In vivo最新文献

Background/aim: Hallux valgus (HV) is the most common deformity of the forefoot. Although HV has been strongly associated with a family history, its genetic underpinnings remain unclear. Few studies have examined the relationship between folic acid metabolism, which is critical in normal bone development, and HV. The study aimed to investigate the contribution of methylenetetrahydrofolate reductase (MTHFR) genotypes to the risk of HV.

Materials and methods: The MTHFR rs1801133 and rs1801131 genotypes were analyzed in 150 patients with HV and 600 controls without HV, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: The results highlighted a significant difference in the genotypic frequency distributions of MTHFR rs1801133 between the HV cases and non-HV controls (p for trend=0.0024). Specifically, individuals with the homozygous TT genotype at MTHFR rs1801133 exhibited a 2.57-fold increased risk of HV (95% confidence interval=1.49-4.42, p=0.0009). However, those with the CT genotype did not show an elevated risk. Stratified analysis showed no correlation between MTHFR rs1801133 genotypic distributions and different age groups (below or above 51 years) or sex (both p>0.05). Furthermore, no associations were identified between MTHFR rs1801133 and height, weight, or body mass index in relation to HV risk.

Conclusion: The TT genotype of MTHFR rs1801133 is associated with an increased risk of HV. Subgrouping HV patients based on their MTHFR genotypes and related comorbidities, such as rheumatoid arthritis, may offer a new approach to diagnosis.

Background/aim: Tumors exhibit impaired blood flow and hypoxic areas, which can reduce the effectiveness of treatments. Characterizing these tumor features can inform treatment decisions, including the use of vasculature modulation therapies. Imaging provides insight into these characteristics, with techniques varying between clinical and preclinical settings.

Materials and methods: To investigate changes in different tumor regions over time, R2* values from blood oxygen-level dependent MRI (BOLD-MRI), blood flow from power Doppler ultrasound, and oxygen saturation from photoacoustic ultrasound were analyzed and compared to CD31⁺ and pimonidazole tissue staining. To aid in preclinical translation, the fluorescence of a hypoxia probe was also compared to ultrasound techniques.

Results: The imaging techniques detected tumor heterogeneity and an overall decrease in blood flow and oxygen levels over time. The analysis found varying correlations between regions, indicating an indirect relationship between imaging outcomes, which is influenced by external factors. Regional analysis allowed for more accurate results, as areas less affected by various factors were examined separately from highly impacted regions, aiding in their identification.

Conclusion: Examining tumor regions with multiple imaging techniques allowed for better understanding and identification of modality-specific limitations, as certain techniques may incorrectly suggest that tumors are more vascularized and less hypoxic than they are.

Background/aim: To assess the ability of apparent diffusion coefficient (ADC) at baseline in predicting overall survival in patients who undergo Y90-radioembolization (Y90-RE) for liver-dominant metastatic colorectal cancer (mCRC) in the salvage situation.

Patients and methods: A retrospective review of 411 lesions in 63 patients with refractory mCRC treated with Y90-RE was conducted. Manual region of interest (ROI) measurements were applied using a whole lesion and volume method. Minimum and mean ADC values were measured, and averages were calculated per patient. Ratios combining tumor volume and ADC were correlated with OS, and a receiver-operating characteristic (ROC) analysis defined a cut-off value. Cox regression analysis was performed, and the log-rank test confirmed prognostic cut-off levels for survival.

Results: The median survival was 6.4 months. Multivariate Cox regression identified tumor volume divided by minimum ADC (ADC_{tumor volume, min}) as an independent predictor of OS (HR=1.814, 95%CI=1.188-2.770, p=0.006). Neither ADCmin nor ADCmean were significantly associated with survival. Optimal prediction was identified with a ADC_{tumor volume, min} cut-off of 0.3673 arbitrary units (AU) yielding 76.0% sensitivity and 70.3% specificity. Patients with ADC_{tumor volume min} <0.3673 had a median OS of 10.4 months, compared to 4.7 months for those above the cut-off (p<0.001).

Conclusion: Tumor volume divided by minimum ADC at baseline (ADC_{tumor volume, min}) was identified as an independent predictor of OS in mCRC scheduled for Y90-radioembolization in the salvage situation and may improve future patient selection.

Background/aim: Low molecular weight heparin (LMWH) is widely employed to prevent postoperative venous thromboembolism (VTE). This study aimed at analyzing LMWH use and evaluating its efficacy and safety in immediate implant-based post-mastectomy breast reconstruction.

Patients and methods: A monocentric retrospective analysis was conducted on patients who underwent immediate implant-based breast reconstruction (IBR) from January 2021 to December 2023. Preoperative characteristics, Caprini score, type of mastectomy procedure, administration of LMWH, postoperative outcomes, and any adverse events linked to LMWH usage, with particular attention to hematoma or VTE, were collected and analyzed.

Results: A total of 211 breast procedures were performed on 179 patients - with a mean age of 50.9 years (SD 12.3) and a mean Caprini score of 6.8 (SD 1.4). In total, 133 patients received LMWH by subcutaneous injection (enoxaparin 40 mg/day) post-operatively and 46 only had mechanical thromboprophylaxis. The overall complication rate was higher but statistically significant in the LMWH group with 27.8% compared to 17.4% in the no-LMWH group (p=0.159). Hematoma occurred in 17 patients (12.8%) in the LMWH group compared to two (4.4%) patients in the no-LMWH group (p=0.164). Moreover, 15 (11.2%) patients who received LMWH required reoperation compared to one (2.2%) in patients who did not receive LMWH (p=0.074). There were no VTE events in either group.

Conclusion: There were no significant differences in complications and especially hematoma rate in patients who received LMWH after mastectomy and immediate IBR, compared to patients who did not. Moreover, no difference in VTE rate was observed across groups.

Background/aim: Genetic polymorphisms in DNA repair mechanisms can modulate overall DNA repair capacity, potentially influencing individual susceptibility to cancer. This study investigated the relationship between polymorphic variations in DNA ligase 1 and the risk of childhood acute lymphocytic leukemia (cALL).

Materials and methods: The genotypes of DNA ligase 1 rs20579 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The study assessed the potential association between DNA ligase 1 rs20579 genotypes and cALL risk in a Taiwanese cohort, consisting of 266 cALL cases and an equal number of age- and sex-matched controls.

Results: The distribution of GG, AG, and AA genotypes for DNA ligase 1 rs20579 was 78.6%, 19.5%, and 1.9% among controls, and 76.0%, 21.4%, and 2.6% among cALL cases, respectively (p for trend=0.7111). No significant difference was observed in the distribution of AG and AA genotypes between the two groups (p=0.6340 and 0.7381, respectively). Allelic frequency analysis revealed that carriers of the variant A allele of DNA ligase 1 rs20579 had a non-significant increase in cALL risk compared to those with the wild-type G allele [odds ratio (OR)=1.17, 95% confidence interval (CI)=0.81-1.68, p=0.4583]. While no significant genotype distribution difference was noted among males (p=0.4635), females carrying the AG and AA genotypes exhibited a significantly increased risk of cALL (p=0.0328).

Conclusion: In the Taiwanese population, the variant A allele of DNA ligase 1 rs20579 may serve as a potential diagnostic marker for elevated cALL risk in young females.

Background/aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model.

Materials and methods: HT1080 human fibrosarcoma cells were used for in vitro experiments. Four groups were analysed in vitro: No-treatment control; A1-R; chloroquine; A1-R plus chloroquine. The nude-mouse models of HT1080 human fibrosarcoma were randomly assigned into four groups: G1: untreated control; G2: Oral A1-R [5×10⁷ colony forming units (CFU)/body, twice a week, 2 weeks]; G3: Chloroquine [100 mg/kg/body, intraperitoneal (IP) administration, twice a week, 2 weeks]; G4: Oral A1-R (5×10⁷ CFU/body), twice a week, 2 weeks plus chloroquine (100 mg/kg/body, IP), twice a week, 2 weeks. Each cohort consisted of five mice. Tumor volume and body weight were assessed biweekly.

Results: A1-R combined with chloroquine synergistically decreased the viability of HT1080 cells in vitro compared to other groups. Orally-administered A1-R at 5×10⁷ CFU combined with IP-administered chloroquine eradicated HT1080 tumors in nude mice, without body-weight decrease.

Conclusion: The combination treatment of A1-R plus chloroquine demonstrated synergy against HT1080 cancer cells in vitro and in vivo. A1-R was administered orally, suggesting its potential as a probiotic. The present results suggest the clinical potential of the combination of A1-R and chloroquine for soft-tissue sarcoma therapy, a recalcitrant disease.

Breast cancer research heavily relies on diverse model systems to comprehend disease progression, develop novel diagnostics, and evaluate new therapeutic strategies. This review offers a comprehensive overview of mammary cancer models, covering both ex vivo and in vivo approaches. We delve into established techniques, such as cell culture and explore cutting-edge advancements, like tumor-on-a-chip and bioprinting. The in vivo section encompasses spontaneous, induced, and transplanted models, genetically engineered models, chick chorioallantoic membrane assays, and the burgeoning field of in silico models. Additionally, this article briefly highlights the key discoveries made using these models, significantly enhancing our understanding of breast cancer. In essence, this article serves as a comprehensive compass, charting the trajectory of mammary cancer modeling from its early beginnings to the promising vistas of tomorrow.

Background: Coronary artery disease (CAD), primarily caused by atherosclerosis, is a leading cause of death, presenting as angina or myocardial infarction. Advances in cardiac imaging, angiography, and procedures like percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery have improved early detection and management of this condition. This report presents the case of a man who experienced worsening exertional chest pain and discomfort while at rest.

Case report: A 66-year-old man with a history of neurogenic syncope and asthma presented at the same-day emergency care (SDEC) unit with worsening exertional chest pain and discomfort whilst at rest. Despite normal ECG and cardiac enzyme results, further cardiac computed tomography angiography (CTCA) revealed significant CAD with moderate stenosis in the right coronary artery (RCA) and severe stenosis at the left anterior descending artery (LAD) bifurcation, leading to CABG surgery. Echocardiography showed a left ventricular ejection fraction of 50-54% with mid-inferior and basal to mid-inferoseptal hypokinesia. The cardiology-cardiothoracic multidisciplinary team concluded that CABG surgery would provide the most durable long-term outcome.

Conclusion: This case demonstrates the high importance of clinical suspicion of CAD despite normal initial investigations in the early identification and timely investigation as well as the role multidisciplinary teams and CABG can play in the timely management of complex CAD, ultimately leading to improved patient outcomes.

Background/aim: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, though rare, is the most common form of autoimmune encephalitis, predominantly affecting young individuals, particularly females. Standard treatments include corticosteroids, intravenous immunoglobulins (IVIG), and plasmapheresis, with rituximab recommended for those unresponsive to first-line therapies. However, reliable biomarkers for clinical assessment remain elusive. This study investigated the efficacy of adjunctive hydrogen therapy in a patient with anti-NMDAR encephalitis.

Case report: This case report describes a 14-year-old boy with anti-NMDAR encephalitis who exhibited poor response to initial treatment, but showed significant improvement with rituximab and adjunctive hydrogen therapy. Immunophenotyping revealed correlations between treatment outcomes and shifts in B cell subsets, PD-1+ cytotoxic T cells, and regulatory T cell subtypes.

Conclusion: This case underscores the importance of integration traditional clinical assessments with advanced diagnostics such as flow cytometry-based immunophenotyping, and suggests a potential role for hydrogen therapy in modulating immune response in this complex autoimmune condition.

Background/aim: Dysregulation of claudin 6 (CLDN6) expression has been widely documented in various malignancies. CLDN6 is aberrantly expressed in many types of human carcinomas; however, its clinical significance in endometrial carcinoma has seldom been investigated. This study aimed to examine the immunohistochemical expression status of CLDN6 in low-grade, early-stage endometrioid endometrial carcinoma (LGES-EEC) and to assess its clinicopathological significance.

Materials and methods: We performed immunostaining for CLDN6 in 118 tissue samples from LGES-EECs. Protein expression levels were interpreted using a semi-quantitative histoscore method. All statistical analyses were performed.

Results: CLDN6 was primarily localized along the membranes of the tumor cells. We considered histoscore ≥10 (the staining proportion ≥5% and intensity ≥2) as positive immunoreactivity for CLDN6. Twenty-six of the 118 patients (22.0%) showed CLDN6 positivity. Positive CLDN6 expression was significantly associated with deeper myometrial invasion (p=0.001), higher initial stage (p=0.015), and substantial lymphovascular space invasion (p=0.018).

Conclusion: Aberrant CLDN6 expression is involved in tumor progression in LGES-EECs. In addition, targeting CLDN6 may offer clinical utility in patients with endometrial carcinoma.