholly owned subsidiary Chala One SAC ("Chala One"). The Company's 90 day ramp-up has now passed its...
News Article | November 21, 2016
VANCOUVER, Nov. 21, 2016 /PRNewswire/ - INCA ONE GOLD CORP. (TSX.V: IO) ("Inca One" or the "Company") is pleased to provide the following ramp-up update on operations from its wholly owned subsidiary Chala One SAC ("Chala One"). In the initial 31 day period from the commencement of...
Tilli T.M.,Instituto Nacional Of Cancer Inca |
Mello K.D.,Instituto Nacional Of Cancer Inca |
Ferreira L.B.,Instituto Nacional Of Cancer Inca |
Matos A.R.,Instituto Nacional Of Cancer Inca |
And 6 more authors.
Prostate | Year: 2012
BACKGROUND Alternative splicing of the osteopontin (opn, spp1) gene generates three protein splicing isoforms (OPN-SI), designated as OPNa, OPNb, and OPNc, which have demonstrated specific roles in different tumor models. This work aims to investigate the roles of each OPN-SI in prostate cancer (PCa) progression by using in vivo and in vitro functional assays. METHODS The expression levels of OPN-SI in prostate cell lines were analyzed by qRT-PCR. PC-3 was stably transfected with expression vectors containing OPNa, OPNb, and OPNc, as well as empty vector controls. PC-3 cells overexpressing each construct were analyzed for in vivo tumor growth and in relation to different aspects mimicking tumor progression, such as cell proliferation, migration, invasion, and soft agar colony formation. RESULTS OPN-SI are overexpressed in PCa as compared to non-tumoral prostate cell lines. OPNc and OPNb overexpressing cells significantly activated enhanced xenograft tumor growth and PC-3 proliferation, migration, invasion, and soft agar colony formation, as well as the expression of MMP-2, MMP-9, and VEGF. These isoforms also support sustained proliferative survival. We found that both OPNc and OPNb pro-tumorigenic roles are mainly mediated through PI3K signaling. Inhibition of this pathway by using LY294002 specifically inhibited tumor progression features evoked by OPNc and OPNb overexpression. CONCLUSIONS Our data provide evidence that both OPNc and OPNb splicing isoforms promote distinct aspects of PCa progression by inducing PI3K signaling. These data give support to strategies aiming to downregulate OPNc and OPNb expression as an approach to inhibit PCa progression. Copyright © 2012 Wiley Periodicals, Inc.
De Albuquerque A.K.A.C.,Instituto Nacional Of Cancer Inca |
De Oliveira Romano S.,INCA |
Eisenberg A.L.A.,Federal University of Fluminense
Jornal Brasileiro de Patologia e Medicina Laboratorial | Year: 2013
Introduction: Hemangioendotheliomas are locally aggressive vascular tumors with intermediate malignity and metastasis risk. The epithelioid variant, the most aggressive one, equally affects men and women at any age and it is rare in children. It occurs as a solitary tumor, which is usually painful, affecting superficial or deep soft tissues. Furthermore, it is less frequent in the liver, lung, bones, skin, lymph nodes and central nervous system. Microscopically, they present epithelioid cells with intracytoplasmic vacuoles, low mitotic activity and little or no necrosis. Additionally, its vascular nature is confirmed by immunohistochemical studies (CD31, CD34 and factor VIII). Objective, material and methods: Through search in the archives of the Pathology Division of the National Cancer Institute (Instituto Nacional de Cancer [INCA]) from 1996 to 2011, 13 cases of epithelioid hemangioendothelioma (HEE) were identified and analyzed. Results and discussion: seven cases occurred in male patients and six in female patients, mean age 42 years, ranging from 7-66. The most common locations were: soft tissue (three patients; 23%); head and neck, mediastinum, bone and lung (two patients each; 15%); liver and lymph nodes (one patient each; 8%). There was clinical follow-up of nine patients: five were alive and disease-free (one to six years after diagnosis); three out of four patients with aggressive disease progressed to death (one month to five years after diagnosis); one relapsed two years after diagnosis and is alive with disease. Conclusion: This series of 13 cases of HEE, whose diagnoses were based on morphological and/or immunohistochemical analyses, demonstrates the different patterns of clinical presentation and biologic behavior of this disease.
News Article | February 28, 2017
LONDON, UK, February 28, 2017 – Superfast rural connectivity schemes using fixed wireless broadband technology will be pivotal for alternative network providers (Altnets) hoping to win a major slice of the latest BDUK funding programme, operators were told today. Speaking as part of the Independent Network Co-operative Association (INCA) seminar “Bidding For BDUK Projects & The Better Broadband Scheme,” Dan McCarthy, Cambium Networks’ UK sales manager for the UK, Ireland and Nordics, highlighted the qualities of wireless connectivity as being particularly suitable for the UK market. Cambium Networks is a leading provider of wireless networking solutions, deployed by network operators, public and private, of all sizes around the world. “As the Government looks to meet superfast connectivity targets, fixed wireless technology will play a key role in building the networks to enable ubiquitous broadband across the country,” said McCarthy. “Altnets which utilise this technology will find themselves in a very good position to secure funding due to the many advantages wireless networks offer to operators; they are quick, simple and cost-effective to deploy and enable the high-capacity connections stipulated for Superfast coverage of 30 Mbps downlink and 6 Mbps uplink.” Despite the suitability of Fixed Wireless Access, McCarthy went on to warn operators that not all solutions are the same when it comes to being successful with BDUK bids. “When it comes to wireless solutions, it is easy to see them all as being equal but some are more equal than others,” said McCarthy. “When choosing a vendor, operators who select one offering BDUK-compliant equipment will find themselves at an advantage when applying for funding. A simple and fast migration path from Superfast broadband to ultrafast broadband, such as the one offered by our portfolio, will also stand them in good stead.” McCarthy demonstrated the sort of success such a solution can bring with a Cambium Networks customer – Quickline, which delivers fast reliable Internet connectivity to Business, Public Sector and Residential customers via an independent Fibre and Fixed Wireless Access network, alongside its partner networks. Cambium Networks provided its PMP 450 and ePMP™ Elevate solutions to boost Quickline’s networks in Yorkshire, enabling 50Mbps throughput to more than 1,000 subscribers to be connected to superfast broadband. Quickline’s Managing Director Steve Jagger said: “The expertise and experience which the Cambium Networks’ team brought to this project really helped its success. We were also very impressed by the product set, which has the advantage of simplifying deployment and has predictable, reliable NGA characteristics required for State Aid Compliance.” McCarthy also highlighted how a number of grants have recently been awarded to Altnets under the BDUK scheme. Currently, more than £100m of funding is available to suppliers able to serve rural areas with superfast broadband services, with £400m of gainshare funding from the original BDUK contracts potentially available. INCA is working with BDUK to help more Altnets take advantage of the funding, with today’s seminar part of these efforts. The second part of the event – NGA Compliance for Local Access Providers – will take place tomorrow at the De Vere Grand Connaught Rooms in London. About Cambium Networks: Cambium Networks is a leading global provider of trusted wireless solutions that connect the unconnected – People, Places and Things. Through its extensive portfolio of reliable, scalable and secure wireless narrowband and broadband platforms, Cambium Networks makes it possible for all service providers and industrial, enterprise and government network operators to build affordable, reliable, high-performance connectivity. The company currently has over six million radios deployed in thousands of demanding networks in more than 150 countries. Headquartered outside Chicago and with R&D centers in the U.S., U.K. and India, Cambium Networks sells through a range of trusted global distributors. For more information, visit www.cambiumnetworks.com and www.connectingtheunconnected.org. For more information: Dan McCarthy Sales Manager UK, Ireland and Nordics E-mail: firstname.lastname@example.org
News Article | February 24, 2017
— The Global Maca Extract Market Research Report 2017 is a professional and in-depth study on the current state of the Maca Extract industry. In a word, This report studies Maca Extract in Global market, especially in North America, Europe, China, Japan, Southeast Asia and India, focuses on top manufacturers in global market, with capacity, production, price, revenue and market share for each manufacturer. Key companies included in this research are Koken, Peruvian Nature, ZANACEUTICA, INCA HEALTH, Pebani, StandPeru, Phyto Life Sciences, Jiaherb, Pioneer Herbs, Green Life, Yuansn Biological, Bettering, Yongyuan Bio-Tech, Naturalin, Berbchem Biotech, Tengmai and Huike. Market Segment by Region, this report splits Global into several key Region, with sales, revenue, market share and growth rate of Maca Extract in these regions, from 2011 to 2022 (forecast), like North America, Europe, China, Japan, Southeast Asia and India. Firstly, Maca Extract Market On the basis of product, this report displays the production, revenue, price, market share and growth rate of each type, primarily split into White to Yellow, Light Pink to Dark Purple and Light Gray to Dark Gray. On the basis on the end users/applications, this report focuses on the status and outlook for major applications/end users, consumption (sales) , market share and growth rate of Maca Extract for each application, including Health Drugs, Healthy Foods and Nutritional Supplements. 7.1 Koken 7.1.1 Company Basic Information, Manufacturing Base, Sales Area and Its Competitors 7.1.2 Maca Extract Product Category, Application and Specification 220.127.116.11 Product A 18.104.22.168 Product B 7.1.3 Koken Maca Extract Capacity, Production, Revenue, Price and Gross Margin (2012-2017) 7.1.4 Main Business/Business Overview 7.2 Peruvian Nature 7.2.1 Company Basic Information, Manufacturing Base, Sales Area and Its Competitors 7.2.2 Maca Extract Product Category, Application and Specification 22.214.171.124 Product A 126.96.36.199 Product B 7.2.3 Peruvian Nature Maca Extract Capacity, Production, Revenue, Price and Gross Margin (2012-2017) 7.2.4 Main Business/Business Overview 7.3 ZANACEUTICA 7.3.1 Company Basic Information, Manufacturing Base, Sales Area and Its Competitors 7.3.2 Maca Extract Product Category, Application and Specification 188.8.131.52 Product A 184.108.40.206 Product B 7.3.3 ZANACEUTICA Maca Extract Capacity, Production, Revenue, Price and Gross Margin (2012-2017) 7.3.4 Main Business/Business Overview Table Production Base and Market Concentration Rate of Raw Material Figure Price Trend of Key Raw Materials Table Key Suppliers of Raw Materials Figure Manufacturing Cost Structure of Maca Extract Figure Manufacturing Process Analysis of Maca Extract Figure Maca Extract Industrial Chain Analysis Table Raw Materials Sources of Maca Extract Major Manufacturers in 2016 Table Major Buyers of Maca Extract Table Distributors/Traders List Figure Global Maca Extract Capacity, Production and Growth Rate Forecast (2017-2022) Figure Global Maca Extract Revenue and Growth Rate Forecast (2017-2022) Figure Global Maca Extract Price and Trend Forecast (2017-2022) Table Global Maca Extract Production Forecast by Region (2017-2022) Figure Global Maca Extract Production Market Share Forecast by Region (2017-2022) Table Global Maca Extract Consumption Forecast by Region (2017-2022) Figure Global Maca Extract Consumption Market Share Forecast by Region (2017-2022) Figure North America Maca Extract Production and Growth Rate Forecast (2017-2022) Figure North America Maca Extract Revenue and Growth Rate Forecast (2017-2022) Table North America Maca Extract Production, Consumption, Export and Import Forecast (2017-2022) Figure Europe Maca Extract Production and Growth Rate Forecast (2017-2022) Figure Europe Maca Extract Revenue and Growth Rate Forecast (2017-2022) Table Europe Maca Extract Production, Consumption, Export and Import Forecast (2017-2022) Figure China Maca Extract Production and Growth Rate Forecast (2017-2022) Figure China Maca Extract Revenue and Growth Rate Forecast (2017-2022) Table China Maca Extract Production, Consumption, Export and Import Forecast (2017-2022) Figure Japan Maca Extract Production and Growth Rate Forecast (2017-2022) Figure Japan Maca Extract Revenue and Growth Rate Forecast (2017-2022) Table Japan Maca Extract Production, Consumption, Export and Import Forecast (2017-2022) Figure Southeast Asia Maca Extract Production and Growth Rate Forecast (2017-2022) Figure Southeast Asia Maca Extract Revenue and Growth Rate Forecast (2017-2022) Table Southeast Asia Maca Extract Production, Consumption, Export and Import Forecast (2017-2022) Figure India Maca Extract Production and Growth Rate Forecast (2017-2022) Figure India Maca Extract Revenue and Growth Rate Forecast (2017-2022) Table India Maca Extract Production, Consumption, Export and Import Forecast (2017-2022) For more information, please visit http://www.reportsweb.com/global-maca-extract-market-research-report-2017