Early over‐expression of GRP receptors in prostatic carcinogenesis

Körner, Meike; Waser, Beatrice; Rehmann, Ruth; Reubi, Jean Claude

doi:10.1002/pros.22743

Cited by 71 publications

(51 citation statements)

References 31 publications

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“…This hypothesis was rejected, with a storage pool being necessary to simulate growth, particularly for containerized seedlings (Sim A, Table 3). The approach of simulating growth from current-day photosynthate is commonly used in models, particularly for evergreen plants (e.g., Jain and Yang, 2005;Law et al, 2006;Thornton et al, 2007), but several authors have proposed the need for a storage pool to balance the C sources and sinks in the short term, as well as to simulate the effects of photosynthetic downregulation in the long term (Pugh et al, 2016;Richardson et al, 2013;Fatichi et al, 2016). Our results support the need for an NSC pool in CBMs.…”

Section: Effects Of Sink Limitation On C Balancesupporting

confidence: 81%

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Inferring the effects of sink strength on plant carbon balance processes from experimental measurements

et al. 2018

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Abstract. The lack of correlation between photosynthesis and plant growth under sink-limited conditions is a long-standing puzzle in plant ecophysiology that currently severely compromises our models of vegetation responses to global change. To address this puzzle, we applied data assimilation to an experiment in which the sink strength of Eucalyptus tereticornis seedlings was manipulated by restricting root volume. Our goals were to infer which processes were affected by sink limitation and to attribute the overall reduction in growth observed in the experiment to the effects on various carbon (C) component processes. Our analysis was able to infer that, in addition to a reduction in photosynthetic rates, sink limitation reduced the rate of utilization of nonstructural carbohydrate (NSC), enhanced respiratory losses, modified C allocation and increased foliage turnover. Each of these effects was found to have a significant impact on final plant biomass accumulation. We also found that inclusion of an NSC storage pool was necessary to capture seedling growth over time, particularly for sink-limited seedlings. Our approach of applying data assimilation to infer C balance processes in a manipulative experiment enabled us to extract new information on the timing, magnitude and direction of the internal C fluxes from an existing dataset. We suggest that this approach could, if used more widely, be an invaluable tool to develop appropriate representations of sink-limited growth in terrestrial biosphere models.

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Section: Effects Of Sink Limitation On C Balancesupporting

confidence: 81%

“…We have dubbed this the "wasteful plant" hypothesis; this hypothesis corresponds to the assumption embedded in some models that respiration is upregulated when labile C accumulates; e.g., CABLE, O-CN (Law et al, 2006;Zaehle and Friend, 2010).…”

Section: Introductionmentioning

confidence: 99%

Inferring the effects of sink strength on plant carbon balance processes from experimental measurements

et al. 2018

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“…Moreover, GRPR expression was positively correlated with androgen receptor expression (26). Kömer et al found a progressive increase in GRPR density over atypical glands from normal prostate gland to high-grade prostatic intraepithelial neoplasia but no further increase to invasive carcinoma (27). These findings are of importance when interpreting GRP imaging studies.…”

Section: Breast Cancermentioning

confidence: 95%

Targeting Neuropeptide Receptors for Cancer Imaging and Therapy: Perspectives with Bombesin, Neurotensin, and Neuropeptide-Y Receptors

et al. 2014

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Learning Objectives: On successful completion of this activity, participants should be able to list and discuss (1) the presence of bombesin receptors, neurotensin receptors, or neuropeptide-Y receptors in some major tumors; (2) the perspectives offered by radiolabeled peptides targeting these receptors for imaging and therapy; and (3) the choice between agonists and antagonists for tumor targeting and the relevance of various PET radionuclides for molecular imaging.Financial Disclosure: The authors of this article have indicated no relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through October 2017.Receptors for some regulatory peptides are highly expressed in tumors. Selective radiolabeled peptides can bind with high affinity and specificity to these receptors and exhibit favorable pharmacologic and pharmacokinetic properties, making them suitable agents for imaging or targeted therapy. The success encountered with radiolabeled somatostatin analogs is probably the first of a long list, as multiple peptide receptors are now recognized as potential targets. This review focuses on 3 neuropeptide receptor systems (bombesin, neurotensin, and neuropeptide-Y) that offer high potential in the field of nuclear oncology. The underlying biology of these peptide/receptor systems, their physiologic and pathologic roles, and their differential distribution in normal and tumoral tissues are described with emphasis on breast, prostate, and lung cancers. Radiolabeled analogs that selectively target these receptors are highlighted.

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“…Prostate cancer expresses gastrin-releasing peptide (GRP) receptors in more than 90% of the primary tumor (16), including tumors at a very early stage of development (17). Metastases, in particular hormone-independent metastases, appear to express GRP receptors-less often than primary tumors, however (16).…”

Section: Prostate Cancermentioning

confidence: 99%

“…The tracers target different biologic processes and therefore do not have the same sensitivity with regard to lymph node detection. It appears that GRP receptors are targets highly expressed already at an early stage of tumor development (17), whereas PSMA is highly expressed in patients with high Gleason scores. Therefore, patients may benefit from both tracers, and the development and optimization of heterobivalent compounds seem to be warranted, as does the use of a cocktail if a single-agent image is not conclusive.…”

Section: Modifications Of Cocktail Approach: Sequential Application Omentioning

confidence: 99%

Approaches to Multireceptor Targeting: Hybrid Radioligands, Radioligand Cocktails, and Sequential Radioligand Applications

Reubi

Maecke

2017

J Nucl Med

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Modern drug discovery highly depends on the identification and validation of the drug targets. Using the method of in vitro quantitative receptor autoradiography, we demonstrated that-for instance, in neuroendocrine tumors-up to 3 receptors can be coexpressed at a relatively high density. In addition, nonendocrine tumors such as breast, prostate, and brain tumors concomitantly express several G protein-coupled receptors at a high density. We propose 3 strategies for exploiting these findings for multireceptor targeting in vivo: use of heterobivalent or heteromultivalent ligands, which may bind simultaneously or monovalently to their different molecular targets; coinjection of a cocktail of radioligands; and sequential injection of different radioligands. Any of these strategies may help to remedy some of the major problems in cancer targeting: heterogeneity, change in phenotype during disease progression, and resistance.

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Early over‐expression of GRP receptors in prostatic carcinogenesis

Abstract: GRP receptor over-expression may be a novel, specific marker of early prostatic neoplastic transformation, arising in low grade PIN, and progressively increasing during malignant progression. This should be considered when interpreting in vivo GRP receptor imaging in males.

Cited by 71 publications

References 31 publications

Inferring the effects of sink strength on plant carbon balance processes from experimental measurements

Inferring the effects of sink strength on plant carbon balance processes from experimental measurements

Targeting Neuropeptide Receptors for Cancer Imaging and Therapy: Perspectives with Bombesin, Neurotensin, and Neuropeptide-Y Receptors

Approaches to Multireceptor Targeting: Hybrid Radioligands, Radioligand Cocktails, and Sequential Radioligand Applications

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