Head and neck squamous cell carcinoma (HNSC) remains one of the main causes of cancer-related deaths among male patients with cancer. Although surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy are available, their success in controlling the disease remains limited. Novel targets and therapeutics for HNSC therefore await identification, which is frequently pursued using bioinformatics approaches. Bioinformatics analyses were conducted to evaluate prognosis, differential gene expression, pathways, therapeutics, immunohistochemistry, and expression correlations. Experimental procedures included gene knockdown, proliferation assays, cell cycle analysis, drug treatment, 3D assays, proximity ligation assays, immunoprecipitation, and immunohistochemistry. In the present study, a prognostic factor for HNSC with concordant expression changes was identified. Ring finger protein 149 (RNF149) was shown to predict poor prognosis and to be upregulated during tumorigenesis. Pathway and therapeutic analyses revealed that RNF149-high HNSCs were enriched for cell cycle dysregulation, which might be counteracted by cyclin-dependent kinase inhibitors (CDKi). Cell line experiments validated that RNF149 knockdown in HNSC decreased proliferation and altered the response to CDKi in both 2D and 3D environments. Multi-omics analysis and tissue staining revealed that this ubiquitin ligase might ubiquitinate cyclin-dependent kinase inhibitor 2C (CDKN2C) in HNSC. This regulation was experimentally verified using proximity ligation assays (PLA) and immunoprecipitation. Finally, tissue array staining confirmed a negative correlation between RNF149 and CDKN2C expression in HNSC. This study provides insights into RNF149-mediated proteolysis in HNSC.

Despite advancements in therapeutic agents, cancer treatment, especially for leukemia, is still a formidable challenge for the clinician. The promyelocytic leukemia cell line, HL-60, is widely used for the assessment of the antileukemic potential of new compounds. The current study is designed to investigate the anti-cancer potential of 1,5-diaryl-1,4-pentadien-3-one (DPO) derivatives [Elliptinium Acetate 1, Naphthol AS-BI 2, Alpha-Cyclopiazonic acid 3, Naphthalen-1-yl(1-pentyl-1H-pyrrol-3-yl) methanone 4, and Oxaprozin 5] using cell viability assay and induction of apoptosis. The anticancer activity was checked against the HL-60 cell line using an MTT assay, followed by apoptotic assay, molecular docking, and molecular dynamics (MD) simulation studies. The Desmond simulation package of Schrodinger (v.2022-1) was employed to perform MD simulations analysis. The DPO derivatives reduce the cell viability of HL-60 cell lines. Similarly, the active compounds are tested against a human fibroblast cell line (BJ cells). Compound 2 was noncytotoxic, while compounds 1 and 5 were cytotoxic to the BJ cell line. The apoptotic assay was performed for compound 2, which showed 0.5% necrotic cells, 67.2% early, and 22.6% late apoptosis in HL-60 cells after 24 h of incubation. Molecular docking demonstrated that the tested compound (compound 2) interacted with topoisomerase IIb via hydrophobic interactions. Moreover, the topoisomerase II interacted with several residues within the hydrophobic pocket, including Ile125, Pro126, Val137, and Ile217. The RMSD plots for compounds 1-5 and doxorubicin in complex with topoisomerase IIb indicated stabilization of the topoisomerase IIb complex over time. Naphthol AS-BI 2 exhibits significant antileukemic activity and warrants further investigation to explore its clinical potential in leukemia therapy.

This study evaluated the association between lymph node ratio (LNR) and long-term prognosis in pathological node-positive patients with obstructive colorectal cancer (CRC) who underwent colonic stent insertion as a bridge to surgery. This retrospective multicenter study included 75 node-positive patients with obstructive CRC treated with a colonic stent. Receiver operating characteristic analysis for 5-year relapse-free survival identified an optimal LNR cut-off of 0.125. Patients were thus classified into high-LNR (LNR-H, n=40) and low-LNR (LNR-L, n=35) groups. Clinicopathological factors, surgical outcomes, and survival were assessed. The LNR-H group had a higher median number of metastatic lymph nodes (4 vs. 1; p<0.001), and a lower lymph node yield (21 vs. 27; p=0.022). LNR-H was associated with worse 5-year relapse-free survival (32.0% vs. 60.1%; p=0.012) and overall survival (51.2% vs. 72.7%; p=0.006). Multivariate analysis identified LNR-H (relapse-free survival: hazard ratio=2.371, 95% confidence interval=1.157-4.862; p=0.018; overall survival: hazard ratio=4.301, 95% confidence interval=1.595-11.569; p=0.004) and blood loss as independent predictors of prognosis. LNR appears to represent a practical biomarker, with an elevated LNR independently predicting long-term outcomes among patients with node-positive obstructive CRC undergoing stent placement before surgery.

Ovarian cancer is predominantly diagnosed in the late stages of the disease. Ascites can be collected before the start of neoadjuvant treatment or during the treatment course and may serve as a potential biological surrogate for tumor tissue (TT), representing metastases located in the peritoneal cavity. The minimally invasive nature of ascites collection makes it an alternative to tumor biopsies. The aim was to investigate ascites samples alongside corresponding fresh frozen TT to clarify the potential of ascites in reflecting the genetic composition of TT. Secondly, we wanted to investigate if ascites can be used as biological material for molecular analyses, predicting possible molecular targets associated with FDA-approved drugs. We used next-generation sequencing, natural language processing, and network analysis to assess the recall of genetic variants between corresponding TT and ascites samples in a cohort of 32 patients with ovarian cancer. Patients median age was 68.5 years. Seventy two percent were diagnosed at late stage disease. Overall, the analysis showed that 156 (76%) of the identified variants overlapped between ascites and TT. Ascites had 28 (14%) unique identified variants, while TT had 21 (10%). We identified 25 (76%) pathogenic or likely pathogenic variants in TT that were also present in the corresponding ascites sample. Three variants (9%) were unique for the ascites samples, while five (15%) were unique for the TT samples. We identified all pathogenic and likely pathogenic actionable variants within a clinical perspective in ascites. Clinicians may consider using ascites, particularly for patients with fluid accumulation who are not candidates for surgery at the time of diagnosis.

Breast cancer remains one of the leading causes of cancer-related mortality among women. The molecular heterogeneity of breast cancer, reflected in its numerous subtypes with variable responses to conventional and targeted therapies, necessitates the development of novel therapeutic strategies. Speckle-type POZ protein (SPOP), a substrate adaptor for Cul3-dependent ubiquitin ligase complexes, is frequently downregulated in breast cancer, yet the mechanisms linking SPOP loss to breast oncogenesis are poorly understood. This study aimed to elucidate the role of SPOP deficiency in breast cancer progression and identify potential therapeutic vulnerabilities associated with this molecular context. MCF-7 breast cancer cells were subjected to SPOP knockdown to assess effects on cell proliferation and Sonic Hedgehog (SHH) signaling activity. A natural compound library was screened to identify agents selectively targeting SPOP-deficient cells. Candidate compounds were evaluated for effects on cell viability, GLI3 target gene expression, and clonogenic growth. SPOP knockdown in MCF-7 cells increased proliferation and led to hyperactivation of GLI3-dependent SHH signaling. Screening of the natural compound library identified gossypol as a selective inhibitor of SPOP-deficient cells. Gossypol treatment significantly reduced cell viability, suppressed GLI3 target gene expression and impaired clonogenic growth in SPOP-deficient cells, while exerting minimal effects on control cells. These findings identify a novel oncogenic role for SPOP loss in promoting breast cancer progression via GLI3-dependent SHH signaling. Furthermore, gossypol is highlighted as a potential targeted therapeutic agent for breast cancers characterized by SPOP deficiency.

Bladder cancer is one of the most common urological malignancies, with 5-year survival rates below 40% in advanced cases. Oncologic immunotherapy has become a popular approach to treating cancer and programmed death ligand 1 (PDL1), programmed death ligand 2 (PDL2), intercellular adhesion molecule 2 (ICAM2) and 4-1BB ligand (4-1BBL) are key costimulatory molecules in oncologic immunotherapy. Previous research has shown plant phytochemicals can act as immunomodulators by regulating costimulatory functions to increase T-cell activation and thus to inhibit malignant proliferation. However, the role of Aloe vera in the growth of bladder cancer and in the expression of these key costimulatory molecules has not been elucidated yet. This study is designed to investigate if Aloe vera could have a role in the growth of bladder cancer and if it has any effect on the expression of these key costimulatory molecules in bladder cancer. Clonogenic survival assay and immunohistochemistry (IHC) for PCNA staining were used to evaluate growth of a widely used bladder cancer cell line, T24, in the presence or absence of Aloe vera extract (AE). RT-PCR and IHC were performed to investigate the expression of important costimulatory molecules PDL1, PDL2, ICAM2, and 4-1BBL. Clonogenic survival assay showed a reduction in the percentage of bladder cancer cell colonies, and this result was supported by decreased PCNA staining intensity upon treatment with AE. RT-PCR revealed decreased expression levels of PDL1 and PDL2, which are pro-oncogenic costimulatory molecules and increased expression levels of ICAM2 and 4-1BBL, which are anti-oncogenic costimulatory molecules. Their expression levels were further supported by IHC staining. Aloe vera inhibits bladder cancer growth. Aloe vera upregulates the expression of ICAM2 and 4-1BBL and downregulates the expression of PDL1 and PDL2.

This study aimed to compare the dosimetric parameters of the simultaneous integrated boost (SIB) technique using volumetric modulated arc therapy (VMAT) guided by 99mTc-labeled diethylenetriamine pentaacetate-galactosyl human serum albumin (99mTc-GSA) single-photon emission computed tomography (SPECT) image with those of conventional three-dimensional conformal radiotherapy (3D-CRT). Five patients with diffuse liver metastases underwent 99mTc-GSA SPECT and computed tomography (CT) imaging before RT planning. A SPECT threshold was used for determining the functional liver structure (FLS). The 3D-CRT plan included anterior-posterior opposed beams. The prescribed dose was 8 Gy in one fraction, with a goal of 95% of the planning target volume (PTV), D95, receiving at least 95% of the prescribed dose. The absorbed dose received by 2 cm3 of organ at risk (OAR) volume (D2cc) was below 10 Gy. The VMAT plan comprised two or three arcs. The goals for the PTV and OARs matched those of 3D-CRT. The PTV dose in SIB (PTVboost) defined according to FLS was optimized at an isodose line [~80% of the maximum dose (Dmax)] received at D95 of PTVboost. Two plans were compared using the dose-volume histogram parameters of PTV, PTVboost, FLS, and OARs. Dosimetric parameters including Dmean, Dmax, V110%, and V120% for PTV were significantly higher in the VMAT plan than in the 3D-CRT plan. Likewise, for PTVboost, the VMAT plan had significantly higher values of dosimetric parameters (D95, Dmean, Dmax, V110%, and V120%) than the 3D-CRT plan. The FLS and OAR parameters did not significantly differ between the two plans, except for the spinal cord. 99mTc-GSA SPECT image-guided VMAT planning using SIB allows selective target dose increase in palliative radiotherapy for diffuse liver metastases.

Neuroblastoma (NB) is a primary malignant tumor of the peripheral sympathetic nervous system. Although immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) has emerged as novel antitumor therapy, high-risk NB tumors are refractory to ICI therapy. Oncolytic virotherapy is expected to potentiate the antitumor immune response by inducing immunogenic cell death (ICD). In the present study, we assessed the therapeutic potential of OBP-301 and OBP-702, telomerase-specific oncolytic adenoviruses, for the induction of ICD and combined effect with PD-1 blockade against NB cells. The cytopathic activity of OBP-301 and OBP-702 was assessed using three human MYCN-amplified NB cell lines (IMR-32, LA-N-5, and NB-1) and a murine non-MYCN-amplified NB cell line (Neuro-2a). Virus-mediated antitumor effect was assessed by analyzing cell viability, secretion of extracellular adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1), apoptosis, autophagy, and PD-L1 levels. A subcutaneous Neuro-2a tumor model was used to evaluate the in vivo antitumor effect of combination therapy with OBP-702 and anti-PD-1 antibody. OBP-702 exhibited stronger cytopathic activity, inducing ICD with secretion of ATP and HMGB1, compared to OBP-301 in human and murine NB cells. OBP-301 and OBP-702 increased apoptosis, autophagy, and PD-L1 expression in murine NB cells. Moreover, OBP-702 significantly prolonged the survival of tumor-bearing mice compared to monotherapy with PD-1 blockade. OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors.

Gene therapy has emerged as a promising therapeutic strategy in oncology by targeting the molecular mechanisms that drive malignant transformation. Among gene-based approaches, oncolytic viruses (OVs) are distinctive in their ability to selectively replicate within tumor cells, induce direct oncolysis, and simultaneously stimulate systemic antitumor immunity by exploiting defects in cancer cell antiviral responses. Recent studies have identified Coxsackievirus A11 (CVA11) as a highly potent immunostimulatory OV. CVA11 demonstrates strong tumor-selective replication, robust cytolytic activity, and marked induction of antitumor immune responses. Notably, CVA11 has been shown to induce complete tumor regression in human non-small cell lung cancer models. In addition, CVA11 enhances chemosensitivity in oxaliplatin-resistant colorectal cancer and may have broader applicability in treatment-refractory malignancies, including pancreatic cancer. This review summarizes current gene therapy strategies for malignant tumors with a particular focus on the biological properties and therapeutic potential of CVA11. We discuss its mechanisms of tumor selectivity, immune activation, and potential integration with chemotherapy and gene-based cancer vaccines. Collectively, these findings position CVA11 as a promising next-generation oncolytic virus for cancer gene therapy and immunotherapy.

Real-world data regarding the efficacy of immunotherapy and targeted agents in advanced biliary tract cancer (BTC) remain limited. We evaluated treatment patterns, outcomes, and molecular characteristics in this evolving landscape. We retrospectively analyzed clinical data of patients with advanced BTC who initiated palliative systemic therapy at Chung-Ang University Hospital between March 2022 and February 2025. Genomic profiles were evaluated using next-generation sequencing (NGS), and actionable alterations were defined based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) tier I. Among 85 patients included in the analysis, 43 (50.6%) received second-line chemotherapy, and 16 (18.8%) received third-line or later treatments. Immunotherapy was administered to 56 patients (65.9%) during the treatment course, including 38 (44.7%) who received first-line chemoimmunotherapy. NGS was performed in 51 patients (60.0%), and actionable genomic alterations (ESCAT tier I) were identified in eight patients: ERBB2 amplification (n=4), IDH1 mutations (n=2), FGFR2 fusion (n=1), and deficient mismatch repair (n=1). The most frequently observed mutations were TP53 mutations (n=23, 27.1%), followed by KRAS (n=15, 17.6%) and ARID1A (n=8, 9.4%). The median progression-free survival (PFS) for first-line and second-line chemotherapy was 6.5 months [95% confidence interval (CI)=4.35-8.71] and 2.7 months (95%CI=1.76-3.64), respectively. The median overall survival (OS) was 12.1 months (95%CI=7.64-16.6). Notably, within the NGS-tested cohort, patients treated with matched targeted therapy in the second-line setting demonstrated significantly superior outcomes compared to those treated with conventional chemotherapy (median PFS 9.7 vs. 2.1 months; p=0.012; median OS: 27.7 vs. 11.0 months, p=0.026). The integration of NGS and the subsequent use of matched targeted therapy significantly improved survival outcomes in selected patients with advanced BTC, highlighting the importance of precision medicine strategies.