scholarly journals Thymidylate Synthase as a Predictive Biomarker for Pemetrexed Response in NSCLC

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ali A. Bukhari ◽  
Ranjit K. Goudar
Keyword(s):  
Thymidylate Synthase ◽  
Clinical Laboratory ◽  
New Technology ◽  
Tumor Biology ◽  
Predictive Ability ◽  
Predictive Biomarker ◽  
Patient Harm ◽  
Clinical Laboratory Improvement Amendment ◽  
Reduced Toxicity ◽  
Personalized Chemotherapy

In recent years, major strides in cancer research have made it possible to select personalized chemotherapy recommendations based on an individual patient’s tumor biology. The prognostic and/or predictive ability of biomarkers seeks to tailor the use of targeted chemotherapy and can result in improved clinical outcomes with reduced toxicity. A proliferation of new technology and pharmacotherapeutics in the setting of current FDA Clinical Laboratory Improvement Amendment (CLIA) standards has resulted in a recent surge in direct-to-physician biomarker tests. However, in the absence of clinical validation, there is the concern that the biomarkers may be utilized prematurely, resulting in improper chemotherapy selection and patient harm. Thymidylate synthase (TS) has been marketed as a predictive biomarker for the use of pemetrexed in NSCLC. We will examine the evidence behind the use of TS as a predictive biomarker to predict response to pemetrexed in NSCLC. At this time, the evidence does not currently support using TS assays to guide chemotherapy selection outside of a clinical research protocol.

Document Control Practices in 120 Clinical Laboratories

2009 ◽  
Vol 133 (6) ◽  
pp. 942-949
Author(s):  
Paul N. Valenstein ◽  
Ana K. Stankovic ◽  
Rhona J. Souers ◽  
Frank Schneider ◽  
Elizabeth A. Wagar
Keyword(s):  
Patient Outcomes ◽  
Clinical Laboratory ◽  
Standard Setting ◽  
Clinical Laboratory Improvement Amendment ◽  
Clinical Laboratories ◽  
Policies And Procedures ◽  
Laboratory Results ◽  
Control Failures

Abstract Context.—A variety of document control practices are required of clinical laboratories by US regulation, laboratory accreditors, and standard-setting organizations. Objective.—To determine how faithfully document control is being implemented in practice and whether particular approaches to document control result in better levels of compliance. Design.—Contemporaneous, structured audit of 8814 documents used in 120 laboratories for conformance with 6 generally accepted document control requirements: available, authorized, current, reviewed by management, reviewed by staff, and archived. Results.—Of the 8814 documents, 3113 (35%) fulfilled all 6 document control requirements. The requirement fulfilled most frequently was availability of the document at all shifts and locations (8564 documents; 97%). Only 4407 (50%) of documents fulfilled Clinical Laboratory Improvement Amendment requirements for being properly archived after updating or discontinuation. Policies and procedures were more likely to fulfill document control requirements than forms and work aids. Documents tended to be better controlled in some laboratory sections (eg, transfusion service) than in others (eg, microbiology and client services). We could not identify document control practices significantly associated with higher compliance rates. Conclusions.—Most laboratories are not meeting regulatory and accreditation requirements related to control of documents. It is not clear whether control failures have any impact on the quality of laboratory results or patient outcomes.

scholarly journals The Calgary Biofilm Device: New Technology for Rapid Determination of Antibiotic Susceptibilities of Bacterial Biofilms

1999 ◽  
Vol 37 (6) ◽  
pp. 1771-1776 ◽  
Author(s):  
H. Ceri ◽  
M. E. Olson ◽  
C. Stremick ◽  
R. R. Read ◽  
D. Morck ◽  
...  
Keyword(s):  
Antibiotic Susceptibility ◽  
Clinical Laboratory ◽  
Rapid Determination ◽  
New Technology ◽  
Growth Curves ◽  
National Committee ◽  
Standard Group ◽  
Antibiotic Susceptibilities ◽  
Significant Difference

Determination of the MIC, based on the activities of antibiotics against planktonic bacteria, is the standard assay for antibiotic susceptibility testing. Adherent bacterial populations (biofilms) present with an innate lack of antibiotic susceptibility not seen in the same bacteria grown as planktonic populations. The Calgary Biofilm Device (CBD) is described as a new technology for the rapid and reproducible assay of biofilm susceptibilities to antibiotics. The CBD produces 96 equivalent biofilms for the assay of antibiotic susceptibilities by the standard 96-well technology. Biofilm formation was followed by quantitative microbiology and scanning electron microscopy. Susceptibility to a standard group of antibiotics was determined for National Committee for Clinical Laboratory Standards (NCCLS) reference strains: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, andStaphylococcus aureus ATCC 29213. Growth curves demonstrated that biofilms of a predetermined size could be formed on the CBD at specific time points and, furthermore, that no significant difference (P > 0.1) was seen between biofilms formed on each of the 96 pegs. The antibiotic susceptibilities for planktonic populations obtained by the NCCLS method or from the CBD were similar. Minimal biofilm eradication concentrations, derived by using the CBD, demonstrated that for biofilms of the same organisms, 100 to 1,000 times the concentration of a certain antibiotic were often required for the antibiotic to be effective, while other antibiotics were found to be effective at the MICs. The CBD offers a new technology for the rational selection of antibiotics effective against microbial biofilms and for the screening of new effective antibiotic compounds.

Thymidylate synthase (TS) gene expression in patients with ALK positive (+) non-small cell lung cancer (NSCLC): Implications for therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7582-7582 ◽  
Author(s):  
David R. Gandara ◽  
Eric Huang ◽  
Sonal Desai ◽  
Philip C. Mack ◽  
Laurel Beckett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thymidylate Synthase ◽  
Predictive Biomarker ◽  
Rt Pcr ◽  
Kras Mutations ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Report Analysis ◽  
Increased Sensitivity ◽  
Alk Positive

7582 Background: ALK+ NSCLC represents a molecular target-defined patient population highly responsive to the ALK inhibitor crizotinib. Previous reports have also suggested increased sensitivity of ALK+ NSCLC to the chemotherapeutic agent pemetrexed. Thymidylate synthase (TS) is a candidate predictive biomarker for pemetrexed activity. Here we report analysis of the Response Genetics Inc. (RGI) database for this association and implications for therapy. Methods: ALK fusion was identified by a novel RT-PCR assay (Danenberg et al: ASCO 2010). For TS, RNA from microdissected formalin-fixed paraffin-embedded tumors was analyzed as previously described, reported as the ratio of gene expression to β-actin. For reference, a TS level <2.33 is the cutpoint for sensitivity. Results: TS levels were available from 63 ALK+ patients and 1,698 ALK- control lung adenocarcinoma patients. All ALK+ patients had adenocarcinomas without EGFR or KRAS mutations. Median age: 59.0 (range 33-88), gender (male/female) 32/31 (51%/49%). Median TS RNA level in ALK+ patients was 2.02, range (0.55-19.44), and in ALK- patients was 3.32 (0.36-53.51), p<0.0001 (Mann-Whitney test). The majority of ALK+ patients (N=43, 68%) had a TS level <2.33 cutpoint, compared to only 32% of ALK- patients (N=551, p<0.0001). Conclusions: This analysis demonstrates relatively low TS gene expression in ALK+ patient tumors as determined by RT-PCR. These data provide a mechanism of action supportive of pemetrexed sensitivity for ALK+ NSCLC. [Table: see text]

Genomic alterations in 670 patients with diverse cancers analyzed by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11593-11593
Author(s):  
Maria Clemence Schwaederle ◽  
Ranajoy Chattopadhyay ◽  
Shumei Kato ◽  
Paul T. Fanta ◽  
Kimberly Banks ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Head And Neck ◽  
Clinical Laboratory ◽  
Circulating Tumor Dna ◽  
Head And Neck Tumors ◽  
Clinical Laboratory Improvement Amendment ◽  
Variants Of Unknown Significance ◽  
Neck Tumors ◽  
Unknown Significance ◽  
Next Generation Sequencing Ngs

11593 Background: NGS of blood-derived ctDNA allows non-invasive tumor profiling. Liquid biopsy studies with clinical correlation have so far been mainly limited to small size cohorts. Methods: We performed comprehensive plasma genomic testing of ctDNA (NGS) in 670 patients (pts) (54-70 genes); Guardant Health, Inc.; (Clinical Laboratory Improvement Amendment certified and College of American Pathologists accredited). Results: The most represented cancers were gastrointestinal (31.8%), brain (22.7%), and lung (20.7%) (Table). Sixty-three percent of pts (N = 423) had ≥1 alteration. The most frequent alterations (characterized and variants of unknown significance (VUSs)) were in TP53 (32.5% of pts), followed by EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, the breakdown was 30.7% ( TP53), 7.6% ( EGFR), 12.2% ( KRAS), and 7.7% ( PIK3CA). Interestingly, 32% of brain tumors had ≥1 ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations (P=0.019). Forty-eight percent of pts (320/670) had potentially actionable alterations; in 241, (75% of 320), by an FDA-approved drug (mostly off label). Illustrative examples of clinical utility will be presented such as a patient with gastric cancer and EGFRamplification in ctDNA who received anti-EGFR treatment (60% regression), as well a patient with aggressive gynecologic malignancy who received immunotherapy based on a hypermutated ctDNA profile. Conclusions: Most pts, including a subset of those with brain tumors, demonstrated ctDNA alterations. Pts with head and neck tumors harbored higher numbers of alterations. Overall, three quarters of pts with alteration(s) had ≥1 aberration that could potentially be pharmacologically tractable, suggesting the need to further assess the utility of ctDNA in a therapeutic setting. [Table: see text]

N6-Methyladenosine Modification of PTTG3P Contributes to Colorectal Cancer Progression via IGF2BP2

2021 ◽  
Author(s):  
yang zheng ◽  
guilin yu ◽  
longfei xie ◽  
yue wang ◽  
guohua zhao
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Hippo Pathway ◽  
Predictive Ability ◽  
Predictive Biomarker ◽  
Receiver Operating Curve ◽  
Loss Of Function ◽  
Mice Model ◽  
Atp Assay ◽  
Rna Immunoprecipitation

Abstract Background N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) emerged as crucial players in colorectal cancer (CRC) progression, but the m6A modified lncRNA PTTG3P in CRC are still need to be systematically defined. Methods qRT-PCR was adopted to measure the PTTG3P expression. Survival analysis was used to explore the correlation between the expression of PTTG3P and CRC patients prognosis. Receiver operating curve (ROC) was tested to evaluate the PTTG3P predictive ability. Functional studies were examined by CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay and xenograft mice model. Mechanistic studies were explored by GSEA, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA immunoprecipitation (RIP).Results PTTG3P was upregulated in CRC and closely related to poor prognosis. Through gain and loss of function approaches, PTTG3P facilitated proliferation and glycolysis through Hippo pathway, and glycolysis inhibitor (2-DG ,3-BG) and LDHA knockdown could rescue cell proliferation. Mechanically, m6A methylation induced the elevation of PTTG3P by increasing its stability , and insulin like growth factor-2 mRNA binding proteins 2 (IGF2BP2) involved in the progression. Finally, rescue assays validated the effect of METTL3/PTTG3P/YAP1 axis in CRC progression. Conclusions m6A-induced PTTG3P could facilitates CRC development via interacting with IGF2BP2, which provides a predictive biomarker and theraperutic target for CRC.

scholarly journals Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Cristina Chamizo ◽  
Sandra Zazo ◽  
Manuel Dómine ◽  
Ion Cristóbal ◽  
Jesús García-Foncillas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Thymidylate Synthase ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Selecting Statistical Procedures for Quality Control Planning Based on Risk Management

2016 ◽  
Vol 62 (7) ◽  
pp. 959-965 ◽  
Author(s):  
Martín Yago ◽  
Silvia Alcover
Keyword(s):  
Risk Management ◽  
Clinical Laboratory ◽  
Traditional Approach ◽  
Performance Measure ◽  
Patient Harm ◽  
Management Concepts ◽  
Close Relationship ◽  
The Relationship ◽  
Expected Increase ◽  
Selection Of

Abstract BACKGROUND According to the traditional approach to statistical QC planning, the performance of QC procedures is assessed in terms of its probability of rejecting an analytical run that contains critical size errors (PEDC). Recently, the maximum expected increase in the number of unacceptable patient results reported during the presence of an undetected out-of-control error condition [Max E(NUF)], has been proposed as an alternative QC performance measure because it is more related to the current introduction of risk management concepts for QC planning in the clinical laboratory. METHODS We used a statistical model to investigate the relationship between PEDC and Max E(NUF) for simple QC procedures widely used in clinical laboratories and to construct charts relating Max E(NUF) with the capability of the analytical process that allow for QC planning based on the risk of harm to a patient due to the report of erroneous results. RESULTS A QC procedure shows nearly the same Max E(NUF) value when used for controlling analytical processes with the same capability, and there is a close relationship between PEDC and Max E(NUF) for simple QC procedures; therefore, the value of PEDC can be estimated from the value of Max E(NUF) and vice versa. QC procedures selected by their high PEDC value are also characterized by a low value for Max E(NUF). CONCLUSIONS The PEDC value can be used for estimating the probability of patient harm, allowing for the selection of appropriate QC procedures in QC planning based on risk management.

Robotics in the medical laboratory

1990 ◽  
Vol 36 (9) ◽  
pp. 1534-1543 ◽  
Author(s):  
R A Felder ◽  
J C Boyd ◽  
K Margrey ◽  
W Holman ◽  
J Savory
Keyword(s):  
Clinical Laboratory ◽  
New Technology ◽  
Robotic Systems ◽  
Medical Laboratory ◽  
Laboratory Automation ◽  
Control Software ◽  
New Era ◽  
Robotic Devices ◽  
Cost Efficient ◽  
Robotic Automation

Abstract Robotic systems specifically designed for the automation of laboratory tasks are now available commercially. Equipped with computer, analytical hardware, and supporting software, these devices may soon revolutionize the concept of the clinical laboratory and usher in a new era in laboratory testing. We review the types of robots and motion-control software currently available and discuss examples of their applications that extend across many analytical areas. Several ongoing projects are concerned with the systematic integration of robotic devices with other laboratory automation. The integrated robotic laboratories emerging from this work portend a bright future for robotic automation. Many challenges remain, however, in training the individuals needed to develop and manage robotic laboratories, and in making this new technology cost-efficient.

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