Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models. Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis. Conclusions NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.