Malignant gastrointestinal neuroectodermal tumor: a clinicopathological analysis of three cases / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.

Recombinant human bone morphogenetic protein-2 promotes the proliferation of mesenchymal stem cells in vivo and in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bone morphogenetic protein (BMP) is a member of the superfamily of transforming growth factor-beta. Recent studies show that it is an indispensable factor in hematopoiesis. To better characterize the effect of recombinant human BMP (rhBMP)-2 in hematopoiesis, we set out to determine whether rhBMP-2 could promote the proliferation of mesenchymal stem cells (MSCs) and increase the levels of hematopoietic cytokines in MSCs.</p><p><b>METHODS</b>2, 3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino) carbonyl)-2H-tetrazolium hydroxide (XTT), real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the effects of rhBMP-2 on the proliferation and hematopoietic cytokine levels of MSCs. In addition, MSCs marked with Hoechst33342 were transplanted into BALB/c mice by the intravenous route or intra-bone marrow transplantation, and cluster numbers were counted.</p><p><b>RESULTS</b>The XTT test revealed that rhBMP-2 significantly induced proliferation of MSCs in doses ranging from 10 ng/ml to 0.1 mg/ml in a dose-dependent manner. The experiments in vivo showed that there were more clusters of donor cells in bone marrow, spleen, liver and lung of the BMP group than those in the control group after both intra-bone marrow transplantation (P < 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively) and intravenous transplantation (P < 0.001, P < 0.001, and P < 0.001 respectively). The results of real-time PCR and ELISA revealed that rhBMP-2 significantly increased mRNA expressions and protein levels of IL-6, IL-7, IL-11, G-CSF, M-CSF and SCF.</p><p><b>CONCLUSIONS</b>The treatment with rhBMP-2 promotes the proliferation of MSCs in vivo and in vitro and increases the levels of hematopoietic cytokines in MSCs, which may contribute to the improvement of hematopoietic function.</p>

Research on relationship of survivin gene expression with malignant proliferation and apoptosis of brain glioma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression level of inhibitor of apoptosis protein survivin gene in human brain glioma and its role in malignant proliferation and antiapoptosis of brain glioma.</p><p><b>METHODS</b>Eighty-three cases of brain glioma specimen was chosen, protein expression of survivin and proliferating cell nuclear antigen (PCNA) was investigated by immunohistochemistry streptavidin-biotin complex (SABC) method, the immunoreactivity score (IRS) of survivin and the proliferative index (PI) were counted. Apoptotic cells were screened by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method, and the apoptotic index (AI) of brain glioma was calculated.</p><p><b>RESULTS</b>The survivin IRS, PI and AI of brain glioma were 3.8 +/- 3.9, (28.4 +/- 19.5)% and (1.0 +/- 0.8)% respectively, and all of them were elevated with the increase of pathological grade of brain glioma (P < 0.01 for all). PI in survivin positive group was significantly higher than that in survivin negative group (P < 0.01), and PI was positively correlated with survivin IRS (r = 0.740, P < 0.01). There was no significant difference between AI in survivin positive group and that in survivin negative group (P > 0.05), however, AI was negatively correlated with survivin IRS (r = -0.307, P < 0.01).</p><p><b>CONCLUSIONS</b>Survivin is overexpressed in brain glioma, and which may play important roles in malignant proliferation and antiapoptosis of brain glioma.</p>