10 septiembre 2006

Yondelis: Request for feedback

Yondelis: Request for feedback .

Posted by ------ on 01/20/2006, 18:52:31



My wife has recurrent liposarcoma. We've been offered to start clinical trial of Yondelis (ET-743) next week. I writing to request that anyone who has taken the drug please email me or post their experiences so far.




Re: Yondelis: Request for feedback.


Posted by ------- on 01/24/2006, 09:56:03





Hi,

I'm getting ready to start my 8th treatment with the ET-743. It is very tolerable. The first three days after treatment, I'm pretty wiped out and experience the feeling of nausea, but the anti-nausea meds keep me from actually vomiting. I feel very weak until day three, but afterwards, I'm up and running again. As long as I eat, I feel much better--but, the drug makes me feel full during the three days and I forget that I need something on my stomach. Also, I have some mild diarrhea during this period, but other than these symptoms, I find the chemo easier than others. Oh yes and the red and white blood counts drop. I get Aranesp for the red blood counts and Nuelasta for the white. Feel free to email me directly if you would like more details.

Dana Farber . G . Demetri sobre el Yondelis: Actividad clinica importante

http://www.dana-farber.org/res/physician/detail.asp?personID=50&RD=True&group=(Clinician+and+Researcher)

George D. Demetri, MD
Associate Professor of Medicine, Harvard Medical School
Contact Information
George D. Demetri, MD
Dana-Farber Cancer Institute
44 Binney Street
Shields-Warren 530
Boston, MA 02115
USA
Office phone: (617) 632-3985
Appointment phone: (617) 632-5122
Fax: (617) 632-3408

Preferred contact method: office phone

Research
Sarcomas are a microcosm of solid tumor oncology: different sarcomas are increasingly being defined by molecular signatures and biological characteristics rather than by simple histopathology. Our group is translating this research on the basic biology of sarcomas into new therapeutics directed at novel targets.

The foremost example of our team's work has been the development of tyrosine kinase inhibitors as effective therapies for patients with gastrointestinal stromal tumor (GIST). By targeting the specific molecular signals of GIST, we have validated the concept that a human solid tumor can be treated by signal transduction inhibitors. This work led to the development and FDA approval of imatinib mesylate (Gleevec) as an effective therapy for patients with metastatic or unresectable GIST, and underlies our ongoing research in other novel agents, such as the kinase inhibitor SU11248.

Another example of molecular targeting of sarcomas in drug development is our pioneering interest in differentiation therapy for patients with liposarcomas. This research targets a nuclear receptor known as PPAR-gamma, which plays a role in the normal development of fat cells, and induces differentiation in liposarcomas to decrease proliferation. Larger studies based on our pilot data are now being designed to test the clinical value of this treatment, which we are refining with newer agents and methods.

Our group also is developing other agents against sarcomas, such as the natural product known as ET-743, derived from a marine organism. This drug, which binds to the DNA minor groove, has shown important clinical activity against several subtypes of sarcomas both in the laboratory and in extensive clinical trials. We are optimizing the dosage for this agent and moving forward in collaboration with other cancer centers to test the worth of this new drug.

Our multidisciplinary research team, including dedicated representatives from surgical oncology, radiation oncology, pathology, and other clinical arenas, works closely with laboratory investigators so that we can offer promising treatments of scientific merit to patients with sarcomas of soft tissue and bone .

Yondelis , Aplidin , Kahalalide ...the development of new marine-derived anticancer agents

Adding pharmacogenomics to the development of new marine-derived anticancer agents
Jose Jimeno , Miguel Aracil and Juan Carlos Tercero

Journal of Translational Medicine 2006, 4:3 doi:10.1186/1479-5876-4-3

Published 9 January 2006



http://www.translational-medicine.com/content/pdf/1479-5876-4-3.pdf

CSIC en Blanes investiga Yondelis .

Diari de Girona 18 - 1 - 2006 .

El CSIC de Blanes investiga un medicament anticàncer que es vendrà als Estats Units

J.ALONSO, BLANES.

Un equip del Centre d´Estudis Avançats de Blanes, encapçalat per la investigadora Maria Jesús Uriz, ha col·laborat en l´elaboració d´un medicament anticancerigen anomenat Yondelis que l´empresa espanyola PharmaMar -que pertany a la multinacional Zeltia- podria comercialitzar properament als Estats Units.
El medicament té aplicacions principalment en sarcomes de teixits tous, tot i que també per càncer d´ovaris, de pròstata i de mama. El seu procés d´elaboració es remunta a l´any 1989 quan es va establir la col·laboració amb PharmaMar, que està especialitzada en la investigació de nous fàrmacs anticancerígens a partir d´organismes marins. Aleshores, el CEAB es va encarregar d´orientar l´empresa «sobre quins ambients i quins organismes eren potencialment més interessants per aquest medicament», segons explica Uriz.
Maria Jesús Uriz. La investigadora està especialitzada en invertebrats que viuen fixos al fons marí.
La investigadora està especialitzada en invertebrats que viuen fixes al fons marí. Maria Jesús Uriz va explicar, en declaracions a Ràdio Blanes, que aquests tipus d´organismes es comporten com si fossin plantes i desenvolupen substàncies per defensar-se d´altres organismes «en processos de supervivència».
Així, va apuntar que es van fer assajos de molts organismes: més d´un miler, dels quals es va fer una selecció dels que «eren potencialment interessants». Finalment, es va optar per un organisme anomenat Ecteinascidia turbinata que pertany al grup dels asidis, «uns invertebrats més propers als vertebrats», ha comentat Uriz.
Tot i que va assenyalar que l´organisme és del mateix grup que l´organisme anomenat patata de mar, la investigadora va remarcar que es tracta d´un organisme petit i que és molt abundant en zones tropicals. D´aquest, s´ha obtingut una substància (ET-743) que forma part de la molècula que compon el medicament. «Es van fer activitats prèvies en el laboratori amb cel·lules que són embrionàries i que tenen les mateixes característiques que les tumorals, és a dir, que es divideixen contínuament sense parar», va aclarir. Posteriorment, es va aplicar el medicament a malalts terminals i malalts amb possibilitats de curar-se per comprovar-ne l´efectivitat.
Uriz, que es va mostrar satisfeta per l´anunci de la possible comercialització del medicament, després de 17 anys d´investigació, va dir que la col·laboració amb l´empresa PharmaMar encara continua.

Genomica SAU presenta su Software para genotipado de HPV en Medica 2005 .

Software para genotipado de HPV de GENOMICA presente en MEDICA 2005.
3/10/2005

El software para el genotipado de Papillomavirus de Genomica se mostrará en el stand de Clondiag Chip Technologies GmbH durante la muestra Medica 2005, que se celebrará en Düsseldorf entre los días 16 y 19 de Noviembre. Dicho Software está desarrollado para su utilización en lectores ATS y sobre el programa de análisis de imágenes Iconoclust de Clondiag.

El software permite determinar, de forma exacta y precisa, los 35 genotipos principales de Papillomavirus, incluyendo co-infecciones, forma parte del producto ClinicalArrays®-HPV de GENOMICA para detección y genotipado de este tipo de virus.

Genomica SAU firma un acuerdo con la Guardia Civil .

06/01/20 06
Genómica , de Zeltia , firma un acuerdo con la Guardia Civil
La filial de Zeltia, Genómica, ha firmado con fecha de 26 de octubre de 2005 un acuerdo con la Dirección General de la Guardia Civil por el que se ha adjudicado el servicio de asistencia de realización de trabajos técnicos para la elaboración de informes sobre ADN.

Nanotecnologia . J.C.Tercero , H.H.Riesse ......

Detecting minimal traces of DNA using DNA covalently attached to superparamagnetic nanoparticles and direct PCR-ELISA.

Fuentes M, Mateo C, Rodriguez A, Casqueiro M, Tercero JC, Riese HH, Fernandez-Lafuente R, Guisan JM.

Laboratorio de Tecnologia Enzimatica, Departamento de Biocatalisis, Instituto de Catalisis y Petroleoquimica-CSIC, Campus UAM, Cantoblanco, 28049 Madrid, Spain.




A single bond covalent immobilization of aminated DNA probes on magnetic particles suitable for selective molecular hybridization of traces of DNA samples has been developed. Commercial superparamagnetic nanoparticles containing amino groups were activated by coating with a hetero-functional polymer (aldehyde-aspartic-dextran). This new immobilization procedure provides many practical advantages: (a) DNA probes are immobilized far from the support surface preventing steric hindrances; (b) the surface of the nanoparticles cannot adsorb DNA ionically; (c) DNA probes are bound via a very strong covalent bond (a secondary amine) providing very stable immobilized probes (at 100 degrees C, or in 70% formamide, or 0.1N NaOH). Due to the extreme sensitivity of this purification procedure based on DNA hybridization, the detection of hybridized products could be coupled to a PCR-ELISA direct amplification of the DNA bond to the magnetic nanoparticles. As a model system, an aminated DNA probe specific for detecting Hepatitis C Virus cDNA was immobilized according to the optimised procedure described herein. Superparamagnetic nanoparticles containing the immobilized HCV probe were able to give a positive result after PCR-ELISA detection when hybridized with 1mL of solution containing 10(-18)g/mL of HCV cDNA (two molecules of HCV cDNA). In addition, the detection of HCV cDNA was not impaired by the addition to the sample solution of 2.5 million-fold excess of non-complementary DNA. The experimental data supports the use of magnetic nanoparticles containing DNA probes immobilized by the procedure here described as a convenient and extremely sensitive procedure for purification/detection DNA/RNA from biological samples. The concentration/purification potential of the magnetic nanoparticles, its stability under a wide range of conditions, coupled to the possibility of using the particles directly in amplification by PCR greatly reinforces this methodology as a molecular diagnostic tool.

Thiocoraline .

2006 Jan 12


Deciphering the Biosynthesis Pathway of the Antitumor Thiocoraline from a Marine Actinomycete and Its Expression in Two Streptomyces Species.

Lombo F, Velasco A, Castro A, de la Calle F, Brana AF, Sanchez-Puelles JM, Mendez C, Salas JA

Departamento de Biologia Funcional e Instituto Universitario de Oncologia del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain, Fax: (+34) 985103652.

Thiocoraline is a thiodepsipeptide antitumor compound produced by two actinomycetes Micromonospora sp. ACM2-092 and Micromonospora sp. ML1, isolated from two marine invertebrates (a soft coral and a mollusc) found of the Indian Ocean coast of Mozambique. By using oligoprimers derived from nonribosomal peptide synthetase (NRPS) consensus sequences, six PCR fragments containing putative NRPS adenylation domains were amplified from the chromosome of Micromonospora sp. ML1. Insertional inactivation of each adenylation domain showed that two of them generated nonproducing mutants, thereby indicating that these domains were involved in thiocoraline biosynthesis. Sequencing of a 64.6 kbp DNA region revealed the presence of 36 complete open reading frames (ORFs) and two incomplete ones. Heterologous expression of a region of about 53 kbp, containing 26 of the ORFs, in Streptomyces albus and S. lividans led to the production of thiocoraline in these streptomycetes. Surprisingly, the identified gene cluster contains more NRPS modules than expected on the basis of the number of amino acids of thiocoraline. TioR and TioS would most probably constitute the NRPS involved in the biosynthesis of the thiocoraline backbone, according to the colinearity of the respective modules. It is proposed that two other NRPSs, TioY and TioZ, could be responsible for the biosynthesis of a small peptide molecule which could be involved in regulation of the biosynthesis of thicoraline in Micromonospora sp. ML1. In addition, a pathway is proposed for the biosynthesis of the unusual starter unit, 3-hydroxy-quinaldic acid .

NeuroPharma : PROPIEDADES BLOQUEANTES DE CANALES DE CALCIO Y

PROPIEDADES BLOQUEANTES DE CANALES DE CALCIO Y

SELECTIVIDAD DE NUEVOS COMPUESTOS MARINOS Y SUS DERIVADOS

R. Alvarez1, C. de Austria2, M. del Monte2, D. Alonso2, E. García-Palomero2, R. de Pascual1, A. Martínez2, M. Medina2 y L. Gandía1

1Instituto Teófilo Hernando, Depto. Farmacología; Fac. Medicina, U.A.M.;

2Neuropharma S.A.U., Tres Cantos, Madrid

La alteración en la homeostasia del calcio (Ca2+) es relevante en la patogénesis de enfermedades neurodegenerativas como la enfermedad de Alzheimer (EA). Los potenciales beneficios terapéuticos de estabilizar la homeostasia del Ca2+ celular mediante el uso de antagonistas del Ca2+ en seres humanos, sin embargo, no ha mostrado un efecto neuroprotector significativo. La teoría colinérgica de la EA que relaciona la disfunción colinérgica con el déficit cognitivo ha permitido desarrollar inhibidores de acetilcolinesterasa (ACE) para mejorar la función colinérgica pero con beneficios solo a nivel sintomático. Nuestro objetivo es encontrar nuevas moléculas con actividad combinada como inhibidores de ACE y bloqueantes de canales de calcio voltaje-dependientes (CCVD). Postulamos que estas propiedades combinadas pueden ser una estrategia útil para el tratamiento de la EA. Tras una criba de 1750 compuestos marinos se obtuvieron 17 moléculas con actividad neuroprotectora en células SH-SY5Y incubadas con KCl durante 24 h. Aquellos compuestos que mostraron un efecto neuroprotector se estudiaron en células SH-SY5Y cargadas con Fluo-4 para medir su efecto sobre los cambios de Ca2+ intracelular en respuesta a despolarización con KCl. Los compuestos con propiedades bloqueantes de canales de Ca2+ en células SH-SY5Y se evaluaron como bloqueantes de CCVD en células cromafines bovinas (CCB) con la técnica de patch-clamp. Los compuestos aerothionina, homoaerothionina y 11,19-dideoxifistularina aislados de la esponja Aplysina cavernicola, palinurina (Ircinia variabilis) y leucetamol B (Leucetta primigenia) bloquearon de forma parcial (15,3±1,9%; 23,9±5,5%; 13,1±2,1%; 15,2±3,7% y 24,4±3,5% a 10 μM, respectivamente) y dosis-dependiente los CCVD. En presencia de 10 μM de nifedipino, la 11,19-dideoxifistularina (10 μM) y la palinurina (10 μM) produjeron un bloqueo adicional de la IBa (5,9% y 31,3%, respectivamente) indicando un efecto (parcial y total, respectivamente) sobre los CCVD no-L. Para mejorar la posible selectividad sobre los CCVD no-L se sintetizaron los análogos estructurales, el SD-25 derivado de fistularina y el NP0427 derivado de palinurina. El bloqueo por SD- 25 fue dosis-dependiente (0,1% a 3 μM; 19% a 10 μM y 73% a 100 μM) y más potente que el producido por 11,19-dideoxifistularina. En presencia de nifedipino (10 μM) el SD-25 produjo un bloqueo adicional (30% a 10 μM) sugiriendo un efecto sobre CCVD no-L. En presencia de nifedipino y ω-ctx GVIA, el SD-25 mostró un efecto adicional (8,8%) atribuible a un bloqueo de CCVD tipo-P/Q. De forma similar, en presencia de nifedipino y agatoxina IVA se observó un bloqueo adicional (4,8%) que podría corresponder al bloqueo de CCVD tipo-N. Nuestros resultados sugieren que el análogo SD-25 posee interesantes propiedades como posible bloqueante de CCVD no-L, con un efecto parcial sobre CCVD tipo-N y tipo P/Q.

Yondelis Total Synthesis .

11 January 2006 .

Total synthesis of ecteinascidin 743.

Chen J, Chen X, Bois-Choussy M, Zhu J

Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.

A convergent total synthesis of ecteinascidin 743 is realized from five building blocks of almost equal size. It takes 23 steps from l-3-hydroxy-4-methoxy-5-methyl phenylalanol (5) with an overall yield of 3%

NeuroPharma en el Proyecto Tifanis .

http://www.celtic-initiative.org/~pub/Project-leaflets/Webquality/tifanis-lq.pdf

Abstract

Tele-Immersion is, perhaps, the most relevant new multimedia application being currently demonstrated in the US within the Internet2 initiative. It basically consists of putting two partners into contact in such a way that both of them will have the realistic feeling of being physically in front of each other, interacting in a natural way and having both the possibility of handling, in addition, 3D objects or visualizing a 3D animation embedded in their virtual environment, or having other advanced possibilities such as interacting with labs tools.

Tele-Immersion applications request a high performance from the network platform concerning QoS requirements that must be guaranteed such as low round trip delay and high bandwidth, otherwise the application rendering performance will be degraded up to unacceptable levels. The TIFANIS Project aims at providing a Tele-Immersion application prototype oriented to support two different services. One will encompass a collaborative tool, as well, oriented to the bio-engineering field where two researchers can interact with complex 3D models (protein 3D models, for instance), even following complex virtually animated process (like the unfolding of a protein molecule). The second one will provide the capability of remote handling of instruments and tools in a typical R&D environment.

Therefore, the project, in addition of dealing with the application designing process, will provide with fields trials, where users from the three application sectors, will make hands on experience with the tools and will provide with detailed feedback information of the actual use and usefulness of the tools to the project, that will enhance the final application release.

Yondelis / Xeloda ; Yondelis / Taxol .

Phase I Trials
General Eligibility Criteria:

Biopsy-proven cancer

PS < 2 with life expectancy of > 12 weeks and adequate organ function

No active brain metastasis (must have completed local therapy and be off steroids, anticonvulsants)

18 years or older, unless otherwise specified.

No chemotherapy or therapeutic radiotherapy 3-4 weeks prior to starting on study.



ET-743/Capecitabine

Mechanism: ET-473 is a natural alkaloid that inhibits gene activation by both a promoter-specific mechanism and through the transcription-dependent nucleotide excision-repair system.

Regimen: (21-day cycle) ET-743 0.4 -1.3 mg/m2 IV on Day 1; Capecitabine 800 -1000 mg/m2 PO BID on Days 2-15. Patients must have normal LFTs and a central line.

Study Status: Opened October 2002. 22 patients have been enrolled. Combination is well tolerated. A partial response was noted in a patient with cholangiocarcinoma and prolonged stabilization (> 10 mos.) in a patient with chondrosarcoma and a patient with ovarian cancer.

Potential Target Tumors: sarcoma, breast, colorectal, and ovarian cancers.


*******************************

ET-743+Paclitaxel
ET-743 is a tetrahydroisoquinoline alkaloid isolated from a natural product of marine origin (sea squirt). It binds to the minor groove of DNA producing structural abnormalities. This is a combination study of sequential intravenous administration of paclitaxel on day 1, followed by ET-743 on day 2, every 2 weeks (Consider for all solid tumors and lymphomas, particularly soft-tissue sarcomas and breast cancer)

NeuroPharma y la siguiente generacion Farmacos contra el AD .

2006 Jan 15

Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease.

Martinez A, Castro A

NeuroPharma, Avda de la Industria 52, 28760 Madrid, Spain.






Current pharmacotherapy for Alzheimer's disease involves compounds that are aimed at increasing the levels of acetylcholine in the brain by facilitating cholinergic neurotransmission through inhibition of cholinesterase. These drugs, known as acetylcholinesterase inhibitors, have been shown to improve cognition and global functions but have little impact on improving the eventual progression of the disease; however, there is evidence that other cholinesterases such as butyrylcholinesterase can play an important role in cholinergic function in the brain, and the long-suspected non-cholinergic actions of acetylcholinesterase, mainly the interference with the beta-amyloid protein cascade, have recently driven a profound revolution in cholinesterase drug research. Several disease-modifying agents are under development that target these enzymes and have hope of becoming the next generation of effective drugs in the treatment of Alzheimer's disease.