Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response

Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response. Methodology/Principal Findings: We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response. Conclusion: Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.United States. National Cancer Institute (grant RO1CA/AI838801)United States. National Cancer Institute (grant R01AI050875

The bile acid receptor, TGR5, regulates basal and cholinergic-induced secretory responses in rat colon.

Bile acids (BA) are becoming increasingly appreciated as enteric hormones that regulate many aspects of intestinal physiology. The BA receptor, TGR5, has been recently shown to be expressed on enteric nerves and enterochromaffin cells (ECs), where its activation regulates small intestinal and colonic motility. Here, we show that TGR5 is also expressed on colonic epithelial cells and that its activation decreases basal secretory tone and inhibits cholinergic-induced secretory responses. Our data demonstrate a new role for TGR5 in regulating colonic fluid and electrolyte transport and suggest that the receptor represents a good therapeutic target for intestinal transport disorders.</p

O espectro clínico e radiológico da pneumonia em organização: análise retrospectiva de 38 casos Clinical and radiographic spectrum of organizing pneumonia: retrospective analysis of 38 cases

A pneumonia em organização, acompanhada ou não de bronquiolite obliterante, é uma condição anatomopatológica pulmonar específica com uma grande variedade de apresentações clínicas e radiológicas. A pneumonia em organização pode ser idiopática ou secundária a várias doenças, incluindo infecções e drogas. Objetivos: Descrever as manifestações clínicas, dados radiológicos e espirométricos de pacientes com pneumonia em organização. Métodos: Análise retrospectiva de pacientes com o diagnóstico de pneumonia em organização. Resultados: 38 pacientes foram incluídos na análise. Quatorze apresentavam também condições clínicas relacionadas à pneumonia em organização, e estes mais freqüentemente apresentaram infiltração pulmonar difusa (três de quatro casos) e bronquiolite obliterante associada (57% vs. 20%, p = 0,05). Dos 13 pacientes com bronquiolite obliterante associada apenas um era assintomático e dois apresentavam lesões localizadas (15%). De oito pacientes assintomáticos com lesões localizadas, nenhum possuía bronquiolite obliterante associada, e a apresentação radiológica freqüentemente mimetizou carcinoma brônquico. A espirometria de modo geral não contribuiu sobremaneira para o diagnóstico, provavelmente devido à alta prevalência de tabagismo na amostra. Conclusões: A pneumonia em organização possui apresentação clínica e radiológica variada. Fatores que sugerem a ausência de bronquiolite obliterante são a ausência de sintomas e lesões radiológicas localizadas, e esta forma da doença mais freqüentemente deve ser diferenciada de carcinoma brônquico na prática clínica.<br>Organizing pneumonia, whether or not accompanied by bronchiolitis obliterans, is a specific anatomicopathological condition of the lungs that can present in a variety of clinical and radiographic ways. It can be either idiopathic or secondary to a number of diseases, including infection and drugs. Objectives: To describe the clinical manifestations, radiographic and spirometric data seen in patients with organizing pneumonia. Methods: Retrospective analysis of patients with a diagnosis of organizing pneumonia. Results: 38 patients were included in the analysis. Fourteen also had clinical conditions related to organizing pneumonia, and they presented more frequently with diffuse pulmonary infiltrates (three of four cases) and associated bronchiolitis obliterans (57% vs. 20%, p = 0,05). Of the 13 patients with bronchiolitis obliterans, only one was asymptomatic and two had localized lesions (15%). Of the eight asymptomatic patients with localized lesions, no one had associated bronchiolitis obliterans, and the radiographic appearance often resembled bronchial carcinoma. Spirometry was generally of little value to diagnosis, probably because of the high prevalence of smoking in the sample. Conclusion: The clinical and radiographic presentation of organizing pneumonia is variable. Factors that suggest the absence of coexisting bronchiolitis obliterans are the absence of symptoms and localized radiographic lesions, and this form of the disease has to be more often differentiated from bronchial carcinoma in clinical practice

Primary Chemotherapy and Radiation as a Treatment Strategy for HPV-Positive Oropharyngeal Cancer

The incidence of human papillomavirus-positive oropharyngeal cancer (HPV/OPSCC) is rapidly increasing, which will represent a major public health burden for decades to come. Although HPV/OPSCC is generally associated with a better prognosis than HPV-negative OPSCC, the survival rate of individuals with higher-risk clinical and pathologic features remains unchanged. Emerging evidence suggests that HPV/OPSCC is pathologically and molecularly distinct from HPV-negative OPSCC. This review focuses on summarizing treatment strategies for HPV/OPSCC by reviewing the peer-reviewed literature and noting ongoing and planned clinical trials in this disease. We also discuss the potential of designing targeted therapy based on the recent genomic findings of HPV/OPSCC