The aryl hydrocarbon receptor in tumor immunity

The aryl hydrocarbon receptor (AHR) binds environmental toxins and mediates immune regulation. The tryptophan metabolite kynurenine has now been identified as an endogenous ligand of the human AHR constitutively produced by gliomas and other types of cancer via tryptophan-2,3-dioxygenase (TDO), thereby suppressing antitumor immune responses via the AHR. Thus, this pathway represents an important novel target for cancer immunotherapy

Signals of CP Violation Beyond the MSSM in Higgs and Flavor Physics

We study an extension of the Higgs sector of the Minimal Supersymmetric Standard Model (MSSM), considering the effects of new degrees of freedom at the TeV scale, and allowing for sources of CP violation beyond the MSSM (BMSSM). We analyze the impact of the BMSSM sources of CP violation on the Higgs collider phenomenology and on low energy flavor and CP violating observables. We identify distinct Higgs collider signatures that cannot be realized, either in the case without CP violating phases or in the CP violating MSSM, and investigate the prospects to probe them at the Tevatron and the LHC. The most striking benchmark scenario has three neutral Higgs bosons that all decay dominantly into W boson pairs and that are well within the reach of the 7 TeV LHC run. On the other hand, we also present scenarios with three Higgs bosons that have masses M_Hi > 150 GeV and decay dominantly into b bbar. Such scenarios are much more challenging to probe and can even lie completely outside the reach of the 7 TeV LHC run. We explore complementary scenarios with standard MSSM Higgs signals that allow to accommodate a sizable B_s mixing phase as indicated by D0, as well as the excess in B_s --> mu+ mu- candidates recently reported by CDF. We find that, in contrast to the MSSM, a minimal flavor violating soft sector is sufficient to generate significant corrections to CP violating observables in meson mixing, compatible with EDM constraints. In particular, a sizable B_s mixing phase, S_psiphi < 0.4, can be achieved for specific regions of parameter space. Such a large B_s mixing phase would unambiguously imply a sizable suppression of S_psiKs with respect to the SM prediction and a BR(B_s --> mu+ mu-) close to the 95% C.L. upper bound reported by CDF.Comment: 58 pages, 15 figures, 2 tables, v2 matches published versio

Anticoagulation for radiation-induced neurotoxicity revisited

No effective treatment for delayed radiation-induced neurotoxicity has been established. Its natural course is highly variable, but spontaneous recovery has been well documented. Here we report our experience with therapeutic anticoagulation in patients with cerebral lesions (n=3), cranial nerve lesions (n=1) or myelopathy (n=4) attributed to irradiation. Two of three patients with cerebral lesions and the patient with cranial nerve lesions showed a minor improvement of clinical symptoms. In contrast, none of the patients with radiation myelopathy improved. No patient suffered hemorrhage or other adverse effects of anticoagulation. Overall, anticoagulation therapy demonstrates only modest activity for delayed radiation-induced neurotoxicity in this small case serie

Anaplastic Oligodendroglioma: A New Treatment Paradigm and Current Controversies

Opinion statement: Anaplastic oligodendroglial tumors have gained increasing interest with the emerging role of molecular markers and systemic chemotherapy during the past years. The long-term results of two landmark trials, RTOG 9402 and EORTC 26961, have resulted in a reconsideration of the appropriate therapeutic approaches for patients with these tumors. Both trials indicate that patients whose tumors harbor a 1p/19q co-deletion benefit particularly from the addition of procarbazine/lomustine (CCNU)/vincristine (PCV) chemotherapy to radiation therapy (RT). The median survival of patients with co-deleted tumors treated within the RTOG trial with PCV before irradiation was 14.7years compared with 7.3years of patients who received RT alone. Median overall survival has not been reached in the RT plus PCV arm of the EORTC trial, but a similar difference can be anticipated after a follow-up of more than 12years. In contrast, no such benefit was observed for patients with tumors lacking 1p/19q co-deletion. Outside clinical trials, patients with anaplastic oligodendroglial tumors, and 1p/19q co-deletion therefore should be offered a combined treatment modality regimen, including radio- and chemotherapy. PCV, however, is associated with significant hematological toxicity and also nonhematological side effects, which probably translate into reduced quality of life for long-term survivors. Therefore, it might be warranted to replace PCV by temozolomide, which displays a more favorable side effect profile. Data from the NOA-04 study suggest that PCV and temozolomide have similar effects. However, long-term data on the benefit from temozolomide are lacking, making a definite answer on the equivalence of temozolomide and PCV in anaplastic oligodendroglioma (AO) impossible. The current evidence precludes RT alone for AO patients. Neither the RTOG nor the EORTC trial defined the role of chemotherapy alone. A comparison of combined modality treatment with chemotherapy alone followed by RT at progression is pending. Long-term follow-up of NOA-04 patients and results from future trials may help to clarify these questions. With more and more AO patients living 10years or more, particular attention must be paid to late side effects, such as neurotoxicity, and careful monitoring is required for all treated patient

Therapeutic options in recurrent glioblastoma-An update

INTRODUCTION Standards of care are not yet defined in recurrent glioblastoma. METHODS We reviewed the literature on clinical trials for recurrent glioblastoma available in PubMed and American Society of Clinical Oncology (ASCO) abstracts until June 2015. RESULTS Evidence is limited due to the paucity of randomized controlled studies. Second surgery or re-irradiation are options for selected patients. Alkylating chemotherapy such as nitrosoureas or temozolomide and the vascular endothelial growth factor (VEGF) antibody, bevacizumab, exhibit comparable single agent activity. Phase III data exploring the benefit of combining bevacizumab and lomustine are emerging. Novel approaches in the fields of targeted therapy, immunotherapy, and tumor metabolism are coming forward. Several biomarkers are being explored, but, except for O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation, none has assumed a role in clinical practice. CONCLUSION Proper patient selection, development of predictive biomarkers and randomized controlled studies are required to develop evidence-based concepts for recurrent glioblastoma