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Cytoreductive surgery with HIPEC has shown promising results in the interval setting of advanced epithelial ovarian cancer. Its role in upfront setting has not yet been established. All eligible patients underwent CRS-HIPEC as per institution protocol. Relevant data was collected prospectively in institutional HIPEC registry and analyzed retrospectively for the study period from February 2014 to February 2020. Out of 190 patients, 80 underwent CRS-HIPEC in upfront setting and 110 in interval setting. The median age was 54 ± 7.45 years, upfront group had higher PCI (14.1 ± 8.75 vs. 9.6 ± 5.2. 2), and required longer duration of surgery (10.6 ± 1.73 vs. 8.4 ± 1.71 h) had more blood loss (1025 ± 668.76 vs. 680 ± 302.23 ml). The upfront group required more diaphragmatic resections, bowel resections, and multivisceral resections. The overall G3-G4 morbidity was comparable (25.4% vs. 27.3%), upfront group had more surgical morbidity (20% vs. 9.1%) whereas interval group had more medical morbidity, i.e., electrolyte imbalance and hematological. After a median follow-up of 43 months, median DFS was 33 months in the upfront vs. 30 months in the interval group, p = 0.75, median OS was 46 months interval group and was not yet achieved in upfront group.(p = 0.13). Four-year OS was 85% vs. 60%. In patients of advanced EOC upfront CRS HIPEC showed promising outcomes and trend towards better survival with similar morbidity and mortality. The upfront group had more surgical morbidity whereas interval group had more medical morbidity. Multiinstitutional randomized studies are needed to define patient selection and study morbidity patterns and compare the outcomes between CRS-HIPEC in the upfront and interval setting for advanced epithelial ovarian cancer.

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Visual cues coming from the lower visual field (VF) play an important role in the visual guidance of upper and lower limb movements. A recently described region situated in the dorsomedial parietal cortex, area hPEc (Pitzalis et al. in NeuroImage 202:116092, 2019), might have a role in integrating visually derived information with somatomotor signals to guide limb interaction with the environment. In macaque, it has been demonstrated that PEc receives visual information mostly from the lower visual field but, to date, there has been no systematic investigation of VF preference in the newly defined human homologue of macaque area PEc (hPEc). Here we examined the VF preferences of hPEc while participants performed a visuomotor task implying spatially directed delayed eye-, hand- and foot-movements towards different spatial locations within the VF. By analyzing data as a function of the different target locations towards which upcoming movements were planned (and then executed), we observed the presence of asymmetry in the vertical dimension of VF in area hPEc, being this area more strongly activated by limb movements directed towards visual targets located in the lower compared to the upper VF. This result confirms the view, first advanced in macaque monkey, that PEc is involved in processing visual information to guide body interaction with the external environment, including locomotion. We also observed a contralateral dominance for the lower VF preference in the foot selective somatomotor cortex anterior to hPEc. This result might reflect the role of this cortex (which includes areas PE and S-I) in providing highly topographically organized signals, likely useful to achieve an appropriate foot posture during locomotion.

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Antagonists for the serotonin receptor 2B (5-HT2B) have clinical applications towards migraine, anxiety, irritable bowl syndrome, and MDMA abuse; however, few selective 5-HT2B antagonists have been identified. Previous studies from these labs identified a natural product, 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC, 2) as the first non-nitrogenous ligand for the 5-HT2B receptor. Studies on 5-HPEC optimization led to the identification of 5-hydroxy-2-(3-phenylpropyl)chromone (5-HPPC, 3), which showed a tenfold improvement in binding affinity over 2 at 5-HT2B. This study aimed to further improve receptor pharmacology of this unique scaffold. Guided by molecular modeling studies modifications at the C-3' and C-4' positions of 3 were made to probe their effects on ligand binding affinity and efficacy. Among the derivatives synthesized 5-hydroxy-2-(3-(3-cyanophenyl)propyl)chromone (5-HCPC, 3d) showed the most promise with a multifold improvement in binding affinity (pKi = 7.1 ± 0.07) over 3 with retained antagonism.

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INTRODUCTION: Netrin-4 is a secreted member of the laminin-related protein family, known to be involved in axonal guidance and endothelial cell survival, proliferation, and migration. We have recently reported the cellular localization of netrin-4 and its receptor neogenin in human first trimester and term placenta. A strong expression of netrin-4 was observed in trophoblast and in endothelial cells, suggesting a potential role of this protein in placental angiogenesis. In relation to human pregnancy, it has been reported that circulating netrin-4 were increased in fetal umbilical cord blood of intrauterine growth restriction IUGR compared to normal pregnancy suggesting an adverse effect of this protein on placental and fetal development. The aim of this study was to determine the role of netrin-4 in placental angiogenesis. METHODS: The effects of netrin-4 on proliferation, migration, tube-like organization, and spheroid sprouting of human placental microvascular endothelial cells (HPEC) were studied. RESULTS: We demonstrated that netrin-4 inhibits HPEC proliferation, tube-like formation, migration and spheroid sprouting, suggesting a direct role of netrin-4 in the regulation of intra-villus angiogenesis. DISCUSSION: This is the first report of an anti-angiogenic activity of netrin-4 in human placenta. This study brings new insights into netrin-4 roles in placental angiogenesis and suggests possible involvements of netrin-4 in angiogenesis-related pathologies such as IUGR.

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