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Yang Yang, Joseph Bteich, Shyh-Dar Li
Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of significant cancers, but many of these drugs suffer from poor water solubility and low selectivity, limiting their clinical efficacy. To overcome these shortcomings, Cellax™ drug delivery platform was developed. Cellax™ is a polymer-based nanoparticle drug delivery system designed to solubilize hydrophobic drugs and target them to solid tumors, thereby enhancing the efficacy and reducing the side effects. Cellax-docetaxel (Cellax-DTX) displayed improved pharmacokinetic, safety, and efficacy profiles compared to native DTX (Taxotere®) and Nab-paclitaxel (Nab-PTX, Abraxane®) in multiple animal models...
November 21, 2016: AAPS Journal
Anna Polomska, Marc A Gauthier, Jean-Christophe Leroux
Drug nanocrystals (NCs) are colloidal dispersions composed almost entirely of drug. As such, there is substantial interest in targeting them to diseased tissues, where they can locally deliver high doses of the therapeutic. However, because of their uncontrolled dissolution characteristics in vivo and uptake by the monomolecular phagocyte system, achieving tumor accumulation is challenging. To address these issues, a layer-by-layer approach is adopted to coat paclitaxel NCs with alternating layers of oppositely charged polyelectrolytes, using a PEGylated copolymer as the top layer...
October 17, 2016: Small
Dan Ai, Yan Guan, Xiu-Ju Liu, Chu-Feng Zhang, Peng Wang, Hong-Lu Liang, Qi-Sen Guo
PURPOSE: The purpose of this study was to observe the clinical efficacy and toxicity of cisplatin in combination with gemcitabine or Abraxane as first-line chemotherapy for stage III/IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 200 patients with advanced NSCLC, which was confirmed by pathology or cytology, were enrolled into our research by reviewing previous complete and retrievable medical records data of our hospital. A total of 100 patients were treated with gemcitabine (1,000 mg/m(2), day 1 and day 8) in combination with cisplatin (75 mg/m(2), days 1-3; GP group) and another 100 patients were treated with Abraxane (260 mg/m(2), day 1) in combination with cisplatin (75 mg/m(2), days 1-3; TP group)...
2016: OncoTargets and Therapy
Xilin Sun, Lili Yang, Xuefeng Yan, Yingying Sun, Dongliang Zhao, Yang Ji, Kai Wang, Xiaoyuan Chen, Baozhong Shen
Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI)...
2016: PloS One
Yuka Hosotani, Takanobu Morimatsu, Masashi Takata, Osamu Mimura
BACKGROUND: We report a case of a corneal disorder after breast cancer treatment with a microtubule inhibitor, nab-paclitaxel (Abraxane). CASE: A 55-year-old woman, who was referred to our clinic, presented with blurred vision. 2 weeks previously, she had been undergoing treatment with nab-paclitaxel, trastuzumab and pertuzumab. Visual acuity was 20/60 in right eye and 20/40 in left eye. Slit-lamp examination showed an atypical epithelium invasion of the cornea in both eyes and small epithelial defect in left eye...
June 2016: Nippon Ganka Gakkai Zasshi
Ezequiel Bernabeu, Lorena Gonzalez, Maria J Legaspi, Marcela A Moretton, Diego A Chiappetta
Nanomedicines have become an attractive platform for the development of novel drug delivery systems in cancer chemotherapy. Polymeric nanoparticles (NPs) represent one of the best well-investigated nanosized carriers for delivery of antineoplastic compounds. The "Pegylation strategy" of drug delivery systems has been used in order to improve carrier biodistribution, however, some nanosized systems with PEG on their surface have exhibited poorly-cellular drug internalization. In this context, the purpose of the present study was to compare in vitro performance of two paclitaxel (PTX)-loaded NPs systems based on two biocompatible copolymers of alpha tocopheryl polyethylene glycol 1000 succinate-block-poly(ε-caprolactone) (TPGS-b-PCL) and methoxyPEG- block-poly(ε-caprolactone) (mPEG-b-PCL) in terms of citotoxicity and PTX cellular uptake...
January 2016: Journal of Nanoscience and Nanotechnology
Joyoti Dey, William S Kerwin, Marc O Grenley, Joseph R Casalini, Ilona Tretyak, Sally H Ditzler, Derek J Thirstrup, Jason P Frazier, Daniel W Pierce, Michael Carleton, Richard A Klinghoffer
While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors...
2016: PloS One
Annemieke van Wamel, Per Christian Sontum, Andrew Healey, Svein Kvåle, Nigel Bush, Jeffrey Bamber, Catharina de Lange Davies
Acoustic cluster therapy (ACT) is a novel approach for ultrasound mediated, targeted drug delivery. In the current study, we have investigated ACT in combination with paclitaxel and Abraxane® for treatment of a subcutaneous human prostate adenocarcinoma (PC3) in mice. In combination with paclitaxel (12mg/kg given i.p.), ACT induced a strong increase in therapeutic efficacy; 120days after study start, 42% of the animals were in stable, complete remission vs. 0% for the paclitaxel only group and the median survival was increased by 86%...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
G Dranitsaris, B Yu, L Wang, Y Peng, W Sun, Y Zhou, J King, S Kaura, A Zhang
No abstract text is available yet for this article.
November 2014: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Wendy K Nevala, Sarah A Buhrow, Daniel J Knauer, Joel M Reid, Elena A Atanasova, Svetomir N Markovic
Antibody-directed chemotherapy (ADC) offers an advantage over conventional chemotherapy because it provides antibody-directed targeting, with resultant improvement in therapeutic efficacy and reduced toxicity. Despite extensive research, with notable exceptions, broad clinical application of ADC remains elusive; major hurdles include the instability of antibody-chemotherapy linkers and reduced tumor toxicity of the chemotherapy when bound to the antibody. To address these challenges, we have developed a platform technology that utilizes the nab-paclitaxel formulation of paclitaxel, Abraxane, in which hydrophobic paclitaxel is suspended in 130-nm albumin nanoparticles and thus made water-soluble...
July 1, 2016: Cancer Research
R Thadakapally, Arshiya Aafreen, J Aukunuru, M Habibuddin, S Jogala
The aim of present research was to prepare novel serum stable long circulating polymeric nanoparticles for curcumin with a modification to the well known and novel nanoparticle albumin bound technology. polyethylene glycol-albumin-curcumin nanoparticles were prepared using serum albumin and poly ethylene glycol using desolvation technique. Nanoparticles were characterized for encapsulation efficiency, particle size and surface morphology. Drug excipient compatibility was determined using fourier transform infrared spectroscopy...
January 2016: Indian Journal of Pharmaceutical Sciences
Satoshi Sakai, Caname Iwata, Hiroyoshi Y Tanaka, Horacio Cabral, Yasuyuki Morishita, Kohei Miyazono, Mitsunobu R Kano
Pancreatic cancer is notorious for its poor prognosis. The histopathologic characteristic of pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer, is fibrosis within tumor tissue. Although fibrosis within tumor tissue is thought to impede drug therapy by interfering with the intratumoral accumulation of anti-tumor drugs, this hypothesis has yet to be proven directly in preclinical models. Here, we evaluated the effect of enhanced fibrosis on intratumoral accumulation of macromolecular drugs by increasing fibrosis in a murine tumor model of subcutaneously xenografted BxPC-3, a human PDAC cell line...
May 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Vinoth-Kumar Lakshmanan
Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and time-dependent manner...
January 2016: Investigative and Clinical Urology
Suzanne Russo, John Ammori, Jennifer Eads, Jennifer Dorth
Controversy remains regarding neoadjuvant approaches in the treatment of pancreatic cancer. Neoadjuvant therapy has several potential advantages over adjuvant therapy including earlier delivery of systemic treatment, in vivo assessment of response, increased resectability rate in borderline resectable patients and increased margin-negative resection rate. At present, there are no randomized data favoring neoadjuvant over adjuvant therapy and multiple neoadjuvant approaches are under investigation. Combination chemotherapy regimens including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine have been used in the neoadjuvant setting...
March 2016: Future Oncology
Lorena Simón-Gracia, Hedi Hunt, Pablo D Scodeller, Jens Gaitzsch, Gary B Braun, Anne-Mari A Willmore, Erkki Ruoslahti, Giuseppe Battaglia, Tambet Teesalu
Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer-related mortality, with a median survival of 1 to 3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here, we used flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice...
April 2016: Molecular Cancer Therapeutics
Gopalakrishna Pillai, Maria L Ceballos-Coronel
Nanomedicine, the medical applications of devices based on nanotechnology, promises an endless range of applications from biomedical imaging to drug and gene delivery. The size range of the nanomaterials is strictly defined as 1-100 nm, although many marketed nanomedicines are in the submicron range of 100-1000 nm. The major advantages of using nanomaterials as a carrier for anticancer agents are the possibility of targeted delivery to the tumor; their physical properties such as optical and magnetic properties, which can be exploited for developing contrast agents for tumor imaging; their ability to hold thousands of molecules of a drug and deliver at the required site and also the ability to overcome solubility and stability issues...
2013: SAGE Open Medicine
Tingjie Yin, Lihui Dong, Bei Cui, Lei Wang, Lifang Yin, Jianping Zhou, Meirong Huo
Clinically, paclitaxel (PTX) is one of most commonly prescribed therapies against a wide range of solid neoplasms. Despite its success, the clinical applicability of PTX (Taxol) is severely hampered by systemic toxicities induced by Cremophor EL. While attempts to bypass the need for Cremophor EL have been developed through platforms such as Abraxane, nab relies heavily on the use of organic solvents, namely, chloroform. The toxicity introduced by residual chloroform poses a potential risk to patient health...
2015: International Journal of Nanomedicine
Tingjie Yin, Han Cai, Jiyong Liu, Bei Cui, Lei Wang, Lifang Yin, Jianping Zhou, Meirong Huo
Since its approval by the FDA, Abraxane™ has been established as a clinical standard of paclitaxel (PTX)-based therapy against a variety of cancers. Despite success, Abraxane™ is still limited by suboptimal biodistribution, unfavorable pharmacokinetics and chronic toxicities from chloroform used during preparation. Accordingly, a PTX-loaded nanosuspension based on human serum albumin (HSA) with PEG modifiers (PTX-PEG-HSA) has been developed to optimize the in-vivo biodistribution, pharmacokinetics and safety of PTX over traditional PTX-HSA nanosuspensions prepared using the accepted method for Abraxane™...
February 15, 2016: European Journal of Pharmaceutical Sciences
Iwao Ojima, Brendan Lichtenthal, Siyeon Lee, Changwei Wang, Xin Wang
INTRODUCTION: Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In the year 2010, a new taxane, cabazitaxel, was approved by FDA for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer. Albumin-bound paclitaxel (nab™-paclitaxel; abraxane) nanodroplet formulation was another notable invention (FDA approval 2005 for refractory, metastatic, or relapsed breast cancer)...
2016: Expert Opinion on Therapeutic Patents
Joy Wolfram, Motao Zhu, Yong Yang, Jianliang Shen, Emanuela Gentile, Donatella Paolino, Massimo Fresta, Guangjun Nie, Chunying Chen, Haifa Shen, Mauro Ferrari, Yuliang Zhao
Nanomedicine involves the use of nanoparticles for therapeutic and diagnostic purposes. During the past two decades, a growing number of nanomedicines have received regulatory approval and many more show promise for future clinical translation. In this context, it is important to evaluate the safety of nanoparticles in order to achieve biocompatibility and desired activity. However, it is unwarranted to make generalized statements regarding the safety of nanoparticles, since the field of nanomedicine comprises a multitude of different manufactured nanoparticles made from various materials...
2015: Current Drug Targets
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