BACKGROUND/AIM:Nintedanib, an antifibrotic drug, is expected to slow the progression of interstitial lung diseases (ILDs). This study aimed to evaluate the usefulness of nintedanib for patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) who would otherwise be excluded due to being unable to undergo invasive tests. PATIENTS AND METHODS:We retrospectively reviewed the medical records of all IPF and PPF patients who received nintedanib at our hospitals. This study included 187 patients whose severity could be assessed using the Japanese Respiratory Society classification, which allows for non-invasive severity evaluation, rather than the Gender-Age-Physiology score. Patients were classified into three groups based on their nintedanib administration status: a continuation group, a dose reduction group, and a discontinuation group. RESULTS:There were no significant differences in patient characteristics among the three groups. The duration of nintedanib administration in the discontinuation group was shorter than in the continuation and dose reduction groups. There was a significant difference in survival time from the start of nintedanib administration, with a shorter survival time in the discontinuation group. In addition, the incidence of acute exacerbations was lower in the continuation and the dose reduction groups than in the discontinuation group. Developing an acute exacerbation and discontinuation of nintedanib administration were identified as poor prognostic factors. CONCLUSION:Even in patients with ILD who would be excluded due to selection bias, continuing nintedanib might show positive effects on survival. The results obtained in this study are considered worthy of further verification.
BACKGROUND/AIM:Pterygium is a common ocular surface disorder associated with long-term ultraviolet exposure and/or oxidative DNA damage. Accumulated evidence suggests that defects in DNA repair pathways may contribute to pterygium risk. DNA ligase I (LIG1), a key enzyme involved in DNA replication and base excision repair, has been involved in the etiology of several human diseases, including cancers. However, its role in pterygium has never been examined before. This study aimed at exploring the association between the LIG1 genotypes and pterygium risk in a Taiwanese population. PATIENTS AND METHODS:The hospital-based case-control study was conducted including 165 patients with pterygium and 320 age- and sex-matched non-pterygium controls. LIG1 rs20579 genotypes were accessed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Stratified analysis and the calculation of odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used for evaluating the associations between genotypes and pterygium risk. RESULTS:Individuals carrying the homozygous variant AA genotype exhibited a significantly elevated risk of pterygium compared with those carrying the GG genotype (OR=2.74, 95% CI=1.17-6.43, p=0.0305). Under the recessive model, the AA genotype conferred a 2.65-fold elevated risk (95% CI=1.14-6.18, p=0.0350). The variant A allele was also associated with increased susceptibility (OR=1.46, 95% CI=1.03-2.07, p=0.0413). Stratified analyses revealed significant associations specifically among individuals aged ≥60 years (OR=5.64, 95% CI=1.67-19.04, p=0.0039) and males (OR=5.23, 95% CI=1.74-15.73, p=0.0034), but not those of younger ages or females. CONCLUSION:The LIG1 rs20579 genotype is significantly associated with pterygium susceptibility in Taiwanese individuals, particularly among elderly and male subjects. These findings support the involvement of impaired DNA repair machinery in pterygium pathogenesis and suggest that LIG1 rs20579 may serve as a novel genetic biomarker for risk assessment and early detection of pterygium.
BACKGROUND/AIM:The phosphatidylinositol 3-Kinase (PI3K) pathway is thought to be oncogenic in cancers when it is mutated at various sites. However, drugs targeting this mutated pathway have had only modest efficacy. Recently, a new inhibitor targeting the PI3K pathway, inavolisib (IVB), has been developed. In the present study, we determined whether IVB is synergistic with recombinant methioninase (rMETase) on breast-cancer cells compared to normal fibroblasts. MATERIALS AND METHODS:Cell viability was determined using the WST-8 cell-viability assay. The half-maximal inhibitory concentrations (IC50) of IVB and rMETase were determined on MCF-7 human breast-cancer cells compared to Hs-27 human normal fibroblasts in vitro. The efficacy of rMETase combined with IVB, at their respective IC50 values, on MCF-7 breast-cancer cells and Hs-27 normal fibroblasts was evaluated. RESULTS:The IC50 of IVB on MCF-7 breast-cancer cells of 83 nM was significantly lower than the IC50 on Hs-27 normal fibroblasts, which was 8.8 μM. The combination of rMETase and IVB was synergistic on MCF-7 breast-cancer cells, resulting in an inhibition of 76.2%. In contrast, the combination of rMETase and IVB was not synergistic on Hs-27 normal fibroblasts. CONCLUSION:IVB had a very low IC50 on MCF-7 breast-cancer cells compared to Hs-27 normal fibroblasts. IVB had increased efficacy on MCF-7 breast-cancer cells when combined with rMETase, showing strong synergy. In contrast, the combination of rMETase and IVB showed no synergy on Hs-27 normal fibroblasts. Therefore, IVB in combination with rMETase has strong clinical potential for breast cancer and possibly other cancers.
BACKGROUND/AIM:The standard surgical procedure for inducing myocardial infarction (MI) in rat models via left anterior descending (LAD) coronary artery ligation typically requires invasive endotracheal intubation. While recent techniques have avoided intubation, they necessitate completing the ligation within a critically short period of less than five minutes. In this study, we developed an improved, simple and safe mask ventilation technique to extend this crucial timeframe. MATERIALS AND METHODS:Male Sprague-Dawley rats (6-8 weeks old) were anesthetized with isoflurane and ventilated using a custom size syringe mask. A high-viscosity ultrasound gel was used to create an airtight seal and prevent air leaks. Ventilation pressure was maintained between 8-12 cmH2O. The LAD was ligated 1-2 mm distal to the left atrial appendage. A sham control group underwent the same procedure without LAD ligation. Post-operative cardiac function was serially assessed by echocardiography. Histological analysis was performed using hematoxylin and eosin (H&E) staining, and infarct size was quantified with Van Gieson's staining. RESULTS:The MI group demonstrated a significant reduction in ejection fraction one week after surgery. The average infarct size was 27.1±3.45% in the MI group. Post-operative mortality was comparable between the MI and sham control groups. CONCLUSION:This improved mask ventilation technique provides a simple and effective method for inducing reproducible MI in rats. It allows a substantially longer procedural time duration (~10 min) for careful and effective LAD ligation intervention and, eliminating the need for complex endotracheal intubation while maintaining a high survival rate.
BACKGROUND/AIM:To compare two different devices for computed tomography (CT)-guided preoperative localization of impalpable pulmonary nodules in terms of effectiveness, technical and clinical success and complications rate. PATIENTS AND METHODS:CT-guided preoperative localization procedures of small or ground glass (i.e., impalpable) pulmonary nodules performed in our center from April 2018 to December 2021 before lung resection with video-assisted thoracic surgery (VATS) were retrospectively analyzed. Two different markers were used: spiral-wire (SpW) and hydrogel plug (HyP). For each nodule the density, size and pleural distance were evaluated. Technical (correct CT-guided positioning of the marker) and clinical (its correct localization in VATS) success were assessed for each device. Complications as displacement, pneumothorax and parenchymal hemorrhage (PH) were registered. Statistical analysis was made by Chi-square, Wilcoxon and Fisher tests. RESULTS:Eighty-five consecutive patients (46/39 males/female; mean age 42 years, range=4-80 years) with 85 pulmonary nodules (maximum diameter: 8.5±6.4 mm in the SpW group and 17.0±4.2 mm in the HyP group) underwent preoperative CT-guided localization with SpW (65/85, 76.5%) or HyP (20/85, 23.5%) device. Correct CT-guided landmark positioning was obtained in 100% of cases. VATS revealed 4/65 (6.2%) cases of marker displacement in the SpW group and 3/17 (17.6%) cases in the HyP group (p=0.0353). Pneumothorax occurred in 40/65 (61.5%) cases in the SpW group and in 11/20 (55.0%) cases in the HyP group (p=0.602); no drainage tube was needed. PH occurred in 34/65 (52.3%) cases in SpW group and in 14/20 (70.0%) cases in HyP group (p=0.0163). CONCLUSION:Both markers are effective for the preoperative localization of impalpable pulmonary nodules in VATS. SpW seems to be slightly more stable and safer than HyP lung marker in relation to the displacement and PH rate.
BACKGROUND/AIM:TROP2 has become a therapeutic target in urothelial carcinoma following the approval of TROP2-directed antibody-drug conjugates (ADCs), yet its expression in transurethral resection (TURBT) material remains poorly characterized. This study aimed to evaluate TROP2 protein expression using immunohistochemistry (IHC) in bladder TURBT samples and to investigate its association with histological grade, tumor stage, lymphovascular invasion (LVI), carcinoma in situ (CIS), recurrence, and survival outcomes. MATERIALS AND METHODS:A total of 79 bladder TURBT specimens were included. Histological grading was performed according to the WHO/ISUP two-tier classification system (low grade / high grade) and pathological staging was based on the AJCC/UICC TNM Classification, 8th edition. TROP2 expression was assessed using IHC and quantified using the H-score method. Statistical analyses were performed using the chi-square test, Fisher's exact test, Mann-Whitney U and Kruskal-Wallis tests, Spearman's correlation analysis, receiver operating characteristic analysis, Kaplan-Meier estimates with log-rank tests, and Cox proportional hazards regression. RESULTS:Mean age was 65.87±11.46 years (91.1% male). Mean TROP2 H-score was 173.99±48.15 (median 160.0; range 30-280). A significant negative correlation was identified between TROP2 and histological grade (rho=-0.410; p=0.0003); median H-scores were 200.0 in low-grade versus 150.0 in high-grade tumors. Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.736 (sensitivity 92.3%, specificity 45.0%; cut-off 200). No significant association was found with pT stage, LVI, CIS, recurrence, disease-free survival (log-rank p=0.886), or overall survival (log-rank p=0.752). Cox regression confirmed no independent prognostic effect on survival. CONCLUSION:TROP2 inversely correlates with histological grade in bladder TURBT specimens (AUC=0.736) and may guide pathologists in diagnostically challenging cases - limited tissue, cautery artifact, or incomplete resection - where a low H-score suggests high-grade disease. TROP2 may complement WHO/ISUP grading and serve as a candidate predictive biomarker for TROP2-targeted ADC therapies.
BACKGROUND/AIM:Ring chromosomes (r) are rare cytogenetic circular structures associated with highly heterogeneous clinical phenotypes, primarily resulting from dynamic ring instability and mosaicism, as well as, unbalanced gene dosage. Consequently, establishing precise genotype-phenotype correlations in individuals with ring chromosomes remains challenging. PATIENTS AND METHODS:We performed a retrospective, single-laboratory study to investigate constitutional ring chromosomes identified by conventional cytogenetic analysis spanning the last 50 years. RESULTS:Twenty-five patients carrying constitutional ring chromosomes were identified and details of each are provided. Twelve cases involved autosomal-derived ring chromosomes with r(22) being the most frequent. Five cases were mosaics, whereas seven were non-mosaic. Molecular confirmation was obtained in six cases, while a de novo origin was determined in another six. Additionally, thirteen female patients were identified with mosaic ring X chromosomes, each presenting one cell line carrying a non-supernumerary ring X chromosome (46,X,r(X)) and another with monosomy X (45,X). In four individuals, the origin of the X ring chromosome was confirmed using FISH, while a de novo origin was demonstrated in six cases. CONCLUSION:Conventional karyotyping remains the gold-standard method for detecting ring chromosomes, recognizing their origin, evaluating mosaicism and identifying secondary instability at the single-cell level. Nevertheless, complementary advanced cytogenomic approaches are essential for improving diagnosis, refining genotype-phenotype correlations, and improving genetic counseling, risk assessment, and overall clinical management.
BACKGROUND/AIM:Postoperative dysphagia is a common and clinically important complication after esophagectomy; however, perioperative changes in swallowing function and airway-protective reflexes have not been well characterized. Here, we aimed to evaluate perioperative changes in swallowing function and airway-protective reflexes after minimally invasive esophagectomy with cervical esophagogastric anastomosis. PATIENTS AND METHODS:This prospective observational study included 20 patients who underwent minimally invasive esophagectomy between March 2023 and October 2024 at Hyogo Medical University. Swallowing physiology was assessed using videofluoroscopic swallowing studies performed preoperatively and before discharge. Cough reflex sensitivity was evaluated using a citric acid cough test as a complementary assessment of airway protection. Perioperative changes were analyzed descriptively using paired comparisons. RESULTS:Among 18 patients with complete data, three postoperative parameters showed postoperative deterioration: hyoid bone movement (p=0.013), pharyngeal transit time (p=0.041), and the Penetration-Aspiration Scale score (p=0.017). The perioperative cough latency remained relatively stable (p=0.131). Postoperative swallowing parameters and cough latency did not show clear differences between patients with and without aspiration pneumonia. CONCLUSION:This study demonstrated measurable postoperative impairment in swallowing physiology after minimally invasive esophagectomy, whereas perioperative cough reflex sensitivity remained relatively stable. These findings underscore the clinical value of detailed swallowing assessment and may inform future postoperative swallowing rehabilitation strategies.
BACKGROUND/AIM:Pretreatment nutritional and inflammatory indices have been associated with prognosis in patients with oral squamous cell carcinoma (OSCC) undergoing surgery or chemoradiotherapy; however, their prognostic significance in patients treated with superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) remains unknown. The present study aimed to clarify this point. PATIENTS AND METHODS:This study analyzed 35 patients who underwent RADPLAT at our institution between March 2014 and June 2024. Pretreatment geriatric nutritional risk index (GNRI), body mass index (BMI), serum albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC) were evaluated as potential prognostic parameters for event-free survival (EFS), overall survival (OS), and local control (LC). Univariate Cox proportional hazards analysis was performed for all endpoints, and stepwise multivariate analysis was additionally performed for EFS and OS. RESULTS:The 2-year EFS, OS, and LC rates were 63.1%, 86.2%, and 92.9%, respectively. On univariate analysis, lower GNRI and BMI were significantly associated with poorer EFS, OS, and LC. GNRI remained an independent prognostic factor for both EFS and OS on multivariate analysis. Kaplan-Meier analysis demonstrated significantly worse EFS and OS in the low-GNRI group (GNRI <92) compared with the high-GNRI group (GNRI ≥92) (log-rank p=0.011 and p=0.027, respectively). In contrast, PNI, NLR, and ALC were not significantly associated with any endpoint. CONCLUSION:Pretreatment GNRI was associated with clinical outcomes in patients with OSCC undergoing RADPLAT, suggesting that nutritional status might be a useful prognostic parameter. These findings require validation in larger prospective studies.
BACKGROUND/AIM:Pembrolizumab combined with pemetrexed is efficacious in older patients with metastatic non-squamous non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of <50%. However, treatment-related pneumonitis is concerning, and its impact on clinical outcomes is not fully understood. In this study, we examined the effect of pneumonitis on treatment efficacy and survival in the CJLSG1901 study, with a focus on differences in baseline patient characteristics. PATIENTS AND METHODS:Subgroup analyses were performed to explore the efficacy and safety of pembrolizumab plus pemetrexed in older patients with metastatic non-squamous NSCLC, focusing on whether pneumonitis developed after treatment initiation. RESULTS:Of the 48 patients included, five and four patients developed grade 1-2 and grade 3 pneumonitis, respectively. The pneumonitis group was predominantly male; postoperative recurrence was nearly twice as common in the group. Patients with pneumonitis received fewer treatment cycles. The objective response rates were 44.4% and 35.9% in the pneumonitis and non-pneumonitis groups, respectively. The median progression-free survival was shorter in the former. In contrast, the median overall survival was comparable between the groups. CONCLUSION:Although patients with pneumonitis had numerically higher response rates, their survival outcomes were comparable to those of patients without pneumonitis.
BACKGROUND/AIM:Dihydrotestosterone (DHT) plays a critical role in hair loss. However, research on DHT has mostly focused on its effects on dermal papilla cells expressing androgen receptor (AR). Accordingly, studies on the roles of DHT in keratinocytes, which undergo active proliferation and cell death during hair cycle progression, are lacking. This study investigated the effects of DHT on extracellular signal-regulated kinase (ERK) and Wnt/β-catenin signaling, which are involved in cell proliferation, cell death, and hair cycle regulation. MATERIALS AND METHODS:Changes in human immortalized keratinocyte (HaCaT) cell proliferation were investigated by WST assay after treatment with DHT without fetal bovine serum. Apoptosis induction was investigated using Hoechst33342 staining, immunoblotting, and Annexin V/7AAD staining. The involvement of specific signaling pathways was analyzed using WST assay with AR antagonist, Ras/Raf/mitogen-activated protein kinase kinase (MEK) inhibitor, or glycogen synthase kinase-3β (GSK3β) inhibitors. Changes in mRNA levels were analyzed using quantitative reverse transcription-polymerase chain reaction. RESULTS:DHT inhibited HaCaT cell proliferation via apoptosis induction. The AR antagonist bicalutamide had no effect on DHT-induced proliferation inhibition. DHT treatment increased phospho-ERK levels, which was attenuated by pretreatment with the MEK inhibitor U0126. Pretreatment with U0126 suppressed DHT-induced increase in cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) levels. U0126 restored DHT-induced decrease in HaCaT cell proliferation. Further, DHT increased dickkopf-1 and CXXC-type zinc finger protein 5 levels but decreased total and cytoplasmic β-catenin levels. Moreover, GSK3β inhibitors (LiCl and CHIR99021) did not prevent DHT-induced proliferation inhibition. CONCLUSION:DHT induces apoptosis in HaCaT cells through ERK activation, independently of AR, and Wnt/β-catenin pathways. These findings provide a basis for understanding the effects of DHT on hair follicle keratinocytes.
BACKGROUND/AIM:Long-term management of systemic lupus erythematosus (SLE) requires a persistent balance between intensive immunosuppression and the prevention of opportunistic infections. This is particularly challenging in patients with a multi-decade disease history and evolving renal pathology. CASE REPORT:We report a female patient diagnosed with SLE in 2001 (Age 25). Following biopsy-proven class IV lupus nephritis (LN) in 2003, she achieved a remarkable 20-year clinical remission after receiving a 12-cycle induction regimen of intravenous cyclophosphamide (IV-CYC). In December 2025, the patient presented with a severe refractory flare-up; a repeat renal biopsy revealed progression to mixed Class IV+V LN. Management included steroid pulse therapy and rituximab (RTX) infusion. The post-RTX clinical course was complicated by Salmonella bacteremia and cytomegalovirus (CMV) viremia with associated acute kidney injury. A multidisciplinary approach utilizing targeted antibiotics (Meropenem/Ciprofloxacin) and antivirals (Valganciclovir) successfully resolved the infections while maintaining control of the underlying LN. CONCLUSION:This case highlights the long-term efficacy of IV-CYC induction and the complexities of managing refractory LN flares. It underscores the critical necessity of vigilant monitoring and prompt intervention for multi-microbial opportunistic infections following intensive B-cell depletion therapy in long-standing SLE patients.
BACKGROUND/AIM:5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX), a radiosensitizer that selectively accumulates in tumor cells. Radiodynamic therapy (RDT) using 5-ALA has demonstrated antitumor effects after systemic administration; however, its efficacy after local administration remains unclear. This study evaluated the therapeutic efficacy of RDT using locally administered 5-ALA in an osteosarcoma xenograft mouse model. MATERIALS AND METHODS:The murine osteosarcoma cell line (LM8) was subcutaneously inoculated into the backs of 5-week-old male BALB/c mice. After tumor establishment (tumor diameter >10 mm), the mice were randomly assigned to three groups (n=5 per group): control (no treatment), irradiation alone (Rx group; single dose of 5 Gy), and 5-ALA RDT group. In the RDT group, 5-ALA (25 mg/kg equivalent; 500 μg/ml, 1 ml) was locally administered to the peritumoral region, followed by a single dose of 5 Gy X-ray irradiation. Tumor volume and body weight were measured over two weeks. The primary outcome was the change in tumor volume. RESULTS:Fourteen days after treatment, tumor growth was significantly suppressed in the 5-ALA RDT group compared to the control and irradiation groups. No significant differences in body weight were observed among the groups, and no abnormal behaviors were detected. Radiodynamic therapy with locally administered 5-ALA demonstrated significant antitumor effects in a murine model of osteosarcoma. Despite the reduced dose compared to systemic administration, local delivery effectively enhanced the radiosensitizing effect. CONCLUSION:The local administration of 5-ALA represents a promising and less toxic therapeutic strategy for osteosarcoma.
BACKGROUND/AIM:To analyze failure patterns and evaluate the clinical necessity of lower neck irradiation (LNI) during elective neck irradiation (ENI) in patients with parotid gland cancers (PGCs). PATIENTS AND METHODS:Forty patients with PGCs who received postoperative radiotherapy (PORT) following parotidectomy between 2006 and 2024 were included. LNI was defined as the elective inclusion of neck levels III and IV in the irradiated field. The primary endpoint was progression-free survival (PFS), while secondary endpoints included local-regional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS:The median follow-up time was 68.7 months. Among the 40 patients, 19 (47.5%) received LNI as part of their PORT. Five-year rates of LRFFS, DMFS, OS, and PFS were 91.2%, 80.2%, 88.7%, and 76.3%, respectively. While LNI showed no significant association with survival outcomes, multivariate analysis confirmed that perineural invasion (PNI) was a significant prognostic factor for PFS [hazard ratio (HR)=5.17, p=0.028], OS (HR=7.97, p=0.017), and DMFS (HR=9.67, p=0.009). The major failure pattern was distant metastasis (N=8). Regional failures were infrequent (5%), involving level II (N=1) and levels Ib, II, and IV (N=1). CONCLUSION:Regional failures in PGC are rare and predominantly confined to the upper neck. Omitting LNI did not compromise regional control. Treatment strategies for PGCs with PNI should focus on the intensification of systemic therapy and close monitoring for distant metastasis.
BACKGROUND/AIM:This study aimed to determine whether lesion visibility on magnetic resonance imaging (MRI) predicts rebiopsy outcomes during active surveillance for prostate cancer. PATIENTS AND METHODS:We retrospectively analyzed data from 111 patients enrolled in the Prostate Cancer Research International Active Surveillance study (Japan) at Kagawa University (January 2010-February 2025). After excluding 19 patients who discontinued active surveillance within one year, 92 patients were included in the analysis. MRI findings were classified as visible [Prostate Imaging Reporting and Data System (PI-RADS) score ≥3] or invisible (score ≤2). We assessed the association between visibility and rebiopsy outcomes, defined as reclassification progression beyond active surveillance criteria or no cancer. RESULTS:MRI was performed at diagnosis in 32.6% (n=32) of patients, at one year in 37.0% (n=34), and at four years in 47.7% (n=21). Lesion visibility at diagnosis was not associated with continuation of active surveillance compared with invisibility [median 43 months, 95% confidence interval (12-not available) vs. not available (17-not available), p=0.404]. However, at the 1-year rebiopsy, reclassification occurred significantly more frequently in patients with visible lesions than in those with invisible lesions (42.1% vs. 7.1%, p=0.047). Conversely, no cancer was more common in patients with invisible lesions (50.0% vs. 10.5%, p=0.019). CONCLUSION:At one year, a PI-RADS score ≥3 was associated with a higher risk of reclassification, whereas a score ≤2 was associated with a greater likelihood of no cancer on rebiopsy. These findings highlight the prognostic value of MRI in guiding active surveillance.
Plexiform fibrohistiocytic tumor (PFHT) is a rare locally aggressive and rarely metastasizing mesenchymal neoplasm that most commonly arises in the upper extremities of children and young adults. It typically presents as a small, slow-growing, painless, dermal or subcutaneous mass. Magnetic resonance imaging (MRI) often reveals a plaque-like or infiltrative lesion with intermediate signal intensity on T1-weighted sequences and high signal intensity on T2-weighted sequences. Contrast-enhanced MRI demonstrates moderate or avid enhancement. Histologically, PFHT is characterized by a multinodular or plexiform proliferation of a variable admixture of histiocyte-like cells, osteoclast-like giant cells and elongated spindle cells. Immunohistochemically, the histiocyte-like and osteoclast-like giant cells express CD68, CD163 and CD11c, whereas the spindle cells are focally positive for smooth muscle actin. Most notably, cyclin D1 immunostaining demonstrates nuclear expression in the histiocyte-like and osteoclast-like giant cells as well as spindle cells. Wide local excision with long-term follow-up is generally considered optimal management for conventional cases. This review provides an updated overview of the clinical, radiological, histological, immunohistochemical, cytogenetic and molecular genetic features of PFHT and discusses the differential diagnosis of this enigmatic neoplasm.
BACKGROUND/AIM:Magnesium-based alloys are promising materials for fabrication of bioresorbable medical devices. The application is limited by rapid degradation and associated adverse tissue responses. In this study, nanometer-thin composite polyelectrolyte/wax (PEM/W) coatings were fabricated on magnesium-based implant prototypes to delay their degradation. MATERIALS AND METHODS:Coatings were applied using a layer-by-layer technique. Cytocompatibility was assessed according to DIN ISO 10993-5 using NIH/3T3 fibroblasts and human umbilical vein endothelial cells (HUVECs). Degradation behavior was monitored by high-resolution micro-computed tomography (μ-CT), while tissue compatibility and host responses were evaluated histologically following DIN EN ISO 10993-6. RESULTS:The coatings were continuous, hydrophobic (water contact angles exceeding 100°), with sub-micrometer thicknesses and were found to improve in vitro cytocompatibility of magnesium biomaterials. In vivo evaluation using a rat subcutaneous implantation model demonstrated that the effectiveness of magnesium degradation modulation depends on the type of employed PEM. Micro-computed tomography analyses revealed that the hyaluronic acid/chitosan/wax coating provided the most robust protection over 60 days, exhibiting the lowest volume loss and superior preservation of implant geometry compared to the uncoated samples. Correspondingly, hydrogen-related gas cavity formation was reduced and temporally delayed in coated implants, indicating a more controlled degradation process. Histopathological analysis shows a moderate inflammatory response characteristic of biodegradable metallic implants, dominated by macrophages and lymphocytes. Importantly, coated implants were associated with reduced late-stage fibrosis and necrosis compared to uncoated magnesium. CONCLUSION:Overall, composite PEM/W coatings, especially those based on natural polyelectrolytes, represent a promising surface-engineering strategy for improving the safety and performance of resorbable magnesium implants.
BACKGROUND/AIM:Hospital stays are often associated with emotional strain, influenced by environmental, procedural, and communication factors. While supportive interventions hold promise for improving patient well-being, understanding the lived experiences and needs of patients is essential for designing effective, patient-centered solutions. This study seeks to explore these factors to inform future strategies for enhancing emotional support during hospital stays. PATIENTS AND METHODS:A 2023 cross-sectional survey at the Department of Radiology and Nuclear Medicine at the University Hospital Mannheim was conducted as an exploratory assessment to characterize patient-reported emotional stressors and care experiences during hospitalization. The survey employed a mixed-methods approach. The data was analyzed using descriptive and inferential statistics, with qualitative responses coded for thematic patterns. RESULTS:The survey revealed that prolonged waiting times (>1 hour, 74% of participants) and communication problems were associated with lower self-reported mental well-being (mean score dropped from 4.45 to 3.57 out of 5, p<0.001). Language barriers and organizational inefficiencies exacerbated distress, while staff empathy and social visits improved well-being. Prior to procedures, the most common stated emotions by participants were apprehension (68% therapeutic procedure and 58% diagnostic procedure) and anxiety (47% therapeutic, 21% diagnostic), with these emotions shifting to confidence (78% therapeutic, 57% diagnostic) and hope (44% therapeutic, 43% diagnostic) post-procedure. CONCLUSION:Communication delays and procedural anxiety are important contributors to emotional distress during hospitalization. These findings delineate empirically grounded stress domains that may guide structured investigation of supportive intervention strategies. By integrating such innovations alongside the irreplaceable value of human-centered care, future research can build on these insights to create holistic, patient-tailored solutions. Co-design with patients and clinicians, followed by rigorous validation, will be key to unlocking this potential.
BACKGROUND/AIM:Sorafenib is a standard targeted therapy for renal cell carcinoma; however, resistance and limited efficacy remain clinical challenges. Magnolol, a bioactive compound derived from Magnolia officinalis, exhibits anti-cancer properties, and may enhance therapeutic responses. This study investigated whether magnolol potentiates the anti-tumor effects of sorafenib in murine renal carcinoma (Renca) cells and explored the underlying molecular mechanisms. MATERIALS AND METHODS:Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and drug interactions were analyzed using the Chou-Talalay method. Apoptosis was evaluated by Annexin V/propidium iodide (PI) staining, cell-cycle analysis, and caspase activation. Western blotting and flow cytometry were performed to examine apoptotic pathways and epidermal growth factor receptor (EGFR)/SRC proto-oncogene, non-receptor tyrosine kinase (SRC)/nuclear factor kappa B (NF-κB) signaling. Transwell assays and protein expression profiling were used to analyze migration, invasion, and epithelial-mesenchymal transition (EMT) markers. RESULTS:Combination treatment synergistically reduced cell viability, with a combination index (CI) <1, and significantly enhanced apoptosis via activation of intrinsic and extrinsic pathways. Co-treatment suppressed EGFR/SRC proto-oncogene, SRC/ NF-κB signaling and reduced migration, invasion, and EMT-associated markers. CONCLUSION:Magnolol enhances sorafenib efficacy by promoting apoptosis and inhibiting survival and metastatic signaling pathways in renal carcinoma cells.
BACKGROUND/AIM:Cisplatin is a widely used anti-cancer agent, but it can cause testicular dysfunction, leading to infertility and hypogonadism. Currently, pharmacological agents for preventing testicular dysfunction during chemotherapy are limited. Ramelteon, an insomnia medication that selectively targets melatonin receptor type 1 and type 2, exerts cytoprotective effects across organs via anti-inflammatory and anti-apoptotic mechanisms. Ramelteon has an established safety profile in humans; however, its efficacy against chemotherapy-induced testicular toxicity remains unclear. We therefore examined the protective efficacy of ramelteon against cisplatin-induced testicular dysfunction in a rat model. MATERIALS AND METHODS:Male 8-week-old Jcl:Wistar rats were randomized to control (saline+vehicle), ramelteon (10 mg/kg/day orally on days 1-7), cisplatin (7 mg/kg intraperitoneally once on day 1), or cisplatin+ramelteon (n=8 per group). On day 8, blood, testes, and epididymides were collected. Endpoints included sperm parameters, testicular histopathology, Ki-67 immunostaining, serum testosterone, and testicular quantitative polymerase chain reaction (qPCR) for steroid synthesis-related (Star, Cyp11a1, Cyp17a1, Hsd17b3) and apoptosis- and inflammation-related (Casp3, Il6) transcript levels. RESULTS:Cisplatin administration induced histological damage to the seminiferous tubules, reduced sperm counts and motility, decreased testosterone levels, increased testicular interstitial Ki-67 positivity, suppressed steroid synthesis-related gene expression, and increased apoptosis-related and inflammation-related gene expression. Co-administration of ramelteon significantly attenuated these changes, resulting in reduced pathological tissue damage in the testes, attenuation of deterioration in sperm parameters and testosterone levels, and improvement in steroid synthesis-related and inflammation-related gene expression. CONCLUSION:Ramelteon mitigated acute cisplatin-induced testicular damage in rats by attenuating deterioration in sperm parameters and steroidogenesis-related changes. These findings suggest that ramelteon may be a candidate for further investigation as a strategy to mitigate acute chemotherapy-induced testicular injury.
