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Results for “Neovascularization, Pathologic”

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PubMed2000

Increased cellularity of tumor-encased native vessels in prostate carcinoma is a marker for tumor progression.

Changes in the native vasculature of the prostate gland associated with prostate adenocarcinoma have not been well characterized. Eighty-nine whole mounts of entirely submitted radical prostatectomies were reviewed. Thirty prostates with a minimum of five native arteries surrounded by carcinoma with corresponding control arteries were found and included in this study. The number of nuclei in the media of native arteries was recorded per 0.138 mm2 using a 40x objective. The number of nuclei in vessels embedded in carcinoma (n = 204) was increased when compared with controls (26.37 versus 20.58 mean nuclei per 0.138 mm2; P < .001). Pathologic Stage T3 carcinomas contained vessels that were more cellular than stage T2 (P < .001). Vessels embedded in Gleason Grade 4 showed more cellularity than arteries embedded in Gleason Grade 3 (P < .002). Increased media cellularity of native prostate vessels encased in carcinoma is a histologic feature of higher grade/stage prostate carcinoma and provides positive indicator of advanced prostate cancer.

Adenocarcinoma↗

PubMed1994

Angiogenesis and endothelial cell function.

Endothelial cell growth is tightly regulated. During embryonic development endothelial cells rapidly proliferate thereby forming new blood vessels. Two different mechanisms contribute to the development of the vascular system: vasculogenesis, the development of blood vessels from in situ differentiating endothelial cells, and angiogenesis, the formation of capillaries from preexisting vessels. In the adult, endothelial cell turnover is very low but under a variety of pathological conditions such as tumor growth these cells quickly enter the cell cycle and divide. Vascular endothelial growth factor (VEGF) has been identified as a key regulatory paracrine growth factor for endothelial cells. Transient VEGF expression correlates with embryonic and tumor angiogenesis. On the other hand, constitutive expression of this factor in choroid plexus and kidney glomerular epithelium and its cognate receptors in adjacent fenestrated endothelium suggests a role for this ligand-receptor system in organotypic endothelial cell differentiation and capillary permeability of fenestrated endothelium.

Animals↗

PubMed2000

The effect of age on inflammatory responses and nerve root injuries after lumbar disc herniation: an experimental study in a canine model.

STUDY DESIGN: An experimental investigation on the effect of age on pathologic events surrounding the herniated disc and at the adjacent nerve root. OBJECTIVES: To investigate the role of age on the inflammatory responses and nerve root damage surrounding a sequestered lumbar disc fragment using a dog model. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation is manifested in patients by variable clinical findings, natural history, and resorption phenomena in which the variability is particularly noted among patients with different ages. There are no previous reports on the effect of age on pathologic events induced by the herniated disc. METHODS: Six beagle dogs, including two animals of each age group of 6, 12, and 24 months (human equivalent ages of 10, 15, and 24 years), were used in this study. The dogs underwent L4-L5, L5-L6, and L6-L7 laminotomy and discectomy under general anesthesia. An autologous intervertebral disc from the tail was divided into anulus fibrosus and nucleus pulposus fragments. The anulus fibrosus and nucleus pulposus fragments were placed in the anterolateral epidural space of L5-L6 and L6-L7, respectively. The L4-L5 discectomy site served as a control. Dogs were killed at 12 weeks after surgery. The lumbar spine was removed en bloc, and histologic sections were prepared consecutively and examined. RESULTS: In the nucleus pulposus group at L6-L7, neovascularity, and intensive infiltration of lymphocytes, macrophages, and fibroblasts were observed surrounding the nucleus pulposus fragment in the 24-month-old group only. Degenerative changes of the nerve root fibers were observed in the 24-month-old group only. In the control and anulus fibrosus groups at L4-L5 and L5-L6, there were no marked inflammatory reactions in all age groups. The nerve root fibers around the anulus fibrosus were normal in all age groups. CONCLUSIONS: There is an effect of age on the inflammatory response and nerve root injury caused by the herniated disc. The apparent neuroprotective mechanism in the young animal, and the apparent inflammatory and resorption changes of the nucleus pulposus fragment in the older animal are quite intriguing.

Aging↗

PubMed1999

Vascularity index as a novel parameter for the in vivo assessment of angiogenesis in patients with cervical carcinoma.

BACKGROUND: The importance of angiogenesis now is well recognized. Conventionally, tumor angiogenesis is assessed by determination of microvessel density (MVD) in the surgical specimen. This study examines tumor angiogenesis using power Doppler ultrasound and a quantitative image processing system. The authors hope to develop an in vivo and noninvasive method for quantitating tumor angiogenesis. METHODS: Thirty-five patients with FIGO Stage IB-IIA cervical carcinoma exhibiting visible cervical tumors by transvaginal ultrasound were included in this study. All patients underwent radical abdominal hysterectomy and pelvic lymph node dissection. Transvaginal power Doppler ultrasound was performed before surgery to search for blood flow signals from the tumor. The intratumoral vascularity index (VI) and resistance index (RI) were calculated. The VI was defined as the number of colored pixels divided by the number of total pixels in the defined tumor section. Maximal VI and minimal RI of a certain tumor were used for analysis. Clinical and pathologic data also were recorded. The MVD of the excised tumor was assessed immunohistochemically using a monoclonal antibody against CD34. RESULTS: Significantly higher VI values were noted in Stage II tumors compared with Stage 1 tumors (19.01+/-10.90% vs. 9.09+/-6.59%; P = 0.008), tumors invad-ing+/-50% of the cervical stroma compared with tumors invading < 50% of the cervical stroma (13.20+/-8.20% vs. 5.72+/-5.00%; P = 0.003), tumors with lymphovascular emboli compared with tumors without lymphovascular emboli (17.28+/-8.26% vs. 6.98 +/- 5.09%; P = 0.001), and tumors with pelvic lymph node metastases compared with tumors without pelvic lymph node metastases (26.16+/-7.88% vs. 8.00+/-4.95%; P = 0.021). None of the variables mentioned earlier showed a significant difference in terms of the RI values. No correlation was noted between intratumoral RI and VI in respective tumors (P = 0.53). Analysis of VI revealed linear regression with regard to tumor size (P < 0.001, correlation coefficient [r] = 0.586) and depth of stromal invasion (P = 0.002, r = 0.497). In addition, the MVD exhibited a linear relation with VI (P = 0.006, r = 0.454), tumor size (P = 0.005, r = 0.465), and depth of stromal invasion (P = 0.009, r = 0.436) using simple regression analysis. No correlation could be found between MVD and RI. CONCLUSIONS: In cervical carcinoma, intratumoral VI assessment by power Doppler ultrasound and quantitative image processing system showed better correlation with tumor stage, tumor size, and pathologic findings including depth of stromal invasion, lymphovascular emboli, and pelvic lymph node metastases than intratumoral RI. The in vivo indicator of angiogenic activity (VI) is well correlated with the conventional indicator of tumor angiogenic activity (MVD). Thus, VI could be a useful parameter for the in vivo assessment of global tumor angiogenesis.

Adenocarcinoma↗

PubMed2001

Protection against ischemia: a physiological function of the renin-angiotensin system.

The renin-angiotensin system (RAS) is involved in a complex mechanism that serves to preserve the blood supply to organs so that they can maintain cellular function. Angiotensin II exerts this effect, independently of the blood pressure generated, through two time-related events: a fast opening of the reserve collateral circulation and a much slower response of new vessel formation or angiogenesis. This effect is observed in rats with ligation of the abdominal aorta and in gerbils with abrupt or progressive unilateral carotid artery ligation. Inhibition of the angiotensin-converting enzyme (ACE) or the angiotensin II receptor represses this effect, and it appears that it is mediated through a non-AT1 receptor site of angiotensin II. Many tumors, both benign and malignant, express renin and angiotensin. It seems that the stimulating action of angiotensin II on angiogenesis could also be involved in preserving the blood supply to tumor cells. Administration of converting enzyme inhibitors increases survival and decreases tumor size in tumor-bearing rats. These observations support the hypothesis that the RAS, directly or indirectly, is involved in situations in which the restoration of blood supply is critical for the viability of cells and that it is present not only in normal but also in pathological conditions such as tumors. In view of the ubiquitous presence of renins and angiotensins, it is also likely to be involved in other conditions, such as inflammation, arthritis, diabetic retinopathy, and retrolental fibroplasia, among others in which angiogenesis is prominent. In addition, angiotensin II could be involved, through the counterbalance of the AT1 and AT2 receptors, in the rarefaction of blood vessels as an etiologic component of essential hypertension.

Angiogenesis Inducing Agents↗

PubMed2002

Drug targeting to specific vascular sites.

The blood vessels of individual tissues are biochemically distinct, and pathological lesions put their own signature on the vasculature. In tumors, both blood and lymphatic vessels differ from normal vessels. New methods, such as in vivo screening of phage libraries, have provided peptides and antibodies that recognize these vascular signatures and can be used in targeted delivery of therapeutic agents. Targeting a therapy to the diseased tissue enhances the efficacy of the treatment while reducing the side effects in mouse experiments. Results from drug delivery to tumor vessels have been particularly encouraging.

Animals↗

PubMed2007

Medical treatment of diabetic retinopathy with somatostatin analogues.

Traditional management strategies for retinal neovascularisation accompanying proliferative diabetic retinopathy include photocoagulation laser therapy. The development of preventative pharmacological treatments aimed at replacing or delaying this acute intervention has been an active research area and somatostatin analogues have shown promise in reducing the progression of retinal vascular pathologies. This review summarises the present knowledge on the molecular and cellular mechanisms of neovascularisation, and the rationale for the therapeutic use of somatostatin analogues as well as the results of two key recent clinical trials using octreotide. The potential use of octreotide and other somatostatin analogues in reducing the risk of severe visual impairment in proliferative diabetic retinopathy is discussed and pharmacological treatment regimens are proposed as an additional strategy or a less invasive alternative to laser therapy.

Animals↗

PubMed1986

Angiogenesis in reproductive tissues.

Angiogenesis is the process of generating new capillaries and leads, therefore, to vascularization of tissues. This process occurs during embryological development and during pathological and physiological conditions in adult life, including those involving the reproductive organs. Recent studies, in the field of tumour biology in particular, have led to the identification of several factors responsible for inducing angiogenesis and the elucidation of ways of modulating their activity. This review summarizes our knowledge of angiogenesis in the ovary, testis, endometrium and placenta, and suggests ways in which further research might contribute to a better understanding of the processes controlling reproduction and identify new approaches to the regulation of fertility.

Endometrium↗

PubMedDate not supplied

Serum endostatin levels in gastric cancer patients: correlation with clinicopathological parameters.

BACKGROUND/AIMS: The aim of this study was to evaluate the predictive role of the circulating levels of endostatin in gastric cancer patients. METHODOLOGY: This study is a retrospective case-control study. We measured serum endostatin levels of 30 patients aged between 34-83 years with gastric cancer and 30 patients without malignant pathology operated for benign pathologies with age ranging from 18 to 69. RESULTS: Serum levels of endostatin were correlated with the Lauren classification. Significantly higher serum endostatin levels were obtained in Lauren intestinal type tumors than Lauren diffuse type tumors. CONCLUSIONS: These data suggest that serum endostatin levels do not correlate with clinicopathological parameters, except tumor histopathology (according to Lauren classification), in gastric cancer patients.

Adult↗

PubMed2006

JUN siRNA regulates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularisation.

Transcription factors link changes in the extracellular environment with alterations in gene expression. As such, these molecules serve as attractive targets for intervention in pathological settings. Since JUN has been linked with microvascular disease in humans, we hypothesised that small interfering RNA (siRNA) targeting this immediate-early gene may be useful agents that suppress endothelial growth and neovascularisation. Here we show that Jun siRNA inhibits Jun mRNA and protein expression in murine microvascular endothelial cells, blocks cell proliferation and suppresses migration in a scratch-wound assay. It also inhibits three-dimensional tubular formation on basement membrane extracts and reduces angiogenesis in mice bearing Matrigel plugs as subcutaneous implants. Single intravitreal administration of Jun siRNA reduces neovascularisation in a murine model of proliferative retinopathy, and suppresses endothelial JUN and matrix metalloproteinase-2 (MMP-2) immunoreactivity in retinal vessels, data supported by its repression of MMP-2 expression and gelatinolytic activity in vitro. Co-administration of TGFbeta with the siRNA reverses this neovascular inhibitory effect, which is in turn abrogated by cis-9-octadecenoyl-N-hydroxylamide, consistent with the involvement of a metalloproteinase such as MMP-2. Thus, JUN siRNA can serve as a specific inhibitor of aberrant endothelial and neovascular growth.

Animals↗

PubMed2000

Human peritoneal adhesions are highly cellular, innervated, and vascularized.

Peritoneal adhesions are a major complication of healing following surgery or infection and can lead to conditions such as intestinal obstruction, infertility, and chronic pain. Mature adhesions are the result of aberrant peritoneal healing and historically have been thought to consist of non-functional scar tissue. The aim of the present study was to analyse the cellular composition, vascularity, and extracellular matrix distribution of human peritoneal adhesions, to determine whether adhesions represent redundant scar tissue or are dynamic regenerating structures. Furthermore, the histological appearance of each adhesion was correlated with the clinical history of the patient, to determine whether maturity or intraperitoneal pathology influences adhesion structure. Human peritoneal adhesions were collected from 29 patients undergoing laparotomy for various conditions and were prepared for histology, immunocytochemistry, and transmission electron microscopy. All adhesions were highly vascularized, containing well-developed arterioles, venules, and capillaries. Nerve fibres, with both myelinated and non-myelinated axons, were present in adhesions from nearly two-thirds of the patients, with increased incidence in those with a malignancy. Approximately one-third of the adhesions contained conspicuous smooth muscle cell clusters lined by collagen fibres of heterogeneous size. Adipose tissue was a consistent feature of all the adhesions, with some areas displaying fibrosis. There appeared to be no correlation between the estimated maturity or site of each adhesion and its histological appearance. However, intraperitoneal pathology at the time of surgery did influence the incidence of some histological features, such as the presence of nerve fibres, clusters of smooth muscle cells, and inflammation. This study challenges previous concepts that adhesions represent non-functional scar tissue and clearly demonstrates that established adhesions are highly cellular, vascularized, and innervated, features more consistent with dynamic, regenerating structures.

Adult↗

PubMed2005

Morphological changes in the Royal College of Surgeons rat retina during photoreceptor degeneration and after cell-based therapy.

There are concomitant morphological and functional changes in the inner retina during the course of photoreceptor degeneration in a range of animal models of retina degeneration and in humans with eye disease. One concern that has been raised is that the changes occurring in the inner retina might compromise attempts to rescue or restore visual input by various interventional approaches. It is known that cell-based therapy can preserve significant visual capability for many months. In this study, we examine the overall changes in the Royal College of Surgeons (RCS) rat during degeneration and the effects of cell transplantation by means of immunohistochemistry and confocal microscopy. The degenerative changes are complex, and they progress with age. They involve the neurons with which both rods and cones interconnect--retinal second- and third-order neurons underwent dramatic modification, including sprouting, retraction as photoreceptor loss progressed--as well as Müller glia and secondary vascular changes, which were associated at later times with neuronal migration. The pathological vascular changes led to major disruption of inner retina. After introducing a retinal pigment epithelial cell line to the subretinal space early in the progress of photoreceptor degeneration, most inner retinal changes were held in abeyance for up to at least 10 months of age. Given the concern that has been raised regarding whether inner retinal changes might compromise any graft-related benefit, this is an encouraging finding.

Animals↗

PubMed2004

Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases.

The recent landmark Phase III clinical trial with a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Here we show that VEGFR2 blockade creates a "normalization window"--a period during which combined radiation therapy gives the best outcome. This window is characterized by an increase in tumor oxygenation, which is known to enhance radiation response. During the normalization window, but not before or after it, VEGFR2 blockade increases pericyte coverage of brain tumor vessels via upregulation of Ang1 and degrades their pathologically thick basement membrane via MMP activation.

Angiogenesis Inhibitors↗

PubMed2001

[Genetic factors related to intracranial arteriovenous malformations].

Genetic studies are interesting not only in the diagnosis and screening of new cases within a family harboring a particular disease, but also in understanding the underlying genetic and molecular factors related to that disease. Such studies revealed 3 categories of cerebral arteriovenous malformations in relationship to possible genetic factors. The first one concerns cerebral arteriovenous malformations in relationship to inherited diseases where a genetic support is clearly identified. Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) represents the most classical picture. The second category corresponds to familial cases of cerebral arteriovenous malformations were several members and relatives of the same family harboring the pathology without clear demonstration of any genetic basis. The third category includes cerebral arteriovenous malformations described in association with neurocutaneous disorders issued from maldevelopment events. Sturge-Weber disease and Wyburn-Mason syndrome best illustrate this category. A review of these categories will help in a better understanding of some genetic issues related to cerebral arteriovenous malformations.

Abnormalities, Multiple↗

PubMedDate not supplied

A pilot study with long term follow up of hyperbaric oxygen pretreatment in patients with locally advanced breast cancer undergoing neo-adjuvant chemotherapy.

Work in an animal cancer model suggests that pretreatment with hyperbaric oxygen can improve tumor vascularity rendering chemotherapy more effective. Accordingly 32 subjects with locally advanced breast carcinoma (>5cm diameter) entered into a randomized clinical trial where a course was administered of six intravenous pulses of cyclophosphamide 1000mg/m2 i.v., doxorubicin 50mg/m2 i.v. and vincristine 1.5mg/m2 i.v. In the case group this was preceded by ten, once daily, sessions of hyperbaric oxygen therapy (HBO2) administered either at 2.4 or 2.0 atmospheres absolute. Eleven out of 15 subjects tolerated a full course of HBO2 and chemotherapy. All 17 control subjects tolerated a full course of chemotherapy. Tumor extravascular extracellular or edema fluid was reduced after HBO2 but there was no reduction in tumor cell volume and no indication of increased vascularity on MRI. Clinical and pathological responses to chemotherapy were the same in both groups and there was no evidence of neovascularisation. Five year survival in those who tolerated the trial regime was 73% and did not differ between the groups. This mortality was cancer related.

Adult↗

PubMed2006

Cellular and molecular imaging with targeted contrast ultrasound.

There is growing interest in the availability of methods for imaging disease at the level of the cellular and/or molecular mediators. Techniques for imaging molecular alterations have been develop for essentially all non-invasive cardiac imaging modalities. Molecular imaging with contrast-enhanced ultrasound relies on the detection of novel site-targeted contrast agents. These microbubbles or nanoparticles are retained within regions of a specific disease process, thereby allowing phenotypic characterization of tissue. Since most of these tracers remain within the intravascular space, the disease processes assessed must be characterized by antigens that are expressed within the vascular compartment. Accordingly, the pathologic states that have been targeted include inflammation, ischemia-and tumor-related angiogenesis, and thrombus formation; all of which are mediated in part by molecular events within the vascular space. This review describes: 10 different strategies that have been employed to target ultrasound contrast agents to regions of disease, 2) the unique challenges for imaging targeted ultrasound contrast agents, and 3) some of the early experience imaging molecular events in animal models of disease.

Animals↗

PubMed1994

Effect of platelet activating factor (PAF) on the formation of blood vessels in subcutaneous implants in mice.

Angiogenesis accompanies inflammatory processes and many other pathological conditions. We have studied the effect of platelet-activating factor (PAF) a well-known inflammatory mediator, as a promoter of angiogenesis in the sponge implant model in mice. Development of blood vessels and blood flow were monitored by use of a 133Xe washout technique. The results showed PAF to have angiogenic activity, which was inhibited by WEB 2086, and the PAF-induced vasculature to have normal pharmacological reactivity.

Angiotensin II↗

PubMed1997

Microvascular pathology in the skeletal muscle paraneoplastic phenomenon.

An electron microscopic investigation was made in order to study capillary alterations in the muscle paraneoplastic phenomenon associated with different malignant tumours. Several abnormalities were found including basement membrane widening and lamination, endothelial hypertrophy, a varied degree of lumen occlusion, and proliferative changes in pericytes. A degenerative process leading to capillary necrosis was also observed. A mononuclear cell infiltrate formed by macrophages, lymphocytes and mast cells was seen. The capillary changes observed suggest the existence of an autoimmune vascular factor in the etiopathogenesis of muscle damage in this phenomenon.

Capillaries↗