Clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumor.

OBJECTIVE: Brainstem tumors present a significant challenge in surgical treatment, and the prognostic factors in children are lacking. This study aimed to investigate clinical characteristics and prognostic factors of surgical treatment in children with brainstem tumors. PATIENTS AND METHODS: 50 children with brainstem tumors who underwent surgical treatment, including frameless- or frame-based stereotactic biopsy and resection, were included and followed up for clinical and biological analysis. Factors of outcomes were assessed by univariate and multivariate analysis. RESULTS: 27 cases (54.0%) underwent resection in all children with brainstem tumors. The rate of resection reached as high as 81.8% in children with non-diffuse intrinsic pontine glioma (DIPG), while in children with DIPG, biopsy was performed in the majority, and resection was obtained in the minority with focal necrosis. A rare complication was found following the surgery. Multivariate analysis considered World Health Organization (WHO) grade 3-4, with hazard ratio (HR)=4.48, 95% confidence interval (CI) of 2.84-8.69, p=0.001, H3K27M mutation (HR=2.50, 95% CI 1.73-5.69, p=0.015), and hydrocephalus (HR=2.17, 95% CI 1.08-5.32, p=0.014) as independent adverse prognostic factors. For Kaplan-Meier analysis, children with WHO grade 3-4, Ki-67 LI ≥ 20%, TP53 mutation, H3K27M mutation, DIPG, and hydrocephalus had significantly decreased overall survival (OS). CONCLUSIONS: A high rate of resection has been obtained in non-DIPG, and surgical intervention is remarkably safe and efficient for children with brainstem tumors. WHO grade 3-4, H3K27M mutation, and hydrocephalus indicate poor prognosis in children with brainstem tumors.

Characterization of a TIR-NBS-LRR gene associated with downy mildew resistance in grape.

Grapevine downy mildew, caused by Plasmopara viticola, is a devastating disease that results in considerable economic losses as well as environmental damage through the repeated application of fungicides. The nucleotide-binding site leucine-rich repeat gene family functions in plant immunoactivity against various pathogens and pests. In this study, the 5' and 3' ends of the resistance gene homology fragment RGA5 were obtained by rapid amplification of cDNA ends. The 4282-base pair full-length cDNA was obtained using gene-specific primers, and the corresponding 1335-amino acid protein sequence contained characteristic nucleotide-binding site leucine-rich repeat domains of plant resistance proteins, including the toll-interleukin receptor type region. Expression of RGA5 during P. viticola infection and abiotic stress was investigated using quantitative real-time polymerase chain reaction. The results showed that treatment with P. viticola and 4 abiotic stimuli (salicyclic acid, methyl-jasmonate, abscisic acid, H2O2) significantly induced RGA5 within 12 days of inoculation. Therefore, RGA5 may play a critical role in protecting grapevines against P. viticola via signaling pathways involving these molecules.

Alteration of HLA-F and HLA I antigen expression in the tumor is associated with survival in patients with esophageal squamous cell carcinoma.

Alteration of human leukocyte antigen (HLA) expression, such as decreased HLA I (HLA-A, -B and -C) antigens and elevated nonclassical HLA I antigens (HLA-E, -F and -G), was reported to have an unfavorable prognosis in various cancers. In our study, HLA-F expression in 105 primary esophageal squamous cell carcinoma (ESCC) lesions and 62 case-matched adjacent normal tissues, and HLA I antigens among 68 cases were analyzed by immunohistochemistry. Data revealed that HLA-F expression was observed in 58.1% (61/105) of the ESCC lesions and in 54.8% (34/62) of the normal esophageal tissues. Among the 62 case-matched samples, HLA-F expression (lesion vs. normal tissue) was upregulated, unchanged and downregulated in 13 (21.0%), 6 (9.6%) and 43 (69.4%) cases, respectively. Patients with HLA-F positive had a worse survival than those with HLA-F negative (p = 0.040). Patients with upregulated HLA-F expression (lesion vs. normal tissue) had significantly worse survival than those with HLA-F unchanged and downregulated (p = 0.010). Furthermore, decreased HLA I expression was observed in 41.2% (28/68) patients and was with worse prognosis in comparison to those with preserved HLA I expression (p = 0.001). Multivariate analysis using Cox's proportional hazards model revealed that upregulated HLA-F expression (p = 0.026) and downregulated HLA I expression (p = 0.013) could be an independent unfavorable prognostic factor. In conclusion, our study provided the evidence that alteration of HLA I and HLA-F antigen expression was associated with survival in patients with ESCC.

HLA-G expression is irrelevant to prognosis in patients with acute myeloid leukemia.

Human leukocyte antigen (HLA)-G could contribute to escape of cancer cells from host anti-tumor responses, and its potential clinical relevance in various malignancies was also addressed. However, the prognostic value of HLA-G in acute myeloid leukemia (AML) remains debated. In this study, HLA-G expression in malignant blasts was analyzed from 77 de novo AML patients (AML-M2, n=26; AML-M3, n=24; AML-M4, n=10; AML-M5, n=17) with flow cytometry. The proportion of HLA-G expressing blasts varied from 0% to 93.96% (median: 0.42%; 95% CI: 0-89.0%). Blasts with 0.5% or fewer HLA-G expressing were defined as negative according to its expression in normal CD34(+)CD45(+) cells (n=20, range: 0-0.5%; median: 0.13%; 95% CI: 0-0.42%). HLA-G expression status on leukemic blasts was not associated with the clinical parameters such as patient age at diagnosis, sex, sub-type of AML, percentage of blasts at diagnosis. Survival analysis revealed that HLA-G expression status on leukemic blasts is unrelated to the prognosis (p=0.884). The mean overall survival time for the HLA-G negative and positive patients was 20.7 months (95% CI: 16.1-25.3) and 20.1 months (95% CI: 14.3-25.8), respectively. Taken together, our findings indicated that HLA-G expression is of no significance for the prognosis of patients with AML.

VNTR polymorphism of human IL1RN in Chinese Han and She ethnic populations.

Interleukin 1 receptor antagonist (IL-1Ra) is an important anti-inflammatory molecule encoded by the IL1RN gene. The polymorphism of IL1RN characterized by variable numbers of an 86 bp tandem repeat (VNTR) sequence in intron 2 has been described. Moreover, frequencies of the IL1RN alleles vary among different ethnics. In the present study, we analysed the IL1RN polymorphism in intron 2 in 256 Chinese Han and 252 Chinese She individuals. Four alleles including IL1RN*1, *2, *3 and IL1RN*4 were identified in this study. Data revealed that the distribution of the IL-1RN genotypes and allele was significantly different between the two Chinese populations (P < 0.001). Among them, 66.8% (171/256) and 86.5% (218/252) were homozygous for the allele IL-1RN*1 in Chinese Han and She individuals respectively. Homozygosity for allele IL-1RN*2 was only observed in Chinese Han with the percentage of 0.8% (2/256). Heterozygosity for IL-1RN*1/2, IL1RN*1/3 and IL1RN*1/4 was 30.9% (79/256), 0.4% (1/256) and 1.2% (3/256) in Chinese Han, whereas only heterozygosity for IL-1RN*1/2 was found in Chinese She (13.5%, 34/252). Frequencies of the most common allele IL-1RN*1 and IL-1RN*2 were 83.0% and 16.2% for Chinese Han and 93.3% and 6.7% for Chinese She respectively. The rare allele IL-1RN*3 and IL-1RN*4 was only observed in the Chinese Han population with the frequency of 0.2% and 0.6% respectively. Our findings suggested that the ethnic background plays an important role in IL-1Ra gene variation in different populations.

A possible role of initial cell death due to mechanical stretch in the regulation of subsequent cell proliferation in experimental vein grafts.

The proliferation of vascular cells contributes to the formation of neointima and hypertrophy of the blood vessel wall. Here we show that mechanical stretch possibly regulates the proliferation of vascular cells via the mediation of cell death in a rat vein graft model. The wall of vein grafts is subject to a suddenly increased mechanical stretch due to exposure to arterial blood pressure. Such a stretch induces rapid cell death with a reduction in cell density by approximately 60% within the first day after surgery. The initial cell death was followed by an increase in the percentage of proliferating cells, as shown by a BrdU incorporation assay (1.55 +/- 1.27%, 8.48 +/- 2.27%, 11.93 +/- 2.36%, 6.36 +/- 1.77%, and 5.60 +/- 1.46% at days 1, 5, 10, 20, and 30, respectively). When mechanical stretch was reduced by restraining the vein graft using a polytetrafluoroethylene sheath, the percentage of proliferating cells reduced significantly (0.76 +/- 0.76%, 1.70 +/- 0.46%, 1.29 +/- 0.56%, 0.99 +/- 0.83%, and 0.47+/-0.52% at days 1, 5, 10, 20, and 30, respectively). A further reduction in cell density, induced by local administration of a cell death inducer ceramide to experimental vein grafts (without sheath), enhanced subsequent cell proliferation. In contrast, a prevention of cell death, induced by local administration of a cell death inhibitor tetrapeptide-aldehyde DEVD-CHO to experimental vein grafts (without sheath), significantly reduced subsequent cell proliferation. These results suggest that mechanical stretch induces cell death, which possibly mediates subsequent cell proliferation in the present model.