Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor

Ikoma, Yoko; Hamashima, Takeru; Yamamoto, Seiji; Sasahara, Masakiyo

doi:10.1111/pin.12530

Cited by 36 publications

(19 citation statements)

References 113 publications

(236 reference statements)

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“…Platelets contribute to sustaining proliferative signals, and cancer cells produce platelet-derived growth factors in large quantities. These growth factors are found to promote tumor progression [ 35 ]. Elevated platelet counts in peripheral blood have been found to be associated with a worse prognosis in patients with lung cancer [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer

Cho¹,

Park²,

Im³

et al. 2018

PLoS ONE

105

132

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Systemic inflammatory markers derived from peripheral blood cell, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), have been demonstrated as prognostic markers in several types of malignancy. Here, we investigated and compared the association between systemic inflammatory markers and survival and developed a prognostic nomogram in breast cancer patients. We reviewed the clinical and pathological records of 661 patients diagnosed with invasive breast carcinoma between 1993 and 2011. The NLR, dNLR, PLR and LMR in the immediate preoperative period were assessed. We analyzed the relationship between these inflammatory markers and clinicopathologic variables, disease-specific survival (DSS), and disease-free survival (DFS) in patients. A nomogram was developed to predict 3- and 5-year DSS for breast cancer. In the univariate analysis, high NLR, dNLR, PLR and low LMR were all significantly associated with poor DSS and DFS. In the multivariate analysis, only the PLR (HR 3.226, 95% CI 1.768–5.885 for DSS and HR 1.824, 95% CI 1.824–6.321 for DFS) was still identified as an independent predictor of outcomes. A subgroup analysis revealed that the PLR was the sole independent marker predicting poor DSS in patients with lymph node metastasis (HR 2.294, 95% CI 1.102–4.777) and with luminal subtype (HR 4.039, 95% CI 1.905–8.562). The proposed nomogram, which includes the PLR, shows good accuracy in predicting DSS with a concordance index of 0.82. PLR is an indicator of systemic inflammation as a part of the host immune response. As an independent prognostic factor, an elevated preoperative PLR is superior to the NLR, dNLR, and LMR in predicting clinical outcomes in patients with breast cancer. Moreover, the nomogram incorporating the PLR could accurately predict individualized survival probability in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer

Cho¹,

Park²,

Im³

et al. 2018

PLoS ONE

105

132

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“…Papadopolous and Lennartsson recently reviewed the approaches to inhibit PDGF signaling in cancer therapies and provided a detailed description of current and future therapies that target the PDGF system [11] . Indeed, beyond the neuroprotective roles discussed here, the PDGF system holds the potential to better understand and perhaps treat several non-neuronal disease states including cancer, fibrosis/connective tissue disorders, and vascular disease [12] .…”

Section: Therapeutic Approaches To Modulating Pdgf Signalingmentioning

confidence: 99%

Neuroprotective effects of direct activation and transactivation of PDGFβ receptors

Vasefi¹,

Beazely²

2020

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Platelet-derived growth factor (PDGF) receptors are expressed throughout the body, including the central nervous system (CNS). Although the physiological role of PDGF receptors in the developed CNS is not fully characterized, PDGF signaling appears to provide neuroprotective effects against several neuronal insults. One of the bestcharacterized neuroprotective effects of PDGF type-b receptors is against human immunodeficiency virus (HIV) protein-induced neurotoxicity, with potential physiological relevance to HAD. PDGFb receptors are also neuroprotective against glutamate excitotoxicity, which is associated with both stroke and neurodegenerative diseases, including Alzheimer's disease. The neuroprotective effects of PDGFb receptors occur both via direct activation by ligand (PDGF-BB), as well as by PDGFb receptors activated downstream of G protein-coupled receptor signaling. In addition to the involvement of PDGF signaling in various pathologies and potential therapies, there is also an emerging body of evidence that PDGF may serve as a biomarker for neurological or psychiatric diseases.

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“…Aberrant PDGF signaling is primarily tumorigenic and it regulates the surrounding micro-environment; PDG is a major mitogen and chemoattractant for mesenchymal and glial cells [21] . The contrasting profiles of autocrine versus paracrine mechanisms involve a diverse cell series of subpopulation diversities that are potentially highly characterizable within the systems of cooperative pathway dynamics.…”

Section: Modulated Effects Of Receptor Dimerizationmentioning

confidence: 99%

Distinctive PDGF Biology of Autocrine Action Versus Paracrine Effects in Tumor Cell Growth/Proliferation Versus Metastatic Spread

2017

Med One

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Highly distinctive diversity patterns of operational dysfunction allow for the contrasting biology of autocrine attributes versus the promotional effects of paracrine action of the PDGF ligand/receptor complex. Indeed, the metastatic capabilities of malignant cells contrast with a primary localization of the parent tumor lesion within scopes of a predominant stromal series of activation as exerted by the PDGF/receptor complex. Homologous pairing of the PDGF ligand polypeptides contrasts with the heterologous pairing of the A-B polypeptides of the PDGF ligand in an extensive cross-talk of pathway effects and of receptor-receptor interactivity within the tumor cell membrane. Overall predominance of stromal biologic effects may paradoxically render the parent malignant cells with potent capabilities in metastatic deposition and further spread.

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Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor

Cited by 36 publications

References 113 publications

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer

Neuroprotective effects of direct activation and transactivation of PDGFβ receptors

Distinctive PDGF Biology of Autocrine Action Versus Paracrine Effects in Tumor Cell Growth/Proliferation Versus Metastatic Spread

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