Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing αVβ3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and αVβ3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0–60%) expressed LH39, while αVβ3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5–90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed

BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs

Background: BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W) with germline BAP1 mutations and increased risk of malignant mesothelioma.Methods: Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson χ2 test or two-tailed Fisher's exact test).Results: Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline BAP1 mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call " melanocytic BAP1-mutated atypical intradermal tumors" (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p ≤ 0.001).Conclusions: Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a marker to identify individuals who may carry germline BAP1 mutations and thus are at high risk of developing associated cancers. © 2012 Carbone et al.; licensee BioMed Central Ltd

Influence of High Pressure-High Temperature Method on the Selected Mechanical Properties of Steel AISI 316L with 2% TiB2

AISI 316L/TiB2/2p composites were manufactured by HP-HT using different pressures (5 and 7 GPa) and temperatures (900-1300°C), with constant reinforcing particle content 2 vol%. The mechanical properties of the composites were evaluated on the basis of hardness (HV0.3) and compression tests (20°C, 10-5 s-1). The results showed that the role of sintering pressure increased with increasing process temperature. At temperatures of 900°C and pressures of 5 and 7 GPa the difference in measured values of compressive strength was 1-2%, while at 1300°C they reached 20%. At constant pressure of 5 GPa, a change in hardness and compressive strength of 40% were obtained with a temperature change of 900 to 1300°C. Changes in mechanical properties in the composite occurred without substantial changes in density, microstructure, reinforcement phase distribution, and phase composition in the matrix

Characteristics of the Nial/Ni3al Matrix Composite With Tib2 Particles Fabricated By High Pressure – High Temperature Sintering

The article presents the results of tests carried out on the manufactured composite materials based on a two-phase NiAl/Ni3Al matrix, which was enriched with the addition of TiB2 ceramic particles added in an amount of 4 and 7 vol%. The resulting mixtures were sintered by the High Pressure High Temperature (HP-HT) process. The results were compared to the results obtained for the sole matrix material produced under the same conditions. It has been shown that, at a lower density, the addition of reinforcing particles increases the composite hardness, Young’s modulus and resistance to frictional wear. However, higher addition of TiB2 (7 vol%) was observed to yield less satisfactory results, and despite higher hardness and lower density caused a decrease in other properties tested. The produced materials were characterized by a compact and highly differentiated microstructure free from any noticeable cracks and pores

Characteristics of the NiAl/Ni3Al Matrix Composite with TiB2 Particles Fabricated by High Pressure - High Temperature Sintering

The article presents the results of tests carried out on the manufactured composite materials based on a two-phase NiAl/Ni3Al matrix, which was enriched with the addition of TiB2 ceramic particles added in an amount of 4 and 7 vol%. The resulting mixtures were sintered by the High Pressure High Temperature (HP-HT) process. The results were compared to the results obtained for the sole matrix material produced under the same conditions. It has been shown that, at a lower density, the addition of reinforcing particles increases the composite hardness, Young’s modulus and resistance to frictional wear. However, higher addition of TiB2 (7 vol%) was observed to yield less satisfactory results, and despite higher hardness and lower density caused a decrease in other properties tested. The produced materials were characterized by a compact and highly differentiated microstructure free from any noticeable cracks and pores

Maternal and newborn immunization with a human immunodeficiency virus-1 immunogen in a rodent model

We examined immunization with an inactivated, gp120-depleted human immunodeficiency virus (HIV) antigen in incomplete Freund’s adjuvant (IFA), also containing a sequence of immunostimulatory (ISS) DNA, during the last trimester of pregnancy and neonatally in a rat model. Pregnant rats were immunized in the third trimester and their litters were immunized during the newborn period. In addition, litters of rats from non-immunized mothers were immunized during the neonatal period. As another control, pregnant rats were immunized and their litters analysed. Supernants from peripheral blood mononuclear cells (PBMCs) were assayed from newborns at 4 weeks of age for HIV-specific interferon-γ (IFN-γ), HIV-specific regulated on activation, normal, T-cell expressed, and secreted (RANTES), and serum for p24 antigen-specific immunoglobulin G (IgG) production. In the animals whose pregnant mothers were immunized and were also immunized during the neonatal period, we observed HIV-specific IFN-γ production and HIV-specific RANTES production, but weak p24 IgG antibody production. Animals immunized only during the neonatal period developed the highest levels of HIV-specific IFN-γ production, but somewhat lower levels of HIV-specific RANTES and p24 IgG antibody production. The group of animals whose mothers had received immunizations during the last trimester of pregnancy, but were not immunized during the neonatal period, developed the strongest p24 IgG antibody levels, but little or undetectable HIV-specific IFN-γ or RANTES production. Neonatal immunization resulted primarily in cell-mediated immune responses, while animals born to mothers who were immunized during the last trimester had primarily an antibody-mediated immune response. Immunization of pregnant animals followed by neonatal immunization resulted in a mixed cell-mediated/antibody type profile in the neonatal animal. Future studies should provide insights into neonatal immunity and potential vaccine approaches to prevent neonatal infection and perinatal transmission