Magnetic Resonance Imaging Detection of Glucose-Stimulated Zinc Secretion in the Enlarged Dog Prostate as a Potential Method for Differentiating Prostate Cancer From Benign Prostatic Hyperplasia

Khalighinejad, Pooyan; Parrott, Daniel; Jordan, Veronica Clavijo; Chirayil, Sara; Preihs, Christian; Rofsky, Neil M.; Xi, Yin; Sherry, A. Dean

doi:10.1097/rli.0000000000000760

Cited by 10 publications

(10 citation statements)

References 53 publications

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“…The SR-XRF data also showed that glucose promotes the movement of Zn 2+ pools (∼1 mM) from the glandular lumen of the lateral lobe into the stromal/smooth muscle surrounding the glands. More recently, GdL1 was used to detect glucose-stimulated Zn 2+ -secretion in older dogs with clinically diagnosed benign prosthetic hypertrophy (BPH) [86]. This observation is important because in man, differentiation of prostate cancer from BPH tissues on MRI scans can be challenging, so translation of this technology to the clinic could be diagnostically important.…”

Section: Figurementioning

confidence: 99%

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

2020

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Paramagnetic metal ion complexes, mostly based on gadolinium (Gd3+), have been used for over 30 years as magnetic resonance imaging (MRI) contrast agents. Gd3+-based contrast agents have a strong influence on T1 relaxation times and are consequently the most commonly used agents in both the clinical and research environments. Zinc is an essential element involved with over 3000 different cellular proteins, and disturbances in tissue levels of zinc have been linked to a wide range of pathologies, including Alzheimer’s disease, prostate cancer, and diabetes mellitus. MR contrast agents that respond to the presence of Zn2+ in vivo offer the possibility of imaging changes in Zn2+ levels in real-time with the superior spatial resolution offered by MRI. Such responsive agents, often referred to as smart agents, are typically composed of a paramagnetic metal ion with a ligand encapsulating it and one or more chelating units that selectively bind with the analyte of interest. Translation of these agents into clinical radiology is the next goal. In this review, we discuss Gd3+-based MR contrast agents that respond to a change in local Zn2+ concentration.

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Section: Figurementioning

confidence: 99%

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

2020

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“…The authors also record a similar association between urinary Zn level and pre-diabetes. It is a possibility that the prostatic Zn gets increasingly secreted out and eventually ends up in urine when levels of blood glucose or dextrose increase [ 188 , 189 ].…”

Section: Resultsmentioning

confidence: 99%

“…Using magnetic resonance imaging with a gadolinium-based Zn-responsive contrast agent and glucose-stimulated Zn secretion has been detected in BPH tissue compared to prostate cancer in a dog model [ 189 ]. If this contrast can be adapted to be used on humans, that will support differentiating BPH from prostate cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Post-radical prostatectomy prostate tissue analyses for levels of Zn will improve understanding of the extent of malignancy and prognosis based on tissue Zn level and distribution alongside standard clinical grading and staging of the disease [ 54 ]. Prostate tissue Zn level and distribution assessed through advanced imaging technologies in dog models were able to differentiate between prostate cancer and BPH [ 189 ]. If this is translated to be implemented in men, may help substantiate the differentiation between prostate cancer and BPH.…”

Section: Discussion and Commentarymentioning

confidence: 99%

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Zinc in Prostate Health and Disease: A Mini Review

Karunasinghe

2022

Biomedicines

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Introduction-With the high global prevalence of prostate cancer and associated mortalities, it is important to enhance current clinical practices for better prostate cancer outcomes. The current review is towards understanding the value of Zn towards this mission. Method-General information on Zn in biology and multiple aspects of Zn involvement in prostate health and disease were referred to in PubMed. Results-The most influential feature of Zn towards prostate health is its ability to retain sufficient citrate levels for a healthy prostate. Zn deficiencies were recorded in serum, hair, and prostate tissue of men with prostate cancer compared to non-cancer controls. Zn gut absorption, albumin binding, and storage compete with various factors. There are multiple associations of Zn cellular influx and efflux transporters, Zn finger proteins, matrix metalloproteinases, and Zn signaling with prostate cancer outcomes. Such Zn marker variations associated with prostate cancer recorded from biological matrices may improve algorithms for prostate cancer screening, prognosis, and management when coupled with standard clinical practices. Discussion-The influence of Zn in prostatic health and disease is multidimensional, therefore more personalized Zn requirements may be beneficial. Several opportunities exist to utilize and improve understanding of Zn associations with prostate health and disease.

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“…Malignant epithelium interacts with other components of the tumor microenvironment and, when corrupted, CAFs induce the Warburg effect, which indirectly or directly results in the production and secretion of important metabolic intermediaries involved in energy production [ 184 ]. Unlike dogs, studies in humans have shown some mechanisms and expression of markers involved in the modulation of PC energy metabolism [ 185 , 186 ]. One of the signaling pathways involved is related to the role of the STAT3 oncogene in the regulation of genes related to cell metabolism [ 187 ].…”

Section: Molecular Biology Of Prostate Cancermentioning

confidence: 99%

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions

Nascente

Amorim

Fonseca-Alves

et al. 2022

Cancers

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First described in 1817, prostate cancer is considered a complex neoplastic entity, and one of the main causes of death in men in the western world. In dogs, prostatic carcinoma (PC) exhibits undifferentiated morphology with different phenotypes, is hormonally independent of aggressive character, and has high rates of metastasis to different organs. Although in humans, the risk factors for tumor development are known, in dogs, this scenario is still unclear, especially regarding castration. Therefore, with the advent of molecular biology, studies were and are carried out with the aim of identifying the main molecular mechanisms and signaling pathways involved in the carcinogenesis and progression of canine PC, aiming to identify potential biomarkers for diagnosis, prognosis, and targeted treatment. However, there are extensive gaps to be filled, especially when considering the dog as experimental model for the study of this neoplasm in humans. Thus, due to the complexity of the subject, the objective of this review is to present the main pathobiological aspects of canine PC from a comparative point of view to the same neoplasm in the human species, addressing the historical context and current understanding in the scientific field.

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Magnetic Resonance Imaging Detection of Glucose-Stimulated Zinc Secretion in the Enlarged Dog Prostate as a Potential Method for Differentiating Prostate Cancer From Benign Prostatic Hyperplasia

Abstract: Supplemental digital content is available in the text.

Cited by 10 publications

References 53 publications

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

Zinc in Prostate Health and Disease: A Mini Review

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions

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