scholarly journals Can new immunoassay techniques improve bladder cancer diagnostics With protein biomarkers?

2021 ◽  
Vol 7 ◽  
Author(s):  
Yuri M. Shlyapnikov ◽  
Ekaterina A. Malakhova ◽  
Andrey Z. Vinarov ◽  
Andrey A. Zamyatnin ◽  
Elena A. Shlyapnikova

The search for new diagnostic tests for cancer or ways to improve existing tests is primarily driven by the desire to identify the disease as early as possible. In this report, we summarize the current knowledge of the most promising diagnostic protein bladder cancer (BC) markers reported over the last decade. Unfortunately, analysis of published data suggests that a reliable, highly sensitive biomarker test-system based on ELISA for detecting BC has not yet been developed. The use of more sensitive assays to detect ultra-low concentrations of biomarkers not available for ELISA, could be very beneficial. Based on the literature and pilot experimental data, we conclude that a highly sensitive immunoassay using microarrays and magnetic labels, could be an effective and cheap technique suitable for the detection of diagnostically relevant BC biomarkers.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6016
Author(s):  
Mariangela Mancini ◽  
Marialaura Righetto ◽  
Elfriede Noessner

In contrast with other strategies, immunotherapy is the only treatment aimed at empowering the immune system to increase the response against tumor growth. Immunotherapy has a role in the treatment of bladder cancer (BC) due to these tumors’ high tumor mutational burden (TMB) and mostly prominent immune infiltrate. The therapy or combination has to be adjusted to the tumor’s immunobiology. Recently, a new class of immunotherapeutic agents, immune checkpoint inhibitors (ICI), has shown potential in increasing treatment chances for patients with genitourinary cancers, improving their oncological outcomes. The clinical efficacy of ICI has been shown in both the first-line treatment of cisplatin-ineligible patients, with programmed death ligand 1 (PD-L1)-positive tumors (atezolizumab, pembrolizumab), and in second-line settings, for progression after platinum-based chemotherapy (atezolizumab, pembrolizumab, and nivolumab for FDA and EMA; durvalumab and avelumab for FDA alone). Predicting the response to ICI is important since only a subset of patients undergoing ICI therapy develop a concrete and lasting response. Most of the patients require a different therapy or therapy combination to achieve tumor control. The cancer immunity cycle provides a conceptual framework to assist therapy selection. Biomarkers to predict response to ICI must identify where the cancer immunity cycle is disrupted. We reviewed the current knowledge on ICI treatment in BC, going from basic science to current data and available clinical evidence. Secondly, a critical analysis of published data is provided, and an original panel of biomarkers able to predict response to ICI treatment, based on tumor-specific immune profiling, is proposed.


Author(s):  
F. A. Durum ◽  
R. G. Goldman ◽  
T. J. Bolling ◽  
M. F. Miller

CMP-KDO synthetase (CKS) is an enzyme which plays a key role in the synthesis of LPS, an outer membrane component unique to gram negative bacteria. CKS activates KDO to CMP-KDO for incorporation into LPS. The enzyme is normally present in low concentrations (0.02% of total cell protein) which makes it difficult to perform large scale isolation and purification. Recently, the gene for CKS from E. coli was cloned and various recombinant DNA constructs overproducing CKS several thousandfold (unpublished data) were derived. Interestingly, no cytoplasmic inclusions of overproduced CKS were observed by EM (Fig. 1) which is in contrast to other reports of large proteinaceous inclusion bodies in various overproducing recombinant strains. The present immunocytochemical study was undertaken to localize CKS in these cells.Immune labeling conditions were first optimized using a previously described cell-free test system. Briefly, this involves soaking small blocks of polymerized bovine serum albumin in purified CKS antigen and subjecting them to various fixation, embedding and immunochemical conditions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Maddalena Tumedei ◽  
Sara Ravaioli ◽  
Federica Matteucci ◽  
Monica Celli ◽  
Ugo De Giorgi ◽  
...  

AbstractBladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples (p = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.


2021 ◽  
Vol 9 (5) ◽  
pp. 972
Author(s):  
Joana Abrantes ◽  
Ana M. Lopes

Since the early 1980s, the European rabbit (Oryctolagus cuniculus) has been threatened by the rabbit hemorrhagic disease (RHD). The disease is caused by a lagovirus of the family Caliciviridae, the rabbit hemorrhagic disease virus (RHDV). The need for detection, identification and further characterization of RHDV led to the development of several diagnostic tests. Owing to the lack of an appropriate cell culture system for in vitro propagation of the virus, much of the methods involved in these tests contributed to our current knowledge on RHD and RHDV and to the development of vaccines to contain the disease. Here, we provide a comprehensive review of the RHDV diagnostic tests used since the first RHD outbreak and that include molecular, histological and serological techniques, ranging from simpler tests initially used, such as the hemagglutination test, to the more recent and sophisticated high-throughput sequencing, along with an overview of their potential and their limitations.


2011 ◽  
Vol 121-126 ◽  
pp. 3195-3199
Author(s):  
Li Feng Yang ◽  
Jun Yuan ◽  
Wei Na Liu ◽  
Xiu Ming Nie ◽  
Xue Liang Pei

Use Kingview to acquire and display the centrifugal pump performance parameters for the real-time data, and will stored the collected experimental data in Access databases, using VB database read, and drawing function for the data processing and rendering performance parameters of relationship curves.


2018 ◽  
Vol 6 (24) ◽  
pp. 4146-4150 ◽  
Author(s):  
Mengqi Zou ◽  
Daxiu Li ◽  
Ruo Yuan ◽  
Yun Xiang

Target-triggered operation of an aptamer machine leads to amplified and highly sensitive detection of protein biomarkers.


CFD letters ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 13-27
Author(s):  
Mohamad Lutfi Samsudin ◽  
Hasril Hasini

Meshing of domain in CFD is an important step to ensure accuracy of the solution. In the past, hexahedral or tetrahedral mesh systems were commonly used, and both have their merits and demerits. For large and complex geometry, polyhedral is another option but its accuracy is claimed to be lacking. In this paper, the use of polyhedral mesh system by past researchers are reviewed. Evaluation on the application of polyhedral mesh system for the study of the vortex formation with a simple single pump sump model is made. Validation was made through the comparison of the results from hexahedral, tetrahedral and polyhedral mesh sizes and the experimental data from published data. The polyhedral mesh system was found to perform satisfactorily and was able to match the results from the hexahedral mesh system as well as the experimental data.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Bryana N Harris ◽  
Laura Woo ◽  
Jeffrey J Saucerman

Rationale: Heart failure is caused by the inability of adult mammalian hearts to overcome the loss of cardiomyocytes (CMs). This is due partly to the limited proliferative capacity of CMs, which exit the cell cycle and do not undergo cell division. Current knowledge in cardiac regeneration lacks an understanding of the molecular regulatory networks that determine whether CMs will progress through the cell cycle to proliferate. Our goal is to use computational modeling to understand the expression and activation levels of the core cell cycle network, specifically cyclins and cyclin-cyclin-dependent kinase (CDK) complexes. Methods: A model of core cell cycle dynamics was curated using previously published studies of CM proliferation regulators. This model incorporates those regulators known to stimulate G1/S and G2/M transitions through the core CDKs. The activity of each of the 22 network nodes (22 reactions) was predicted using a logic-based differential equation approach. The CDK model was then coupled with a minimal ODE model of cell cycle phase distributions and validated based on descriptions and experimental data from the literature. To prioritize key nodes for experimental validation, we performed a sensitivity analysis by stimulating individual knockdown for every node in the network, measuring the fractional activity of all nodes. Results: Our model confirmed that the knockdown of p21 and Rb protein and the overexpression of E2F transcription factor and cyclinD-cdk4 showed an increase in cells going through DNA synthesis and entering mitosis. A combined knockdown of p21 and p27 showed an increase of cells entering mitosis. Cyclin D-cdk4 and p21 overexpression showed a decrease and increase of Rb expression, respectively. Of the 14 model predictions, 12 agreed with experimental data in the literature. A comprehensive knockdown of the model nodes suggests that E2F (a key transcription factor driving DNA synthesis) is positively regulated by cyclin D while negatively regulated by GSK3B, SMAD3, and pRB. Conclusion: This model enables us to predict how cardiomyocytes respond to stimuli in the CDK network and identify potential therapeutic regulators that induce cardiomyocyte proliferation.


Author(s):  
Sayed A. Nassar ◽  
Ramanathan M. Ranganathan ◽  
Saravanan Ganeshmurthy ◽  
Gary C. Barber

This experimental study investigates the effect of tightening speed and coating on both the torque – tension relationship and wear pattern in threaded fastener applications. The fastener torque – tension relationship is highly sensitive to normal variations in the coefficients of friction between threads and between the turning head and the surface of the joint. Hence, the initial level of the joint clamp load and the overall integrity and reliability of a bolted assembly is significantly influenced by the friction coefficients. The effect of repeated tightening and loosening is also investigated using M12, Class 8.8, fasteners with and without zinc coating. The torque – tension relationship is examined in terms of the non-dimensional nut factor K. The wear pattern is examined by monitoring the changes in surface roughness using a WYKO optical profiler and by using a LECO optical microscope. A Hitachi S-3200N Scanning Electron Microscope (SEM) is used to examine the contact surfaces, under the fastener head, after each tightening/loosening cycle. Experimental data on the effect of variables and the tightening speed, fastener coating and repeated tightening on the nut factor are presented and analyzed for M8 and M12, class 8.8, fasteners.


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