Clinical validation of CTC subtype frequency to prognosis OS in mCRPC patients.

302 Background: CellSearch is an FDA cleared assay that enumerates intact CK+, DAPI+, CD45- cells via EpCAM capture. CTC number is prognostic for survival pre- and post- systemic therapy. These cells are a subset of confirmed genomically altered CTC’s in blood. We report the prognostic significance for OS in mCRPC of CTC subtypes not enumerated by CellSearch including apoptotic CTCs, CK- CTCs, small CTCs, and CTC clusters. Methods: 221 blood samples from 179 unique patients were collected from pts about to begin AR directed (n = 150) or taxane (n = 71) therapy for progressive CRPC. Samples were analyzed utilizing the Epic Sciences platform to enumerate traditional (CK+, abnormal morph), apoptotic (CK+, fragmented nuclei), CK- (CK-/abnormal morph), small (CK+, normal morph), and CTC clusters. Patients were followed for up to 2.3 yrs. Paired CellSearch and Epic traditional CTC counts were collected on 173 patient samples. Results: In paired analysis, Epic traditional CTCs were identified in 86% of patients vs. 67% by CellSearch, and any Epic CTC subtype was found in 96% of the patient samples. Increased frequency of any CTC subtype was a univariate predictor of OS (see table). Conclusions: Epic identified CTC subtypes not identified by CellSearch or other technologies that select or sort based upon size or epithelial expression. Cells were detected in 96% of the patient samples and all 5 subtypes were found to be prognostic for survival. The biologic characterization of CTC subtypes as a biomarker of drug sensitivity is ongoing. The increased clinical sensitivity of subtypes and prevalence of CTCs identified on the Epic platform provides a greatly expanded array of clinically relevant biomarkers to develop predictive liquid biopsy signatures in the metastatic setting. [Table: see text]

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Isolation and characterization of circulating pro-vascular progenitor cell subsets from human whole blood samples

STAR Protocols ◽

10.1016/j.xpro.2021.100311 ◽

2021 ◽

Vol 2 (1) ◽

pp. 100311

Author(s):

Daniella C. Terenzi ◽

Ehab Bakbak ◽

Justin Z. Trac ◽

Mohammad Al-Omran ◽

Adrian Quan ◽

...

Keyword(s):

Whole Blood ◽

Progenitor Cell ◽

Blood Samples ◽

Human Whole Blood ◽

Isolation And Characterization ◽

Whole Blood Samples

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STUDIES ON THE BIOLOGIC CHARACTERIZATION OF HUMAN GONADOTROPINS. V. COMPARISON WITH SHEEP LUTEINIZING HORMONE*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-20-8-1059 ◽

1960 ◽

Vol 20 (8) ◽

pp. 1059-1065 ◽

Cited By ~ 1

Author(s):

A ALBERT ◽

IONE DERNER

Keyword(s):

Luteinizing Hormone ◽

Biologic Characterization

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Doxorubicin-resistant variants of human prostate cancer cell lines DU 145, PC-3, PPC-1, and TSU-PR1: characterization of biochemical determinants of antineoplastic drug sensitivity.

International Journal of Oncology ◽

10.3892/ijo.17.6.1077 ◽

2000 ◽

Cited By ~ 5

Author(s):

G L David-Beabes ◽

M J Overman ◽

J A Petrofski ◽

P A Campbell ◽

A M de Marzo ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Drug Sensitivity ◽

Prostate Cancer Cell ◽

Antineoplastic Drug ◽

Human Prostate Cancer ◽

Human Prostate Cancer Cell ◽

Prostate Cancer Cell Lines

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Purification and biologic characterization of a specific tumor necrosis factor α inhibitor

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)80161-2 ◽

1989 ◽

Vol 264 (20) ◽

pp. 11966-11973

Author(s):

P Seckinger ◽

S Isaaz ◽

J M Dayer

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Specific Tumor ◽

Factor Α ◽

Biologic Characterization ◽

Necrosis Factor

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Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8029 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8029-8029

Author(s):

Binod Dhakal ◽

Shruti Sharma ◽

Svetlana Shchegrova ◽

Minu Maninder ◽

Meenakshi Malhotra ◽

...

Keyword(s):

Bone Marrow ◽

Residual Disease ◽

Prognostic Significance ◽

Unmet Need ◽

Progression Free Survival ◽

Multiparameter Flow Cytometry ◽

High Dose ◽

Blood Samples ◽

Ctdna Analysis

8029 Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), MM patients invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker. Currently, MRD in MM is monitored via bone marrow aspirate sampling. Marrow MRD assays are limited by the spatial heterogeneity of marrow MM localization; extramedullary disease and sampling variability of marrow aspiration. Sensitive, non-invasive blood-based MRD assay is an unmet need. ctDNA as a noninvasive biomarker can be utilized to predict relapse in MM. Here we attempt to evaluate MRD using ctDNA in AHCT recipients with MM. Methods: In this retrospective, single-center study, we analyzed ctDNA MRD in blood samples collected from 28 patients with MM after upfront AHCT. A total of 80 plasma timepoints were available pre and post AHCT with a median follow-up of 92.4 months. Multiparameter flow cytometry (MFC) at 10-4 level was used to assess the MRD from the BM biopsy. Individual bone marrow aspirates or FFPE slides from the time of MM diagnosis and matched normal blood were whole-exome sequenced, and somatic mutations were identified. MRD assessment at 3 months post-AHCT was performed by ctDNA analysis using a personalized, tumor-informed (SignateraTM, bespoke mPCR NGS assay). The prognostic value of ctDNA was evaluated by correlating MRD status with clinical outcomes. Results: Table provides the baseline disease characteristics. Median age was 67 [41-75] years and 16 [57.1%] were males. ctDNA was detectable in 70.8% (17/24) of pre-AHCT, 53.6% (15/28) of ̃3 months post-AHCT, and 39.2% (11/28) of patients during the surveillance phase post-AHCT. Of the 15 ctDNA MRD positive patients, 93.3% (n=14) experienced relapse on follow-up (hazard ratio: 5.64; 95% CI: 1.8-17; p=0.0003). Patients negative for ctDNA at 3 months post-AHCT had significantly superior progression-free survival (PFS) compared to positive (median PFS, 84 months vs. 31 months; p=0.003) The positive predictive value (PPV) for relapse among patients positive for ctDNA at 3 months post-AHCT was 93.3%, and significantly higher than marrow MFC of 68.4%. Conclusions: Our study shows the feasibility that a tumor-informed assay on archival blood samples is predictive of relapse post-AHCT. Future prospective studies with real-time marrow NGS and ctDNA samples are needed to define the role of ctDNA in MM and its prognostic significance.[Table: see text]

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Study of Antibiotics Sensitivity Pattern And Molecular Characterization of Staphylococcus Aureus Isolated From Human And Animal Pyogenic Cases

10.21203/rs.3.rs-501903/v1 ◽

2021 ◽

Author(s):

Jayshree Singh ◽

Amit Kumar ◽

Sharad K. Yadav ◽

Ritika Yadav ◽

Vinod K. Singh

Keyword(s):

Staphylococcus Aureus ◽

Molecular Characterization ◽

Drug Sensitivity ◽

Methicillin Resistance ◽

Phenotypic Characterization ◽

Resistance Pattern ◽

Sensitivity Pattern ◽

Drug Resistance Pattern ◽

Animal Isolates

Abstract Staphylococcus aureus has been described as the most common cause of human and animal diseases and has emerged as superbug due to multidrug resistance. Considering these, a total of 175 samples were collected from pyogenic cases of humans (75) and animals (100), to establish the drug resistance pattern and also for molecular characterization of human and animal isolates. Thermonuclease (nuc) gene amplification was used to confirm all presumptive S. aureus isolates and then antibiotic sensitivity and slide coagulase tests were used for phenotypic characterization of isolates. Following that, all of the isolates were subjected to PCR amplification to detect the existence of the methicillin resistance (mecA) and coagulase (coa) genes. Lastly, typing was done by using the Randomly Amplified Polymorphic DNA-PCR. The overall prevalence of S. aureus in human and animal samples was found to be 39.4%. Drug sensitivity revealed the highest resistance against the β-lactam antibiotics such as ampicillin (94.8%) and penicillin (90.6%), followed by cephalosporin (cefixime-67.7%) and quinolone (ciprofloxacin-52.1%) group of drugs. The drug sensitivity was the highest against antibiotics like chloramphenicol (95%) followed by gentamicin (90%). Among the 69 S. aureus isolates, the overall presence of MRSA was 40.5% (27.5% and 50% in human and animal isolates respectively). Total 33 isolates exhibited coa genes amplification of more than one amplicons and variable in size of 250, 450, 800, and 1100 bp. The RAPD typing revealed amplification of 5 and 6 different band patterns in humans and animals, respectively, with two common patterns suggesting a common phylogenetic profile.

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Development and Clinical Validation of a Droplet Digital PCR Method for Detection of Acinetobacter baumannii and Klebsiella pneumonia in Patients with Suspected Bloodstream Infections

10.22541/au.162337143.35366523/v1 ◽

2021 ◽

Author(s):

Yang Zheng ◽

Jun Jin ◽

Ziqiang Shao ◽

Jingquan Liu ◽

Run Zhang ◽

...

Keyword(s):

Blood Culture ◽

Acinetobacter Baumannii ◽

Limit Of Detection ◽

Early Stage ◽

Bloodstream Infections ◽

Digital Pcr ◽

Droplet Digital Pcr ◽

Klebsiella Pneumonia ◽

Clinical Validation ◽

Blood Samples

The relatively long turnaround time and low sensitivity of traditional blood culture may delay the effective antibiotic therapy in patients with bloodstream infection (BSI). To reduce the morbidity and mortality of BSI, a rapid and sensitive pathogen detection method is urgently required. Acinetobacter baumannii and Klebsiella pneumonia are two major microorganisms responsible for BSI. Here we reported a novel droplet digital PCR (ddPCR) method that can detect A. baumannii and K. pneumonia in whole blood samples within 4 h, with a specificity of 100% for each strain and limit of detection at 0.93 copies/microliter for A. baumannii and 0.27 copies/microliter for K. pneumonia. Clinical validation in 170 patients with suspected BSIs showed that, compared with blood culture that reported 4 (2.4%) A. baumannii cases and 7 (4.1%) K. pneumonia cases, ddPCR detected 23 (13.5%) A. baumannii cases, 26 (15.3%) K. pneumonia cases, and 4 (2.4%) dual infection cases, including the 11 positive patients reported by blood culture. In addition, the positive patients reported by ddPCR alone (n = 42) had significantly lower serum concentrations of procalcitonin and lactate, SOFA and APACHE II scores, and 28-day mortality than those reported by both blood culture and ddPCR (n = 11), suggesting that patients with less severe manifestations can potentially benefit from the guidance of ddPCR results. In conclusion, our study suggests that ddPCR represents a sensitive and rapid method to identify causal pathogens in blood samples and to guide the treatment decisions in the early stage of BSI.

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Investigation of the Antimicrobial Activity and Hematological Pattern of Nano-Chitosan and its Developed Nano-Copper Composite

10.21203/rs.3.rs-149486/v1 ◽

2021 ◽

Author(s):

Somia Ahmed ◽

Hadeer Mohamed ◽

Abeer Al-Subaie ◽

Ahoud Al-Ohali ◽

Nesrine Mahmoud

Keyword(s):

Antimicrobial Activity ◽

High Sensitivity ◽

Ionic Gelation ◽

Clotting Time ◽

Blood Samples ◽

Gram Negative ◽

Inhibition Concentration ◽

Copper Composite ◽

Biogenic Nanoparticles

Abstract Novel synthesized Chitosan-Copper oxide nanocomposite (Cs-CuO) was prepared using pomegranate peels extract as green precipitating agents to improve the biological activity of Cs-NP's which was synthesized through ionic gelation method. The characterization of biogenic nanoparticles Cs-NP's and Cs-CuO-NP's were investigated structurally, morphologically to determine the full descriptive features of those nanoparticles. Antimicrobial activity was tested for both Cs-NP's and Cs-CuO-NP's via Minimum inhibition concentration and zone analysis against fungus, gram positive and gram negative. The results of the antimicrobial test showed high sensitivity of Cs-CuO-NP's to all microorganisms that are tested in concentration less than 20 mg/ml while the sensitivity of Cs-NP's against all microorganisms under test started from a concentration of 20 mg/ml to 40 mg/ml except for the C.albicans species. Hematological activity was also tested in via measuring the RBCs, platelets count and clotting time against healthy, diabetic and hypercholesterolic blood samples. Measurement showed a decrease in RBCs and platelets count by adding Cs-NP’s or Cs-CuO-NP's to the three blood samples. Cs-NP’s success to decrease the clotting time for healthy and diabetic blood acting as a procoagulant agent, while adding biogenic CuO-NP’s to Cs-NP’s increased clotting time considering as an anticoagulant agent for hyperchloesterolic blood samples.

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