Leukeran (chlorambucil) / GSK 
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  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Enhanced Sampling Molecular Dynamics Simulations Reveal Transport Mechanism of Glycoconjugate Drugs through GLUT1. (Pubmed Central) -  May 25, 2024   
    Here, we employed all-atom molecular dynamics simulations, coupled to steered and umbrella sampling techniques, to examine the thermodynamics governing the transport of glucose and two glycoconjugate drugs (i.e., 6-D-glucose-conjugated methane sulfonate and 6-D-glucose chlorambucil) by GLUT1...Importantly, our results described, for the first time, the free energy profiles of GLUT1-transporting glycoconjugate drugs, and demonstrated that H160 and W388 served as important gates to regulate their transport via GLUT1. These findings provide novel atomic-scale insights for understanding the transport mechanism of GLUT1, facilitating the discovery and rational design of GLUT1-targeted anticancer drugs.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Review, Journal:  Pharmacology of drugs used in autoimmune dermatopathies in cats and dogs: A narrative review. (Pubmed Central) -  May 6, 2024   
    This review paper will focus on the mechanism of action, pharmacokinetics and pharmacodynamics, clinical uses and adverse effects of immunosuppressive drugs used to treat autoimmune dermatoses in cats and dogs. These include glucocorticoids, ciclosporin A, azathioprine, chlorambucil, mycophenolate mofetil, oclacitinib and Bruton's tyrosine kinase inhibitors.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal, Lipid Nanoparticle:  Delivery of Chlorambucil to the Brain Using Surface Modified Solid Lipid Nanoparticles. (Pubmed Central) -  May 3, 2024   
    The in vivo biodistribution and brain uptake in C57BL6 mice and SPECT/CT imaging in Wistar rats investigated using 99mTc-labeled SLN and autoradiography suggest that the SLNs have an increasing brain uptake. We have demonstrated the delivery of the anticancer drug chlorambucil (CLB) to glioma.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal, Combination therapy, Metastases:  Dual-responsive chondroitin sulfate self-assembling nanoparticles for combination therapy in metastatic cancer cells. (Pubmed Central) -  Mar 15, 2024   
    Our study confirmed the guarded prognosis of MRD in cats and identified risk factors for shorter survival times. In this study, we developed self-assembling nanoparticles (LCPs) able to trigger the release of Chlorambucil (Chl) and Doxorubicin (DOX) to MDA-MB-231 cells by exploiting the enzyme and redox signals...The results allowed the selective release of the payloads to be detected: Chl release of 0 and 41% were obtained after 2
  • ||||||||||  Leukeran (chlorambucil) / GSK
    True dsDNA Hydrogels: Design, synthesis, and applications (In-person; Mardi Gras Blrm Salon C (New Orleans Marriott)) -  Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_104;    
    To achieve this, we functionalized polyethylene glycol (PEG, M w = 2000) with chlorambucil, diethanolamine, and 2-(methylamino)ethanol...We also demonstrate that the mechanical properties of our hydrogels can easily be tuned by changing cross-linker concentration and identity. We are currently exploring the potential of this new class of DNA materials to be used as a model network to study polymer structure-property relationships, as scaffolds for 3D cell culture, and for cell-free protein/mRNA synthesis.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Review, Journal:  Pt(IV) Complexes in the Search for Novel Platinum Prodrugs with Promising Activity. (Pubmed Central) -  Feb 24, 2024   
    We have discussed the structure activity relationship (SAR) and the effects of the ligands on the biological activity of Pt(IV) complexes with cisplatin, oxaliplatin, carboplatin and the Pt core other than approved drugs. This literature work will help researchers to get an idea about Pt(IV) complexes that have been classified based on the aspects of their biological activity.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  A Novel Adductomics Workflow Incorporating FeatureHunter Software: Rapid Detection of Nucleic Acid Modifications for Studying the Exposome. (Pubmed Central) -  Jan 10, 2024   
    The capability and effectiveness of FeatureHunter was demonstrated by analyzing various NA modifications induced by formaldehyde or chlorambucil in mixtures of calf thymus DNA, yeast RNA and proteins, and by analyzing the NA modifications present in the pooled urines of smokers and nonsmokers. The incorporation of FeatureHunter into the NA adductomics workflow offers a powerful tool for the identification and classification of various types of NA modifications induced by reactive chemicals in complex biological samples, providing a valuable resource for studying the exposome.
  • ||||||||||  Retrospective data, Review, Journal:  Group I pharmaceuticals of IARC and associated cancer risks: systematic review and meta-analysis. (Pubmed Central) -  Jan 8, 2024   
    Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen?+?oncovin?+?procarbazine?+?prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen?+?ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide?+?bleomycin?+?cisplatin and treosulfan]. In the systematic review, methoxsalen?+?UV and MOPP were
  • ||||||||||  Journal:  Dual-targeted regimens for the frontline treatment of CLL. (Pubmed Central) -  Dec 9, 2023   
    These dual-targeted regimens provide remarkable efficacy while allowing for an all-oral approach and fixed duration of treatment. Current investigations under way are evaluating the utility of a triplet approach with the addition of obinutuzumab in comparison to a doublet approach.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal, Combination therapy:  Prolonging Treatment Window of Photodynamic Therapy with Self-Amplified H O -Activated Photodynamic/Chemo Combination Therapeutic Nanomedicines. (Pubmed Central) -  Nov 27, 2023   
    DPPa NP is prepared via encapsulating a hydrophobic oxidized bovine serum albumin (BSA-SOH)-conjugatable PS DPPa with amphiphilic H O -activatable chlorambucil (CL) prodrug mPEG-TK-CL...More importantly, such conjugation transfers DPPa from a small molecule PS into a macromolecular PS with long tumor retention time and treatment window of PDT, which enables multiple PDT. This study thus provides an effective strategy to prolong the treatment window of PDT and enables tumor-specific fluorescence imaging-guided combination therapy.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Review, Journal:  Therapy of necrobiotic xanthogranuloma - case series and review of the literature. (Pubmed Central) -  Nov 13, 2023   
    The combination of prednisolone and chlorambucil as well as intravenous immunoglobulins seem to be effective therapeutic options. We present four cases from our clinic as well as the current results of the literature in this mini-review and would like to highlight the therapeutic challenge as well as the need for the development of guidelines.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal:  Synchronized activating therapeutic nano-agent: Enhancement and tracing for hypoxia-induced chemotherapy. (Pubmed Central) -  Nov 6, 2023   
    In this nano-prodrug, a self-destructive tether is introduced to break the mindset, and achieves the activation by hypoxia of chemotherapy based on Chlorambucil (CB), whose efficacy can be augmented and traced by photodynamic therapy (PDT) and fluorescence from Cyanine dyes (Cy)...Experiments demonstrate that Mal@Cy-NTR-CB specifically responds to hypoxic tumors, and achieve synchronous activation, enhancement and feedback of chemotherapy and PDT, inhibiting the tumor growth effectively. This study broadens the design ideas of activatable prodrugs and provides the possibility of multifunctional nano-prodrugs to improve the generalization and prognosis in precision oncology.
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Journal, Combination therapy:  Hypoxia-Responsive Tetrameric Supramolecular Polypeptide Nanoprodrugs for Combination Therapy. (Pubmed Central) -  Nov 5, 2023   
    stacking, and host-guest interactions...Both in vitro and in vivo biological studies showcased synergistic cancer-killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia-responsive nanoprodrug for potential combo PDT-CT transition.
  • ||||||||||  Calquence (acalabrutinib) / AstraZeneca
    Elevate-TN: Impact of First-Year Dose Modifications in Patients with Treatment-Naive Chronic Lymphocytic Leukemia Treated with Acalabrutinib (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_6095;    
    P3
    OS outcomes in patients who required dose reductions or breaks but did not discontinue treatment in the first year were similar to those in patients who did not require dose modification. Accepting the limitations of retrospective analysis, these data suggest that patients who are unable to tolerate standard-dose acala or who require treatment breaks may benefit from continuing or resuming treatment at a reduced dose rather than stopping treatment altogether.
  • ||||||||||  Calquence (acalabrutinib) / AstraZeneca
    Analysis of Ventricular Arrhythmias and Sudden Death with Acalabrutinib from 5 Prospective Clinical Trials (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_6093;    
    Accepting the limitations of retrospective analysis, these data suggest that patients who are unable to tolerate standard-dose acala or who require treatment breaks may benefit from continuing or resuming treatment at a reduced dose rather than stopping treatment altogether. Incidence and relative risk of nonfatal and fatal VAs and SDs were analyzed using pooled data from 5 prospective acalabrutinib clinical trials (nonrandomized trials: CL-001 [acalabrutinib monotherapy], CL-003 [acalabrutinib + obinutuzumab]; randomized trials: CL-006 [acalabrutinib vs ibrutinib], CL-007 [acalabrutinib
  • ||||||||||  Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
    Frequency and Outcomes of Obinutuzumab-Induced Thrombocytopenia (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_5383;    
    Methods After obtaining local ethics review, we collected the total number of patients who received Obi as part of multi-agent chemotherapy for the following hematological diseases from 01/01/2015 -01/01/2023: FL (Obi-bendamustine +/- Obi maintenance; Obi-cyclophosphamide/vincristine/prednisone +/-doxorubicin +/- Obi maintenance, Obi-Zanubrutinib (Rosewood trial) and CLL (Obi-venetoclax; Obi-chlorambucil)...Obi was changed to rituximab...It may be self-limiting whereas some cases have been treated with steroids, IVIg, and TPO-RA. Further studies are required to delineate the incidence, pathophysiology, diagnosis, and management.
  • ||||||||||  Lunsumio (mosunetuzumab) / Roche, Biogen
    Marsun, a Phase III, Multicenter, Open Label, Randomized, Controlled Study Investigating Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients with Relapsed or Refractory Margin... (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_4013;    
    Previous treatment lines must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles) with or without chemotherapy (CHOP, bendamustine, CVP, chlorambucil) or targeted treatment such as ibrutinib...For each patient, investigator choice must be decided before randomization between R-Len (12 cycles) and R-chemotherapy (R-Bendamustine or R-CHOP followed by a 6 months maintenance)...The study will comprise a first stage of 10 patients in a safety cohort with mosunetuzumab-lenalidomide followed by a stage 2 with patients randomized 1:1 to receive M-len or investigator choice (125 patients per arm). The sponsor of the trial is the Lymphoma Academic Research Organisation (LYSARC) in collaboration with GLA and FIL with the support of F.Hoffmann-La Roche Ltd.
  • ||||||||||  Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
    Acalabrutinib  (Grand Hyatt - Seaport Ballroom ABCD) -  Nov 3, 2023 - Abstract #ASH2023ASH_3320;    
    P3
    With a median follow-up of 74.5 mo, the efficacy and safety of A+O and A monotherapy were maintained in pts with TN CLL, including in pts with high-risk genetic features. At 6 years of follow-up, PFS was significantly longer in pts treated with A+O vs A. Median OS was NR in any treatment arm and was significantly longer in pts treated with A+O vs O+Clb.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Imbruvica (ibrutinib) / AbbVie, J&J
    First-Line Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) Versus Chlorambucil Plus Obinutuzumab (Clb+O): 55-Month Follow-up from the Glow Study (Grand Hyatt - Seaport Ballroom ABCD) -  Nov 3, 2023 - Abstract #ASH2023ASH_3318;    
    P3
    Among patients treated with Ibr+Ven, benefit in PFS was particularly observed in patients with uIGHV who achieved uMRD at EOT+3 and in patients with mIGHV regardless of MRD status at EOT+3. Moreover, Ibr+Ven fixed-duration combination treatment continues to demonstrate an OS advantage versus chemoimmunotherapy in patients with previously untreated CLL.
  • ||||||||||  Zydelig (idelalisib) / Gilead
    Immunomodulatory Effects of Chemo-Immunotherapy  (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_1863;    
    P3
    Patients were randomly assigned to receive ofatumumab plus either bendamustine or chlorambucil, with or without idelalisib. CIT results in profound immune changes that persists up to 18.5 [16.1
  • ||||||||||  Leukeran (chlorambucil) / GSK
    Review, Journal:  Chlorambucil-Bearing Hybrid Molecules in the Development of Potential Anticancer Agents. (Pubmed Central) -  Oct 14, 2023   
    Hence, its combination with other pharmacophores has been reported to result in effective anticancer agents with fewer side effects and high therapeutic outcomes. Furthermore, this review gives an update (2010 to date) on the developments of chlorambucil hybrid compounds with anticancer activity, and the structure-activity relationship (SAR), and also highlights future strategies for developing novel anticancer agents.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
    Expanded T-cell clones in CLL persist during combination therapy with BCL-2 inhibitor Venetoclax (X1) -  Sep 30, 2023 - Abstract #DGHO2023DGHO_288;    
    P3
    In this small subset of patients with MRD relapse after ClbG or VenG patient groups showed different clonal expansion. Whether the observed results are caused by biological factors or the treatment has to be investigated on larger patient numbers.