Home About us Contact
|
Home About us Contact | ||
|
|
||
New Blood Vessels (new + blood_vessel)
Selected AbstractsCell and molecular mechanisms of insulin-induced angiogenesisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 11-12 2009Yan Liu Abstract Angiogenesis, the development of new blood vessel from pre-existing vessels, is a key process in the formation of the granulation tissue during wound healing. The appropriate development of new blood vessels, along with their subsequent maturation and differentiation, establishes the foundation for functional wound neovasculature. We performed studies in vivo and used a variety of cellular and molecular approaches in vitro to show that insulin stimulates angiogenesis and to elucidate the signalling mechanisms by which this protein stimulates microvessel development. Mice skin injected with insulin shows longer vessels with more branches, along with increased numbers of associated ,-smooth muscle actin-expressing cells, suggesting the appropriate differentiation and maturation of the new vessels. We also found that insulin stimulates human microvascular endothelial cell migration and tube formation, and that these effects occur independently of VEGF/VEGFR signalling, but are dependent upon the insulin receptor itself. Downstream signalling pathways involve PI3K, Akt, sterol regulatory element-binding protein 1 (SREBP-1) and Rac1; inhibition of these pathways results in elimination of endothelial cell migration and tube formation and significantly decreases the development of microvessels. Our findings strongly suggest that insulin is a good candidate for the treatment of ischaemic wounds and other conditions in which blood vessel development is impaired. [source] Current methods for assaying angiogenesis in vitro and in vivoINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2004Carolyn A. Staton Summary Angiogenesis, the development of new blood vessels from an existing vasculature, is essential in normal developmental processes and in numerous pathologies, including diabetic retinopathy, psoriasis and tumour growth and metastases. One of the problems faced by angiogenesis researchers has been the difficulty of finding suitable methods for assessing the effects of regulators of the angiogenic response. The ideal assay would be reliable, technically straightforward, easily quantifiable and, most importantly, physiologically relevant. Here, we review the advantages and limitations of the principal assays in use, including those for the proliferation, migration and differentiation of endothelial cells in vitro, vessel outgrowth from organ cultures and in vivo assays such as sponge implantation, corneal, chamber, zebrafish, chick chorioallantoic membrane (CAM) and tumour angiogenesis models. [source] Modulation of angiogenesis is effective in a model of rheumatoid arthritisJOURNAL OF ANATOMY, Issue 5 2002A. O. Afuwape A feature of rheumatoid arthritis (RA) is prominent hyperplasia of the synovium, which results in an increased distance between the invasive pannus and the existing synovial vasculature. Concomitantly the hyperplastic tissue imposes an augmented metabolic demand on the pre-existing vasculature. As a consequence the synovium in RA becomes hypoxic, resulting in an increased rate of formation of new blood vessels, to supply nutrients and oxygen. Targeting the vasculature in RA is a potential therapeutic approach in RA. VEGF, a key vascular permeability and angiogenic factor, is expressed in RA. In this study we utilised adenovirus expressing the secreted form of the extracellular domain of the Flt-1 VEGF receptor (sFlt-1) to inhibit VEGF in the collagen-induced arthritis (CIA) model, to determine whether blocking the effects of vegf might be an effective treatment for RA. AdvsFlt-1, administered intravenously on the first day of arthritis, significantly suppressed CIA. For example, on d 6 of arthritis the mean increase in paw thickness, which reflects oedema, for untreated and null adenovirus-treated animals was 0.23 ± 0.05 mm and 0.38 ± 0.08, respectively, compared to 0.07 ± 0.05 for AdvsFlt-1-treated mice (P < 0.001 vs. Adv0-treated and untreated mice by 2-way anova). Western blot analyses revealed the presence of a 100-kDa band, corresponding to human sFlt-1, in liver extracts from arthritic mice infected with AdvsFlt-1 at 24 h but not 72 h after infection. This band was absent in liver extracts from Adv0-infected mice and all synovial extracts. Measurement of protein levels by ELISA demonstrated the presence of sFlt-1 in liver, synovium and serum, although levels declined by 72 h post infection. These data suggest efficient but transient expression of sFlt-1. Sera from adenovirus infected mice were found to contain antiviral antibodies and additionally, sera from AdvsFlt-1-infected but not Adv0-infected mice recognised human recombinant sFlt-1. These observations demonstrate that adenoviral mediated delivery of human sFlt-1 leads to transient gene expression and suppression of CIA. This effect is reduced later in the course of disease due to the expression of antiadenovirus as well as antisFlt-1 antibodies. Future studies will assess the effect of combination treatment, using AdvsFlt-1 together with anti-TNF(antibody, to prolong the beneficial effects of VEGF blockade. These results suggest that blocking the pro-angiogenic and permeability action of VEGF may be beneficial for treatment of RA. [source] Cell and molecular mechanisms of insulin-induced angiogenesisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 11-12 2009Yan Liu Abstract Angiogenesis, the development of new blood vessel from pre-existing vessels, is a key process in the formation of the granulation tissue during wound healing. The appropriate development of new blood vessels, along with their subsequent maturation and differentiation, establishes the foundation for functional wound neovasculature. We performed studies in vivo and used a variety of cellular and molecular approaches in vitro to show that insulin stimulates angiogenesis and to elucidate the signalling mechanisms by which this protein stimulates microvessel development. Mice skin injected with insulin shows longer vessels with more branches, along with increased numbers of associated ,-smooth muscle actin-expressing cells, suggesting the appropriate differentiation and maturation of the new vessels. We also found that insulin stimulates human microvascular endothelial cell migration and tube formation, and that these effects occur independently of VEGF/VEGFR signalling, but are dependent upon the insulin receptor itself. Downstream signalling pathways involve PI3K, Akt, sterol regulatory element-binding protein 1 (SREBP-1) and Rac1; inhibition of these pathways results in elimination of endothelial cell migration and tube formation and significantly decreases the development of microvessels. Our findings strongly suggest that insulin is a good candidate for the treatment of ischaemic wounds and other conditions in which blood vessel development is impaired. [source] Methylene blue inhibits angiogenesis in chick chorioallontic membrane through a nitric oxide-independent mechanismJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2006N. Zacharakis Abstract Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study was to evaluate the effect of methylene blue in chick chorioallantoic membrane angiogenesis model in vivo. In this well characterized model, methylene blue inhibited angiogenesis in a concentration-dependent manner. In addition, when methylene blue was combined with sodium nitroprusside, a spontaneous generator of nitric oxide, an inhibition of angiogenesis was evident which was comparable with that observed by the application of methylene blue alone. Sodium nitroprusside, alone, caused a significant inhibition in basal angiogenesis. These results provide evidence that methylene blue inhibits angiogenesis independently of nitric oxide pathway and suggest that methylene blue may be useful for treating angiogenesis-dependent human diseases. [source] Effect of cell-based VEGF gene therapy on healing of a segmental bone defectJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009Ru Li Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0,×,106 fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n,=,9); control groups were treated with fibroblasts (Group 2) (n,=,7), or saline (Group 3) (n,=,7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p,<,0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:8,14, 2009 [source] CYR61 (CCN1) Protein Expression during Fracture Healing in an Ovine Tibial Model and Its Relation to the Mechanical Fixation StabilityJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2006Jasmin Lienau Abstract The formation of new blood vessels is a prerequisite for bone healing. CYR61 (CCN1), an extracellular matrix-associated signaling protein, is a potent stimulator of angiogenesis and mesenchymal stem cell expansion and differentiation. A recent study showed that CYR61 is expressed during fracture healing and suggested that CYR61 plays a significant role in cartilage and bone formation. The hypothesis of the present study was that decreased fixation stability, which leads to a delay in healing, would lead to reduced CYR61 protein expression in fracture callus. The aim of the study was to quantitatively analyze CYR61 protein expression, vascularization, and tissue differentiation in the osteotomy gap and relate to the mechanical fixation stability during the course of healing. A mid-shaft osteotomy of the tibia was performed in two groups of sheep and stabilized with either a rigid or semirigid external fixator, each allowing different amounts of interfragmentary movement. The sheep were sacrificed at 2, 3, 6, and 9 weeks postoperatively. The tibiae were tested biomechanically and histological sections from the callus were analyzed immunohistochemically with regard to CYR61 protein expression and vascularization. Expression of CYR61 protein was upregulated at the early phase of fracture healing (2 weeks), decreasing over the healing time. Decreased fixation stability was associated with a reduced upregulation of the CYR61 protein expression and a reduced vascularization at 2 weeks leading to a slower healing. The maximum cartilage callus fraction in both groups was reached at 3 weeks. However, the semirigid fixator group showed a significantly lower CYR61 immunoreactivity in cartilage than the rigid fixator group at this time point. The fraction of cartilage in the semirigid fixator group was not replaced by bone as quickly as in the rigid fixator group leading to an inferior histological and mechanical callus quality at 6 weeks and therefore to a slower healing. The results supply further evidence that CYR61 may serve as an important regulator of bone healing. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Anti-angiogenic drugs: from bench to clinical trialsMEDICINAL RESEARCH REVIEWS, Issue 4 2006Ana R. Quesada Abstract Angiogenesis, the generation of new capillaries through a process of pre-existing microvessel sprouting, is under stringent control and normally occurs only during embryonic and post-embryonic development, reproductive cycle, and wound repair. However, in many pathological conditions (solid tumor progression, metastasis, diabetic retinopathy, hemangioma, arthritis, psoriasis and atherosclerosis among others), the disease appears to be associated with persistent upregulated angiogenesis. The development of specific anti-angiogenic agents arises as an attractive therapeutic approach for the treatment of cancer and other angiogenesis-dependent diseases. The formation of new blood vessels is a complex multi-step process. Endothelial cells resting in the parent vessels are activated by an angiogenic signal and stimulated to synthesize and release degradative enzymes allowing endothelial cells to migrate, proliferate and finally differentiate to give rise to capillary tubules. Any of these steps may be a potential target for pharmacological intervention. In spite of the disappointing results obtained initially in clinical trials with anti-angiogenic drugs, recent reports with positive results in phases II and III trials encourage expectations in their therapeutic potential. This review discusses the current approaches for the discovery of new compounds that inhibit angiogenesis, with emphasis on the clinical developmental status of anti-angiogenic drugs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 4, 483,530, 2006 [source] Myocardial Gene Expression of Angiogenic Factors in Human Chronic Ischemic Myocardium: Influence of Acute Ischemia/Cardioplegia and ReperfusionMICROCIRCULATION, Issue 3 2006YONGZHONG WANG ABSTRACT Objective: Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression. Methods: Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors. Results: There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium. Conclusion: These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium. [source] Chronic hypoxia-induced morphological and neurochemical changes in the carotid bodyMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2002Zun-Yi Wang Abstract The carotid body (CB) plays an important role in the control of ventilation. Type I cells in CB are considered to be the chemoreceptive element which detects the levels of PO2, PCO2, and [H+] in the arterial blood. These cells originate from the neural crest and appear to retain some neuronal properties. They are excitable and produce a number of neurochemicals. Some of these neurochemicals, such as dopamine and norepinephrine, are considered to be primarily inhibitory to CB function and others, such as adenosine triphosphate, acetylcholine, and endothelin, are thought to be primarily excitatory. Chronic hypoxia (CH) induces profound morphological as well as neurochemical changes in the CB. CH enlarges the size of CB and causes hypertrophy and mitosis of type I cells. Also, CH changes the vascular structure of CB, including inducing marked vasodilation and the growth of new blood vessels. Moreover, CH upregulates certain neurochemical systems within the CB, e.g., tyrosine hydroxylase and dopaminergic activity in type I cells. There is also evidence that CH induces neurochemical changes within the innervation of the CB, e.g., nitric oxide synthase. During CH the sensitivity of the CB chemoreceptors to hypoxia is increased but the mechanisms by which the many CH-induced structural and neurochemical changes affect the sensitivity of CB to hypoxia remains to be established. Microsc. Res. Tech. 59:168,177, 2002. © 2002 Wiley-Liss, Inc. [source] Vascular endothelial growth factor and the nervous systemNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2004A. Brockington Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascularization, but also in neuronal proliferation, and the growth of coordinated vascular and neuronal networks. After injury to the nervous system, activation of VEGF and its receptors may restore blood supply and promote neuronal survival and repair. There is a growing body of evidence that VEGF is essential for motor neurone survival, and that aberrant regulation of VEGF may play a role in the degeneration of neurones in diseases such as amyotrophic lateral sclerosis. [source] Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with malignant bone tumors,PEDIATRIC BLOOD & CANCER, Issue 6 2001Gerold Holzer MD Abstract Background Vascular endothelial growth factor (VEGF) is recognized as an important stimulator of angiogenesis. Formation of new blood vessels by angiogenic factors occurs in many biological processes, both physiological and pathological, among others in growth of primary solid malignant tumors and metastasis. This implies that the inhibition of angiogenic factors like VEGF would result in a suppression of tumor growth and metastasis formation. The aim of the present study was to compare preoperative serum VEGF levels of patients having malignant bone tumors with healthy controls to identify serum VEGF levels as a tumor marker. Procedure Blood sera from patients with high-grade osteosarcoma (n,=,17), chondrosarcoma (n,=,4) and Ewing sarcoma (n,=,6) were taken at the time of diagnosis before biopsy and compared with sera from 129 healthy persons. To measure VEGF levels in serum, a commercially available ELISA was used (Quantikine Human VEGF Immunoassay; R&D Systems). Results The observed geometric mean VEGF levels and 95% confidence intervals are 232.0 pg ml,1 (168.9,318.5) for patients with high-grade osteosarcoma, 325.5 pg ml,1 (169.3,625.8) for patients with chondrosarcoma, 484.3 pg ml,1 (284.0,826.0) for patients with Ewing sarcoma, as compared to 216.2 pg ml,1 (192.8,242.5) for healthy individuals. Conclusions While the sample means for the three groups of sarcoma patients were higher than the respective mean for the healthy controls, only the mean for the group with Ewing sarcoma is statistically significantly higher than the mean for the healthy controls. Despite the significant difference, VEGF levels are not suitable as a marker for Ewing sarcoma. Med. Pediatr. Oncol. 36:601,604, 2001. © 2001 Wiley-Liss, Inc. [source] Angiogenesis in Developing Follicle and Corpus LuteumREPRODUCTION IN DOMESTIC ANIMALS, Issue 4 2004C Tamanini Contents Angiogenesis is a process of vascular growth that is mainly limited to the reproductive system in healthy adult animals. The development of new blood vessels in the ovary is essential to guarantee the necessary supply of nutrients and hormones to promote follicular growth and corpus luteum formation. In developing follicles, the pre-existing endothelial cells that form the vascular network in the theca layer markedly develop in response to the stimulus of several growth factors, mainly produced by granulosa cells, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The angiogenic factors also promote vessel permeability, thus favouring the antrum formation and the events inducing follicle rupture. After ovulation, newly formed blood vessels cross the basement membrane between theca and granulosa layers and continue a rapid growth to sustain corpus luteum development and function. The length of luteal vascular growth varies in cycling and pregnant animals and among species; both angiogenesis and subsequent angioregression are finely regulated by systemic and local factors. The control of angiogenic development in the ovary could be a useful tool to improve animal reproductive performances. [source] Angiogenesis in skin aging and photoagingTHE JOURNAL OF DERMATOLOGY, Issue 9 2007Jin Ho CHUNG ABSTRACT Angiogenesis, the process of generating new blood vessels, is affected by various physiological and pathological conditions of skin. The skin aging process can be divided into intrinsic aging and photoaging. With aging, cutaneous blood vessels undergo pronounced alterations. A reduction of the cutaneous microvasculature has been observed in the skin of elderly individuals. Human skin is exposed daily to solar ultraviolet (UV) radiation, infrared rays and heat, and these stimuli are known to induce skin angiogenesis. Interestingly, although acute UV irradiation stimulates skin angiogenesis, cutaneous blood vessels are decreased in chronically photodamaged skin. The reason for the differential effects of acute and chronic UV exposure on skin angiogenesis remains to be elucidated. This review discusses the vascularization changes in intrinsically aged and photoaged human skin, the effects of UV irradiation, infrared rays and heat on skin angiogenesis, and the effects of topical retinoic acid treatment on UV-induced angiogenesis and cutaneous vascularity in aged and photoaged human skin. An understanding of the molecular mechanisms of aging- and photoaging-dependent changes of skin angiogenesis may provide us with new insights to prevent and treat the skin aging process. [source] Mapping pro- and antiangiogenic factors on the surface of prostasomes of normal and malignant cell originTHE PROSTATE, Issue 8 2010Adil A. Babiker Abstract BACKGROUND Angiogenesis is the formation of new blood vessels by capillary sprouting from pre-existing vessels. Tumor growth is angiogenesis-dependent and the formation of new blood vessels is associated with the increased expression of angiogenic factors. Prostasomes are secretory granules produced, stored and released by the glandular epithelial cells of the prostate. We investigated the expression of selected angiogenic and anti-angiogenic factors on the surface of prostasomes of different origins as well as the direct effect of prostasomes on angiogenesis. METHODS VEGF, endothelin-1, endostatin, and thrombospondin-1 were determined on prostasomes from seminal fluid and human prostate cancer cell lines (DU145,PC-3,LNCaP) using different immunochemical techniques. Human dermal microvascular endothelial cells were incubated with seminal and DU145 cell-prostasomes and with radioactive thymidine. The effect of prostasomes on angiogenesis was judged by measuring the uptake of labeled thymidine. The presence of any deleterious effects of prostasomes on the endothelial cells was investigated using thymidine assay and confocal laser microscopy. RESULTS VEGF and endothelin-1 were determined on malignant cell-prostasomes (no difference between cell lines) but not determined on seminal prostasomes. The same applies for the expression of endostatin but with much higher expression on malignant cell-prostasomes with obvious differences between them. Seminal and DU145 cell-prostasomes were found to have anti-angiogenic effect which was more expressed by DU145 cell-prostasomes. No deleterious effect of prostasomes on endothelial function was detected using either thymidine assay or microscopy. CONCLUSIONS Prostasomes contain pro- and anti-angiogenic factors that function to counteract each other unless the impact from one side exceeds the other to bring about dysequilibrium. Prostate 70: 834,847, 2010. © 2010 Wiley-Liss, Inc. [source] Angiogenesis and Interstitial Pressure in a Rat Tumour ModelANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005H. Hünigen Introduction and Aim:, Angiogenesis, the formation of new blood vessels, is a crucial process in physiological and pathological growth. Pathological angiogenesis is responsible for growth and metastasis of solid tumours, and, when blocked, improves prognosis. As a result of the angiogenic cascade in solid tumours an irregular, leaky capillary network develops. The aim of the present study was to define malignant tumours' vascular characteristics and reveal functional anatomy by quantification of the microvasculature and interstitial pressure (IP) in relation to tumour fluid dynamics as visualized by contrast enhanced magnetic resonance imaging (MRI). Material and Methods:, Dynamic MRI and measurement of the IP was performed in 21 rats implanted with colon carcinomas subcutaneously. Angiogenesis was studied by morphometry of the capillaries, and immunolocalization of the angiogenic factor VEGF and VEGF-Receptor 2. Results and Conclusions:, Histology, immunohistochemistry and MRI confirmed concentric arrangement of 4 tumour zones. The tumour margin included loose connective tissue with abundant mononuclear cells. Many large microvessels were seen in this most intensely vascularized zone. IP measurement in this zone was adjusted to the zero level. Diameter of the peripheral zone of vital cells measured 1.3 mm. Capillaries were smaller and sparse. Dynamic MRI revealed peripheral washout of the contrast agent in this zone. After an initial increase of the signal intensity a hypo-intense rim was formed within a few minutes. The intermediate region was characterized by islands of vital tumour cells containing 3% capillaries (hot spots). The innermost area, the necrotic zone, took 35% of the total tumour area with less than 0.5% vessels. The IP increased from the periphery to the centre. VEGF and VEGF-receptor 2 was found in the vessels of the tumour margin and vital tumour cells of the peripheral zone. From this can be concluded that the peripheral washout phenomenon seems to be correlated with elevated interstitial pressure and increased capillary density and therefore may be a reliable sign of malignancy. [source] Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissectionARTHRITIS & RHEUMATISM, Issue 4 2007Atsushi Hashimoto Objective In rheumatoid arthritis (RA), formation of new blood vessels is necessary to meet the nutritional and oxygen requirements of actively proliferating synovial tissue. The aim of this study was to analyze the specific synovial vascular expression profiles of several angiogenesis-related genes as well as CD82 in RA compared with osteoarthritis (OA), using laser-mediated microdissection (LMM). Methods LMM and subsequent real-time polymerase chain reaction were used in combination with immunohistochemical analysis for area-specific analysis of messenger RNA (mRNA) and protein expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1), VEGFR-2, hypoxia-inducible factor 1, (HIF-1,), HIF-2,, platelet-derived growth factor receptor , (PDGFR,), PDGFR,, inhibitor of DNA binding/differentiation 2 (Id2), and CD82 in RA and OA synovial microvasculature and synovial lining. Results Expression of Id2 mRNA was significantly lower in RA synovial vessels compared with OA synovial vessels (P = 0.0011), whereas expression of VEGFR-1 was significantly higher in RA (P = 0.0433). No differences were observed for the other parameters. At the protein level, no statistically significant differences were observed for any parameter, although Id2 levels were 2.5-fold lower in RA (P = 0.0952). However, the number of synovial blood vessels and the number of VEGFR-2,expressing blood vessels were significantly higher in RA compared with OA. Conclusion Our results underscore the importance of area-specific gene expression analysis in studying the pathogenesis of RA and support LMM as a robust tool for this purpose. Of note, our results indicate that previously described differences between RA and OA in the expression of angiogenic molecules are attributable to higher total numbers of synovial and vascular cells expressing these molecules in RA rather than higher expression levels in the individual cells. [source] A phase 2 pilot trial of low-dose, continuous infusion, or "metronomic" paclitaxel and oral celecoxib in patients with metastatic melanomaCANCER, Issue 7 2010Rupal S. Bhatt MD Abstract BACKGROUND: Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX-2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM. METHODS: Patients received paclitaxel 10 mg/m2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6-week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study. RESULTS: Twenty patients were enrolled. Twelve of 20 patients (60%) had received ,2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment-related grade 3/4 toxicities were limited to catheter-related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43-151 days), and the median overall survival was 212 days (95% confidence interval, 147-811 days). CONCLUSIONS: Low-dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society. [source] Role of hematopoietic lineage cells as accessory components in blood vessel formationCANCER SCIENCE, Issue 7 2006Nobuyuki Takakura In adults, the vasculature is normally quiescent, due to the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. However, blood vessels in adults retain the capacity for brisk initiation of angiogenesis, the growth of new vessels from pre-existing vessels, during tissue repair and in numerous diseases, including inflammation and cancer. Because of the role of angiogenesis in tumor growth, many new cancer therapies are being conducted against tumor angiogenesis. It is thought that these anti-angiogenic therapies destroy the tumor vessels, thereby depriving the tumor of oxygen and nutrients. Therefore, a better understanding of the molecular mechanisms in the process of sprouting angiogenesis may lead to more effective therapies not only for cancer but also for diseases involving abnormal vasculature. It is widely believed that after birth, endothelial cells (EC) in new blood vessels are derived from resident EC of pre-existing vessels. However, evidence is now emerging that cells derived from the bone marrow may also contribute to postnatal angiogenesis. Most studies have focused initially on the contribution of endothelial progenitor cells in this process. However, we have proposed a concept in which cells of the hematopoietic lineage are mobilized and then entrapped in peripheral tissues, where they function as accessory cells that promote the sprouting of resident EC by releasing angiogenic signals. Most recently we found that hematopoietic cells play major roles in tumor angiogenesis by initiating sprouting angiogenesis and also in maturation of blood vessels in the fibrous cap of tumors. Therefore, manipulating these entrapment signals may offer therapeutic opportunities to stimulate or inhibit angiogenesis. (Cancer Sci 2006; 97: 568,574) [source] | |||||||||||||