U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Real-world study of lazertinib as second-line or greater treatment in advanced non-small cell lung cancer.

BACKGROUND: Lazertinib is an oral, third-generation EGFR-TKI, which specifically targets the EGFR T790M mutation along with activating mutations Ex19del and L858R. More real-world data are needed to evaluate its efficacy and safety in treating locally advanced and metastatic non-small cell lung cancer (NSCLC) following prior EGFR TKI treatment. METHODS: This multicenter retrospective study was conducted at seven university hospitals affiliated to the Catholic Medical Center (CMC) in Korea. A clinical data warehouse (CDW) platform was used to access and extract information. RESULTS: A total of 48 patients were assessed. The majority were female (75%) and diagnosed with adenocarcinoma (95.8%). All patients had the EGFR mutation at diagnosis, 27 (56.3%) had the exon 19 deletion, 20 (41.7%) had the L858R mutation, and one (2.0%) had the exon 18 mutation. The median progression-free survival (PFS) was 15.4 months. At 6, 12, and 18 months, PFS rates were 79.1%, 53.6%, and 27.3%, respectively. When PFS was analyzed by prior TKI duration (<18 months vs. >18 months), significant differences were noted at the 6 and 9-month mark (p = 0.013 and p = 0.010, respectively). In multivariate analysis for PFS, only prior TKI duration and ECOG score showed statistical significance (p = 0.026 and p = 0.049, respectively). In the multivariate analysis for OS, ECOG score showed statistical significance (p = 0.006). Among 48 patients, 34 (70.8%) experienced adverse events (AEs) related to lazertinib. The most frequent AEs were skin reaction (29.8%), diarrhea (21.3%), and peripheral neuropathy (20.8%). CONCLUSIONS: The results suggest that lazertinib is effective in second or more line settings, with tolerable safety profile. More patient data are necessary to find possible prognostic markers associated with patient outcome.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Factors for progressive pulmonary fibrosis in connective tissue disease-related interstitial lung disease.

BACKGROUND: Progressive fibrosis can occur in connective tissue disease (CTD)-related interstitial lung disease (ILD) and make the prognosis worse. OBJECTIVES: This study aimed to investigate factors related to progressive pulmonary fibrosis (PPF) phenotype in CTD-ILDs. DESIGN: Medical records of patients diagnosed as CTD and ILD at a single, tertiary hospital in South Korea were retrospectively reviewed. METHODS: Patients whose lung functions were followed up for more than a year were included in analysis. PPF was defined as forced vital capacity (FVC) declined ⩾10% or diffusion capacity of carbon monoxide (DLco) ⩾15%. RESULTS: Of 110 patients with CTD-ILD, 24.5% progressed into PPF. Rheumatoid arthritis (RA) and Sjogren's disease accounted for more than 63% of PPF. Compositions of CTD type were similar between PPF and non-PPF. Clinical characteristics and proportion of usual interstitial pneumonia (UIP) pattern on chest images were also similar between PPF and non-PPF. Approximately 10% of patients in both groups were treated with anti-fibrotic agents. Use of systemic steroids and/or other immunomodulating agents lowered the risk of developing PPF in CTD-ILD patients after adjusting for gender-age-physiology score and smoking status (adjusted odds ratio: 0.25, 95% confidence interval: 0.07-0.85). CONCLUSION: About a quarter of CTD-ILD progressed into PPF. The use of immunomodulating agents lowered the risk of developing PPF. To improve outcomes of patients, future studies need to detect patients at higher risk for PPF earlier and set up clinical guidelines for treatment strategies in the process of PPF.

Controlled Mesoscopic Growth of Polymeric Fibers Using Liquid Crystal Template.

Orientation-controlled polymeric fiber is one of the most exciting research topics to rationalize the multifunctionality for various applications. In order to realize this goal, the growth of polymeric fibers should be controlled using various techniques like extrusion, molding, drawing, and self-assembly. Among the various candidates to fabricate the orientation-controlled polymeric fibers, the template-assisted assembly guided by a liquid crystal (LC) matrix is the most promising because the template can be manipulated easily with various methods like surface anchoring, rubbing, geometric confinement, and electric field. This review introduces the recent progress toward the directed growth of polymeric fibers using the LC template. Three representative LC-templated polymerization techniques to fabricate fibers include chemical or physical polymerization from the monomers mixed in LC matrix, patterned fibers formed from LC-templated reactive mesogens, and orientation-controlled nanofibers by infiltrating vaporized monomers between LC molecules. The orientation-controlled polymeric fibers will be used in electro-optical switching tools, tunable hydrophilic or hydrophobic surfaces, and control of phosphorescence, which can open a way to design, fabricate, and modulate nano- to micron-scale fibers with various functions on demand.

Comparison of the diagnostic criteria for progressive pulmonary fibrosis in connective tissue disease related interstitial lung disease.

BACKGROUND: Progressive pulmonary fibrosis (PPF) is possible among patients with connective tissue disease (CTD) related interstitial lung disease (ILD). Our aim herein was to compare the prevalence and clinical characteristics of patients with CTD-ILD, with and without PPF, according to the different diagnostic criteria currently used in practice. METHODS: This retrospective study included patients diagnosed with CTD-ILD, with a ≥1-year follow-up of their lung function, at a single tertiary hospital in South Korea. Diagnostic criteria from two clinical trials (RELIEF and TRAIL1) and from a recently updated guideline (ATS/ERS/JRS/ALAT) were applied. RESULTS: Of the 107 patients included, 80% tested positive for Sjogren's disease, rheumatoid arthritis, and systemic sclerosis. The prevalence of CTD-ILD with PPF for the different diagnostic criteria was as follows: RELIEF, 25.2%; TRAIL1, 20.6%; and ATS/ERS/JRS/ALAT, 38.3%. More previous history of pulmonary tuberculosis and less positivity for antinuclear antibodies were identified in the PPF group. The radiologic pattern of ILD did not differ between patients with and without PPF, with a usual interstitial pneumonia pattern identified in 34.6% of the patients. Systemic steroids and immunomodulatory agents were used in about 80% of patients with PPF and 50% without PPF, irrespective of the diagnostic criteria used. Antifibrotic therapy was used in a limited number of patients in both groups. CONCLUSIONS: The proportion of patients with CTD-ILD and PPF was higher for the ATS/ERS/JRS/ALAT guideline criteria, without a between-group difference in clinical characteristics.

Patterned Hydrophobic Liquid Crystalline Fibers Fabricated from Defect Arrays of Reactive Mesogens via Electric Field Modulation.

We have fabricated patterned fibers using a small-molecular-weight liquid crystal (LC) and reactive mesogens (RMs) under controlled electric fields in which defect arrays are generated depending on the electrode configuration. For this, the AC electric field with interdigitated electrodes is used to develop versatile defect structures of the LC phase. Hydrophobic LC network (LCN) fibers exhibiting porous morphologies have been made by removing the LC part after the polymerization of RM. The resulting LCN fibers show a surface tension reduction characteristic compared to the neat RM film and a sticky characteristic with the water droplet, suggesting a facile way to fabricate the hydrophobic surface that can be used in microdroplet transport.

Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8+ T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy.

Oncolytic virotherapy has garnered attention as an antigen-agnostic therapeutic cancer vaccine that induces cancer-specific T cell responses without additional antigen loading. As anticancer immune responses are compromised by a lack of antigenicity and chronic immunosuppressive microenvironments, an effective immuno-oncology modality that converts cold tumors into hot tumors is crucial. To evaluate the immune-activating characteristics of oncolytic vaccinia virus (VACV; JX-594, pexastimogene devacirepvec), diverse murine syngeneic cancer models with different tissue types and immune microenvironments were used. Intratumorally administered mJX-594, a murine variant of JX-594, potently increased CD8+ T cells, including antigen-specific cancer CD8+ T cells, and decreased immunosuppressive cells irrespective of tissue type or therapeutic efficacy. Remodeling of tumors into inflamed ones by mJX-594 led to a response to combined anti-PD-1 treatment, but not to mJX-594 or anti-PD-1 monotherapy. mJX-594 treatment increased T cell factor 1-positive stem-like T cells among cancer-specific CD8+ T cells, and anti-PD-1 combination treatment further increased proliferation of these cells, which was important for therapeutic efficacy. The presence of functional cancer-specific CD8+ T cells in the spleen and bone marrow for an extended period, which proliferated upon encountering cancer antigen-loaded splenic dendritic cells, further indicated that long-term durable anticancer immunity was elicited by oncolytic VACV.

A Nanostructured Phthalocyanine/Albumin Supramolecular Assembly for Fluorescence Turn-On Imaging and Photodynamic Immunotherapy.

Smart phototheranostic nanomaterials are of significant interest for high-quality imaging and targeted therapy in the precision medicine field. Herein, a nanoscale photosensitizer (NanoPcM) is constructed through the self-assembly of morpholine-substituted silicon phthalocyanine (PcM) and albumin. NanoPcM displays a turn-on fluorescence depending on the acid-induced abolition of the photoinduced electron transfer effect (change in molecular structure) and disassembly of the nanostructure (change in supramolecular structure), which enables low-background and tumor-targeted fluorescence imaging. In addition, its efficient type I photoreaction endows NanoPcM with a superior immunogenic photodynamic therapy (PDT) effect against solid tumors. The combination of NanoPcM-based PDT and αPD-1-based immunotherapy can efficiently inhibit tumor growth, reduce spontaneous lung metastasis, and trigger abscopal effects. This study should provide a perspective for the future design of nanomaterials as promising phototheranostics for cancer imaging and therapy.

Relationship of sociodemographic and anthropometric characteristics, and nutrient and food intakes with osteoarthritis prevalence in elderly subjects with controlled dyslipidaemia: a cross-sectional study.

BACKGROUND AND OBJECTIVES: Several studies have suggested that abnormal levels of serum cholesterol may be a major risk factor for osteoarthritis. However, no studies have been conducted to prevent osteoarthritis under controlled conditions of serum cholesterol. This study aimed to examine the relationship of sociodemographic and anthropometric characteristics, and nutrient and food intakes with osteoarthritis prevalence in Korean elderly subjects with controlled dyslipidaemia. METHODS AND STUDY DESIGN: This study included 314 subjects aged ≥65 years who were diagnosed and treated for dyslipidaemia (data from the Seventh Korea National Health and Nutrition Examination Survey, 2016). Among them, 108 were also diagnosed with osteoarthritis. Sociodemographic, health, and nutritional data were analysed. RESULTS: Osteoarthritis prevalence was higher in females, highereducated subjects, unmarried subjects, non-smokers, and subjects with high body mass index (p<0.05). After adjusting for the multiple variables, the non-osteoarthritis group had significantly higher vitamin C intake (132±11.0 vs 93.1±11.1 mg/day), fish intake (172±30.0 vs 79.0±12.9 g/day), and seaweed intake (93.7±19.3 vs 38.3±13.4 mg/day) than the osteoarthritis group. Furthermore, the lowest vitamin C, fish, seaweed intake group (quartile 1) each had 3.20, 2.76, 9.93 times higher risk of osteoarthritis than the highest vitamin C, fish, seaweed intake group (quartile 4) (p<0.05). CONCLUSIONS: Among Korean elderly subjects with controlled dyslipidaemia, those with osteoarthritis had lower vitamin C, fish, seaweed intakes than those without osteoarthritis. Although our results do not prove that low vitamin C, fish, seaweed intakes cause osteoarthritis, such relationship is worth exploring for a preventive perspective.

Decision feedback equalizer for holographic data storage.

Holographic data storage (HDS) has attracted much attention as a next-generation storage medium. Because HDS suffers from two-dimensional (2D) inter-symbol interference (ISI), the partial-response maximum-likelihood (PRML) method has been studied to reduce 2D ISI. However, the PRML method has various drawbacks. To solve the problems, we propose a modified decision feedback equalizer (DFE) for HDS. To prevent the error propagation problem, which is a typical problem in DFEs, we also propose a reliability factor for HDS. Various simulations were executed to analyze the performance of the proposed methods. The proposed methods showed fast processing speed after training, superior bit error rate performance, and consistency.