Ulriksentonnesen4380

Background Peritoneal dissemination is common in advanced ovarian cancer. The completeness of cytoreduction is an independent prognostic factor. Y-27632 concentration The intraoperative fluorescence imaging via tumor-specific near-infrared fluorophore might improve staging and surgical completeness. A promising target for ovarian cancer is the gonadotropin-releasing hormone receptor (GnRHR). This study aimed to develop a GnRHR-targeted near-infrared imaging probe for the detection of peritoneal metastases of ovarian cancer. Methods Indocyanine green (ICG) was conjugated with GnRH antagonist peptide to develop an ovarian cancer-selective fluorescence probe GnRHa-ICG. GnRHR expression was detected in ovarian cancer tissues. The binding capacity of GnRHa-ICG and ICG was detected in both cancer cell lines and mouse models of peritoneal metastatic ovarian cancer using fluorescence microscopy, flow cytometry, and near-infrared fluorescence imaging. Results Tissue microarray analysis revealed the overexpression of GnRHR in ovarian cancere feasible for clinical applications in fluorescence-guided surgery. Our GnRHR imaging concept may be effective in other hormone-related tumors with upregulated GnRHR expression. Copyright © 2020 Liu, Zhou, Feng, Pu, Li, Li, Kang, Zhang and Xu.Background Emerging evidence points to potential roles of the humoral immune responses in the development of pancreatic cancer. Epidemiological studies have suggested involvement of viral and bacterial infections in pancreatic carcinogenesis. Experimental studies have reported high expression levels of antigens in pancreatic cancer cells. Therefore, we aimed to investigate the role of different components of humoral immunity in the context of pancreatic cancer. We evaluated associations between pre-diagnostic serum markers of the overall humoral immune system [immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM)], and the risk of pancreatic cancer in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study. Methods We selected all participants (≥20 years old) with baseline measurements of IgA, IgG or IgM (n = 41,900, 136,221, and 29,919, respectively). Participants were excluded if they had a history of chronic pancreatitis and individuals were free from pancreatic cancer at baseline. Multivariate Cox proportional hazards regression was used to estimate risk of pancreatic cancer for medical cut-offs of IgA, IgG, and IgM. Results Compared to the reference level of 6.10-14.99 g/L, risk of pancreatic cancer was elevated among those with IgG levels less then 6.10 g/L [HR 1.69 (95% CI 0.99-2.87)], and an inverse association was observed among those with IgG levels ≥15.00 g/L [0.82 (95% CI 0.64-1.05); Ptrend = 0.027]. The association appeared to be stronger for women than men [HR 0.64 (95% CI 0.43-0.97) and 0.95 (95% CI 0.69-1.29), respectively]. No associations were observed with IgA or IgM. Conclusion An inverse association was observed between pre-diagnostic serum levels of IgG and risk of pancreatic cancer. Our findings highlight the need to further investigate the role of immune response in pancreatic cancer etiology. Copyright © 2020 Sollie, Santaolalla, Michaud, Sarker, Karagiannis, Josephs, Hammar, Walldius, Garmo, Holmberg, Jungner and Van Hemelrijck.Chimeric antigen receptor (CAR) T cells targeting CD19 have been successful treating patients with relapsed/refractory B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas. However, relapse after CAR T cell therapy is still a challenge. In addition, preclinical and early clinical studies targeting acute myeloid leukemia (AML) have not been as successful. This can be attributed in part to the presence of an AML microenvironment that has a dampening effect on the antitumor activity of CAR T cells. The AML microenvironment includes cellular interactions, soluble environmental factors, and structural components. Suppressive immune cells including myeloid derived suppressor cells and regulatory T cells are known to inhibit T cell function. Environmental factors contributing to T cell exhaustion, including immune checkpoints, anti-inflammatory cytokines, chemokines, and metabolic alterations, impact T cell activity, persistence, and localization. Lastly, structural factors of the bone marrow niche, secondary lymphoid organs, and extramedullary sites provide opportunities for CAR T cell evasion by AML blasts, contributing to treatment resistance and relapse. In this review we discuss the effect of the AML microenvironment on CAR T cell function. We highlight opportunities to enhance CAR T cell efficacy for AML through manipulating, targeting, and evading the anti-inflammatory leukemic microenvironment. Copyright © 2020 Epperly, Gottschalk and Velasquez.Mitochondria play multifaceted roles in malignant tumor progression. Beyond their bioenergetic role, mitochondria are essential for providing malignant cells a higher plasticity to face the harsh environmental conditions. Cell-autonomous metabolic deregulation of cancer cells, or metabolic adaptation to microenvironmental cues (lack of nutrients, stromal supply, hypoxia, etc.), represent the triggering event of mitochondria overexploitation to orchestrate nutrient sensing and upload, signaling, and redox circuits. As readout of their higher function, mitochondria produce high amounts of reactive oxygen species (ROS) that are functional for multiple signaling networks underlying tumor proliferation, survival, and metastatic process. To compensate for the higher rate of mitochondrial ROS production, cancer cells have evolved adaptive mechanisms to increase their antioxidant systems and to address ROS activating pathways useful for the tumor cell adaptation to environmental changes. As these properties are critical for cancer progression, mitochondrial ROS have recently become an attractive target for anti-cancer therapies. We discuss how understanding of mitochondrial function in the tumor-specific generation of ROS will impact on the development of novel redox-based targeted therapeutic strategies. Copyright © 2020 Ippolito, Giannoni, Chiarugi and Parri.