IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

To what extent does IQ 'explain' socio-economic variations in function?

Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Salivary disease in childhood

Salivary disease in childhood is uncommon. Clinical features are much the same as in adult disease, however, congenital, inflammation, and functional disease is more common. Management is governed by the same general principles in all age groups. Congenital abnormalities are rare. Inflammation, either bacterial or viral, is the most common disease. Chronic sialadenitis usually resolves at puberty. Neoplasia is rare, and the majority of tumors are benign and occur in the parotid gland. Malignancy is suggested by rapid growth, pain, skin fixation, and lymphadenopathy. Surgical treatment of sialorrhea should only be considered after careful assessment. Relocation of the submandibular ducts is the treatment of choice.     

INTERFERONS IN ONCOLOGY

SUMMARY The interferons are natural glycoproteins secreted in response to various stimuli, including viral infection. They have antiviral, antiproliferative and immunomodulatory effects on different target cell populations. Since recombinant human interferons have become available, they have been tested in a wide range of malignancies. They are well established in the treatment of hairy cell leukaemia, chronic myelogenous leukaemia and multiple myeloma. Although they have documented activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours, their role in the treatment of these tumours is less clear. In the common solid tumours, such as lung cancer and colorectal cancer, the use of interferons remains experimental. Here we will summarise their practice applications in oncology, using randomised studies where available to establish their place in multi-modality treatment. We will not discuss their use as antiviral or immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or after organ transplantation.     

Sexual abuse of children: an area with room for professional reforms

The cases of 46 children who had been abused sexually an average of 2.6 years previously, were reviewed and the non-offending parents were interviewed with emphasis on how they viewed the professional persons who had seen their children, and their opinions of the legal processes that were instituted. The parents found most professional groups helpful, with officers from the Department of Youth and Community Services being seen as the least helpful. Twenty-one of the cases went to court; in 12 cases this resulted in a conviction, and prison sentences were imposed on six of the offenders. Children found the court experience distressing and most parents expressed dissatisfaction with the outcome of the court hearing. Children were more likely to be required to give evidence in court if the offender had legal representation. Persisting behavioural problems and poor school performance were more likely to occur in those cases in which there had been court hearings. A review of Police Department records of children who had attended the hospital for the management of sexual assault, showed that 10 of the 107 children who are now aged over 14 years, have themselves been convicted of violent crimes since their episode of sexual assault. Long-term intervention is required to help many of these children, some legal reforms are necessary to reduce the stress that they experience when there is a court hearing, and all the professional groups that are likely to become involved with the problem of the sexual abuse of children need to be better informed about its seriousness and consequences.