Insulin-like growth factor-I and prostate cancer: a meta-analysis

Shi, Runhua; Berkel, Hans J.; Yu, He

doi:10.1038/sj.bjc.6691961

Cited by 21 publications

(14 citation statements)

References 11 publications

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“…40 Concerning AKT a survival kinase upstream of mTOR, we also did not find differences of the pAKT levels among patients with antidiabetic drugs (metformin and insulin) or those without antidiabetic medication. This finding might support the hypothesis of an AKT-independent regulation of mTOR by mitogen-responsive pathways as described by Memmott et al 41 As we observed an AMPK and AKT independent mTOR regulation, we speculated abn involvement of the IRS-1 and found that pIRS-S639 is significantly decreased in benign cores of metformin users compared to the control (p = 0.002) indicating an activated mTOR pathway. Both metformin and insulin use reduced pmTOR levels in both benign and cancer areas compared to no medication and thereby may exert antitumor effects.…”

supporting

confidence: 92%

Antidiabetic drugs influence molecular mechanisms in prostate cancer

Pircher

Zieher

Eigentler

et al. 2018

Cancer Biology & Therapy

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Background: We investigated the role of diabetes mellitus (DM) and the molecular mechanisms of antidiabetic drugs in prostate cancer (PCa). Patients and Methods: 167 patients with both DM and PCa underwent radical prostatectomy (RPE). We divided our patient collective into "metformin" users, "insulin" users, "other antidiabetic drug" users and those with "no antidiabetic drug/diet only" (control group) and analyzed differences in PCa aggressiveness and laboratory parameters among treatment groups. In addition, we generated a tissue-micro-array (TMA) from RPE specimens for the analysis of candidate target pathways of antidiabetic drugs by immunohistochemistry (IHC). Results: Gleason score of both biopsy and RPE, biopsy undergrading, tumor stage as well as positive resection margins did not significantly change among groups. Preoperative body mass-index, PSA, fPSA and prostate volume/weight did not change among the treatment groups. As well, CRP, GOT, GPT, yGT, LDH, amylase, hemoglobin, TSH, FT3 and FT4 did not differ. Metformin or insulin use was not associated with changes in biochemical tumor recurrence or PCa specific mortality rates. However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group. In addition, we were able to show that the androgen receptor and the epithelial-cell contact marker E-cadherin decreased upon metformin use compared to the control group. Conclusion: We did not find a connection between antidiabetic drugs and PCa aggressiveness or progression. However, tumor biology seems to be different among patients with and without antidiabetic drugs.

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supporting

confidence: 92%

Antidiabetic drugs influence molecular mechanisms in prostate cancer

Pircher

Zieher

Eigentler

et al. 2018

Cancer Biology & Therapy

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“…Meta-analyses suggest that high circulating levels of insulin-like growth factor is associated with increased risk of prostate cancer (46) and predictive of advanced disease (47) However, dietary effects on IGF have been mixed. Earlier studies with rat prostate cancer lines treated with genistein demonstrated a decrease in IGF whereas dietary intervention trials with soy isoflavones in men with prostate cancer had shown no significant change in IGF (48) or increase in IGF (49).…”

Section: Discussionmentioning

confidence: 99%

Isoflavone Pharmacokinetics and Metabolism after Consumption of a Standardized Soy and Soy–Almond Bread in Men with Asymptomatic Prostate Cancer

Ahn‐Jarvis

Clinton

Grainger

et al. 2015

Cancer Prevention Research

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Epidemiological associations suggest populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, cross-over trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy-bread and soy-almond bread. The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance and assessment of biomarkers linked to prostate carcinogenesis. Two distinct soy breads were formulated to deliver ~60 mg aglycone equivalents of isoflavones/day. The isoflavones were present as aglycones (~78% as aglycones,) in the soy-almond bread (SAB) while in the standard soy bread (SB) predominantly as glucosides (18% total isoflavones as aglycones). Compliance to SB (97% ± 4%) and SAB (92% ± 18%) was excellent, toxicity was rare and limited to grade I gastrointestinal complaints. Pharmacokinetic studies between SB and SAB showed modest differences. Peak serum concentration time (Tmax) was significantly faster with SAB meal compared with SB in some isoflavonoids and AUC0 to 24 hr of dihydrodaidzein and O- desmethylangolensin was significantly greater after a SB meal. An exploratory cluster analysis was used to identify four isoflavone metabolizing phenotypes. Insulin-like growth factor binding protein increased significantly by 41% (p=0.024) with soy intervention. Findings from this study provide the necessary framework to study isoflavone metabolizing phenotypes as a strategy for identification of individuals that might benefit or show resistance to cancer preventive strategies using dietary soy. A standardized soy bread used for future large-scale randomized clinical trials to impact human prostate carcinogenesis is feasible.

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“…These studies could help explain experimental [9–11] and epidemiological evidence suggesting that the IGF axis plays a role in carcinogenesis [10]. For example, epidemiological evidence suggests that higher levels of IGF-I and lower levels of IGF binding protein 3 (IGFBP-3) or changes in their ratio are associated with increased risk of breast [12], colorectal [13] and prostate cancer [13,14]. Note that changes in the ratio of IGF-1:IGFBP-3 are thought to reflect changes in bio-available IGF-I [4,8,15,16].…”

Section: Introductionmentioning

confidence: 99%

Race/ethnic variation in serum levels of IGF-I and IGFBP-3 in US adults

Berrigan

Potischman

Dodd

et al. 2009

Growth Hormone & IGF Research

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Objectives-The IGF axis plays a significant role in normal growth and development and variation in IGFs is associated with health outcomes. Past studies report variation in IGF levels among race/ ethnic groups known to differ in disease incidence. This paper reports on race/ethnic variation in serum levels of IGF-I and IGF-BP3 in a nationally representative and ethnically diverse sample of US adults.Design-Serum IGF-I and IGFBP-3 levels from the fasting subsample (n = 6061) of respondents to the US National Health and Nutrition Examination Survey III (NHANES III) were analyzed using an IGF-I ELISA (Diagnostic Systems Laboratory (DSL) 10-5600) and an IGFBP-3 IRMA (DSL 6600). The NHANES is a combined examination and interview survey of a nationally representative sample of US adults. Regression analyses were used to estimate cross-sectional associations between the IGF axis and demographic variables.Results-In unadjusted analyses, serum IGF-I levels were higher in males than in females, and IGFBP-3 levels were higher in females than in males. Both analytes were lower in older adults. Univariate analyses indicate that serum levels of IGF-I are lower in female Non-Hispanic Whites (NHW) (256 [4.9]) and Hispanics (249 [6.6]) than in Non-Hispanic Blacks (NHB) (281 [4.9]). However, in males, IGF levels in NHWs (287 [3.6]) and NHBs (284 [4.3]) are similar and levels in Mexican-Americans are only moderately reduced (265 [3.4]). Notably, NHB's have the highest molar ratio of IGF-I:IGFBP-3 at all ages. After adjustment for age and BMI, gender and race/ethnicity differences persist.Conclusions-These cross-sectional data support exploration of the IGF axis as an explanation for some race/ethnic differences in cancer incidence.

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Insulin-like growth factor-I and prostate cancer: a meta-analysis

Cited by 21 publications

References 11 publications

Antidiabetic drugs influence molecular mechanisms in prostate cancer

Antidiabetic drugs influence molecular mechanisms in prostate cancer

Isoflavone Pharmacokinetics and Metabolism after Consumption of a Standardized Soy and Soy–Almond Bread in Men with Asymptomatic Prostate Cancer

Race/ethnic variation in serum levels of IGF-I and IGFBP-3 in US adults

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