1,218 research outputs found
Intussusceptive microvascular growth in tumors
No full textIntussusception is an alternative to the sprouting mode of angiogenesis. The advantage of this mechanism of vascular growth is that blood vessels are generated more rapidly and the capillaries thereby formed are less leaky. This review article summarizes our current knowledge concerning the role played by intussusceptive microvascular growth in tumor growth. Interestingly, an angiogenic switch from sprouting to intussusceptive angiogenesis occurs after treatment with angiogenesis inhibitors and may be considered as a tumor-protective adaptative response
The mammary gland vasculature revisited
No full textConcomitant with the extensive growth and differentiation of the mammary epithelium during pregnancy and lactation, and epithelial involution after weaning, the vasculature of the mammary gland undergoes repeated cycles of expansion and regression. Vascular expansion is effected by sprouting angiogenesis, intussusception and conceivably also vasculogenesis. The capacity of the epithelial cells to stimulate vascular growth and differentiation is dependent on the constellation of systemic and local hormones and growth factors as well as the changing demands for oxygenation and nutrient supply. This results in the release of angiogenic factors which stimulate endothelial cell growth and regulate vascular architecture. In contrast to the angiogenic phase of the mammary gland cycle, little is known about the control of vascular regression although this would possibly offer new insights into therapeutic possibilities against breast cancer. In this review we summarize knowledge regarding the mechanisms regulating the vasculature of the mammary gland and delineate the importance of the vasculature in the attainment of organ function. In addition, we discuss the angiogenic mechanisms observed during mammary carcinogenesis and their consequences for breast cancer therapy
Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish
No full textAlthough well investigated, the importance of collagen fibers in supporting angiogenesis is not well understood. In this study, we demonstrate that extracellular collagen fibers provide guidance cues for endothelial cell migration during regenerative angiogenesis in the caudal zebrafish fin. Inhibition of collagen cross-linking by β-Aminopropionitrile results in a 70% shorter regeneration area with 50% reduced vessel growth and disintegrated collagen fibers. The disrupted collagen scaffold impedes endothelial cell migration and induces formation of abnormal angioma-like blood vessels. Treatment of the Fli//colRN zebrafish line with the prodrug Nifurpirinol, which selectively damages the active collagen-producing 1α2 cells, reduced the regeneration area and vascular growth by 50% with wider, but less inter-connected, capillary segments. The regenerated area contained larger vessels partially covered by endothelial cells embedded in atypical extracellular matrix containing cell debris and apoptotic bodies, macrophages and granulocytes. Similar experiments performed in early embryonic zebrafish suggested that collagens are important also during embryonic angiogenesis. In vitro assays revealed that collagen I allows for the most efficient endothelial cell migration, followed by collagen IV relative to the complete absence of exogenous matrix support. Our data demonstrates severe vascular defects and restricted fin regeneration when collagens are impaired. Collagen I therefore, provides support and guidance for endothelial cell migration while collagen IV is responsible for proper lumen formation and vascular integrity
Anatomical and Functional Study of the Ostrich (Struthio camelus) Lung through Macroscopic Analysis in Combination with Optical and Electron Microscopy Techniques.
No full textThe Ostrich occupies a unique position as the largest bird on the planet. Like other ratites, it has been reputed to have a phylogenetically primitive lung. We used macroscopy, light microscopy, transmission and scanning electron microscopy as well as silicon rubber casting to elucidate the functional design of its lung and compare it with what is already documented for the avian species. The neopulmonic region was very small and poorly developed. The categories of the secondary bronchi (SB) present and their respective numbers included laterodorsal (8-10), lateroventral (4-5), medioventral (4-6) and posterior (16-24). The lateral aspects of the laterodorsals were covered with a transparent collapsible membrane internally lined with a squamous to cuboidal epithelium. The bulk of these SB were in close proximity to intercostal spaces and the intercostal muscles and were thought to be important in the propulsion of gases. The lung parenchyma was rigid, with the atria well supported by septa containing smooth muscles, connective tissue interparabronchial septa were absent, and blood capillaries were supported by epithelial bridges. There were two categories of epithelia bridges: the homogenous squamous type comprising two leaflets of type I cells and the heterogeneous type consisting of a type I pneumocyte and type II cell. Additional type two cells were found at the atrial openings as well as the walls of the infundibulae and the air capillaries. The atria were shallow and opened either directly into several air capillaries or into a few infundibulae. The presence of numerous type II cells and the absence of interparabronchial connective tissue septa may imply that the ostrich lung could be capable of some degree of compliance
The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.
No full textMedulloblastoma (MB) is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K) pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi)-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α) was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH) subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation
Angiogenesis in cancer - general pathways and their therapeutic implications
No full textA vast amount of data shows that angiogenesis has a pivotal role in tumor growth, progression, invasiveness and metastasis. This is a complex process involving essential signaling pathways such as vascular endothelial growth factor (VEGF) and Notch in vasculature, as well as additional players such as bone marrow-derived endothelial progenitor cells. Primary tumor cells, stromal cells and cancer stem cells strongly influence vessel growth in tumors. Better understanding of the role of the different pathways and the crosstalk between different cells during tumor angiogenesis are crucial factors for developing more effective anticancer therapies. Targeting angiogenic factors from the VEGF family has become an effective strategy to inhibit tumor growth and so far the most successful results are seen in metastatic colorectal cancer (CRC), renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLL). Despite the initial enthusiasm, the angiogenesis inhibitors showed only moderate survival benefit as monotherapy, along with a high cost and many side effects. Obviously, other important pathways may affect the angiogenic switch, among them Notch signaling pathway attracted a large interest because its ubiquitous role in carcinogenesis and angiogenesis. Herein we present the basics for VEGF and Notch signaling pathways and current advances of targeting them in antiangiogenic, antitumor therapy
Quantitative assessment of brain tumor radiation treatment reveals decrease in tumor-supporting vessels
No full text---
title: Quantitative assessment of brain tumor radiation treatment reveals decrease in tumor-supporting vessels
author:
- David Haberthür^1^
- Ruslan Hlushchuk^1^
- Marine Potez^1^
- Audrey Bouchet^1^
- Valentin Djonov^1^
include-before: ^1^ Institute of Anatomy, University of Bern, Switzerland
date: \today
---
# Aims
Angiogenesis---the formation of new blood vessels---is an important factor for tumor growth [@Sherwood1971].
Reducing tumor-supporting vessels by radiation treatment is a powerful option for treating tumors; specialized treatments that deliver high radiation doses have shown to enable *excellent* survival rate [@Laissue1998].
Among rodent models for brain tumors, the 9L-gliosarcoma model is a widely used one, since it mimics important features of human brain tumor growth.
Our aim is to extract and assess biologically relevant values of brain tumors (tumor and vessel volume, vessel surface, etc.) from rats that underwent different radiation treatments.
These values are extracted based on two imaging modalities, namely microCT and magnetic resonance imaging (MRI).
# Method
Brain tumors were induced in 10-week-old Fisher 344 rats (n=59) by inoculation of gliosarcoma cells into the right caudate nucleus through the skull [@Bouchet2014].
Ten days after inoculation, tumor volume was assessed by MRI performed with a 4.7 T [Bruker Avance III](https://www.bruker.com/products/mr/nmr/overview.html) console [@Lemasson2015].
Based on tumor volume, animals were split into groups with comparable tumor size ready for either microbeam radiation therapy (`MRT`), conventional radiation therapy (so called broad beam, `BB`) or no therapy (`CTRL`).
Irradiation was performed at the [ID17 biomedical beamline](http://www.esrf.eu/UsersAndScience/Experiments/CBS/ID17) at the European Synchrotron Radiation Facility.
Details on the facility and the radiation treatment are described by @Bouchet2016.
Briefly, rats were irradiated ten days after inoculation using two 8 x 10 mm irradiation fields focused onto the tumor location in the anterior part of the right hemisphere.
For the `MRT`-animals, the irradiation field was split into 40 microbeams (width 50 μm, 200 μm on-center spacing) using a multislit collimator.
The in-microbeam entrance dose was 250 Gy, the valley dose approximately 9 Gy.
For the `BB`-animals, the irradiation was homogeneously applied to the same area with a dose equivalent to the `MRT` valley dose.
On days 6, 10 and 14 after radiation treatment, rats were again imaged by MRI.
Subsequently, they were infused with a contrast agent (μAngiofil, @Schaad2017) and their brains extracted.
Fifty-four of those brains were imaged with a [Bruker SkyScan 1272](http://bruker-microct.com/products/1272.htm).
The brains were immersed in 4 % PFA in a custom-made sample holder and imaged at 5 μm voxel size.
After manually delineating the tumor regions of interest (ROIs) in CTAn we used a custom image processing pipeline in Python to assess the data sets and extract the aforementioned values.
The automatic assessment pipeline analyzes the 54 data sets fully autonomous and in a reproducible way.
Due to the contrast agent, separating blood vessels from the tumor volume was as easy as using standard gray value thresholding.
This makes it possible to easily extract values like tumor and vessel volume and thus the vessel volume ratio.
With a distance transformation we can also extract the vessel diameter and the vessel surface.
# Results
Tumor ROIs can easily be visualized.
Figure 1 shows three example tumors from the whole set of scans.
Radiation treatment reduces the vasculature in the tumor, as can be seen in Figure 2.
# Conclusion
Using the described approach, we show that radiation treatment decreases the vasculature in the tumor, i.e. less vessels are available to provide the tumor with nutrients.
Our unbiased, automatic assessment shows that the performed radiation treatment is successful.
In parallel to performing the scans, we developed the analysis pipeline.
The reproducible analysis made it possible to easily add more samples, i.e. preliminary results could be obtained early on in this study
Alf Nilsen-Børsskog — The Author Chosen by the Language
No full textThis article discusses Alf Nilsen-Børsskog’s four-volume series of novels Elämän jatko [Continuation of life, 2004–2015], seen as the first literary works treating the Kven culture from a native perspective. Nilsen-Børsskog’s novels are analysed as constituting a “counterstory”, a term coined in the postcolonial cultural research paradigm to refer to self-representation. The Kvens have been considered a national minority in Norway since 1999, and their language has been an official minority language since 2005. The present author scrutinizes how Nilsen-Børsskog’s work differs from previous literary descriptions of this minority, often marked by the frequent use of stereotypes of the Kven language and culture
Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Ocular Graft-Versus-Host Disease
No full textOcular GVHD (oGVHD), manifested by severe injury of corneal epithelial cells, meibomian and lacrimal glands’ dysfunction, is a serious complication of systemic GVHD which develops as a consequence of donor T and natural killer cell-driven inflammation in the eyes of patients who received allogeneic hematopoietic stem cell transplantation. Mesenchymal stem cells (MSC) are, due to their enormous differentiation potential and immunosuppressive characteristics, considered as a potentially new remedy in ophthalmology. MSC differentiate in corneal epithelial cells, suppress eye inflammation, and restore meibomian and lacrimal glands’ function in oGVHD patients. MSC-sourced exosomes (MSC-Exos) are extracellular vesicles that contain MSC-derived growth factors and immunoregulatory proteins. Due to the lipid membrane and nano-sized dimension, MSC-Exos easily by-pass all biological barriers in the eyes and deliver their cargo directly in injured corneal epithelial cells and eye-infiltrated leukocytes, modulating their viability and function. As cell-free agents, MSC-Exos address all safety issues related to the transplantation of their parental cells, including the risk of unwanted differentiation and aggravation of intraocular inflammation. In this review article, we summarized current knowledge about molecular mechanisms which are responsible for beneficial effects of MSC and MSC-Exos in the therapy of inflammatory eye diseases, emphasizing their therapeutic potential in the treatment of oGVHD
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