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https://www.readbyqxmd.com/read/27913103/ontogeny-aging-and-gender-related-changes-in-hepatic-multidrug-resistant-protein-genes-in-rats
#1
Qiong-Ni Zhu, Wei-Yu Hou, Shang-Fu Xu, Yuan-Fu Lu, Jie Liu
: Multidrug resistance proteins (Mrps) are efflux transporters playing important roles in endogenous substances and xenobiotics transport out of the liver. Children, elderly, gender and physio-pathological conditions could influence their expression and result in changes in drug disposition. AIM: This study was aimed to examine the development-, ageing-, and sex-dependent changes in Mrp1-4 and ATP-binding cassette sub-family G member 2 (Abcg2) gene expressions in livers of rats...
November 29, 2016: Life Sciences
https://www.readbyqxmd.com/read/27911857/yap1-regulates-abcg2-and-cancer-cell-side-population-in-human-lung-cancer-cells
#2
Yuyuan Dai, Shu Liu, Wen-Qian Zhang, Yi-Lin Yang, Phillip Hang, Hui Wang, Li Cheng, Ping-Chih Hsu, Yu-Chen Wang, Zhidong Xu, David M Jablons, Liang You
A small population of cancer cells called cancer-initiating cells or cancer stem cells (CSCs) are involved in drug resistance, metastasis, and cancer relapse. Finding pathways that regulate CSC is very important for clinical therapy. ATP-binding cassette sub-family G member 2 (ABCG2) plays a role in side population (SP) cell formation and contributes to chemotherapy resistance in common forms of cancer. Yes-associated protein 1 (YAP1) is a major transcriptional effector of the Hippo pathway, which plays important roles in organ size control and tumorigenesis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911610/successful-consecutive-expansion-of-limbal-explants-using-a-biosafe-culture-medium-under-feeder-layer-free-conditions
#3
Marina López-Paniagua, Teresa Nieto-Miguel, Ana de la Mata, Sara Galindo, José M Herreras, Rosa M Corrales, Margarita Calonge
PURPOSE: Transplantation of in vitro cultured limbal epithelial stem cells (LESCs) is a treatment widely used for LESC deficiency. However, the number of limbal tissue donors is limited, and protocols for LESC cultivation often include compounds and/or feeder layers that can induce side effects and/or increase the cost of the culture procedure. We investigated the feasibility of obtaining more than one limbal primary culture (LPC) from the same biopsy using a culture medium in which several potentially harmful compounds were replaced at the same time by biosafe supplements, allowing the LESC cultivation without feeder layers...
December 2, 2016: Current Eye Research
https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#4
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27906625/uric-acid-metabolism-of-kidney-and-intestine-in-a-rat-model-of-chronic-kidney-disease
#5
Michito Nagura, Yoshifuru Tamura, Takanori Kumagai, Makoto Hosoyamada, Shunya Uchida
Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27862636/a-novel-method-for-a-high-enrichment-of-human-corneal-epithelial-stem-cells-for-genomic-analysis
#6
Jhansi Rani Kasinathan, Venkatesh Prajna Namperumalsamy, Muthukkaruppan Veerappan, Gowri Priya Chidambaranathan
Understanding the molecular mechanisms that regulate the corneal epithelial stem cells (CESCs) in maintaining corneal homeostasis remains elusive largely due to the lack of a specific marker for their isolation. This study aims to enrich CESCs from human donor limbal epithelium and to evaluate the level of enrichment based on expression of ΔNp63α, a putative CESC marker. A two-stage enrichment of CESCs was carried out. (a) The limbal basal epithelial cells were isolated by differential enzymatic treatment and five-fold enrichment was achieved from 2% of CESCs present in the total limbal epithelium...
December 2016: Microscopy Research and Technique
https://www.readbyqxmd.com/read/27861472/-rheumatoid-arthritis-ra-disease-activity-predicts-function-of-abcb1-p-gp-and-abcg2-bcrp1-drug-efflux-transporters
#7
Virginia Pascual-Ramos, Yemil Atisha-Fregoso, Guadalupe Lima, Hilda Fragoso-Loyo, Juan Jákez-Ocampo, Irazú Contreras-Yáñez, Luis Llorente
BACKGROUND: P-gp and BCRP1 are transporter proteins that may confer drug resistance. OBJECTIVE: To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity. METHODS: We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry...
November 2016: Gaceta Médica de México
https://www.readbyqxmd.com/read/27857072/dormant-cancer-cells-accumulate-high-protoporphyrin-ix-levels-and-are-sensitive-to-5-aminolevulinic-acid-based-photodynamic-therapy
#8
Taku Nakayama, Shimpei Otsuka, Tatsuya Kobayashi, Hodaka Okajima, Kentaro Matsumoto, Yuichiro Hagiya, Keiji Inoue, Taro Shuin, Motowo Nakajima, Tohru Tanaka, Shun-Ichiro Ogura
Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856956/the-efflux-transporter-abcg2-maintains-prostate-stem-cells
#9
Neha G Sabnis, Austin Miller, Mark A Titus, Wendy J Huss
: Prostate Stem Cells (PSCs) are characterized by their intrinsic resistance to Androgen Deprivation Therapy (ADT), possibly due to the lack of Androgen Receptor (AR) expression. PSCs resistance to ADT and PSC expansion in Castration Recurrent Prostate Cancer (CRPC) has sparked great interest in using differentiation therapy as an adjuvant to ADT. Understanding the mechanisms, by which PSCs maintain their undifferentiated phenotype, thus has important implications in differentiation therapy...
November 17, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27856528/in-vivo-hepatic-enhancer-elements-in-the-human-abcg2-locus
#10
Rachel J Eclov, Mee J Kim, Robin P Smith, Xiaomin Liang, Nadav Ahituv, Deanna L Kroetz
ABCG2 encodes the mitoxantrone resistance protein (MXR, BCRP), an ATP-binding cassette (ABC) efflux membrane transporter. Computational analysis of the ~300 kb region of DNA surrounding ABCG2 (chr4:88911376-89220011, hg19) identified 30 regions with potential cis-regulatory capabilities. These putative regulatory regions were tested for their enhancer and suppressor activity in a human liver cell line using luciferase reporter assays. The in vitro enhancer and suppressor assays identified four regions that decreased gene expression and five regions that increased expression >1...
November 17, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27852063/depression-induces-poor-prognosis-associates-with-the-down-regulation-brain-derived-neurotrophic-factor-of-serum-in-advanced-small-cell-lung-cancer
#11
Yufeng Wu, Ruirui Si, Sen Yang, Suhua Xia, Zelai He, Lili Wang, Zhen He, Qiming Wang, Hong Tang
Patients with lung cancer often experience a state of depression, and these conditions may severely affect their quality of life (QoL) and prescription compliance. The current study was conducted to delineate the complex links between depression and the prognosis of patients with small cell lung cancer (SCLC) and the underlying mechanism was also explored.186 patients who received platinum-based chemotherapy for newly diagnosed stage III or stage IV SCLC were enrolled. The Self-Rating Depression Scale (SDS) questionnaire was completed the day before the start of chemotherapy to assess the depression status of the patients...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27852006/a-combination-of-photodynamic-therapy-and-chemotherapy-displays-a-differential-cytotoxic-effect-on-human-metastatic-melanoma-cells
#12
Fa Nsole Biteghe, L M Davids
BACKGROUND: Cutaneous melanoma represents the most lethal form of skin cancer and remains refractory to current therapies. Failure of treatment has been attributed to the over-expression of ABC transporters which efflux the drugs, below their cytotoxic threshold within cells. Therefore, this study set to investigate; the efficacy of a combinatorial approach comprising chemotherapy (Dacarbazine) and photodynamic therapy (PDT) to overcome resistance in pigmented and unpigmented metastatic melanoma and potentially identify resistant mechanisms...
November 8, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27851764/kinetic-modeling-of-abcg2-transporter-heterogeneity-a-quantitative-single-cell-analysis-of-the-side-population-assay
#13
Adam F Prasanphanich, Douglas E White, Margaret A Gran, Melissa L Kemp
The side population (SP) assay, a technique used in cancer and stem cell research, assesses the activity of ABC transporters on Hoechst staining in the presence and absence of transporter inhibition, identifying SP and non-SP cell (NSP) subpopulations by differential staining intensity. The interpretation of the assay is complicated because the transporter-mediated mechanisms fail to account for cell-to-cell variability within a population or adequately control the direct role of transporter activity on staining intensity...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27845419/abc-transporter-polymorphisms-are-associated-with-irinotecan-pharmacokinetics-and-neutropenia
#14
M Li, E L Seiser, R M Baldwin, J Ramirez, M J Ratain, F Innocenti, D L Kroetz
Neutropenia is a common dose-limiting toxicity associated with irinotecan treatment. Although UGT1A1 variants have been associated with neutropenia, a fraction of neutropenia risk remains unaccounted for. To identify additional genetic markers contributing to variability in irinotecan pharmacokinetics and neutropenia, a regression analysis was performed in 78 irinotecan-treated patients to analyze comprehensively three hepatic efflux transporter genes (ABCB1, ABCC1 and ABCG2). rs6498588 (ABCC1) and rs12720066 (ABCB1) were associated with increased SN-38 exposure, and rs17501331 (ABCC1) and rs12720066 were associated with lower absolute neutrophil count nadir...
November 15, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27832326/silencing-of-histone-deacetylase-2-suppresses-malignancy-for-proliferation-migration-and-invasion-of-glioblastoma-cells-and-enhances-temozolomide-sensitivity
#15
Zhiqiang Zhang, Yunmin Wang, Jiehan Chen, Qijia Tan, Caijun Xie, Cong Li, Wengang Zhan, Mei Wang
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in glioblastoma multiforme (GBM) are not well known. Our present study investigated the expression of class I HDACs (HDAC1, 2, 3, 8) in GBM U87, A172, U251, and LN229 cells and compared their levels with that in primary normal human astrocytes (NHA) cells. It showed that HDAC2 expression is significantly up-regulated in GBM cells. Silencing of HDAC2 via its specific siRNAs can suppress the in vitro proliferation, migration, and invasion of GBM U87 and A172 cells...
November 10, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27816545/effect-of-abemaciclib-ly2835219-on-enhancement-of-chemotherapeutic-agents-in-abcb1-and-abcg2-overexpressing-cells-in-vitro-and-in-vivo
#16
Tong Wu, Zhen Chen, Kenneth K W To, Xiaona Fang, Fang Wang, Bin Cheng, Liwu Fu
Multidrug resistance (MDR) is the major obstacle of the success in cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, play a significant role in mediating MDR by pumping anticancer drugs out of cancer cells. Abemaciclib (LY2835219) is an orally bioavailable CDK4/6 inhibitor under phase III clinical trials. Here, we found that LY2835219 remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo...
November 2, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27812982/ampk-and-cancer
#17
Zhiyu Wang, Neng Wang, Pengxi Liu, Xiaoming Xie
This chapter focuses on the role of AMPK as a stress-response molecule with an emphasis on its duplex implication in carcinogenesis and cancer drug resistance. AMPK is closely correlated to the tumor-suppressive functions of LKB1 and P53, consequently modulating the activity of cellular survival signaling such as mTOR and Akt, leading to cell growth inhibition and cell cycle arrest. On the contrary, AMPK is tightly involved in cancer drug resistance via interacting with multiple known mechanisms of chemoresistance such as ABCG2 expression, autophagy induction, and cancer stem cells enrichment...
2016: EXS
https://www.readbyqxmd.com/read/27810353/pyrrolopyrimidine-derivatives-and-purine-analogs-as-novel-activators-of-multidrug-resistance-associated-protein-1-mrp1-abcc1
#18
Sven Marcel Schmitt, Katja Stefan, Michael Wiese
Multidrug resistance (MDR) is the main cause of diminished success in cancer chemotherapy. ABC transport proteins are considered to be one important factor of MDR. Besides P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) is associated with non-response to chemotherapy in different cancers. While considerable effort was spent in overcoming MDR during the last two decades, almost nothing is known with respect to activators of transport proteins...
October 31, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27798870/immunological-and-clinical-impact-of-cancer-stem-cells-in-vulvar-cancer-role-of-cd133-cd24-abcg2-expressing-cells
#19
Chiara Napoletano, Filippo Bellati, Ilary Ruscito, Milena Pernice, Ilaria Grazia Zizzari, Salvatore Caponnetto, Federica Tomao, Luigi Frigerio, Marco Liberati, Aurelia Rughetti, Donatella Caserta, Pierluigi Benedetti Panici, Marianna Nuti
BACKGROUND: Cancer stem cells (CSCs) are tumour-initiating cells with self-renewal properties and chemo/radio-resistance. Regulatory T-cells (Tregs) influence CSCs through several mechanisms. In different solid tumours, the presence of both cell populations correlated with poor survival. In vulvar cancer, little is known regarding biological markers able to predict patient prognosis. We investigated the presence and clinical impact of CSCs and infiltrating Treg in primary vulvar cancer...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27787353/modelling-of-atorvastatin-pharmacokinetics-and-the-identification-of-the-effect-of-a-bcrp-polymorphism-in-the-japanese-population
#20
Nikolaos Tsamandouras, Yingying Guo, Thierry Wendling, Stephen Hall, Aleksandra Galetin, Leon Aarons
AIM: Ethnicity plays a modulating role in atorvastatin pharmacokinetics (PK), with Asian patients reported to have higher exposure compared with Caucasians. Therefore, it is difficult to safely extrapolate atorvastatin PK data and models across ethnic groups. This work aims to develop a population PK model for atorvastatin and its pharmacologically active metabolites specifically for the Japanese population. Subsequently, it aimed to identify genetic polymorphisms affecting atorvastatin PK in this population...
October 26, 2016: Pharmacogenetics and Genomics
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