Guldagerseerup3625
Due to the poor genomic integrity, annotations of the SNPs or Indels in H. discus hannai did not yield missense mutant sites. FREP genes with polymorphisms were ubiquitously expressed in all the tested tissues; however, the expression is lowest in the hemolymph. BI-4020 chemical structure In response to Vibrio parahemolyticus infection, expression of FREP genes was significantly upregulated at different exposure times in gills, hepatopancreas, and hemolymph in H. discus hannai. Overall, this study documented the FREP genes of abalones and shed light on the role of FREPs in the innate immune system of these aquaculture species for the prevention and control of diseases.
We report efficacy of a prospective Phase II trial (YYYY) of salvage low dose rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiotherapy (EBRT) with minimum 5- years' follow up.
Eligible patients had low/intermediate risk prostate cancer (PCa) prior to EBRT and biopsy-proven LF > 30 months after EBRT, with PSA < 10 ng/mL and no regional/distant disease. The primary endpoint, late GI/GU Adverse Events (AEs) (CTCAE V3.0 ≥ Grade 3) was 14%. With minimum 5-year follow up after salvage BT, secondary clinical outcomes including disease-free (DFS; includes death from any cause), disease-specific (DSS), and overall survival (OS) were estimated using the Kaplan-Meier method and modelled using Cox proportional hazards regression. Local tumor progression (LF), distant and biochemical failure (DF/BF) were estimated using cumulative incidence. Time to LF, DF and BF were modeled by cause-specific Cox proportional hazards regression.
From 05/2007 -01/2014, 20 centers regthough further LF is rare (5%), BF climbs to 46% by10-years.
The goal of this study is to clarify the underlying mechanisms of metastasis suppression by CiDC (carbon-ion radiotherapy (CIRT) combined with immature dendritic cell (iDC) immunotherapy), which was previously shown to significantly suppress pulmonary metastasis in a NR-S1-bearing C3H/He mouse model.
Mouse carcinoma cell lines (LLC, LM8, Colon-26 and Colon-26MGS) were grafted into the right hind paw of syngeneic mice (C57BL/6J, C3H/He and BALB/c). Seven days later, the tumors on the mice were locally irradiated with carbon-ions (290 MeV/n, 6 cm SOBP, 1 or 2 Gy). At 1.5 days after irradiation, bone marrow-derived immature dendritic cells were administrated intravenously into a subset of the mice. The number of lung metastases was evaluated within three weeks after irradiation. In vitro cultured cancer cells were irradiated with carbon-ion (290 MeV/n, mono-energy, LET approximately 70 ∼ 80 keV/µm), and then co-cultured with iDCs for three days to determine the DC maturation.
CiDC effectively repressed distant lung metastases in cancer cell (LLC and LM8)-bearing C57BL/6J and C3H/He mouse models. However, Colon-26 and Colon-26MGS-bearing BALB/c models did not show enhancement of metastasis suppression by combination treatment. This was further evaluated by comparing LM8-bearing C3H/He and LLC-bearing C57BL/6J models with a Colon-26-bearing BALB/c model. In vitro co-culture assays demonstrated that all irradiated cell lines were able to activate C3H/He or C57BL/6J-derived iDCs into mature DCs, but not BALB/c-derived iDCs.
The genetic background of the host may have a strong impact on the potency of combination therapy. Future animal and clinical testing should evaluate host genetic factors when evaluating treatment efficacy.
The genetic background of the host may have a strong impact on the potency of combination therapy. Future animal and clinical testing should evaluate host genetic factors when evaluating treatment efficacy.
Many patients experience bowel and bladder toxicity during the acute phase of radiotherapy for prostate cancer. Recent literature indicates that hypofractionation (HF) might increase this acute response but little is known on patient-reported outcome during this phase with HF. We evaluated the course of patient-reported acute symptoms during HF vs standard fractionated (SF) radiotherapy within the hypofractionated irradiation for prostate cancer (XXXX) trial.
In the XXXX trial patients were treated with either 64.4 Gy (HF) in 19 fractions (3x per week) or 78 Gy (SF) in 39 fractions (5x per week). NTD
for acute toxicity (α/β ratio=10) for HF was 72.1 Gy with a similar dose rate of 10.2 Gy/week. Among the 794 patients who were previously eligible for acute Grade ≥2 toxicity assessment, N=717 had filled out ≥1 symptom questionnaires. For each maximum symptom we scored "any complaint" and "moderate-severe complaint". Differences were tested by Chi-square test and associations with clinical factors were testased bladder symptoms with HF was not identified previously. These observations contradict the NTD2Gy calculations. We observed no patterns of persisting complaints with HF after the acute period, therefore HF is well tolerated and only associated with a temporary increase of symptoms.Glioblastoma multiform (GBM) is considered as the most lethal tumor among CNS malignancies. Although immunotherapy has achieved remarkable advances in cancer treatment, it has not shown satisfactory results in GBM patients. Biomaterial science, along with nanobiotechnology, is able to optimize the efficiency of immunotherapy in these patients. They can be employed to provide the specific activation of immune cells in tumor tissue and combinational therapy as well as preventing systemic adverse effects resulting from hyperactivation of immune responses and off-targeting effect. Advance biomaterials in this field are classified into targeting nanocarriers and localized delivery systems. This review will offer an overview of immunotherapy strategies for glioblastoma and advance delivery systems for immunotherapeutics that may have a high potential in glioblastoma treatment.Careful assessment of the biological fate and immune response of inorganic nanoparticles is crucial for use of such carriers in drug delivery and other biomedical applications. Many studies have elucidated the cellular and molecular mechanisms of the interaction of inorganic nanoparticles with the components of the immune system. The biodegradation and dissolution of inorganic nanoparticles can influence their ensuing immune response. While the immunological properties of inorganic nanoparticles as a function of their physicochemical properties have been investigated in detail, little attention has been paid to the immune adverse effects towards the degradation products of these nanoparticles. To fill this gap, we herein summarize the cellular mechanisms of immune response to inorganic nanoparticles and their degradation products with specific focus on immune cells. We also accentuate the importance of designing new methods and instruments for the in situ characterization of inorganic nanoparticles in order to assess their safety as a result of degradation. This review further sheds light on factors that need to be considered in the design of safe and effective inorganic nanoparticles for use in delivery of bioactive and imaging agents.With rapid emergence of multi-drug resistant microbes, it is imperative to seek alternative means for infection control. Optical waveguides are an auspicious delivery method for precise administration of phototherapy. Studies have shown that phototherapy is promising in fighting against a myriad of infectious pathogens (i.e. viruses, bacteria, fungi, and protozoa) including biofilm-forming species and drug-resistant strains while evading treatment resistance. When administered via optical waveguides, phototherapy can treat both superficial and deep-tissue infections while minimizing off-site effects that afflict conventional phototherapy and pharmacotherapy. Despite great therapeutic potential, exact mechanisms, materials, and fabrication designs to optimize this promising treatment option are underexplored. This review outlines principles and applications of phototherapy and optical waveguides for infection control. Research advances, challenges, and outlook regarding this delivery system are rigorously discussed in a hope to inspire future developments of optical waveguide-mediated phototherapy for the management of infection and beyond.Many new chemical entities (NCEs) have been discovered with the development of the pharmaceutical industry. However, the main disadvantage of these drugs is their low aqueous solubility, which results in poor bioavailability, posing a challenge for pharmaceutical scientists in the field of drug development. Solid dispersion (SD) technology is one of the most successful techniques used to resolve these problems. SD has been widely used to improve the solubility and bioavailability of poorly water-soluble drugs using several methods such as melting, supercritical fluid (SCF), solvent evaporation, spray drying, hot-melt extrusion, and freeze-drying. Among them, SCF with carbon dioxide (CO2) has recently attracted great attention owing to its enhanced dissolution and bioavailability with non-toxic, economical, non-polluting, and high-efficiency properties. Compared with the conventional methods using organic solvents in the preparation of the formulation (solvent evaporation method), SCF used CO2 to replace the organic solvent with high pressure to avoid the limitation of solvent residues. The solubility of a substance in CO2 plays an important role in the success of the formulation. In the present review, the various processes involved in SCF technology, application of SCF to prepare SD, and future perspectives of SCF are described.Spray-drying is an extensively used technology for engineering inhalable particles. Important technical hurdles are however experienced when lipid-based excipients (LBEs) are spray-dried. Stickiness, extensive wall deposition, or simply inability to yield a solid product have been associated to the low melting points of LBEs. In this work, solutions containing polyglycerol esters of behenic acid (PGFA-behenates), or other high melting point LBEs, were spray-dried to produce ibuprofen (IBU)-loaded inhalable lipid-microparticles. Prior to spray-drying, rational boundaries for the outlet temperature of the process were defined using LBE-IBU phase diagrams. Despite spray-drying the solutions at outlet temperatures below the boundaries, process performance and yield among LBEs were entirely different. Lipid crystallization into polymorphs or multi-phases negatively impacted the yield (10-47%), associated to liquid fractions unable to recrystallize at the surrounding gas temperature in the spray-dryer. The highest yields (76-82%), ascribed to PGFA-behenates, resulted from monophasic crystallization and absence of polymorphism. Lipid-microparticles, composed of a PGFA-behenate, were characterized by a volume mean diameter of 6.586 µm, tap density of 0.389 g/cm3 and corrugated surface. Application as carrier-free dry powder for inhalation resulted in high emitted fraction (90.9%), median mass aerodynamic diameter of 3.568 µm, fine particle fraction of 45.6% and modified release in simulated lung fluid.Physical drug delivery enhancement in skin has been shown to enhance cosmeceutical actives efficacy. Among the physical drug delivery enhancement technologies, microneedle is the most commercially successful technology. However, there are pros and cons like other physical enhancement technologies including variabilities in penetration depth and lack of efficacy. In this study, three physical topical dug delivery enhancements, elongated microparticles, microneedles and dermaroller, were applied to ex vivo pig skin and compared. The model topical drug that was used is 5-Aminolevulinic acid, the most commonly used photosensitiser prodrug. The skin was pre-treated before mounting on to Franz cell diffusion apparatus. Transdermal epidermal water loss was measured, and receptor fluids were collected at 7 time points for HPLC analysis. The results show that all three technologies disrupted the skin surface. All microporation pre-treatments significantly enhanced mALA cumulative permeation over 8 h (p elongated microparticles.
