Menée à partir de données médicales portant sur 190 patients atteints d'une tumeur rénale traitée entre novembre 2007 et mars 2012, cette étude multicentrique évalue, du point de vue de données intra-opératoires, de la préservation des fonctions rénales et du taux de survie globale à 1, 2 et 3 ans, l'efficacité d'une néphrectomie partielle laparo-endoscopique avec accès unique

Analysis of oncological outcomes and renal function after laparoendoscopic single-site (LESS) partial nephrectomy: a multi-institutional outcome analysis

Springer, Christopher ; Greco, Francesco ; Autorino, Riccardo ; Rha, Koon H. ; Derweesh, Ithaar ; Cindolo, Luca ; Richstone, Lee ; Herrmann, Thomas R. W. ; Liatsikos, Evangelos ; Sun, Yinghao ; Fanizza, Caterina ; Nagele, Udo ; Stolzenburg, Jens-Uwe ; Rais-Bahrami, Soroush ; Liss, Michael A. ; Schips, Luigi ; Kassab, Ahmad ; Wang, Linhui ; Kallidonis, Panagiotis ; Wu, Zhenjie ; Young, Shin Tae ; Altieri, Vincenzo M. ; Haber, Georges-Pascal ; Fornara, Paolo ; Kaouk, Jihad H.

Objective : To report on a large multi-institutional series of laparoendoscopic single-site (LESS) partial nephrectomy (PN) and analyse renal function and short-term oncological outcomes. Material and Methods : We conducted a retrospective analysis of consecutive cases of LESS-PN performed between November 2007 and March 2012 at 11 participating institutions. Demographic data and data on the main peri-operative outcomes and complications were gathered and analysed. Kidney function was evaluated [...]

Menée in vitro et in vivo, cette étude montre qu'un composé appelé SC-60, dérivé du sorafenib, permet de surmonter une résistance au sorafenib dans le traitement d'un carcinome hépatocellulaire

SC-60, a dimer-based sorafenib derivative, shows a better anti-HCC effect than sorafenib in a preclinical HCC model

Tai, Wei-Tien ; Shiau, Chung-Wai ; Li, Yong-Shi ; Chen, Yao-Li ; Chu, Pei-Yi ; Huang, Jui-Wen ; Hsu, Cheng-Yi ; Hsu, Yi-Chieh ; Chen, Pei-Jer ; Chen, Kuen-Feng

Sorafenib is the first approved targeted therapeutic reagent for hepatocellular carcinoma (HCC). Here, we report that SC-60, a dimer-based sorafenib derivative, overcomes the resistance of sorafenib and shows a better anti-HCC effect in vitro and in vivo. SC-60 substantially increased SHP-1 phosphatase activity in HCC cells and purified SHP-1 proteins, suggesting that SC-60 affects SHP-1 directly. Molecular docking and truncated mutants of SHP-1 further confirmed that SC-60 interferes with the [...]

Menée sur des lignées cellulaires de cancer du côlon, cette étude met en évidence des mécanismes d'action différents pour quatre inhibiteurs d'histone désacétylase (vorinostat, entinostat, apidicine et acide valproïque) en fonction de l'expression du gène p53

p53-dependent and p53-independent anticancer effects of different histone deacetylase inhibitors

Sonnemann, J. ; Marx, C. ; Becker, S. ; Wittig, S. ; Palani, C. D. ; Kramer, O. H. ; Beck, J. F.

Background: Histone deacetylase inhibitors (HDACi) are promising antineoplastic agents, but their precise mechanisms of actions are not well understood. In particular, the relevance of p53 for HDACi-induced effects has not been fully elucidated. We investigated the anticancer effects of four structurally distinct HDACi, vorinostat, entinostat, apicidin and valproic acid, using isogenic HCT-116 colon cancer cell lines differing in p53 status. Methods: Effects were assessed by MTT assay, [...]

Menée in vitro et in vivo, cette étude évalue l'activité antitumorale d'un composé appelé LGK974, un inhibiteur de l'acétyltransférase PORCN, pour le traitement des cancers liés à la signalisation Wnt

Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974

Liu, Jun ; Pan, Shifeng ; Hsieh, Mindy H. ; Ng, Nicholas ; Sun, Fangxian ; Wang, Tao ; Kasibhatla, Shailaja ; Schuller, Alwin G. ; Li, Allen G. ; Cheng, Dai ; Li, Jie ; Tompkins, Celin ; Pferdekamper, AnneMarie ; Steffy, Auzon ; Cheng, Jane ; Kowal, Colleen ; Phung, Van ; Guo, Guirong ; Wang, Yan ; Graham, Martin P. ; Flynn, Shannon ; Brenner, J. Chad ; Li, Chun ; Villarroel, M. Cristina ; Schultz, Peter G. ; Wu, Xu ; McNamara, Peter ; Sellers, William R. ; Petruzzelli, Lilli ; Boral, Anthony L. ; Seidel, H. Martin ; McLaughlin, Margaret E. ; Che, Jianwei ; Carey, Thomas E. ; Vanasse, Gary ; Harris, Jennifer L.

Wnt signaling is one of the key oncogenic pathways in multiple cancers, and targeting this pathway is an attractive therapeutic approach. However, therapeutic success has been limited because of the lack of therapeutic agents for targets in the Wnt pathway and the lack of a defined patient population that would be sensitive to a Wnt inhibitor. We developed a screen for small molecules that block Wnt secretion. This effort led to the discovery of LGK974, a potent and specific small-molecule [...]

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels un composé appelé MK2206, un inhibiteur de la signalisation AKT, permet de surmonter une résistance aux glucocorticoïdes dans le traitement d'une leucémie lymphoblastique aiguë de type T

Direct Reversal of Glucocorticoid Resistance by AKT Inhibition in Acute Lymphoblastic Leukemia

Piovan, Erich ; Yu, Jiyang ; Tosello, Valeria ; Herranz, Daniel ; Ambesi-Impiombato, Alberto ; Da Silva, Ana Carolina ; Sanchez-Martin, Marta ; Perez-Garcia, Arianne ; Rigo, Isaura ; Castillo, Mireia ; Indraccolo, Stefano ; Cross, Justin R ; de Stanchina, Elisa ; Paietta, Elisabeth ; Racevskis, Janis ; Rowe, Jacob M ; Tallman, Martin S ; Basso, Giuseppe ; Meijerink, Jules P ; Cordon-Cardo, Carlos ; Califano, Andrea ; Ferrando, Adolfo A

Glucocorticoid resistance is a major driver of therapeutic failure in T cell acute lymphoblastic leukemia (T-ALL). Here, we identify the AKT1 kinase as a major negative regulator of the NR3C1 glucocorticoid receptor protein activity driving glucocorticoid resistance in T-ALL. Mechanistically, AKT1 impairs glucocorticoid-induced gene expression by direct phosphorylation of NR3C1 at position S134 and blocking glucocorticoid-induced NR3C1 translocation to the nucleus. Moreover, we demonstrate that [...]

Menée in vitro, cette étude met en évidence un mécanisme par lequel une mutation du gène BRAF (L505H) confère une résistance au vémurafenib, puis montre que les cellules de mélanome présentant cette mutation sont sensibles à une nouvelle génération d'inhibiteurs de BRAF tel que le composé appelé PLX8394

Identification of PLX4032-Resistance Mechanisms and Implications for Novel RAF Inhibitors

Choi, Jaehyuk ; Landrette, Sean ; Wang, Tiffany ; Evans, Perry ; Bacchiocchi, Antonella ; Bjornson, Robert ; Cheng, Elaine ; Stiegler, Amy L. ; Gathiaka, Symon ; Acevedo, Orlando ; Boggon, Titus J. ; Krauthammer, Michael ; Halaban, Ruth ; Xu, Tian

BRAF inhibitors improve melanoma patient survival, but resistance invariably develops. Here we report the discovery of novel BRAF mutation that confers resistance to PLX4032 employing whole-exome sequencing of drug-resistant BRAFV600K melanoma cells, BRAF Leu505 to His substitution (BRAFL505H) and describe a new screening approach, a genome-wide piggyBac mutagenesis screen that revealed clinically relevant aberrations (N-terminal BRAF truncations and CRAF overexpression). The BRAFL505H is the [...]

Menée in vitro et à l'aide de xénogreffes, cette étude suggère l'intérêt d'un composé appelé NMS-P715, un inhibiteur de MPS1, pour le traitement d'un adénocarcinome canalaire du pancréas

Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the mitotic MPS1 kinase inhibitor, NMS-P715

Slee, Roger B ; Grimes, Brenda R. ; Bansal, Ruchi ; Gore, Jesse ; Blackburn, Corinne ; Brown, Lyndsey ; Gasaway, Rachel ; Jeong, Jaesik ; Victorino, Jose ; March, Keith L. ; Colombo, Riccardo ; Herbert, Brittney-Shea ; Korc, Murray

Most solid tumors, including pancreatic ductal adenocarcinoma (PDAC), exhibit structural and numerical chromosome instability (CIN). While often implicated as a driver of tumor progression and drug resistance, CIN also reduces cell fitness and poses a vulnerability which can be exploited therapeutically. The spindle assembly checkpoint (SAC) ensures correct chromosome-microtubule attachment, thereby minimizing chromosome segregation errors. Many tumors exhibit up-regulation of SAC components [...]

Menée in vitro et in vivo, cette étude suggère qu'un inhibiteur de CXCL12, une protéine de fibroblastes associés au cancer, permet d'augmenter l'efficacité d'une immunothérapie anti PDL1 dans le traitement d'un adénocarcinome canalaire du pancréas

Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer

Feig, Christine ; Jones, James O. ; Kraman, Matthew ; Wells, Richard J. B. ; Deonarine, Andrew ; Chan, Derek S. ; Connell, Claire M. ; Roberts, Edward W. ; Zhao, Qi ; Caballero, Otavia L. ; Teichmann, Sarah A. ; Janowitz, Tobias ; Jodrell, Duncan I. ; Tuveson, David A. ; Fearon, Douglas T.

An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8+ T cells, the mice, like human patients with PDA, did not respond to two immunological checkpoint antagonists that promote the function of T cells: anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) and α-programmed cell death 1 ligand 1 (α-PD-L1). Immune control of PDA [...]

Menée à l'aide d'un modèle murin, cette étude évalue la faisabilité d'une technologie permettant l'administration par inhalation de petits ARNs interférents pour le traitement d'un cancer du poumon

A novel platform to enable inhaled naked RNAi medicine for lung cancer

Fujita, Yu ; Takeshita, Fumitaka ; Mizutani, Takayuki ; Ohgi, Tadaaki ; Kuwano, Kazuyoshi ; Ochiya, Takahiro

Small interfering RNA (siRNA)-based therapeutics have been used in humans and offer distinct advantages over traditional therapies. However, previous investigations have shown that there are several technical obstacles that need to be overcome before routine clinical applications are used. Currently, we are launching a novel class of RNAi therapeutic agents (PnkRNA™, nkRNA) that show high resistance to degradation and are less immunogenic, less cytotoxic, and capable of efficient intracellular [...]

Menée in vitro et in vivo, cette étude suggère l'intérêt du crizotinib pour surmonter une résistance thérapeutique chez les patients atteints d'un cancer du poumon à petites cellules

Targeting epithelial to mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer

Canadas, Israel ; Rojo, Federico ; Taus, Alvaro ; Arpi, Oriol ; Arumi-Uria, Montserrat ; Pijuan, Lara ; Menendez, Silvia ; Zazo, Sandra ; Dómine, Manuel ; Salido, Marta ; Mojal, Sergio ; Garcia de Herreros, Antonio ; Rovira, Ana ; Albanell, Joan ; Arriola, Edurne

Purpose: Met receptor phosphorylation is associated with poor prognosis in human SCLC. The aim of our work was to investigate the effects of hepatocyte growth factor (HGF)/Met mediated epithelial mesenchymal transition in SCLC and to evaluate the role of Met inhibition in mesenchymal/chemorefractory SCLC models. Experimental design: SCLC models of HGF-induced EMT were evaluated in vitro and in vivo (subcutaneous xenografts in BALB/c nude mice) for chemosensitivity and response to Met inhibition [...]

Menée à l'aide de xénogreffes de cancer colorectal, cette étude met en évidence des mécanismes par lesquels, en ciblant les cellules initiatrices du cancer, un inhibiteur de BMI-1 réduit la croissance tumorale

Self-renewal as a therapeutic target in human colorectal cancer

Kreso, Antonija ; van Galen, Peter ; Pedley, Nicholas M. ; Lima-Fernandes, Evelyne ; Frelin, Catherine ; Davis, Thomas ; Cao, Liangxian ; Baiazitov, Ramil ; Du, Wu ; Sydorenko, Nadiya ; Moon, Young-Choon ; Gibson, Lianne ; Wang, Yadong ; Leung, Cherry ; Iscove, Norman N. ; Arrowsmith, Cheryl H. ; Szentgyorgyi, Eva ; Gallinger, steven ; Dick, John E. ; O'Brien, Catherine A.

Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, [...]

Menée sur des lignées cellulaires de tumeurs malignes de l'enveloppe des nerfs périphériques puis à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels un composé appelé Cpd21 induit une apoptose

Preclinical therapeutic efficacy of a novel pharmacological inducer of apoptosis in malignant peripheral nerve sheath tumors

Chau, Vincent ; Lim, S. Kyun ; Mo, Wei ; Liu, Chiachi ; Patel, Amish J. ; McKay, Renee M. ; Wei, Shuguang ; Posner, Bruce A. ; De Brabander, Jef K. ; Williams, Noelle S. ; Parada, Luis F. ; Le, Lu Q.

Neurofibromatosis Type 1 (NF1) is an autosomal disorder that affects neural crest-derived tissues, leading to a wide spectrum of clinical presentations. Patients commonly present with plexiform neurofibromas, benign but debilitating growths that can transform into malignant peripheral nerve sheath tumors (MPNSTs), a main cause of mortality. Currently, surgery is the primary course of treatment for MPNST, but with the limitation that these tumors are highly invasive. Radiation therapy is another [...]

Cet article passe en revue les perspectives offertes, pour le diagnostic et le traitement d'un cancer du sein, par les travaux récents sur le rôle des micro-ARNs dans le développement de la maladie

microRNAs in breast cancer development and treatment

Serpico, Danila ; Molino, Leonardo ; Di Cosimo, Serena

microRNAs (herein after miRNAs) represent a recently uncovered class of small and endogenous non-coding RNAs. miRNAs play a well conserved and crucial role in normal biological processes, such as cell differentiation, proliferation and apoptosis through a complicated gene regulation networking. The recent rise of interest in miRNAs in cancer research is ascribed to the breakthrough of their role in many pathological processes, including malignant transformation. miRNAs signatures have been [...]

Menée sur des échantillons de tumeurs primitives et de métastases prélevés sur des patientes atteintes d'un cancer du sein, puis in vitro et à l'aide de xénogreffes, cette étude met en évidence le role joué par l'expression du récepteur GPR30 dans la résistance au tamoxifène

GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer

Mo, Zhiqiang ; Liu, Manran ; Yang, Fangfang ; Luo, Haojun ; Li, Zhenhua ; Tu, Gang ; Yang, Guanglun

INTRODUCTION:Tamoxifen is widely used to treat hormone-dependent breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Here, we investigated the role of estrogen G-protein coupled receptor 30 (GPR30) on Tamoxifen resistance in breast cancer. METHODS:Primary tumors (PTs) of breast cancer and corresponding metastases (MTs) were used to evaluate the expression of GPR30 and epidermal growth factor receptor (EGFR) immunohistochemically. Tamoxifen-resistant [...]

Mené sur 90 patients atteints d'un cancer avancé de l'estomac, cet essai de phase II compare l'efficacité, du point de vue de la survie globale, et la toxicité de deux modes d'administration du paclitaxel

Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer

Shitara, K. ; Yuki, S. ; Tahahari, D. ; Nakamura, M. ; Kondo, C. ; Tsuda, T. ; Kii, T. ; Tsuji, Y. ; Utsunomiya, S. ; Ichikawa, D. ; Hosokawa, A. ; Ishiguro, A. ; Sakai, D. ; Hironaka, S. ; Oze, I. ; Matsuo, K. ; Muro, K.

Background: This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC). Methods: Ninety patients were randomised to a standard dose of wPTX (80 mg m−2) or an escalated dose of wPTX (80–120 mg m−2) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8. Results: The median OS showed a trend towards longer survival in the dose-escalated [...]

A partir d'une revue de la littérature (21 essais cliniques identifiés, 14 776 patients au total), cette étude évalue l'incidence et le risque d'événements indésirables fatals associés à un traitement par cetuximab ou panitumumab

Incidence and Risk of Treatment-Related Mortality with Anti-Epidermal Growth Factor Receptor Monoclonal Antibody in Cancer Patients: A Meta-Analysis of 21 Randomized Controlled Trials

Li, Xing ; Shan, Bao-En ; Wang, Juan ; Xing, Lian-Ping ; Guo, Xiao-Jin ; Zhang, Yue-Hua ; Shi, Peng-Hui ; Wang, Zhi-Yu

Background : Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) cetuximab and panitumumab have emerged as an effective targeted therapy in the treatment of cancer patients, but the overall incidence and risk of fatal adverse events (FAEs) associated with these agents is still unclear. Methods : Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective [...]

Mené sur 10 patients atteints de la forme variante de la leucémie à tricholeucocytes, cet essai évalue l'efficacité, du point de vue du taux de rémission complète, et la toxicité d'un traitement combinant cladribine et rituximab

Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia

Kreitman, Robert J. ; Wilson, Wyndham ; Calvo, Katherine R. ; Arons, Evgeny ; Roth, Laura ; Sapolsky, Jeffrey ; Zhou, Hong ; Raffeld, Mark ; Stetler-Stevenson, Maryalice

Purpose: In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, [...]

Cet article passe en revue les travaux récents sur le rôle du vémurafenib et autres thérapies ciblées dans le traitement d'un mélanome présentant une mutation du gène BRAF

Treatment of BRAF-Mutant Melanoma: The Role of Vemurafenib and Other Therapies

Jang, S. ; Atkins, M. B.

The discovery of activating BRAF mutations in melanomas has led to the investigation of small molecular inhibitors targeting BRAF mutation and MEK, a downstream protein within the mitogen-activated protein kinase (MAPK) pathway. This article reviews the role of mutant BRAF in melanoma and summarizes the results of clinical trials evaluating inhibitors of BRAF and MEK in BRAF-mutant melanoma. We further describe recent findings on the mechanisms of resistance to BRAF inhibitors and discuss [...]

Mené sur 42 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde, de stade localement avancé ou métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité de l'aflibercept en combinaison avec du cisplatine et du pemetrexed

A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer

Chen, H. ; Modiano, M. R. ; Neal, J. W. ; Brahmer, J. R. ; Rigas, J. R. ; Jotte, R. M. ; Leighl, N. B. ; Riess, J. W. ; Kuo, C. J. ; Liu, L. ; Gao, B. ; DiCioccio, A. T. ; Adjei, A. A. ; Wakelee, H. A.

Background: This study evaluated the efficacy and safety of ziv-aflibercept in combination with cisplatin and pemetrexed in non-small cell lung cancer (NSCLC). Methods: This single arm, multicentre phase II trial enrolled patients with previously untreated, locally advanced or metastatic non-squamous NSCLC. Patients received intravenous ziv-aflibercept 6 mg kg−1, pemetrexed 500 mg m−2, and cisplatin 75 mg m−2, every 21 days for up to six cycles. Maintenance administration of ziv-aflibercept was [...]

Mené sur 74 patients atteints d'un lymphome folliculaire (âge : 28 à 80 ans ; durée médiane de suivi : 3,1 ans), cet essai international multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression, de la survie sans traitement et de la survie globale à 3 ans, et la toxicité d'une immunoradiothérapie fractionnée à base d'ibritumomab tiuxétan conjugué à l'Yttrium-90

Fractionated 90Y-Ibritumomab Tiuxetan Radioimmunotherapy As an Initial Therapy of Follicular Lymphoma: An International Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria

Illidge, Tim M. ; Mayes, Sam ; Pettengell, Ruth ; Bates, Andrew T. ; Bayne, Mike ; Radford, John A. ; Ryder, W. David J. ; Le Gouill, Steven ; Jardin, Fabrice ; Tipping, Jill ; Zivanovic, Maureen ; Kraeber-Bodere, Francoise ; Bardies, Manuel ; Bodet-Milin, Caroline ; Malek, Emmanuel ; Huglo, Damien ; Morschhauser, Franck

Purpose : We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated 90Y-ibritumomab tiuxetan (90Y-IT) as initial therapy of follicular lymphoma (FL). Patients and Methods : A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d’Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% [...]

Cet article passe en revue les études récentes concernant l'efficacité de diverses stratégies thérapeutiques (traitements chirurgicaux, systémiques ou régionaux) pour traiter des métastases hépatiques ayant pour origine un mélanome oculaire ou cutané

Metastatic melanoma to the liver: A contemporary and comprehensive review of surgical, systemic, and regional therapeutic options

Agarwala, Sanjiv S. ; Eggermont, Alexander M. M. ; O'Day, Steven ; Zager, Jonathan S.

Effective management of hepatic metastases from ocular and cutaneous melanoma remains a major therapeutic challenge. Treatment options include hepatic resection, hepatic intra-arterial (HIA) chemotherapy, chemoembolization, and hepatic perfusions. Evaluating the efficacy of these interventions is limited by the retrospective nature of most of the data, although controlled phase 3 studies are starting to emerge. Studies of hepatic resection are strongly suggestive of a survival benefit following [...]

Cet article fait le point sur les avancées thérapeutiques et technologiques permettant d'optimiser une chimioradiothérapie concomitante dans le traitement d'un cancer du poumon non à petites cellules de stade III et inopérable

How can we optimise concurrent chemoradiotherapy for inoperable stage III non-small cell lung cancer?

Bayman, Neil ; Blackhall, Fiona ; McCloskey, Paula ; Taylor, Paul ; Faivre-Finn, Corinne

Latest evidence sets a clear mandate for concurrent chemoradiotherapy as the current standard of care for inoperable stage III non small cell lung cancer patients with good performance status and minimal comorbidities. However, a survival plateau has been reached, with disappointing results from dose escalation studies using conventional fractionation and studies investigating the addition of systemic doses of chemotherapy delivered before or after concurrent chemoradiotherapy. It is clear that [...]

Menée à l'aide de xénogreffes de glioblastome, cette étude montre qu'un anticorps anti-YKL-40 et une radiothérapie inhibent de façon synergique la vascularisation et la progression de la tumeur

Anti-YKL-40 antibody and ionizing irradiation synergistically inhibit tumor vascularization and malignancy in glioblastom

Shao, Rong ; Francescone, Ralph ; Ngernyuang, Nipaporn ; Bentley, Brooke ; Taylor, Sherry L ; Moral, Luis ; Yan, Wei

Chemo/radiotherapies are the most common adjuvant modality treated for patients with glioblastoma (GBM) following surgery. However, the overall therapeutic benefits are still uncertain, as the mortality remains high. Elevated expression of YKL-40 in GBM was correlated with increases in mural cell-associated vessel coverage, stability and density, and decreases in vessel permeability and disease survival. To explore the potential role of YKL-40 in mural cell-mediated tumor vascularization, we [...]

Menée en Italie sur 40 patients atteints d'un carcinome du thymus, cette étude multicentrique évalue, du point de vue des taux de survie à 5 et 10 ans, l'intérêt d'une résection complète dans le cadre d'un traitement multimodal

Outcome of surgically resected thymic carcinoma: A multicenter experience

Filosso, Pier Luigi ; Guerrera, Francesco ; Rendina, Angelo Erino ; Bora, Giulia ; Ruffini, Enrico ; Novero, Domenico ; Ruco, Luigi ; Vitolo, Domenico ; Anile, Marco ; Ibrahim, Mohsen ; Casadio, Caterina ; Rena, Ottavio ; Terzi, Alberto ; Lyberis, Paraskevas ; Oliaro, Alberto ; Venuta, Federico

Objective : Thymic Carcinoma (TC) is a rare and invasive mediastinal tumor, with poor prognosis. Most of the previous published papers are single-Institution based, reporting small series of patient, sometimes including palliative resection. This study collected patients with TC treated in 5 high-volume Italian Thoracic Surgery Institutions. Methods : a multicenter retrospective study of patients operated for TC between 2000 and 2011, was conducted. Exclusion criteria were: Neuroendocrine [...]

Menée à partir de données d'un registre portant sur 8 128 patients atteints d'un cancer localisé de la prostate traité entre 1990 et 2011, cette étude américaine analyse, par rapport à d'autres options thérapeutiques, l'utilisation de la curiethérapie en traitement unique avant et après la publication de deux recommandations nationales

Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer

Tseng, Yolanda D. ; Paciorek, Alan T. ; Martin, Neil E. ; D'Amico, Anthony V. ; Cooperberg, Matthew R. ; Nguyen, Paul L.

BACKGROUND : In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. METHODS : From 1990 to 2011, 8 128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor [...]

Cet article passe en revue les différentes stratégies possibles pour mener des essais cliniques randomisés de phase III lorsque des travaux antérieurs ont suggéré l'intérêt d'un biomarqueur prédictif de la réponse thérapeutique

Biomarker enrichment strategies: matching trial design to biomarker credentials

Freidlin, Boris ; Korn, Edward L.

The use of biomarkers to identify patients who can benefit from treatment with a specific anticancer agent has the potential to both improve patient care and accelerate drug development. The development of targeted agents and their accompanying biomarkers frequently occurs contemporaneously, and confidence in a putative biomarker's performance might, therefore, be insufficient to restrict the definitive testing of a new agent to the subgroup of biomarker-positive patients. This Review considers [...]

Cet article fait le point sur l'incidence du lymphome primitif du testicule, ses caractéristiques cliniques et ses facteurs pronostiques, passe en revue les études concernant l'efficacité de diverses stratégies thérapeutiques, puis analyse le rôle de la radiothérapie et l'intérêt des nouveaux traitements

Primary testicular lymphoma

Cheah, Chan Y. ; Wirth, Andrew ; Seymour, John F.

Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. The vast majority of cases are histologically diffuse large B-cell lymphoma, but rarer subtypes are clinically important and must be recognised. In this review we discuss the incidence, clinical presentation and prognostic factors of PTL and present a summary of the recent advances in our understanding of the pathophysiology which may account for the characteristic clinical features. Although [...]