159 research outputs found
Очищення циркуляційної води індустріальних рибницьких господарств у фітореакторі з рясковими
The feasibility of using Lemnoideae as treatment agents from nitrogen compounds during treatment of circulating water win CWS is justified in the work. The intensity of transformation of nitrogen compounds in the application of nitridenitrification is limited by the relatively low rates of nitrobacteria metabolism, sensitivity to pH fluctuations, competitive relations with heterotrophic biota of biofilters-nitrifiers. Assimilation of ammonium nitrogen by plants occurs in the process of their growth, so the intensity of water treatment will be determined only by the rate of growth of plant biomass in phytoreactors. The artificial lighting system of the phytoreactor allows, regardless of the presence and level of natural insolation, to provide the necessary effect of removal of nitrogen compounds and other biogenic elements. The expediency of using various types of lamps for lighting of the phytoreactor with Lemnoideae is investigated. The dependence of the growth of plant biomass on the duration and intensity of lighting by different types of lamps is determined. The time of plant doubling during cultivation in contaminated circulation water in CWS is 4.5–6 days with the lighting duration within 4 hours to 2–2.5 days with the lighting duration within 14–16 hours per day. It is also confirmed that the lighting intensity is important for the growth rates of Lemnoideae. When fluorescent lamps are used, the rational limits for the lighting intensity of the phytoreactor surface are 6500–6650 lux. The treatment power by nitrogen of the phytoreactor with Lemnoideae in the specific biomass of plants in the range of 4–6 kg/m2 is 9.6–14.4 gN/(m2·day). Based on the obtained results, it is possible to calculate the required area of the phytoreactor and the power of the lighting system, depending on the load on the biological treatment facilities for ammonium nitrogenИсследовано влияние абиотических факторов на эффективность удаления соединений азота при очистке циркуляционной воды индустриальных рыбоводных хозяйств в фитореакторе с рясковыми. Проведен анализ целесообразности использования люминесцентных и светодиодных ламп в фитореакторе. Определены рациональные значения основных параметров системы искусственного освещения для обеспечения удаления соединений азота из циркуляционной водыДосліджено вплив абіотичних факторів на ефективність видалення сполук нітрогену при очищенні циркуляційної води індустріальних рибницьких господарств у фітореакторі з рясковими. Здійснено аналіз доцільності використання люмінесцентних та світлодіодних ламп в фітореакторі. Визначено раціональні значення основних параметрів системи штучного освітлення для забезпечення видалення сполук нітрогену з циркуляційної вод
Дексмедетомідин для седації в інтенсивній терапії. Огляд літератури та клінічний досвід
Dexmedetomidine is a fairly new and promising drug for use in intensive care and surgery. Due to the fact that it is an agonist of alpha-2-adrenoceptors, dexmedetomidine has an analgesic, sedative effect and affects hemodynamic parameters. Due to the fact that dexmedetomedin does not have the ability to suppress respiration, it is used in patients with respiratory disorders. Dexmedetomidine has minimal side effects and a wide range of uses.Дексмедетомидин — довольно новый и перспективный препарат для использования в интенсивной терапии и при оперативных вмешательствах. Учитывая то, что он является агонистом альфа-2-адренорецепторов, дексмедетомидин имеет анальгетический, седативный эффект и влияет на показатели гемодинамики. Благодаря тому, что дексмедетомидин не обладает способностью подавлять дыхание, он может использоваться у пациентов с нарушением дыхания. Дексмедетомидин имеет минимальное количество побочных эффектов и широкий спектр использования.Дексмедетомідин є доволі новим і перспективним препаратом у використанні в інтенсивній терапії та при оперативних втручаннях. Враховуючи те, що він є агоністом альфа-2-адренорецепторів, дексмедетомідин має аналгетичний, седативний ефект і впливає на показники гемодинаміки. Завдяки тому, що дексмедетомідин не має здатності пригнічувати дихання, він може використовуватись у пацієнтів з порушенням дихання. Дексмедетомідин має мінімальну кількість побічних ефектів та широкий спектр використання
AT-101 ( R -(−)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model
Prostate cancer remains a leading cause of cancer death in American men. Androgen deprivation therapy (ADT) is the most common treatment for advanced prostate cancer patients; however, ADT fails in nearly all cases resulting in castration resistant or androgen-insensitive (AI) disease. In many cases, this progression results from dysregulation of the pro-survival Bcl-2 family proteins. Inhibition of pro-survival Bcl-2 family proteins, therefore, may be an effective strategy to delay the onset of AI disease. Gossypol, a small molecule inhibitor of pro-survival Bcl-2 family proteins, has been demonstrated to inhibit AI prostate cancer growth. The apoptotic effect of gossypol, however, has been demonstrated to be attenuated by the presence of androgen in a prostate cancer xenograft mouse model (Vertebral Cancer of Prostate [VCaP]) treated with AT-101 ( R -(−)-gossypol acetic acid). This study was undertaken to better understand the in vitro effects of androgen receptor (AR) on AT-101-induced apoptosis. VCaP cells treated with AT-101 demonstrated an increase in apoptosis and downregulation of Bcl-2 pro-survival proteins. Upon AR activation in combination with AT-101 treatment, apoptosis is reduced, cell survival increases, and caspase activation is attenuated. Akt and X inhibitor of apoptosis (XIAP) are downregulated in the presence of AT-101, and AR stimulation rescues protein expression. Combination treatment of bicalutamide and AT-101 increases apoptosis by reducing the expression of these pro-survival proteins. These data suggest that combination therapy of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer patients. J. Cell. Biochem. 110: 1187–1194, 2010. Published 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77515/1/22633_ftp.pd
The Hippo Pathway in Prostate Cancer
Despite recent efforts, prostate cancer (PCa) remains one of the most common cancers in men. Currently, there is no effective treatment for castration-resistant prostate cancer (CRPC). There is, therefore, an urgent need to identify new therapeutic targets. The Hippo pathway and its downstream effectors—the transcriptional co-activators, Yes-associated protein (YAP) and its paralog, transcriptional co-activator with PDZ-binding motif (TAZ)—are foremost regulators of stem cells and cancer biology. Defective Hippo pathway signaling and YAP/TAZ hyperactivation are common across various cancers. Here, we draw on insights learned from other types of cancers and review the latest advances linking the Hippo pathway and YAP/TAZ to PCa onset and progression. We examine the regulatory interaction between Hippo-YAP/TAZ and the androgen receptor (AR), as main regulators of PCa development, and how uncontrolled expression of YAP/TAZ drives castration resistance by inducing cellular stemness. Finally, we survey the potential therapeutic targeting of the Hippo pathway and YAP/TAZ to overcome PCa
A sensitive array-based assay for identifying multiple TMPRSS2:ERG fusion gene variants
Studies of gene fusions in solid tumors are not as extensive as in hematological malignancies due to several technical and analytical problems associated with tumor heterogeneity. Nevertheless, there is a growing interest in the role of fusion genes in common epithelial tumors after the discovery of recurrent TMPRSS2:ETS fusions in prostate cancer. Among all of the reported fusion partners in the ETS gene family, TMPRSS2:ERG is the most prevalent one. Here, we present a simple and sensitive microarray-based assay that is able to simultaneously determine multiple fusion variants with a single RT–PCR in impure RNA specimens. The assay detected TMPRSS2:ERG fusion transcripts with a detection sensitivity of <10 cells in the presence of more than 3000 times excess normal RNA, and in primary prostate tumors having no >1% of cancer cells. The ability to detect multiple transcript variants in a single assay is critically dependent on both the primer and probe designs. The assay should facilitate clinical and basic studies for fusion gene screening in clinical specimens, as it can be readily adapted to include multiple gene loci
Long-range activation of FKBP51 transcription by the androgen receptor via distal intronic enhancers
Androgen receptor (AR) is a ligand-controlled transcription factor frequently deregulated in prostate carcinomas. Since there is scarce information on the action of AR on the chromatin level, we have elucidated the molecular mechanisms underlying the androgen-dependent regulation of immunophilin FKBP51 in prostate cancer cells. In comparison to the canonical AR target PSA, FKBP51 is more rapidly and strongly induced by androgen, with the regulation occurring merely at the transcriptional level. FKBP51 locus harbors 13 in silico-predicted androgen response elements (AREs), with most of them located downstream from transcription start site (TSS) and capable of binding AR in vitro. Chromatin immunoprecipitation assays in VCaP and LNCaP prostate cancer cells indicate that activation of the locus by the AR relies on four major intronic sites, with the compound ARE-containing sites ≥90 kb downstream from the TSS playing critical roles. Binding of agonist-loaded AR onto these sites in vivo was accompanied with significant recruitment of RNA polymerase II and BRM-containing chromatin remodeling complexes to the FKBP51 locus, which resulted in changes in the histone density of the locus. Our results indicate that very distal AREs act as genuine and robust enhancers, highlighting the importance of long-range regulation of transcription by the AR
Identification of Replication Competent Murine Gammaretroviruses in Commonly Used Prostate Cancer Cell Lines
A newly discovered gammaretrovirus, termed XMRV, was recently reported to be present in the prostate cancer cell line CWR22Rv1. Using a combination of both immunohistochemistry with broadly-reactive murine leukemia virus (MLV) anti-sera and PCR, we determined if additional prostate cancer or other cell lines contain XMRV or MLV-related viruses. Our study included a total of 72 cell lines, which included 58 of the 60 human cancer cell lines used in anticancer drug screens and maintained at the NCI-Frederick (NCI-60). We have identified gammaretroviruses in two additional prostate cancer cell lines: LAPC4 and VCaP, and show that these viruses are replication competent. Viral genome sequencing identified the virus in LAPC4 and VCaP as nearly identical to another known xenotropic MLV, Bxv-1. We also identified a gammaretrovirus in the non-small-cell lung carcinoma cell line EKVX. Prostate cancer cell lines appear to have a propensity for infection with murine gammaretroviruses, and we propose that this may be in part due to cell line establishment by xenograft passage in immunocompromised mice. It is unclear if infection with these viruses is necessary for cell line establishment, or what confounding role they may play in experiments performed with these commonly used lines. Importantly, our results suggest a need for regular screening of cancer cell lines for retroviral “contamination”, much like routine mycoplasma testing
Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts
Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the68Ga-labelled bombesin analogue AMBA with metabolism-based tar
Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo
Human prostate cancers (PCa) express great variability in their ability to metastasize to bone. The identification of molecules associated with aggressive phenotypes will help to define PCa subsets and will ultimately lead to better treatment strategies. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others. The present investigation extends our previous investigations by determining the expression of CXCR4 and CXCL12 in humans using high-density tissue microarrays constructed from clinical samples obtained from a cohort of over 600 patients. These data demonstrate that CXCR4 protein expression is significantly elevated in localized and metastastic cancers. At the RNA level, human PCa tumors also express CXCR4 and message, but overall, they were not significantly different suggesting post-transcriptional regulation of the receptor plays a major role in regulating protein expression. Similar observations were made for CXCL12 message, but in this case more CXCL12 message was expressed by metastastic lesions as compared to normal tissues. PCa cell lines also express CXCL12 mRNA, and regulate mRNA expression in response to CXCL12 and secrete biologically active protein. Furthermore, neutralizing antibody to CXCL12 decreased the proliferation of bone homing LNCaP C4-2B and PC3 metastastic tumor cells. These investigations provide important new information pertaining to the molecular basis of how tumors may ‘home’ to bone, and the mechanisms that may account for their growth in selected end organs. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34903/1/10522_ftp.pd
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