Abstract Background and Aim: Immune checkpoint inhibitors (ICIs) have been widely used for the initial treatment of non-small cell lung cancer (NSCLC). Although both ICI monotherapy and the combination of ICI plus chemotherapy (chemo-ICI) are promising therapeutic options for patients with a programmed cell death ligand-1 tumor proportion score of 50% or higher (high PD-L1), the patient's clinical background and biomarkers differentiating the two options are still not well-defined. In our prior research, we found that a history of proton pump inhibitor (PPI) use independently have negative impact with significantly shorter overall survival (OS) and progression-free survival (PFS) in NSCLC patients harboring high PD-L1 with pembrolizumab monotherapy, but not with chemo-ICI. However, this OS data remain immature. Therefore, in our current study, we extended the follow-up period and conduct additional analysis including OS data to confirm this trend. Method: Advanced NSCLC patients with high PD-L1 who had received pembrolizumab or chemo-ICI as the first-line treatment between March 2017 and December 2020 at 13 hospitals in Japan were analyzed. Survival outcomes were estimated using the Kaplan- Meier method and were compared using the log-rank test. Results: A total of 425 patients with NSCLC were included in the study, with 271 patients (median [range] age, 72 [43-90] years; 215 [79%] men) receiving pembrolizumab monotherapy as their first-line treatment and 154 patients (median [range] age, 69 [36-86] years; 121 [79%] men) receiving chemo-ICI as their first-line treatment. The median follow-up duration was 22.8 months. Among patients with a history of PPI use, both median PFS (19.3 months vs. 6.8 months; HR, 0.53; 95% CI, 0.35-0.78; P = .003) and the median OS(not reached vs. 20.4 months; HR, 0.53; 95% CI, 0.34-0.85; P = .04) were significantly longer in the chemo-ICI group compared to the pembrolizumab monotherapy group. For patients without a history of PPI use, both median PFS (11.4 months vs. 10.8 months; HR, 0.99; 95% CI, 0.76-1.3; P = .36) and the median overall survival (42.2 months vs. 29.9 months, HR, 0.84; 95% CI, 0.62-1.16; P = .33) showed no significant differences between the groups. Discussion and Conclusion: This retrospective study showed that a concomitant treatment with PPI is poor prognostic factor in patients harboring high PD-L1 and treated with ICI monotherapy compared with chemo-ICI in Japanese cohort and this tendency is durable in long-term follow-up. These results indicate that when deciding on an ICI treatment, with or without chemotherapy, it is essential to take into account a concomitant treatment with PPI. Citation Format: Ryo Sawada, Hayato Kawachi, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Takashi Kijima, Koichi Takayama. Impact of proton pump inhibitor on ICI with or without chemotherapy for NSCLC with high PD-L1 TPS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3730.
We have developed a microlaser Doppler velocimeter in which the laser diode, photodiode, and optical waveguide are monolithically integrated on a GaAs substrate. This integration eliminates the difficult optical alignment and susceptibility to environmental disturbances which are disadvantages of the conventional laser Doppler velocimeter. Our velocimeter showed good linearity between relative velocity and output frequency, and it can detect very low velocities of less than 5 /spl mu/m/s. It can also measure the flow speed of a liquid containing particles. Moreover, the addition of a step at the end of the waveguide and one more photodiode enables the phase difference to be used for directional discrimination.
This paper describes the etching rates and morphologies of etched surfaces of fluorinated polyimides having fluorine concentrations, when a magnetic field parallel to the cathode surface was varied during magnetically controlled reactive ion etching (MC RIE). The fluorine concentration of fluorinated polyimides is a key parameter used to control the etching rate in MC RIE and the etching rate can also be increased by applying a high magnetic field. The etching rate was maximum when the fluorine concentration was 15-23 wt%, and the peaks became sharper as the magnetic field increased. The surface morphology also became smoother with increasing magnetic field, and SEM observation revealed that the surface morphology of 23 wt% fluorine polyimide was smoothest when a high etching rate and a high magnetic field were used.
Dysregulation of tumor necrosis factor-α (TNFα), a pro-inflammatory cytokine, causes several diseases, making it an important therapeutic target. Here, we identified a novel DNA aptamer against human TNFα using in vitro selection, which included a high exclusion pressure process against non-binding and weak binders through microbead-assisted capillary electrophoresis (MACE) in only three rounds. Among the 15 most enriched aptamers, Apt14 exhibited the highest inhibitory activity for the interaction between TNFα and its cognate receptor in mouse L929 cells. For further improving the bioactivity of the aptamer, dimerization programed by hybridization was evaluated, resulting in the Apt14 dimer exhibited a twofold higher binding affinity and stronger inhibition compared to the monomer counterpart. Rapid identification of bioactive aptamers using MACE in combination with facile dimerization by hybridization accelerates the discovery of novel bioactive aptamers, paving the way toward replacing current monoclonal antibody therapy with the less expensive and non-immunogenic aptamer therapy.
Optically induced mechanical angular alignment of trapped birefringent micrometer-sized objects resulting from the transfer of angular momentum produced by birefringence using linearly polarized light has been experimentally demonstrated. Fluorinated polyimide (PMDA/TFDB) micro-objects having a large birefringence of $\ensuremath{\Delta}{n=n}_{\mathrm{slow}}\ensuremath{-}{n}_{\mathrm{fast}}=0.13$ (refractive indices ${n}_{\mathrm{slow}}=1.62,$ ${n}_{\mathrm{fast}}=1.49),$ which were fabricated by micromachining (reactive ion etching) and suspended in water $(n=1.33),$ were trapped and manipulated by radiation pressure from a single focused Gaussian beam (wavelength $\ensuremath{\lambda}=1.064\ensuremath{\mu}\mathrm{m},$ $\mathrm{power}>130\ensuremath{\mu}\mathrm{W}).$ The effect of the linearly polarized light on such micro-objects showed that they were angularly aligned about the laser beam axis and their angular position could be smoothly controlled by rotating the vibration plane of the electric field. We have shown that the retardation of the birefringent micro-object determines which axis (fast or slow) of the micro-object coincides with the vibration plane of the electric field of the incident light.
The development of optical trapping by a single focused laser beam, also known as optical tweezers (1), has made it possible to manipulate various particles including biological cells, metallic particles (2), and low-refractive-index micro-objects (3). We recently reported the application of optical trapping to rotational manipulation of artificial micro-objects in micro-mechanical systems (4). Rotation was due to the optical torque from the optical radiation pressure exerted on the outside of micro-objects that had shape anisotropy. The axis of this rotation coincided with the incident laser beam axis (2, 4, 5). In an effort to change the direction of the optically induced torque, this paper investigates the possibility of optical trapping and simultaneous rotation about an axis perpendicular to the incident laser beam axis by illuminating an object with a strongly focused laser beam.
This paper describes improvements made to a single-crystal mirror actuated electrostatically by terraced electrodes with a high-aspect ratio torsion spring. The improvements are reduced mirror pitch, increased mirror size, and higher stability from the electrical viewpoint.
Two types of small and highly sensitive accelerometers that can measure a wide range of acceleration have been tentatively developed. The accelerometer incorporates an optical linear-micro-laser encoder. The measurable range is unlimited because the encoder can measure relative displacement to a long linear grating scale attached to a parallel two-plate cantilever with a seismic mass.
The design and characteristics of a 3D MEMS mirror array and a compact optical fiber array as well as the free-space optical cross connect (OXC) switch module comprising them are presented.
