In vivo最新文献

Background/aim: Salmonella typhimurium A1-R has been shown to target and inhibit many types of cancers in mouse models without continuous infection of normal tissue. The objective of the present study was to determine the effective dose of orally-administered Salmonella typhimurium A1-R, expressing-green fluorescent protein (GFP), on an HT1080 human-fibrosarcoma nude-mouse model.

Materials and methods: The HT1080-human- fibrosarcoma nude-mouse models were randomized into the following three groups: G1: untreated control; G2: Oral Salmonella typhimurium A1-R (5×10⁷ colony forming units [CFU]/body, twice a week, 2 weeks); G3: Oral Salmonella typhimurium A1-R (3.3×10⁸ CFU/body, twice a week, 2 weeks). Each group comprised five mice. Body weight and tumor volume were measured twice a week. The number of colonies of Salmonella typhimurium A1-R-GFP in excised tumors and excised livers in groups G2 and G3 were determined on day 3, day 7 and 14 by growth on agar plates. Tukey-Kramer analysis was used to examine the relationships between variables. Statistically-significant results are defined as those with p≤0.05.

Results: Salmonella typhimurium A1-R was administered orally at a dose of 3.3×10⁸ CFU, which successfully regressed the HT1080 tumor in nude mice. However, this effect was not observed at a lower dose of 5×10⁷ CFU. After administering Salmonella typhimurium A1-R at 3.3×10⁸ CFU, tumors and liver tissues were harvested, homogenized, and cultured on days 3, 7 and 14. Resulting GFP-expressing Salmonella typhimurium A1-R colonies were then counted. The number of GFP-bacterial colonies derived from excised tumors at intervals of 3, 7, and 14 days increased over time post-administration of oral GFP-Salmonella typhimurium. Conversely, the number of GFP-Salmonella typhimurium A1-R colonies that could be grown from excised livers decreased over time, following oral administration of GFP-Salmonella typhimurium. Additionally, the GFP-bacterial colonies grown from the excised tumors were significantly larger than those grown from the excised livers.

Conclusion: The present study showed that an aggressive fibrosarcoma could be regressed by orally-administered Salmonella typhimurium A1-R which accurately targeted tumors without continuous growth in normal organs. The present results suggested the potential of orally-administered Salmonella typhimurium A1-R as a probiotic to treat aggressive soft-tissue sarcoma.

Background/aim: Post-gastrectomy lean body mass (LBM) decrease has a significant negative impact on postoperative survival in patients with cancer. This study investigated the effect of intake of at least one-third of the daily protein requirement at breakfast on the maintenance of LBM in patients during the first month post-gastrectomy.

Patients and methods: Among patients with gastric cancer who underwent curative distal gastrectomy between April 2011 and December 2018, without adjuvant chemotherapy, we evaluated 401 patients who had consumed more than the daily protein requirement in the first month postoperatively, using the FFQW82 nutrition intake questionnaire. Patients were divided into those who consumed more (≥1/3 intake group, n=160) and those who consumed less than one-third of the daily protein requirement at breakfast (<1/3 intake group, n=241). We compared the LBM reduction rate at one month postoperatively between groups. Univariate and multivariate analyses were performed to determine clinicopathological factors predicting LBM reduction at one month postoperatively.

Results: The LBM reduction rate at one month post-curative distal gastrectomy was significantly higher in the <1/3 intake group than in the ≥1.3 intake group (p=0.01) at breakfast. Multivariate analysis showed that morning protein intake below one-third of the daily requirement independently predicted LBM reduction (odds ratio=1.75, 95% confidence interval=1.14-2.68, p<0.01).

Conclusion: Consuming at least one-third of the daily protein requirement at breakfast may be effective in maintaining LBM in patients undergoing curative distal gastrectomy. These results may be very important for prognosis, since maintaining LBM influences the continuation of adjuvant chemotherapy and thus survival after curative resection in patients with gastric cancer.

Background/aim: We hypothesized that the inflammatory burden index (IBI) is a promising biomarker for esophageal cancer (EC) treatment and management. To confirm our hypothesis, we evaluated the prognostic impact of IBI in patients with EC who received curative treatment.

Patients and methods: We conducted a retrospective review of medical records and collected data from consecutive patients with EC who underwent curative resection at Yokohama City University between 2005 and 2020. The IBI score was calculated as the C-reactive protein level multiplied by the neutrophil-to-lymphocyte ratio.

Results: In total, 180 patients with EC were included in this study. The 3- and 5-year overall survival (OS) rates were 72.9% and 63.4%, respectively, in the IBI-low group, and 38.2% and 32.5% in the IBI-high group (p<0.001). In the multivariate analysis, IBI was identified as a significant prognostic factor for OS [hazard ratio (HR)=2.372; 95% confidence interval CI=1.478-3.806, p<0.001]. In addition, the 3- and 5-year recurrence-free survival (RFS) rates were 52.9% and 47.8%, respectively, in the IBI-low group, and 22.9% and 17.2% in the IBI-high group (p<0.001). In the multivariate analysis, IBI was identified as a significant prognostic factor for RFS (HR=2.484; 95%CI=1.373-4.494, p<0.001). When comparing the recurrence patterns between the IBI-high and IBI-low groups, there were significant differences in lymph node recurrence (46.0% vs. 26.2%, p=0.010) and hematological recurrence (52.0% vs. 18.5%, p<0.001).

Conclusion: IBI affects both the short- and long-term oncological outcomes. Thus, IBI may be a promising prognostic factor for the treatment and management of EC.

Background/aim: Atherosclerosis is a chronic and progressive pathological condition marked by the accumulation of lipids, fibrous materials, and inflammatory cells, within the arterial walls. MicroRNAs (miRNAs) are single-stranded, evolutionarily conserved, non-coding small RNAs, that play a pivotal role in controlling various pathophysiological cellular functions and molecular signalling cascades associated with the development of atherosclerosis. Additionally, dysregulation in cholesterol and lipid metabolism is known to increase susceptibility to atherosclerosis. In this study, we aimed to determine the changes in serum levels of miRNA-199a-5p, examine its relationship with LDL cholesterol, and investigate its diagnostic value in patients diagnosed with atherosclerosis.

Materials and methods: MiRNA-199a-5p expression analysis was conducted using PCR on serum samples from 20 patients diagnosed with atherosclerosis and 26 completely healthy, voluntary control subjects. The blood biochemical analysis values for all groups participating in the study were obtained from their records.

Results: The data analysis revealed significant up-regulation of miRNA-199a-5p in the serum of the patient group. Additionally, miRNA-199a-5p expression levels positively correlated with LDL cholesterol levels.

Conclusion: miRNA-199a-5p can be considered a reliable biomarker in patients with atherosclerosis, potentially informing and guiding future therapeutic approaches. Additionally, a significant relationship was found between lipid metabolism and miRNA-199a-5p in atherosclerosis.

Background/aim: Non-small-cell lung cancer (NSCLC) is the most frequently diagnosed malignancy and the first cause of cancer-related death. Thus, finding alternative therapeutic options is crucial. Drug repurposing offers therapeutic options in a simplified and affordable manner, especially to cancer patients in developing countries. Several drugs including antihistamines and beta-adrenergic receptor blockers (beta-blockers) display antiproliferative properties on cancer cells. Interestingly, NSCLC patients who had used either antihistamines or beta-blockers showed improved response to chemotherapy or reduced mortality in comparison to non-users of any of these drugs. However, combination therapy is gaining substantial interest in many cancers including non-EGFR mutated NSCLC. Here, we investigated the antineoplastic effect of the combination of the antihistamine loratadine, the beta-blocker nebivolol, and the tyrosine-kinase inhibitor gefitinib on NSCLC cell lines.

Materials and methods: A-549 and NCI-H1975 cell lines were used. The effect of nebivolol, gefitinib, and loratadine on the metabolic activity was studied using the MTT assay. The inhibitory concentrations (IC₂₀ and IC₅₀) were calculated and used in the drug-combination experiments. Apoptosis was investigated using flow cytometry; and cell survival using the colony formation assay.

Results: The combination nebivolol-loratadine-gefitinib produced a significant synergistic effect on inhibiting the metabolic activity and colony formation, as well as on promoting apoptosis in both cell lines. Noteworthy, the effect on the cell line carrying the EGFR mutation (NCI-H1975) was very similar to the cell line that does not exhibit such mutation (A-549 cells).

Conclusion: The nebivolol-gefitinib-loratadine combination may be a promising alternative for lung cancer treatment.

Background/aim: Tremelimumab plus durvalumab is an approved first-line therapy for advanced hepatocellular carcinoma (HCC). Previous studies identified WNT/β-catenin mutations or CD8+ tumor-infiltrating lymphocytes (TILs) as biomarkers that can predict responsiveness to immune checkpoint inhibitor therapy in HCC. However, biomarkers for effectiveness of tremelimumab plus durvalumab in HCC have not been reported. This study investigated whether evaluation of WNT/β-catenin signaling and CD8+ TILs by immunohistochemical staining of tumor biopsy tissues can predict the response to tremelimumab plus durvalumab in patients with HCC.

Patients and methods: Fifteen HCC patients who underwent tumor biopsies were classified into three groups based on WNT/β-catenin signal activation and CD8+ TIL infiltration. The clinical responses to treatment in the groups were evaluated.

Results: Four patients had HCC with WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration, four patients had HCC with WNT/β-catenin signal activation and low-level CD8+ TIL infiltration, and seven patients had WNT/β-catenin signal activation and high-level CD8+ TIL infiltration or WNT/β-catenin signal inactivation and low-level CD8+ TIL infiltration. A better response rate was observed in the WNT/β-catenin signal inactivation and high-level CD8+ TIL infiltration group, and a worse response rate was observed in the WNT/β-catenin signal activation and low-level CD8+ TIL infiltration group.

Conclusion: Although the present study involved a small number of patients, the findings suggest that the efficacy of tremelimumab plus durvalumab may be affected by WNT/β-catenin signaling and CD8+ TIL infiltration.

Background/aim: The adenocarcinoma (ADC) and other malignant neoplasm (OMN) terminologies of The Bethesda System represent various histological types of uterine and extrauterine malignancies. This study aimed to clarify the incidences of ADC not otherwise specified (ADC-NOS), ADC extrauterine (ADC-EXT), and OMN in our institution and describe their characteristic cytomorphological features.

Patients and methods: We searched the database to identify all patients diagnosed with carcinoma, including those diagnosed through cervical liquid-based cytology (LBC), between January 2019 and December 2023. The electronic medical records and all available slides were reviewed.

Results: Overall, 30 of the 149,197 (0.02%) patients were diagnosed with ADC-NOS, ADC-EXT, and OMN. All three groups included various histological types of both gynecological and non-gynecological origin. More than two-thirds (23/30; 76.7%) were of uterine origin, but seven patients had metastatic carcinoma of extrauterine organ origin, including the ovary, lung, stomach, breast, colon, urethra, and pancreas. In all patients, the cytological features were concordant with the histological features.

Conclusion: In LBC, ADC-NOS does not only encompass uterine cervical tumors, but also various types of extrauterine malignancies. ADC-EXT and OMN also represent both extrauterine and uterine tumors. Awareness of the morphological features observed in LBC samples of non-gynecological malignancies may be helpful in obtaining the correct diagnosis.

Background/aim: Malignant triton tumor (MTT) is a rare, highly aggressive malignant nerve sheath tumor with rhabdomyoblastic differentiation. The overall 5-year survival rate is extremely low, and no standardized treatment exists. We report a case of MTT in the distal femur that was treated with surgery and chemotherapy.

Case report: A 16-year-old male was referred to our hospital due to severe pain during physical activity and difficulty in walking. He showed no café-au-lait spots and no family history of Neurofibromatosis-1. He underwent an incisional biopsy and was diagnosed with MTT of the distal femur. After administering preoperative chemotherapy using adriamycin, ifosfamide, and cisplatin, wide resection surgery was performed for MTT. Subsequently, postoperative chemotherapy using methotrexate, in addition to the agents mentioned above, was administered. One and a half years after the surgery, he can walk without pain, and there are no signs of local recurrence or metastasis.

Conclusion: The combined modality treatment, integrating chemotherapy and surgery, has successfully prevented local recurrence and accomplished favorable outcomes without lung metastasis.

Background/aim: In the pursuit of translating stem cell therapy technology into clinical practice, ensuring the safety and efficacy of treatments is paramount. Despite advancements, the effectiveness of stem cell applications often falls short of clinical requirements. This study aimed to address the challenge of limited efficacy by investigating the safety and effectiveness of canine adipose tissue-derived mesenchymal stem cells (cATMSCs) preconditioned with deferoxamine (DFO).

Materials and methods: Different concentrations of DFO were used to evaluate its impact on cATMSC activity. The therapeutic potential of these preconditioned cells was validated using a mouse model of systemic inflammation. Comprehensive evaluations, including clinical hematological and radiological assessments before and after intravenous injection of preconditioned cells were conducted.

Results: The study showed a notable reduction in inflammatory markers and an overall decrease in the inflammatory response in the mouse model. The data collected from the clinical hematological and radiological assessments provided essential insights.

Conclusion: This study lays the groundwork for the future clinical deployment of DFO-preconditioned cATMSCs, demonstrating their potential to improve the efficacy and safety of stem cell therapies.

Background/aim: Patients with bone tumors in their femurs are at risk of developing pathological fractures. Tumors with high fracture risk, especially fragile malignant lesions, are treated surgically. However, it is difficult to estimate bone strength based on clinical and radiographic findings. This study aimed to determine whether finite element analysis (FEA) provides useful information on the bone strength of femurs with tumors and tumor-like lesions.

Patients and methods: Total femoral computed tomography (CT) data (slice thickness, 0.5 mm) were retrospectively obtained from 18 patients with femoral bone tumors. Three-dimensional FEA of femurs were developed using CT data. The virtual femoral head compression test and direct three-point bending test were performed on the femurs using FEA to predict bone strength and fracture location. The compression direction was parallel to the mechanical axis, whereas that of the three-point bending test was applied to the tumor itself.

Results: In the femoral head compression test using FEA, 13 out of 18 femurs with bone tumors fractured at the femoral head, while 14 out of 18 femurs fractured at the tumor site during the virtual direct three-point bending test. The median loads predicted using the femoral head compression test were significantly higher than those predicted by the direct three-point bending test.

Conclusion: The FEA results indicated that pathological fractures are unlikely to occur during normal walking. Direct external forces applied to the tumor body may lead to fractures.