Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for immune checkpoint inhibitors in biliary tract cancer.

PURPOSE: Anti-PD-1/L1 has been demonstrated for its efficacy when combined with cytotoxic chemotherapy in randomized phase 3 trials for advanced biliary tract cancer (BTC). However, no biomarker predictive of benefit has been established for anti-PD-1/L1 in BTC. Here, we evaluated tumor-infiltrating lymphocytes (TILs) using artificial intelligence-powered immune phenotype (AI-IP) analysis in advanced BTC treated with anti-PD-1. PATIENTS AND METHODS: Pre-treatment H&E-stained whole-slide images from 339 advanced BTC patients who received anti-PD-1 as second-line treatment or beyond, were utilized for AI-IP analysis and correlative analysis between AI-IP and efficacy outcomes with anti-PD-1. Next, data and images of BTC cohort from The Cancer Genome Atlas (TCGA) were additionally analyzed to evaluate the transcriptomic and mutational characteristics of various AI-IPs in BTC. RESULTS: Overall, AI-IPs were classified as inflamed (high intratumoral TIL [iTIL]) in 40 patients (11.8%), immune-excluded (low iTIL and high stromal TIL) in 167 (49.3%), and immune-deserted (low TIL overall) in 132 (38.9%). The inflamed IP group showed a significantly higher overall response rate compared to the non-inflamed IP groups (27.5% vs. 7.7%, P<0.001). Median overall survival and progression-free survival were significantly longer in the inflamed IP group than in the non-inflamed IP group (OS: 12.6 vs. 5.1 months, P=0.002; PFS: 4.5 vs. 1.9 months, P<0.001). In the analysis using TCGA cohort, the inflamed IP showed increased cytolytic activity scores and an interferon-gamma signature compared to the non-inflamed IP. CONCLUSIONS: AI-powered IP based on spatial TIL analysis was effective in predicting the efficacy outcomes in patients with BTC treated with anti-PD-1.

Genomic and transcriptomic profiles associated with response to eribulin and nivolumab combination in HER-2-negative metastatic breast cancer.

BACKGROUND: Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863). METHODS: We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise. FINDINGS: Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months). INTERPRETATION: Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.

Single/Multi-Network Conductive Hydrogels-A Review.

Hydrogels made from conductive organic materials have gained significant interest in recent years due to their wide range of uses, such as electrical conductors, freezing resistors, biosensors, actuators, biomedical engineering materials, drug carrier, artificial organs, flexible electronics, battery solar cells, soft robotics, and self-healers. Nevertheless, the insufficient level of effectiveness in electroconductive hydrogels serves as a driving force for researchers to intensify their endeavors in this domain. This article provides a concise overview of the recent advancements in creating self-healing single- or multi-network (double or triple) conductive hydrogels (CHs) using a range of natural and synthetic polymers and monomers. We deliberated on the efficacy, benefits, and drawbacks of several conductive hydrogels. This paper emphasizes the use of natural polymers and innovative 3D printing CHs-based technology to create self-healing conductive gels for flexible electronics. In conclusion, advantages and disadvantages have been noted, and some potential opportunities for self-healing single- or multi-network hydrogels have been proposed.

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP.

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Radiation-Induced Hydrogel for Water Treatment.

Along with serving as drug delivery sensors and flexible devices, hydrogels are playing pioneering roles in water purification. Both chemical and radiation methods can produce hydrogels, with the latter method gaining preference for its pure adducts. The water treatment process entails the removal of heavy and toxic metals (above the threshold amount), dyes, and solid wastes from industrial effluents, seawater, and groundwater, as well as sterilization for microorganism destruction. This review analyzed the different types of hydrogels produced by applying various radiations for water treatment. Particularly, we examined the hydrogels created through the application of varying levels of gamma and electron beam radiation from the electron gun and Co-60 sources. Moreover, we discuss the optimized radiation doses, the compositions (monomers and polymers) of raw materials required for hydrogel preparation, and their performance in water purification. We present and predict the current state and future possibilities of radiation-induced hydrogels. We explain and compare the superiority of one radiation method over other radiation methods (UV-visible, X-ray, microwave, etc.) based on water treatment.

Potential of Carbon Aerogels in Energy: Design, Characteristics, and Applications.

In energy applications, the use of materials with hierarchical porous structures and large surface areas is essential for efficient charge storage. These structures facilitate rapid electron and ion transport, resulting in high power density and quick charge/discharge capabilities. Carbon-based materials are extensively utilized due to their tunable properties, including pore sizes ranging from ultra- to macropores and surface polarity. Incorporating heteroatoms such as nitrogen, oxygen, sulfur, phosphorus, and boron modifies the carbon structure, enhancing electrocatalytic properties and overall performance. A hierarchical pore structure is necessary for optimal performance, as it ensures efficient access to the material's core. The microstructure of carbon materials significantly impacts energy storage, with factors like polyaromatic condensation, crystallite structure, and interlayer distance playing crucial roles. Carbon aerogels, derived from the carbonization of organic gels, feature a sponge-like structure with large surface area and high porosity, making them suitable for energy storage. Their open pore structure supports fast ion transfer, leading to high energy and power densities. Challenges include maintaining mechanical or structural integrity, multifunctional features, and scalability. This review provides an overview of the current progress in carbon-based aerogels for energy applications, discussing their properties, development strategies, and limitations, and offering significant guidance for future research requirements.

In Vitro Anti-Rotaviral Activity of Bavachin Isolated from Psoralea corylifolia L. (Fabaceae).

Rotavirus is the main causative agent of viral gastroenteritis among young animals worldwide. Currently, no clinically approved or effective antiviral drugs are available to combat rotavirus infections. Herein, we evaluated the anti-rotaviral activities of extracts and bavachin isolated from Psoralea corylifolia L. (Fabaceae) (P. corylifolia) against the bovine rotavirus G8P[7] and porcine rotavirus G5P[7] in vitro. Two assay strategies were performed: (1) a virucidal assay to reduce viral infectivity by virus neutralization and (2) a post-treatment assay to assess viral replication suppression. The results from the virucidal assay showed that the extracts and bavachin did not exert anti-rotaviral activities. In the follow-up analysis after treatment, bavachin exhibited robust antiviral efficacy, with 50% effective concentration (EC50) values of 10.6 µM (selectivity index [SI] = 2.38) against bovine rotavirus G8P[7] and 13.0 µM (SI = 1.94) against porcine rotavirus G5P[7]. Bavachin strongly suppressed viral RNA synthesis in the early (6 h) and late stages (18 h) after rotaviral infection. These findings strongly suggest that bavachin may have hindered the virions by effectively inhibiting the early stages of the virus replication cycle after rotaviral infection. Furthermore, confocal imaging showed that bavachin suppressed viral protein synthesis, notably that of the rotaviral protein (VP6). These results suggest that bavachin has strong antiviral activity against rotaviruses, inhibits viral replication, and is a candidate natural therapeutic drug targeting rotaviral infection. The utilization of bavachin isolated from P. corylifolia may contribute to decreased mortality rates, lower medication expenses, and enhanced economic viability in domestic farms.

Conductive Gels for Energy Storage, Conversion, and Generation: Materials Design Strategies, Properties, and Applications.

Gel-based materials have garnered significant interest in recent years, primarily due to their remarkable structural flexibility, ease of modulation, and cost-effective synthesis methodologies. Specifically, polymer-based conductive gels, characterized by their unique conjugated structures incorporating both localized sigma and pi bonds, have emerged as materials of choice for a wide range of applications. These gels demonstrate an exceptional integration of solid and liquid phases within a three-dimensional matrix, further enhanced by the incorporation of conductive nanofillers. This unique composition endows them with a versatility that finds application across a diverse array of fields, including wearable energy devices, health monitoring systems, robotics, and devices designed for interactive human-body integration. The multifunctional nature of gel materials is evidenced by their inherent stretchability, self-healing capabilities, and conductivity (both ionic and electrical), alongside their multidimensional properties. However, the integration of these multidimensional properties into a single gel material, tailored to meet specific mechanical and chemical requirements across various applications, presents a significant challenge. This review aims to shed light on the current advancements in gel materials, with a particular focus on their application in various devices. Additionally, it critically assesses the limitations inherent in current material design strategies and proposes potential avenues for future research, particularly in the realm of conductive gels for energy applications.

Novel microbiota Mesosutterella faecium sp. nov. has a protective effect against inflammatory bowel disease.

A novel Gram-negative, obligate anaerobe, non-motile, flagella-lacking, catalase- and oxidase-negative, coccobacilli-shaped bacterial strain designated AGMB02718T was isolated from swine feces. The 16S rRNA gene analysis indicated that strain AGMB02718T belonged to the genus Mesosutterella with the highest similarity to M. multiformis 4NBBH2T (= DSM 106860T) (sequence similarity of 96.2%), forming a distinct phylogenetic lineage. Its growth occurred at 25-45°C (optimal 37°C) and in 0.5-1% NaCl (optimal 0.5%). Strain AGMB02718T was asaccharolytic and contained menaquinone 6 (MK-6) and methylmenaquinone 6 (MMK-6) as the predominant respiratory quinones. The major cellular fatty acids in the isolate were C18:1ω9c and C16:0. Based on the whole-genome sequencing analysis, strain AGMB02718T had a 2,606,253 bp circular chromosome with a G + C content of 62.2%. The average nucleotide identity value between strain AGMB02718T and M. multiformis 4NBBH2T was 72.1%, while the digital DNA-DNA hybridization value was 20.9%. Interestingly, genome analysis suggested that strain AGMB02718T possessed a low-toxicity lipopolysaccharide (LPS) because the genome of the isolate does not include lpxJ and lpxM genes for Kdo2-Lipid A (KLA) assembly, which confers high toxicity to LPS. Moreover, in vitro macrophage stimulation assay confirmed that AGMB02718T produced LPS with low toxicity. Because the low-toxicity LPS produced by the Sutterellaceae family is involved in regulating host immunity and low-toxicity LPS-producing strains can help maintain host immune homeostasis, we evaluated the anti-inflammatory activity of strain AGMB02718T against inflammatory bowel disease (IBD). As a result, strain AGMB02718T was able to prevent the inflammatory response in a dextran sulfate sodium (DSS)-induced colitis model. Therefore, this strain represents a novel species of Mesosutterella that has a protective effect against DSS-induced colitis, and the proposed name is Mesosutterella faecium sp. nov. The type strain is AGMB02718T (=GDMCC 1.2717T = KCTC 25541T).

Factors associated with engraftment success of patient-derived xenografts of breast cancer.

BACKGROUND: Patient-derived xenograft (PDX) models serve as a valuable tool for the preclinical evaluation of novel therapies. They closely replicate the genetic, phenotypic, and histopathological characteristics of primary breast tumors. Despite their promise, the rate of successful PDX engraftment is various in the literature. This study aimed to identify the key factors associated with successful PDX engraftment of primary breast cancer. METHODS: We integrated clinicopathological data with morphological attributes quantified using a trained artificial intelligence (AI) model to identify the principal factors affecting PDX engraftment. RESULTS: Multivariate logistic regression analyses demonstrated that several factors, including a high Ki-67 labeling index (Ki-67LI) (p < 0.001), younger age at diagnosis (p = 0.032), post neoadjuvant chemotherapy (NAC) (p = 0.006), higher histologic grade (p = 0.039), larger tumor size (p = 0.029), and AI-assessed higher intratumoral necrosis (p = 0.027) and intratumoral invasive carcinoma (p = 0.040) proportions, were significant factors for successful PDX engraftment (area under the curve [AUC] 0.905). In the NAC group, a higher Ki-67LI (p < 0.001), lower Miller-Payne grade (p < 0.001), and reduced proportion of intratumoral normal breast glands as assessed by AI (p = 0.06) collectively provided excellent prediction accuracy for successful PDX engraftment (AUC 0.89). CONCLUSIONS: We found that high Ki-67LI, younger age, post-NAC status, higher histologic grade, larger tumor size, and specific morphological attributes were significant factors for predicting successful PDX engraftment of primary breast cancer.

Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

BACKGROUND: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. METHODS: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. RESULTS: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT was administered in 166 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.73-5.58, P <0.001] based on cutoff value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels less than 37 IU/l (median survival; 35.5 vs. 20.9 months, P <0.001) and CA19-9 levels at least 37 IU/l (median survival; 34.3 vs. 17.8 months, P =0.03). In patients suspected to be Lewis antigen negative, the predictive performance of MTV was found to be limited ( P =0.84). CONCLUSION: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

Proteomic analysis of breast cancer based on immune subtypes.

BACKGROUND: Immunotherapy is applied to breast cancer to resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on the distribution of immune cells. We assessed the clinicopathological features, each subtype's prognostic value and differentially expressed proteins between immune subtypes. METHODS: Immune subtyping and proteomic analysis were performed on 56 breast cancer cases with neoadjuvant chemotherapy. The immune subtyping was based on the level of tumor-infiltrating lymphocytes (TILs) and Klintrup criteria. If the level of TILs was ≥ 10%, it was classified as immune-inflamed type without consideration of the Klintrup criteria. In cases of 1-9% TIL, Klintrup criteria 1-3 were classified as the immune-excluded subtype and Klintrup criteria not available (NA) was classified as NA. Cases of 1% TILs and Klintrup 0 were classified as the immune-desert subtype. Mass spectrometry was used to identify differentially expressed proteins in formalin-fixed paraffin-embedded biopsy tissues. RESULTS: Of the 56 cases, 31 (55%) were immune-inflamed, 21 (38%) were immune-excluded, 2 (4%) were immune-desert and 2 (4%) were NA. Welch's t-test revealed two differentially expressed proteins between immune-inflamed and immune-excluded/desert subtypes. Coronin-1A was upregulated in immune-inflamed tumors (adjusted p = 0.008) and α-1-antitrypsin was upregulated in immune-excluded/desert tumors (adjusted p = 0.008). Titin was upregulated in pathologic complete response (pCR) than non-pCR among immune-inflamed tumors (adjusted p = 0.036). CONCLUSIONS: Coronin-1A and α-1-antitrypsin were upregulated in immune-inflamed and immune-excluded/desert subtypes, respectively. Titin's elevated expression in pCR within the immune-inflamed subtype may indicate a favorable prognosis. Further studies involving large representative cohorts are necessary to validate these findings.

Comprehensive Insights and Advancements in Gel Catalysts for Electrochemical Energy Conversion.

Continuous worldwide demands for more clean energy urge researchers and engineers to seek various energy applications, including electrocatalytic processes. Traditional energy-active materials, when combined with conducting materials and non-active polymeric materials, inadvertently leading to reduced interaction between their active and conducting components. This results in a drop in active catalytic sites, sluggish kinetics, and compromised mass and electronic transport properties. Furthermore, interaction between these materials could increase degradation products, impeding the efficiency of the catalytic process. Gels appears to be promising candidates to solve these challenges due to their larger specific surface area, three-dimensional hierarchical accommodative porous frameworks for active particles, self-catalytic properties, tunable electronic and electrochemical properties, as well as their inherent stability and cost-effectiveness. This review delves into the strategic design of catalytic gel materials, focusing on their potential in advanced energy conversion and storage technologies. Specific attention is given to catalytic gel material design strategies, exploring fundamental catalytic approaches for energy conversion processes such as the CO2 reduction reaction (CO2RR), oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and more. This comprehensive review not only addresses current developments but also outlines future research strategies and challenges in the field. Moreover, it provides guidance on overcoming these challenges, ensuring a holistic understanding of catalytic gel materials and their role in advancing energy conversion and storage technologies.

A nationwide real-world study for evaluation of effectiveness and safety of T-DM1 in patients with HER2-positive metastatic breast cancer in Korea (KCSG BR19-15).

Purpose: This study aimed to investigate clinical practices and factors related to the outcomes of T-DM1 use in patients with HER2-positive metastatic breast cancer (mBC). Methods: We included patients with HER2-positive mBC who received T-DM1 as a palliative therapy between August 2017 and December 2018. The safety and outcomes of T-DM1, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) for mortality or progression to HER2-positive mBC. Results: In total, 824 patients were enrolled during the study period. The mean age of patients was 58 years, and 516 (62.6%) patients relapsed after curative treatment. Excluding a history of endocrine therapy, 341 (41.4%) patients previously received none or first-line chemotherapy, 179 (21.7%) received second-line therapy, and 303 (36.9%) received third-or later-line chemotherapy before T-DM1 therapy. During a median follow-up of 16.8 months, the ORR was 35%, the median PFS was 6.6 months, and the median OS was not reached. The clinical factors associated with the hazard of progression were age (<65 years), poor performance status (⩾2), advanced line of palliative chemotherapy (⩾2), prior pertuzumab use, and treatment duration of palliative trastuzumab (<10 months). Common grade 3-4 adverse events were thrombocytopenia (n = 107, 13.2%), neutropenia (n = 23, 2.8%), anemia (n = 21, 2.6%), and elevated liver enzyme (n = 20, 2.5%). Hypokalemia (⩽3.0 mmol/L) and any-grade bleeding events occurred in 25 (3.1%) and 94 (22.6%) patients, respectively. Conclusion: This is the first nationwide real-world study of T-DM1 use in patients with HER2-positive mBC in Korea. The effectiveness and toxicity profiles of T-DM1 in real-world practice were comparable to those in randomized trials. Moreover, patient factors and previous anti-HER2 therapy could predict the outcomes of T-DM1 therapy.

21-gene expression assay and clinical outcomes of premenopausal patients with hormone receptor-positive breast cancer.

The prognostic role of the recurrence score (RS) based on the 21-gene expression assay in premenopausal women is not well delineated, and we investigated the association of outcomes and the RS in premenopausal patients who had 21-gene expression assay at Asan Medical Center, Seoul, Korea, between June 2005 and July 2018. Invasive breast cancer-free survival (IBCFS) by STEEP version 2.0 was compared according to the RS and clinical risk factors. A total of 554 patients were included in our study and 116 patients (20.9%) had age <40 years, 238 patients (43.0%) had luminal B subtype (Ki67 ≥ 20%), and 83 patients (15.0%) had RS >25. All patients received adjuvant tamoxifen ± chemotherapy. Overall, patients with RS >25 showed trend toward worse IBCFS from multivariable analysis (adjusted HR 1.89 [95% CI: 0.95-3.73], P = .069). When comparing outcomes according to age and luminal subtypes, patients with luminal B subtype and age <40 years (n = 60) showed significantly worse outcomes compared to the others (luminal A or luminal B + age ≥40 years, n = 494; adjusted HR 2.95 [95% CI: 1.49-5.82], log-rank P < .001). Among patients with luminal B subtype and age <40 years, there was no significant association observed between IBCFS and the RS (log-rank P = .51). In conclusion, while RS >25 showed association with poor outcomes in premenopausal women, it may have less prognostic significance among those with luminal B subtype and age <40 years.

Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open-label, multicenter, phase II trial.

INTRODUCTION: Metastatic breast cancer refractory to anthracycline and taxanes often shows rapid progression. The development of effective and tolerable combination regimens for these patients is needed. This phase II trial investigated the efficacy of pemetrexed plus vinorelbine in patients with metastatic breast cancer. METHODS: This randomized, open-label, phase II trial was conducted in 17 centers in Korea. Patients with advanced breast cancer who had previously been treated with anthracyclines and taxanes were randomly assigned in a 1:1 ratio to receive either vinorelbine or pemetrexed plus vinorelbine. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included the objective response rate, overall survival, safety, and quality of life. RESULTS: Between March 2017 and August 2019, a total of 125 patients were enrolled. After a median follow-up duration of 14.1 months, 118 progression events and 88 death events had occurred. Sixty-two patients were assigned to the pemetrexed plus vinorelbine arm, and 63 were assigned to the vinorelbine arm. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine (5.7 vs. 1.5 months, p < 0.001). The combination arm had higher disease control rate (76.8% vs. 45.9%, p = 0.001) and a tendency toward longer overall survival (16.8 vs. 10.5 months, p = 0.102). Anemia was more frequent in the pemetrexed plus vinorelbine arm per cycle compared with vinorelbine (7.9% vs. 1.9%, p < 0.001), but there was no difference in the incidence of grade 3-4 neutropenia per cycle between the pemetrexed plus vinorelbine arm and the vinorelbine single arm (14.7% vs. 19.5%, p = 0.066). CONCLUSIONS: This phase II study showed that pemetrexed plus vinorelbine led to a longer PFS than vinorelbine. Adverse events of pemetrexed plus vinorelbine were generally manageable.

Bacterial cancer therapy using the attenuated fowl-adapted Salmonella enterica serovar Gallinarum.

We report here a novel anti-cancer therapy based on an avian-host-specific serotype Salmonella enterica serovar Gallinarum (S. Gallinarum) deficient in ppGpp synthesis. To monitor the tumor targeting, a bioluminescent ΔppGpp S. Gallinarum was constructed and injected intravenously into mice bearing syngeneic and human xenograft tumors. Strong bioluminescent signals were detected specifically in all grafted tumors at 2 days post-injection (dpi). The bacterial counts in normal and tumor tissue at 1 dpi revealed that ΔppGpp S. Gallinarum reached >108 CFU/g in tumor tissue and 106-107 CFU/g in endothelial organs; counts were much lower in other organs. At 16 dpi, ΔppGpp S. Gallinarum counts in tumor tissue decreased to ∼106 CFU/g, while those in the other organs became undetectable. A strong anti-cancer effect was observed after the injection of ΔppGpp S. Gallinarum into BALB/c mice grafted with CT26 colon cancer cells. This could be attributed to reduced virulence, which allowed the administration of at least a 10-fold greater dose (108 CFU) of ΔppGpp S. Gallinarum than other attenuated strains of S. enterica serovar Typhimurium (≤107 CFU). An advantage of the avian-specific S. Gallinarum as a cancer therapeutic should be a reduced capacity to cause infections or harm in humans.

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP.

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Anti-obesity activity of human gut microbiota Bacteroides stercoris KGMB02265.

Obesity is a global health threat that causes various complications such as type 2 diabetes and nonalcoholic fatty liver disease. Gut microbiota is closely related to obesity. In particular, a higher Firmicutes to Bacteroidetes ratio has been reported as a biomarker of obesity, suggesting that the phylum Bacteroidetes may play a role in inhibiting obesity. Indeed, the genus Bacteroides was enriched in the healthy subjects based on metagenome analysis. In this study, we determined the effects of Bacteroides stercoris KGMB02265, a species belonging to the phylum Bacteroidetes, on obesity both in vitro and in vivo. The cell-free supernatant of B. stercoris KGMB02265 inhibited lipid accumulation in 3T3-L1 preadipocytes, in which the expression of adipogenic marker genes was repressed. In vivo study showed that the oral administration of B. stercoris KGMB02265 substantially reduced body weight and fat weight in high-fat diet induced obesity in mice. Furthermore, obese mice orally administered with B. stercoris KGMB02265 restored glucose sensitivity and reduced leptin and triglyceride levels. Taken together, our study reveals that B. stercoris KGMB02265 has anti-obesity activity and suggests that it may be a promising candidate for treating obesity.

Analysis of random mutations in Salmonella Gallinarum dihydropteroate synthase conferring sulfonamide resistance.

In bacteria and primitive eukaryotes, sulfonamide antibiotics block the folate pathway by inhibiting dihydropteroate synthase (FolP) that combines para-aminobenzoic acid (pABA) and dihydropterin pyrophosphate (DHPP) to form dihydropteroic acid (DHP), a precursor for tetrahydrofolate synthesis. However, the emergence of resistant strains has severely compromised the use of pABA mimetics as sulfonamide drugs. Salmonella enterica serovar Gallinarum (S. Gallinarum) is a significant source of antibiotic-resistant infections in poultry. Here, a sulfonamide-resistant FolP mutant library of S. Gallinarum was generated through random mutagenesis. Among resistant strains, substitution of amino acid Arginine 171 with Proline (R171P) in the FolP protein conferred the highest resistance against sulfonamide. Substitution of Phe28 with Leu or Ile (F28L/I) led to modest sulfonamide resistance. Structural modeling indicates that R171P and Phenylalanine 28 with leucine or isoleucine (F28L/I) substitution mutations are located far from the substrate-binding site and cause insignificant conformational changes in the FolP protein. Rather, in silico studies suggest that the mutations altered the stability of the protein, potentially resulting in sulfonamide resistance. Identification of specific mutations in FolP that confer resistance to sulfonamide would contribute to our understanding of the molecular mechanisms of antibiotic resistance.