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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27911272/foxo4-expression-is-related-to-stem-cell-like-properties-and-resistance-to-treatment-in-diffuse-large-b-cell-lymphoma
#2
Kyung Ju Ryu, Chaehwa Park, Mineui Hong, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim
Cancer stem cells are proposed to be responsible for resistance to chemotherapeutic agents, including doxorubicin. As phenylbutyrate enhances cancer stem cell properties, we analyzed surviving lymphoma cells after treatment with doxorubicin and phenylbutyrate. Human B-cell lymphoma cell lines, including Toledo, BJAB, Daudi, and Raji were incubated with IC90 concentrations of doxorubicin (300 nM) or phenylbutyrate (8 mM). After 48 h, live cells were sorted and analyzed for their resistance to treatment by examining gene expression profiles using cDNA microarray and biological characteristics...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#3
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910972/a-liver-microphysiological-system-of-tumor-cell-dormancy-and-inflammatory-responsiveness-is-affected-by-scaffold-properties
#4
A M Clark, S E Wheeler, C L Young, L Stockdale, J Shepard Neiman, W Zhao, D B Stolz, R Venkataramanan, D Lauffenburger, L Griffith, A Wells
Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells...
December 2, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27910892/dynamic-microenvironment-induces-phenotypic-plasticity-of-esophageal-cancer-cells-under-flow
#5
Gizem Calibasi Kocal, Sinan Güven, Kira Foygel, Aaron Goldman, Pu Chen, Shiladitya Sengupta, Ramasamy Paulmurugan, Yasemin Baskin, Utkan Demirci
Cancer microenvironment is a remarkably heterogeneous composition of cellular and non-cellular components, regulated by both external and intrinsic physical and chemical stimuli. Physical alterations driven by increased proliferation of neoplastic cells and angiogenesis in the cancer microenvironment result in the exposure of the cancer cells to elevated levels of flow-based shear stress. We developed a dynamic microfluidic cell culture platform utilizing eshopagael cancer cells as model cells to investigate the phenotypic changes of cancer cells upon exposure to fluid shear stress...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910856/acquired-resistance-of-pancreatic-cancer-cells-to-cisplatin-is-multifactorial-with-cell-context-dependent-involvement-of-resistance-genes
#6
R Mezencev, L V Matyunina, G T Wagner, J F McDonald
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal of malignancies, in large measure, due to the propensity of PDAC cells to acquire resistance to chemotherapeutic agents. A better understanding of the molecular basis of acquired resistance is a major focus of contemporary PDAC research. We report here the results of a study to independently develop cisplatin resistance in two distinct parental PDAC cell lines, AsPC1 and BxPC3, and to subsequently examine the molecular mechanisms associated with the acquired resistance...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910780/naringenin-ameliorates-doxorubicin-toxicity-and-hypoxic-condition-in-dalton-s-lymphoma-ascites-tumor-mouse-model-evidence-from-electron-paramagnetic-resonance-imaging
#7
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27908756/a-novel-curcumin-derivative-which-inhibits-p-glycoprotein-arrests-cell-cycle-and-induces-apoptosis-in-multidrug-resistance-cells
#8
Vanessa Lopes-Rodrigues, Ana Oliveira, Marta Correia-da-Silva, Madalena Pinto, Raquel T Lima, Emília Sousa, M Helena Vasconcelos
Cancer multidrug resistance (MDR) is a major limitation to the success of cancer treatment and is highly associated with the overexpression of drug efflux pumps such as P-glycoprotein (P-gp). In order to achieve more effective chemotherapeutic treatments, it is important to develop P-gp inhibitors to block/decrease its activity. Curcumin (1) is a secondary metabolite isolated from the turmeric of Curcuma longa L.. Diverse biological activities have been identified for this compound, particularly, MDR modulation in various cancer cell models...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27908748/the-chemotherapeutic-agent-paclitaxel-selectively-impairs-learning-while-sparing-source-memory-and-spatial-memory
#9
Alexandra E Smith, Richard A Slivicki, Andrea G Hohmann, Jonathon D Crystal
: Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments...
November 28, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27906685/targeted-chimera-delivery-to-ovarian-cancer-cells-by-heterogeneous-gold-magnetic-nanoparticle
#10
Yao Chen, Mengjiao Xu, Yi Guo, Keyao Tu, Weimin Wu, Jianjun Wang, Xiaowen Tong, Wenjuan Wu, Lifeng Qi, Donglu Shi
Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera...
December 1, 2016: Nanotechnology
https://www.readbyqxmd.com/read/27906188/large-scale-pharmacological-profiling-of-3d-tumor-models-of-cancer-cells
#11
Lesley A Mathews Griner, Xiaohu Zhang, Rajarshi Guha, Crystal McKnight, Ian S Goldlust, Madhu Lal-Nag, Kelli Wilson, Sam Michael, Steve Titus, Paul Shinn, Craig J Thomas, Marc Ferrer
The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906173/sensitivity-of-gbm-cells-to-camp-agonist-mediated-apoptosis-correlates-with-cd44-expression-and-agonist-resistance-with-mapk-signaling
#12
Paul M Daniel, Gulay Filiz, Theo Mantamadiotis
In some cell types, activation of the second messenger cAMP leads to increased expression of proapoptotic Bim and subsequent cell death. We demonstrate that suppression of the cAMP pathway is a common event across many cancers and that pharmacological activation of cAMP in glioblastoma (GBM) cells leads to enhanced BIM expression and apoptosis in specific GBM cell types. We identified the MAPK signaling axis as the determinant of cAMP agonist sensitivity in GBM cells, with high MAPK activity corresponding to cAMP resistance and low activity corresponding to sensitization to cAMP-induced apoptosis...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905569/shikonin-induces-mitochondria-mediated-apoptosis-and-enhances-chemotherapeutic-sensitivity-of-gastric-cancer-through-reactive-oxygen-species
#13
Wenquan Liang, Aizhen Cai, Guozhu Chen, Hongqing Xi, Xiaosong Wu, Jianxin Cui, Kecheng Zhang, Xudong Zhao, Jiyun Yu, Bo Wei, Lin Chen
The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905327/potential-therapeutic-effect-of-epigenetic-therapy-on-treatment-induced-neuroendocrine-prostate-cancer
#14
Xiang Xu, Yu-Hua Huang, Yan-Jing Li, Alexa Cohen, Zhen Li, Jill Squires, Wei Zhang, Xu-Feng Chen, Min Zhang, Jiao-Ti Huang
Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model (LNCaP/NE1.8) to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy...
November 29, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27904781/microrna-497-regulates-cisplatin-chemosensitivity-of-cervical-cancer-by-targeting-transketolase
#15
Hui Yang, Xiao-Li Wu, Kai-Hua Wu, Rong Zhang, Li-Li Ju, Ying Ji, Yan-Wei Zhang, Song-Lin Xue, Ye-Xin Zhang, Yong-Feng Yang, Min-Min Yu
Cervical cancer is one of the most lethal malignancies amongst women, partially because it is unresponsive to many chemotherapeutic drugs. The mechanism underlying cisplatin (DDP) resistance in cervical cancer remains largely elusive. In this study, by detecting the 12 most reported down-regulated miRNAs in chemotherapy-sensitive and -resistant cervical cancer cells, we found that miR-497 was significantly reduced in chemotherapy-resistant HeLa/DDP cells and contributed to DDP chemosensitivity. Transketolase (TKT), a thiamine-dependent enzyme that plays a role in the channeling of excess glucose phosphates to glycolysis in the pentose phosphate pathway, was identified as a direct target of miR-497...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904761/vincristine-induced-peripheral-neuropathy-in-pediatric-cancer-patients
#16
REVIEW
Erika Mora, Ellen M Lavoie Smith, Clare Donohoe, Daniel L Hertz
Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904580/quercetin-and-ovarian-cancer-an-evaluation-based-on-a-systematic-review
#17
REVIEW
Arefe Parvaresh, Roghaye Razavi, Nahid Rafie, Reza Ghiasvand, Makan Pourmasoumi, Maryam Miraghajani
Some studies have suggested chemopreventive and therapeutic effects of quercetin (Q) on carcinogenesis. The aim of this review was to evaluate the association between Q and ovarian cancer risk among human researches and induced sensitivity to some types of chemotherapeutic drugs and antiproliferative effects of this flavonoid in the animals and cell lines studies. Data for this systematic review were achieved through searches of the MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, SID, and Magiran databases for studies published up to May 2015...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27903750/nuclear-export-of-ubiquitinated-proteins-determines-the-sensitivity-of-colorectal-cancer-to-proteasome-inhibitor
#18
Tingyu Wu, Wei Chen, Yongwang Zhong, Xiaodan Hou, Shengyun Fang, Chen-Ying Liu, Guanghui Wang, Tong Yu, Yu-Yang Huang, Xuesong Ouyang, Henry Q X Li, Long Cui, Yili Yang
Although proteasome inhibitors such as Bortezomib had significant therapeutic effects in multiple myeloma and mantel cell lymphoma, they exhibited minimal clinical activity as a mono-therapy for solid tumors, including colorectal cancer. We found in the present study that proteasome inhibition induced a remarkable nuclear exportation of ubiquitinated proteins. Inhibition of CRM1, the nuclear export carrier protein, hampered protein export and synergistically enhanced the cytotoxic action of Bortezomib on colon cancer cells containing wild type p53, which underwent G2/M cell cycle block and apoptosis...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27903673/combining-anti-mir-155-with-chemotherapy-for-the-treatment-of-lung-cancers
#19
Katrien Van Roosbroeck, Francesca Fanini, Tetsuro Setoyama, Cristina Ivan, Cristian Rodriguez-Aguayo, Enrique Fuentes-Mattei, Lianchun Xiao, Ivan Vannini, Roxana Redis, Lucilla D'Abundo, Xinna Zhang, Milena S Nicoloso, Simona Rossi, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Manuela Ferracin, Fortunato Morabito, Antonino Neri, Peter Ruvolo, Vivian R Ruvolo, Chad V Pecot, Dino Amadori, Lynne Aruzzo, Steliana Calin, Xuemei Wang, M James You, Alessandra Ferrajoli, Robert Z Orlowski, William Plunkett, Tara Lichtenberg, Ramana V Davuluri, Ioana Berindan-Neagoe, Massimo Negrini, Ignacio I Wistuba, Kantarjian Hagop, Anil K Sood, Gabriel Lopez-Berestein, Michael J Keating, Muller Fabbri, George A Calin
Purpose The oncogenic miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#20
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
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