Mossy Fiber Sprouting in Temporal Lobe Epilepsy: The Impact of Netrin-1, DCC, and Gene Expression Changes.

Background: Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy, often associated with hippocampal sclerosis (HS), which involves selective neuronal loss in the Cornu Ammonis subregion 1 CA1 and CA4 regions of the hippocampus. Granule cells show migration and mossy fiber sprouting, though the mechanisms remain unclear. Microglia play a role in neurogenesis and synaptic modulation, suggesting they may contribute to epilepsy.

DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma.

Background: Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs.

Measurable disease as baseline criterion for response assessment in glioblastoma: A comparison of PET -based (PET RANO 1.0) and MRI-based (RANO) assessments.

Background: Recently, criteria based on amino acid positron emission tomography (PET) have been proposed for response assessment in diffuse gliomas (PET RANO 1.0). In this study, we compare the prevalence of measurable disease according to PET RANO 1.

An AMP-activated protein kinase-PGC-1α axis mediates metabolic plasticity in glioblastoma.

Glioblastoma, the most frequent primary malignant brain tumour in adults, is characterised by profound yet dynamic hypoxia and nutrient depletion. To sustain survival and proliferation, tumour cells are compelled to acquire metabolic plasticity with the induction of adaptive metabolic programs. Here, we interrogated the pathways necessary to enable processing of nutrients other than glucose.

Efficacy of subsequent therapies in patients with advanced ovarian cancer who relapse after first-line olaparib maintenance: results of the PAOLA-1/ENGOT-ov25 trial.

Background: The use of first-line poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is increasing in advanced ovarian cancer. Understanding the efficacy of first subsequent therapy (FST) in patients experiencing disease progression in the first-line setting is important to optimize postprogression treatments. We evaluated the efficacy of FST in patients from PAOLA-1/ENGOT-ov25 (NCT02477644) who received first-line olaparib maintenance.

Atypical chemokine receptor 2 expression is directly regulated by hypoxia inducible factor-1 alpha in cancer cells under hypoxia.

Lack of significant and durable clinical benefit from anti-cancer immunotherapies is partly due to the failure of cytotoxic immune cells to infiltrate the tumor microenvironment. Immune infiltration is predominantly dependent on the chemokine network, which is regulated in part by chemokine and atypical chemokine receptors. We investigated the impact of hypoxia in the regulation of Atypical Chemokine Receptor 2 (ACKR2), which subsequently regulates major pro-inflammatory chemokines reported to drive cytotoxic immune cells into the tumor microenvironment.

How to optimize and evaluate diversity in gynecologic cancer clinical trials: statements from the GCIG Barcelona Meeting.

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups.

Safety and tolerability of mirvetuximab soravtansine monotherapy for folate receptor alpha-expressing recurrent ovarian cancer: An integrated safety summary.

Objective: Mirvetuximab soravtansine-gynx (MIRV) is a novel antibody-drug conjugate targeting folate receptor alpha (FRα), which is overexpressed in epithelial ovarian cancer (EOC), with limited expression on normal tissues. This integrated safety summary sought to characterize the safety profile of MIRV monotherapy in participants with FRα-expressing recurrent EOC.

Methods: Safety data were retrospectively analyzed from 4 clinical studies (phase 1 trial [NCT01609556], phase 3 FORWARD I [NCT02631876], phase 2 SORAYA [NCT04296890], phase 3 MIRASOL [NCT04209855]) that evaluated participants with FRα-expressing recurrent EOC who received ≥1 dose of MIRV 6 mg/kg adjusted ideal body weight every 3 weeks.

How long is long enough? An international survey exploring practice variations on the recommended duration of maintenance therapy with PARP inhibitors in patients with platinum sensitive recurrent ovarian cancer and long-term outcomes.

Objective: There are no data, and thus no consensus, on the optimal duration of poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy for exceptional responders (here defined as progression-free for 5 years or longer) with platinum sensitive recurrent ovarian cancer. The current licence is to continue PARP inhibitors until progression or toxicity; however, international practice varies considerably. The risks of late progression and late-onset myeloid malignancies, defined as occurring beyond 5 years of PARP inhibition, are unknown.

Dual MAPK Inhibition Triggers Pro-inflammatory Signals and Sensitizes BRAF Glioma to T Cell-Mediated Checkpoint Therapy.

BRAF pediatric low-grade gliomas frequently transform into high-grade gliomas (HGG) and poorly respond to chemotherapy, resulting in high mortality. Although combined BRAF and MEK inhibition (BRAFi+MEKi) outperforms chemotherapy, ∼70% of BRAF HGG patients are therapy resistant and undergo unbridled tumor progression. BRAF glioma have an immune-rich microenvironment suggesting that they could be responsive to immunotherapy but effects of BRAFi+MEKi on anti-tumor immunity are unclear.

PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cell in lung cancer brain metastasis.

Background: Lung cancer brain metastasis has a devastating prognosis, necessitating innovative treatment strategies. While chimeric antigen receptor (CAR) T-cell show promise in hematologic malignancies, their efficacy in solid tumors, including brain metastasis, is limited by the immunosuppressive tumor environment. The PD-L1/PD-1 pathway inhibits CAR T-cell activity in the tumor microenvironment, presenting a potential target to enhance therapeutic efficacy.

Impact of metformin, statins, and beta blockers on survival in patients with primary ovarian cancer: combined analysis of four prospective trials of AGO-OVAR and ENGOT/GCIG collaborators.

Objective: The aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer.

Methods: Individual data from three phase III, randomized controlled trials (AGO-OVAR 11, AGO-OVAR 12, and AGO-OVAR 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were classified as ever user if the specific co-medication was documented at least once during the trial, and were compared with never users as controls.

Reproductive outcomes after fertility-sparing surgery for cervical cancer - results of the multicenter FERTISS study.

Introduction: Fertility-sparing treatment (FST) for patients with cervical cancer intends to achieve oncologic outcomes comparable to those after radical treatment while maximizing reproductive outcomes, including the ability to conceive and minimizing the risk of prematurity.

Methodology: International multicentre retrospective FERTISS study focused on patients treated with FST analysed timing of FST relative to pregnancy, conception attempts and methods, abortion rates, prophylactic procedures reducing the risk of severe prematurity, pregnancy duration, and delivery mode.

Results: Of the 733 patients treated at 44 centres in 13 countries, 49.

Epigenetic profiling of prostate cancer reveals potential prognostic signatures.

Purpose: While epigenetic profiling discovered biomarkers in several tumor entities, its application in prostate cancer is still limited. We explored DNA methylation-based deconvolution of benign and malignant prostate tissue for biomarker discovery and the potential of radiomics as a non-invasive surrogate.

Methods: We retrospectively included 30 patients (63 [58-79] years) with prostate cancer (PCa) who had a multiparametric MRI of the prostate before radical prostatectomy between 2014 and 2019.