Benign Orbital Tumors with Bone Destruction in Children

Purpose: To present rare benign orbital tumors with bone destruction in children who could not be diagnosed presurgically and may simulate malignant ones. Methods: A retrospective review of cases. Clinical, operative and pathological records in all children with a diagnosis of benign orbital tumors who showed remarkable bone destruction at a tertiary Ophthalmic Center in China between Jan 1, 2000 and Dec 31, 2009 were reviewed. All patients had definitive histopathologic diagnosis. Results: Eight patients with benign orbital tumors showed obvious bone destruction, including six cases of eosinophilic granuloma, one case of leiomyoma and one case of primary orbital intraosseous hemangioma. Among them, three patients were females and five patients were males. Tumors were unilateral in all cases, with both the right and left side affected equally. Age ranged from 3 to 7 years (mean 4.1 years). Symptom duration ranged from 1 to 5 weeks (mean 4.8 weeks). Eyelid swelling and palpable mass were the most common complaint. There was no evidence for multifocal involvement in cases with eosinophilic granuloma. Among six patients with eosinophilic granuloma, two were treated with low dose radiation (10 Gy), three received systemic corticosteroid and one was periodically observed only after incisional biopsy or subtotal curettage. There was no postoperative therapeutic intervention in the two patients with leiomyoma and intraosseous hemangioma. All eight patients regained normal vision without local recurrence after a mean follow-up time o

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in causespecific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = .45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.This work was supported by NIH grants RO1 CA56678, RO1 CA114524, and P50 CA97186; additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute

CXCR4/CXCL12 Participate in Extravasation of Metastasizing Breast Cancer Cells within the Liver in a Rat Model

INTRODUCTION: Organ-specific composition of extracellular matrix proteins (ECM) is a determinant of metastatic host organ involvement. The chemokine CXCL12 and its receptor CXCR4 play important roles in the colonization of human breast cancer cells to their metastatic target organs. In this study, we investigated the effects of chemokine stimulation on adhesion and migration of different human breast cancer cell lines in vivo and in vitro with particular focus on the liver as a major metastatic site in breast cancer. METHODS: Time lapse microscopy, in vitro adhesion and migration assays were performed under CXCL12 stimulation. Activation of small GTPases showed chemokine receptor signalling dependence from ECM components. The initial events of hepatic colonisation of MDA-MB-231 and MDA-MB-468 cells were investigated by intravital microscopy of the liver in a rat model and under shRNA inhibition of CXCR4. RESULTS: In vitro, stimulation with CXCL12 induced increased chemotactic cell motility (p,0.05). This effect was dependent on adhesive substrates (type I collagen, fibronectin and laminin) and induced different responses in small GTPases, such as RhoA and Rac-1 activation, and changes in cell morphology. In addition, binding to various ECM components caused redistribution of chemokine receptors at tumour cell surfaces. In vivo, blocking CXCR4 decreased extravasation of highly metastatic MDA-MB-231 cells (p < 0.05), but initial cell adhesion within the liver sinusoids was not affected. In contrast, the less metastatic MDA-MB-468 cells showed reduced cell adhesion but similar migration within the hepatic microcirculation. CONCLUSION: Chemokine-induced extravasation of breast cancer cells along specific ECM components appears to be an important regulator but not a rate-limiting factor of their metastatic organ colonization.Claudia Wendel, André Hemping-Bovenkerk, Julia Krasnyanska, Sören Torge Mees, Marina Kochetkova, Sandra Stoeppeler and Jörg Haie

CXCR4 Expression in Prostate Cancer Progenitor Cells

Tumor progenitor cells represent a population of drug-resistant cells that can survive conventional chemotherapy and lead to tumor relapse. However, little is known of the role of tumor progenitors in prostate cancer metastasis. The studies reported herein show that the CXCR4/CXCL12 axis, a key regulator of tumor dissemination, plays a role in the maintenance of prostate cancer stem-like cells. The CXCL4/CXCR12 pathway is activated in the CD44+/CD133+ prostate progenitor population and affects differentiation potential, cell adhesion, clonal growth and tumorigenicity. Furthermore, prostate tumor xenograft studies in mice showed that a combination of the CXCR4 receptor antagonist AMD3100, which targets prostate cancer stem-like cells, and the conventional chemotherapeutic drug Taxotere, which targets the bulk tumor, is significantly more effective in eradicating tumors as compared to monotherapy

The Current status of density stratification of Koggala lagoon

A field observation was conducted on 22nd November 2011 to estimate the present state of density stratification of Koggala lagoon. Vertical variation of salinity, water temperature and dissolved oxygen were measured with neap and ebb. The same measurements were taken from inflow streams. The observations indicate that main water body of the lagoon is salinity stratified despite the strong or partial mixing at the mouth. Particularly, strong saline stratification is prominent in the deep central part of the lagoon. Firstly, the current hydraulic state and then bulk parameter of Koggala lagoon is analysed. The relationship between the mixing state and the values of parameters of Koggala lagoon agree with Fisher’s plot. The effects of modification of lagoon mouth are discussed based on these parameters. Temporal and spatial complexities of lagoon mouth affect transport and mixing of saline water and intrusion into the lagoon. In future, a modified bulk parameter will be needed for better understanding of stratification behaviour of the Koggala lagoon