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Catherine M Chan, Courtney H Zwahlen, Louis-Philippe de Lorimier, Stephen M Yeomans, Karon L Hoffmann, Antony S Moore
CASE DESCRIPTION 4 dogs with a slow-growing mass in the cervical region were evaluated. CLINICAL FINDINGS All dogs had no clinical signs at the time of the evaluation. There was no apparent evidence of visceral metastases or other primary tumor based on available CT or MRI data for any dog. TREATMENT AND OUTCOME For each dog, surgery to remove the mass was performed. Histologic examination of the excised tissue revealed a completely excised grade 1 or 2 lymph node hemangiosarcoma. All dogs received adjuvant chemotherapy; 2 dogs underwent curative intent chemotherapy, 1 dog underwent metronomic treatment with cyclophosphamide, and 1 dog underwent metronomic treatment with chlorambucil...
November 1, 2016: Journal of the American Veterinary Medical Association
Nazanin Ebrahimiadib, Bobeck S Modjtahedi, Samaneh Davoudi, C Stephen Foster
PURPOSE: To evaluate the efficacy of chlorambucil in the treatment of serpiginous choroiditis. METHODS: Patient records from the Massachusetts Eye Research and Surgery Institution (MERSI) were reviewed from over the past 10 years. In total, 17 patients with the diagnosis of serpiginous choroiditis treated with chlorambucil were identified. QuantiFERON gold was negative in all of them. Chlorambucil was started at 0.15 mg/kg and dosage was titrated up using weekly white blood cell (WBC) count to achieve a target cell number of 3...
October 18, 2016: Ocular Immunology and Inflammation
Yarra Venkatesh, Yetirajam Rajesh, Sambath Karthik, Chetan Anabur C, Mahitosh Mandal, Avijit Jana, N D Pradeep Singh
A new fluorescent photoremovable protecting group (FPRPG) based on acetylcarbazole framework has been explored for the first time release of single and dual (similar or different) substrates from single chromophore. Mechanistic studies of the photorelease process revealed that photorelease of two (similar or different) substrates from acetyl carbazole proceeds via a stepwise pathway. Further, we constructed photoresponsive dual drug delivery system (DDS) to release of two different anticancer drugs (Caffeic acid and Chlorambucil 1 equivalent each)...
October 18, 2016: Journal of Organic Chemistry
Ivana Milosevic
A 76-years old man presented with leucocytosis (86x109/l), fever, pneumonia and significant weight loss. He had a history of chronic lymphocytic leukemia diagnosed five years earlier and he responded with partial remission to the treatment with continuous low doses of chlorambucil. Analysis of blood smear, bone marrow aspiration and bone marrow biopsy revealed predomination of small lymphocytes, but 22% of cells were blasts negative to cytochemical stainings (Figure 1). Flow cytometric analysis showed two distinct populations: 65% of cells was small to moderate in size, CD19+, CD45+, CD5+, CD20+/-, but 30% of cells were large, CD34+, CD13+, HLA DR+, CD65+, CD45+, MPO weakly positive and CD33, CD14, CD15, CD16 negative...
October 18, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
A Prica, F Baldassarre, L K Hicks, K Imrie, T Kouroukis, M Cheung
Rituximab is the first monoclonal antibody to be approved for use by the US Food and Drug Administration in cancer. Its role in the treatment of non-Hodgkin lymphoma, including chronic lymphocytic leukaemia (CLL), has evolved significantly. We aimed to systematically review and update the literature on rituximab in lymphoma and CLL, and provide evidence-based consensus guidelines for its rational use. Validated methodology from the Cancer Care Ontario Program in Evidence-based Care was used. A comprehensive literature search was completed by a methodologist from the Hematology Disease Site Group of Cancer Care Ontario...
October 13, 2016: Clinical Oncology: a Journal of the Royal College of Radiologists
Pradeep Singh, Yarra Venkatesh, S Karthik, Y Rajesh, Mahitosh Mandal, Avijit Jana
Here we report the design, synthesis and in vitro biological studies of a Biotin-Carbazole-Dicyanovinyl-Chlorambucil conjugate (Bio-CBZ-DCV-CBL). This conjugate (6) is a multifunctional single molecule appliance composed of thiol-sensor Dicyanovinyl functionality, a Carbazole derived phototrigger and the fluorescent reporter, chlorambucil (CBL) as the anticancer drug, and biotin as the cancer-targeting ligand. In conjugate 6, the dicyanovinyl bond undergoes thiol-ene click reaction at pH< 7 with intracellular thiols thereby shuttingdown the internal charge transfer between donor carbazole and acceptor dicyanovinyl unit results in change of fluorescence color from green to blue and thereby sense the tumor microenvironment, followed by photoirradiation results in release of the anticancer drug CBL in controlled manner...
October 5, 2016: Chemistry, An Asian Journal
Luis Felipe Casado, Amparo Burgos, Eva González-Haba, Javier Loscertales, Tania Krivasi, Javier Orofino, Carlos Rubio-Terres, Darío Rubio-Rodríguez
OBJECTIVE: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System. METHODS: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death...
2016: ClinicoEconomics and Outcomes Research: CEOR
Sara E F Kost, Eric D J Bouchard, Élise LaBossière, Xibiao Ye, Michelle L Queau, William S Liang, Versha Banerji, Spencer B Gibson, Sachin Katyal, James B Johnston
Bendamustine (BEN) has structural similarities to an alkylating agent and a nucleoside analog, and effective against tumor cells that are resistant to standard therapy. In this study we compared the activities of BEN against that of the alkylating agent, chlorambucil (CLB), and the nucleoside analogs, fludarabine (FLU) and deoxyadenosine/pentostatin (dADO/PEN), in primary chronic lymphocytic leukemia (CLL) cells in vitro. Cross-resistance was observed between BEN, CLB and FLU, with previously treated patients or those with a deletion 17p being most resistant...
September 20, 2016: Leukemia Research
Artin Assadi, Vahideh Sharifi Najafabadi, Seyed Ataollah Sadat Shandiz, Azadah Shayeq Boroujeni, Sepehr Ashrafi, Ali Zaman Vaziri, Seyedeh Masoumeh Ghoreishi, Mohammad Reza Aghasadeghi, Seyed Esmaeil Sadat Ebrahimi, Morteza Pirali-Hamedani, Mehdi Shafiee Ardestani
Evaluating the efficacy of anticancer drugs is an evolving and research-oriented issue. The objective of this study was to reduce the insolubility of chlorambucil (CBL) in water and improve the anticancer activity of CBL in vitro and in vivo through the conjugation of CBL with anionic linear-globular dendrimer (second generation, G2). In the current study, the anticancer activity among three groups that include CBL, CBL-G2 dendrimer, and control was measured in vitro and in vivo. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which conjugated to the CBL exterior through an ester linkage, was able to significantly improve the treatment efficacy over clinical CBL alone with respect to proliferation assay, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; half maximal inhibitory concentration (IC50) was calculated to be 141 µg/mL for CBL alone and 27...
2016: OncoTargets and Therapy
Ziad Hilal, Franziska Hartmann, Askin Dogan, Cem Cetin, Harald Krentel, Sven Schiermeier, Beate Schultheis, Clemens B Tempfer
BACKGROUND: Lymphoma of the uterine cervix (LUCX) is rare and may occur as a primary or secondary manifestation of this disease. Clinical and cytological presentations of LUCX vary and establishing diagnosis is often difficult. Surgery followed by radiation or chemotherapy is the mainstay of treatment. CASE REPORT: We present the case of a 73-year-old woman with recurrent pathological PAP smears of the cervix and a history of chronic lymphatic leukemia 15 years ago...
September 2016: Anticancer Research
Hongzhong Chen, Huijun Phoebe Tham, Chung Yen Ang, Qiuyu Qu, Lingzhi Zhao, Pengyao Xing, Linyi Bai, Si Yu Tan, Yanli Zhao
Targeted drug delivery systems having controlled drug release property with an inherent fluorescence reporter have drawn a lot of attention in nanomedicine. However, only very few prodrugs can be directly used to construct such delivery systems. Herein, we report that an amphiphilic chlorambucil-based prodrug consisting of a fluorescence reporter and a d-mannose targeting ligand could directly self-assemble into glutathione-responsive nanovesicles for selective cancer therapy and intracellular imaging. These nanovesicles could be dissociated to release the chlorambucil drug with obviously red-shifted fluorescence when internalized by d-mannose receptor-overexpressed MCF-7 cancer cells...
September 21, 2016: ACS Applied Materials & Interfaces
Benigno C Valdez, Yang Li, David Murray, Jonathan E Brammer, Yan Liu, Chitra Hosing, Yago Nieto, Richard E Champlin, Borje S Andersson
HDAC inhibitors, DNA alkylators and nucleoside analogs are effective components of combination chemotherapy. To determine a possible mechanism of their synergism, we analyzed the effects of HDAC inhibitors on the expression of drug transporters which export DNA alkylators. Exposure of PEER lymphoma T-cells to 15 nM romidepsin (Rom) resulted in 40%-50% reduction in mRNA for the drug transporter MRP1 and up to ~500-fold increase in the MDR1 mRNA within 32-48 hrs. MRP1 protein levels concomitantly decreased while MDR1 increased...
August 24, 2016: Oncotarget
Talal Alfaadhel, Daniel Cattran
BACKGROUND: Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome (NS) in adults in Western countries. In 2012, the KDIGO (Kidney Disease: Improving Global Outcomes) working group published guidelines for the management of glomerulonephritis, thus providing a template for the treatment of this condition. While being aware of the impact of the clinicians' acumen and that patients may choose a different therapeutic option due to the risks of specific drugs and also of the evolving guidelines, this review details our approach to the management of patients with IMN in a Western center (Toronto)...
September 2015: Kidney Diseases
Jing Xu, Xiaofan Hu, Jingyuan Xie, Nan Chen
BACKGROUND: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults, accounting for about 20.0% of all NS cases. With an increasing prevalence, especially in the elderly, it has received great attention in Asia. SUMMARY: Recently, the prevalence of idiopathic MN (IMN) has significantly increased among the elderly people in Asia and other places in the world. Although the exact mechanism of IMN remains unveiled, the identification of new antigens such as PLA2R and THSD7A has greatly enhanced our understanding of its pathogenesis...
September 2015: Kidney Diseases
Nicolas Städler, Aijing Shang, Francesc Bosch, Andrew Briggs, Valentin Goede, Aurelien Berthier, Corinne Renaudin, Veronique Leblond
INTRODUCTION: Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients. METHODS: For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm...
October 2016: Advances in Therapy
Jian-Xin Guo, Ya-Hong Zhou, Jing-Xin Pan, Xi-Zhe Guo, Shi-Xin Wu, Yue-Qin Huang
OBJECTIVE: To explore the action mechanism of chlorambucil against mantle cell lymphoma cell line Jeko-1. METHODS: The effect of chlorambucil on Jeko-1 cell proliferation was measured by MTT method. The effect of chlorambucil on the apoptosis of Jeko-1 cell was detected by Hoechst staining and Annexin V-FITC dual staining. The activation of PI3K/AKT signaling pathway and the expression of BAX, BCL-2, procaspase 3, procaspase 8 and procaspase 9 were detected by Western blot...
August 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Peter Hillmen, Ann Janssens, K Govind Babu, Janusz Kloczko, Sebastian Grosicki, Stephanie Manson, Astrid McKeown, Ira Gupta, Chai-Ni Chang, Fritz Offner
BACKGROUND: Patients diagnosed with chronic lymphocytic leukemia (CLL) are usually elderly and frequently have a number of comorbidities. Health-related quality of life (HRQoL) for these patients is of utmost importance and should be taken into consideration when assessing new treatment options. The combination of ofatumumab with chlorambucil has shown longer progression-free survival compared with chlorambucil alone. In this study, we aim to assess how this treatment combination affects patients' health-related quality of life and patient-reported symptoms...
September 2016: Acta Oncologica
Anna Maria Frustaci, Alessandra Tedeschi, Paola Picardi, Maddalena Mazzucchelli, Roberto Cairoli, Marco Montillo
The management of patients with chronic lymphocytic leukemia (CLL) has radically improved over the last few years with the addition of anti-CD20 monoclonal antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades as a suitable therapeutic option for frail patients. Taking into account the advantage offered by the addition of MoAbs to chemotherapy, different studies up to now have explored the feasibility of chlorambucil-based chemoimmunotherapies in treatment-naïve CLL. COMPLEMENT1 is a prospective, randomized, open-label trial evaluating the efficacy and safety of ofatumumab added to chlorambucil, compared with chlorambucil in monotherapy, in the setting of untreated patients with CLL considered unsuitable for a fludarabine-based approach...
August 2016: Therapeutic Advances in Hematology
D Miguel, J Lukacs, T Illing, P Elsner
Necrobiotic xanthogranuloma (NXG) is an uncommon non-Langerhans cell histiocytosis involving skin and extracutaneous tissues. The lesions are usually asymptomatic and commonly appear in the periorbital area. Paraproteinemia is closely associated with NXG and its pathogenesis remains unclear. NXG prognosis is poor with several treatments showing variable results. Treatment of monoclonal gammopathy with alkylating agents does not necessarily influence the activity of the skin disease and vice versa. The aim of this systematic review is to summarize all reported treatments of necrobiotic xanthogranuloma of the skin, with or without underlying malignant condition and based on articles from the PubMed database using the query 'necrobiotic xanthogranuloma treatment', both in English and German, about 'human' subjects and published between 1980 and 2014, documenting adequate treatment for NXG...
July 19, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Saurav J Sarma, Aslam A Khan, Lalit N Goswami, Satish S Jalisatgi, M Frederick Hawthorne
The construction and application of a unique monodisperse closomer drug-delivery system (CDDS) integrating three different functionalities onto an icosahedral closo-dodecaborane [B12 ](2-) scaffold is described. Eleven B-OH vertices of [closo-B12 (OH)12 ](2-) were used to attach eleven copies of the anticancer drug chlorambucil and the targeting vector glucosamine through a bifurcating lysine linker. The remaining twelfth vertex was used to attach a fluorescent imaging probe. The presence of multiple glucosamine units offered a monodisperse and highly water-soluble CDDS with a high payload of therapeutic cargo...
August 26, 2016: Chemistry: a European Journal
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