Jeroen stelde me de vraag waar de bosbessen onder codenaam ECB-46 te koop zijn. Een google search laat zien dat deze bosbessen onder de code naam EBC-46 kankerpatienten geneest binnen enkele dagen van hun tumor door een injectie direct in de tumor. De googlesearch levert dit op te bestellen bij o.a. Amazon en E-bay.

Inmiddels het abstract en volledige studierapport gevonden en is hier in te zien. Zie ook onderaan dit artikel.

Het ECB-46 ios inmiddels onder de naam tigilanol tiglate (eerder ECB-46 genoemd) bij Qbiotics in onderzoek en ook verkrijgbaar dus wereldwijd. Ook de FDA heeft toestemming gegeven voor gebruik van dit op bosbessen gebaseerde medicijn, maar alleen bij honden, zie deze toestemming onder de naam STELFONTA bij de FDA.

Wel loopt er een fase II studie inmiddels met tigilanol tiglate (eerder ECB-46 genoemd) bij patiënten met weke delen sarcoma in het Memorial Sloan Kettering Cancer Center, zie dit studieprotocol: A Phase IIa open label study evaluating the preliminary efficacy of intratumoural tigilanol tiglate in advanced and/or metastatic soft tissue sarcoma of the extremities and body wall.

Als ik alles moet geloven is dit toch wel een spectaculair medicijn zonder noemenswaardige bijwerkingen en als een arts meewerkt snel en gemakkelijker te injecteren.

Zie ook verder in dit artikel

Update artikel 21 februari 2018:

Foto: De bosbessen uit Australië die kanker kunnen genezen

Op de website van Qbiotics staat onder veelgestelde vragen een uitleg waarom ECB-46, inmiddels tiginalol tiglate geheten nog steeds niet beschikbaar is voor kankerpatiënten. (Hoewel de bosbessen wel op Alibaba te koop zijn geweest.)

Het is Qbiotics gelukt om een natuurlijke stof toch te patenteren door de oprichting van Ecologic dat zegt natuurwouden te beschermen.

Als ik probeer het studie abstract van de fase I studie: Phase I Dose-Escalation Extension Study to Determine the Safety and Tolerability of Intratumoural Injection(s) of EBC-46 in te zien kan dat niet. En krijg geen informatie daarover behalve dat de studie completed is en het abstract juli 2017 is gepubliceerd. Inmiddels het abstract en volledige studierapport gevonden en is hier in te zien. Zie ook onderaan dit artikel:

Dit is toch wel beetje vreemd zeker als je dit leest:

Net als curcuma, zo schrijven de auteurs van de volgende studie lijkt het bosbessenextract ECB-48 moeilijk in een vaste dosering te maken en daardoor te patenteren begrijp ik uit een zin uit dit onderzoek: Population genetic analysis of a medicinally significant Australian rainforest tree, Fontainea picrosperma C.T. White (Euphorbiaceae): biogeographic patterns and implications for species domestication and plantation establishment

Hoewel dit onderzoek over erfelijke mutaties bij de Australische bevolking gaat is deze zin opvallend:

Laboratory synthesis of EBC-46 is unlikely to be commercially feasible and consequently production of the molecule is via isolation from F. picrosperma grown in plantations.

Waarom dan wel de fase 1 studie wel het volledige aantal patienten heeft geworven, daarover zelfs resultaten zijn gepubliceerd maar het abstract niet beschikbaar is toch wel vreemd m.i..

Zeker als je ziet welke goede resultaten met het bosbessenextract zijn gevonden. Zie hieronder en zie ook deze reviewstudie bij dieren.

26 september 2016: Bron: verschillende media

Bosbessenextract onder de code naam EBC-46 geneest kankerpatienten binnen enkele dagen van hun tumor door een injectie direct in de tumor. Dit meldden verschillende buitenlandse media afgelopen maand. Met een kort verhaal van een kankerpatiente Denise Powell, op video erbij: The Australian Berry that could cure cancer (verhaal van Denise Powell komt na de reclame video van 15 seconden)

Het extract EHC-46 is gemaakt van bosbessen die alleen in Australië / Nieuw-Zeeland groeien, aldus de nieuwsberichten. EHC-46 werkt min of meer als een versnelde vorm van immuuntherapie of misschien nog wel beter gezegd als een vorm van een operatie techniek. Zo snel werkt het.

Denise Powell vertelt aan de nieuwszender dat de tumor binnen enkele uren blauw en zwart werd en binnen enkele dagen was verdwenen. En ook niet meer is teruggekomen. Andere patiënten uit een fase I trial (sorry de link is niet meer goed en ik kan nergens andere link vinden n het Australische trialregister. hebben dezelfde ervaringen aldus de onderzoekers.

Er lopen inmiddels studies bij

Vormen van huidkanker. zowel basaal carcinomen als melanomen
Hoofd- en halstumoren
Borstkanker
Prostaatkanker
Darmkanker

Maar ongetwijfeld komen alle solide tumoren die bereikbaar zijn voor een injectie in aanmerking gezien het werkingsmechanisme.

Op de website van Qbiotics de producent van dit extract staat deze informatier:

EBC-46 & Humans

An outstanding candidate for a human anti-cancer treatment

EBC-46 is a novel natural product small molecule with anticancer activity being developed as a local treatment for solid tumours in humans and companion animals (dogs, cats and horses). EBC-46 was discovered by applying the EcoLogic™ approach to drug discovery from the tropical rainforests of Far North Queensland. EcoLogic™ was developed by QBiotics’ parent entity EcoBiotics.

QBiotics plans to develop EBC-46 as a human pharmaceutical to Clinical Phase II and then seek a development partner for final development and marketing of the drug. QBiotics has already demonstrated very compelling proof-of-concept of the drug's efficacy and safety by successfully treating advanced, spontaneous tumours in companion animals that were considered untreatable with current standards of care. As the principles behind the development of cancer in animals and humans are analogous, it is likely that EBC-46 will have similar effects in humans as in animals.

Potential indications for the drug include:

Testing EBC-46 in vitro against various cancer cell lines, in mouse models of cancer, and in companion animals with cancer, has demonstrated that the drug has broad activity against many different tumour types including:

Skin cancers, such as squamous cell carcinomas (SCC), basal cell carcinomas (BCC) and melanomas;
Head & neck cancers;
Breast cancers;
Prostate cancers; and
Colorectal cancers.

Al eerder in 2014 werden door Qbiotics resultaten bekendgemaakt van dit extract bij muizen met ook spectaculaire goede resultaten. Zie dit studieverslag uit 2014:

Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models

Zie hier het abstract van deze studie:

World-first human trials of an extract from a berry found in Australian rainforests that is thought to help cure cancer.

Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models

Glen M. Boyle ,
Marjorie M. A. D'Souza ,
Carly J. Pierce,
Ryan A. Adams,
Aaron S. Cantor,
Jenny P. Johns,
Lidia Maslovskaya,
Victoria A. Gordon,
Paul W. Reddell,
Peter G. Parsons

Published: October 1, 2014
http://dx.doi.org/10.1371/journal.pone.0108887

Abstract

Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-βI, -βII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer.

Figures

Citation: Boyle GM, D'Souza MMA, Pierce CJ, Adams RA, Cantor AS, Johns JP, et al. (2014) Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models. PLoS ONE 9(10): e108887. doi:10.1371/journal.pone.0108887

Editor: Qiming Jane Wang, University of Pittsburgh School of Medicine, United States of America

Received: March 25, 2014; Accepted: September 4, 2014; Published: October 1, 2014

Copyright: © 2014 Boyle et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

Funding: This work was supported by the National Health and Medical Research Council of Australia Development Grant, Number APP1017676 (PGP, GMB, PWR). MMAD was supported by the University of Queensland International Research Tuition Award (UQIRTA) and a University of Queensland Research Scholarship (UQIRS). GMB was supported by a Smart Futures Researcher-in-Residence fellowship from the Queensland Government, and is currently supported by the Wilson Fellowship for Skin Cancer Research administered by the Perpetual Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors of this manuscript have the following competing interests: GMB was a previous recipient of a fellowship co-sponsored by QBiotics and the Queensland State Government. PGP has received consulting payments and contract research funding from QBiotics Ltd. VAG and PWR have ownership interests (including patents) in QBiotics Ltd. and the compound. No potential conflicts of interest were disclosed by the other authors. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Intratumoral tigilanol tiglate was generally well tolerated, the maximum tolerated dose was not reached, and clinical activity was observed in 9 tumor types including complete response in four patients. These results support the continued development of tigilanol tiglate for intratumoral administration.

Research paperVolume 50p433-441December 2019Open access

Phase I dose-escalation study to determine the safety, tolerability, preliminary efficacy and pharmacokinetics of an intratumoral injection of tigilanol tiglate (EBC-46)

Benedict J. Panizzaa b.panizza@uq.edu.au ∙ Paul de Souzab ∙ Adam Cooperb ∙ Aflah Roohullahb ∙ Christos S. Karapetisc ∙ Jason D. Lickliterd

Abstract

Evidence before this study

Intratumoral injection therapy for cancer currently remains a topic of intense interest, even though current clinical research is heavily focused on immunotherapy. As of January 2019, the PubMed database lists 3671 references under the search term "intratumoral injection”. Injection of antineoplastic agents directly into a tumor not only reduces systemic exposure, minimizes off-target toxicity, and limits the total amount of drug used but also induces robust antitumor activity in the injected lesion and, potentially, in noncontiguous non-injected lesions. Tigilanol tiglate possesses antitumor activity and appears to be effective and well tolerated when injected intralesionally as an alternative to surgery for canine mast cell tumors and soft tissue sarcomas in veterinary settings. Studies in syngeneic and xenograft mouse models showed that intratumoral injection of tigilanol tiglate into subcutaneous tumors resulted in PKC-dependent hemorrhagic necrosis within 24 h, complete loss of viable tumor cells, and marked vascular disruption at 24 h after treatment.

Added value of this study

Although surgery and radiotherapy constitute the great majority of local therapies for tumors, their application and effectiveness can be limited by many factors such as the overall status of the patient, proximity and/or infiltration of tumors into adjacent tissues, tumor inaccessibility, large tumour volume, intolerance of normal tissue to repeated courses of treatment, the presence of metastases and the availability of local facilities in developing nations. As a consequence, better local therapies are still needed for a wide range of tumors to reach the expanding network of infiltrating malignant cells that can be missed by surgery, to spare nearby normal tissue that would be damaged by radiation, and to control tumors that are otherwise untreatable. This study contributes to the body of knowledge supporting the utility of intratumoral injection as a component of local anticancer therapy and specifically to the role of PKC activation in solid tumor treatment.

Implications of all the available evidence

This first-in-human, dose-escalation, clinical study of the novel small molecule tigilanol tiglate administered intratumorally to patients with a range of cutaneous, subcutaneous, or nodal tumors showed that intratumoral administration of tigilanol tiglate is generally well tolerated, a maximum tolerated dose was not declared, and there were preliminary signs of efficacy. These results support the continued development of tigilanol tiglate for intratumoral administration. Future studies could include dosing levels based on target tumor volume ranges. To elucidate further the potential clinical usefulness of intratumoral therapy generally and tigilanol tiglate particularly, longer follow-up periods (for wound healing and efficacy assessments) and volumetric dosing assessments on treatment day (baseline) instead of at screening for RECIST response evaluations should be considered.

Data sharing

QBiotics Group will make available to qualified scientific and medical researchers, upon signing a data access agreement, de-identified data that underlie the results of the study reported in this Article including text, tables, figures and appendices. Email requests for the data should be made to qbioticspublications@qbiotics.com. Provision of data will be completed without external investigator support.

Declaration of Competing Interest

BP reports consulting fees received from QBiotics for the development of future trials with EBC-46. PDS reports personal fees from BioSceptre Australia Pty Ltd, outside the submitted work. All other authors declare no competing interests.

Acknowledgments

We thank the patients and families, who participated in the Tigilanol Tiglate (EBC-46) trial. We would also like to thank all the study teams involved at the participating sites.

Funding source

QBiotics sponsored and funded the study and were involved in study design and study management support. QBiotics funded; INC Research and EMR Associates (independent project management and study monitoring) and Wolff Medical Communications (manuscript writing and editorial support). QBiotics had no input into data acquisition, data analysis, data interpretation or manuscript preparation, but assisted with minor adjustments to the final draft. All authors had access to the raw data and had final responsibility for the submitted paper.

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