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https://www.readbyqxmd.com/read/29045885/fabrication-and-use-of-plga-based-formulations-designed-for-modified-release-of-5-fluorouracil
#1
REVIEW
Nattawut Leelakanok, Sean Geary, Aliasger Salem
5-fluorouracil (5-FU) is a chemotherapeutic agent that has been used for the treatment of a variety of malignancies since its initial introduction to the clinic in 1957.(1) Due to its short biological half-life, multiple dosings are generally required to maintain effective 5-FU plasma concentrations throughout the therapeutic period. Clinical studies have shown that continuous 5-FU administration is generally superior to bolus injection as exhibited by lower toxicities and increased therapeutic efficacy.(2,3) Optimal therapeutic efficacy, however, is often compromised by the limiting therapeutic index...
October 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29045513/dpyd-genotype-guided-dose-individualization-to-improve-patient-safety-of-fluoropyrimidine-therapy-call-for-a-drug-label-update
#2
L M Henricks, F L Opdam, J H Beijnen, A Cats, J H M Schellens
The fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and capecitabine, are frequently prescribed for several types of cancer, including breast, colorectal, head and neck and gastric cancer. In the current drug labels of 5-FU and capecitabine in the European Union and the United States of America no adaptive dosing strategies are incorporated for polymorphic metabolism of 5-FU.Although treatment with fluoropyrimidines is generally well tolerated, a major clinical limitation is that a proportion of the treated population experiences severe, sometimes life-threatening, fluoropyrimidine-related toxicity...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29044544/primary-systemic-therapy-in-resectable-pancreatic-ductal-adenocarcinoma-using-mfolfirinox-a-pilot-study
#3
Robert de W Marsh, Mark S Talamonti, Marshall S Baker, Mitchell Posner, Kevin Roggin, Jeffrey Matthews, Daniel Catenacci, Mark Kozloff, Blase Polite, Michele Britto, Chi Wang, Hedy Kindler
BACKGROUND AND OBJECTIVES: Surgery followed by gemcitabine and/or a fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX (oxaliplatin 85 mg/m(2) , irinotecan 180 mg/m(2) , leucovorin 400 mg/m(2) Day 1, 5-FU 2400 mg/m(2)  × 48 h IV, peg-filgrastim 6 mg SQ day 3, every 14 days) has substantial activity in metastatic PDAC. We wished to determine the tolerability/efficacy of peri-operative mFOLFIRINOX in resectable PDAC. METHODS: Patients with resectable PDAC (ECOG PS 0/1) received four cycles of mFOLFIRINOX pre- and post-surgery...
October 16, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29042944/pien-tze-huang-induces-apoptosis-and-inhibits-proliferation-of-5-fluorouracil-resistant-colorectal-carcinoma-cells-via-increasing-mir-22-expression
#4
Zhaorong Chen, Aling Shen, Liya Liu, Youqin Chen, Jianfeng Chu, Qiaoyan Cai, Fei Qi, Thomas Joseph Sferra, Jun Peng
The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The results identified that PZH significantly reduced the viability and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner (P<0...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042284/the-synergism-and-attenuation-effect-of-selenium-se-enriched-grifola-frondosa-se-polysaccharide-on-5-fluorouracil-5-fu-in-heps-bearing-mice
#5
Guanghua Mao, Qian Li, Chunmeng Deng, Yaqian Wang, Yangyang Ding, Weijie Zhang, Yao Chen, Ting Zhao, Fengfeng Wei, Liuqing Yang, Xiangyang Wu
Previous study revealed that Se-GP11 could exhibited its antitumor activity by improving the immune functions. 5-Fu, as a chemotherapeutic drugs, can kill many immune cells in addition to tumor cells. Accordingly, the enhanced antitumor and reduced toxicity of Se-GP11 on 5-Fu were estimated in this study. The results demonstrated that Se-GP11 could evidently increase the antitumor activity of 5-Fu. Furthermore, Se-GP11 could enhance the immune functions during the tumor inhibition process of 5-Fu for increasing the cytokines secretion (IL-2 and TNF-α) and immune organs weights...
October 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29039607/downregulation-of-mir-874-3p-promotes-chemotherapeutic-resistance-in-colorectal-cancer-via-inactivation-of-the-hippo-signaling-pathway
#6
Kaiqian Que, Yuanhe Tong, Ganbo Que, Li Li, Hongcheng Lin, Shuai Huang, Ruoyu Wang, Langlang Tang
Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR‑874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect...
October 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29039496/gsk-3%C3%AE-inhibitor-6-bromo-indirubin-3-oxime-promotes-both-adhesive-activity-and-drug-resistance-in-colorectal-cancer-cells
#7
Kunping Liu, Jinbang Li, Xuefang Wu, Meixiang Chen, Feng Luo, Jun Li
Multi-targets inhibitor 6-bromo-indirubin-3'-oxime (BIO) has diverse biological effects on cancer cells. The key component of the β-catenin destruction complex glycogen synthase kinase 3β (GSK-3β), one of the major target for BIO, polyubiquitination and degradation of the main oncoprotein β-catenin in colorectal cancer (CRC). In the present study, we evaluated the effect of BIO on drug resistance and biological properties of CRC cells. Whole-genome transcriptional profiling revealed that differentially expressed genes were mainly centered on well-characterized signaling pathways including stem cell, cell adhesion and cell growth in BIO-treated CRC cells...
October 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039459/bc-02-eradicates-liver-cancer-stem-cells-by-upregulating-the-ros-dependent-dna-damage
#8
Chunhui Dou, Chunyan Fang, Yan Zhao, Xiaoyan Fu, Yufei Zhang, Dongqi Zhu, Huina Wu, Huijie Liu, Jian Zhang, Wenfang Xu, Zhijun Liu, Hongyan Wang, Daqi Li, Xuejian Wang
Cancer stem cells (CSCs) are responsible for chemoresistance, tumor recurrence and metastasis. Reportedly, aminopeptidase N (APN, also known as CD13) is a marker for semi-quiescent CSCs and a therapeutic target in human liver CSCs. In the present study, the effect of BC-02, a compound obtained by conjugating a CD13 inhibitor bestatin and fluorouracil (5-FU), was investigated toward liver CSCs. Tumor spheres formed in serum-free culture conditions have been successfully used to enrich CSCs. In this study, the sphere cells were shown to have several characteristics of CSCs, including drug resistance, high tumorigenicity, epithelial-mesenchymal transition (EMT) phenotype, lower reactive oxygen species (ROS) levels, greater colony-forming efficiency and increased proliferation capacity in vitro...
October 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039072/first-line-bolus-5-fluorouracil-plus-leucovorin-for-peritoneally-disseminated-gastric-cancer-with-massive-ascites-or-inadequate-oral-intake
#9
Hiroki Hara, Shigenori Kadowaki, Masako Asayama, Akira Ooki, Toko Yamada, Takako Yoshii, Kensei Yamaguchi
BACKGROUND: There are few chemotherapeutic options for advanced gastric cancer with severe disseminated peritoneal metastases, which are usually accompanied by ascites. Bolus 5-fluorouracil (5-FU) plus leucovorin therapy has been widely used against gastrointestinal malignancies, with resulting mild toxicities. METHODS: We retrospectively analyzed the efficacy and safety of first-line chemotherapy with bolus 5-FU plus l-leucovorin in 30 advanced gastric cancer patients who had massive ascites and/or inadequate oral intake...
October 16, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29034831/graphene-oxide-based-metallic-nanoparticles-and-their-some-biological-and-environmental-application
#10
Aftab Aslam Parwaz Khan, Anish Khan, Abdullah M Asiri, Basma Galeb Alhogbia, Ghulam Md Ashraf
Recently the decoration of graphene with metallic nanoparticles by a synchronized reduction of graphene oxide (GO) and synthesis of metallic nanoparticles has gained energy. Metal-decorated carbon substrates, for example, carbon nanotubes and graphene oxide have been of mind boggling excitement to the scientific group all through the past three decades on account of different potential applications.The utilization of graphene oxide as the nano scale substrates for the formation of nanocomposites with metal oxides is a novel thought to acquire a hybrid which would show both the properties of GO as an interesting paper-shape material and the elements of single nano-sized metal particles...
October 16, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29031952/antitumor-efficacy-and-toxicity-of-5-fu-loaded-plga-pellets
#11
Nattawut Leelakanok, Sean M Geary, Aliasger K Salem
The aim of this study was to formulate a biodegradable implant capable of imparting local anti-tumor activity through the sustained release of the chemotherapeutic agent, 5-fluorouracil (5-FU). Thus injectable pellets (< 1.2 mm diameter) made from poly(lactide co-glycolide (PLGA) and loaded with 5-FU at varying drug:polymer ratios were fabricated using hot-melt extrusion and tested for their ability to provide sustained release of 5-FU in in vitro and in vivo settings. In addition, these formulations were compared against soluble 5-FU for their antitumor activity in vivo as well as for their toxicity...
October 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29031198/tretinoin-loaded-lipid-core-nanocapsules-overcome-the-triple-negative-breast-cancer-cell-resistance-to-tretinoin-and-show-synergistic-effect-on-cytotoxicity-induced-by-doxorubicin-and-5-fluororacil
#12
Eduarda Schultze, Julieti Buss, Karine Coradini, Karine Rech Begnini, Silvia S Guterres, Tiago Collares, Ruy Carlos Ruver Beck, Adriana R Pohlmann, Fabiana Kömmling Seixas
Nanostructured drug delivery systems have been extensively studied, mainly for applications in cancer therapy. The advantages of these materials include protection against drug degradation and improvement in both the relative solubility of poorly water soluble drugs as in targeting of therapy, due to the enhanced permeability and retention effect on tumor sites. In this work, we evaluate the antitumor activity of tretinoin-loaded lipid core nanocapsules (TT-LNC) in a tretinoin-resistant breast cancer cell-line, MDA-MB- 231, as well as the synergistic effect of combination of this treatment with 5-FU or DOXO...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29030256/ficus-virens-proanthocyanidins-induced-apoptosis-in-breast-cancer-cells-concomitantly-ameliorated-5-fluorouracil-induced-intestinal-mucositis-in-rats
#13
Xiao-Xin Chen, Kar Ho Lam, Qing-Xi Chen, George Pak-Heng Leung, Sydney Chi Wai Tang, Stephen Cho-Wing Sze, Jian-Bo Xiao, Feng Feng, Ying Wang, Kalin Yan-Bo Zhang, Zhang-Jin Zhang
5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent for breast cancer. However, its use often leads to drug resistance and mucositis. This study aimed to investigate whether proanthocyanidins from Ficus virens possessed anti-breast cancer and anti-mucositis activities. The results showed that the cytotoxic effects of the proanthocyanidins against MDA-MB-231 and MCF-7 breast cancer cells were in the order of stem barks proanthocyanidins (SPAs) > leaves proanthocyanidins > fruits proanthocyanidins...
October 10, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29028251/monitoring-surface-contamination-by-antineoplastic-drugs-in-italian-hospitals-performance-based-hygienic-guidance-values-hgvs-project
#14
Cristina Sottani, Elena Grignani, Enrico Oddone, Beatrice Dezza, Sara Negri, Simona Villani, Danilo Cottica
Antineoplastic drugs (ADs) will continue to represent a potential risk for personnel involved in the handling of these compounds and great concerns have been raised by the presence of ADs in many surveyed workplaces. Eight hospitals were investigated by means of wipe sampling for surface residue determination. Each wipe sample was tested for five ADs considered suitable exposure markers. Cyclophosphamide (CP), gemcitabine (GEM), 5-fluorouracil (5-FU), platinum-containing drugs (Pt), and epi-doxorubicin (EPI) contamination levels were measured in 85 per cent of the studied pharmacies and 93 per cent of outpatient care units (OpCUs)...
October 1, 2017: Annals of Work Exposures and Health
https://www.readbyqxmd.com/read/29026967/a-rat-model-of-folfox-induced-neuropathy-effects-of-oral-dimiracetam-in-comparison-with-duloxetine-and-pregabalin
#15
Lorenzo Di Cesare Mannelli, Mario Maresca, Laura Micheli, Carlo Farina, Michael W Scherz, Carla Ghelardini
BACKGROUND AND AIM: The FOLFOX family of chemotherapy regimens are hampered by the development of a painful neuropathy. Current clinical treatments are inadequate, and furthermore, the research of innovative drugs is strongly disadvantaged by the absence of a preclinical model based on the complete mixture of FOLFOX components. The aim of this study was to set up a rat model of FOLFOX-induced neuropathy in rats, validate its predictability by reference drugs, and evaluate the effectiveness of the new anti-neuropathic compound dimiracetam...
October 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29026541/molecular-features-that-predict-the-response-to-antimetabolite-chemotherapies
#16
Mahya Mehrmohamadi, Seong Ho Jeong, Jason W Locasale
BACKGROUND: Antimetabolite chemotherapeutic agents that target cellular metabolism are widely used in the clinic and are thought to exert their anti-cancer effects mainly through non-specific cytotoxic effects. However, patients vary dramatically with respect to treatment outcome, and the sources of heterogeneity remain largely unknown. METHODS: Here, we introduce a computational method for identifying gene expression signatures of response to chemotherapies and apply it to human tumors and cancer cell lines...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/29019589/role-of-the-route-of-leukotrienes-in-an-experimental-model-of-oral-mucositis-induced-by-5-fluorouracil-1
#17
Viviane Carvalho da Silva, Renata Ferreira de Carvalho Leitão, Gerly Anne de Castro Brito, Conceição da Silva Martins, Gildenio Estevam Freire, Karoline Saboia Aragão, Carlos Wagner de Souza Wanderley, Marcos Rabelo de Freitas
PURPOSE: To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. METHODS: Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation...
September 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29016350/a-novel-design-of-ha-coated-nanoparticles-co-encapsulating-plasmid-metase-and-5-fu-shows-enhanced-application-in-targeting-gastric-cancer-stem-cells
#18
Weifeng Yanga, Houting Zhanga, Lin Xin
Nanoparticles (NPs) is recognized as an attractive vehicles for cancer treatment due to their targeting drug release. Gastric cancer is an important death-related disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). MTT and Transwell assays were used to determine cell viability and apoptosis. In vivo experiments were performed to validate the effects of NPs on tumor growth. METase/5-Fu co-encaspulated NPs showed highest zeta size and lowest zeta potential than other NPs...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28992935/initial-experience-in-the-treatment-of-borderline-resectable-pancreatic-adenocarcinoma
#19
Juli Busquets, Juan Fabregat, Helena Verdaguer, Berta Laquente, Núria Pelaez, Luis Secanella, David Leiva, Teresa Serrano, María Cambray, Rafael Lopez-Urdiales, Emilio Ramos
INTRODUCTION: A borderline resectable group (APBR) has recently been defined in adenocarcinoma of the pancreas. The objective of the study is to evaluate the results in the surgical treatment after neoadjuvancy of the APBR. METHOD: Between 2010 and 2014, we included patients with APBR in a neoadjuvant and surgery protocol, staged by multidetector computed tomography (MDCT). Treatment with chemotherapy was based on gemcitabine and oxaliplatin. Subsequently, MDCT was performed to rule out progression, and 5-FU infusion and concomitant radiotherapy were given...
October 6, 2017: Cirugía Española
https://www.readbyqxmd.com/read/28990068/macc1-facilitates-chemoresistance-and-cancer-stem-cell%C3%A2-like-properties-of-colon-cancer-cells-through-the-pi3k-akt-signaling-pathway
#20
Jiankai Wang, Wenjuan Wang, Hongyi Cai, Binbin Du, Lijuan Zhang, Wen Ma, Yongguo Hu, Shifang Feng, Guoying Miao
With regards to colon cancer, resistance to 5‑fluorouracil (5‑FU)‑based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis‑associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC‑like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted...
October 4, 2017: Molecular Medicine Reports
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