Prof. Iana Tsoneva, Institute of Biophysics and Biomedical Engineering, Bulg. Acad. Sci. , “Acad. G. Bonchev” Str. , bl. 21, 1113 Sofia, Bulgaria, MC member of COST Action TD 1104; Our results from participation in European network for development of electroрoration-base technologies (EP 4 Bio 2 Med) 2012 -2016, Chair of the Action – Prof. Damijan MIKLAVCIC (SI)
The kick off meeting was on –the April 9, 2012, but the first financial year starts on the 1 -st July 2012.
The project brins together 445 participants from 150 institutions from around the world (32 countries) by now. In the beginning the countries were 22
EP 4 Bio 2 Med Objectives (from Miclavcic poster) 1. To bring together and coordinate European community research in different domains of electroporation 2. To promote existing and establish new links with industrial partners and synchronise academic and industrial research 3. To optimise and further develop existing electroporation-based applications and explore new applications in biology, medicine, pharmacy and food industry 3. To provide comprehensive training for students 4. To stimulate and promote collaborative research by structuring and developing proposals for future applications of additional funding on the national and European level 5. To synthesize and disseminate new and updated knowledge on mechanisms of electroporation, new applications and technological developments
WG of COST TD 1104 in paper of D. Miclavcic, in J Membrane Biol (2012) 245: 591– 598, DOI 10. 1007/s 00232 -012 -9493 -8.
200 150 100 50 0 female ts Ph . D St ud en ES ar c es e R Gender balance: 34% group leaders are female researchers Statistics is given by D. Miclavcic R male he rs Number of participants Participants structure
www. electroporation. net Newsletter No. 17 , October 2013 During the last year, there were 8, 379 visits to the site, made by 3, 793 unique visitors.
According Prof. Roland Pochet, who is also BMBS (Biomedicine and Molecular Biosciences) domain chair , www. electroporation. net is “the best web page” and he has offered the Newsletter reporting on STSMs as an example to other chairs within the BMBS domain. (Information is from Newsletter)
What are our activities in COST action
The Project has 5 WGs WG 1, Basic Mechanisms of Electroporation and Modeling; WG 2, Food Processing and Pharmaceuticals; WG 3, Medical Applications; WG 4, Sustainable Environmental, Applications and Biomass Processing; WG 5, Technology Development and Transfer
MC members Acad. Alexander Petrov, Solid State Physics, BAS Prof. Bojidar Galutsov, Biological Faculty, Sofia
Договор на тема „Третиране на ракови клетки и солидни тумори чрез подходящ избор на електрични импулси” Д 0 02/178, финансиран от Националния Фонд за научни изследвания с кординатор проф. , д. б. н. Яна Цонева, И-т по биофизика биомедицинско инженерство, БАН приключи на 30 юни 2012 г. Title “Treatment of cancer cells and solid tumors by suitable choice of electrical pulses”, DО 02/178
The project was scientifically and biothecnologically related to a development of new approaches for electrotreatment of tumor cells and solid tumors by multidisciplinary researches 1. Institute of Biophysics and Biomedical Engineering, BAS 2. Dermatologic Clinic at Specialized Hospital for Active Treatment of Oncology, Sofia 3. Institute of Electronics, BAS
The new type electroporators Chemipulse III and Chemipulse IV were designed and constructed. In the last version three elements (electroporator, QRS synhronisator and device for patient current) were incorporated in one body. The new instrument is with battery supply, enhanced protection against electrical hazards both for patient and the physician. By using the electroporator with QRS synchronization the patients with pacemakers and heard problems can be treated also. Data collection of the pulse parameters and the impedances of treated patients with surface tumors could be used to support the optimization of the voltage shock setting and the evaluation of the procedure effectiveness. The constructed electroporators are small and portable
Electrochemotherapy of patients included in the studies are with clinically and cytologically verified diagnosis Carcinoma basocellulare, Carcinoma spinocellulare, Kaposi sarkoma and Mycosis fungoides, in stage I (T 1 N 0 M 0) and the application and study was approved by the ethics committee of the hospital and all patients gave written information consent before beginning treatment. All treatments were carried out at Dermatologic Clinic at Specialized Hospital for Active Treatment of Oncology, Sofia. The total number of successfully treated by electrochemotherapy patients with device developed during the project was 49, number of the treated lesions was 60. The majority of the lesions are at the visible places at the body and the collection of the material from the lesions for the following of the effect of therapy will lead to the scars the new method light induced spectroscopy was applied.
Dotsinsky, I. , Nikolova, B. , Peycheva, E. , Tsoneva, I. 2012, New modality for electrochemotherapy of surface tumors, Biotechnol. & Biotechnol. Eq. 26, 6, 3402 -3406. Николова, Б. , Цонева, Я. , Мудров, Н. , Пейчева, Е. 2011, Клинично приложение на електрохимиотерапията: лесен, високо ефективен и безопасен метод за третиране на кожни тумори. Онкология, 39, 3, 31 -35. 54 years old woman 1. 5 ml bleomycin and 1000 V A)before treatment, B)one week after treatment, C)one month after electrochemotherapy 82 years old woman 2 ml intralesional bleomycin and 1000 V D) before treatment, E) one week later, F) one month follows up 57 years old man 1 ml bleomycin and 900 V G) before treatment, H) 24 h after treatment- edema at the site of the treatment, I) 18 months follows up
Advantages of electrochemotherapy Electrochemotherapy after surgical operation A B C A) before treatment, B) treatment, C) one week after electrochemotherapy; Electrochemotherapy B A C A) before treatment, B) one week after treatment C) one month after electrochemotherapy;
Fundamental studies are related to the increasing the amount of the drugs into the cancer cells or tumors thus reducing toxicity in normal tissue and increasing therapeutic response. Investing the mechanisms of DNA transfer, adhesion behavior of cancer cells proliferation and invasiveness we achied higher efficiency in electricity (chemo) therapy of tumors.
Electrotreatment in the presence of antibiotic rifampicin on Ha. Cat cells (keratinocytes) Fluorescent imaging of Е-cadxerin (immunostaining) A) control, B) Ha. Cat cells, treated with 20 μg/m. L rifampicin alone, C) Ha. Cat cells, 24 h after electroporation, (D-F) Ha. Cat cells, treated with 20 μg/m. L electroporation, rifampicin -200 V, 500 V, 1000 V, Magnigication -63 x Fluorescent imaging of actin (BODIPY 558/568 phalloidinlabelled) Nikolova, B. , Kostadinova, A. , Dimitrov, B. , Zhelev, Z. , Bakalova, R. , Aoki, I. , Tsoneva, I. 2013, Fluorescent Imaging for Assessment of the Molecular Mechanisms of Combined Application of Electroporation and Rifampicin on Ha. Ca. T Cells as a New Therapeutic Approach in Psoriasis, Sensors, 13, 36253634.
1). 4 – Ph. D students from our Department visited the International course Electroporation for Medicine & Basic Knowledge, Applications and Technologies, Bucharest, Rumania, October 25 -27, 2012, financiated by COST action TD 1104 2) one Ph. D student was 3 months in Lubliana, Slovenia, Short-Term Scientific Missions (STSMs), financiated by COST action TD 1104
As a result of our work in the last 4 years the 15 papers in journals with impact factor were publeshed (2 are from bilateral work with France and Rumaniaparticipants in COST action TD 1104), 4 oral presentations and 8 posters were presented on the international congreses, 5 diploma works and 3 Ph. D thesis are defended. There is a film about Electrochemotherapy on the web pages of Institute of Biophysics and Biomedical Engineering, BAS and Dermatologic Clinic at Specialized Hospital for Active Treatment of Oncology, Sofia
Българско подзаглавие: Eлектроиндуцирано въвеждане на конвенционални лекарствени средства и транспортиращи наночастици в клетки и тумори ръководител проекта за съфинансиране - проф. дбн Яна Цонева, член на Мениджмънт комитет от ИБФБМИ, БАН Electroinduced delivery of conventional drugs and transporting nanoparticles in cells and tumors ( proposal is given on 2. 07. 2013, N 94 -14977)
1. Билатерално сътрудничество със Словения 2. Билатерално сътрудничество с Румъния 3. Билатерално сътрудничество с Украйна
Ин витро изледвания - Да се създадат условия за локално увеличение на концентрацията на конвенционални противотуморни лекарства в ракови клетки чрез електропорация. Използване на наночастици за лечение на тумори. - Да се използват възможностите на електропорацията за въвеждане на лекарства като милтефозин и еруфозин (нова група алкилфосфохолини- противотуморни и противо възпалителни агенти) в керетиноцитни клетки Ha. Ca. T (ин витро модел на псориасис). - Изучаване на механизмите на действие на електропорацията при ко-култури (соматични и неопластични клетки) – Целта е да се изясни как взаимодействат ракови и здрави клетки при ръба на тумора след електрохимиотерапия, тъй като макар и рядко рецидив на заболявнето се появява именно на това място. - Използване на 2 D и 3 D култири с оглед доближаване на условията на електропорацията на ниво тъкан.
Клинични изследвания - Да се оптимизират протоколите на електрохимиотерапия на кожни тумори и оздравителния ефект при тумори, разположени на различни места по тялото. Да се конкретизира персонализиран подход за лечение на кожни тумори. - Използване на неинвазивни физични подходи за проследяване на оздравителния процес на човешки кожни тумори.
Електроди 1. Нови електроди, съобразени с размера и локализацията на тумора и подсигурени с подходяща изолоция.
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