bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1294: Inhibition of angiogenesis in lymph node metastasis
Authors: Aki Ryoichi , Amoh Yasuyuki , Kishimoto Hiroyuki , Kimura Hiroaki , Suetsugu Atsushi , Momiyama Masashi , Katsuoka Kensei , Hoffman Robert M. 
Published: February 2011

Abstract
Cancer invasion of the lymphatic system and spread to draining lymph nodes is a common occurrence and is often a first step of the metastatic pathway. Suppression of tumor angiogenesis in the lymph node should inhibit cancer growth and further spread from the lymph node. In the present study, we evaluated angiogenesis inhibitors in lymph node metastasis using GFP imaging. Transgenic nude mice expressing GFP under the control of the nestin promoter (ND-GFP mice) were used as hosts. Nascent blood vessels express GFP in these mice (Cancer Res. 65, 5352-5357, 2005). B16F10-RFP mouse melanoma cells were injected into the efferent lymph vessel of the inguinal lymph node of the transgenic ND-GFP nude mice to establish experimental metastasis in the axillary lymph node. The mice were given daily i.p. injections of doxorubicin or vehicle controls at days 0, 1, and 2 after implantation of tumor cells. The axillary lymph nodes of the mice were observed at day 8 after injection of tumor cells. Angiogenesis was quantified in the tumor-involved lymph node by measuring the total length of ND-GFP nascent blood vessels. The number of ND-GFP-expressing blood vessels in the tumor-involved lymph nodes was significantly less in the doxorubicin-treated animals than in vehicle control mice. Treatment with doxorubicin significantly decreased the volume of the metastatic axillary-node tumor as well as nascent blood vessel formation. These results show the utility of the dual-color ND-GFP-mouse and RFP-cancer-cell model to visualize and quantitate angiogenesis in tumor-involved lymph nodes and to screen for angiogenesis inhibitors at this site.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1294.
Abstract 1297: IL-1a promotes neovascularization in prostate cancer via activated macrophages by BMP-6
Authors: Lee Geun Taek , Kwon Seok Joo , Lee Jae-ho , Jung Yeon Suk , Kim Isaac Yi 
Published: February 2011

Abstract
Prostate cancer is the most commonly diagnosed non-cutaneous cancer in men in the US. Active surveillance, radiation, and surgery are the recommended treatments for localized prostate cancer. However, approximately 35% of patients eventually develop biochemical recurrence within 5 years after the initial treatment. In the present study, we have investigated the significance of prostate cancer derived BMP-6 in the context of macrophages. BMP-6 activated macrophages and dramatically increased the production of interleukin-1α (IL-1α) in vitro. Mechanistically, optimal ligand/receptor/Smad combination for IL-1α induction was BMPRII (BMP type II receptor), ALK3 (BMP type I receptor), and Smad 1(R-Smad)/4(Co-Smad). We used a serial promoter deletion assay and found that −1,856 −1,655 bp region of IL-1α promoter contained the BMP-6 responsive element. Surprisingly, this region did not have the consensus Smad binding element. Additional analysis of this 200 bp region demonstrated multiple NF-κB binding sites. When NF-κB was inhibited, IL-1α induction was completely blocked. Moreover, BMP-6 increased NF-κB reporter vector activity and phosphorylated p50 and p65, suggesting NF-κB's role in induction of IL-1α [[Unsupported Character - &#61472;]]by BMP-6. Immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) showed that Smad1 binds to the 200 bp region and interacts with NF-κB directly. Finally, VEGF expression increased in TRAMP-C2 prostate cancer cells co-cultured with macrophages. Based on these results, we propose that tumor-derived BMP-6 induces IL-1α expression in macrophages and that this induction requires Smad and NF-κB pathways; IL-1α, in turn, induces angiogenesis in prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1297.
Abstract 13: Regulation of breast cancer stem cells by miR-93
Authors: Liu Suling , Ginestier Christophe , Ibarra Ingrid , Patel Shivani H. , Heath Amber , Ou Sing J. , Jagirdar Raj , Clouthier Shawn G. , Korkaya Hasan , Charafe-Jauffret Emmanuelle , Hannon Gregory J. , Birnbaum Daniel , Wicha Max S. 
Published: February 2011

Abstract
There is increasing evidence that the growth and metastasis of many tumors, including breast cancer, are driven by a cellular population displaying stem cell properties. Like their normal counterparts, these breast cancer stem cells may be regulated by MicroRNAs (miRNAs). We have previously demonstrated that breast cancer cell lines contain subpopulations with stem cell properties that can be isolated by virtue of their expression of Aldehyde dehydrogenase (ALDH) as assessed by the Aldefluor assay. We compared miRNA expression in Aldefluor-positive and Aldefluor-negative populations in a series of five breast cancer cell lines. We identified specific miRNA expression profiles for each population. Among the differentially expressed miRNAs was miR-93 whose expression was significantly increased in Aldefluor-negative compared to Aldefluor-positive populations. To confirm the regulation of miR-93 during cell differentiation we constructed a miR-93 sensor tagged with GFP and demonstrated that sensor-positive (miR-93-negative) cells had significantly increased tumor initiating capacity in NOD/SCID mouse xenografts compared to sensor-negative (miR-93-positive cells). Furthermore, miR-93-negative cells gave rise to tumors containing both miR-93-negative and miR-93-positive cell populations. Utilizing a tetracycline inducible lentivirus driving miR-93 expression, we found that induction of miR-93 expression decreased the ALDH-positive population in vitro as well as in mouse xenografts where this reduction was associated with decreased tumor growth. Furthermore, induction of miR-93 expression immediately upon orthotopic implantation or intracardiac injection completely blocked subsequent tumor growth and metastasis formation. These studies demonstrate that miR-93 plays a functional role in the self-renewal and differentiation of breast cancer stem cells. Furthermore, the TET-inducible miR-93 system allows for the controlled regulation of cancer stem cell function providing a valuable model to simulate the effects of CSC-directed therapies on breast cancer growth and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 13.
Abstract 1300: Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow-derived endothelial progenitor cell incorporation into Lewis Lung cancer (LLC) tumors
Authors: Liang Paulina H. , Tian Fang , Lu Yi , Stolz Donna B. , Li Lu-Yuan 
Published: February 2011

Abstract
Bone marrow-derived endothelial progenitor cells (EPC) have been shown to be a critical component of supporting tumor neovascularization. We have shown in a variety of cancer and angiogenesis models that recombinant vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits angiogenesis and tumor growth via specific elimination of mature endothelial cells (EC) in established tumor vasculature. We report here that VEGI treatment leads to a significantly decreased population of EPC in tumors. We transplanted whole bone marrow from green fluorescent protein (GFP) transgenic mice into C57BL/6 recipient mice. The mice were then inoculated with Lewis Lung cancer (LLC) cells and treated with VEGI or vehicle. In the tumors of the VEGI-treated group, we saw both a significant inhibition of tumor growth and decreased density of CD31+ vasculature compared to vehicle treated mice. Flow cytometric analysis of the peripheral blood of tumor bearing mice revealed an initial increase of EPCs derived from the bone marrow (GFP+Flk1+) prior to the timeframe when EPCs are incorporated into the tumor. After this timeframe, the EPC in peripheral blood decreased markedly. Monitoring for EPC by GFP+CD31+ immunostaining, we found that the number of EPC in VEGI treated tumors notably decreased compared to that of the untreated group. EPC incorporation into the tumor vasculature of VEGI-treated mice was also less than that in the untreated group. TUNEL staining of the tumor sections showed a large extent of apoptosis overall in VEGI-treated tumors. These findings indicate that VEGI plays an important role in modulating bone marrow-derived EPC incorporation into LLC carcinomas, resulting in the inhibition of EPC supported tumor vasculogenesis and tumor growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1300.
Abstract 1301: Involvement of VEGFR-1 signal in solid tumor growth and tumor angiogenesis via recruitment of macrophage-lineage cells
Authors: Muramatsu Masashi , Yamamoto Seiji , Osawa Tsuyoshi , Shibuya Masabumi 
Published: February 2011

Abstract
VEGF/VEGFR signaling is essential for pathological angiogenesis. It has been reported that Flt-1 (VEGFR-1) is expressed not only in vascular endothelial cells but also in monocyte/macrophages. Previously, we and others reported that bone marrow derived cells which expressed Flt-1 were involved in the formation of pre-metastatic niche in mouse tumor model. However, the role of Flt-1 signal in tumorigenesis is not fully understood.
To clarify the involvement of Flt-1 in solid tumor growth, we used wild type (Wt) mice and Flt-1 tyrosine kinase-deficient (Flt-1 TK-/-) mice which developed basically normal blood vessels and survived. In allograft cancer model, tumor growth was significantly slower in Flt-1 TK-/- mice compared with that in Wt mice. Survival rate of Flt-1 TK-/- mice were also higher than Wt mice under tumor-bearing condition. The degree of tumor angiogenesis and infiltration of macrophage-lineage cells in tumor tissues were remarkably suppressed in Flt-1 TK-/- mice compared with those in Wt mice. Surprisingly, endothelial cells and macrophage-lineage cells at the surrounding tissue of tumors were similar in both mice. The number of pericyte marker-positive cells covered with vascular endothelial cells was reduced in tumor tissue in Flt-1 TK-/- mice compared with that in Wt mice.
To distinguish which Flt-1 signal on the vascular endothelial cell or on the macrophage is important, we performed bone marrow transplantation. Tumor volume in Wt mice implanted with bone marrow derived from Flt-1 TK-/- mice was significantly smaller than that in Wt mice implanted with bone marrow derived from Wt mice. In tumor tissue inoculated in Wt mice implanted with Flt-1 TK-/- bone marrow, angiogenesis and infiltration of macrophage-lineage cells were significantly decreased compared with Wt mice implanted with Wt bone marrow. Based on these results, we suggest that, in some tumors, Flt-1 signaling is important for bone marrow-derived macrophage-migration into tumors which promotes tumor angiogenesis and tumor growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1301.
Abstract 1303: Inhibition of human breast cancer cell (MDA-MB231) migration, neoangiogensis and tumor growth by selective disruption of annexin II function: in vitro and in vivo studies
Authors: Sharma Mahesh C. , Ownbey Robert T. , Blackman Marc R. , Sharma Meena 
Published: February 2011

Abstract
Annexin II, an abundant phospholipid binding cell surface protein, binds tissue plasminogen activator (tPA) and functions as a regulator of fibrinolysis. Annexin II also mediates angiogenesis and enhances tumor growth and metastasis. However, the mechanism supporting this role is not known. Using a human breast cancer model we found that invasive human breast cancer cells (MDA-MB231) synthesize annexin II and tPA. Annexin II interacted with tPA in vitro leading to conversion of zymogen plasminogen to the reactive enzyme plasmin. Cell surface generated plasmin inhibited the migration of MDA-MB231 cells. Silencing of the annexin II gene in mDA-MB231 cells abolished tPA binding thereby inhibiting tPA dependent plasmin generation. Moreover these annexin II suppressed MDA-MB231 cells exhibited reduced motility. Immunohistochemical analysis of prediagnosed clinical specimens showed abundant secretion of tPA and expression of annexin II on the surface of invasive cancer cells which correlates with neovascularization of the tumor. Intravenous administration of the anti-annexin II antibody to mice bearing MDA-MB231 tumors significantly inhibited tumor growth possibly due to blocked neoangiogenic activity. Taken together, these data suggest that annexin II dependent plasmin generation may be an early event switching breast cancer from the prevascular phase to the vascular phase with the possibility of metastasis. Annexin II may be an attractive target for therapeutic strategies aimed to inhibit neoangiogenesis and breast cancer metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1303.
Abstract 1304: Induction of pericyte migration by autotaxin in angiogenesis
Authors: Lin Chi-yen , Leinwand Joshua , Maier Cheryl , Pober Jordan , Chang William , Braddock Demetrios 
Published: February 2011

Abstract
Angiogenesis is essential for tumor cell growth and progression. Recent studies have shown that autotaxin (ATX) is a critical angiogenic factor since ATX knock-out mice exhibit severe vascular defects. ATX also has the ability to stimulate tumor cell motility by enzymatically generating lysophosphatidic acid (LPA). To form a new and stable blood vessel, interactions between pericytes and endothelial cells play important roles. A previous study has shown that endothelial cells can be induced to generate ATX; however little is known about how ATX and LPA are involved in these interactions. The focus of our study is to define the role of ATX in angiogenesis by examining pericyte and endothelial cell response to ATX.
To test the effects on cell migration, we treated pericytes and endothelial cells with ATX and other angiogenic factors (including Vascular Endothelial Growth Factor (VEGF) and Platelet Derived Growth Factor (PDGF)). Pericytes responded strongly to ATX and LPA stimulation, but human umbilical vein endothelial cells (HUVEC) and skin microvescular cells (HDMEC) showed little or no effect. PDGF elicits a qualitatively similar response. In contrast, endothelial cells migrated when treated with VEGF, but pericytes showed no such stimulation. Pericytes treated with ATX and PDGF together show an additive response. Moreover, in a checkerboard assay the migratory response to ATX or LPA is chemokinetic, whereas PDGF is chemotactic.
We then utilized RT-PCR to examine the mRNA levels of four major LPA receptors in pericytes when treated with angiogenic factors. Treatment with PDGF increases LPAR1 mRNA levels and decreases LPAR4 levels. Treatment with ATX also increases LPAR1, but shows no change in LPAR4 levels. By contrast, VEGF treatment has no effect on the LPAR1 mRNA level, but increases the LPAR4 mRNA level. The amount of migration appears to correlate with an increase of LPAR1 and perhaps a decrease of LPAR4. As such, certain angiogenic factors might affect cell motility, in part, through the differential expression of various LPA receptors.
These studies suggest that the ATX/LPA signaling pathway effects the formation of mature blood vessels by promoting the pericyte coverage of immature blood vessels. The role of the ATX/LPA pathway in the formation of mature blood vessels provides the scientific rationale for targeting the pathway in the development of novel anti-angiogenic compounds.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1304.
Abstract 1305: The proangiogenic role of brain-derived neurotrophic factor in tumor development
Authors: Lam CT , Yang ZF , Fan ST , Poon RTP 
Published: February 2011

Abstract
Background and Aim: Hepatocellular carcinoma is a hypervascularized solid tumor which requires angiogenesis for its growth. Previous studies suggested that neurotrophins, such as brain-derived neurotrophic factor (BDNF), may serve as angiogenic factors. The involvement of BDNF in tumor angiogenesis, however, remains unclear. The present study aimed at elucidating the role of BDNF in regulating angiogenesis and tumor development. Materials and Methods: BDNF was overexpressed in a normal mouse endothelial cell line by transfection. The angiogenic properties, including proliferation, cell motility, invasiveness and cell survival, of the transfectants were subsequently assessed by MTT, cell migration, invasion and Annexin V labeling assays, respectively. Microarray analysis was performed to explore the BDNF-mediated angiogenic pathway. An in vivo cell co-injection model, using a mouse transformed hepatocyte cell line and BDNF transfectants, was used to study the role of BDNF in tumor development. Results: Firstly, overexpression of BDNF could promote endothelial cell proliferation, migration, invasion and survival. Secondly, the gene expression profiling data suggested that the BDNF-induced angiogenic effects could be attributed to a dozen of genes including transcription factors, cell adhesion molecules, chemokines and growth factors. Thirdly, the in vivo cell co-injection experiment showed that high BDNF-expressing endothelial cells are able to promote growth of tumors with significantly higher number of microvessels. On the other hand, knock-down of BDNF in a tumor-derived endothelial cell line by shRNAs impairs such tumor promoting effect. Conclusion: The present study showed that BDNF is crucial for tumor angiogenesis and may serve as a potential target for anti-angiogenic treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1305.
Abstract 1308: Cytogenetic abnormalities of tumor endothelial cells in human malignant tumors
Authors: Hida Kyoko , Akino Tomoshige , Hida Yasuhiro , Tsuchiya Kunihiko , Freedman Deborah , Muraki Chikara , Ohga Noritaka , Matsuda Kouhei , Akiyama Kosuke , Kurosu Takuro , Kondo Miyako , Maishi Nako , Harabayashi Toru , Shinohara Nobuo , Nonomura Katsuya , Klagsbrun Michael , Shindoh Masanobu 
Published: February 2011

Abstract
An important concept in tumor angiogenesis has been that tumor blood vessels contain genetically normal and stable endothelial cells (ECs), unlike tumor cells, which typically display genetic instability. Chromosomal aberration in human tumor endothelial cells (hTECs) in carcinoma has not yet been investigated. Here we isolated TECs from 20 human renal cell carcinomas (RCCs) and analyzed their cytogenetic abnormalities. The degree of aneuploidy was analyzed by fluorescence in situ hybridization using chromosome 7 and chromosome 8 DNA probes in isolated hTECs. In human RCCs, 22-58% (median 33%) of uncultured hTECs were aneuploid, whereas normal ECs were diploid. The mechanisms of TEC aneuploidy were studied using mouse TECs (mTECs) isolated from xenografts of human epithelial tumors. To investigate the contribution of progenitor cells to aneuploidy in mTECs, CD133 positive and CD133 negative mTECs were compared for aneuploidy. CD133 positive mTECs showed aneuploidy more frequently than CD133 negative mTECs. This is the first report showing cytogenetic abnormality of hTECs in carcinoma, contrary to traditional belief. It is suggested that cytogenetic alterations in tumor vessels of carcinoma can occur and may play a signicant role in modifying tumor-stromal interactions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1308.
Abstract 1319: Proton irradiation exerts antiangiogenic and other tumor progression-limiting effects
Authors: Girdhani Swati , Lamont Clare , Hahnfeldt Philip , Weremowicz Janusz , Anaya Zachary , Beheshti Afshin , Abdollahi Amir , Hlatky Lynn 
Published: February 2011

Abstract
The precise targeting and energy deposition characteristics of proton theapy have attracted considerable attention in the clinical oncology community. An increasing number of proton facilities are being established to exploit the physical advantages of this radiation for cancer treatment. However, the fact that there may also be biologically-based advantages for the use of protons has essentially been overlooked. We here demonstrate that proton irradiation inhibits expression of major pro-angiogenic factors and multiple angiogenesis-associated processes, including invasion and endothelial cell proliferation, which are critical to cancer progression. Dose-dependent suppression of angiogenic signaling was demonstrated for human tumor, fibroblasts and microvascular endothelial cells. Pan-genomic microarray analysis and RT-PCR revealed that post-irradiation (0.5, 1.0 2.0 Gy) critical pro-angiogenic signaling factors, including vascular endothelial growth factor (VEGF), interleukin 6 and 8 (IL-6, IL-8) and the hypoxia-inducible factor-1 alpha (HIF-1α), were significantly downregulated. Co-culture studies demonstrated proliferation and invasion of endothelial cells was inhibited by irradiation of both tumor and fibroblast cells, suggesting that proton irradiation may contribute to angiogenesis suppression through paracrine signalings from targeted cells as well as by direct action. Addition of recombinant IL-8 or VEGF partially restored these functions, once again indicating that suppression of these factors plays a functional role in inhibition of tumor progression. Finally an attenuated growth rate and a reduced invasive capacity was demonstrated in vivo for proton-irradiated human lung cancer, A549. Taken together, these findings provide novel preclinical evidence that proton irradiation may, in addition to its physical advantages, have important biological ramifications that should be a consideration in the optimization of proton therapy.
This work was supported by NASA NSCOR grant #NNJ06HA28G
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1319.