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Dural tail sign and increased caliber of branches of the external carotid artery (ECA) are common findings in meningioma and they have been rarely reported in intra-axial lesions. Anyway, some cases of glioblastoma (GBM) are reported in the literature, mostly superficially localized, characterized by these 2 findings and therefore, misdiagnosed with meningioma. The aim of this study is to verify the prevalence of dural tail sign and hypertrophy of middle meningeal artery (MMA) in a large cohort of GBMs. 180 GBM patients were retrospectively evaluated. Deep or superficial localization of GBM was established and the presence of dural tail sign and hypertrophy of the ipsilateral MMA were assessed. The rate of tumor necrosis and the incidence of dural metastases during the radiological follow-up were also evaluated. Inter-rater reliability was calculated using Cohen's K-test. Dural tail sign and enlarged MMA were evident in 30% and 19% of 96 superficial GBM, respectively. Deep GBM did not present those signs. Only one patient developed dural metastasis at follow-up and no differences in terms of tumor necrosis and hypoxic biomarkers expression were evident among GBMs with and without dural and vessel signs. Dural tail sign and hypertrophy of the MMA in superficial GBM are more common than expected. They probably represent reactive rather than a neoplastic infiltration. Knowing these radiological signs may be important in terms of neurosurgery planning and avoiding excessive bleeding. Anyway, this hypothesis should be confirmed by a prospective neurosurgery studio. [ABSTRACT FROM AUTHOR]

Abstract: Loss of heterozygosity at the FHIT locus is coincident with activation of DNA damage response checkpoint proteins; thus damage at fragile loci may trigger checkpoint activation. We examined preneoplastic lesions adjacent to non-small cell lung carcinomas for alterations to expression of Fhit and activated checkpoint proteins. Expression scores were analyzed for pair-wise associations and correlations among proteins and type of lesion. Hyperplastic and dysplastic lesions were positive for nuclear γH2AX expression; 12/20 dysplastic lesions were negative for Fhit expression. Fhit positive lesions showed expression of most checkpoint proteins examined, while Fhit negative lesions showed absence of expression of Chk1 and phosphoChk1. The results show that loss of expression of Fhit is significantly directly correlated with absence of activated Chk1 in dysplasia, and suggest a connection between loss of Fhit and modulation of checkpoint activity. [Copyright &y& Elsevier]

Objective: To analyze the frequency of peritoneal natural killer (NK) cells expressing the human leukocyte antigen (HLA)-E receptor CD94/NKG2A in patients with endometriosis. Design: Case–control study. Setting: University hospital. Patient(s): Stage III and stage IV endometriosis, according to the revised American Society for Reproductive Medicine classification, was laparoscopically and histologically confirmed in 11 and 9 patients, respectively; 13 subjects without endometriosis were selected for the control group. Intervention(s): Collection of peripheral venous blood, peritoneal fluid, endometriotic tissue, and normal endometrium in subjects undergoing laparoscopy. Main Outcome Measure(s): Surface expression levels of CD94/NKG2A and CD94/NKG2C were detected by three-color cytofluorometric analysis. Semiquantitative HLA-E messenger RNA expression analysis was performed in endometriotic lesions and in eutopic endometrium. NK cell-mediated cytotoxic activity toward HLA-E positive target, DT360 cell line, was also determined. Result(s): In women with endometriosis, the percentage of CD94/NKG2A–positive peritoneal NK cells was significantly higher than in the control group. The CD94/NKG2A ligand, HLA-E, was detected at high levels in endometriotic tissue as messenger RNA transcript. Target cells bearing HLA-E were resistant to NK cell–mediated lysis in a CD94/NKG2A-dependent manner. Conclusion(s): Increased expression of CD94/NKG2A in peritoneal NK cells may mediate the resistance of endometriotic tissue to NK cell–mediated lysis, thus contributing to the progression of the disease. [Copyright &y& Elsevier]

Presents a letter to the editor about Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8.

The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the accuracy of the TRIMprob in the diagnosis of prostate neoplasm. Methods: Consecutive patients referred for prostate biopsy were prospectively enrolled. Patients had history taken, physical examination by digital rectal examination (DRE) of the prostate, assessment of total and free serum prostate-specific antigen (PSA) levels, prostate transrectal ultrasonography (TRUS), and TRIMprob test. Indications for prostate biopsy included one or more of the following conditions: total serum PSA levels of 4.0 ng/mL or more, free/total serum PSA ratio of 0.18 or less, positive results on DRE, and suspicious findings on TRUS. Twelve-core, TRUS-guided biopsies were performed with local anesthesia. A blinded investigator performed the TRIMprob test; the lowest value of the signal at 465 MHz was looked for and recorded, although data of the electromagnetic signal at 930 and 1295 MHz were also recorded. Results: One hundred eleven patients (aged 64.9 ± 8.1 years, mean ± standard deviation), enrolled between November 2004 and August 2005, were analyzed. Total serum PSA level was 8.4 ± 3.6 ng/mL, and free/total serum PSA ratio was 0.15 ± 0.7. TRIMprob sensitivity for the diagnosis of prostate cancer was 0.86%; specificity and positive and negative predictive values were 0.60 and 0.88; accuracy was 72%. TRIMprob accuracy outperformed any other diagnostic parameter considered, including the rule of chance. The association of TRIMprob and DRE offered a sensitivity and a negative predictive value of 0.86% or greater. Conclusions: TRIMprob had the highest accuracy rate, among all other tests, for the diagnosis of prostate cancer. Electromagnetic detection with the TRIMprob test seems to be a promising technology and a useful additional tool for the early detection of prostate cancer. [Copyright &y& Elsevier]

Abstract: Poly(ADP-ribose) polymerase (PARP)-1 has recently been shown to promote tumour progression. Since angiogenesis is an essential requirement for tumour growth, we examined whether PARP inhibition/deletion might affect endothelial cell functions. To this end, the influence of PARP inhibitors on endothelial cell proliferation, migration, tube formation and angiogenesis in PARP-1 knock-out mice, using an in vivo matrigel plug assay, was investigated. The results indicated that the PARP inhibitor GPI 15427 (IC50 on endothelial PARP: 237±27nM), at concentrations devoid of cytotoxic effects (0.5–1μM), abrogated migration in response to vascular endothelial growth factor or placenta growth factor, hampered formation of tubule-like networks and impaired angiogenesis in vivo. The anti-angiogenic effect of the PARP inhibitor was confirmed in PARP-1 knock-out mice that displayed a defect of angiogenesis induced by growth factors. These results provide evidence for targeting PARP for anti-angiogenesis, adding novel therapeutic implications to the use of PARP inhibitors in cancer treatment. [Copyright &y& Elsevier]