Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, characterized by dysregulated lipid metabolism and therapy resistance, leading to a poorer prognosis than other subtypes. This study investigates the role of the immune checkpoint molecule CD276 in lipid metabolic reprogramming and the regulation of ferroptosis in ccRCC. Clinical sample analysis, in vitro experiments, and animal models revealed that CD276 is significantly overexpressed in ccRCC and positively correlated with an unfavorable prognosis. Mechanistically, CD276 activates the transcription factor sterol regulatory element-binding protein 1 (SREBP1), upregulates the expression of fatty acid synthase (FASN), promotes de novo fatty acid synthesis, and drives lipid accumulation. Concurrently, CD276-mediated lipid metabolic reprogramming suppresses ferroptosis in ccRCC cells by increasing reduced glutathione levels and enhancing glutathione peroxidase 4 activity. In vivo experiments confirmed that inhibiting CD276 significantly suppresses tumor growth and enhances the efficacy of ferroptosis inducers. This study reveals the pivotal role of the CD276-SREBP1-FASN axis in regulating lipid metabolism and ferroptosis in ccRCC, providing a theoretical basis for CD276-targeted therapy combined with ferroptosis induction as a treatment strategy for ccRCC.

Motivated by an ongoing collaboration with clinical oncologists and pathologists, we develop a hybrid partial differential equation-ordinary differential equation (PDE-ODE) framework that captures (i) competition between susceptible and resistant phenotypes, (ii) stromal state switching, and (iii) a clinically realistic open-loop, single-dose therapeutic agent I with diffusion and clearance. Clinical management of solid tumors is increasingly limited by spatial heterogeneity and therapy-induced resistance niches that are difficult to predict from well-mixed models. We establish a rigorous mathematical backbone with forward invariance of the nonnegative cone and global-in-time well-posedness. Exploiting the decoupled drug equation ∂ t I = d I Δ I - γ I I , we prove a long-time reduction during washout and show that the damped base dynamics admit no diffusion-driven (Turing-type) instability. We then formulate a directionality-damping principle: unidirectional (open-loop) sensing yields at most transient focusing, whereas bidirectional (closed-loop) feedback reshapes the effective mobility and produces explicit thresholds separating stable homogeneity, finite-band patterning (resistance niche formation), and aggregation when strong parabolicity is violated. Reproducible simulations corroborate this classification and highlight when flux regularization is required for physical realism.

Recently, the application of Intensity-Modulated Radiotherapy (IMRT) and changes in fractionation schedules have been increasingly introduced in radiotherapy practice for esophageal cancer. However, the extent of their adoption and prevalence in real-world clinical practice remains unclear. This study aimed to describe nationwide trends in radiotherapy for esophageal cancer using a large-scale health insurance claims database.

Using the DeSC database, we identified patients newly diagnosed with esophageal cancer between April 2017 and March 2023. Patients treated with definitive radiotherapy (defined as 25-35 treatment days in patients without distant metastasis) were selected. We analyzed temporal trends in radiotherapy, regional differences, and the incidence of radiation pneumonitis.

Among patients with an identified initial treatment, the proportion of radiotherapy declined from 28.6% in 2017 to 19.6% in 2022. A total of 1,324 patients were included in the definitive radiotherapy group. The use of IMRT increased substantially from 10.7% in 2017 to 44.9% in 2022. Regarding fractionation, treatments of 25-28 days increased from 25.0% to 35.9%, while those of 31-35 days decreased. While CDDP/5-FU remained the dominant concurrent chemotherapy, its proportion declined as other platinum-based regimens increased. Urban facilities showed significantly higher implementation of Image-Guided Radiotherapy (IGRT) compared with rural facilities. The cumulative incidence of hospitalization for radiation pneumonitis at 12 months was 1.5%. The cumulative incidence was not significantly altered by IMRT use (sHR: 0.32, p = 0.13), whereas it was lower in patients receiving IGRT (sHR: 0.39, p = 0.04).

This nationwide study demonstrated increased use of advanced techniques including IMRT and IGRT, and shorter fractionation schedules in radiotherapy for esophageal cancer in Japanese clinical practice.

Low rectal cancer lies deep in the pelvis, close to the pelvic autonomic nerves and urogenital structures. Surgery must therefore balance oncological clearance, sphincter preservation, and functional outcomes. Total mesorectal excision (TME) remains the fundamental oncological principle across open, laparoscopic, robotic, and transanal approaches. A deep, narrow male pelvis, obesity, a very low tumor, fibrosis after neoadjuvant treatment, and restricted distal transection can make transabdominal TME technically demanding. Robotic transabdominal TME (rTME) provides three-dimensional high-definition visualization, wristed instruments, tremor filtration, and a stable operating platform. These features address several limitations of conventional laparoscopy. rTME may therefore be suitable for most patients with mid-to-low rectal cancer when distal dissection and transection remain controllable from above. Against this background, the role of transanal total mesorectal excision (TaTME) should be reassessed rather than dismissed. Current evidence neither renders TaTME obsolete nor establishes a universal advantage across all low rectal cancers. Instead, TaTME is better positioned as a selective technical complement for very low tumors, restricted distal exposure or transection, and composite difficult-pelvis scenarios. At the same time, the development of robot-assisted TaTME (R-TaTME), hybrid TaTME, single-port robotic systems, and flexible transanal platforms offers new technological avenues. These platforms may improve procedural stability and instrument dexterity during transanal surgery. This review reappraises TaTME in the robotic era, focusing on indication refinement, pathological quality, training and quality assurance, functional preservation, and platform development.

Seed brachytherapy treats a range of localized solid tumors, where efficacy and normal-tissue sparing depend on precise dose control. Advancing it from geometry-controlled execution toward autonomous, dose-controlled delivery is obstructed by the irreversibility of implantation: once released, a seed fixes its dosimetric contribution permanently. Errors arising from plan-to-anatomy mismatch, placement imprecision, and limited intraoperative assessment therefore become embedded in the realized dose distribution, beyond postoperative correction. Correction is available only during the procedure, which places the robot in the path from a computed dose strategy to a verified outcome. Real-time imaging aids visualization, yet the feedback it supports falls short in resolution, in latency, or in its coupling to execution, and does not close the loop. This narrative review maps the technologies for robot-assisted closed-loop dose control onto a five-layer control architecture. The architecture is organized around robotic execution as the physical core of the loop (actuation), together with the layers built upon it: intraoperative sensing and anatomical updating (perception); real-time dose computation (computation); adaptive replanning (decision); formal safety assurance (supervision). Each layer has advanced, though none has reached the threshold for clinical deployment. We identify the bottlenecks and propose a roadmap driven by real-time seed localization resolved for orientation, intraoperative contour recovery, near-real-time dose surrogates, irreversibility-aware replanning, and formally verifiable safety architectures. Beyond brachytherapy, these requirements point toward verifiable autonomy in image-guided interventional surgery, where irreversible actions require robotic execution under provable safety guarantees.

Tertiary lymphoid structure (TLS) correlates with improved prognosis in melanoma. The role of solute carrier family 52 member A2 (SLC52A2) in mediating this interplay and influencing melanoma progression remains unclear. Integrated bioinformatics analysis of melanoma datasets (GSE3189, GSE19234, GSE46801, GSE4587, GSE238207, GSE53223) were applied to identify TLS-associated candidate genes. Machine learning was performed to screen key genes validated in independent cohorts and clinical blood samples. In vitro functional assays and in vivo syngeneic models assessed the impact of SLC52A2 knockdown. TLS-related indicators were evaluated by immunohistochemistry, multiplex immunofluorescence (mIF), flow cytometry, and enzyme-linked immunosorbent assay. Furthermore, the downstream pathway of SLC52A2 was identified by bioinformatics analysis. CD8⁺ T cell depletion and pathway feedback experiments were conducted to validate mechanistic dependencies. Herein, SLC52A2 was identified as a key hub gene associated with TLSs. Silencing SLC52A2 significantly inhibited melanoma cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo, reducing Ki67 expression. SLC52A2 knockdown enhanced TLS formation, evidenced by increased CD4/CD20/CD68 infiltration, elevated CD3+/CD8+ T-cell infiltration with enhanced cytotoxic function (granzyme B⁺ and interferon-γ⁺), and upregulated TLS-organizing chemokines. mIF and quantitative TLS scoring confirmed significantly increased TLS abundance and maturity upon SLC52A2 silencing. Depletion of CD8⁺ T cells reversed both the TLS enhancement and the tumor-suppressive effects induced by SLC52A2 silencing. Mechanistically, interleukin (IL)- 17 signaling pathway was screened as the downstream pathway of SLC52A2. Experimentally, SLC52A2 knockdown reduced IL-17A/IL-17RA protein levels, and IL-17 receptor antagonist LY3509754 exhibited the anti-tumor role in vitro. Collectively, SLC52A2 drives melanoma progression by inhibiting TLS-mediated anti-tumor immunity and activating the IL-17 pathway, positioning SLC52A2 as a promising therapeutic target for melanoma.

BRAF V600E-mutated metastatic colorectal cancer (mCRC) is a biologically distinct subtype characterized by right-sided predominance, frequent overlap with serrated-pathway biology, and historically poor outcomes with conventional chemotherapy. Therapeutic progress has been driven by the recognition that BRAF inhibition alone is inadequate in colorectal cancer because adaptive epidermal growth factor receptor (EGFR)-mediated feedback rapidly restores MAPK signaling.

This narrative review evaluates the clinical development and practical integration of BRAF-targeted therapy in BRAF V600E-mutated mCRC, with particular emphasis on first-line treatment, MMR/MSI status, patient fitness, and treatment sequencing in the post-BREAKWATER era.

Combined BRAF and EGFR inhibition established encorafenib plus cetuximab as a standard option after prior therapy. The phase 3 BREAKWATER program has now moved BRAF-targeted treatment into first-line practice by demonstrating improved outcomes with encorafenib plus cetuximab combined with fluoropyrimidine-basedchemotherapy, including mFOLFOX6 and FOLFIRI backbones. These data define a chemo-targeted approach for fit patients with non-MSI-H/dMMR disease. For MSI-H/dMMR tumors, first-line immune checkpoint blockade should be prioritized irrespective of BRAF V600E status unless immunotherapy is absolutely contraindicated.

Important uncertainties remain regarding whether BRAF/EGFR targeting should be added to immunotherapy in MSI-H/dMMR disease, as well as the management of frail or oxaliplatin-ineligible patients, maintenance therapy, local treatment integration, and sequencing after frontline encorafenib exposure. Treatment selection in the post- BREAKWATER era should therefore integrate molecular context, patient fitness, and remaining evidence gaps.

Obesity is an established risk factor for breast cancer and is associated with alterations in gut microbial composition. We evaluated associations among body mass index (BMI), breast density, gut microbial diversity and composition and microbial functional pathways in women undergoing surgery for benign, high-risk/non-invasive, and invasive breast disease.

Preoperative stool samples were collected from 131 women (median age 59) with benign (n = 23), high-risk/non-invasive (n = 47), or malignant (n = 61) disease. Shallow shotgun metagenomic sequencing was performed. Taxonomic profiling used Sourmash 4.2.4 (GTDBv207 reference database); functional profiling employed HUMAnN 3.6 with gene families mapped to MetaCyc pathways.

α-diversity differed across diagnosis groups and inversely correlated with increasing BMI (Inverse Simpson p = 0.025). β-diversity differed by diagnosis group and BMI. No significant differences in diversity were observed based on age, menopausal status or mammographic breast density. BMI was also associated with enrichment of Dorea, Blautia, and Streptococcus species. Functional pathway profiling showed greater relative abundance of genes involved in NAD biosynthesis, folate metabolism, and aromatic amino acid metabolism pathways with higher BMI. Cross-referencing the most significant taxonomic and functional pathway findings suggested enrichment of Blautia species, via tryptophan metabolism, might link to NAD biosynthesis.

In this study of women with benign, high-risk/non-invasive, and invasive breast disease, BMI was associated with distinct differences in gut microbial taxonomy and functional pathway profiles. These hypothesis-generating findings provide a rationale for future study to determine how the obesity-associated microbiome contributes to breast cancer development.

Not applicable.

To map and synthesize the available scientific evidence supporting the effectiveness and safety of endodontic therapy in patients who underwent head and neck radiotherapy, considering clinical and radiographic outcomes and treatment-related complications, particularly osteoradionecrosis (ORN).

This scoping review followed the Arksey and O'Malley framework, informed by the Joanna Briggs Institute Manual for Evidence Synthesis, and was reported according to PRISMA-ScR guidelines. Comprehensive searches were conducted in PubMed, Embase, Scopus, Web of Science, MEDLINE, LILACS, and gray literature sources, with no date restrictions. Clinical studies evaluating endodontic therapy in irradiated patients were included. Data were charted and narratively synthesized using a Population-Concept-Context framework. Consistent with scoping review methodology, no critical appraisal was performed.

Of 174 identified records, five studies met the inclusion criteria. Reported success rates ranged from 18 to 100%, with lower rates observed in earlier studies employing outdated techniques. More recent investigations demonstrated high clinical success, improved radiographic stability, and no reported cases of ORN. Across all studies, endodontic therapy was not associated with ORN. However, methodological heterogeneity was noted, particularly regarding outcome definitions and follow-up duration.

Endodontic therapy appears to be a safe and conservative treatment option for patients with head and neck cancer who underwent radiotherapy and may reduce the need for invasive procedures associated with ORN risk. However, the limited and heterogeneous evidence highlights the need for well-designed prospective studies to support standardized clinical decision-making within supportive oncology care.

The increasing role of molecular testing in thyroid pathology, from the pre-operative stratification of indeterminate fine-needle aspiration (FNA) categories to the management of advanced carcinomas, has prompted the development of institution-specific custom NGS solutions as a locally deployable alternative to centralized tests. The aim of the present study is to validate a new custom NGS panel dedicated to the molecular analysis of routine thyroid pathology specimens. The panel was evaluated on thyroid cancer cell lines, 124 FFPE thyroid tissue specimens, and 43 FNA samples. Nexthyro 2.0 achieved a high sequencing success rate on both histological (100%) and cytological (95.3%) material, with analytical sensitivity down to 0.5% dilution point. Mutational profiles across thyroid neoplasm histotypes and FNA categories were consistent with established molecular-morphological correlates. Nexthyro 2.0 represents a reliable local solution for thyroid molecular testing across cytological and histological specimens encountered in routine clinical practice.