Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

Downregulation of the Phosphatase PHLPP1 Contributes to NNK-induced Malignant Transformation of Human Bronchial Epithelial Cells (HBECs).

Cigarette smoking (CS) is one of the greatest health concerns, which can cause lung cancer. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, and has been well-documented for its carcinogenic activity in both epidemiological and laboratory studies. PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and phosphatase and tensin homolog (PTEN) are two well-known phosphatase tumor suppressors that have been reported to be downregulated in human lung cancer tissues.

Tertiary Lymphoid Structures as a Biomarker in Immunotherapy and Beyond: Advancing Towards Clinical Application.

Tertiary lymphoid structures (TLSs) are ectopic immune cell clusters formed in nonlymphoid tissues affected by persistent inflammation, such as in cancer and prolonged infections. They have features of the structure and function of secondary lymphoid organs, featuring central CD20+ B cells, surrounded by CD3+ T cells, CD21+ follicular dendritic cells, and CD68+ macrophages, with a complex vascular system. TLS formation is governed by lymphotoxin-α1β2, TNF, and chemokines like CCL19, CCL21, and CXCL13, differing from secondary lymphoid organ development in developing later in life at sites of chronic inflammation.

Heterotrophic denitrification enhancement via effective organic matter degradation driven by suitable iron dosage in sediment.

The control of internal pollution was important throughout the restoration of the lake, especially the removal of sediment internal nitrogen. Experiments involving incubation were conducted in this study to investigate the effects of iron remediation on nitrogen in both water and sediment. Adding iron with varying dosage had different effects on the nutrients content and other properties of water and sediment in remediation.