https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.

https://arpi.unipi.it/bitstream/11568/951412/1/Cappello%2c%20SciRep2016.pdf

Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease.

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion. Intratumoral hypoxia and genetic alterations can lead to HIF-1alpha overexpression, which has been associated with increased patient mortality in several cancer types. In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics.

Targeting HIF-1 for cancer therapy

Lelio Orci, chairman of the Department of Morphology at the University of Geneva Medical School in Switzerland, was one of the most eminent morphologists of the last century, author of fundamental contributions to the study of microanatomy, especially regarding the ultrastructure of the endocrine pancreas and of the molecular mechanisms of cell secretion. In his work, Orci transformed EM-ultrastructure into a creative art form. The aim of this article is to demonstrate, through a few examples of the scientific work of this extraordinary scientist the reality of this assertion. 

Morphology and art in the work of Lelio Orci.

Neuroblastoma (NB) is an embryonal tumor originating from the simpatico‐adrenal lineage of the neural crest and developing virtually at any site of the sympathetic nervous system. It approximately accounts for about 15% of all paediatric oncology deaths. NB is characterized by different clinical presentations and courses. Metastatic tumors at diagnosis remains a clinical challenge, despite advances in multimodal therapy. Retinoids are a class of compounds known to induce both terminal differentiation and apoptosis/necrosis of NB cells. Among them, fenretinide (HPR), thanks to its good safety profile in humans, has been considered one of the most promising synthetic retinoids tested as chemopreventive agent but it is only partially efficacious due to both a scanty oral delivery and a rapid methabolism. Here, we have developed a novel liposomal HPR by which the drug was encapsulated into sterically stabilized liposomes [SL‐(HPR)] according to the reverse‐phase evaporation method. This procedure led to a higher drug encapsulation and to better size and stability in organic fluids when compared to our previously HPR‐entrapped liposome preparation (Pagnan et al., Int.J.Cancer 1999;81:268). Moreover, liposomes were coupled with NGR peptides that target the tumor endothelial cell marker, the aminopeptidase N [NGR‐SL‐(HPR)] (Pastorino et al, Cancer Res 2006;66:10073). The in vivo sensitivity of NB to the HPR liposomal preparations was tested against an established orthotopic NB xenograft animal model. Tumor‐bearing mice treated with NGR‐SL‐(HPR) lived statistically longer than mice un‐treated or treated with free HPR [NGR‐SL‐(HPR) vs both control and HPR: P The use of this novel targeted delivery system for the apoptotic and anti‐angiogenic drug, fenretinide, could be considered as an adjuvant tool in the future treatment of NB patients. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A130.

Abstract A130: Effects of a novel liposomal formulation of fenretinide on human neuroblastoma cell growth, apoptosis and angiogenesis

The vesicles and vacuoles of the endothelia, morphological expression of endocytosis and transendothelial transport, are quite absent in the mature neural endothelia. In order to study the temporal sequence of the vesicle and vacuole modifications during the blood brain barrier (bbb) setting up, the extent of these structures was morphometrically analyzed on electron micrographs of neural microvessels in the optic tectum of 8, 14, and 17 day chick embryos, fixed after an intracardial injection of the permeability marker horseradish peroxidase. During the development, endocytosis and transendothelial transport change, since a statistically significant reduction of both vesicles and vacuoles was recorded at the 17th incubation day. The temporal coincidence between decrease of endocytosis-transport processes and appearance of astrocytic endfeet close to the vessel wall, suggests that the glial cells might control, besides the tight junction formation, the expression of other properties of the bbb-provided endothelia.

Le vescicole endoteliali come sistema di trasporto nella barriera ematoencefalica. Studio morfometrico durante lo sviluppo.

Mast cells and tumour

Vascular Targeting: A New Antitumor Activity

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