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Enhancing effect of X-ray irradiation on a new blood vessel formation in mice tested by lymphocyte induced angiogenesis assay.

X-irradiation enhanced a new blood vessel formation occurring in the course of a local GvH reaction in mice. Maximal enhancing effect was exerted by single total body irradiation doses ranging from 700 to 1050 R. Fractionation in daily doses smaller than 200 R did not exhibit enhancing effect. Proliferative ability of angiogenesis inducing cells is not necessary for enhancing effect of irradiation.

Angiogenesis Inducing Agents

Melanoma. Tumor angiogenesis and human neoplasia.

Transparent hamster-cheek-pouch chambers were used to document angiogenesis induced by implants of human malignant melanoma. Capillary proliferation was observed with direct implantation of melanoma fragments and with tumor implants place on microporous membrane filters. The pattern of capillary neovascularization was recorded and correlated with clinical and histopathologic parameters.

Animals

RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.

The number of total joint replacements (TJRs) in the United States is increasing annually. Cementless implants are intended to improve upon traditional cemented implants by allowing bone growth directly on the surface to improve implant longevity. One major complication of TJR is implant loosening, which is related to deficient osseointegration in cementless TJRs. Although poor osseointegration in aged patients is typically attributed to decreased basal bone mass, little is known about the molecular pathways that compromise the growth of bone onto porous titanium implants. To identify the pathways important for osseointegration that are compromised by aging, we developed an approach for transcriptomic profiling of peri-implant tissue in young and aged mice using our murine model of osseointegration. Based on previous findings of changes of bone quality associated with aging, we hypothesized that aged mice have impaired activation of bone anabolic pathways at the bone-implant interface. We found that pathways most significantly downregulated in aged mice relative to young mice are related to angiogenic, Notch, and Wnt signaling. Downregulation of these pathways is associated with markedly increased expression of inflammatory and immune genes at the bone-implant interface in aged mice. These results identify osseointegration pathways affected by aging and suggest that an increased inflammatory response in aged mice may compromise peri-implant bone healing. Targeting the Notch and Wnt pathways, promoting angiogenesis, or modulating the immune response at the peri-implant site may enhance osseointegration and improve the outcome of joint replacement in older patients. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

AGING

Phosphoproteomic Profiling of Early-Stage Non-Small Cell Lung Cancer Provides Preliminary Evidence of Phosphorylation-Regulated Rho GTPase Signaling Driving Cytoskeletal Remodeling, Angiogenesis, and Cell Cycle Progression.

Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related deaths worldwide. This can be attributed to the difficulty in early detection and the limited efficacy of available treatments, partly due to an incomplete understanding of the disease biology. Identification of key proteins involved in early-stage progression and understanding the underlying mechanisms can greatly contribute to the development of diagnostic and treatment strategies for NSCLC. Quantitative phosphoproteomic analysis was done on paired tumor tissues and adjacent normal lung tissues from early-stage NSCLC adenocarcinoma (LUAD) patients to allow for the identification of proteins with differential phosphorylation and their associated pathways. A total of 6483 phosphoproteins were identified, with 1229 proteins having significantly higher phosphorylation and 701 proteins having significantly lower phosphorylation in the tumor tissues. All MS data were deposited in ProteomeXchange with the identifier PXD071583. Function enrichment analysis showed that the differentially phosphorylated proteins and phosphosites were primarily involved in Rho GTPase signaling and cytoskeleton remodeling. Analysis of protein interaction networks suggests that the predicted kinase activity likely drives malignant transformation in NSCLC LUAD, presumably through Rho GTPase-mediated angiogenesis and cell cycle progression. More importantly, this study identified several protein phosphosites with differential phosphorylation and inferred kinase-phosphosite activities that have not previously been reported in NSCLC LUAD.

Humans

Inhibition of tumor angiogenesis mediated by cartilage.

Capillary proliferation induced by tumor is shown to be inhibited by neonatal scapular cartilage. Using the rabbit cornea as an assay, the cartilage implant decreased the rate of capillary growth, induced by tumor, by an average of 75%. Vascularization was prevented completely in 28% of tumors. The inhibitory effect of small cartilage implants operates over distances of up to 2.0 mm and displays a gradient from the cartilage source. The experiments suggest that the cartilage inhibitor does not antagonize tumor angiogenesis factor, but appears to inhibit capillary proliferation directly. The inhibitory material does not elicit an inflammatory response in either the rabbit cornea or in the chick chorioallantoic membrane. Thus with further purification, it may prove useful as a means of maintining tumor dormancy by "antiangiogenesis."

Animals

Angiogenesis in the mouse cornea.

We have developed a method that permits analysis of neovascular responses in the mouse cornea. Using this method we have demonstrated that both allogeneic lymphocytes and a variety of tumors can induce angiogenesis, but that only the latter appear capable of eliciting secondary capillary sprouting.

Animals

Local graft-versus-host reaction in mice evoked by Peyer's patch and other lymphoid tissue cells tested in a lymphocyte-induced angiogenesis assay.

The competence of murine Peyer's patch cells to evoke a local GVH reaction was compared with that displayed by lymphoid cells of spleen, lymph nodes, thymus, bone marrow, peritoneal cavity and peripheral blood. The local GVH reaction was assessed in a lymphocyte-induced angiogenesis assay in which an intradermal injection of lymphoid cells results in a new blood vessel formation at the injection site, and the number of vessels corresponds to the number of the immunocompetent cells injected. Peyer's patch cells were capable of mounting a local GVH reaction of intensity comparable to that evoked by the corresponding number of thymus cells or a four times lower number of spleen cells. The highest activity was exhibited by lymph node and peripheral blood cells while bone marrow cells were the least active. A striking increase in angiogenic response was observed after X-irradiation of the recipients with 700R.

Animals

A spectrum of cutaneous angiogenesis.

A spectrum of cutaneous angiogenesis was observed ranging from normal epidermis to hyperproliferative-but-benign psoriatic epidermis to wildly proliferating neoplastic epidermis. This spectrum of vascular response appears to parallel the metabolic and mitotic activity of the tissues studied.

Animals

Nature of the stimulus leading to lymphocyte-induced angiogenesis.

Experiments are described that characterize the nature of the stimulus leading to lymphocyte-induced angiogenesis (LIA), a reaction previously shown to reflect a local in vivo graft-vs-host reaction. The studies demonstrate that circulating cells of the host animal provide the stimulation essential for activation of donor lymphocytes and that the major allogeneic stimulus in congenic lines of mice is correlated with I-region disparity, primarily associated with IA-controlled determinants. The results are readily compatible with the hypothesis that is proposed that LIA is in large part of the consequence of the release of soluble mediators or lymphokines that may act either directly on endothelial cells or indirectly by activating macrophages, which in turn generate the vascular reaction.

Animals

Perineural angiogenesis in mice bearing subcutaneous tumours.

Cells of myeloma or fibrosarcoma were inoculated s.c. into BALB/c mice. Intact skins and tissue sections from animals killed at periodic intervals after inoculation of tumor cells were examined macroscopically and microscopically. The development of new blood vessels, probably involved in vascularization of the tumor, was observed around the nerves adjacent to the deposit of tumour cells. This occurred 5 days after inoculation of cells and before the tumour had a mean diameter of less than 1 mm. Lesser degrees of "perineural angiogenesis" were noted after s.c. inoculation of mineral oil, Freund's complete adjuvant or implantation of intact spleen, but none was observed with killed tumour cells.

Animals

Demonstration of angiogenesis-activity in the corpus luteum of cattle.

The angiogenetic potency of corpus luteum tissue and of extracts of it was tested in three different biological model systems: the chorioallantoic membrane of the chicken (CMA), the ventral subcutaneous pouch of the mouse and the cheeck pouch of the Syrian hamster. The formation of new capillaries after transplantation of the materials was scored macroscopically and stereomicroscopically. In all three systems strong capillary reactions at the periphery of the transplants could be observed indicating the presence of a capillary inducing potency in the tissue of corpus luteum of the cattle.

Angiogenesis Inducing Agents

Angiogenesis of cervical neoplasia.

Recent studies concerning the role of an angiogenic factor in cancer have produced a renewed interest in vascular studies of the cervix. Colposcopic and histochemical vascular studies demonstrate changes in the vascular pattern of cervical neoplasia which progress from early dysplasia to carcinoma in situ. There is a restructuring of the terminal vascular network of the pre-existing columnar epithelium in noninvasive cervical neoplasia which is caused by compression of the capillaries by the epithelial proliferation. In contrast, neovascularization is observed in those cases of carcinoma in situ which will progress to invasive cancer. The position is taken that this process of neovascularization, which is recognized by the development of horizontal vessels, may be the direct effect of an angiogenic factor. Evidence is also presented that the initial vascular changes may precede the histopathologic criteria of cervical neoplasia.

Angiogenesis Inducing Agents