Embryonal rhabdomyosarcoma (ERMS) predominantly occurs in children; primary cervical ERMS in adults is exceedingly rare and readily misdiagnosed, as its typical presentations-abnormal vaginal bleeding and a cervical mass-closely resemble gestational trophoblastic disease and uterine sarcomas.

We present two cases of high-grade cervical ERMS in reproductive-age women; both presented \with abnormal vaginal bleeding and were diagnosed with stage IVB disease with regional lymph node metastasis at initial admission. Case 1 was complicated by synchronous bilateral pulmonary and multiple osseous metastases, while Case 2 exhibited a massive cervical tumor with extensive lymphatic dissemination. The two patients received distinct multimodal treatment regimens: one underwent primary surgery followed by adjuvant chemotherapy; the other received interventional embolization, neoadjuvant chemotherapy, radical resection, sequential chemoradiotherapy, and exploratory targeted maintenance therapy.

Adult cervical ERMS is highly aggressive and prone to early distant spread. Immunohistochemical markers are mandatory to confirm the rhabdomyogenic origin of this tumor. For patients with advanced disease, multimodal regimens combining neoadjuvant chemotherapy, radical resection (when surgically feasible), and adjuvant chemoradiotherapy may serve as a primary comprehensive approach to potentially prolong overall survival. In patients with actionable somatic alterations identified through comprehensive molecular profiling and formal HRD testing, individualized exploratory targeted therapy may be explored only in highly selected patients. Further clinical investigations are warranted to refine treatment strategies and improve long-term outcomes.

Photodynamic priming (PDP), a fallout of photodynamic therapy, transiently modulates the tumor microenvironment (TME), enhances therapeutic susceptibility, and promotes immunogenic cell death through the release of damage-associated molecular patterns (DAMPs). Pancreatic ductal adenocarcinoma (PDAC) remains non-responsive to current therapies with a desmoplastic and immunosuppressive TME that limits drug delivery and blunts responses to immune checkpoint blockade. We investigated whether PDP could enhance anti-PD1 therapy responses in PDAC using patient-derived organoids (PDOs). PDOs were treated with Visudyne and red light (25, 75, and 100 J/cm²), followed by assessment of cytotoxicity, DAMP expression (HSP60, calreticulin, HMGB1), and transcriptomic changes. Monocyte-derived dendritic cells (mDCs) from healthy donors were cocultured with PDP-treated (25 J/cm²) PDOs, then with matched naïve T cells. mDC and T cell activation markers were analyzed. Pembrolizumab (anti-PD1) was added to PDO-mDC-T cell cocultures to evaluate combined effects on PDO viability and T cell activation. PDP induced dose-dependent cytotoxicity and upregulated DAMPs. Gene profiling in PDOs showed increased IFN-γ, TNF-α, and CXCL12, with reduced PD-L1, TGF-β1, and FOXP1 expression. mDCs exposed to PDP-treated PDOs upregulated CD40, CD86, and MHC-II, driving activation of CD4⁺ and CD8⁺ T cells, evidenced by elevated PD1 expression. Addition of pembrolizumab further decreased PDO viability and amplified effector cytokines (IFN-γ, TNF-α, FASLG, granzyme B, IL-2, IL-21). PDP was associated with modulation of the PDAC TME toward a more immunogenic phenotype by enhancing tumor immunogenicity, activating dendritic cells and T cells, and potentiating PD1 blockade. These findings provide mechanistic support for further preclinical and clinical evaluation of PDP combined with checkpoint inhibition in PDAC.

Presacral neoplasms are rare retrorectal tumors with highly heterogeneous histogenesis and obscure clinical manifestations. Due to their deep anatomical location and non-specific perianal symptoms, they are frequently misdiagnosed as perianal mimics (benign inflammatory anorectal lesions that mimic presacral tumors clinically), leading to delayed intervention, increased malignant progression risk, and compromised oncological prognosis. The present study aimed to identify core H&E-stained morphological features associated with preoperative misdiagnosis of presacral neoplasms, evaluate their value for lowering preoperative misdiagnosis, and establish a practical pathological diagnostic system for clinical oncological practice. A retrospective diagnostic cohort study was conducted in 112 patients with pathologically confirmed primary presacral neoplasms. H&E sections were independently reviewed by senior pathologists, and logistic regression was applied to identify independent morphological features. The impact of standardized H&E morphological criteria on misdiagnosis rate was quantitatively analyzed. The results identified that three independent H&E morphological features correlated with misdiagnosis risk among presacral neoplasm specimens: specific tumor cell morphology (OR = 6.25, 95% CI:2.48-15.76, P < 0.001), cystic/solid mixed architecture (OR = 5.82, 95% CI:2.31-14.65, P < 0.001), and absence of perianal tissue-specific structures (OR = 5.18, 95% CI:2.05-13.08, P < 0.001). After implementation of the standardized diagnostic criteria, the overall preoperative misdiagnosis rate decreased from 29.5% to 10.2% (P < 0.001), and the biopsy-related misdiagnosis rate dropped from 84.8% to 9.1% (P < 0.001). A representative case of presacral gastrointestinal stromal tumor (GIST) was comprehensively demonstrated with integrated imaging, endoscopic, intraoperative, gross, and H&E pathological features. In conclusion, standardized evaluation based on key H&E morphological features helps lower the preoperative misdiagnosis rate of presacral neoplasms. Standardized interpretation of these indicators significantly reduces misdiagnosis, facilitates early oncological recognition, and improves clinical management efficiency. This strategy is particularly suitable for primary and secondary medical institutions and requires prospective clinical verification.

Esophagogastroduodenoscopy (EGD) is a standard method for upper gastrointestinal (UGI) tumor screening. However, differing opinions persist regarding the impact of sedation on the detection rate of early adenocarcinoma of the gastric cardia (EGCA). This study evaluated the effect of sedation on the detection of EGCA, other upper digestive tract early cancer (UDTEC) and microscopic upper gastrointestinal (UGI) lesion detection.

We retrospectively analyzed 313,503 symptomatic and screening patients undergoing EGD (2018-2025) at Zhejiang Provincial Hospital of Traditional Chinese Medicine and Zhejiang Provincial People's Hospital. Histopathological biopsy data defined positive outcomes as EGCA and other UGI early cancers (esophageal, gastric, duodenal). Propensity score matching (PSM) assessed sedation-tumor detection associations. Primary outcomes included UGI precancerous lesions, UDTEC rates, and microscopic tumor yield (lesions/subjects). Secondary outcomes identified detection determinants via logistic regression.

Sedation was associated with modest but statistically significant higher detection rates of EGCA, overall UDTEC and UGI microscopic tumor foci compared with non-sedated EGD (EGCA: p< 0.001; UDTEC: p< 0.001; UGI microscopic tumor lesions: p< 0.001). Univariate/multivariate analyses identified gender, age, title of examining physician, years of practice, and examination time as independent detection predictors. After PSM (198,846 patients in total), sedation remained significantly associated with increased detection of EGCA (OR = 1.400, 95% CI 1.030-1.901, p = 0.026), overall UDTEC (OR = 1.196, 95% CI 1.102-1.295, p< 0.001) and microscopic tumor foci (OR = 6.861, 95% CI 3.278-14.367, p < 0.001).

In this large retrospective cohort study of over 300,000 EGD subjects, sedation was associated with statistically significant but modestly higher detection rates of early gastric cardia adenocarcinoma, upper gastrointestinal precancerous lesions and overall upper digestive tract early cancers. The most prominent benefit of sedation was the improved detection of easily missed microscopic tumor foci. These findings support the consideration of sedation as a quality improvement option to enhance diagnostic yield for subtle early neoplasms, while acknowledging the relatively limited absolute gains in overall detection rates for unselected populations.

Autophagy is a process that diversely impacts the stages of both tumor initiation and progression. Elucidating the molecular mechanisms underlying autophagy and its role in tumorigenesis is a key component of anticancer strategies in both prostate cancer and other malignancies. Because advanced prostate cancer frequently exploits enhanced autophagy as a defense mechanism against therapy-induced stress (e.g., from abiraterone), the pharmacological modulation of miRNA levels presents a tremendous opportunity to block the tumor's escape route and overcome drug resistance.

A comprehensive literature review was conducted to evaluate the molecular pathways determining cancer cell survival and death. The analysis focused on the dual nature of autophagy (functioning as a 'double-edged sword') within the tumor microenvironment, microRNA (miRNA) regulatory networks, and the efficacy of synergistic therapeutic strategies in overcoming treatment resistance.

The primary focus of this paper is the dual and complex role of autophagy, which serves, on the one hand, as a cellular protective shield against metabolic stress-thereby facilitating metastasis-and, on the other hand, as a potential pathway leading to autophagic cell death. The progression of this crucial process is regulated by intricate interactions (crosstalk) with apoptotic pathways, mediated by Bcl-2 family proteins, key kinases (such as mTOR, JNK, and DAPK), and transcription factors, such as p53. Furthermore, the autophagic machinery is precisely regulated by specific miRNA molecules (e.g., miR-21, miR-141, and miR-375). These not only act as crucial intracellular modulators of autophagy but also serve as promising circulating biomarkers, enabling the monitoring of this process's activity throughout disease progression.

Autophagy, and in particular its modulation via miRNA signaling networks, represents a major and highly promising translational target. By directly impairing this autophagic survival mechanism, 'double-hit' combination therapies-integrating autophagy inhibitors (such as hydroxychloroquine or VPS34 inhibitors) with standard antiandrogen or cytotoxic agents-demonstrate promising preclinical potential in overcoming treatment resistance and favorably modulating the immune microenvironment in advanced prostate cancer.

Triphala is a traditional three-fruit formulation with potential anticancer activity, but its ferroptosis-related mechanisms in oral cancer remain unclear. We integrated network pharmacology, transcriptomic analyses, prognostic modeling, Mendelian randomization, immune and drug-response analyses, molecular docking, and in vitro validation to investigate the Triphala-ferroptosis-oral cancer axis. Fifty-eight candidate functional genes were identified, and an eight-gene signature comprising AKR1C3, CA9, EGFR, GSTA1, MAPK8, MGST1, PPARG, and RB1 showed prognostic value across multiple cohorts. Mendelian randomization supported causal associations of MAPK8, MGST1, and PPARG with oral cancer risk. Seven Triphala-derived compounds, including epigallocatechin gallate, quercetin, kaempferol, luteolin, ellagic acid, gallic acid, and quinine, displayed favorable predicted interactions with key targets. In CAL-27 cells, Triphala altered the expression of signature genes, reduced GPX4 and SLC7A11 protein levels, increased Fe²⁺and malondialdehyde, depleted glutathione and glutathione peroxidase activity, and enhanced lipid peroxidation; these effects were partially modulated by ferrostatin-1. This study advances the field by linking Triphala to a ferroptosis-based prognostic framework and experimentally demonstrating its regulation of the SLC7A11-GSH-GPX4 axis in oral cancer.

Head and neck cancers (HNCs) are aggressive malignancies, with recurrence contributing substantially to poor patient outcomes. We used spatial transcriptomics to identify tumour and immune features associated with recurrence.

Pathologist-annotated tumour and stromal regions from recurrent and non-recurrent HNC samples were analysed using spatially resolved transcriptomics. Exploratory differential expression analysis was used to nominate tumour-associated candidate markers for recurrence. Selected candidates were assessed by immunohistochemistry and further evaluated using independent spatial transcriptomic and bulk RNA-sequencing cohorts. Immune-cell abundance and spatial co-localisation were also examined.

PAEP, MARCO, PNPLA3, and FMO2 emerged as leading candidate markers associated with recurrence. Increased expression of PAEP, MARCO, and PNPLA3 was supported by immunohistochemistry. Integrative analysis across independent spatial and bulk RNA cohorts demonstrated consistent PAEP overexpression in recurrent HNC, particularly within tumour regions, with this pattern reproduced across datasets and profiling platforms. Non-recurrent tumours showed a trend towards greater T- and B-cell infiltration, with these populations frequently co-localising within the tumour microenvironment. In recurrent tumour regions, PAEP expression showed an inverse trend with B-cell and plasma-cell abundance, which was higher in non-recurrent samples.

Spatial transcriptomics identified tumour-intrinsic and immune microenvironmental features associated with HNC recurrence. PAEP emerged as the most reproducible candidate biomarker across internal and external cohorts and may be associated with reduced B-cell and plasma-cell infiltration. These findings support further validation of PAEP and related immune signatures for recurrence-risk stratification and personalised treatment.

Circular RNAs (circRNAs) represent key regulators in cancer pathogenesis; however, their involvement in alternative splicing (AS) remains poorly understood.

Expression of circFut8 was detected in bladder cancer (BC) tissues/cell lines; RNA pull-down, cross-linking immunoprecipitation (CLIP) assays verified circFut8's interaction with splicing factor SRSF9. CircFut8 overexpression was performed to assess its effects on BC cell proliferation in vitro (CCK-8, colony formation) and tumor growth in vivo (xenograft models), and its modulation of FUT8 pre-mRNA splicing was analyzed.

Here, we identify circFut8-a conserved exonic circRNA originating from FUT8 gene exon 3-as a BC tumor suppressor, which is significantly downregulated in BC tissues and cell lines, correlating with advanced tumor grade and invasion. Mechanistically, circFut8 competitively binds the splicing factor SRSF9, thereby modulating the inclusion/exclusion of exon 3 in FUT8 pre-mRNA and promoting the production of the FUT8-4 splice variant. Functional assays confirm that circFut8 overexpression inhibits BC proliferation in vitro and suppresses tumor growth in vivo, while RNA pull-down and cross-linking immunoprecipitation (CLIP) assays confirm its direct interaction with SRSF9.

Our findings unveil a novel circRNA-mediated regulatory axis wherein circFut8 fine-tunes pre-mRNA splicing through competition with SRSF9, suggesting its potential as a candidate for further therapeutic exploration.

Although promising results have been obtained for anaplastic thyroid cancer (ATC) therapy, this therapy still needs to be improved. In addition to the currently approved therapies, radiotherapy alone or combined with adjuvant immunotherapy could be beneficial for patients affected by ATC. The patients affected by this aggressive solid malignancy could benefit from the modulation of autophagy in cancer cells. This study focused on detecting autophagy players in ATCs and bursting autophagy process via photon irradiation to induce decay in irradiated ATCs. The transcript expression of autophagy genes was detected in tumor tissue resected from 19 patients and in C643 cells, four primary ATC cell lines and primary follicular thyroid cell line (Nthy-ori-3-1) photons irradiated with 4 or 6 Gy. The protein level of Beclin1 was detected by immunofluorescence in 10/19 patients. The levels of autophagy markers were detected by RT‒qPCR and western blotting in irradiated cells. Autophagy and maturation of autophagosome vesicles were monitored in C643 cells stably transfected with the GFP-RFP-LC3B plasmid. All patients included in the study exhibited significant overexpression of autophagy transcripts. Additionally, the Beclin1 protein was expressed in resected tumor tissue. Furthermore, the analysis of autophagy-related gene transcripts revealed significant increases in the expression of these genes in C643, Patient 2 and Patient 3 cells irradiated with 4 or 6 Gy. Additionally, irradiation with 4 or 6 Gy downregulated the expression of all the proteins involved in the autophagy process. Thus, the ongoing catabolic process was confirmed. Interestingly, the levels of AMPKα and its active phosphorylated form were strongly downregulated, which excluded its involvement in autophagy activation. 6 Gy photon irradiation caused an increase in both green and red fluorescence in C643-derived spheroids. An increase in fluorescence was detectable for up to 28 days. The spheroids gradually exhibited an increase in fluorescence, which probably caused the dismantling of their ultrastructure. This finding provides evidence of the bursting of autophagy and its ability to affect spheroid integrity. Photon irradiation exacerbates autophagy in anaplastic thyroid cancer cells and could represent a valid target for focused therapy against this aggressive malignancy.

Cyanotoxin events are among the most serious consequences of cyanobacterial harmful algal blooms. Microcystins (MCs), among the most prevalent cyanotoxins, are known to adversely affect human health. Recently, respiratory exposure has emerged as an important exposure route for MCs, with potential downstream effects on the gut microbiome through the lung-gut axis. In this pilot study, we investigated acute respiratory immune responses and gut microbiome alterations following MC inhalation using female C57BL/6J mice. Mice were assigned to three dose groups: control (0 µg/kg body weight), medium (25 µg/kg), and high (50 µg/kg). MC-LR was administered intranasally once daily for 3 days. Fecal samples were collected daily for 16S rRNA sequencing, and bronchoalveolar lavage (BAL) fluids were collected following sacrifice for immune cell analysis. MC exposure resulted in significantly increased monocyte counts (p < 0.1), while neutrophil, macrophage, and total cell counts did not significantly change (p > 0.1), suggesting selective lower respiratory tract inflammation. Functional prediction analysis of gut microbiota revealed significant increases (p < 0.1) in pathways associated with host health, including heme biosynthesis, sulfur oxidation, carbon metabolism, and antibiotic resistance. These findings suggest that inhaled MCs may induce respiratory inflammation and contribute to gut microbiome dysbiosis via the lung-gut axis.