In vivo最新文献

Background/aim: Wound healing is difficult to study due to interspecies variation in healing mechanisms, rates, and genetic factors. This study aimed to characterize tracheal wound healing in Wistar rats (Rattus norvegicus) following a thin, partial-thickness injury using a modified Derby-Perry Excavator.

Materials and methods: Four male Wistar rats underwent endotracheal wounding under ketamine anesthesia. Each rat was euthanized at one, three, five, or six days post-injury. Excised tracheas were bisected for histological examination (Hematoxylin and Eosin staining) and quantitative RT-PCR analysis of COL3A1 mRNA expression.

Results: Partial-thickness tracheal injury resulted in accelerated wound healing. Histology and COL3A1 expression indicated rapid progression of healing phases. Inflammation resolved by day 3, with the proliferative phase beginning around day 2, peaking at day 3, and transitioning to maturation by day 5. The rapid timeline likely reflects the small, superficial nature of the wound.

Conclusion: Partial-thickness tracheal injury using a modified Derby-Perry Excavator produced a reproducible, rapidly healing model suitable for studying airway repair mechanisms.

Background/aim: Prostate cancer features profound transcriptional dysregulation within the androgen receptor (AR) signaling axis. The pioneer factor FOXA1, which facilitates AR binding to chromatin, is recurrently altered in 10-40% of tumors. Recent studies classify FOXA1 mutations as Class 1 Wing 2 mutations, which enhance AR-dependent tumorigenesis, and Class 2 C-terminal truncations, which promote lineage plasticity and therapy resistance. The interplay of FOXA1 alterations with TMPRSS2-ERG fusions and PROX1 remains incompletely understood.

Materials and methods: Data from The Cancer Genome Atlas (TCGA) Prostate Adenocarcinoma (PRAD) cohort (n=492) were analyzed via UCSC Xena and cBioPortal. FOXA1 mutations were categorized following Eyunni et al. Copy number was assessed by log₂(tumor/normal) ratios. Mutual exclusivity and co-occurrence were evaluated using Fisher's exact test with false-discovery-rate correction. Associations between FOXA1 status and genomic instability were assessed using the fraction genome altered (FGA) metric.

Results: FOXA1 was broadly expressed, with subsets showing elevation. Class 1 mutations localized to the Wing 2 region, while Class 2 truncations clustered in the C-terminal domain. Copy number changes were infrequent, indicating mutation-driven reprogramming as the main oncogenic mechanism. TMPRSS2 and ERG strongly co-occurred (log2 OR >3, q<0.001), whereas FOXA1 was mutually exclusive with both TMPRSS2 and ERG (q<0.001). Although FOXA1 alterations showed no significant Pearson correlation with FGA (r=-0.01, p=0.76), a moderate Spearman correlation (ρ=0.52, p<0.001) suggested enrichment in genomically unstable tumors.

Conclusion: FOXA1 defines a major oncogenic axis in prostate cancer, distinct from TMPRSS2-ERG fusion and PROX1 induction. Class 1 and 2 FOXA1 mutations drive alternative transcriptional programs leading to therapy resistance, highlighting FOXA1 as a critical biomarker and target for chromatin-directed interventions.

Background/aim: Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, can cause severe liver injury, leading to treatment discontinuation. We report five cases of patients treated with a combined regimen of a CDK4/6 inhibitor and hormone therapy for metastatic breast cancer. Following the development of serious liver dysfunction (grade ≥3) during abemaciclib therapy, switching to palbociclib allowed continuation of CDK4/6 inhibitor treatment.

Case report: The causative role of abemaciclib was assessed using the drug-induced liver injury scoring system (RECAM-J 2023), which evaluates multiple factors, including time to onset, course after onset, prior reports of liver injury, exclusion of other potential causes, and effects of re-administration. A score of ≥8 indicates a high likelihood of drug-induced liver injury; all five cases in this study met this criterion, with one case reaching a maximum score of 17. Because CDK4/6 inhibitors are administered alongside hormonal agents, we also evaluated the potential contribution of concomitant endocrine therapy. The likelihood of hormonal agents causing liver injury was assessed as "Possible." Each patient underwent further hepatological evaluation, including testing for viral hepatitis and autoimmune hepatitis. Based on these assessments, the hepatologist confirmed drug-induced liver injury. injury. Following normalization of liver function test values, patients were switched to palbociclib. No recurrence of liver dysfunction was observed, allowing CDK4/6 inhibitor therapy to continue successfully.

Conclusion: These cases suggest that severe liver damage induced by abemaciclib, does not necessarily preclude continued CDK4/6 inhibitor therapy. Switching to palbociclib may be a feasible strategy, provided liver function has recovered before reinitiating treatment.

Background/aim: Appendiceal adenocarcinomas are rare tumours with aggressive traits, most often diagnosed incidentally after routine appendectomy. Survival rates vary greatly between the different subgroups, and adenocarcinoma has the worst prognosis. Surgery is the only curative treatment, however, the long-term benefit of extended surgical resections over appendectomy has not been established. This study aimed to investigate survival outcomes in patients with appendiceal adenocarcinoma that undergo appendectomy versus right hemicolectomy (RHC).

Materials and methods: This study involved a systematic literature search in databases PubMed, Embase and Cochrane Library using the COVIDENCE software. Cohort studies reporting survival outcomes for patients with non-metastasised appendiceal adenocarcinoma undergoing appendectomy versus RHC were included. A random-effects model was used to pool hazard ratios (HRs) in the meta-analysis performed in Review Manager. The ROBINS-I V2 tool was used for risk of bias assessment.

Results: A total of nine retrospective registry-based cohort studies were identified. Seven studies, with a total of 17,802 patients, reported overall survival (OS) from multivariable Cox- regression analysis. The pooled effect of adjusted HRs demonstrated increased OS [random-effects HR=0.69, 95% confidence interval (CI)=0.58-0.83] for patients undergoing RHC, with similar results in the sensitivity analysis excluding potential overlapping data (random-effects HR=0.70, 95% CI=0.51-0.96). No significant difference in OS was found in studies reporting subgroup analysis for well-differentiated adenocarcinoma.

Conclusion: This systematic review highlights the complexity of surgical treatment guidelines in appendiceal adenocarcinoma. The findings suggest a survival advantage for RHC compared to appendectomy. In well differentiated early-stage adenocarcinoma, appendectomy may be sufficient, although this may not apply to all subgroups.

Background/aim: Placenta accreta spectrum (PAS) is characterized by abnormal placental adherence/invasion at a scarred implantation bed. Endoplasmic reticulum (ER) stress signaling via inositol-requiring enzyme 1 (IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) shapes trophoblast behavior, but its interface-specific role in PAS is unclear. We evaluated IRE1 and PERK immunoreactivity in extravillous trophoblast (EVT) subsets to test associations with PAS severity and maternal outcomes.

Patients and methods: In a retrospective series from a tertiary center, cesarean hysterectomy specimens for PAS and gestational age-matched cesarean controls were analyzed. Immunohistochemistry for IRE1 and PERK was performed on basal plate regions, with semiquantitative immunoreactivity score (IRS:0-12) recorded for EVT subtypes. Associations with clinicopathological parameters and with negative controls were examined with bivariate analyses.

Results: IRE1 expression showed no significant associations with clinicopathological parameters. PERK IRS was significantly higher in PAS obstetrical hysterectomy specimens than in controls (mean 9.40±1.96 vs. 4.17±1.52; p<0.001). Across PAS subtypes (accreta/increta/percreta), PERK-IRS varied numerically but not significantly. Within PAS, PERK-IRS was negatively associated with maternal complications (p=0.035).

Conclusion: PERK-IRS was elevated at the stressed implantation interface in PAS relative to normal placentation, while IRE1 showed no clear differential signal with the current assay. Paradoxically, within PAS, lower local PERK-IRS signal correlated with complications, suggesting that the magnitude/timing of PERK engagement may influence operative risk. Larger studies incorporating activation-specific markers are warranted to refine biological stratification and prognostication in PAS.

Calcifying aponeurotic fibroma (CAF) is a rare benign but locally aggressive mesenchymal tumor that primarily occurs in the distal extremities of children and adolescents. It typically presents as a slow-growing, painless, poorly circumscribed mass, often of prolonged duration. Radiographs may reveal a soft-tissue mass with a variable extent of fine stippled calcifications. On magnetic resonance imaging, CAF usually appears as an ill-defined subcutaneous mass with low to intermediate signal intensity on T1-weighted sequences and heterogenous high signal intensity on T2-weighted sequences. Areas of calcification exhibit low signal intensity on all pulse sequences. Intense heterogeneous enhancement is seen after intravenous contrast administration. Histologically, CAF is characterized by a fibromatosis-like component and a nodular calcified component. By immunohistochemistry, the tumor cells are variably positive for smooth muscle actin, muscle-specific actin and CD99 but negative for desmin and β-catenin. Moreover, frequent expression of ETS transcription factor ERG (ERG) and epidermal growth factor (EGF) has been demonstrated. Recent molecular studies have identified the presence of a recurrent fibronectin 1 (FN1)-EGF gene fusion. Surgical excision is the treatment of choice for CAF, but local recurrence is common due to its infiltrative nature. This review provides an updated overview of the clinical, radiological, morphological, immunohistochemical and molecular genetic features of CAF and discusses the differential diagnosis of this uncommon condition.

Background/aim: Peritoneal metastasis is associated with poor prognosis and low response rates to systemic chemotherapy due to multidrug resistance. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has improved local drug delivery but remains limited by uneven drug distribution, with most aerosol deposition concentrated opposite the nozzle. To overcome this, rotational intraperitoneal aerosol chemotherapy (RIPAC) was developed. This study aimed to design a universal electric medical clamp enabling stable nozzle rotation for RIPAC.

Materials and methods: A prototype device was constructed using a miniaturized electric motor mounted within a modular clamp to induce conical pendulum motion of the aerosol nozzle. Iterative design optimizations addressed instability and vibration, evolving from simple fixed joints to reinforced mechanical assemblies and finally a hydraulic joint system. Prototypes were evaluated in benchtop and porcine models for motion stability, spray uniformity, and mechanical robustness under operative conditions.

Results: The initial mockup device achieved pendulum-like motion but failed to maintain stability during in vivo testing due to shifts in the nozzle's center of gravity and joint collapse. Reinforced joint designs improved stability but required cumbersome adjustments. The final hydraulic joint-integrated clamp provided enhanced fixation strength, increased degrees of freedom, and smoother fine-tuned positioning, while accommodating motor load. This configuration enabled consistent nozzle motion with greater clinical feasibility.

Conclusion: A universal electric medical clamp was successfully developed for RIPAC, providing stable rotational motion and improved drug distribution potential compared with PIPAC. This innovation lays the groundwork for clinical translation of RIPAC as a promising strategy to enhance intraperitoneal chemotherapy efficacy.

Background/aim: Osteoarthritis (OA) is a degenerative joint disease affecting both humans and companion animals, characterized by progressive cartilage destruction, inflammation, and functional impairment. Current therapies provide mainly symptomatic relief, emphasizing the need for regenerative strategies. Decellularized extracellular matrix (dECM) hydrogels preserve native biochemical cues and biocompatibility, making them potential candidates for cartilage protection and regeneration. This study aimed to evaluate the biocompatibility, anti-inflammatory activity, and chondroprotective potential of meniscus-derived dECM (Meni-dECM) hydrogel.

Materials and methods: Meniscus tissue was decellularized and processed into hydrogel form. In vitro cytocompatibility and chondrogenic potential were assessed using stem cells cultured within the hydrogel. For in vivo evaluation, OA was induced in rats by intra-articular monosodium iodoacetate (MIA) injection. The therapeutic efficacy of intra-articularly injected Meni-dECM hydrogel was compared with control using gross joint assessment, cytokine analysis, and histological evaluation.

Results: In vitro assays confirmed excellent cell viability, proliferation, and upregulation of chondrogenic gene expression within the Meni-dECM hydrogel. In vivo, Meni-dECM-treated rats exhibited significantly reduced joint swelling, lower serum levels of IL-1β, IL-6, and TNF-α, and improved cartilage preservation compared with control. Histological analysis revealed decreased synovial hyperplasia, reduced inflammatory infiltration, and enhanced proteoglycan retention in Meni-dECM-treated joints.

Conclusion: Meni-dECM hydrogels demonstrated protective effects against OA progression by modulating inflammation and preserving cartilage architecture. These findings support Meni-dECM hydrogel as a promising injectable biomaterial for OA management in both veterinary and translational medicine. Further studies are warranted to confirm long-term stability, elucidate molecular mechanisms, and evaluate clinical feasibility.

Background/aim: Growth hormone (GH) secretion patterns differ across species. Humans exhibit a nocturnal surge, while rodents exhibit ultradian pulses. In cynomolgus monkeys, diurnal and daily variations and responsiveness to exogenous GH-releasing hormone (GHRH) remain insufficiently defined in non-clinical studies. This study aimed to characterize GH secretion patterns and evaluate responsiveness to exogenous GHRH in adult male cynomolgus monkeys for pituitary toxicity studies.

Materials and methods: Serum from 10 animals was collected between 10:00 and 22:30 and again at 10:30 on the following day to evaluate diurnal variation. Serum from 10 additional animals was collected once daily between 9:00 and 10:00 across five days to evaluate daily variation. In the GH stimulation test, four animals received intravenous pralmorelin hydrochloride (as GHRH) and four received physiological saline between 11:00 and 11:30. Serum was collected before and at 0.5, 1, and 2 h after administration. GH concentration was measured with enzyme-linked immunosorbent assay.

Results: Diurnal variation was observed, with concentrations increasing from 10:00 to 11:30, transiently dropping to their lowest at 12:30 and peaking at 22:30, similar to the pattern in humans. Daily variation was also observed inter- and intra-individually across five days. In the stimulation test, compared to the control group, the GHRH group showed higher GH concentrations at 0.5 h (p<0.05), as in humans, and a greater area under the curve (p<0.05).

Conclusion: In adult male cynomolgus monkeys, diurnal and daily GH variations and responsiveness to exogenous GHRH were confirmed. Morning GHRH administration in the stimulation test, when basal GH is low and diurnal influence is minimal, and multi-timepoint sampling are recommended for reliable GH assessment. These findings suggest that cynomolgus monkeys are a suitable model for pituitary toxicity studies.

Background/aim: Splenectomy is performed in ovarian cytoreductive surgery when pre-operative imaging and intra-operative examination suggest disease involvement. This study aimed to evaluate the incidence of splenectomy, the diagnostic accuracy of pre-operative imaging and intra-operative assessment, and the associated short- and long-term peri-operative complications.

Patients and methods: We conducted a single institution retrospective study to assess rates of splenectomy, accuracy of imaging and intra-operative assessment, peri-operative complications and patient compliance with prophylactic antimicrobial therapy and immunizations.

Results: Over a period of 8 years (2014-2022), 469 cytoreductive surgeries for International Federation of Obstetrics and Gynaecology (FIGO) stage III-IV epithelial ovarian cancer were undertaken. A splenectomy was performed in 61 (13%) patients. Complete cytoreduction was achieved in 50 cases (82%) undergoing a splenectomy. On pre-operative imaging assessment, splenic disease was suspected in 36 patients (7.7%) and a further 23 (4.9%) patients had malignancy suspected at intraoperative assessment. In five patients (1%), the spleen was removed due to omental disease inseparable from the spleen. In three (0.6%) cases a splenectomy was performed due to intraoperative trauma. Postoperative pathology confirmed splenic disease in 49 (80.3%) patients. A biochemical leak of no clinical significance was identified in 15/61 (24.6%) splenectomy cases, and one case (1.6%) of post-operative pancreatic fistula (POPF) was identified. Remaining living patients were audited for adherence to recommended post-operative management. Seventeen of the eighteen patients (94%) had received recommended vaccinations between 2-6 weeks post-surgery, and 17/18 (94%) consistently continued ongoing vaccinations. Additionally, 16 (88.9%) adhered to prescribed daily prophylactic antibiotics.

Conclusion: Splenectomy, integral to ovarian cytoreduction, facilitates high rates of complete cytoreduction. Preoperative and intraoperative assessments can predict the existence of malignancy in the spleen, confirmed by pathology. Traumatic splenectomy was rare. Emphasising adherence to a post-splenectomy protocol is crucial to mitigate post-splenectomy complications such as POPF, which can significantly delay the initiation of chemotherapy.