Nuclear Medicine Methods for Assessment of Chronic Chagas Heart Disease

Abstract Several different imaging methods can be used to evaluate patients with Chagas heart disease (CHD) for diagnostic and prognostic purposes, including plain chest radiography; echocardiography; myocardial perfusion scintigraphy, for detection of ischemia and fibrosis; radionuclide gated-angiography, for evaluation of biventricular function; 123I-MIBG labeling of sympathetic myocardial innervation; MRI, for detection and quantitation of myocardial fibrosis; and coronary angiography. This study aims to review the contributions of these nuclear medicine methods to understanding of the pathophysiology of chronic Chagas cardiomyopathy (CCC). Careful analysis and integration of findings provided by these imaging methods in patients with CCC at different stages has contributed significantly to improving understanding of several peculiarities of the disease. Clinical and experimental studies in animal models show that perfusion abnormalities detected in association with dysfunctional but viable myocardium are a common finding in CCC patients and correspond to areas of cardiac sympathetic denervation, as assessed by 123I-MIBG imaging. Furthermore, recent reports have demonstrated a close relationship between coronary microvascular disturbances and myocardial inflammation. Thus, ongoing research, mainly focused on refinements of 18F-FDF -PET techniques and further exploration of nuclear methods, such as SPECT, have the potential to contribute to detection and monitoring of early subclinical myocardial damage thereby enabling evaluation of therapeutic strategies targeting inflammation and microvascular ischemia that could result in better prognostic stratification of patients with CHD.

Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma.

The relation between dermoscopy and histopathology of basal cell carcinoma

Abstract BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. .

Methods for the morphological and functional evaluation of microvascular damage in systemic sclerosis

Systemic sclerosis is a connective tissue disease characterized by alterations in microvascular structure and function. In these patients, numerous studies have demonstrated a relationship between capillary morphology and peripheral blood perfusion. Nailfold videocapillaroscopy reveals the peripheral microvascular morphology and thus allows classification and scoring of capillary abnormalities with respect to different microangiopathy patterns (early, active, and late). Laser Doppler flowmetry and laser speckle contrast analysis can be used to estimate cutaneous blood flow through microvessels and to assess and quantify blood perfusion at peripheral sites. These two methods are also used to identify changes in digital blood perfusion after the infusion of vasodilators.

Immunolocalization of FGF-2 and VEGF in rat periodontal ligament during experimental tooth movement

OBJECTIVE: This article aimed at identifying the expression of fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) in the tension and pressure areas of rat periodontal ligament, in different periods of experimental orthodontic tooth movement. METHODS: An orthodontic force of 0.5 N was applied to the upper right first molar of 18 male Wistar rats for periods of 3 (group I), 7 (group II) and 14 days (group III). The counter-side first molar was used as a control. The animals were euthanized at the aforementioned time periods, and their maxillary bone was removed and fixed. After demineralization, the specimens were histologically processed and embedded in paraffin. FGF-2 and VEGF expressions were studied through immunohistochemistry and morphological analysis. RESULTS: The experimental side showed a higher expression of both FGF-2 and VEGF in all groups, when compared with the control side (P < 0.05). Statistically significant differences were also found between the tension and pressure areas in the experimental side. CONCLUSION: Both FGF-2 and VEGF are expressed in rat periodontal tissue. Additionally, these growth factors are upregulated when orthodontic forces are applied, thereby suggesting that they play an important role in changes that occur in periodontal tissue during orthodontic movement. .

OBJETIVO: o objetivo desse estudo foi identificar a expressão do fator de crescimento de fibroblastos 2 (FGF-2) e do fator de crescimento vascular endotelial (VEGF) nos lados de tensão e pressão do ligamento periodontal de ratos, durante movimento ortodôntico experimental, em diferentes períodos de tempo. MÉTODOS: uma força ortodôntica de 0,5N foi aplicada no primeiro molar superior direito de 18 ratos Wistar machos, por períodos de 3 (grupo I), 7 (grupo II) e 14 dias (grupo III). O primeiro molar do lado oposto foi utilizado como controle. Os animais foram sacrificados nos períodos de tempo mencionados, sendo a arcada superior removida e fixada. Após a desmineralização, os espécimes foram processados histologicamente e embebidos em parafina. A expressão do FGF-2 e do VEGF foram estudadas por meio de análise imuno-histoquímica. RESULTADOS: o ligamento periodontal dos dentes submetidos à movimentação ortodôntica mostraram maior expressão tanto de FGF-2 quanto de VEGF, em todos os grupos experimentais, quando comparados com os dentes do lado controle (p < 0,05). Diferenças estatisticamente significativas entre os lados de tensão e pressão também foram encontradas nos dentes submetidos à movimentação ortodôntica. CONCLUSÕES: tanto o FGF-2 quanto o VEGF são expressos no tecido periodontal de ratos, e esses fatores de crescimento são aumentados quando forças ortodônticas são aplicadas, sugerindo que esses desempenham um papel importante na reorganização do periodonto durante o movimento ortodôntico. .

FASN expression, angiogenesis and lymphangiogenesis in central and peripheral giant cell lesions

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) are non-neoplastic proliferative processes of the jaws. PGCL is a reactive process induced by irritant local factors and CGCL is an intra-osseous lesion of unknown etiology. Both lesions exhibit similar histologic features showing abundant mononuclear cells, admixed with a large number of multinucleated giant cells and a rich vascularized stroma with extravasated erythrocytes, hemosiderin deposition, and blood-filled pools. Recent studies have linked fatty acid synthase (FASN) with angiogenesis. Objective: To evaluate angiogenesis and lymphangiogenesis and their relationship with FASN expression in CGCL and PGCL. Material and Methods: Thirteen CGCL and 14 PGCL of the jaws were selected for immunoexpression of FASN; CD34 and CD105 (to assess blood microvessel density [MVD] and microvessel area [MVA]); and D2-40 (to assess lymphatic MVD and MVA). Results: Within PGCL and CGCL, MVD-CD34 was signifcantly higher than MVD-CD10S, followed by MVD-D2-40. Moreover, a signifcantly higher number of FASN-positive multinucleated giant cells than mononuclear cells were observed. Between PGCL and CGCL, only MVD-CD34 and all MVA were signifcantly higher in PGCL. Positive correlation between MVA-CD10S with FASNpositive mononuclear cells in both lesions was observed. Conclusions: Our results show both lesions exhibiting similar levels of FASN expression and neoangiogenesis, suggesting constitutive processes that regulate tissue maintenance. .

Tumor-Infiltrating Macrophage and Microvessel Density in Oral Squamous Cell Carcinoma

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Macrófagos associados a tumores (MAT) representam o componente principal do estroma de muitos tumores, além de participar da angiogênese tumoral. Este estudo comparou a microdensidade vascular (MDV) e densidade de macrófagos infiltrando o tumor (DMIT) em carcinoma escamocelular da boca (CEC) com diferentes graus histológicos de malignidade. Análise histomorfométrica foi empregada após técnica imuno-histoquímica para os anticorpos fator von-Willebrand e CD68. Uma diferença significante entre MDV e carcinomas bem e moderadamente diferenciados foi observada (p<0,05). MAT estavam fortemente presentes em todos os tumores estudados e a DMIT não foi diferente entre os diferentes graus histológicos de malignidade do CEC (p=0,381). Correlação significante entre MDV e DMIT não foi observada (p=0,870). Em conclusão, os resultados desse estudo sugerem a influência de MAT e angiogênese nos diferentes graus histológicos de malignidade do CEC. Entretanto, a ausência de correlação entre MDV e DMIT sugere que a angiogênese não depende do número de macrófagos presentes neste tipo de câncer, mas do fenótipo predominante. Outros estudos devem ser realizados a fim de contribuir para melhor compreensão da participação de MAT na angiogênese tumoral.

Morphometric study of microvessels, epidermal characteristics and inflammation in psoriasis vulgaris with their correlations.

Background: Vascular proliferation, inflammation and epidermal changes are important features in the pathogenesis of psoriasis. Aims: In this study we attempted an objective evaluation of these parameters using morphometry. Methods: Inflammation, microvessels and epidermal parameters were assessed in 50 newly diagnosed cases of psoriasis vulgaris (between 01 Nov 2008 and 31 Oct 2011) by morphometry. Parameters studied were microvessel density, microvessel caliber, inflammatory cell density in dermis, ratio between inner and outer epidermal length, maximum epidermal thickness, minimum epidermal thickness and difference between maximum epidermal thickness and minimum epidermal thickness. Results: Microvessel caliber showed moderate correlation (r = 0.645) and microvessel density, weak correlation (r = 0.226) with inflammatory cell density in dermis. Both these parameters also showed mild positive correlation with "ratio between inner and outer epidermal length". All parameters except minimum epidermal thickness showed mild positive correlation with inflammatory cell density in dermis. Conclusion: All microvessels and epidermal parameters showed positive correlation with dermal inflammation; and epidermal parameters exhibited positive correlation with micro-vascular dilation. It is likely that inflammation is a key factor in the pathogenesis of psoriasis.

Vascular endothelial growth factor and KIT expression in relation with microvascular density and tumor grade in supratentorial astrocytic tumors

PURPOSE: To evaluate the relationship between microvascular density and the expression of vascular endothelial growth factor (VEGF) and KIT as possible markers of angiogenic stimulus in astrocytic tumors and correlate it with histopathological grading. METHODS: We enrolled 99 surgical specimens of supratentorial astrocytic tumors for analysis of VEGF and KIT and subsequent correlation with MVD and grading. RESULTS: KIT and VEGF expression correlated with microvascular density (p<0.005) and both VEGF and microvascular density correlated with grading (p<0.005). KIT had no significant relationship with grading (p=0.657). CONCLUSION: KIT and VEGF constitute important pathways in the angiogenesis of astrocytomas and therefore are promising prognostic tools and options for therapeutic intervention.

Avaliação da capilaroscopia usando Endotelina-1 como um marcador de ativação endotelial na lesão microvascular e úlceras cutâneas / Evaluation of the capillaroscopy using endothelin-1 as a marker of endothelial activation in microvascular injury and cutaneous ulcerations

OBJETIVO: Avaliar a presença da ET-1 em pacientes portadores de esclerodermia e a sua correlação com o nível de atividade da doença; verificar se os níveis de endotelina estão associados com o perfil clínico e de autoanticorpos da esclerodermia e, ainda, se há associação com lesão microvascular detectada pela capilaroscopia periungueal. MÉTODOS: Um total de 74 pacientes, sendo 37 portadores de esclerodermia e o restante controle, foram submetidos à dosagem de ET-1 por meio de teste de ELISA. Pacientes com esclerodermia foram analisados através de um questionário sobre características da doença e pesquisa de autoanticorpos. A gravidade da doença foi definida pelos critérios de Medsger e a doença microvascular foi acessada através de capilaroscopia periungueal. RESULTADOS: Dos 37 pacientes com esclerodermia três (8,1%) eram homens e 34 (91,89%) mulheres, com idade média de 48,97 ? 13,36 anos e tempo médio de doença de 42,54 ? 13,35 anos. Os valores da ET-1 nos controles foram de 0,41 a 5,65 pg/ml (mediana de 2,26 pg/ml) e nos com esclerodermia de 0,41 a 8.82 pg/ml (mediana de 0,41 pg/ml) com p de 0,0007. Não houve correlação com o tempo de doença, idade do paciente e com o nível de acometimento cutâneo. Não encontrou-se correlação entre nível de ET-1 sérica e gravidade da doença (p=0,13). Níveis maiores de ET-1 foram observados na forma de superposição (1,49 a 6,82 pg/ml). CONCLUSÃO: Os níveis de ET-1 em esclerodérmicos mostraram-se inferiores aos controles. Não houve associação dos níveis de ET-1 com as variáveis estudadas.

Objectives: To evaluate the presence of ET-1 in patients with scleroderma and its correlation with the level of disease activity; to verify if the levels of endothelin are associated with the clinical profile and autoantibodies of scleroderma, and even if there is an association with microvascular injury detected by nailfold capillaroscopy. METHODS: A total of 74 patients, 37 patients with scleroderma, the remaining being controls, were subjected to measurement of ET-1 by ELISA. Patients with scleroderma were evaluated through a questionnaire about characteristics of the disease and determination of autoantibodies. Disease severity was defined by the criteria of Medsger and microvascular disease was accessed through nailfold capillaroscopy. RESULTS: Of the 37 patients with scleroderma, three (8.1%) were men and 34 (91.89%) women, with a mean age of 48.97 ± 13.36 years and mean disease duration of 42.54 ± 13, 35. The amounts of ET-1 in the controls was 0.41 to 5.65 pg / ml (median of 2.26 pg / ml) and, in the scleroderma group, from 0.41 to 8.82 pg / ml (median, 0.41 pg / ml), with p = 0.0007. There was no correlation with disease duration, patient age and the degree of skin involvement. No correlation was found between serum levels of ET-1 and disease severity (p = 0.13). Higher levels of ET-1 were observed in the form of overlap (1.49 to 6.82 pg / ml). CONCLUSION: The levels of ET-1 in scleroderma were inferior to controls. There was no association of ET-1 levels with the variables studied.

M2-Polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma

OBJECTIVES: Tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. However, the activated phenotype (M1 or M2) of tumor-associated macrophages remains unknown in solid tumors. Therefore, this study examined the density and prognostic significance of M2-polarized tumor-associated macrophages in lung adenocarcinoma. METHODS: Tumor specimens from 65 lung adenocarcinoma patients were assessed by ELISA for Th1/Th2 cytokine concentrations. The activated phenotype (M1 or M2) of tumor-associated macrophages was determined utilizing immunofluorescence staining. Additionally, to evaluate lymphangiogenesis, peritumoral lymphatic microvessel density was measured using D2-40. The correlation between tumor-associated macrophage subtype and overall patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A shift toward Th2 cytokine expression was detected within lung adenocarcinoma microenvironments. Approximately 79.71±16.27 percent of tumor-associated macrophages were M2 polarized; the remaining 20.35±5.31 percent were M1 polarized. The infiltration of M2-polarized macrophages was significantly associated with P-TNM staging and lymph node metastasis. The peritumoral lymphatic microvessel density was significantly higher in the high M2-polarized tumor-associated macrophage group than in the low M2-polarized tumor-associated macrophage group. A significant difference in overall patient survival was detected not only between patients with tumors with high and low macrophage counts but also between patients with tumors with high and low counts of M2-polarized macrophages. CONCLUSION: Tumor-associated macrophages in lung adenocarcinoma have an M2-polarized subtype and are associated with poor prognoses, perhaps resulting from accelerated lymphangiogenesis and lymph node metastasis.

Vimentin and laminin are altered on cheek pouch microvessels of streptozotocin-induced diabetic hamsters

OBJECTIVE: Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Hyperglycemia impairs this response and contributes to microvascular complications, which result in deleterious effects to the endothelium. This work aimed to evaluate cheek pouch microvessel morphological characteristics, reactivity, permeability, and expression of cytoskeleton and extracellular matrix components in hamsters after the induction of diabetes with streptozotocin. METHODS: Syrian golden hamsters (90-130 g) were injected with streptozotocin (50 mg/kg, i.p.) or vehicle either 6 (the diabetes mellitus 6 group) or 15 (the diabetes mellitus 15 group) days before the experiment. Vascular dimensions and density per area of vessels were determined by morphometric and stereological measurements. Changes in blood flow were measured in response to acetylcholine, and plasma extravasation was measured by the number of leakage sites. Actin, talin, α-smooth muscle actin, vimentin, type IV collagen, and laminin were detected by immunohistochemistry and assessed through a semiquantitative scoring system. RESULTS: There were no major alterations in the lumen, wall diameters, or densities of the examined vessels. Likewise, vascular reactivity and permeability were not altered by diabetes. The arterioles demonstrated increased immunoreactivity to vimentin and laminin in the diabetes mellitus 6 and diabetes mellitus 15 groups. DISCUSSION: Antibodies against laminin and vimentin inhibit branching morphogenesis in vitro. Therefore, laminin and vimentin participating in the structure of the focal adhesion may play a role in angiogenesis. CONCLUSIONS: Our results indicated the existence of changes related to cell-matrix interactions, which may contribute to the pathological remodeling that was already underway one week after induction of experimental diabetes.

Endoglin [CD105] positive microvessel density and its relationship with lymph node metastasis in squamous cell carcinoma of the tongue

Neovascularization is an important factor for predicting tumor behavior. Evidence suggests that endoglin [CD105] is a powerful marker of neovascularization and determination of microvessel density in several malignancies, and can be used as an agent to predict lymph node metastasis. However, it is controversial, particularly in head and neck squamous cell carcinoma. We studied CD105-MVD in tongue squamous cell carcinoma and evaluated its correlation with lymph node metastasis in relation to sex, age, and histopathologic grade. This study analyzed a total of 40 cases of tongue squamous cell carcinoma by dividing patients into two groups, a] with meta-static lymph nodes [N+] and b] without metastatic lymph nodes [N-]. By CD105 immunostaining, microvessel density was determined in three different areas [intratumoral, invasive front and adjacent normal tissue] of all cases. Statistically, we evaluated the relation between microvessel density and lymph node involvement, in addition to other clinicopathologic factors by using the Kolmogorov-Smirnov test, f-test, and other analyses. CD105-MVD in the invasive front [P<0.001] and intratumoral [P<0.006] areas of the N+ group was significantly higher than in the N-group. In addition, there was a correlation between CD105-MVD and differentiation in the invasive front area [P< 0.013] No relation existed between CD105-MVD and other clinicopathologic features. CD105-MVD, as a prognostic factor, may be helpful for determining the possibility of lymph node metastasis of primary SCC of the tongue

Evaluation of Antiangiogenic Effects of a New Synthetic Candidate Drug KR-31831 on Xenografted Ovarian Carcinoma Using Dynamic Contrast Enhanced MRI

OBJECTIVE: The purpose of this research was to investigate the anti-angiogenic inhibitory effect of KR-31831, a newly developed anti-angiogenic agent, on an in vivo human ovarian carcinoma model using dynamic contrast-enhanced (DCE) MRI. MATERIALS AND METHODS: Xenografted ovarian tumors were established by subcutaneous injection of SKOV3 cells into mice. The mice were treated daily with KR-31831 at 50 mg/kg for 21 days. Tumor tissues were excised corresponding to the DCE-MRI sections for evaluation of MVD with CD31 immunohistochemistry. All in vivo MRIs were performed on a 7.0 Tesla micro-MRI System. DCE-MRI was acquired prior to initiating treatment with KR-31831 and again on days 3 and 21 after treatment. The permeability parameters (Ktrans, ve, and vp) were estimated using a pharmacokinetic model. RESULTS: Qualitatively, the Ktrans parametric mapping showed different changes before and after treatment with KR-31831 in the treatment group. For quantification of this change, the median of Ktrans values were compared before and after treatments in the control and KR-31831-treated groups. A non-parametric statistical test (Wilcoxon signed-rank test) showed decreasing Ktrans values on day 21 compared to days 0 and 3 in the KR-31831-treated group (p < 0.05), whereas there was no significant difference in the control group (p = 0.84). CONCLUSION: Our results suggest that DCE-MRI can be a useful tool by which to evaluate the anti-angiogenic effect of KR-31831 on a xenografted human ovarian carcinoma model.

Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

OBJECTIVE: To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. MATERIALS AND METHODS: A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 x 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. RESULTS: Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r = -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). CONCLUSION: Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

Immunohistochemical evaluation of mast cells and angiogenesis in oral squamous cell carcinoma.

Objectives : Angiogenesis is a complex event mediated by angiogenic factors released from cancer cells and immune cells. It has been reported to be associated with progression, aggressiveness and metastases of various malignant tumors including oral squamous cell carcinoma (OSCC). Similarly, mast cells have also been reported to play a role in tumor progression and metastases by promoting angiogenesis. The present study aims at comparison of microvascular density (MVD) and mast cell density (MCD) in normal oral mucosa (NM) and among various grades of OSCC. Materials and Methods : MVD was assessed immunohistochemically using anti-Factor VIII related von Willebrand factor, and MCD using anti-mast cell tryptase in a study sample of 30 cases of OSCC and 10 cases of clinically normal oral mucosa. Results : The mast cells in normal oral mucosa and oral squamous cell carcinoma strongly expressed mast cell tryptase. The density of mast cells and micro vessels were significantly higher in OSCC compared to normal oral mucosa. The MCD and MVD were higher in moderately differentiated OSCC than in well differentiated OSCC ( P > 0.05) and normal oral mucosa ( P < 0.05). Pearson's correlation revealed a positive correlation between MCD and MVD ( r=0.33; P=0.077). Conclusion : These findings indicate that mast cells may play a role in up regulation of tumor angiogenesis in OSCC probably through mast cell tryptase.