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Anne-Sophie Michallet, Melih Aktan, Wolfgang Hiddemann, Osman Ilhan, Peter Johansson, Kamel Laribi, Balkis Meddeb, Carol Moreno, João Raposo, Anna Schuh, Ali Ünal, Tom Widenius, Alf Bernhardt, Kerstin Kellershohn, Dimitri Messeri, Stuart Osborne, Véronique Leblond
MABLE (NCT01056510) investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every 4 weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients...
February 1, 2018: Haematologica
Cheng-Qiong Luo, Yu-Xin Zhou, Tian-Jiao Zhou, Lei Xing, Peng-Fei Cui, Minjie Sun, Liang Jin, Na Lu, Hu-Lin Jiang
Prodrug-based stimuli-responsive vectors have emerged as highly promising platform. Inspired by the fact that antioxidant systems including glutathione (GSH) make cancer cells adapt to oxidative stress and play a role in the inactivation of alkylating agents like chlorambucil (CHL) inside tumor cells, while arylboronic acid could transform into GSH depleting agent quinone methide (QM) upon degradation by reactive oxygen species (ROS) over-expressed in tumor cells, a ROS-responsive nanoprodrug (denoted by PPAHC) of CHL was established by integrating CHL into diols-containing hydrophilic polymer with self-immolative linker 4-(hydroxymethyl)phenylboronic acid (HPBA)...
February 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Chak-Shing Kwan, Rundong Zhao, Michel A Van Hove, Zongwei Cai, Ken Cham-Fai Leung
Type III-B rotaxane dendrimers (T3B-RDs) are hyperbranched macromolecules with mechanical bonds on every branching unit. Here we demonstrate the design, synthesis, and characterization of first to third (G1-G3), and up to the fourth (G4) generation (MW > 22,000 Da) of pure organic T3B-RDs and dendrons through the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. By utilizing multiple molecular shuttling of the mechanical bonds within the sphere-like macromolecule, a collective three-dimensional contract-extend molecular motion is demonstrated by diffusion ordered spectroscopy (DOSY) and atomic force microscopy (AFM)...
February 5, 2018: Nature Communications
Richa Sinha, William Ken Redekop
BACKGROUND: Ibrutinib shows superiority over obinutuzumab with chlorambucil (G-Clb) in untreated patients with chronic lymphocytic leukemia with comorbidities who cannot tolerate fludarabine-based therapy. However, ibrutinib is relatively more expensive than G-Clb. In this study we evaluated the cost-effectiveness of ibrutinib compared with G-Clb from the United Kingdom (UK) health care perspective. MATERIALS AND METHODS: A 3-state semi-Markov model was parameterized to estimate the lifetime costs and benefits associated with ibrutinib compared with G-Clb as first-line treatment...
February 2018: Clinical Lymphoma, Myeloma & Leukemia
Y Y Mao, X X Cao, H Cai, D B Zhou, J Li
Objective: To evaluate the clinical characteristics, diagnosis criteria, treatment and prognosis in patients with Bing-Neel Syndrome (BNS) . Methods: The clinical characteristics, lab data, treatment and outcomes of 3 Bing-Neel syndrome patients diagnosed at Peking Union Medical College Hospital were collected. Results: The clinical presentation was heterogeneous without any specific common signs or symptoms. One patient was diagnosed with BNS 42 months after diagnosis of Waldenström macroglobulinemia (WM) by cerebrospinal fluid (CSF) cytology and flow cytometry, but dead of infection during the first course of chemotherapy...
December 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Yi Lin, Xiao-Fang Jiang, Xiangyan Duan, Fang Zeng, Bo Wu, Shuizhu Wu
Using light as the sole stimulus and employing the generated singlet oxygen as a therapeutic agent and the trigger to activate chemo-drug release could serve as an elegant way to bring into full play the advantageous features of light and enhance therapeutic efficacy through a combination of chemotherapy and photodynamic therapy. Herein a liposomal drug system has been developed by embedding a fluorescent photosensitizer and a prodrug into phospholipid vesicles. Upon one- or two-photon light irradiation, the photosensitizer generates singlet oxygen, which removes the protecting group of the prodrug and subsequently causes the release of the active drug chlorambucil...
January 11, 2018: ACS Medicinal Chemistry Letters
Leonardo Bianchi, Katharina Hansel, Simona Pelliccia, Marta Tramontana, Luca Stingeni
No abstract text is available yet for this article.
February 2018: Contact Dermatitis
Emanuele Cencini, Alberto Fabbri, Francesco Lauria, Monica Bocchia
There is no consensus about the best treatment option for patients with HP-negative gastric MALT lymphomas or persistent disease after HP eradication.We have investigated fludarabine and mitoxantrone with rituximab (R-FM) as first-line treatment. A cohort of 13 patients was analyzed. Induction treatment consisted of fludarabine (25 mg/m2 i.v. on days 2 to 4), mitoxantrone (10 mg/m2 i.v. on day 2), and rituximab (375 mg/m2 i.v. on day 1), for up to six cycles every 28 days. All patients achieved a complete remission, a median of four cycles was given...
January 16, 2018: Annals of Hematology
Gengo Kashiwazaki, Rina Maeda, Takashi Kawase, Kaori Hashiya, Toshikazu Bando, Hiroshi Sugiyama
N-Methylpyrrole-N-methylimidazole (PI) polyamides are a class of DNA minor groove binders with DNA sequence-specificity. DNA-alkylating PI polyamide conjugates are attractive candidates as anticancer drugs acting through DNA damage and its subsequent inhibition of cell proliferation. One example is a chlorambucil-PI polyamide conjugate targeting the runt-related transcription factor (RUNX) family. RUNX1 has pro-oncogenic properties in acute myeloid leukemia, and recently the chlorambucil-PI polyamide conjugate was demonstrated to have anticancer effects...
January 1, 2018: Bioorganic & Medicinal Chemistry
Guangbiao Zhou, Xinchun Zhao
Recently, Ng et al. reported that the A:T > T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome...
December 5, 2017: Frontiers of Medicine
Anthony J Berdis
Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis...
2017: Frontiers in Molecular Biosciences
Luca Arcaini, Thierry Lamy, Jan Walewski, David Belada, Jiri Mayer, John Radford, Wojciech Jurczak, Franck Morschhauser, Julia Alexeeva, Simon Rule, José Cabeçadas, Elias Campo, Stefano A Pileri, Tsvetan Biyukov, Meera Patturajan, Marie-Laure Casadebaig Bravo, Marek Trnĕný
In the mantle cell lymphoma (MCL)-002 study, lenalidomide demonstrated significantly improved median progression-free survival (PFS) compared with investigator's choice (IC) in patients with relapsed/refractory MCL. Here we present the long-term follow-up data and results of preplanned subgroup exploratory analyses from MCL-002 to evaluate the potential impact of demographic factors, baseline clinical characteristics and prior therapies on PFS. In MCL-002, patients with relapsed/refractory MCL were randomized 2:1 to receive lenalidomide (25 mg/day orally on days 1-21; 28-day cycles) or single-agent IC therapy (rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine)...
January 2018: British Journal of Haematology
Steven Coutre, Alessandra Tedeschi, Tadeusz Robak, Paul M Barr, Carolyn Owen, Osnat Bairey, Jan Burger, Cathy Zhou, Lori Styles, Danelle F James, Thomas J Kipps
No abstract text is available yet for this article.
November 23, 2017: Haematologica
J-X Guo, Y-H Zhou, Y-Q Huang, G-J Liu, J-X Pan
OBJECTIVE: Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) can induce the apoptosis of tumor cells, but leaving its effect on malignant lymphoma largely insignificant, as these tumors may develop drug resistance. Chlorambucil (CLB) had definitive treatment efficacy on low-malignant non-Hodgkin lymphoma (NHL), but with unclear efficacy on highly malignant Burkitt lymphoma. A study has been shown that CLB could enhance the sensitivity of chronic lymphatic leukemia cells against TRAIL...
October 2017: European Review for Medical and Pharmacological Sciences
Soheil Tavakolpour
Systemic administration of corticosteroid (CS) remains the standard gold treatment for pemphigus. However, because of several long-term adverse effects, steroid-sparing agents are usually prescribed in combination with CSs. Despite the high number of available studies, the choice of best drugs to treat pemphigus remains controversial. Therapeutic approaches for pemphigus can be divided into traditional treatment and emerging ones. Personalized medicine, which aims to increase the efficacy as well as reduce adverse effects of treatments, could be considered as the future option...
December 2017: International Immunopharmacology
Sabina Kersting, Suzanne I M Neppelenbroek, Hein P J Visser, Michel van Gelder, Mark-David Levin, Rogier Mous, Ward Posthuma, Hanneke M van der Straaten, Arnon P Kater
INTRODUCTION: In recent years, considerable progress has been made in the treatment of patients with chronic lymphocytic leukemia (CLL), and new potent drugs have become available. Therefore, the CLL working party revised the Dutch guidelines. Not only efficacy but also quality of life and socio-economic impact were taken into account in the formulation of treatment recommendations. MATERIALS AND METHODS: The working party discussed a set of questions regarding diagnostic tests and treatment and wrote the draft guideline...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
Idanna Innocenti, Francesco Autore, Raffaella Pasquale, Francesca Morelli, Dimitar G Efremov, Luca Laurenti
Elderly patients with chronic lymphocytic leukemia (CLL) or patients with comorbidities are often treated with chlorambucil (Chl) as front-line therapy despite relatively low response rates. The addition of a monoclonal anti-CD20 antibody to Chl substantially increases response rates and prolongs progression-free survival (PFS) in these patients, without increasing toxicity. As a result, the ESMO guidelines recommend that previously untreated CLL patients with relevant co-morbidity, but without TP53 deletion/mutation, should be treated with the combination of Chl plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab)...
December 2017: Expert Review of Hematology
Shaojun Li, Haiping Yang, Pengfei Guo, Xiaoxiao Ao, Junli Wan, Qiu Li, Liping Tan
BACKGROUND: Conventional meta-analyses and randomized controlled trials have shown inconsistent results regarding the efficacy of immunosuppressants for pediatric steroid-resistant nephrotic syndrome (SRNS). OBJECTIVE: To conduct a network meta-analysis aimed at evaluating the efficacy and safety of available immunosuppressive agents in pediatric patients with SRNS. STUDY METHODS: MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE were searched on January 2017...
September 22, 2017: Oncotarget
J Lane, J Price, A Moore, J R S Dandrieux, C Clifford, K Curran, K Choy, C Cannon
OBJECTIVES: To report the clinical presentation, treatment and prognosis of dogs with low-grade gastrointestinal lymphoma. MATERIALS AND METHODS: Cases were solicited from the American College of Veterinary Internal Medicine Oncology Diplomate listserv. Medical records of dogs with low-grade gastrointestinal lymphoma diagnosed via a combination of histology and immunohistochemistry with or without analysis of polymerase chain reaction for antigen receptor rearrangement were included...
October 13, 2017: Journal of Small Animal Practice
P Quaglino, M Maule, H M Prince, P Porcu, S Horwitz, M Duvic, R Talpur, M Vermeer, M Bagot, J Guitart, E Papadavid, J A Sanches, E Hodak, M Sugaya, E Berti, P Ortiz-Romero, N Pimpinelli, O Servitje, A Pileri, P L Zinzani, T Estrach, R Knobler, R Stadler, M T Fierro, S Alberti Violetti, I Amitay-Laish, C Antoniou, C Astrua, S Chaganti, F Child, A Combalia, S Fabbro, P Fava, V Grandi, C Jonak, E Martinez-Escala, M Kheterpal, E J Kim, C McCormack, T Miyagaki, D Miyashiro, S Morris, C Muniesa, V Nikolaou, G Ognibene, F Onida, S Osella-Abate, S Porkert, C Postigo-Llorente, C Ram-Wolff, S Ribero, K Rogers, M Sanlorenzo, R Stranzenbach, N Spaccarelli, A Stevens, D Zugna, A H Rook, L J Geskin, R Willemze, S Whittaker, R Hoppe, J Scarisbrick, Y Kim
Background: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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