valproate semisodium (Depakote ER / divalproex ER)

Clinical impact of 18F-FES PET/CT-detected ER-positive conversion in metastatic breast cancer with ER-negative primary tumors.

Feng Sanxing S, Xie Yizhao Y, Liu Cheng C, Li Yumeng Y et al.

Receptor discordance between primary and metastatic breast cancer is increasingly recognized and may influence treatment decisions in metastatic breast cancer (MBC) patients. 18F-fluoroestradiol (18F-FES) PET/CT enables non-invasive whole-body assessment of estrogen receptor (ER) expression and may provide additional information beyond tissue-based evaluation. This study aimed to investigate the clinical significance of 18F-FES-positive conversion in patients with MBC whose primary tumors were ER-negative, and to evaluate the potential role of 18F-FES PET/CT in treatment stratification. This retrospective study screened 1330 patients with metastatic breast cancer who underwent 18F-FES PET/CT, identified 51 patients with ER-negative primary breast tumors, and finally included 40 evaluable patients in the analysis. 18F-FES positivity was defined by focal uptake visually distinguishable from local background together with a lesional SUVmax ≥ 1.8. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. 18F-FES-positive conversion occurred in 37.5% (15/40) of patients. Primary progesterone receptor (PR) positivity was more frequent in patients with 18F-FES-positive conversion than in those without conversion (60.0% vs. 24.0%; P = 0.042). After imaging, endocrine-based therapy predominated among patients with 18F-FES-positive conversion whereas chemotherapy was more common in 18F-FES-negative patients. Patients with 18F-FES-positive conversion showed significantly longer PFS than those remaining 18F-FES-negative (median PFS, 15.2 vs. 7.3 months; P = 0.005). ER-positive conversion assessed by 18F-FES PET/CT can occur in clinically selected patients with metastatic breast cancer and ER-negative primary tumors. 18F-FES PET/CT may provide clinically meaningful information for treatment stratification in this patient population.

ASO Author Reflections: Can We Preserve Fertility without Compromising Oncologic Outcomes?: Preoperative Oncofertility for ER-Positive Breast Cancer.

Chen Jennifer H JH, Peregrin-Alvarez Irene I, Warneke Carla L CL, McKenzie Laurie J LJ et al.

A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer.

Zheng Yang Y, Cheng Caleb C, Cao Yizhi Y, Cruz Gabriel G et al.

Neuroendocrine prostate cancer (NEPC) persists in a profoundly hypoxic microenvironment, yet the mechanisms enabling tumor adaptation to this metabolically challenging niche remain undefined. Here, we identify the lipid kinase PIKfyve as overexpressed in NEPC, functioning as a central node in a stress-adaptive lipid kinase axis that supports adaptation to persistent endoplasmic reticulum (ER) stress. Mechanistically, NEPC requires PIKfyve-mediated lysosomal degradation and lipid recycling to maintain metabolic homeostasis under hypoxia. PIKfyve inhibition disrupts lysosomal function, exacerbates ER stress, and activates a compensatory sterol regulatory element-binding protein (SREBP)-dependent de novo lipogenesis program essential for NEPC survival. This stress-lipid axis creates a synthetic vulnerability between PIKfyve and fatty acid synthase (FASN), where dual inhibition synergistically amplifies ER stress, triggers the terminal unfolded protein response, and induces tumor cell death. These findings reveal a metabolic adaptation in NEPC and provide preclinical evidence that co-targeting PIKfyve and FASN can overcome hypoxia-associated stress adaptation.

Ecological risk index integrating metal contamination and ecotoxicological data for estuarine sediments.

Teixeira Matheus M, Cesar Ricardo R, de Souza Abessa Denis Moledo DM, Araujo Cristiano V M CVM et al.

This study proposes an ecological risk index (EcoRI) for metal-contaminated sediments from tropical estuaries. The EcoRI is composed of two sub-indexes: (i) chemical risk (CR), whose estimation is based on the comparison with local threshold limits, the numerical ranking of enrichment factors (EF), classes of geoaccumulation index (IGEO) and metal toxicity factors taken from the literature; and (ii) ecotoxicological risk (ER), based on bioassays with ecologically relevant organisms and the weighting of their trophic position, type of exposure (acute or chronic) and type of endpoint. EcoRI was calculated by attributing weights 1 and 2 for CR and ER, respectively, and a risk classification was proposed using four equal intervals (low, moderate, high and extreme). Secondary data from Itaipu-Piratininga Lagoon System (RJ, Brazil) was used to test the feasibility of the index. The results indicated that the lagoon system can be considered at moderate risk, and Zn, Cu, Cd and Cr were the elements that most contributed to increase CR, ER and EcoRI, especially in the canal connecting the lagoons. Hg, As and Pb were not associated with EcoRI, CR and ER, despite their known high toxicity. Increased risk scores might be associated with urbanized areas directly impacted by the discharge of domestic sewage, urban runoff and other anthropic wastes. Such areas include river mouths, the urbanized margins of the Camboatá Canal and its connections with both lagoons. Finally, EcoRI appears to be a useful tool for identifying critical areas at relevant environmental risk and key contaminants for further remediation.