Diaphyseal nonunions after bone tumor resection present a significant reconstructive challenge. We report a 39-year-old woman who developed a diaphyseal humeral nonunion after giant cell tumor resection and reconstruction with vascularized fibula graft. She presented with symptomatic segmental bone loss and hardware failure. Two-stage Masquelet-induced membrane procedure was performed, resulting in complete union and excellent functional recovery at 12 months postoperatively.

This case highlights the potential of the Masquelet technique in reconstruction of refractory nonunions despite previous failed reconstructive attempts.

Drugs that inhibit KRAS signaling delay the development of pancreatic cancer in mice.

Transformation of pancreatic epithelial cells to malignant pancreatic ductal adenocarcinoma (PDAC) typically involves the progression of precancerous pancreatic intraepithelial neoplasia (PanINs) bearing oncogenic KRAS mutations. Here, we tested the impact of PDAC interception using either RAS(ON) multiselective or RAS(ON) G12D-selective pharmacological inhibitors [RAS(ON) inhibitors] in mouse models of PDAC. Treatment of PanIN-bearing mice with RAS(ON) inhibitors prompted regression of premalignant lesions that translated into a delay in tumor onset and an increase in overall survival (OS). Long-term interception in tumor-prone mice resulted in a median OS of more than 1 year compared with less than 5 months in nonintercepted control mice (P < 0.0001). Comparing the survival benefits of RAS(ON) inhibition for cancer interception versus RAS(ON) inhibition for cancer treatment, we found that interception provided a greater survival benefit to mice. These findings suggest that a pharmacological approach may reduce premalignant burden and increase survival in PDAC.

This study aimed to evaluate the dosimetric benefits of magnetic resonance (MR)-guided radiotherapy (MRgRT) compared to computed tomography (CT)-guided RT for partial breast treatment. First, treatment plan quality was compared between MRgRT with step-and-shoot (S&S) IMRT and CT-guided RT with volumetric-modulated arc therapy (VMAT). Second, the dosimetric benefit of online adaptation in MRgRT was assessed by comparing the initial planned doses with daily MR-defined target geometry to those with planning CT-defined target geometry. Plan quality for MRgRT was comparable to, or slightly lower than, CT-guided RT. The V95% of the planning target volume (PTV) was lower by 1.72% and 1.94%, respectively, with a lower minimum dose and a higher maximum dose. For the OARs, the dosimetric parameters were generally similar, but for the skin, the Dmax, D0.5mL, and D1mL were slightly higher in MRgRT. Evaluation of the initial planned doses with the daily MR-based target definition resulted in a maximum deviation of 46% for the PTV V95%, demonstrating uncertainty in CT-based target definition. Although the MRgRT planning quality may be slightly compromised due to the S&S IMRT technique, the dosimetric benefits from online adaptation can be substantial when CT-based target definitions need to be modified based on daily MR imaging guidance.

Keratin-positive giant cell-rich tumor (KPGCT) is a rare bone and soft tissue neoplasm, with pediatric and metastatic cases being exceedingly uncommon.

We report a 1.5-month-old male infant presenting with multifocal metastatic disease involving the skull, adrenal glands, vertebrae, mandible, soft tissue, and long bones. Histopathologic evaluation confirmed KPGCT, molecular testing was negative for HMGA2 rearrangement. Treatment with imatinib resulted in marked regression of lesions and clinical improvement without toxicity.

This case expands the clinical spectrum of pediatric KPGCT and suggests that imatinib may be an effective treatment option in infants with advanced disease, even canonical HMGA2::NCOR2 fusion absent.

Entinostat, a selective HDAC1/3 inhibitor, has shown anti-tumor activity in small cell lung cancer (SCLC), but the precise molecular mechanisms underlying its efficacy remain incompletely understood. This study aimed to investigate the functional role and mechanism of Entinostat in SCLC, with a focus on HDAC1 inhibition and its downstream effects on cell death pathways. The anti-tumor effects of Entinostat were evaluated in SCLC cell lines and a xenograft mouse model using MTT, flow cytometry, immunofluorescence, western blotting, and rescue experiments with HDAC1 overexpression and pathway-specific inhibitors. We found that Entinostat significantly inhibited SCLC cell viability and induced both apoptosis and autophagy. Mechanistically, Entinostat downregulated HDAC1 protein levels, increased p53 acetylation and phosphorylation, activated AMPK, and suppressed mTOR signaling. HDAC1 overexpression reversed these molecular changes and attenuated Entinostat-induced cytotoxicity. In vivo, Entinostat suppressed tumor growth and consistently modulated the HDAC1/p53/AMPK/mTOR pathway. In conclusion, Entinostat exerts potent anti-tumor activity in SCLC by simultaneously inducing apoptosis and autophagy through epigenetic modulation of p53 via HDAC1 inhibition and subsequent regulation of the AMPK/mTOR axis.

Melanoma is an aggressive malignancy characterized by high metastatic potential and resistance to conventional therapies. Emerging evidence suggests that purinergic P2X receptors, particularly P2X7, play critical roles in regulating tumor cell proliferation, apoptosis, and invasion. However, the transcriptional regulation of P2X receptor subtypes in response to therapeutic compounds remains incompletely characterized. This study aimed to investigate the transcriptional modulation of all seven P2X receptor subtypes (P2XR1-7) in G361 melanoma cells following exposure to selected phenolic compounds and chemotherapeutic agents. Cell viability was evaluated by MTT assay, and half-maximal inhibitory concentrations (IC₅₀) were determined using non-linear regression analysis in GraphPad Prism software. Chemotherapeutic agents, including paclitaxel and sunitinib, exhibited strong cytotoxic effects under the experimental conditions employed, whereas phenolic compounds (quercetin, retinoic acid, and resveratrol) demonstrated moderate anti-proliferative activity. Quantitative real-time PCR analyses revealed compound-specific transcriptional response patterns. Quercetin induced upregulation across multiple P2X receptor subtypes, retinoic acid exhibited a partially suppressive profile, and resveratrol showed selective downregulation. In contrast, chemotherapeutic agents generally induced mRNA upregulation, particularly in P2XR4, P2XR5, and P2XR7 subtypes. These findings demonstrate that P2X receptor genes are differentially modulated at the transcriptional level by natural and synthetic compounds. The present work provides a transcriptional framework identifying subtype-specific response patterns and nominates candidate P2X receptors for future protein-level and functional validation studies in melanoma.

Tumor progression is governed not only by genetic alterations but also by the dynamic interplay within the tumor microenvironment (TME). In gliomas, this microenvironment is shaped by diverse immune populations, including regulatory T cells and tumor-associated macrophages (TAMs), which influence tumor growth through direct interactions and cytokine signaling. A central challenge in glioma therapy is predicting patient response to immunotherapy, as both glioma cells and the TME evolve from diagnosis to recurrence. Advances in spatial transcriptomics and proteomics reveal that gliomas are composed of distinct molecular regions with unique lineage markers and biological behaviors. This heterogeneity underscores the limitations of single biopsies and highlights the need for multi-regional and longitudinal sampling. Serial biopsies and resections are therefore essential to capture tumor evolution and guide personalized immunotherapy. Standard glioblastoma (GBM) treatments, including radiation and temozolomide, also reshape immune cell dynamics, yet their contributions to therapy resistance remain incompletely understood. Clarifying these effects may inform more effective combination strategies. While TAMs dominate current research due to their prevalence in the glioma milieu, expanding focus to other immune cell subsets is critical for a more complete understanding of tumor-immune interactions. This review explores how radiotherapy, chemotherapy, and emerging immunotherapies reprogram the glioma TME by altering immune cell infiltration, cytokine networks, and stromal interactions. A deeper understanding of these processes will be vital for developing personalized and durable therapeutic approaches for glioma patients.

To synthesize qualitative evidence on the experiences and perceptions of social isolation in colorectal cancer patients with ostomy.

A systematic qualitative meta-synthesis was conducted. Nine electronic databases (PubMed, Web of Science, EBSCO, Cochrane, Scopus, CNKI, Wanfang, VIP, and CBM) were searched from inception to November 2024. Qualitative studies exploring experiences of social isolation in ostomy patients were included. Methodological quality was assessed using the CASP checklist. Data were analyzed via a meta-aggregative approach.

Eleven studies were included. Four synthesized findings were identified: (1) antecedents and multidimensional perceptions of social isolation, (2) social relationship rupture and structural transformation, (3) psychological distress and self-identity crisis, and (4) multidimensional support needs and positive adaptation. Social isolation arose from physiological limitations, self-care challenges, and stigma, leading to behavioral withdrawal, family tension, and emotional distress. Support and self-adjustment were found to facilitate coping.

Social isolation in ostomy patients is a multifaceted phenomenon shaped by individual, relational, and environmental factors. A comprehensive support framework involving healthcare providers, families, and communities is essential to mitigate social isolation and promote social reintegration. Future interventions should adopt dyadic or systemic approaches to address communal challenges.

Ostomy patients may experience significant social isolation influenced by complex factors. Holistic, needs-based support from multiple stakeholders is crucial to facilitate adaptation and improve quality of life.

The diagnostics of small bowel diseases represent a special challenge as this intestinal segment is not readily accessible endoscopically and the clinical symptoms are often nonspecific. The assessment is further complicated by the bowel motility and the dependency on contrast agent administration and luminal distension. Modern cross-sectional imaging techniques, particularly computed tomography (CT) and magnetic resonance (MR) enterography, have revolutionized the diagnostics of inflammatory, neoplastic and vascular small bowel diseases. The precise differentiation of the various small bowel pathologies requires thorough knowledge of characteristic imaging patterns. Bowel wall thickening, the extent, distribution and pattern of contrast enhancement uptake, mesenteric vascular changes and associated extraintestinal findings provide crucial diagnostic indications. The integration of clinical parameters with morphological and functional imaging criteria enables timely and targeted treatment planning.