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Cancer multidrug resistance

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
Yumeng Wei, Panjing Yang, Shousong Cao, Ling Zhao
5-Fluorouracil (5-FU) alone or in combination with other therapeutic drugs has been widely used for clinical treatment of various cancers. However, 5-FU-based chemotherapy has limited anticancer efficacy in clinic due to multidrug resistance and dose-limiting cytotoxicity. Some molecules and genes in cancer cells, such as nuclear factor kappa B, insulin-like growth factor-1 receptor, epidermal growth factor receptor, cyclooxygenase-2, signal transducer and activator of transcription 3, phosphatase and tensin homolog deleted on chromosome ten and Bcl-2 etc...
December 11, 2017: Archives of Pharmacal Research
Simona A Iacob, Diana G Iacob
The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs...
2017: Frontiers in Microbiology
Junheng Zheng, Lixiao Xu, Yubin Pan, Shuyi Yu, Hongbo Wang, Derek Kennedy, Yan Zhang
Sox2 (Sry-box2) is essential for a variety of stem cells and is also expressed in colorectal cancer (CRC). However, the underlying mechanism by which Sox2 enhances CRC progression remains unclear. In the present study, we show that elevated Sox2 expression is significantly correlated with poor clinical prognosis. CRC is phenotypically heterogeneous, and harbors several subtypes of cancer cells. Elevated Sox2 expression was always detected in rounded-shape cells, which co-located to poorly differentiated regions, the invasive frontier and metastatic lesions...
November 17, 2017: Oncotarget
Bing Tian, Zhen-Ning Lu, Xiu-Li Guo
Hepatocellular carcinoma (HCC) chemoresistance, which is regarded as a kind of stress management reaction to chemotherapy drugs, severely hinders the therapy outcomes of HCC treatment. Stress management is generally achieved by activating certain signal pathways and chemical factors, among which, nuclear factor-E2-related factor2 (Nrf2) is a key factor in HCC chemoresistance formation. Nrf2 is a nuclear factor that coordinates the induction and expression of a battery of genes encoding cytoprotective proteins when participating in the Nrf2antioxidant response element (Nrf2/ARE) pathway, which is one of the most important intracellular antioxidant stress pathways...
December 6, 2017: Chemico-biological Interactions
Juan Xu, Jiacong Wu, Chenyang Fu, Fang Teng, Siyu Liu, Chencheng Dai, Rong Shen, Xuemei Jia
Most ovarian cancer patients are chemosensitive initially, but finally relapse with acquired chemoresistance. Multidrug-resistance is the extremely terrible situation. The mechanism for the acquired chemoresistance of ovarian cancer patients is still not clear. LncRNAs have been recognized as the important regulator of a variety of biological processes, including the multidrug-resistant process. Here, we carried out the lncRNA sequencing of the ovarian cancer cell line A2780 and the paxitaxel resistant cell line A2780/PTX which is also cross resistant to the cisplatin and epirubicin...
December 8, 2017: Journal of Cellular Physiology
Natalia Conde-Martínez, Alejandro Acosta-González, Luis E Díaz, Edisson Tello
BACKGROUND: Water evaporation in solar salterns creates salinity gradients that promote the adaptation of microbial species to different salinities. This competitive habitat challenges the metabolic capabilities of microorganisms and promotes alterations in their production of secondary metabolites. Thus, solar salterns are a potentially important source of new natural products. In Colombia, the most important and representative solar saltern is located in Manaure (La Guajira) in the north of Colombia...
December 8, 2017: BMC Microbiology
Matteo Romio, Giulia Morgese, Lucca Trachsel, Samuel Babity, Cristina Paradisi, Davide Brambilla, Edmondo Maria Benetti
Functional block-copolymers based on poly(2-oxazoline)s are versatile building blocks for the fabrication of dual-drug delivery nanoparticles (NPs) that show promising properties for the development of a anticancer chemotherapy. Core-shell NPs are fabricated from diblock-copolymers featuring a long and hydrophilic poly(2-methyl-2-oxazoline) (PMOXA) block, coupled to a relatively short and functionalizable poly(2-methylsuccinate-2-oxazoline) (PMestOXA) segment. The PMOXA block stabilizes the NP dispersions, whereas the PMestOXA segment is used to conjugate pterostilbene (PTS), a natural bioactive phenolic compound that is used as lipophilic model-drug and constitutes the hydrophobic core of the designed NPs...
December 7, 2017: Biomacromolecules
Jun Li, Priyank Kumar, Nagaraju Anreddy, Yun-Kai Zhang, Yi-Jun Wang, Yanglu Chen, Tanaji T Talele, Kanav Gupta, Louis D Trombetta, Zhe-Sheng Chen
Previous reports have shown that some tyrosine kinase inhibitors (TKIs) could inhibit the ATP-binding cassette (ABC) transporters involved in multidrug resistance (MDR). Quizartinib (AC220), a potent class III receptor tyrosine kinase inhibitor (TKI), was synthesized to selectively inhibit FMS-like tyrosine kinase-3 (FLT3), a target in the treatment of acute myeloid leukemia (AML). Quizartinib is currently under clinical trials for FLT3 ITD and wild-type AML and is tested in combination with chemotherapy. While non-toxic to cell lines, quizartinib at 3 μM showed significant reversal effect on wild-type and mutant ABCG2 (R482T)-mediated MDR, and only a moderate reversal effect on mutant ABCG2 (R482G)-mediated MDR...
November 7, 2017: Oncotarget
Qi Jiang, Meizhen Xu, Yina Liu, Yudi Chen, Jiarong Feng, Xuelin Wang, Shuang Liang, Dan Li, Xiaoqin Yang
PURPOSE: Multidrug resistance mediated by ABCB1 has been perceived to be one of the obstacles for cancer chemotherapy. This meta-analysis was performed to verify the effect of the ABCB1 rs1045642 and rs1128503 polymorphisms on the response to Taxane-containing chemotherapy. METHODS: Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of these two ABCB1 polymorphisms. R scripts were developed to perform the meta-analysis...
December 5, 2017: Cancer Chemotherapy and Pharmacology
Xiaqing Rong-Mullins, Michael C Ayers, Mahmoud Summers, Jennifer E G Gallagher
Cellular metabolism can change the potency of a chemical's tumorigenicity. 4-nitroquinoline-1-oxide (4NQO) is a tumorigenic drug widely used on animal models for cancer research. Polymorphisms of the transcription factor, Yrr1, confer different levels of resistance to 4NQO in Saccharomyces cerevisiae To study how different Yrr1 alleles regulate gene expression leading to resistance, transcriptomes of three isogenic Scerevisiae strains carrying different Yrr1 alleles were profiled via RNA sequencing (RNA-Seq) and chromatin immunoprecipitation coupled with sequencing (ChIP-Seq) in presence and absence of 4NQO...
December 5, 2017: G3: Genes—Genomes—Genetics
Mikko Gynther, Ilaria Proietti Silvestri, Jacob C Hansen, Kasper B Hansen, Tarja Malm, Yevheniia Ishchenko, Younes Larsen, Liwei Han, Silke Kayser, Seppo Auriola, Aleksanteri Petsalo, Birgitte Nielsen, Darryl S Pickering, Lennart Bunch
The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells...
December 5, 2017: Journal of Medicinal Chemistry
Li-Na Pan, Yuan Zhang, Chang-Jun Zhu, Zhi-Xiong Dong
Multidrug resistance (MDR) is the major impediment to cancer chemotherapy. The expression of lung resistance-related protein (LRP), a non-ATP-binding cassette (ABC) transporter, is high in tumor cells, resulting in their resistance to a variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance is not yet explicit. Our previous studies had shown that Kinesin KIF4A was overexpressed in cisplatin (DDP)-resistant human lung adenocarcinoma cells (A549/DDP cells) compared with A549 cells. The expression of KIF4A in A549 or A549/DDP cells significantly affects cisplatin resistance but the detailed mechanisms remain unclear...
2017: Journal of Zhejiang University. Science. B
Jeong-Hyeon Ko, Gautam Sethi, Jae-Young Um, Muthu K Shanmugam, Frank Arfuso, Alan Prem Kumar, Anupam Bishayee, Kwang Seok Ahn
Abstract: Natural product compounds have recently attracted significant attention from the scientific community for their potent effects against inflammation-driven diseases, including cancer. A significant amount of research, including preclinical, clinical, and epidemiological studies, has indicated that dietary consumption of polyphenols, found at high levels in cereals, pulses, vegetables, and fruits, may prevent the evolution of an array of diseases, including cancer. Cancer development is a carefully orchestrated progression where normal cells acquires mutations in their genetic makeup, which cause the cells to continuously grow, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain...
December 1, 2017: International Journal of Molecular Sciences
Magdalena Katarzyna Guzowska, Monika Kalinowska, Wlodzimierz Lewandowski
The constant search for a successful cancer therapies lasts for decades. Apart from the huge scientific effort and enormous sum of spent money, only a small amount of newly developed medicines move into clinical use (only 94 registered anticancer drugs in the last 12 years [1]). Anticancer regimes are still overcome by drugs invented over 50 years ago such as cisplatin and doxorubicin. Significant progress in the development of improved anticancer drugs was made due to multiple studies on the relationship between the molecular structure of chemical compounds and their cytostatic activity...
November 29, 2017: Anti-cancer Agents in Medicinal Chemistry
Rajendra Awasthi, Michael John Rathbone, Philip Michael Hansbro, Mary Bebawy, Kamal Dua
MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker as well as new therapeutic targets in cancer therapy. miRNAs are gaining significant interest due to extensive advancements in knowledge since their discovery and, more recently, their translational application as therapeutic moieties and targets in the management of disease. miRNAs used in the treatment of cancer would position them as a new class of emerging therapeutic agents. Indeed, numerous candidate miRNAs have been identified as having therapeutic application in the treatment of cancer, but there is still much to learn about how to transform these into effective, patient-compliant, and targeted drug delivery systems...
November 28, 2017: Drug Delivery and Translational Research
Songwei Tan, Chenming Zou, Wei Zhang, Mingxing Yin, Xueqin Gao, Qing Tang
Cancer remains an obstacle to be surmounted by humans. As an FDA-approved biocompatible drug excipient, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely applied in drug delivery system (DDS). Along with in-depth analyses of TPGS-based DDS, increasingly attractive results have revealed that TPGS is able to act not only as a simple drug carrier but also as an assistant molecule with various bio-functions to improve anticancer efficacy. In this review, recent advances in TPGS-based DDS are summarized...
November 2017: Drug Delivery
Zong-Lin Zhang, Qing-Cheng Jiang, Su-Rong Wang
BACKGROUND: Multidrug resistance (MDR) in breast cancer therapy occurs frequently. Thus, anti-MDR agents from natural products or synthetic compounds were tested extensively. We have also explored the reverse effect and mechanism of Schisandrin A (Sch A), a natural product, on MCF-7 breast cancer doxorubicin (DOX)-resistant subline MCF-7/DOX. METHODS: MTT assay was performed to measure the viability of MCF-7 cells to assess the reverse effect of Sch A. Western blot analysis was used to study the protein levels...
November 27, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Anna M Badowska-Kozakiewicz, Maria Sobol, Janusz Patera
Introduction: Overexpression of the mdr-1 gene is the earliest discovered mechanism of multidrug resistance, which is associated with P-glycoprotein (P-gp) - a cell membrane protein responsible for the efflux of drugs of various structures out of cancer cells. Although the expression of P-glycoprotein has been demonstrated in many cancer types, its relation to markers of hypoxia such as HIF-1α, EPO-R or EPO in invasive breast cancer is not well established. The aim of this research was to analyze the co-expression of P-glycoprotein and the markers of tissue hypoxia HIF-1α, EPO, and EPO-R by immunohistochemistry in invasive breast cancer classified according to the presence of steroid receptors and the HER2 receptors...
October 2017: Archives of Medical Science: AMS
Jinjin Shi, Yu Su, Wei Liu, Junbiao Chang, Zhenzhong Zhang
Recently, stimuli-responsive drug delivery systems (DDSs) with high spatial/temporal resolution bring many benefits to cancer treatment. However, cancer cells always develop ways to resist and evade treatment, ultimately limit the treatment efficacy of the DDSs. Here, we introduce photo-activated nanoliposomes (PNLs) that impart light-induced cytotoxicity and reversal of drug resistance in synchrony with a photoinitiated and rapid release of antitumor drug. The PNLs consist of a nanoliposome doped with a photosensitizer (hematoporphyrin monomethyl ether [HMME]) in the lipid bilayer and an antitumor drug doxorubicin (DOX) encapsulated inside...
2017: International Journal of Nanomedicine
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