Cíl: Prezentovat vzácný případ částečného molárního těhotenství implantovaného do jizvy po předchozím císařském řezu a shrnout literaturu. Kazuistika: Žena, 33 let (gravida 5, dva předchozí císařské řezy, dva spontánní potraty), se dostavila s vaginálním špiněním a bolestmi v podbřišku v 6. týdnu těhotenství. Transvaginální ultrasonografie odhalila v místě jizvy po císařském řezu gestační váček o rozměrech 28 × 19 mm, který obsahoval 4-mm plod s pozitivní srdeční aktivitou. Pod ultrazvukovým dohledem byla provedena vakuová kyretáž. Deset dní po zákroku vzbudily rostoucí hladiny beta-hCG v séru a přetrvávající cystická masa na ultrazvuku podezření na molární těhotenství. Byla podána jednorázová systémová dávka methotrexátu. Histopatologie potvrdila částečné molární těhotenství. Hladiny beta-hCG v séru pacientky se normalizovaly do 8 týdnů. Závěr: Částečné molární těhotenství v jizvě po císařském řezu je extrémně vzácný stav, který se může projevovat vaginálním krvácením a bolestí v pánvi. Včasné rozpoznání pomocí ultrazvuku a laboratorního vyšetření v kombinaci s včasnou intervencí včetně kyretáže a léčby methotrexátem mohou vést k úplnému vyřešení. Lékaři by měli tuto diagnózu zvážit u pacientek s předchozími císařskými řezy, aby zajistili optimální výsledky.

The aim of this case report is to present the impact of multimodal prehabilitation on the quality of life, cognitive performance, physical fitness, and nutritional status in a patient with advanced ovarian cancer.

A 74-year-old woman with high grade serous ovarian carcinoma pT3bN1a was scheduled for radical surgery following three cycles of neoadjuvant chemotherapy. She underwent a three-week intensive multimodal prehabilitation program in a 4/7 regimen involving physiotherapy, occupational therapy, nutritional counselling, psychological support, and supervision by a rehabilitation physician. The effect was evaluated using functional and cognitive tests, stress and disability scales, and body composition analysis (InBody).

Improvement was observed across all major domains: reduction in disability (WHODAS 20 ® 5%), enhancement of cognitive function (MoCA 22 ® 25), decreased perceived stress (PSS-10 17 ® 11), reduction in frailty (FI 3 ® 1), and restoration of full independence in activities of daily living (Katz Index 6/6). Physical performance showed marked gains (6MWT +42 m, 5×SST -6.5 s, handgrip strength +4 kg), while pulmonary function tests confirmed improved ventilatory capacity (FVC, FEV1, PEF). Nutritional assessment indicated a reduced risk of malnutrition according to the MUST screening tool, although bioimpedance analysis demonstrated a mild increase in total body fat and visceral adipose tissue.

Intensive multimodal prehabilitation positively influenced the patient's psychosensory-motor potential, reduced disability, enhanced perioperative fitness, and confirmed its indispensable role in oncogynecology.

Complete mesocolic excision (CME) may increase lymph node retrieval and provide a more complete oncologic excision compared with D2 dissection, although its perioperative safety remains uncertain. This systematic review and Bayesian meta-analysis compared clinical and operative outcomes between CME and D2 in right colectomy.

PubMed, EMBASE, and Cochrane Central were searched through November 2025. Randomized controlled trials comparing CME with D2 were included. Frequentist analyses used random-effects models with DerSimonian-Laird estimation. Bayesian random-effects models applied weakly informative priors (binary outcomes: log[RR] ∼ N(0, 1.5²), τ ∼ Half-Normal(0.5); blood loss: μ ∼ N(0, 100²), τ ∼ Half-Normal(100); lymph node yield: μ ∼ N(0, 6²), and τ ∼ Half-Normal(3)). Heterogeneity was assessed using I² and Cochran's Q. Analyses were conducted in R (v4.4.2) with bayesmeta.

Three randomized trials (1378 patients; CME 678, D2 700) met inclusion criteria. CME resulted in higher lymph node harvest (MD + 3.9; 95% CI: 2.8 to 5.0; P < .001) and longer operative time (MD + 11.6 minutes; 95% CI: 6.6 to 16.7; P < .001). No significant differences were found in blood loss, overall complications, severe complications, intraoperative complications, conversion, or 30-day mortality. Bayesian modeling provided very strong evidence for increased nodal yield (P[CME > D2] = 99.1%) and hemostatic equivalence (P[equivalent ± 50 mL] = 95.9%), with a modest probability favoring fewer severe complications (P[RR < 1] = 82.9%).

CME offers superior oncologic radicality, reflected by higher lymph node retrieval, while maintaining perioperative outcomes equivalent to D2. Bayesian evidence reinforces CME as an effective and safe surgical strategy for right-sided colon cancer.

Metabolic reprogramming is a key cancer hallmark, with dysregulated fatty acid metabolism critical for tumorigenesis and progression. The acyl-CoA synthetase long-chain (ACSL) family (ACSL1-ACSL6) catalyzes ATP-dependent activation of long-chain fatty acids into acyl-CoA, a bioactive intermediate in lipid synthesis, β-oxidation, membrane biogenesis, and signal transduction. Dysregulated ACSL expression is widespread in malignancies, but their non-metabolic functions (ferroptosis regulation, tumor immune microenvironment remodeling) and translational potential of targeted therapies remain to be systematically summarized.

This narrative review comprehensively synthesizes existing literature on the biological functions of ACSL family members in cancer. We retrieved and analyzed studies focusing on ACSL-mediated lipid metabolic reprogramming, ferroptosis modulation, and immunomodulatory effects, with particular emphasis on isoform-specific mechanisms and the context-dependent roles (pro-tumorigenic or tumor-suppressive) of the ACSL family across different cancer types. Additionally, we summarized emerging therapeutic strategies targeting ACSL isoforms and their translational potential.

ACSL isoforms exert distinct context-dependent effects:ACSL1 promotes immunosuppressive TIME via M2 macrophage polarization;ACSL3/4 have antagonistic roles in ferroptosis;ACSL5 exerts dual effects via lipid metabolism, apoptosis, and immunity;ACSL6 involves autophagy and hematological malignancies. Dysregulation correlates with tumor progression, drug resistance, and immunotherapy response, while emerging ACSL-targeted drugs show substantial translational potential.

The ACSL family serves as a key regulatory node integrating lipid metabolism, ferroptosis, and tumor immunity. Its isoform-specific mechanisms and context-dependent characteristics highlight its potential as a precise therapeutic target. Future research should focus on optimizing isoform-selective inhibitors, clarifying their synergistic effects with existing therapies (e.g., immune checkpoint inhibitors, radiotherapy), and validating their translational efficacy through clinical trials to advance the development of innovative cancer treatment strategies.

Pediatrics often faces ethical challenges when families request unproven therapies. We respond to a clinical case described in "A Parental Request for an Unproven Treatment for a Rare Pediatric Cancer: Sound Reasons for Not Going Off-Label," by Margot Hedlin and Louis Voigt, in the same issue of this journal. The case concerns Natalie, a three-year-old in remission from ependymoma, whose parents requested metformin to prevent recurrence. Although Natalie's neuro-oncologist opposed the use of the drug, its favorable safety profile, pediatric Food and Drug Administration approval for other indications, emerging evidence in cancer research, and endorsement by a specialist support careful consideration. Off-label prescribing is common in pediatric oncology due to issues presented by rare diseases and due to the limitations of clinical trials. With informed consent, monitoring, and interdisciplinary input about the patient's care, prescribing metformin may be ethically justifiable despite uncertain efficacy. This case illustrates the balance between evidence-based practice, patient- and family-centered care, and the realities of pediatric cancer treatment.

CAR-T therapy has revolutionized treatments for many hematologic malignancies, but it has shown far less efficacy against solid tumors. One reason for this lower efficacy in solid tumors is increased antigen heterogeneity. This study utilizes a ligand-based CAR-T approach, which allows targeting of multiple receptors by a single ligand. A high expression of the ligand oncostatin M's (OSM) receptors, oncostatin M receptor (OSMR), and/or leukemic inhibitory factor receptor (LIFR) were noted in osteosarcoma cell lines and patient samples. Osteosarcoma is a bone cancer where treatment options have been stagnant for close to 40 years. Thus, this study explores the therapeutic potential of OSM ligand-based CAR-T cells against osteosarcoma.

Third-generation CAR-T cells expressing human OSM on their surface were created, with the surface expression of OSM confirmed by flow cytometry. Co-incubation of OSM CARs and osteosarcoma in vitro was performed, with cell death assessed via Incucyte and PI detection by flow cytometry. CAR-Ts were injected i.v. into mice with osteosarcoma cell line xenografts, and metastatic osteosarcoma. New patient-derived samples were tested for OSMR and LIFR expression and vulnerability to OSM CAR T cells. A new PDX model (named KKOS) from a patient with metastatic treatment-resistant osteosarcoma was characterized and tested for its susceptibility to OSM CAR T cells. All cytotoxic in vivo experiments were performed with n=3-6 mice per group per experiment.

OSM-CAR-T cells displayed cytotoxicity against osteosarcoma cell lines and patient samples expressing either one of OSM's receptors in vitro and in vivo. Large increases in cytokine release, specifically IFNγ, were noted in a target-specific manner. One injection of OSM-CAR-T cells intravenously reduced tumor burden in two different mouse xenograft models. A similar anti-tumor effect was also noted in a metastatic model and a mouse model with multiple implanted KKOS tumors.

Human ligand-based OSM CAR-T cells displayed anti-tumor effects against multiple osteosarcoma cell lines and patient samples. These effects were demonstrated in vitro, in xenograft models, and against a model simulating metastatic disease. Overall, this data supports the continued study of OSM-CAR-T cells as a new therapeutic avenue for osteosarcoma.

TNF Receptor Superfamily Member 19 (TNFRSF19) has been implicated in the advancement of several types of cancer. However, its function and mechanism in cervical cancer (CC) remain unclear. Additionally, while ER stress is proposed as a therapeutic target in cancer, its relationship with TNFRSF19 in CC is unknown. This study aimed to investigate the role and underlying mechanisms of TNFRSF19 in CC. The expression of TNFRSF19 was investigated utilizing the GEPIA database and subsequently validated in 35 paired clinical CC tissue samples. The impact of TNFRSF19 overexpression on cellular proliferation, apoptosis, and endoplasmic reticulum (ER) stress was evaluated in C33A and HeLa cell lines through CCK-8 assays, colony formation assays, and flow cytometry. The interaction between TNFRSF19 and LGR5, along with its inhibitory effect on the Wnt/β-catenin pathway, was analyzed using co-immunoprecipitation (Co-IP), immunofluorescence, and western blotting techniques. Additionally, an in vivo xenograft tumor model in nude mice was developed to substantiate the tumor-suppressive function of TNFRSF19. TNFRSF19 expression was significantly reduced in CC tissues and cell lines. TNFRSF19 overexpression substantially inhibited cell proliferation and colony formation, and induced apoptosis in vitro, while also suppressing tumor growth in vivo. Mechanistically, TNFRSF19 facilitated apoptosis through the activation of ER stress and directly interacted with LGR5 to inhibit the LGR5/Wnt/β-catenin pathway. The pro-apoptotic and tumor growth-inhibitory effects induced by TNFRSF19 were diminished by the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Moreover, the inhibitory effect on cell proliferation mediated by TNFRSF19 was effectively reversed upon the restoration of LGR5 expression. This study demonstrates that TNFRSF19 functions as a novel tumor suppressor in CC by activating ER stress and inhibiting the LGR5/Wnt/β-catenin pathway, highlighting its potential as a therapeutic target for CC treatment.

Pyroptosis, which rapidly releases cellular contents through pyroptotic pores, is an ideal method for inducing in situ cancer vaccines, evoking systemic antitumor immunity, and suppressing primary and metastatic tumors. However, the clinical translation of pyroptosis-based therapy is hindered by the inability to spatially control the activation of inert precursors and the inefficient catalytic activity of nanozymes, which often fail to generate sufficient reactive oxygen species for effective treatment. To address this, we designed a conductive coordination nanozyme prodrug, Cu-DHN. Its π-conjugated polyphenol backbone functions as an intrinsic "electron highway," enabling rapid electron shuttling to utilize the entire nanoparticle volume for catalysis, thereby achieving exceptional peroxidase-like activity. Upon systemic administration, Cu-DHN remains inert in circulation but is precisely activated within the tumor microenvironment by a tandem GSH-depletion and H₂O₂-responsive logic gate. This triggers a self-cascade reaction that locally transforms the coordinated prodrug into juglone, which concurrently reverses gasdermin D epigenetic silencing and activates the NLRP3 inflammasome for caspase-1-mediated cleavage. This single-agent, tumor-specific initiation of pyroptosis, augmented by concomitant cuproptosis, elicits potent immunogenic cell death and robust systemic antitumor immunity, effectively suppressing primary and metastatic tumors while exhibiting a pristine safety profile. Our work establishes electron-shuttling coordination polymers as a versatile platform for developing safe and potent catalytic immunotherapies.

Nanoparticle-based phototherapy represents a paradigm shift in precision medicine, harnessing light-activated mechanisms to modulate cellular pathways across a spectrum of diseases. By integrating nanoparticles, phototherapeutic modalities achieve enhanced light absorption and improved targeting and amplification effects, such as reactive oxygen species generation in photodynamic therapy and localized heating in photothermal therapy. Gold nanoparticles and hybrid constructs have attracted considerable attention in both photothermal and photodynamic therapies, while delivery platforms, such as liposomes and dendrimers, fine-tune biodistribution and release kinetics. At the molecular level, phototherapy induces oxidative stress, triggers apoptotic and autophagic cascades and modulates immune responses by altering cytokine profiles and T-cell activity processes, which are critical not only in cancer therapy but also in managing various chronic conditions, including cardiovascular, neurodegenerative, metabolic and autoimmune disorders. In this review, we chart the evolution of nanoparticle-based phototherapy systems by examining their core components, classification schemes and delivery platforms that drive treatment specificity. We then dissect the underlying signaling pathways, highlighting how light-triggered interventions intersect with key molecular networks in chronic disease contexts. Additionally, we critically evaluate FDA-approved agents and insights from recent clinical trials, outlining the major challenges to clinical translation, including nanoparticle optimization, efficient light delivery and regulatory hurdles. By integrating molecular insights with clinical advancements, nanoparticle-based phototherapy has emerged as a transformative, noninvasive strategy poised to revolutionize therapeutic approaches for a wide range of diseases.

Immunogenic cell death (ICD) converts dying tumor cells into an endogenous vaccine, but clinically applicable pyroptosis-inducing agents remain scarce. Penicillide (PEN), a fungal metabolite, has not previously been examined for anticancer activity. PEN elicits potent, concentration-dependent cytotoxicity across six human cancer cell lines by triggering pyroptosis rather than apoptosis, necroptosis, ferroptosis, or autophagy. Electron microscopy observations showed that PEN causes noticeable damage to the cell membrane. PEN activates the canonical NLRP3/caspase-1/GSDMD axis, as evidenced by marked up-regulation of NLRP3, CASP1, and GSDMD transcripts, accumulation of cleaved GSDMD, and rescue of viability by their specific inhibitor and GSDMD siRNA. Mechanistically, PEN induces mitochondrial hyperpolarization followed by depolarization, depletes reduced glutathione, elevates malondialdehyde and reactive oxygen species, and activates NF-κB signaling via IκBα degradation and p65 nuclear translocation; all cytotoxic effects are reversed by the ROS scavenger N-acetylcysteine or the thiol-reducing agent dithiothreitol. PEN-treated cells exhibit hallmark features of immunogenic cell death-surface calreticulin exposure, nucleocytoplasmic HMGB1 translocation, and extracellular ATP release-and function as an effective prophylactic vaccine in Balb/c mice, delaying tumor outgrowth and augmenting intratumoral CD8⁺ cytotoxic T lymphocyte and CD11c⁺ cell infiltration. These findings establish PEN as a novel pyroptosis-inducing agent that couples oxidative stress and NF-κB signaling to elicit robust antitumor immunity, offering translational potential for ICD-based cancer immunotherapy.