Junta Yamamichi

Surface chemical approach to single-step measurement of antibody in human serum using localized surface plasmon resonance biosensor on microtiter plate system

AbstractIn clinical settings, serum antibody levels serve as markers of pathology. For example, antibodies related to autoimmune diseases are among the conventional targets in laboratory tests. Simple clinical tests can improve the efficacy of laboratory practice. This study describes a single-step, wash-free technique for optically detecting antibodies in human serum through the localized surface plasmon resonance (LSPR) of gold nanoparticles. As a proof-of-concept experiment, the amount of antibiotin dissolved in human serum was measured with a LSPR-based biosensor in a wash-free manner using a conventional 96-well microtiter plate and a plate reader. For an efficient surface modification of biosensors, zwitterionic copolymer was used as a scaffold on the gold nanoparticle surface to immobilize antigen and blocking reagent. Single-step, wash-free measurement of antibiotin in human serum was successfully achieved. In addition, nonspecific responses from serum contents were significantly reduced because both the copolymer and hydrophilic antigen reagent that we employed were composed of poly(ethylene oxide) spacer. Comparative experiments of the antigen-antibody reaction in serum to that in buffered solution revealed that serum is a favorable environment for the biological reaction. In conclusion, our gold-nanoparticle-based LSPR method may provide a rapid and simple way to measure the amount of antibody in serum quantitatively in clinical practice. FigureExperimental setups illustrating two different methods of surface modification for the gold nanoparticles: biotinylated BSA and zwitterionic copolymer. The amount of antibiotin that attached to biotin on the surface was measured by the peak shift of LSPR spectra using a 96-well microtiter plate with immobilized gold nanoparticles

Automatic digital quantification of bone marrow myeloma volume in appendicular skeletons - clinical implications and prognostic significance

Multiple myeloma (MM) is a clonal plasma cell disorder originating in bone marrow. Whole body low-dose multidetector CT (MDCT) can depict bone marrow infiltration by myeloma cells into the adipose-rich fatty marrow of the appendicular skeleton. However, automated and objective volume measurement of bone marrow infiltration has not been established, and its clinical relevance remains unclear. We therefore developed novel CT post-processing software (MABLE software) and measured the total sum of CT values (cumulative CT value, cCTv) representing bone marrow infiltration, by combining volume and voxel-based CT values. The cCTv was greater in patients with symptomatic MM than in those with smouldering MM or monoclonal gammopathy of unknown significance. Patients with revised International Staging System (R-ISS) III had a higher cCTv than those with R-ISS I or II. Age, albumin, and M-protein levels independently predicted cCTv. Mixed graphical model analysis revealed direct relationships between cCTv and age or R-ISS. Tree-structured survival analysis and multivariate Cox analysis revealed that a cCTv greater than or equal to 4.4 was independently prognostic for overall survival. Anti-myeloma therapy reduced cCTv after treatment. These findings suggest that the automatically calculated cCTv reflects disease aggressiveness and is useful for accurate prognostic prediction in MM patients.

Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer

Background Although tumor response evaluated with radiological imaging is frequently used as a primary endpoint in clinical trials, it is difficult to obtain precise results because of inter- and intra-observer differences. Purpose To evaluate usefulness of a cloud-based local-read paradigm implementing software solutions that standardize imaging evaluations among international investigator sites for clinical trials of lung cancer. Material and Methods Two studies were performed: KUMO I and KUMO I Extension. KUMO I was a pilot study aiming at demonstrating the feasibility of cloud implementation and identifying issues regarding variability of evaluations among sites. Chest CT scans at three time-points from baseline to progression, from 10 patients with lung cancer who were treated with EGFR tyrosine kinase inhibitors, were evaluated independently by two oncologists (Japan) and one radiologist (France), through a cloud-based software solution. The KUMO I Extension was performed based on the results of KUMO I. Results KUMO I showed discordance rates of 40% for target lesion selection, 70% for overall response at the first time-point, and 60% for overall response at the second time-point. Since the main reason for the discordance was differences in the selection of target lesions, KUMO I Extension added a cloud-based quality control service to achieve a consensus on the selection of target lesions, resulting in an improved rate of agreement of response evaluations. Conclusion The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites.

Evaluation of the 95% limits of agreement of the volumes of 5-year clinically stable solid nodules for the development of a follow-up system for indeterminate solid nodules in CT lung cancer screening

Background This study sought to evaluate the 95% limits of agreement of the volumes of 5-year clinically stable solid nodules for the development of a follow-up system for indeterminate solid nodules. Methods The volumes of 226 solid nodules that had been clinically stable for 5 years were measured in 186 patients (53 female never-smokers, 36 male never-smokers, 51 males with <30 pack-years, and 46 males with ≥30 pack-years) using a three-dimensional semiautomated method. Volume changes were evaluated using three methods: percent change, proportional change and growth rate. The 95% limits of agreement were evaluated using the Bland-Altman method. Results The 95% limits of agreement were as follows: range of percent change, from ±34.5% to ±37.8%; range of proportional change, from ±34.1% to ±36.8%; and range of growth rate, from ±39.2% to ±47.4%. Percent change-based, proportional change-based, and growth rate-based diagnoses of an increase or decrease in ten solid nodules were made at a mean of 302±402, 367±455, and 329±496 days, respectively, compared with a clinical diagnosis made at 809±616 days (P<0.05). Conclusions The 95% limits of agreement for volume change in 5-year stable solid nodules may enable the detection of an increase or decrease in the solid nodule at an earlier stage than that enabled by a clinical diagnosis, possibly contributing to the development of a follow-up system for reducing the number of additional Computed tomography (CT) scans performed during the follow-up period.