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Background/aim: The standard of care for patients with muscle-invasive bladder cancer (MIBC) is treatment with radical cystectomy (RC) and perioperative platinum-based chemotherapy (neoadjuvant or adjuvant). Perioperative treatment can improve overall survival (OS), and the most robust evidence favors neoadjuvant chemotherapy (NAC). The RealBLADDER study assessed the efficacy and safety of perioperative chemotherapy in patients with MIBC in an Italian real-world setting.

Patients and methods: RealBLADDER enrolled patients with MIBC treated with perioperative chemotherapy from June 2018 to June 2023. The primary endpoint was the rate of non-invasive downstaging (NID) (ypT0/pTis/pTaN0 or

Results: A total of 173 eligible patients were identified. One hundred and thirty-seven patients (79.2%) received NAC and 36 (20.8%) received adjuvant chemotherapy (AC). The NID rate was 36.8%, and pCR achieved in 33.6% of patients treated with NAC. The rate of surgical morbidity and mortality were 20.9% and 0%, respectively. The 12-month DFS was 73.7% [95% confidence interval (CI)=0.672-0.808]. The 12-month OS rate in the entire population was 92.1% (95%CI=0.880-0.963). Compared to AC, DFS was improved in patients treated with NAC (p=0.019).

Conclusion: NAC is associated with an improved DFS compared to AC, a high rate of NID and pCR and low rate of surgical morbidity and mortality, supporting NAC as the preferred perioperative strategy for MIBC in clinical practice.

Background/aim: This study compares the biocompatibility of a novel hybrid bone substitute material based on biphasic granules in a type I collagen scaffold using both subcutaneous and calvarial implantation models, in accordance with DIN EN ISO 10993-6. Given the distinct biological environments, materials may exhibit different behaviors in connective versus bone tissue. The aim was to evaluate irritation scores and cellular tissue responses to better understand the material's performance in both settings.

Materials and methods: This study evaluated the biocompatibility and host tissue response of test materials in male Wistar rats through subcutaneous and calvaria implantation models, following DIN EN ISO 10993-6, assessing cellular responses, material degradation, and bone regeneration at 10-, 30-, and 60-days post-implantation.

Results: Subcutaneous implants elicited a stronger inflammatory reaction with higher counts of polymorphonuclear cells, lymphocytes, multinucleated giant cells, and plasma cells at day 10, alongside consistently elevated irritancy scores. In contrast, calvaria implants showed increased neovascularization, reflecting bone-specific regenerative processes. Although capsule formation and cellular infiltration were similar between models, material degradation and phagocytosis were significantly greater subcutaneously at day 60.

Conclusion: These results highlight the critical impact of implantation site on immune activation, vascularization, and biomaterial resorption, underlining the importance of model selection in preclinical biomaterial assessment.

Background/aim: Cancer and its treatments often lead to patient malnutrition. The aim of the study was to identify the difficulties that cancer patients face in relation to their nutrition, to determine the importance of nutrition in their daily lives and to identify the reasons for their weight loss. In addition, the study aimed to capture the perspectives of the healthcare professionals and determine how the nutritional status of the individual patients plays a role in everyday clinical practice.

Patients and methods: Using an interview guide with open questions, structured interviews were conducted with ten patients who had suffered unintentional weight loss of more than 5% in the last three to six months, five nurses, and five doctors on an oncology ward in Bad Hersfeld hospital. Responses were analysed qualitatively using Mayring's content analysis method.

Results: All patients reported diet-related symptoms. The main causes cited were side effects of treatment. All patients had questions about their nutrition. Healthcare professionals indicated that the patients considered the problem of malnutrition to be high, but that there was no uniform treatment concept or general screening. Perceptions of interdisciplinary communication were mixed. There was a lack of information regarding sources of information and counselling services among both professional groups.

Conclusion: Standardised interviews should be conducted as part of treatment to identify individual patient problems. As there has been no standardised approach to detection, prevention and treatment, an interdisciplinary reassessment and discussion of treatment issues is required to understand and address the complex problem of malnutrition.

Background/aim: Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases and has high mortality, especially in advanced stages. MicroRNAs (miRNAs) and immunoregulatory genes such as suppressor of cytokine signaling 3 (SOCS3) play critical roles in cancer progression and immune evasion. miR-30d-5p is known to act as a tumor suppressor by down-regulating oncogenic pathways, while SOCS3 modulates immune responses and tumor microenvironment interactions. This study aimed to evaluate the clinical relevance of circulating miR-30d-5p and serum SOCS3 protein levels in patients with NSCLC versus healthy controls and to assess their potential as diagnostic and prognostic biomarkers.

Materials and methods: Serum samples were collected from 35 patients with NSCLC and 26 healthy individuals. miR-30d-5p expression was measured using RT-qPCR, and SOCS3 protein levels were determined using ELISA. Statistical comparisons were performed, and diagnostic performance was evaluated using Receiver Operating Characteristic (ROC) analysis. The correlation between SOCS3 and miR-30d-5p was assessed with Spearman's rank test.

Results: SOCS3 levels were significantly elevated in patients with NSCLC (120.84±117.62 pg/ml) compared to controls (16.88±11.91 pg/ml, p<0.0001). Contrarily, miR-30d-5p expression was significantly decreased (fold change: 0.24, p<0.002). A moderate negative correlation was observed between SOCS3 and miR-30d-5p levels (ρ=-0.439, p=0.025). ROC analysis displays good diagnostic accuracy for both SOCS3 [area under curve (AUC)=0.821] and miR-30d-5p (AUC=0.878). SOCS3 levels increased significantly with clinical stage.

Conclusion: Increased SOCS3 and decreased miR-30d-5p expression were observed in patients with NSCLC, indicating their involvement in tumor progression and immune disruption. The inverse correlation between these biomarkers suggests a regulatory interaction that may influence the JAK/STAT signaling pathway. These findings highlight the diagnostic and therapeutic potential of targeting the miR-30d-5p/SOCS3 axis in NSCLC.

Background/aim: Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, benign, histiocytic proliferative disorder characterized by nonpainful lymphadenopathy. Nonmalignant histiocytes can also infiltrate extranodal sites such as in the skin and central nervous system. On imaging, RDD can mimic other disorders such as meningioma, which is more common, and requires histology and immunohistochemistry to elucidate diagnosis.

Case report: Herein we report a case of a 20-year-old female who presented to the emergency department (ED) after near-syncope episode following methamphetamine and opioid use. Initial computed tomography (CT) found a 2.3 cm mass in the right frontoparietal region. Further examinations with magnetic resonance imaging (MRI) revealed findings compatible with meningioma. After one month of persistent symptoms, the "meningioma" was resected and the intraoperative frozen sections (FS) and touch preparation cytopathology of the mass showed mixed inflammatory infiltrates and scattered large, atypical appearing cells that display emperipolesis, raising suspicions of an RDD diagnosis instead of meningioma. The permanent sections confirmed the histological findings on FS. The large atypical lesional histiocytes showing emperipolesis with engulfment of lymphocytes, plasma cells and neutrophils. The lesional cells were immunoreactive for protein S100, cluster of differentiation 163 (CD163), and B cell lymphoma 1 (BCL-1), negative for CD1a. Based on histology and immunohistochemical profile, the final diagnosis was Rosai-Dorfman Disease. Postoperatively, there was immediate improvement in patient's strength and symptoms. At the 9-month follow up post-surgery, she was doing well, and MRI revealed no evidence of residual or recurrent disease.

Conclusion: This case is a rare example of RDD clinically and radiologically mimicking meningioma and illustrates the importance of rigorous histological analysis for accurate diagnosis, particularly during the intraoperative consultation, to ensure proper treatment.

Background/aim: Mixed histological lung cancers, such as combined small-cell carcinoma (SCLC) and adenocarcinoma, are rare and often present diagnostic and therapeutic challenges due to intratumoral heterogeneity. In such cases, conventional tissue biopsies may fail to detect key genetic alterations, especially when sampling is limited or affected by tumor evolution. Liquid biopsy has emerged as a complementary approach capable of capturing broader genomic information in a non-invasive manner.

Case report: We describe a 73-year-old woman with metastatic lung cancer initially diagnosed as EGFR wild-type adenocarcinoma via tissue biopsy. The patient underwent multiple lines of therapy, including immune checkpoint inhibitors and cytotoxic chemotherapy. Over time, the histology shifted, and repeat biopsy identified small-cell carcinoma. Due to the tumor's evolving nature and limited biopsy accessibility, a liquid biopsy using FoundationOne Liquid CDx was performed. This identified an EGFR exon 19 deletion (T751_A755del) that had not been detected in prior tissue analyses. Targeted therapy with osimertinib was initiated as fifth-line treatment, resulting in temporary disease stabilization and reduction in tumor markers.

Conclusion: This case illustrates the clinical value of liquid biopsy in detecting actionable mutations in patients with mixed histological lung cancers where tissue-based testing is inconclusive. Liquid biopsy enabled a personalized therapeutic approach without the need for further invasive procedures. Such strategies may be essential in managing histologically and genomically heterogeneous tumors.

Background/aim: Lymphovascular invasion is a well-established poor prognostic factor following limited resection in lung cancer patients. Therefore, predicting the presence of lymphovascular invasion based on clinical factors may facilitate the selection of the most appropriate surgical procedure. The aim of the present study was to identify preoperative predictive factors associated with pathological lymphovascular invasion.

Patients and methods: A total of 248 primary lung cancer patients with cN0, computed tomography findings of ≤2.0 cm overall diameter, were included in this retrospective study. The presence of lymphovascular invasion was evaluated on a pathological basis, using resection specimens for factors of lymphatic and vascular invasions. Positive results for one or both factors were defined as positive for lymphovascular invasion. The diagnosis of lymphatic invasion was examined using immunostaining for D2-40. The presence of vascular invasion was evaluated using the elastic van Gieson staining method.

Results: Univariate analysis indicated that the presence of a smoking history, a consolidation tumor ratio (CTR) >0.5, an elevated CYFRA, and a tumor in the hilar location were significant predictive factors for lymphovascular invasion. In multivariate analysis, the CTR >0.5, elevation of CYFRA, and tumor hilar location were independent predictive factors for lymphovascular invasion. A statistically significant correlation between tumor location and lymphovascular invasion was also observed in both the adenocarcinoma and squamous cell carcinoma subgroups.

Conclusion: Central lesions tended to exhibit higher frequency of lymphovascular invasion. Therefore, the expansion of limited resection for centrally located tumor lesions in small-sized NSCLC should be carefully considered.

Background/aim: Despite advances in critical care, postoperative liver failure remains a substantial complication of liver resection, with high mortality rates. Adipose-derived stem cells (ADSCs) have demonstrated potential in various regenerative applications; however, their precise mechanisms in liver repair remain unclear. This study investigated the effects of ADSC sheets on the vascular and cellular responses in a mouse model of partial hepatectomy.

Materials and methods: Human ADSCs were cultured with magnetic nanoparticle-containing liposomes and formed multilayered cell sheets. Following partial hepatectomy in BALB/c nude mice, ADSC or collagen control sheets were attached to liver resection sites. Immunohistochemical analysis assessed angiogenesis (CD31), hepatic stellate cell activation (α-SMA), and cellular origin. Mice were sacrificed on postoperative days 4 and 7. Statistical analysis was conducted using Bonferroni's method (p<0.05).

Results: Compared to cell-free collagen sheets (control), ADSC sheets demonstrated significantly enhanced neovascularization, with higher CD31 expression on postoperative days 4 and 7. Immunohistochemical analysis revealed that these CD31-positive cells were predominantly of mouse origin, rather than differentiated from transplanted human ADSCs, indicating host cell migration into the sheets. Additionally, ADSC sheets significantly increased α-SMA expression compared to that with collagen sheets, with expression levels progressively increasing from day 4 to 7, suggesting continuous activation of hepatic stellate cells. These findings indicate that ADSC sheets induce angiogenesis and hepatic stellate cell activation during liver regeneration, likely through paracrine mechanisms that recruit host cells, rather than through direct differentiation of transplanted ADSCs.

Conclusion: This study lays the groundwork for the clinical application of ADSC sheets, demonstrating their potential to enhance liver regeneration after hepatectomy by promoting host cell-mediated angiogenesis and hepatic stellate cell activation.

Background/aim: This study investigated the prognostic impact of human epidermal growth factor-2 receptor (HER2) status on the survival of patients with metastatic triple-negative breast cancer (TNBC).

Patients and methods: This multicenter, retrospective study included 168 patients diagnosed with recurrent or de novometastatic TNBC between April 2013 and September 2024. Patients were categorized into two groups: HER2-negative (n=121, 72%) and HER2-low (n=47, 28%). Clinicopathological features and survival outcomes were compared between groups.

Results: The median follow-up was 44 months [95% confidence interval (CI)=35.7-52.2]. All patients received systemic chemotherapy as part of their first-line treatment. The median progression-free survival (PFS) in all patients was 9 months (95%CI=7.7-10.3 months). The median overall survival (OS) in all patients was 22 months (95%CI=17.4-26.5 months). Higher Ki67 value at diagnosis was a significant poor prognostic factor for median OS (29 months vs. 15 months, p<0.001). HER2-negative patients had significantly worse median OS than HER2-low patients (19 months vs. 33 months, p=0.026). In multivariate analysis, the HER2-low group had significantly longer median OS than the HER2-negative group [hazard ratio=0.64 (95%CI=0.42-0.98), p=0.040].

Conclusion: HER2-low expression was associated with significantly improved survival compared with HER2-negative status in metastatic TNBC. These findings highlight HER2 status as a potential prognostic factor, particularly relevant in settings with limited access to novel therapies such as immunotherapy or antibody-drug conjugates.

Background/aim: Type 2 diabetes mellitus (T2DM) is a prevalent disorder characterized by an increased concentration of blood glucose and impaired insulin function. Throughout the course of the disease, β-cell function fails and insulin production decreases. Studying the molecular systems responsible for insulin production, release, and action is crucial for the management and treatment of the disease. Thus, this study aimed to scrutinize the therapeutic efficacies of oxytocin (OXT) on nicotinamide (NA)/streptozotocin (STZ)-induced diabetes in rats and elucidate the underlying mechanisms.

Materials and methods: Wistar rats were supplied a single intraperitoneal (i.p.) dose of NA (120 mg/kg) 15 min before an i.p. injection of STZ (60 mg/kg) after fasting for 16 h. Ten days later, the diabetic rats were orally administered OXT every day for eight weeks at dose levels 0.5, 1, and 2 IU/kg.

Results: The treatment of diabetic rats with OXT significantly improved oral glucose tolerance, serum insulin and C-peptide concentrations, and pancreatic islets' structure and function. Furthermore, the activities of liver glucose-6-phospatase and glycogen phosphorylase significantly decreased. OXT treatment also resulted in an increase in serum adiponectin levels, while the levels of serum resistin, omentin, vaspin, and free fatty acids significantly decreased. Additionally, OXT significantly alleviated the mRNA levels of components of the PI3K-AKT and AMPK signaling pathways as well as their effectors including PPARγ, insulin receptor (IR), IR substrates 1 and 2 (IRS1 & IRS2), PI3K, AKT, AMPK, and glucose transporter 4 (GLUT4) in visceral adipose tissues of diabetic rats.

Conclusion: OXT can exert antidiabetic effects and may be useful for developing multiple targeted therapeutic strategies for diabetes treatment. The effects may be mediated via improvement in β-cell function, insulin secretory response, and insulin sensitivity.