Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment.

Background: Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios.

Methods: Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβγ biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models respond and pancreatic ductal adenocarcinoma (PDAC) progresses.

Audiovisual Simultaneity Judgements in Synaesthesia.

Synaesthesia is a multimodal phenomenon in which the activation of one sensory modality leads to an involuntary additional experience in another sensory modality. To date, normal multisensory processing has hardly been investigated in synaesthetes. In the present study we examine processes of audiovisual separation in synaesthesia by using a simultaneity judgement task.

[Addictive disorders in physicians].

Despite their knowledge about the risks and treatment options for substance abuse disorders, physicians are not immune to them. Meanwhile, a number of studies have shown that physicians have an increased risk of depression, addictive diseases and burnout due to the occupation-linked mental and physical burden and in particular an increased prevalence of substance-related disorders, especially alcohol abuse or dependence and drug abuse. Drug dependence among physicians seems to be even higher than in the general population due to the relatively easy access to psychoactive medications, in particular hypnotic drugs, benzodiazepines, ketamine and opioids; however, the prognosis is good.

Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer.

In the context of cancer, naïve T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical efficacy. Our preclinical study in TRAMP mice comparing 14 different immune interventions identified anti-CD40 + IL2/anti-IL2 complexes + IL12Fc as a uniquely efficacious treatment that prevents tolerance induction, promotes priming of sustained, protective tumor-specific CD8(+) T cells, and cures late-stage cancer when given together with adoptively transferred tumor-specific T cells.

Spontaneous peripheral T-cell responses toward the tumor-associated antigen cyclin D1 in patients with clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples.

Functional and structural basis for a bacteriophage homolog of human RAD52.

In eukaryotes, homologous recombination proteins such as RAD51 and RAD52 play crucial roles in DNA repair and genome stability. Human RAD52 is a member of a large single-strand annealing protein (SSAP) family [1] and stimulates Rad51-dependent recombination [2, 3]. In prokaryotes and phages, it has been difficult to establish the presence of RAD52 homologs with conserved sequences.

Stimulation of fission yeast and mouse Hop2-Mnd1 of the Dmc1 and Rad51 recombinases.

Genetic analysis of fission yeast suggests a role for the spHop2-Mnd1 proteins in the Rad51 and Dmc1-dependent meiotic recombination pathways. In order to gain biochemical insights into this process, we purified Schizosaccharomyces pombe Hop2-Mnd1 to homogeneity. spHop2 and spMnd1 interact by co-immunoprecipitation and two-hybrid analysis.

Genome sequence and global gene expression of Q54, a new phage species linking the 936 and c2 phage species of Lactococcus lactis.

The lytic lactococcal phage Q54 was previously isolated from a failed sour cream production. Its complete genomic sequence (26,537 bp) is reported here, and the analysis indicated that it represents a new Lactococcus lactis phage species. A striking feature of phage Q54 is the low level of similarity of its proteome (47 open reading frames) with proteins in databases.

Blood flow velocities in middle cerebral artery branches after subarachnoid hemorrhage.

In a prospective study, 55 patients were examined by transcranial duplex sonography (TCCS) after subarachnoid hemorrhage (SAH) to determine whether additional transcranial duplex examination on the middle cerebral artery M2 segments would aid in the examination of the MCA stem segment. The mean blood flow velocities and pulsatility index were correlated to the occurrence of delayed ischemic neurologic deficits (DIND). Out of 47 patients included, 21 did not experience any delayed deficit (group I), 15 did (group II), and in 11 the extent to which vasospasm contributed to a neurologic deficit was unclear (group III).

[Neuro-monitoring using visual evoked potentials in comatose neurologic intensive care patients].

The application of visual evoked potentials (VEP) as a monitoring tool was studied in 40 comatose neurological intensive care patients. With increasing depth of coma, the number of detectable VEP components decreased. In deeply comatose patients, VEP were regularly displayed as a negative wave with a latency of app.