The Characteristic Structural Features of the Blood Vessels of the Lewis Lung Carcinoma (A Light Microscopic and Scanning Electron Microscopic Study)

Vascular corrosion casts of Lewis lung carcinomas (LLC) grown subcutaneously in C57BL/6-mice are correlated with histological sections and with tumor tissue prepared for scanning electron microscopy (SEM). By making low, medium and high pressure cast preparations we studied the influence of perfusion and injection pressure on the resulting cast sample. Three types of vascular proliferations are distinguishable in LLC: 1) Small globular outgrowths on sinusoidal dilated tumor capillaries, caused by proliferation of their endothelial cells. 2) New sprouts on surrounding host vessels, invading the small, still avascular implant. 3) Superficially located, centrifugally running sprouts in peripheral regions of large tumors. They invade the surrounding host tissue. Vascular sprouts are of venous origin, have a fragmentary endothelium and are rather leaky if casted. High pressure preparations of large tumors reveal central avascular cavities surrounded by centripetally running, compressed and blind ending tumor vessels. Irrespective of the applied injection pressure, the casts always exhibit extravasal channels caused by degeneration of the endothelium of central tumor vessels. We show that SEM of vascular corrosion casts combined with histology not only demonstrates such contrary processes as the development of tumor blood vessels and the simultaneously occurring vascular degeneration, but also elucidates all other morphological characteristics of the tumor vascular system

The Angioarchitecture of the Lewis Lung Carcinoma in Laboratory Mice (A Light Microscopic and Scanning Electron Microscopic Study)

53 Lewis lung carcinomas implanted subcutaneously into C57BL/6-mice were examined. The animals were killed at various stages of tumor growth (TG) and prepared for histology and for scanning electron microscopy (critical-point-dried tissue; vascular corrosion casts). Prior to casting animals were rinsed using different perfusion pressures. Casting was done by manual injection of the resin, whereby different influx-rates were applied resulting in low, medium and high pressure preparations. We discern 3 phases of tumor angiogenesis (TA) occurring during 4 stages of TG among which vasodilation establishes the first reaction of the host vascular system to a growing tumor implant. During this stage 1 of TG, tumor nidation, nearby sinusoidal dilated host capillaries form globular outgrowings (phase 1 of TA) Subsequently radially arranged sprouts, which preferentially arise from venous host vessels, grow into the centre of the implant (phase 2 of TA). Stage 2 of TG, early tumor growth, is characterized by necrosis of the central tumor tissue and the development of a central avascular cavity. Thus the tumor vascular system is organized like a hollow sphere with a central cavity and a peripheral vascular envelope with large vessels embracing the tumor and centrifugally growing vascular sprouts, which arise from the venous part of the vascular envelope and invade the surrounding host tissue (phase 3 of TA). During stage 3 of TG, late tumor growth, many vessels of the basket-like vascular envelope obliterate. In stage 4 of TG, prefinal phase, the peripheral vascular density decreases continuously. Thus vascular sprouting and proliferation of viable tumor cells is confined to basal regions of the tumor

THE EVOLUTION OF MODELLING PRACTICES ON CANADA’S PARLIAMENT HILL: AN ANALYSIS OF THREE SIGNIFICANT HERITAGE BUILDING INFORMATION MODELS (HBIM)

In this paper, we explore the evolution of modelling practices used to develop three significant Heritage Building Information Models (HBIM) on Canada’s Parliament Hill National Historic Site – West Block, Centre Block, and The Library of Parliament. The unique scope, objective, and timeline for each model required an in-depth analysis to select the appropriate classification for Level of Detail (LOD) and Level of Accuracy (LOA). With each project, the refinement of modelling practices and workflows evolved, culminating in one of our most complex and challenging projects – the Library of Parliament BIM. The purpose of this paper is to share ideas and lessons learned for the intricate challenges that emerge when using LOD and LOA classifications including trade-offs between model performance, tolerances, and anticipated BIM use. In addition, we will evaluate how these decisions effected managing the digitization, data processing, data synthesis, and visualisation of the models

International symposium: "Evolution of permian marine biota," and problems concerning permian sections in the type region

The main results of the International Symposium "Evolution of Permian Marine Biota," are presented. The Artinskian to Ufimian part of the section at the Kozhim River (Polar Urals) is briefly described including its paleontological characteristics. Potentials for further study of Permian deposits in the Urals and possibilities of using the Uralian stages as international standards are discussed. Copyright © 1997 by MAHK Hayka/Interperiodica Publishing

Brachiopods from the Cisuralian–Guadalupian of Darvaz, Tajikistan and implications for Permian stratigraphic correlations

In this paper, we describe the upper Cisuralian Safetdara and Gundara formations of the Darvaz mountains, North Pamir, which were part ofthe Kunlun Arc, developed along the active Eurasian margin. The Safetdara Formation comprises massive limestones (mainly cyanobacterial,Tubiphytes and Archaeolithoporella boundstones) alternating with well-bedded bioclastic and oncoidal limestones and an interval of recessiveshales. The formation crops out above the Chelamchi Formation consisting of turbiditic siltstones and sandstones with bioclastic silty limestonesyielding massive limestone olistoliths. The Gundara Formation consists of fine sandstones at the base, followed by well-bedded marly bioclastic,oncoidal and microbial limestones, bearing a rich silicified brachiopod fauna in life-position. Two new taxa have been identified in this association:the cemented coralliform Gundaria insolita n. gen. n. sp. and the pedicle attached Hemileurus politus n. sp. The inferred environmental setting isthat of shoal deposits of warm, shallow, high energy, clear marine waters for the Safetdara Formation. The agglutinated microbial reefs to clusterreefs of the Gundara Formation were probably growing in a muddier, quieter and probably slightly deeper setting.The foraminifers of the Brevaxina Zone suggest a Bolorian age for the top of the Chelamchi Formation, the Safetdara Formation and the baseof the Gundara Formation. Kungurian conodonts have been found in the lower part of the Safetdara Formation. The biostratigraphic data from thesedimentary succession of North Pamir, integrated with those already obtained from Southeast Pamir, allow to refine the correlations between theTethyan regional scale and the International Time Scale. In particular, it seems now clear that the Bolorian and the lower part of the Kubergandiancorrelate to the Kungurian

A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines

Introduction: Inhibiting the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of breast carcinoma cells, and this is linked to human epidermal growth factor receptor 2 (HER2) signaling pathways in models of simultaneous expression of FASN and HER2. Methods: In a xenograft model of breast carcinoma cells that are FASN+ and HER2+, we have characterised the anticancer activity and the toxicity profile of G28UCM, the lead compound of a novel family of synthetic FASN inhibitors. In vitro, we analysed the cellular and molecular interactions of combining G28UCM with anti-HER drugs. Finally, we tested the cytotoxic ability of G28UCM on breast cancer cells resistant to trastuzumab or lapatinib, that we developed in our laboratory. Results: In vivo, G28UCM reduced the size of 5 out of 14 established xenografts. In the responding tumours, we observed inhibition of FASN activity, cleavage of poly-ADPribose polymerase (PARP) and a decrease of p-HER2, p- protein kinase B (AKT) and p-ERK1/2, which were not observed in the nonresponding tumours. In the G28UCM-treated animals, no significant toxicities occurred, and weight loss was not observed. In vitro, G28UCM showed marked synergistic interactions with trastuzumab, lapatinib, erlotinib or gefitinib (but not with cetuximab), which correlated with increases in apoptosis and with decreases in the activation of HER2, extracellular signal-regulated kinase (ERK)1/2 and AKT. In trastuzumab-resistant and in lapatinib-resistant breast cancer cells, in which trastuzumab and lapatinib were not effective, G28UCM retained the anticancer activity observed in the parental cells. Conclusions: G28UCM inhibits fatty acid synthase (FASN) activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development