Two-Fermion Bound States within the Bethe-Salpeter Approach

To solve the spinor-spinor Bethe-Salpeter equation in Euclidean space we propose a novel method related to the use of hyperspherical harmonics. We suggest an appropriate extension to form a new basis of spin-angular harmonics that is suitable for a representation of the vertex functions. We present a numerical algorithm to solve the Bethe-Salpeter equation and investigate in detail the properties of the solution for the scalar, pseudoscalar and vector meson exchange kernels including the stability of bound states. We also compare our results to the non relativistic ones and to the results given by light front dynamics.Comment: 32 pages, XIII Tables, 8 figure

The M3 muscarinic receptor Is required for optimal adaptive immunity to Helminth and bacterial infection

Innate immunity is regulated by cholinergic signalling through nicotinic acetylcholine receptors. We show here that signalling through the M3 muscarinic acetylcholine receptor (M3R) plays an important role in adaptive immunity to both Nippostrongylus brasiliensis and Salmonella enterica serovar Typhimurium, as M3R-/- mice were impaired in their ability to resolve infection with either pathogen. CD4 T cell activation and cytokine production were reduced in M3R-/- mice. Immunity to secondary infection with N. brasiliensis was severely impaired, with reduced cytokine responses in M3R-/- mice accompanied by lower numbers of mucus-producing goblet cells and alternatively activated macrophages in the lungs. Ex vivo lymphocyte stimulation of cells from intact BALB/c mice infected with N. brasiliensis and S. typhimurium with muscarinic agonists resulted in enhanced production of IL-13 and IFN-γ respectively, which was blocked by an M3R-selective antagonist. Our data therefore indicate that cholinergic signalling via the M3R is essential for optimal Th1 and Th2 adaptive immunity to infection

Extended-schedule dose-dense temozolomide in refractory gliomas

This multicenter phase II study conducted by the Spanish Neuro-Oncology Group evaluated the activity of an extended, dose-dense temozolomide regimen in patients with temozolomide-refractory malignant glioma. Adult patients (at least 18 years of age) with WHO grade III or IV glioma and a Karnofsky Performance Status of 60 or higher were treated with temozolomide (85 mg/m2/day) for 21 consecutive days every 28-day cycle until disease progression or unacceptable toxicity. All patients had developed progressive disease either during or less than 3 months after completing previous temozolomide treatment. Forty-seven patients were treated with a median of 2 (range, 1–13) cycles of temozolomide. Before study entry, patients had received a median of 6 cycles of temozolomide: 39 (83%) as part of initial therapy and 23 (49%) as second-line therapy. Three patients (6.4%) had a partial response with durations of 8.0, 3.5, and 3.2 months; 15 patients (31.9%) had stable disease with a median duration of 2.1 months, including 2 patients with stable disease (SD) for greater than 6 months (14 and 16 months). Median time to progression was 2 months, and median overall survival from study entry was 5.1 months. The 6-month progression-free survival rate was 16.7%. The most common hematologic toxicities were lymphopenia, thrombocytopenia, and leukopenia. Lymphopenia occurred in 83% of patients and was grade 3 in 28%, but no opportunistic infections occurred. In conclusion, this extended dose-dense schedule of temozolomide appears to have modest activity in patients refractory to previous treatment with temozolomide and is associated with manageable toxicity

Chemotherapy with BCNU in recurrent glioma: Analysis of clinical outcome and side effects in chemotherapy-naïve patients

Background: To date, standardized strategies for the treatment of recurrent glioma are lacking. Chemotherapy with the alkylating agent BCNU (1,3-bis (2-chloroethyl)-1-nitroso-urea) is a therapeutic option even though its efficacy and safety, particularly the risk of pulmonary fibrosis, remains controversial. To address these issues, we performed a retrospective analysis on clinical outcome and side effects of BCNU-based chemotherapy in recurrent glioma. Methods: Survival data of 34 mostly chemotherapy-naïve glioblastoma patients treated with BCNU at 1st relapse were compared to 29 untreated control patients, employing a multiple Cox regression model which considered known prognostic factors including MGMT promoter hypermethylation. Additionally, medical records of 163 patients treated with BCNU for recurrent glioma WHO grade II to IV were retrospectively evaluated for BCNU-related side effects classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0. Results: In recurrent glioblastoma, multiple regression survival analysis revealed a significant benefit of BCNU-based chemotherapy on survival after relapse (p = 0.02; HR = 0.48; 95 % CI = 0.26–0.89) independent of known clinical and molecular prognostic factors. Exploratory analyses suggested that survival benefit was most pronounced in MGMT-hypermethylated, BCNU-treated patients. Moreover, BCNU was well tolerated by 46 % of the 163 patients analyzed for side effects; otherwise, predominantly mild side effects occurred (CTCAE I/II; 45 %). Severe side effects CTCAE III/IV were observed in 9 % of patients including severe hematotoxicity, thromboembolism, intracranial hemorrhage and injection site reaction requiring surgical intervention. One patient presented with a clinically apparent pulmonary fibrosis CTCAE IV requiring temporary mechanical ventilation. Conclusion: In this study, BCNU was rarely associated with severe side effects, particularly pulmonary toxicity, and, in case of recurrent glioblastoma, even conferred a favorable outcome. Therefore BCNU appears to be an appropriate alternative to other nitrosoureas although the efficacy against newer drugs needs further evaluation

Health-related quality of life in glioma patients in China

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life (HRQOL) has been increasingly emphasized in cancer patients. There are no reports comparing baseline HRQOL of different subgroups of glioma patients prior to surgery.</p> <p>Methods</p> <p>HRQOL assessments by the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0), the Mini-Mental State Examination and Karnofsky Performance Status were obtained from glioma patients prior to surgery.</p> <p>Results</p> <p>Ninety-two pathologically confirmed glioma patients were recruited. There were 84.8% patients with emotional impairment, 75% with social and cognitive impairment, 70.7% with physical impairment, and 50% with role impairment. Eighty-two percent of patients reported fatigue symptoms, 72.8% reported pain, 50% reported appetite loss, 39.1% reported insomnia, and 36.9% reported nausea/vomiting, whereas other symptoms (dyspnea, diarrhea, constipation) in the QLQ-C30 were reported by fewer than 30% of patients. Fatigue and pain symptoms and all "functioning" scales were strongly correlated with global health status/quality of life (QoL). Fatigue was strongly related to all functioning scales, pain, appetite loss, and global health status/QoL. No difference in baseline HRQOL prior to surgery was reported between females and males, among different lesion locations, or between normal- and abnormal-cognition subgroups of glioma patients. Age, KPS, WHO grade, and tumor recurrence significantly affected HRQOL in glioma patients.</p> <p>Conclusions</p> <p>These data provided the baseline HRQOL in glioma patients prior to surgery in China. Most pre-surgery glioma patients indicated emotional, social, cognitive, physical, and role impairment. Fatigue, pain, appetite loss, insomnia, and nausea/vomiting were common in these patients. The fatigue and pain symptoms and all types of functioning strongly affected global health status/QoL. Old age, worse performance status, WHO grade IV and tumor recurrence had deleterious effects on HRQOL.</p

Conversion of a molecular classifier obtained by gene expression profiling into a classifier based on real-time PCR: a prognosis predictor for gliomas

<p>Abstract</p> <p>Background</p> <p>The advent of gene expression profiling was expected to dramatically improve cancer diagnosis. However, despite intensive efforts and several successful examples, the development of profile-based diagnostic systems remains a difficult task. In the present work, we established a method to convert molecular classifiers based on adaptor-tagged competitive PCR (ATAC-PCR) (with a data format that is similar to that of microarrays) into classifiers based on real-time PCR.</p> <p>Methods</p> <p>Previously, we constructed a prognosis predictor for glioma using gene expression data obtained by ATAC-PCR, a high-throughput reverse-transcription PCR technique. The analysis of gene expression data obtained by ATAC-PCR is similar to the analysis of data from two-colour microarrays. The prognosis predictor was a linear classifier based on the first principal component (PC1) score, a weighted summation of the expression values of 58 genes. In the present study, we employed the delta-delta Ct method for measurement by real-time PCR. The predictor was converted to a Ct value-based predictor using linear regression.</p> <p>Results</p> <p>We selected <it>UBL5 </it>as the reference gene from the group of genes with expression patterns that were most similar to the median expression level from the previous profiling study. The number of diagnostic genes was reduced to 27 without affecting the performance of the prognosis predictor. PC1 scores calculated from the data obtained by real-time PCR showed a high linear correlation (r = 0.94) with those obtained by ATAC-PCR. The correlation for individual gene expression patterns (r = 0.43 to 0.91) was smaller than for PC1 scores, suggesting that errors of measurement were likely cancelled out during the weighted summation of the expression values. The classification of a test set (n = 36) by the new predictor was more accurate than histopathological diagnosis (log rank p-values, 0.023 and 0.137, respectively) for predicting prognosis.</p> <p>Conclusion</p> <p>We successfully converted a molecular classifier obtained by ATAC-PCR into a Ct value-based predictor. Our conversion procedure should also be applicable to linear classifiers obtained from microarray data. Because errors in measurement are likely to be cancelled out during the calculation, the conversion of individual gene expression is not an appropriate procedure. The predictor for gliomas is still in the preliminary stages of development and needs analytical clinical validation and clinical utility studies.</p