Animals ; Male ; Neovascularization, Pathologic ; diagnosis ; Vasa Vasorum ; physiology

BACKGROUNDAccumulating evidence indicates a potential role of adventitial vasa vasorum (VV) dysfunction in the pathophysiology of restenosis. However, characterization of VV vascularization in restenotic arteries with primary lesions is still missing. In this study, we quantitatively evaluated the response of adventitial VV to vascular injury resulting from balloon angioplasty in diseased arteries.

METHODSPrimary atherosclerotic-like lesions were induced by the placement of an absorbable thread surrounding the carotid artery of New Zealand rabbits. Four weeks following double-injury induced that was induced by secondary balloon dilation, three-dimensional patterns of adventitial VV were reconstructed; the number, density, and endothelial surface of VV were quantified using micro-computed tomography. Histology and immunohistochemistry were performed in order to examine the development of intimal hyperplasia.

RESULTSResults from our study suggest that double injured arteries have a greater number of VV, increased luminal surface, and an elevation in the intima/media ratio (I/M), along with an accumulation of macrophages and smooth muscle cells in the intima, as compared to sham or single injury arteries. I/M and the number of VV were positively correlated (R2 = 0.82, P < 0.001).

CONCLUSIONSExtensive adventitial VV neovascularization occurs in injured arteries after balloon angioplasty, which is associated with intimal hyperplasia. Quantitative assessment of adventitial VV response may provide insight into the basic biological process of postangioplasty restenosis.

Angioplasty, Balloon, Coronary ; Animals ; Male ; Neovascularization, Pathologic ; diagnosis ; Rabbits ; Vasa Vasorum ; physiology ; X-Ray Microtomography

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in adults and children worldwide. NAFLD has become a severe health issue and it can progress towards a more severe form of the disease, the non-alcoholic steatohepatitis (NASH). A combination of environmental factors, host genetics, and gut microbiota leads to excessive accumulation of lipids in the liver (steatosis), which may result in lipotoxicity and trigger hepatocyte cell death, liver inflammation, fibrosis, and pathological angiogenesis. NASH can further progress towards liver cirrhosis and cancer. Over the last few years, cell-derived extracellular vesicles (EVs) have been identified as effective cell-to-cell messengers that transfer several bioactive molecules in target cells, modulating the pathogenesis and progression of NASH. In this review, we focused on recently highlighted aspects of molecular pathogenesis of NASH, mediated by EVs via their bioactive components. The studies included in this review summarize the state of art regarding the role of EVs during the progression of NASH and bring novel insight about the potential use of EVs for diagnosis and therapeutic strategies for patients with this disease.
Adult ; Cell Death ; Child ; Diagnosis ; Fatty Liver* ; Fibrosis ; Genetics ; Hepatocytes ; Humans ; Inflammation ; Liver ; Liver Cirrhosis ; Liver Diseases ; Microbiota ; Neovascularization, Pathologic

As a recently emerging molecular imaging technique, fluorescent molecular imaging has the advantage of fast imaging, simple operation, high sensitivity, low cost, nonionizing radiation and so on. Through the real-time, non-invasive, specific tracking and detection of tumorigenesis, metastases, angiogenesis, and the therapeutic response to antitumor drugs in vivo, we can study the physiological and pathological processes within tumors at cellular and molecular levels. Fluorescent molecular imaging provides effective methods for the early detection and targeted therapy of tumor, for the intraoperative visualization of tumor foci, as well as for the development of new antitumor drugs in the future clinical practice.
Animals ; Green Fluorescent Proteins ; metabolism ; Humans ; Indocyanine Green ; Molecular Imaging ; methods ; Molecular Probe Techniques ; Neoplasms ; blood supply ; diagnosis ; Neoplasms, Experimental ; blood supply ; diagnosis ; Neovascularization, Pathologic ; diagnosis

Aged ; Diagnosis, Differential ; Drug Therapy, Combination ; Female ; Humans ; Liver ; blood supply ; pathology ; Multiple Myeloma ; diagnostic imaging ; drug therapy ; pathology ; Neovascularization, Pathologic ; diagnosis ; pathology ; Tomography, X-Ray Computed

INTRODUCTIONThe extent of lymph nodes (LNs) metastasis is a major determinant for the staging and the most reliable adverse prognostic factor. Primary tumours can induce lymphatics and vasculature reorganisations within sentinel LN before the arrival of cancer cells and these key blood vessels are identified as high endothelial venules (HEV). The alterations of HEV in the presence of cancer, coupled with the increased proliferation rate of the endothelial cells, results in a functional shift of HEV from immune response mediator to blood flow carrier. We aim to evaluate tumour-induced vascularisation in regional LN of cancer patients by studying the morphological and functional alterations of HEV and its correlation to clinico-pathological features.

MATERIALS AND METHODSThis multi-centre study with a prospective database identified 65 consecutive patients with tongue squamous cell carcinoma (SCC) who underwent primary surgical treatment from 2001 to 2005. Immunohistochemical staining for HEV and image analysis were performed and analysed with correlation to the patients' clinico-pathological features.

RESULTSThe total number of HEV is significantly associated to disease-free interval when controlling for the group (P = 0.022) as well as combining both groups as one cohort (P = 0.023). There is also a similar association comparing the HEV parameters to overall survival.

CONCLUSIONOur results suggest that HEV possibly plays a key role in the pathogenesis of lymphatic and subsequent distant metastases and may provide the missing link in cancer metastasis. Confirmation of this hypothesis would offer a novel therapeutic approach to preventing metastasis by blocking the remodeling processes of HEV in LN.

Awards and Prizes ; Biomarkers ; Databases, Factual ; Endothelial Cells ; physiology ; General Surgery ; Humans ; Lymph Nodes ; blood supply ; pathology ; Neoplasm Metastasis ; diagnosis ; Neovascularization, Pathologic ; pathology ; Prospective Studies ; Venules ; pathology

OBJECTIVETo study the changes in quantitative kinetic parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during radiotherapy and their value for efficacy evaluation in patients with nasopharyngeal carcinoma (NPC).

METHODSTwenty-four patients with NPC that had been pathologically confirmed as poorly differentiated squamous cell carcinoma underwent conventional MRI and DCE-MRI scans 1-2 days before radiotherapy (Pre-RT), during radiotherapy (RT 50 Gy), and upon completion of radiotherapy (RT 70 Gy). Based on the two-compartment model and using the arterial input function deconvolution technique, we calculated the quantitative kinetic parameters of DCE-MRI (K(trans), kep, and Ve) of the tumor tissues, examined the correlation between the tumor regression rate (RS0-50) and the parameters on Pre-RT and RT 50 Gy, and compared the parameters for RT 70 Gy among the groups with different prognosis.

RESULTSThe K(trans) value of the tumor tissue decreased after radiotherapy and showed a significant difference between Pre-RT and RT 70 Gy, but not between Pre-RT and RT 50 Gy. The kep value decreased and Ve value increased after radiotherapy. The tumor regression rate was found to be positively correlated with the K(trans) value for Pre-RT (P=0.005) but negatively with the K(trans) value for RT 50 Gy (P=0.001). During the follow-up for 3 years, 5 patients died and 3 patients had distant metastases. No statistical differences in K(trans), kep, or Ve were found between the groups with different prognosis.

CONCLUSIONSThe kinetic parameters in DCE-MRI, which vary significantly during radiotherapy, allow monitoring of tumor angiogenesis and vascular permeability and quantitative assessment of treatment efficacy for NPC. K(trans) value for Pre-RT and RT 50 Gy can serve as an indicator for early efficacy assessment of radiotherapy and for treatment adjustment, but its relation with the long-term outcomes awaits further study.

Algorithms ; Capillary Permeability ; Carcinoma ; Carcinoma, Squamous Cell ; diagnosis ; Humans ; Magnetic Resonance Imaging ; Nasopharyngeal Neoplasms ; blood supply ; radiotherapy ; Neovascularization, Pathologic ; Prognosis ; Treatment Outcome

OBJECTIVETo review the current status and progress on nuclear medical molecular imaging of angiogenesis.

DATA SOURCESA literature search was performed in Medline and PubMed published in English up to May 31, 2012. The search terms were molecular imaging, nuclear medicine and angiogenesis.

STUDY SELECTIONArticles studying molecular imaging of angiogenesis using radionuclide were selected and reviewed.

RESULTSMolecular imaging has been used for studying angiogenesis by targeting integrin αVβ3, VEGF/VEGFR, and matrix metalloproteinases (MMPs) with radionuclide-labeled tracers. The technology has been shown to be able to assess the angiogenesis status and/or predict the efficacy of anti-angiogenic therapy. Future directions of the research on the molecular imaging of angiogenesis include development of new tracers with better tumor targeting efficacy, desirable pharmacokinetics, and easy translation to clinical applications.

CONCLUSIONAdvances in molecular imaging of angiogenesis using radioculcide will make the technology a valuable tool for personalized anti-angiogenesis treatment.

Humans ; Integrins ; analysis ; Matrix Metalloproteinases ; analysis ; Neoplasms ; blood supply ; Neovascularization, Pathologic ; diagnosis ; Receptors, Vascular Endothelial Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; analysis

OBJECTIVETo study the application of cluster analysis in micrangium detection in malignant nasal and paranasal sinus tumor.

METHODSMicrovessel density (MVD) counting and cluster analysis were used to detect the micrangium in patients with malignant nasal and paranasal sinus tumor to assess the association between the malignancy and MVD.

RESULTSAccording to cluster analysis, the MVD counting could be clustered into two groups, and the MVD showed significant differences between the tumor tissues, adjacent normal tissue and the control group (P<0.01), a result consistent with that by analysis of variance of the MVD.

CONCLUSIONCluster analysis can be used in clustering of MVD counting in malignant nasal and paranasal sinus tumor to simplify MVD counting, and offers an important analytic method for micrangium analysis in tumors.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Cluster Analysis ; Female ; Humans ; Male ; Microvessels ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Paranasal Sinus Neoplasms ; blood supply ; diagnosis ; Young Adult

OBJECTIVETo explore the characteristics of 3.0T dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging of lung cancer and its correlation with microvessel density (MVD).

METHODSThirty-seven patients with pathologically proven lung cancer underwent DCE-MR with liver acquisition with volume acceleration sequence. DCE-MR images were acquired intermittently for a total of 4 minutes on a 3.0T MR scanner. The relative enhancing percentage (SI%) at each time point was measured. The shapes of T-SI% curves were defined as A (rapidly ascending followed by a descending branch) and B (rapidly ascending branch followed by a plateau). The early peak enhancement (SIEP%), early peak time (TEP), maximum enhancement (SIpeak%), and peak time (Tpeak) were recorded and compared according to different dimensions, locations, histological types, and differentiation grades of lung cancer. Tumour specimens were immunostained for CD31 and CD34 in ten patients who had undergone surgical resections. The enhancement values were correlated with MVD. Results The SIEP% and SIpeak% of tumors with smaller dimensions (< or = 5 cm) were significantly higher than those with larger dimensions (> 5 cm) (P = 0.014, P = 0.024). The SIEP% and SIpeak% were positively correlated with the tumor MVD. Conclusion The SIEP% and SIpeak% of lung cancer correlate with tumor dimension and can reflect MVD in tumor.

Adenocarcinoma ; blood supply ; diagnosis ; Adult ; Aged ; Carcinoma, Squamous Cell ; blood supply ; diagnosis ; Contrast Media ; Female ; Humans ; Image Enhancement ; methods ; Lung Neoplasms ; blood supply ; diagnosis ; Magnetic Resonance Imaging ; methods ; Male ; Microvessels ; pathology ; Middle Aged ; Neovascularization, Pathologic ; diagnosis