Lu Yuntao

MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1.

Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers.In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb) and proliferating cell nuclear antigen (PCNA) in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3′-untranslated regions (3′-UTR) of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.

The arachnoid sleeve enveloping the pituitary stalk: anatomical and histologic study.

BACKGROUNDThe arachnoid membrane in the suprasellar region may affect the growth pattern of sellar and suprasellar tumors however, the topographic relationships between the pituitary stalk and the surrounding arachnoid membranes remained unclear. OBJECTIVEThe aim of this study was to evaluate the anatomical and histological characteristics of the arachnoid membranes. METHODSMicrosurgical dissection and anatomical observation were performed in 16 formalin-fixed adult cadaver heads. In the other 5 adult cadaver heads, histologic sections of sellar-suprasellar specimens were studied under light microscopy. RESULTSAn arachnoid sleeve enveloping the pituitary stalk of variable length presented in all specimens, which was formed by direct upward extension of the basal arachnoid membrane covering the diaphragma sellae. In the majority of specimens, the arachnoid sleeve was reinforced by the arachnoid trabeculae originating from the basal arachnoid membrane, the Liliequist membrane, and the medial carotid membrane. CONCLUSIONThe relationship between the pituitary stalk and the surrounding arachnoid membrane is important in evaluating the growth patterns of the sellar and suprasellar tumors, and their topographical relationships.

Association between the XRCC1 Arg399Gln polymorphism and risk of cancer: evidence from 297 case-control studies.

Background The Arg399Gln polymorphism in the X-ray cross-complementing group 1 (XRCC1) had been implicated in cancer susceptibility. The previous published data on the association between XRCC1 Arg399Gln polymorphism and cancer risk remained controversial. Methodology/Principal Findings To derive a more precise estimation of the association between the XRCC1 Arg399Gln polymorphism and overall cancer risk, we performed a meta-analysis of 297 case-control studies, in which a total of 93,941 cases and 121,480 controls were included. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR] = 1.04, 95% confidence interval [CI] = 1.01–1.07; recessive model: OR = 1.08, 95% CI = 1.03–1.13; additive model: OR = 1.09, 95% CI = 1.04–1.14) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly elevated hepatocellular and breast cancers risk were observed in Asians (dominant model: OR = 1.39, 95% CI = 1.06–1.84) and in Indians (dominant model: OR = 1.64, 95% CI = 1.31–2.04; recessive model: OR = 1.94, 95% CI = 1.09–3.47; additive model: OR = 2.06, 95% CI = 1.50–2.84), respectively. Conclusions/Significance This meta-analysis suggests the participation of XRCC1 Arg399Gln is a genetic susceptibility for hepatocellular cancer in Asians and breast cancer in Indians. Moreover, our work also points out the importance of new studies for Arg399Gln association in some cancer types, such as glioma, gastric cancer, and oral cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC1 Arg399Gln polymorphism in cancer development.

Membranous layers of the pituitary gland: histological anatomic study and related clinical issues.

OBJECTIVE The purpose of this study was to examine the membranous layers of the human pituitary gland and their relationships with invasive adenomas. METHODS Histological and microdissection techniques were used to study 8 fetal and 10 adult human cadavers, respectively. The distribution of the membranous layers was observed, and their thickness was measured. The results were analyzed histologically and anatomically. RESULTS In all specimens, the pituitary glands were found to be coated by 2 membranous layers, the inner layer being referred to here as the lamina propria and the outer as the pituitary capsule. In all specimens, the 2 membranes were intact with no histological defects. An interstice or cavity between the 2 layers was found on the surface of the adenohypophysis. However, as these 2 layers got closer and closer to each other, they began to adhere on the surface of the neurohypophysis. The thickness of the pituitary capsule was not constant like that of the lamina propria: the inferolateral part of the capsule was thicker than the other parts. The medial wall of the cavernous sinus (CS) was also a bilayered membrane just like the other CS walls: the 2 layers of the medial CS wall were composed of the lateral part of the pituitary capsule and the fibrous layer. Many fibrous trabeculae arising from this fibrous layer divided the CS into several small venous spaces and connected the internal carotid arteries with the medial wall. CONCLUSION The terminology for the 2 membranous layers, the lamina propria and the pituitary capsule, seemed to be more appropriate and representative of the histological features of the pituitary layers. The lateral part of the capsule and the fibrous layer constituted the medial wall of the CS, which has a superior part that is weaker than the thicker inferior part. It is still difficult to postulate the criteria needed to predict CS invasion. However, the distance between the 2 sides of the internal carotid artery might be another predictive criterion to preoperatively diagnose CS invasion by adenomas. Enhanced knowledge of these membranes may be of assistance in finding a useful criterion.

Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis?

Calcification in adamantinomatous craniopharyngioma (ACP) is troublesome for surgical intervention. The aim of this study was to examine the osteogenic proteins that play important roles in the calcium deposition of the odontogenic/osteogenic tissues in craniopharyngioma.

TPD52L2 impacts proliferation, invasiveness and apoptosis of glioblastoma cells via modulation of wnt/β-catenin/snail signaling

Intratumoral heterogeneity greatly hinders efficiency of target therapy in glioblastoma (GBM). To decipher the underlying mechanisms of heterogeneity, patient-derived adult GBM cells were separately isolated from margins of T1 gadolinium enhancing tumor lesions (PNCs) and T1 gadolinium enhancing core lesions (ECs). Single clone culture was conducted in ECs and U87MG cell line to screen clones with distinct biological phenotypes. Single cell clones with diverse phenotypes were simultaneously separated from ECs and U87 cell line. PNCs, GCs(H) and U87(H) exhibited longer cellular protrusion than ECs, GCs(L) and U87(L), respectively. Cell strains with longer protrusion exhibited higher invasive ability and lower sensitivity to temozolomide (TMZ) and radiation. Subsequently, TPD52L2 was verified as the functional protein to regulate the cellular heterogeneity by the proteomics analysis. Downregulation of TPD52L2 enhanced cell invasion whereas inhibited cell proliferation rate and sensitivity to chemotherapy in vivo and in vitro, this condition was reversed when TPD52L2 was overexpressed. The invasiveness was facilitated by up-regulating CTNNB1/β-catenin and SNAI1/Snail mediated EMT process. In addition, the clinical data of 88 GBM cases in our neurosurgery center was analyzed to reveal the influence of TPD52L2 in the prognosis of GBM. Low expression of TPD52L2 exacerbated prognosis of GBM patients received standard radiotherapy plus concomitant and adjuvant TMZ (Stupp strategy). Taken together, TPD52L2 is an important biomarker influencing GBM prognosis.