bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A22: Identification of novel tumor derived factors that inhibit angiogenesis
Authors: Walshe Tony E. , Bourdelais Justin , Lee Arleide , Ouro-Djobo Rakibou , Vishnudas Vivek , Sarangarajan Rangaprasad , Narain Niven 
Published: December 2015

Abstract
Background: Cell-cell communication in the tumor micro-environment drive tumor growth and facilitate neovessel recruitment from the adjacent vasculature. The present study was designed to identify novel cancer derived factors that modulate the vascular endothelial response in a paracrine manner.
Methods: An array of cancer cell lines from multiple tissue types (Panc1; HepG2; LnCap; Skmel; Hep3B; PL45; SCC25; CaCo2; PaCa2; SKBR3) were grown under normoxic or hypoxic (1% oxygen) conditions for a total of 20 different conditions. After 48 hours, conditioned media was collected and filtered prior to testing on endothelial cells. The effects of the conditioned media on endothelial apoptosis, proliferation and tube formation were investigated. In tandem with these endothelial cell fate assays, the proteomic profile of these 20 conditions was profiled and assessed using the Berg Interrogative Biology™ platform.
Results & Discussion: Our results reveal that conditioned media from all cancer cells tested can alter endothelial cell apoptosis, proliferation rate and tube formation in 3D matrigel assays i.e. critical cell fate decisions that enable formation of nascent vessel formation. As predicted, the predominant effect of tumor-derived conditioned media on endothelial apoptosis was a protective anti-apoptotic effect, with the discernable exception of normoxic Panc1 derived media. An unexpected finding was the general anti-proliferative effects of tumor-derived conditioned media on endothelial cell growth, with the exception of Hep2G, LnCap and PaCa2 cell derived media. Using a media fractionation strategy and Interrogative Biology™, we identified several endothelial anti-apoptotic candidates from Panc1 cells within a unique molecular weight range. Upon application of ASO gene knockdown in Panc1 cells, these targets were verified for apoptotic and proliferation effects on vascular endothelial cells.
Conclusion: Specific factors that determine paracrine cell-cell interaction in the tumor microenvironment have been identified and validated employing Berg Interrogative Biology™. The technology presented herein represents a viable platform for identifying clinically relevant biomarkers and factors that alter cancer angiogenesis.
Citation Format: Tony E. Walshe, Justin Bourdelais, Arleide Lee, Rakibou Ouro-Djobo, Vivek Vishnudas, Rangaprasad Sarangarajan, Niven Narain. Identification of novel tumor derived factors that inhibit angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr A22.
Abstract B01: Profiling of serum and plasma angiogenic biomarkers in breast cancer and colon cancer using Luminex xMAP technology-based human angiogenesis multiplex immunoassay panels
Authors: Lie Wen-Rong , Droll Deborah , Mistry Jehangir 
Published: December 2015

Abstract
Tumors require neovascularization for growth. Consequently, the angiogenesis process is key to understanding tumor development and progression, as well as diagnosis and treatment. Measuring the levels of pro- and anti-angiogenic factors in plasma or serum in cancer patients may provide prognostic information concerning disease processes and mechanisms and the elucidation of potential biomarkers for epidemiological studies or clinical trials. The Luminex xMAP technology, a bead-based multiplex immunoassay for the simultaneous measurement of multiple analytes in a small sample size, has been widely used in cancer biomarker discoveries. We report here the use of two newly developed multiplex human angiogenesis panels to profile the circulating biomarkers commonly used in the angiogenesis pathway analysis. The two panels are 1) MILLIPLEX MAP Human Angiogenesis Panel 1, a 17-plex multiplex immunoassay for the simultaneous quantification of the following 17 angiogenesis biomarkers: Angiopoietin-2, BMP-9, EGF, Endoglin, Endothelin-1, FGF-1, FGF-2, Follistatin, G-CSF, HB-EGF, HGF, IL-8, Leptin, PLGF, VEGF-A, VEGF-C, and VEGF-D, and 2) MILLIPLX MAP Human Angiogenesis Panel 2, a 20-plex multiplex immunoassay for simultaneous quantitation of the following 20 human angiogenesis biomarkers: Angiostatin, soluble E-Selectin, Osteopontin, PDGF-AB/BB, PECAM-1/sCD31, Tenascin C, Thrombospondin-2 (TSP-2), soluble AXL, soluble c-Kit, soluble EGFR, soluble Her2/ErbB2, soluble Her3/ErbB3, soluble HGFR/c-Met, soluble IL-6Rα, soluble Neuropilin-1, soluble Tie-2, soluble urokinase receptor (suPAR), soluble VEGFR1, soluble VEGFR2, and soluble VEGFR3. In this study, we report the use of these 37 angiogenic, growth factor and soluble receptor biomarkers to profile serum samples and plasma samples from a panel of breast cancer and colon cancer patients, with a similar number of normal serum and plasma samples, as a corresponding set, to generate a tumor profile of angiogenic factors using the Luminex xMAP platform. The results of this study demonstrated the utility of these human angiogenesis panels in studying cancer development and cancer biomarker discovery, as well as its potential application in translational research.
Citation Format: Wen-Rong Lie, Deborah Droll, Jehangir Mistry. Profiling of serum and plasma angiogenic biomarkers in breast cancer and colon cancer using Luminex xMAP technology-based human angiogenesis multiplex immunoassay panels. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B01.
Abstract B12: Endothelial stabilizer SAC-1004 normalizes tumor vasculature and potentiates docetaxel chemotherapy in prostate cancer
Authors: Kang Yoo Hyun , Heo Jun Hyeok , Jin Hyun A , Park Ki Chung , Hong Sung Joon , Han Kyung Seok 
Published: December 2015

Abstract
Background: Since tumor requires excessive oxygen and nutrients due to their rapid growth, tumor is generally vascular. However, tumor vasculature is not physiologic but leaky, dilated, and tortuous. The inefficiency of tumor vessels in terms of perfusion induces hypoxic stress that makes the tumor more aggressive. Here, we investigated the role of a novel endothelial stabilizer SAC-1004 on tumor vascular normalization and its effects on tumor growth in prostate cancer.
Methods: Human vascular endothelial cell (HUVEC) was used to evaluate the effects of SAC-1004 on endothelial cells. Immunocytochemical staining and immunofluorescent confocal imaging was performed for E-cadherin expression in HUVECs. MTS assay was performed to assess cell proliferation of HUVECs and PC-3 cells after SAC-1004 treatment. Immunohistochemical staining with anti-CD31 and anti-SMA antibodies was performed to assess vasculature in vivo. PC-3 subcutaneous xenografts were developed to evaluate the effects of SAC-1004 on tumor vasculature and tumor growth in prostate cancer. Magnetic resonance images were taken to assess vascular perfusion in xenografts. SAC-1004 was administrated via tail vein once a day for 7 days. Docetaxel was administrated intravenously once a week.
Results: SAC-1004 restored junction protein E-cadherin in vitro in endothelial cells and significantly reduced VEGF-induced retinal vascular leakage. SAC-1004 promoted proliferation of HUVECs in vitro in a dose-dependent manner. However, proliferation of cancer cells was not significantly affected by SAC-1004 treatment. Reduced vascular leakiness was found in PC-3 xenografts treated with SAC-1004 treatment and magnetic resonance imaging after SAC-1004 treatment for 7 days confirmed improved perfusion in the PC-3 xenografts treated with SAC-1004 compared with control. Interestingly, SAC-1004 treatment suppressed tumor growth in PC-3 xenografts but SAC-1004 followed by intravenous docetaxel treatment showed the most potent tumor suppression compared with control in PC-3 xenografts.
Conclusions: SAC-1004 restored abnormal leak vasculature of tumor by restoring endothelial cell junction in prostate cancer. Vascular normalization by SAC-1004 induced tumor regression and combination with docetaxel following vascular normalization potentiated anti-tumor effects of docetaxel in prostate cancer.
Citation Format: Yoo Hyun Kang, Jun Hyeok Heo, Hyun A Jin, Ki Chung Park, Sung Joon Hong, Kyung Seok Han. Endothelial stabilizer SAC-1004 normalizes tumor vasculature and potentiates docetaxel chemotherapy in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B12.
Abstract B19: Anti-VEGF treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery
Authors: Datta Meenal , Via Laura E. , Kamoun Walid S. , Liu Chong , Chen Wei , Seano Giorgio , Weiner Danielle M. , Schimel Daniel , England Kathleen , Martin John D. , Gao Xing , Xu Lei , Barry Clifton E. , Jain Rakesh K. 
Published: December 2015

Abstract
Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. TB patients require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low molecular weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced vascular endothelial growth factor (VEGF) expression in both species. In tumors, anti-angiogenic, specifically anti-VEGF, treatments can “normalize” their vasculature, reducing hypoxia and creating a window-of-opportunity for conjunctive chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential new avenue to improve delivery and efficacy of current treatment regimens.
Citation Format: Meenal Datta, Laura E. Via, Walid S. Kamoun, Chong Liu, Wei Chen, Giorgio Seano, Danielle M. Weiner, Daniel Schimel, Kathleen England, John D. Martin, Xing Gao, Lei Xu, Clifton E. Barry, III, Rakesh K. Jain. Anti-VEGF treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B19.
Abstract IA19: Immune checkpoint blockade in cancer therapy: New insights and opportunities
Authors: Allison James P. 
Published: December 2015

Abstract
The existence of multiple non-redundant inhibitory pathways that limit T cell responses offers novel strategies for unleasing the immune system to attack cancer cells. The best characterized of these immune checkpoints is CTLA-4, which inhibits T cell proliferation by interfering with the interaction of the costimulatory molecule CD28 with its ligands B7-1 and B7-2 on the surface of antigen presenting cells. Antibodies to CTLA-4 have proven effective against multiple tumor types in both pre-clinical and clinical studies. Ipilimumab, an antibody to human CTLA-4, showed long term (&gt;10 years) survival benefit in about 20% of patients in a randomized, placebo-controlled trial in late stage melanoma. In 2011 it was approved by the FDA for treatment of late stage melanoma and is now a standard of care for that disease.
The mechanism(s) of action of anti-CTLA-4 are still being elucidated. We and others have shown that CLTA-4 limits T cell proliferation by a cell intrinsic mechanism. However, there is also evidence that anti-CTLA-4 has to engage the target on both effector (Teff) and regulatory (Treg) T cells. Thus anti-CTLA-4 exerts its anti-tumor effects by multiple mechanisms.
PD-1, another checkpoint, recruits a phosphatase and seems to interfere with T cell antigen receptor mediated signaling. It has two ligands, PD-L1 and PD-L2, which are both expressed on dendritic cells. However, many tumor cells also express PD-L1. Antibodies to PD-1 and PD-L1 have both shown objective responses against several tumor types in clinical trials with response rates of about 25% . A recent phase II trial of a combination of anti-PD-1 and anti-CTLA-4 in melanoma showed objective responses in about 50% of late stage melanoma patients.
These studies and their implications for cancer therapy will be discussed.
Citation Format: James P. Allison. Immune checkpoint blockade in cancer therapy: New insights and opportunities. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr IA19.
Abstract IA21: Vascular phenotyping: Using genomics to inform antiangiogenesis
Authors: Benjamin Laura E. 
Published: December 2015

Abstract
Anti-angiogenesis therapy has proven to be an important tool for oncologists particularly in metastatic disease. To date much of the success has been built on targeting the VEGF/VEGFR pathways and FDA approvals have been granted in many disease settings including CRC, RCC, NSCLC, and others. In 2014 Cervical Cancer and Gastric cancer were new cancers added to this list. Still, it's fair to say that we have a limited understanding of how to identify the patients who will receive optimal benefit from the available therapeutic agents, and how inhibitors of non-VEGF pathways will compare or combine with currently approved therapies. This presentation will discuss new findings that use molecular analysis to understand heterogeneity in cancer vascular beds and how they relate to preclinical efficacy for VEGF pathway inhibitors. Linking these findings to clinical outcomes in the future may provide a bridge between the wealth of data being generated in cancer genomics and patients most likely to derive benefit from anti-angiogenesis.
Citation Format: Laura E. Benjamin. Vascular phenotyping: Using genomics to inform antiangiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr IA21.
Abstract PR06: Formation of lymph node metastases is not angiogenesis dependent
Authors: Jones Dennis , Jeong Han-sin , Liao Shan , Padera Timothy P. 
Published: December 2015

Abstract
Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting. The presence of lymph node metastases dictate treatment decisions, however their reliance on angiogenesis for growth has not been described. Furthermore, recent data show that radiation and chemotherapy can treat limited lymph node disease in breast cancer patients with equal efficacy to complete lymph node dissection. This has led to a reduction in the use of complete lymph node dissection as the primary treatment option in these patients. Thus, greater numbers of patients will have cancer in lymph nodes after surgery that requires adjuvant therapy.
Methods: Here, we developed a novel chronic lymph node window (CLNW) model to longitudinally image the growth and spread of lymph node metastases using intravital optical microscopy techniques. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes. We further test our results in murine and patient samples using molecular and biochemical methods. Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW.
Results: We reveal the surprising lack of sprouting angiogenesis during metastatic growth in lymph nodes using both intravital microscopy and ex vivo methods. Vascular endothelial growth factor was not produced by the metastatic lesion despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases in our models. We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab.
Conclusion: We provide pre-clinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, which reveals a mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases. Based on longitudinal intravital imaging, it appears that metastatic cancer cells in the lymph node invade the lymph node parenchyma where the native blood vessels reside in order to secure a supply of oxygen and nutrients for the survival and growth of the metastatic lesion.
Citation Format: Dennis Jones, Han-sin Jeong, Shan Liao, Timothy P. Padera. Formation of lymph node metastases is not angiogenesis dependent. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr PR06.
Narrativas e fronteiras em duas jornadas latino-americanas
Authors: Guerreiro Alexandre Silva 
Published: December 2015

<p>A transposição da fronteira entre México e EUA ocupa um lugar comum nos filmes baseados em jornadas de heróis latinos em busca de uma vida melhor. A partir dos limites da representação dessa jornada, propomos uma discussão, com ênfase na análise fílmica, de duas obras latino-americanas, a saber, <em>Maria Full of Grace</em> e <em>La Jaula de Oro,</em> como exemplares da travessia obrigatória almejada pelos seus protagonistas. Interessa-nos observar o modo como a <em>narcofronteira</em> é apresentada nesses dois filmes, bem como de que maneira a narrativa se constrói em torno dessa fronteira e a forma como uma certa repetição inscreve a transposição da fronteira como elemento fundamental às <em>narconarrativas de fronteiras</em> latino-americanas.</p>
Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects
Authors: Ronsein Graziella E. , Hutchins Patrick M. , Isquith Daniel , Vaisar Tomas , Zhao Xue-Qiao , Heinecke Jay W. 
Published: December 2015

Objective—
We investigated relationships between statin and niacin/statin combination therapy and the concentration of high-density lipoprotein particles (HDL-P) and cholesterol efflux capacity, 2 HDL metrics that might better assess cardiovascular disease risk than HDL-cholesterol (HDL-C) levels.

Approach—

In the Carotid Plaque Composition Study, 126 subjects with a history of cardiovascular disease were randomized to atorvastatin or combination therapy (atorvastatin/niacin). At baseline and after 1 year of treatment, the concentration of HDL and its 3 subclasses (small, medium, and large) were quantified by calibrated ion mobility analysis (HDL-P
IMA
). We also measured total cholesterol efflux from macrophages and ATP-binding cassette transporter A1 (ABCA1)–specific cholesterol efflux capacity.

Results—

Atorvastatin decreased low-density lipoprotein cholesterol by 39% and raised HDL-C by 11% (
P
=0.0001) but did not increase HDL-P
IMA
or macrophage cholesterol efflux. Combination therapy raised HDL-C by 39% (
P
<0.0001) but increased HDL-P
IMA
by only 14%. Triglyceride levels did not correlate with HDL-P
IMA
(
P
=0.39), in contrast to their strongly negative correlation with HDL-C (
P
<0.0001). Combination therapy increased macrophage cholesterol efflux capacity (16%,
P
<0.0001) but not ABCA1-specific efflux. ABCA1-specific cholesterol efflux capacity decreased significantly (
P
=0.013) in statin-treated subjects, with or without niacin therapy.

Conclusions—

Statin therapy increased HDL-C levels but failed to increase HDL-P
IMA
. It also reduced ABCA1-specific cholesterol efflux capacity. Adding niacin to statin therapy increased HDL-C and macrophage efflux, but had much less effect on HDL-P
IMA
. It also failed to improve ABCA1-specific efflux, a key cholesterol exporter in macrophages. Our observations raise the possibility that niacin might not target the relevant atheroprotective population of HDL.
Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due To Combined Estrogen Plus Progestin Therapy
Authors: Johnson Karen C. , Aragaki Aaron K. , Jackson Rebecca , Reiner Alex , Sandset Per Morten , Rosing Jan , Dahm Anders E.A. , Rosendaal Frits , Manson JoAnn E. , Martin Lisa W. , Liu Simin , Kuller Lewis H. , Cushman Mary , Rossouw Jacques E. 
Published: December 2015

Objective—
To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy.

Approach and Results—

Prospective nested case–control study of 205 cases of CHD and 481 matched controls in the Women’s Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (
P
=0.01) and APC resistance (
P
=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk.

Conclusions—
Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00000611.