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drug resistance cancer

Amr El-Sayed, Mohamed Kamel
The invention of new techniques to manipulate materials at their nanoscale had an evolutionary effect on various medical sciences. At the time, there are thousands of nanomaterials which can be divided according to their shape, origin, or their application. The nanotechnology provided new solutions for old problems. In medical sciences, they are used for diagnostic or therapeutic purposes. They can also be applied in the preparation of nanovaccines and nanoadjuvants. Their use in the treatment of cancer and in gene therapy opened the door for a new era in medicine...
December 13, 2018: Environmental Science and Pollution Research International
Alexandra Leary, Christophe Le Tourneau, Andrea Varga, Marie-Paule Sablin, Carlos Gomez-Roca, Nicolas Guilbaud, Aurelie Petain, Mariya Pavlyuk, Jean-Pierre Delord
Purpose To determine the maximum tolerated dose (MTD) of F14512, a topoisomerase II inhibitor designed to target cancer cells through the polyamine transport system, (three-hour daily infusion given for 3 consecutive days every 3 weeks) in platinum-refractory or resistant ovarian cancer. Other objectives were safety, pharmacokinetics (PK), PK/pharmacodynamics relationship, and efficacy. Methods This was an open-label, dose-escalation, multicenter phase I study. Results Eleven patients were enrolled and were treated at dose levels (DLs) of 10 and 5 mg/m2 /day...
December 14, 2018: Investigational New Drugs
Bo Yang, Tingjun Liu, Yang Qu, Hangbo Liu, Song Guo Zheng, Bin Cheng, Jianbo Sun
Head and neck cancer is the 6th most common malignancy worldwide and urgently requires novel therapy methods to change the situation of low 5-years survival rate and poor prognosis. Targeted therapy provides more precision, higher efficiency while lower adverse effects than traditional treatments like surgery, radiotherapy, and chemotherapy. Blockade of PD-1 pathway with antibodies against PD-1 or PD-L1 is such a typical targeted therapy which reconstitutes anti-tumor activity of T cell in treatments of cancers, especially those highly expressing PD-L1, including head and neck cancers...
2018: Frontiers in Oncology
Ching-Hon Pui, Kim E Nichols, Jun J Yang
Advances in genomic research and risk-directed therapy have led to improvements in the long-term survival and quality of life outcomes of patients with childhood acute lymphoblastic leukaemia (ALL). The application of next-generation sequencing technologies, especially transcriptome sequencing, has resulted in the identification of novel molecular subtypes of ALL with prognostic and therapeutic implications, as well as cooperative mutations that account for much of the heterogeneity in clinical responses observed among patients with specific ALL subtypes...
December 13, 2018: Nature Reviews. Clinical Oncology
Benny Zhitomirsky, Anna Yunaev, Roman Kreiserman, Ariel Kaplan, Michal Stark, Yehuda G Assaraf
Transcription factor EB (TFEB) is a master transcriptional regulator playing a key role in lysosomal biogenesis, autophagy and lysosomal exocytosis. TFEB activity is inhibited following its phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) on the surface of the lysosome. Phosphorylated TFEB is bound by 14-3-3 proteins, resulting in its cytoplasmic retention in an inactive state. It was suggested that the calcium-dependent phosphatase calcineurin is responsible for dephosphorylation and subsequent activation of TFEB under conditions of lysosomal stress...
December 13, 2018: Cell Death & Disease
Nina Qu, Dandan Shi, Mengmeng Shang, Sujuan Duan, Lu Guo, Song Ning, Jie Li
BACKGROUND Ultrasound/microbubble (USMB)-mediated sonoporation is a new strategy with minimal procedural invasiveness for targeted and site-specific drug delivery to tumors. The purpose of this study was to explore the effect of different breast cancer cell lines on sonoporation efficiency, and then to identify an optimal combination of USMB parameters to maximize the sonoporation efficiency for each tumor cell line. MATERIAL AND METHODS Three drug-sensitive breast cell lines - MCF-7, MDA-MB-231, and MDA-MB-468 - and 1 multidrug resistance (MDR) cell line - MCF-7/ADR - were chosen...
December 14, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Feixiong Cheng, Han Liang, Atul J Butte, Charis Eng, Ruth Nussinov
Recent remarkable advances in genome sequencing have enabled detailed maps of identified and interpreted genomic variation, dubbed "mutanomes." The availability of thousands of exome/genome sequencing data has prompted the emergence of new challenges in the identification of novel druggable targets and therapeutic strategies. Typically, mutanomes are viewed as one- or two-dimensional. The three-dimensional protein structural view of personal mutanomes sheds light on the functional consequences of clinically actionable mutations revealed in tumor diagnosis and followed up in personalized treatments, in a mutanome-informed manner...
January 2019: Pharmacological Reviews
Xiaoling Hong, Siying Li, Wanying Li, Min Xie, Zhentong Wei, Haoran Guo, Wei Wei, Songling Zhang
Surgery and chemotherapy are the gold-standard treatments for ovarian cancer. The major cause of treatment failure in patients with ovarian cancer is tumoral heterogeneity and drug resistance. Paclitaxel (PTX) is one of the most commonly used first-line drugs for ovarian cancer chemotherapy. Unfortunately, the mechanisms of PTX chemoresistance remain unclear. Here, we examined the effects of post-translational neddylation on the sensitivity of ovarian cancer cells (OCCs) to PTX-induced apoptosis. Disruption of protein neddylation with the first-in-class inhibitor MLN4924 dramatically neutralized PTX-mediated antiproliferative, antimigration, and apoptotic effects in human OCCs...
December 11, 2018: Biochemical and Biophysical Research Communications
Ming Shao, Qiankun Yang, Weitao Zhu, Huifang Jin, Jing Wang, Jie Song, Yongkui Kong, Xianping Lv
BACKGROUND: Liver cancer is one of the most deadly cancers in the world. There are various cells in liver tumor bulk, including liver tumor initiating cells (TICs), which account for liver tumorigenesis, drug resistance, relapse and metastasis. The homeobox (HOX) transcription factors play critical roles in many physiological and pathological processes, while, their roles in liver TICs and liver tumorigenesis remain unknown. METHODS: An unbiased screening was performed using online-available datasets...
December 13, 2018: Molecular Cancer
Nopnithi Thonghin, Richard F Collins, Alessandro Barbieri, Talha Shafi, Alistair Siebert, Robert C Ford
BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein. RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution...
December 13, 2018: BMC Structural Biology
Jessica Ruzzolini, Silvia Peppicelli, Elena Andreucci, Francesca Bianchini, Arianna Scardigli, Annalisa Romani, Giancarlo la Marca, Chiara Nediani, Lido Calorini
Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained scientific interest thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate the cytotoxicity of conventional drugs used to treat melanoma, disclosing a potentially new therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 µM, to stimulate apoptosis, while at a non-toxic dose of 250 µM, it affected cell proliferation and induced the downregulation of the pAKT/pS6 pathway...
December 8, 2018: Nutrients
Bernhard Englinger, Sebastian Kallus, Julia Senkiv, Anna Laemmerer, Patrick Moser, Lisa Gabler, Diana Groza, Christian R Kowol, Petra Heffeter, Michael Grusch, Walter Berger
Knowledge of intracellular pharmacokinetics of anticancer agents is imperative for understanding drug efficacy as well as intrinsic and acquired cellular resistance mechanisms. However, the factors driving subcellular drug distribution are complex and poorly understood. Here, we describe for the first time the intrinsic fluorescence properties of the fibroblast growth factor receptor inhibitor PD1703074 as well as utilization of this physicochemical feature to investigate intracellular accumulation and compartmentalization of this compound in human lung cancer cells...
December 8, 2018: Cells
Chao Guo, Fangyuan Liu, Jie Qi, Jiahui Ma, Shiqi Lin, Caiyun Zhang, Qian Zhang, Hangyu Zhang, Rong Lu, Xia Li
10-oxo-5-(3-(pyrrolidin-1-yl) propyl)-5,10-dihydroindeno [1,2-b] indol-9-yl propionate (LS-2-3j) is a new chemically synthesized indole compound and some related analogues are known to be inhibitors (such as alectinib and Ko143) of ATP-binding cassette (ABC) transporters, especially the ABC transporter subfamily B member 1 (ABCB1) and the ABC transporter subfamily G member 2 (ABCG2). This study aimed to evaluate the multidrug resistance (MDR) reversal effects and associated mechanisms of LS-2-3j in drug-resistant cancer cells...
December 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ping-Chih Hsu, Cheng-Ta Yang, David M Jablons, Liang You
The programmed death-ligand 1(PD-L1)/PD-1 pathway is an immunological checkpoint in cancer cells. The binding of PD-L1 and PD-1 promotes T-cell tolerance and helps tumor cells escape from host immunity. Immunotherapy targeting the PD-L1/PD-1 axis has been developed as an anti-cancer therapy and used in treating advanced human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Yes-associated protein (YAP) is a key mediator of the Hippo/YAP signaling pathway, and plays important roles in promoting cancer development, drug resistance and metastasis in human NSCLC and MPM...
December 7, 2018: Biomedicines
Alessandro Leonetti, Yehuda G Assaraf, Paraskevi D Veltsista, Btissame El Hassouni, Marcello Tiseo, Elisa Giovannetti
The introduction of EGFR-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and prognosis of non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. However, these patients display disease progression driven by the onset of acquired mechanisms of drug resistance that limit the efficacy of EGFR-TKI to no longer than one year. Moreover, a small fraction of EGFR-mutated NSCLC patients does not benefit from this targeted treatment due to primary (i...
November 28, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Elisena Franzese, Sara Centonze, Anna Diana, Francesca Carlino, Luigi Pio Guerrera, Marilena Di Napoli, Ferdinando De Vita, Sandro Pignata, Fortunato Ciardiello, Michele Orditura
Poly-ADP-ribosepolymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. In this review, we provide an updated overview of the available results of recent clinical trials on the three Food and Drug Administrationand European Medicines Agency approved PARPis in ovarian cancer: olaparib, niraparib, and rucaparib...
December 4, 2018: Cancer Treatment Reviews
Tohid Kazemi, Najibeh Shekari, Faezeh Asghari, Navideh Haghnavaz, Dariush Shanehbandi, Vahid Khaze, Behzad Baradaran
BACKGROUND: MicroRNAs are noncoding RNAs which play critical roles in response to anti-cancer agents. Let-7a and miR-21 are well-known tumor-suppressor and oncomiR miRNAs, respectively. They are involved in tumorigenesis of gastric cancer and have potential to be used as markers for response to the therapy. OBJECTIVE: We aimed to study alterations in the expression of let-7a and miR-21 and their targets in gastric cancer cell lines after treatment with docetaxel...
December 12, 2018: Anti-cancer Agents in Medicinal Chemistry
Taha Bartu Hayal, Binnur Kıratlı, Hatice Burcu Şişli, Fikrettin Şahin, Ayşegül Doğan
Mesenchymal Stem Cells (MSCs) are adult stem cells; isolated from various body parts including bone marrow, adipose tissue and dental tissue, have been characterized well and used in regenerative medicine applications. The promising potential of MSCs makes them great candidates in many disorders. It has been well known in the literature that MSCs interact with cancer cells and regulate the carcinogenesis process at different stages. The dual role of MSCs in cancer progression should be clearly identified at the physiological and molecular level to identify clinical potential in cancer treatment...
December 13, 2018: Advances in Experimental Medicine and Biology
Samil Jung, Hyung-In Moon, Subeen Kim, Nguyen Thi Ngoc Quynh, Jimin Yu, Zolzaya Sandag, Dan-Diem Thi Le, Hyegyeong Lee, Hyojeong Lee, Myeong-Sok Lee
In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time- and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells...
November 2, 2018: Oncology Reports
Lei Zhu, Xiao-Xia Li, Liang Shi, Jing Wu, Jia-Yi Qian, Tian-Song Xia, Wen-Bin Zhou, Xi Sun, Xu-Jie Zhou, Ji-Fu Wei, Qiang Ding
A total of 70% of breast cancers express the estrogen receptor (ER)α; therefore, targeting the ER may be an effective endocrine therapy with which to inhibit breast cancer growth. Tamoxifen is the most common‑used clinically used drug for the treatment of advanced or metastatic ER‑positive (ER+) breast cancer. However, a substantial proportion of patients become resistant to endocrine therapies. To overcome this limitation, in this stud, we sought to maximize the benefits associated with tamoxifen therapy via drug combination strategies...
November 1, 2018: Oncology Reports
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