Induction of Immune Mediators in Glioma and Prostate Cancer Cells by Non-Lethal Photodynamic Therapy

BACKGROUND: Photodynamic therapy (PDT) uses the combination of photosensitizing drugs and harmless light to cause selective damage to tumor cells. PDT is therefore an option for focal therapy of localized disease or for otherwise unresectable tumors. In addition, there is increasing evidence that PDT can induce systemic anti-tumor immunity, supporting control of tumor cells, which were not eliminated by the primary treatment. However, the effect of non-lethal PDT on the behavior and malignant potential of tumor cells surviving PDT is molecularly not well defined. METHODOLOGY/PRINCIPAL FINDINGS: Here we have evaluated changes in the transcriptome of human glioblastoma (U87, U373) and human (PC-3, DU145) and murine prostate cancer cells (TRAMP-C1, TRAMP-C2) after non-lethal PDT in vitro and in vivo using oligonucleotide microarray analyses. We found that the overall response was similar between the different cell lines and photosensitizers both in vitro and in vivo. The most prominently upregulated genes encoded proteins that belong to pathways activated by cellular stress or are involved in cell cycle arrest. This response was similar to the rescue response of tumor cells following high-dose PDT. In contrast, tumor cells dealing with non-lethal PDT were found to significantly upregulate a number of immune genes, which included the chemokine genes CXCL2, CXCL3 and IL8/CXCL8 as well as the genes for IL6 and its receptor IL6R, which can stimulate proinflammatory reactions, while IL6 and IL6R can also enhance tumor growth. CONCLUSIONS: Our results indicate that PDT can support anti-tumor immune responses and is, therefore, a rational therapy even if tumor cells cannot be completely eliminated by primary phototoxic mechanisms alone. However, non-lethal PDT can also stimulate tumor growth-promoting autocrine loops, as seen by the upregulation of IL6 and its receptor. Thus the efficacy of PDT to treat tumors may be improved by controlling unwanted and potentially deleterious growth-stimulatory pathways

Prevalence of sexually transmitted infections among women attending antenatal clinics in Tanga, north eastern Tanzania

This study aimed to determine the prevalence of sexually transmitted infections (STIs) among HIV-infected and uninfected pregnant women in Tanga, Tanzania. Retrospective data on syphilis and HIV status during 2008-2010 were collected from antenatal clinic (ANC) records. Prospective data were collected from HIV-infected (n = 105) and HIV-uninfected pregnant women (n = 100) attending ANCs between April 2009 and August 2010. Syphilis prevalence showed a declining trend (3.1%, 1.4% and 1.3%), while HIV prevalence was stable (6.1%, 6.4% and 5.4%) during 2008-2010. HIV-infected women had significantly higher prevalence of trichomoniasis (18.8% versus 5.0%; P < 0.003) and candidiasis (16.5% versus 2.0%; P < 0.001) while the higher rate of gonorrhoea (3.5% versus 0%; P = 0.095) was not statistically significant when compared with HIV-uninfected women. There were no statistically significant differences in prevalence of chlamydial infection (0% versus 3.0%; P = 0.156) or syphilis (2.4% versus 3.0%; P = 1) between HIV-infected and uninfected women. Other STIs were common in both HIV-infected and uninfected pregnant women

Identification of Novel Biomarkers in Seasonal Allergic Rhinitis by Combining Proteomic, Multivariate and Pathway Analysis

Background: Glucocorticoids (GCs) play a key role in the treatment of seasonal allergic rhinitis (SAR). However, some patients show a low response to GC treatment. We hypothesized that proteins that correlated to discrimination between symptomatic high and low responders (HR and LR) to GC treatment might be regulated by GCs and therefore suitable as biomarkers for GC treatment. Methodology/Principal Findings: We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and performed multivariate analysis to identify a combination of proteins that best separated symptomatic HR and LR. Pathway analysis showed that those proteins were most enriched in the acute phase response pathway. We prioritized candidate biomarkers for GC treatment based on the multivariate and pathway analysis. Next, we tested if those candidate biomarkers differed before and after GC treatment in nasal fluids from 40 patients with SAR using ELISA. Several proteins including ORM (P&lt;0.0001), APOH (P&lt;0.0001), FGA (P&lt;0.01), CTSD (P&lt;0.05) and SERPINB3 (P&lt;0.05) differed significantly before and after GC treatment. Particularly, ORM (P&lt;0.01), FGA (P&lt;0.05) and APOH (P&lt;0.01) that belonged to the acute phase response pathway decreased significantly in HR but not LR before and after GC treatment. Conclusions/Significance: We identified several novel biomarkers for GC treatment response in SAR with combined proteomics, multivariate and pathway analysis. The analytical principles may be generally applicable to identify biomarkers in clinical studies of complex diseases.Funding Agencies|European Commission|223367|MultiMod||Swedish Medical Research Council||</p

Tumores nasossinusais raros: série de casos e revisão de literatura Rare nasosinusal tumors: case series and literature review

Os tumores nasossinusais são patologias pouco freqüentes na prática clínica. Aproximadamente 0,8% de todos os cânceres humanos localizam-se nessa região. Apesar de rara, a neoplasia nasossinusal manifesta-se habitualmente através de sintomas inespecíficos e comuns a inúmeras patologias inflamatórias. Este estudo se propõe a descrever uma série de casos de tumores nasossinusais não-epiteliais raros, incluindo estesioneuroblastoma, granuloma central de células gigantes, plasmocitoma extramedular, hemangiopericitoma sinonasal, neurofibroma e fibroma cemento-ossificante, diagnosticados no Hospital Geral de Fortaleza, SESA/SUS. Faz-se uma breve revisão de literatura de cada patologia, salientando-se a necessidade do diagnóstico anatomopatológico preciso para condução adequada de cada caso.<br>Tumors of the nasal cavity and paranasal sinuses are unusual pathologies found in clinical practice. Approximately 0.8% of all human cancers are located in this area. Despite being rare, nasosinusal neoplasms usually manifest through nonspecific symptoms that are common to numerous inflammatory pathologies. The aim of this study is to describe a series of rare nasosinusal tumors, including esthesioneuroblastomas, central giant cell granulomas, extramedullary plasmocytomas, nasosinusal hemangiopericytomas, neurofibromas and cemento-ossifying fibromas, diagnosed at the Fortaleza General Hospital. We, hereby, briefly review each of the aforementioned pathologies, stressing the need for a precise histological diagnosis for proper treatment in each case

Neuroendocrine Neoplasms of the Upper Aerodigestive Tract, Ear, and Salivary Glands

Neuroendocrine neoplasms (NENs) of the head and neck (H&amp;N) region include a heterogeneous group of neoplastic proliferations arising in the nasal cavity, paranasal sinuses, nasopharynx, larynx, salivary glands, middle ear, and skin. In addition to epithelial neoplasms, H&amp;N paraganglioma and olfactory neuroblastoma can be included in this group. The morphological and clinical features of H&amp;N NENs depend on several different factors, including their degree of differentiation, site of origin, and molecular background. Indeed, H&amp;N NENs encompass a wide spectrum of neoplasms, ranging from indolent neuroendocrine tumors to highly aggressive neuroendocrine carcinomas