scholarly journals Radiolabelled Aptamers for Theranostic Treatment of Cancer

2018 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Umair Khalid ◽  
Chris Vi ◽  
Justin Henri ◽  
Joanna Macdonald ◽  
Peter Eu ◽  
...  
Keyword(s):  
Binding Affinity ◽  
High Specificity ◽  
Cancer Diagnostics ◽  
Molecular Biomarker ◽  
Specificity And Sensitivity ◽  
Number Of Patients ◽  
Incidence And Mortality ◽  
High Incidence ◽  
High Binding Affinity ◽  
As Toxicity

Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a large number of patients will also present with micrometastasis tumours which are often missed, as conventional medical imaging modalities are unable to detect micrometastases due to the lack of specificity and sensitivity. Recent advances in radiochemistry and the development of nucleic acid based targeting molecules, have led to the development of novel agents for use in cancer diagnostics. Monoclonal antibodies may also be used, however, they have inherent issues, such as toxicity, cost, unspecified binding and their clinical use can be controversial. Aptamers are a class of single-stranded RNA or DNA ligands with high specificity, binding affinity and selectivity for a target, which makes them promising for molecular biomarker imaging. Aptamers are presented as being a superior choice over antibodies because of high binding affinity and pH stability, amongst other factors. A number of aptamers directed to cancer cell markers (breast, lung, colon, glioblastoma, melanoma) have been radiolabelled and characterised to date. Further work is ongoing to develop these for clinical applications.

Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?

2007 ◽  
Vol 25 (15) ◽  
pp. 1967-1973 ◽  
Author(s):  
Davide Campana ◽  
Francesca Nori ◽  
Lidya Piscitelli ◽  
Antonio Maria Morselli-Labate ◽  
Raffaele Pezzilli ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Plasma Levels ◽  
Chromogranin A ◽  
Imaging Techniques ◽  
High Specificity ◽  
Endocrine Tumors ◽  
Cell Hyperplasia ◽  
Specificity And Sensitivity ◽  
Ecl Cell ◽  
Number Of Patients

Purpose We evaluated the pattern of chromogranin A (CgA) plasma levels in a large number of patients with neuroendocrine tumors (NETs), in a series of patients with chronic atrophic gastritis (CAG) with and without enterochromaffin-like (ECL) cell hyperplasia, and in healthy participants (HPs). Patients and Methods Two hundred thirty-eight patients with NETs, 42 patients with CAG with or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent a baseline visit, biochemical routine check-up, imaging techniques, endoscopy, and histologic determination. Results CgA plasma levels were higher in patients with NETs compared with CAG patients or HPs (P < .001). In the NET group, we observed higher CgA levels in patients with diffuse disease compared with patients with local or hepatic disease (P < .001). CgA plasma levels were significantly higher in patients with Zollinger-Ellison syndrome compared with other types of endocrine tumors (P < .001). We found the best cutoff range between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity, 95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and disease-free patients) and patients with endocrine tumors, the best cutoff range was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%). Conclusion Our study confirms the high specificity and sensitivity of CgA in diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87 U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding patients in whom the CgA was elevated as a result of other non-neoplastic diseases.

scholarly journals The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic

2019 ◽  
Author(s):  
Zhaoduan Liang ◽  
Lili Qin ◽  
Lei Chen ◽  
Wenhui Li ◽  
Chao Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Regression ◽  
Individual Treatment ◽  
Cytotoxic Lymphocyte ◽  
Oncogenic Mutations ◽  
Incidence And Mortality ◽  
High Incidence ◽  
The Common ◽  
High Binding Affinity

ABSTRACTColorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world, as the result of the traditional treatments. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to individual treatment, resulting from the unique neoantigens. Many shared oncogenic mutations are detected, but whether the common neoantigens can be identified in CRC is unknown. Using the somatic mutations data from 321 CRC patients combined with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and presentation score (>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens were proved to be naturally processed and presented on constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) to secrete IFN-γ. However, only 2 out of 25 common neoantigens were simultaneously presented and immunogenic. Moreover, using cell-sorting technology combined with single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens with presentation and immunogenicity could be found in CRC, which would be developed as the universal targets for CRC immunotherapy.

scholarly journals A throughput serological Western blot system using whole virus lysate for the concomitant detection of antibodies against SARS-CoV-2 and human endemic Coronaviridae

2020 ◽  
Author(s):  
Simon Fink ◽  
Felix Ruoff ◽  
Aaron Stahl ◽  
Matthias Becker ◽  
Philipp Kaiser ◽  
...  
Keyword(s):  
Western Blot ◽  
High Specificity ◽  
Diagnostic Specificity ◽  
Virus Particles ◽  
Specificity And Sensitivity ◽  
Assay Performance ◽  
High Incidence ◽  
High Concordance ◽  
Set Up

BACKGROUND: Seroreactivity against human endemic coronaviruses has been linked to disease severity after SARS-CoV-2 infection. Assays that are capable of concomitantly detecting antibodies against endemic coronaviridae such as OC43, 229E, NL63, and SARS-CoV-2 may help to elucidate this question. We set up a platform for serum-screening and developed a bead-based Western blot system, namely DigiWest, capable of running hundreds of assays using microgram amounts of protein prepared directly from different viruses. METHODS: The parallelized and miniaturised DigiWest assay was adapted for detecting antibodies using whole protein extract prepared from isolated SARS-CoV-2 virus particles. After characterisation and optimization of the newly established test, whole virus lysates of OC43, 229E, and NL63 were integrated into the system. RESULTS: The DigiWest-based immunoassay system for detection of SARS-CoV-2 specific antibodies shows a sensitivity of 87.2 % and diagnostic specificity of 100 %. Concordance analysis with the SARS-CoV-2 immunoassays available by Roche, Siemens, and Euroimmun indicates a comparable assay performance (Cohen's Kappa ranging from 0.8799-0.9429). In the multiplexed assay, antibodies against the endemic coronaviruses OC43, 229E, and NL63 were detected, displaying a high incidence of seroreactivity against these coronaviruses. CONCLUSION: The DigiWest-based immunoassay, which uses authentic antigens from isolated virus particles, is capable of detecting individual serum responses against SARS-CoV-2 with high specificity and sensitivity in one multiplexed assay. It shows high concordance with other commercially available serologic assays. The DigiWest approach enables a concomitant detection of antibodies against different endemic coronaviruses and will help to elucidate the role of these possibly cross-reactive antibodies.

A Comprehensive Study on Aptasensors For Cancer Diagnosis

2020 ◽  
Vol 21 ◽  
Author(s):  
Sambhavi Animesh ◽  
Yengkhom Disco Singh
Keyword(s):  
Point Of Care ◽  
High Specificity ◽  
Molecular Probes ◽  
Cancer Diagnostics ◽  
New Class ◽  
Point Of Care Diagnostics ◽  
Efficient Detection ◽  
Specificity And Sensitivity ◽  
Highly Sensitive ◽  
Cancer Tumor

: Cancer is the most devastating disease in the present scenario, killing millions of people every year. Early detection, accurate diagnosis, and timely treatment are considered to be the most effective ways to control this disease. Rapid and efficient detection of cancer at their earliest stage is one of the most significant challenges in cancer detection and cure. Numerous diagnostic modules have been developed to detect cancer cells early. As the nucleic acid is equivalent to antibodies, aptamers emerge as a new class of molecular probes that can identify cancer-related biomarkers or circulating rare cancer/tumor cells with very high specificity and sensitivity. The amalgamation of aptamers with the biosensing platforms gave birth to "Aptasensors." The advent of highly sensitive aptasensors has opened up many new promising point-of-care diagnostics for cancer. This comprehensive review focuses on the newly developed aptasensors for cancer diagnostics.

Prevalence of Inhibitors in a Population of 3435 Hemophilia Patients in France

1992 ◽  
Vol 67 (06) ◽  
pp. 600-602 ◽  
Author(s):  
Y Sultan ◽  
Keyword(s):  
Hemophilia A ◽  
Hemophilia B ◽  
Study Group ◽  
Cooperative Study ◽  
Population Prevalence ◽  
French Study ◽  
Number Of Patients ◽  
High Incidence ◽  
Recombinant Fviii ◽  
High Responders

SummaryA cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia B patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind.

Neuropsychiatric Symptoms and Antipsychotic Therapy in the Elderly Patients with Dementia

Psychiatry ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 6-15
Author(s):  
I. V. Kolykhalov
Keyword(s):  
Neuropsychiatric Symptoms ◽  
The Elderly ◽  
Psychotic Symptoms ◽  
Mixed Dementia ◽  
Short Term ◽  
Antipsychotic Therapy ◽  
Dementia Patients ◽  
Frequency Of Use ◽  
Number Of Patients ◽  
High Incidence

The objective of the study was to investigate syndromal-nosological specificities of neuropsychiatric symptoms (NPS) and the frequency of use of antipsychotics in patients with various types of dementias, institutionalized to geriatric units of mental hospitals.Patients and methods: a total of 106 in-patients of three psychogeriatric units were examined. The median age of patients is 75 years [69; 80].The diagnostic distribution of patients at the time of the examination was as follows: in 33 subjects (31.1%) Alzheimer’s disease (AD) was diagnosed, in 25 (23.6%) - mixed dementia (MD), in 32 (30.2%) - vascular dementia (VD) and in 16 (15.1%) patients had dementia of complex origin (DCO).Results: a high incidence (54.7%) of NPS was found in patients with dementia of various origins. The greatest number of patients with behavioral and psychotic symptoms was found in AD and MD. The proportion of dementia patients with such disorders in each of these types of dementia is about 70%, while in CGD and VD, the proportion of patients with NPS is noticeably smaller (30% and 40%, respectively). For the treatment of NPS, antipsychotics were most often prescribed, but their use caused adverse events (AEs) in 1/3 of cases. Patients with VD are most susceptible to the development of AE, and AD patients are the least susceptible.Conclusion: the study showed that NPS are one of the important components of dementia, regardless of the nosology and stage of the disease. The treatment of NPS in dementia is particularly challenging because, although the symptoms cause significant distress, there are currently no effective alternative therapies. The risk of AE can be minimized by carefully considering the indications for prescribing antipsychotics and their short-term use, regular monitoring of the patient’s condition, and educating caregivers.

Prospective Application of Aptamer-based Assays and Therapeutics in Bloodstream Infections

2020 ◽  
Vol 20 (10) ◽  
pp. 831-840
Author(s):  
Weibin Li
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Diagnosis ◽  
Bloodstream Infections ◽  
High Specificity ◽  
Peptide Sequence ◽  
High Morbidity ◽  
Specificity And Sensitivity ◽  
Prospective Application ◽  
Small Molecule Therapeutics

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

scholarly journals SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

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