Effect of torrefaction on rice straw physicochemical characteristics and particulate matter emission behavior during combustion.

In this work, the effects of different torrefaction temperatures and durations on the physicochemical properties of rice straw (RS), and the emission characteristic of PM10 (particulate matter with aerodynamic diameters of ≤10 µm) during torrefied RS combustion, were investigated. Results indicate that the release of Cl and K, and decomposition of the organic matrix demonstrated a promoting effect during torrefaction. However, the removal of Cl and K did not reduce the emission of PM1. The emission concentration of PM1 and PM1-10 generated from torrefied RS was enhanced, and the yields of PM1-10 was much higher than those of PM1. The concentrations of K and Cl in PM1-10 increased with torrefaction temperature, combined with the microstructure, indicating that the torrefaction pretreatment promoted the heterogeneous condensation of KCl vapour to form PM1-10.

Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study.

Immunostimulating oligodeoxynucleotides containing CpG motifs (CpG-ODN) have shown promising efficacy in cancer models when injected locally. In a phase I clinical trial, intratumoral infusions of CpG-ODN in glioblastoma (GBM) patients were well tolerated at doses up to 20 mg. This phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with recurrent GBMs. Patients with recurrent GBM occurring at least 3 months after radiotherapy, and previously treated with 1 or 2 regimens of chemotherapy received 20 mg of CpG-ODN (CpG-28) by convection-enhanced delivery. The primary endpoint was the percentage of patients without tumor progression 6 months after inclusion. Secondary endpoints were tolerance, survival, and radiological response. Thirty-four patients were enrolled in two centers between November 2004 and March 2006. Thirty-one patients received CpG-ODN treatment. The progression-free survival (PFS) at 6 months was 19%. One partial response and 3 minor responses were observed. The median overall survival was 28 weeks. Eight patients (24%) were alive 1 year after inclusion and 5 patients (15%) were alive after 2 years. Treatment was usually well tolerated. As reported previously, the most common toxicities were lymphopenia, mild fever, seizures, and transient neurological worsening. Despite a few cases showing a radiological response, CpG-28 showed modest activity on the 6-month PFS in this patient population. The molecular or clinical characteristics of a subgroup of patients that could potentially benefit from such an approach remain to be defined.

Expression of TLR9 within human glioblastoma.

Immunostimulating oligonucleotides containing CpG motifs (CpG-ODN) have shown promising antitumor activity in preclinical glioma models. CpG motifs are specifically recognized by the Toll-like receptor 9 (TLR9), mainly expressed in plasmacytoid dendritic cells (pDCs) and B cells. Expression of TLR9 within human glioma samples has not been investigated. As CpG-ODN is currently under clinical trials in glioma patients, we investigated whether TLR9 is expressed at the RNA levels in a series of 37 human glioblastomas (GBM) by quantitative PCR. TLR9 expression was detected at variable levels, which might suggest that some patients are more likely to benefit from treatment with CpG-ODN than others. No significant relationships between TLR9 expression and age, sex, tumor location, lymphocytes infiltration, oligodendroglial components or survival were found. TLR9 is unlikely to be expressed by tumor cells as no TLR9 expression was detected in pure human GBM xenografts. Immunocytochemistry studies showed TLR9 expression in some macrophages/microglial cells. The expression of TLR9 within human GBM strengthens the rationale for the utilization of CpG-ODN in this disease.

Recent advances in immunotherapy for human glioma.

PURPOSE OF REVIEW: The present review focuses on recent progress in tumour immunology and immunotherapeutic trials in malignant gliomas. RECENT FINDINGS: Major advances have been made in the understanding of antitumour immunity in patients with glioma. Patients with glioblastoma can spontaneously develop antitumour activity with activated CD8+ T cells. Infiltration of myeloid suppressor cells into tumours and increased regulatory T-cell fraction appear to play a critical role in tumour tolerance, however. T-regulatory removal suppresses CD4+ T-cell proliferative defects and can induce tumour rejection in a murine model. Clinical trials using active immunotherapy with dendritic cells loaded with tumour-eluted peptides or tumour lysate have successfully induced antitumour cytotoxicity and some radiologic responses. Other promising approaches targeting the mechanisms of tolerance that could be referred to as 'corrective immunotherapy' are currently on going. SUMMARY: Improvements in clinical methods and large randomized trials are now needed to prove the usefulness of cancer vaccines. Indeed, comprehensive analysis of tumour immunology and new immunization protocols suggest that immunotherapy can become an efficacious treatment in the near future. Combination with radiotherapy or chemotherapy should be investigated.

Successful combination of local CpG-ODN and radiotherapy in malignant glioma.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) display broad immunostimulating activity and are currently under clinical trial in various malignancies, including recurrent glioblastomas. Combining CpG-ODN with another therapy that could induce antigen release might enhance tumor-specific immune response. We investigated whether radiotherapy (RT) could be associated advantageously to intratumoral injections of CpG-ODN. Fisher rats bearing 9L glioma were treated with various combinations of RT and CpG-28, an oligonucleotide with good immunostimulating activity. RT and CpG-28 induced complete tumor remission in one-third of the animals. When both treatments were combined, complete tumor remission was achieved in two-thirds of the animals (p < 0.001 when compared to non-treated rats, p < 0.03 when compared to CpG-28 alone). Such efficacy was not observed in nude mice, underlying the role of T cells in antitumor effects. The combination of both treatments appeared optimal when the delay between RT and CpG-28 administration was <3 days (from 100% survival for a 3 days delay, to 57% survival for a 21 days delay, p < 0.05). Tumor infiltration by immune cells and expression within tumors of the CpG receptor, TLR9, were not modified by irradiation. These results support an attractive strategy of sequential radiotherapy and immunotherapy by CpG-ODN and have potential implications for future clinical trials with CpG-ODN.