Long-Term Complete Response to Trastuzumab Deruxtecan in a Case of Unresectable Gastric Cancer.

Introduction: Trastuzumab deruxtecan (T-Dxd) has been approved for the treatment of HER2-positive gastric cancer. However, there are only a limited number of cases of gastric cancer where a long-term complete response (CR) has been maintained. Consequently, we report a case of gastric cancer in which long-term CR was maintained. Case Presentation: A woman in her late 60s underwent a gastrointestinal endoscopy, which revealed a type 2 lesion with ulceration in the lesser curvature of the vestibule, and a biopsy, which revealed an adenocarcinoma. Computed tomography (CT) revealed wall thickening of the gastric antecubital region, metastatic liver tumor, and extra-regional lymph node metastasis; a diagnosis of T4a, N3a, M1 (H, LYN), and cStage IVB (HER2 3+) was confirmed. Trastuzumab, oxaliplatin, and S-1 were administered initially. After 9 months, ascites appeared, and progressive disease was diagnosed. Paclitaxel and ramucirumab were started as second-line treatments but discontinued owing to neutropenia and increasing ascites. Third-line treatment with T-Dxd was initiated, and 11 months later, CT showed the disappearance of metastases. Even after 31 months, the CR was maintained. Conclusion: To the best of our knowledge, this is one of the few cases in which long-term CR was maintained with third-line T-Dxd treatment. Treatment strategies for patients with gastric cancer to achieve long-term CR require careful consideration.

Improved waveguide-based ultraviolet light generation and pulsed squeezing at 795 nm.

We report on the waveguide-based generation of pulsed squeezed light at 795 nm, suitable for quantum enhanced measurements with rubidium atoms. Pulsed ultraviolet second harmonic light with a power of more than 400 mW is produced using a periodically poled LiNbO3 (PPLN) waveguide and is injected into another PPLN waveguide to generate quadrature squeezing. We find that the phase of the second harmonic pulse is shifted within a pulse, and we attribute the shift to heating due to blue-light induced infrared absorption (BLIIRA) from a comparison between the experiment and a numerical simulation. A squeezing level of -1.5(1) dB is observed in homodyne detection when we apply a linear phase shift to the local oscillator. The experiment and simulation imply that the squeezing level can be further improved by reducing BLIIRA.

Dissipation-Assisted Coherence Formation in a Spinor Quantum Gas.

We report the formation of magnetic eigenstates assisted by naturally occurring particle dissipation in a Bose-Einstein condensate of spin-2 ^{87}Rb atoms. Although the atomic interaction energetically favors the nonferromagnetic state, we observed the spontaneous evolution of an unpolarized spin state into the transverse ferromagnetic state. Under such dynamics, the spin-dependent dissipation of atoms enhances the synchronization of the relative phases among five magnetic sublevels to promote magnetization. Through numerical simulations based on mean-field theory, we show that another exotic magnetic eigenstate, the cyclic state, can also be formed through the spin-dependent dissipation of atoms.

Diacylglycerol kinase ß induces filopodium formation via its C1, catalytic and carboxy-terminal domains and interacts with the Rac1-GTPase-activating protein, ß2-chimaerin.

The ß-isoform of diacylglycerol kinase (DGK) localizes predominantly to neurons and induces neurite outgrowth and spine formation. However, the detailed molecular mechanisms underlying the functions of DGKß remain elusive. During the course of studies on other DGK isozymes, we unexpectedly found that the overexpression of wild-type DGKß in COS-7 cells markedly induced filopodium formation. Because filopodium formation is closely related to neurite outgrowth and spine formation, we constructed various DGKß mutants and compared their abilities to induce filopodium formation in order to elucidate the structure-function relationships of DGKß. We found that the C-terminal, C1 and catalytic domains and catalytic activity were indispensable for filopodium formation, but the recoverin homology domain and EF-hand motifs were not. Moreover, the extent of plasma membrane localization and F-actin colocalization were positively correlated with filopodium formation. Intriguingly, DGKß selectively interacted and colocalized at the plasma membrane with a Rac1-GTPase-activating protein, ß2-chimaerin, which is an inducer of filopodia; it also interacted, to lesser extent, with α2-chimaerin, but not with α1- or ß1-chimaerin. Moreover, DGKß enhanced the plasma membrane localization of ß2-chimaerin. These results suggest that DGKß plays an important role in neurite outgrowth and spine formation in neurons via its ability to induce filopodium formation.

Excitation enhancement in electric multipole transitions near a nanoedge.

We investigate enhancement of electric multipole excitations of atoms in the vicinity of an object with a nanoscale edge resulted from a large electromagnetic field gradient. We calculate the excitation efficiencies of a Rb atom around a nanoedge and find the excitations are enhanced by several orders of magnitude. The efficiencies with the change in the magnetic quantum number resolved are also examined. Each resolved efficiency shows rotationally symmetric spatial distribution, with continuous modification in shape from the far field to the near field. Furthermore, we estimate photon emission rates accompanied with multipole excitations in alkali (Rb and Cs) atoms and discuss the possibility to observe the enhancement in the multi-pole excitation in cold atoms.

Laser spectroscopic probing of coexisting superfluid and insulating states of an atomic Bose-Hubbard system.

A system of ultracold atoms in an optical lattice has been regarded as an ideal quantum simulator for a Hubbard model with extremely high controllability of the system parameters. While making use of the controllability, a comprehensive measurement across the weakly to strongly interacting regimes in the Hubbard model to discuss the quantum many-body state is still limited. Here we observe a great change in the excitation energy spectra across the two regimes in an atomic Bose-Hubbard system by using a spectroscopic technique, which can resolve the site occupancy in the lattice. By quantitatively comparing the observed spectra and numerical simulations based on sum rule relations and a binary fluid treatment under a finite temperature Gutzwiller approximation, we show that the spectra reflect the coexistence of a delocalized superfluid state and a localized insulating state across the two regimes.

Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout.

By using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type 1 (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic ß cells. By contrast, hDTR was expressed in the pancreatic ß cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic ß cells and depletion of serum insulin were observed within 3days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34(+) human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic ß cells of these Tg mice is highly useful for diabetogenic research.

Control of resonant interaction between electronic ground and excited states.

We observe magnetic Feshbach resonances in a collision between the ground and metastable states of two-electron atoms of ytterbium (Yb). We measure the on-site interaction of doubly occupied sites of an atomic Mott-insulator state in a three-dimensional optical lattice as a collisional frequency shift in a high-resolution laser spectroscopy. The observed spectra are well fitted by a simple theoretical formula, in which two particles with an s-wave contact interaction are confined in a harmonic trap. This analysis reveals a wide variation of the interaction with a resonance behavior around a magnetic field of about 1.1 G for the energetically lowest magnetic sublevel of 170Yb, as well as around 360 mG for the energetically highest magnetic sublevel of 174Yb. The observed Feshbach resonance can only be induced by an anisotropic interatomic interaction. This scheme will open the door to a variety of studies using two-electron atoms with tunable interaction.