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Identification of a characteristic vascular belt zone in human colorectal cancer.

ABSTRACT: BLOOD VESSELS IN CANCER:Intra-tumoral blood vessels are of supreme importance for tumor growth, metastasis and therapy. Yet, little is known about spatial distribution patterns of these vessels. Most experimental or theoretical tumor models implicitly assume that blood vessels are equally abundant in different parts of the tumor, which has far-reaching implications for chemotherapy and tumor metabolism. In contrast, based on histological observations, we hypothesized that blood vessels follow specific spatial distribution patterns in colorectal cancer tissue. We developed and applied a novel computational approach to identify spatial patterns of angiogenesis in histological whole-slide images of human colorectal cancer. A CHARACTERISTIC SPATIAL PATTERN OF BLOOD VESSELS IN COLORECTAL CANCER:In 33 of 34 (97%) colorectal cancer primary tumors blood vessels were significantly aggregated in a sharply limited belt-like zone at the interface of tumor tissue to the intestinal lumen. In contrast, in 11 of 11 (100%) colorectal cancer liver metastases, a similar hypervascularized zone could be found at the boundary to surrounding liver tissue. Also, in an independent validation cohort, we found this vascular belt zone: 22 of 23 (96%) samples of primary tumors and 15 of 16 (94%) samples of liver metastases exhibited the above-mentioned spatial distribution. SUMMARY AND IMPLICATIONS:We report consistent spatial patterns of tumor vascularization that may have far-reaching implications for models of drug distribution, tumor metabolism and tumor growth: luminal hypervascularization in colorectal cancer primary tumors is a previously overlooked feature of cancer tissue. In colorectal cancer liver metastases, we describe a corresponding pattern at the invasive margin. These findings add another puzzle piece to the complex concept of tumor heterogeneity.

SUBMITTER: Kather JN

PROVIDER: S-EPMC5333981 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Identification of a characteristic vascular belt zone in human colorectal cancer.

Kather Jakob Nikolas JN Zöllner Frank Gerrit FG Schad Lothar R LR Melchers Susanne Maria SM Sinn Hans-Peter HP Marx Alexander A Gaiser Timo T Weis Cleo-Aron CA

PloS one 20170302 3

<h4>Blood vessels in cancer</h4>Intra-tumoral blood vessels are of supreme importance for tumor growth, metastasis and therapy. Yet, little is known about spatial distribution patterns of these vessels. Most experimental or theoretical tumor models implicitly assume that blood vessels are equally abundant in different parts of the tumor, which has far-reaching implications for chemotherapy and tumor metabolism. In contrast, based on histological observations, we hypothesized that blood vessels f ...[more]

PMID: 28253263

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Project description:Distant metastasis is the major cause of mortality in colorectal cancer (CRC). We performed a systemic, comprehensive discovery for expression patterns of metastasis-specific microRNAs (miRNAs) by directly comparing primary CRCs (pCRCs) and matched liver metastases (LMs) and evaluated the feasibility of their clinical application as metastasis-specific biomarkers.CRC metastasis-specific miRNA profiles were generated by analyzing nine pairs of pCRC and LM tissues, followed by quantitative validation in an independent cohort of 58 pairs of matched pCRC and LM tissues. We evaluated associations between miRNA expression and patient survival and ability to predict metastasis in another 84 patients with CRC. Subsequently, associations were quantitatively validated in 175 CRC tissues and 169 serum samples. Kaplan-Meier, Cox regression, and logistic regression analyses were used. All statistical tests were two-sided.Twenty-three miRNAs were identified that were differentially expressed between pCRC and LM (P < .001; FDR < .5). Four miRNAs downregulated in LM (let-7i, miR-10b, miR-221, and miR-320a) and one upregulated miR (miR-885-5p) were quantitatively validated in pCRC (P < .0001). Low let-7i expression in pCRC tissue predicted worsened prognosis (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 1.0 to 24.4, P = .0479) as well as distant metastasis (odds ratio [OR] = 5.5, 95% CI = 1.1 to 26.8, P = .0334). High miR-10b expression in pCRC tissue independently predicted distant metastasis (OR = 4.9, 95% CI = 1.2 to 19.7, P = .0248). High serum miR-885-5p expression independently predicted prognosis (HR = 2.9, 95% CI = 1.1 to 7.5, P = .0323), LN metastasis (OR = 3.0, 95% CI = 1.3 to 7.2, P = .0116), and distant metastasis (OR = 3.1, 95% CI = 1.0 to 10.0, P = .0456), whereas tissue miR-885-5p expression did not. Expression patterns of miRNAs were confirmed by in situ hybridization.We discovered a metastasis-specific miRNA signature in pCRCs and discovered novel tissue- and serum-based CRC metastasis-specific miRNA biomarkers through intensive validation. These unique miRNAs may be clinically applicable to predict prognosis and distant metastasis in CRC.

Project description:The atmospheres of the four giant planets of our Solar System share a common and well-observed characteristic: they each display patterns of planetary banding, with regions of different temperatures, composition, aerosol properties and dynamics separated by strong meridional and vertical gradients in the zonal (i.e., east-west) winds. Remote sensing observations, from both visiting spacecraft and Earth-based astronomical facilities, have revealed the significant variation in environmental conditions from one band to the next. On Jupiter, the reflective white bands of low temperatures, elevated aerosol opacities, and enhancements of quasi-conserved chemical tracers are referred to as 'zones.' Conversely, the darker bands of warmer temperatures, depleted aerosols, and reductions of chemical tracers are known as 'belts.' On Saturn, we define cyclonic belts and anticyclonic zones via their temperature and wind characteristics, although their relation to Saturn's albedo is not as clear as on Jupiter. On distant Uranus and Neptune, the exact relationships between the banded albedo contrasts and the environmental properties is a topic of active study. This review is an attempt to reconcile the observed properties of belts and zones with (i) the meridional overturning inferred from the convergence of eddy angular momentum into the eastward zonal jets at the cloud level on Jupiter and Saturn and the prevalence of moist convective activity in belts; and (ii) the opposing meridional motions inferred from the upper tropospheric temperature structure, which implies decay and dissipation of the zonal jets with altitude above the clouds. These two scenarios suggest meridional circulations in opposing directions, the former suggesting upwelling in belts, the latter suggesting upwelling in zones. Numerical simulations successfully reproduce the former, whereas there is a wealth of observational evidence in support of the latter. This presents an unresolved paradox for our current understanding of the banded structure of giant planet atmospheres, that could be addressed via a multi-tiered vertical structure of "stacked circulation cells," with a natural transition from zonal jet pumping to dissipation as we move from the convectively-unstable mid-troposphere into the stably-stratified upper troposphere.

Dataset Information

Identification of a characteristic vascular belt zone in human colorectal cancer.

Publications

Identification of a characteristic vascular belt zone in human colorectal cancer.

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