Response to pretransplant hypomethylating agents influences the outcome of allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndromes

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2‐yr disease‐free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G‐COR (group of continuous response, n = 19), G‐NoC (group of no change, n = 15), G‐LOR (group of loss of response, n = 6), and G‐DP (group of disease progression, n = 4), respectively. When dichotomized as G‐COR/G‐NoC versus G‐LOR/G‐DP, significantly different 2‐yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G‐LOR/G‐DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G‐LOR/G‐DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher‐risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G‐COR showed a trend of better DFS compared with G‐NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS.     

Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin

Baicalin (baicalein-7-glucuronide) is a flavonoid purified from Scutellaria baicalensis Georgi that has traditionally been used for treatment of hypertension, cardiovascular diseases, and viral hepatitis. In this study, the effects of intestinal microbiota on the pharmacokinetics of baicalin were investigated in normal and antibiotic-pretreated rats following p.o. administration of 100 mg/kg baicalin by using liquid chromatography/ion trap mass spectrometry. When rats were pretreated orally with cefadroxil, oxytetracycline and erythromycin for 3 days to control the number of intestinal bacteria, the pharmacokinetic parameters of oral baicalin were significantly affected by antibiotics: C_max, T_1/2(β), K_el and AUC values were significantly changed compared to those in normal rats. These results indicate that intestinal microbiota might play a key role in the oral pharmacokinetics of baicalin.     

Dosimetric evaluation of a three-phase adaptive radiotherapy for nasopharyngeal carcinoma using helical tomotherapy

Adaptive radiotherapy (ART) has been introduced to correct the radiation-induced anatomic changes in head and neck cases during a treatment course. This study evaluated the potential dosimetric benefits of applying a 3-phase adaptive radiotherapy protocol in nasopharyngeal carcinoma (NPC) patients compared with the nonadaptive single-phase treatment protocol. Ten NPC patients previously treated with this 3-phase radiation protocol using Hi-Art Tomotherapy were recruited. Two new plans, PII-ART and PIII-ART, were generated based on the up-to-date computed tomography (CT) images and contours and were used for treatment in phase two (PII; after 25th fraction) and phase three (PIII; after 35th fraction), respectively. To simulate the situation of no replanning, 2 hybrid plans denoted as PII-NART and PIII-NART were generated using the original contours pasted on the PII- and PIII-CT sets by CT-CT fusion. Dosimetric comparisons were made between the NART plans and the corresponding ART plans. In both PII- and PIII-NART plans, the doses to 95% of all the target volumes (D₉₅) were increased with better dose uniformity, whereas the organs at risk (OARs) received higher doses compared with the corresponding ART plans. Without replanning, the total dose to 1% of brainstem and spinal cord (D₁) significantly increased 7.87 ± 7.26% and 10.69 ± 6.72%, respectively (P = 0.011 and 0.001, respectively), in which 3 patients would have these structures overdosed when compared with those with two replannings. The total maximum doses to the optic chiasm and pituitary gland and the mean doses to the left and right parotid glands were increased by 10.50 ± 10.51%, 8.59 ± 6.10%, 3.03 ± 4.48%, and 2.24 ± 3.11%, respectively (P = 0.014, 0.003, 0.053, and 0.046, respectively). The 3-phase radiotherapy protocol showed improved dosimetric results to the critical structures while keeping satisfactory target dose coverage, which demonstrated the advantages of ART in helical tomotherapy of NPC.     

Evaluation of the angiographic outcomes after clipping of intracranial aneurysms: determination of predisposing factors for occurrence of aneurysm remnants

ABSTRACT

Objectives: Aneurysm remnants after microsurgical clipping have a risk of regrowth and rupture and have not been validated in the era of three-dimensional angiography. Therefore, this study aimed to evaluate the angiographic outcome using three-dimensional rotational images and determine the predictors for remnants after microsurgical clipping.

Methods: Between January 2014 and May 2017, 139 aneurysms in 106 patients who were treated with microsurgical clipping, were eligible for this study. For the determination of aneurysm remnants after microsurgical clipping, the angiographic outcomes were evaluated using follow-up digital subtraction angiography within 7 days for unruptured aneurysms or within 2 weeks for ruptured aneurysms. According to the Sindou classification, the aneurysm remnants were dichotomized, and subgroup analysis was performed to identify the predictors of aneurysm remnants after clipping with various imaging parameters and clinical information.

Results: The overall rate of aneurysm remnants was 29.5% (41/139), in which retreatments were needed in 6.5% (9/139). The neck size and maximum diameter of aneurysms were independent predisposing factors for the aneurysm remnants that need retreatment (OR: 2.30; p < 0.001; OR: 1.38; p < 0.001, respectively).

Conclusions: This study demonstrated a low incidence of aneurysm remnants after microsurgical clipping which need to retreatment. However, selective postoperative angiography could provide us clear information of surgical result and evidence for long-term follow-up for some aneurysms with larger neck size (>5.7 mm) and maximum diameter (>7.1 mm).     

Protective activity of a novel resveratrol analogue,HS-1793, against DNA damage in 137Cs-irradiated CHO-K1 cells

Resveratrol has received considerable attention as a polyphenol with anti-oxidant, anti-carcinogenic, and anti-inflammatory effects. Radiation is an important component of therapy for a wide range of malignant conditions. However, it causes damage to normal cells and, hence, can result in adverse side effects. This study was conducted to examine whether HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, induces a protective effect against radiation-induced DNA damage. HS-1793 effectively scavenged free radicals and inhibited radiation-induced plasmid DNA strand breaks in an in vitro assay. HS-1793 significantly decreased reactive oxygen species and cellular DNA damage in 2 Gy-irradiated Chinese hamster ovary (CHO)-K1 cells. In addition, HS-1793 dose-dependently reduced the levels of phosphorylated H2AX in irradiated CHO-K1 cells. These results indicate that HS-1793 has chemical radioprotective activity. Glutathione levels and superoxide dismutase activity in irradiated CHO-K1 cells increased significantly following HS-1793 treatment. The enhanced biological anti-oxidant activity and chemical radioprotective activity of HS-1793 maintained survival of irradiated CHO-K1 cells in a clonogenic assay. Therefore, HS-1793 may be of value as a radioprotector to protect healthy tissue surrounding tumor cells during radiotherapy to obtain better tumor control with a higher dose.     

Immune Response and the Tumor Microenvironment: How They Communicate to Regulate Gastric Cancer

Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world''s population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.     

Comparison of allergen-specific IgE levels between Immulite 2000 and ImmunoCAP systems against six inhalant allergens and ten food allergens

Abstract

In vitro allergen-specific immunoglobulin E (sIgE) measurement has been used as an important diagnostic tool for allergic diseases. Currently, quantitative sIgE levels are detected mainly by using ImmunoCAP and Immulite 2000 assay system. These two systems have the same calibration scale at 0–100 kUA/L, but they differ in used allergens, detection methods and automation systems. We compared 1600 paired sIgE results for 204 allergic patients, including 100 paired sIgE assay results for each of 16 allergens (Alternaria alternata, birch-alder mix, cat dander, D. farinae, D. pteronyssinus, dog dander, buckwheat, crab, egg white, mackerel, milk, peach, peanut, shrimp, soybean and wheat flour). Inter-method comparison was performed for qualitative data with a cutoff of 0.35 kUA/L and a detection limit of 0.1 kUA/L, semi-quantitative class results and quantitative data. In qualitative comparisons, the overall concordance rate ranged from 81.0% to 99.0% (k: 0.599–0.949) with the cutoff value of 0.35 kUA/L. It also ranged from 80.0% to 99.0% (k: 0.521–0.951) with the detection limit of 0.1 kUA/L. The class results from these two assays showed good agreements for all allergens. For quantitative sIgE results, these two assays showed moderate positive correlations for Dog dander (r?=?0.683) and Mackerel (r?=?0.573) but high to very high correlations for the other 14 allergens (r?=?0.734–0.972). Immulite 2000 and ImmunoCAP assays demonstrated good concordance and correlation for 16 common allergens, but international standards against each specific allergen for calibration and harmonization of sIgE tests are still needed.