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https://www.readbyqxmd.com/read/28534989/enhanced-cancer-stem-cell-properties-of-a-mitotically-quiescent-subpopulation-of-p75ntr-positive-cells-in-esophageal-squamous-cell-carcinoma
#1
Hirofumi Kojima, Tomoyuki Okumura, Tetsuji Yamaguchi, Takeshi Miwa, Yutaka Shimada, Takuya Nagata
Mitotically quiescent cancer stem cells (CSCs) possess higher malignant potential than other CSCs, indicating their higher contribution to therapeutic resistance than that of other CSCs. In esophageal squamous cell carcinoma (ESCC), p75 neurotrophin receptor (p75NTR) is expressed in a candidate CSC population showing high tumorigenicity and chemoresistance. In the present study, we isolated and characterized quiescent CSCs population in ESCC based on p75NTR expression and cell cycle status. Expression of p75NTR and Ki-67 in ESCC cell lines (KYSE cells) and surgically resected ESCC specimens was detected by performing immunocytochemical analysis...
May 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534954/uncaria-alkaloids-reverse-abcb1-mediated-cancer-multidrug-resistance
#2
Bao-Yuan Huang, Yu Zeng, Ying-Jie Li, Xiao-Jun Huang, Nan Hu, Nan Yao, Min-Feng Chen, Zai-Gang Yang, Zhe-Sheng Chen, Dong-Mei Zhang, Chang-Qing Zeng
The overexpression of ATP-binding cassette (ABC) transporters is the main cause of cancer multidrug resistance (MDR), which leads to chemotherapy failure. Uncaria alkaloids are the major active components isolated from uncaria, which is a common Chinese herbal medicine. In this study, the MDR-reversal activities of uncaria alkaloids, including rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine (Icory), hirsutine and hirsuteine, were screened; they all exhibited potent reversal efficacy when combined with doxorubicin...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534260/pharmacogenetics-of-cannabinoids
#3
Szymon Hryhorowicz, Michal Walczak, Oliwia Zakerska-Banaszak, Ryszard Słomski, Marzena Skrzypczak-Zielińska
Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28525328/establishment-of-5-fluorouracil-resistant-canine-mammary-tumor-cell-line
#4
B Zhou, D Zhang, S M Pei, H Zhang, H C Du, Y P Jin, D G Lin
Canine mammary tumors are the most common neoplasms in intact female dogs. The surgery cannot always solve the problem, chemotherapy are recommend to these patients. However, chemotherapy could always fail because of multidrug resistance (MDR). Through stepwise increasing 5-Fluorouracil (5-FU) concentration in the culture medium, a 5-FU-resistant canine mammary tumor cell line CMT7364/5-FU was established to disclose the molecular mechanism of the drug resistance. Cell morphology, cell sensitivity to drugs, growth curves, expression of proteins, and chemo-sensitivity in vivo were compared between the parental cell line and resistant cell line...
March 28, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#5
Heloísa Lizotti Cilião, Rossana Batista Oliveira Camargo-Godoy, Marilesia Ferreira de Souza, Mariana Bisarro Dos Reis, Lorena Iastrenski, Vinicius Daher Alvares Delfino, Silvia Regina Rogatto, Ilce Mara de Syllos Cólus
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype-gene expression associations were also assessed...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28522192/overcoming-photodynamic-resistance-and-tumor-targeting-dual-therapy-mediated-by-indocyanine-green-conjugated-gold-nanospheres
#6
Wei Li, Xiaomeng Guo, Fenfen Kong, Hanbo Zhang, Lihua Luo, Qingpo Li, Chunqi Zhu, Jie Yang, Yongzhong Du, Jian You
Photodynamic therapy (PDT) and photothermal therapy (PTT) have captured much attention due to the great potential to cure malignant tumor. Nevertheless, photodynamic resistance of cancer cells has limited the further efficacy of PDT. Unfortunately, the resistance mechanism and efforts to overcome the resistance still have been rarely reported so far. Here, we report a nanosystem with specific tumor targeting for combined PDT and PTT mediated by near-infrared (NIR) light, which was established by covalently conjugating indocyanine green (ICG) and TNYL peptide onto the surface of hollow gold nanospheres (HAuNS)...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28518118/harnessing-the-dna-dye-triggered-side-population-phenotype-to-detect-and-purify-cancer-stem-cells-from-biological-samples
#7
Maximilian Boesch, Elisabeth Hoflehner, Dominik Wolf, Guenther Gastl, Sieghart Sopper
Cancer is a stem cell-driven disease and eradication of these cells has become a major therapeutic goal. Deciphering vulnerabilities of Cancer Stem Cells (CSCs) and identifying suitable molecular targets relies on methods that allow their specific discrimination in heterogeneous samples such as cell lines and ex vivo tumor tissue. Flow cytometry/FACS is a powerful technology to multi-parametrically dissect biological samples at the single cell level and is to date the method of choice to recover live cells for downstream analyses...
May 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518053/effects-of-genetic-variants-in-ugt1a1-slco1b3-abcb1-abcc2-abcg2-orm1-on-pk-pd-of-telmisartan-in-chinese-patients-with-mild-to-moderate-essential-hypertension%C3%A2
#8
Qi Pei, Liu Yang, Hong-Yi Tan, Shi-Kun Liu, Yang Liu, Lu Huang, Rong-Hui Li, Qian Wan, Jie Huang, Cheng-Xian Guo, Xiao-Cong Zuo, Jingle Li, Guo-Ping Yang
PURPOSE: This study aimed to understand the effects of single nucleotide polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood pressure) of telmisartan in Chinese patients. METHODS: 58 Han Chinese patients (aged 45 - 72 years) with mild to moderate essential hypertension were included and received 80 mg/day telmisartan for 4 weeks. The plasma concentration and genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry, respectively...
May 18, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28498438/dexamethasone-reduces-side-population-fraction-through-downregulation-of-abcg2-transporter-in-mcf-7-breast-cancer-cells
#9
Jong Bin Kim, Sung Eun Hwang, Sang-Pil Yoon
Side population (SP) cells represent a rare population among breast cancer cells. SP cells have been reported to act as cancer stem‑like cells, and to participate in the development of multidrug resistance via modulating the expression of ATP-binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid drug that has been used as an adjuvant treatment to enhance the efficacy of chemotherapeutic agents; however, its effects in breast cancer have yet to be thoroughly investigated. In the present study, the effects of dexamethasone were investigated using the human MCF‑7 breast cancer cell line, and SPs were examined in detail...
May 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28489881/hypoxia-activated-prodrug-th-302-decreased-survival-rate-of-canine-lymphoma-cells-under-hypoxic-condition
#10
Hiroki Yamazaki, Yu-Chang Lai, Morihiro Tateno, Asuka Setoguchi, Yuko Goto-Koshino, Yasuyuki Endo, Munekazu Nakaichi, Hajime Tsujimoto, Naoki Miura
We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28485193/preclinical-absorption-distribution-metabolism-excretion-and-pharmacokinetics-of-a-novel-selective-inhibitor-of-breast-cancer-resistance-protein-bcrp
#11
Mingxiang Liao, Bei-Ching Chuang, Qing Zhu, Yuexian Li, Emily Guan, Shaoxia Yu, Johnny Yang, Prakash Shimoga, Cindy Q Xia
1. Breast cancer resistance protein (BCRP) plays an important role in drug absorption, distribution, and excretion. It is challenging to evaluate BCRP functions in preclinical models because commonly used BCRP inhibitors are nonspecific or unstable in animal plasma. 2. In the present work, in vitro absorption, distribution, metabolism and elimination (ADME) assays and pharmacokinetic (PK) experiments in Bcrp knockout (KO) (Abcg2-/-) and wild-type (WT) FVB mice and Wistar rats were conducted to characterize the preclinical properties of a novel selective BCRP inhibitor (ML753286, a Ko143 analog)...
May 9, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28474563/opioids-and-the-blood-brain-barrier-a-dynamic-interaction-with-consequences-on-drug-disposition-in-brain
#12
Catarina Chaves, Fernando Remião, Salvatore Cisterninoa, Xavier Declèves
Opioids are widely used in pain management whose effects are due to binding to classical opioid receptors and/or Toll-like receptors (TLR) present at the central nervous system (CNS). At the blood-brain barrier (BBB), several influx and/or efflux transporters are expressed, such as the ATP-binding cassette (ABC) P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRP, ABCC) transporters, and solute carrier transporters (SLC), and are responsible for the transport of many xenobiotics from the brain into the bloodstream or vice versa...
May 3, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28471656/4-anilino-2-pyridylquinazolines-and-pyrimidines-as-highly-potent-and-nontoxic-inhibitors-of-breast-cancer-resistance-protein-abcg2
#13
Michael K Krapf, Jennifer Gallus, Michael Wiese
Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transport proteins remains a major problem in the chemotherapeutic treatment of cancer and might be overcome by inhibition of the transporter. Because of the lack of understanding, the complex mechanisms involved in the transport process, in particular for breast cancer resistance protein (BCRP/ABCG2), there is a persistent need for studies of inhibitors of ABCG2. In this study, we investigated a systematic series of 4-substituted-2-pyridylquinazolines in terms of their inhibitory potency as well as selectivity toward ABCG2...
May 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28470471/expression-and-activity-of-breast-cancer-resistance-protein-bcrp-abcg2-in-human-distal-lung-epithelial-cells-in-vitro
#14
Sabrina Nickel, Mohammed Ali Selo, Juliane Fallack, Caoimhe G Clerkin, Hanno Huwer, Nicole Schneider-Daum, Claus-Michael Lehr, Carsten Ehrhardt
PURPOSE: Breast cancer resistance protein (BCRP/ABCG2) has previously been identified with high expression levels in human lung. The subcellular localisation and functional activity of the transporter in lung epithelia, however, remains poorly investigated. The aim of this project was to study BCRP expression and activity in freshly isolated human alveolar epithelial type 2 (AT2) and type 1-like (AT1-like) cells in primary culture, and to compare these findings with data obtained from the NCI-H441 cell line...
May 3, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28463231/disruption-of-lineage-specification-in-adult-pulmonary-mesenchymal-progenitor-cells-promotes-microvascular-dysfunction
#15
Christa F Gaskill, Erica J Carrier, Jonathan A Kropski, Nathaniel C Bloodworth, Swapna Menon, Robert F Foronjy, M Mark Taketo, Charles C Hong, Eric D Austin, James D West, Anna L Means, James E Loyd, W David Merryman, Anna R Hemnes, Stijn De Langhe, Timothy S Blackwell, Dwight J Klemm, Susan M Majka
Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28462920/evaluating-the-association-of-single-nucleotide-polymorphisms-with-tenofovir-exposure-in-a-diverse-prospective-cohort-of-women-living-with-hiv
#16
S M Baxi, R M Greenblatt, P Bacchetti, M Cohen, J A DeHovitz, K Anastos, S J Gange, M A Young, B E Aouizerat
Higher exposure to tenofovir (TFV) increases the risk for kidney function decline, but the impact of genetic factors on TFV exposure is largely unknown. We investigated whether single-nucleotide polymorphisms (SNPs, n=211) in 12 genes are potentially involved in TFV exposure. Participants (n=91) from the Women's Interagency HIV Study, underwent a 24 h intensive pharmacokinetic sampling of TFV after witnessed dose and TFV area under the time-concentration curves (AUCs) were calculated for each participant...
May 2, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28461764/abcg2-polymorphisms-in-gout-insights-into-disease-susceptibility-and-treatment-approaches
#17
REVIEW
M C Cleophas, L A Joosten, L K Stamp, N Dalbeth, O M Woodward, Tony R Merriman
As a result of the association of a common polymorphism (rs2231142, Q141K) in the ATP-binding cassette G2 (ABCG2) transporter with serum urate concentration in a genome-wide association study, it was revealed that ABCG2 is an important uric acid transporter. This review discusses the relevance of ABCG2 polymorphisms in gout, possible etiological mechanisms, and treatment approaches. The 141K ABCG2 urate-increasing variant causes instability in the nucleotide-binding domain, leading to decreased surface expression and function...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28458315/multiple-gouty-tophi-with-bone-erosion-and-destruction-a-report-of-an-early-onset-case-in-an-obese-patient
#18
Reiko D Hayashi, Masaya Yamaoka, Hitoshi Nishizawa, Shiro Fukuda, Yuya Fujishima, Takekazu Kimura, Jyunji Kozawa, Shunbun Kita, Taka-Aki Matsuoka, Michio Otsuki, Akihisa Imagawa, Kimiyoshi Ichida, Atsuo Taniguchi, Norikazu Maeda, Tohru Funahashi, Iichiro Shimomura
A 27 year-old severely obese man (BMI, 35.1) had hyperuricemia and multiple gouty tophi with bone erosion and destruction, resulting in gait disturbance for 6 years after the early onset of gout at 21 years of age. His hyperuricemia was associated with hyperinsulinemia in obesity and a genetic variant of the ABCG2 gene. In addition, multiple gouty tophi with bone erosion and destruction might have been caused by hypoadiponectinemia and the elevation of the patient' s pro-inflammatory cytokine (IL-1β) level with the accumulation of visceral fat...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28455266/suppression-of-abcg2-mediated-mdr-in-vitro-and-in-vivo-by-a-novel-inhibitor-of-abcg2-drug-transport
#19
Atish Patel, Tian-Wen Li, Nagaraju Anreddy, De-Shen Wang, Kamlesh Sodani, Sanket Gadhia, Rishil Kathawala, Dong-Hua Yang, Changmei Cheng, Zhe-Sheng Chen
Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo...
April 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28438662/never-let-it-go-stopping-key-mechanisms-underlying-metastasis-to-fight-pancreatic-cancer
#20
REVIEW
E Giovannetti, C L van der Borden, A E Frampton, A Ali, O Firuzi, G J Peters
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis...
April 21, 2017: Seminars in Cancer Biology
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