Clinical implications of insulin-like growth factor I (IGF-I) and II (IGF-II) in stage IIIB cervical cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15505-e15505
Author(s):  
Pooja Nandwani Patel ◽  
Rakesh Vyas ◽  
Maitrik Mehta

e15505 Background: The IGF (Insulin like Growth Factor) family has been implicated in the pathogenesis of cervical cancer. We aim to correlate pre and post treatment levels of IGF-I and IGF-II in stage IIIB cervical cancer and identify if serum IGF-I and IGF-II can be used as a marker to predict response to chemo-radiotherapy. Methods: We recruited 80 previously untreated patients of histopathologically proven squamous cell carcinoma of stage IIIB cancer of uterine cervix from January 2011 to May 2011. The age of patients ranged from 30 to 65 years and were of ECOG performance status of less than or equal to 2. Along with the routine investigations the pretreatment serum levels of IGF-I and IGF-II were done by ELISA kits in all the patients. The serum level of IGF-I was 246.3 ± 72.5 ng/ml and IGF-II was 1585 ± 352 ng/ml. All patients were given concurrent cisplatin (30 mg/m2) weekly along with radiation (50Gy/25#) with conventional portals followed by two sittings of intracavitory radiotherapy (7.5 Gy each) on mHDR. Blood samples for IGF-I and IGF-II levels were collected before the start of the therapy, 1 month after the completion of treatment and 6 months after the completion of the treatment. Results: The trend seen was that mean IGF-I levels were always in the lower range as compared to IGF-II levels in all individuals. The mean serum levels of IGF-I and IGF-II in patients who achieve complete response (45%) returned to normal whereas the mean serum levels of IGF-I and IGF-II in patients who achieved partial response (43%) was 149 ng/ml and 838 ng/ml respectively. The mean serum levels of IGF-I and IGF-II in patients who achieved no response (12%) was 331 ng/ml and 1840 ng/ml respectively. Conclusions: The serum levels of IGF-I and IGF-II may be a reliable prognostic and predictive marker in cervical cancer however further large randomized studies are required to validate the results. IGF-I and IGF-II can serve as potential markers in cervical cancer to risk stratify patients, assess treatment response and possibly act as therapeutic targets in the future.

1991 ◽  
Vol 128 (2) ◽  
pp. 197-204 ◽  
Author(s):  
F. J. Ballard ◽  
S. E. Knowles ◽  
P. E. Walton ◽  
K. Edson ◽  
P. C. Owens ◽  
...  

ABSTRACT Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 °C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1–3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1–3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1–3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4·59, 1·20 and 1·34 ml/min per kg respectively. The mean steadystate volume of distribution was larger for des(1–3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1–3)IGF-I > IGF-I > IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. Journal of Endocrinology (1991) 128, 197–204


2013 ◽  
Vol 151 (1-2) ◽  
pp. 163-167
Author(s):  
Flaviane A. Pinho ◽  
Nilton A. Magalhães ◽  
Kleverton R. Silva ◽  
Aline A. Carvalho ◽  
Fernando L.L. Oliveira ◽  
...  

1995 ◽  
Vol 144 (1) ◽  
pp. 75-82 ◽  
Author(s):  
B W Gallaher ◽  
B H Breier ◽  
W F Blum ◽  
S N McCutcheon ◽  
P D Gluckman

Abstract Although insulin-like growth factor-binding protein-2 (IGFBP-2) is an abundant IGFBP in fetal and postnatal plasma, its regulation is not yet clearly understood. To address this question in sheep, we purified ovine IGFBP-2 and developed a homologous radioimmunoassay. We have studied its ontogenesis and measured serum concentrations of ovine IGFBP-2 after bovine growth hormone (bGH), ovine placental lactogen (oPL) and IGF-I treatment. Concentrations of IGFBP-2 were high at 125 days of gestation (550 ± 15 μg/l) but fell after birth P<0·05) and plateaued after 1 year of age (340 ± 20 μg/l). In lactating ewes, bGH treatment for 7 days significantly reduced (21%; P<0·05) IGFBP-2 relative to the saline-treated group. Similarly, in neonatal lambs, bGH treatment from day 3 to day 23 of life reduced (P<0·05) IGFBP-2 by 23% relative to the saline-treated group. oPL had no effect on serum levels of IGFBP-2 in the ewe or the neonatal lamb. In well-fed yearling lambs, treatment with IGF-I reduced IGFBP-2 values by 27% (P<0·05) relative to control animals. In yearling lambs, reduced nutrition increased plasma IGFBP-2 (41%; P<0·05). However this increase was abolished by IGF-I treatment. The changes in plasma levels of IGFBP-2 were positively related to changes in IGF-II while there was a negative relationship between circulating IGF-I and IGFBP-2 such that both IGF-I and IGF-II may play a role in the regulation of IGFBP-2 in serum. Journal of Endocrinology (1995) 144, 75–82


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19671-19671
Author(s):  
T. Takahata ◽  
M. Munakata ◽  
Y. Sakata ◽  
K. Nakagawa ◽  
T. Mukaiyama ◽  
...  

19671 Background: Pituitary and thyroid hormones are known to be altered in anorexia nervosa, but few hormonal studies have been performed in cancer anorexia-cachexia syndrome. This study focused on growth hormone (GH) and Insulin-like Growth Factor (IGF)-I axis in cancer patients. Methods: To investigate the relationship among performance status (PS), nutritional and hormonal status, blood sampling was performed to measure GH, IGF-I, IGF-binding protein 3(IGFBP-3), T3, T4, complete blood counts and blood chemistry profiles for 15 cancer patients in each of PS0–1, PS2, PS3 and PS4 after the informed consent was obtained. Results: A total of 58 patients were evaluated including 15 patients in PS0–1, PS2 and PS3 and 13 in PS4. Hemoglobin and albumin levels went down along with progression of PS. GH level was high and T3 was low in poor PS. T4 and IGFBP-3 were lower in PS4 than those of other PS. There is a tendency of low IGF-I and thyroid hormones and high GH levels in poor PS as compared with those of good PS (p=0.0064 for IGF-I, p<0.001 for T3, and T4, not significant for GH analyzed by ANOVA). Conclusions: Abnormal GH - IGF-I axis was more pronounced in poor PS. It is conceivable that normalization of this abnormality can improve cancer anorexia-cachexia syndrome and new drug development for such normalizing agents is warranted. No significant financial relationships to disclose.


1992 ◽  
Vol 134 (1) ◽  
pp. 133-139 ◽  
Author(s):  
R. C. Baxter ◽  
H. Saunders

ABSTRACT A radioimmunoassay has been established for the insulin-like growth factor-binding protein, IGFBP-6, isolated from a human transformed fibroblast cell-line. The binding proteins IGFBP-I and IGFBP-3 did not cross-react, but both IGF-I and IGF-II markedly inhibited IGFBP-6 tracer binding to antiserum. This inhibition, greater for IGF-II than for IGF-I, was fully reversed by the addition of IGFBP-3 to sequester the IGFs. After fractionation of human serum and follicular fluid samples by gel chromatography, interference in the radioimmunoassay by fractions corresponding to the 150 kDa IGF-IGFBP complex could be eliminated by IGFBP-3. The equivalent fractions from cerebrospinal fluid and amniotic fluid fractionation did not interfere in the assay. The mean IGFBP-6 level in adult human serum was 0·221 ±0·110 mg/l, with values significantly higher in men than women, and slightly decreased in pregnancy. Similar values were seen in umbilical cord serum and in amniotic and follicular fluid samples, while the mean level in cerebrospinal fluid was slightly lower, 0·152±0·049 mg/l. This assay will facilitate studies on the regulation of IGFBP-6 production, and its role as an IGF carrier. Journal of Endocrinology (1992) 134, 133–139


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