Targeting Angiogenesis and the Tumor Microenvironment

Samples, Jennifer; Willis, Monte S.; Klauber-DeMore, Nancy

doi:10.1016/j.soc.2013.06.002

Cited by 51 publications

(34 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…vatalanib, cediranib, sunitinib, etc. have been used against VEGF-VEGFR pathway to control abnormal angiogenesis in clinical trials [14, 21, 50, 62-64]. Regrettably, benefits of AATs are at best transitory, and this period of clinical benefit is followed by restoration of tumor growth [49].…”

Section: Discussionmentioning

confidence: 99%

Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks

et al. 2015

View full text Add to dashboard Cite

Glioblastoma (GBM) is a hypervascular and malignant form of brain tumors. Anti-angiogenic therapies (AAT) were used as an adjuvant against VEGF-VEGFR pathway to normalize blood vessels in clinical and preclinical studies, which resulted into marked hypoxia and recruited bone marrow derived cells (BMDCs) to the tumor microenvironment (TME). In vivo animal models to track BMDCs and investigate molecular mechanisms in AAT resistance are rare. We exploited recently established chimeric mouse to develop orthotopic U251 tumor, which uses as low as 5×106 GFP+ BM cells in athymic nude mice and engrafted >70% GFP+ cells within 14 days. Our unpublished data and published studies have indicated the involvement of immunosuppressive myeloid cells in therapeutic resistance in glioma. Similarly, in the present study, vatalanib significantly increased CD68+ myeloid cells, and CD133+, CD34+ and Tie2+ endothelial cell signatures. Therefore, we tested inhibition of CSF1R+ myeloid cells using GW2580 that reduced tumor growth by decreasing myeloid (Gr1+ CD11b+ and F4/80+) and angiogenic (CD202b+ and VEGFR2+) cell signatures in TME. CSF1R blockade significantly decreased inflammatory, proangiogenic and immunosuppressive molecular signatures compared to vehicle, vatalanib or combination. TCK1 or CXCL7, a potent chemoattractant and activator of neutrophils, was observed as most significantly decreased cytokine in CSF1R blockade. ERK MAPK pathway was involved in cytokine network regulation. In conclusion, present study confirmed the contribution of myeloid cells in GBM development and therapeutic resistance using chimeric mouse model. We identified novel molecular networks including CXCL7 chemokine as a promising target for future studies. Nonetheless, survival studies are required to assess the beneficial effect of CSF1R blockade.

show abstract

Section: Discussionmentioning

confidence: 99%

Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To our knowledge, tumor and systemic inflammation have close relationships between each other . It confirmed that inflammatory response plays an essential role in the progression of tumor microenvironment and some changes of inflammatory cells might be as a predictor for prognosis.…”

Section: Discussionmentioning

confidence: 99%

Predictive impact of the inflammation‐based indices in colorectal cancer patients with adjuvant chemotherapy

et al. 2018

View full text Add to dashboard Cite

Increasing evidences reported that cancer‐triggered inflammation was associated with survival prognosis from colorectal cancer (CRC). However, the comprehensive effects of inflammatory‐based coNLR‐PLR that combines neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) rarely remain to be determined during chemotherapy. We retrospectively analyzed clinical data and baseline laboratory parameters from 153 colorectal cancer patients who underwent palliative adjuvant chemotherapy between January 2009 to January 2012. Receiver operating characteristic (ROC) curves and linear regression analyzed the predictive ability of NLR, and PLR for calculating the score of coNLR‐PLR. Overall survival (OS) and recurrence‐free survival (RFS) rates were estimated using the Kaplan‐Meier method and analyzed by the Cox proportional hazards model in univariate and multivariate analysis. The optimal cut‐off value of NLR and PLR was 2.24 and 186 by the ROC analysis. Kaplan‐Meier method showed that patients with high coNLR‐PLR score was associated with poorer OS and RFS (all P < .05). In univariate and multivariate analysis, it obtained that the coNLR‐PLR severed as a strong independent prognostic factor for OS and RFS (all P < .05). These results highlight that coNLR‐PLR index severed as a strong predictor of prognosis biomarker in CRC patients receiving adjuvant chemotherapy. Furthermore, its assessment could contribute to accurately predicting prognosis after chemotherapy in clinical practice.

show abstract

“…Angiogenesis is essential for tumor growth and metastasis (45,46). Previous studies have demonstrated that miRNAs are able to regulate angiogenesis and tumor cell survival (47)(48)(49)(50)(51).…”

Section: Angiogenesismentioning

confidence: 99%

MicroRNAs and cancer: Key paradigms in molecular therapy (Review)

et al. 2017

View full text Add to dashboard Cite

Abstract. MicroRNAs (miRNAs) are a type of small non-coding RNA molecule that performs an important role in post-transcriptional gene regulation. Since miRNAs were first identified in 1993, a number of studies have demonstrated that they act as tumor suppressors or oncogenes in human cancer, including colorectal, lung, brain, breast and liver cancer, and leukemia. Large high-throughput studies have previously revealed that miRNA profiling is critical for the diagnosis and prognosis of patients with cancer, while certain miRNAs possess the potential to be used as diagnostic and prognostic biomarkers or therapeutic targets in cancer. The present study reviews the studies and examines the roles of miRNAs in cancer diagnosis, prognosis and treatment, and discusses the potential therapeutic modality of exploiting miRNAs.

show abstract

Targeting Angiogenesis and the Tumor Microenvironment

Cited by 51 publications

References 64 publications

Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks

Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks

Predictive impact of the inflammation‐based indices in colorectal cancer patients with adjuvant chemotherapy

MicroRNAs and cancer: Key paradigms in molecular therapy (Review)

Contact Info

Product

Resources

About