Close relationship between mediators of inflammation and pancreatic cancer: Our experience.

In this editorial, we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer. Cancer of the pancreas remains one of the deadliest cancer types. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends of pancreatic cancer incidence and mortality vary considerably worldwide. A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease. Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche. In this editorial, we highlight the foundational studies that have driven our understanding of these processes. In our experimental center, we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer. We focused on the role of mast cells (MCs). MCs contain pro-angiogenic factors, including tryptase, that are associated with increased angiogenesis in various tumors. In this editorial, we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue. The assessment includes the density of c-Kit receptor-positive MCs, the density of tryptase-positive MCs, the area of tryptase-positive MCs, and angiogenesis in terms of microvascularization density.

Young blood-mediated cerebromicrovascular rejuvenation through heterochronic parabiosis: enhancing blood-brain barrier integrity and capillarization in the aged mouse brain.

Age-related cerebromicrovascular changes, including blood-brain barrier (BBB) disruption and microvascular rarefaction, play a significant role in the development of vascular cognitive impairment (VCI) and neurodegenerative diseases. Utilizing the unique model of heterochronic parabiosis, which involves surgically joining young and old animals, we investigated the influence of systemic factors on these vascular changes. Our study employed heterochronic parabiosis to explore the effects of young and aged systemic environments on cerebromicrovascular aging in mice. We evaluated microvascular density and BBB integrity in parabiotic pairs equipped with chronic cranial windows, using intravital two-photon imaging techniques. Our results indicate that short-term exposure to young systemic factors leads to both functional and structural rejuvenation of cerebral microcirculation. Notably, we observed a marked decrease in capillary density and an increase in BBB permeability to fluorescent tracers in the cortices of aged mice undergoing isochronic parabiosis (20-month-old C57BL/6 mice [A-(A)]; 6 weeks of parabiosis), compared to young isochronic parabionts (6-month-old, [Y-(Y)]). However, aged heterochronic parabionts (A-(Y)) exposed to young blood exhibited a significant increase in cortical capillary density and restoration of BBB integrity. In contrast, young mice exposed to old blood from aged parabionts (Y-(A)) rapidly developed cerebromicrovascular aging traits, evidenced by reduced capillary density and increased BBB permeability. These findings underscore the profound impact of systemic factors in regulating cerebromicrovascular aging. The rejuvenation observed in the endothelium, following exposure to young blood, suggests the existence of anti-geronic elements that counteract microvascular aging. Conversely, pro-geronic factors in aged blood appear to accelerate cerebromicrovascular aging. Further research is needed to assess whether the rejuvenating effects of young blood factors could extend to other age-related cerebromicrovascular pathologies, such as microvascular amyloid deposition and increased microvascular fragility.

Role of CD34-immunopositive Microvascular Density in Juvenile Nasopharyngeal Angiofibroma.

Objective: To assess the microvascular density (MVD) in juvenile nasopharyngeal angiofibroma (JNA) with CD34 immunostaining and evaluate its relationship with clinico-demographic features. Methods: This prospective study included patients with JNA undergoing endoscopic excision. The histopathological specimen was stained using CD-34 antibodies to calculate MVD. MVD and clinico-demographic features were correlated. Results: The study included 12 patients with a median age of 15.5 years. The mean MVD was 39 vessels/high power field (range 5 to 151 vessels). MVD was significantly associated only with the volume of tumour (r = 0.65, p = 0.02). The recurrence occurred in one patient with an MVD of 107. The median follow-up was 38 months. Conclusion: MVD is significantly associated with tumour volume in JNA, which implies a robust role of angiogenesis in the pathology of the tumour. Also, higher MVD may be a risk factor for recurrence.

Retinal Vascular Changes in Heart Failure with Preserved Ejection Fraction Using Optical Coherence Tomography Angiography.

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

Evaluation of the diagnostic utility of MCAM-1 (CD146) in a group of common gynecological cancers: A case-control study.

Objective: MCAM-1 (CD146) is an endothelial cell adhesion molecule belonging to the immunoglobulin superfamily. Recent studies have identified CD146 expression as a critical marker for tumor progression, migration, and metastasis in various malignancies. This study aimed to evaluate CD146 immunohistochemical expression in various gynecological cancers. Materials and Methods: This study was conducted in a tertiary medical center in central India. A total of 49 gynecological cancer cases and 16 site-matched controls were included. The cases comprised 27 cervical, 10 endometrial, 10 ovarian, and two miscellaneous cancers. CD146 immunohistochemistry was performed and assessed for immunoreactivity score (IRS), microvascular density (MVD), and microvascular caliber (MVC). An IRS of 5 or more was considered CD146 positive. Results: The p-values for CD146 positivity for cases vs. control were 0.0531, 0.0580, and 0.007 for cervical, endometrial, and ovarian sites, respectively. The mean MVD was found to be significantly higher in cases compared with benign tissues (p-value <0.00001), and the mean MVC of cases was found to be smaller when compared with the controls (p-value <0.0001). Conclusion: MVD by CD146 was found to be higher in gynecological malignancies, highlighting its role in cancer neo-angiogenesis and its potential therapeutic role. CD146 epithelial expression was also significantly higher in ovarian cancers. Further studies with a larger sample size are required to confirm that this protein may be a potential theognostic target in gynecological cancers.

Negative impact of ratio of the microvascular area to tumor area on the response to EGFR-TKI in non-small cell lung cancer with an EGFR mutation.

Background: The clinical impact of tumor microvessels on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC) is unclear. Thus, the aim of this study was to investigate whether a tumor microenvironment, abundant in microvessels, affects EGFR-TKI efficacy in patients with NSCLC and EGFR mutations. Methods: We retrospectively studied the data of 40 post-operative patients with recurrent NSCLC and EGFR mutations who received EGFR-TKIs as a first-line treatment at Kumamoto University Hospital from January 2010 to February 2021. Tumor sections were retrieved from the tissue registry and analyzed for CD34-positive microvessels using immunohistochemical techniques. The ratio of microvascular area to tumor area (RMV), which is the CD34-positive microvascular area compared to the total tumor area, was measured using StrataQuest. The predictive value of RMV on treatment outcome, assessed via progression-free survival (PFS), was evaluated using a multivariate Cox proportional hazard model. Results: The median PFS in the high RMV group (≥0.058) was significantly shorter than that in the low RMV group [<0.058; 296 days, 95% confidence interval (CI): 217-374 vs. 918 days, 95% CI: 279-1,556, P=0.002]. Multivariate analysis revealed that high RMV was an independent negative predictor of PFS (hazard ratio, 3.21; 95% CI: 1.18-8.76, P=0.022). Conclusions: High RMV may critically affect EGFR-TKI resistance in patients with NSCLC and EGFR mutations.

Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound.

The purpose of this study was to investigate whether doxorubicin nanobubbles (DOX-NB) combined with diagnostic ultrasound (DUS) irradiation could downregulate the expression of carbonic anhydrase IX (CAIX) in mouse xenograft nasopharyngeal carcinoma (NPC) model. In this study, the prepared DOX-NB was round and well dispersed. The average diameter of DOX-NB was 250.9 ± 50.8 nm, with an average polydispersity of 0.321 ± 0.05. The cumulative release of DOX in the DOX-NB + DUS group was significantly higher compared with that of the DOX-NB group (p < 0.05). DOX-NB combined with DUS irradiation could significantly inhibit cell viability (p < 0.05). The expression of CAIX and microvessel density (MVD) in the xenografted tumors was the lowest in the DOX-NB + DUS group compared with that of other groups (p < 0.05). In conclusion, DOX-NB combined with DUS irradiation could improve DOX-NB drug release and synergistically inhibit NPC cell activity. DOX-NB combined with DUS irradiation can downregulate the expression of CAIX in mouse xenograft NPC model. This may be due to the synergistic effect of DUS combined with DOX-NB in reducing MVD in NPC.

Decreased retinal capillary density as a beneficial response to 24-week high-speed circuit resistant training in healthy older adults.

PURPOSE: To determine the changes in retinal microvascular density after a 24-week high-speed circuit resistance training program (HSCT) in healthy older adults. METHODS: Thirty healthy older adults were recruited and randomly assigned to either a training group (HSCT) or a non-training (CON) group. Fifteen subjects (age 73.3 ± 7.76 yrs) in the HSCT group exercised three times per week on non-consecutive days for 24 weeks. Fifteen subjects in the CON group (age 72.2 ± 6.04 yrs) did not have formal physical training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at the 24-week follow-up. The vessel densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured. RESULTS: There were no demographic differences between the study groups. There were significant decreases in the retinal vessel densities of RVN, SVP and DVP in the HSCT group (P < 0.05). However, there were no significant changes in all three vascular measurements in the CON group (P > 0.05), although the changes showed a decreasing trend. The decreased vessel densities were doubled in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05). CONCLUSIONS: This is the first study to reveal the decreased retinal vessel densities as a possible imaging marker for the beneficial effects of the 24-week HSCT program in older adults.

The Predictive Role of the Histopathological Scoring System in Adipose Tumors-Lipoma, Atypical Lipomatous Tumor, and Liposarcoma.

Lipomatous tumors are the most frequent soft tissue neoplasms. Sometimes their differential diagnosis is difficult to perform only by microscopic analysis. This study aims to create a histopathological scoring system and highlight the impact of intratumoral microvascular density. This study was conducted over 10 years. We analyzed the main pathogenic pathways (MDM2 and CDK4), as well as the tumor microvascularization (CD31 and CD34) by immunohistochemical tests. We also analyzed the status of the MDM2 gene by CISH. These data, together with the clinical and histopathological information, were statistically analyzed by appropriate tests. We identified 112 eligible cases, with most of the patients being in their sixth decade of life, with a slight predominance of the female sex. We found important associations like tumor location linked to nuclear pleomorphism severity and microvascularization density correlated with atypia severity. Also, we observed that a maximum diameter of a tumor of at least 69 mm is associated with the presence of tumor necrosis. The score designed in this study shows an increased sensitivity and specificity for the diagnosis of lipomas (100%, respectively, 97%), atypical lipomatous tumors (93.8%, respectively, 82.3%), and liposarcomas (100%, respectively, 90.5%). This present study enhances the present data by bringing to attention the histopathological score with a role in differential diagnosis, as well as in the prediction of immunohistochemical and genetic tests. Also, we highlighted the importance of microvascular density, especially in the diagnosis of liposarcomas.

Dietary nitrate accelerates the healing of infected skin wounds in mice by increasing microvascular density.

As skin injuries resulting from acute trauma, burns, and chronic diseases present significant challenges to healthcare systems worldwide, the promotion of skin wound healing remains an unmet therapeutic area. Dietary nitrate serves as a crucial pathway for the production of nitric oxide, which plays various physiological roles in the body, including vasodilation, increased blood flow, and antioxidant activity. However, the impact of dietary nitrate on skin wound healing remains uncertain. This study aimed to investigate the role of dietary nitrate in infected skin wound healing using a mouse model. We created a full-thickness wound infection model in mice and examine the effects of dietary nitrate (0.5 mmol/kg/d and 1 mmol/kg/d) on wound healing. The results demonstrated that dietary nitrate significantly increased serum nitrate and nitrite levels, leading to accelerated wound healing by increasing microvascular density, promoting collagen deposition and re-epithelialization. Moreover, nitrate supplementation exhibited a certain degree of reduction in inflammatory factors within the body. Our study also found that 1 mmol/kg/d nitrate has a more effective therapeutic effect and can increase blood perfusion and expedite the formation of new blood vessels, thereby promoting skin wound healing. These results indicate that dietary nitrate presents a novel therapeutic approach for infected skin wound healing.

Microvessel density (Cluster of Differentiation-34 & Vascular Endothelial growth factor) in Nasopharyngeal Angiofibroma: Clinical correlation.

BACKGROUND: The literature on microvessel density (MVD) signifying neoangiogenesis/tumour-activity in juvenile nasopharyngeal angiofibroma (JNA) is limited. Accordingly, this study evaluates and correlates MVD characteristics with clinical parameters/aggressiveness/recurrence. MATERIAL AND METHODS: Sixty-two paraffin blocks of JNA were studied histopathologically and MVD was assessed following immunohistochemistry using VEGF and CD34 as vascular markers. A clinical correlation of MVD was undertaken in 43 cases. RESULTS: MVD scores of VEGF and CD34 showed strong inter-correlation. The 'age', 'duration of disease' and 'haemoglobin%' were the only clinical parameters that revealed significance with MVD. Significantly higher MVD scores were appreciated in recurrent cases as well as some other clinical differences from upfront cases. CONCLUSION: This is the first study of MVD with CD34 and VEGF simultaneously depicting clinical correlation. The strong correlation, supports a prognostic role of MVD scores in JNA and this can be better established in a larger multicentre study involving comprehensive examination of tumour dimensions.

Search for Inhibitors of Mycobacterium tuberculosis Transketolase in a Series of Sulfo-Substituted Compounds.

As a result of the computer screening of a library of sulfo-substituted compounds, molecules capable of binding to the active site of transketolase from Mycobacterium tuberculosis were identified. An experimental verification of the inhibitory activity of the most promising compound, STK045765, against a highly purified recombinant enzyme preparation was carried out. It was shown that the STK045765 molecule competes for the binding site of the pyrophosphate group of the thiamine diphosphate cofactor and, at a micromolar concentrations, is able to suppress the activity of mycobacterial transketolase. The discovered furansulfonate scaffold may serve as the basis for the creation of anti-tuberculosis drugs.

Cell Therapy: A New Technology for Cerebral Circulation Restoration after Ischemia/Reperfusion.

Cell therapy with mesenchymal stem cells (MSCs) may be a promising technique for cerebral blood flow restoration after transient ischemia. Before a practical application of the cell material, 7-9 days are required for its cultivation. We studied the efficacy of human MSC (hMSC) transplantation performed 7 days after cerebral ischemia/reperfusion (I/R) to help recover cerebral circulation. The intravital micrograph technique was used to comparatively evaluate the vasculature density in the pia mater and the reactivity of the pial arteries in response to acetylcholine (ACh) in rats after I/R (clamping of both carotid arteries and a simultaneous decrease in and strict maintenance of the mean BP at 45 ± 2 mm Hg for 12 min) and with/without hMSC transplantation. Perfusion (P) in the sensorimotor cortex was assessed using laser dopplerography. After 14 and 21 days, the vasculature density in I/R-affected rats was 1.2- to 1.4-fold and 1.2- to 1.3-fold lower, respectively, than that in the controls. The number of ACh-dilated arteries decreased 1.6- to 1.9-fold and 1.2- to 1.7-fold 14 and 21 days after I/R, respectively. After 21 days, the P level decreased 1.6-fold, on average. Administration of hMSCs on day 7 after I/R resulted in complete recovery of the vasculature density by day 14. ACh-mediated dilatation fully recovered only in arteries of less than 40 µm in diameter within 21 days. After 21 days, the P level was 1.2-fold lower than that in the controls but significantly higher than that in rats after I/R without hMSCs. Delayed administration of MSCs after a transient cerebral ischemic attack affords the time for the procedures required to prepare cell material for transplantation and provides a good therapeutic response in the pial microvasculature.

Association of retinal microvascular density and complexity with incident coronary heart disease.

BACKGROUND AND AIMS: The high mortality rate and huge disease burden of coronary heart disease (CHD) highlight the importance of its early detection and timely intervention. Given the non-invasive nature of fundus photography and recent development in the quantification of retinal microvascular parameters with deep learning techniques, our study aims to investigate the association between incident CHD and retinal microvascular parameters. METHODS: UK Biobanks participants with gradable fundus images and without a history of diagnosed CHD at recruitment were included for analysis. A fully automated artificial intelligence system was used to extract quantitative measurements that represent the density and complexity of the retinal microvasculature, including fractal dimension (Df), number of vascular segments (NS), vascular skeleton density (VSD) and vascular area density (VAD). RESULTS: A total of 57,947 participants (mean age 55.6 ± 8.1 years; 56% female) without a history of diagnosed CHD were included. During a median follow-up of 11.0 (interquartile range, 10.88 to 11.19) years, 3211 incident CHD events occurred. In multivariable Cox proportional hazards models, we found decreasing Df (adjusted HR = 0.80, 95% CI, 0.65-0.98, p = 0.033), lower NS of arteries (adjusted HR = 0.69, 95% CI, 0.54-0.88, p = 0.002) and venules (adjusted HR = 0.77, 95% CI, 0.61-0.97, p = 0.024), and reduced arterial VSD (adjusted HR = 0.72, 95% CI, 0.57-0.91, p = 0.007) and venous VSD (adjusted HR = 0.78, 95% CI, 0.62-0.98, p = 0.034) were related to an increased risk of incident CHD. CONCLUSIONS: Our study revealed a significant association between retinal microvascular parameters and incident CHD. As the lower complexity and density of the retinal vascular network may indicate an increased risk of incident CHD, this may empower its prediction with the quantitative measurements of retinal structure.

Relationship of microvascular density on histological and immunohistochemical features in endometrioid adenocarcinomas of the uterus: experimental study.

The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells and their stroma. The neovascularization of EA tissues and level of microvascular density (MVD) influence tumor progression. Our study aims to establish the relationship between MVD in EA tissue and the histological and immunohistochemical features of tumors. Materials and methods: The authors studied 30 cases of endometrial ЕА and compared their histological and immunohistochemical characteristics with the MVD of tumor tissues. Results: Our study indicated that MVD in EA tissue depends on the grade of the tumors and their FIGO stage. Increased MVD was correlated with a depression of E-cadherin and PR expression and enhanced expression of VEGF and Ki-67. MVD enhancement during VEGF overexpression is a manifestation of the functional activity of these proteins. The increase in MVD was accompanied by more frequent metastasis of the EA to the lymph nodes. Conclusion: EA progression is accompanied by qualitative and quantitative variations of parenchymal and stromal patterns of tumors. Dedifferentiation of EA leads to overexpression of VEGF, which becomes diffuse in tumors cells, resulting in an increase of adenocarcinomas' MVD and their metastatic potential. Correlations between histological and immunohistochemical features of EAs indicate the synchronicity of the occurrence and progression of morphological and immunological anaplasia, which can be used in predicting the course of the disease.

Retinal alterations in evaluation of rheumatoid arthritis with chloroquine treatment: A new approach.

OBJECTIVE: To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients. METHODS: Ten healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups. RESULTS: The vascular density in RA group in superficial microvascular was significantly lower than that in control group (p < 0.001). Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (p < 0.001) and deep microvascular (p = 0.018). Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r = 0.868, p = 0.0048). CONCLUSIONS: The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease.

Low-Grade Mammary Gland Tumors in Dogs Have Greater VEGF-A and BMP2 Immunostaining and Higher CD31 Blood Vessel Density.

Tumor angiogenesis is an important process in tumor growth, and different molecules are involved in its regulation including VEGF-A, BMP2, and CD31, which can be considered possible prognostic markers. The aim of this study was to verify whether the VEGF-A and BMP2 immunostaining area, and microvascular density (MVD) might be associated with the degree of malignancy in malignant mammary neoplasms of dogs. For this purpose, samples of mammary malignancies from female dogs embedded in wax were used and separated into 4 main histomorphological types: tubulopapillary carcinomas, solid, complex, and carcinosarcoma, which were separated based on high and low degrees of malignancy. Immunohistochemical analysis was performed on tissue microarray blocks using anti-CD31 antibodies for evaluation of MVD and vascular lumen area, and with anti-VEGF-A and anti-BMP2 to determine the immunostaining area using the DAKO EnVision FLEX+ kit. MVD and vascular lumen area were higher in tubulopapillary carcinomas as were the areas stained by VEGF-A and BMP2. Immunostaining for CD31 was higher in low-grade carcinomas as well as in areas immunostained by VEGF-A and BMP2. There was a positive correlation between VEGF and BMP2 in high (r = 0.556, P < .0001) and low-grade (r = 0.287, P < .0001) carcinomas and between MVD and VEGF-A in low-grade carcinomas (r = 0.267, P = .0064). Thus, the markers evaluated showed greater immunostaining in canine mammary tumors with a lower degree of malignancy.

intravoxel incoherent motion diffusion-weighted MRI assessing the effect of the vascular disrupting agent CA4P on VX2 liver tumors in rabbits.

OBJECTIVE: This study aimed to assess the response of combretastatin-A4-phosphate (CA4P) in rabbit VX2 liver tumors using intravoxel incoherent motion diffusion-weighted MRI (IVIM DW-MRI). METHODS: Forty rabbits with implanted VX2 liver tumors underwent baseline MRI and were then given 10 mg/kg CA4P (n=20) or saline (n=20). After 4 h, 10 rabbits from each group underwent an MRI examination and were then sacrificed. The remaining rabbits underwent MRI after 1, 3, and 7 days and were then sacrificed. Liver samples were processed for H&E and immunohistochemical staining. IVIM parameters (D, f, D*) were compared in the treatment and control groups, and the correlations of IVIM parameters with microvascular density (MVD) were determined. RESULTS: At 4 h, the two treatment groups had significantly different f and D* values (p<0.001), and these values were at their minimum in the treatment group. The treatment group had moderate correlations between MVD and f at 4 h (r=0.676, p=0.032) and 7 days (r=0.656, p=0.039) and with D* at 4 h (r=0.732, p=0.016) and 7 days (r=0.748, p=0.013), but no correlation was reported between MVD and f or D* in the control group (all P>0.05). CONCLUSION: IVIM DW-MRI is a sensitive imaging technique. It successfully evaluated the effect of CA4P on VX2 liver tumors in rabbits. The f and D* values correlated with MVD at 4 h and 7 days after using CA4P, indicating that these parameters have the potential to be used as indicators of tumor angiogenesis after treatment.

Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin: A mathematical study.

Anti-angiogenesis as a treatment strategy for normalizing the microvascular network of tumors is of great interest among researchers, especially in combination with chemotherapy or radiotherapy. According to the vital role that angiogenesis plays in tumor growth and in exposing the tumor to therapeutic agents, this work develops a mathematical framework to study the influence of angiostatin, a plasminogen fragment that shows the anti-angiogenic function, in the evolutionary behavior of tumor-induced angiogenesis. Angiostatin-induced microvascular network reformation is investigated in a two-dimensional space by considering two parent vessels around a circular tumor by a modified discrete angiogenesis model in different tumor sizes. The effects of imposing modifications on the existing model, i.e., the matrix-degrading enzyme effect, proliferation and death of endothelial cells, matrix density function, and a more realistic chemotactic function, are investigated in this study. Results show a decrease in microvascular density in response to the angiostatin. A functional relationship exists between angiostatin's ability to normalize the capillary network and tumor size or progression stage, such that capillary density decreases by 55%, 41%, 24%, and 13% in tumors with a non-dimensional radius of 0.4, 0.3, 0.2, and 0.1, respectively, after angiostatin administration.

Microvascular density and tumor budding in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant head and neck tumor, excluding the nonmelanoma skin cancer. Despite recent advances in the diagnosis and treatment, the disease's mortality rate is nonetheless high. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, named tumor budding, is associated with a worse prognosis in OSCC. Angiogenesis has also been recognized as a determining factor in the progression of malignancies and in the development of metastases. Several studies have investigated the assessment of microvascular density (MVD) as a potential prognostic factor in OSCC. This study aimed to evaluate, in OSCC, differences in MVD between tumors with high-intensity tumor budding and tumors with low-intensity or no tumor budding. In samples with high-intensity tumor budding, differences in MVD between the budding area and the area outside the budding were also evaluated. Moreover, the study assessed differences in MVD concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size. Material and methods: One hundred and fifty [150] samples of OSCC were subjected to immunohistochemistry to assess the intensity of tumor budding (by immunostaining for multi-cytokeratin) and MVD (by immunostaining for CD34 and CD105, independently). The data were treated using descriptive and analytical statistics. (AU)