Insulin-like growth factor (IgF)-I, IgF binding protein-3, and prostate cancer: correlation with gleason score

Kim²,

et al. 2018

Cancer Medicine

BackgroundWe evaluated the association between serum levels of insulin‐like growth factor‐1 (IGF‐1), bioavailable testosterone, and surgical Gleason score (GS).MethodsWe analyzed 793 patients who underwent radical prostatectomy and 272 men with negative prostate biopsy. Serum levels of IGF‐1 and testosterone were measured before surgery or biopsy.ResultsThe mean IGF‐1 levels of prostate cancer patients and men with a negative biopsy were 143.8 and 118.9 ng/mL, respectively (P < 0.001). Men with high serum IGF‐1 were more likely to have prostate cancer (highest vs lowest quartile, odds ratio [OR] = 3.35; P trend < 0.001). However, among men with prostate cancer, the mean IGF‐1 levels of those with low (GS ≤ 6), intermediate (GS = 7), and high surgical GS (GS ≥8) were 151.7, 144.1, and 132.9 ng/mL, respectively (P < 0.001). Using quartile analysis, high serum IGF‐1 levels were shown to be associated with a low risk of high surgical GS (OR = 0.464; P trend = 0.006). Serum bioavailable testosterone concentration was positively correlated with serum IGF‐1 level (r = 0.157, P < 0.001). High bioavailable testosterone level was also associated with a low risk of high surgical GS in patients without diabetes mellitus (OR = 0.569; P trend = 0.040). Among men with biopsy GS ≤ 3 + 4 (n = 460), upgrading to high surgical GS was more frequent in patients with low IGF‐1 level (≤116.0 ng/mL; 9.9%) or low bioavailable testosterone level (≤0.85 ng/mL; 9.3%) than in patients with normal IGF‐1 and bioavailable testosterone levels (2.6%; P = 0.004).ConclusionsSerum levels of IGF‐1 and bioavailable testosterone show inverse associations with high surgical GS. This suggests that high‐grade prostate cancer develops independently of these two substances.

Section: Discussionmentioning

confidence: 92%

“…All three of the quoted studies demonstrated trends toward lower IGF‐1 level in high‐grade disease, but these fell short of statistical significance 28, 29, 30. Of these previous studies, the one with the largest sample size ( n = 242) used a GS based on prostatic biopsy, rather than surgical pathology 30.…”

Section: Discussionmentioning

confidence: 96%

Association between serum levels of insulin‐like growth factor‐1, bioavailable testosterone, and pathologic Gleason score

Kim²,

et al. 2018

Cancer Medicine

“…The inverse correlation between PSA and IGFBP-3 could make IGFBP-3 a possible biochemical marker of disease control in prostate cancer patients. (25) The present study has limitations such as not performing measurements on IGFBP-3 and not doing more clinical examinations, such as a digital rectalexaminations for confirmation of any abnormality in the prostate of subjects with PSA levels above 4 ng/L.…”

Section: Discussionmentioning

confidence: 92%

Blood cadmium levels increase prostate specific antigen and insulin-like growth factor-1 among cadmium exposed workers

Roestijawati¹,

Maurits²,

Sugiyanto³

2017

UnivMed

BACKGROUND Cadmium (Cd) is a heavy metal that is classified as a human carcinogen (group IA), one of the cancers that it can cause being prostate cancer. The development of prostate cancer on a molecular basis involves oncogenes such as insuline-like growth factor-1 (IGF-1). Prostate cancer can be detected in the laboratory through the examination of prostate specific antigen (PSA). The present study aimed to determine the relationship of Cd levels with levels of PSA and IGF-1 in exposed and unexposed workers.METHODS The study design was cross sectional. The subjects of the studycame from two groups of workers, ie. the group of Cd exposed workers who were welding shop workers and the group of unexposed workers who were office workers. The minimum samplesize was 85 people. The independent variable was blood Cd level. The dependent variables were PSA and IGF-1 levels. Blood Cd levels were measured by atomic absorption spectrometry (AAS), while PSA and IGF-1 were measured using ELISA. Data analysis was performed using the Mann-Whitney test and the Spearman correlation test.RESULTS Mean blood Cd level in the exposed workers was 6.5 mg/L and in the unexposed workers 2.15 mg/L. There was a relationship between blood Cd and PSA levels (p<0.05) and between blood Cd levels and IGF-1 (p <0.05).CONCLUSIONS There was a relationship of blood Cd with PSA and IGF-1 levels.among workers. PSA and IGF-1 could be a biochemical markers of disease control in cadmium exposed workers.

Molecular Cancer Research

“…On the other hand, metformin treatment in HFD-fed mice was associated with decreased expression of GHR and IGFBP3. Interestingly, GHR appeared to be upregulated in colorectal and breast cancer samples (48), and its downregulation is associated with better metabolic profile and lower cancer incidence (49), whereas IGFBP3 levels are elevated in patients with prostate cancer (50), suggesting that metformin could be partially exerting its beneficial effects under HFD conditions through the regulation of the local expression of different GH/IGF1 axis components. Remarkably, whether these expression changes are accompanied by alterations in protein levels is still to be defined.…”

Section: Discussionmentioning

confidence: 99%

Metformin Reduces Prostate Tumor Growth, in a Diet-Dependent Manner, by Modulating Multiple Signaling Pathways

Sarmento‐Cabral

L‐López

Gahete

et al. 2017

Prostate-cancer is strongly influenced by obesity, wherein metformin could represent a promising treatment; however, the endocrine metabolic/cellular/molecular mechanisms underlying these associations and effects are still unclear. To determine the beneficial antitumoral effects of metformin on prostate cancer progression/aggressiveness and the relative contribution of high-fat diet (HFD; independently of obesity), we used HFD-fed immunosuppressed mice inoculated with PC3 cells (which exhibited partial resistance to diet-induced obesity) compared with low-fat diet (LFD)-fed control mice. Moreover, gene expression analysis was performed on cancer-associated genes in the xenografted tumors, and the antitumorigenic role of metformin on tumoral (PC3/22Rv1/LNCaP) and normal (RWPE1) prostate cells was evaluated. The results demonstrate that HFD is associated with enhanced prostate cancer growth irrespective of body weight gain and endocrine metabolic dysregulations and that metformin can reduce prostate cancer growth under LFD but more prominently under HFD, acting through the modulation of several tumoral-associated processes (e.g., cell cycle, apoptosis, and/or necrosis). Moreover, the actions observed could be mediated by the modulation of the local expression of GH/IGF1 axis components. Finally, it was demonstrated that metformin had disparate effects on proliferation, migration, and prostate-specific antigen secretion from different cell lines. Altogether, these data reveal that metformin inhibits prostate cancer growth under LFD and, specially, under HFD conditions through multiple metabolic/tumoral signaling pathways. The current study linking dietary influence on metformin-regulated signaling pathways and antitumoral response provides new and critical insight on environment-host interactions in cancer and therapy. .