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AIM To investigate the correlation of iodine concentration (IC) generated by spectral computed tomography (CT) with micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression in patients with advanced gastric carcinoma (GC). METHODS Thirty-four advanced GC patients underwent abdominal enhanced CT in the gemstone spectral imaging mode. The IC of the primary lesion in the arterial phase (AP) and venous phase (VP) were measured, and were then normalized against that in the aorta to provide the normalized IC (nIC). MVD and VEGF were detected by immunohistochemical assays, using CD34 and VEGF-A antibodies, respectively. Correlations of nIC with MVD, VEGF, and clinical-pathological features were analyzed. RESULTS Both nICs correlated linearly with MVD and were higher in the primary lesion site than in the normal control site, but were not correlated with VEGF expression. After stratification by clinical-pathological subtypes, nIC-AP showed a statistically significant correlation with MVD, particularly in the group with tumors at stage T4, without nodular involvement, of a mixed Lauren type, where the tumor was located at the antrum site, and occurred in female individuals. nIC-VP showed a positive correlation with MVD in the group with the tumor at stage T4 and above, had nodular involvement, was poorly differentiated, was located at the pylorus site, of a mixed and diffused Lauren subtype, and occurred in male individuals. nIC-AP and nIC-VP showed significant differences in terms of histological differentiation and Lauren subtype. CONCLUSION The IC detected by spectral CT correlated with the MVD. nIC-AP and nIC-VP can reflect angiogenesis in different pathological subgroups of advanced GC.

Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma (MM). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2years after treatment. A population-based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors (HIF), vascular endothelial growth factor (VEGF, also termed VEGFA) and micro-vessel density (MVD) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma (EMP) while 66% had a solitary plasmacytoma of the bone (SBP). Median follow-up was 89months, (7-293months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19months (5-293). Three patients (12%) with EMP developed MM. High expression of VEGF and HIF-2 (also termed EPAS1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM. In conclusion, this population-based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy.

Jian-Song Ji,1,2,* Min Xu,1,* Jing-Jing Song,1,* Zhong-Wei Zhao,1,* Min-Jiang Chen,1 Wei-Qian Chen,1 Jian-Fei Tu,1 Xiao-Ming Yang2 1Department of Radiology, Affiliated Lishui Hospital of Zhejiang University, Fifth Affiliated Hospital of Wenzhou Medical University, Central Hospital of Zhejiang Lishui, Lishui, People’s Republic of China; 2Department of Radiology, Lab-Yang, University of Washington, Seattle, WA, USA *These authors contributed equally tothis work Abstract: MicroRNA-126 (miR-126) has been found to promote angiogenesis, but the underlying mechanisms are still unclear. So, we conducted this study to explore the effect of miR-126 expression on angiogenesis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The expression levels of miR-126 and sprouty-related, EVH1 domain containing protein (Spred)1 in surgically resected HCC tissue, HCC tissue with TACE+ operation, and tumor-adjacent tissues were determined by quantitative real-time polymerase chain reaction. The expression levels of miR-126, Spred1, and vascular endothelial growth factor were found by quantitative real-time polymerase chain reaction and Western blot. The microvessel density (MVD) of tumor tissues was determined by immunohistochemical staining. The miR-126 and Spred1 expressions in HCC tissue with TACE + operation were elevated and decreased, respectively, as compared to those in surgically resected HCC tissues and tumor-adjacent tissues (all P

Aims Angiogenesis is essential for malignancies growth. CD105 is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. The aim of this study has been to determine the expression of CD105 in laryngeal squamous cell carcinoma (SCC) and to investigate the role of CD105-assessed mean vascular density (MVD) in predicting patients’ prognosis. Methods The sections of 43 consecutive cases of laryngeal SCC were stained with mouse monoclonal antibody CD105. All the measures were performed by a computer-based image analysis system. The percentage of the fields occupied by CD105-assessed micro-vessels was determined. Results The mean CD105-assessed MVD were 11% and 6% in laryngeal SCC with and without malignancy recurrence, respectively. Multivariate logistic regression stated that CD105-assessed MVD was significantly related to disease recurrence ( p = 0.030). Conclusions Our preliminary results suggest that CD105-assessed MVD may be a valuable parameter for predicting patients having an increased risk of developing laryngeal carcinoma loco-regional recurrence.

Aims: Angiogenesis, as measured by degree of micro vessel density, has been associated with tumor progression in many tumor types, but does not always correlate with clinical outcome. Aggressive tumor cells were shown to form blood-conducting tubes not lined by endothelial cells, and this phenomenon was termed vasculogenic mimicry. Merkel cell carcinoma is a very aggressive but rare form of skin cancer, of neuroendocrine origin and with increasing incidence. We investigated the presence of vasculogenic mimicry in Merkel cell carcinoma in the Groene Hart Hospital, The Netherlands between 1990-2012. Methods: Tumor tissues of all patients diagnosed with primary Merkel cell carcinoma in the period 1990-2012 in the Groene Hart Ziekenhuis were assessed on the presence of vasculogenic mimicry. Results: We found vasculogenic mimicry in 11 (100%) out of the eleven patients primary diagnosed with Merkel cell carcinoma. Conclusions: Vasculogenic mimicry is present in all Merkel cell carcinoma we found in our database and appears to be comparable to vasculogenic mimicry described in other tumors. Further investigation to vasculogenic mimicry can probably help us in finding a better understanding of the behaviour of Merkel cell carcinoma consequently a better treatment.

Angiogenesis plays a key role in the initiation of growth and metastatic process in cancers. The angiogenic switch may be one of the earliest events in conferring a metastatic potential to the tumor. Further evolution in this multi-step cascade is controlled by the positive and negative regulators of angiogenesis. Recent advances in molecular biology have given a better insight into the mechanisms governing head neck cancer with promising data elaborating the role of angiogenesis. Metastasis to neck nodes is a very important determinant of prognosis, and is more frequently encountered than distant metastasis in head and neck cancers. Systematic PUBMED search of English-language literature of studies involving humans between 1990 and 2008 using the Mesh terms 'pathologic neovascularization', 'head and neck neoplasms', 'lymphatic metastasis' was performed. Quality assessment of selected studies included clinical pertinence, publication in peer reviewed journals, adequate number of enrolled patients. The present article reviews the utility value of various angiogenic parameters and markers that have been utilized to predict regional metastasis including micro vessel density, positive and negative regulators of angiogenesis, and genetic markers for angiogenesis. Although there seems promising preclinical and clinical evidence paving way for novel diagnostic and therapeutic interventions, the implicit role of angiogenesis in metastatic head and neck cancers needs further substantiation.

Purpose: Micro vessel density dictated by the oxygen concentration is one of the most important biomarkers used for cancer recurrence. This work aims at simulating a representative map of tumor micro‐vasculature and observes the growth of vasculature with respect to two simulation parameters: oxygen concentration and vessel coverage. Method and Materials: The tissue volume was simulated as a 3‐dimensional matrix in MATLAB. A corresponding matrix containing oxygen concentration data determines the regional micro‐vascular density. The vasculature map was simulated via stochastic modeling governed by the following two factors: (a) A region of higher oxygen concentration indicates a higher capillary concentration; vessels are simulated to grow along increasing oxygen gradients, so that the final vasculature developed has a greater vessel concentration in these regions. (b) The vessels avoid other vessels so that they can effectively cover the tissue volume. The simulations were carried out varying the degree of competition between the two factors. This vasculature simulation model was tested for various oxygen map scenarios and applied to experimental mouse data of known vasculature and oxygenation concentration obtained via hypoxia imaging. Results: While a simulation partial to vessel coverage yielded a vasculature incapable of showing the general trend of oxygen gradients, a simulation partial to oxygen gradients yielded an unrealistic vasculature unable to cover the tissue volume effectively. When balanced, the two factors yielded a vasculature which demonstrated the general trend of oxygen gradients and micro‐vessel density coverage as determined by the oxygenation mask. The model tested against experimental mouse data from micro‐PET/CT images and yielded a suitable comparative vessel structure. Conclusion: A balance between the two driving factors is essential for the growth of a proper microvasculature. The model is a prospective tool for investigating functional dependencies between tumor growth and angiogenesis.