Interferon-ß produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells.

Interferons (IFNs) have been tested for the therapeutic effects in various types of malignancy, but mechanisms of the anti-tumors effects and the differential biological activities among IFN members are dependent on respective cell types. In this study, we examined growth inhibitory activities of type I and III IFNs on 5 kinds of human mesothelioma cells bearing wild-type p53 gene, and showed that type I IFNs but not type III IFNs decreased the cell viabilities. Moreover, growth inhibitory activities and up-regulated expression levels of the major histocompatibility complexes class I antigens were greater with IFN-ß than with IFN-α treatments. Cell cycle analyses demonstrated that type I IFNs increased S- and G2/M-phase populations, and subsequently sub-G1-phase fractions. The cell cycle changes were also greater with IFN-ß than IFN-α treatments, and these data collectively showed that IFN-ß had stronger biological activities than IFN-α in mesothelioma. Type I IFNs-treated cells increased p53 expression and the phosphorylation levels, and activated apoptotic pathways. A combinatory use of IFN-ß and cisplatin or pemetrexed, both of which are the current first-line chemotherapeutic agents for mesothelioma, produced synergistic anti-tumor effects, which were also evidenced by increased sub-G1-phase fractions. These data demonstrated firstly to our knowledge that IFN-ß produced synergistic anti-tumor effects with cisplatin or pemetrexed on mesothelioma through up-regulated p53 expression.

Successful resection of schwannoma from an intercostal nerve causing bloody pleural effusion: report of a case.

We report a case of schwannoma arising from the 9th intercostal nerve, which caused a bloodstained pleural effusion. The patient, a 37-year-old woman, presented with left-sided back pain. A chest X-ray showed left pleural effusion, which was subsequently found to be bloodstained but without malignant cells. Chest magnetic resonance imaging showed a 76-mm tumor arising from the 9th intercostal nerve. The tumor and intercostal nerve were successfully resected. Histological examination revealed that the tumor comprised spindle cells with both Antoni types A and B patterns. There were necrotic changes and cystic degeneration, but no atypical or mitotic cells. Based on these findings, benign schwannoma was diagnosed. Schwannoma is rarely accompanied by bloody pleural effusion, which we assume was caused by partial tumor rupture. Magnetic resonance imaging proved very useful in localizing and characterizing the tumor in this case.

New endobronchial ultrasound imaging for differentiating metastatic site within a mediastinal lymph node.

A newly developed endobronchial ultrasound processor system (EU-ME1; Olympus Ltd., Tokyo, Japan) improves the quality of ultrasound image by elevating cycles per minute. We report identification of mediastinal lymph node metastasis in a patient with small cell lung cancer. The new endobronchial ultrasound system images enabled visualization of metastatic site within the subcarinal lymph node by the combination of ultrasound image and Doppler mode.

Eradication of intractable malignant ascites by abdominocentesis, reinfusion of concentrated ascites, and adoptive immunotherapy with dendritic cells and activated killer cells in a patient with recurrent lung cancer: a case report.

INTRODUCTION: Malignant ascites is often a sign of a terminal stage in several malignant diseases. To control ascites, drainage and intra-abdominal chemotherapy are often used in those patients but eradication of ascites is difficult and prognosis is poor. CASE PRESENTATION: A 55-year-old woman was admitted to our hospital on 26 January 2007 with dyspnea, abdominal distention and oliguria. Abdominocentesis revealed peritoneal carcinomatosis resulting from abdominal recurrence from lung cancer. To alleviate the dyspnea and abdominal distention, we drained the ascites aseptically and infused them intravenously back into the patient after removal of tumor cells by centrifugation, and then concentration by apheresis. After the drainage of ascites, we intraperitoneally infused activated killer cells and dendritic cells from the patient's tumor-draining lymph nodes, together with 4.5 x 105U interleukin-2 in 50 ml saline by 2.1 ml/hour infuser balloon.Drastic decreases in the tumor cell count and in ascite retention were observed after several courses of ascites drainage, intravenous infusion and intraperitoneal immunotherapy. The plasma protein level was maintained during the treatment notwithstanding the repeated drainage of ascites. Cell surface marker analysis, cytotoxic activities against autologous tumor cells and interferon-gamma examination of ascites suggested the possibility that these effects were mediated by immunological responses of activated killer cells and dendritic cells infused intraperitoneally. CONCLUSION: Combination of local administration of immune cells and infusion of concentrated cell free ascites may be applicable for patients afflicted with refractory ascites.

Prospective phase II study of post-surgical adjuvant chemo-immunotherapy using autologous dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes in primary lung cancer patients.

BACKGROUND: The efficacy and toxicity of adjuvant chemo-immunotherapy using dendritic cells and activated killer cells are not clear in post-surgical primary lung cancer patients. PATIENTS AND METHODS: Pathologically diagnosed N2 lung cancer patients were selected for postsurgical adjuvant chemo-immunotherapy. The activated killer cells and dendritic cells (AKT-DC) obtained from tissue cultures of tumor-draining lymph nodes (TDLN) or from TDLN co-cultured with peripheral blood lymphocytes (TDLN-Pb) were used for the adoptive transfer of immunotherapy. The patients received 4 courses of chemotherapy along with immunotherapy every 2 months for 2 years. RESULTS: There were 31 N2 patients eligible for the study. Three cases were excluded because of refusal by the patients after 1-2 courses of immunotherapy. For the 28 cases treated, a total of 313 courses of immunotherapy were administered. The main toxicities were fever (78.0%), chill (83.4%), fatigue (23.0%) and nausea (17.0%) on the day of cell transfer. The 2- and 5-year survival rates were 88.9 % (95.9-81.9; 95% confidence interval, C.I.) and 52.9% (76.4-29.4; C.I.). CONCLUSION: Adoptive transfer of activated killer cells and dendritic cells from the tumor-draining lymph nodes of primary lung cancer patients is feasible and safe, and a large-scale multi-institutional study is necessary for evaluation of the efficacy of this treatment.