Microvessels In Patients Research Articles

Advances in endoscopic imaging of gastric mucosal microvessels in patients with early gastric cancer

Advances in endoscopic imaging of gastric mucosal microvessels in patients with early gastric cancer

Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling

It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3), Akt, and extracellular signal-regulated kinase (ERK) in a panel of head and neck squamous cell carcinoma (HNSCC) cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A). Gene expression analysis demonstrated that interleukin-6 (IL- 6), interleukin-8 (CXCL8), and epidermal growth factor (EGF) are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells.

Erythropoietin and retinopathy: the beginning of an understanding

I would like to congratulate Kase and his colleagues for their work finding that erythropoietin (EPO) receptors (EPOR) are strongly expressed in the microvessels of patients with proliferative diabetic retinopathy.1...

Inflammatory marker levels and peripheral blood circulation in skin microvessels in patients with chronic obstructive pulmonary disease

Levels of inflammatory markers and skin microcirculation were studied in patients with chronic obstructive pulmonary disease. Proinflammatory cytokine concentrations and number of desquamated endothelial cells in blood flow were significant increased during exacerbation compared with controls. The increase in proinflammatory cytokine concentrations in exacerbation was accompanied by increased skin perfusion, increased oscil lation amplitudes in the frequency ranges of respiratory rhythm and higher endothelial activity compared with controls. In stable condition, the lev els of proinflammatory cytokines decreased compared with those in exacerbation. Myogenic activity was decreased twice in patients with stable con dition compared with healthy persons. The endothelialdependent vasodilation did not change and the endothelialindependent vasodilation increased in all patients compared with controls.

Ultrastructural study of brain microvessels in patients with traumatic cerebral contusions

Ultrastructural study of brain microvessels in patients with traumatic cerebral contusions

The histo- and ultrastructural characteristics of the myocardium and vascular wall in patients with type 2 diabetes mellitus

The histo- and ultrastructural characteristics ofmyocardial and vascular lesions were studied in 27 patients (15 males and 12 females) with type 2 diabetes mellitus (DM), coronary heart disease (CHD), and atherosclerosis obliterans of lower extremity vessels. The lifetime endomyocardial biopsy specimens, intraoperative leg arterial biopsy specimens taken from intact tissues during leg amputation and поп-infarction areas of the left ventricular myocardium, autoptically taken from 32 patients who had died from complications due to atherosclerosis were examined. Myocardial ultrastructural derangement in type 2 DM was found to primarily affect the structures responsible for the energy and plastic metabolism in the cardiomyocytes. Moreover, the most pronounced functional changes were associated with cardiac diastolic function. The morphological pattern of damage to endotheliocytes, working cells of the myocardium and the ultrastructural organization of microvessels in patients with type 2 DM are directly related to the severity of hormone metabolic disorders, hyperinsulinemia and hyperglycemia in particular. The changes found in the microcirculatory system in type 2 DM were pronounced to the extent that the presence of coronary artery stenoses aggravated the typical changes in the architectonics and cardiomyocytic functions no longer.

Iron Deficiency Status in Polycythemia Vera Correlates Well with Bone Marrow Angiogenesis in Patients Treated with Phlebotomy.

Background: Polycythemia vera (PV) is a chronic myeloproliferative disorder derived from multipotent hematopoetic precursors. The pathogenesis of PV is still poorly understood; furthermore, it is not clear, why the bone marrow (BM) of patients with PV has an increased microvessel density. Aims: For these reasons, we aimed to investigate, if BM angiogenesis and pathogenesis in PV are associated, and if the increased angiogenesis can elucidate pathophysiologic mechanisms of PV. Methods: BM biopsies were taken from patients with PV before and during treatment. A total of 38 samples from 35 patients were analyzed. In three patients, we investigated biopsies in 12 months intervals. Also, eight patients with iron deficiency were studied. BM angiogenesis in thin sections was determined by immunostaining of endothelial cells (CD34, vWF) and counting the microvessels. The microvessel counts were correlated to hematologic features such as treatment modalities and iron metabolism parameters (zinc protoporphyrin (ZPP), ferritin). Iron deficiency was classified to be mild for ZPP ≤ 100 micromol/mol hem (normal value < 40) and for ferritin 7 to 35 microgramm/l (normal value > 35), and to be severe for ZPP > 100 micromol/mol hem and for ferritin < 7 microgramm/l. Results: When compared to healthy controls, the number of BM microvessels in patients with iron deficient anemia was indistinguishable from healthy individuals. As expected, the BM microvessel numbers of patients with PV at diagnosis (n= 6) or with only mild iron deficiency treated with various therapy schedules (n=20) showed no significant difference (p=n. s.). In contrast, in patients with severe iron deficiency, we detected a highly significant difference between two different treatment modalities: phlebotomy alone was associated with a normal microvessel density (n=7; mean 3.6/mm2, range 2.7 to 5.7/mm2), whereas other treatment modalites or a combination with phlebotomy were associated with a high microvessel density (n=10; mean 10.4/mm2; range 4.5 to 15.7/mm2; p=0.0004). The microvessel counts of the patients from who two sequential biopsies were investigated are in line with these results: the microvessel numbers in a patient who received an oral iron treatment increased from 9.3 to 15/mm2; the microvessels of another patient who was treated with hydroxy urea and phlebotomy showed almost unchanged microvessel counts, whereas, in a third patient, who was treated exclusively by phlebotomy, a clear decrease of BM microvessel density from 15.7 to normal value of 4.5/mm2 was observed. Conclusions: We conclude that i) iron deficiency per se does not induce increased microvessel density in the BM, ii) a severe iron deficiency induced by phlebotomy alone can reduce the BM microvessel density in patients with PV to normal. Provided that the increased BM angiogenesis is associated with pathogenesis in PV, which means that the multipotent hematologic precursors account for the increased angiogenesis, efficient iron depletion by phlebotomy represents the highly potent treatment for PV.

Paradoxical increase in coronary flow velocity after termination of acetylcholine infusion is a marker of the impaired vasodilatation at coronary microvessels in patients with angina and normal coronary arteries.

Some patients with anginal chest pain and normal coronary arteries exhibit a paradoxical increase in coronary flow velocity after termination of acetylcholine infusion. The aim of this study was to investigate whether this paradoxical increase in the flow velocity is associated with the impaired microvascular dilatation to pharmacological stimuli. We infused graded doses of endothelium-dependent vasodilator acetylcholine (10, 50, and 100 microg/min for 2 min) and the endothelium-independent vasodilators, papaverine and nitroglycerin, into the left coronary artery in 15 patients with chest pain and normal coronary arteries. Coronary blood flow responses were evaluated by Doppler guidewire and quantitative angiography in the proximal left anterior descending coronary artery. Seven patients showed a paradoxical increase in coronary flow velocity after termination of acetylcholine infusion with the highest dose (100 microg/min), whereas eight showed no change or a decrease in the flow velocity. This was also observed in 50 microg/min of acetylcholine infusion. In patients with a paradoxical increase in the flow velocity, coronary flow velocity responses to acetylcholine during three graded doses were significantly blunted in comparison to those without a paradoxical increase. In contrast, coronary flow reserve to papaverine and nitroglycerin was similar in the two groups. Epicardial artery vasoreactivity to acetylcholine did not differ between the two groups. Papaverine and nitroglycerin also caused a similar degree of coronary dilatation in both groups. These results suggest that the paradoxical increase in coronary flow velocity observed immediately after termination of the intracoronary acetylcholine infusion is a marker of impaired nitric oxide-dependent dilatation of the coronary microvessels in patients with normal coronary arteries. Cathet. Cardiovasc. Intervent. 48:170-177, 1999.

Paradoxical increase in coronary flow velocity after termination of acetylcholine infusion is a marker of the impaired vasodilatation at coronary microvessels in patients with angina and normal coronary arteries

Paradoxical increase in coronary flow velocity after termination of acetylcholine infusion is a marker of the impaired vasodilatation at coronary microvessels in patients with angina and normal coronary arteries

Tumor angiogenesis in stage II colorectal carcinoma: association with survival.

We studied the frequency of microvessels in T3 N0 M0 colorectal carcinomas from patients with widely different survival times. Microvessels (<50 microm diameter) were enhanced by immunostaining with antibody to factor VIII-related antigen and counted in 40x high-power fields in sections of resected carcinomas from 9 patients who died of disease in 24 months or less (short-term survivors) and 13 who had no evidence of disease at 109 months or longer (long-term survivors). The means of the 10 highest counts for each case were compared between the long- and short-term survivor groups. The mean +/- SD microvessel count was 25.4 +/- 6.5 for the short-term survivors and 30.3 +/- 6.4 for the long-term survivors. Median counts were 27.2 and 29.4, respectively. The distribution of microvessel counts was skewed toward higher counts in the long-term survivors. There was no correlation between microvessel counts and tumor site, size, or grade; lymphovascular invasion; or the presence of a mucinous component. Although there was a trend toward a higher frequency of microvessels in patients with longer survival, it is unlikely that microvessel count is an independent prognostic indicator for patients with T3 N0 M0 colorectal carcinoma because there is only a small difference in microvessel frequency between patients with widely different survival times.

Ultrastructural study of brain microvessels in patients with traumatic cerebral contusions.

Brain tissue from 11 patients with traumatic cerebral contusions submitted to surgery was studied. Control biopsy specimens were obtained from 5 patients undergoing ventriculo-peritoneal shunts for "communicating" hydrocephalus. After collection, the small fragments were fixed by immersion in glutaraldehyde-osmium and embedded in Epon. Semi-thin sections stained with toluidine blue were observed with the light microscope. Thin sections stained with lead citrate and uranyl acetate were observed using a Jeol electron microscope. In tissues from patients with head trauma a clear space most probably corresponding to fluid accumulation was systematically observed around microvessels. Ultrastructurally endothelial cells from these specimens exhibited signs of marked intracellular oedema, tight junctions being intact. Pinocytotic activity was increased, mainly at the abluminal surface. Swelling of astrocytic perivascular processes and the appearance of macrophagic cells with voluminous lysosomes were also observed. The authors conclude that the oedema of endothelial cells probably represent a central fact in the pathophysiology of traumatic brain oedema and speculate on the putative involvement of stretch-activated receptors in this condition.

Angiogenesis in head and neck tumor

To clarify the correlation between tumor angiogenesis and tumor growth in head and neck carcinomas, we investigated the number of microvessels, using immunohistochemical factor VIII. No correlations among this number, differences in the primary lesion, histological differentiation and T classification were detected. The incidence of neck lymph node metastases increased as microvessel numbers increased in tumor sites. The number of microvessels increased as N and Stage classification progressed. The number of microvessels in CR cases after induction chemotherapy were increased. The numbers of microvessels in patients without recurrence were apparently greater than those in patients with recurrence. The results of this study suggest that the number of microvessels in a primary tumor correlates with the metastatic ability of the tumor.