Tumor-associated macrophages and individual chemo-susceptibility are influenced by iron chelation in human slice cultures of gastric cancer. | LitMetric
Presence of tumor-associated macrophages (TAM) and high levels of ferritin and lipocalin 2 (Lcn2) in the tumor microenvironment are associated with poor prognosis in many types of cancer. Here we investigate whether iron deprivation influences TAM phenotype and chemotherapy resistance in tumor slice cultures (TSC) of gastric cancer. TAM remained morphologically and functionally stable for four DIV. DFO treatment for 72 h decreased ferritin expression in TAM and in the tumor stroma but did not alter Lcn2 expression. TAM phenotype was altered after 72 h of cisplatin or DFO treatment compared with control conditions. Single DFO treatment and combined treatment with cytotoxic drugs significantly increased tumor cell apoptosis in TSC of gastric cancer. TSC were manufactured by cutting tissue of gastric cancer resection specimens in 350 μm thick slices and cultivating them under standard conditions on a filter membrane, at an air-liquid interface. After 24 h , TSC were treated with irinotecan (100 nM) or cisplatin (10 μM) alone and in combination with deferoxamine (DFO; 10 μM, 100 μM), respectively, for 72 h. After four days (DIV) the TSC were fixated with paraformaldehyde, paraffin embedded and analyzed by immunohistochemistry for apoptosis (cPARP), proliferation (Ki67), TAM (CD68, CD163), ferritin, and Lcn2 expression. TAM are well preserved and can be studied in TSC of gastric cancer. Iron deprivation significantly increased tumor cell apoptosis.
Gastric cancer remains a significant health burden globally, especially prevalent in Asian and European regions. Despite a notable decline in incidence in the United States and Western Europe over recent decades, the disease's persistence underscores the urgency for advanced research in its pathogenesis and treatment strategies. Central to this pursuit is the exploration of the mitogen-activated protein kinase (MAPK) pathway, a pivotal cellular mechanism implicated in the complex processes of gastric cancer development, including cellular proliferation, invasion, migration, and metastasis.
Department of Radiology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, No.283, Tongzipo Road, Changsha, Hunan, 410013, China.
Background: Although stage I gastric cancer (GC) presents a favorable survival rate, outcomes for patients experiencing recurrence remain poor. This research focuses on assessing the prognosis and identifying risk factors for stage I GC patients, further assessing the necessity of adjuvant chemotherapy (AC).
Methods: The study involved a retrospective analysis of 902 patients with stage I GC who received curative resection from November 2010 to December 2020.
Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC.
Background: Accumulating studies have focused on long noncoding RNAs (lncRNAs) because of their regulatory effects on multiple cancers. However, the biological functions and molecular mechanisms of lncRNAs in gastric cancer (GC) remain to be elucidated in depth.
Methods: Long intergenic nonprotein coding RNA 1094 (LINC01094), a differentially expressed lncRNA between GC tissues and adjacent normal tissues, was identified.
