Investigating the TeV Morphology of MGRO J1908+06 with VERITAS

We report on deep observations of the extended TeV gamma-ray source MGRO J1908+06 made with the VERITAS very high energy (VHE) gamma-ray observatory. Previously, the TeV emission has been attributed to the pulsar wind nebula (PWN) of the Fermi-LAT pulsar PSR J1907+0602. We detect MGRO J1908+06 at a significance level of 14 standard deviations (14 sigma) and measure a photon index of 2.20 +/- 0.10_stat +/- 0.20_sys. The TeV emission is extended, covering the region near PSR J1907+0602 and also extending towards SNR G40.5--0.5. When fitted with a 2-dimensional Gaussian, the intrinsic extension has a standard deviation of sigma_src = 0.44 +/- 0.02 degrees. In contrast to other TeV PWNe of similar age in which the TeV spectrum softens with distance from the pulsar, the TeV spectrum measured near the pulsar location is consistent with that measured at a position near the rim of G40.5--0.5, 0.33 degrees away.Comment: To appear in ApJ, 8 page

Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer

Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis, the process of new lymphatics formation. The present study investigated VEGF-C mRNA expression in invasive cervical cancer tissue. Additionally, the association of VEGF-C mRNA with clinicopathological features was examined. VEGF-C mRNA expression was assessed by reverse transcription-polymerase chain reaction using β-action as an internal control. 75 patients presenting with invasive cervical cancer were included in the trial. VEGF-C mRNA expression was markedly higher in tumours in which pelvic lymph node metastasis was diagnosed by magnetic resonance (MR) imaging (P = 0.002). 53 patients displaying stage Ib–IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. VEGF-C expression was significantly higher in tumours exhibiting deep stromal invasion, pelvic lymph node metastasis and lymph-vascular space involvement (P = 0.016, P = 0.006 and P = 0.036, respectively). Multivariate analysis revealed VEGF-C mRNA expression to be the sole independent factor influencing pelvic lymph node metastasis. Subjects demonstrating VEGF-C mRNA expression displayed significantly poorer prognoses than those lacking VEGF-C mRNA expression (P = 0.049). These findings provide evidence supporting the involvement of VEGF-C expression in the promotion of lymph node metastasis in cervical cancer. Furthermore, examination of VEGF-C expression in biopsy specimens may be beneficial in the prediction of pelvic lymph node metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice

<p>Abstract</p> <p>Background</p> <p>Mutations of the <it>MEN1 </it>gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that <it>Men1 </it>disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the <it>Men1 </it>mutant mice.</p> <p>Methods</p> <p>To study the occurrence of prostate lesions, we followed a male mouse cohort of 47 <it>Men1</it>^+/-mice and 23 age-matched control littermates, starting at 18 months of age, and analysed the prostate glands from the cohort.</p> <p>Results</p> <p>Six <it>Men1</it>^+/-mice (12.8%) developed prostate cancer, including two adenocarcinomas and four <it>in situ </it>carcinomas, while none of the control mice developed cancerous lesions. The expression of menin encoded by the <it>Men1 </it>gene was found to be drastically reduced in all carcinomas, and partial LOH of the wild-type <it>Men1 </it>allele was detected in three of the five analysed lesions. Using immunostaining for the androgen receptor and p63, a basal epithelial cell marker, we demonstrated that the menin-negative prostate cancer cells did not display p63 expression and that the androgen receptor was expressed but more heterogeneous in these lesions. Furthermore, our data showed that the expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a <it>Men1 </it>target gene known to be inactivated during prostate cell tumorigenesis, was notably decreased in the prostate cancers that developed in the mutant mice.</p> <p>Conclusion</p> <p>Our work suggests the possible involvement of <it>Men1 </it>inactivation in the tumorigenesis of the prostate gland.</p

Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception

Elevated level of inhibin-α subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer

The biological function of inhibin-α subunit (INHα) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHα in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHα. We conducted a cross-sectional study to determine a link between INHα expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHα in advanced cancer. Elevated expression of INHα in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Over-expressing INHα in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INHα-positive LNCaP demonstrated reduced tumour growth whereas INHα-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INHα associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INHα expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa

A model for co-expression pattern analysis of genes implicated in angiogenesis and tumour cell invasion in cervical cancer

To date, numerous genes have been identified which are involved in both tumour neovascularisation (angiogenesis) and tumour cell invasion, and most of them are also expressed to some extent under normal physiological conditions. However, little is known about how these genes co-express in these settings. This study was undertaken to quantitate mRNA levels in normal and malignant cervical tissues of nine selected genes (VEGF121, VEGF165, VEGF189, VEGF-C, eIF-4E, b-FGF, TSP-2, MMP-2 and MMP-9) implicated in the above processes using real-time quantitative RT–PCR. In addition, the Spearman's rank correlation was used to determine their co-expression patterns. The transcript levels for the different VEGF-A splice variants (VEGF121, VEGF165, VEGF189) were at least 10-fold higher in the cancer cases, with the highest levels in the primary tumours demonstrating lympho-vascular space involvement. The lymphangiogenic factor VEGF-C and MMP-9 were upregulated 130- and 80-fold respectively in cervical cancers. The highest levels of VEGF-C mRNA were found in the lymph-node positive group. The transcript levels for b-FGF were similar in normal cervical tissue and early-stage cervical cancer, however, higher levels were found in the cervical cancers with advanced stage disease. Comparing gene transcript levels between recurrent and non-recurrent cervical cancer patients revealed significant differences (P=0.038) in transcript levels for the angiogenesis inhibitor TSP-2, with the highest levels in non-recurrent cases. Co-expression pattern analysis in normal cervical tissue revealed highly significant co-expressions (P<0.0001) between TSP-2 and most other genes analysed (VEGF121, VEGF165, VEGF-C, b-FGF and MMP-2). In cervical cancer, TSP-2 appears only to be highly co-expressed with MMP-2 (P<0.0001). In contrast to normal cervical tissue, we found a highly significant co-expression (P<0.0001) between MMP-9 and VEGF189 in cervical cancer. The combined application of real-time quantitative RT–PCR and Spearman's rank correlation identifies gene transcripts which are simultaneously co-expressed. Our results revealed a significant co-expression between the angiogenesis inhibitor TSP-2 and most other genes analysed in normal cervical tissue. In cervical cancer, we found a strong upregulation of VEGF-C and MMP-9 mRNA, with a highly significant co-expression between MMP-9 and VEGF189

VERITAS: Status and Highlights

The VERITAS telescope array has been operating smoothly since 2007, and has detected gamma-ray emission above 100 GeV from 40 astrophysical sources. These include blazars, pulsar wind nebulae, supernova remnants, gamma-ray binary systems, a starburst galaxy, a radio galaxy, the Crab pulsar, and gamma-ray sources whose origin remains unidentified. In 2009, the array was reconfigured, greatly improving the sensitivity. We summarize the current status of the observatory, describe some of the scientific highlights since 2009, and outline plans for the future.Comment: Presented at the 32nd ICRC, Beijing, 201