Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors. (J. Clin. Invest. 1990Invest. . 86:1503Invest. -1510

Background/aims: Several studies have reported that sodium hyaluronate is able to improve both symptoms and signs in patients with dry eye but none have demonstrated an improvement of conjunctival epithelial cell abnormalities of the ocular surface. The aim of this study was to explore the effect of sodium hyaluronate-containing eye drops on the ocular surface of patients with dry eye during long term treatment. Methods: A randomised double blind study was undertaken in 86 patients with medium to severe dry eye (that is, rose bengal and/or fluorescein test score of at least 3, tear film break up time <10 seconds, or Schirmer's test <5.5 mm). Patients were treated with either preservative-free sodium hyaluronate or saline for 3 months at a dose of one drop 4-8 times a day. Bulbar impression cytology, slit lamp examinations, and subjective symptoms were evaluated after 1, 2, and 3 months. Impression cytology was considered the primary efficacy parameter of the study. Results: The efficacy analysis was performed on a total of 44 patients who were able to fully adhere to the protocol. After 3 months of treatment sodium hyaluronate improved impression cytology score (p = 0.024 v baseline). At the same time also the difference with respect to placebo was statistically significant (p = 0.036). Study medication was well tolerated and no treatment related adverse events occurred during the study. Conclusions: Sodium hyaluronate may effectively improve ocular surface damage associated with dry eye syndrome.

The human insulin analogue ASPB10 has been reported to have increased affinity for the insulin receptor and to cause breast cancer in female rats. In the study reported here, we investigated whether ASPB10 has an increased mitogenic potency and induces a transformed phenotype in cultured human breast cells. In both MCF-10 cells (a non-malignant human breast line) and MCF-7 cells (a human breast cancer cell line), ASPB10 was approximately twofold more potent than insulin in competing for 125I-insulin binding but sevenfold to tenfold more potent than insulin in competing for 125I-insulin-like growth factor (IGF)-I binding. In addition, ASPB10 was twofold more potent than insulin in stimulating insulin receptor autophosphorylation but significantly more potent in stimulating IGF-I receptor autophosphorylation in both cell lines. Moreover, ASPB10 was approximately sevenfold more potent than insulin in stimulating the growth of MCF-10 and MCF-7 cells. This increased mitogenic effect of ASPB10 was significantly inhibited (but not abolished) when cells were cultured in the presence of alpha-IR3, a monoclonal antibody to the IGF-I receptor. ASPB10, but not insulin, caused phenotypic changes (focus formation) in MCF-10 cells. Neither agent caused colony formation in soft agar in MCF-10 cells, but ASPB10 was more potent than insulin in stimulating colony formation in MCF-7 cells. These observations indicate that in human breast cells, ASPB10 has enhanced mitogenic effects and induces phenotypic changes as a consequence of its activation of both insulin and IGF-I receptors.

A significant reduction in evaporation and improvement in symptoms in all therapy groups were found from baseline to 90 days. However, no significant effect was seen on TTR for any group. The emulsion drops were shown to perform best, improving tear stability, and decreasing osmolarity and corneal staining. These results are consistent with improvements in the lipid layer of the tear film as a result of prolonged use of emulsion drops.

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