Boditech Med (South Korea)

BackgroundPanic disorder is characterized by sudden panic attacks and persistent anticipatory anxiety. While pharmacotherapy remains effective, patients with panic disorder often experience residual symptoms and functional impairments. Lifestyle factors influence symptom severity but are often unaddressed in routine psychiatric care. Most current digital therapeutics for panic disorder have a limited scope, lack integration with clinicians, and fail to consider behavioral patterns. To address these limitations, our research team developed a prescription-based app that supports structured cognitive behavioral therapy practice, real-life symptom management, and lifestyle modifications for patients with panic disorder, and a management console—a web-based platform that allows clinicians to monitor the patients’ engagement and progress as well as determine therapeutic options if necessary.ObjectiveThis study aimed to test the usability of the app and management console by evaluating their interface, functionality, and user experience. The primary goal was to identify the strengths and areas for further improvement of these software devices and to develop a list of modifications to improve the user experience and clinical applicability in updates to refine the devices for a future clinical trial.MethodsUsability data were collected by investigators at a medical device usability research center without the involvement of the development research team, and the participants were 15 patients with panic disorder and 15 psychiatrists. Each group completed experimental use of the app or management console and scored the convenience and safety of its modules, questionnaire evaluations for the acceptability, and presentation of verbal subjective feedback on areas for improvement. Based on the participants’ suggestions, a list of items that need to be modified to improve functionality and ease of use for each device was created.ResultsPatients completed 155 assigned tasks for the app with more than 98% success, and psychiatrists completed 34 tasks for the management console with more than 86% success. The convenience and safety scores for the app and management console exceeded the neutral threshold (mean >4.5). For all statements about the acceptability, both patients and psychiatrists responded at the level of agreeing with a score exceeding 3 (mean: 3.6~4.3 and 4~4.7, respectively). There were 38 suggestions for app improvements and 66 suggestions for management console improvements, most of which were incorporated in the modification list.ConclusionsPatients reported that the app might be easy to use and help manage anxiety, and psychiatrists found the management console practical and well-suited for outpatients. By combining patient-facing therapeutic tools with clinician-driven prescription and monitoring, the devices offer a solution aligned with clinically integrated, real-world psychiatric care. Modified devices based on the improvement suggestions presented in this study will be evaluated in future clinical trials for their impact on engagement and treatment outcomes.

Undifferentiated pleomorphic sarcomas (UPSs) are tumours of mesenchymal origin typically seen in soft tissues and histologically characterized by pleomorphic tumour cell and multinucleated giant cell (MGC) infiltration. Here, we report UPS in a 23-month-old Sprague-Dawley rat, notable for the absence of MGC infiltration and the presence of mast cells. The tumour was located in the left axillary region and was assessed using haematoxylin and eosin, Masson's trichrome, and toluidine blue staining, along with immunohistochemistry. Neoplastic cells showed pleomorphism and storiform arrangement, with no MGCs, but with significant mast cell infiltration. Vimentin positivity confirmed the mesenchymal origin. The results in this case indicate a potential role of mast cells in UPS pathology and emphasize the need for further studies on their role in tumour progression.

Background: The Boditech iCHROMA point of care immunoassay analyser has a Covid-19 antibody assay for the qualitative determination of IgG/IgM antibodies in human whole blood/serum/plasma. It is helpful as an aid in the screening of early mild asymptomatic or acute patients for identifying Covid-19 infection with high sensitivity. Objectives: To determine the clinical agreement (sensitivity and specificity) of the Boditech iCHROMA Covid-19 antibody assay and the Abbott Architect SARS-CoV-2 IgG assay for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal type of cancer and the third leading cause of cancer death with the lowest 5-year survival rate. Heterogeneity, difficulty in diagnosis, and rapid metastatic progression are the causes of high mortality in pancreatic cancer. Recent studies have shown that Protein arginine methyltransferase 5 (PRMT5) is overexpressed in pancreatic cancers, and these patients have a worse prognosis. Recently, PRMT5 as an anti-cancer target has gained considerable interest. In this study, we investigated whether inhibition of PRMT5 activity was synergistic with blockade of TGF-β1 signaling, which plays an important role in the construction of the desmoplastic matrix in pancreatic cancer and induces therapeutic vulnerability. Compared with T1-44, a selective inhibitor of PRMT5 activity, the combination of T1-44 with the TGF-β1 signaling inhibitor Vactosertib significantly reduced tumor size and surrounding tissue invasion and significantly improved long-term survival. RNA sequencing analysis of mouse tumors revealed that the combination of T1-44 and Vactosertib significantly altered the expression of genes involved in cancer progression, such as cell migration, extracellular matrix, and apoptotic processes. In particular, the expression of Btg2, known as a tumor suppressor factor in various cancers, was markedly induced by combination treatment. Ectopic overexpression of Btg2 inhibited the EMT response, blocking cell migration, and promoted cancer cell death. These data demonstrate that the combination therapy of T1-44 with Vactosertib is synergistic for pancreatic cancer, suggesting that this novel combination therapy has value in the treatment strategy of patients with pancreatic cancer.

Abstract Death‐associated protein kinase‐related apoptosis‐inducing protein kinase 2 (DRAK2) has become a promising target for drug development. In search of novel and selective DRAK2 inhibitor motif, in vitro screen kinase assay was established performed using in‐house chemical libraries. After through hit triage procedure, N2‐(3,5‐dichlorophenyl)‐5‐fluoro‐N4‐methylpyrimidine‐2,4‐diamine (1) was selected as initial hit with structural novelty and drug‐likeness. During hit validation, structure–activity relationship of 1 was thoroughly disclosed and TRD‐93 was finally validated as hit for DRAK2 inhibition. TRD‐93 is small (mw = 290) but selectively potent to DRAK2 (IC50 = 0.16 μM) over other kinases including DAPK family kinases. Molecular binding model study of TRD‐93 to DRAK2 is also discussed.

Although accumulating evidence indicates that alternative splicing is aberrantly altered in many cancers, the functional mechanism remains to be elucidated. Here, we show that epithelial and mesenchymal isoform switches of leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) regulated by epithelial splicing regulatory protein 1 (ESRP1) correlate with metastatic potential of gastric cancer cells. We found that expression of the splicing variants of LRRFIP2 was closely correlated with that of ESRP1. Surprisingly, ectopic expression of the mesenchymal isoform of LRRFIP2 (variant 3) dramatically increased liver metastasis of gastric cancer cells, whereas deletion of exon 7 of LRRFIP2 by the CRISPR/Cas9 system caused an isoform switch, leading to marked suppression of liver metastasis. Mechanistically, the epithelial LRRFIP2 isoform (variant 2) inhibited the oncogenic function of coactivator-associated arginine methyltransferase 1 (CARM1) through interaction. Taken together, our data reveals a mechanism of LRRFIP2 isoform switches in gastric cancer with important implication for cancer metastasis.

Abstract Immune checkpoint inhibitors (ICIs) have been applied in patients with various solid tumors since they were approved by U.S. FDA in 2011. However, only less than 20% of patients benefit from ICIs including anti-programmed cell death protein 1 (aPD-1). Recently, many studies to improve the response of ICIs are in progress, and especially, vascular endothelial growth factor receptors (VEGFR) pathway was emerged as major target. VEGFR inhibitors regulate the differentiation of tumor-associated macrophage, antigen presenting dendritic cell, and T cell infiltration, so they make a synergic antitumor effect with ICIs. In this study, we investigated the effect of lenvatinib combined with anti-mouse PD-1 in syngeneic murine cervical cancer models to show whether VEGFRi enhance the antitumor effect of ICIs. We established syngeneic mouse models of cervical cancer to confirm synergic effect by lenvatinib combined with aPD-1. 1x107 cells of U14 cells were injected subcutaneously into the flanks of BALB/c wild- type (immunocompetent) mice and BALB/c nude (immunocompromised) mice. They were treated with lenvatinib when the tumor volume reached at 200 mm3, subsequently, aPD-1 was administered in immunocompetent mice. We administrated lenvatinib (10 mg/kg, orally, daily) and aPD-1(200 µg per mouse, intraperitoneally (I.P), twice a week) for 3 weeks. Tumor volume was measured twice a week. After the end of the experiment, we harvested tumors and spleens, and performed histological analysis. All experiments were approved by the Institutional Animal Use and Care Committee (IACUC) in Asan Institute for Life Science.Although the tumor was increased despite lenvatinib treatment in immunocompromised model with BALB/c nude mice, on the 17th day after injection, the tumor growth was inhibited in lenvatinib group compared with vehicle group (2914 mm3 vs. 3663 mm3, respectively) (P=0.0014). On the other hand, the tumor volume was significantly reduced by lenvatinib in the immunocompetent model (278 mm3 in Len vs. 490 mm3 in Veh) (P=0.0347), particularly the tumor size was decreased since 2 weeks of injection. Subsequently, we investigated the synergistic effects of combination with lenvatinib and aPD-1 in immunocompetent model. Each single treatment group showed the reduction of tumor volume compared to vehicle group (278 mm3 in Len and 258 mm3 in aPD-1 vs. 490 mm3 in Veh). Furthermore, the lenvatinib plus aPD-1 combination group reduced tumor volume to 110mm3 on the 24th day after injection and it was significantly different compared to each single treatment group (P=0.13868 and P=0.27385, respectively).In this study, anti-tumor effect of aPD-1 was enhanced by the regulation of tumor microenvironment with lenvatinib in immunocompetent murine cervical cancer models. In conclusion, addition of lenvatinib is expected to increase the efficacy of ICIs in patients with cervical cancer who have the resistance or insensitivity to ICIs. Citation Format: Su-Bin Park, Ji-Sik Kang, Min-Je Kim, Shin-Wha Lee, Dong-Woo Kang, Yong-Man Kim. Anti-tumor effects of lenvatinib plus anti-PD-1 in syngeneic murine cervical cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6190.

Abstract Proteasome inhibitors (PIs) have remarkably improved the survival of multiple myeloma (MM) patients but dose-limiting toxicities and the development of drug resistance limit their long-term utility. Elevated TGF-β levels in MM patient sera correlate with chemoresistance, disease progression, metastasis and poor prognosis. Therefore, we evaluated the anti-MM therapeutic potential of a TGF-β type I receptor kinase inhibitor, Vactosertib. In vitro treatment of Vactosertib synergistically inhibited the growth of PI-resistant MM cells in combination with the ixazomib by suppressing TGF-β activation of Smad2/3 and expression of PSMB5, which encodes the proteasome 5 catalytic subunit targeted by PIs. Oral administration of Vactosertib as a single agent inhibited MM progression and induced a decrease in mortality and an increase in body weight of the mice bearing MM. Vactosertib alone also attenuated TGF-β activation of Smad2/3, reduced the expansion of CD11b+Gr-1+ myeloid derived suppressor cells (MDSCs) in bone marrow tumor microenvironment, and diminished the population of Foxp3+ regulatory T cells (Treg) in the spleen. Combination therapy of Vactosertib plus ixazomib was exhibited a synergistic anti-tumor effect when compared to either Vactosertib or ixazomib alone by greatly prolonged survival and significant a reduction in both MDSCs and Tregs. Taken together, our data provide the rationale for clinical evaluation of Vactosertib in MM and demonstrate proof-of-concept that combination of Vactosertib and PIs may overcome chemoresistance and enhance durable patient responses. Supported by 1R03CA259901-01A1

Background: Molecular tests are generally not suited for public health screening, antibody tests are more suited and the more portable, the better. The Boditech iCHROMA™ point of care immunoassay analyser has a Covid-19 antibody assay for the qualitative determination of IgG/IgM antibodies in human whole blood/serum/plasma. It is helpful as an aid in the screening of early mild asymptomatic or acute patients for identifying Covid-19 infection with high sensitivity. Objectives: To determine the clinical agreement (sensitivity and specificity) of the Boditech iCHROMA™ Covid-19 antibody assay and the Abbott Architect SARS-CoV-2 IgG assay for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma. Results: Of the 50 plasma samples, 20 (40%) of the plasma samples assayed were reported as positive by both the Abbott Architect SARS-CoV-2 IgG assay and the Boditech iCHROMA™ Covid-19 IgG antibody assay. The remaining 30 (60%) of the plasma samples were reported as negative by Abbott Architect SARS-CoV-2 IgG antibody assay. However, the Boditech iCHROMA™ Covid-19 IgG antibody assay, reported only 27 of the 30 (90%) samples as negative. Conclusion: There was an overall agreement of 95%, with a sensitivity of 100% and a specificity of 90% of the Boditech iCHROMA™ Covid-19 IgG antibody assay and the Abbott Architect SARS-CoV-2 IgG assay.