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US 20090 143280A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0143280 A1 Kristiansen (43) Pub. Date: Jun. 4, 2009 (54) ANT-CANCER COMBINATION TREATMENT Related U.S. Application Data AND KIT OF-PARTS (60) Provisional application No. 60/690,482, filed on Jun. 15, 2005, provisional application No. 60/761,743, (75) Inventor: Bjorn Kristiansen, Frederikstad filed on Jan. 25, 2006. (NO) (30) Foreign Application Priority Data Correspondence Address: Jun. 15, 2005 (DK) ........................... PA 2005 OO882 BROWDY AND NEIMARK, P.L.L.C. Jan. 25, 2006 (DK)........................... PA 2006 OO116 624 NINTH STREET, NW Publication Classification SUTE 300 (51) Int. Cl. WASHINGTON, DC 20001-5303 (US) A638/16 (2006.01) A 6LX 3L/75 (2006.01) (73) Assignee: MediMush A/S, Horsholm (DK) A6II 3L/20 (2006.01) A63L/7088 (2006.01) (21) Appl. No.: 11/917,521 A6IP35/00 (2006.01) (52) U.S. Cl. .................. 514/8: 514/54: 514/558: 514/44 (22) PCT Fled: Jun. 14, 2006 (57) ABSTRACT In one aspect the present invention relates to pharmaceutical (86) PCT NO.: PCT/DKO6/OO339 kits of parts Suitable for treating neoplastic diseases such as cancer comprising an anti-cancer medicament, a Basidi S371 (c)(1), omycete bioactive agent in Solid or liquid form, and, option (2), (4) Date: Sep. 12, 2008 ally instructions for a dosing regime. Patent Application Publication Jun. 4, 2009 Sheet 1 of 2 US 2009/O143280 A1 Fig. 1 E. coli K12 5 culture time (h) Patent Application Publication Jun. 4, 2009 Sheet 2 of 2 US 2009/O143280 A1 Fig. 2 Bioactive agent 50 -- MRC-5 --Kelly 100- --- -- MT-1 SS moto C-26. g MRC-5 -- FEMX 50 Kel FEMX O C-26 OO O. O.2 O3 0.4 O.5 mgiml US 2009/O 143280 A1 Jun. 4, 2009 ANT-CANCER COMBINATION TREATMENT or humans (Borchers et al., “Mushrooms, Tumors and Immu AND KIT OF-PARTS nity: an update'. Experimental Biology and Medicine 229: 393-406). 0001 All patent and non-patent references cited in the SUMMARY OF THE INVENTION present application are hereby incorporated by reference in their entirety. 0006. The present invention relates to a pharmaceutical kit of parts comprising TECHNICAL FIELD OF THE INVENTION 0007 a) an anti-cancer medicament, 0002 The present invention relates to pharmaceutical kits 0008 b) a Basidiomycete bioactive agent in solid or of parts Suitable for treating neoplastic diseases such as can liquid form, and, optionally C. 0009 c) instructions for a dosage regime for said kits of parts. BACKGROUND OF THE INVENTION 0010. In another aspect, the present invention relates to a method of treatment comprising the step of administering Medicinal Mushrooms said pharmaceutical kit of parts simultaneously (optionally in 0003 Mushrooms have been used for medicinal purposes a co-formulation) or sequentially according to a set dosage for centuries in many cultures. Several members of the regime. Basidiomycete mushroom class, such as for e.g. members of 0011. Another aspect of the present invention relates to the Agaricus mushroom family have been used for medicinal use of a medicament. Such as an anti-cancer medicament, and and health-related purposes. a Basidiomycete bioactive agent in Solid or liquid form in the 0004. A number of researchers have suggested anticancer, manufacture of a kit of parts for the treatment of an individual antitumour or antimutagenic properties of e.g. Agaricus in need thereof. Such as an individual Suffering from, or at risk mushrooms (Kimura, Y. In Vivo 2005, Vol 19, Iss 1, p 37-60; of Suffering from, a neoplastic disease such as cancer. Kim et al., Food Science and Biotechnology 2004, Vol 13, Iss 0012 Another aspect of the present invention relates to a 6, p. 852; Kim et al., Food Science and Biotechnology 2004, method for enhancing a therapeutic effect of an anti-cancer Vol 13, Iss 3. p 347-352; Guterrez et al., Texicology in Vitro drug, comprising co-administering (simultaneously or in any 2004, Vol 18, Iss 3. p 301-309; Ribeiro et al., Mutation order) with said anti-cancer drug (such as any of the anti Research Reviews in Mutation Research 2003, Vol 54, Iss cancer drugs described herein) a Basidiomycete bioactive 2-3, p 195.201; Pinheiro et al., Food and Chemical Toxicol agent (Such as any of the Basidiomycete bioactive agents ogy 2003, Vol. 41, Iss 11, p 1543-1550; (Inhibiting tumour described herein). growth) Lee et al., Experimental Animals 2003, Vol. 52, p 0013 Bioactive agents produced by Agaricus sp. (any 371-375; Luiz et al., Mutation research-Fundamental and basidiomycetous fungal species of the genus agaricus of the Molecular Mechanisms of Mutagenesis 2003, Vol. 528, Iss family agaricaceae and the order agaricales and the Subclass 1-2, p 75-79; Bellini et al., Texicology in Vitro 2003, Vol 17, agaricomycetidae), Schizophyllum sp. (any basidiomycetous Iss 4, p. 465-469; Ashida et al., Food Factors in Health Pro fungal species of the genus schizophyllum of the family motion and Disease Prevention 2003, Vol. 851, p. 235-248; Schizophyllaceae and the order agaricales and the Subclass (antigenotoxic effect) de Oliveira et al., Food and Chemical agaricomycetidae), Lentinus sp. (any basidiomycetous fungal Toxicology 2002, Vol. 40, Iss 12, p 1775-1780; Kuo et al., species of the genus lentinus of the family polyporaceae and Journal of Laboratory and clinical medicine 2002, Vol. 140, the order polyporales and the Subclass agaricomycetidae (L. Iss3, p 176-187: Oshiman et al., Planta Medica 2002, Vol. 68, edodes is also termed Lentinula edodes, which is placed in the lss 7, p 610-614; Meloni et al., Mutation Research Genetic family Marasmiaceae, in the order Agaricales and the Sub Toxicology and Environmental Mutagenesis 2001, Vol. 496, class agaricomycetidae)), Trametes sp. (any basidiomycetous Iss 1-2, p 5-13: Osaki et al., Yakugaku Zasshi Journal of the fungal species of the genus trametes of the family polypora Pharmaceutical Society of Japan 1994, Vol. 114, Iss 5, p ceae and the order polyporales and the Subclass agarico 342-350; Itoh et al., Japanese Journal of Pharmacology 1994, mycetidae), Ganoderma sp. (any basidiomycetous fungal Vol. 66, Iss 2, p 265-271. Ito et al., Anticancer Research species of the genus ganoderma of the family ganodermata 1997, Vol. 17, Iss 1A, p 277-284: Fujimiya et al., Cancer ceae and the order polyporales and the Subclass agarico Immunology Immunotherapy 1998, Vol. 46, Iss 3. p 147-159; mycetidae), and Grifola sp. (any basidiomycetous fungal spe Fujimiya et al., Journal of the Japanese Society for Food cies of the genus grifola of the family meripilaceae and the Science and Technology—Nippon Shokuhin Kagaku order polyporales and the Subclass agaricomycetidae) are Kogaku Kaishi 1998. Vol 45, Iss 4. p 246-252: Ebina et al., preferred in one embodiment of the present invention. Biotherapy 1998, Vol. 11, Iss 4. p 259-265; Fujimiya et al., Anticancer Research 1999, Vol. 19, Iss 1A, p 113-118; FIGURE LEGENDS Mizuno et al., Biochemistry and Molecular Biology Interna tional 1999, Vol. 47, Iss 4, p. 707-717: Takaku et al., Journal of 0014 FIG. 1: bacteriostatic effect of different dilutions Nutrition 2001, Vol. 131, Iss 5, p. 1409-1413: Ohno et al., (1:10, 1:20 and 1:40) of the bioactive agent obtained by the Biological and Pharmaceutical Bulletin 2001, Vol. 24, Iss 7, p method as described in example 1 on E. coli K12. A culture 820-828; Delmanto et al., Mutation Research—Genetic Toxi without the bioactive agent was used as control (Ref). The cology and Environmental Mutagenesis 2001, Vol. 496, Iss experiment is described in detail in Example 4. 1-2, p 15-21). 0015 FIG. 2: cancer-cell specific cytotoxicity of different 0005. There is however a surprising paucity of epidemio concentrations of LentineX—comprising an embodiment of logic and experimental studies that address the biologic the bioactive agent of the present invention—on 4 different activities of mushrooms after oral administration to animals human and mouse cancer cell lines. The MRC-5 cell line from US 2009/O 143280 A1 Jun. 4, 2009 normal human fetal lung fibroblasts was used as control. The ease. Also included are agents capable of reducing or elimi experiment is described in detail in Example 5. nating any side effect(s) that may be caused by some cancer treatmentS. DEFINITIONS 0028 Neoplasm: tissue composed of cells that grow in an 0016 Mycelium: Mass of hyphae constituting the body abnormal way. Neoplasms may be benign or malignant (thallus) of the fungus. (metastatic). Benign tumors remain localized as a discrete 0017 Agaricus sp.: A basidiomycetous fungal species of mass. A system has been devised to classify malignant tissue the genus agaricus of the family agaricaceae and the order according to the degree of malignancy, from grade 1, barely agaricales and the Subclass agaricomycetidae. malignant, to grade 4, highly malignant. One preferred neo 0018 Schizophyllum sp.: A basidiomycetous fungal spe plasm type treated is a cancer. An individual Suffering from a cies of the genus schizophyllum of the family Schizophyl neoplastic disease is defined as having at least one neoplasm. laceae and the order agaricales and the Subclass agarico mycetidae. Neoplastic diseases as used herein includes any abnormal and 00.19 Lentinus sp.: A basidiomycetous fungal species of uncontrolled cell growth (mitosis) that results in the produc the genus lentinus of the family polyporaceae and the order tion of a tumour (i.e. a neoplasm). polyporales and the Subclass agaricomycetidae. L. edodes is 0029 Kit of parts: a kit of parts as used in the present also termed Lentinula edodes, which is placed in the family invention provides the Basidiomycete bioactive agent and Marasmiaceae, in the order Agaricales and the Subclass agari anti-cancer medicament for administration in combination.
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  • Drivers of Macrofungal Composition and Distribution in Yulong Snow Mountain, Southwest China

    Drivers of Macrofungal Composition and Distribution in Yulong Snow Mountain, Southwest China

    Mycosphere 7 (6):727–740 (2016) www.mycosphere.org ISSN 2077 7019 Article Doi 10.5943/mycosphere/7/6/3 Copyright © Guizhou Academy of Agricultural Sciences Drivers of macrofungal composition and distribution in Yulong Snow Mountain, southwest China Luo X1,2,3,4,6, Karunarathna SC1,2,5, Luo YH5, Xu K7, Xu JC1,2,5, Chamyuang S3 and Mortimer PE1,2,5* 1Centre for Mountain Ecosystem Studies, Kunming Institute of Botany, Chinese Academy of Sciences, 650201, Kunming, China 2 World Agroforestry Centre, East and Central Asia Office, 132 Lanhei Road, Kunming 650201, China 3School of science, Mae Fah Luang University, Chiang Rai, 57100, Thailand 4Center of Excellence in Fungal Research, and School of Science, Mae Fah Luang University, 57100, Chiang Rai, Thailand 5Key laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China 6School of Biology and Food Engineering, Chuzhou University, Chuzhou, 239000, China 7Lijiang Alpine Botanic Garden, Lijiang, 674100, China Luo X, Karunarathna SC, Luo YH, Xu K, Xu JC, Chamyuang S, Mortimer PE 2016 – Drivers of macrofungal composition and distribution in Yulong Snow Mountain, southwest China. Mycosphere 7(6), 727–740, Doi 10.5943/mycosphere/7/6/3 Abstract Although environmental factors strongly affect the distribution of macrofungi, few studies have so far addressed this issue. Therefore, to further our understanding of how macrofungi respond to changes in the environment, we investigated the diversityand community composition of fungi based on the presence of fruiting bodies in different environments along an elevation gradient in a subalpine Pine forest at Yulong Snow Mountain in southwest China.
  • Re-Thinking the Classification of Corticioid Fungi

    Re-Thinking the Classification of Corticioid Fungi

    mycological research 111 (2007) 1040–1063 journal homepage: www.elsevier.com/locate/mycres Re-thinking the classification of corticioid fungi Karl-Henrik LARSSON Go¨teborg University, Department of Plant and Environmental Sciences, Box 461, SE 405 30 Go¨teborg, Sweden article info abstract Article history: Corticioid fungi are basidiomycetes with effused basidiomata, a smooth, merulioid or Received 30 November 2005 hydnoid hymenophore, and holobasidia. These fungi used to be classified as a single Received in revised form family, Corticiaceae, but molecular phylogenetic analyses have shown that corticioid fungi 29 June 2007 are distributed among all major clades within Agaricomycetes. There is a relative consensus Accepted 7 August 2007 concerning the higher order classification of basidiomycetes down to order. This paper Published online 16 August 2007 presents a phylogenetic classification for corticioid fungi at the family level. Fifty putative Corresponding Editor: families were identified from published phylogenies and preliminary analyses of unpub- Scott LaGreca lished sequence data. A dataset with 178 terminal taxa was compiled and subjected to phy- logenetic analyses using MP and Bayesian inference. From the analyses, 41 strongly Keywords: supported and three unsupported clades were identified. These clades are treated as fam- Agaricomycetes ilies in a Linnean hierarchical classification and each family is briefly described. Three ad- Basidiomycota ditional families not covered by the phylogenetic analyses are also included in the Molecular systematics classification. All accepted corticioid genera are either referred to one of the families or Phylogeny listed as incertae sedis. Taxonomy ª 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved. Introduction develop a downward-facing basidioma.
  • The Classification of Lower Organisms

    The Classification of Lower Organisms

    The Classification of Lower Organisms Ernst Hkinrich Haickei, in 1874 From Rolschc (1906). By permission of Macrae Smith Company. C f3 The Classification of LOWER ORGANISMS By HERBERT FAULKNER COPELAND \ PACIFIC ^.,^,kfi^..^ BOOKS PALO ALTO, CALIFORNIA Copyright 1956 by Herbert F. Copeland Library of Congress Catalog Card Number 56-7944 Published by PACIFIC BOOKS Palo Alto, California Printed and bound in the United States of America CONTENTS Chapter Page I. Introduction 1 II. An Essay on Nomenclature 6 III. Kingdom Mychota 12 Phylum Archezoa 17 Class 1. Schizophyta 18 Order 1. Schizosporea 18 Order 2. Actinomycetalea 24 Order 3. Caulobacterialea 25 Class 2. Myxoschizomycetes 27 Order 1. Myxobactralea 27 Order 2. Spirochaetalea 28 Class 3. Archiplastidea 29 Order 1. Rhodobacteria 31 Order 2. Sphaerotilalea 33 Order 3. Coccogonea 33 Order 4. Gloiophycea 33 IV. Kingdom Protoctista 37 V. Phylum Rhodophyta 40 Class 1. Bangialea 41 Order Bangiacea 41 Class 2. Heterocarpea 44 Order 1. Cryptospermea 47 Order 2. Sphaerococcoidea 47 Order 3. Gelidialea 49 Order 4. Furccllariea 50 Order 5. Coeloblastea 51 Order 6. Floridea 51 VI. Phylum Phaeophyta 53 Class 1. Heterokonta 55 Order 1. Ochromonadalea 57 Order 2. Silicoflagellata 61 Order 3. Vaucheriacea 63 Order 4. Choanoflagellata 67 Order 5. Hyphochytrialea 69 Class 2. Bacillariacea 69 Order 1. Disciformia 73 Order 2. Diatomea 74 Class 3. Oomycetes 76 Order 1. Saprolegnina 77 Order 2. Peronosporina 80 Order 3. Lagenidialea 81 Class 4. Melanophycea 82 Order 1 . Phaeozoosporea 86 Order 2. Sphacelarialea 86 Order 3. Dictyotea 86 Order 4. Sporochnoidea 87 V ly Chapter Page Orders. Cutlerialea 88 Order 6.