Unique nesting biology of Osmia ( Melanosmia) uncinata, a Palaearctic osmiine bee specialized on thick-barked conifers (Hymenoptera, Megachilidae)

Osmia (Melanosmia) uncinata Gerstäcker is a Palaearctic megachilid bee distributed from temperate and northern Europe eastwards to the Russian Far East. The discovery of over 80 nests in Switzerland, southern Germany and Scotland enabled for the first time a closer investigation of its nesting biology and prompted the assessment of the species’ phenology, distribution and habitat. O. uncinata nested in self-excavated burrows inside the bark of both living trunks and dead stumps of Pinus sylvestris. The nests were excavated at a height of 10–220 cm above ground either on the underside of prominences of longitudinal bark ribs or inside beetle borings and extended more or less vertically upwards. They consisted of a single straight to slightly curved burrow with rarely one to three side burrows, had a total length of 1.2–12.0 cm and contained 1–6 brood cells. The brood cells, which faced downwards with the larval provisions being located in the upper cell half, were separated from each other by one-layered walls of chewed leaves (“leaf pulp”). The nests were sealed with a plug of 2–4 closely adjacent walls of leaf pulp. DNA metabarcoding of cell and plug walls revealed that Potentilla and Fragaria (Rosaceae) served as leaf pulp sources. Pre-imaginal mortality amounted to 77%, partly caused by brood parasites such as Sapyga similis (Sapygidae) and Cacoxenus indagator (Drosophilidae) or predators such as snakeflies (Raphidioptera). At low elevations, O. uncinata needs one year for its development and overwinters as imago inside the nest, whereas in the subalpine zone of the Alps it has a two-year cycle passing the first winter as prepupa and the second winter as imago. O. uncinata starts to emerge between the end of March at low elevations and the end of May at higher elevations qualifying as an early flying bee like the other European O. (Melanosmia) species. The distribution of O. uncinata in Central Europe and Scotland largely coincides with the occurrence of P. sylvestris. As in the pine, it extends over a wide altitudinal range from below 100 m up to 1900 m a.s.l. and encompasses dry and wet as well as warm and cold habitats including open pine forests, inner and outer forest edges dominated by pine and isolated pine groups. At a few locations in the subalpine zone of the Alps, O. uncinata occurs in the absence of P. sylvestris; here, the thick bark of Larix decidua serves as a substitute nesting substrate

Protein-based oncopanel as addition to target sequencing in head and neck squamous cell carcinoma to individualize treatment decisions

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers and patients have limited therapy options if primary treatment fails. Therefore, additional information about the biology of the tumor is essential. Here we performed a feasibility study of concurrently applying two precision diagnostic tools in a consecutive series of HNSCC patients. We analyzed tumor samples of 31 patients using a genomic (oncomine) and a proteomic, immunohistochemical approach (oncopanel) and compared the result, also in the focus on their overlapping therapeutical targets. We found no strong correlation between the two approaches and observed a higher proportion of marker expression for the immunohistochemical panel. However, both panels show in our HNSCC cohort distinct patterns with druggable targets. The data suggest that both approaches complement one another and can be applied side-by-side to identify the best targets for the development of individual treatment options for HNSCC patients

Analysis of expression profiles of MAGE-A antigens in oral squamous cell carcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>The immunological response to solid tumours is insufficient. Therefore, tumour specific antigens have been explored to facilitate the activation of the immune system. The cancer/testis antigen class of MAGE-A antigens is a possible target for vaccination. Their differential expression profiles also modulate the course of the cancer disease and its response to antineoplastic drugs.</p> <p>Methods</p> <p>The expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in five own oral squamous cell carcinoma cell lines were characterised by rt-PCR, qrt-PCR and immunocytochemistry with a global MAGE-A antibody (57B) and compared with those of an adult keratinocyte cell line (NHEK).</p> <p>Results</p> <p>All tumour cell lines expressed MAGE-A antigens. The antigens were expressed in groups with different preferences. The predominant antigens expressed were MAGE-A2, -A3 and -A6. MAGE-A10 was not expressed in the cell lines tested. The MAGE-A gene products detected in the adult keratinocyte cell line NHEK were used as a reference.</p> <p>Conclusion</p> <p>MAGE-A antigens are expressed in oral squamous cell carcinomas. The expression profiles measured facilitate distinct examinations in forthcoming studies on responses to antineoplastic drugs or radiation therapy. MAGE-A antigens are still an interesting aim for immunotherapy.</p

Oral acantholytic squamous cell carcinoma shares clinical and histological features with angiosarcoma

<p>Abstract</p> <p>Background</p> <p>acantholytic squamous cell carcinomas (ASCC) and intraoral angiosarcoma share similar histopathological features. Aim of this study was to find marker for a clear distinction.</p> <p>Methods</p> <p>Four oral acantholytic squamous cell carcinomas and one intraoral angiosarcoma are used to compare the eruptive intraoral growth-pattern, age-peak, unfavourable prognosis and slit-like intratumorous spaces in common histological staining as identical clinical and histopathological features. Immunohistochemical staining for pancytokeratin, cytokeratin, collagen type IV, γ2-chain of laminin-5, endothelial differentiation marker CD31 and CD34, F VIII-associated antigen, Ki 67-antigen, β-catenin, E-cadherin, α-smooth-muscle-actin and Fli-1 were done.</p> <p>Results</p> <p>Cytokeratin-immunoreactive cells can be identified in both lesions. The large vascularization of ASCC complicates the interpretation of vascular differential markers being characteristic for angiosarcoma. Loss of cell-cell-adhesion, monitored by loss of E-cadherin and β-catenin membrane-staining, are indetified as reasons for massive expression of invasion-factor ln-5 in ASCC and considered responsible for unfavourable prognosis of ASCC. Expression of Fli-1 in angiosarcoma and cellular immunoreaction for ln-5 in ASCC are worked out as distinguishing features of both entities.</p> <p>Conclusion</p> <p>Fli-1 in angiosarcoma and ln-5 in ASCC are distinguishing features.</p

Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.

Purpose: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Methods: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. Results: Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. Conclusion: CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

An adult spindle cell rhabdomyosarcoma in the head and neck region with long-term survival: a case report

Introduction Spindle cell rhabdomyosarcoma of the head and neck is a very rare tumor in adults. We report on one case with long-term survival. Case presentation A 41-year-old nonsmoking Caucasian man presented in June 2007 with a painless swelling under his tongue. A diagnosis of a soft tissue sarcoma, and a myofibrosarcoma in particular, was made via biopsy. After multimodal treatment, including local and systemic therapy, our patient remained disease-free until September 2010. The local recurrence was treated unsuccessfully with various chemotherapy regimens. In September 2011, our patient underwent surgical resection again, and a spindle cell rhabdomyosarcoma was diagnosed. To analyze the mismatch between the original diagnosis of a myofibrosarcoma and the second diagnosis, the two specimens were reassessed, and a final diagnosis of a spindle cell rhabdomyosarcoma was made. In 2012 and 2013, our patient suffered further recurrences that were surgically treated, and he is still alive with disease six years and 10 months after the initial diagnosis in June 2007. Conclusions In adults, the spindle cell rhabdomyosarcoma tumor is very rare in the head and neck region. In contrast to childhood tumors, spindle cell rhabdomyosarcoma in adulthood is often associated with a poor prognosis. In the present case, the radical surgical treatment might have helped to prolong the patient’s overall survival, which has lasted more than six years. To our knowledge, this is the longest overall survival reported so far for this tumor entity in the head and neck region

Unique nesting biology of Osmia ( Melanosmia) uncinata, a Palaearctic osmiine bee specialized on thick-barked conifers (Hymenoptera, Megachilidae)

Osmia (Melanosmia) uncinata Gerstäcker is a Palaearctic megachilid bee distributed from temperate and northern Europe eastwards to the Russian Far East. The discovery of over 80 nests in Switzerland, southern Germany and Scotland enabled for the first time a closer investigation of its nesting biology and prompted the assessment of the species’ phenology, distribution and habitat. O. uncinata nested in self-excavated burrows inside the bark of both living trunks and dead stumps of Pinus sylvestris. The nests were excavated at a height of 10–220 cm above ground either on the underside of prominences of longitudinal bark ribs or inside beetle borings and extended more or less vertically upwards. They consisted of a single straight to slightly curved burrow with rarely one to three side burrows, had a total length of 1.2–12.0 cm and contained 1–6 brood cells. The brood cells, which faced downwards with the larval provisions being located in the upper cell half, were separated from each other by one-layered walls of chewed leaves (“leaf pulp”). The nests were sealed with a plug of 2–4 closely adjacent walls of leaf pulp. DNA metabarcoding of cell and plug walls revealed that Potentilla and Fragaria (Rosaceae) served as leaf pulp sources. Pre-imaginal mortality amounted to 77%, partly caused by brood parasites such as Sapyga similis (Sapygidae) and Cacoxenus indagator (Drosophilidae) or predators such as snakeflies (Raphidioptera). At low elevations, O. uncinata needs one year for its development and overwinters as imago inside the nest, whereas in the subalpine zone of the Alps it has a two-year cycle passing the first winter as prepupa and the second winter as imago. O. uncinata starts to emerge between the end of March at low elevations and the end of May at higher elevations qualifying as an early flying bee like the other European O. (Melanosmia) species. The distribution of O. uncinata in Central Europe and Scotland largely coincides with the occurrence of P. sylvestris. As in the pine, it extends over a wide altitudinal range from below 100 m up to 1900 m a.s.l. and encompasses dry and wet as well as warm and cold habitats including open pine forests, inner and outer forest edges dominated by pine and isolated pine groups. At a few locations in the subalpine zone of the Alps, O. uncinata occurs in the absence of P. sylvestris; here, the thick bark of Larix decidua serves as a substitute nesting substrate.ISSN:2535-088