<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author><author><style face="normal" font="default" size="100%">Harfouche, Rania</style></author><author><style face="normal" font="default" size="100%">Soni, Shivani</style></author><author><style face="normal" font="default" size="100%">Chimote, Geetanjali</style></author><author><style face="normal" font="default" size="100%">Mashelkar, Raghunath Anant</style></author><author><style face="normal" font="default" size="100%">Sengupta, Shiladitya</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy</style></title><secondary-title><style face="normal" font="default" size="100%">Proceedings of the National Academy of Sciences of the United States of America</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">cancer</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal transduction</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2009</style></year><pub-dates><date><style  face="normal" font="default" size="100%">MAY</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">19</style></number><publisher><style face="normal" font="default" size="100%">NATL ACAD SCIENCES</style></publisher><pub-location><style face="normal" font="default" size="100%">2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA</style></pub-location><volume><style face="normal" font="default" size="100%">106</style></volume><pages><style face="normal" font="default" size="100%">7957-7961</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The MAPK signal transduction cascade is dysregulated in a majority of human tumors. Here we report that a nanoparticle-mediated targeting of this pathway can optimize cancer chemotherapy. We engineered nanoparticles from a unique hexadentate-polyD, L-lactic acid-co-glycolic acid polymer chemically conjugated to PD98059, a selective MAPK inhibitor. The nanoparticles are taken up by cancer cells through endocytosis and demonstrate sustained release of the active agent, resulting in the inhibition of phosphorylation of downstream extracellular signal regulated kinase. We demonstrate that nanoparticle-mediated targeting of MAPK inhibits the proliferation of melanoma and lung carcinoma cells and induces apoptosis in vitro. Administration of the PD98059-nanoparticles in melanoma-bearing mice inhibits tumor growth and enhances the antitumor efficacy of cisplatin chemotherapy. Our study shows the nanoparticle-mediated delivery of signal transduction inhibitors can emerge as a unique paradigm in cancer chemotherapy.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">19</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">10.43
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author><author><style face="normal" font="default" size="100%">Soni, Shivani</style></author><author><style face="normal" font="default" size="100%">Pandey, Ambarish</style></author><author><style face="normal" font="default" size="100%">Roy, Bhaskar</style></author><author><style face="normal" font="default" size="100%">Oh, Michael S.</style></author><author><style face="normal" font="default" size="100%">Chin, Kenneth T.</style></author><author><style face="normal" font="default" size="100%">Paraskar, Abhimanyu S.</style></author><author><style face="normal" font="default" size="100%">Sarangi, Sasmit</style></author><author><style face="normal" font="default" size="100%">Connor, Yamicia</style></author><author><style face="normal" font="default" size="100%">Sabbisetti, Venkata S.</style></author><author><style face="normal" font="default" size="100%">Kopparam, Jawahar</style></author><author><style face="normal" font="default" size="100%">Kulkarni, Ashish</style></author><author><style face="normal" font="default" size="100%">Muto, Katherine</style></author><author><style face="normal" font="default" size="100%">Amarasiriwardena, Chitra</style></author><author><style face="normal" font="default" size="100%">Jayawardene, Innocent</style></author><author><style face="normal" font="default" size="100%">Lupoli, Nicola</style></author><author><style face="normal" font="default" size="100%">Dinulescu, Daniela M.</style></author><author><style face="normal" font="default" size="100%">Bonventre, Joseph V.</style></author><author><style face="normal" font="default" size="100%">Mashelkar, Raghunath Anant</style></author><author><style face="normal" font="default" size="100%">Sengupta, Shiladitya</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity</style></title><secondary-title><style face="normal" font="default" size="100%">Proceedings of the National Academy of Sciences of the United States of America</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">chemotherapy</style></keyword><keyword><style  face="normal" font="default" size="100%">nanomedicine</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JUL</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">28</style></number><publisher><style face="normal" font="default" size="100%">NATL ACAD SCIENCES</style></publisher><pub-location><style face="normal" font="default" size="100%">2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA</style></pub-location><volume><style face="normal" font="default" size="100%">109</style></volume><pages><style face="normal" font="default" size="100%">11294-11299</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O -&amp;gt; Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC50 values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras(LSL/+/)Pten(fl/fl) ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a nextgeneration platinum-based agent in the clinics.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">28</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">10.66
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kulkarni, Ashish A.</style></author><author><style face="normal" font="default" size="100%">Roy, Bhaskar</style></author><author><style face="normal" font="default" size="100%">Rao, Poornima S.</style></author><author><style face="normal" font="default" size="100%">Wyant, Gregory A.</style></author><author><style face="normal" font="default" size="100%">Mahmoud, Ayaat</style></author><author><style face="normal" font="default" size="100%">Ramachandran, Madhumitha</style></author><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Goldman, Aaron</style></author><author><style face="normal" font="default" size="100%">Kotamraju, Venkata Ramana</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author><author><style face="normal" font="default" size="100%">Mashelkar, Raghunath Anant</style></author><author><style face="normal" font="default" size="100%">Ruoslahti, Erkki</style></author><author><style face="normal" font="default" size="100%">Dinulescu, Daniela M.</style></author><author><style face="normal" font="default" size="100%">Sengupta, Shiladitya</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Supramolecular nanoparticles that target phosphoinositide-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Research</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">DEC</style></date></pub-dates></dates><number><style face="normal" font="default" size="100%">23</style></number><publisher><style face="normal" font="default" size="100%">AMER ASSOC CANCER RESEARCH</style></publisher><pub-location><style face="normal" font="default" size="100%">615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA</style></pub-location><volume><style face="normal" font="default" size="100%">73</style></volume><pages><style face="normal" font="default" size="100%">6987-6997</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The centrality of phosphoinositide-3-kinase (PI3K) in cancer etiology is well established, but clinical translation of PI3K inhibitors has been limited by feedback signaling, suboptimal intratumoral concentration, and an insulin resistance ``class effect.'' This study was designed to explore the use of supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and potentially overcome these limitations. PI3K inhibitor structures were rationally modified using a cholesterol-based derivative, facilitating supramolecular nanoassembly with L-alpha-phosphatidylcholine and DSPE-PEG [1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polythylen e glycol)]. The supramolecular nanoparticles (SNP) that were assembled were physicochemically characterized and functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using 4T1 breast cancer and K-Ras(LSL/+)/Pten(fl/fl) ovarian cancer models, with effects on glucose homeostasis evaluated using an insulin sensitivity test. The use of PI103 and PI828 as surrogate molecules to engineer the SNPs highlighted the need to keep design principles in perspective; specifically, potency of the active molecule and the linker chemistry were critical principles for efficacy, similar to antibody-drug conjugates. We found that the SNPs exerted a temporally sustained inhibition of phosphorylation of Akt, mTOR, S6K, and 4EBP in vivo. These effects were associated with increased antitumor efficacy and survival as compared with PI103 and PI828. Efficacy was further increased by decorating the nanoparticle surface with tumor-homing peptides. Notably, the use of SNPs abrogated the insulin resistance that has been associated widely with other PI3K inhibitors. This study provides a preclinical foundation for the use of supramolecular nanochemistry to overcome current challenges associated with PI3K inhibitors, offering a paradigm for extension to other molecularly targeted therapeutics being explored for cancer treatment. (C)2013 AACR.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">23</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">9.284</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ghosh, Chandramouli</style></author><author><style face="normal" font="default" size="100%">Gupta, Neha</style></author><author><style face="normal" font="default" size="100%">More, Piyush</style></author><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Mallick, Abhik</style></author><author><style face="normal" font="default" size="100%">Santra, Manas Kumar</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Engineering and in vitro evaluation of acid labile cholesterol tethered MG132 nanoparticle fortargeting ubiquitin-proteasome system in cancer</style></title><secondary-title><style face="normal" font="default" size="100%">Chemistryselect</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">OCT</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">1</style></volume><pages><style face="normal" font="default" size="100%">5099-5106</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">In recent years, proteasome has evolved as one of the important alternative targets in cancer chemotherapy. However, selective targeting of proteasome system in cancer cells still remains a major challenge. To address this, a potent peptide based proteasome inhibitor MG132 was chemically conjugated with biocompatible-biodegradable cholesterol by acid cleavable hydrazone linkage. Spherical nanoparticles (MG132-NPs) were engineered from cholesterol-MG132 conjugate. Increased amount of free MG132 was released from these nanoparticles in acidic environment compared to physiological milieu in a slow and controlled manner. These MG132-NPs were taken up by breast cancer MCF7 cells into lysosomes within 6 h. Proteasome system was inhibited by these MG132-NPs leading to stabilization of beta-catenin, cyclin A and cyclin B in HEK-293T cells. Interestingly, MG132-NPs induced much improved cell death in drug resistant MDA-MB-231 cells with insignificant toxicity in healthy cells (HEK293 and L929) even in higher concentration.</style></abstract><issue><style face="normal" font="default" size="100%">16</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">0.00</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Nandi, Aditi</style></author><author><style face="normal" font="default" size="100%">Mallick, Abhik</style></author><author><style face="normal" font="default" size="100%">More, Piyush</style></author><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Ballav, Nirmalya</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Cisplatin-induced self-assembly of graphene oxide sheets into spherical nanoparticles for damaging sub-cellular DNA</style></title><secondary-title><style face="normal" font="default" size="100%">Chemical Communications</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JAN</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">53</style></volume><pages><style face="normal" font="default" size="100%">1409-1412</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">This report describes the hitherto unobserved cisplatin induced self-assembly of 2D-graphene oxide sheets into 3D-spherical nano-scale particles. These nanoparticles can encompass dual DNA damaging drugs simultaneously. A combination of confocal microscopy, gel electrophoresis and flow cytometry studies clearly demonstrated that these novel nanoparticles can internalize into cancer cells by endocytosis, localize into lysosomes, and damage DNA, leading to apoptosis. Cell viability assays indicated that these nanoparticles were more cytotoxic towards cancer cells compared to healthy cells.</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">6.567</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Palvai, Sandeep</style></author><author><style face="normal" font="default" size="100%">Anandi, Libi</style></author><author><style face="normal" font="default" size="100%">Sarkar, Sujit</style></author><author><style face="normal" font="default" size="100%">Augustus, Meera</style></author><author><style face="normal" font="default" size="100%">Roy, Sudip</style></author><author><style face="normal" font="default" size="100%">Lahiri, Mayurika</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Drug-triggered self-assembly of linear polymer into nanoparticles for simultaneous delivery of hydrophobic and hydrophilic drugs in breast cancer cells</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Omega</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">DEC</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">2</style></volume><pages><style face="normal" font="default" size="100%">8730-8740</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Breast cancer is the most devastating disease among females globally. Conventional chemotherapeutic regimen relies on the use of highly cytotoxic drugs as monotherapy and combination therapy leading to severe side effects to the patients as collateral damage. Moreover, combining hydrophobic and hydrophilic drugs create erratic biodistribution and suboptimal medicinal outcome. Hence, packaging multiple drugs of diverse mechanisms of action and biodistribution for safe delivery into tumor tissues with optimal dosages is indispensable for next-generation breast cancer therapy. To address these, in this report, we describe a unique cisplatin-triggered self-assembly of linear polymer into 3D-spherical sub 200 nm particles. These nano-particles comprise a hydrophobic (paclitaxel) and hydrophilic drug (cisplatin) simultaneously in a single particle. Molecular dynamics simulation revealed hydrophilic-hydrophilic interaction and interchain H-bonding as underlying mechanisms of self-assembly. Confocal microscopy studies evidently demonstrated that these novel nanoparticles can home into lysosomes in breast cancer cells, fragment subcellular nuclei, and prevent cell division, leading to improved breast cancer cell death compared to free drug combination. Moreover, 3D-breast tumor spheroids were reduced remarkably by the treatment of these nanoparticles within 24 h. These dual-drug-loaded self-assembled polymeric nanoparticles have prospective to be translated into a clinical strategy for breast cancer patients.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">12</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">0.75</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Palvai, Sandeep</style></author><author><style face="normal" font="default" size="100%">Kuman, Meenu Mahesh</style></author><author><style face="normal" font="default" size="100%">Sengupta, Poulonu</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Hyaluronic acid layered chimeric nanoparticles: targeting MAPK-P13K signaling hub in colon cancer cells</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Omega</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">NOV</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">2</style></volume><pages><style face="normal" font="default" size="100%">7868-7880</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Colon cancer has emerged as one of the most devastating diseases in the whole world. Mitogen-activated protein kinase (MAPK)-phosphatidylinsitol-3-kinase (PI3K) signaling hub has gained lots of attention due to its deregulation in colon cancer cells. However, selective targeting of oncogenic MAPK-PI3K hub in colon cancer has remained highly challenging, hence it has mostly been unexplored. To address this, we have engineered a hyaluronic acid layered lipid-based chimeric nanoparticle (HA-CNP) consisting of AZD6244 (MAPK inhibitor), PI103 (PI3K inhibitor), and cisplatin (DNA impairing drug) ratiometrically in a single particle. Electron microscopy (field emission scanning electron microscopy and atomic force microscopy) and dynamic light scattering were utilized to characterize the size, shape, morphology, and surface charge of the HA-CNPs. Fluorescent confocal laser scanning microscopy and flow cytometry analysis confirmed that HA-CNPs were taken up by HCT-116 colon cancer cells by merging of clathrin and CD44 receptor-mediated endocytosis along with macropinocytosis to home into acidic organelles (lysosomes) within 1 h. A gel electrophoresis study evidently established that HA-CNPs simultaneously inhibited MAPK-PI3K signaling hub with DNA damage in HCT-116 cells. These HA-CNPs stalled the cell cycle into G0/G1 phase, leading to induction of apoptosis (early and late) in colon cancer cells. Finally, these HA-CNPs exerted remarkable cytotoxicity in HCT-116 colon cancer cells at 24 h compared to that of the free triple drug cocktail as well as HA-coated dual drug-loaded nanoparticles without showing any cell death in healthy L929 fibroblast cells. These HA-coated CNPs have potential to be translated into clinics as a novel platform to perturb various oncogenic signaling hubs concomitantly toward next-generation targeted colon cancer therapy.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;Not Available&lt;/p&gt;</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chung, Ivy</style></author><author><style face="normal" font="default" size="100%">Zhou, Kun</style></author><author><style face="normal" font="default" size="100%">Barrows, Courtney</style></author><author><style face="normal" font="default" size="100%">Banyard, Jacqueline</style></author><author><style face="normal" font="default" size="100%">Wilson, Arianne</style></author><author><style face="normal" font="default" size="100%">Rummel, Nathan</style></author><author><style face="normal" font="default" size="100%">Mizokami, Atsushi</style></author><author><style face="normal" font="default" size="100%">Basu, Sudipta</style></author><author><style face="normal" font="default" size="100%">Sengupta, Poulomi</style></author><author><style face="normal" font="default" size="100%">Shaikh, Badaruddin</style></author><author><style face="normal" font="default" size="100%">Sengupta, Shiladitya</style></author><author><style face="normal" font="default" size="100%">Bielenberg, Diane R.</style></author><author><style face="normal" font="default" size="100%">Zetter, Bruce R.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Unbiased phenotype-based screen identifies therapeutic agents selective for metastatic prostate cancer</style></title><secondary-title><style face="normal" font="default" size="100%">Frontiers in Oncology</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">bone</style></keyword><keyword><style  face="normal" font="default" size="100%">carcinoma</style></keyword><keyword><style  face="normal" font="default" size="100%">drug-screen</style></keyword><keyword><style  face="normal" font="default" size="100%">Metastasis</style></keyword><keyword><style  face="normal" font="default" size="100%">Prostate</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">MAR </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">10</style></volume><pages><style face="normal" font="default" size="100%">594141</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;In American men, prostate cancer is the second leading cause of cancer-related death. Dissemination of prostate cancer cells to distant organs significantly worsens patients' prognosis, and currently there are no effective treatment options that can cure advanced-stage prostate cancer. In an effort to identify compounds selective for metastatic prostate cancer cells over benign prostate cancer cells or normal prostate epithelial cells, we applied a phenotype-based in vitro drug screening method utilizing multiple prostate cancer cell lines to test 1,120 different compounds from a commercial drug library. Top drug candidates were then examined in multiple mouse xenograft models including subcutaneous tumor growth, experimental lung metastasis, and experimental bone metastasis assays. A subset of compounds including fenbendazole, fluspirilene, clofazimine, niclosamide, and suloctidil showed preferential cytotoxicity and apoptosis towards metastatic prostate cancer cells in vitro and in vivo. The bioavailability of the most discerning agents, especially fenbendazole and albendazole, was improved by formulating as micelles or nanoparticles. The enhanced forms of fenbendazole and albendazole significantly prolonged survival in mice bearing metastases, and albendazole-treated mice displayed significantly longer median survival times than paclitaxel-treated mice. Importantly, these drugs effectively targeted taxane-resistant tumors and bone metastases - two common clinical conditions in patients with aggressive prostate cancer. In summary, we find that metastatic prostate tumor cells differ from benign prostate tumor cells in their sensitivity to certain drug classes. Taken together, our results strongly suggest that albendazole, an anthelmintic medication, may represent a potential adjuvant or neoadjuvant to standard therapy in the treatment of disseminated prostate cancer.&lt;/p&gt;
</style></abstract><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;Foreign&lt;/p&gt;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;4.848&lt;/p&gt;
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