<b><i>Background:</i></b> Gastric cancer (GC) is recorded as the fifth most common cancer globally. The classic resemblance of early symptoms of chronic gastritis including nausea, dysphagia, and dyspepsia with GC is the current challenge limiting the early diagnosis of GC. The current diagnostic procedures of GC are limited due to their invasive nature. This directs the research question toward alternative approaches, specifically at the molecular level. Recent advances in molecular regulation of cancer suggest the prominence of circular RNAs (circRNAs) in the multistep process of tumourigenesis. <b><i>Summary:</i></b> CircRNAs are a class of non-coding RNAs, abundant in eukaryotes, with key roles in regulating genes and miRNAs as well as the alteration of processes involved in pathological conditions. Research studies have demonstrated the participation of circRNAs in the initiation and progression of tumours. This review provides a comprehensive insight into the potential of circRNAs as disease biomarkers for the early detection and treatment of GC. <b><i>Key Messages:</i></b> This study is an amalgamation of the implications and future prospects of circRNAs for the detection and potential treatment of GC.

The overall patient survival rate drops dramatically when localized prostate cancer (PCa) progresses to bone metastatic prostate cancer (BM-PCa). The treatment for BM-PCa is limited to palliative therapy, and it is currently incurable. Neutrophils are the most prevalent immune cell in the bone, and we have found that PCa enhances their recruitment and infiltration into the prostate tumor-bone microenvironment of patients with BM-PCa. Additionally, we observed that bone marrow neutrophils directly induce apoptosis of PCa cells both in vitro and in vivo and that this is mediated by the inhibition of STAT5, a transcription factor that promotes PCa progression. Moreover, STAT5 has also been found to contribute to the development of resistance to standard care androgen deprivation therapy. Neutrophils specifically target and kill only cells that express STAT5, as stable knockdown of STAT5 in BM-PCa cells makes them resistant to neutrophil-mediated cytotoxicity, while the overexpression of STAT5 in STAT5-negative PCa cells, which are generally resistant to killing by neutrophils, sensitizes them to neutrophil-mediated killing. Furthermore, transcriptomic analyses derived from the STAT5 knockdown and STAT5 overexpressing cells suggest that STAT5 expression in PCa induces pro-inflammatory signaling and that neutrophil-mediated cytotoxicity may be exerted via STAT5-induced IL-1 and/or IL-6. Preliminary data in our laboratory show that STAT5-induced production of IL-1 by PCa cells leads to their death by neutrophils, as knocking out the IL-1 receptor on neutrophils reduces their cytotoxic potential against STAT5-positive PCa cells. Interestingly, in addition to killing BM-PCa cells, we have demonstrated that bone marrow-derived neutrophils are also capable of killing pancreatic cancer cells. Further delineation of the role of neutrophils in STAT5 signaling in BM-PCa growth holds promise for enhancing neutrophil cytotoxicity in the bone which could lead to novel therapeutic options for bone metastatic prostate cancer. Citation Format: Sanjana Rajgopal, Massar Alsamraae, Diane Costanzo-Garvey, Leah Cook. Anti-tumor actions of neutrophils are mediated via STAT5 inhibition. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3647.

Pregnancy is not nearly as successful as laypersons might assume, challenged as it is by several complications such as threatened abortion, spontaneous miscarriage, preeclampsia, and preterm delivery, among others. The maternal immune system has been shown to contribute to the etiopathogenesis of some of these pregnancy complications. Pro-inflammatory and anti-inflammatory cytokines have been studied for their effects on pregnancy because of their powerful and versatile effects on cells and tissues. This review addresses the relationship between pro-inflammatory cytokines and recurrent miscarriage, which is an important complication of pregnancy. References for this review were identified by using PRISMA-IPD (Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data) Guidelines by conducting searches for published articles from January 1, 1990 until March 1, 2020 in the following databases: PubMed, Google Scholar, and MEDLINE via OVID by the use of the search terms “recurrent spontaneous miscarriage,” “cytokines,” “progesterone,” “progestogen,” “dydrogesterone,” and “immunomodulation.” This review also presents the proposed mechanisms of action of pro-inflammatory cytokines in pregnancy loss, and then goes on to discuss the modulation of cytokine profiles to a state that is favorable to the success of pregnancy. In addition to its indispensable endocrinologic role of progesterone in pregnancy, it also has some intriguing immunomodulatory capabilities. We then summarize studies that show that progesterone and dydrogesterone, an orally-administered progestogen, suppress the production of pro-inflammatory cytokines and enhance the production of anti-inflammatory cytokines before mentioning clinical studies on progestogen supplementation. These studies support the contention that progestogens should be explored for the immunotherapeutic management of pregnancy complications.

No abstract