Assessment Of Microvessel Density Research Articles

Impaired Angiogenesis and Th1/Th17 Polarization: A Possible Explanation for the Decreased Incidence of Rosacea in the Aged.

Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30-50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging. We analyzed the incidence of rosacea across 8340 individuals without systemic diseases. The effects of LL37-induced rosacea-like erythema and inflammation were evaluated in both young and aged mice. Immunofluorescence analysis was performed to assess microvessel density, whereas the expression levels of angiogenesis-related factors, including matrix metalloproteinases (MMPs) and vascular endothelial growth factor α (VEGFα), were quantified. Additionally, immune responses were assessed at both the cellular and systemic levels. Aged mice displayed milder LL37-induced rosacea-like erythema and inflammation compared to their young counterparts. Immunofluorescence analysis revealed a decrease in microvessel density in rosacea models of the aged group. The expression of angiogenesis-related factors, including MMPs and VEGFα, was decreased in aged mice compared to young mice, indicating a reduced responsiveness to LL37 stimulation. Furthermore, we found that suppressed Th1- and Th17-polarized immune responses, one of the major pathogenic mechanisms of rosacea, were reduced in aged mice in response to LL37 stimulation at both cellular and systemic levels. The findings suggest that impaired angiogenesis and attenuated Th1/Th17 immune responses underlie the age-related decline in rosacea incidence.

The prognostic significance of CD117-positive mast cells and microvessel density in colorectal cancer.

The prognostic significance of angiogenesis has been demonstrated in various types of cancer. However, in colorectal cancer (CRC), there are conflicting results regarding the relationship between angiogenesis and clinical-histopathological prognostic factors. Mast cells are immune system cells found in the inflammatory microenvironment; their role in carcinogenesis and prognosis remains unclear although they are considered to cause cancer development and progression. The present study aims to evaluate the prognostic significance of mast cell accumulation and angiogenesis assessed by microvessel density (MVD) in patients with CRC. Patients who underwent curative resection and who were not treated with neoadjuvant chemotherapy were included. The anti-CD34 antibody and anti-CD117 antibody were utilized for the immunohistochemical assessment of MVD and the mast cell count (MCC) in the tissue samples, respectively. The relationship between MCC, MVD, survival and clinical-histopathological prognostic factors were evaluated. A total of 94 patients were enrolled to the study. In a median 49-month follow-up, 65 patients (69.1%) died. The 5-year disease-free survival was 61.1% and 31.3% for the group with CD34 < 18.3% and CD34 > 18.3%, respectively (P = .001). The same groups presented 5-year overall survival rates of 77, 1% and 51, 4%, respectively (P, .012). The MVD was found to be associated with the pathological T stage, lymph node metastasis and distant metastasis (P < .05). Although the MCC was positively correlated with MVD, there was no association between the MCC and clinical-histopathological prognostic factors. MVD-assessed angiogenesis was significantly related to survival and the clinical-histopathological prognostic factors in patients diagnosed with CRC.

Microvessel Density Assessment and Related Factors in Patients with Endometrial Cancer: A Cross-Sectional Study

Background: Studying microvessel density (MVD) as an angiogenesis indicator enhances insights into tumor diversity, predicting invasive or metastatic tendencies. It assists in tailoring treatment approaches based on angiogenesis expression in different tumors. Objectives: This study aimed at assessing MVD using the CD31 marker and its associated factors in individuals with endometrial malignancies. Methods: This cross-sectional study involved 118 patients with endometrial cancer (EC) at Imam Hussein Educational and Medical Center, Tehran, Iran spanning from 2018 to 2023. Data, gathered from patient medical files using a researcher-made checklist, included a quantitative assessment of angiogenesis using the CD31 endothelial marker for MVD. Linear regression models were utilized to identify predictors of MVD-CD31 in patients with EC. Results: Patients had a mean age of 57.35 ± 11.16 years. The overall mean MVD-CD31 was 157.06 ± 94.31 (range, 32 - 385). Those with over 50% invasion depth exhibited a higher MVD-CD31 (79.59 units) compared to those with no invasion depth (P = 0.003). Higher MVD-CD31 levels were also associated with lymph node involvement and metastasis to other organs (P &lt; 0.001). In comparison to grade 1 tumors, grade 2 tumors showed elevated MVD-CD31 (mean difference: 64.85, P = 0.007). Clear cell carcinoma tumor type had significantly higher MVD-CD31 than low-grade endometrioid carcinoma (mean difference: 225.84, P = 0.005). Conclusions: Our results suggest that some tumor characteristics such as invasion depth, lymph node involvement, tumor grade, and tumor type may play a role in angiogenesis in patients with EC. These findings suggest that tumor features play a crucial role in modulating angiogenesis in EC.

Evaluation of Vasculogenic Factors in the Developing Embryo at Weeks Five and Seven With a Special Focus on CD133 and TIE2 Markers.

Background Human embryo vasculogenesis (blood vessel development starting from endothelial precursors) includes the ability of mesenchymal cells and pluripotent stem cells to differentiate into endothelial cells. Quantification of endothelial progenitor cells is difficult to assess during the early steps of human embryo development due to several factors, especially due to the paucity of human embryo tissue which is usually discarded after early-stage pregnancy abortive methods. CD133 (Promimin-1) is a general marker of progenitor cells, but combined with other endothelial markers such as CD34, it may identify endothelial progenitor cells during embryonic development. CD34 immunohistochemistry was previously performed by our team to identify human embryo capillaries and comparatively assess microvessel density between different human embryonic tissues.TIE2 is an angiopoietin receptor strongly involved in the newly formed blood vessel maturation due to its expression in some mesenchymal precursors for future pericytes. CD34 assesses the presence of endothelial cells but its single use does not evaluate the endothelial progenitor state as CD133 may do nor vessel maturation as TIE2 may do. Data about the dynamics of CD133/TIE2 expression in the early stages of human embryo development are scarce. Hence, in this study, we aimed tocomparatively assess the dynamic of CD133+ endothelial precursors and TIE2 expression on five and seven-week-old human embryonic tissues with a special emphasis on their expression on embryonic vascular beds. Methodology CD133 and TIE2 immunohistochemistry was performed on five and seven-week-old human embryonic tissues followed by their quantification using the Qu Path digital image analysis (DIA) automated method. Results CD133 and TIE2 showed divergent patterns of expression during the initial phases of human embryonic development, specifically in the vascular endothelium of tiny capillaries. The expression of CD133 in endothelial cells lining the perfused lumen gradually decreased from five to seven-week-old embryos. It remained expressed with greater intensity in cells located at the tip of the vascular bud that emerged into pre-existing capillaries. TIE2 was much more specific than CD133, being restricted to the level of the vascular endothelium; therefore, it was easier to quantify using digital image analysis. The endothelium of the embryonic aorta was an exception to the divergent expression, as CD133 and TIE2 were consistently co-expressed in the seven-week-old embryo. The Qu Path DIA assessment increased the accuracy of CD133 and TIE2 evaluation, being the first time they were quantified by using automated software and not manually. Conclusions High heterogeneity of CD133 and TIE2 was observed between five and seven-week-old embryonic tissues as well as between different embryonic regions from the same gestational age. The unique finding of CD133/TIE2 co-expression persistenceinside aortic endothelium needs further studies to elucidate the role of this co-expression.

Microvessel Density Assessment in Gynecological Malignancies

Microvessel Density Assessment in Gynecological Malignancies

Utility of CD34 in Assessing Microvessel Density and Its Correlation With Clinicopathological Parameters in Colorectal Carcinoma Patients.

Currently, the most commonly practiced method of reporting cases of colorectal carcinoma is done according to guidelines provided by the College of American Pathologists (8th edition) and the Royal College of Pathologists (UK). These guidelines include various histopathological parameters like tumor site, extent, histologic type, grade, margins, tumor budding, lymphovascular invasion, and perineural invasion. However, in the present guidelines, the immunohistochemistry-based marker of mean vessel density (MVD) has not been addressed as an important parameter. The present study gives an overview of the importance of MVD.MVD was statistically significant when correlated with tumor size, lymph node metastasis, grade, and vascular invasion. However, no statistical significance was observed when compared with age, perineural invasion, and stage of the tumor.

Immunohistochemical Assessment of Microvessel Density in OSCC: Spatial Heterogeneity of Angiogenesis and Its Impact on Survival.

(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a hallmark of cancer, is known to contribute to cancer progression and metastasis. High microvessel density (MVD) has been linked to poor clinical outcomes in various types of cancer. (2) Methods: In this study, we aimed to investigate the spatial heterogeneity of blood vessels by comparing the tumor center and invasion front and to evaluate its prognostic value in OSCC. A total of 71 OSCC patient specimens were collected. The tissue was immunohistochemically stained using CD31 antibody to assess the MVD in the tumor center and the invasion front. Furthermore, the associations between the histopathological parameters, including MVD, disease-free survival (DFS), and overall survival (OS) were computed. (3) Results: In our study, we found a significantly higher presence of blood vessels at the invasion front of OSCCs compared to the tumor center. However, we did not observe any significant differences in MVD between different tumor stages. High intratumoral MVD was shown to be a positive prognostic factor for DFS (p = 0.047). (4) Conclusions: To the best of our knowledge, we were the first to analyze MVD as a prognostic factor by considering its spatial heterogeneity in OSCC. However, further studies are warranted to further elucidate the complexity of microvascular spatial heterogeneity and its influence on prognosis.

The promoting effect of modified Dioscorea pills on vascular remodeling in chronic cerebral hypoperfusion via the Ang/Tie signaling pathway.

The objective of this study was to investigate the effect of modified Dioscorea pills (MDP) on microcirculatory remodeling in the hippocampus of rats with chronic cerebral hypoperfusion (CCH) through the angiopoietin (Ang)/tyrosine kinase receptor tyrosine kinase with immunoglobulin-like and EGF-like domains (Ang receptor) 2 (Tie-2) signaling pathways, which may underlie the cognitive improvement observed in CCH rats. Forty male Sprague-Dawley rats raised under specific pathogen-free conditions were randomly divided into three groups: control group (10 rats), model group (15 rats), and MDP group (15 rats). The rats in the model group and MDP group underwent bilateral common carotid artery occlusion using the 2-vessel occlusion (2-VO) method to induce CCH. Rats in the control group underwent the same surgical procedures as those in the model group, except for ligation and occlusion of the carotid arteries. After 1 week of 2-VO, rats in the MDP group were administered MDP condensed decoction intragastrically at a dose of 1 ml/100 g body weight (prepared by the Preparation Room of Hubei Provincial Hospital of Traditional Chinese Medicine) for 45 days, while rats in the other two groups received normal saline intragastrically with the same dose and duration as the MDP group. After the intervention, all rats were euthanized, and brain perfusion was performed to obtain the hippocampal tissue for analysis. Immunohistochemical staining for CD43 was performed to assess microvessel density (MVD); western blot and the reverse transcription-polymerase chain reaction (RT-PCR) were used to analyze the expression of proteins and genes in angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-2, and vascular endothelial growth factor (VEGF) proteins and genes in the hippocampal tissue and compute the Ang-1/Ang-2 ratio. MDP treatment reduced neuronal loss and promoted restoration of the damaged hippocampal structure in CCH rats. The model group showed significantly higher MVD (14.93 ± 1.92) compared to the control group (5.78 ± 1.65) (P < 0.01), whereas MDP treatment further increased MVD (21.19 ± 2.62). Western blot and RT-PCR analysis revealed that CCH significantly increased the expression of Ang-1, Ang-2, Tie-2, and VEGF proteins and genes, while MDP treatment further significantly upregulated the expression of these proteins and genes. In addition, MDP significantly elevated the gene and protein expression of the Ang-1/Ang-2 ratio compared to the control group (P = 0.041, P = 0.029). CCH induces microvascular neogenesis in the hippocampus, and MDP promotes angiogenesis and microcirculation remodeling in CCH rats via the Ang/Tie signaling pathway, which may be an important mechanism for its restorative effects on hippocampal perfusion and improvement of cognitive function in CCH rats.

Dynamic characterization of vascular response and treatment in oral traumatic ulcer in mice via photoacoustic imaging.

Dynamic surveillance of vasculature is essential for evaluating the healing of oral ulcer. Existing techniques used in vascular imaging face limitations, such as inadequate spatial resolution, restricted diagnostic depth, and the necessity of exogenous contrast agents. Therefore, this study aimed to use robust photoacoustic imaging (PAI) for the dynamic monitoring of vascular response during healing and the associated treatment process of oral ulcer. Kunming mice (male, 8 weeks old, 31-41 g) were treated with 50% acetic acid for 90 s on the tongue mucosa for induction of oral traumatic ulcer. Mice were randomly divided into three groups (n=12): the control, compound chamomile and lidocaine hydrochloride gel (CCLH), and phycocyanin (PC) groups. PAI was then conducted on days 0, 2, 3, 5, and 7 to obtain vessel parameters of the ulcer area, including vessel intensity, density, mean diameter, maximum diameter, and curvature. Immunohistochemical and hematoxylin and eosin (HE) staining were performed on days 3 and 7 to assess microvessel density and inflammation score. The ulcer healing rate and body weight changes were evaluated for clinical observation. Beginning on the second day after ulcer induction, there was a progressive increase over time in blood intensity and vessel parameters, including vascular density and diameter. On day 7, the CCLH and PC groups demonstrated significantly higher measures than did the control group in terms of blood intensity (P<0.05 and P<0.01), vascular density (both P values <0.05), mean diameter (both P values <0.01), and maximum diameter (P<0.01 and P<0.05). Vessel curvature in the two treatment groups exhibited no significant differences compared to that in the control group (both P values >0.05). The effects of vascular morphological changes were further supported by the histological and clinical outcomes. On day 7, compared to that of the control group, the level of microvessel density was significantly higher in both the CCLH (P<0.01) and PC (P<0.05) groups. The histopathological score in PC group was significantly lower than that of the control group on day 7 (P<0.05). Additionally, compared to that of the control group, the healing rates of the CCLH (P<0.01) and PC groups (P<0.05) were superior on day 7. On day 3, the control group showed more weight loss than did the CCLH (P<0.05) and PC (P<0.01) groups. These findings indicate that PAI is a valuable strategy for the dynamic and quantitative analysis of vascular alterations in oral traumatic ulcers and support its prospective application in improving clinical treatment.

Preoperative assessment of microvessel density in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)

Preoperative assessment of microvessel density in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)

Preoperative assessment of microvessel density in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)

BackgroundHypervascularization is a typical feature of pancreatic neuroendocrine tumors, and it frequently allows their recognition at imaging studies. However, the density of microvessels in pancreatic neuroendocrine tumors changes according to their biological behavior, and a low microvessel density is associated with higher disease aggressiveness. The primary aim was to investigate the relationship between microvessel density and aggressiveness of nonfunctioning pancreatic neuroendocrine tumors. The secondary aim was to evaluate the ability of contrast-enhanced computed tomography and contrast-enhanced endoscopic ultrasound in predicting tumor microvessel density. MethodsThe patients who underwent surgery for nonfunctioning pancreatic neuroendocrine tumors (n = 66) with an available preoperative contrast-enhanced computed tomography (n = 39) and/or contrast-enhanced endoscopic ultrasound (n = 37) performed at San Raffaele Hospital (2016–2020) were included. The tumor vascularization was assessed by CD-34 staining, contrast-enhanced computed tomography, and contrast-enhanced endoscopic ultrasound. Median microvessel density (165 microvessels/mm2) was chosen as the cutoff to define low microvessel density and high microvessel density. ResultsThe patients with a low microvessel density showed a significantly higher frequency of nodal metastases (P = .026), G2–G3 tumors (P = .022), and death domain-associated protein/α-thalassemia/mental retardation syndrome X-linked loss (P = .011) compared to patients with high microvessel density. The contrast-enhanced computed tomography tumor density in the arterial phase was significantly higher in patients with high microvessel density compared to those with low microvessel density (P = .016). The patients with a low microvessel density showed a significantly higher frequency of contrast-enhanced endoscopic ultrasound arterial hypoenhancement (P = .042) and late washout (P = .034). Contrast-enhanced computed tomography arterial hypoenhancement (P = .007) and contrast-enhanced endoscopic ultrasound late washout (P = .048) independently predicted a low microvessel density in the patients who underwent contrast-enhanced computed tomography and contrast-enhanced endoscopic ultrasound, respectively. ConclusionA low microvessel density represents a marker of aggressiveness in the patients with nonfunctioning pancreatic neuroendocrine tumors. Contrast-enhanced computed tomography and contrast-enhanced endoscopic ultrasound are reliable and easily available tools for preoperative assessment of microvessel density.

Inhibition of AXL and VEGF-A Has Improved Therapeutic Efficacy in Uterine Serous Cancer.

Simple SummaryUterine serous cancer (USC) is an aggressive form of endometrial cancer. USC constitutes less than 10% of endometrial cancer cases but is responsible for up to 40% of endometrial cancer deaths. Response to standard platinum and taxane therapy is modest, particularly in the recurrent setting. Thus, novel therapeutic strategies are needed to overcome this drug resistance. We hope that our findings provide strong preclinical support for the combination of an AXL inhibitor with bevacizumab in USC clinical trials in the recurrent setting.Endometrial cancer remains the most prevalent gynecologic cancer with continued rising incidence. A less common form of this cancer is uterine serous cancer, which represents 10% of endometrial cancer cases. However, this is the most aggressive cancer. The objective was to assess whether inhibiting the receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve response in uterine serous cancer. To prove this, we conducted multiple angiogenesis assays including tube formation assays and angiogenesis invasion assays. In addition, we utilized mouse models with multiple cells lines and subsequently analyzed harvested tissue through immunohistochemistry CD31 staining to assess microvessel density. The combination treatment arms demonstrated decreased angiogenic potential in each assay. In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis.

Dynamic contrast‑enhanced MRI as a predictor of programmed death ligand‑1 expression in patients with oral squamous cell carcinoma

Immune checkpoint inhibitors (ICIs) targeting programmed death ligand-1 (PD-L1) are highly promising therapies for oral squamous cell carcinoma (OSCC). The assessment of PD-L1 expression may help predicting the therapeutic effect of ICIs and, thus, benefit patient selection. Contrast index (CI) parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been proven as efficient to assess microvessel density (MVD) in OSCC. The present study aimed to determine the correlation between DCE-MRI parameters and MVD and between DCE-MRI parameters and PD-L1 expression to determine whether DCE-MRI could be used non-invasively to evaluate PD-L1 expression in patients with OSCC. A total of 21 patients with primary OSCC who had undergone a 3T MRI scan, including DCE-MRI, were included in the present study, and CI curve-derived parameters were examined. The MVD and PD-L1 expression in the surgically resected specimens were analyzed using immunohistochemistry (IHC) staining for CD31 and IHC staining for PD-L1, respectively. The results demonstrated that the expression levels of these markers were correlated with DCE-MRI parameters. PD-L1 expression levels were found to be significantly correlated with the maximum CI (CI-max; P=0.007), peak CI (CI-peak; P=0.007), maximum CI gain (CI-gain; P=0.006) and MVD (P=0.001) values. The mean CI-max, CI-peak, CI-gain and MVD values were significantly higher in tumors with high PD-L1 expression (P<0.05). MVD levels were also significantly correlated with the time of CI-max (T-max; P=0.003) and CI-gain (P=0.037). The mean CI-gain was significantly increased, and the mean T-max was significantly shorter in high MVD tumors (P<0.05 and P<0.01, respectively). In summary, the findings from the present study confirmed the correlation between CI parameters, derived from DCE-MRI, and MVD, and suggested that these parameters may be correlated with PD-L1 expression in OSCC tumor cells.

Ultrasound-Targeted Microbubble Destruction Enhances Inhibitory Effect of Apatinib on Angiogenesis in Triple Negative Breast Carcinoma Xenografts.

Ultrasound-targeted microbubble destruction (UTMD) has been proven as an effective technique to assist drugs to cross the vascular wall and cell membrane. This study was aimed at evaluating the synergistic antiangiogenic and growth-inhibiting effects of apatinib (APA) and UTMD on the triple negative breast cancer (TNBC). The TNBC xenograft model was established in nude mice (n = 40) which were then randomly divided into the APA plus UTMD (APA-U) group, UTMD group, APA group, and model control (M) group (n = 10 per group). Corresponding treatment was done once daily for 14 consecutive days. The general condition and body weight of tumor-bearing nude mice were monitored. Routine blood test and detection of liver and kidney function were done after treatments. The tumor size and microcirculation were examined by two-dimensional ultrasonography (2DUS) and contrast-enhanced ultrasonography (CEUS), respectively. Then, the tumor tissues were harvested for the detection of vascular endothelial growth factor (VEGF) by immunohistochemistry and for CD31-PAS double staining to assess microvessel density (MVD) and heterogeneous vascular positivity rate. After treatments, the tumor growth and angiogenesis were significantly inhibited in the APA group and the APA-U group, and these effects were more obvious in the APA-U group. The tumor volume, CEUS parameters, VEGF expression, and MVD in the APA-U group were significantly lower than those in the APA group (P < 0.05), while there were no marked differences in the heterogeneous vascular positivity rate, body weight, and blood parameters between the two groups (P > 0.05). In the UTMD group, the tumor growth and angiogenesis were not significantly inhibited, and all the parameters were similar to those in the M group (P > 0.05). During the experiment, all mice survived and generally had good condition. In conclusion, APA combined with UTMD may exert synergistic antiangiogenic and growth-inhibiting effects on the TNBC and not increase the heterogeneous vasculature and the severity of APA-related systemic side effects.

Contrast-Enhanced Ultrasound Characteristics of Renal Pelvis Urothelial Carcinoma and Its Relationship with Microvessel Density

We studied the characteristics of contrast-enhanced ultrasound (CEUS) in renal pelvic urothelial carcinomas and explored its performance in assessing microvessel density (MVD) of tumor tissues. We retrospectively analyzed the characteristics of 125 cases, which were confirmed pathologically to be renal pelvic urothelial carcinomas using CEUS. We performed CEUS and found that most tumors presented with an enhanced mode of “slow-in (mean = 16.7 ± 2.6 s, range: 12–25 s), hypo-enhancement and fast-out (mean = 69.3 ± 16.2 s, range: 42–113 s).” However, the wash-in pattern, homogeneity and wash-out pattern observed with CEUS was not correlated with pT stage and grade (p > 0.05). But advanced-pT-stage and high-grade tumors had a higher peak enhancement than early-pT-stage and low-grade tumors (p < 0.01). Peak enhancement obtained with CEUS can be used to evaluate the pT stage and grade of renal pelvic urothelial carcinomas more effectively. The MVD of those tissues was observed using immunohistochemical staining of cluster of differentiation 34 (CD34). MVD in the advanced-pT-stage and high-grade groups was significantly higher than that in the early-pT-stage and low-grade groups (p < 0.01). As tumor pT stage and grade improved, CEUS peak enhancement intensity and MVD of tumors also exhibited an upward trend. CEUS peak enhancement intensity has the potential to determine MVD of renal pelvic urothelial carcinomas.

Endoglin Expression as a Measure of Microvessel Density in Oral Head and Neck Cancer by Immunohistochemical Study.

Abstract Background and Aim: Tumor growth is limited by the balance between the need for oxygen and nutrients and diffusion of these substances from vessels around tumors. Therefore, angiogenesis, development of new blood vessels from previous blood vessels, is necessary for tumor growth and metastasis. This study was carried out with the aim of evaluating the angiogenesis in oral cancer by assessing microvessel density (MVD) using Endoglin (CD105). This work also correlated the expressions of marker with histopathological grades of oral squamous cell carcinoma. Material and Methods: Immunohistochemical staining with Streptavidin peroxidase was used to analyze the CD105 expression in 25 cases of oral squamous cell carcinoma. Results: All studied cases showed positive of CD105 immunoreactivity. The study revealed a highly significant increase of CD105-MVD in poorly differentiated OSSC than well differentiated OSCC. Conclusion: Increased expression of CD 105 in high grade tumors suggests that Endoglin is likely to contribute significantly to resistance in response to therapy.

Tumor budding index and microvessel density assessment in patients with endometrial cancer: A pilot study.

The present study aimed to analyze the association between tumor budding index (TBI) and microvessel density (MVD) and selected clinicopathological features in female patients with endometrial cancer (EC). The present study included 137 patients, of whom 117 had endometrial endometrioid cancer and 3 had non-endometrioid EC (NEEC). Additionally, 8 cases of simple endometrial hyperplasia and 9 cases of atypical endometrial hyperplasia were included in the present study. Patient age, menopausal status, tumor histological type, grade and International Federation of Gynecologists and Obstetricians (FIGO) clinical stage were investigated. Immunohistochemistry was utilized to detect MVD using a CD34 antibody, and a laminin-5γ2 antibody was used for TBI assessment. In nonmalignant endometrial lesions, the TBI was significantly lower than that in patients with EC and NEEC (P=0.002). Significant differences in median TBI (MD-TBI) were also observed between patients with low-grade EC (MD-TBI, 4.5) and high-grade EC (MD-TBI, 16.2; P=0.01). Age, body mass index and tumor FIGO stage were not indicated to be associated with the MD-TBI. Premenopausal patients with EC had lower MD-TBI values than postmenopausal patients (0.3 vs. 11.1; P<0.005). The median MVD-CD34 in the study group was 19 (range, 13–29). Significant differences in MVD-CD34 were observed between malignant and nonmalignant endometrial lesions (P=0.01). Histological grade was markedly associated with tumor MVD-CD34 (P=0.001). The MVD was higher in high-grade cancer (G3; MVD-CD34, 24.9) than in grade G1 and G2 lesions (MVD-CD34, 14 and 18.6, respectively; P=0.01). FIGO clinical stage was not associated with MVD-CD34 in low and high stage lesions (MD, 18.4 for FIGO stage I/II; MD, 17.6 for FIGO stage III/IV; P=0.2). High MVD was markedly associated with high MD-TBI (P=0.0002). In conclusion, TBI could be a valuable indicator of tumor aggressiveness in patients with EC. The presence of the tumor budding phenomenon with increased MVD may have the potential to further refine clinical management decisions when endometrial malignancy is detected.

Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma

To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model. White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67). At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8-55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec-1 and decreased to 4.48 ± 9.00sec-1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071). The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time.

Effects of arterial blood supply and venous return on multi-territory perforator flap survival

This study aimed to design arterial ischemic and venous congested areas on the same multi-territory perforator flap, assessing the effects of arterial blood supply and venous return on flap survival. Totally 68 rats were randomly divided into the experimental (Exp) and control (Con) groups. In the Exp group, flaps were based on left superficial epigastric artery and right superficial epigastric vein. In the Con group, flaps were based on the left superficial epigastric artery and vein. Immediate postoperative ink-gelatin angiography, epidermal metabolite levels detection, tissue edema measurement, survival rate evaluation in half of the flaps and average microvessel density assessment were performed. Blood in the Exp group flowed through most angiosomes, but only flowed around pedicled vessels in the Con group; metabolite levels of left halves in the Con and Exp groups were comparable with those of right halves. Angiosomes with high water contents occurred in the Exp group. Survival rates of left halves in the Con and Exp groups were higher than those of right halves, and more microvessels were found in the left ventral areas of both groups compared with the right ventral area in the Exp group. These findings revealed that on the same multi-territory perforator flap, arterial blood supply, affected by venous return, is a prerequisite for flap survival.

Significance of assessment of microvessel density (MVD) and mast cell density (MCD) by combined immunohistochemical and histochemical methods in cutaneous malignancies

Introduction: Angiogenesis is a complex event mediated by several angiogenic factors released from cancer cells and immune cells. There is compelling evidence that mast cell accumulation among the peritumoral inflammatory infiltrates contributes to a favourable microenvironment for tumor development and metastasis. The present study aimed to evaluate the relationship between mast cells and microvessels by applying the double staining CD34/toluidine blue in cutaneous malignancies. Materials and Methods: The study consisted of 50 cases of cutaneous malignancies. Combined Immunohistochemical and Histochemical methods used to study the microvessels and mast cells. Results: A significant correlation between the mast cell count and microvessel density was observed in all 3 cutaneous malignancies. Statistical analysis of the linear correlation between MCD and MVD was also performed (P