Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target

Medulloblastomas are the most common malignant brain tumors in children. They express high levels of COX-2 and produce PGE2, which stimulates tumor cell proliferation. Human cytomegalovirus (HCMV) is prevalent in the human population and encodes proteins that provide immune evasion strategies and promote oncogenic transformation and oncomodulation. In particular, HCMV induces COX-2 expression; STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor, and IL-6; and tumor formation in vivo. Here, we show that a large proportion of primary medulloblastomas and medulloblastoma cell lines are infected with HCMV and that COX-2 expression, along with PGE2 levels, in tumors is directly modulated by the virus. Our analysis indicated that both HCMV immediate-early proteins and late proteins are expressed in the majority of primary medulloblastomas. Remarkably, all of the human medulloblastoma cell lines that we analyzed contained HCMV DNA and RNA and expressed HCMV proteins at various levels in vitro. When engrafted into immunocompromised mice, human medulloblastoma cells induced expression of HCMV proteins. HCMV and COX-2 expression correlated in primary tumors, cell lines, and medulloblastoma xenografts. The antiviral drug valganciclovir and the specific COX-2 inhibitor celecoxib prevented HCMV replication in vitro and inhibited PGE2 production and reduced medulloblastoma tumor cell growth both in vitro and in vivo. Ganciclovir did not affect the growth of HCMV-negative tumor cell lines. These findings imply an important role for HCMV in medulloblastoma and suggest HCMV as a novel therapeutic target for this tumor.     

A genome-wide association scan on estrogen receptor-negative breast cancer

Introduction

Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.

Methods

We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.

Results

Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of small P-values for SNPs with known regulatory functions in cancer-related pathways was found (global P = 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer.

Conclusions

ER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers.     

Hydatid cyst of the parotid gland

Primary hydatid cyst of the parotid gland is extremely rare, even in the endemic areas. A 23-year-old woman presented with slowly progressive swelling in the right periauricular region. Computed tomography (CT) scan of the head and neck revealed a round, well-demarcated water-density mass in the right parotid gland. At the operation, the cystic mass replacing most of the superficial part of right parotid gland was demonstrated. Superficial parotidectomy was carried out. Histopathological examination confirmed the diagnosis of hydatid disease. CT scan is a valuable imaging method for diagnosis of parotid cystic lesions; however, other acquired and congenital cystic lesions of parotid gland may have similar appearance and should be differentiated. Where the incidence of the disease is high, hydatid cyst of parotid gland should be considered in the differential diagnosis of lesions causing swelling of the parotid area.     

马蹄肾经皮肾取石术的疗效

本文主要评价了经皮肾取石术治疗马蹄肾结石的疗效. 从1995～2005年,Mahboub等对9例马蹄肾结石患者进行了经皮肾取石术,其中3例为单个结石,其余为多个结石.     

Protective vaccination against experimental canine visceral leishmaniasis using a combination of DNA and protein immunization with cysteine proteinases type I and II of L. infantum

Leishmania infantum is known to be associated with visceral leishmaniasis in Iran and canids are natural reservoirs. Control of disease in dogs appears to be one of the most effective approaches for interrupting the domestic cycle of the disease. In search for successful vaccine strategies, we evaluated the cysteine proteinases (CPs) type I and II using a heterologous prime-boost regime for vaccination against experimental visceral leishmaniasis in dogs. Following vaccination and challenge, dogs were followed for 12 months. Ten dogs vaccinated by prime/boost with DNA/recombinant CPs (in combination with CpG ODN and Montanide 720) remained free of infection in their bone morrow. In contrast, three out of four dogs in the control groups had infection in their bone marrow. The peripheral lymphocytes from protected animals had generally higher proliferation responses to F/T antigen, recombinant CPA (rCPA) and recombinant CPB (rCPB) than controls. During post-challenge period, the difference in stimulation index is significant (p<0.05) on months 11 and 12 to F/T antigens, all months for rCPA and 5, 7, 9, 11 and 12 months for rCPB. Analysis of cytokine mRNA level suggested that vaccinated dogs had elevated IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC), whereas there was a consistent increase in the level of IL-10 in the control groups and some vaccinated dogs. The level of total IgG and IgG2, but not IgG1, to rCPA and rCPB was significantly higher in the vaccinated group (p<0.05) than the control groups. We also showed that with the exception of one dog, all dogs in the vaccinated group in comparison to control dogs had strong DTH responses. We propose that the combination of DNA and recombinant protein vaccination using CPs could be instrumental to control (VL) in dogs.     

Nephrolithiasis as primary symptom in sarcoidosis

A 30-year-old black woman presented with a 1-year history of repeated episodes of worsening weight loss and fatigue. Physical examination showed no skin lesions and a chest roentgenogram was normal. Workup showed no obvious cause of recurrent renal stones. Finally, the detection of lymphadenopathy led to the diagnosis of extrapulmonary sarcoidosis. Up to 4% of all cases of sarcoidosis may present with urolithiasis only. Renal stones may be more common in severe cases of sarcoidosis, which affect blacks most frequently. Although not generally recommended for diagnostic purposes in sarcoidosis, in this case determination of the angiotensin-converting enzyme level was helpful in making the correct diagnosis. It is important that physicians are aware of the possibility that sarcoidosis may present as urolithiasis, even in the presence of a negative chest roentgenogram.     

Conventional and diffusion magnetic resonance imaging in the acute phase of severe traumatic brain injury

Neuro-imaging is essential for the initial evaluation and subsequent control in the acute stage of severe head injury. In these indications tomodensitometry (TDM) has a pivotal role. Despite the well recognized contribution of magnetic resonance imaging (MRI) to the investigation of most of acute neurological pathologies, MRI is not still a routine procedure for the initial investigation of patients with acute head injury. The superiority of morphological and functional MRI on TDM in this indication is discussed.     

Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women

Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01–0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.