In vivo最新文献

Background/aim: Allopurinol is a standard agent used for lowering uric acid levels. Human leukocyte antigen (HLA)-B5801 positivity increases the incidence of severe cutaneous adverse reactions (SCARs) in allopurinol users. HLA alleles HLA-B27 and HLA-B51 are frequently found in patients with ankylosing spondylitis and Behçet's disease, showing an association with distinct clinical features. In this study, we investigated the association between the HLA-B5801 genotype and patient characteristics and outcomes in gout.

Patients and methods: We retrospectively reviewed the medical records of 263 patients with gout who were not receiving uric acid-lowering therapy and were tested for HLA-B5801 positivity between March 2020 and February 2024. Patients were classified according to their HLA-B5801 status, and patient demographics and laboratory variables were compared. The incidence of gout flares or severe flares requiring hospital care within one year was investigated.

Results: A total of 37 participants were HLA-B5801 positive (37/263, 14.1%). However, no significant differences were observed in demographic or laboratory variables between the HLA-B5801 positive and negative groups. Subgroup analyses of patients with new-onset gout, males, and those with an estimated glomerular filtration rate ≥60 ml/min/1.73 m² also demonstrated no significant differences related to HLA-B5801 genotype positivity. The incidence of disease flares or severe flares between patients in the HLA-B5801 positive and negative groups was comparable during the one-year follow-up.

Conclusion: Although HLA-B5801 was a significant predictor of allopurinol-associated SCARs, the impact of HLA-B5801 positivity on the clinical characteristics or flares was not evident in this population of patients with gout.

Background/aim: This study evaluated the influence of the body mass index (BMI) on outcomes of gastric cancer resection, with a specific focus on curative gastrectomy.

Patients and methods: A total of 756 patients who underwent gastric cancer resection, including 372 cases of curative gastrectomy, were analyzed. The impact of BMI on overall, systemic, and surgical complications, as well as on relaparotomy, perioperative mortality, and 5-year survival was examined.

Results: Underweight (BMI <18.5 kg/m²), and obesity (BMI ≥30 kg/m²) were identified as independent risk factors for overall complications (p<0.0001, and p<0.0001), systemic complications (p<0.0001, and p=0.001), and surgical complications (p<0.0001, and p=0.023) in all gastric cancer resections. Similar trends were observed for curative gastrectomy, where underweight and obese patients demonstrated more overall complications (p<0.0001, and p<0.0001), systemic complications (p<0.001, and p=0.0001), and surgical complications (p<0.0001, and p=0.0032). No differences in 5-year survival were observed among BMI categories in 372 cases of curative gastrectomy. However, being underweight was associated with a poorer 5-year survival in all 756 cases of gastric cancer resection (odds ratio=0.45, 95% confidence interval= 0.27-0.73, p=0.0016).

Conclusion: BMI significantly influences the outcomes of gastric cancer resection, with underweight and obese patients demonstrating higher complication rates. Underweight status is also linked to poorer long-term survival in the broader gastric cancer population but not in curative resection cases.

Background/aim: Cryopreservation of allogeneic hematopoietic cells can be an necessary step in the preparation of a graft for transplantation. The purpose of this study was to evaluate the safety of cryopreservation of allogeneic hematopoietic cells and the clinical outcomes of patients who received a cryopreserved transplant.

Patients and methods: The study included data from a comparative analysis conducted on a group of 100 patients diagnosed with acute myeloid leukemia who received cryopreserved (50 patients) and fresh (50 patients) transplants. Both quantitative and qualitative parameters of the grafts were evaluated, as well as the patients' hematopoietic recovery.

Results: Statistical analysis of the time to engraftment of neutrophils, nucleated cells, and platelets showed no differences between the group of patients who received cryopreserved transplants and those who received fresh transplants. A higher count of CD34+ cells in the graft significantly reduced the time required for patients to reach their reference values of neutrophils, nuclear cells, and platelets (p<0.05).

Conclusion: Cryopreservation of allogenic transplants should be reserved as an option when fresh grafts are not feasible for various reasons.

Background/aim: Salmonella typhimurium A1-R (A1-R) expresses green fluorescent protein (GFP) and has the ability to selectively target and inhibit all major cancer types in murine models without persistently infecting healthy tissue. A1-R is being developed for tumor targeting by oral administration. The aim of the present study was to demonstrate real-time imaging of orally-administered A1-R in a fibrosarcoma nude-mouse model and to visualize its trafficking through the gastrointestinal system to the tumor and normal organs.

Materials and methods: A1-R-GFP (3.3×10⁸ colony-forming units/ml) was administered orally to HT1080 human fibrosarcoma nude-mouse models which were fasted the day before administration. Fluorescence images of A1-R-GFP inside the gastrointestinal tract at 0, 2 and 4 hours after oral gavage were captured. The number of colonies of A1-R-GFP in tumors and liver were determined at 4 hours, and on days 1, 3 and 4 by growth from homogenized tumor and liver tissue on agar plates.

Results: The trafficking of A1-R-GFP through the murine gastrointestinal tract post-gavage was monitored in real-time via GFP fluorescence imaging. Bacteria, initially observed in the stomach, migrated to the small intestine and the colon and subsequently to the subcutaneously-implanted fibrosarcoma. A1-R-GFP proliferated in the tumors over time. In contrast, A1-R-GFP in the liver diminished over time.

Conclusion: The present study showed the pathway of orally administered A1-R-GFP in the gastrointestinal system and to the tumor and liver. A1-R selectively proliferated continuously in tumors and was cleared from the liver. These results are critical for future clinical trials of orally-administered A1-R-GFP.

Background/aim: The impact of enfortumab vedotin (EV) dose reduction and/or interruption on its efficacy for advanced urothelial carcinoma (UC) is unclear.

Patients and methods: We retrospectively analyzed consecutive patients with advanced UC who received EV after the failure of platinum-based chemotherapy and immune checkpoint inhibitors from December 2021 to June 2024. Patients were categorized into three groups based on the calculated relative dose intensity (RDI): RDI<50%, RDI ≥50 to <80%, and RDI ≥80%.

Results: A total of 26 patients (male, n=15; median age, 72 years) were enrolled. The RDI was categorized as follows: ≥80% (n=13; 50.0%), ≥50 to <80% (n=7; 26.9%), and <50% (n=6; 23.1%). There were no marked differences in the overall response (p=0.921) or disease control rates (p=0.859) among the three groups categorized by the RDI. A log-rank test revealed no significant differences in either the progression-free survival (p=0.309) or the overall survival (p=0.704) according to RDI. There were no marked differences in the incidence of any-grade adverse events (AEs) (p=0.405) or grade ≥3 AEs (p=0.018) according to RDI. There were significant differences in the incidence of any-grade cutaneous AEs (p=0.038) and grade ≥3 cutaneous AEs (p=0.007) according to RDI. A multivariate analysis revealed that ECOG PS≥2 (p=0.009) and mixed UC (p=0.011) were independently associated with the prognosis.

Conclusion: Despite frequent dose reductions and interruptions required to manage treatment-emergent AEs during EV therapy, these adjustments did not significantly impair the drug's efficacy in patients with advanced UC.

Background/aim: Autologous stem cell transplantation (ASCT) is the standard strategy after induction therapy for newly diagnosed transplant-eligible multiple myeloma. High-dose melphalan (HDM) conditioning has been the recommended treatment regimen for a long time. No other conditioning regimen has been proven safer and more effective. Because bortezomib has a synergistic effect with melphalan, bortezomib with HDM (Bor-HDM) as a conditioning regimen has shown favorable outcomes, improved complete response rates after ASCT, and no prolonged hematological toxicities. However, few studies have reported long-term follow-up data. This study aimed to evaluate the long-term progression-free survival (PFS) and overall survival (OS) of patients receiving Bor-HDM conditioning, compared to those treated with HDM alone.

Patients and methods: This single-center retrospective study included 36 patients newly diagnosed with transplant-eligible myeloma from 2008 to 2020. In total, 15 patients received a Bor-HDM regimen, while 21 patients received HDM as a conditioning regimen. The probabilities of PFS and OS were plotted using the Kaplan-Meier method. All statistical analyses were performed using EZR software.

Results: After a median follow up of 77 months, no severe hematological toxicities were observed. The PFS and OS rates in the Bor-HDM group as compared with the HDM group were 0.762 vs. 0.60 (p=0.409) and 0.80 vs. 0.904 (p=0.476) respectively. No significant differences were observed between the two groups.

Conclusion: These long-term results show that Bor-HDM is a safe and effective option for ASCT conditioning regimens.

Background/aim: Enhanced recovery after surgery (ERAS) protocol is adopted in clinical practice worldwide, but a lack of evidence for measurable benefits after upper gastrointestinal (GI) surgeries can be detected especially regarding early oral feeding.

Patients and methods: A propensity score-matching study was conducted at the Department of Surgery of the University of Pécs between January 2020 and December 2023. The study included patients who underwent upper GI cancer surgery and were treated according to an early oral feeding protocol (EOF). Investigational and control groups were analyzed and compared from prospectively collected datasets.

Results: We enrolled 72 patients, 36 in the EOF group, and 36 case-matched patients in the traditional late oral feeding (LOF) group. Oral feeding in the EOF group started on an average of 1.94 days postoperatively, while in the LOF group, it began on an average of 5.72 days postoperatively. EOF could reduce the average length of hospital stay. Statistically significant decreases were observed in the EOF group concerning the time until the first bowel movements, and the length of postoperative intravenous fluid therapy. No significant differences were detected regarding mortality, anastomosis insufficiency, inflammation and stricture or seroma formation.

Conclusion: Early oral nutritional support positively impacts the recovery of patients following upper GI surgery without increasing mortality or anastomosis insufficiency rates compared to traditional protocols. Significant improvements were observed in quality of life indicators for patients in the early oral feeding group. This approach aligns with ERAS goals and suggests a valuable strategy for postoperative care in upper GI cancer surgeries.

The human bowel is exposed to numerous biotic and abiotic external noxious agents. Accordingly, the digestive tract is frequently involved in malfunctions within the organism. Together with the commensal intestinal flora, it regulates the immunological balance between inflammatory defense processes and immune tolerance. Pathological changes in this system often cause chronic inflammatory bowel diseases including Crohn's disease and ulcerative colitis. This review article highlights the complex interaction between commensal microorganisms, the intestinal microbiome, and the intestinal epithelium-localized local immune system. The main functions of the human intestinal microbiome include (i) protection against pathogenic microbial colonization, (ii) maintenance of the barrier function of the intestinal epithelium, (iii) degradation and absorption of nutrients and (iv) active regulation of the intestinal immunity. The local intestinal immune system consists primarily of macrophages, antigen-presenting cells, and natural killer cells. These cells regulate the commensal intestinal microbiome and are in turn regulated by signaling factors of the epithelial cells and the microbiome. Deregulated immune responses play an important role and can lead to both reduced activity of the commensal microbiome and pathologically increased activity of harmful microorganisms. These aspects of chronic inflammatory bowel disease have become the focus of attention in recent years. It is therefore important to consider the immunological-microbial context in both the diagnosis and treatment of inflammatory bowel diseases. A promising holistic approach would include the most comprehensive possible diagnosis of the immune and microbiome status of the patient, both at the time of diagnostics and during therapy.

Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapy-induced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects.

Background/aim: Alzheimer's disease is a complex, incurable to date, multifactorial disease, which suggests the need for continued development of pharmacotherapy.

Materials and methods: A comprehensive literature search was conducted to identify known ligands with anticholinesterase activity, resulting in the discovery of over 100 alkaloids that are also available in the PubChem database. Subsequently, the ligands underwent molecular docking to evaluate their affinity for the target enzyme. The ligands with the greatest affinity were selected for ligand-based virtual screening.

Results: Three potential compounds were identified for further investigation: ZINC000055042508, ZINC000096316348, and ZINC000067 446933. Computational models of absorption, distribution, metabolism, and excretion (ADME) properties prediction using SwissADME suggested that ZINC000055042508 and ZINC000067446933 can permeate the blood-brain barrier and exhibit non-substrate behavior with respect to P-glycoprotein. In contrast, the ProTox-III prediction indicated the potential for all three compounds to penetrate the blood-brain barrier.

Conclusion: These alkaloid derivatives warrant further investigation as potential acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.