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Effect of living conditions on biochemical and hematological parameters of the cynomolgus monkey 下载免费PDF全文
Liang Xie Qinming Zhou Shigang Liu Fan Xu Carol A. Shively Qingyuan Wu Wei Gong Yongjia Ji Liang Fang Leilei Li Narayan D. Melgiri Peng Xie 《American journal of primatology》2014,76(11):1011-1024
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Wang X Yin L Rao P Stein R Harsch KM Lee Z Heston WD 《Journal of cellular biochemistry》2007,102(3):571-579
Over a half century ago, Charles Huggins demonstrated the response of prostate cancer to androgen deprivation therapy. Subsequently, many discoveries and evolving findings continued to support a research rationale focused on the androgen receptor (AR) as a key target for prostate cancer. More recently, preliminary trials have suggested that other targets could also be useful in the treatment of prostate cancer, and the proposed strategies for treatment have ranged from targeted toxins to immunotherapeutic agents. We provide an overview of some of these approaches, with an emphasis on those that employ prostate specific membrane antigen (PSMA) as a target. 相似文献
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Dual‐labeled chemiluminescence enzyme immunoassay for simultaneous measurement of total prostate specific antigen (TPSA) and free prostate specific antigen (FPSA) 下载免费PDF全文
The specificity for early diagnostic of prostate‐specific antigen (PSA) is low because the current technology mostly allows the detection of only one biomarker at one time. In this work, a dual‐labeled chemiluminescence enzyme immunoassay (CLEIA) for simultaneous measurement of total PSA (TPSA) and free PSA (FPSA) was proposed. Anti‐PSA McAb (Mab1) was immobilized on a microplate as the solid phase, horseradish peroxidase (HRP)‐labeled anti‐TPSA monoclonal antibody (McAb2) and alkaline phosphatase (ALP)‐labeled anti‐FPSA McAb3 were used as detection antibodies. Two chemiluminescence reactions of HRP with luminol and ALP with 4‐methoxy‐4‐(3‐phosphate‐phenyl)‐spiro‐(1,2‐dioxetane‐3,2′‐adamantane) (AMPPD) were used as the signal detecting system. Based on a sandwich model, the amount of FPSA and TPSA could be determined simultaneously. The effects of several physico‐chemical parameters were studied and optimized. Cross‐reactivities of six common tumor markers in serum were studied. The proposed method presented the sensitivity of 0.03 ng ml?1 and 0.05 ng ml?1 for FPSA and TPSA respectively, with low cross‐reactivities. Compared with the results from commercial chemiluminescent kits there was good correlation, indicating that this established method could be used to simultaneously to measure the concentrations of FPSA and TPSA in one serum sample and also could greatly facilitate the early diagnosis for PCa in clinical practice. 相似文献
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Mahmoud Hassani Fatemeh Hajari Taheri Zahra Sharifzadeh Arash Arashkia Jamshid Hadjati Wytske M. van Weerden Mohammad Hossein Modarressi Mohsen Abolhassani 《Journal of cellular biochemistry》2019,120(6):10787-10795
Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) is considered to be a novel anticancer therapy. To date, in most cases, single-chain variable fragments (scFvs) of murine origin have been used in CARs. However, this structure has limitations relating to the potential immunogenicity of mouse antigens in humans and the relatively large size of scFvs. For the first time, we used camelid nanobody (VHH) to construct CAR T cells against prostate specific membrane antigen (PSMA). The nanobody against PSMA (NBP) was used to show the feasibility of CAR T cells against prostate cancer cells. T cells were transfected, and then the surface expression of the CAR T cells was confirmed. Then, the functions of VHH-CAR T cell were evaluated upon coculture with prostate cancer cells. At the end, the cytotoxicity potential of NBPII-CAR in T cells was approximated by determining the cell surface expression of CD107a after encountering PSMA. Our data show the specificity of VHH-CAR T cells against PSMA+ cells (LNCaP), not only by increasing the interleukin 2 (IL-2) cytokine (about 400 pg/mL), but also the expression of CD69 by almost 38%. In addition, VHH-CAR T cells were proliferated by nearly 60% when cocultured with LNCaP, as compared with PSMA negative prostate cancer cell (DU-145), which led to the upregulation of CD107a in T cells upto 31%. These results clearly show the possibility of using VHH-based CAR T cells for targeted immunotherapy, which may be developed to target virtually any tumor-associated antigen for adoptive T-cell immunotherapy of solid tumors. 相似文献
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To establish reproductive biological techniques in mammals, it is important to understand the growth environment of the embryo. Oviduct epithelial cells are in close proximity to the embryo during pre-implantation development. We, therefore, established an immortalized oviduct epithelial cell line from the cynomolgus monkey, evaluated the usefulness of these cells as feeder cells for embryo culture, and investigated the gene expression of several growth factors and cytokines in the cells. The immortalized cells were positive for the anti-cytokeratin antibody, as determined by immunocytochemistry, indicating that they are epithelial. They also expressed oviductin, which is specific to oviduct epithelial cells, glyceraldehyde-3-phosphate dehydrogenase (control), leukemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor 1, transforming growth factor beta-2, and interleukin 4. Mouse embryo development was improved when the immortalized cells were used as feeder cells. This cell line is also useful for studying the factors secreted by oviduct epithelial cells. 相似文献
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Elena L. Sun Danielle G. Aspar Roger G. Ulrich George W. Melchior 《In vitro cellular & developmental biology. Plant》1990,26(2):147-150
Summary A method is described for the preservation and subsequent recovery of hepatocytes obtained by collagenase perfusion of cynomolgus
monkey (Macaca, fascicularis) livers. The fresh cells are suspended in fetal bovine serum containing 10% dimethylsulfoxide and, using a microprocessor-controlled,
liquid nitrogen freezing chamber and a specific cooling protocol, processed in such a way that they can be stored in liquid
nitrogen for several months and still restored to active culture. When the cryopreserved cells were established in culture
they were found to actively synthesize and secrete both albumin and apolipoprotein A-I. That, taken together with morphologic
evidence, was viewed as indication that the cells recovered in culture were in fact hepatocytes and not some other cell type
from the monkey liver. The availability of this procedure for storing hepatocytes should contribute significantly to the efficient
use of nonhuman primates as models with which to study hepatic metabolism. 相似文献
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Ide H Nakagawa T Terado Y Kamiyama Y Muto S Horie S 《Biochemical and biophysical research communications》2008,369(2):292-296
Protein tyrosine kinase plays a central role in the proliferation and differentiation of various types of cells. One of these protein kinases, Tyk2, a member of the Jak family kinases, is known to play important roles in receptor signal transduction by interferons, interleukins, growth factors, and other hormones. In the present study, we investigated Tyk2 expression and its role in the growth and invasiveness of human prostate cancer cells. We used a small interfering RNA targeting Tyk2 and an inhibitor of Tyk2, tyrphostin A1, to suppress the expression and signaling of Tyk2 in prostate cancer cells. We detected mRNAs for Jak family kinases in prostate cancer cell lines by RT-PCR and Tyk2 protein in human prostate cancer specimens by immunohistochemistry. Inhibition of Tyk2 signaling resulted in attenuation of the urokinase-type plasminogen activator-enhanced invasiveness of prostate cancer cells in vitro without affecting the cellular growth rate. These results suggest that Tyk2 signaling in prostate cancer cells facilitate invasion of these cells, and interference with this signaling may be a potential therapeutic pathway. 相似文献
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Herpes B virus replication and viral lesions in the liver of a cynomolgus macaque which died from severe disease with rapid onset 下载免费PDF全文
Stefan Pöhlmann Michael Suntz Valerij Akimkin Martina Bleyer Artur Kaul 《Journal of medical primatology》2017,46(5):256-259
Herpes B virus (BV, Macacine alphaherpesvirus 1) infects macaques asymptomatically, with rare exceptions, but can cause fatal encephalitis in humans. Here, we report disseminated BV infection in a cynomolgus macaque that had died within 12 hour after the onset of unspecific symptoms. Multifocal lesions surrounded by viral antigen were detected in liver while other organs remained inconspicuous, indicating that the liver is a major target. Moreover, high copy numbers of viral DNA were found in feces, underlining the excrements are a potential source of transmission. 相似文献
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Haoyong Li Zhe Ma Zhifei Che Qi Li Jinfeng Fan Zhiyan Zhou Yaoxi Wu Yingxia Jin Peiyu Liang Xianping Che 《Journal of cellular and molecular medicine》2020,24(17):10202-10215
Current treatments including androgen deprivation fail to prevent prostate cancer (PrCa) from progressing to castration‐resistant PrCa (CRPC). Accumulating evidence highlights the relevance of prostate‐specific antigen (PSA) in the development and progression of PrCa. The underlying mechanism whereby PSA functions in PrCa, however, has yet been elucidated. We demonstrated that PSA knockdown attenuated tumorigenesis and metastasis of PrCa C4‐2 cells in vitro and in vivo, whereas promoted the apoptosis in vitro. To illuminate the comprehensive role of PSA in PrCa, we performed an isobaric tag for relative and absolute quantitation (iTRAQ)‐based proteomic analysis to explore the proteomic change induced by PSA knockdown. Among 121 differentially expressed proteins, 67 proteins were up‐regulated, while 54 proteins down‐regulated. Bioinformatics analysis was used to explore the mechanism through which PSA exerts influence on PrCa. Protein‐protein interaction analysis showed that PSA may mediate POTEF, EPHA3, RAD51C, HPGD and MCM4 to promote the initiation and progression of PrCa. We confirmed that PSA knockdown induced the up‐regulation of MCM4 and RAD51C, while it down‐regulated POTEF and EPHA3; meanwhile, MCM4 was higher in PrCa para‐cancerous tissue than in cancerous tissue, suggesting that PSA may facilitate the tumorigenesis by mediating MCM4. Our findings suggest that PSA plays a comprehensive role in the development and progression of PrCa. 相似文献
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Several attempts have been made over the past decade to explore the concept of prodrug strategies that exploit PSA as a molecular target for the release of anticancer drugs in prostate tumors using various prostate specific antigen (PSA)-cleavable peptide linkers, but the desired antitumor and antimetastatic efficacy has not yet been fully achieved. We set out to look for new PSA-cleavable peptide substrates that could be cleaved more rapidly and efficiently than the previously used peptides. To look for the most susceptible PSA-cleavable peptide substrates, we used the so-called spot technology. With the following general formula, we designed 25 different fluorogenic heptapeptides; Cellulose-P5-P4-P3-P2-P1-P1′-P2’ (Fluorophore). The increase of the fluorescence in the supernatant of the reaction mixture was monitored using a 96-well fluorometric plate reader with excitation of λex 485 nm and λem 535 nm. Three sequences showed a high fluorogenic liberation after incubation with PSA, i.e., Arg-Arg-Leu-His-Tyr-Ser-Leu (7), Arg-Arg-Leu-Asn-Tyr-Ser-Leu (8) and Arg-Ser-Ser-Tyr-Arg-Ser-Leu (23). Future incorporation of these optimized substrates in the PSA-cleavable prodrug formulations could further optimize the cleavage pattern and so the release characteristics of these prodrugs to rapidly and efficiently liberate the free cytotoxic agents inside the tumor tissues. 相似文献
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Characterization of a PRISTANE‐induced lupus‐associated model in the non‐human primate cynomolgus monkey 下载免费PDF全文
Jing Wang Hui Shen Yuqiang Zhu Ying Zhu Lei Cai Zhiyao Wang Qin Shi Yuhua Qiu 《Journal of medical primatology》2018,47(1):18-28
Background
Lupus is an autoimmune disease with complex syndrome. Rodent models have limitations for recapitulating the spectrum of the disease. A more powerful translational model is desirable.Method
Lupus‐associated model in cynomolgus monkeys was induced by two intraperitoneal injections of 2, 6, 10, 14‐tetramethylpentadecane (PRISTANE). Lupus‐specific biomarkers and manifestations over a 246‐day period were observed at multilevel. To visualize and quantify kidney function in real time, contrast‐enhanced ultrasound was used.Results
The indicative biomarkers and manifestations fulfilled major diagnosis criteria according to the “Criteria of Lupus” of the American College of Rheumatology. Significant changes in time‐intensity curve parameters were observed, indicating impaired renal function and the method as a feasible, non‐invasive diagnostic method in primate model.Conclusions
We successfully induced lupus‐associated model with systemic lupus syndrome. This primate model can be a valuable translational model for further pathogenesis and symptomology studies and for exploring therapeutic candidates. 相似文献19.
Indicators of transport stress were investigated in blood parameters of five male cynomolgus monkeys obtained from abroad. They underwent air and ground travel-related stress in transport cages for a 15-hour transit time. On arrival, hematological parameters of white blood cell count, red blood cell count, hemoglobin concentration, and hematocrit values were within the limits of reference range, indicating that these parameters were not typical changes derived from transport stress loading. An increase in neutrophil-to-lymphocyte (N/L) ratio with a marked increase in neutrophils and a decrease in lymphocytes was observed on arrival, and the increased N/L ratio returned approximately to the normal level 1 week after arrival. The serum cortisol level markedly increased on the day of arrival and it returned to normal 1 week after arrival. These findings indicate that the transport process was stressful for animals, showing increases in N/L ratio as well as cortisol level. Thus, it is possible that an increase in N/L ratio may be utilized as an indirect indicator of transport stress in newly acquired cynomolgus monkeys, as it has the similar pattern of change in cortisol with an increased cortisol level on the day of arrival. 相似文献