• Journal of Veterinary Science
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• v.22 no.6
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• pp.77.1-77.10
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• 2021

Background: Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. Objectives: This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. Methods: The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5-175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5-79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2-57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6-70.5]) in healthy dogs. Conclusions: The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.

• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.449-462
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• 2023

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6299-6303
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• 2012

Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2=48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation.

• Clinical and Experimental Pediatrics
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• v.48 no.11
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• pp.1172-1178
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• 2005

Purpose : Childhood Obesity is increasing throughout the world, and it is known to incur many diseases especially in later life such as diabetes and cardiovascular disorders. The purpose of this study was to investigate the association between obesity and insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3(IGFBP-3) and know if these factors are useful in predicting cardiovascular diseases. Methods : The study group consisted of 64 moderate and severe obese adolescents and the controls were normal adolescents of the same age. body mass index(BMI) was calculated by height and weight; systolic and diastolic blood pressure was measured at resting state. After 10-hour fasting period, blood cholesterol, triglyceride, high density lipoprotein(HDL) cholesterol, low density lipoprotein(LDL) cholesterol, glucose, insulin, free fatty acid, IGF-I and IGFBP-3 were measured. Results : Insulin was significantly higher in the obese adolescent group than the control group(obese group $15.6{\pm}7.0{\mu}IU/mL$, P<0.01). IGF-I was also significantly higher in the obese adolescent group than the control group(obese group $498.1{\pm}122.2ng/mL$, P<0.05). In addition, IGFBP-3 was significantly higher in the obese adolescent group than the control group(obese group $3,777{\pm}4,721ng/mL$, P<0.05). Insulin showed significantly positive correlation with BMI(r=0.3944) and obesity index(r=0.34). IGFBP-3 were significantly correlated with obesity index(r=0.419), diastolic blood pressure (r=0.264) and BMI(r=0.247). Insulin resistance index significantly positive correlation with BMI(r=0.595), blood triglycerid level(r=0.515) and obesity index(r=0.469). Conclusion : Serum insulin, insulin resistance index, IGF-I and IGFBP-3 levels may be useful to predict cardiovascular diseases in adolescent obesity.

• Journal of Animal Science and Technology
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• v.57 no.9
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• pp.31.1-31.11
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• 2015

Background: This study was conducted to investigate the potential association of variation in the insulin-like growth factor binding protein 2 (IGFBP2) gene with growth, carcass and meat quality traits in pigs. IGFBP2 is a member of the insulin-like growth factor binding protein family that is involved in regulating growth, and it maps to a region of pig chromosome 15 containing significant quantitative trait loci that affect economically important trait phenotypes. Results: An IGFBP2 polymorphism was identified in the Michigan State University (MSU) Duroc ${\times}$ Pietrain $F_2$ resource population (n = 408), and pigs were genotyped by MspI PCR-RFLP. Subsequently, a Duroc pig population from the National Swine Registry, USA, (n = 326) was genotyped using an Illumina Golden Gate assay. The IGFBP2 genotypic frequencies among the MSU resource population pigs were 3.43, 47.06 and 49.51 % for the AA, AB and BB genotypes, respectively. The genotypic frequencies for the Duroc pigs were 9.82, 47.85, and 42.33 % for the AA, AB and BB genotypes, respectively. Genotype effects (P < 0.05) were found in the MSU resource population for backfat thickness at $10^{th}$ rib and last rib as determined by ultrasound at 10, 13, 16 and 19 weeks of age, ADG from 10 to 22 weeks of age, and age to reach 105 kg. A genotype effect (P < 0.05) was also found for off test Longissimus muscle area in the Duroc population. Significant effects of IGFBP2 genotype (P < 0.05) were found for drip loss, 24 h postmortem pH, pH decline from 45 min to 24 h postmortem, subjective color score, CIE $L^*$ and $b^*$, Warner-Bratzler shear force, and sensory panel scores for juiciness, tenderness, connective tissue and overall tenderness in MSU resource population pigs. Genotype effects (P < 0.05) were found for 45-min pH, CIE $L^*$ and color score in the Duroc population. Conclusions: Results of this study revealed associations of the IGFBP2 genotypes with growth, carcass and meat quality traits in pigs. The results indicate IGFBP2 as a potential candidate gene for growth rate, backfat thickness, loin muscle area and some pork quality traits.

• Korean Journal of Veterinary Research
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• v.46 no.2
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• pp.97-105
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• 2006

All-trans retinoic acid (AtRA) induces growth inhibition and apoptosis in a variety of tumer cells, including MCF-7 cells. Insulin-like growth factors (IGFs) system has been reported to be associated with the development of cancer. Although MCF-7 cell with AtRA is to be the major stimulus for the cell growth and apoptosis, the mechanism of insulin-like growth factor-I (IGF-I)/insulin-like growth factor binding protein-3 (IGFBP-3) system remains to be elucidated. Thus, this study was conducted to the effect of AtRA on the gene expression and level of IGF-I and IGFBP-3. In addition, we investigated the involvement of PKC-${\delta}$ on the IGF-I and IGFBP-3 secretion in MCF-7 cell. AtRA(${\geq}10^{-7}M$) decreased the IGF-1 secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cells. Especially, the treatment of AtRA at 72 hours caused a significant reduction in the IGF-I secretion and mRNA expressions but increment in IGFBP-3 secretion and mRNA expressions (p < 0.05). $10^{-7}M$ AtRA activated PKC-${\delta}$ that is one among PKC-$\iota$, ${\alpha}$, ${\lambda}$ and ${\delta}$ in MCF-7 cell. Rotllerin, a PKC-${\delta}$ inhibitor, blocked AtRA-induced inhibition of the IGF-I and mRNA expressions, and increase of lGFBP-3 and mRNA expressions in MCF-7 cell. Together, AtRA inhibited the IGF-I secretion and mRNA expressions, but increased IGFBP-3 secretion and mRNA expressions in MCF-7 cell. Furthermore, AtRA-induced alteration of IGF-I, IGFBP-3 secretion, and the gene expressions were mediated via PKC-${\delta}$ activity.

• Journal of Life Science
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• v.16 no.5
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• pp.734-739
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• 2006

This study investigated the hepatoprotective effects of mesangi (Capsosiphon fulvecens) in carbon tetrachloride $(CCI_4)$-induced liver injury. Thirty healthy male Sprague-Dawley rats were divided into three groups : the normal (Normal), $CCI_4$-treated $(CCI_4)$, and mesangi-treated (Exp-CF) groups. Administration of $CCI_4$ increased the levels of GOT, GPT, and LDH in serum, while the levels were significantly decreased by the addition of mesangi. Higher levels of HDL-cholesterol were found in the Normal and Exp-CF groups, which has lower levels of total and LDL-cholesterol. Administration of $CCI_4$ also increased IGFBP-1 expression in serum, but it was decreased in the Exp-CF group. This suggests that $CCI_4$ is involved in the change in IGFBP-1 expression via its hepatotoxicity. The results indicate that mesangi has a hepatoprotective effect in rats given $CCI_4$.

• Journal of Embryo Transfer
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• v.33 no.3
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• pp.177-183
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• 2018

The identification of biomarkers of a living tissues is essentially required to understand specific functions of the cells. In previous study, we reported IGFBP 3 as one of the putative biomarkers, by showing specific expression at porcine spermatogonial stem cells (SSCs) of early stage of porcine testis. In this study, we analyzed the expression of seven members of IGFBP family (IGFBPs) in SSCs and histological expression pattern of pregnancy-associated plasma protein-A (PAPP-A), which plays a role on the growth promoting enzyme by cleavage of IGFBPs in testis of 5 days old pig. RT-PCR analysis showed that IGFBP 1, 2, 3, 4, and 6 were expressed at high level specifically in porcine SSCs compared with whole testis. We performed immunohisotochemical staining of testis sections with PAPP-A and protein gene product 9.5 (PGP9.5) which are the known biomarkers for SSCs. We were not able to find co-expression of PAPP-A and PGP9.5; PAPP-A was expressed only in Sertoli cells and PGP9.5 expression was confirmed in spermatogonium. Additionally, we were able to confirm the GATA4 expression in Sertoli and Leydig cells as a regulator of Sertoli cell function was not detected PGP9.5 expressing cells, indicating indirect evidence of that cytolocalization of PAPP-A expression is limited in Sertoli cells. These results suggested that the PAPP-A expressed in Sertoli cells may play role on regulation of development and differentiation of testicular cells through the IGF axis in neonatal porcine testis.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.483-490
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• 1999

Objectives: Polycystic ovary syndrome (PCOS) has the feature of excessive LH, hyperandrogenism and disturbance of folliculogenesis. Also, insulin, IGF-I and IGFBP-l are involved in the pathogenesis of PCOS. Various surgical and medical therapies have been used and the action mechanisms are related to the endocrine effect. Laparoscopic ovarian electrocautery or laser vaporization is effective in the restoration of ovulation and normal menstrual cycle with minimal invasive procedure especially in the patients resistant to medical therapy. Clomiphen citrate (CC) is used for the ovulation induction in pcas and the resistance is known to be related to insulin, IGF-I, IGFBP-l levels. This study was performed to evaluate the effect of the laparoscopic laser vaporization on the levels of LH, FSH, testosterone, IGF-I and IGFBP-l and on the ovarian response to clomiphen citrate in patients with CC-resistant PCOS. Materials and Methods: The fasting basal serum LH, FSH, testosterone, IGF-I and IGFBP-l level were measured in 10 PCOS patients with CC-resistance and 7 normal controls with regular menstrual cycle. In PCOS, after laparoscopic $CO_2$ laser vaporization, endocrine levels were measured in 1 week interval for 4 weeks and then compared with preoperative levels. Results: In PCOS group, mean serum LH/FSH ratio, testosterone, IGF-I levels were higher and IGFBP-l level was lower than control. LH/FSH ratio decreased from $2.51{\pm}0.67$ to $1.7{\pm}0.6$ (p<0.05) in 2 weeks, to $0.56{\pm}0.2$ (p<0.01) in 3 weeks and to $1.41{\pm}0.3$ (p<0.01) in 4 weeks after operation. Testosterone level decreased from $1.51{\pm}0.82ng/ml$ to $0.65{\pm}0.34ng/ml$ (p<0.05) in 2 weeks, to $0.56{\pm}0.67ng/ml $(p<0.01) in 3 weeks after operation. IGF-I level also decreased from $436{\pm}47.5{\mu}g/l$ to $187{\pm}38{\mu}g/l$ (p<0.0l) in 1 week, to $167{\pm}42{\mu}g/l$ (p<0.01) in 2 weeks, $179{\pm}55{\mu}g/l$ (p<0.01) in 3 weeks and to $120{\pm}43{\mu}g/l$ (p<0.01) in 4 weeks after operation. IGFBP-l level showed no significant change. In 8 of 10 PCOS patients, ovulation was induced with low dose clomiphen citrate. Conclusion: Laparoscopic $CO_2$ laser vaporization restores normal menstrual cycle and ovulation through endocrine effect of decreasing LH/FSH ratio, testosterone and IGF-I level and increases the response to CC. Therefore it is useful for restoration of normal menstruation and induction of ovulation in CC resistant PCOS patients.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.3
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• pp.379-384
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• 2010

The principal objective of this experiment was to determine the effects of dietary betaine on IGF-I, IGFBP-3 and IGFBP-1 secretion and IGF-I mRNA gene expression in the serum and liver of laying hens. A total of 72 ISA-Brown laying hens were fed with four different levels of betaine (0, 300, 600, 1,200 ppm) based on a corn-soybean meal diet containing 2,800 kcal/kg of metabolizable energy (ME) and 16% crude protein (CP) for four weeks. The results indicated significantly higher serum and liver IGF-I concentrations in the laying hens fed with 600 and 1,200 ppm betaine (p<0.05) compared to controls. IGF-I gene expression in liver showed a statistically correlated increase in 600 and 1,200 ppm betaine-fed groups as compared to the controls (p<0.05). Serum IGFBP-3 concentrations were elevated significantly in the groups fed 600 ppm of betaine. However, the secretion of IGFBP-1 in the liver of laying hens fed on 600 and 1,200 ppm of betaine was significantly lower than in the controls (p<0.05). The results of this experiment showed that dietary betaine supplementation plays a pivotal role in changes of the IGFs system in laying hens.