Multicellular 3D models to study myocardial ischemia-reperfusion injury.

Coronary heart disease is a major global health threat, with acute myocardial ischemia-reperfusion injury (IRI) being a major contributor to myocardial damage following an ischemic event. IRI occurs when blood flow to ischemic tissues is restored and exacerbates the cellular damage caused by ischemia/hypoxia. Although animal studies investigating IRI have provided valuable insights, their translation into clinical outcomes has been limited, and translation into medical practice remains cumbersome.

Impact of HA-PCI on self-reported cognitive functioning and brain metastases in small-cell lung cancer: Pooled findings of NCT01780675 and PREMER trials.

Background: Cognitive decline is an arising concern in patients who need cranial irradiation. We used the pooled longitudinal individual patient data of two phase III trials: NCT01780675 and PREMER to investigate whether hippocampal avoidance (HA)-PCI is associated with improved self-reported cognitive functioning (SRCF) compared with PCI without increasing brain metastases (BM) development within the HA area.

Methods: Patients with stage I-IV small cell lung cancer (SCLC) were randomized to PCI or HA-PCI.

Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients.

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies.

Patients And Methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed.

Acid-exposed and hypoxic cancer cells do not overlap but are interdependent for unsaturated fatty acid resources.

Cancer cells in acidic tumor regions are aggressive and a key therapeutic target, but distinguishing between acid-exposed and hypoxic cells is challenging. Here, we use carbonic anhydrase 9 (CA9) antibodies to mark acidic areas in both hypoxic and respiring tumor areas, along with an HRE-GFP reporter for hypoxia, to isolate distinct cell populations from 3D tumor spheroids. Transcriptomic analysis of CA9-positive, hypoxia-negative cells highlights enriched fatty acid desaturase activity.

Understanding serine and glycine metabolism in cancer: a path towards precision medicine to improve patient's outcomes.

In this perspective, we highlight and reflect on the current knowledge with respect to serine/glycine metabolism in cancer, therapeutic resistance, and precision medicine opportunities for therapeutic targeting and treatment follow-up. Cancer subtypes with high mortality rates include lung cancer and glioblastomas. In order to improve future therapeutic opportunities, patient stratification need to be performed to select patients that might benefit from adjuvant serine/glycine targeting compounds.

Sertraline/chloroquine combination therapy to target hypoxic and immunosuppressive serine/glycine synthesis-dependent glioblastomas.

The serine/glycine (ser/gly) synthesis pathway branches from glycolysis and is hyperactivated in approximately 30% of cancers. In ~13% of glioblastoma cases, we observed frequent amplifications and rare mutations in the gene encoding the enzyme PSPH, which catalyzes the last step in the synthesis of serine. This urged us to unveil the relevance of PSPH genetic alterations and subsequent ser/gly metabolism deregulation in the pathogenesis of glioblastoma.

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.

Silver nanoparticle induced immunogenic cell death can improve immunotherapy.

Cancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift the TME from an immunologically 'cold' to 'hot' tumor and hereby improve current immune checkpoint blockades (ICB). One particular hot topic is the use of combination therapies.

Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial.

Background: The phase II PRIMMO trial investigated a pembrolizumab-based regimen in patients with recurrent and/or metastatic cervical (CC) or endometrial (EC) carcinoma who had at least one prior line of systemic therapy. Here, exploratory studies of the gut microbiome (GM) are presented.

Methods: The microbial composition of 77 longitudinal fecal samples obtained from 35 patients (CC, n = 15; EC, n = 20) was characterized using 16S rRNA gene sequencing.

Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8 T cells to suppress anti-tumor immunity.

Systemic levels of methylmalonic acid (MMA), a byproduct of propionate metabolism, increase with age and MMA promotes tumor progression via its direct effects in tumor cells. However, the role of MMA in modulating the tumor ecosystem remains to be investigated. The proliferation and function of CD8 T cells, key anti-tumor immune cells, declines with age and in conditions of vitamin B12 deficiency, which are the two most well-established conditions that lead to increased systemic levels of MMA.

Antigen targeting and anti-tumor activity of a novel anti-CD146 Pb internalizing alpha-radioimmunoconjugate against malignant peritoneal mesothelioma.

Malignant mesothelioma, a highly aggressive cancer that primarily affects the serosal membranes, has limited therapeutic options, particularly for cavitary tumors, such as peritoneal and pleural malignant mesothelioma. Intracavitary administration of a radioimmunoconjugate to locally target mesothelioma cancer cells has been proposed as a treatment. CD146, upregulated in mesothelioma but not in healthy tissues, is a promising therapeutic target.

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.

Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer.

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.

Trial watch: anticancer vaccination with dendritic cells.

Dendritic cells (DCs) are critical players at the intersection of innate and adaptive immunity, making them ideal candidates for anticancer vaccine development. DC-based immunotherapies typically involve isolating patient-derived DCs, pulsing them with tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs), and utilizing maturation cocktails to ensure their effective activation. These matured DCs are then reinfused to elicit tumor-specific T-cell responses.