In vivo最新文献

Background/aim: Atypical polypoid adenomyoma (APA) is an uncommon biphasic uterine tumor characterized by irregularly shaped, atypical endometrial glands haphazardly distributed within a fibromuscular stroma. APA is frequently associated with atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) and endometrioid endometrial carcinoma (EC). This study aimed to characterize the clinicopathological features and outcomes of APA concomitant with AH/EIN and EC.

Patients and methods: Nineteen cases of APA coexisting with AH/EIN or EC were retrospectively analyzed. Clinical presentation, pathological findings, treatment modalities, and outcomes were reviewed.

Results: Most patients (78.9%) were of reproductive age (26-45 years). The most common presenting symptom was abnormal uterine bleeding (47.4%), while 26.3% were asymptomatic. EC and AH/EIN were identified in 14 (73.7%) and five (26.3%) patients, respectively. Compared with AH/EIN, EC more often demonstrated cribriform architecture, papillary intraluminal growth, and stromal desmoplasia. Six of the 14 patients with EC underwent hysterectomy and remained recurrence-free. Of the eight patients managed with progestin therapy, four had persistent EC or AH/EIN on follow up curettage at three months. Similarly, one of the five patients with AH/EIN treated conservatively showed persistent disease after three months of progestin therapy. Nevertheless, all patients were disease-free at the last follow-up.

Conclusion: In APA, meticulous pathological evaluation is essential to detect concurrent AH/EIN or EC. Although conservative management may be appropriate for selected patients, close surveillance is necessary to monitor for persistence or recurrence. Hysterectomy remains a definitive and reliable therapeutic option.

Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and cartilage destruction. Tripartite motif-containing 22 (TRIM22) is involved in intracellular signal transduction, protein regulation, and innate immunity through E3 ubiquitin ligase activity. In this study, we examined the expression of TRIM22 and its potential role in synovial inflammation in RA.

Materials and methods: Human rheumatoid fibroblast-like synoviocytes (RFLS) were cultured and treated with polyinosinic:polycytidylic acid (poly I:C), a toll-like receptor 3 (TLR3) ligand. Poly I:C was applied at different concentrations for different treatment durations. RNA interference was performed by pre-treating RFLS with either non-silencing control small interfering RNA (siRNA) or siRNA targeting TRIM22, interferon β (IFNB), and nuclear factor-kappa B (NFKB) p65. TRIM22 expression in RA synovial tissue was analyzed by immunohistochemistry.

Results: TRIM22 expression in RFLS was induced by poly I:C in a concentration and time-dependent manner, and TRIM22 and C-C motif chemokine ligand 5 (CCL5) were regulated by IFN-β and NF-κB pathways. TRIM22 knockdown reduced poly I:C-induced expression of CCL5 and IFN-β. Immunohistochemistry confirmed higher TRIM22 expression in RA synovial tissue compared to osteoarthritis tissue.

Conclusion: Treatment of cultured RFLS with a TLR3 agonist led to the upregulation of TRIM22 expression. TRIM22 is regulated through the IFN-β and NF-κB-mediated pathways and TRIM22 positively regulates poly I:C-induced CCL5 and IFN-β expression. TRIM22 may have an important role in synovial inflammation associated with RA.

Background/aim: Worldwide, osteoarthritis causes pain in many patients, reducing their quality of life. Unfortunately, there are limited ways to alleviate the pain of osteoarthritis patients. Today, advances in genetic analysis have made it possible to analyze various causes of disease, including osteoarthritis. However, genetic analysis of osteoarthritis patients in the Korean population has rarely been performed. This study aims to find specific gene expression patterns in synovium tissues of Korean osteoarthritis patients through transcriptome analysis.

Materials and methods: Transcriptome analysis was performed on eight tissue samples obtained from osteoarthritis patients and seven tissue samples obtained from normal individuals. To functionally analyze the differentially expressed genes (DEGs) identified from the transcriptome analysis, Gene Ontology (GO) term enrichment analysis, network analysis, and Gene Set Enrichment Analysis (GSEA) analysis were conducted.

Results: After performing GO analysis on the top 50 DEGs, 11 candidate genes were selected based on adjusted p-value <0.05 and |log₂ fold change (FC)| ≥2. Gene network analysis of the 11 DEGs confirmed their association with immune responses. Furthermore, GSEA analysis of the 11 DEGs revealed that all of them showed positive correlations with the corresponding GO terms.

Conclusion: We identified 11 candidate genes associated with immune responses that are abnormally overexpressed in the synovium tissues of Korean osteoarthritis patients. Establishment of the strategies for targeting these genes may help alleviate pain in Korean osteoarthritis patients.

Background/aim: The epidermal growth factor receptor (EGFR) is a key driver in bladder cancer progression. This study investigated the tumor-suppressive role of miR-124-3p and its regulatory effect on EGFR.

Materials and methods: TSGH8301 and T24 bladder cancer cells were treated with the EGFR inhibitor erlotinib or transfected with an miR-124-3p mimic. Cell viability, proliferation, migration, and invasion were assessed using MTT, colony formation, and transwell assays. EGFR targeting was confirmed via Western blot, immunofluorescence, and luciferase reporter assays.

Results: Erlotinib and miR-124-3p both reduced cell viability and proliferation. miR-124-3p significantly inhibited EGFR phosphorylation and expression, suppressed migration and invasion, and downregulated the EGFR downstream targets MMP2, MMP9, and VEGF-A. Luciferase assays confirmed the direct binding of miR-124-3p to EGFR 3'UTR.

Conclusion: miR-124-3p suppresses bladder cancer cells progression by directly targeting and inactivating EGFR, thereby impairing cell proliferation, migration, and invasion. These findings highlight miR-124-3p as a potential therapeutic agent in EGFR-driven bladder cancer.

Background/aim: The oropharynx, hypopharynx, and esophagus share similar epithelial characteristics, rendering them highly susceptible to the development of synchronous or metachronous multiple primary cancers. As endoscopic technologies, including Narrow Band Imaging (NBI) and high-resolution imaging systems, have advanced, early-stage pharyngeal cancers are increasingly detected during routine endoscopic evaluations or follow-up examinations for other head and neck or esophageal malignancies. This study aimed to retrospectively evaluate the clinical features, treatment modalities, occurrence of synchronous/metachronous multiple primary cancers, and prognoses in patients with early-stage (Tis, T1, T2/N0) oropharyngeal and hypopharyngeal squamous cell carcinoma who underwent initial treatment between January 2016 and December 2021.

Patients and methods: Seventy-six patients with early-stage oropharyngeal or hypopharyngeal squamous cell carcinoma were included in the analysis. Parameters evaluated included patient demographics, tumor classification and localization, detection methods, therapeutic interventions, presence and type of multiple primary cancers, and clinical outcomes.

Results: While the disease-specific survival (DSS) rates were generally favorable across T stages, overall survival (OS) rates were comparatively lower, with many deaths attributable to the progression of multiple primary cancers, especially those involving the upper gastrointestinal tract. Detection of Tis and T1 lesions often occurred incidentally during gastrointestinal endoscopy performed for other indications. In contrast, T2 lesions were predominantly detected following the onset of pharyngeal symptoms and ENT examination. Multiple primary cancers were highly prevalent, particularly esophageal and gastric carcinomas.

Conclusion: Despite favorable DSS outcomes in early-stage oropharyngeal and hypopharyngeal cancers, OS remains compromised due to secondary malignancies. These findings underscore the critical need for early, isolated detection of pharyngeal carcinoma through interdepartmental collaboration, particularly with gastroenterologists and screening physicians, to enhance comprehensive cancer control and improve patient survival.

Background/aim: Difluorodeoxycytidine (dFdC) has been reported to increase radiosensitivity, although its mechanism of action is unknown. The objective of this study was to determine the early and late effects of dFdC on mouse cell radiosensitivity in vivo.

Materials and methods: The early effects of dFdC on bone marrow cell radiosensitivity were evaluated a few minutes after dFdC treatment using single-cell gel electrophoresis. Four groups of mice were set up: non-treated, dFdC-treated, radiation-treated, and dFdC plus radiation-treated. To evaluate the late effects of dFdC, the kinetics of micronucleus production and the inhibition of proliferation were measured in mouse normoblasts in vivo.

Results: The early radiosensitization index was 1.7 and correlated with the proportion of severely damaged cells, likely in S phase. Late effects of dFdC were additive with radiation in both micronucleus induction and cytotoxicity. The pattern and duration of micronucleus formation suggest a dependency on dFdC incorporation into DNA. Although cytotoxicity increased over time, it did not influence the radiosensitization index.

Conclusion: dFdC enhances early radiosensitivity in bone marrow cells, likely by inhibiting DNA synthesis and generating reactive oxygen species (ROS)-induced DNA breaks. Late genotoxic effects were additive and kinetically linked to dFdC incorporation. Both dFdC alone and in combination with radiation exerted prolonged cytotoxic effects on normoblast precursors, with slightly greater toxicity observed in the combination group.

Background/aim: Hepatocellular carcinoma (HCC) is a significant global health concern, ranking as the sixth most common neoplasm and the third leading cause of cancer-related deaths. This study aimed to consolidate data on HCC to provide a comprehensive epidemiological profile in Brazil.

Patients and methods: This retrospective study analyzed secondary data extracted from the Mortality Information System (SIM), Hospital Cancer Registry (RHC), and Population-Based Cancer Registry (RCBP) from 2000 to 2019. The analysis included 26,349 HCC cases, incorporating variables such as age, sex, stage at diagnosis, treatment modalities, and mortality rates. Statistical analyses were performed using the chi-square test, Student's t-test, and logistic regression models.

Results: The number of HCC cases in Brazil has progressively increased over time. Most patients were male (16,631 of 26,349; 63.1%), with a mean age of 60-61 years. A large proportion of patients were diagnosed at an advanced stage (4,991 of 10,645; 46.9%), which limited curative treatment options. Only 38.7% (10,064) of 26,349 patients received any form of treatment. Mortality was significantly increased, 60.6% (5,891 of 9,727 cases).

Conclusion: These findings highlight the critical need for improved epidemiological surveillance, expanded screening programs, and standardized diagnostic and treatment protocols for HCC in Brazil. The high prevalence of late-stage diagnoses and limited access to treatment underscores the urgent need to implement effective public health policies to promote early detection and improve disease management.

Background/aim: Sideroflexin 4 (SFXN4) is important for mitochondrial function and relatively unstudied in relation to cancer. The aim of the study was to examine the SFXN4 gene and protein expression in patients with colorectal cancer (CRC) to identify associations with various clinicopathological parameters and evaluate the diagnostic and prognostic significance.

Patients and methods: SFXN4 protein and mRNA expression in cancer and paired normal tissues was determined in patients with CRC using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Immunohistochemical staining was used to study the cell type origin of the SFXN4 expression. SFXN4 was silenced in HT-29 cells and several genes known to be involved in colorectal carcinogenesis were examined on mRNA level by RT-qPCR.

Results: The protein and mRNA level of SFXN4 was 35 and 19% higher in tumor tissue compared to those in normal paired tissue (p<0.05). Non-mucinous type expressed 21% higher protein level compared to levels in the mucinous type (p<0.05). Immunohistochemistry revealed SFXN4 cytoplasmic staining mainly in the epithelial cells in cancer and normal tissue. A 19% higher SFXN4 mRNA level was observed in smaller tumors and in left colon compared to right colon cancer (p<0.05). Silencing of SFXN4 in HT-29 cells resulted in an up-regulation of IL-8 by 63% and increased proliferation (p<0.05).

Conclusion: The findings indicate the importance of SFXN4 in colorectal carcinogenesis and extended studies are necessary to elucidate its role as a prognostic biomarker.

Background/aim: Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE), marked by vascular remodeling, immune dysregulation, and progressive right heart failure. Molecular hydrogen therapy, a selective antioxidant and anti-inflammatory agent, has the capacity to modulate immune responses in these autoimmune disease patients. This case report details the clinical improvement in an SLE patient with PAH after starting adjunctive hydrogen capsule therapy, highlighting its potential as a novel approach for this challenging complication.

Case report: A 45-year-old Taiwanese woman with SLE-PAH who received hydrogen capsule therapy, during which serial immunophenotyping revealed dynamic changes in T cell exhaustion markers, regulatory T cell (Treg) subsets, and regulatory B cells (Breg). Notably, KLRG1+ T cells and CD39+Helios- Tregs were suppressed during therapy but rebounded after cessation, suggesting transient immune suppressing followed by regulatory rebalancing. Bregs also showed a similar pattern, declining during therapy and recovering after discontinuation.

Conclusion: These findings suggest a biphasic immunomodulatory effect of hydrogen therapy, that is, initially dampening immune activation, followed by a regulatory rebound after hydrogen therapy.

Background/aim: Sinonasal papilloma is a histologically benign tumor that demonstrates locally aggressive behavior, with a propensity for recurrence and potential for malignant transformation. This study aimed to evaluate the clinical characteristics, recurrence patterns, and malignant transformation of sinonasal papillomas and to propose appropriate follow-up strategies.

Patients and methods: A retrospective analysis was conducted on 83 patients diagnosed with sinonasal papilloma at our institution. Clinical features, surgical treatments, recurrence intervals, and oncologic outcomes were analyzed. Tumors were staged using the Krouse classification for benign cases and UICC TNM staging for carcinoma-associated with papilloma cases.

Results: Among 83 patients (62 men, 21 women; median age 68), 74 (89.2%) were diagnosed as benign papillomas and nine (10.8%) as carcinoma-associated with papilloma. The recurrence rate among benign cases was 14.9% (11/74), with a median time to recurrence of 5 years and two months. Recurrence intervals exhibited a trimodal distribution: within two years (36.4%), between 2-10 years (36.4%), and after 10 years (27.3%). Malignant transformation occurred in one case (1.2%), and eight additional cases were found to be associated with carcinoma. Five of these were initially misdiagnosed as benign, underscoring the diagnostic limitations of imaging modalities. Krouse T3/T4 lesions were more frequently associated with recurrence and malignancy. Approximately 48.6% of patients discontinued follow-up, often before reaching the threshold for late recurrence.

Conclusion: Sinonasal papillomas require long-term surveillance beyond five years due to their potential for late recurrence and malignant transformation. Preoperative suspicion of malignancy remains challenging, particularly in Krouse T3 lesions. Clinicians should consider extended follow-up, especially in patients with advanced tumor stage, and adopt a tailored surgical strategy to achieve complete resection. Patient education regarding recurrence risk is essential for optimizing long-term outcomes.