Loma Linda University

About: Loma Linda University is a education organization based out in Loma Linda, California, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 9220 authors who have published 13485 publications receiving 447094 citations. The organization is also known as: University of Loma Linda.

Early diagnostic value of survivin and its alternative splice variants in breast cancer

Abstract: The inhibitor of apoptosis (IAP) protein Survivin and its splice variants are differentially expressed in breast cancer tissues. Our previous work showed Survivin is released from tumor cells via small membrane-bound vesicles called exosomes. We, therefore, hypothesize that analysis of serum exosomal Survivin and its splice variants may provide a novel biomarker for early diagnosis of breast cancer. We collected sera from forty breast cancer patients and ten control patients who were disease free for 5 years after treatment. In addition, twenty-three paired breast cancer tumor tissues from those same 40 patients were analyzed for splice variants. Serum levels of Survivin were analyzed using ELISA and exosomes were isolated from this serum using the commercially available ExoQuick kit, with subsequent Western blots and immunohistochemistry performed. Survivin levels were significantly higher in all the breast cancer samples compared to controls (p < 0.05) with exosome amounts significantly higher in cancer patient sera compared to controls (p < 0.01). While Survivin and Survivin-∆Ex3 splice variant expression and localization was identical in serum exosomes, differential expression of Survivin-2B protein existed in the exosomes. Similarly, Survivin and Survivin-∆Ex3 proteins were the predominant forms detected in all of the breast cancer tissues evaluated in this study, whereas a more variable expression of Survivin-2B level was found at different cancer stages. In this study we show for the first time that like Survivin, the Survivin splice variants are also exosomally packaged in the breast cancer patients’ sera, mimicking the survivin splice variant pattern that we also report in breast cancer tissues. Differential expression of exosomal-Survivin, particularly Survivin-2B, may serve as a diagnostic and/or prognostic marker, a “liquid biopsy” if you will, in early breast cancer patients. Furthermore, a more thorough understanding of the role of this prominent antiapoptotic pathway could lead to the development of potential therapeutics for breast cancer patients.

Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants.

Abstract: Importance Umbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation. Objective To determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping. Design, Setting, and Participants Noninferiority randomized clinical trial of preterm infants (born at 23-31 weeks’ gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018. Interventions Participants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238). Main Outcomes and Measures The primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin. Results Among 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, −2% to 9%];P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%];P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks’ gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%];P = .002). Conclusions and Relevance In this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks’ gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulting post hoc nature of the analyses preclude definitive conclusions. Trial Registration ClinicalTrials.gov Identifier:NCT03019367

Role of Interleukin-1β in Early Brain Injury after Subarachnoid Hemorrhage in Mice

Abstract: Background and Purpose— The role of interleukin (IL)-1β remains unknown in early brain injury (EBI) after subarachnoid hemorrhage (SAH), although IL-1β has been repeatedly reported to increase in the brain and cerebrospinal fluid. The aim of this study is to examine the effects of IL-1β inactivation on EBI after SAH in mice. Methods— The endovascular perforation model of SAH was produced and 112 mice were assigned to sham, SAH+ vehicle, and SAH+ N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK, 6 and 10 mg/kg) groups. Ac-YVAD-CMK, a selective inhibitor of IL-1β converting enzyme, or vehicle was administered intraperitoneally 1 hour post-SAH. EBI was assessed in terms of mortality within 24 hours, neurological scores, brain water content at 24 and 72 hours, Evans blue dye extravasation and Western blot for IL-1β, c-Jun N-Terminal kinase (JNK), matrix metalloproteinase (MMP)-9, and zonula occludens (ZO)-1 at 24 hours after SAH. Results— High-dose (10 mg/kg) but not low-dose (6 mg/kg) treatment group si...