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https://www.readbyqxmd.com/read/28102869/design-considerations-to-minimize-the-impact-of-drug-absorption-in-polymer-based-organ-on-a-chip-platforms
#1
V S Shirure, S C George
Biocompatible polymers, such as polydimethylsiloxane (PDMS), are the materials of choice for creating organ-on-a-chip microfluidic platforms. Desirable qualities include ease of fabrication, optical clarity, and hydrophobicity, the latter of which facilitates oxygen transport to encased cells. An emerging and important application of organ-on-a-chip technology is drug discovery; however, a potential issue for polymer-based microfluidic devices has been highlighted by recent studies with PDMS, which have demonstrated absorption (and thus loss) of hydrophobic drugs into PDMS under certain experimental conditions...
January 19, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28101795/locally-advanced-pancreatic-cancer-successfully-treated-by-distal-pancreatectomy-with-celiac-axis-resection-dp-car-after-s-1-with-radiation-therapy-followed-by-gemcitabine-nab-paclitaxel-therapy-a-case-report
#2
Kyohei Ariake, Fuyuhiko Motoi, Masamichi Mizuma, Keigo Murakami, Tatsuyuki Takadate, Hideo Ohtsuka, Koji Fukase, Kunihiro Masuda, Hiroki Hayashi, Kei Nakagawa, Naoaki Sakata, Takanori Morikawa, Shimpei Maeda, Takeshi Naitoh, Shinichi Egawa, Michiaki Unno
BACKGROUND: The prognosis for pancreatic cancer remains dismal because many patients are diagnosed with unresectable cancer at the initial diagnosis. Recently, conversion surgery was reported as an effective treatment for initially unresectable pancreatic cancer with a favorable response to non-surgical treatment lasting over 240 days. Here, we describe a case of locally advanced pancreatic cancer (LAPC) successfully resected after treatment with S-1 and radiation followed by gemcitabine/nab-paclitaxel therapy...
December 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28101033/maximizing-the-benefit-cost-ratio-of-anthracyclines-in-metastatic-breast-cancer-case-report-of-a-patient-with-a-complete-response-to-high-dose-doxorubicin
#3
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28099947/short-term-efficacy-of-different-chemotherapy-regimens-in-the-treatment-of-advanced-gastric-cancer-a-network-meta-analysis
#4
Mi-Ma Duo-Ji, Ba-Sang Ci-Ren, Zi-Wen Long, Xiao-Hua Zhang, Dong-Lin Luo
OBJECTIVE: A network meta-analysis was performed to compare the short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer. METHODS: Randomized controlled trials of different chemotherapy regimens for advanced gastric cancer were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the odds ratio and draw surface under the cumulative ranking curves of different chemotherapy regimens in advanced gastric cancer...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28097871/redox-responsive-self-assembly-micelles-from-poly-n-acryloylmorpholine-block-2-acryloyloxyethyl-ferrocene-carboxylate-amphiphilic-block-copolymers-as-drug-release-carriers
#5
Feng Xu, He Li, Yan-Ling Luo, Wei Tang
Novel well-defined redox-responsive ferrocene-containing amphiphilic block copolymers (PACMO-b-PAEFC) were synthesized by ATRP, with poly(N-acryloylmorpholine) (PACMO) as hydrophilic blocks and poly(2-acryloyloxyethyl ferrocenecarboxylate) (PAEFC) as hydrophobic blocks. The copolymers were characterized by FTIR, 1H NMR, and gel permeation chromatography, and the crystalline behavior was determined by X-ray diffraction and small-angle X-ray scattering. The results showed that the size of the lamellar crystals and crystallinity vary with the systematic compositions while the periodic structure of the lamellar stacks has no obvious change...
January 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28096700/sequential-combination-chemotherapy-of-dacarbazine-dtic-with-carboplatin-and-paclitaxel-for-patients-with-metastatic-mucosal-melanoma-of-nasal-cavity-and-paranasal-sinuses
#6
W Omata, A Tsutsumida, K Namikawa, A Takahashi, K Oashi, N Yamazaki
By the recent introduction of molecular targeting drugs against BRAF mutation and immune checkpoint inhibitors, the prognosis of patients with melanoma in advanced stage is now improving, but still in the minority. Mucosal melanoma lacks the BRAF mutations, and hence conventional chemotherapeutic regimens must be improved. We have conventionally used dacarbazine (DTIC) for patients with metastatic mucosal melanoma. However, the efficacy of DTIC in patients with metastatic mucosal melanoma has been limited. Therefore, we explored other possibilities to improve the prognosis of patients suffering from metastatic mucosal melanoma...
2017: Clinical Medicine Insights. Case Reports
https://www.readbyqxmd.com/read/28095398/aurora-b-expression-modulates-paclitaxel-response-in-non-small-cell-lung-cancer
#7
Ahmed Sk Al-Khafaji, Michael Pa Davies, Janet M Risk, Michael W Marcus, Maria Koffa, John R Gosney, Richard J Shaw, John K Field, Triantafillos Liloglou
BACKGROUND: Taxanes are mitotic poisons widely used in the treatment of non-small cell lung cancer (NSCLC), however, little is known about potential molecular modulators of response to these compounds. Aurora B (AURKB) is a critical regulator of the mitotic spindle assembly, previously shown overexpressed in NSCLC. Here we investigated the hypothesis that AURKB expression modulates the efficacy of taxanes in NSCLC cells. METHODS: AURKB mRNA expression was determined by qPCR in 132 frozen NSCLC tissues and nine NSCLC cell lines...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28094989/-bitter-sweet-polymeric-micelles-formed-by-block-copolymers-from-glucosamine-and-cholic-acid
#8
Kun Zhang, Yongguang Jia, I-Huang Tsai, Satu Strandman, Li Ren, Liangzhi Hong, Guangzhao Zhang, Ying Guan, Yongjun Zhang, Julian X X Zhu
Natural compounds glucosamine and cholic acid have been used to make acrylic monomers which are subsequently used to prepare amphiphilic block copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization. Despite the striking difference in polarity and solubility, three diblock copolymers consisting of glucosamine and cholic acid pendants with different hydrophilic and hydrophobic chain lengths have been synthesized without the use of protecting groups. They are shown to self-assemble into polymeric micelles with a "bitter" bile acid core and "sweet" sugar shell in aqueous solutions as evidenced by dynamic light scattering and transmission electron microscopy...
January 17, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28094954/backbone-degradable-hpma-copolymer-conjugates-with-gemcitabine-and-paclitaxel-impact-of-molecular-weight-on-activity-toward-human-ovarian-carcinoma-xenografts
#9
Jiyuan Yang, Rui Zhang, Huaizhong Pan, Yuling Li, Yixin Fang, Libin Zhang, Jindrich Kopecek
Degradable diblock and multiblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer - gemcitabine (GEM) and - paclitaxel (PTX) conjugates were synthesized by RAFT copolymerization followed by click reaction for preclinical investigation. The aim was to validate the hypothesis that long-circulating conjugates are needed to generate a sustained concentration gradient between vasculature and a solid tumor, resulting in significant anticancer effect. To evaluate the impact of molecular weight of the conjugates on treatment efficacy, diblock-, tetrablock- and hexablock GEM and PTX conjugates were administered intravenously to nude mice bearing A2780 human ovarian xenografts...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28094765/selective-antagonism-of-muscarinic-receptors-is-neuroprotective-in-peripheral-neuropathy
#10
Nigel A Calcutt, Darrell R Smith, Katie Frizzi, Mohammad Golam Sabbir, Subir K Roy Chowdhury, Teresa Mixcoatl-Zecuatl, Ali Saleh, Nabeel Muttalib, Randy Van der Ploeg, Joseline Ochoa, Allison Gopaul, Lori Tessler, Jürgen Wess, Corinne G Jolivalt, Paul Fernyhough
Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28094573/advanced-gastric-adenocarcinoma-optimizing-therapy-options
#11
Dilsa Mizrak Kaya, Kazuto Harada, Yusuke Shimodaira, Fatemeh G Amlashi, Quan Lin, Jaffer A Ajani
Gastric adenocarcinoma (GAC) is the fifth most common cancer and third leading cause of cancer related mortality worldwide. When localized, cure is achievable with surgery and adjunctive therapies in some patients, however, once advanced, GAC is not a curable condition. Only two targeted agents (trastuzumab and ramucirumab) have been approved and apatinib was approved only in China. Because of the heterogeneous nature of GAC, it is not possible to assess a standard therapeutic approach. Areas Covered: In this review, we aimed to describe the optimal systemic therapy regimens for advanced GAC...
January 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28094402/mesoporous-carbon-nanoshells-for-high-hydrophobic-drug-loading-multimodal-optical-imaging-controlled-drug-release-and-synergistic-therapy
#12
Hui Wang, Kui Wang, Qingxin Mu, Zachary R Stephen, Yanyan Yu, Shuiqin Zhou, Miqin Zhang
Loading and controlled release of sufficient hydrophobic drugs to tumor cells has been the bottleneck in chemotherapy for decades. Herein we report the development of a fluorescent and mesoporous carbon nanoshell (FMP-CNS) that exhibits a loading capacity for the hydrophobic drug paclitaxel (PTX) as high as ∼80 wt% and releases the drug in a controllable fashion under NIR irradiation (825 nm) at an intensity of 1.5 W cm(-2). The high drug loading is primarily attributed to its mesoporous structure and to the supramolecular π-stacking between FMP-CNSs and PTX molecules...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28091920/comparative-study-of-antitumor-efficiency-of-intraperitoneal-and-intravenous-cytostatics-in-experimental-rats-with-disseminated-ovarian-cancer
#13
V G Bespalov, E A Vyshinskaya, I N Vasil'eva, A L Semenov, M A Maidin, N V Barakova, A N Stukov
Antitumor efficiencies of cytostatics dioxadet, cisplatin, mitomycin C, melphalan, and paclitaxel after a single intraperitoneal or intravenous injection in doses of 1.5, 4, 1.5, 2, and 5 mg/kg, respectively, were studied on the model of transplanted ovarian tumor in 124 rats. The antitumor effects were evaluated by the increase in median survival. Dioxadet, cisplatin, and melphalan injected intraperitoneally significantly prolonged the lifespan median - by 79, 88, and 114%, respectively, and were in fact ineffective, when injected intravenously...
January 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28090373/hgbp-1-expression-predicts-shorter-progression-free-survival-in-ovarian-cancers-while-contributing-to-paclitaxel-resistance
#14
Suzan Wadi, Aaron R Tipton, Jill A Trendel, Sadik A Khuder, Deborah J Vestal
Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance...
December 2016: Journal of Cancer Therapy
https://www.readbyqxmd.com/read/28090074/targeting-of-wnt-%C3%AE-catenin-by-anthelmintic-drug-pyrvinium-enhances-sensitivity-of-ovarian-cancer-cells-to-chemotherapy
#15
Chongyuan Zhang, Zhenge Zhang, Shuirong Zhang, Wenrong Wang, Ping Hu
BACKGROUND Aberrant activation of Wnt/β-catenin has been shown to promote ovarian cancer proliferation and chemoresistance. Pyrvinium, an FDA-approved anthelmintic drug, has been identified as a potent Wnt inhibitor. Pyrvinium may sensitize ovarian cancer cells to chemotherapy. MATERIAL AND METHODS The effect of pyrvinium alone and its combination with paclitaxel in ovarian cancer was investigated using an in vitro culture system and in vivo xenograft models. The mechanisms of its action were also analyzed, focusing on the Wnt/β-catenin pathway...
January 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28089762/long-terms-results-of-a-trial-of-concurrent-chemotherapy-and-escalating-doses-of-radiation-for-unresectable-non-small-cell-lung-cancer-ncctg-n0028-alliance
#16
Steven E Schild, Shauna L Hillman, Angelina D Tan, Helen J Ross, William L McGinnis, Yolanda A Garces, David L Graham, Alex A Adjei, James R Jett
INTRODUCTION OR HYPOTHESIS: This phase I/II trial was originally designed to determine the maximally tolerated dose(MTD) of thoracic radiotherapy(TRT) as part of a combined modality approach. This report includes the long-term outcome of patients treated on this study. The phase II portion was never completed as RTOG-0617 opened before it was concluded. METHODS: The MTD was defined as 74Gy in 37 fractions in this study. Twenty-five patients with unresectable non-small cell lung cancer(NSCLC) were treated with 2Gy daily fractions and concurrent weekly carboplatin and paclitaxel...
January 12, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28089377/phase-ii-trial-of-albumin-bound-paclitaxel-and-granulocyte-macrophage-colony-stimulating-factor-as-an-immune-modulator-in-recurrent-platinum-resistant-ovarian-cancer
#17
John B Liao, Ron E Swensen, Kelsie J Ovenell, Katie M Hitchcock-Bernhardt, Jessica L Reichow, Minjun C Apodaca, Leonard D'Amico, Jennifer S Childs, Doreen M Higgins, Barbara J Buening, Barbara A Goff, Mary L Disis
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m(2) days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28089376/chemotherapy-completion-in-elderly-women-with-ovarian-primary-peritoneal-or-fallopian-tube-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#18
Vivian E von Gruenigen, Helen Q Huang, Jan H Beumer, Heather A Lankes, William Tew, Thomas Herzog, Arti Hurria, Robert S Mannel, Tina Rizack, Lisa M Landrum, Peter G Rose, Ritu Salani, William H Bradley, Thomas J Rutherford, Robert V Higgins, Angeles Alvarez Secord, Gini Fleming
PURPOSE: A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7days delay in elderly ovarian cancer patients. PATIENTS AND METHODS: Patients' age ≥70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135mg/m(2)) or C (Carboplatin AUC 5), both given every 3weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28089147/sequent-please-vs-pantera-lux-drug-coated-balloon-angioplasty-in-real-life-results-from-the-d%C3%A3-sseldorf-dcb-registry
#19
Athena Assadi-Schmidt, Annemarie Mohring, Eva Liebsch, Lisa Dannenberg, Alina Achilles, Martin Pöhl, Shazia Afzal, Verena Veulemans, Patrick Horn, Roberto Sansone, Florian Bönner, Bodo Levkau, Malte Kelm, Tobias Zeus, Amin Polzin
BACKGROUND: In-stent restenosis (ISR) is still a major concern in interventional cardiology. Drug coated balloon (DCB) angioplasty has been shown to be a promising option in treatment of ISR. However heterogeneity of different DCBs in suppression of neointimal growth has been described in a porcine model of coronary ISR. Therefore, in this registry analysis, we compared two frequently used paclitaxel eluting DCBs, the SeQuent Please and the Pantera Lux DCB. METHODS: 571 patients were treated with DCB angioplasty at the Heinrich-Heine University Düsseldorf between 2009 and 2012...
December 13, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28088572/bcs-class-iv-drugs-highly-notorious-candidates-for-formulation-development
#20
REVIEW
Rohan Ghadi, Neha Dand
BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs...
January 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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