Cell locomotion, including cancer cell invasion, is closely associated with the dynamics of cytoskeletal structures. Previous in vitro studies indicated that tubulin isotype composition may affect polymerization properties and dynamics of microtubules. Colorectal cancer is a good model for studying tumour invasion because of the easily detectable invasive front. Hence, we investigated the localization of beta(III)-tubulin in colorectal cancer specimens. Immunohistochemical staining for beta(III)-tubulin was evident in cancer cells apparently budding from adjacent malignant cells with a higher differentiation and negative staining. An association between beta(III)-tubulin immunoreactivity and tumour budding grade was demonstrated. To the best of our knowledge, this is the first report documenting a preferential localization of beta(III)-tubulin in the invading epithelium. From this finding arises the possibility that changes in tubulin isotypes could modulate the invading activity of cancer cells. Further investigations are needed to determine whether our findings have clinical implications.
Twelve subjects with insulin-dependent diabetes mellitus were treated using continuous subcutaneous insulin infusion (CSII) and intraportal insulin infusion (IPII) via the umbilical vein for 4 mo. Glucose control improved in both CSII and IPII groups, but a decrease in glucose and HbAIc was more rapid and more significant in the IPII group than in CSII, even though insulin requirement was lower during IPII than CSII (40 +/- 2 vs. 50 +/- 2 U/day, P less than 0.05). The insulin plasma fasting levels were different (88 +/- 10.7 in the IPII group vs. 263 +/- 23 pM in CSII, P less than 0.001). High plasma levels of lactate, pyruvate, alanine, cortisol, and growth hormone were decreased in both groups, with their full normalization only in the IPII group. Glucagon concentrations were low in both groups at the beginning of the study (30.0 +/- 4.1 in the CSII group and 32.3 +/- 1.8 ng/L in IPII); they were equalized to control values in the IPII group and were low in the CSII group at the study's end (46.0 +/- 3.7 in IPII vs. 31.7 +/- 3.1 ng/L in CSII, P less than 0.05. We conclude that intraportal administration of insulin via the umbilical vein at rates of 0.01-0.05 U.kg-1.hr-1 reduces plasma levels of glucose, three carbon precursors, cortisol, and growth hormone by a direct action on the liver, and the hepatic action of peripherally administered insulin is manifested only when the infusion rate is increased to 0.1-0.3 U.kg-1.hr-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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