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Trabectedine

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https://www.readbyqxmd.com/read/28284173/patient-derived-solitary-fibrous-tumour-xenografts-predict-high-sensitivity-to-doxorubicin-dacarbazine-combination-confirmed-in-the-clinic-and-highlight-the-potential-effectiveness-of-trabectedin-or-eribulin-against-this-tumour
#1
S Stacchiotti, M Saponara, R Frapolli, M Tortoreto, D Cominetti, S Provenzano, T Negri, G P Dagrada, A Gronchi, C Colombo, B Vincenzi, G Badalamenti, V Zuco, S L Renne, P Collini, C Morosi, A P Dei Tos, E Bello, S Pilotti, P G Casali, M D'Incalci, N Zaffaroni
BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice...
March 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28274512/practical-use-and-utility-of-fluorescence-in-situ-hybridization-in-the-pathological-diagnosis-of-soft-tissue-and-bone-tumors
#2
Shintaro Sugita, Tadashi Hasegawa
During routine pathological examination, fluorescence in situ hybridization (FISH) plays a significant role in the genetic analysis of samples. FISH can detect genetic abnormalities such as chromosomal translocations, gene amplifications, and deletions in formalin-fixed, paraffin-embedded (FFPE) specimens. Due to its practical advantages, FISH is already used in many pathology laboratories. It is especially useful for the diagnosis of translocation-related sarcomas (TRSs), which comprise about 25% of soft tissue sarcomas...
March 5, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/28260930/update-on-the-role-of-trabectedin-in-the-treatment-of-intractable-soft-tissue-sarcomas
#3
REVIEW
Federica Recine, Alberto Bongiovanni, Nada Riva, Valentina Fausti, Alessandro De Vita, Laura Mercatali, Chiara Liverani, Giacomo Miserocchi, Dino Amadori, Toni Ibrahim
Soft tissue sarcomas (STS) represent a variety of tumors of mesenchymal origin, accounting for about 1% of all adult cancers. This group of tumors comprises over 60 different histotypes with different biology showing different sensitivity to therapeutic agents. For decades, the standard first-line systemic treatment of metastatic STS has comprised anthracycline based-chemotherapy. Second-line therapy options include agents such as ifosfamide, gemcitabine, and pazopanib, but the optimal sequential therapy for the management of metastatic disease has yet to be defined...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28209496/uterine-leiomyosarcoma-epidemiology-contemporary-treatment-strategies-and-the-impact-of-uterine-morcellation
#4
REVIEW
Stephanie Ricci, Rebecca L Stone, Amanda N Fader
Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma...
February 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28181940/stable-disease-in-a-patient-with-metastatic-leiomyosarcoma-treated-with-trabectedin
#5
Ketty Tavella, Alessandro Villanucci, Laura Vannini, Daniele Lavacchi, Silvia Montelatici, Gianni Amunni, Teresita Mazzei
Leiomyosarcomas represent the most common variant of uterine sarcomas, and are also considered to be the least chemosensitive. To date, adriamycin and ifosfamide are believed to be the most effective drugs for its treatment, in addition to docetaxel and gemcitabine. Recently, the introduction of trabectedin has provided clinicians with another treatment option, and the drug may have some benefits for patients as it may allow for long-term treatment. We present the case of a patient who previously failed multiple cycles of chemotherapy and who was subsequently treated with 30 cycles of trabectedin as third-line therapy for multiple metastases of uterine leiomyosarcoma...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28166781/mechanism-of-action-of-trabectedin-in-desmoplastic-small-round-cell-tumor-cells
#6
S Uboldi, I Craparotta, G Colella, E Ronchetti, L Beltrame, S Vicario, S Marchini, N Panini, G Dagrada, F Bozzi, S Pilotti, C M Galmarini, M D'Incalci, R Gatta
BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive disease, that can be described as a member of the family of small round blue cell tumors. The molecular diagnostic marker is the t(11;22)(p13;q12) translocation, which creates an aberrant transcription factor, EWS-WT1, that underlies the oncogenesis of DSRCT. Current treatments are not very effective so new active drugs are needed. Trabectedin, now used as a single agent for the treatment of soft tissue sarcoma, was reported to be active in some pre-treated DSRCT patients...
February 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28163887/central-venous-access-related-adverse-events-after-trabectedin-infusions-in-soft-tissue-sarcoma-patients-experience-and-management-in-a-nationwide-multi-center-study
#7
Michiel C Verboom, Jan Ouwerkerk, Neeltje Steeghs, Jacob Lutjeboer, J Martijn Kerst, Winette T A van der Graaf, Anna K L Reyners, Stefan Sleijfer, Hans Gelderblom
BACKGROUND: Trabectedin has shown efficacy against soft tissue sarcomas (STS) and has manageable toxicity. Trabectedin is administered through central venous access devices (VAD), such as subcutaneous ports with tunneled catheters, Hickman catheters and PICC lines. Venous access related adverse events are common, but have not yet been reported in detail. METHODS: A retrospective analysis of patient files of STS patients receiving trabectedin monotherapy between 1999 and 2014 was performed in all five STS referral centers in the Netherlands...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28140689/the-efficacy-of-trabectedin-in-treating-ovarian-cancer
#8
REVIEW
Eleonora Teplinsky, Thomas J Herzog
The majority of women with epithelial ovarian cancer present with advanced stage disease and there is a critical need for novel drugs and treatment strategies to improve outcomes. Trabectedin is a unique cytotoxic agent with a complex mechanism of action. It binds to guanines in the N2 position in the minor groove of DNA and its cytotoxicity involves DNA repair pathways and transcription regulation. Trabectedin's activity is also related to the drug-induced changes of the tumor microenvironment. It has been shown to improve progression-free survival in combination with pegylated liposomal doxorubicin in patients with platinum-sensitive relapsed ovarian cancer...
February 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28103739/newer-medical-therapies-for-metastatic-soft-tissue-sarcoma
#9
Akash Tiwari, Vineet Govinda Gupta, Sameer Bakhshi
Metastatic/advanced soft tissue sarcoma has a poor prognosis conventionally, treatment options have been limited. In recent years, this area has been a rich ground for research with many new drugs being approved and several more in the pipeline. With multiple new treatment options available, it is vital to keep up pace with this rapidly changing field. Areas covered: Recent data regarding use of novel agents in advanced soft tissue sarcoma is reviewed with a focus on clinical applicability. The goal is to guide the clinician into choosing appropriate lines of therapy for the individual patient in light of recent availability of multiple new treatment options...
March 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28101677/emesis-and-nausea-related-to-single-agent-trabectedin-in-ovarian-cancer-patients-a-sub-study-of-the-mito15-project
#10
Marilena Di Napoli, Chiara Della Pepa, Laura Arenare, Giovanni Scambia, Domenica Lorusso, Francesco Raspagliesi, Gabriella Ferrandina, Vanda Salutari, Roberto Sorio, Anna Maria Mosconi, Giorgia Mangili, Lucia Borgato, Stefano Lepori, Angela Salvino, Sandro Pignata, Sabrina Chiara Cecere
The MITO 15 was a prospective, single-arm trial, evaluating trabectedin monotherapy in patients with recurrent ovarian cancer (OC) who were BRCA mutation-carriers or had a BRCAness phenotype. It is largely reported that trabectedin may induce nausea and vomiting but the real emetogenic potential of the drug, in the different schedules, has never been fully described; furthermore, OC patients are known to have an enhanced risk of developing nausea and vomiting due to female gender, abdominal spreading of the disease, and major surgery experienced by most of them...
January 19, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28095394/loss-of-cul4a-expression-is-underlying-cisplatin-hypersensitivity-in-colorectal-carcinoma-cells-with-acquired-trabectedin-resistance
#11
B Englinger, M Mair, W Miklos, C Pirker, T Mohr, S van Schoonhoven, D Lötsch, W Körner, F Ferk, S Knasmüller, P Heffeter, B K Keppler, M Grusch, W Berger
BACKGROUND: Colorectal carcinoma (CRC) is the third most common cancer worldwide. Platinum-based anticancer compounds still constitute one mainstay of systemic CRC treatment despite limitations due to adverse effects and resistance development. Trabectedin has shown promising antitumor effects in CRC, however, again resistance development may occur. In this study, we aimed to develop strategies to circumvent or even exploit acquired trabectedin resistance in novel CRC treatment regimens...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28072764/antitumour-activity-of-trabectedin-in-myelodysplastic-myeloproliferative-neoplasms
#12
Michela Romano, Matteo Giovanni Della Porta, Anna Gallì, Nicolò Panini, Simonetta Andrea Licandro, Ezia Bello, Ilaria Craparotta, Vittorio Rosti, Elisa Bonetti, Richard Tancredi, Marianna Rossi, Laura Mannarino, Sergio Marchini, Luca Porcu, Carlos M Galmarini, Alberto Zambelli, Marco Zecca, Franco Locatelli, Mario Cazzola, Andrea Biondi, Alessandro Rambaldi, Paola Allavena, Eugenio Erba, Maurizio D'Incalci
BACKGROUND: Juvenile myelomonocytic leukaemia (JMML) and chronic myelomonocytic leukaemia (CMML) are myelodysplastic myeloproliferative (MDS/MPN) neoplasms with unfavourable prognosis and without effective chemotherapy treatment. Trabectedin is a DNA minor groove binder acting as a modulator of transcription and interfering with DNA repair mechanisms; it causes selective depletion of cells of the myelomonocytic lineage. We hypothesised that trabectedin might have an antitumour effect on MDS/MPN...
January 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27958379/a-systems-biology-approach-to-investigate-the-mechanism-of-action-of-trabectedin-in-a-model-of-myelomonocytic-leukemia
#13
L Mannarino, L Paracchini, I Craparotta, M Romano, S Marchini, R Gatta, E Erba, L Clivio, C Romualdi, M D'Incalci, L Beltrame, L Pattini
This study was designed to investigate the mode of action of trabectedin in myelomonocytic leukemia cells by applying systems biology approaches to mine gene expression profiling data and pharmacological assessment of the cellular effects. Significant enrichment was found in regulons of target genes inferred for specific transcription factors, among which MAFB was the most upregulated after treatment and was central in the transcriptional network likely to be relevant for the specific therapeutic effects of trabectedin against myelomonocytic cells...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27918201/the-importance-of-treating-by-histological-subtype-in-advanced-soft-tissue-sarcoma
#14
REVIEW
Javier Martín Broto, Axel Le Cesne, Peter Reichardt
While surgical resection (±radiotherapy) is standard treatment for localized soft tissue sarcomas (STS), chemotherapy is the mainstay for managing locally advanced and metastatic disease. Expanding knowledge of the biologies and sensitivities of STS histotypes, in conjunction with results from a growing collection of retrospective reviews and prospective randomized studies, point to the importance of treating in consideration of histological subtype. Doxorubicin ± ifosfamide continues to be standard first-line therapy for most STS subtypes...
January 2017: Future Oncology
https://www.readbyqxmd.com/read/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#15
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895579/pharmacodynamic-modeling-of-cell-cycle-effects-for-gemcitabine-and-trabectedin-combinations-in-pancreatic-cancer-cells
#16
Xin Miao, Gilbert Koch, Sihem Ait-Oudhia, Robert M Straubinger, William J Jusko
Combinations of gemcitabine and trabectedin exert modest synergistic cytotoxic effects on two pancreatic cancer cell lines. Here, systems pharmacodynamic (PD) models that integrate cellular response data and extend a prototype model framework were developed to characterize dynamic changes in cell cycle phases of cancer cell subpopulations in response to gemcitabine and trabectedin as single agents and in combination. Extensive experimental data were obtained for two pancreatic cancer cell lines (MiaPaCa-2 and BxPC-3), including cell proliferation rates over 0-120 h of drug exposure, and the fraction of cells in different cell cycle phases or apoptosis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27843394/trabectedin-followed-by-irinotecan-can-stabilize-disease-in-advanced-translocation-positive-sarcomas-with-acceptable-toxicity
#17
J Herzog, F von Klot-Heydenfeldt, S Jabar, A Ranft, C Rossig, U Dirksen, J Van den Brande, M D'Incalci, I von Luettichau, P J Grohar, W E Berdel, St Burdach
Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program...
2016: Sarcoma
https://www.readbyqxmd.com/read/27797624/factors-to-consider-and-questions-to-ask-in-the-management-of-recurrent-ovarian-cancer-a-focus-on-the-role-of-trabectedin-pegylated-liposomal-doxorubicin
#18
Antonio González-Martín, Andreas du Bois
Given the heterogeneity of both disease and clinical situation, recurrent ovarian cancer continues to be a considerable therapeutic challenge. While newer treatment options have led to improved clinical outcomes, treatment selection has become more complex. An increasing number of clinical questions must be addressed before the optimal strategy and sequence can be decided for an individual patient. Areas covered: In this review, evidence is examined to guide decision-making for the main treatment options of surgery, chemotherapy and targeted therapy...
November 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27797622/experience-with-trabectedin-pegylated-liposomal-doxorubicin-for-recurrent-platinum-sensitive-ovarian-cancer-unsuited-to-platinum-rechallenge
#19
Nicoletta Colombo, Anne-Claire Hardy-Bessard, Gabriella Ferrandina, Christian Marth, Ignacio Romero
As most patients with ovarian cancer experience multiple remissions and relapses, oncologists must prepare ahead for long-term treatment. While platinum-based regimens are standard of care for platinum-sensitive recurrence, there are circumstances in which platinum rechallenge is not the best approach. These situations include patients with limited sensitivity to platinum; patients with residual toxicity from previous platinum therapy; and patients at risk of developing hypersensitivity reactions. An alternative regimen for these patients is the non-platinum combination of trabectedin + pegylated liposomal doxorubicin (PLD)...
November 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27782906/trabectedin-in-advanced-desmoplastic-round-cell-tumors-a-retrospective-single-center-series
#20
Benjamin Verret, Charles Honore, Sarah Dumont, Philippe Terrier, Julien Adam, Andrea Cavalcanti, Isabelle Sourrouille, Guillaume Klausner, Marion Ahlenc-Gelas, Nicolas Kiavue, Gabriella Domitrescu, Lamiae El Amarti, Olivier Mir, Axel Le Cesne
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy that occurs with unpredictable chemosensitivity and limited treatment options in the advanced setting. Prognosis is poor, and exploring new treatment options for such diseases is difficult because of its rarity. Clinical activity of trabectedin for advanced DSRCT was scarcely reported in the literature. Here, we report a series of six patients treated with trabectedin for an unresectable DSRCT. After receiving trabectedin, two patients had stable disease with a time to progression of 3 and 3...
January 2017: Anti-cancer Drugs
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