Cross-sectional TEM preparation of hybrid inorganic/organic materials systems by ultramicrotomy

Preparation of hybrid inorganic-organic systems (HIOS) for transmission electron microscopy (TEM) in cross sectional view is the key for understanding the interfacial structure. Strikingly different materials properties like hardness, cleavability and heat sensitivity limit the number of applicable preparation strategies. Successful preparation of a HIOS system combining ZnO and para-sexiphenyl (6P) is realized by ultramicrotomy. It is shown that the alignment of the cutting plane with respect to the (0001) cleavage plane of ZnO plays a decisive role for successful preparation of extended TEM lamellae and the preservation of the HIOS structure. In particular, for (0001) oriented ZnO substrates the optimum cut direction is parallel to the HIOS interface. In cross-sectional high-resolution TEM images (100) lattice planes of 6P are observed proving the appropriate preparation strategy.Peer Reviewe

Long-term responders to trastuzumab monotherapy in first-line HER-2+ advanced breast cancer: characteristics and survival data.

The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response. This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed. Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31-72) and of 18% (95%CI 10-30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit. Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies. NCT00004935 ; first posted 27.01.2003, retrospectively registered

Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

BACKGROUND: Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic. METHODS: A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA) and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH) was performed. RESULTS: Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck) Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH. CONCLUSION: Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present it is not yet clear, if and to what extent proposed Ck5-positive progenitor cells contribute to the immunohistochemical and morphological heterogeneity of these neoplasms of the breast

Steady state creep of fine grain granite at partial melting

Steady state creep under constant stress has been measured in a fine grain granite (aplite) from Schauinsland, Germany for the temperature range of partial melting 860°–1060°C, under a hydrostatic pressure of 4.2 kbar, and at low shear stresses of 5–50 bar. The apparatus used is described briefly. Rheological measurements are complemented by microscopic investigations. With a melt fraction of up to about 20%, creep can be described by a power law with a stress exponent of 3-4 and an activation energy of 80 kcal/mole, typical for creep in solids. Above 1010°C or 20% melt, the activation energy increases rapidly to a value of 200 kcal/mole simultaneously with a rapid increase of the melt fraction and a decrease of feldspar content. From the grain structure and from etching tests it is concluded that quartz contributes little to the plastic deformation which is governed mainly by the stress and temperature induced recrystallization of feldspar. The large temperature dependence of the creep rate above 1010° C may be caused by the decreasing area of grain contacts and consequent rise in local stress. These results support those of Arzi (1974) and Roscoe (1952).           ARK: https://n2t.net/ark:/88439/y060550 Permalink: https://geophysicsjournal.com/article/258 &nbsp

Lung neuroendocrine tumors: correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN

BACKGROUND: The tumor suppressor phosphatase and tensin homolog (PTEN) is a pleiotropic enzyme, inhibiting phosphatidyl-inositol-3 kinase (PI3K) signaling in the cytosol and stabilizing the genome in the nucleus. Nucleo-cytosolic partitioning is dependent on the post-translational modifications ubiquitinylation and sumoylation. This cellular compartmentalization of PTEN was investigated in lung neuroendocrine tumors (lung NET). METHODS: Tumor tissues from 192 lung NET patients (surgical specimens = 183, autopsies = 9) were investigated on tissue microarrays. PTEN was H-scored by two investigators in nucleus and cytosol using the monoclonal antibody 6H2.1. Results were correlated with immunoreactivity for USP7 (herpes virus-associated ubiquitin-specific protease 7) and SUMO2/3 (small ubiquitin-related modifier protein 2/3) as well as PTEN and p53 FISH gene status. Clinico-pathologic data including overall survival, proliferation rate and diagnostic markers (synaptophysin, chromogranin A, Mib-1, TTF-1) were recorded. RESULTS: The multicentre cohort included 58 typical carcinoids (TC), 42 atypical carcinoids (AC), 32 large cell neuroendocrine carcinomas (LCNEC) and 60 small cell lung carcinomas (SCLC). Carcinoids were smaller in size and had higher synaptophysin and chromogranin A, but lower TTF-1 expressions. Patients with carcinoids were predominantly female and 10 years younger than patients with LCNEC/SCLC. In comparison to the carcinoids, LCNEC/SCLC tumors presented a stronger loss of nuclear and cytosolic PTEN associated with a loss of PTEN and p53. Concomitantly, a loss of nuclear USP7 but increase of nuclear and cytosolic SUMO2/3 was found. Loss of nuclear and cytosolic PTEN, loss of nuclear USP7 and increase of cytosolic SUMO2/3 thus correlated with poor survival. Among carcinoids, loss of cytosolic PTEN was predominantly found in TTF1-negative larger tumors of male patients. Among SCLC, loss of both cytosolic and nuclear PTEN but not proliferation rate or tumor size delineated a subgroup with poorer survival (all p-values <0.05). CONCLUSIONS: Cellular ubiquitinylation and sumoylation likely influence the functional PTEN loss in high grade lung NET. Both nuclear and cytosolic PTEN immunoreactivity should be considered for correlation with clinico-pathologic parameters

CGH analysis shows genetic similarities and differences in atypical fibroxanthoma and undifferentiated high grade pleomorphic sarcoma

BACKGROUND: Atypical fibroxanthoma (AFX) and undifferentiated high grade pleomorphic sarcoma (UpS) are histologically very similar, if not identical. However, they differ significantly in clinical outcome. MATERIALS AND METHODS: We used comparative genomic hybridization (CGH) to screen 24 AFX and 12 UpS for genomic alterations. RESULTS: DNA copy number changes were observed in 20/24 AFX and in all UpS. The most frequent alterations occurring with comparable frequency in both tumors were deletions on chromosomes 9p and 13q. We also detected statistically significant differences of genetic alterations between the two tumors concerning deletions on 1q, 3p, 5q, 11p, 11q, gains on 7q, 12q and high level gains on 5p and 11q. CONCLUSION: Despite their very similar histology, AFX and UpS show clear differences in their genetic alterations. This might contribute to the different biological behavior of the two tumors. On the other hand the similarities in genetic alterations on chromosomes 9p and 13q might suggest a common pathogenetic pathway