Microvessel Density Research Articles

Exact radiological-pathological correlation of chondrosarcomas using a patient-specific 3D mold.

To identify aggressive regions in high-grade and dedifferentiated chondrosarcomas on MRI by obtaining an exact correlation between radiology and histopathology. One chondrosarcoma grade II (CSII), chondrosarcoma grade III (CSIII) and dedifferentiated chondrosarcoma (DDCS) were segmented on (DCE-)MRI images. Around the segmentations, a patient specific mold was constructed and 3D-printed with cutting grooves perfectly aligned with selected MRI slices. In this way, resection specimens could be cut at the same locations as the MRI slices. Histopathology slides were stained with hematoxylin-eosin and CD31 (vascularization) and correlated with the (DCE-)MRI. Histopathologically, atypical cartilaginous tumor (ACT), CSII, CSIII and DDCS regions were delineated and vascular hotspots were selected by an experienced pathologist. Exact point-to-point correlation was performed. ACT, CSII, CSIII and DDCS regions all had similar mean signal intensity on T1-weighted images. On fat-saturated T2-weigthed images, CSII and CSIII regions had a higher mean signal intensity. On fat-saturated T1-weighted images after gadolinium contrast injection and on wash-in parametric maps DDCS regions had the highest mean signal intensity and highest wash-in values. There was a higher microvessel density in CSII and CSIII regions. This corresponded with a thick enhancing rim on fat-saturated T1-weighted images after gadolinium contrast injection and with a higher wash-in. This new 3D mold helps to identify high-grade chondrosarcoma regions with myxoid. This may be useful for targeted biopsy and histopathological investigation.

Vascularity of the gastric conduit predicts complications after Ivor-Lewis esophagectomy.

Anastomotic leakage (AL) contributes to postoperative morbidity and mortality after Ivor-Lewis esophagectomy. Vascular high-risk patients show a significantly increased risk of AL. We previously showed that laparoscopic ischemic conditioning (ISCON) of the stomach prior esophagectomy in these high-risk patients is a safe procedure that induces neoangiogenesis at the anastomotic site. Our data also suggested that this directly impacts on anastomotic healing. To further investigate the hypothesis that gastric conduit vascularization directly influences postoperative morbidity, we evaluated gastric conduit vascularity in a cohort of patients undergoing two-stage esophagectomy prior to the ISCON era. Seventy-nine patients who underwent two-stage esophagectomy from 2016 to 2021 at our center were retrospectively analyzed from a prospectively maintained database. Microvessel density (MVD) of the gastric conduit at the anastomotic region was evaluated by CD34 staining of the gastric stapler ring. Analysis of microvessel density (MVD) was performed using ImageJ. Patients were stratified into low- and high-MVD groups, and MVD was correlated with clinical outcomes. Patients with a high MVD showed a significantly lower rate of anastomotic leakage (AL) in comparison to patients with low MVD (6.25% vs. 22.58% p=0.043). Furthermore, a high MVD was associated with a lower rate of major complications (Clavien Dindo ≥ IIIb) (12.50% vs. 38.71% p=0.012) and a shorter hospital stay (17.9 days vs. 23.1 days, p=0.045). Vascularization of the stomach might function as surgical biomarker of AL in patients undergoing two-stage esophagectomy. Prospective trials have to further substantiate this finding.

Human umbilical cord mesenchymal stem cells improve the survial of flaps by promoting angiogenesis in mice

BackgroundFlap necrosis post-operation disturbs surgeons during plastic and reconstructive surgery. This is caused by hypoperfusion and subsequent ischemia–reperfusion injury, where restricted blood flow followed by restored circulation paradoxically exacerbates tissue damage. Mesenchymal stem cells, which show multidirectional differentiation, provide hematopoietic support and are involved in immune regulation and anti-fibrosis, have inspired research on improving the blood supply of flaps.MethodsPrimary human umbilical cord mesenchymal stem cells (HuMSCs), were obtained and subcultured for expansion. The cells of the third generation were incubated in a gelatin sponge. Thirty Kunming mice were randomly divided into three groups, and saline, HuMSCs, and HuMSCs-CM were injected preoperatively into the skin of the back. The vessel density was assessed on the tenth day. Forty-eight Kunming mice were divided into two groups. Group A was subdivided into the saline group, HuMSCs, and HuMSCs-CM groups and pretreated as described above. In Group B, the intervention was changed from injection to subcutaneous embedding. Random flaps were made on the back in both groups on the tenth day after pretreatment. The survival rate of the flap was calculated on the seventh day.ResultsHuMSCs-CM significantly increased the microvessel density on the tenth day after pretreatment. The flap survival rate was higher in the cell and CM groups, rising from approximately 13% to 60% in Group A, and to about 75% in Group B. Moreover, subcutaneous embedding of cell-carrying gelatin sponges improved flap survival compared to other interventions.ConclusionImproved cell incubation conditions can enhance its utility. The application of HuMSCs and their conditioned medium promoted the survival of the flap by inducing neovasculogenesis.

Kaempferol promotes angiogenesis through HIF-1α/VEGF-A/Notch1 pathway in ischemic stroke rats.

Kaempferol promotes angiogenesis through HIF-1α/VEGF-A/Notch1 pathway in ischemic stroke rats.

IFN-γ-mediated suppression of ANGPT2-Tie2 in endothelial cells facilitates tumor vascular normalization during immunotherapy

IntroductionTumor angiogenesis is a critical biological hallmark of cancer, which involves multiple molecularly regulated signaling pathways, including the angiopoietin (ANGPT)-Tie2 and the vascular endothelial growth factor (VEGF) signaling pathways. Despite initial optimism, targeting tumor angiogenesis in the treatment of lung adenocarcinoma (LUAD) has been unsatisfactory. Currently, monotherapy with PD-1/PD-L1 inhibitors, or their combination with bevacizumab, is considered the standard therapeutic approach for LUAD. Recent studies have shown that immunotherapy suppresses tumor angiogenesis and facilitates vascular normalization. However, whether and how anti-PD-L1 therapy influences tumor vasculature remains unclear.MethodsTo investigate the impact of immunotherapy on the vasculature of LUAD, a mouse model of lung adenocarcinoma was established by subcutaneous implantation of Lewis lung carcinoma cells in vivo. The effects of different treatments on microvessel density and pericyte coverage were explored, and the expression of angiogenesis-related factors was analyzed. Furthermore, to explore the molecular mechanisms through which IFN-γ regulates tumor blood vessels during immunotherapy, we elucidated the specific mechanisms in vitro by means of techniques such as siRNA, ChIP, RT-qPCR, Western blot, and immunofluorescence. Finally, the effects of IFN-γ on the proliferation, migration, and angiogenic function of endothelial cells (ECs) were evaluated through CCK-8, Transwell, and HUVEC tube formation assays.ResultsEmploying a mouse model of LUAD, we demonstrated that PD-L1 blockade therapy inhibits tumor angiogenesis and normalizes vasculature in an IFN-γ-signaling-dependent manner. Notably, anti-PD-L1 therapy reduced Tie2 and ANGPT2 expression, and these effects were reversed by the JAK1/2 inhibitor. Mechanistically, we demonstrated that IFN-γ inhibited Tie2 and ANGPT2 expression in ECs, and suppressed ANGPT2 gene transcription through the AKT-FOXO1 signaling pathway. Interestingly, IFN-γ-mediated activation of STAT1 exerts negative regulation by directly binding to the promoter regions of the ANGPT2 and TEK genes. Functionally, IFN-γ limits the migration, proliferation, and tube formation of ECs.DiscussionIn conclusion, our results revealed a novel mechanism wherein IFN-γ-mediated inhibition of ANGPT2-Tie2 facilitates vascular normalization during immunotherapy in LUAD, which performs an essential function in the antitumor efficacy of immunotherapy.

Structural and functional analysis of a homotrimeric collagen peptide.

This study aimed to chemically synthesize a homotrimeric collagen peptide, evaluate its safety, and assess its effectiveness in promoting collagen synthesis. A homotrimeric collagen peptide was synthesized and structurally characterized using circular dichroism and infrared spectroscopy. Thermal stability was analyzed by TG-DSC, and molecular weight and amino acid composition were determined. In vitro cytotoxicity testing assessed safety, while UV-induced photoaging experiments evaluated its effects on collagen and elastin synthesis. In vivo studies in BALB/c mice examined its impact on collagen content, skin structure, and angiogenesis. The synthesized collagen peptide exhibited high purity (99.1%) and an amino acid composition of glycine, proline, and hydroxyproline in a balanced ratio (15:17:13). Structural analysis confirmed a stable triple-helical conformation similar to type I collagen with excellent thermal stability (Tm = 326.15°C). Cytotoxicity testing showed no adverse effects on cell viability. In vitro, the peptide significantly enhanced collagen and elastin synthesis in fibroblasts. In vivo, intradermal and subcutaneous injection increased collagen content, improved skin structure, and enhanced microvessel density. This study presents a chemically synthesized homotrimeric collagen peptide with superior purity, structural stability, and biological efficacy in promoting collagen synthesis. Compared to previous studies, this biomimetic material exhibits exceptional thermal stability (Tm = 326.15°C) and a well-balanced amino acid composition, enabling applications in cosmetics and medical devices requiring heat sterilization (e.g., autoclaving), as validated by our patented method (China Patent No. ZL202410309842.9).

Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus

Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10–15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.

Systematic review and meta-analysis on macrovascular and microvascular anatomy of preputial skin in hypospadias and its implications.

Hypospadias repair is challenging due to complications like urethrocutaneous fistula and flap necrosis, often linked to preputial vascular anatomy. While macrovascular and microvascular patterns are studied, findings are inconsistent. The impact of preoperative hormonal therapy (PHT) on vascularity and outcomes is unclear. This review and meta-analysis evaluates preputial vascular anatomy in hypospadias and its surgical implications. A systematic review (2000-2024) was conducted in PubMed, MEDLINE, and Cochrane following PRISMA guidelines. The inclusion criteria used the PICOS framework. The bias was assessed using Robvis and microvessel density (MVD) differences were analyzed via meta-analysis with heterogeneity quantified (I2). Effects of PHT on vascularity were also reviewed. Fourteen studies (707 hypospadias, 106 controls) revealed predominant net-like vascular patterns in severe cases. MVD was significantly lower in hypospadias (pooled Mean, 28.85/HPF) versus controls (pooled Mean, 45.46/HPF), correlating with severity of hypospadias, the MVD varied a lot across different population worldwide. The meta-analysis showed high heterogeneity (I2 = 98%). PHT increased MVD and vessel diameter, improving outcomes in three studies. Hypospadias alters preputial vascular anatomy, show varied patterns, with reduced MVD linked to surgical challenges. A lot of variation exist in MVD across various population. PHT enhances vascularity but requires further validation. Standardized vascular assessments and advanced imaging are essential for optimizing surgical outcomes. PROSPERO registration number CRD42025640297.

Abstract 3848: Smoking promotes angiogenesis and epithelial to mesenchymal transition in breast cancer

Introduction: Nicotine, the addictive component of cigarettes, induces tumor progression via the α7-nicotine acetylcholine receptor (α7-nAChR) subtype in lung cancer. However, the molecular mechanisms by which nicotine impacts tumor progression of breast cancer (BC) remain unclear. In this study, we evaluated the effects of nicotine/smoking on tumor angiogenesis, and epithelial-mesenchymal transition (EMT) signaling mechanisms that are involved in BC progression. Experimental Design: BC cell spheroids from the MCF7, a non-invasive cell line was treated with nicotine (0.3 to 3μM) for 14 days. Sections of tumor tissue from the human BC (smoking vs. never smoking) were assessed for phenotypic expressions of α7-nAChR, and vimentin by immunostaining (IHC). CD31 staining was used to evaluate tumor angiogenesis, as measured by microvessel density (MVD). Western blot (WB) analyses were also performed on lysates of both cell lines and tumors to assess the effect of nicotine on the signaling pathways that promote BC progression. Results: The present study revealed that nicotine treated spheroids have increased expression of Ki67, Mdr1, Oct4 signatures that are indicative of BC progression. IHC analysis indicated that tumor from patients that smoked displayed increased expression of α7-nAChR. Furthermore, the expression of Oct4 (marker for cancer stem-cell), and vimentin (marker for EMT) that correlates with advanced disease and metastasis were found to be higher in smokers. However, tumors from non-smokers had low expression of Oct4 and vimentin. It was also found that tumors from patients who smoked had well established vascularity, while tumors from non-smokers had very little vascularization. Indeed, the mean MVD was lower in tumors from non-smokers compared to tumors from smokers. Conclusions: These findings offer significant novel insights into the mechanism by which nicotine contributes to the increased aggressiveness of BC. This work was supported in part by NIH/NCI Workforce Diversity Grant R21-CA171251. Citation Format: Venkat Katkoori, Shreeya R. Kandukuri, Madhukar V. Burra, James E. Trosko, Deimante M. Tamkus, Cherly Leece, Lakshimipathi R. Kareti, George S. Abela, Harvey L. Bumpers. Smoking promotes angiogenesis and epithelial to mesenchymal transition in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3848.

Abstract 5692: Distinct effectors of FSTL1 promote melanoma growth and angiogenesis and FSTL1 blockade mitigates resistance to BRAF and MEK inhibitors

Melanoma is a highly lethal form of skin cancer due to its propensity for metastasis through angiogenesis, which confers melanoma initiating cells with resistance to BRAF and MEK inhibitors. However, current drugs for targeting angiogenesis have shown limited efficacy, highlighting the need to develop new anti-angiogenic therapies to effectively combat this devasting malignancy. Here, we found that Follistatin-like 1 (FSTL1) expression is significantly increased in metastatic melanoma, and correlates with higher microvessel density, and poor prognosis. FSTL1 is both required and sufficient for the growth, metastasis, and angiogenesis of melanoma. FSTL1 functions downstream of SOX10-DLC1-FOXK1 to mediate its oncogenic activity, which can be inhibited by FSTL1 neutralizing antibody (FSTL1 nAb). Mechanistically, intracellular FSTL1 promotes G1/S transition in proliferative melanoma cells by activating an AKT/Lamin B2 axis. Secreted FSTL1 activates endothelial expression of TMSB4X to induce nuclear NF-kB-dependent regulation of angiogenesis. Furthermore, FSTL1 expression is selectively upregulated in melanoma-initiating cells that are resistant to BRAF and MEK inhibitors, driving stemness through interactions with the tumor microvasculature. Treatment with FSTL1 nAb depletes melanoma-initiating cells and slows down drug resistance development, suggesting that FSTL1 nAb may be a promising adjunct therapy to BRAF and MEK inhibitors for melanoma treatment. Citation Format: Umar Patel, Jiaying Ng, Chiu Wang Chau, Alex To, Ryohichi Sugimura, Martin Cheung. Distinct effectors of FSTL1 promote melanoma growth and angiogenesis and FSTL1 blockade mitigates resistance to BRAF and MEK inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5692.

Transplantation of adipose tissue to areas with increased vascularization

Objective. To study in experiment the possibility of improving the processes of revascularization of fat grafts with preserved lobular structure by moving them to a well–vascularized recipient site. Materials and Methods. Expanded skin–muscle–fat vascularized tissues were formed based on the artificial generation of the flap vascular system by implantation of a dilator into the subflap space, various types of expanded flaps with subsequent implantation of a fat graft. Flap and fat graft samples at 1 week and 4 weeks after transplantation were evaluated for the presence of intact and nuclear fat cells, cysts and vacuoles, inflammation, fibrosis, etc., as well as neovascularization. Results. At 4 weeks after transplantation, the density of microvessels in the expanded skin–muscle flaps of the rats of the main group slightly decreased compared to the corresponding indicator after 1 week and amounted to 15.20 ± 0.95 in subgroup A and 14.70 ± 0.72 in subgroup B (p=0.97). After 4 weeks, the density of blood vessels in the flaps of the control group rats slightly increased compared to the density of blood vessels after 1 week and amounted to 10.33 ± 1.31 (p=1.00). The density of microvessels in adjacent fat grafts in subgroup A of the main group – 3.08 ± 0.16 and subgroup B of the main group – 2.98 ± 0.25 was also higher than in the control group 2.30 ± 0.52 (p<0.01). Conclusions. A significant difference in capillary density was found in fat grafts of rats with expanded flaps and rats with non–expanded flaps.

Integrated network pharmacology, proteomics, molecular docking, and experiments in vivo and in vitro to explore the efficacy and potential mechanism of bufalin against hepatocellular carcinoma angiogenesis.

Integrated network pharmacology, proteomics, molecular docking, and experiments in vivo and in vitro to explore the efficacy and potential mechanism of bufalin against hepatocellular carcinoma angiogenesis.

LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1.

LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1.

Biomarker analyses from the phase III randomized CLEAR trial: lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma.

Biomarker analyses from the phase III randomized CLEAR trial: lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma.

Closer proximity of pre-treatment CD4+ T cells to CD8+ T cells favor response to neoadjuvant immunotherapy in patients with PD-L1 low-expressing non-small cell lung cancer.

Neoadjuvant chemo-immunotherapy improves non-small cell lung cancer (NSCLC) outcomes, but remission rates vary, emphasizing the need for biomarkers. This study aimed to investigate the impact of the baseline intratumoral CD4+ T-cell-adjacent microenvironment on the efficacy of neoadjuvant immunotherapy in NSCLC and its correlation with hypoxia-inducible factor-1α (HIF-1α), microvessel density (MVD), and cancer-associated fibroblasts (CAFs). Tumor samples from 49 NSCLC patients before neoadjuvant immunotherapy were retrospectively collected and subjected to multiplex immunohistochemistry staining (panel 1: DAPI/CK/CD4/CD8/CD68; Panel 2: DAPI/CK/CD4/HIF-1α/CD31/α-SMA) to characterize CD4+ T cells, CD8+ T cells CD68+ macrophages, HIF-1α+ cells, HIF-1α+CD4+ cells, MVD, and CAF. Mann-Whitney U test and receiver operating characteristic (ROC) curve were used to assess the relationship between the number and spatial distribution of each metric and the efficacy of the treatment, and Spearman's rank correlation was used to assess the correlation of each metric. In 49 NSCLC patients, responders (54.2%) and non-responders (45.8%). Single-indicator analysis revealed a positive correlation between high infiltration of CD8+ T cells in the stromal area and response to treatment in overall and programmed cell death-ligand 1 (PD-L1) low-expressing patients [CD8+ T (str) density: overall patient, 38 vs. 16, P=0.03; tumor proportion score (TPS) 1-49% subgroup, 37 vs. 14, P=0.04], with an area under curve (AUC) 0.684 and 0.746, respectively. CD4+ T cells combined with CD8+ T cells or CD68+ macrophages were analyzed and found to be more efficacious than CD4+ThiCD8+Thi compared to CD4+TloCD8+Tlo in patients with low expression of PD-L1 (P=0.03). Assessment of the nearest neighbor distance (NND) of CD4+ T cells and their adjacent cells revealed that the closer the CD4+ T cells and CD8+ T cells in the overall compartment, the better the efficacy in NSCLC patients, especially in patients with low PD-L1 expression [CD4+ T to CD8+ T (all) NND: overall patients, 34 vs. 47 μm, P=0.03; TPS 1-49% subgroup, 34 vs. 69 μm, P=0.006], and the AUC was 0.670 and 0.830, respectively. Notably, this favorable spatial interaction may not be dependent on direct contact between CD4+ T cells and CD8+ T cells within 10/20/30 μm (P>0.05). Furthermore, in overall and PD-L1 low-expressing patients, the closer the distance between CD4+ T cells and CD8+ T cells, the higher the MVD (overall patients, r=-0.39, P=0.008; TPS 1-49% subgroup, r=-0.49, P=0.01). The baseline intratumoral CD4+ T-cell-adjacent microenvironment in NSCLC is associated with the efficacy of neoadjuvant immunotherapy for NSCLC, with the closer proximity of pre-treatment CD4+ T cells and CD8+ T cells, the better the treatment efficacy in NSCLC patients (even especially in the low-expressing PD-L1 population), and is associated with high MVD.

Unveiling the Angiogenic Potential and Functional Decline of Valve Interstitial Cells During Calcific Aortic Valve Stenosis Progression.

Valve interstitial cells (VICs) play a critical role in aortic valve calcification and angiogenic processes associated with calcific aortic valve stenosis (CAVS). Within the same valve, VICs from differently calcified regions can exhibit diverse phenotypic and functional properties. We hypothesised that VICs isolated from noncalcified (NC-VICs) and calcified (C-VICs) areas of human aortic valves possess distinct angiogenic characteristics. In this study, we isolated C-VICs and NC-VICs from 23 valves obtained after aortic valve replacement due to CAVS. Both VIC types exhibited similar phenotypes in culture, characterised by morphology, expression of mesenchymal/fibroblastic markers, proliferation and osteogenic differentiation. No significant differences were observed in the secretion of angiogenic factors, including VEGF-A, Ang-1, Ang-2, PlGF, bFGF between NC-VICs and C-VICs. However, when co-injected with endothelial colony-forming cells (ECFCs) into Matrigel implants invivo in mice, implants containing NC-VICs showed significantly higher microvessel density compared to those with C-VICs (p < 0.001). Additionally, NC-VICs co-cultured with ECFCs expressed significantly higher levels of the perivascular markers αSMA and calponin compared to C-VICs (p < 0.001 and p < 0.05, respectively). In conclusion, our study reveals the heterogeneity in VIC plasticity within the aortic valve during CAVS. The diminished capacity of VICs from calcified areas to differentiate into perivascular cells suggests a loss of function as valve disease progresses. Furthermore, the ability of VICs to undergo perivascular differentiation may provide insights into valve homeostasis, angiogenesis and the exacerbation of calcification.

Characterization of microvessels in the human forehead dermis using intravascular dual perfusion and immunofluorescence staining

Skin microcirculation provides essential insights in clinical practice. However, the specific characteristics and distribution patterns of dermal microarterioles and microvenules remain insufficiently explored. This study aimed to analyze their structural differences and distribution in the human forehead skin using an innovative intravascular dual perfusion technique combined with immunofluorescence staining to distinguish microvessel types within the dermis. Using two post-mortem cadaver specimens, lead oxide-gelatin perfusion was applied to label microarterioles, and latex was used for microvenules. Tissue sections underwent hematoxylin and eosin and immunofluorescence staining, with cluster of differentiation 31 (CD31) serving as a general vascular marker and monocarboxylate transporter 1 (MCT1) as a venule-specific marker. The analysis revealed significant structural differences between dermal layers: vessels in the deep dermis had larger diameters and thicker walls than those in the superficial layer, while microvessel density was higher in the superficial dermis. These findings demonstrate distinct patterns and significant differences in microvessel distribution between the superficial and deep dermal layers, reflecting their layer-specific functional demands. Furthermore, MCT1 was identified as a specific marker for microvenules, and a novel method combining CD31 and MCT1 immunofluorescent staining was introduced to differentiate dermal microarterioles from microvenules. These results offer valuable implications for surgical planning, skin grafting, and diagnostics related to microcirculation.

Functional MRI and Tumor Vasculature Correlation in Ewing Sarcoma Xenografts: A Prospective Study Based on MRI-Pathology Co-Alignment.

Limited studies have evaluated vascular markers of Ewing sarcoma (ES) using MRI. To explore the correlation between tumor vascular markers and MRI perfusion parameters in ES xenografts based on MRI-pathology co-alignment. Prospective. Thirty-four ES xenograft models were established in female athymic nude mice using the human-derived A673 cell line. 3 T MRI, T1-weighted (T1w) with fast spin echo sequence, T2w with fast recovery fast spin echo sequence, intravoxel incoherent motion (IVIM) with echo-planar diffusion-weighted sequence, and dynamic contrast-enhanced MRI (DCE-MRI) with the liver acquisition with volume acceleration sequence. IVIM parameters (D, D*, and f), DCE-MRI semiquantitative parameters (maximum slope of increase [MSI], contrast-enhancement ratio [CER], and initial area under the gadolinium curve [iAUGC]), and DCE-MRI quantitative parameters (Ktrans, Kep, and Ve). The expression of vascular endothelial growth factor (VEGF), microvessel density (MVD), and vascular mimicry (VM) was evaluated by immunohistochemical staining. Intraclass correlation coefficient (ICC), bootstrap resampling, Fisher's Z transformation, Pearson or Spearman correlation analysis, receiver operating characteristic curve (ROC) analysis, and DeLong's test. p < 0.05 was considered statistically significant. Ktrans, Kep, f, and D* values showed significant correlations with VEGF (r = 0.697, 0.630, 0.781, 0.695, respectively). D*, f, Ktrans, MSI, and CER values showed significant correlations with MVD (r = 0.42, 0.554, 0.486, 0.461, 0.416, respectively). D and f values showed significant correlations with VM (r = -0.552, 0.384, respectively). Ktrans, f, D*, and Kep values were good diagnostics in distinguishing between high- and low-expression groups of VEGF (AUC = 0.833-0.954). D* and D values were good diagnostics in distinguishing between high- and low-expression groups of MVD and VM (AUC = 0.727, 0.739, respectively). IVIM and DCE-MRI can be utilized to assess tumor vasculature in ES xenografts. 1. Stage 3.

Intratumoral vessel caliber and microvascular density in hepatocellular carcinoma

PurposeIt is generally acknowledged that tumor vascularity, caliber, and quantity play a large role in effective locoregional treatment with particle embolization. To date, little has been documented in terms of actual measurements of arterial caliber and quantity (a.k.a. microvascular density) within hepatocellular carcinoma (HCC). The goal of this study was directly to measure intratumoral caliber and micro-vessel densities within HCCs.Methods29 explanted HCCs were randomly retrieved from the pathology archives; 20 tumors (from 20 patients) with no-to-minimal necrosis on gross evaluation were selected and evaluated histopathologically. 1639 arteries were quantified and measured.ResultsMeasurements, with corrective adjustments for the tissue attenuation secondary to pathology preparation, demonstrated the arterial caliber to vary between 6.4 and 281.86 µm, with 60.7% of vessels smaller than 20 µm, 80.29% smaller than 30 µm, and 88.95% smaller than 40 µm. The microvascular densities varied from 13 to 222 arteries per 13.5-mm2 region of interest on a 4-µm-thick section.ConclusionTumor vascularity plays a significant role in particle size selection in transarterial embolization for treatment of HCC. Appropriate particle size must be chosen to ensure maximal ischemia and decrease risk of adverse outcomes. The reported distribution of arterial caliber and density may serve as a guide for interventional radiologist performing particle embolization of HCC.

Evaluation of Regeneration Potential of Bone Marrow-Derived Mesenchymal Stem Cells on Induced Damaged Submandibular Salivary Gland in Mice.

The ultimate goal of stem cell (SC) transplantation is the regeneration of salivary gland function by transplanted SCs differentiating into salivary gland cells. Therefore, this study aimed to evaluate the regenerative capacity of bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation in irradiated mice using the immunohistochemical markers Ki-67 and CD34. Four groups of male mice were included in the study. Group I (normal control) comprised six mice that were not subjected to gamma radiation. Group II comprised six irradiated mice that were not treated with BM-MSCs. Group III comprised 12 irradiated mice that were treated with intraglandular injection of labeled BM-MSCs into their submandibular salivary glands, 24 hours postradiation. Group IV comprised 12 irradiated mice that were treated with intraglandular injection of labeled BM-MSCs into their submandibular salivary glands, on day 11 postradiation. Data were presented as mean and standard deviation. The different groups were compared using a one-way analysis of variance (ANOVA). The ANOVA test revealed that the difference between all groups was extremely statistically significant (p < 0.003), and Tukey's post hoc test revealed a statistically significant difference between group II and groups I, III, and IV included in the study regarding microvessel density of CD34 immunoexpression in different groups. BM-MSCs have a regeneration potential on induced damaged submandibular salivary glands in mice; time is an essential factor in the regeneration capacity of BM-MSCs.