Ovarian cancer remains a major cause of mortality in women aged 74 years and under. Dysregulation of the PI3K/AKT/mTOR and NFκB signaling pathways has been associated with poor outcomes and treatment resistance. This study evaluated three potential anticancer agents targeting these pathways: buparlisib (a pan-PI3K/mTORC1 inhibitor), SN32976 (a PI3K p110α inhibitor), and pterostilbene (a resveratrol analogue that downregulates PI3K/AKT and NFκB signaling). Their efficacy was tested in 3D collagen models of ovarian cancer, using SKOV3 and OVCAR8 cell lines, activated by tumor necrosis factor-alpha (TNFα) and lysophosphatidic acid (LPA). Using concentrations derived from 2D assays, viability, collagen gel sizes, secretion of interleukin 6/8 (IL-6/8) and signal pathway proteins were analyzed. All compounds were less effective in 3D models than in 2D cultures, with high cell viability maintained. TNFα and LPA did not significantly alter drug sensitivity, and collagen gel contraction was largely unaffected. While the compounds did not consistently change signaling protein levels, they generally reduced secretion of pro-inflammatory cytokines IL-6 and IL-8. Growth in 3D collagen gels conferred drug resistance on OVCAR8 but not SKOV3 models. Overall, these findings provide preclinical support for further investigation of SN32976 and pterostilbene in ovarian cancer models.

Research on biomarkers reflecting tumor biology and systemic metabolism is crucial for improving the accuracy and personalization of breast cancer (BC) prognosis. We investigated circulating dodecanoic acid in 229 patients undergoing radiotherapy (RT) and assessed its association with progression-free survival and overall survival over six years. Patients were classified into two phenotypes based on post-RT changes in dodecanoic acid: The Increase Phenotype (IP) had lower baseline concentrations and showed a post-RT rise, whereas the Decrease Phenotype (DP) had higher pre-RT levels and declined after treatment. Dodecanoic acid levels were lower in tumors than in peritumoral samples, and their association with phenotypes varied by sampling region, suggesting that systemic changes reflect broader metabolic adaptations rather than local tissue concentrations. Post-RT increases in dodecanoic acid were associated with higher paraoxonase-1 activity, suggesting a link with antioxidant status. Patients in the IP group had a significantly lower risk of progression than those in the DP group, whereas no significant differences in overall survival were observed. These findings highlight the potential utility of dodecanoic acid measurement as a prognostic biomarker and suggest that modulating fatty acid metabolism could be explored as a therapeutic strategy.

Hepatocellular carcinoma is one of the most aggressive malignancies worldwide, with limited treatment options and high resistance to conventional therapies. Developing novel therapeutic strategies that target alternative cell death mechanisms is crucial for overcoming treatment resistance. This study evaluated the cytotoxicity of eight sulfonated silver(I) and gold(I) N-heterocyclic carbene (NHC) complexes-four newly synthesized-against human liver cancer cells and investigated the mechanisms of the compounds that exhibited higher selectivity for cancer cells compared to non-malignant liver cells. Morphological analysis revealed distinct features of autophagy rather than apoptosis, as confirmed by the absence of chromatin condensation, caspase-3 activation, and PARP-1 cleavage. Instead, both complexes strongly upregulated Beclin-1 and LC3-II expression-key autophagy markers-while inhibiting the AKT/mTOR signaling pathway. The observed cytotoxic effects were associated with a significant increase in reactive oxygen species (ROS) production. Pre-treatment with the antioxidant N-acetyl-L-cysteine completely abolished both cytotoxicity and autophagy induction. These findings demonstrate that silver(I) and gold(I) NHC complexes induce ROS-dependent autophagic cell death in this kind of cancer cells. The ability of these compounds to trigger non-apoptotic cell death mechanisms highlights their potential as promising candidates for overcoming apoptosis resistance in HCC therapy, warranting further in vivo investigations.

Jaw cysts are a common, yet diverse group of lesions often detected incidentally during routine dental examinations. While many cysts remain asymptomatic, larger, or aggressive, cysts can lead to significant complications, including tooth displacement, jaw fractures and nerve damage. This article reviews the pathophysiology, classification and management of jaw cysts, focusing on odontogenic cysts, which account for most cases presenting to oral and maxillofacial surgery. Various surgical techniques exist, including enucleation, marsupialisation, decompression, and en bloc resection, each with advantages, limitations, and indications based on cyst size, location, and recurrence risk. We present a case study illustrating a successful outcome using a two-staged treatment approach for a large dentigerous cyst. Selecting the appropriate management strategy requires careful consideration of lesion characteristics, patient factors, and recurrence risk, with the goal of minimising morbidity and optimising patient recovery and long-term outcomes.

Lactate is recognized as a crucial signalling molecule within the tumor microenvironment, where it shapes immune responses by modulating various cell populations, including T cells and macrophages. However, its effect on natural killer (NK) cells, key effectors of early antitumor immunity, remains poorly understood. This study investigates how intratumoral lactate accumulation affects NK cell function in breast cancer, a neoplasm characterized by elevated glycolytic flux. An in-silico analysis of 882 breast cancer patients revealed that high lactate metabolism is inversely correlated with NK cell activation genes and is associated with poor prognosis. To corroborate these findings, NK cells from healthy donors were cultured under lactate-rich or control conditions. Lactate exposure impaired NK cell proliferation, downregulated activation markers and cytotoxic molecules, disrupted mitochondrial bioenergetics, and induced lipid accumulation, as demonstrated by flow cytometry, metabolic profiling, and Raman spectroscopy. Functional assays using microfluidic devices and degranulation tests revealed that lactate-exposed NK cells exhibited reduced chemotaxis and diminished cytotoxicity against MCF-7 and MDA-MB-231 breast cancer spheroids, accompanied by decreased CXCL9 and CXCL10 production. Pharmacologic inhibition of lactate transport, via Syrosingopine or MSC-4381 and AZD3965 combination, restored NK cell cytotoxicity in tumor co-cultures, as shown by increased NK cell degranulation, caspase-3/7-mediated tumor apoptosis, and spheroid shrinkage. Finally, GPR81 deletion mirrored these effects, enhancing NK cell activity. These findings identify lactate as a driver of NK cell suppression and highlight lactate transport and receptor targeting as a strategy to enhance NK cell-based immunotherapies in breast cancer and other lactate-rich tumors.

Osteosarcoma, the most common primary malignant bone tumour, presents significant treatment challenges due to its complex tumour microenvironment and the development of chemoresistance. This study employs single-cell transcriptomics to investigate chemotherapy-induced changes in osteosarcoma at both the cellular and molecular levels. Single-cell RNA sequencing data were analysed to identify cell subpopulations and their responses to chemotherapy. Differential gene expression and pathway enrichment analyses were performed to elucidate chemotherapy-induced changes. Additionally, we developed and validated a predictive model based on pyroptosis-related genes, named Pyroscore, using 101 different machine-learning algorithms. Chemotherapy led to an increased proportion of osteoclasts, endothelial cells, mesenchymal stem cells and pericytes, while decreasing T and NK cells, B cells, chondroblasts, monocytes and macrophages. Chemotherapy markedly upregulates the pyroptosis pathway in tumour cells, suggesting that chemotherapy induces programmed cell death in cancer cells through the activation of pyroptosis. Metabolic pathway analysis revealed significant inhibition of sulphur metabolism, starch and sucrose metabolism, pentose phosphate pathway, inositol phosphate metabolism, nitrogen metabolism and fatty acid metabolism. The Pyroscore model, which incorporates BAK1, CASP1, CASP5 and CASP6, demonstrated robust prognostic value across multiple data sets, with high scores correlating with improved survival outcomes. This study highlights the impact of chemotherapy on osteosarcoma cell subpopulations and the tumour microenvironment. The activation of the pyroptosis pathway and the development of the pyroscore prognostic model provide new insights into the mechanisms of chemotherapy response and potential therapeutic targets. These findings underscore the importance of personalized treatment strategies in improving outcomes for osteosarcoma patients.

Anaplastic Hemangiopericytoma (AHPC), now known as Solitary Fibrous Tumor (SFT) Grade III, is a rare biologically aggressive neoplasm with a high rate of recurrence. Owing to its rarity, the existing literature is limited regarding its clinical characteristics, prognostic factors, management, and treatment strategies. In this study, we evaluate the association between patient demographics, clinical variables, and treatment modalities with overall survival in patients with intracranial AHPC/SFT Grade III.

The National Cancer Database (NCDB) was queried for the clinical and care parameters of patients ≥ 18-years-old diagnosed with AHPC between 2004 and 2017. Multivariable Cox proportional hazards model was implemented to determine factors associated with overall survival.

427 patients were identified with a mean age of 52.6 ± 0.7 years. Most patients were between 40-70 years old (67.0%) with patients ≤ 40-years-old making up 21.3% and those ≥ 70-years-old making up only 11.7%. Overall median survival was 10.8 years. When stratified based on age, those ≤ 40-years-old had increased mean survival compared to those ≥ 70-years-old (10.8 vs. 6.6 years; p < 0.001). On multivariable analysis, increasing age (p = 0.006) and the receipt of chemotherapy was associated with decreased overall survival. In contrast, private insurance and managed care (p = 0.021), treatment with surgery alone (p = 0.003), or combined surgery and radiation therapy (p = 0.001) were independently associated with significantly improved overall survival.

In this NCDB cohort of intracranial grade III SFT/HPC, improved overall survival was associated with younger age, private insurance status, and treatment with surgery alone or surgery combined with radiation therapy. Chemotherapy was not associated with a survival benefit. Interpretation of treatment effects should be cautious, given the potential for selection bias in chemotherapy utilization and the risk of immortal time bias analyses of radiotherapy. Continued advances in therapeutic strategies are needed to further improve survival in this rare and clinically devastating disease.

Acute intestinal obstruction is a common surgical emergency, defined as a partial or complete interruption of the forward flow of intestinal contents. It is associated with significant morbidity and mortality, and timely diagnosis and management are essential. This study aimed to evaluate the causes, clinical presentation, management, and outcomes of patients admitted with intestinal obstruction to Al-Thawra Modern General Hospital, Sana'a, Yemen. A prospective descriptive study was conducted on 105 patients diagnosed with intestinal obstruction between January 1 and December 31, 2024. Patients younger than 10 years or with early postoperative obstruction were excluded. Data on demographics, clinical features, laboratory and radiological findings, management, complications, and outcomes were collected and analyzed using SPSS. Of the 105 patients, 74 (70.5%) were male, with a male-to-female ratio of 2.38:1 and mean age of 45.2 ± 19 years; the 31-60 years age group was most affected (35.2%). Mechanical obstruction accounted for 75 cases (71.5%), while 30 cases (28.5%) were due to intestinal ileus. Adhesions and malignancy were equally the most common causes (21% each), followed by secondary peritonitis (18.1%), hernia (11.4%), and volvulus (15.3%). The majority of patients presented within 3-7 days of symptom onset, although 81% of malignant obstructions occurred in patients aged 19-60 years and often presented after more than 14 days. Conservative management was successful in 13.3% of patients, while the remainder required surgical intervention according to etiology and intraoperative findings. Postoperative complications occurred in 19% of patients, and overall mortality was 14.3%, highest among patients with malignancy, mesenteric ischemia, and obstructed hernia. Mechanical obstruction is the predominant type of intestinal obstruction, with adhesions and malignancy as leading causes. Advanced age, comorbidities, ischemia, and recurrent neoplasm were associated with poor outcomes. Preventive strategies, including reduction of adhesions, elective hernia repair, early cancer screening, and timely surgical intervention, are essential to reduce morbidity and mortality associated with intestinal obstruction.

Inactivation of cyclin-dependent kinase 12 (CDK12) characterizes a subset of prostate cancers but it is not understood how cells adapt to declining activity of this major transcription elongation kinase. To probe this response, we developed a cell line resistant to an inhibitor targeting CDK12 and its paralog, CDK13. CDK13 can compensate for the loss of CDK12, which is why we used the dual inhibitor THZ531. Targeted drug screening of the parental and resistant cell lines revealed cross-resistance to other transcriptional kinases but no clear acquired point of vulnerability. Using genome-wide mapping of mRNA-stabilization based on metabolic labelling of RNA, we report selective mRNA stabilization of factors promoting oxidative phosphorylation in the resistant cells. We go on to show that loss of CDK12 activity enhances ATP production both in cell line models and in patient tumours. Finally, we show that dual inhibition of CDK12/13 results in excessive phosphorylation of the DNA damage H2AX in prostate cancer cells but not in our CDK12/13 inhibitor-resistant model system. In brief, we propose that inactivation of CDK12 rewires cellular energy metabolism to suppress DNA damage.