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https://www.readbyqxmd.com/read/28792728/an-environment-activatable-nanoprodrug-two-step-surveillance-in-the-anticancer-drug-release
#1
Sandipan Biswas, Joyjyoti Das, Shrabani Barman, Bhaskara Rao Pinninti, Tapas K Maiti, N D Pradeep Singh
Remedial cancer therapy deals with a large number of theranostic applications. However, systems, so far known, are only capable of single surveillance for both diagnostic and therapeutic modes of actions. A nanosystem, which can be localized to the cancer and deliver the chemotherapeutic agent on demand, will provide effective therapeutic activity. Herein, we designed a single component nanoprodrug ANPD-X (Activatable Nano Pro-Drug-X) which indentified the tumor sites by fluorescent colour change (signal 1, blue to green fluorescence) using H2O2-mediated oxidation of boronate fluorophore...
August 9, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28791810/cytotoxicity-of-anticancer-drugs-and-pj-34-poly-adp-ribose-polymerase-1-parp-1-inhibitor-on-hl-60-and-jurkat-cells
#2
Maciej Stępnik, Sylwia Spryszyńska, Anna Gorzkiewicz, Magdalena Ferlińska
BACKGROUND: The majority of the clinical trials with poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors were conducted or are ongoing in patients with solid tumors, while trials with leukemia patients are less frequent. Surprisingly scarce data is available on the combinatory effects of PARP inhibitors with DNA damaging antitumor drugs in leukemic cells (primary cells or established lines). OBJECTIVES: The aim of the present study was to assess the effect of PJ-34 (PARP-1 inhibitor) on the cytotoxicity of different antileukemic drugs with different DNA damaging mechanisms and potency (doxorubicin, etoposide, cytarabine and chlorambucil) in human leukemic Jurkat and HL-60 cells...
May 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28782884/chronic-lymphocytic-leukemia-2017-update-on-diagnosis-risk-stratification-and-treatment
#3
REVIEW
Michael Hallek
DISEASE OVERVIEW: Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B cells. DIAGNOSIS: The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen and B-cell markers...
September 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28759056/redox-responsive-xanthene-coumarin-chlorambucil-based-fret-guided-theranostics-for-activatable-combination-therapy-with-real-time-monitoring
#4
Moumita Gangopadhyay, Rakesh Mengji, Amrita Paul, Yarra Venkatesh, Venugopal Vangala, Avijit Jana, N D Pradeep Singh
A FRET donor-acceptor xanthene-coumarin conjugate has been designed for redox-regulated synergic treatment of photodynamic therapy and chemotherapy with real-time monitoring. The "locked" FRET pair was selectively "unlocked" by biological reducing thiols via rupture of a sacrificial disulfide linker. A distinct change in fluorescence color and selective cancer cell toxicity were observed in vitro.
July 31, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28720586/a-malt-lymphoma-prognostic-index-generated-from-the-dataset-of-the-ielsg-19-prospective-clinical-trial
#5
Catherine Thieblemont, Luciano Cascione, Annarita Conconi, Barbara Kiesewetter, Markus Raderer, Gianluca Gaidano, Maurizio Martelli, Daniele Laszlo, Bertrand Coiffier, Armando Lopez Guillermo, Valter Torri, Franco Cavalli, Peter W Johnson, Emanuele Zucca
There are no widely accepted prognostic indices for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). This study aimed to develop and validate a specific prognostic tool to personalize and optimize lymphoma treatment of patients with MALT lymphoma. A prognostic index was built by Cox regression (stepwise selection) using data from 401 patients enrolled in the international randomized IELSG-19 trial (NCT 00210353). A validation set, including 633 patients, was obtained by merging three independent cohorts of MALT lymphoma patients...
July 18, 2017: Blood
https://www.readbyqxmd.com/read/28720054/impact-of-novel-agents-on-patient-relevant-outcomes-in-patients-with-previously-untreated-cll-who-are-not-eligible-for-fludarabine-based-therapy
#6
Moushmi Singh, Stuart Mealing, Simona Baculea, Sarah Cote, Jo Whelan
BACKGROUND: Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings...
July 19, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28710962/discovery-of-potent-molecular-chimera-cm358-to-treat-human-metastatic-melanoma
#7
Y Gilad, H Tuchinsky, G Ben-David, R Minnes, A Gancz, H Senderowitz, G Luboshits, M A Firer, G Gellerman
The resistance of cancer cells to chemotherapeutic agents, whether through intrinsic mechanisms or developed resistance, motivates the search for new chemotherapeutic strategies. In the present report, we demonstrate a facile synthetic strategy towards the discovery of new anti-cancer substances. This strategy is based on simple covalent coupling between known anti-cancer drugs, which results in novel 'chimeric' small molecules. One of these novel compounds, CM358, is the product of an amide bond formation between the known Topoisomerase II (Topo II) inhibitor amonafide (AM) and the known DNA mustard alkylator chlorambucil (CLB)...
June 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28688466/leukemic-transformation-in-myeloproliferative-neoplasms-a-literature-review-on-risk-characteristics-and-outcome
#8
REVIEW
Meera Yogarajah, Ayalew Tefferi
Myeloproliferative neoplasms (MPNs) operationally include essential thrombocythemia, polycythemia vera, primary myelofibrosis (PMF), and prefibrotic PMF. All 4 MPN variants might progress into blast-phase disease (MPN-BP). For essential thrombocythemia, reported risk factors for leukemic transformation include advanced age, extreme thrombocytosis, anemia, leukocytosis, and sequence variants/mutations involving TP53 and EZH2 (for expansion of gene symbols, see www.genenames.org); for polycythemia vera, advanced age, leukocytosis, abnormal karyotype, mutations involving SRSF2 and IDH2, and treatment with pipobroman, chlorambucil, or P32; and for PMF, increased blast percentage, thrombocytopenia, abnormal karyotype, triple-negative driver mutational status, and sequence variants/mutations involving SRSF2, RUNX1, CEBPA, and SH2B3...
July 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28685928/management-of-patients-with-previously-untreated-chronic-lymphocytic-leukaemia-with-obinutuzumab-and-chlorambucil
#9
REVIEW
Constantine Tam, Bryone Kuss, Stephen Opat, Joy Boulos, Paula Marlton
Patients with chronic lymphocytic leukaemia (CLL) are generally older, with many considered 'unfit' for fludarabine-cyclophosphamide-rituximab therapy. In these patients, the combination of obinutuzumab-chlorambucil may be an appropriate therapeutic choice. Obinutuzumab-chlorambucil has been demonstrated to improve overall survival rates compared to chlorambucil alone and to improve progression-free survival and overall response rates compared to rituximab-chlorambucil. This combination can lead to certain toxicities that need to be addressed through appropriate patient selection, pre-medication and management...
July 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28669992/treatment-of-membranous-nephropathy-time-for-a-paradigm-shift
#10
REVIEW
Piero Ruggenenti, Fernando C Fervenza, Giuseppe Remuzzi
In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition...
July 3, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28596282/chlorambucil-plus-rituximab-as-front-line-therapy-for-elderly-and-or-unfit-chronic-lymphocytic-leukemia-patients-correlation-with-biologically-based-risk-stratification
#11
Luca Laurenti, Idanna Innocenti, Francesco Autore, Stefania Ciolli, Francesca Romana Mauro, Donato Mannina, Giovanni Del Poeta, Giovanni D'Arena, Massimo Massaia, Marta Coscia, Sandro Molica, Gabriele Pozzato, Dimitar G Efremov, Barbara Vannata, Roberto Marasca, Piero Galieni, Antonio Cuneo, Sonia Orlando, Alfonso Piciocchi, Riccardo Boncompagni, Donatella Vincelli, Anna Marina Liberati, Filomena Russo, Robin Foa'
No abstract text is available yet for this article.
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28592762/chronic-lymphocytic-leukemia-pathophysiology-and-current-therapy
#12
Jun Takizawa
Chronic lymphocytic leukemia (CLL) is the most frequent adult leukemia in western countries, but it is rare in Japan. Several mutations have been identified in patients with CLL using next-generation sequencing, but disease-specific mutations were not found. Some mutations, such as those in TP53, NOTCH1, SF3B, and BIRC3 are useful for risk stratification and prognosis prediction in patients with CLL. Strategies for treating CLL are rapidly evolving, with targeted agents such as the B-cell receptor signaling pathway inhibitors (ibrutinib, idelalisib), novel anti-CD20 monoclonal antibody (obinutuzumab), and Bcl-2 inhibitor (venetoclax) being approved by the US Food and Drug Administration...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28586717/conjugation-of-platinum-iv-complexes-with-chlorambucil-to-overcome-cisplatin-resistance-via-a-joint-action-mode-toward-dna
#13
Xiaodong Qin, Lei Fang, Feihong Chen, Shaohua Gou
Two platinum(IV) complexes were designed and prepared by conjugation of cisplatin and oxaliplatin units with a DNA-damaging agent, chlorambucil, respectively. By taking a joint action to enhance the damage of DNA, the conjugates displayed potent antitumor activity against all the tested cancer cell lines comparable to cisplatin and oxaliplatin, and notably could overcome cisplatin resistance at certain degree. Complex 4, a hybrid of cisplatin and chlorambucil, arrested the cell cycle at the S and G2 phases, distinctive from those of cisplatin and oxaliplatin...
September 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28573505/comparative-efficacy-of-ibrutinib-versus-obinutuzumab%C3%A2-%C3%A2-chlorambucil-in-first-line-treatment-of-chronic-lymphocytic-leukemia-a-matching-adjusted-indirect-comparison
#14
Suzy Van Sanden, Simona Baculea, Joris Diels, Sarah Cote
INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias...
July 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28565930/current-perspectives-on-the-role-of-chemotherapy-in-chronic-lymphocytic-leukemia
#15
Clemens-Martin Wendtner, Michael Gregor
Chemotherapy has long been integral to the treatment of chronic lymphocytic leukemia (CLL). Fludarabine/cyclophosphamide, chlorambucil and bendamustine are commonly used as a backbone, depending on the patient's age and general health. The advent of the anti-CD20 monoclonal antibodies, such as rituximab and obinutuzumab, altered the face of treatment, and chemoimmunotherapy still forms the current standard first-line approach. However, the landscape is changing following the emergence of novel targeted agents, such as ibrutinib, idelalisib and venetoclax, which offer the chance for improved efficacy over standard therapy alone, with no substantial increase in toxicity...
June 1, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28560846/outcome-following-treatment-of-feline-gastrointestinal-mast-cell-tumours
#16
L E Barrett, K Skorupski, D C Brown, N Weinstein, C Clifford, A Szivek, S Haney, S Kraiza, E L Krick
Prognosis of feline gastrointestinal mast cell tumours (FGIMCT), based on limited available literature, is described as guarded to poor, which may influence treatment recommendations and patient outcome. The purpose of this study is to describe the clinical findings, treatment response, and outcome of FGIMCT. Medical records of 31 cats diagnosed with and treated for FGIMCT were retrospectively reviewed. Data collected included signalment, method of diagnosis, tumour location (including metastatic sites), treatment type, cause of death and survival time...
May 31, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28545160/-99m-tc-labeled-ngr-chlorambucil-conjugate-99m-tc-hynic-clb-c-ngr-for-targeted-chemotherapy-and-molecular-imaging
#17
Kusum Vats, Drishty Satpati, Rohit Sharma, Chandan Kumar, Haladhar D Sarma, Ashutosh Dash
Targeted delivery of chemotherapeutic drug at the tumor site enhances the efficacy with minimum systemic exposure. Towards this, drugs conjugated with peptides having affinity towards a particular molecular target are recognized as affective agents for targeted chemotherapy. Thus, in the present study, tumor-homing asparagine-glycine-arginine (NGR) peptide ligand was conjugated to DNA alkylating nitrogen mustard, chlorambucil (CLB). The peptide-drug conjugate (PDC), CLB-c(NGR), was radiolabeled with (99m) Tc-HYNIC core to trace its pharmacokinetics and biodistribution pattern...
May 25, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28479418/development-of-an-assay-for-cellular-efflux-of-pharmaceutically-active-agents-and-its-relevance-to-understanding-drug-interactions
#18
Benigno C Valdez, Moustapha Hassan, Borje S Andersson
Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs, and understanding how these drugs interact is of the utmost importance. The pharmacokinetics of busulfan, melphalan, and cyclophosphamide, drugs commonly used for HSCT, are known to be affected by a variety of other drugs with differing molecular structures. We hypothesized that these structurally unrelated drugs affect the transport of DNA-alkylating agents...
August 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28477146/inducing-controlled-release-and-increased-tumor-targeted-delivery-of-chlorambucil-via-albumin-liposome-hybrid-nanoparticles
#19
Quan Zhang, Li Zhang, Zemin Li, Xingliang Xie, Xiurong Gao, Xiaohong Xu
Liposomes possess good biocompatibility and excellent tumor-targeting capacity. However, the rapid premature release of lipophilic drugs from the lipid bilayer of liposomes has negative effect on the tumor-targeted drug delivery of liposomes. In this study, a lipophilic antitumor drug-chlorambucil (CHL)-was encapsulated into the aqueous interior of liposomes with the aid of albumin to obtain the CHL-loaded liposomes/albumin hybrid nanoparticles (CHL-Hybrids). The in vitro accumulative release rate of CHL from CHL-Hybrids was less than 50% within 48 h, while the accumulative CHL release was more than 80% for CHL-loaded liposomes (CHL-Lip)...
May 5, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28470340/comprehensive-strategy-for-the-design-of-precision-drugs-and-identification-of-genetic-signature-behind-proneness-of-the-disease-a-pharmacogenomic-approach
#20
REVIEW
Preethi M Iyer, S Karthikeyan, P Sanjay Kumar, P K Krishnan Namboori
The proneness of diseases and susceptibility towards drugs vary from person to person. At present, there is a strong demand for the personalization of drugs. The genetic signature behind proneness of the disease has been studied through a comprehensive 'octopodial approach'. All the genetic variants included in the approach have been introduced. The breast cancer associated with BRCA1 mutation has been taken as the illustrative example to introduce all these factors. The genetic variants associated with the drug action of tamoxifen have been fully illustrated in the manuscript...
July 2017: Functional & Integrative Genomics
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