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Accueil Nota Bene Cancer V2 Numéro 127 du 13 March 2012 Traitements

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Nota Bene Cancer Numéro 127 du 13 March 2012 RSS

Traitements

Traitements localisés : découverte et développement

Menée sur 160 patients atteints d'un cancer du poumon non à petites cellules de stade 1et inopérables selon l'indice de comorbidité de Charlson, cette étude évalue les résultats cliniques à moyen terme d'un traitement par cryoablation percutanée

  • Percutaneous Cryoablation for the Treatment of Medically Inoperable Stage I Non-Small Cell Lung Cancer
    PLoS ONE, Vol. 7 (3), pp. e33223, 2012 (article en libre accès)
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    Menée sur 160 patients atteints d'un cancer du poumon non à petites cellules de stade 1et inopérables selon l'indice de comorbidité de Charlson, cette étude évalue les résultats cliniques à moyen terme d'un traitement par cryoablation percutanée

    “Percutaneous Cryoablation for the Treatment of Medically Inoperable Stage I Non-Small Cell Lung Cancer”

    • Yamauchi, Yoshikane;Izumi, Yotaro;Hashimoto, Kohei;Yashiro, Hideki;Inoue, Masanori;Nakatsuka, Seishi;Goto, Taichiro;Anraku, Masaki;Ohtsuka, Takashi;Kohno, Mitsutomo;Kawamura, Masafumi;Nomori, Hiroaki

    Background : To evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer. Methodology/Principal Findings : Between January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be medically inoperable with Charlson comorbidity index of 3 or greater. Follow-up was based primarily on computed tomography. There were 22 patients with 34 tumors who underwent 25 sessions of cryoablation treatment. Complications were pneumothoraces in 7 treatments (28%, chest tube required in one treatment), and pleural effusions in 8 treatments (31%). The observation period ranged from 12–68 months, average 29±19 months, median 23 months. Local tumor progression was observed in one tumor ...


Mots clés : Poumon; Traitements (Traitements localisés : découverte et développement)

Traitements localisés : applications cliniques

Menée sur 26 851 patients atteints d'un cancer localisé et invasif de la vessie et ayant reçu un traitement conservateur, cette étude américaine évalue l'impact du taux d'utilisation d'une radiothérapie définitive sur la survie globale des patients

  • Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    Menée sur 26 851 patients atteints d'un cancer localisé et invasif de la vessie et ayant reçu un traitement conservateur, cette étude américaine évalue l'impact du taux d'utilisation d'une radiothérapie définitive sur la survie globale des patients

    “Bladder Preservation for Localized Muscle-Invasive Bladder Cancer: The Survival Impact of Local Utilization Rates of Definitive Radiotherapy”

    • Kozak, Kevin R.;Hamidi, Maryam;Manning, Matthew;Moody, John S.

    This study examines the management and outcomes of muscle-invasive bladder cancer in the United States. Patients with muscle-invasive bladder cancer diagnosed between 1988 and 2006 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified according to three mutually exclusive treatment categories based on the primary initial treatment: no local management, radiotherapy, or surgery. Overall survival was assessed with Kaplan-Meier analysis and Cox models based on multiple factors including treatment utilization patterns. The study population consisted of 26,851 patients. Age, sex, race, tumor grade, histology, and geographic location were associated with differences in treatment (all p < 0.01). Patients receiving definitive radiotherapy tended to be older and have less differentiated tumors than patients undergoing surgery (RT, median age 78 years old and 90.6% grade 3/4 tumors; surgery, median age 71 years old and 77.1% grade 3/4 ...


Mots clés : Vessie; Traitements (Traitements localisés : applications cliniques)

A partir d'une revue systématique de la littérature publiée jusqu'en janvier 2012 (389 articles, 28 études et 6 essais randomisés), cette étude évalue les résultats cliniques associés à différentes techniques chirurgicales pour traiter un cancer du rein localisé

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    A partir d'une revue systématique de la littérature publiée jusqu'en janvier 2012 (389 articles, 28 études et 6 essais randomisés), cette étude évalue les résultats cliniques associés à différentes techniques chirurgicales pour traiter un cancer du rein localisé

    “Systematic Review of Oncologic Outcomes Following Surgical Management of Localised Renal Cancer”

    • Steven, MacLennan;Mari, Imamura;Marie, C. Lapitan;Muhammad Imran, Omar;Thomas, B. L. Lam;Ana, M. Hilvano-Cabungcal;Pam, Royle;Fiona, Stewart;Graeme, MacLennan;Sara, J. MacLennan;Steven, E. Canfield;Sam, McClinton;T. R. Leyshon Griffiths;Börje, Ljungberg;James, N.;x,;Dow,;Ucan Systematic Review Reference Group;for the, E. A. U. Renal Cancer Guideline Panel n

    Context : Renal cell carcinoma (RCC) accounts for 2–3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Objective : Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1–2N0M0). Evidence acquisition : Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The main outcomes were overall survival, cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using ...


Mots clés : Rein; Traitements (Traitements localisés : applications cliniques)

A partir d'une revue de la littérature publiée entre 1991 et 2012, cet article évalue les résultats cliniques et les complications d'une cryoablation de sauvetage pour traiter un cancer de la prostate récidivant localement après une radiothérapie primaire

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    A partir d'une revue de la littérature publiée entre 1991 et 2012, cet article évalue les résultats cliniques et les complications d'une cryoablation de sauvetage pour traiter un cancer de la prostate récidivant localement après une radiothérapie primaire

    “Salvage Cryoablation for Locally Recurrent Prostate Cancer Following Primary Radiotherapy”

    • Vladimir, Mouraviev;Philippe, E. Spiess;J. Stephen Jones

    Context : The purpose of this paper is to review current salvage cryoablation (SCA) outcomes in patients with locally recurrent prostate cancer (PCa) following primary radiation therapy. Objective : The objectives of this review are (1) to analyze the eligibility criteria for careful patient selection for these salvage modalities and (2) to evaluate the oncologic results and reported complication rates for these respective modalities. Evidence acquisition : A Medline/PubMed literature search was performed of peer-reviewed scientific articles published from 1991 to 2012 regarding salvage therapy for radiorecurrent PCa. The following search terms and various permutations were used: radiorecurrent prostate cancer, local salvage treatment, salvage radical prostatectomy, salvage cryoablation, salvage brachytherapy, and salvage high-intensity focused ultrasound. Only articles written in English were included. Evidence synthesis : SCA is a feasible and efficacious treatment modality, ...


Mots clés : Prostate; Traitements (Traitements localisés : applications cliniques)

Mené sur 25 patients atteints d'un carcinome épidermoïde de l'œsophage (durée médiane de suivi : 48 mois), cet essai de phase II évalue, du point de vue de la réponse complète et de la survie globale à 3 ans, l'efficacité et la toxicité d'une photothérapie dynamique de sauvetage pour traiter des lésions locales après l'échec d'une chimioradiothérapie

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    Mené sur 25 patients atteints d'un carcinome épidermoïde de l'œsophage (durée médiane de suivi : 48 mois), cet essai de phase II évalue, du point de vue de la réponse complète et de la survie globale à 3 ans, l'efficacité et la toxicité d'une photothérapie dynamique de sauvetage pour traiter des lésions locales après l'échec d'une chimioradiothérapie

    “Photodynamic therapy as salvage treatment for local failure after chemoradiotherapy in patients with esophageal squamous cell carcinoma: A phase II study”

    • Yano, Tomonori;Muto, Manabu;Minashi, Keiko;Iwasaki, Junko;Kojima, Takashi;Fuse, Nozomu;Doi, Toshihiko;Kaneko, Kazuhiro;Ohtsu, Atsushi

    Local failure at the primary site is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC). Salvage surgery is the only treatment option with curative intent, but it is associated with high morbidity and mortality. The aim of this study was to evaluate the efficacy and safety of salvage photodynamic therapy (PDT) after CRT. Patients with histologically proven local failure limited to the submucosal layer, and without any metastasis after definitive CRT (≥50 Gy) for ESCC were enrolled in the study. PDT began with intravenous administration of 2 mg/kg of porfimer sodium followed 48–72 hr later by excimer dye laser irradiation with a fluence of 75 J/cm2. The primary endpoint was a complete response (CR) to treatment with PDT, and the secondary endpoints were toxicity related to PDT, progression-free survival (PFS) and overall survival (OS). Twenty-five patients were enrolled in the study. A CR was attained in 19 of 25 patients ...


Mots clés : Oesophage; Traitements (Traitements localisés : applications cliniques)

Menée sur 13 patients atteints d'un lymphome hodgkinien médiastinal, cette étude compare l'impact dosimétrique d'une protonthérapie, d'une radiothérapie conformationnelle tridimensionnelle et d'une radiothérapie avec modulation d'intensité sur les différentes composantes du système cardiaque

  • Effective Dose Reduction to Cardiac Structures Using Protons Compared with 3DCRT and IMRT in Mediastinal Hodgkin Lymphoma
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    Menée sur 13 patients atteints d'un lymphome hodgkinien médiastinal, cette étude compare l'impact dosimétrique d'une protonthérapie, d'une radiothérapie conformationnelle tridimensionnelle et d'une radiothérapie avec modulation d'intensité sur les différentes composantes du système cardiaque

    “Effective Dose Reduction to Cardiac Structures Using Protons Compared with 3DCRT and IMRT in Mediastinal Hodgkin Lymphoma”

    • Hoppe, Bradford S.;Flampouri, Stella;Su, Zhong;Latif, Naeem;Dang, Nam H.;Lynch, James;Joyce, Michael;Sandler, Eric;Li, Zuofeng;Mendenhall, Nancy P.

    We investigated the dosimetric impact of proton therapy (PT) on various cardiac subunits in patients with Hodgkin lymphoma (HL). From June 2009 through December 2010, 13 patients were enrolled on an institutional review board-approved protocol for consolidative involved-node radiotherapy (INRT) for HL. Three separate treatment plans were developed prospectively by using three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT. Cardiac subunits were retrospectively contoured on the 11 patients with intravenous-contrast simulation scans, and the doses were calculated for all treatment plans. A Wilcoxon paired test was performed to evaluate the statistical significance (p < 0.05) of 3DCRT and IMRT compared with PT. The mean heart doses were 21 Gy, 12 Gy, and 8 Gy (relative biologic effectiveness [RBE]) with 3DCRT, IMRT, and PT, respectively. Compared with 3DCRT and IMRT, PT reduced the mean doses to the left and right atria; the left and right ...


Mots clés : Lymphome; Traitements (Traitements localisés : applications cliniques)

Traitements systémiques : découverte et développement

Menée in vitro et in vivo, cette étude analyse l'intérêt d'un traitement combinant le lapatinib et un composé appelé INK-128 dans le cancer du sein réfractaire au trastuzumab

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    Menée in vitro et in vivo, cette étude analyse l'intérêt d'un traitement combinant le lapatinib et un composé appelé INK-128 dans le cancer du sein réfractaire au trastuzumab

    “Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy”

    • Garcia, Celina;Ibrahim, Yasir H;Serra, Violeta;Calvo, Maria Teresa;Guzman, Marta;Grueso, Judit;Aura, Claudia;Perez, Jose;Jessen, Katti A;Liu, Yi;Rommel, Christian;Tabernero, Josep;Baselga, Jose;Scaltriti, Maurizio

    Purpose: The PI3K/Akt/mTOR pathway is an attractive target in HER2 positive breast cancer that is refractory to anti-HER2 therapy. The hypothesis is that suppression of this pathway results in sensitization to anti-HER2 agents. However, this combinatorial strategy has not been comprehensively tested in models of trastuzumab and lapatinib resistance. Experimental Design: We analyzed in vitro cell viability and induction of apoptosis in five different cell lines resistant to trastuzumab and lapatinib. Inhibition of HER2/HER3 phosphorylation, PI3K/Akt/mTOR and ERK signaling pathways was evaluated by western blot. Tumor growth inhibition following treatment with lapatinib, INK-128 or the combination of both agents was evaluated in three different animal models: two cell-based xenograft models refractory to both trastuzumab and lapatinib, and a xenograft derived from a patient who relapsed on trastuzumab-based therapy. Results: The addition of lapatinib to INK-128 prevented both HER2 and ...


Mots clés : Sein; Traitements (Traitements systémiques : découverte et développement)

Menée sur 84 patients atteints d'un cancer métastatique du poumon non à petites cellules, cette étude analyse la présence d'une réponse immunitaire spontanée à une chimiothérapie

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    Menée sur 84 patients atteints d'un cancer métastatique du poumon non à petites cellules, cette étude analyse la présence d'une réponse immunitaire spontanée à une chimiothérapie

    “Analysis of spontaneous tumor-specific CD4 T cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response”

    • Godet, Yann;Fabre-Guillevin, Elizabeth;Dosset, Magalie;Lamuraglia, Michele;Levionnois, Emeline;Ravel, Patrice;Benhamouda, Nadine;Cazes, Aurelie;Le Pimpec-Barthes, Francoise;Gaugler, Beatrice -;Langlade-Demoyen, Pierre;Pivot, Xavier;Saas, Philippe;Maillere, Bernard;Tartour, Eric;Borg, Christophe;ADOTEVI, Olivier

    Purpose:To investigate the presence and impact of spontaneous telomerase-specific CD4 T cell responses in cancer patients. Experimental Design:A multi-step approach was used to design novel pan-HLA-DR-restricted peptides from telomerase. T cell clones isolated from cancer patient were used to characterize the polarization of telomerase-specific CD4 response. The presence of spontaneous CD4 T cell response against telomerase was monitored in 84 metastatic non-small cell lung cancer (NSCLC) patients prior first line chemotherapy using IFN-gamma ELISPOT assay. Then we analyzed the impact of the pretherapeutic telomerase-specific CD4 T immunity on clinical outcome in patients according to their respective response to chemotherapy. Results:We described four novel telomerase-derived CD4 epitopes referred as universal cancer peptides (UCP) that effectively bind to most commonly found human MHC class II alleles. UCP-specific CD4 T cell repertoire is present in human and UCP-specific CD4 T ...


Mots clés : Poumon; Traitements (Traitements systémiques : découverte et développement)

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale de nanoparticules, sur lesquelles ont été fixées le peptide OA02, pour le traitement d'un cancer de l'ovaire

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    Menée in vitro et in vivo, cette étude évalue l'activité antitumorale de nanoparticules, sur lesquelles ont été fixées le peptide OA02, pour le traitement d'un cancer de l'ovaire

    “"OA02" Peptide Facilitates the Precise Targeting of Paclitaxel-Loaded Micellar Nanoparticles to Ovarian Cancer In Vivo”

    • Xiao, Kai;Li, Yuanpei;Lee, Joyce S.;Gonik, Abby M.;Dong, Tiffany;Fung, Gabriel;Sanchez, Eduardo;Xing, Li;Cheng, R. Holland;Luo, Juntao;Lam, Kit S.

    Micellar nanoparticles (NPs) based on linear polyethylene glycol (PEG)-block-dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. The micellar NPs have been decorated with a high-affinity "OA02" peptide against alpha-3 integrin receptor to improve the tumor targeting specificity which is overexpressed on the surface of ovarian cancer cells. "Click chemistry" was used to conjugate alkyne-containing OA02 peptide to the azide group at the distal terminus of the PEG chain in a representative PEG5k-CA8 telodendrimer (micelle forming unit). The conjugation of OA02 peptide had negligible influence on the physicochemical properties of PEG5k-CA8 NPs and as hypothesized, OA02 peptide dramatically enhanced the uptake efficiency of PEG5k-CA8 NPs in SKOV-3 and ES-2 ovarian cancer cells via receptor-mediated endocytosis, but not in alpha-3 integrin negative K562 leukemia cells. When loaded with ...


Mots clés : Ovaire; Traitements (Traitements systémiques : découverte et développement)

Menée sur 20 patients atteints d'un mélanome métastatique, cette étude met en évidence un mécanisme de résistance au vémurafenib

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    Menée sur 20 patients atteints d'un mélanome métastatique, cette étude met en évidence un mécanisme de résistance au vémurafenib

    “Melanoma whole-exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance”

    • Shi, Hubing;Moriceau, Gatien;Kong, Xiangju;Lee, Mi-Kyung;Lee, Hane;Koya, Richard C.;Ng, Charles;Chodon, Thinle;Scolyer, Richard A.;Dahlman, Kimberly B.;Sosman, Jeffrey A.;Kefford, Richard F.;Long, Georgina V.;Nelson, Stanley F.;Ribas, Antoni;Lo, Roger S.

    The development of acquired drug resistance hampers the long-term success of B-RAF inhibitor therapy for melanoma patients. Here we show V600EB-RAF copy-number gain as a mechanism of acquired B-RAF inhibitor resistance in 4 out of 20 (20%) patients treated with B-RAF inhibitor. In cell lines, V600EB-RAF overexpression and knockdown conferred B-RAF inhibitor resistance and sensitivity, respectively. In V600EB-RAF amplification-driven (versus mutant N-RAS-driven) B-RAF inhibitor resistance, extracellular signal-regulated kinase reactivation is saturable, with higher doses of vemurafenib down-regulating phosho-extracellular signal-regulated kinase and re-sensitizing melanoma cells to B-RAF inhibitor. These two mechanisms of extracellular signal-regulated kinase reactivation are sensitive to the MEK1/2 inhibitor AZD6244/selumetinib or its combination with the B-RAF inhibitor vemurafenib. In contrast to mutant N-RAS-mediated V600EB-RAF bypass, which is sensitive to C-RAF knockdown, ...


Mots clés : Mélanome; Traitements (Traitements systémiques : découverte et développement)

Menée sur un modèle murin, cette étude suggère que l'inhibition de l'enzyme LSD1 pourrait, en combinaison avec un traitement à l'acide tout-trans-rétinoïque, être utile pour le traitement d'une forme de leucémie promyélocytaire aiguë

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    Menée sur un modèle murin, cette étude suggère que l'inhibition de l'enzyme LSD1 pourrait, en combinaison avec un traitement à l'acide tout-trans-rétinoïque, être utile pour le traitement d'une forme de leucémie promyélocytaire aiguë

    “Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia”

    • Schenk, Tino;Chen, Weihsu Claire;Gollner, Stefanie;Howell, Louise;Jin, Liqing;Hebestreit, Katja;Klein, Hans-Ulrich;Popescu, Andreea C.;Burnett, Alan;Mills, Ken;Casero, Robert A.;Marton, Laurence;Woster, Patrick;Minden, Mark D.;Dugas, Martin;Wang, Jean C. Y.;Dick, John E.;Muller-Tidow, Carsten;Petrie, Kevin;Zelent, Arthur

    Acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML), characterized by the t(15;17)-associated PML-RARA fusion, has been successfully treated with therapy utilizing all-trans-retinoic acid (ATRA) to differentiate leukemic blasts. However, among patients with non-APL AML, ATRA-based treatment has not been effective. Here we show that, through epigenetic reprogramming, inhibitors of lysine-specific demethylase 1 (LSD1, also called KDM1A), including tranylcypromine (TCP), unlocked the ATRA-driven therapeutic response in non-APL AML. LSD1 inhibition did not lead to a large-scale increase in histone 3 Lys4 dimethylation (H3K4me2) across the genome, but it did increase H3K4me2 and expression of myeloid-differentiation–associated genes. Notably, treatment with ATRA plus TCP markedly diminished the engraftment of primary human AML cells in vivo in nonobese diabetic (NOD)-severe combined immunodeficient (SCID) mice, suggesting that ATRA in ...


Mots clés : Leucémie; Traitements (Traitements systémiques : découverte et développement)

Menée sur 54 patients atteints d'un lymphome cutané à cellules T réfractaire ou récidivant, cette étude évalue l'efficacité et la toxicité de diverses doses de pralatrexate

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    Menée sur 54 patients atteints d'un lymphome cutané à cellules T réfractaire ou récidivant, cette étude évalue l'efficacité et la toxicité de diverses doses de pralatrexate

    “Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL)”

    • Horwitz, Steven M.;Kim, Youn H.;Foss, Francine;Zain, Jasmine M.;Myskowski, Patricia L.;Lechowicz, Mary Jo;Fisher, David C.;Shustov, Andrei R.;Bartlett, Nancy L.;Delioukina, Maria L.;Koutsoukos, Tony;Saunders, Michael E.;O'Connor, Owen A.;Duvic, Madeleine

    Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after ≥1 prior systemic therapy. The starting dose and schedule was 30 mg/m2/week intravenously for 3/4 weeks. Subsequent starting doses were 20, 15, 10 mg/m2/week for 3/4 or 2/3 weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m2/week for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated ...


Mots clés : Leucémie; Traitements (Traitements systémiques : découverte et développement)

Menée sur des lignées cellulaires de carcinome hépatocellulaire et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'une petite molécule, appelée FQI1, inhibant le facteur de transcription LSF

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    Menée sur des lignées cellulaires de carcinome hépatocellulaire et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale d'une petite molécule, appelée FQI1, inhibant le facteur de transcription LSF

    “Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma”

    • Grant, Trevor J.;Bishop, Joshua A.;Christadore, Lisa M.;Barot, Girish;Chin, Hang Gyeong;Woodson, Sarah;Kavouris, John;Siddiq, Ayesha;Gredler, Rachel;Shen, Xue-Ning;Sherman, Jennifer;Meehan, Tracy;Fitzgerald, Kevin;Pradhan, Sriharsa;Briggs, Laura A.;Andrews, William H.;Sarkar, Devanand;Schaus, Scott E.;Hansen, Ulla

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the prevalence of HCC, there is no effective, systemic treatment. The transcription factor LSF is a promising protein target for chemotherapy; it is highly expressed in HCC patient samples and cell lines, and promotes oncogenesis in rodent xenograft models of HCC. Here, we identify small molecules that effectively inhibit LSF cellular activity. The lead compound, factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity both in vitro, as determined by electrophoretic mobility shift assays, and in cells, as determined by ChIP. Consistent with such inhibition, FQI1 eliminates transcriptional stimulation of LSF-dependent reporter constructs. FQI1 also exhibits antiproliferative activity in multiple cell lines. In LSF-overexpressing cells, including HCC cells, cell death is rapidly induced; however, primary or immortalized hepatocytes are unaffected by treatment with FQI1. The highly ...


Mots clés : Foie; Traitements (Traitements systémiques : découverte et développement)

Cette étude compare les effets de la doxorubicine, ainsi que du cisplatine, sur le microenvironnement tumoral dans des modèles tri- et bi-dimensionnels de cancer de l'endomètre

  • The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer
    Journal of Translational Medicine, Vol. 10 (1), pp. 38, 2012 (article en libre accès)
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    Cette étude compare les effets de la doxorubicine, ainsi que du cisplatine, sur le microenvironnement tumoral dans des modèles tri- et bi-dimensionnels de cancer de l'endomètre

    “The resistance of intracellular mediators to doxorubicin and cisplatin are distinct in 3D and 2D endometrial cancer”

    • Chitcholtan, Kenny;Sykes, Peter;Evans, John

    BACKGROUND:Advanced endometrial cancer often shows resistance to clinical chemotherapy although potencies of anticancer drugs in vitro are promising. The disparity suggests that in vivo microenvironments are not recapitulated by in vitro models used for preclinical testing. However, spheroids replicate some important properties of tumours in vivo. Therefore, for the first time, we compared effects of doxorubicin and cisplatin on 3D multicellular structures and 2D cell monolayers of endometrial cancer cells.METHODS:3D multicellular structures were generated by culturing cancer cells on non-adherent surfaces; and for comparison cell monolayers were cultured on adherent culture plates. Ishikawa, RL95-2, and KLE cell lines were studied. Morphologies of 3D multicellular structures were examined. After 48 hours treatment with anticancer drugs, apoptosis, proliferation, glucose metabolism and vascular endothelial growth factor (VEGF) were analysed. Immunostaining of PCNA, Glut-1, p-Erk1/2, ...


Mots clés : Corps de l'utérus; Traitements (Traitements systémiques : découverte et développement)

Menée in vitro et in vivo, cette étude évalue l'intérêt d'un antagoniste du récepteur CXCR2, en combinaison avec l'oxaliplatine, pour le traitement d'un cancer colorectal

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    Menée in vitro et in vivo, cette étude évalue l'intérêt d'un antagoniste du récepteur CXCR2, en combinaison avec l'oxaliplatine, pour le traitement d'un cancer colorectal

    “The CXCR2 antagonist, SCH-527123, demonstrates antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models”

    • Ning, Yan;LaBonte, Melissa J;Zhang, Wu;Bohanes, Pierre;Gerger, Armin;Yang, Dongyun;Benhaim, Leonor;Paez, David;Rosenberg, David O;Nagulapalli Venkata, Kalyan C;Louie, Stan G;Petasis, Nicos A;Ladner, Robert D;Lenz, Heinz-Josef D.

    Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States. Recent studies showed that interleukin-8 (IL-8) and its receptors (CXCR1 and CXCR2) are significantly upregulated in both the tumor and its microenvironment, and act as key regulators of proliferation, angiogenesis and metastasis. Our previous study demonstrated that IL-8 overexpression in CRC cells triggers the upregulation of the CXCR2-mediated proliferative pathway. The aim of this study was to investigate if the CXCR2 antagonist, SCH-527123, inhibits CRC proliferation and if it can sensitize CRC cells to oxaliplatin both in vitro and in vivo. SCH-527123 demonstrated concentration dependent anti-proliferative effects in HCT116, Caco2 and their respective IL-8 overexpressing variants CRC cell lines. Moreover, SCH-527123 was able to suppress CXCR2 mediated signal transduction as demonstrated through decreased phosphorylation of the NFkappaB/MAPK/AKT pathway. These findings ...


Mots clés : Colon-rectum; Traitements (Traitements systémiques : découverte et développement)

Menée sur des cellules de levure, des lignées cellulaires de divers types de cancer et des modèles murins de neuroblastome, cette étude évalue l'intérêt de plusieurs cycles de jeûne pour augmenter l'efficacité d'une chimiothérapie

  • Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy
    Science Translational Medicine, Vol. 4 (124), pp. 124ra27, 2012 (résumé)
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    Menée sur des cellules de levure, des lignées cellulaires de divers types de cancer et des modèles murins de neuroblastome, cette étude évalue l'intérêt de plusieurs cycles de jeûne pour augmenter l'efficacité d'une chimiothérapie

    “Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy”

    • Lee, Changhan;Raffaghello, Lizzia;Brandhorst, Sebastian;Safdie, Fernando M.;Bianchi, Giovanna;Martin-Montalvo, Alejandro;Pistoia, Vito;Wei, Min;Hwang, Saewon;Merlino, Annalisa;Emionite, Laura;de Cabo, Rafael;Longo, Valter D.

    Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs—but not either treatment alone—resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles ...


  • Impersonalized Medicine
    Science Translational Medicine, Vol. 4 (124), pp. 124ps6, 2012 (commentaire)
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    Menée sur des cellules de levure, des lignées cellulaires de divers types de cancer et des modèles murins de neuroblastome, cette étude évalue l'intérêt de plusieurs cycles de jeûne pour augmenter l'efficacité d'une chimiothérapie

    “Impersonalized Medicine”

    • Scrable, Heidi

    Research reported in this issue of Science Translational Medicine illustrates the benefits of short-term food withdrawal (fasting) in the treatment of cancer. Fasting exploited fundamental differences in the way tumor cells and normal cells respond to stress, simultaneously strengthening normal cell function and weakening tumor cell survival in the presence of toxic doses of chemotherapeutic drugs.


Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Cet article passe en revue les travaux récents sur le développement de petites molécules pour le traitement des cancers

  • Discovery of small molecule cancer drugs: Successes, challenges and opportunities
    Molecular Oncology, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le développement de petites molécules pour le traitement des cancers

    “Discovery of small molecule cancer drugs: Successes, challenges and opportunities”

    • Hoelder, Swen;Clarke, Paul A.;Workman, Paul

    The discovery and development of small molecule cancer drugs has been revolutionised over the last decade. Most notably, we have moved from a one-size-fits-all approach that emphasized cytotoxic chemotherapy to a personalised medicine strategy that focuses on the discovery and development of molecularly targeted drugs that exploit the particular genetic addictions, dependencies and vulnerabilities of cancer cells. These exploitable characteristics are increasingly being revealed by our expanding understanding of the abnormal biology and genetics of cancer cells, accelerated by cancer genome sequencing and other high-throughput genome-wide campaigns, including functional screens using RNA interference. In this review we provide an overview of contemporary approaches to the discovery of small molecule cancer drugs, highlighting successes, current challenges and future opportunities. We focus in particular on four key steps: Target validation and selection; chemical hit and lead ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Menée in vitro, cette étude suggère qu'un traitement inhibiteur de la voie ERK pourrait permettre de surmonter l'apparition d'une résistance à un traitement inhibiteur de la voie MEK

  • ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors
    Molecular Cancer Therapeutics, sous presse, 2012 (résumé)
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    Menée in vitro, cette étude suggère qu'un traitement inhibiteur de la voie ERK pourrait permettre de surmonter l'apparition d'une résistance à un traitement inhibiteur de la voie MEK

    “ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors”

    • Hatzivassiliou, Georgia;Liu, Bonnie;O'Brien, Carol;Spoerke, Jill M.;Hoeflich, Klaus P.;Haverty, Peter M.;Soriano, Robert;Forrest, William F.;Heldens, Sherry;Chen, Huifen;Toy, Karen;Ha, Connie;Zhou, Wei;Song, Kyung;Friedman, Lori S;Amler, Lukas C;Hampton, Garret M.;Moffat, John;Belvin, Marcia;Lackner, Mark R.

    The RAS/RAF/MEK pathway is activated in over 30% of human cancers, most commonly via mutation in the K-ras oncogene but also via mutations in BRAF. Several allosteric MEK inhibitors, aimed at treating tumors with RAS/RAF pathway alterations, are in clinical development. However, acquired resistance to these inhibitors has been documented both in preclinical and clinical samples. To identify strategies to overcome this resistance, we have derived three independent MEK inhibitor-resistant cell lines. Resistance to allosteric MEK inhibitors in these cell lines was consistently linked to acquired mutations in the allosteric binding pocket of MEK. In one cell line, concurrent amplification of mutant K-ras was observed in conjunction with MEK allosteric pocket mutations. Clonal analysis showed both resistance mechanisms occur in the same cell and contribute to enhanced resistance. Importantly, in all cases the MEK resistant cell lines retained their addiction to the MAPK pathway, as ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Cet article passe en revue les perspectives offertes par le ciblage du métabolisme tumoral pour le traitement des cancers

  • Tumor metabolism as modulator of immune response and tumor progression
    Seminars in Cancer Biology, sous presse, 2012 (résumé)
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    Cet article passe en revue les perspectives offertes par le ciblage du métabolisme tumoral pour le traitement des cancers

    “Tumor metabolism as modulator of immune response and tumor progression”

    • Gottfried, Eva;Kreutz, Marina;Mackensen, Andreas

    About a century ago Otto Warburg observed that tumor cells exhibited increased glycolysis despite the presence of oxygen and stated this metabolic shift to glycolysis as the origin of cancer cell. In the meantime it has become clear, that the altered glucose metabolism is only one piece of the tumor metabolome puzzle. In addition, amino acid, lipid and adenosine metabolism are adapted to fulfill the tumors needs for energy and generation of building blocks such as lipids and nucleotides for new cell structures. The altered tumor metabolism leads to accumulation of specific metabolites in the tumor environment and creates a favorable milieu for tumor growth, progression and metastasis. These tumor-derived metabolites are important players in immune escape mechanisms beside other known factors such as cytokines, chemokines and growth factors. A variety of metabolites re-educate immune cells and prevent an effective immune response against tumor cells. Furthermore, tumor infiltrating ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : découverte et développement)

Traitements systémiques : applications cliniques

Menée sur 732 patientes atteintes d'un carcinome canalaire in situ, cette étude évalue l'association entre le statut des récepteurs hormonaux et le risque de cancer du sein après un traitement au tamoxifène (durée médiane de suivi : 14,5 ans)

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    Menée sur 732 patientes atteintes d'un carcinome canalaire in situ, cette étude évalue l'association entre le statut des récepteurs hormonaux et le risque de cancer du sein après un traitement au tamoxifène (durée médiane de suivi : 14,5 ans)

    “Adjuvant Tamoxifen Reduces Subsequent Breast Cancer in Women With Estrogen Receptor–Positive Ductal Carcinoma in Situ: A Study Based on NSABP Protocol B-24”

    • Allred, D. Craig;Anderson, Stewart J.;Paik, Soonmyung;Wickerham, D. Lawrence;Nagtegaal, Iris D.;Swain, Sandra M.;Mamounas, Elefetherios P.;Julian, Thomas B.;Geyer, Charles E.;Costantino, Joseph P.;Land, Stephanie R.;Wolmark, Norman

    Purpose The NSABP (National Surgical Adjuvant Breast and Bowel Project) B-24 study demonstrated significant benefit with adjuvant tamoxifen in patients with ductal carcinoma in situ (DCIS) after lumpectomy and radiation. Patients were enrolled without knowledge of hormone receptor status. The current study retrospectively evaluated the relationship between receptors and response to tamoxifen.Patients and Methods Estrogen (ER) and progesterone receptors (PgR) were evaluated in 732 patients with DCIS (41% of original study population). An experienced central laboratory determined receptor status in all patient cases with available paraffin blocks (n = 449) by immunohistochemistry (IHC) using comprehensively validated assays. Results for additional patients (n = 283) determined by various methods (primarily IHC) were available from enrolling institutions. Combined results were evaluated for benefit of tamoxifen by receptor status at 10 years and overall follow-up (median, 14.5 ...


  • Refining the Use of Endocrine Therapy for Ductal Carcinoma In Situ
    Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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    Menée sur 732 patientes atteintes d'un carcinome canalaire in situ, cette étude évalue l'association entre le statut des récepteurs hormonaux et le risque de cancer du sein après un traitement au tamoxifène (durée médiane de suivi : 14,5 ans)

    “Refining the Use of Endocrine Therapy for Ductal Carcinoma In Situ”

    • Morrow, Monica


Mots clés : Sein; Traitements (Traitements systémiques : applications cliniques)

Menée sur 29 patients atteintes d'un cancer du sein HER2+ ayant progressé après un traitement au trastuzumab, cette étude évalue l'efficacité et la toxicité du pertuzumab en monothérapie, avec ou sans réintroduction ultérieure du trastuzumab

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    Menée sur 29 patients atteintes d'un cancer du sein HER2+ ayant progressé après un traitement au trastuzumab, cette étude évalue l'efficacité et la toxicité du pertuzumab en monothérapie, avec ou sans réintroduction ultérieure du trastuzumab

    “Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer”

    • Cortés, Javier;Fumoleau, Pierre;Bianchi, Giulia Valeria;Petrella, Teresa M.;Gelmon, Karen;Pivot, Xavier;Verma, Shailendra;Albanell, Joan;Conte, Pierfranco;Lluch, Ana;Salvagni, Stefania;Servent, Veronique;Gianni, Luca;Scaltriti, Maurizio;Ross, Graham A.;Dixon, Joanna;Szado, Tania;Baselga, José

    Purpose The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) –positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy.Patients and Methods Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of ...


  • Doubling Down on Human Epidermal Growth Factor Receptor 2
    Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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    Menée sur 29 patients atteintes d'un cancer du sein HER2+ ayant progressé après un traitement au trastuzumab, cette étude évalue l'efficacité et la toxicité du pertuzumab en monothérapie, avec ou sans réintroduction ultérieure du trastuzumab

    “Doubling Down on Human Epidermal Growth Factor Receptor 2”

    • Krop, Ian


Mots clés : Sein; Traitements (Traitements systémiques : applications cliniques)

Cet article passe en revue les travaux récents sur les essais de phase II ou III évaluant des vaccins thérapeutiques pour le traitement des cancers

  • Therapeutic Cancer Vaccines: Current Status and Moving Forward
    Journal of the National Cancer Institute, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur les essais de phase II ou III évaluant des vaccins thérapeutiques pour le traitement des cancers

    “Therapeutic Cancer Vaccines: Current Status and Moving Forward”

    • Schlom, Jeffrey

    Concurrent with US Food and Drug Administration (FDA) approval of the first therapeutic cancer vaccine, a wide spectrum of other cancer vaccine platforms that target a diverse range of tumor-associated antigens is currently being evaluated in randomized phase II and phase III trials. The profound influence of the tumor microenvironment and other immunosuppressive entities, however, can limit the effectiveness of these vaccines. Numerous strategies are currently being evaluated both preclinically and clinically to counteract these immunosuppressive entities, including the combined use of vaccines with immune checkpoint inhibitors, certain chemotherapeutics, small-molecule targeted therapies, and radiation. The potential influence of the appropriate patient population and clinical trial endpoint in vaccine therapy studies is discussed, as well as the potential importance of biomarkers in future directions of this field.


  • The Challenges of Cancer Vaccines
    Journal of the National Cancer Institute, sous presse, 2012 (communiqué de presse)
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    Cet article passe en revue les travaux récents sur les essais de phase II ou III évaluant des vaccins thérapeutiques pour le traitement des cancers

    “The Challenges of Cancer Vaccines”


Mots clés : Cancer (général); Traitements (Traitements systémiques : applications cliniques)

A partir de données portant sur 373 patients présentant des métastases osseuses et ayant reçu régulièrement du denosumab pendant 3 ans, cette étude évalue différents dosages et durées du cycle d'administration du traitement

  • Denosumab Dose Selection for Patients with Bone Metastases from Solid Tumors
    Clinical Cancer Research, sous presse, 2012 (résumé)
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    A partir de données portant sur 373 patients présentant des métastases osseuses et ayant reçu régulièrement du denosumab pendant 3 ans, cette étude évalue différents dosages et durées du cycle d'administration du traitement

    “Denosumab Dose Selection for Patients with Bone Metastases from Solid Tumors”

    • Doshi, Sameer;Sutjandra, Liviawati;Zheng, Jenny;Sohn, Winnie;Peterson, Mark;Jang, Graham;Chow, Andrew T;Perez-Ruixo, Juan Jose

    Purpose: Quantitatively characterize the longitudinal dose-exposure-response (urinary N-telopeptide normalized to urinary creatinine [uNTx/Cr] suppression) relationship for denosumab in patients with bone metastases from solid tumors. Experimental Design: Data from 373 patients, who received denosumab as single or multiple subcutaneous doses ranging from 30 to 180 mg (0.01 to 3 mg/kg) and administered every 4 or 12 weeks (Q4W, Q12W) for up to 3 years were used in this analysis. An inhibitory sigmoid IMax model was used to characterize the time course of uNTx/Cr as a function of serum denosumab concentrations and the M3 method was used to analyze the 52% of uNTx/Cr below the limit of quantification in the context of a mixed-effects model. Age, weight, sex, race and cancer type were evaluated as potential covariates. Model-based simulations were undertaken to explore and predict the role of denosumab dose and regimen on uNTx/Cr suppression. Results: The typical value (between-subject ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : applications cliniques)

Cet article passe en revue les travaux récents ayant évalué les effets des agents stimulant l'érythropoïèse sur la progression du cancer chez les patients sous chimiothérapie

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    Cet article passe en revue les travaux récents ayant évalué les effets des agents stimulant l'érythropoïèse sur la progression du cancer chez les patients sous chimiothérapie

    “Effects of erythropoietin receptors and erythropoiesis-stimulating agents on disease progression in cancer”

    • Aapro, M.;Jelkmann, W.;Constantinescu, S. N.;Leyland-Jones, B.

    Erythropoiesis-stimulating agents (ESAs) increase red blood cell (RBC) production in bone marrow by activating the erythropoietin receptor (EpoR) on erythrocytic-progenitor cells. Erythropoiesis-stimulating agents are approved in the United States and Europe for treating anaemia in cancer patients receiving chemotherapy based on randomised, placebo-controlled trials showing that ESAs reduce RBC transfusions. Erythropoiesis-stimulating agent-safety issues include thromboembolic events and concerns regarding whether ESAs increase disease progression and/or mortality in cancer patients. Several trials have reported an association between ESA use and increased disease progression and/or mortality, whereas other trials in the same tumour types have not provided similar findings. This review thoroughly examines available evidence regarding whether ESAs affect disease progression. Both clinical-trial data on ESAs and disease progression, and preclinical data on how ESAs could affect tumour ...


Mots clés : Cancer (général); Traitements (Traitements systémiques : applications cliniques)

Combinaison de traitements localisés et systémiques

Menée sur des lignées cellulaires de méduloblastome et à l'aide d'échantillons tumoraux, cette étude montre que l'inhibition de l'enzyme "Polo-like kinase 1" supprime la croissance tumorale et augmente la sensibilité des cellules cancéreuses aux rayonnements ionisants

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    Menée sur des lignées cellulaires de méduloblastome et à l'aide d'échantillons tumoraux, cette étude montre que l'inhibition de l'enzyme "Polo-like kinase 1" supprime la croissance tumorale et augmente la sensibilité des cellules cancéreuses aux rayonnements ionisants

    “Polo-like kinase 1 (PLK1) inhibition suppresses cell growth and enhances radiation sensitivity in medulloblastoma cells”

    • Harris, Peter;Venkataraman, Sujatha;Alimova, Irina;Birks, Diane;Donson, Andrew;Knipstein, Jeffrey;Dubuc, Adrian;Taylor, Michael;Handler, Michael;Foreman, Nicholas;Vibhakar, Rajeev

    BACKGROUND : Medulloblastoma is the most common malignant brain tumor in children and remains a therapeutic challenge due to its significant therapy-related morbidity. Polo-like kinase 1 (PLK1) is highly expressed in many cancers and regulates critical steps in mitotic progression. Recent studies suggest that targeting PLK1 with small molecule inhibitors is a promising approach to tumor therapy. METHODS : We examined the expression of PLK1 mRNA in medulloblastoma tumor samples using microarray analysis. The impact of PLK1 on cell proliferation was evaluated by depleting expression with RNA interference (RNAi) or by inhibiting function with the small molecule inhibitor BI 2536. Colony formation studies were performed to examine the impact of BI 2536 on medulloblastoma cell radiosensitivity. In addition, the impact of depleting PLK1 mRNA on tumor-initiating cells was evaluated using tumor sphere assays. RESULTS : Analysis of gene expression in two independent cohorts revealed that PLK1 ...


Mots clés : Système nerveux central; Traitements (Combinaison de traitements localisés et systémiques)

Menée sur 36 patients atteints d'un cancer localisé de la prostate (durée médiane de suivi : 76, 79 ou 98 mois selon les groupes), cette étude évalue l'efficacité et la toxicité d'un traitement combinant une radiothérapie externe avec un vaccin à base de poxvirus et d'interleukine 2

  • Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy
    Prostate Cancer and Prostatic Diseases, sous presse, 2012 (résumé)
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    Menée sur 36 patients atteints d'un cancer localisé de la prostate (durée médiane de suivi : 76, 79 ou 98 mois selon les groupes), cette étude évalue l'efficacité et la toxicité d'un traitement combinant une radiothérapie externe avec un vaccin à base de poxvirus et d'interleukine 2

    “Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy”

    • Kamrava, M.;Kesarwala, A. H.;Madan, R. A.;Lita, E.;Kaushal, A.;Tsang, K. Y.;Poole, D. J.;Steinberg, S. M.;Ferrara, T.;Dahut, W.;Schlom, J.;Gulley, J. L.

    Background : Vaccine therapy in combination with radiation therapy may improve distant and/or local control in prostate cancer. We present long-term follow-up data on the secondary and exploratory endpoints of safety and biochemical failure, respectively, from patients with clinically localized prostate cancer treated definitively with a poxviral vector-based therapeutic vaccine combined with external beam radiation therapy (EBRT). Methods : Thirty-six prostate cancer patients received definitive EBRT plus vaccine. A total of 18 patients were treated with adjuvant standard-dose interleukin-2 (S-IL-2) (4 MIU m–2) and 18 were treated with very low-dose IL-2 (M-IL-2) (0.6 MIU m–2). Seven patients were treated with EBRT alone. Twenty-six patients treated with EBRT plus vaccine returned for follow-up, and we reviewed the most recent labs and clinical notes of the remaining patients. Results : Median follow-up for the S-IL-2, M-IL-2 and EBRT-alone groups was 98, 76 and 79 ...


Mots clés : Prostate; Traitements (Combinaison de traitements localisés et systémiques)

Menée sur 1 900 patients atteints d'un cancer de la prostate traité par prostatectomie (durée médiane de suivi : 5,4 ans), cette étude rétrospective montre qu'une radiothérapie de sauvetage combinée à un traitement anti-androgénique concomitant peut améliorer les résultats biochimiques chez les patients dont le niveau urinaire de l'antigène prostatique spécifique augmente après l'intervention chirurgicale

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    Menée sur 1 900 patients atteints d'un cancer de la prostate traité par prostatectomie (durée médiane de suivi : 5,4 ans), cette étude rétrospective montre qu'une radiothérapie de sauvetage combinée à un traitement anti-androgénique concomitant peut améliorer les résultats biochimiques chez les patients dont le niveau urinaire de l'antigène prostatique spécifique augmente après l'intervention chirurgicale

    “Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA”

    • Jang, Joanne W.;Hwang, Wei-Ting;Guzzo, Thomas J.;Wein, Alan J.;Haas, Naomi B.;Both, Stefan;Vapiwala, Neha

    The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. We retrospectively reviewed the medical records from more than 1,900 post-prostatectomy patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. ...


Mots clés : Prostate; Traitements (Combinaison de traitements localisés et systémiques)

Menée sur 99 patientes atteintes d'un lymphome de Hodgkin, cette étude rétrospective évalue l'impact de différentes approches thérapeutiques, combinant ou non une radiothérapie avec une chimiothérapie, sur l'issue de la grossesse démarrée après les traitements

  • Impact of Different Treatment Approaches on Pregnancy Outcomes in 99 Women Treated for Hodgkin Lymphoma
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    Menée sur 99 patientes atteintes d'un lymphome de Hodgkin, cette étude rétrospective évalue l'impact de différentes approches thérapeutiques, combinant ou non une radiothérapie avec une chimiothérapie, sur l'issue de la grossesse démarrée après les traitements

    “Impact of Different Treatment Approaches on Pregnancy Outcomes in 99 Women Treated for Hodgkin Lymphoma”

    • De Sanctis, Vitaliana;Filippone, Francesco Romeo;Alfò, Marco;Muni, Roberta;Cavalieri, Elena;Pulsoni, Alessandro;Annechini, Giorgia;Valeriani, Maurizio;Osti, Mattia Falchetto;Minniti, Giuseppe;Enrici, Riccardo Maurizi

    The aim of this study was to evaluate the pregnancy outcomes in women with Hodgkin lymphoma (HL) diagnosis, treated between 1972 and 1999 at Department of Radiotherapy and Hematology of University “Sapienza” of Roma. We retrospectively studied 99 female patients that conceived after treatment for HL. Fifty-nine (59%) were treated with chemotherapy and radiotherapy, 32 (32%) with radiotherapy alone as supradiaphragmatic or as infradiaphragmatic and 8 (8%) patients with chemotherapy alone. Ninety-nine patients reported 145 pregnancies. We observed 132 deliveries (2 of them twin births) after a median of 55 months (range, 14–278 months) from the end of therapy. Twelve women (12%) experienced 13 miscarriages after a median of 50 months (range, 13–120) from the end of therapy. We recorded 9/132 (7%) premature births and 3/134 babies (2%) were underweight at the time of birth. We recorded 2 cases of congenital malformations. No statistical differences were recorded when adverse ...


Mots clés : Lymphome; Traitements (Combinaison de traitements localisés et systémiques)

Ressources et infrastructures (Traitements)

Cet article présente une méthode qui, à base de séquençage et de screening à haut débit, vise à accélérer le processus de découverte de nouveaux médicaments anticancéreux

  • Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery
    Proceedings of the National Academy of Sciences, sous presse, 2012 (résumé)
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    Cet article présente une méthode qui, à base de séquençage et de screening à haut débit, vise à accélérer le processus de découverte de nouveaux médicaments anticancéreux

    “Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery”

    • Li, Hairi;Zhou, Hongyan;Wang, Dong;Qiu, Jinsong;Zhou, Yu;Li, Xiangqiang;Rosenfeld, Michael G.;Ding, Sheng;Fu, Xiang-Dong

    The advent of powerful genomics technologies has uncovered many fundamental aspects of biology, including the mechanisms of cancer; however, it has not been appropriately matched by the development of global approaches to discover new medicines against human diseases. Here we describe a unique high-throughput screening strategy by high-throughput sequencing, referred to as HTS2, to meet this challenge. This technology enables large-scale and quantitative analysis of gene matrices associated with specific disease phenotypes, therefore allowing screening for small molecules that can specifically intervene with disease-linked gene-expression events. By initially applying this multitarget strategy to the pressing problem of hormone-refractory prostate cancer, which tends to be accelerated by the current antiandrogen therapy, we identify Peruvoside, a cardiac glycoside, which can potently inhibit both androgen-sensitive and -resistant prostate cancer cells without triggering severe ...


Mots clés : Prostate; Traitements (Ressources et infrastructures (Traitements))

Cet article analyse les diverses significations associées au critère de survie globale dans les essais cliniques

Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))

Menée sur 687 patients inclus dans 36 essais cliniques de phase I ayant évalué une thérapie ciblée, cette étude analyse le degré de sévérité des effets indésirables associés aux traitements

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    Menée sur 687 patients inclus dans 36 essais cliniques de phase I ayant évalué une thérapie ciblée, cette étude analyse le degré de sévérité des effets indésirables associés aux traitements

    “Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: a single centre experience”

    • Molife, L. R.;Alam, S.;Olmos, D.;Puglisi, M.;Shah, K.;Fehrmann, R.;Trani, L.;Tjokrowidjaja, A.;de Bono, J. S.;Banerji, U.;Kaye, S. B.

    Background: This study defined the risk of serious toxicity in phase I trials of molecularly targeted agents (MTA).Patients and methods: A retrospective analysis of toxicity data from patients treated in phase I trials of MTAs was carried out to define the rate of treatment-related grade 3/4 toxic effects, deaths and risk factors associated with grade 3 or more toxicity.Results: Data from 687 patients [median age, 59.1 years (range 12.5–85.5)] treated in 36 trials were analysed. Two hundred and eleven patients were of Eastern Cooperative Oncology Group performance status (PS) zero, 432 of PS one, 38 of PS two and 6 unknown. The rate of grade 3 and 4 events was 14.1% (n = 97) and 1.9% (n = 13), respectively. Twenty-four percent of events were gastrointestinal, 22% constitutional and 20% metabolic. PS two was associated with a higher risk of toxicity [odds ratio (OR), 2.6; 95% confidence interval (CI) 1.1–6.1; P = 0.032] as was receiving >100% of maximum tolerated dose or maximum ...


Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))

Cet article passe en revue les modèles mathématiques permettant de choisir les critères de jugement les plus adaptés dans les essais cliniques de phase II

  • Choosing Phase II Endpoints and Designs: Evaluating the possibilities
    Clinical Cancer Research, sous presse, 2012 (résumé)
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    Cet article passe en revue les modèles mathématiques permettant de choisir les critères de jugement les plus adaptés dans les essais cliniques de phase II

    “Choosing Phase II Endpoints and Designs: Evaluating the possibilities”

    • LeBlanc, Michael L.;Tangen, Catherine M.

    Selecting the Phase II design and endpoint to achieve the best possible chance of success for a confirmatory Phase III study in a particular disease and treatment setting is challenging but critical. Simulating from existing clinical trial data sets, and mathematical models, can be useful tools for evaluating statistical properties.


Mots clés : Cancer (général); Traitements (Ressources et infrastructures (Traitements))

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