Glutaminase‐1 (GLS1) has garnered considerable interest as a metabolic target in cancer due to its heightened involvement and activity. However, the precise fate of glutaminolysis catalysed by GLS1 in cancer cells remains elusive. We found that GLS1 knockout led to significant suppression of cancer cell proliferation, which can be reversed or partially restored by supplementation of glutamate or non‐essential amino acids that can be converted into glutamate. The addition of spliceosomal KGA or GAC ameliorates cancer cell growth in vitro and in vivo, providing both simultaneously completely reverse the effect. The primary metabolic fate of glutamate produced through glutaminolysis in cancer cells is mainly used to produce glutathione (GSH) for redox homeostasis, not entering the tricarboxylic acid cycle or synthesising nucleotides. GSH monoethyl ester (GSH‐MEE) effectively rescues the inhibition of cancer cell proliferation caused by GLS1 knockout. Deletion of GLS1 results in an elevation of reactive oxygen species (ROS) and malondialdehyde (MDA), a reduction of NADPH/NADP ⁺ ratio, and an augmented susceptibility of cells to ferroptosis. Glutathione Peroxidase 4 (GPX4) and GPX1 exhibit complementary roles in redox regulation, with GLS1 knockout promoting GPX4 degradation. Pharmacological inhibition of GLS1 synergises with GPX4 inhibitor to suppress tumour growth. Dual targeting of GPX4 and GPX1 presents a potent anti‐cancer strategy. This metabolic mechanism facilitates a deeper comprehension of the abnormal glutamine metabolism in cancer cells, establishing a theoretical basis for the potential clinical utilisation of GLS1 inhibitors and presenting novel perspectives for advancing combinatorial therapeutic approaches.

Background. Pancreatic cancer patients were particularly predisposed to develop Escherichia coli (E. coli) bloodstream infection (BSI); however, little information is currently available. We set out to find E. coli BSI’s risk factors in pancreatic cancer to provide valuable experience. Methods. We retrospectively analyzed the clinical data of pancreatic cancer patients (31 cases with E. coli BSI and 93 cases without BSI) by a case-control study. SPSS 17.0 was adopted to perform univariate and multivariate analyses. Bacterial resistance analysis was performed by Whonet 5.6. Results. Hospitalization days ≥7 days, number of admissions ≥2 times, surgery, chemotherapy, the type of antibiotics used ≥2 species, albumin<40.0 g/L, and prealbumin < 0.2 g/L were the potential risk factors for pancreatic cancer patients with E. coli BSI ( ). Multivariate logistic regression showed hospitalization days ≥7 days (OR = 11.196, 95% CI = 0.024–0.333, ), surgery (OR = 32.053, 95% CI = 0.007–0.137, ), and chemotherapy (OR = 6.174, 95% CI = 0.038–0.688, ) were the independent risk factors for E. coli BSI of pancreatic cancer patients. E. coli resistant to carbapenems was rare; they were susceptible to cephamycin and piperacillin/tazobactam. The 90-day mortality rate of the infected group was significantly higher than the control group (41.9% versus 8.6%, ). Conclusions. Hospitalization days ≥7 days, surgery, and chemotherapy are the independent risk factors for E. coli BSI of pancreatic cancer patients, which allows us to identify patients at potential risk and perform preventive treatment in time.

Breast cancer (BRCA) has a high incidence and mortality rate among women. Different molecular subtypes of breast cancer have different prognoses and require personalized therapies. It is imperative to find novel therapeutic targets for different molecular subtypes of BRCA. Here, we demonstrated for the first time that Cytochromeb561 (CYB561) is highly expressed in BRCA and correlates with poor prognosis, especially in HER2-positive BRCA. Overexpression of CYB561 could upregulate macroH2A (H2AFY) expression in HER2-positive BRCA cells through inhibition of H2AFY ubiquitination, and high expression of CYB561 in HER2-positive BRCA cells could promote the proliferation and migration of cells. Furthermore, we have demonstrated that CYB561 regulates H2AFY expression, thereby influencing the expression of NF-κB, a downstream molecule of H2AFY. These findings have been validated through in vivo experiments. In conclusion, we propose that CYB561 may represent a novel therapeutic target for the treatment of HER2-positive BRCA.

Background To study the common pathogens and cancer types of bloodstream infection (BSI) in cancer patients, find the risk factors and conduct clinical analysis.Methods The clinical data of 2302 patients with BSI in Tianjin Medical University Cancer Institute and Hospital (TMUCIH) from January 2011 to December 2018 were retrospectively analyzed. 31 pancreatic cancer patients complicated with Escherichia coli BSI and 93 pancreatic cancer patients without BSI at the same period with similar sex and age were divided into infection group and non-infection group.Results 645 strains (28%) of Escherichia coli were the main pathogens causing BSI in patients with cancer. 57 cases (8.8%) of cancer patients with Escherichia coli BSI were from pancreatic oncology department, among which 31 cases were diagnosed as pancreatic cancer by pathology. Multivariate logistic regression analysis showed that hospitalization days≥7, chemotherapy and neutrophil>5.5×10 9 /L were independent risk factors for pancreatic cancer patients complicated with BSI (P < 0.05). Quantitative analysis of serum-related indicators in infection patients and non-infection patients showed significant differences between albumin, prealbumin and neutrophils in infection and non-infection group. The ratio of Escherichia coli producing extended-spectrum ß-lactamase is 49.3 and 48.1 in pancreatic cancer and non-pancreatic patients. Escherichia coli resistant to carbapenems is rare, they were highly sensitive to Cephamycin and Piperacillin/tazobactam.Conclusions Escherichia coli, the main pathogen causing BSI of cancer patients, is more common in pancreatic cancer patients. The independent risk factors include hospitalization days≥7 days, chemotherapy and neutrophils larger than 5.5×10 9 /L. Quantitative indicators of neutrophil counts, albumin and prealbumin contribute to the early diagnosis of bloodstream infections. Early use of medication, while timely adjustment based on clinical drug sensitivity results will help reduce patient morbidity and mortality.

Cancer cells adapt to hypoxia through coordinated transcriptional and metabolic reprogramming; however, how metabolite transport integrates these processes with immune regulation remains poorly understood. Here, we identify SLCO4A1 as a hypoxia-inducible transporter that links metabolic adaptation to immune evasion. Mechanistically, hypoxia activates AMPK, which promotes TFE3 nuclear translocation and stability, enabling direct transcriptional activation of SLCO4A1. Functionally, SLCO4A1 relocalizes to the plasma membrane under hypoxia and regulates bidirectional metabolite transport. Loss of SLCO4A1 selectively impairs tumor growth under hypoxic conditions in vitro and in vivo, while re-expression restores proliferation. Metabolomic analyses further reveal that SLCO4A1 promotes the export of xanthosine, which acts as an extracellular immunosuppressive metabolite that attenuates NK cell activation, induces IL-6 production, and reprograms immune cell metabolism. Collectively, our findings define an AMPK–TFE3–SLCO4A1 signaling axis as an immunometabolic checkpoint that couples hypoxia-driven metabolic reprogramming to suppression of anti-tumor immunity. Targeting SLCO4A1 or xanthosine-mediated signaling may therefore represent a potential strategy to enhance NK cell–dependent anti-tumor responses in hypoxic cancers.