HMGA1 accelerates the malignant progression of gastric cancer through stimulating EMT.

OBJECTIVE: To clarify the role of HMGA1 in influencing proliferation and migration abilities, and EMT (epithelial-mesenchymal transition) in gastric cancer (GC) cells. MATERIALS AND METHODS: Differential expressions of HMGA1 in GC tissues and normal gastric tissues were analyzed in the GEPIA dataset. Its influence on overall survival of GC patients was evaluated as well. Moreover, HMGA1 levels in GC cells and gastric mucosal cells were detected. Regulatory effects of HMGA1 on the proliferation and migration abilities in SGC7901 and MGC803 cells were assessed through a series of functional experiments. At last, influences of HMGA1 on the expression levels of EMT-related genes, E-cadherin, Snail, and Slug were determined in GC cells. RESULTS: Analysis of data in TCGA GEPIA dataset revealed that HMGA1 was upregulated in GC tissues, and GC patients with a high expression level of HMGA1 suffered poorer prognosis. In addition, HMGA1 was identically upregulated in GC cells, and the overexpression of HMGA1 improved the proliferation and migration abilities of SGC7901 and MGC803 cells, downregulated E-cadherin, and upregulated Snail and Slug in GC cells, while silence of HMAG1 yielded the opposite results CONCLUSIONS: HMGA1 is upregulated in GC tissues and predicts poor prognosis, and it aggravates the progression of GC via stimulating EMT.

[Measurement of morphological parameters of internal acousticmeatus using thin-section CT].

Objective: This study aimed to measure the morphological parameters of the internal acoustic meatus(IAM) and its adjacent structures using temporal-bone thin-section CT(computed tomography). Methods: CT images were obtained from 50 Chinese adult patients (25 males and 25 females, 100 sides) which had no visible lesion in the petrous part of the temporal bone and inner ear, the morphological parameters of all inner ear parts were sectionally measured on the specified plane using SPSS 22.0 software for statistical analysis. Results: The integral morphological characteristics of the IAM were observed. These results revealed that anterior-posterior diameter of the internal acoustic poer(IAP)(CD) was (6.93±1.85)mm, the superior-inferior diameter of the IAP(EF) was (4.40±0.86)mm, the length of the IAM(AB) was (9.30±1.60)mm, the superior-inferior diameter of the IAM(the intersection of inner 1/3 section and middle 1/3 section) was (4.13±0.83)mm, the superior-inferior diameter of the IAM(the intersection of middle 1/3 section and outer 1/3 section) was (4.61±1.02)mm, the anterior-posterior diameter of the IAM(the intersection of inner 1/3 section and middle 1/3 section) was (6.62±1.92)mm, the anterior-posterior diameter of the IAM(the intersection of middle 1/3 section and outer 1/3 section) was (6.28±1.65)mm, the depth of transverse crest (superior wall) was (3.10±0.75)mm, the depth of transverse crest (interior wall)the was (1.46±0.59)mm, the distance from transverse crest vertex A to the superior wall of the IAM was (2.05±0.42)mm, the distance from transverse crest vertex A to the interior wall of the IAM was (2.93±0.41)mm, the thickness of the superior bone wall of the IAM (the intersection of inner 1/3 section and middle 1/3 section) was (4.45±1.34)mm, the thickness of the superior bone wall of the IAM (the intersection of middle 1/3 section and outer 1/3 section) was (4.32±1.12)mm, the thickness of the superior bone wall of the IAM (the intersection of outer 1/3 section and transverse crest vertex) was (4.37±1.28)mm, and the appearance ratio of the cells in the whole IAM superior wall was 32%.The whole IAM assumed the shape of short cylinder, inclining about 1 cm outward, with the upper-lower diameter and anterior-posterior diameter about 5 mm. Conclusion: It is necessary for carrying out preoperative the temporal-bone thin-section CT to obtain the morphological parameters of the IAM, determine its basic morphology, and provide references to avoid damaging the other important structures during IAM surgeries.

[An association between obstructive sleep apnea hypopnea syndrome and deep vein thrombosis and pulmonary embolism].

OSAHS is a kind of the sleep-related breathing disorder, with lack of oxygen. OSAHS can induce many kinds of cardiovascular system diseases. Deep vein thrombosis and pulmonary embolism (deep vein thrombosis and/or pulmonary embolism, DVT and PE) is caused by deep vein thrombosis embolism pulmonary artery trunk or branch pulmonary disorder, potentially lethal diseases of the cardiovascular system. In recent years, researchers have found that OSAHS may have something to do with DVT-PE. So in this review, the relationship was summarized between OSAHS and DVT-PE in epidemiology, pathophysiology, assessment and treatment measures.

Transplantation of RADA16-BDNF peptide scaffold with human umbilical cord mesenchymal stem cells forced with CXCR4 and activated astrocytes for repair of traumatic brain injury.

Due to the poor self-regeneration of brain tissue, stem cell transplantation therapy is purported to enable the replacement of lost neurons after traumatic brain injury (TBI). The main challenge of brain regeneration is whether the transplanted cells can survive and carry out neuronal functions in the lesion area. The brain is a complex neuronal network consisting of various types of cells that significantly influence on each other, and the survival of the implanted stem cells in brain is critically influenced by the surrounding cells. Although stem cell-based therapy is developing rapidly, most previous studies just focus on apply single type of stem cells as cell source. Here, we found that co-culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) directly with the activated astrocytes benefited to the proliferation and neuron differentiation of hUC-MSCs in vitro. In this study, hUC-MSCs and the activated astrocytes were seeded in RADA16-BDNF peptide scaffold (R-B-SPH scaffold), a specifical self-assembling peptide hydrogel, in which the environment promoted the differentiation of typical neuron-like cells with neurites extending in three-dimensional directions. Moreover, the results showed co-culture of hUC-MSCs and activated astrocytes promoted more BDNF secretion which may benefit to both neural differentiation of ectogenic hUC-MSCs and endogenic neurogenesis. In order to promote migration of the transplanted hUC-MSCs to the host brain, the hUC-MSCs were forced with CXC chemokine receptor 4 (CXCR4). We found that the moderate-sized lesion cavity, but not the large cavity caused by TBI was repaired via the transplantation of hUC-MSCsCXCR4 and activated astrocytes embedded in R-B-SPH scaffolds. The functional neural repair for TBI demonstrated in this study is mainly due to the transplantation system of double cells, hUC-MSCs and activated astrocytes. We believe that this novel cell transplantation system offers a promising treatment option for cell replacement therapy for TBI. STATEMENT OF SIGNIFICANCE: In this reach, we specifically linked RGIDKRHWNSQ, a functional peptide derived from BDNF, to the C-terminal of RADARADARADARADA (RADA16) to structure a functional self-assembling peptide hydrogel scaffold, RADA16-BDNF (R-B-SPH scaffold) for the better transplantation of the double cell unit. Also, the novel scaffold was used as cell-carrier for transplantation double cell unit (hUC-MSCs/astrocyte) for treating traumatic brain injury. The results of this study showing that R-B-SPH scaffold was pliancy and flexibility to fit the brain lesion cavity and promotes the outgrowth of axons and dendrites of the neurons derived from hUC-MSCs in vitro and in vivo, indicating the 3D R-B-SPH scaffold provided a suitable microenvironment for hUC-MSC survival, proliferation and differentiation. Also, our results showing the double-cells transplantation system (hUC-MSCs/astrocyte) may be a novel cell-based therapeutic strategy for neuroregeneration after TBI with potential value for clinical application.

Defining gross tumor volume using positron emission tomography/computed tomography phantom studies.

Tumor volume and standard uptake value (SUV) calculated from positron emission tomography/computed tomography (PET/CT) images differ from their real values. Besides errors introduced by scintillation materials, photomultiplier tubes, and image reconstruction algorithms, measurements are affected by patients' prostheses, body movements, and body shape. To address these problems, we calculated tumor volume and SUV using the standard phantom (PET Phantom-NEMA IEC/2001) and obtained calibration constants. We found that while tumor volume increases with increasing SUV and tumor diameter, it also increases with increasing SUV and decreasing tumor diameter. Conversely, tumor volume decreases with decreasing SUV and tumor diameter and with decreasing SUV and increasing diameter. These results suggest that a correction factor should be applied to SUV and tumor volume obtained from PET/CT images.

Lung cancer cell migration is regulated via repressing growth factor PTN/RPTP ß/ζ signaling by menin.

Menin encoded by the multiple endocrine neoplasia type 1 (MEN1) gene is associated with chromatin and the nuclear matrix and exerts multiple biological functions including regulation of cell proliferation and adhesion. Men1 mutations increase the likelihood of lung cancer development in mice. Menin expression is reduced in certain human non-small cell lung cancer cells, and reduction of menin is closely correlated with increased lung cancer metastasis to lymph nodes. However, it is poorly understood whether menin affects migration of lung cancer cells. In this study, we show that menin-regulated A549 lung cancer cell migration, which was mediated by growth factor pleiotrophin (PTN) and its cell surface receptor, protein tyrosine phosphatase beta/zeta (RPTP ß/ζ). Ectopic menin expression significantly repressed PTN transcription, but indirectly inhibited RPTP ß/ζ expression through repressing PTN expression. Further studies revealed that menin-regulated cell migration through PTN/RPTP ß/ζ, in conjunction with integrin α(v)ß(3), focal adhesion kinase, phosphatidylinositol 3-kinase and phosphorylated extracellular signal regulated kinase 1/2. These findings provide mechanistic insights into the molecular basis for menin/PTN-mediated regulation of A549 lung cancer cell migration.

Suppression of lung adenocarcinoma through menin and polycomb gene-mediated repression of growth factor pleiotrophin.

Menin upregulates transcription of cell-cycle inhibitors to suppress endocrine tumors, but it is poorly understood how menin suppresses non-endocrine tumors such as lung cancer. Here, we show that menin inhibits proliferation of human lung cancer cells and growth of lung cancer in mice. The menin-mediated tumor suppression requires repression of growth factor pleiotrophin (PTN), which binds to its cell surface receptor, anaplastic lymphoma kinase (ALK) that is activated in certain lung adenocarcinomas. Menin represses PTN transcription and PTN-induced proliferation of human lung cancer cells, and menin expression is substantially reduced in primary human lung adenocarcinomas. Notably, menin binds the PTN locus and enhances Polycomb gene Enhancer of Zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27m3), a negative mark for gene transcription but does not affect histone H3K4 methylation that is usually upregulated by menin in endocrine cells. Together, our findings indicate that menin suppresses lung cancer partly through increasing Polycomb gene-mediated H3K27 methylation and repressing PTN transcription, unraveling a novel, epigenetically regulated PTN-ALK signaling pathway in suppressing lung cancer.

Menin regulates endocrine diseases by controlling histone modification and gene transcription.

Multiple endocrine neoplasia type 1 (MEN1), a human familial tumor syndrome, results from mutations in the Men1 gene. Although much progress has been made in demonstrating the definitive role for menin in suppressing tumorigenesis in endocrine organs, the molecular pathways responsible for menin action in normal tissues and tumors remain poorly defined. Here, we review the recent progress on the molecular functions of menin in controlling cell proliferation, apoptosis, and DNA repair. The majority of these functions are largely executed by menin-mediated influencing of histone modifications and chromatin structure. These findings lead to a new model of understanding menin's tumor-suppressing function, providing insights into understanding of how menin regulates cell proliferation and the development of endocrine tumors. The new knowledge could also be translated into new strategies to improve therapeutic interventions against MEN1 and other endocrine diseases including diabetes.

Whole-body low dose irradiation promotes the efficacy of conventional radiotherapy for cancer and possible mechanisms.

The purpose of the present study was to explore the possibility of establishing cancer radiotherapy protocols that could promote treatment efficacy at a reduced radiation dose. Mouse models of melanoma (B16) and Lewis lung carcinoma (LLC) were used in the experiments. Conventional local radiotherapy was combined with low dose whole-body irradiation (LDWBI) in the presence or absence of gene therapy by intratumor injection of a recombinant plasmid Egr-mIL-18-B7.1 (E18B). After a number of trials with different combinations it was found that a protocol of 2-week treatment with 2 x (E18B + 2 Gy + 0.075 Gy x 2) was found to be able to promote treatment efficacy at a reduced radiation dose. In this protocol local irradiation with 2Gy was administered 24h after intratumor injection of 10 microg of the plasmid E18B followed by LDWBI with 0.075 Gy every other day for 2 sessions in 1 week, and the procedure was repeated for another week. When this combined treatment was compared with conventional radiotherapy, i.e., 2Gy every other day 3 times in one week repeated for 2 weeks, the treatment efficacy was improved, as judged by increased average survival rate, reduced mean tumor weight, reduced pulmonary metastasis and suppressed intratumor capillary growth with a 2/3 reduction of radiation dose. Immunologic studies showed stimulated natural killer (NK) and cytotoxic T lymphocyte (CTL) activity as well as increased interferon-gamma (IFN-gamma) secretion in this combined treatment group as compared with the group receiving local treatment alone. It is suggested that up-regulation of host anticancer immunity by LDWBI and the initiation of expression of immune genes by both the local large dose and LDWBI are important factors in the realization of improved cancer control.