Oral squamous cell carcinoma (OSCC) remains difficult to treat with current modalities. miR-30c-5p, a tumor-suppressive microRNA frequently downregulated in OSCC, inhibits cancer cell proliferation and migration. However, its clinical application is limited by poor stability and inefficient uptake. To address these issues, miR-30c-5p was encapsulated into chitosan nanoparticles (CS-NPs) using ionic gelation to enhance delivery and protect against degradation.

miR-30c-5p-loaded CS-NPs were characterized for particle size, zeta potential, morphology, and encapsulation efficiency. HSC-3 and OEC-M1 cells were treated with free miRNA, CS-NPs, or CS-miRNA-NPs at final concentrations of 5%, 10%, 25%, and 50% (v/v) in culture medium. Cellular uptake was assessed by confocal microscopy. Ex vivo porcine buccal membrane studies evaluated mucosal penetration. Cytotoxicity was determined using MTT assays, while gene regulation was analyzed via quantitative polymerase chain reaction and Western blotting.

The prepared CS-NPs had particle sizes ranging from 434 to 452 nm and encapsulation efficiencies between 79% and 87%. Confocal imaging revealed significantly greater cytoplasmic uptake of CS-miRNA-FAM NPs versus free miRNA. Ex vivo studies showed that CS-miR-30c-5p-FAM NPs penetrated mucosa up to 80-160 μm with a 5.42-fold higher fluorescence intensity than free miR-30c-5p-FAM. Cytotoxicity testing showed high cell viability (>93%) for all treatments at concentrations ≤25% (v/v). At 50% (v/v) nanoparticle suspension, viability significantly decreased in OEC-M1 cells (84.41% for naked miRNA, 54.52% for CS-NPs, 61.10% for CS-miRNA-NPs; P < 0.001). After 48 h, greater reductions were observed at 50% (v/v), with cell viability in HSC-3 cells decreasing to 85.55% (free miRNA), 42.72% (CS-NPs), and 51.82% (CS-miRNA-NPs), and in OEC-M1 cells to 73.98%, 33.00%, and 39.89%, respectively. Functional assays showed vimentin mRNA reductions of 85% in HSC-3 and 30% in OEC-M1, with protein decreases confirmed by Western blot.

CS-NPs enhance miRNA delivery and gene-silencing efficacy in OSCC cells. These findings support CS-based systems for miRNA therapeutics in oral cancer.

Schwannomas are rare, typically benign tumors arising from Schwann cells. Parapharyngeal space tumors account for only about 0.5% of all head and neck neoplasms, with schwannomas representing ~31% of these. Among these, schwannomas originating from the cervical sympathetic chain (CSC) are particularly rare but clinically important. These tumors grow slowly and often present with vague symptoms such as mild dysphagia, which delays diagnosis. Imaging techniques such as computed tomography (CT) and magnetic resonance imaging aid evaluation. This report presents a rare CSC schwannoma case and reviews 54 others to highlight diagnostic and clinical features.

A 44-year-old Arab female presented with a 4-month history of mild dysphagia and right-sided throat discomfort. Physical examination revealed a smooth, non-tender submucosal bulge along the right lateral pharyngeal wall. Contrast-enhanced CT demonstrated a well-circumscribed, homogeneously enhancing mass in the right paravertebral space, displacing the carotid sheath-radiologically consistent with a schwannoma. The tumor was excised via a transcervical approach and found intraoperatively to originate from the CSC. Histopathology confirmed a benign schwannoma. Postoperatively, the patient developed first-bite syndrome (FBS), managed conservatively with gradual symptom improvement. At 6-month follow-up, she remained asymptomatic with no evidence of recurrence.

Parapharyngeal schwannomas are rare neurogenic tumors that often present with vague symptoms, delaying diagnosis. CSC schwannomas, though uncommon, carry a high risk of postoperative complications such as FBS and Horner's syndrome. Accurate imaging, early recognition, and multidisciplinary planning are essential for safe surgical resection and optimal patient outcomes. This case, alongside our literature review, emphasizes the importance of correlating tumor origin with clinical behavior and postoperative sequelae.

Invasive pleomorphic lobular carcinoma (IPLC) is a rare and aggressive variant of invasive lobular breast cancer, characterized by its distinct histological features and potential for metastatic spread. This case report aims to highlight the diagnostic challenges of IPLC, particularly regarding its imaging and pathological characteristics, and to review the latest treatment protocols.

A 43-year-old female presented with a painless right breast mass that had persisted for 4 months. The breast ultrasound and mammography did not provide an accurate assessment, whereas MRI indicated multiple abnormal signals throughout the right breast, classified as BI-RADS 4c. Surgical intervention and subsequent pathological examination confirmed the diagnosis of multifocal invasive pleomorphic lobular carcinoma with lymph node metastasis.

IPLC presents diagnostic challenges due to its rare and aggressive nature, requiring a high degree of clinical suspicion. This case underscores the importance of comprehensive imaging and pathological assessment for the accurate diagnosis and treatment of IPLC. The standard treatment involves modified radical mastectomy, lymph node dissection, and postoperative chemotherapy.

While prior research linked ZNF468 to radioresistance in oesophageal squamous cell carcinoma (ESCC), its broader role in ESCC progression remained unclear. This study elucidates these functions and underlying mechanisms. Immunohistochemistry on clinical ESCC tissues demonstrated ZNF468 upregulation, which correlated with unfavourable patient outcomes and increased Aurora A expression. In vitro experiments, including assessments of proliferation, apoptosis, migration and invasion, revealed that ZNF468 overexpression enhanced these oncogenic phenotypes in ESCC cells, while its knockdown produced inhibitory effects. These findings were corroborated in vivo using subcutaneous tumour and lung metastasis models. Mechanistically, ZNF468 was found to upregulate AURKA expression, subsequently activating the PI3K/AKT signalling pathway, thereby promoting cell proliferation and epithelial-mesenchymal transition (EMT). Importantly, pharmacological inhibition of AURKA or the PI3K/AKT pathway significantly attenuated the pro-tumorigenic effects driven by ZNF468. Furthermore, AKT was shown to augment ZNF468 protein stability and transcriptional activity, establishing a ZNF468/AURKA/PI3K/AKT positive feedback loop. In conclusion, this study identifies a critical positive feedback mechanism involving ZNF468/AURKA/PI3K/AKT that significantly promotes ESCC progression, underscoring ZNF468 as a potential therapeutic target.

Taxanes and other tubulin-targeting medications are essential for treating advanced malignancies, especially in patients undergoing less aggressive chemotherapy. However, their clinical efficacy is often limited by significant off-target toxicity and adverse side effects. In this study, the synthesis and characterisation of novel steroidal A-ring-fused isoxazoles, which were obtained through iodine-mediated oxidative cyclization of dihydrotestosterone (DHT)-derived α,β-unsaturated oximes, are reported. According to mechanistic studies, the most potent compounds induced mitotic arrest and disrupted cytoskeletal integrity at low micromolar concentrations. The lead compound, 2j, notably increased the rate of tubulin polymerisation in vitro and stabilised polymerised tubulin in the cells, leading to a G2/M block of the cell cycle. Molecular docking studies indicated that 2j is bound preferably to the taxane site on tubulin, forming conserved interactions. MicroScale Thermophoresis was used to further study this binding and showed a nanomolar K_D for 2j. The fact that 2j maintained its activity in docetaxel-resistant prostate cancer cells, demonstrating its ability to circumvent resistance pathways linked to existing therapies with taxane-like drugs, supports its clinical relevance. Therefore, our results encourage additional research and development for its potential therapeutic use in cancer treatment, particularly in resistant cases.

Platinum-based and pyrimidine drugs are first-line treatments for gastric cancer (GC), but their efficacy is often affected by drug resistance. High spalt-like transcription factor 4 (SALL4) expression is associated with poor prognosis, but its role in 5-fluorouracil (5-FU) resistance is not yet clear. In this study, we investigated the effect of SALL4 on 5-FU resistance in GC cells by bioinformatics analysis, real-time quantitative reverse transcription polymerase chain reaction, cell counting kit-8, colony formation assay, and western blot. The results showed that SALL4 was highly expressed in GC and significantly correlated with the fatty acid oxidation (FAO) pathway. Knockdown of SALL4 resulted in a notable attenuation of cellular proliferative capacity and heightened susceptibility to 5-FU resistance in GC cells, while overexpression of SALL4 enhanced 5-FU resistance. Rescue assays confirmed that SALL4 fostered 5-FU resistance in GC cells by enhancing FAO. Our research confirmed that SALL4 promoted the resistance of GC cells to 5-FU by enhancing the FAO pathway. This suggests that drug development targeting SALL4 may help overcome chemotherapy resistance in GC.

BACKGROUND Ectopic adrenocortical adenomas are rare and can produce aldosterone autonomously, causing resistant hypertension and hypokalemia. Atypical locations pose diagnostic challenges. This report describes a 45-year-old man with malignant hypertension and hypokalemia due to an aldosterone-producing ectopic adrenal adenoma located between the pancreas and left adrenal gland. CASE REPORT A 45-year-old man with a 9-year history of poorly controlled hypertension presented with dizziness, vomiting, and fatigue. On admission, blood pressure was 192/110 mmHg and serum potassium was 2.07 mmol/L. Physical examination revealed left ventricular hypertrophy and hypertensive end-organ damage. Laboratory test results showed elevated plasma aldosterone (47.61 ng/dL) and suppressed renin (0.04 ng/mL/h), yielding an aldosterone-to-renin ratio of 1190. Abdominal CT and MRI identified a 3-cm solid cystic mass between the pancreatic tail and lateral branch of the left adrenal gland. Cortisol circadian rhythm, dehydroepiandrosterone sulfate, and plasma metanephrines were within normal limits, excluding other functional adrenal tumors. The patient underwent complete surgical resection of the ectopic adrenal adenoma. Histopathology confirmed adrenal cortical adenoma with focal adrenal medullary hyperplasia. At 1-year follow-up, he had normal blood pressure and serum potassium levels on an antihypertensive regimen. CONCLUSIONS This case highlights a rare ectopic aldosterone-producing adrenal adenoma near the pancreas. A thorough biochemical and imaging workup was essential for diagnosis, and surgical resection achieved clinical resolution. Ectopic adrenal tumors should be considered in the differential diagnosis of resistant hypertension with hypokalemia when standard adrenal imaging is inconclusive.

Hepatocellular carcinoma (HCC), the most common subtype of primary liver cancer, remains a major cause of cancer-related mortality worldwide. Although 2-hydroxy-3-methylanthraquinone (HMA), a natural anthraquinone compound, has demonstrated antitumor activity in various malignancies, its specific role and underlying mechanisms in HCC are not fully understood. This study aimed to evaluate the antitumor effects and molecular mechanisms of HMA in HCC. Human HCC cell lines were treated with HMA, and cell proliferation and apoptosis were assessed using Cell Counting Kit-8 and flow cytometry assays, respectively. A heterotopic xenograft tumor model was established in nude mice to evaluate in vivo tumor growth and weight. Immunohistochemical staining for Ki67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to assess tumor cell proliferation and apoptosis. Network pharmacology analysis was conducted to predict potential targets of HMA in HCC. Quantitative real-time polymerase chain reaction and Western blotting were used to evaluate mRNA and protein expression levels. Cell migration and invasion were assessed using wound healing and transwell assays. Our data revealed that HMA significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion in both HCC cells and tumor tissues. Mechanistically, HMA downregulated Annexin A5 (ANXA5) expression and inhibited activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Silencing of ANXA5 replicated the inhibitory effects of HMA and further enhanced its pro-apoptotic and anti-invasive activities. Conversely, overexpression of ANXA5 restored PI3K/AKT signaling activity and reversed the inhibitory effects of HMA on HepG2 cell proliferation, migration, and invasion. These reversal effects were abolished by treatment with LY294002, a selective PI3K inhibitor. In summary, HMA suppresses the progression of HCC by targeting ANXA5 and inhibiting the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic agent for HCC.

Introduction of immune checkpoint inhibitors (ICI) has improved overall survival (OS) for advanced non-small cell lung cancer (NSCLC). However, responses differ greatly amongst patients. Additional radiotherapy (RT) may promote tumor-specific immunity and synergize with ICI to improve tumor control. The multicenter phase II FORCE trial evaluated safety and efficacy of nivolumab with additional palliative radiotherapy (5 × 4 Gy) as clinically indicated in pre-treated metastatic non-squamous NSCLC (group A, n = 41), including pretreated patients without an indication for radiotherapy in a parallel cohort as real-world controls (group B, n = 60). With an objective response rate (ORR) of 8.3% in group A (n = 41), the primary endpoint was not met (p = 0.991). ORR in group B (n = 60) was 23.8%. Patient characteristics indicated a significantly poorer baseline clinical condition for group A compared to B, including worse Eastern Cooperative Oncology Group (ECOG) performance status (PS, p = 0.020) and more metastatic sites (p = 0.009). Consequently, group A had shorter progression-free survival (median PFS, 1.9 versus 3.7 months, hazard ratio [HR] 1.69 [95% CI (1.10, 2.58)]) and OS (median 6.0 versus 12.6 months, HR 1.75 [95% CI (1.07, 2.84)]). In multivariable analyses for the intention-to-treat (ITT) population, ORR, PFS and OS were inversely associated with the patients' ECOG PS (ORR odds ratio [OR] 0.126, p = 0.004) and correlated positively with tumor PD-L1 expression (ORR OR 12.8, p = 0.022), but not with radiotherapy administration (p = 0.169-0.854). Adverse events were distributed equally in both groups. Addition of palliative radiotherapy to nivolumab was safe and feasible, but not associated with improved efficacy. Patients with an indication for palliative radiotherapy have an inherently worse prognosis which cannot be overcome by radiation-induced immunostimulation. Clinical features and PD-L1 expression influence clinical outcomes more than radiotherapy administration and should be considered when evaluating the effectiveness of immuno-/radiotherapy combinations.ClinicalTrials.gov identifier: NCT03044626.

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and fewer long-term side effects. Dendritic cell (DC) vaccines have been shown to induce tumor specific cytotoxic T-cell (CTL) responses both in vitro and in vivo; however, due to the nature of the disease, resistance to immunotherapy is often developed. Various modifications, such as the implementation of viral vectors, tumor RNA, or even tumor-specific peptides (neoantigens), have been studied as a means to avoid resistance and enhance the effectiveness of the vaccines. In this review, we aim to assess the effects of neoantigen-loaded DC vaccines (naDCVs) on the immune response against gastric cancer cells.

A thorough literature search was conducted on PubMed and clinicaltrials.gov for studies assessing the efficacy of naDCVs against gastric cancer both in vivo and in vitro. The studies were assessed for eligibility by two independent reviewers based on predetermined inclusion and exclusion criteria. The search was completed following the PRISMA guidelines.

Eleven studies were included in our systematic review. In five of the studies, the effects of the naDCVs were tested in vitro; in two and in four they were examined both in vitro and in vivo. The in vitro studies showed that the naDCVs resulted in a more robust immune response against the cancer cells in the study groups compared to the control groups. The in vivo studies conducted on mice showed that tumor volume was reduced in the groups treated with the naDCV compared to the untreated groups. What is more, the cytotoxic effect of CTLs against tumor cells was also increased in the vaccine groups. One of the studies was conducted on humans as a phase I study. The results show increased CTL proliferation and cytokine production in the vaccinated group compared to the control, but no difference regarding the tumor size was observed.

Neoantigen-loaded DC vaccines can stimulate a strong immune response against specific gastric cancer cell peptides and enhance tumor cell lysis, therefore hindering or even reversing disease progression, offering great potential for the treatment of patients with gastric cancer.