Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.
Background: Successful multimodality management of advanced soft tissue sarcomas (STS) remains a clinical challenge. Although immune checkpoint blockade has shown great promise, only a minority of patients respond. Improved biomarkers could benefit the treatment choice, since cytotoxic therapies and radiotherapy (RT) can alter the immune milieu. The objective of this study was to characterize PD-L1 expression in locally advanced STS with or without preoperative RT. Design: Tissue microarrays (TMA) were constructed using formalin-fixed, paraffin-embedded STS cases (N=17). A composite H-scoring system was applied to analyze/ quantify the protein expression. TMA sections were immunostained using a rabbit anti-human PD-L1 antibody (Sino Biological, Clone: 015). The intensity and percentage of PDL-1-positive cells were calculated and scored blindly. Patients were categorized into PD-L1 high and low-expressing based on H-score above or below the median. Parametric and non-parametric statistics were used as appropriate. Results: Mean age was 55±21, 82% were female, and 53% of STS tumors were located on the extremity. Median tumor size was 15.5 cm (range 2.4-24.8 cm). Half of the cases received preoperative RT. We observed 9 recurrences, and 5 sarcoma deaths. Overall, PD-L1 expression was significantly lower among RT patients (62.5±23.1 vs 139±90.5, p=0.04), and tumor stem cell markers EGFR/CD44 were also significantly lower among chemotherapy patients (p < 0.05). Distant recurrences were more common in PDL-1 high patients (5/8, 62%) than PDL-1 low patients (2/9, 22%). Conclusions: RT is associated with decreased PD-L1 expression in locally advanced STS, and lower PD-L1 expression is associated with improved longterm outcome. The modulation of PDL-1 expression by RT and the impact on prognosis in STS warrants further study. Background: Dedifferentiated liposarcoma (DDLPS) sometimes exhibit heterologous differentiation, and its influence on prognostic outcome is still controversial. As for ossification, it is also not clear whether the bone component means heterologous differentiation or it can be formed by reactive (non-neoplastic) mesenchymal cells. We aimed to investigate the neoplastic nature of the bones formed in DDLPS, and make clear the clinical and pathological characteristics of DDLPS with ossification. Design: We examined 27 cases of DDLPS with ossification by comparing them with 24 cases of DDLPS without ossification and 17 cases of primary extraskeletal osteosarcoma (ESOS) without MDM2 amplification or overexpression. The clinical and pathological findings were reviewed. Histological grade was determined using 'modified' FNCLCC grading system proposed before emphasizing the importance of tumor differentiation scoring. Results: MDM2 amplification was confirmed in osteocytes and/or osteoblastic cells in all DDLPS cases with ossification where Fluorescence In-Situ Hybridization (FISH) was successfully performed in bone forming area (22/22). The bones found in DDLPS were mainly mature in most cases (20/27), and ...
OBJECTIVE -To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment.
RESEARCH DESIGN AND METHODS-This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 Ϯ 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA 1c Ͻ7.5%, n ϭ 93 (group G), and poor HbA 1c Ն7.5%, n ϭ 57 (group P); and survival was followed until December 1999, with a mean follow-up period of 2.7 years.RESULTS -Group G had better survival than group P (the control group) (P ϭ 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA 1c was a significant predictor of survival (hazard ratio 1.133 per 1.0% increment of HbA 1c , 95% CI 1.028 -1.249, P ϭ 0.012), as were Cre and CTR.CONCLUSIONS -Good glycemic control (HbA 1c Ͻ7.5%) predicts better survival of diabetic ESRD patients starting hemodialysis treatment.
Diabetes Care 24:909 -913, 2001
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.