In vivo最新文献

Background/aim: To investigate the feasibility of establishing a mandibular osteosarcoma model in Sprague-Dawley (SD) rats using tissue block transplantation, providing a foundational model for osteosarcoma research.

Materials and methods: Fourteen male SD rats, 3 weeks old and SPF grade, were randomly divided into a control group (n=4) and a mandibular osteosarcoma group (n=10). Using tissue block transplantation, UMR106 cell-induced tumor tissues were transplanted subcutaneously into the left mandibular marrow cavity of the SD rats. Observations included behavioral changes, weight variations, tumor growth, and tumor formation rate. Bone changes were monitored via micro-CT scanning, and histological analysis was conducted using HE staining.

Results: Two weeks post-transplantation, the mandibular osteosarcoma group exhibited significant left facial swelling, malocclusion, eating difficulties, and weight loss compared to the control group. The tumor formation rate was 80% (8/10). Micro-CT scans indicated significant bone destruction in the osteosarcoma group. HE staining revealed high cellular atypia and pathological mitoses in both subcutaneous and mandibular osteosarcoma cells, with no notable abnormalities in lung tissues.

Conclusion: Tissue block transplantation is a viable method to establish a mandibular osteosarcoma model in SD rats. This method is simple, with a high tumor formation rate, providing an ideal animal model for mandibular osteosarcoma research.

Background/aim: This study aimed to evaluate the diagnostic accuracy of prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) in pelvic nodal staging, using postoperative histopathology data as the reference standard.

Patients and methods: From January 2020 to June 2024, 78 patients with clinically significant prostate cancer (PCa) (ISUP Grade Group 2) underwent radical prostatectomy plus extended pelvic lymph node dissection (ePLND): 60 (77%) vs. 18 (23%) men had an intermediate vs. high risk PCa. All the patients underwent PSMA PET/TC before surgery for clinical staging and nodes focal uptake (standardized uptake value "SUVmax) was evaluated to rule out the presence of metastases.

Results: PSMA PET/CT was suspicious for nodes metastases in 16/78 (20.5%) men (median SUVmax 26.2), conversely, histology demonstrated nodes metastases in 18/78 (23.1%). PSMA PET/CT was negative for nodal involvement in all Grade Group 2 (GG2) PCa, positive in 4/4 (100%) GG3 PCa, and in 10/14 (71.4%) GG5 PCa. In detail, PSMA PET/CT was false negative in 2/4 PCa, characterized by GG5 plus ductal adenocarcinoma. Overall, PSMA PET/CT sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy in diagnosing nodal metastases were equal to 87.5, 96.8, 87.5 96.7, and 92.3%, respectively.

Conclusion: PSMA PET/CT demonstrated an overall diagnostic accuracy of 92.3% in nodal staging (100% in GG2 PCa), which decreased to 63.6% in GG5 PCa. In high-risk patients or in case of ductal adenocarcinoma, a negative PSMA PET/CT does not rule out the need for ePLND.

Background/aim: In several studies, Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been reported to increase hemoglobin (Hb) levels. In a study in which Hb levels were compared between patients who received SGLT2i and dipeptidyl peptidase-4 inhibitors, some patients exhibited increased Hb levels (>1.0 g/dl), whereas some exhibited unchanged Hb levels. Notably, several factors may influence the Hb-increasing effect of SGLT2i. This study aimed to analyze the factors influencing the Hb-increasing effect of SGLT2i.

Patients and methods: Type 2 diabetes patients were divided into three groups: SGLT2i (SGLT2i only group, n=36), those receiving a combination of SGLT2i and angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) (SGLT2i+ACEi/ARBs group, n=32), and those not receiving these drugs (control group, n=49). We retrospectively analyzed Hb changes in these groups. Kaplan-Meier curves compared Hb changes from SGLT2i initiation to day 63, with an Hb increase defined as ≥0.5 g/dl. In addition, sex, age, ACEi/ARBs, estimated glomerular filtration rate, and hematocrit levels were analyzed using Cox proportional hazards as factors influencing Hb-increasing events.

Results: Hb-increasing event rates were 61%, 41%, and 20% in the SGLT2i only, SGLT2i+ACEi/ARBs, and control groups, respectively. The Kaplan-Meier curves showed significantly higher Hb-increasing event rates in the SGLT2i only group than in the control and SGLT2i+ACEi/ARBs groups. In the Cox proportional hazards model, ACEi/ARBs use was associated with a 39% reduction in the incidence of Hb-increasing events.

Conclusion: SGLT2i exhibit a Hb-increasing effect, which may be reduced by ACEi/ARBs.

Background/aim: Radiotherapy is one of the most frequently used options for prostate cancer (PCa). However, adverse effects related to irradiation of surrounding normal organs are significant clinical concerns. Specifically, genitourinary toxicity can dramatically reduce the quality of life. This clinical trial investigated the efficacy of oral 5-aminolevulinic acid phosphate combined with sodium ferrous citrate (ALA-SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source.

Patients and methods: The AMBER study was a prospective single-center trial involving patients with localized PCa who underwent LDR-BT without external-beam radiotherapy (jRCTs051190077). Fifty patients were included and instructed to take capsules of ALA-SFC twice a day (200 mg phosphate salt and 229.42 mg per day) for six months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data were collected before implantation, during ALA-SFC treatment, and at 1, 3, 6, 9, and 12 months post-LDR-BT. The primary endpoint of this trial was urinary frequency at three months. Other patient-reported outcomes, investigator-reported adverse events, and oncological outcomes were secondary endpoints.

Results: Of 50 enrolled cases (45 in the per-protocol analysis, 49 in the safety analysis), urinary frequency and its increase from baseline did not differ from 141 historical controls at any time point, including at three months post-LDR-BT. Propensity score matched analysis confirmed no time-course differences in frequency, volume, or urinary symptom scores between groups. Biochemical failure-free and metastasis-free survival also remained similar.

Conclusion: Oral supplementation of ALA-SFC to LDR-BT did not alleviate radiation-induced toxicity or improve oncological outcomes.

Background/aim: Hypertriglyceridemia is a known cardiovascular risk factor. However, the relationship between serum triglyceride (TG) levels and the clinical outcomes in patients with acute myocardial infarction (AMI) is unclear.

Patients and methods: We conducted a single-center, retrospective observational study involving 538 consecutive patients with AMI who underwent emergent percutaneous coronary intervention within 12 hours of onset. Patients were categorized into three groups based on their serum TG levels at admission as follows: T1 group (TG <78 mg/dl, n=172), T2 group (78≤TG<141 mg/dl, n=177), and T3 group (141 mg/dl ≤TG, n=176). The primary endpoint was major adverse cardiovascular events (MACEs) defined as a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The median follow-up period was 2.4 (1.5-4.2) years.

Results: Patients in the T1 group were older, had a higher proportion of females, and had fewer cardiovascular risk factors. However, they also had a higher prevalence of multi-vessel coronary artery disease and severely calcified culprit lesions. The T1 group had a significantly higher rate of MACEs (20.4% in T1, 12.4% in T2 and 8.5% in T3, p<0.05 by Log-rank test, respectively). Multivariate analysis revealed that T1 was an independent predictor of MACEs (hazard ratio=2.19, 95% confidence interval=1.16-4.14, p<0.05).

Conclusion: Although patients with AMI with low TG levels at admission had fewer coronary risk factors, they had more severe calcified culprit lesions and worse clinical outcomes.

Background/aim: Most nontraumatic subarachnoid hemorrhages (SAHs) are caused by ruptured saccular aneurysms, often resulting in a devastating clinical event characterized by high mortality and significant morbidity among survivors. Numerous studies have confirmed the neuroprotective effects of the molecular hydrogen due to its unique biological properties.

Case report: We present the case of a 44-year-old female with aneurysmal SAH with rheumatoid arthritis (RA) and newly diagnosed systemic lupus erythematosus (SLE), complicated by acute ischemic infarction. Despite surgical, pharmacological and non-pharmacological interventions, including embolization of the aneurysm, immunosuppressant, non-vitamin K antagonist oral anticoagulant (NOAC), and plasmapheresis, loss of consciousness continued. The patient began daily treatment with hydrogen capsules, resulting in increased in Treg cells, Breg cells, increased TIM3+ expression on Tc cells, and the conversion of anti-dsDNA from positive to negative. Her clinical symptoms stabilized without adverse effects.

Conclusion: This case highlights the potential benefits of molecular hydrogen therapy in managing aneurysmal SAH with underlying autoimmune disease, warranting further research.

Background/aim: Alkaline extracts of several plants which contain lignin degradation products have several unique biological activities. In order to search for new biological activities of alkaline extracts of pine seed shell (APs), their anti-ultraviolet C (UVC) and macrophage stimulation activity were investigated.

Materials and methods: Anti-UVC activity was determined by the ratio of the 50% cytotoxic concentration against human melanoma cell line COLO679 to the 50% UVC-protective concentration. Extracellularly secreted nitrite (NO₂ ^-) by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like cells RAW264.7 was determined by Griess method.

Results: APs showed significantly higher anti-UVC activity than previously reported hot-water extracts of medical herbs. Anti-UVC activity of AP and vanillic acid was maintained for much longer than that of sodium ascorbate and vanillin. APs enhanced the production of NO₂ ^- to the level induced by LPS. Simultaneous addition of AP and LPS did not further increase NO₂ ^- production, suggesting their mechanisms of action overlap.

Conclusion: The present study suggests the possible application of APs as UVC protectors and immunopotentiators via macrophage activation.

Background/aim: The aim of our study was to investigate the outcome of colon cancer with bladder invasion after surgical intervention.

Patients and methods: Between 2011 and 2022, a total of 41 patients diagnosed with colon cancer and bladder invasion underwent surgical procedures at Taichung Veterans General Hospital. The impact of various risk factors on overall survival (OS) was assessed using Kaplan-Meier analyses and Cox proportional hazards models.

Results: Among the enrolled patients, 21 underwent radical cystectomy, while 20 underwent partial cystectomy. Twelve had tumors located in the rectum, 19 in the sigmoid colon, and 10 in both the rectum and sigmoid colon. The median OS was 71.8 months in stage 2, 50.8 months in stage 3, and 11.2 months in stage 4 (p=0.061). Median OS was 71.8 months in patients with negative surgical margins and 10.5 months in those with positive surgical margins (p=0.003). In multivariate regression analysis, positive surgical margins [hazard ratio (HR)=3.64, 95% confidence interval (CI)=1.28-10.34, p=0.015] and emergency operations (HR=4.57, 95%CI=1.34-15.55, p=0.015) significantly impacted OS.

Conclusion: Complete resection of colon cancer with bladder invasion can yield excellent oncologic outcomes. The decision between partial and radical cystectomy should balance surgical margin clearance and the preservation of quality of life. Both surgical margin involvement and emergency operations are independent risk factors for OS.

Background/aim: Biomarkers for patients suffering from glioblastoma (GBM) are scarce. Extracellular vesicles (EV) are a promising candidate for a potential biomarker. Therefore, EV concentration could be a potential biomarker of tumor burden, volume, and prognosis.

Patients and methods: Large EV (lEV) and small EV (sEV) were isolated from 36 GBM patients' blood plasma by differential centrifugation. Nanoparticle tracking was used to measure EV concentration. Quantitative analysis of tumor volume was performed by evaluating T2/FLAIR relaxation times.

Results: The mean size of lEV was 173.3 nm ± 18.2 nm, while sEV measured 148.3 ± 9.0 nm. Patients with higher lEV concentrations showed a trend towards longer overall survival (36.1 vs. 16.5 months, p=0.08). Regarding inflammatory markers, higher leukocyte count was positively correlated with higher sEV concentration (r²=0.3887, DF 21, p=0.0015). No significant relationship was found between lEV or sEV concentration and tumor volume.

Conclusion: Overall EV concentration in the peripheral blood is not a predictor of tumor volume. sEV concentration is associated with a potential pro-inflammatory metabolism.

Background/aim: In the pencil beam scanning carbon-ion radiotherapy, spot positions are arranged in three dimensions throughout the entire target region. Therefore, dose deviations can occur due to spot position errors in the target. However, performing three-dimensional measurements for routine patient-specific quality assurance (PSQA) is difficult because a simple measurement method has not been established. This study aimed to establish a three-dimensional dose verification method using beam delivery log data.

Materials and methods: Pencil beam dose distributions in water were generated through Monte Carlo (MC) calculations. Treatment beam dose distribution was calculated by superposing the pencil beam dose distributions, considering given spot positions and monitor units (referred to as semi-MC, SMC). The aim of this study was to perform gamma analysis (GA) using dose distributions of log data-based SMC instead of measured dose for PSQA. To verify SMC, the SMC depth-dose curves were compared with the measured dose. To assess the equivalence between the proposed and measurement-based methods, pass rates of two-dimensional GA were compared. Furthermore, a three-dimensional GA was performed to investigate clinically suitable criteria.

Results: The SMC dose curves were consistent with measured dose, with a deviation <5%. In two-dimensional GA, pass rates for the proposed method were generally lower than those for measurement-based method. The results of the three-dimensional GA indicated that the proposed method, with criteria of 3%-3 mm and 3%-2 mm, had capabilities comparable to the measurement-based method.

Conclusion: The developed three-dimensional log data-based PSQA method with criteria of 3%-3 mm and 3%-2 mm is clinically applicable.