1,937 results match your criteria ptx binding

Quantification of kappa opioid receptor ligand potency, efficacy and desensitization using a real-time membrane potential assay.

Biomed Pharmacother 2021 Sep 15;143:112173. Epub 2021 Sep 15.

Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE, USA.

We explored the utility of the real-time FLIPR Membrane Potential (FMP) assay as a method to assess kappa opioid receptor (KOR)-induced hyperpolarization. The FMP Blue dye was used to measure fluorescent signals reflecting changes in membrane potential in KOR expressing CHO (CHO-KOR) cells. Treatment of CHO-KOR cells with kappa agonists U50,488 or dynorphin [Dyn (1-13)NH] produced rapid and concentration-dependent decreases in FMP Blue fluorescence reflecting membrane hyperpolarization. Read More

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September 2021

Liposomal paclitaxel induces apoptosis, cell death, inhibition of migration capacity and antitumoral activity in ovarian cancer.

Biomed Pharmacother 2021 Aug 20;142:112000. Epub 2021 Aug 20.

Department of Genetics & Morphology, Institute of Biological Sciences, University of Brasília, Brasília, DF 70910-900, Brazil. Electronic address:

The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX. Read More

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Pure redox-sensitive paclitaxel-maleimide prodrug nanoparticles: Endogenous albumin-induced size switching and improved antitumor efficiency.

Acta Pharm Sin B 2021 Jul 5;11(7):2048-2058. Epub 2020 Dec 5.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Read More

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Targeted Liposomal Chemotherapies to Treat Triple-Negative Breast Cancer.

Cancers (Basel) 2021 Jul 26;13(15). Epub 2021 Jul 26.

Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA.

Triple-negative breast cancers (TNBCs) are highly aggressive and recurrent. Standard cytotoxic chemotherapies are currently the main treatment options, but their clinical efficacies are limited and patients usually suffer from severe side effects. The goal of this study was to develop and evaluate targeted liposomes-delivered combined chemotherapies to treat TNBCs. Read More

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Functional Interaction between Transient Receptor Potential V4 Channel and Neuronal Calcium Sensor 1 and the Effects of Paclitaxel.

Mol Pharmacol 2021 Sep 28;100(3):258-270. Epub 2021 Jul 28.

Laboratory of Cell Physiology, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Colombia (J.C.S.), and Departments of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut (B.E.E.)

Neuronal calcium sensor 1 (NCS1), a calcium-binding protein, and transient receptor potential V4 (TRPV4), a plasma membrane calcium channel, are fundamental in the regulation of calcium homeostasis. The interactions of these proteins and their regulation by paclitaxel (PTX) were investigated using biochemical, pharmacological, and electrophysiological approaches in both a breast cancer epithelial cell model and a neuronal model. TRPV4 and NCS1 reciprocally immunoprecipitated each other, suggesting that they make up a signaling complex. Read More

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September 2021

Peptide-Targeted High-Density Lipoprotein Nanoparticles for Combinatorial Treatment against Metastatic Breast Cancer.

ACS Appl Mater Interfaces 2021 Aug 20;13(30):35248-35265. Epub 2021 Jul 20.

Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

The sonic hedgehog (SHH) signaling pathway exhibits aberrant activation in triple-negative breast cancer (TNBC), wherein it regulates several malignant phenotypes related to tumor metastasis. GANT61, an inhibitor of the SHH signaling pathway, may offer promise when administered in combination with conventional chemotherapy to treat metastatic TNBC. However, poor bioavailability and substantial off-target toxicity limit its clinical application. Read More

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Chemokine CCL20 promotes the paclitaxel resistance of CD44CD117 cells via the Notch1 signaling pathway in ovarian cancer.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.

Studies have found that C‑C motif chemokine ligand 20 (CCL20)/C‑C motif chemokine receptor 6 (CCR6)/notch receptor 1 (Notch1) signaling serves an important role in various diseases, but its role and mechanism in ovarian cancer remains to be elucidated. The aim of the present study was to investigate the underlying mechanism of CCL20/CCR6/Notch1 signaling in paclitaxel (PTX) resistance of a CD44CD117 subgroup of cells in ovarian cancer. The CD44CD117 cells were isolated from SKOV3 cells, followed by determination of the PTX resistance and the CCR6/Notch1 axis. Read More

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September 2021

Pentoxifylline Enhances Antioxidative Capability and Promotes Mitochondrial Biogenesis in D-Galactose-Induced Aging Mice by Increasing Nrf2 and PGC-1 through the cAMP-CREB Pathway.

Oxid Med Cell Longev 2021 22;2021:6695613. Epub 2021 Jun 22.

Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.

Aging is a complex phenomenon associated with oxidative stress and mitochondrial dysfunction. The objective of this study was to investigate the potential ameliorative effects of the phosphodiesterase inhibitor pentoxifylline (PTX) on the aging process and its underlying mechanisms. We treated D-galactose- (D-gal-) induced aging mice with PTX and measured the changes in behavior, degree of oxidative damage, and mitochondrial ultrastructure and content as well as the expression of nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant genes and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha- (PGC-1-) dependent mitochondrial biogenesis genes. Read More

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A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer.

Oncogene 2021 Jul 23;40(30):4906-4918. Epub 2021 Jun 23.

Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai, 201508, China.

The primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Read More

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Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer.

PeerJ 2021 25;9:e11486. Epub 2021 May 25.

Ultrasound Medicine Department, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, Shapingba District, China.

Background: Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging.

Purpose: To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer. Read More

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Structure-based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies.

Sci Rep 2021 Jun 10;11(1):12293. Epub 2021 Jun 10.

Macromolecular Structural Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Telangana, 502285, India.

Phosphodiesterase (PDE) inhibitors, such as pentoxifylline (PTX), are used as pharmacological agents to enhance sperm motility in assisted reproductive technology (ART), mainly to aid the selection of viable sperm in asthenozoospermic ejaculates and testicular spermatozoa, prior to intracytoplasmic sperm injection (ICSI). However, PTX is reported to induce premature acrosome reaction (AR) and, exert toxic effects on oocyte function and early embryo development. Additionally, in vitro binding studies as well as computational binding free energy (ΔG) suggest that PTX exhibits weak binding to sperm PDEs, indicating room for improvement. Read More

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Preparation and Performance of Chemotherapy Drug-Loaded Graphene Oxide-Based Nanosheets That Target Ovarian Cancer Cells via Folate Receptor Mediation.

J Biomed Nanotechnol 2021 May;17(5):960-970

Harbin Medical University, Harbin, 150001, China.

Graphene oxide (GO) is one of the most popular nanomaterials that widely used to achieve effective cancer treatment. In this study, a novel, folic acid-decorated graphene oxide (FA-GO)-mediated drug delivery system was synthesized by loading the chemotherapy drug cisplatin (CDDP) or paclitaxel (PTX) to the large surface area of GO for ovarian cancer target therapy. study showed that the therapeutic effects of FA-GO-CDDP or FA-GO-PTX were increased with folate-binding protein (FBP) expression levels. Read More

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Self-promoted Albumin-Based Nanoparticles for Combination Therapy against Metastatic Breast Cancer via a Hyperthermia-Induced "Platelet Bridge".

ACS Appl Mater Interfaces 2021 Jun 27;13(22):25701-25714. Epub 2021 May 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China.

It has been a great challenge to simultaneously inhibit the outgrowth of both the primary tumor and metastasis in metastatic cancer treatment. Substantial studies have evidenced that the interaction of platelets and cancer cells supports tumor metastasis, and platelets are considered to have metastasis-targeting property. Inspired by injury-targeting and metastasis-targeting properties of platelets, we constructed a photothermal therapy strategy with activated platelet-targeting albumin-based nanoparticles, PSN-HSA-PTX-IR780, to amplify drug delivery in the primary tumor at mild temperatures and simultaneously inhibit metastasis via a "platelet bridge". Read More

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Assessment of the effect of external and internal triggers on adsorption and release of paclitaxel from the PEI functionalized silicene nanosheet: A molecular dynamic simulation.

J Mol Graph Model 2021 07 6;106:107930. Epub 2021 May 6.

Department of Chemistry, University of Birjand, Birjand, Iran. Electronic address:

In order to examine the adsorption mechanisms of paclitaxel (PTX) on silicene nanosheet (SNS) molecular dynamics (MD) simulations are carried out. The MD outcomes show that the adsorption of PTX on the pristine SNS is exothermic and spontaneous. The interaction between the PTX molecule and the pristine SNS is mainly due to the formation of π-π interactions through their aromatic rings, which are supplemented by X-π (X = N-H, C-H, and CO) interactions. Read More

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Landscape of toll-like receptors expression in tumor microenvironment of triple negative breast cancer (TNBC): Distinct roles of TLR4 and TLR8.

Gene 2021 Aug 20;792:145728. Epub 2021 May 20.

Department of Molecular and Cellular Biology, National Institute for Research on Reproductive Health, Mumbai, India. Electronic address:

TNBC is the most aggressive and hormone receptor-negative subtype of breast cancer with molecular heterogeneity in bulk tumors hindering effective treatment. Toll-like receptors (TLRs) have the potential to ignite diverse immune responses in the tumor microenvironment (TME). This encouraged us to screen their transcript expression in the publically available TCGA datasets. Read More

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Phenylboronic acid modified nanoparticles simultaneously target pancreatic cancer and its metastasis and alleviate immunosuppression.

Eur J Pharm Biopharm 2021 Aug 19;165:164-173. Epub 2021 May 19.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China. Electronic address:

Pancreatic ductal adenocarcinoma is one of the most lethal malignant tumors, its drug resistance, immunosuppression and metastasis makes the traditional chemotherapy and immunotherapy inefficient. Here we confirmed a 3-aminophenylboronic acid-modified low molecular weight heparin-D-α-tocopheryl succinate micellar nanoparticle (PBA-LMWH-TOS NP, PLT NP) could inhibit orthotopic pancreatic tumor and its spontaneous metastases. The small particle size and high affinity of PBA to sialic acid residue (SA) made PLT/PTX NPs significantly targeted and accumulated in both pancreatic tumor tissues and metastases. Read More

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Network pharmacology-based evaluation of natural compounds with paclitaxel for the treatment of metastatic breast cancer.

Toxicol Appl Pharmacol 2021 07 14;423:115576. Epub 2021 May 14.

Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India. Electronic address:

Metastatic breast cancer is a prevalent life-threatening disease. Paclitaxel (PTX) is widely used in metastatic breast cancer therapy, but the side effects limit its chemotherapeutic application. Multidrug strategies have recently been used to maximize potency and decrease the toxicity of a particular drug by reducing its dosage. Read More

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Structure-Based Discovery of Pyrimidine Aminobenzene Derivatives as Potent Oral Reversal Agents against P-gp- and BCRP-Mediated Multidrug Resistance.

J Med Chem 2021 05 3;64(9):6179-6197. Epub 2021 May 3.

Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.

Overexpression of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), is an important factor leading to multidrug resistance (MDR) in cancer treatments. Three subclasses of dual inhibitors of P-gp and BCRP were designed based on the active moieties of BCRP inhibitors, tyrosine kinase inhibitors, and P-gp inhibitors, of which compound possessed low cytotoxicity, high reversal potency, and good lipid distribution coefficient. also increased the accumulation of Adriamycin (ADM) and Mitoxantrone (MX), blocked Rh123 efflux, and made no change in the protein expression of P-gp and BCRP. Read More

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Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin.

Sci Rep 2021 Apr 30;11(1):9373. Epub 2021 Apr 30.

Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.

Secretion of pertussis toxin (PT) is the preeminent virulence trait of the human pathogen Bordetella pertussis, causing whooping cough. Bordetella bronchiseptica, although it harbors an intact 12-kb ptx-ptl operon, does not express PT due to an inactive ptx promoter (Pptx), which contains 18 SNPs (single nucleotide polymorphisms) relative to B. pertussis Pptx. Read More

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PMMA-Based Continuous Hemofiltration Modulated Complement Activation and Renal Dysfunction in LPS-Induced Acute Kidney Injury.

Front Immunol 2021 1;12:605212. Epub 2021 Apr 1.

Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Science, University of Foggia, Foggia, Italy.

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. Read More

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Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling.

J Exp Clin Cancer Res 2021 Apr 6;40(1):120. Epub 2021 Apr 6.

Third Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Background: Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Read More

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Antibody-drug nanoparticle induces synergistic treatment efficacies in HER2 positive breast cancer cells.

Sci Rep 2021 Apr 1;11(1):7347. Epub 2021 Apr 1.

Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, 110 Bertelsmeyer Hall, 1101 N. State Street, Rolla, MO, 65409-1230, USA.

Chemotherapeutic drugs suffer from non-specific binding, undesired toxicity, and poor blood circulation which contribute to poor therapeutic efficacy. In this study, antibody-drug nanoparticles (ADNs) are engineered by synthesizing pure anti-cancer drug nanorods (NRs) in the core of nanoparticles with a therapeutic monoclonal antibody, Trastuzumab on the surface of NRs for specific targeting and synergistic treatments of human epidermal growth factor receptor 2 (HER2) positive breast cancer cells. ADNs were designed by first synthesizing ~ 95 nm diameter × ~ 500 nm long paclitaxel (PTX) NRs using the nanoprecipitation method. Read More

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

Int J Pharm 2021 May 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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Hypoxia-Mediated Complement 1q Binding Protein Regulates Metastasis and Chemoresistance in Triple-Negative Breast Cancer and Modulates the PKC-NF-κB-VCAM-1 Signaling Pathway.

Front Cell Dev Biol 2021 23;9:607142. Epub 2021 Feb 23.

Sino-Russian Medical Research Center, Harbin Medical University Cancer Hospital, Harbin, China.

Objectives: Complement 1q binding protein (C1QBP/HABP1/p32/gC1qR) has been found to be overexpressed in triple-negative breast cancer (TNBC). However, the underlying mechanisms of high C1QBP expression and its role in TNBC remain largely unclear. Hypoxia is a tumor-associated microenvironment that promotes metastasis and paclitaxel (PTX) chemoresistance in tumor cells. Read More

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February 2021

Pyxinol bearing amino acid residues: Easily achievable and promising modulators of P-glycoprotein-mediated multidrug resistance.

Eur J Med Chem 2021 Apr 3;216:113317. Epub 2021 Mar 3.

School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China. Electronic address:

The P-glycoprotein (Pgp) is a major transporter involved in multidrug resistance (MDR) of cancer cells leading to chemotherapy failure. In our previous study, we demonstrated that the amide derivatives of pyxinol are promising modulators against Pgp-mediated MDR in cancer. In the present study, we designed and synthesized novel pyxinol derivatives linked to amino acid residues. Read More

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Heterocyclic Substitutions Greatly Improve Affinity and Stability of Folic Acid towards FRα. an In Silico Insight.

Molecules 2021 Feb 18;26(4). Epub 2021 Feb 18.

School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia.

Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Read More

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February 2021

Biocompatible AIEgen/p-glycoprotein [email protected] paclitaxel polymeric prodrug nanoparticles for overcoming chemotherapy resistance in ovarian cancer.

Theranostics 2021 27;11(8):3710-3724. Epub 2021 Jan 27.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Nanoparticle drug delivery system (NDDS) is quite different from the widely studied traditional chemotherapy which suffers from drug resistance and side effect. NDDS offers the straightforward solution to the chemotherapy problem and provides an opportunity to monitor the drug delivery process in real time. In this vein, we developed one NDDS, namely Py-TPE/[email protected], to relieve resistance and side effects during chemotherapy against ovarian cancer. Read More

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Circadian clock protein CRY1 prevents paclitaxel‑induced senescence of bladder cancer cells by promoting p53 degradation.

Oncol Rep 2021 03 30;45(3):1033-1043. Epub 2020 Dec 30.

Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen, Guangdong 518122, P.R. China.

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first‑line treatment is cisplatin‑based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy‑induced senescence can act as a 'back‑up' response to chemotherapy in cancer types that are resistant to apoptosis‑based anticancer therapies. Read More

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The role of non-coding RNAs in ABC transporters regulation and their clinical implications of multidrug resistance in cancer.

Expert Opin Drug Metab Toxicol 2021 Mar 22;17(3):291-306. Epub 2021 Feb 22.

Institution of Drug Metabolism and Pharmaceutical Analysis, Cancer Center of Zhejiang University,Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Introduction: Multi-drug resistance (MDR) is a hindrance toward the successful treatment of cancers. The primary mechanism that gives rise to acquired chemoresistance is the overexpression of adenosine triphosphate-binding cassette (ABC) transporters. The dysregulation of non-coding RNAs (ncRNAs) is a widely concerned reason contributing to this phenotype. Read More

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Recent advances in drug delivery systems for targeting cancer stem cells.

Acta Pharm Sin B 2021 Jan 2;11(1):55-70. Epub 2020 Oct 2.

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

Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Read More

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January 2021