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5 results on '"MESH: Tetrahydroisoquinolines"'

1. A direct label-free MALDI-TOF mass spectrometry based assay for the characterization of inhibitors of protein lysine methyltransferases

Author

Gérard Bolbach, Robert H. Dodd, Emmanuelle Sachon, Olivier Pamlard, Sandra Beaupierre, Dominique Guianvarc'h, Thierry Drujon, Sandrine Sagan, Fabienne Burlina, Catherine Guillou, Karine Guitot, Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse, Interactions Moléculaires et Cellulaires (LBM-E2), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Chimie Moléculaire de Paris Centre (FR 2769), Spectrométrie de Masse et Protéomique [IBPS] (IBPS-SPM), Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Methyltransferase, Adenosine, Pyrrolidines, Histone lysine methylation, [SDV]Life Sciences [q-bio], Lysine, MESH: Sulfonamides, Drug Evaluation, Preclinical, H3K4 methylation, Biochemistry, Methylation, MESH: Tetrahydroisoquinolines, Analytical Chemistry, Chemical library, MESH: Methylation, Small Molecule Libraries, 03 medical and health sciences, Sinefungin, chemistry.chemical_compound, MESH: Small Molecule Libraries, Tetrahydroisoquinolines, Protein lysine methyltransferase, MALDI-TOF MS, Humans, Enzyme Inhibitors, chemistry.chemical_classification, Sulfonamides, MESH: Humans, MESH: Pyrrolidines, 030102 biochemistry & molecular biology, MESH: Histone-Lysine N-Methyltransferase, Enzymatic assay, Inhibitor characterization, Histone-Lysine N-Methyltransferase, MESH: Adenosine, Matrix-assisted laser desorption/ionization, 030104 developmental biology, Enzyme, MESH: Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, chemistry, MESH: Enzyme Inhibitors, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, (R)-PFI-2, MESH: Drug Evaluation, Preclinical
Abstract

International audience; Histone lysine methylation is associated with essential biological functions like transcription activation or repression, depending on the position and the degree of methylation. This post-translational modification is introduced by protein lysine methyltransferases (KMTs) which catalyze the transfer of one to three methyl groups from the methyl donor S-adenosyl-l-methionine (AdoMet) to the amino group on the side chain of lysines. The regulation of protein lysine methylation plays a primary role not only in the basic functioning of normal cells but also in various pathologies and KMT deregulation is associated with diseases including cancer. These enzymes are therefore attractive targets for the development of new antitumor agents, and there is still a need for direct methodology to screen, identify, and characterize KMT inhibitors. We report here a simple and robust in vitro assay to quantify the enzymatic methylation of KMT by MALDI-TOF mass spectrometry. Following this protocol, we can monitor the methylation events over time on a peptide substrate. We detect in the same spectrum the modified and unmodified substrates, and the ratios of both signals are used to quantify the amount of methylated substrate. We first demonstrated the validity of the assay by determining inhibition parameters of two known inhibitors of the KMT SET7/9 ((R)-PFI-2 and sinefungin). Next, based on structural comparison with these inhibitors, we selected 42 compounds from a chemical library. We applied the MALDI-TOF assay to screen their activity as inhibitors of the KMT SET7/9. This study allowed us to determine inhibition constants as well as kinetic parameters of a series of SET7/9 inhibitors and to initiate a structure activity discussion with this family of compounds. This assay is versatile and can be easily adapted to other KMT substrates and enzymes as well as automatized.

Published
2016
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2. A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas

Author

George D. Demetri, Andres Poveda, Federica Grosso, Jaap Verweij, Vicente Alfaro, Jean-Yves Blay, Patrick Schöffski, Antonio Nieto, Paolo G. Casali, Robert G. Maki, Axel Le Cesne, Pilar Lardelli, Carme Balaña, Sara Cresta, Institut Gustave Roussy (IGR), Istituto Nazionale dei Tumori di Milano, Fondazione IRCCS, Sarcoma program, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Pediatric Allergy and Pneumology Unit, Children's Hospital La Fe, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], and Medical Oncology

Subjects
Oncology, Male, Cancer Research, Pathology, Time Factors, Kaplan-Meier Estimate, MESH: Antineoplastic Agents, Alkylating, Translocation, Genetic, MESH: Tetrahydroisoquinolines, 0302 clinical medicine, Tetrahydroisoquinolines, Alveolar soft part sarcoma, MESH: Dioxoles, Trabectedin, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Sarcoma, Middle Aged, Synovial sarcoma, MESH: Translocation, Genetic, 3. Good health, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, Female, Clear-cell sarcoma, MESH: Clinical Trials, Phase II as Topic, medicine.drug, Adult, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dioxoles, Biology, Disease-Free Survival, 03 medical and health sciences, Young Adult, Clinical Trials, Phase II as Topic, Internal medicine, medicine, Humans, Doxorubicin, Survival rate, Antineoplastic Agents, Alkylating, MESH: Kaplan-Meier Estimate, 030304 developmental biology, Aged, Retrospective Studies, MESH: Adolescent, Endometrial stromal sarcoma, MESH: Humans, MESH: Time Factors, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, MESH: Sarcoma, MESH: Disease-Free Survival, MESH: Female
Abstract

International audience; AIMS: Approximately 20% of soft tissue sarcomas (STS) have subtype-specific chromosomal translocations; these generate chimeric oncoproteins which can act as abnormal transcription factors. Since trabectedin can bind to DNA and displace transcription factors, antitumour activity was explored in translocation-related sarcoma (TRS) subtypes. METHODS: The current retrospective pooled analysis includes data from 81 patients with TRS treated in 8 phase II trials. RESULTS: TRS subtypes were: synovial sarcoma (SS, n=45), myxoid-round cell liposarcoma (MRC-L-sarcoma, n=27), alveolar soft part sarcoma (ASPS, n=4), endometrial stromal sarcoma (ESS, n=3) and clear cell sarcoma (CCS, n=2). All but one patient had received prior chemotherapy (median of 2 lines). Patients received a median of 4 trabectedin cycles (range, 1-48; median dose intensity=0.40 mg/m(2)/week). Partial responses according to Response Evaluation Criteria in Solid Tumours (RECIST) occurred in 8 patients (ORR=10%; 95% CI, 4-19%): four in MRC-L-sarcoma; three in SS and one in ESS. Tumour control rate (ORR plus stable disease) was 59% (95% CI, 48-70%). Median PFS was 4.1 months (6-month PFS rate=40%). Median overall survival was 17.4 months (survival rate at 12 months=60%). Trabectedin had a manageable safety profile. CONCLUSION: Trabectedin demonstrates encouraging disease control in TRS. Since these promising results were generally noted in patients following chemotherapy, a phase III randomised trial in first-line is ongoing to compare trabectedin with doxorubicin-based chemotherapy in patients with TRS.

Published
2012
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3. A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials

Author

Robert G. Maki, Juhui James Jiao, Jean-Yves Blay, Jean-Louis Misset, A. Yovine, Antonio Nieto, Axel Le Cesne, Pilar Frontelo, Suzette Delaloge, George D. Demetri, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'Oncologie Médicale, Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sarcoma program, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Centre des maladies du sein, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), PharmaMar Medical, Pharma Mar Medical R&D, Pediatric Allergy and Pneumology Unit, Children's Hospital La Fe, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, medicine.medical_treatment, Phases of clinical research, MESH: Antineoplastic Agents, Alkylating, Rhabdomyolysis, MESH: Tetrahydroisoquinolines, MESH: Aged, 80 and over, 0302 clinical medicine, Neoplasms, Tetrahydroisoquinolines, MESH: Child, MESH: Neoplasms, MESH: Dioxoles, Pharmacology (medical), Child, Trabectedin, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Incidence (epidemiology), Alanine Transaminase, Middle Aged, 3. Good health, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Anesthesia, Vomiting, Female, medicine.symptom, medicine.drug, Adult, medicine.medical_specialty, Neutropenia, Adolescent, MESH: Neutropenia, Nausea, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dioxoles, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, Antineoplastic Agents, Alkylating, Aged, 030304 developmental biology, MESH: Adolescent, Pharmacology, Chemotherapy, MESH: Humans, business.industry, MESH: Adult, medicine.disease, MESH: Rhabdomyolysis, MESH: Male, MESH: Alanine Transaminase, business, MESH: Female
Abstract

International audience; PURPOSE: To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. METHODS: This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n = 570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n = 258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n = 304/1,198 cycles). RESULTS: The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1-59). Nausea, fatigue and vomiting were the most common trabectedin-related adverse events, reported in ≥20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients. CONCLUSION: Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time.

Published
2011
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4. Asymmetric Total Syntheses of (−)-Renieramycin M and G and (−)-Jorumycin Using Aziridine as a Lynchpin

Author

Jieping Zhu, Yan-Chao Wu, Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Stereochemistry, MESH: Molecular Structure, MESH: Porifera, Aziridines, Heterocyclic compounds Role: RCT (Reactant), and (-)-jorunnamycin A using ring opening and Pictet-Spengler reactions of nonracemic amino acid-derived aziridine building blocks as key steps), Stereoselective synthesis (stereoselective prepn. of (-)-renieramycins G and M, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, aziridines, stereoselective prepn. of (-)-renieramycins G and M, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, MESH: Tetrahydroisoquinolines, chemistry.chemical_compound, Nucleophile, Tetrahydroisoquinolines, PREP (Preparation), renieramycin G M stereoselective nonracemic prepn, jorumycin stereoselective nonracemic prepn, jorunnamycin A stereoselective nonracemic prepn, ring opening reaction amino acid derived aziridine prepn renieramycin, Pictet Spengler reaction amino acid derived aziridine prepn renieramycin, Animals, Organic chemistry, MESH: Animals, Reactivity (chemistry), Pictet-Spengler cyclocondensation reaction, Ring opening (stereoselective, Physical and Theoretical Chemistry, Molecular Structure, 010405 organic chemistry, Chemistry, Organic Chemistry, SPN (Synthetic preparation), Stereoisomerism, Aziridine, MESH: Catalysis, MESH: Stereoisomerism, Porifera, 0104 chemical sciences, 3. Good health, Renieramycin M, RACT (Reactant or reagent) (nitrogen, MESH: Aziridines, (-)-jorumycin
Abstract

Using ring opening and Pictet-Spengler reactions of nonracemic amino acid-derived aziridine building blocks as key steps, (-)-renieramycin M I [R = (Z)-MeCH:CMeCO; R = NC; R1 = H], (-)-renieramycin G I [R = (Z)-MeCH:CMeCO; RR1 = O], (-)-jorumycin I (R = MeCO; R1 = HO; R2 = H), and (-)-jorunnamycin A I (R = H; R1 = NC; R2 = H) are prepd. convergently. [on SciFinder (R)]

Published
2009
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5. ERCC5/XPG, ERCC1, and BRCA1 gene status and clinical benefit of trabectedin in patients with soft tissue sarcoma

Author

Juan Carlos Tercero, Roberta Sanfilippo, Isabelle Ray-Coquard, Antoine Italiano, Audrey Laroche, Jean-Yves Blay, Armelle Laurand, Axel Le Cesne, Binh Bui, Jean Michel Coindre, Paolo G. Casali, Jacques Robert, Ian Judson, Antonio Nieto, Philippe Pourquier, José Enrique Garzón Jimeno, Laboratory of Solid Tumors Genetics, Nice University Hospital, Virologie Structurale, Institut Pasteur [Paris], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Equipe 11, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Service d'Oncologie Médicale, Centre Léon Bérard [Lyon], Département d'oncologie médicale, Institut Bergonié - CRLCC Bordeaux, Service de Pathologie, Institut Bergonié, Children’s Hospital La Fe, Laboratoire Aimé Cotton (LAC), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Signalisation et Mecanismes Moleculaires de l'Apoptose, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Scanella, Marie-Pierre, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut Pasteur [Paris] (IP), Service d'Oncologie Médicale, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pediatric Allergy and Pneumology Unit, Children's Hospital La Fe, HEC Montréal (HEC Montréal), Validation et identification de nouvelles cibles en oncologie (VINCO), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Service d'Oncologie Médicale

Subjects
Male, Cancer Research, DNA Repair, [SDV]Life Sciences [q-bio], Genes, BRCA1, MESH: Flow Cytometry, Apoptosis, MESH: Antineoplastic Agents, Alkylating, MESH: Base Sequence, MESH: Tetrahydroisoquinolines, 0302 clinical medicine, MESH: Endonucleases, Tetrahydroisoquinolines, MESH: Dioxoles, skin and connective tissue diseases, Trabectedin, Cell Line, Transformed, MESH: Aged, MESH: DNA Repair, Recombination, Genetic, 0303 health sciences, MESH: Middle Aged, Soft tissue sarcoma, MESH: Polymorphism, Single Nucleotide, Nuclear Proteins, Sarcoma, MESH: Transcription Factors, Middle Aged, Flow Cytometry, 3. Good health, DNA-Binding Proteins, Oncology, 030220 oncology & carcinogenesis, MESH: Recombination, Genetic, Female, medicine.drug, MESH: DNA Primers, Adult, Xeroderma pigmentosum, Adolescent, DNA repair, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dioxoles, Polymorphism, Single Nucleotide, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, MESH: Cell Line, Transformed, RNA, Messenger, Antineoplastic Agents, Alkylating, 030304 developmental biology, MESH: RNA, Messenger, Aged, DNA Primers, MESH: Adolescent, MESH: Humans, Base Sequence, business.industry, MESH: Apoptosis, MESH: Adult, medicine.disease, Endonucleases, MESH: Male, MESH: Sarcoma, Cancer research, ERCC1, business, MESH: Female, MESH: Genes, BRCA1, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins, Nucleotide excision repair, Transcription Factors
Abstract

BACKGROUND: The objective of this study was to determine whether specific single nucleotide polymorphisms (SNPs) from nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways are associated with sensitivity to trabectedin in patients with soft tissue sarcoma (STS). METHODS: The authors analyzed excision repair cross-complementation group 5/xeroderma pigmentosum group G (ERCC5/XPG) (NER), excision repair cross-complementation group 1 (ERCC1) (NER), and breast cancer 1 (BRCA1) (HR) SNPs and messenger RNA expression levels in tumor specimens from 113 patients with advanced STS who were enrolled in previously published phase 2 trials or in a compassionate-use program. The 6-month progression-free rate (PFR), progression-free survival (PFS), and overall survival (OS) were analyzed according to ERCC5, ERCC1, and BRCA1 status using log-rank tests. RESULTS: High expression of the common allele (aspartic acid at codon 1104) of ERCC5, high expression of ERCC1, and BRCA1 haplotype were associated significantly with improved PFR, PFS, and OS. The ERCC1 thymine-to-cytosine (T -> C) SNP at codon 19007 and BRCA1 expression were not associated with outcome. On univariate analysis, tumor histology, favorable NER status (high expression of common ERCC5 and/or high ERCC1 expression status), and favorable BRCA1 haplotype (at least 1 triple-adenine plus guanine [AAAG] allele) were the sole variables associated significantly with PFS and OS. CONCLUSIONS: In the current study, ERCC5, ERCC1, and BRCA1 status represented a potential DNA repair signature that could be used for the prediction of clinical response to trabectedin in patients with STS. Cancer 2011;117:3445-56. (C) 2011 American Cancer Society.

Published
2011
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