Existing drug delivery methods have not led to a significant increase in survival for patients with malignant primary brain tumors. While the combination of conventional therapies consisting of surgery, radiotherapy, and chemotherapy has improved survival for some types of brain tumors (e.g., WNT medulloblastoma), other types of brain tumors (e.g., glioblastoma and diffuse midline glioma) still have a poor prognosis. The reason for the differences in response can be largely attributed to the blood-brain barrier (BBB), a specialized structure at the microvasculature level that regulates the transport of molecules across the blood vessels into the brain parenchyma. This structure hampers the delivery of most chemotherapeutic agents for the treatment of primary brain tumors. Several drug delivery methods such as nanoparticles, convection enhanced delivery, focused ultrasound, intranasal delivery, and intra-arterial delivery have been developed to overcome the BBB in primary brain tumors. However, prognosis of most primary brain tumors still remains poor. The heterogeneity of the BBB in primary brain tumors and the distinct vasculature of tumors make it difficult to design a drug delivery method that targets the entire tumor. Drug delivery methods that combine strategies such as focused ultrasound and nanoparticles might be a more successful approach. However, more research is needed to optimize and develop new drug delivery techniques to improve survival of patients with primary brain tumors.
Prospective or "de novo" biobanking is becoming increasingly popular. Biobanks are installed to provide large collections of biological materials for future medical research. Quality assurance of biobank samples is an important aspect of biobanking. Therefore, it is vital that all samples are collected and processed in a similar manner according to standardized procedures to ensure high-quality samples and reduce variability in the analytical process. We describe the processes of the centralized biobanking facility at the Leiden University Medical Center (LUMC).
Background Diffuse intrinsic pontine glioma (DIPG) is a notoriously difficult tumor to treat, with an overall survival of DIPG patients being only 11 months. One of the major obstacles for the effective treatment of DIPG is the blood–brain barrier (BBB). In order to circumvent the BBB, drug delivery methods are needed that target the pontine area. One such approach is microbubble-mediated focused ultrasound (FUS)—a non-invasive method that can temporarily and locally open the BBB. Previously, it was shown that FUS is safe with minimal side effects and rapid recovery times in preclinical animal models with different DIPG tumors. However, recent studies have shown that combining FUS with a single treatment of the chemotherapeutic drug doxorubicin did not improve survival in a DIPG xenograft model. As the duration of doxorubicin exposure might play a role in tumor response, we hypothesized that the use of a long-circulation (PEGylated) liposomal formulation of doxorubicin could lead to improved overall survival through a longer exposure time to the tumor. Method DIPG xenograft models were established with orthotopic injections of HSJD-DIPG-07 tumor cells into the pontine area of female athymic nude-foxn1nu mice. Tumor engraftment was confirmed with bioluminescence imaging (BLI) 40 days post-inoculation. Mice were randomized into groups receiving either liposomal formulations of doxorubicin (2B3-101 or Caelyx®) or free doxorubicin in combination with or without FUS treatment. Treatment groups received 5 mg/kg 2B3-101 or Caelyx® 1 h before FUS treatment or 5 mg/kg free doxorubicin immediately after FUS. Results Histological analysis, however, revealed liposome extravasation in healthy controls but not in HSJD-DIPG-07 xenograft 24 h after treatment. Furthermore, BLI monitoring did not show reduced signal after treatment, which was further illustrated with a survival analysis, showing no significant difference between treated and control animals (p = 0.3). Conclusion We did not observe a treatment effect after a single dose of free doxorubicin or the liposomal formulations 2B3-101 or Caelyx® in combination with FUS in DIPG-bearing mice.
Aims The aim of the present study was to assess the association between dental implant stability and peripheral blood cell composition and levels of coagulation factors in patients treated with alveolar ridge preservation with platelet‐rich fibrin (PRF) and bovine bone substitute. Materials and methods Fifty patients were included between 2015 and 2017. PRF was prepared from autologous blood, in which blood cells and coagulation factor levels were measured. PRF and bovine bone were placed in the socket, followed by closure with PRF membrane. Implants were placed 14 (±2.5) weeks postextraction. The implant stability quotient was measured at t = 0, t = 10 days, t = 7 weeks, and t = 17 weeks by resonance frequency analysis. Results Erythrocyte count was inversely associated with PRF membrane length, but not with implant stability. Conversely, platelet count did not correlate with membrane size but inversely correlated with implant stability at 7 and 17 weeks. In addition, implant stability was directly correlated with levels FXIII (t = 0, p < .01), active von Willebrand factor (VWF; t = 0 and 7 weeks, p < .05), and total VWF (t = 7 weeks, p = .012). Conclusion Implant stability following alveolar ridge preservation with PRF and bovine bone substitute is associated with circulating blood cells and coagulation factors. In particular, fibrin structure, VWF, and FXIII may be important modulators of implant stability.
Replacement in the esthetic zone can be very unpredictable and difficult to manage in cases with extreme bone and soft tissue loss. In this case report (2.5‐year follow‐up), we demonstrate that the use of platelet‐rich fibrin in combination with bovine bone can result in a stable, esthetic outcome.
Treatment with Platelet Rich Fibrin results in increased oral implant stability, which is associated with peripheral blood cell-and coagulation parameters. BACKGROUND PRF is a membrane clot clinically used to accelerate wound healing and bone regeneration. PRF membranes are prepared from the patient's own blood using a dedicated centrifugation protocol. In oral implantology PRF has been used to improve osseointegration of dental implants achieving improved implant stability. AIMHow PRF improves osseointegration is unknown and therefore we analyzed implant stability development in time in patients treated with autologous PRF. Furthermore, we studied the influence of blood cell-and coagulation parameters on PRF characteristics and oral implant stability outcome. Abstract ref. # 15228 METHODSPRF membranes were prepared according to Choukroun et al. (2001). We included 50 patients to study the effect of platelets, leukocytes and erythrocytes (Sapphire hematology analyzer, Abbott, USA) and coagulation parameters PT, APTT, fibrinogen (STA-Max coagulation analyzer, Stago, France) on PRF characteristics. The oral Implant Stability Quotient (ISQ) using Ostell TM ISQ resonance frequency analysis (Osstell, Sweden) was used to correlate blood values with the clinical outcome.
INTRODUCTION Chemotherapy has been unsuccessful for pediatric diffuse midline glioma (DMG) most likely due to an intact blood-brain barrier (BBB). However, the BBB has not been characterized in DMG and therefore its implications for drug delivery are unknown. In this study we characterized the BBB in DMG patients and compared this to healthy controls. METHODS End-stage DMG pontine samples (n=5) were obtained from the VUmc diffuse intrinsic pontine glioma (DIPG) autopsy study and age-matched healthy pontine samples (n=22) were obtained from the NIH NeuroBioBank. Tissues were stained for BBB markers claudin-5, zonula occludens-1, laminin, and PDGFRβ. Claudin-5 stains were used to determine vascular density and diameter. RESULTS In DMG, expression of claudin-5 was reduced and dislocated to the abluminal side of endothelial cells. In addition, the expression of zonula occludens-1 was reduced. The basement membrane protein laminin expression was reduced at the glia limitans in both pre-existent vessels and neovascular proliferation. PDGFRβ expression was not observed in DMG but was present in healthy pons. Furthermore, the number of blood vessels in DMG was significantly (P< 0.01) reduced (13.9 ± 11.8/mm2) compared to healthy pons (26.3 ± 14.2/mm2). Markedly, the number of small blood vessels (< 10µm) was significantly lower (P< 0.01) while larger blood vessels (> 10µm) were not significantly different (P= 0.223). The mean vascular diameter was larger for DMG 9.3 ± 9.9µm compared to 7.7 ± 9.0µm for healthy pons (P= 0.016). CONCLUSION Both the BBB and the vasculature are altered at end-stage DMG. The reduced vascular density might have implications for several drug delivery methods such as focused ultrasound and convection enhanced delivery that are being explored for the treatment of DMG. The functional effects of the structurally altered BBB remain unknown and further research is needed to evaluate the BBB integrity at end-stage DMG
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