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Open AccessJournal ArticleDOI

Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer.

TLDR
The prognostic significance of stromal PDGF beta-receptor expression was particularly prominent in tumors from premenopausal women and should be considered in ongoing clinical development of PDGF receptor inhibitors.
Abstract
This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF β-receptor status and clinicopathological characteristics in breast cancer. PDGF receptor expression was determined by immunohistochemistry on tumor tissue microarrays. Breast tumor data were combined with prognostic factors and related to outcome endpoints. PDGF α- and β-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF β-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF β-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF β-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF β-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF α- and β-receptor expression is a common, but variable and independent, property of solid tumors. In breast cancer, stromal PDGF β-receptor expression significantly correlates with less favorable clinicopathological parameters and shorter survival. These findings highlight the prognostic significance of stromal markers and should be considered in ongoing clinical development of PDGF receptor inhibitors.

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Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

TL;DR: Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy.
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Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression

TL;DR: How normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state are reviewed.
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Hallmarks of cancer: interactions with the tumor stroma.

TL;DR: The current understanding of tumor cell interactions with the tumor stroma is reviewed with a particular focus on cancer-associated fibroblasts and pericytes.
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Recent developments in myofibroblast biology: paradigms for connective tissue remodeling.

TL;DR: The origin and the specific features of the myofibroblast in diverse fibrotic lesions, such as systemic sclerosis; kidney, liver, and lung fibrosis; and the stromal reaction to certain epithelial tumors are reviewed.
Journal ArticleDOI

Activation of fibroblasts in cancer stroma.

TL;DR: This review focuses mainly on carcinomas and discusses the recent findings regarding the role of activated fibroblasts in driving tumor progression.
References
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Journal ArticleDOI

Fibroblasts in cancer

TL;DR: Fibroblasts are a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.
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Tissue microarrays for high-throughput molecular profiling of tumor specimens

TL;DR: In this paper, an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors is presented. But, it is limited to a single tumor tissue microarray.
Journal ArticleDOI

PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors

TL;DR: Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression, suggesting KIT and PDGFra mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.
Journal ArticleDOI

Putting tumours in context

TL;DR: In this article, the interactions between cancer cells and their micro-and macro-environment create a context that promotes tumour growth and protects it from immune attack, and the functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses.
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