A5003891938- Autophagy in Disease and Therapy
- Multiple Myeloma Research and Treatments
- Pharmaceutical Practices and Patient Outcomes
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- Pharmaceutical studies and practices
- Cancer Treatment and Pharmacology
- Safe Handling of Antineoplastic Drugs
- CRISPR and Genetic Engineering
- Chemotherapy-related skin toxicity
- Ubiquitin and proteasome pathways
- Innovations in Medical Education
- Chronic Lymphocytic Leukemia Research
- Glioma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Colorectal Cancer Treatments and Studies
- Protein Degradation and Inhibitors
- Antibiotics Pharmacokinetics and Efficacy
- Renal cell carcinoma treatment
- Biochemical and Molecular Research
- Cancer Diagnosis and Treatment
- Nuts composition and effects
- Spanish Literature and Culture Studies
- Histone Deacetylase Inhibitors Research
- Neutropenia and Cancer Infections
University of Arizona
2017-2024
London Cancer
2022
London School of Hygiene & Tropical Medicine
2022
Banner - University Medical Center Tucson
2020
Carle Foundation Hospital
2019
University of Arizona Cancer Center
2019
Vermont Oxford Network
2019
Philadelphia University
2009-2018
University of the Sciences
1997-2014
Abramson Cancer Center
2014
Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective this trial was to determine maximum tolerated dose (MTD) and HCQ in combination radiation therapy (RT) temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + phase I design followed by a noncomparative II study conducted GB patients after initial resection. Patients received (200 800 mg oral daily) RT concurrent adjuvant TMZ....
The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), autophagy augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, pharmacodynamics HCQ with TEM cancer patients. In escalation portion, 27 patients advanced solid malignancies were enrolled, followed by a cohort expansion at top level 12 metastatic melanoma. was well tolerated, grade 3 or 4...
Autophagy is a lysosome-dependent degradative process that protects cancer cells from multiple stresses. In preclinical models, autophagy inhibition with chloroquine (CQ) derivatives augments the efficacy of many anticancer therapies, but CQ has limited activity as single agent. Clinical trials are underway combining agents hydroxychloroquine (HCQ), concentrations HCQ required to inhibit not consistently achievable in clinic. We report synthesis and characterization bisaminoquinoline...
The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated activation the autophagy pathway as an alternative mechanism protein degradation. Preclinical studies demonstrate that with hydroxychloroquine augments antimyeloma inhibitor bortezomib. We conducted a phase I trial combining bortezomib and relapsed or refractory myeloma. enrolled 25 patients, including 11 (44%) to prior No protocol-defined dose-limiting toxicities occurred, we...
Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ combination dose-intense temozolomide (TMZ) patients advanced solid malignancies. Forty (73% metastatic melanoma) were treated oral 200 to 1200 mg daily TMZ 150 mg/m2 for 7/14 d. was well no recurrent dose-limiting toxicities...
We previously reported that inhibition of autophagy significantly augmented the anticancer activity histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. thus conducted first-in-human study to investigate safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) combination hydroxychloroquine (HCQ) VOR in patients with advanced solid tumors. Of 27 treated study, 24 were considered fully evaluable for assessments toxicity....
Everolimus inhibits the mTOR, activating cytoprotective autophagy. Hydroxychloroquine On basis of preclinical data demonstrating synergistic cytotoxicity when mTOR inhibitors are combined with an autophagy inhibitor, we launched a clinical trial everolimus and hydroxychloroquine, to determine its safety activity in patients clear-cell renal cell carcinoma (ccRCC).Three centers conducted phase I/II 10 mg daily hydroxychloroquine advanced ccRCC. The objectives were MTD everolimus, estimate...
Abstract Purpose: Preclinical evidence of synergy led to a phase I trial employing combretastatin A-4 phosphate (CA4P), novel tubulin-binding antivascular drug, in combination with carboplatin. Experimental Design: Based on preclinical scheduling studies, patients were treated day 1 21-day cycle. Carboplatin was given as 30-minute i.v. infusion and CA4P 60 minutes later 10-minute infusion. Results: Sixteen solid tumors received 40 cycles therapy at doses 27 36 mg/m2 together carboplatin area...
Abstract Introduction: Clinical research on the predictive value of PIK3CA mutations in hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2–) metastatic breast cancer (mBC) has advanced recent years. However, knowledge epidemiological prevalence not been systematically evaluated. This study aimed to report mutation using different biopsy techniques as well specific hotspot across available literature. Methods: A comprehensive search PubMed/MEDLINE, EMBASE,...
Abstract Introduction Tumors of the central nervous system are among leading causes cancer-related death in children. Population-based cancer survival reflects overall effectiveness a health care managing cancer. Inequity access to world-wide may result disparities. Methods We considered children (0–14 years) diagnosed with brain tumor during 2000–2014, regardless behavior. Data underwent rigorous, three-phase quality control as part CONCORD-3. implemented revised version International...
Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study determine tolerability efficacy gefitinib combination irinotecan, infusional 5-fluorouracil (5-FU) leucovorin (LV), on 2-week schedule. Among 13 patients advanced cancer, 10 required dose reductions 5-FU because...
Although ketorolac is commonly used as an analgesic in the pediatric population, there no information on pharmacokinetics of available for children less than 6 months age. The objective this analysis was to construct a population pharmacokinetic model describe disposition young children. Three neonates and 9 infants, median (range) age 0.4-32 weeks, were administered with 0.5 mg/kg ketorolac. data best described by 2-compartment model, allometric expression body weight effects clearance....
Abstract High-grade malignant peripheral nerve sheath tumors (MPNST) have a poor prognosis with limited responsiveness to systemic therapy. We document case of complete metabolic response pembrolizumab monotherapy in metastatic disease. Tumor molecular profiling identified programmed-death ligand-1 (PD-L1) positivity. This characteristic provided rationale for immune-checkpoint Treatment resulted after four cycles Patients PD-L1–positive, MPNST may be candidates therapy, which produce...
Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering and preventing managing adverse effects associated with this drug. In order to maximize quality life patients undergoing treatment, nurses need thorough knowledge its uses, administration, This article second two-part series about cisplatin. Part I provided review mechanism action, current administration...
HE ARTISTIC and intellectual climate in Spain at the end of nineteenth century developed under influence many European authorities preaching complex often conflicting ideologies. Several studies have defined nature scope Spanish indebtedness to such figures as Nietzsche, Ibsen, Zola, D'Annunzio.1 The reception interpretation Oscar Wilde not been investigated, despite a general acknowledgment his importance enduring appeal.2 history fortunes extends over least two generations, from Modernists...
Background. Protein calorie malnutrition, which is highly prevalent in tumor-bearing hosts, increases toxicity to 5-fluorouracil (5-FU), but the mechanisms are unclear. This study investigated effects of protein depletion on 5-FU vivo hepatic metabolism using F19-nuclear magnetic resonance spectroscopy (19F-NMRS). Methods. Rats received normal (21.5%) or low (2.5%) diet for 25 days. was injected intraperitoneally, and fluorine spectra were obtained. Parallel experiments conducted determine...
The purpose of the study was to demonstrate financial impact addition a dedicated orthopaedic traumatologist private group practice at Level II community-based trauma system.Retrospective review records.Level center and large practice.Office billing data were evaluated for 12 months before dedicated, hospital-based, 2-year period after hiring. Outcomes such as payor mix, collection rates, time breakeven, days off, call days, evenings worked, durable medical equipment, x-ray casting...
Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering and preventing managing adverse effects associated with this drug. In order to maximize quality life patients undergoing treatment, nurses need thorough knowledge its uses, administration, This article first two-part series about cisplatin. Part I will provide review mechanism action, current administration...