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Article ; Online: Myeloid-Derived Suppressor Cells as a Potential Biomarker and Therapeutic Target in COVID-19.

Rowlands, Marianna / Segal, Florencia / Hartl, Dominik

2021 Volume 12, Page(s) 697405

Abstract: Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host ...

Abstract	Clinical presentations of COVID-19 are highly variable, yet the precise mechanisms that govern the pathophysiology of different disease courses remain poorly defined. Across the spectrum of disease severity, COVID-19 impairs both innate and adaptive host immune responses by activating innate immune cell recruitment, while resulting in low lymphocyte counts. Recently, several reports have shown that patients with severe COVID-19 exhibit a dysregulated myeloid cell compartment, with increased myeloid-derived suppressor cells (MDSCs) correlating with disease severity. MDSCs, in turn, promote virus survival by suppressing T-cell responses and driving a highly pro-inflammatory state through the secretion of various mediators of immune activation. Here, we summarize the evidence on MDSCs and myeloid cell dysregulation in COVID-19 infection and discuss the potential of MDSCs as biomarkers and therapeutic targets in COVID-19 pneumonia and associated disease.
MeSH term(s)	Biomarkers ; COVID-19/pathology ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Myeloid-Derived Suppressor Cells/cytology ; Myeloid-Derived Suppressor Cells/immunology ; SARS-CoV-2/immunology ; Severity of Illness Index ; T-Lymphocytes/immunology
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-06-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.697405
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Article ; Online: Efficacy and safety of MAS825 (anti-IL-1β/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function.

Hakim, Alex D / Awili, Mustafa / O'Neal, Hollis R / Siddiqi, Omar / Jaffrani, Naseem / Lee, Richard / Overcash, Jeffrey S / Chauffe, Ann / Hammond, Terese C / Patel, Bela / Waters, Michael / Criner, Gerard J / Pachori, Alok / Junge, Guido / Levitch, Rafael / Watts, Jen / Koo, Philip / Sengupta, Tirtha / Yu, Lili /

Kiffe, Michael / Pinck, Anne / Stein, Richard R / Bendrick-Peart, Jamie / Jenkins, Janet / Rowlands, Marianna / Waldron-Lynch, Frank / Matthews, Jesse

Clinical and experimental immunology

2023 Volume 213, Issue 3, Page(s) 265–275

Abstract: MAS825, a bispecific IL-1β/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to ... ...

Abstract	MAS825, a bispecific IL-1β/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1β and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Interleukin-18 ; Inflammation ; Hospitalization ; Treatment Outcome
Chemical Substances	Interleukin-18
Language	English
Publishing date	2023-06-19
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad065
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Article ; Online: Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma.

Porsbjerg, Celeste M / Menzies-Gow, Andrew N / Tran, Trung N / Murray, Ruth B / Unni, Bindhu / Audrey Ang, Shi Ling / Alacqua, Marianna / Al-Ahmad, Mona / Al-Lehebi, Riyad / Altraja, Alan / Belevskiy, Andrey S / Björnsdóttir, Unnur S / Bourdin, Arnaud / Busby, John / Canonica, G Walter / Christoff, George C / Cosio, Borja G / Costello, Richard W / FitzGerald, J Mark /

Fonseca, João A / Hansen, Susanne / Heaney, Liam G / Heffler, Enrico / Hew, Mark / Iwanaga, Takashi / Jackson, Daniel J / Kocks, Janwillem W H / Kallieri, Maria / Bruce Ko, Hsin-Kuo / Koh, Mariko Siyue / Larenas-Linnemann, Désirée / Lehtimäki, Lauri A / Loukides, Stelios / Lugogo, Njira / Maspero, Jorge / Papaioannou, Andriana I / Perez-de-Llano, Luis / Pitrez, Paulo Márcio / Popov, Todor A / Rasmussen, Linda M / Rhee, Chin Kook / Sadatsafavi, Mohsen / Schmid, Johannes / Siddiqui, Salman / Taillé, Camille / Taube, Christian / Torres-Duque, Carlos A / Ulrik, Charlotte / Upham, John W / Wang, Eileen / Wechsler, Michael E / Bulathsinhala, Lakmini / Carter, Victoria / Chaudhry, Isha / Eleangovan, Neva / Hosseini, Naeimeh / Rowlands, Mari-Anne / Price, David B / van Boven, Job F M

The journal of allergy and clinical immunology. In practice

2022 Volume 10, Issue 5, Page(s) 1202–1216.e23

Abstract: Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine.: Objective: To compare global differences in ease of access to ... ...

Abstract	Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. Objective: To compare global differences in ease of access to biologics. Methods: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. Results: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. Conclusions: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world.
MeSH term(s)	Anti-Asthmatic Agents/therapeutic use ; Asthma/drug therapy ; Asthma/epidemiology ; Biological Products/therapeutic use ; Biological Therapy ; Humans ; Omalizumab/therapeutic use ; Prescriptions
Chemical Substances	Anti-Asthmatic Agents ; Biological Products ; Omalizumab (2P471X1Z11)
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2021.12.027
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Article ; Online: Aggrecan Directs Extracellular Matrix-Mediated Neuronal Plasticity.

Rowlands, Daire / Lensjø, Kristian K / Dinh, Tovy / Yang, Sujeong / Andrews, Melissa R / Hafting, Torkel / Fyhn, Marianne / Fawcett, James W / Dick, Gunnar

The Journal of neuroscience : the official journal of the Society for Neuroscience

2018 Volume 38, Issue 47, Page(s) 10102–10113

Abstract: In the adult brain, the extracellular matrix (ECM) influences recovery after injury, susceptibility to mental disorders, and is in general a strong regulator of neuronal plasticity. The proteoglycan aggrecan is a core component of the condensed ECM ... ...

Abstract	In the adult brain, the extracellular matrix (ECM) influences recovery after injury, susceptibility to mental disorders, and is in general a strong regulator of neuronal plasticity. The proteoglycan aggrecan is a core component of the condensed ECM structures termed perineuronal nets (PNNs), and the specific role of PNNs on neural plasticity remains elusive. Here, we genetically targeted the
MeSH term(s)	Aggrecans/analysis ; Aggrecans/deficiency ; Aggrecans/genetics ; Animals ; Cell Line ; Extracellular Matrix/chemistry ; Extracellular Matrix/genetics ; Extracellular Matrix/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Nerve Net/chemistry ; Nerve Net/metabolism ; Neuronal Plasticity/physiology ; Photic Stimulation/methods ; Visual Cortex/chemistry ; Visual Cortex/metabolism
Chemical Substances	Aggrecans
Language	English
Publishing date	2018-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1122-18.2018
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Article ; Online: Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

Whiting, Penny F / Moore, Theresa H M / Jameson, Catherine M / Davies, Philippa / Rowlands, Mari-Anne / Burke, Margaret / Beynon, Rebecca / Savovic, Jelena / Donovan, Jenny L

BJU international

2016 Volume 118, Issue 2, Page(s) 193–204

Abstract: To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with ... ...

Abstract	To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.
MeSH term(s)	Humans ; Male ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/therapy ; Quality of Life
Language	English
Publishing date	2016-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1462191-5
ISSN	1464-410X ; 1464-4096 ; 1358-8672
ISSN (online)	1464-410X
ISSN	1464-4096 ; 1358-8672
DOI	10.1111/bju.13499
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Article ; Online: Metabolic imbalance and prostate cancer progression.

Burton, Anya J / Tilling, Kate M / Holly, Jeff M / Hamdy, Freddie C / Rowlands, Mari-Anne E / Donovan, Jenny L / Martin, Richard M

International journal of molecular epidemiology and genetics

2010 Volume 1, Issue 4, Page(s) 248–271

Abstract: There is substantial evidence implicating environmental factors in the progression of prostate cancer. The metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production have been linked to prostate ... ...

Abstract	There is substantial evidence implicating environmental factors in the progression of prostate cancer. The metabolic consequences of a western lifestyle, such as obesity, insulin resistance and abnormal hormone production have been linked to prostate carcinogenesis through multiple overlapping pathways. Insulin resistance results in raised levels of the mitogens insulin and insulin-like growth factor-1, both of which may affect prostate cancer directly, or through their effect on other metabolic regulators. Obesity is associated with abnormal levels of adipocyte-derived peptides (adipokines), sex hormones and inflammatory cytokines. Adipokines have been shown to influence prostate cancer in both cell culture studies and observational, population level studies. Testosterone appears to have a complex relationship with prostate carcinogenesis, and it has been suggested that the lower levels associated with obesity may select for more aggressive androgen independent prostate cancer cells. Prostatic inflammation, caused by infection, urinary reflux or dietary toxins, frequently occurs prior to cancer development and may influence progression to advanced disease. High levels of ω-6 fatty acids in the diet may lead to the production of further inflammatory molecules that may influence prostate cancer. Increased fatty acid metabolism occurs within tumour cells, providing a potential target for prostate cancer therapies. Aberrations in amino acid metabolism have also been identified in prostate cancer tissue, particularly in metastatic cancer. This evidence indicates lifestyle interventions may be effective in reducing the incidence of clinical disease. However, much more research is needed before recommendations are made.
Language	English
Publishing date	2010-07-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2553441-5
ISSN	1948-1756 ; 1948-1756
ISSN (online)	1948-1756
ISSN	1948-1756
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Article ; Online: Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis.

Rowlands, Mari-Anne / Gunnell, David / Harris, Ross / Vatten, Lars J / Holly, Jeff M P / Martin, Richard M

International journal of cancer

2009 Volume 124, Issue 10, Page(s) 2416–2429

Abstract: Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations ... ...

Abstract	Insulin-like growth factors (IGF-I, IGF-II) and their binding proteins (IGFBP-1-6) play a key role in cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis. Several epidemiological studies show associations of IGFs with prostate cancer. We searched the published literature for all studies relating levels of IGFs or IGFBPs with prostate cancer. We performed random effects meta-analysis to calculate summary odds ratios. The number of studies (prostate cancer cases) included in each meta-analysis were 42 (7,481) IGF-I; 10 (923) IGF-II; 3 (485) IGFBP-1; 5 (577) IGFBP-2; 29 (6,541) IGFBP-3 and 11 (3,545) IGF-1:IGFBP-3 ratio. The pooled odds ratios (95% confidence intervals) per standard deviation increase in peptide were: IGF-I, OR = 1.21 (1.07, 1.36); IGF-II, OR = 1.17 (0.93, 1.47); IGFBP-1, OR = 1.21 (0.62, 2.33); IGFBP-2, OR = 1.18 (0.90, 1.54); IGFBP-3, OR = 0.88 (0.79, 0.98); IGFI:IGFBP-3 ratio, OR = 1.10 (0.97, 1.24). For all exposures, there was substantial heterogeneity (all I(2) > 75%), partly explained by study design: the magnitude of associations was smaller in prospective vs. retrospective studies, and for IGFBP-3, the inverse association with prostate cancer risk was seen in retrospective but not prospective studies. There was weak evidence that associations of IGF-I and IGFBP-3 with prostate cancer were stronger for advanced disease. Our meta-analysis confirms that raised circulating lGF-I is positively associated with prostate cancer risk. Associations between IGFBP-3 and prostate cancer were inconsistent, and there was little evidence for a role of IGF-II, IGFBP-1 or IGFBP-2 in prostate cancer risk.
MeSH term(s)	Humans ; Insulin-Like Growth Factor Binding Proteins/chemistry ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Male ; Peptides/blood ; Prostatic Neoplasms/blood ; Risk Factors ; Somatomedins/chemistry ; Somatomedins/metabolism
Chemical Substances	Insulin-Like Growth Factor Binding Proteins ; Peptides ; Somatomedins
Language	English
Publishing date	2009-02-17
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.24202
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A cross-sectional analysis of the association between diet and insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2, and IGFBP-3 in men in the United Kingdom.

Young, Nicholas J / Metcalfe, Chris / Gunnell, David / Rowlands, Mari-Anne / Lane, J Athene / Gilbert, Rebecca / Avery, Kerry N L / Davis, Michael / Neal, David E / Hamdy, Freddie C / Donovan, Jenny / Martin, Richard M / Holly, Jeff M P

Cancer causes & control : CCC

2012 Volume 23, Issue 6, Page(s) 907–917

Abstract: Background: There is evidence of associations between insulin-like growth factor I (IGF-I), IGF-II, insulin-like binding protein-2 (IGFBP-2), IGFBP-3, and prostate cancer risk. This study examines the association between dietary factors associated with ... ...

Abstract	Background: There is evidence of associations between insulin-like growth factor I (IGF-I), IGF-II, insulin-like binding protein-2 (IGFBP-2), IGFBP-3, and prostate cancer risk. This study examines the association between dietary factors associated with prostate cancer and serum levels of these peptides. Methods: A cross-sectional analysis of self-reported 12-month dietary intake with serum IGF and IGFBP levels was performed using data from 1,798 subjects screened negative for prostate cancer as part of a UK multicenter trial comparing treatments for this condition. Multivariable linear regression models tested associations of diet with IGFs and IGFBPs. Results: For a one standard deviation (SD) increase in dairy product and dairy protein intake, IGF-I increased by 5.28 ng/mL (95 % confidence interval: 2.64, 7.92 ng/mL) and 6.02 ng/mL (3.34, 8.71 ng/mL), respectively. A 25 % increase in calcium and selenium intake was associated with an increase in IGF-I of 5.92 ng/mL (3.77, 8.07 ng/mL) and 2.61 ng/mL (1.10, 4.13 ng/mL), respectively. A one SD increase in animal protein was associated with a decrease in IGFBP-2 of 6.20 % (-8.91, -3.41 %), and there was some evidence of an inverse association with dairy protein and calcium. There was no evidence of any dietary associations with IGFBP-3 or IGF-II. Conclusions: Diet is associated with IGF-I and IGFBP-2 levels in men in the UK, and these peptides warrant further investigation as part of randomized trials of dietary interventions to reduce the risk or progression of prostate cancer. There is no evidence that IGF-II or IGFBP-3 are mediators of dietary associations with prostate cancer.
MeSH term(s)	Calcium, Dietary/administration & dosage ; Calcium, Dietary/metabolism ; Case-Control Studies ; Cross-Sectional Studies ; Diet ; Dietary Proteins/administration & dosage ; Dietary Proteins/metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 2/blood ; Insulin-Like Growth Factor Binding Protein 3/blood ; Insulin-Like Growth Factor I/metabolism ; Insulin-Like Growth Factor II/metabolism ; Male ; Middle Aged ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/metabolism ; Risk Factors ; Selenium/administration & dosage ; Selenium/metabolism ; United Kingdom
Chemical Substances	Calcium, Dietary ; Dietary Proteins ; IGFBP3 protein, human ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I (67763-96-6) ; Insulin-Like Growth Factor II (67763-97-7) ; Selenium (H6241UJ22B)
Language	English
Publishing date	2012-04-21
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1064022-8
ISSN	1573-7225 ; 0957-5243
ISSN (online)	1573-7225
ISSN	0957-5243
DOI	10.1007/s10552-012-9961-6
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Article ; Online: Insulin-like growth factors (IGFs) and IGF-binding proteins in active monitoring of localized prostate cancer: a population-based observational study.

Rowlands, Mari-Anne / Tilling, Kate / Holly, Jeff M P / Metcalfe, Chris / Gunnell, David / Lane, Athene / Davis, Michael / Donovan, Jenny / Hamdy, Freddie / Neal, David E / Martin, Richard M

Cancer causes & control : CCC

2012 Volume 24, Issue 1, Page(s) 39–45

Abstract: Purpose: Active monitoring of prostate cancer requires the selection of low-risk cancers and subsequent identification of disease progression. Our objective was to determine whether serum insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein ( ... ...

Abstract	Purpose: Active monitoring of prostate cancer requires the selection of low-risk cancers and subsequent identification of disease progression. Our objective was to determine whether serum insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-2 or IGFBP-3 at diagnosis (potential biomarkers of prognosis), and repeated measures of IGFBP-2 (potential biomarker of tumour growth), were associated with annual change in PSA and PSA doubling time (PSADT), proxies for disease progression. Methods: We investigated associations of circulating IGFs and IGFBPs with PSA measures using multilevel models, in 909 men (recruited between 1999 and 2009) with PSA-detected clinically localized prostate cancer undergoing active monitoring in the United Kingdom. Each man had an average of 14 measurements of PSA during a mean of 4-year follow-up. Results: IGF-I, IGF-II, IGFBP-2, and IGFBP-3 were not associated with baseline PSA. There was weak evidence that IGF-I at diagnosis was positively associated with a rapid post-diagnosis PSADT (≤4 years vs. >4 years): OR 1.34 (95 % CI 0.98, 1.81) per SD increase in IGF-I. IGFBP-2 increased by 2.1 % (95 % CI 1.4, 2.8) per year between 50 and 70 years, with no association between serial IGFBP-2 levels and PSADT. There was no evidence that serum IGF-II, IGFBP-2, or IGFBP-3, or post-diagnosis IGFBP-2, were associated with PSA kinetics in men with PSA-detected localized prostate cancer. Conclusions: The weak association of IGF-I with PSADT requires replication in larger datasets, and more definitive evidence will be provided on the maturity of long-term active monitoring cohorts with relevant clinical outcomes (metastasis and prostate cancer mortality).
MeSH term(s)	Aged ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/blood ; Carcinoma/blood ; Carcinoma/diagnosis ; Carcinoma/pathology ; Carcinoma/therapy ; Follow-Up Studies ; Humans ; Insulin-Like Growth Factor Binding Proteins/analysis ; Insulin-Like Growth Factor Binding Proteins/blood ; Insulin-Like Growth Factor Binding Proteins/physiology ; Male ; Middle Aged ; Monitoring, Physiologic/methods ; Observation ; Population ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/therapy ; Somatomedins/analysis ; Somatomedins/physiology
Chemical Substances	Biomarkers, Tumor ; Insulin-Like Growth Factor Binding Proteins ; Somatomedins ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2012-10-21
Publishing country	Netherlands
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1064022-8
ISSN	1573-7225 ; 0957-5243
ISSN (online)	1573-7225
ISSN	0957-5243
DOI	10.1007/s10552-012-0087-7
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Article ; Online: Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT.

Rowlands, Mari-Anne / Holly, Jeff M P / Gunnell, David / Donovan, Jenny / Lane, J Athene / Hamdy, Freddie / Neal, David E / Oliver, Steven / Smith, George Davey / Martin, Richard M

Cancer research

2011 Volume 72, Issue 2, Page(s) 503–515

Abstract: Circulating insulin-like growth factor-I (IGF-I) has been studied extensively in prostate cancer, but there is still little information about IGFs and IGF-binding proteins (IGFBP) in cancers detected by the prostate-specific antigen (PSA) test. Here, we ... ...

Abstract	Circulating insulin-like growth factor-I (IGF-I) has been studied extensively in prostate cancer, but there is still little information about IGFs and IGF-binding proteins (IGFBP) in cancers detected by the prostate-specific antigen (PSA) test. Here, we report the findings of a U.K.-based case-control study to investigate circulating IGFs and IGFBPs in PSA-detected prostate cancer with regard to their potential associations with different cancer stages or grades. PSA testing was offered to 110,000 men aged 50 to 69 years from 2002 to 2009. Participants with an elevated level of PSA (≥3.0 ng/mL) underwent prostate biopsy and measurements of blood serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 obtained at recruitment. We found that serum levels of IGF-II (OR per SD increase: 1.16; 95% CI: 1.08-1.24; P(trend) < 0.001), IGFBP-2 (1.18; 1.06-1.31; P(trend) < 0.01) and IGFBP-3 (1.27; 1.19-1.36; P(trend) < 0.001), but not IGF-I (0.99; 0.93-1.04; P(trend) = 0.62), were associated with PSA-detected prostate cancer. After controlling for IGFBP-3, IGF-II was no longer associated (0.99; 0.91-1.08; P(trend) = 0.62) and IGF-I was inversely associated (0.85; 0.79-0.91; P(trend) < 0.001) with prostate cancer. In addition, no strong associations existed with cancer stage or grade. Overall, these findings suggest potentially important roles for circulating IGF-II, IGFBP-2, and IGFBP-3 in PSA-detected prostate cancer, in support of recent in vitro evidence. Although our findings for IGF-I agree with previous results from PSA screening trials, they contrast with positive associations in routinely detected disease, suggesting that reducing levels of circulating IGF-I might not prevent the initiation of prostate cancer but might, nonetheless, prevent its progression.
MeSH term(s)	Aged ; Case-Control Studies ; Cross-Sectional Studies ; Humans ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Male ; Middle Aged ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/blood ; Prostatic Neoplasms/diagnosis ; Risk Factors ; Somatomedins/metabolism
Chemical Substances	Insulin-Like Growth Factor Binding Proteins ; Somatomedins ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2011-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-11-1601
Database	MEDical Literature Analysis and Retrieval System OnLINE

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