Cisplatin (DDP) is a cornerstone chemotherapeutic agent for gastric cancer, yet its clinical application is often limited by severe adverse effects, particularly dose-dependent nephrotoxicity. Quercetin (Que) is a dietary flavonoid widely present in everyday foods such as onions, apples, tea, and broccoli. It has been reported to possess both renoprotective and antitumor properties. This study evaluated the therapeutic potential of combining DDP with Que in gastric cancer treatment. In vitro, CCK-8 assays, flow cytometry, and scratch wound tests were employed to assess the impact of Que on DDP-induced nephrotoxicity and chemosensitivity, while potential mechanisms were investigated through western blot analysis. In vivo, the combined regimen was tested in tumor-bearing nude mice by monitoring tumor growth and renal function. Our results showed that Que alleviated DDP-induced suppression of proliferation and apoptosis in HK-2 cells, indicating protection against nephrotoxicity. In comparison, in AGS gastric cancer cells, Que potentiated DDP-induced inhibition of proliferation and migration, and improved apoptosis. Mechanistically, Que inhibited ERK1/2 activation in both cell types. In HK-2 cells, ERK1/2 inhibition increased c-Myc expression and decreased cleaved caspase-3 levels, whereas in AGS cells, ERK1/2 inhibition reduced c-Myc and MMP-2 levels while elevating cleaved caspase-3 expression. These effects were reversed upon TBHQ treatment. In vivo, Que enhanced the antitumor efficacy of DDP while attenuating its nephrotoxicity. Collectively, these results indicate that Que achieves the abovementioned dual effect via cell type-specific modulation of the ERK1/2 pathway, supporting its potential as an adjuvant for gastric cancer chemotherapy.

Medical objects play a crucial role in diagnosis and treatment, yet the ways in which individuals experience them remain underexplored in medical discourse. With its attention to lived experiences, graphic medicine can humanize and complement a more sterile biomedical perspective. This article analyzes the representation of medical objects and the experiential realities they constitute with reference to Brian Fies's Mom's Cancer (2006). The article traces how stakeholders' interactions with these objects reveal affective, social, and cultural resonances beyond the objects' clinical function. Reading medical objects as mediators of anxiety, authority, and care, this study challenges the conventional framing of medical objects as inert instruments and repositions them as active participants in the ecology of health care.

A 43-year-old woman presented with recurrent hypoglycemia and episodes of loss of consciousness. On admission, her blood glucose was 37 mg/dL (reference range: 70-99 mg/dl), with recovery after intravenous dextrose, fulfilling Whipple's triad. She had a two-year history of dizziness, fatigue, diaphoresis, and neuroglycopenic symptoms, often relieved by frequent soft drink intake, leading to weight gain. She was previously misdiagnosed with a neurologic disorder, resulting in delayed evaluation. Laboratory findings showed elevated serum insulin levels of 65 μU/mL (reference range: 2.6-24.9 μU/mL) during hypoglycemia. Contrast-enhanced CT identified a 1.7 × 1.3 cm mass in the pancreatic body without metastasis. The patient underwent distal pancreatectomy with splenectomy. Postoperatively, hypoglycemic episodes resolved completely. Histopathology confirmed insulinoma. This case highlights the importance of considering insulinoma in patients with recurrent hypoglycemia. Delayed diagnosis may occur due to nonspecific symptoms and misdiagnosis. Careful clinical assessment, basic biochemical testing, and imaging can facilitate timely diagnosis and effective surgical management in resource-limited settings.

Macrophages are highly plastic immune cells with tumor-homing capacity and immunomodulatory functions, making macrophage-based nanoplatforms attractive for cancer immunotherapy. Macrophage-based nanoplatforms include macrophage-derived extracellular vesicles (EVs), macrophage membrane-coated nanoparticles, and live macrophage carriers. The platforms combine the biological properties of macrophages with the advantages offered by nanocarriers to achieve targeted delivery and immune regulation. Beyond serving as delivery vehicles, macrophages can be therapeutically reprogrammed through strategies such as CD47-SIRPα blockade and TLR7/MyD88 pathway activation to enhance antitumor immunity. Despite promising preclinical outcomes, clinical translation of macrophage-based Biomimetic nano-drug delivery systems (BNDDS) remains challenging due to cytokine release syndrome risk, scalable manufacturing limitations, and species differences between animal models and human immunity. The review provides insights into the development and clinical translation of macrophage-based BNDDS for cancer therapy.

Chest wall tuberculosis (TB) is a rare manifestation of extrapulmonary TB and may present a significant diagnostic challenge, particularly in low-incidence TB countries such as the United Arab Emirates. We report two unusual cases of chest wall TB with distinct clinical presentations. The first case presented as a slowly enlarging chest wall mass that clinically and radiologically mimicked a soft-tissue neoplasm and was ultimately diagnosed as giant tuberculous lymphadenitis. The second case presented as a large posterolateral chest wall abscess without evidence of active pulmonary TB. Both patients were managed surgically for diagnostic and therapeutic purposes, and histopathological examination established the diagnosis of chest wall TB. Both patients received a 6-month course of anti-tuberculous therapy with complete recovery. These cases highlight the diverse clinical spectrum of chest wall TB and emphasize that the disease should be considered in the differential diagnosis of chest wall masses and abscesses, even in low-incidence TB settings. Histopathological confirmation remains essential for establishing the diagnosis and guiding appropriate management.

Adolescents and young adults with gynecologic cancer face distinctive psychosocial challenges. We examined associations between character strengths and psychological distress, anxiety, and depression and identified candidate strength-related nodes for future psychosocial research.

This cross-sectional study included 271 participants diagnosed with gynecologic cancer during adolescence or young adulthood. Gaussian graphical models estimated conditional associations and central and bridge nodes. Bayesian networks explored directed probabilistic dependencies under theory-constrained and unconstrained specifications. In silico simulations estimated model-implied outcome changes following hypothetical 1-standard deviation (SD) increases in individual character strengths.

The prespecified character-strength and psychological-outcome communities showed dense within-community and sparse between-community connections. Leadership, Creativity, Curiosity, and Teamwork had the highest strength centrality among character strengths. Psychological distress had the highest bridge strength among psychological-outcome nodes (0.148); Curiosity and Zest had the highest bridge strengths among character-strength nodes (both = 0.112). Results were similar after covariate adjustment. The theory-constrained and unconstrained Bayesian networks each retained 31 directed edges, 28 of which overlapped. The Curiosity-depression dependency was retained in both models, whereas the orientation of the Zest-distress dependency varied by model specification. A hypothetical 1-SD increase in Curiosity corresponded to the largest model-implied decrease in overall outcome severity (-0.230 SD), including depression (-0.306 SD); the model-implied change for Zest was primarily observed for distress (-0.123 SD).

Curiosity and Zest were candidate strength-related nodes with distinct, model-dependent associations with psychological outcomes. These hypothesis-generating findings require confirmation in longitudinal and intervention studies before clinical application.

We report a case of primary intramedullary infantile fibrosarcoma (IFS) in a 4-week-old infant with rapidly progressive cervical myelopathy. Histology showed a spindle cell tumour with diffuse S100 and pan-TRK expression. RNA sequencing identified an RBPMS::NTRK3 fusion. RNA-based clustering and DNA methylation profiling classified the tumour as IFS. Treatment with the TRK inhibitor, larotrectinib, achieved marked clinical and radiological recovery within 1 month, expanding the spectrum of NTRK-rearranged sarcomas and confirming TRK inhibition's efficacy in primary central nervous system IFS.

Triple-negative breast cancer (TNBC) remains an aggressive disease with limited treatment options. Oncolytic adenoviruses represent a promising platform, but their efficacy as single agents is often insufficient. This study examined whether an oncolytic adenovirus co-delivering decorin (DCN) and CD40 ligand (CD40L), designated rAd.DCN.CD40L, could enhance antitumor activity and immune activation against TNBC. Recombinant adenoviruses expressing DCN (rAd.DCN), CD40L (rAd.CD40L), or both proteins were constructed and evaluated in breast cancer cells using cell viability, apoptosis, migration, invasion, and damage-associated molecular pattern (DAMP) release assays. Compared with rAd.DCN or rAd.CD40L alone, rAd.DCN.CD40L triggered greater apoptosis and tumor cell death and elicited more pronounced DAMP release. Co-culture experiments also revealed enhanced dendritic cell function following rAd.DCN.CD40L treatment. For in vivo evaluation, syngeneic 4T1 and EMT-6 subcutaneous tumor models and a 4T1 lung metastasis model were employed. rAd.DCN.CD40L substantially delayed tumor growth and improved survival in tumor-bearing mice. Flow cytometric and histological analyses further confirmed enhanced local and systemic T-cell responses, elevated CD8⁺ T-cell activity, and modulated inflammatory macrophage phenotypes. Mechanistically, western blot analysis showed that rAd.DCN.CD40L may contribute to extracellular matrix remodeling and the down-regulation of the expression of epithelial-mesenchymal transition (EMT)-associated genes. Notably, CD8⁺ T-cell depletion markedly attenuated the therapeutic efficacy of rAd.DCN.CD40L, demonstrating that CD8⁺ T cells are critical functional effectors of tumor control. Collectively, these findings indicate that a DCN- and CD40L-armed oncolytic adenovirus represents a promising combinatorial strategy for TNBC immunotherapy, and warrants further preclinical and clinical investigation.

Tertiary lymphoid structures (TLS) are local immune microenvironments within tumors housing T cells and B cells, are often coordinating anti-tumor immunity and associated with better responses to immunotherapy. Here, we use H&E morphological assessment and multiplex immunofluorescence to analyze surgical tumor specimens from 71 patients with gastric cancer (GC) after treatment with neoadjuvant anti-PD-1 therapy, chemotherapy, and subsequent gastrectomy. We find increased TLS density and area in the muscularis propria of treatment-resistant GCs. These muscularis TLS are structurally and functionally impaired, with increased naïve B cell presence but reduced germinal center B cell infiltration. Mechanistically, PLA2G2A⁺ tumor cells accumulate adjacent to disrupted muscularis TLS, and PLA2G2A treatment in vitro increases differentiation of a fibroblast cell line into PDGFRA⁺ inflammatory cancer-associated fibroblasts (iCAF), which are linked to CXCL14 secretion and recruitment of naïve B cells. In vitro, PLA2G2A also impairs B cell differentiation and induces T follicular helper cell death, potentially contributing to muscularis TLS dysfunction. Taken together, we propose a tumor cell-iCAF-B cell axis disrupting TLS function, with this axis serving as a potential therapeutic target to overcome immunotherapy resistance.

Neuroendocrine cervical carcinoma (NECC) is an aggressive and rare malignancy comprising 0.9-1.5% of cervical cancers. Its molecular basis remains poorly understood, limiting treatment options. A national multicenter cohort survival analysis showed that NECC patients had a 5.17-fold higher death risk than non-NECC patients and demonstrated broad chemotherapy resistance, which was further validated in both NECC cell lines and patient-derived organoids. To identify therapeutic targets, multi‑omics profiling of NECC tumors and matched normal adjacent tissues revealed pronounced DNA replication stress and hyperactivation of homologous recombination repair (HRR). These findings were validated in cells and patient-derived organoids using DR-GFP reporter and pRPA32 assays, suggesting that NECC may be susceptible to PARP inhibitor therapy. NECC cells exhibited moderate PARP inhibitor sensitivity, greater than that of resistant non‑NECC lines but less than that of highly sensitive A2780 cells. However, combining PARP inhibitors with cisplatin/carboplatin did not enhance efficacy, prompting the exploration of alternative combinatorial targets. Multi-omics analysis and in vitro validation identified Bloom syndrome helicase (BLM) as a key factor overexpressed in NECC that modulates PARP inhibitor sensitivity. Further in vitro and in vivo experiments confirmed that combining PARP and BLM inhibitors achieved potent anticancer effects. Mechanistically, cancer-associated fibroblasts (CAFs) infiltration in the tumor microenvironment upregulated the transcription factor E2F1 via IL6, with ChIP‒qPCR verifying that activated E2F1 directly binds the BLM promoter (hg38, chr15:90,715,346-90,717,346) to drive its expression, suppressing PARP inhibitor sensitivity. Our findings establish dual PARP and BLM inhibition as a promising therapeutic strategy for NECC by blocking HRR pathway compensation.