In this open-label randomized clinical trial, HLA-identical sibling-matched hematopoietic stem cells (HSC) were transplanted (non-MSCs group, n ¼ 15) or cotransplanted with mesenchymal stem cells (MSCs) (MSCs group, n ¼ 10) in hematologic malignancy patients. The median number of MSCs infused was 3.4 Â 10 5 kg À1 (range, 0.3-15.3 Â 10 5 kg À1 ). MSCs infusions were well tolerated. The median time to neutrophil engraftment (absolute neutrophil count 40.5 Â 10 9 l À1 ) was 16 days for MSCs group and 15 days for non-MSCs group. The median time to platelet engraftment (platelet count 450 Â 10 9 l À1 ) was 30 and 27 days, respectively. Grades II-IV acute graft-versus-host disease (GVHD) was observed respectively, in one (11.1%) and eight (53.3%) evaluable patients. Chronic GVHD was found in one (14.3%) and four (28.6%) evaluable patients. The number of patients who relapsed were six (60.0%) and three (20.0%), and the 3-year disease-free survivals were 30.0 and 66.7%, respectively. Thus cotransplantation of MSCs and HSCs may prevent GVHD, but the relapse rate is obviously higher than the control group. We conclude that use of MSCs must be handled with extreme caution before a large-scale clinical trial is performed.
In a systematic review and meta-analysis, we found that endoscopic screening may reduce the risk of death from gastric cancer and not affect incidence in Asian countries. Population-based prospective cohort studies are warranted to confirm our findings.
Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.
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