RC-3095, a Selective Gastrin-Releasing Peptide Receptor Antagonist, Does Not Protect the Lungs in an Experimental Model of Lung Ischemia-Reperfusion Injury

Oliveira-Freitas, Vera L.; Thomaz, Leonardo Dalla Giacomassa Rocha; Simoneti, Lucas Elias Lise; Malfitano, Christiane; Angelis, Kátia De; Ulbrich, Jane Maria; Schwartsmann, Gilberto; Andrade, Cristiano Feijó

doi:10.1155/2015/496378

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…In many cancers, they have an autocrine growth effect [9][10][11][12][13]. Their preferred agonist is gastrin-releasing peptide (GRP), a bombesin-like peptide that is the natural ligand of GRPr in vivo in mammals [14][15][16]. GRP and GRP analogues selectively bind to the GRP receptor family.…”

Section: Introductionmentioning

confidence: 99%

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

et al. 2016

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BACKGROUND The gastrin-releasing peptide receptor (GRPr) is upregulated in early and late-stage human prostate cancer (PCa) and other solid tumors of the mammary gland, lung, head and neck, colon, uterus, ovary, and kidney. However, little is known about its role in prostate cancer. This study examined the effects of a heterologous GRPr agonist, bombesin (BBN), on growth, motility, morphology, gene expression, and tumor phenotype of an osteoblastic canine prostate cancer cell line (Ace-1) in vitro and in vivo. METHODS The Ace-1 cells were stably transfected with the human GRPr and tumor cells were grown in vitro and as subcutaneous and intratibial tumors in nude mice. The effect of BBN was measured on cell proliferation, cell migration, tumor growth (using bioluminescence), tumor cell morphology, bone tumor phenotype, and epithelial-mesenchymal transition (EMT) and metastasis gene expression (quantitative RT-PCR). GRPr mRNA expression was measured in primary canine prostate cancers and normal prostate glands. RESULTS Bombesin (BBN) increased tumor cell proliferation and migration in vitro and tumor growth and invasion in vivo. BBN upregulated epithelial-to-mesenchymal transition (EMT) markers (TWIST, SNAIL, and SLUG mRNA) and downregulated epithelial markers (E-cadherin and β-catenin mRNA), and modified tumor cell morphology to a spindle cell phenotype. Blockade of GRPr upregulated E-cadherin and downregulated VIMENTIN and SNAIL mRNA. BBN altered the in vivo tumor phenotype in bone from an osteoblastic to osteolytic phenotype. Primary canine prostate cancers had increased GRPr mRNA expression compared to normal prostates. CONCLUSION These data demonstrated that the GRPr is important in prostate cancer growth and progression and targeting GRPr may be a promising strategy for treatment of prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

et al. 2016

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“…The emulsion (50µL of CII + CFA) was injected intradermally at the base of the tail on day 0. Moreover, the animals received a reinforcement of CII emulsified with incomplete Freund's adjuvant (without M. tuberculosis) in another site of the tail (booster injection) on day 18 [27]. During the procedures, the mice were anesthetized with isoflurane 10% (Abbott Laboratórios do Brasil Ltda., Brazil) and 90% oxygen.…”

Section: Induction Of Ciamentioning

confidence: 99%

The role of proteasome in muscle wasting of experimental arthritis

et al. 2023

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Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.

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“…Beyond cancer cells, tumour vessels show GRPR expression [ 103 ]. Gastrin-releasing peptide (GRP) and GRP analogues exert specific binding potential to GRPR in mammals [ 104 , 105 , 106 ]. Bombesin (BBN), which shares functional and structural similarities with mammalian GRP, also has high affinity towards GRPR [ 95 , 104 ].…”

Section: Bombesin- and Gastrin-releasing Peptide Receptor (Grpr)mentioning

confidence: 99%

Scandium-44: Diagnostic Feasibility in Tumor-Related Angiogenesis

Trencsényi

Képes

2023

IJMS

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Angiogenesis-related cell-surface molecules, including integrins, aminopeptidase N, vascular endothelial growth factor, and gastrin-releasing peptide receptor (GRPR), play a crucial role in tumour formation. Radiolabelled imaging probes targeting angiogenic biomarkers serve as valuable vectors in tumour identification. Nowadays, there is a growing interest in novel radionuclides other than gallium-68 (68Ga) or copper-64 (64Cu) to establish selective radiotracers for the imaging of tumour-associated neo-angiogenesis. Given its ideal decay characteristics (Eβ+average: 632 KeV) and a half-life (T1/2 = 3.97 h) that is well matched to the pharmacokinetic profile of small molecules targeting angiogenesis, scandium-44 (44Sc) has gained meaningful attention as a promising radiometal for positron emission tomography (PET) imaging. More recently, intensive research has been centered around the investigation of 44Sc-labelled angiogenesis-directed radiopharmaceuticals. Previous studies dealt with the evaluation of 44Sc-appended avb3 integrin–affine Arg-Gly-Asp (RGD) tripeptides, GRPR-selective aminobenzoyl–bombesin analogue (AMBA), and hypoxia-associated nitroimidazole derivatives in the identification of various cancers using experimental tumour models. Given the tumour-related hypoxia- and angiogenesis-targeting capability of these PET probes, 44Sc seems to be a strong competitor of the currently used positron emitters in radiotracer development. In this review, we summarize the preliminary preclinical achievements with 44Sc-labelled angiogenesis-specific molecular probes.

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RC-3095, a Selective Gastrin-Releasing Peptide Receptor Antagonist, Does Not Protect the Lungs in an Experimental Model of Lung Ischemia-Reperfusion Injury

Cited by 4 publications

References 29 publications

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer

The role of proteasome in muscle wasting of experimental arthritis

Scandium-44: Diagnostic Feasibility in Tumor-Related Angiogenesis

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