Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor–based orthotopic xenograft mouse models of pediatric glioma

Background

Seneca Valley virus (SVV-001) is a nonpathogenic oncolytic virus that can be systemically administered and can pass through the blood–brain barrier. We examined its therapeutic efficacy and the mechanism of tumor cell infection in pediatric malignant gliomas.

Methods

In vitro antitumor activities were examined in primary cultures, preformed neurospheres, and self-renewing glioma cells derived from 6 patient tumor orthotopic xenograft mouse models (1 anaplastic astrocytoma and 5 GBM). In vivo therapeutic efficacy was examined by systemic treatment of preformed xenografts in 3 permissive and 2 resistant models. The functional role of sialic acid in mediating SVV-001 infection was investigated using neuraminidase and lectins that cleave or competitively bind to linkage-specific sialic acids.

Results

SVV-001 at a multiplicity of infection of 0.5 to 25 replicated in and effectively killed primary cultures, preformed neurospheres, and self-renewing stemlike single glioma cells derived from 4 of the 6 glioma models in vitro. A single i.v. injection of SVV-001 (5 × 10¹² viral particles/kg) led to the infection of orthotopic xenografts without harming normal mouse brain cells, resulting in significantly prolonged survival in all 3 permissive and 1 resistant mouse models (P < .05). Treatment with neuraminidase and competitive binding using lectins specific for α2,3-linked and/or α2,6-linked sialic acid significantly suppressed SVV-001 infectivity (P < .01).

Conclusion

SVV-001 possesses strong antitumor activity against pediatric malignant gliomas and utilizes α2,3-linked and α2,6-linked sialic acids as mediators of tumor cell infection. Our findings support the consideration of SVV-001 for clinical trials in children with malignant glioma.     

The effect of labour and placental separation on the shedding of syncytiotrophoblast microparticles, cell-free DNA and mRNA in normal pregnancy and pre-eclampsia

The clinical features of the maternal syndrome of pre-eclampsia can be explained by generalised maternal endothelial cell dysfunction, which is a part of a more global maternal systemic inflammatory response. There is growing evidence that these effects are associated with the shedding of cellular debris, including syncytiotrophoblast microparticles (STBM), cell-free DNA and mRNA, from the surface of the placenta (syncytiotrophoblast) into the maternal circulation. The increased shedding of this debris seen in pre-eclampsia is believed to be caused by placental ischaemia, reperfusion and oxidative stress. This study was carried out to determine whether uterine contractions during labour and subsequent placental separation lead to an acute increase in the release of placental debris into the maternal circulation. To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women at varied time points. Similarly to assess the effects of placental delivery, plasma samples were taken from 10 NP and 10 PE women undergoing elective caesarean section. There was a significant increase in the shedding of STBM in pre-eclampsia which was not seen in normal pregnancy and there was a small rise in STBM levels at placental separation in both normal pregnant and pre-eclamptic women undergoing caesarean section, but the differences were not significant. However, levels of placental cell-free corticotrophin releasing hormone mRNA were significantly increased in labour in both normal pregnancy and pre-eclampsia and were still high 24 h after delivery in the pre-eclamptic women. There was no significant increase in fetal or total DNA in labour, but the overall levels of total DNA (maternal and fetal) was increased in labour in pre-eclampsia compared to normal labour. The enhanced shedding of STBM and CRH mRNA in pre-eclampsia labour may have a role in cases of postpartum worsening of pre-eclampsia.     

Preeclampsia--a pressing problem: an executive summary of a National Institute of Child Health and Human Development workshop

On September 21 and 22, 2006, the National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled "Preeclampsia--A Pressing Problem." The purpose of the workshop was to bring together leaders in the field to present and discuss their diverse research areas, which ranged from basic science to clinical trials and management, and to identify scientific gaps. This article is a summary of the proceedings of that workshop. Although much progress is being made in understanding the underpinnings of preeclampsia, a number of research gaps are identified that, if filled, would hasten progress in the field. It is the overall consensus that preeclampsia is a multifactorial disease whose pathogenesis is not solely vascular, genetic, immunologic, or environmental but a complex combination of factors. In addition, a number of specific scientific gaps are identified including insufficient multidisciplinary and collaborative research, clinical trials and studies of patient management, and a lack of in-depth mechanistic research. The research community needs to focus on these gaps to better understand the disease, with the ultimate goal of preventing the disorder.     

Reduction of 4-nitrophenol using green-fabricated metal nanoparticles

Noble metal (silver (Ag), gold (Au), platinum (Pt), and palladium (Pd)) nanoparticles have gained increasing attention due to their importance in several research fields such as environmental and medical research. This review focuses on the basic perceptions of the green synthesis of metal nanoparticles and their supported-catalyst-based reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). The mechanisms for the formation of these nanoparticles and the catalytic reduction of 4-NP are discussed. Furthermore, the parameters that need to be considered in the catalytic efficiency calculations and perspectives for future studies are also discussed.

Noble metal (silver (Ag), gold (Au), platinum (Pt), and palladium (Pd)) nanoparticles have gained increasing attention due to their importance in several research fields such as environmental and medical research.     

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.     

Laparoscopic versus open splenectomy in the pediatric population: a contemporary single-center experience

The purpose of this study was to compare a recent contemporaneous experience between laparoscopic (LS) and open (OS) splenectomy in children. All splenectomy cases between 1994 and 1999 at our institution were reviewed. The study included open and laparoscopic cases performed according to surgeon preference. Emergency splenectomies for trauma were excluded. The patient record was reviewed for the diagnosis, indications, postoperative length of stay, operative technique, postoperative complications, blood loss/blood transfusion, total amount of parenteral narcotics, and time to resumption of oral intake. Chi-square and t tests were used to compare measured differences for statistical significance. Between May 1994 and December 1999, 52 splenectomies were performed at Vanderbilt Children's Hospital. Of these, 45 were elective operations with 29 open and 16 laparoscopic procedures. During four OS and five LS operations a concomitant cholecystectomy was performed. The median patient age was 9.2 years (range 0.5 to 17.3). There was no statistical difference between the two groups in terms of age, weight, American Society of Anesthesiologists class, or estimated blood loss. There were no immediate postoperative complications in either group. There were no conversions from LS to OS. The mean duration of surgery was 264 minutes (LS) versus 169 minutes (OS) (P < 0.05). The average time to first oral intake was shorter in patients undergoing LS (1.1 vs 1.6 days, P < 0.05) and the mean postoperative length of stay was also shorter in the LS group (1.3 vs 3.1 days, P < 0.05). The use of postoperative intravenous narcotics (in morphine-equivalent doses) was significantly less in LS patients than in OS patients (7.5 mg or 0.15 mg/kg vs 46.9 mg or 1.5 mg/kg, P < 0.001), as was the need for PCA pump analgesia (90% in the OS group vs 25% in LS group, P < 0.01). Overall the average hospital charge (anesthesia fee, narcotics charge, and hospital room charge) was $5400 (range $4240-6250) in the OS group and $4950 (range $4450-6240) in the LS group (P < 0.05). Among the nine patients undergoing splenectomy with cholecystectomy, findings between the OS and LS groups were similar except for one late complication consisting of a diaphragmatic hernia in an LS patient. Both LS and OS with or without a concomitant procedure can be accomplished safely in children. LS appears to result in longer operative times but shorter lengths of stay, earlier first oral intake, and significantly fewer requirements for intravenous narcotics; all of these contribute to a reduction in hospital charges compared with the open operation.     

Haemobilia – a rare presentation of intrabiliary hydatid disease

Intrabiliary hydatid cysts have been known to cause complications. We report a rare case of calcified crumpled intrabiliary hydatid cyst causing massive haemobilia due to a hepatic artery pseudoaneurysm, an unusual complication of intrabiliary hydatid cyst. The patient was successfully treated by stenting of the pseudoaneurysm with overlapping stents.     

Effects of Combination of Calcium and Aspirin on Azoxymethane-Induced Aberrant Crypt Foci Formation in the Colons of Mice and Rats

Human intervention studies have suggested an exciting synergistic action between calcium supplementation and aspirin intake in reducing the risk of colorectal cancer. The aim of this study was to determine whether such a synergy can be demonstrated on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) formation in mice and rats. Female CF-1 mice and male F344 rats were injected subcutaneously with AOM and then received diet treatments for 8 wk. The basal control diet contained high fat (20% mixed lipids by weight) and low calcium (1.4 mg/g diet) to mimic the average Western diet. The treatment diets contained enriched calcium (5.2 mg calcium/g diet), aspirin (0.2 mg aspirin/g diet), or calcium plus aspirin (5.2 mg calcium plus 0.2 mg aspirin/g diet). Treatment with calcium, aspirin, or their combination significantly decreased the number of total ACF and aberrant crypt per mouse (by 43–59%) or rat (by 23–38%), but statistically significant differences among the 3 groups were not observed. A hint of additivity between calcium and aspirin was observed in mice but not in rats. These results indicate that the combination of calcium and aspirin did not produce a synergistic effect on the ACF formation in AOM-treated mice and rats.