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Background/aim: Bevacizumab (Bev) often induces hypertension and proteinuria. Optimal antihypertensive management in this setting remains unclear, and studies comparing angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are limited. The objective of this study was to compare the effects of the ARB azilsartan and the CCB amlodipine on hypertension and proteinuria.

Patients and methods: Patients with demonstrated systolic/diastolic blood pressure (SBP/DBP) ≥140/90 mmHg during Bev therapy for colorectal cancer were randomly assigned 1:1 to either the azilsartan group or the amlodipine group and were followed up for 18 weeks. The primary outcome was urinary protein-to-creatinine ratio (UPCR). Secondary outcomes included BP changes and achievement of target BP (<140/90 mmHg). After week six, the attending physician adjusted the antihypertensive medication as needed.

Results: Thirty patients were enrolled, and 26 (13 per group) completed 18 weeks of treatment. Mean baseline SBP was 156.8±9.2 mmHg in the azilsartan group and 158.0±9.4 mmHg in the amlodipine group. At week six, SBP decreased to 151.4±21.9 mmHg and 144.5±15.2 mmHg, respectively, with a significant reduction in the amlodipine group. At week 18, SBP was 136.5±12.9 mmHg vs. 138.7±14.9 mmHg. Target BP was achieved in 23% of patients at week six and in 40-50% at week 18, with no difference between groups. No significant difference in UPCR was observed at any time point. Subgroup analysis revealed that patients with proteinuria consistently had higher BP.

Conclusion: These findings emphasize that adequate BP control, rather than antihypertensive class, may be critical in managing Bev-induced proteinuria.

Background/aim: To identify factors influencing adrenal signal intensity in whole-body magnetic resonance imaging/diffusion-weighted whole-body imaging with background body signal suppression (MRI/DWIBS).

Patients and methods: This retrospective study included patients who underwent whole-body MRI/DWIBS at our institution between April 2019 and April 2025 with no malignant tumor or history of a malignant tumor. Adrenal signal intensity and gland area were measured and analyzed according to sex and age.

Results: The study included 22 male patients (average age of 58.2±11.7) and 38 female patients (average age of 55.9±15.4). The maximum signal intensity (max value) of the left adrenal gland on diffusion-weighted imaging was 1,885.5±352.0, and the mean gland area was 1,198±435.0 mm² in male patients, and 1,517.1±429.5 and 760.5±325.6 mm², respectively, in female patients. The median values for max value of the left adrenal gland on diffusion-weighted imaging were significantly larger in male patients (male: 1855 vs. female: 1,472, p<0.01). The median value for adrenal gland area was significantly larger in male patients (male: 1,159 mm² vs. female: 768.5 mm², p<0.01). Among female patients, those aged <40 years had a significantly lower median max value and adrenal gland area compared to those aged ≥40 years (<40 years: 1,004 vs. ≥40 years: 1,603, p<0.01 and <40 years: 478 mm² vs. ≥40 years: 834 mm², p=0.017, respectively).

Conclusion: Adrenal gland signal intensity and gland size on whole-body DWIBS are significantly higher in males than in females. In females, both signal intensity and adrenal area increase with age, suggesting age-related physiological or hormonal influences on adrenal gland characteristics.

Background/aim: A variety of actions implicated in diabetic nephropathy (DN) are attributed to inflammatory cytokines and apoptosis of tubular epithelial cells. Building on our previous research demonstrating the role of different phosphodiesterase inhibitors (PDEIs) in improving renal microcirculation, glucose lowering, and antioxidant effects in rats with DN, this study aims to further explore the anti-inflammatory and anti-apoptotic properties of PDEIs by measuring their effects on renal expression of pro-inflammatory cytokines in streptozocin (STZ)-induced diabetic nephropathic rats.

Materials and methods: Out of 50 adult male Sprague-Dawley rats, diabetes was induced in 40 rats by a single injection of STZ (45 mg/kg) dissolved in citrate buffer. Ten days after induction of diabetes, rats were divided into five groups (10/group): normal control, diabetic control, and 3 diabetic groups treated with pentoxifylline, sildenafil, and milrinone via drinking water for 15 successive days. Serum and kidney tissue samples were collected to evaluate the effect of treatment with PDEIs on diabetes-induced histopathological changes and expression levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), apoptotic marker Bcl-2 Associated X-protein (Bax) and anti-apoptotic marker B cell lymphoma-2 (Bcl-2) in rat's kidneys.

Results: A significant increase in pro-inflammatory cytokines (TNF-α and IL-6), and apoptosis marker (Bax), with a concomitant decrease in anti-apoptotic protein (Bcl-2) were observed in diabetic rats. Treatment with PDEIs resulted in a significant decrease in renal expression of Bax, TNF-α, and IL-6, with an increase Bcl-2 expression, with slight, though not statistically significant, differences among the PDEI-treated groups.

Conclusion: The tested PDEIs, pentoxifylline, sildenafil, and milrinone, exhibit significant anti-inflammatory and anti-apoptotic effects, highlighting their potential in slowing the progression of diabetic nephropathy.

Cancers of the head and neck, including malignancies of the oral cavity, pharynx, larynx, and salivary glands, are often associated with severe symptoms that negatively impact quality of life. Patients commonly experience pain, nausea, cachexia (severe weight loss), dysphagia (difficulty swallowing), and xerostomia (dry mouth), all of which can be exacerbated by both the disease and its treatments, such as surgery, radiation, and chemotherapy. Research has demonstrated that medical cannabis can be effective in managing symptoms such as chronic pain, nausea, vomiting, and anxiety, making it a valuable option in cancer care. Its ability to interact with the endocannabinoid system to reduce nociception (pain perception) and inflammation makes it particularly suitable for the complex symptom burden of patients with head and neck cancer. This review explores the role of the endocannabinoid system and medical cannabis in mitigating symptoms and improving patient outcomes, as well as its place within the comprehensive care of patients with cancers of the head and neck.

Background/aim: Angioleiomyoma is a benign, pericytic (perivascular) neoplasm that most frequently arises in the dermis or subcutis of the lower extremities. Extensive calcification is extremely uncommon in this condition.

Case report: An 80-year-old woman presented with a 20-year history of a slowly growing, painless mass in the dorsomedial aspect of the left great toe. Physical examination revealed a 2.5-cm, firm, mobile, non-tender mass. Radiographs showed a well-demarcated, densely calcified mass. Computed tomography confirmed the presence of a calcified lesion without bone involvement. Magnetic resonance imaging (MRI) exhibited a well-defined mass with intermediate signal intensity on T1-weightwed sequences and high signal intensity on T2-weighted sequences. Peripheral low signal intensity areas correlating to the calcified portion of the mass were also observed on both T1- and T2-weighted sequences. Contrast-enhanced MRI demonstrated intense, relatively homogeneous enhancement in the non-calcified portion of the mass. The patient underwent an excisional biopsy of the lesion. Histologically, the lesion is composed of bundles of bland, well-differentiated smooth muscle cells with small slit-like vascular channels. In addition, calcium crystal deposits surrounded by aggregates of epithelioid histiocytes and multinucleated giant cells were observed. The patient had no evidence of local recurrence at the latest follow-up.

Conclusion: This unique case provides valuable insights into the understanding and treatment of acral calcified angioleiomyoma. Knowledge of this peculiar neoplasm is important because it can mimic a variety of benign and malignant soft-tissue tumors.

Background/aim: Domestic pigs have become increasingly important models in translational research; however, their large size presents logistical and ethical challenges. Microminipigs offer a practical alternative for long-term studies. This study aimed to develop an effective superovulation protocol using a step-down follicle-stimulating hormone (FSH) regimen to improve zygote collection in microminipigs.

Materials and methods: In experiment 1, four female microminipigs with regular estrous cycles were used in both the control and treatment conditions in a crossover design. Treatment group was received prostaglandin F2α (PGF_2α), followed by step-down FSH, and human chorionic gonadotropin (hCG). Follicle number, area, and diameter were monitored by ultrasonography from day -6 to day +1 of estrus. In experiment 2, three female microminipigs were used. Zygotes were retrieved at day 1 by oviduct flushing.

Results: On day 0, the number of follicles was higher in the treatment group (93.0±7.74) compared to the control (46.8±5.01). Significant differences were observed on days -1 and 0, while by day+1, the number of follicles decreased in both groups. Follicle area was significantly larger in the treatment than in the control group (0.81±0.03 cm² vs. 0.63±0.04 cm²) on day -2, with no significant differences detected on days 0 and +1. Follicle diameter was also significantly greater in the treatment group compared to the control (3.4±0.1 mm vs. 2.7±0.1 mm) on day -2, while no significant differences were found on days -1, 0, and +1. In experiment 2, an average of 14.7 zygotes per animal were recovered. The cleavage and blastocyst formation rates were 62.8% and 59.4%, respectively.

Conclusion: The step-down FSH protocol effectively enhanced ovarian response and embryo yield in microminipigs, marking a foundational step toward the efficient reproductive engineering for this animal model that may contribute to the advancement of translational research.

Background/aim: Lactose intolerance (LI) is a common clinical condition associated with reduced lactase enzyme activity. The oral lactose tolerance test (OLTT), although widely used for diagnosis, has several limitations such as fasting, multiple blood collections, and gastrointestinal discomfort. As an alternative, genetic testing targeting the -13910C>T polymorphism in the MCM6 gene, a regulator of lactase expression, has gained prominence as it is non-invasive, rapid, and unaffected by physiological variation. This study aimed to evaluate the frequency of the -13910C>T polymorphism of the MCM6 gene in the population of Fortaleza and compare the genotyping results with the OLTT, to verify its diagnostic applicability.

Materials and methods: A descriptive study was conducted with data from 2359 patients examined between January 2022 and May 2025 at a private laboratory. Concordance between genotyping and OLTT was analyzed in 24 patients who underwent both tests, with OLTT considered the reference standard. Sensitivity, specificity, accuracy, and Kappa coefficient were calculated. All analyses were performed using R software.

Results: The median age of participants was 7 years (range=0.06-100 years). The observed genotype frequencies were 52.90% for the CC genotype, 38.74% for CT, and 8.35% for TT. The Kappa test demonstrated moderate agreement between the genetic test and OLTT [k=0.583 (p=0.00413)], with a sensitivity of 81.82% [95% confidence interval (CI)=48.22-97.71], overall accuracy of 79.17%, and specificity of 76.92% (95%CI=48.16-94.96).

Conclusion: Genotyping for the -13910C>T polymorphism in the MCM6 gene represents a promising diagnostic alternative for lactose intolerance, offering a feasible and less invasive approach with good sensitivity and specificity.

Background/aim: In advanced renal cell carcinoma (RCC), immune checkpoint inhibitor (ICI) combinations (ICI-ICI) and ICI plus tyrosine kinase inhibitor (TKI) combinations (ICI-TKI) are standard first-line therapies. However, real-world data directly comparing these approaches remain limited. This study aimed to compare treatment outcomes between ICI-ICI and ICI-TKI therapies.

Patients and methods: We retrospectively analyzed 58 patients who received first-line ICI-ICI therapy (ipilimumab plus nivolumab) or ICI-TKI therapy (pembrolizumab plus axitinib, avelumab plus axitinib, nivolumab plus cabozantinib, or pembrolizumab plus lenvatinib) for advanced RCC at Nagasaki University Hospital (March 2018 to June 2024). Primary endpoints were progression-free survival (PFS), overall survival, and objective response rate (ORR). Safety profiles were also evaluated.

Results: We included 36 patients in the ICI-ICI group and 22 in the ICI-TKI group. The median follow-up was 17.5 months. The median age of patients in the ICI-TKI group was significantly older than that in the ICI-ICI group (74 vs. 66 years, p<0.001). The median PFS was 30 months in the ICI-ICI group and 25 months in the ICI-TKI group. The median overall survival was 51 months in the ICI-ICI group and 49 months in the ICI-TKI group, with no significant difference observed for either endpoint. The ORR was also similar between the groups. Notably, two complete responses occurred in the ICI-ICI group. The treatment discontinuation rate due to grade ≥3 adverse events was not significantly different between the ICI-ICI and ICI-TKI groups (30.6% vs. 40.9%).

Conclusion: Across all International Metastatic RCC Database Consortium risk groups, PFS, OS, and ORR showed no significant differences between ICI-ICI and ICI-TKI therapies. Treatment selection should consider patient-specific factors. Validation through larger prospective studies is warranted.

Background/aim: Neoadjuvant therapy enables disease conversion to resectability in selected patients with locally advanced non-small-cell lung cancer (NSCLC) but real-world survival outcomes in this setting are not well defined. This study aimed to evaluate survival outcomes and prognostic factors in patients with initially unresectable, non-metastatic NSCLC in whom complete resection was achieved following neoadjuvant therapy.

Patients and methods: This retrospective cohort study included 35 pa tients with initially unresectable NSCLC who underwent R0 resection after neoadjuvant therapy. Demographic, clinical, radiological, and pathological characteristics, treatment details, and survival outcomes were collected. Factors associated with event-free (EFS) and overall (OS) survival were analyzed.

Results: The mean age at diagnosis was 67.6 years, and 85.7% of patients were male. Patients received a median of 3 (range=2-6) neoadjuvant therapy cycles (77% with carboplatin and paclitaxel). Postoperative pathology revealed mediastinal lymph node involvement in 37.1% and angiolymphatic invasion in 25.7% of patients. Adjuvant treatment was administered to 51.4% of patients, with no factor significantly associated with this decision. During a median follow-up of 40.6 months, the recurrence rate was 37.1%, and the mortality rate was 40%. The median EFS was 25.4 months, while the median OS was not reached. Two-year EFS and OS rates were 53.9% and 66.3%, respectively. Univariate analysis identified mediastinal lymph node involvement, angiolymphatic invasion, and receiving ≥3 neoadjuvant cycles as significant predictors of shorter EFS, while only mediastinal lymph node involvement significantly affected OS. Multivariate analysis did not reveal independent predictors, likely due to collinearity.

Conclusion: Complete resection after neoadjuvant therapy yields favorable long-term survival in selected patients with initially unresectable NSCLC. Postoperative mediastinal lymph node status remains a critical prognostic factor.

Background/aim: Demethylase fat mass and obesity-related protein (FTO), which belongs to the AlkB homologous (ABH) family, is associated with various neurological diseases, cancer, and obesity. This protein, which contains many structurally and functionally different regions, contains a COOH-terminal domain whose function, unlike other ABH members, is not fully understood. This study aimed to investigate the effects of the exonic V493F mutation in this region of FTO on the soluble proteome.

Materials and methods: SH-SY5Y cells stably over-expressing wild-type (WT-FTO) or mutant FTO (V493F-FTO) proteins under the control of the Tet promoter were created and used. Comparative proteomic analysis using two-dimensional gel electrophoresis (2DE) identified over 500 protein spots, with 10 showing significant (≥2-fold) differential expression. These proteins were identified by MALDI-TOF/TOF mass spectrometry and validated by western blotting.

Results: WT-FTO over-expression primarily affected proteins related to DNA replication and repair, including PCNA, whereas V493F-FTO over-expression altered the expression of stress response and endoplasmic reticulum-associated degradation (ERAD) pathway proteins, such as HSPA4, ARHGDIA, and VCP. Although the mutation did not alter the nuclear localization or predicted 3D structure of FTO, it distinctly modulated pathways associated with protein homeostasis and cellular stress.

Conclusion: FTO participates in the regulation of the cellular stress response and the ubiquitin-dependent ERAD pathway, functions potentially independent of its demethylase activity. Importantly, dysregulation of these pathways has been implicated in cancer initiation, progression, and therapeutic resistance. Therefore, our findings provide new insights into how FTO mutations might influence oncogenic processes, highlighting FTO as a potential biomarker and therapeutic target in cancer biology.