This study was aimed at evaluating the possible interference of formulated glyphosate to the endocrine control of ovarian growth exerted by progesterone, in the estuarine crab Neohelice granulata. The addition of Roundup Ultramax® (0.2 mg/L of glyphosate in the incubation medium) was able to potentiate the stimulating effect of progesterone on total vitellogenic protein (Vg) content of ovarian pieces from crabs. Moreover, the sole addition of mifepristone (antagonist of progesterone receptors) was able to produce a decrement of the Vg content, which was not reverted by the addition of Roundup. A similar result was confirmed by means of histological analysis, which showed that mifepristone, both alone and in combination with Roundup, inhibited ovarian maturation, while Roundup alone increased it, in terms of a higher proportion of vitellogenic oocytes. We conclude that Roundup could stimulate the progesterone secretion exerted by the ovary and/or could act as a partial agonist of this hormone in the same tissue. To predict the diagnosis of pelvic lipomatosis (PL) by assessing CT imaging parameters. Fifty clinically proven PL patients and 50 controls were included. Two radiologists recorded the types of bladder shapes and measured the following CT imaging parameters (1) pelvic fat volume (PFV); (2) a set of morphological indices of bladder and rectosigmoid, including the ratio of craniocaudal to anterior-posterior length of bladder (CC/AP), angle between anterior and posterior wall (AAP), relative length of posterior urethra (rLPU), right and left angles between bladder and seminal vesicle (RABS and LABS), distance from verumontanum to anterior wall of rectum (DVR) and rectosigmoid morphological index (RMI). Secondary complications were also noted. The results were evaluated by an unpaired t test, ROC analysis and logistic regression. All CT imaging parameters except RMI (p = 1.000) indicated a statistical difference between PL and controls (p < 0.01). The AUCs of these parameters were between 0.724 (for rLPU) and 0.993 (for AAP). The sensitivity and specificity were 94% and 98% for AAP and 92% and 94% for the combined model, respectively. 23 patients were pathologically diagnosed with cystitis glandular. The incidence of hydronephrosis in the PL group was higher than that in the control group (p < 0.01). CT imaging parameters can predict the diagnosis of PL. The combined model of objective parameters including PFV, rLPU and DVR showed the best diagnostic performance for PL.CT imaging parameters can predict the diagnosis of PL. PD0325901 The combined model of objective parameters including PFV, rLPU and DVR showed the best diagnostic performance for PL.Stimulator of interferon genes (STING) contributes to anti-tumor immunity by activating antigen-presenting cells and inducing mobilization of tumor-specific T cells. A role for tumor-migrating neutrophils in the anti-tumor effect of STING-activating therapy has not been defined. We used mouse tumor transplantation models for assessing neutrophil migration into the tumor triggered by intratumoral treatment with STING agonist, 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Intratumoral STING activation with cGAMP enhanced neutrophil migration into the tumor in an NF-κB/CXCL1/2-dependent manner. Blocking the neutrophil migration by anti-CXCR2 monoclonal antibody impaired T cell activation in tumor-draining lymph nodes (dLNs) and efficacy of intratumoral cGAMP treatment. Moreover, the intratumoral cGAMP treatment did not show any anti-tumor effect in type I interferon (IFN) signal-impaired mice in spite of enhanced neutrophil accumulation in the tumor. These results suggest that both neutrophil migration and type I interferon (IFN) induction by intratumoral cGAMP treatment were critical for T-cell activation of dLNs and the anti-tumor effect. In addition, we also performed in vitro analysis showing enhanced cytotoxicity of neutrophils by IFN-β1. Extrinsic STING activation triggers anti-tumor immune responses by recruiting and activating neutrophils in the tumor via two signaling pathways, CXCL1/2 and type I IFNs.Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [KrasG12D (K), KrasG12DTp53-/-(KP), KrasG12DTp53+/-Lkb1-/- (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU). Increasing the TMB enhanced host anti-tumor T cell responses and improved anti-PD-1 efficacy in syngeneic models across all genetic backgrounds. However, limited anti-PD-1 efficacy was observed in the KPL cell lines with increased TMB, which possessed a distinct immunosuppressed tumor microenvironment (TME) primarily composed of granulocytic myeloid-derived suppressor cells (G-MDSCs). This KPL phenotype is consistent with findings in human KRAS-mutant NSCLC where LKB1 loss is a driver of primary resistance to PD-1 blockade. In summary, these novel Kras-mutant NSCLC murine models with known driver mutations and increased TMB have distinct TMEs and recapitulate the therapeutic vulnerabilities of human NSCLC. We anticipate that these immunogenic models will facilitate the development of innovative immunotherapies in NSCLC. Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous and nodal melanoma lesions in stage IIIB-IVM1a patients. This study set out to identify prognostic factors for achieving a complete response that can be used to optimize patient selection for T-VEC monotherapy. Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2020-01 with a follow-up time > 6months, were included. Data were collected on baseline characteristics, responses and adverse events (AEs). Uni- and multivariable analyses were conducted, and a prediction model was developed to identify prognostic factors associated with CR. A total of 93 patients were included with a median age of 69years, median follow-up time was 16.6months. As best response, 58 patients (62%) had a CR, and the overall response rate was 79%. The durable response rate (objective response lasting > 6months) was 51%.