164 results match your criteria paclitaxel 4-fold

Redox-responsive prodrug for improving oral bioavailability of paclitaxel through bile acid transporter-mediated pathway.

Int J Pharm 2021 Mar 19;600:120496. Epub 2021 Mar 19.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

Most anticancer drugs are not orally bioavailable due to their undesirable physicochemical properties and inherent physiological barriers. In this study, a polymeric prodrug strategy was presented to enhance the oral bioavailability of BCS class IV drugs using paclitaxel (PTX) as the model drug. PTX was covalently conjugated with cholic acid-functionalized PEG by a redox-sensitive disulfide bond. Read More

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Dramatic Response in a Patient with Metastatic Gastric Cancer Using Trifluridine/Tipiracil after Rapid Disease Progression while on Nivolumab.

Case Rep Oncol 2020 Sep-Dec;13(3):1381-1386. Epub 2020 Nov 30.

Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

The introduction of immune checkpoint inhibitors has redefined the treatment strategy and changed the way tumor assessments are made because of its response pattern. Studies have suggested that initiating chemotherapy after checkpoint inhibitors may have high anti-tumor activity in some cancer types. This response pattern has not been reported in patients with gastric cancer, and particularly for the combination of trifluridine/tipiracil. Read More

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November 2020

2-methoxyestradiol sensitizes breast cancer cells to taxanes by targeting centrosomes.

Oncotarget 2020 Dec 1;11(48):4479-4489. Epub 2020 Dec 1.

Department of Obstetrics and Gynecology, Maternal-Fetal Pharmacology and Biodevelopment Laboratories, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.

Centrosomes amplification is a hallmark of cancer. We hypothesize that 2-methoxyestradiol (2-ME) sensitizes breast cancer (BC) cells to taxanes by targeting amplified centrosomes. We assessed the extent by which 2-ME together with paclitaxel (PTX) induces centrosome alterations with subsequent mitotic catastrophe in different BC subtypes. Read More

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December 2020

Paclitaxel-Loaded Colloidal Silica and TPGS-Based Solid Self-Emulsifying System Interferes Akt/mTOR Pathway in MDA-MB-231 and Demonstrates Anti-tumor Effect in Syngeneic Mammary Tumors.

AAPS PharmSciTech 2020 Nov 9;21(8):313. Epub 2020 Nov 9.

Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031, India.

A solid self-emulsifying drug delivery system (SEDDS) of paclitaxel (PTX) was developed that could enhance its oral bioavailability and neutralize other niggles associated with conventional delivery systems of PTX. TPGS-centered SEDDS containing PTX was optimized by Box-Behnken experimental design and then formulated as fumed colloidal silica-based solid SEDDS microparticles (Si-PTX-S-SEDDS). AFM analysis exhibited round-shaped microparticles of approximately 2-3 μM diameter, whereas after reconstitution, particle size measurement showed nanoemulsion droplets of 30. Read More

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November 2020

F-FAraG PET for CD8 Profiling of Tumors and Assessment of Immunomodulation by Chemotherapy.

J Nucl Med 2020 Nov 6. Epub 2020 Nov 6.

CellSight Technologies, United States.

Majority of the clinical trials exploring various combinations of chemo- and immunotherapy rely on serial biopsy to provide information on immune response. The aim of this study was to assess the value of F-FAraG as a non-invasive tool that could profile tumors based on the key players in adaptive antitumor response, CD8+ cells, and evaluate immunomodulatory effects of chemotherapy. To evaluate the ability of F-FAraG to report on the presence of CD8+ cells within the TME, we imaged a panel of syngeneic tumor models (MC38, CT26, LLC, A9F1, 4T1 and B16F10), and correlated the signal intensity with the number of lymphocytes found in the tumors. Read More

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November 2020

The AST/ALT (De Ritis) ratio predicts clinical outcome in patients with pancreatic cancer treated with first-line nab-paclitaxel and gemcitabine: analysis of an Austrian multicenter, noninterventional study.

Ther Adv Med Oncol 2020 10;12:1758835919900872. Epub 2020 Apr 10.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, 8036, Austria.

Background: The pretreatment De Ritis ratio [aspartate transaminase (AST)/alanine transaminase (ALT)] has been shown to be an adverse prognostic marker in various cancer entities. However, its relevance to advanced pancreatic ductal adenocarcinoma (PDAC) has not yet been studied. In the present study we investigated the AST/ALT ratio as a possible predictor of treatment response and disease outcome in patients with advanced PDAC treated with first-line gemcitabine/nab-paclitaxel. Read More

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P-Glycoprotein Inhibition Exacerbates Paclitaxel Neurotoxicity in Neurons and Patients With Cancer.

Clin Pharmacol Ther 2020 Sep 23;108(3):671-680. Epub 2020 May 23.

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.

Paclitaxel-induced peripheral neuropathy (PIPN) is a common and dose-limiting adverse event. The role of P-glycoprotein (P-gp) in the neuronal efflux of paclitaxel was assessed using a translational approach. SH-SY5Y cells were differentiated to neurons and paclitaxel toxicity in the absence and presence of a P-gp inhibitor was determined. Read More

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September 2020

Alteration in the Plasma Concentrations of Endogenous Organic Anion-Transporting Polypeptide 1B Biomarkers in Patients with Non-Small Cell Lung Cancer Treated with Paclitaxel.

Drug Metab Dispos 2020 05 29;48(5):387-394. Epub 2020 Feb 29.

Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, the University of Tokyo, Tokyo, Japan (D.M., T.M., Y.K., G.N., K.M., H.K.); Division of Medical Oncology, Department of Medicine (H.I., Y.S.), and Division of Respiratory Medicine and Allergology, Department of Medicine (S.K.), Showa University School of Medicine, Tokyo, Japan; Drug Metabolism and Pharmacokinetics Tsukuba, Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan (S.I., Y.N.); and Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, Showa University School of Pharmacy, Tokyo, Japan (K.-i.F.)

Paclitaxel has been considered to cause OATP1B-mediated drug-drug interactions at therapeutic doses; however, its clinical relevance has not been demonstrated. This study aimed to elucidate in vivo inhibition potency of paclitaxel against OATP1B1 and OATP1B3 using endogenous OATP1B biomarkers. Paclitaxel is an inhibitor of OATP1B1 and OATP1B3, with K of 0. Read More

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In Vivo Evaluation of Dual-Targeted Nanoparticles Encapsulating Paclitaxel and Everolimus.

Cancers (Basel) 2019 May 29;11(6). Epub 2019 May 29.

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.

A synergistic combination of paclitaxel (PTX) and everolimus (EVER) can allow for lower drug doses, reducing the toxicities associated with PTX, while maintaining therapeutic efficacy. Polymeric nanoparticles (NPs) of high stability provide opportunities to modify the toxicity profile of the drugs by ensuring their delivery to tumor at the synergistic ratio while limiting systemic drug exposure and the toxicities that result. The current study goal is to study the in vivo fate of human epidermal factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) dual-targeted PTX+EVER-loaded NPs (Dual-NPs) in an MDA-MB-231-H2N BC tumor-bearing mouse model. Read More

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Increasing Radiation Dose to the Thoracic Marrow Is Associated With Acute Hematologic Toxicities in Patients Receiving Chemoradiation for Esophageal Cancer.

Front Oncol 2019 15;9:147. Epub 2019 Mar 15.

Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, United States.

To test the hypothesis that increasing radiation dose to the thoracic marrow (TM) contributes to the development of hematologic toxicities (HT) in esophageal cancer (EC) patients receiving chemoradiation therapy (CRT). We identified EC cases treated with curative intent CRT at our institution from 2007 to 2016. The TM was contoured as the union of the vertebral bodies (VB) from T1-L1, the ribs from T1-L1, and the sternum. Read More

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QbD-Based Development of Cationic Self-nanoemulsifying Drug Delivery Systems of Paclitaxel with Improved Biopharmaceutical Attributes.

AAPS PharmSciTech 2019 Feb 21;20(3):118. Epub 2019 Feb 21.

UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.

The present studies describe quality-by-design-based design and characterization of cationic self-nanoemulsifying formulations of paclitaxel for improving its biopharmaceutical attributes. Solubility and phase titration experiments were designed to select the lipidic and emulsifying excipients. Two different types of lipidic nanoformulations were developed using medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs). Read More

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February 2019

Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis.

Theranostics 2018 15;8(10):2830-2845. Epub 2018 Apr 15.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.

Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model targeting CD44 and intracellular, rather than extracellular, MMPs. Read More

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Establishment and characterization of a triple negative basal-like breast cancer cell line with multi-drug resistance.

Oncol Lett 2017 Oct 23;14(4):5039-5045. Epub 2017 Aug 23.

Department of Pathology, Kazan State Medical University, Kazan 420012, Russia.

Triple-negative breast carcinoma (TNBC) is one of the most aggressive subtypes of breast cancer and is associated with an unfavorable prognosis. The management of TNBC is currently based on the use of classical cytotoxic drugs, i.e. Read More

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October 2017

Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition.

J Pharm Sci 2018 02 19;107(2):698-705. Epub 2017 Sep 19.

Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address:

Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) coencapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45. Read More

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February 2018

Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models.

Eur J Pharm Sci 2017 Nov 19;109:131-143. Epub 2017 Jul 19.

Institute of Biomedical Sciences, University of São Paulo, Brazil. Electronic address:

Considering that tumor development is generally multifactorial, therapy with a combination of agents capable of potentiating cytotoxic effects is promising. In this study, we co-encapsulated C6 ceramide (0.35%) and paclitaxel (0. Read More

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November 2017

Tumortropic adipose-derived stem cells carrying smart nanotherapeutics for targeted delivery and dual-modality therapy of orthotopic glioblastoma.

J Control Release 2017 05 21;254:119-130. Epub 2017 Mar 21.

Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan. Electronic address:

Chemotherapy is typically used to treat malignant brain tumors, especially for the tumors in surgically inaccessible areas. However, owing to the existence of blood-brain barrier (BBB), the tumor accumulation and therapeutic efficacy of clinical therapeutics is still of great concerns. To this end, we present herein a prominent therapeutic strategy adopting adipose-derived stem cells (ADSCs) capable of carrying nanotherapeutic payloads selectively toward brain tumors for thermo/chemotherapy. Read More

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An in vitro demonstration of overcoming drug resistance in SKOV3 TR and MCF7 ADR with targeted delivery of polymer pro-drug conjugates.

J Drug Target 2017 Jun 5;25(5):436-450. Epub 2017 Jan 5.

a Department of Pharmaceutical Sciences , Northeastern University , Boston , MA , USA.

Drug resistance is a common phenomenon that occurs in cancer chemotherapy. Delivery of chemotherapeutic agents as polymer pro-drug conjugates (PPDCs) pretargeted with bispecific antibodies could circumvent drug resistance in cancer cells. To demonstrate this approach to overcome drug resistance, Paclitaxel (Ptxl)-resistant SKOV3 TR human ovarian- and doxorubicin (Dox)-resistant MCF7 ADR human mammary-carcinoma cell lines were used. Read More

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Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids.

Neurooncol Pract 2016 Dec 11;3(4):245-260. Epub 2015 Oct 11.

Department of Neurology, Medical Center Haaglanden, The Hague, Netherlands (C.B.); Service Neurologie Mazarin, GH Pitié-Salpêtrière, Paris, France (C.J.V.).

Patients with cancer commonly experience seizures. Combined therapy with anticonvulsant drugs (AEDs) and chemotherapeutic drugs or tyrosine kinase inhibitors carries inherent risks on drug-drug interactions (DDIs). In this review, pharmacokinetic studies of AEDs with chemotherapeutic drugs, tyrosine kinase inhibitors, and glucocorticoids are discussed, including data on maximum tolerated dose, drug clearance, elimination half-life, and organ exposure. Read More

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December 2016

MxA Is a Novel Regulator of Endosome-Associated Transcriptional Signaling by Bone Morphogenetic Proteins 4 and 9 (BMP4 and BMP9).

PLoS One 2016 22;11(11):e0166382. Epub 2016 Nov 22.

Department of. Cell Biology & Anatomy, and Department of Medicine, New York Medical College, Valhalla, New York, United States of America.

There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2. Read More

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Engineering of Taxadiene Synthase for Improved Selectivity and Yield of a Key Taxol Biosynthetic Intermediate.

ACS Synth Biol 2017 02 4;6(2):201-205. Epub 2016 Nov 4.

Whitehead Institute for Biomedical Research , 9 Cambridge Center, Cambridge, Massachusetts 02142, United States.

Attempts at microbial production of the chemotherapeutic agent Taxol (paclitaxel) have met with limited success, due largely to a pathway bottleneck resulting from poor product selectivity of the first hydroxylation step, catalyzed by taxadien-5a-hydroxylase (CYP725A4). Here, we systematically investigate three methodologies, terpene cyclase engineering, P450 engineering, and hydrolase-enzyme screening to overcome this early pathway selectivity bottleneck. We demonstrate that engineering of Taxadiene Synthase, upstream of the promiscuous oxidation step, acts as a practical method for selectivity improvement. Read More

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February 2017

Synergistic effect of piperine and paclitaxel on cell fate via cyt-c, Bax/Bcl-2-caspase-3 pathway in ovarian adenocarcinomas SKOV-3 cells.

Eur J Pharmacol 2016 Nov 15;791:751-762. Epub 2016 Oct 15.

Photobiology Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, India. Electronic address:

Background And Aims: Ovarian cancer is fourth most common and lethal among all gynecologic malignancies. The chemotherapy usually requires in all stages of ovarian cancer but drugs have several side effects. We hypothesized that use of combination therapy of paclitaxel (PTX) and phytochemical piperine (PIP) may reduce the PTX dose as well as toxicity. Read More

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November 2016

F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial.

Clin Cancer Res 2017 Mar 1;23(6):1432-1441. Epub 2016 Sep 1.

Medical Oncology Department, Hospital Universitario La Princesa, Madrid, Spain.

We previously detected promising efficacy of neoadjuvant nintedanib (a multityrosine kinase inhibitor, TKI) in early HER2-negative breast cancer. In a preclinical study, we monitored stromal hypoxia with F-fluoromisonidazole-positron emission tomography (18F-FMISO-PET); we found that reoxygenation of tumors (or lack of it) during a window-of-opportunity (WoO) treatment with TKIs correlated with the benefit (or lack of it) from TKI-plus-chemotherapy combinations. We studied the predictive role of 18F-FMISO-PET for the TKI nintedanib in the neoadjuvant setting in a phase II WoO randomized trial. Read More

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Bile salt liposomes for enhanced lymphatic transport and oral bioavailability of paclitaxel.

Pharmazie 2016 Jun;71(6):320-6

Paclitaxel (PTX), a BCS class IV drug that is characterized by its poor solubility and is a substrate for P-glycoprotein, is one of the most widely used antineoplastic agents. However, oral administration of PTX for chemotherapy is highly challenging. The aim of this study was to develop bile-salt liposomes (BS-Lips) to enhance the absorption of PTX and thus improve its therapeutic outcome. Read More

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Core-shell nanocarriers with high paclitaxel loading for passive and active targeting.

Sci Rep 2016 06 9;6:27559. Epub 2016 Jun 9.

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P.R. China.

Rapid blood clearance and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor tumor selectivity. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide homing to αVβ3 integrins. Herein, core-shell nanocapsules (NCs) and iRGD-modified NCs (iRGD-NCs) with high drug payload for paclitaxel (PTX) were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Read More

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Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel.

Int J Nanomedicine 2016 11;11:2009-19. Epub 2016 May 11.

Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. Read More

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February 2017

Improved safety and efficacy of a lipid emulsion loaded with a paclitaxel-cholesterol complex for the treatment of breast tumors.

Oncol Rep 2016 Jul 6;36(1):399-409. Epub 2016 May 6.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, P.R. China.

The aim of the present study was to develop a lipid emulsion loaded with a paclitaxel-cholesterol complex (PTX-CH Emul) in order to improve the safety and efficacy of paclitaxel (PTX) and evaluate its antitumor activity against commercially available formulation Taxol®. PTX-CH Emul resembling a low density lipoprotein lipid structure, exhibited an ideal particle size, high drug loading capability, high drug encapsulation efficiency and excellent stability. PTX-CH Emul showed superior in vitro anticancer efficacy against triple-negative MDA-MB-231 breast cancer cells when compared with a paclitaxel emulsion (PTX Emul) and Taxol. Read More

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An iTEP-salinomycin nanoparticle that specifically and effectively inhibits metastases of 4T1 orthotopic breast tumors.

Biomaterials 2016 07 22;93:1-9. Epub 2016 Mar 22.

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:

Cancer stem cell (CSC) inhibitors are a new category of investigational drugs to treat metastasis. Salinomycin (Sali) is one of most studied CSC inhibitors and has reached clinical tests. Several drug carriers have been developed to improve efficacy of Sali. Read More

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Sialoganglioside Micelles for Enhanced Paclitaxel Solubility: In Vitro Characterization.

J Pharm Sci 2016 Jan 23;105(1):268-75. Epub 2015 Dec 23.

Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Cátedra de Biotecnología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina. Electronic address:

Efficiency of mono-sialogangliosides to load Paclitaxel (Ptx) has recently been found to depend on the structure of the polysaccharide chain. In this study, we demonstrated that incorporation of only one more sialic acid into the ganglioside molecule, independently of its position, causes a 4-fold increase in Ptx-loading capacity, the maximum being at a 5:1 molar ratio (di-sialoganglioside/Paclitaxel, GD/Ptx). These complexes are stable in solution for at least 3 months, and over 90% of Ptx remains loaded in the micelles after extreme stress conditions such as high-speed centrifugation, lyophilization, or freeze-thaw cycles. Read More

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January 2016

High mitochondrial mass identifies a sub-population of stem-like cancer cells that are chemo-resistant.

Oncotarget 2015 Oct;6(31):30472-86

The Breast Cancer Now Research Unit, Institute of Cancer Sciences, University of Manchester, Manchester, UK.

Chemo-resistance is a clinical barrier to more effective anti-cancer therapy. In this context, cancer stem-like cells (CSCs) are thought to be chemo-resistant, resulting in tumor recurrence and distant metastasis. Our hypothesis is that chemo-resistance in CSCs is driven, in part, by enhanced mitochondrial function. Read More

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October 2015

Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation, in vitro and in vivo characterization.

J Microencapsul 2015 29;32(7):661-8. Epub 2015 Sep 29.

b Nanotechnology Research Center and.

Large porous particles (LPPs) could be used as a useful carrier for non-invasive delivery to the deep lung. Pulmonary delivery of paclitaxel-loaded LPPs (PTX-LPPs) can help to eliminate the highly complicated and harmful solvent used in PTX parenteral formulations. PTX-LPPs with mass median aerodynamic diameter (MMAD) of 5. Read More

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