Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer

AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.METHODS:Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density(LVD)in 40 CRC specimens.The correlation between IGF-1/IGF-1R and LVD was investigated.Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays.A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo. RESULTS:Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis(r=0.715 and 0.569,respectively,P<0.05)and tumor TNM stage(r=0.731 and 0.609,P<0.05).A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis(r=0.405,P<0.05).A positive correlation was found between LVD and IGF-1R expression(r=0.437,P<0.05).Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells.In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.CONCLUSION:IGF-1/IGF-1R signaling induces tumorassociated lymphangiogenesis and contributes to lymphatic metastasis of CRC.

Effects of Dehydroepiandrosterone on Embryo Quality and Follicular Fluid Markers in Patients with Diminished Ovarian Reserves

Background:To examine the effects of dehydroepiandrosterone(DHEA)on in vitro fertilization(IVF)intracytoplasmic sperm injection(ICSI)and the levels of follicular fluid(FF)markers,namely,anti-Müllerian hormone(AMH),insulin-like growth factor(IGF)-1,bone morphogenetic protein(BMP)-15,and growth differentiation factor(GDF)-9,in patients with diminished ovarian reserves(DORs).Methods:116 patients with DOR were randomized into two groups,DHEA group and control group.Each group contained 58 patients.The DHEA group received 75 mg/d of DHEA for 12 weeks prior to the start of IVF treatment,while the control group entered IVF treatment directly.All patients were treated with the same ovarian stimulation protocol.The primary outcome was high-quality embryo yield.Other IVF parameters,such as the clinical pregnancy rate,embryo survival rate,and intact blastomere rate,were compared between the two groups.FF samples from patients of both groups were collected to measure the levels of AMH,IGF-1,DHEA-sulfate,BMP-15,and GDF-9.Blood was also collected on day 3 of the menstrual cycle to define the baseline hormonal profile and to examine ovarian reserve markers.Results:The high-quality embryo yield was higher in DHEA group than that in control group(P=0.033).AMH and IGF-1 concentrations in FF were significantly higher in DHEA group than that in the control group(2.83±1.14 ng/L vs.1.37±0.55 ng/L,P=0.000;94.02±38.28 ng/L vs.74.03±25.46 ng/L,P=0.004,respectively).The BMP-15 level was also higher in DHEA group(relative expression were 1.80±0.41)than that in control group(relative expression were 0.79±0.16,P<0.0001);however,there was no difference in GDF-9 expression between the two groups(relative expression were 1.29±0.54 and 1.16±0.50 respectively,P>0.05)and in the clinical pregnancy rate between the two groups(13.79%vs.7.27%,respectively,P>0.05).Conclusions:In women with DOR undergoing IVF treatment,pretreatment with DHEA may increase the number of high-quality embryos,which may be due to increased levels of AMH,IGF-1,and BMP-15 in the FF.