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https://www.readbyqxmd.com/read/29300279/disease-modifying-actions-of-il-6-blockade-in-a-rat-model-of-bone-cancer-pain
#1
Bethany Remeniuk, Tamara King, Devki Suktankhar, Amy Nippert, Nancy Li, Fuying Li, Kejun Cheng, Kenner C Rice, Frank Porreca
Metastasis of cancer to the skeleton represents a debilitating turning point in the lives of patients. Skeletal metastasis leads to moderate to severe ongoing pain along with bone remodeling that can result in fracture, events that dramatically diminish quality of life. IL-6 levels are elevated in metastatic breast cancer patients and are associated with a lower survival rate. We therefore determined the consequences of inhibition of IL-6 signaling using a novel small molecule antagonist, TB-2-081, on bone integrity, tumor progression, and pain in a rodent model of breast cancer...
December 26, 2017: Pain
https://www.readbyqxmd.com/read/29295867/hexose-6-phosphate-dehydrogenase-controls-cancer-cell-proliferation-and-migration-through-pleiotropic-effects-on-the-unfolded-protein-response-calcium-homeostasis-and-redox-balance
#2
Maria Tsachaki, Natasa Mladenovic, Hana Štambergová, Julia Birk, Alex Odermatt
Hexose-6-phosphate dehydrogenase (H6PD) produces reduced NADPH in the endoplasmic reticulum (ER) lumen. NADPH constitutes a cofactor for many reducing enzymes, and its inability to traverse biologic membranes makes in situ synthesis of NADPH in the ER lumen indispensable. The H6PD gene is amplified in several types of malignancies, and earlier work pointed toward a potential involvement of the enzyme in cancer cell growth. In the present study, we demonstrated a pivotal role of H6PD in proliferation and migratory potential of 3 human breast cancer cell lines...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29246313/assessment-of-the-drug-interaction-potential-of-unconjugated-and-galnac3-conjugated-2-moe-asos
#3
Colby S Shemesh, Rosie Z Yu, Mark S Warren, Michael Liu, Mirza Jahic, Brandon Nichols, Noah Post, Song Lin, Daniel A Norris, Eunju Hurh, Jane Huang, Tanya Watanabe, Scott P Henry, Yanfeng Wang
Antisense oligonucleotides are metabolized by nucleases and drug interactions with small drug molecules at either the cytochrome P450 (CYP) enzyme or transporter levels have not been observed to date. Herein, a comprehensive in vitro assessment of the drug-drug interaction (DDI) potential was carried out with four 2'-O-(2-methoxyethyl)-modified antisense oligonucleotides (2'-MOE-ASOs), including a single triantennary N-acetyl galactosamine (GalNAc3)-conjugated ASO. Several investigations to describe the DDI potential of a 2'-MOE-ASO conjugated to a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors are explored...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29212851/omics-of-bifidobacteria-research-and-insights-into-their-health-promoting-activities
#4
REVIEW
Francesca Bottacini, Douwe van Sinderen, Marco Ventura
Members of the genus Bifidobacterium include gut commensals that are particularly abundant among the microbial communities residing in the gut of healthy breast-fed infants, where their presence has been linked to many beneficial host effects. Next-generation DNA sequencing and comparative and functional genome methodologies have been shown to be particularly useful in exploring the diversity of this genus. These combined approaches have allowed the identification of genetic features related to bifidobacterial establishment in the gut, involving host-microbe as well as microbe-microbe interactions...
December 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29211738/metformin-inhibits-the-development-and-promotes-the-resensitization-of-treatment-resistant-breast-cancer
#5
Gerald Davies, Liubov Lobanova, Wojciech Dawicki, Gary Groot, John R Gordon, Matthew Bowen, Troy Harkness, Terra Arnason
Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors...
2017: PloS One
https://www.readbyqxmd.com/read/29166569/breastfeeding-among-women-with-physical-disabilities-in-the-united-states
#6
Robyn M Powell, Monika Mitra, Suzanne C Smeltzer, Linda M Long-Bellil, Lauren D Smith, Eliana Rosenthal, Lisa I Iezzoni
BACKGROUND: The benefits of breastfeeding are well established, and breastfeeding is now widely practiced in the United States. Although increasing numbers of women with physical disabilities are having children, little information is available about breastfeeding practices among these women. Nonetheless, the children of women with physical disabilities should benefit from breastfeeding just as children of nondisabled mothers do. Research aim: This study aimed to explore the facilitators and barriers to breastfeeding among women with physical disabilities...
November 1, 2017: Journal of Human Lactation: Official Journal of International Lactation Consultant Association
https://www.readbyqxmd.com/read/29164128/peptides-released-from-foremilk-and-hindmilk-proteins-by-breast-milk-proteases-are-highly-similar
#7
Søren D Nielsen, Robert L Beverly, David C Dallas
Human milk contains active proteases that initiate hydrolysis of milk proteins within the mammary gland. Milk expressed at the beginning of feeding is known as foremilk and that at the end of feeding is known as hindmilk. As hindmilk contains higher fat, vitamins A and E, and higher calories than foremilk, feeding only hindmilk initially and reserving foremilk for later are practiced in some neonatal intensive care units. This study investigated the difference in peptide profiles, predicted milk protease activities, and bioactive peptides between foremilk and hindmilk...
2017: Frontiers in Nutrition
https://www.readbyqxmd.com/read/29150934/the-current-status-and-perspectives-regarding-the-clinical-implication-of-intracellular-calcium-in-breast-cancer
#8
REVIEW
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca2+ ) act as second messengers in intracellular signaling. Ca2+ pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca2+ as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca2+ also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29138424/structure-function-relationships-in-abcg2-insights-from-molecular-dynamics-simulations-and-molecular-docking-studies
#9
Ricardo J Ferreira, Cátia A Bonito, M Natália D S Cordeiro, Maria-José U Ferreira, Daniel J V A Dos Santos
Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in the multidrug-resistance (MDR) phenomenon in cancer cells. Herein, we describe a new atomistic model for the MDR-related ABCG2 efflux pump, also named breast cancer resistance protein (BCRP), based on the recently published crystallographic structure of the ABCG5/G8 heterodimer sterol transporter, a member of the ABCG family involved in cholesterol homeostasis. By means of molecular dynamics simulations and molecular docking, a far-reaching characterization of the ABCG2 homodimer was obtained...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29134635/ribociclib-bioavailability-is-not-affected-by-gastric-ph-changes-or-food-intake-in-silico-and-clinical-evaluations
#10
Tanay S Samant, Shyeilla Dhuria, Yasong Lu, Marc Laisney, Shu Yang, Arnaud Grandeury, Martin Mueller-Zsigmondy, Kenichi Umehara, Felix Huth, Michelle Miller, Caroline Germa, Mohamed Elmeliegy
Ribociclib (KISQALI®), a cyclin-dependent kinase 4/6 inhibitor approved for the first-line treatment of HR+/HER2- advanced breast cancer with an aromatase inhibitor, is administered with no restrictions on concomitant gastric pH-elevating agents or food intake. The influence of proton pump inhibitors (PPIs) on ribociclib bioavailability was assessed using (1) biorelevant media solubility, (2) physiologically based pharmacokinetic (PBPK) modeling, (3) non-compartmental analysis (NCA) of clinical trial data, and (4) population PK (PopPK) analysis...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29133279/effect-of-17%C3%AE-estradiol-on-estrogen-receptor-negative-breast-cancer-cells-in-an-osteolytic-mouse-model
#11
D Joshua Cohen, Vaidehi Patel, Anjali Verma, Barbara D Boyan, Zvi Schwartz
17β-Estradiol (E2) promotes metastasis of triple negative breast cancer cells to bone. Recent studies show many triple negative breast cancer cell lines lacking the 66 kDa estrogen receptor (ER) alpha (ERα66) or its splice variant ERα46, express another splice variant, ERα36 associated with membrane-mediated rapid actions of the hormone. qPCR and western blot confirmed that MCF7 cells possessed ERα splice variants ERα66, ERα46 and ERα36, while ER-negative breast cancer cells MDA-MB-231 possessed only ERα36...
November 10, 2017: Steroids
https://www.readbyqxmd.com/read/29131861/delivery-of-epirubicin-via-slow-infusion-as-a-strategy-to-mitigate-chemotherapy-induced-cardiotoxicity
#12
Fang Yang, Qiao Lei, Lu Li, Jian Chang He, Jiajia Zeng, Chunxiang Luo, Sai-Ching Jim Yeung, Runxiang Yang
BACKGROUND: Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. DESIGN AND METHODS: Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control...
2017: PloS One
https://www.readbyqxmd.com/read/29115937/trastuzumab-resumption-after-extremely-severe-cardiotoxicity-in-metastatic-breast-cancer-patient-a-case-report
#13
Santino Minichillo, Ilaria Gallelli, Elena Barbieri, Marta Cubelli, Daniela Rubino, Sara Quercia, Massimo Dall'Olio, Claudio Rapezzi, Claudio Zamagni
BACKGROUND: Trastuzumab-related cardiotoxicity has been reported in patients receiving trastuzumab concurrently with other agents, especially with anthracyclines. Cardiac function damage is generally rare, precox and mild with trastuzumab alone. CASE PRESENTATION: We report the case of a 49 year-old woman affected by metastatic breast cancer who developed trastuzumab-related cardiogenic shock due to pump failure (with LVEF of about 15%) after three months of treatment...
November 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29113667/abcb1-gene-polymorphisms-and-response-to-chemotherapy-in-breast-cancer-patients-a-meta-analysis
#14
Adela Madrid-Paredes, Marisa Cañadas-Garre, Antonio Sánchez-Pozo, Manuela Expósito-Ruiz, Miguel Ángel Calleja-Hernández
The ABCB1 gene encodes the P-glycoprotein, an efflux pump for some antineoplastic agents which acts as a resistance mechanism to chemotherapy. Three SNPs (C3435T, C1236T and G2677T/A), are the most widely studied in ABCB1. The inconsistent conclusions about the association of these polymorphisms and the response to chemotherapy in breast cancer (BC) patients prompted us to conduct a meta-analysis. A total of nine (770 patients), five (566 patients) and three studies (367 patients) relating the ABCB1 C3435T, C1236T and G2677T/A polymorphisms respectively, were included...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29098941/efflux-transporter-breast-cancer-resistance-protein-dominantly-expresses-on-the-membrane-of-red-blood-cells-hinders-partitioning-of-its-substrates-into-the-cells-and-alters-drug-drug-interaction-profiles
#15
Pu Shi, Mingxiang Liao, Bei-Ching Chuang, Robert Griffin, Judy Shi, Marc Hyer, John K Fallon, Philip C Smith, Chao Li, Cindy Q Xia
1. Red blood cell (RBC) partitioning is important in determining pharmacokinetic and pharmacodynamic properties of a compound; however, active transport across RBC membranes is not well understood, particularly without transporter-related cell membrane proteomics data. 2. In this study, we quantified breast cancer resistance protein (BCRP/Bcrp) and MDR1/P-glycoprotein (P-gp) protein expression in RBCs from humans, monkeys, dogs, rats, and mice using nanoLC/MS/MS, and evaluated their effect on RBC partitioning and plasma exposure of their substrates...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29077148/the-effect-of-saikosaponin-d-on-doxorubicin-pharmacokinetics-and-its-mdr-reversal-in-mcf-7-adr-cell-xenografts
#16
C Li, H-G Xue, L-J Feng, M-L Wang, P Wang, X-D Gai
OBJECTIVE: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice. MATERIALS AND METHODS: MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29069726/tubb3-overexpression-has-a-negligible-effect-on-the-sensitivity-to-taxol-in-cultured-cell-lines
#17
Mihoko A Tame, Anna G Manjón, Daria Belokhvostova, Jonne A Raaijmakers, René H Medema
Microtubules are cellular targets for a variety of anticancer therapies because of their critical function in mitosis. Taxol belongs to a class of microtubule targeting agents that suppresses microtubule dynamics and interferes with the functioning of the mitotic spindle, thereby effectively blocking cell cycle progression of rapidly proliferating tumor cells. Despite its antitumor activity, drug resistance remains a common obstacle in improving its overall clinical efficacy. Previous studies have shown that the expression of a specific β-tubulin isotype, βIII-tubulin/TUBB3, is dysregulated in drug-refractory tumors...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29053672/sample-extraction-and-simultaneous-chromatographic-quantitation-of-doxorubicin-and-mitomycin-c-following-drug-combination-delivery-in-nanoparticles-to-tumor-bearing-mice
#18
Rui Xue Zhang, Tian Zhang, King Chen, Ji Cheng, Paris Lai, Andrew M Rauth, K Sandy Pang, Xiao Yu Wu
Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its therapeutic benefit. Nanoparticle-based drug combination has been shown to mitigate the problems encountered by free drug combination therapy. Our previous studies have shown that the combination of two anticancer drugs, doxorubicin (DOX) and mitomycin C (MMC), produced a synergistic effect against both murine and human breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer multidrug resistance and demonstrated enhanced efficacy in breast tumor models...
October 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29051118/sequential-therapy-with-redox-responsive-glucolipid-nanocarrier-separately-delivering-sirna-and-doxorubicin-to-overcome-multidrug-resistance
#19
Tingting Meng, Binbin Lu, Shihong Shao, Ming Yuan, Xuan Liu, Hong Yuan, Xuan Huang, Fuqiang Hu
P-glycoprotein (P-gp) is a major efflux transporter overexpressed on multidrug resistant tumor cells and responsible for pumping drugs out. If anti-tumor drugs are given when P-gp level is low, satisfactory treatment efficiency may be achieved. Thus, a P-gp down-regulating siRNA (siMDR1) and doxorubicin (DOX) were applied to eliminate multidrug resistant breast cancer cells (MCF-7/ADR). A redox-responsive glucolipid conjugate (CSO-ss-SA) was used to condense siRNA (CSO-ss-SA/siRNA) and encapsulate DOX (CSO-ss-SA/DOX) separately...
October 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29040808/independently-tuning-the-biochemical-and-mechanical-properties-of-3d-hyaluronan-based-hydrogels-with-oxime-and-diels-alder-chemistry-to-culture-breast-cancer-spheroids
#20
Alexander E G Baker, Roger Y Tam, Molly S Shoichet
For native breast cancer cell growth to be mimicked in vitro as spheroids, a well-defined matrix that mimics the tumor microenvironment is required. Finding a biomimetic material for 3D cell culture other than Matrigel has challenged the field. Because hyaluronan is naturally abundant in the tumor microenvironment and can be chemically modified, we synthesized a hyaluronan (HA) hydrogel with independently tunable mechanical and chemical properties for 3D culture of breast cancer cells. By modifying HA with distinct bioorthogonal functional groups, its mechanical properties are controlled by chemical cross-linking via oxime ligation, and its biochemical properties are controlled by grafting bioactive peptides via Diels-Alder chemistry...
October 31, 2017: Biomacromolecules
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