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https://www.readbyqxmd.com/read/29235901/a-novel-mixed-polymeric-micelle-for-co-delivery-of-paclitaxel-and-retinoic-acid-and-overcoming-multidrug-resistance-synthesis-characterization-cytotoxicity-and-pharmacokinetic-evaluation
#1
Jaber Emami, Mahboubeh Rezazadeh, Mahboubeh Mashayekhi, Mahboubeh Rostami, Ali Jahanian-Najafabadi
In the current study, retinoic acid (RA) was conjugated to Pluronic F127 (PF127) through an esterification process. Mixed micelles were formed with tocopheryl polyethylene glycol 1000 (TPGS) for co-delivery of paclitaxel (PTX) and RA to the cancer cells. Mixed micelles of RA-PF127 and TPGS in different weight ratios (10:0, 7:3, 5:5, 3:7, 0:10 w/w) were prepared and physicochemical properties including, particle size, zeta potential, critical micelle concentration (CMC), drug loading content, entrapment efficiency, drug release, cellular uptake and in vitro cytotoxicity, were investigated in details...
December 13, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29235360/halo-109-301-a-phase-iii-trial-of-pegph20-with-gemcitabine-and-nab-paclitaxel-in-hyaluronic-acid-high-stage-iv-pancreatic-cancer
#2
Gary J Doherty, Margaret Tempero, Pippa G Corrie
The outlook for patients with advanced pancreatic cancer remains poor, despite significant advances in our understanding of pancreatic tumor biology. One emerging theme highlights the distinct composition of the pancreatic tumor microenvironment. Hyaluronic acid is a hydrophilic glycosaminoglycan whose production within the tumor leads to increased interstitial tumor pressure, thereby limiting the access of potentially effective circulating anticancer drugs via reduced tumor perfusion. PEGylated rHuPH20 is a multiply PEGylated recombinant human hyaluronidase that has shown promising efficacy in preclinical models and early phase clinical trials in pancreatic cancer patients...
October 23, 2017: Future Oncology
https://www.readbyqxmd.com/read/29233683/caspase-mediated-cleavage-of-x-ray-repair-cross-complementing-group-4-promotes-apoptosis-by-enhancing-nuclear-translocation-of-caspase-activated-dnase
#3
Yumi Sunatani, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, Tadashi Matsui, Ryo Sakasai, Mitsumasa Hashimoto, Yasuhito Ishigaki, Yoshihisa Matsumoto, Kuniyoshi Iwabuchi
X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation...
December 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29232475/front-line-therapy-of-advanced-ovarian-cancer-new-approaches
#4
J A Ledermann
Background: The 5-year survival of ovarian cancer has slowly increased but to date much of this has been due to the use of more lines of treatment rather than better first-line therapy. In this setting, there has been little improvement over the past 15 years. The introduction of new treatments to extend time to first progression and overall survival remains a key objective of clinical research. Design: The focus of research in the previous decade has been on the incorporation of anti-angiogenic therapy or dose-dense scheduling of paclitaxel (Taxol) to improve outcome...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232474/is-intraperitoneal-chemotherapy-still-an-acceptable-option-in-primary-adjuvant-chemotherapy-for-advanced-ovarian-cancer
#5
B J Monk, J K Chan
The role of intraperitoneal (i.p.) chemotherapy in treating newly diagnosed advanced epithelial ovarian cancer (EOC) has been the subject of controversy for almost three decades. Three large intergroup phase III trials (GOG 104, 114, 172) have demonstrated a survival benefit associated with i.p. over intravenous (i.v.) therapy in advanced, low-volume EOC. Despite the positive clinical trial results and a subsequent National Cancer Institute alert in 2006, i.p. treatment has not been widely accepted as the standard of care in the United States and is infrequently used in Europe...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232473/front-line-therapy-of-advanced-epithelial-ovarian-cancer-standard-treatment
#6
C Marth, D Reimer, A G Zeimet
Paclitaxel and carboplatin combination chemotherapy has remained the standard of care in the front-line therapy of advanced epithelial ovarian cancer during the last decade. Maintenance chemotherapy has not been proven to impact on overall survival. Acceptable alternatives include weekly paclitaxel plus 3-weekly carboplatin, the addition of bevacizumab to 3-weekly carboplatin and paclitaxel, and intraperitoneal chemotherapy. In particular, anti-angiogenic therapy has been identified as the most promising targeted therapy, and the addition of bevacizumab to first-line chemotherapy followed by a maintenance period of bevacizumab in monotherapy has shown to prolong progression-free survival...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232172/halo-202-randomized-phase-ii-study-of-pegph20-plus-nab-paclitaxel-gemcitabine-versus-nab-paclitaxel-gemcitabine-in-patients-with-untreated-metastatic-pancreatic-ductal-adenocarcinoma
#7
Sunil R Hingorani, Lei Zheng, Andrea J Bullock, Tara E Seery, William P Harris, Darren S Sigal, Fadi Braiteh, Paul S Ritch, Mark M Zalupski, Nathan Bahary, Paul E Oberstein, Andrea Wang-Gillam, Wilson Wu, Dimitrios Chondros, Ping Jiang, Sihem Khelifa, Jie Pu, Carrie Aldrich, Andrew E Hendifar
Purpose Metastatic pancreatic ductal adenocarcinoma is characterized by excessive hyaluronan (HA) accumulation in the tumor microenvironment, elevating interstitial pressure and impairing perfusion. Preclinical studies demonstrated pegvorhyaluronidase alfa (PEGPH20) degrades HA, thereby increasing drug delivery. Patients and Methods Patients with previously untreated metastatic pancreatic ductal adenocarcinoma were randomly assigned to treatment with PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) or nab-paclitaxel/gemcitabine (AG)...
December 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29230166/the-therapeutic-potential-of-monocyte-macrophage-manipulation-in-the-treatment-of-chemotherapy-induced-painful-neuropathy
#8
REVIEW
Karli Montague, Marzia Malcangio
In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN) is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29228548/macrophage-depletion-through-colony-stimulating-factor-1-receptor-pathway-blockade-overcomes-adaptive-resistance-to-anti-vegf-therapy
#9
Yasmin A Lyons, Sunila Pradeep, Sherry Y Wu, Monika Haemmerle, Jean M Hansen, Michael J Wagner, Alejandro Villar-Prados, Archana S Nagaraja, Robert L Dood, Rebecca A Previs, Wei Hu, Yang Zhao, Duncan H Mak, Zhilan Xiao, Brenda D Melendez, Gregory A Lizee, Imelda Mercado-Uribe, Keith A Baggerly, Patrick Hwu, Jinsong Liu, Willem W Overwijk, Robert L Coleman, Anil K Sood
Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the pro-angiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228315/comparison-of-neoadjuvant-nab-paclitaxel-carboplatin-vs-nab-paclitaxel-gemcitabine-in-triple-negative-breast-cancer-randomized-wsg-adapt-tn-trial-results
#10
Oleg Gluz, Ulrike Nitz, Cornelia Liedtke, Matthias Christgen, Eva-Maria Grischke, Helmut Forstbauer, Michael Braun, Mathias Warm, John Hackmann, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, Nikola Bangemann, Christoph Lindner, Sherko Kuemmel, Michael Clemens, Jochem Potenberg, Peter Staib, Andreas Kohls, Raquel von Schumann, Ronald Kates, Ronald Kates, Johannes Schumacher, Rachel Wuerstlein, Hans Heinrich Kreipe, Nadia Harbeck
Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). The optimal chemotherapy regimen is unclear. Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact. We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response. Methods: Patients with TNBC (estrogen receptor/progesterone receptor < 1%, human epidermal growth factor receptor 2-negative, cT1c-cT4c, cN0/+) were randomly assigned to A: nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly (q3w); vs B: nab-paclitaxel 125 mg/m2/carboplatin AUC2 day 1,8 q3w...
December 8, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29228091/a-randomized-phase-ii-study-evaluating-different-maintenance-schedules-of-nab-paclitaxel-in-the-first-line-treatment-of-metastatic-breast-cancer-final-results-of-the-ibcsg-42-12-big-2-12-snap-trial
#11
A Gennari, Z Sun, U Hasler-Strub, M Colleoni, M J Kennedy, R Von Moos, J Cortés, M J Vidal, B Hennessy, J Walshe, K Amillano Parraga, K Ribi, J Bernhard, S Murillo Morales, O Pagani, A Barbeaux, S Borstnar, M Rabaglio-Poretti, R Maibach, M M Regan, G Jerusalem
Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: Arm A, nab-Paclitaxel 150 mg/m2 days 1,15 Q28; Arm B, nab-Paclitaxel 100 mg/m2 days 1,8,15 Q28; Arm C, nab-Paclitaxel 75 mg/m2 days 1,8,15,22 Q28...
December 8, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29224214/facial-swelling-and-foreign-body-granulomatous-reaction-to-hyaluronic-acid-filler-in-the-setting-of-neratinib
#12
Brian P Hibler, Bernice Y Yan, Michael A Marchetti, Shabnam Momtahen, Klaus J Busam, Anthony M Rossi
Cosmetic injection of dermal fillers is common, with late complications increasingly recognized. Herein, we report a granulomatous reaction to hyaluronic acid filler occurring during the use of neratinib. A woman in her fifties, with metastatic adenocarcinoma of unknown primary involving the skin and bones, was referred for new-onset facial swelling. Notable past medical history included progression of disease on carboplatin/paclitaxel and a hemithyroidectomy for papillary thyroid cancer. This article is protected by copyright...
December 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29223619/differential-effects-of-hepatic-cirrhosis-on-the-intrinsic-clearances-of-sorafenib-and-imatinib-by-cyps-in-human-liver
#13
Michael Murray, Tina B Gillani, Sussan Ghassabian, Robert J Edwards, Tristan Rawling
The tyrosine kinase inhibitors sorafenib and imatinib are important in the treatment of a range of cancers but adverse effects in some patients necessitate dosage modifications. CYP3A4 has a major role in the oxidation of sorafenib to its N-oxide and N-hydroxymethyl metabolites and also acts in concert with CYP2C8 to mediate imatinib N-demethylation. CYP3A4 expression and function are impaired in patients with advanced liver disease, whereas the functions of CYP2C enzymes are relatively preserved. We evaluated the biotransformation of sorafenib and imatinib in well-characterized microsomal fractions from 17 control subjects and 19 individuals with hepatic cirrhosis of varying severity...
December 6, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29223097/recent-advances-in-microtubule-stabilizing-agents
#14
REVIEW
Ya-Nan Cao, Ling-Li Zheng, Dan Wang, Xiao-Xia Liang, Feng Gao, Xian-Li Zhou
Highly dynamic mitotic spindle microtubules are superb therapeutic targets for a group of chemically diverse and clinically successful anticancer drugs. Microtubule-targeted drugs disrupt microtubule dynamics in distinct ways, and they are primarily classified into two groups: microtubule destabilizing agents (MDAs), such as vinblastine, colchicine, and combretastatin-A4, and microtubule stabilizing agents (MSAs), such as paclitaxel and epothilones. Systematic discovery and development of new MSAs have been aided by extensive research on paclitaxel, yielding a large number of promising anticancer compounds...
November 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29223048/extraction-protocol-and-liquid-chromatography-tandem-mass-spectrometry-method-for-determining-micelle-entrapped-paclitaxel-at-the-cellular-and-subcellular-levels-application-to-a-cellular-uptake-and-distribution-study
#15
Nan Zheng, Bin Lian, Wenwen Du, Guobing Xu, Jiafu Ji
Paclitaxel-loaded polymeric micelles (PTX-PM) are commonly used as tumor-targeted nanocarriers and display outstanding antitumor features in clinic, but its accumulation and distribution in vitro are lack of investigation. It is probably due to the complex micellar system and its low concentration at the cellular or subcellular levels. In this study, we developed an improved extraction method, which was a combination of mechanical disruption and liquid-liquid extraction (LLE), to extract the total PTX from micelles in the cell lysate and subcellular compartments...
December 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29222647/bevacizumab-for-recurrent-persistent-or-advanced-cervical-cancer-reproducibility-of-gog-240-study-results-in-real-world-patients
#16
A Godoy-Ortiz, Y Plata, J Alcaide, A Galeote, B Pajares, E Saez, E Alba, A Sánchez-Muñoz
PURPOSE: Bevacizumab is the only therapeutic target approved for patients with persistent, recurrent or advanced cervical cancer from a phase III study that combined with chemotherapy; it proves a significant increase in overall survival. To retrospectively assess the efficacy and safety of bevacizumab as the first-line treatment in patients from usual clinical practice with recurrent/persistent or advanced cervical cancer. PATIENTS AND METHODS: Treatment consisted of cisplatin 50 mg/m2 or carboplatin AUC 5 plus paclitaxel 175 mg/m2 for 6-8 cycles and bevacizumab 15 mg/kg every 3 weeks up to progression or unacceptable toxicity...
December 8, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29221990/molecular-and-cellular-mechanisms-of-chemoresistance-in-pancreatic-cancer
#17
REVIEW
Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients...
November 22, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29221445/study-protocol-of-hgcsg1404-snow-study-a-phase-i-ii-trial-of-combined-chemotherapy-of-s-1-nab-paclitaxel-and-oxaliplatin-administered-biweekly-to-patients-with-advanced-gastric-cancer
#18
Yasuyuki Kawamoto, Yoshito Komatsu, Satoshi Yuki, Kentaro Sawada, Tetsuhito Muranaka, Kazuaki Harada, Hiroshi Nakatsumi, Hiraku Fukushima, Atsushi Ishiguro, Masayoshi Dazai, Kazuteru Hatanaka, Michio Nakamura, Ichiro Iwanaga, Minoru Uebayashi, Susumu Sogabe, Yoshimitsu Kobayashi, Takuto Miyagishima, Kota Ono, Naoya Sakamoto, Yuh Sakata
BACKGROUND: In Japan, S-1 plus cisplatin (SP) regimen has become a standard therapy for patients with advanced gastric cancer. Moreover, the S-1 plus oxaliplatin regimen is now a standard treatment. Nab-paclitaxel was developed for chemotherapy of gastric cancer in Japanese clinical practice. Nab-paclitaxel, created with albumin-bound paclitaxel particles, has high transferability to tumour tissues and does not cause hypersensitivity reactions because of a different chemical composition compared with docetaxel and paclitaxel...
December 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29221187/selection-and-characterization-of-a-human-ovarian-cancer-cell-line-resistant-to-auranofin
#19
Ida Landini, Andrea Lapucci, Alessandro Pratesi, Lara Massai, Cristina Napoli, Gabriele Perrone, Pamela Pinzani, Luigi Messori, Enrico Mini, Stefania Nobili
The anti-arthritic drug auranofin exerts also potent antitumour activity in in vitro and in vivo models, whose mechanisms are not yet well defined. From an auranofin-sensitive human ovarian cancer cell line A2780, a highly resistant (>20-fold) subline (A2780/AF-R) was developed and characterized. Marked reduction of gold accumulation occurred in auranofin-resistant A2780 cells. Also, moderately higher thioredoxin reductase activity in A2780/AF-R cells was observed while no changes in intracellular glutathione content occurred...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29219949/a-micrna-200c-cathepsin-l-feedback-loop-determines-paclitaxel-resistance-in-human-lung-cancer-a549-cells-in-vitro-through-regulating-epithelial-mesenchymal-transition
#20
Yi-Fan Zhao, Mei-Ling Han, Ya-Jie Xiong, Long Wang, Yao Fei, Xiao Shen, Ying Zhu, Zhong-Qin Liang
Cathepsin L (CTSL), a cysteine protease, is closely related to tumor occurrence, development, and metastasis, and possibly regulates cancer cell resistance to chemotherapy. miRNAs, especially the miR-200 family, have been implicated in drug-resistant tumors. In this study we explored the relationship of CTSL, micRNA-200c and drug resistance, and the potential regulatory mechanisms in human lung cancer A549 cells and A549/TAX cells in vitro. A549/TAX cells were paclitaxel-resistant A549 cells overexpressing CTSL and characterized by epithelial-mesenchymal transition (EMT)...
December 7, 2017: Acta Pharmacologica Sinica
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