Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer. Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed. Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs. Conclusion The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

The incidence of colon cancer in South Korea has recently been the highest among gastrointestinal cancers. Early diagnosis is critical, and image-enhanced endoscopy (IEE) is a key diagnostic method. Colon tumors primarily include serrated polyps, adenomatous polyps, and colon cancer. Early endoscopic techniques relied on simple visual inspection for diagnosis, with tumor size and shape being the primary considerations. Low-resolution images made these methods ineffective for detecting small or early-stage lesions. IEE now enables detailed examination using high-resolution images and various color and structure analyses. Techniques like narrow band imaging (NBI) allow precise observation of vascular patterns and surface structures.Hyperplastic polyps often appear similar in color to the surrounding mucosa, with no visible vascular pattern. Sessile serrated lesions have a cloudy surface with distinct boundaries and irregular patterns, often with black spots in the crypts. Adenomatous polyps are darker brown, with a visible white epithelial network and various pit patterns. Magnified images help differentiate between low- and high-grade dysplasia, with low-grade showing regular patterns and high-grade showing increased irregularities. The NBI International Colorectal Endoscopic classification identifies malignant colon tumors as brown or dark brown with disorganized vascular patterns. The Japan NBI Expert Team classification includes loose vascular areas and disrupted thick vessels. The Workgroup serrAted polypS and Polyposis classification aids in differentiating between hyperplastic polyps and sessile serrated lesions/adenomas when deciding whether to resect polyps larger than 5 mm. Suspected high-grade dysplasia warrants endoscopic submucosal dissection and follow-up. Future advancements in IEE are expected to further enhance early detection and diagnostic accuracy.

Background: Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. Methods: This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. Results: The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. Conclusion In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

Coronavirus disease 2019 (COVID-19) is one of the most widespread viral infections in human history. As a breakthrough against infection, vaccines have been developed to achieve herd immunity. Here, we report the first case of microscopic polyangiitis (MPA) following BNT162b2 vaccination in Korea. A 42-year-old man presented to the emergency room with general weakness, dyspnea, and edema after the second BNT162b2 vaccination. He had no medical history other than being treated for tuberculosis last year. Although his renal function was normal at last year, acute kidney injury was confirmed at the time of admission to the emergency room. His serum creatinine was 3.05 mg/dL. Routine urinalysis revealed proteinuria (3+) and hematuria. When additional tests were performed for suspected glomerulonephritis, the elevation of myeloperoxidase (MPO) antibody (38.6 IU/mL) was confirmed. Renal biopsy confirmed pauci-immune anti-neutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and MPA was diagnosed finally. As an induction therapy, a combination of glucocorticoid and rituximab was administered, and plasmapheresis was performed twice. He was discharged after the induction therapy and admitted to the outpatient clinic 34 days after induction therapy. During outpatient examination, his renal function had improved with serum creatinine 1.51 mg/dL. We suggest that MPA needs to be considered if patients have acute kidney injury, proteinuria, and hematuria after vaccination.

Objective: AT-rich interactive domain 1A (ARID1A) plays an important role as a tumor suppressor gene in ovarian clear cell carcinoma (OCCC), but the clinical application of ARID1A remains unclear. The aim of this study was to analyze clinicopathological parameters, molecular interactions and immune-infiltration in patients with low ARID1A expression and to provide candidate target drugs. Methods: We investigated the clinicopathologic parameters, specific gene sets/genes, and immunological relevance according to ARID1A expression in 998 OCCC patients from 12 eligible studies (using meta-analyses); 30 OCCC patients from the Hanyang University Guri Hospital (HYGH) cohort; and 52 OCCC patients from gene set enrichment (GSE) 65986 (25 patients), 63885 (9 patients), and 54809 (6 patients and 12 healthy people) of the Gene Expression Omnibus (GEO). We analyzed network-based pathways based on gene set enrichment analysis (GSEA) and performed in vitro drug screening. Results: Low ARID1A expression was associated with poor survival in OCCC from the metaanalysis, HYGH cohort and GEO data. In GSEA, low ARID1A expression was related to the tumor invasion process as well as a low immune-infiltration. In silico cytometry showed that CD8 T cells were decreased with low ARID1A expression. In pathway analysis, ARID1A was associated with angiogenic endothelial cell signaling. In vitro drug screening revealed that cabozantinib and bicalutamide effectively inhibited specific hub genes, such as vascular endothelial growth factor-A and androgen receptor, in OCCC cells with low ARID1A expression. Conclusions Therapeutic strategies making use of low ARID1A could contribute to better clinical management/research for patients with OCCC.

Background and Objectives: Toxoplasmosis is a disease caused by an intracellular parasite, Toxoplasma gondii. There has been only a few studies done on cervical toxoplasma lymphadenitis, and this study was performed to evaluate its clinical characteristics and outcomes.Subjects and Method We retrospectively reviewed the patients diagnosed with cervical toxoplasma lymphadenitis from January 2010 to December 2019. We investigated clinical pathologic findings, treatment and clinical outcomes. Results: Enrolled in the study were 21 patients who were confirmed with typical pathologic findings in an excisional biopsy (16/21) and core needle biopsy (5/21). Nine patients were male and 12 patients were female, with the mean age of 46.1±13.59 (19-70). All patients complained of neck masses and 5 (23.8%) patients showed pain or tenderness. Only one (4.8%) patient had mild fever. Fine needle aspiration cytology was performed in 5 patients, with no resulting pathognomonic outcomes in any one of the patients. CT scan was performed in 15 patients, with 8 (53.3%) patients showing multiple nodal enlargements but 7 (46.6%) patients showing a single enlarged lymph node. The most frequently involved location was level I (53.3%), followed by level II (46.6%), level V (46.6%), level III (40.0%), and level IV (20.0%). The serologic test for toxoplasma revealed positive IgG (100%) and IgM (85.7%). Treatments were excision only (61.9%) and excision with pharmacologic treatment using sulfonamide or pyrimethamine (38.1%). There was no case of recurrence after treatment. Conclusion Cervical toxoplasma lymphadenitis can be diagnosed by biopsy but needle aspiration has little role. It shows favorable clinical outcomes after treatment.

Since 1995, the Korean Society for Cytopathology has overseen the Continuous Quality Improvement program for cytopathology laboratories. The Committee of Quality Improvement has carried out an annual survey of cytology data for each laboratory and set standards for proficiency tests. Methods: Evaluations were conducted four times per year from 2008 to 2018 and comprised statistics regarding cytology diagnoses of previous years, proficiency tests using cytology slides provided by the committee, assessment of adequacy of gynecology (GYN) cytology slides, and submission of cytology slides for proficiency tests. Results: A total of 206 institutes participated in 2017, and the results were as follows. The number of cytology tests increased from year to year. The ratio of liquid-based cytology in GYN gradually decreased, as most of the GYN cytology had been performed at commercial laboratories. The distribution of GYN diagnoses demonstrated nearly 3.0% as atypical squamous cells. The rate for squamous cell carcinoma was less than 0.02%. The atypical squamous cell/squamous intraepithelial lesion ratio was about 3:1 and showed an upward trend. The major discordant rate of cytology-histology in GYN cytology was less than 1%. The proficiency test maintained a major discordant rate less than 2%. The rate of inappropriate specimens for GYN cytology slides gradually decreased. Conclusions: The Continuous Quality Improvement program should be included in quality assurance programs. Moreover, these data can contribute to development of national cancer examination guidelines and facilitate cancer prevention and treatment.

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream signaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.
Brain ; Brain Neoplasms ; Cell Proliferation ; Dermatoglyphics ; Electrophoresis, Polyacrylamide Gel ; GTP-Binding Proteins ; Heterogeneous-Nuclear Ribonucleoproteins ; Humans ; Intracellular Signaling Peptides and Proteins ; Meningioma ; Neuroblastoma ; Pituitary Neoplasms ; Proteomics