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https://www.readbyqxmd.com/read/28350964/promoting-vaginal-distribution-of-e7-and-mcl-1-sirna-silencing-nanoparticles-for-cervical-cancer-treatment
#1
Anna Lechanteur, Tania Furst, Brigitte Evrard, Philippe Delvenne, Geraldine Piel, Pascale Hubert
There is an urgent need to develop a less aggressive and more effective treatment against cervical lesions induced by different high-risk human papillomavirus (HR-HPV). We investigated the potential of a cocktail of small interfering RNA (siRNA) directed against the oncoprotein E6 (E6), the oncoprotein E7 (E7) and/or the anti-apoptotic protein MCL-1 (MCL-1). The combination of siRNA anti-E7 and anti-MCL-1 demonstrated high efficacy on multiple HPV16 and HPV18 cell lines and no effects on healthy keratinocytes...
March 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28350865/multi-drug-loaded-micelles-delivering-chemotherapy-and-targeted-therapies-directed-against-hsp90-and-the-pi3k-akt-mtor-pathway-in-prostate-cancer
#2
Bao Le, Ginny L Powers, Yu Tong Tam, Nicholas Schumacher, Rita L Malinowski, Laura Steinke, Glen Kwon, Paul C Marker
BACKGROUND: Advanced prostate cancers that are resistant to all current therapies create a need for new therapeutic strategies. One recent innovative approach to cancer therapy is the simultaneous use of multiple FDA-approved drugs to target multiple pathways. A challenge for this approach is caused by the different solubility requirements of each individual drug, resulting in the need for a drug vehicle that is non-toxic and capable of carrying multiple water-insoluble antitumor drugs...
2017: PloS One
https://www.readbyqxmd.com/read/28350814/compensatory-changes-in-cyp-expression-in-three-different-toxicology-mouse-models-car-null-cyp3a-null-and-cyp2b9-10-13-null-mice
#3
Ramiya Kumar, Linda C Mota, Elizabeth J Litoff, John P Rooney, W Tyler Boswell, Elliott Courter, Charles M Henderson, Juan P Hernandez, J Christopher Corton, David D Moore, William S Baldwin
Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28350804/syndecan-1-deficiency-promotes-tumor-growth-in-a-murine-model-of-colitis-induced-colon-carcinoma
#4
Adi Binder Gallimidi, Gabriel Nussbaum, Esther Hermano, Barak Weizman, Amichay Meirovitz, Israel Vlodavsky, Martin Götte, Michael Elkin
Syndecan-1 (Sdc1) is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28350784/targeting-smoothened-sensitizes-gastric-cancer-to-chemotherapy-in-experimental-models
#5
Huifa Ma, Yongsheng Tian, Xiangyang Yu
BACKGROUND The Hedgehog pathway receptor smoothened (SMO) has critical roles in tumor progression. However, whether SMO is a key factor regulating gastric cancer chemotherapy resistance is unknown. MATERIAL AND METHODS We investigated the potential functions of SMO in inducing gastric cancer paclitaxel resistance in clinical samples, gastric cancer cell lines (424GC and AGS), and subcutaneous syngeneic mouse models. RESULTS We found high SMO expression in paclitaxel-resistant gastric cancer clinical samples...
March 28, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28350672/purified-adipose-derived-stromal-cells-provide-superior-fat-graft-retention-compared-with-unenriched-stromal-vascular-fraction
#6
Elizabeth R Zielins, Elizabeth A Brett, Charles P Blackshear, John Flacco, Ryan C Ransom, Michael T Longaker, Derrick C Wan
Cell-assisted lipotransfer has shown much promise as a technique to improve fat graft retention in both mouse and human studies. However, the literature varies as to whether fresh stromal vascular fraction or culture-expanded adipose-derived stromal cells are used to augment volume retention. The authors' study sought to determine whether there was a significant advantage to using adipose-derived stromal cells over unpurified stromal vascular fraction cells in a mouse model of cell-assisted lipotransfer.
April 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28350671/enhanced-calvarial-bone-healing-in-cd11c-tlr4-and-myd88-mice
#7
Dan Wang, Gwen M Taylor, James R Gilbert, Joseph E Losee, Chhinder P Sodhi, David J Hackam, Timothy R Billiar, Gregory M Cooper
BACKGROUND: Inflammation is integral to the injury response. The inflammatory response is essential to the host defense against infection and also to tissue regeneration and repair. Toll-like receptors (TLRs) are critical activators of the innate immune response and present attractive therapeutic targets for inflammation-modulated tissue regeneration. The authors' previous study showed that depletion of TLR4 resulted in accelerated skull bone healing concurrent with increased expression of osteoclastogenic genes...
April 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28346918/5-ht1a-receptors-mediate-analgesia-induced-by-emulsified-sevoflurane-in-thermal-nociception-but-have-little-effect-on-chemical-nociception
#8
Chen Yan, Dai Ti-Jun, Li Xin, Cao Gao, Jiang Shen, Tao Hong, Meng Zhi-Xiu
OBJECTIVE: The study aimed to investigate the relationship between the analgesic effect of sevoflurane and 5-serotonin receptor 1A (5-HT1A R) in the spinal cords of mice. METHODS: Analgesic mouse models were established by intraperitoneal injection of emulsified sevoflurane, and the influence of p-MPPF (a specific antagonist of 5-HT1A Rs) intrathecal injection on the changes in tail-flick latency in tail-withdrawal test, pain threshold in hot-plate test (HPPT), and writhing times in acetic acid-induced writhing test were recorded...
March 28, 2017: Pharmacology
https://www.readbyqxmd.com/read/28346765/the-medial-temporal-memory-system-in-down-syndrome-translating-animal-models-of-hippocampal-compromise
#9
Caron A C Clark, Fabian Fernandez, Stella Sakhon, Goffredina Spanò, Jamie O Edgin
Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and serial order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts...
March 27, 2017: Hippocampus
https://www.readbyqxmd.com/read/28346695/contribution-of-small-conductance-k-channels-to-sinoatrial-node-pacemaker-activity-insights-from-atrial-specific-na-ca-2-exchange-knockout-mice
#10
Angelo G Torrente, Rui Zhang, Heidi Wang, Audrey Zaini, Brian Kim, Xin Yue, Kenneth D Philipson, Joshua I Goldhaber
Small conductance K(+) (SK) channels have been implicated as modulators of spontaneous depolarization and electrical conduction that may be involved in cardiac arrhythmia. However, neither their presence nor their contribution to sinoatrial node (SAN) pacemaker activity have been investigated. Using quantitative PCR (q-PCR), immunostaining and patch clamp recordings of membrane current and voltage, we identified all three SK isoforms (SK1, SK2 and SK3) in mouse SAN. Inhibition of SK channels with the specific blocker apamin prolonged action potentials (APs) in isolated SAN cells...
March 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28346493/aberrant-neuronal-activity-induced-signaling-and-gene-expression-in-a-mouse-model-of-rasopathy
#11
Franziska Altmüller, Santosh Pothula, Anil Annamneedi, Saeideh Nakhei-Rad, Carolina Montenegro-Venegas, Eneko Pina-Fernández, Claudia Marini, Monica Santos, Denny Schanze, Dirk Montag, Mohammad R Ahmadian, Oliver Stork, Martin Zenker, Anna Fejtova
Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346476/reduced-dosage-of-%C3%AE-catenin-provides-significant-rescue-of-cardiac-outflow-tract-anomalies-in-a-tbx1-conditional-null-mouse-model-of-22q11-2-deletion-syndrome
#12
Silvia E Racedo, Erica Hasten, Mingyan Lin, Gnanapackiam Sheela Devakanmalai, Tingwei Guo, Ertugrul M Ozbudak, Chen-Leng Cai, Deyou Zheng, Bernice E Morrow
The 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome; DiGeorge syndrome) is a congenital anomaly disorder in which haploinsufficiency of TBX1, encoding a T-box transcription factor, is the major candidate for cardiac outflow tract (OFT) malformations. Inactivation of Tbx1 in the anterior heart field (AHF) mesoderm in the mouse results in premature expression of pro-differentiation genes and a persistent truncus arteriosus (PTA) in which septation does not form between the aorta and pulmonary trunk...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#13
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346421/serpinb2-regulates-stromal-remodelling-and-local-invasion-in-pancreatic-cancer
#14
N L E Harris, C Vennin, J R W Conway, K L Vine, M Pinese, M J Cowley, R F Shearer, M C Lucas, D Herrmann, A H Allam, M Pajic, J P Morton, A V Biankin, M Ranson, P Timpson, D N Saunders
Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346394/engineered-resistant-starch-ers-diet-shapes-colon-microbiota-profile-in-parallel-with-the-retardation-of-tumor-growth-in-in-vitro-and-in-vivo-pancreatic-cancer-models
#15
Concetta Panebianco, Kaarel Adamberg, Signe Adamberg, Chiara Saracino, Madis Jaagura, Kaia Kolk, Anna Grazia Di Chio, Paolo Graziano, Raivo Vilu, Valerio Pazienza
BACKGROUND/AIMS: Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model...
March 27, 2017: Nutrients
https://www.readbyqxmd.com/read/28346347/biosynthesis-of-%C3%AE-glucosidase-inhibitors-by-a-newly-isolated-bacterium-paenibacillus-sp-tku042-and-its-effect-on-reducing-plasma-glucose-in-a-mouse-model
#16
Van Bon Nguyen, Anh Dzung Nguyen, Yao-Haur Kuo, San-Lang Wang
Paenibacillus sp. TKU042, a bacterium isolated from Taiwanese soil, produced α-glucosidase inhibitors (aGIs) in the culture supernatant when commercial nutrient broth (NB) was used as the medium for fermentation. The supernatant of fermented NB (FNB) showed stronger inhibitory activities than acarbose, a commercial anti-diabetic drug. The IC50 and maximum α-glucosidase inhibitory activities (aGIA) of FNB and acarbose against α-glucosidase were 81 μg/mL, 92% and 1395 μg/mL, 63%, respectively. FNB was found to be strongly thermostable, retaining 95% of its relative activity, even after heating at 100 °C for 30 min...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346234/outstanding-animal-studies-in-allergy-i-from-asthma-to-food-allergy-and-anaphylaxis
#17
Erika Jensen-Jarolim, Isabella Pali-Schöll, Franziska Roth-Walter
PURPOSE OF REVIEW: Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. RECENT FINDINGS: While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results...
March 24, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28346225/long-telomeres-protect-against-age-dependent-cardiac-disease-caused-by-notch1-haploinsufficiency
#18
Christina V Theodoris, Foteini Mourkioti, Yu Huang, Sanjeev S Ranade, Lei Liu, Helen M Blau, Deepak Srivastava
Diseases caused by gene haploinsufficiency in humans commonly lack a phenotype in mice that are heterozygous for the orthologous factor, impeding the study of complex phenotypes and critically limiting the discovery of therapeutics. Laboratory mice have longer telomeres relative to humans, potentially protecting against age-related disease caused by haploinsufficiency. Here, we demonstrate that telomere shortening in NOTCH1-haploinsufficient mice is sufficient to elicit age-dependent cardiovascular disease involving premature calcification of the aortic valve, a phenotype that closely mimics human disease caused by NOTCH1 haploinsufficiency...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#19
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345998/pharmacokinetics-of-a-single-dose-of-voriconazole-administered-orally-with-and-without-food-to-red-tailed-hawks-buteo-jamaicensus
#20
Ruth A Parsley, Lisa A Tell, Ronette Gehring
OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed...
April 2017: American Journal of Veterinary Research
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