Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort.

High circulating concentration of insulin-like growth factor-I (IGF-I) and low circulating concentration of IGF binding protein-3 (IGFBP-3) have been associated with increased risk for breast, prostate, and colorectal cancers. Building on previous work in the Multiethnic Cohort (MEC) showing significant differences in IGF-I levels across racial/ethnic groups, we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a random sample of 1,000 MEC participants, which included Native Hawaiian, African American, Japanese, Latino, and White men and women. Crude analyses confirmed the existence of differences in protein levels with race/ethnicity, sex, age, and body size. Reproductive, physical activity, smoking, and diet variables had less consistent effects. In multivariate analyses, IGF-I levels were lower and IGFBP-3 were higher in females versus males. IGF-I and IGFBP-3 declined with increasing age in both genders. Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels; in men, height was significantly positively associated with both proteins. In women, alcohol was directly associated with IGFBP-3. Both proteins were lowest among female Latinos. IGF-I was highest among female African Americans. In men, IGFBP-3 was lowest among African Americans. Overall, although these factors were statistically significant determinants of IGF-related protein levels, they did not explain much of the variation in these levels. A positive correlation was found between IGF-I levels (ng/mL) and colon cancer incidence rates (per 100,000) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer.     

Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer.

PURPOSE: Renal cancer response to interleukin 2 (IL-2) therapy and patient survival has been correlated with tumor histology and carbonic anhydrase IX (CAIX) expression. In an effort to confirm and expand these observations, we examined CAIX expression in pathology specimens from renal cancer patients who had previously received IL-2 therapy. EXPERIMENTAL DESIGN: Paraffin-embedded tissue sections of renal cancer were immunostained with the MN-75 monoclonal antibody to CAIX and expression levels were correlated with histologic findings and clinical outcome. RESULTS: Tissue specimens were obtained from 66 patients; 27 of whom (41%) had responded to IL-2-based therapy. Fifty-eight specimens were assessed as clear cell, with 56, 33, and 4 having alveolar, granular, and papillary features, respectively. Twenty-four (36%), 31 (47%), and 11 (17%) were classified into good, intermediate, and poor prognosis groups according to the Upton pathology model. Forty-one specimens (62%) had high CAIX expression. Twenty-one of 27 (78%) responding patients had high CAIX expressing tumors compared with 20 of 39 (51%) nonresponders (odds ratio, 3.3; P = 0.04). Median survival was prolonged (P = 0.04) and survival >5 years was only seen in high CAIX expressers. In patients with intermediate pathologic prognosis, all nine responders had high CAIX expression versus 11 of 22 nonresponders. A resultant group with good pathologic prognosis alone or with intermediate pathologic prognosis and high CAIX contained 26 of 27 (96%) responders compared with 18 of 39 (46%) nonresponders (odds ratio, 30; P < 0.01) and exhibited longer median survival (P < 0.01). CONCLUSIONS: CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2-based therapy and may enhance prognostic information obtained from pathology specimens.     

IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies.

Prospective cohort studies on breast cancer risk among premenopausal women and insulin-like growth factor I (IGF-I) concentrations have so far included only few cases, and have shown inconsistent relative risk estimates. We pooled 220 cases of breast cancer diagnosed before age 50, and 434 control subjects, from three prospective studies in New York (USA), Ume? (Northern Sweden) and Milan (Italy), and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3 measurements obtained by the common method showed a positive but not significant relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75-2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04 [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only moderate support for an association of blood IGF-I with breast cancer risk in young women.     

Analysis and Comparison of Friction Stir Welding and Laser Assisted Friction Stir Welding of Aluminum Alloy

Friction Stir Welding (FSW) is a solid-state joining process; i.e., no melting occurs. The welding process is promoted by the rotation and translation of an axis-symmetric non-consumable tool along the weld centerline. Thus, the FSW process is performed at much lower temperatures than conventional fusion welding, nevertheless it has some disadvantages. Laser Assisted Friction Stir Welding (LAFSW) is a combination in which the FSW is the dominant welding process and the laser pre-heats the weld. In this work FSW and LAFSW tests were conducted on 6 mm thick 5754H111 aluminum alloy plates in butt joint configuration. LAFSW is studied firstly to demonstrate the weldability of aluminum alloy using that technique. Secondly, process parameters, such as laser power and temperature gradient are investigated in order to evaluate changes in microstructure, micro-hardness, residual stress, and tensile properties. Once the possibility to achieve sound weld using LAFSW is demonstrated, it will be possible to explore the benefits for tool wear, higher welding speeds, and lower clamping force.     

TGF-beta -- an excellent servant but a bad master

ABSTRACT: The transforming growth factor (TGF-beta) family of growth factors controls an immense number of cellular responses and figures prominently in development and homeostasis of most human tissues. Work over the past decades has revealed significant insight into the TGF-beta signal transduction network, such as activation of serine/threonine receptors through ligand binding, activation of SMAD proteins through phosphorylation, regulation of target genes expression in association with DNA-binding partners and regulation of SMAD activity and degradation. Disruption of the TGF-beta pathway has been implicated in many human diseases, including solid and hematopoietic tumors. As a potent inhibitor of cell proliferation, TGF-beta acts as a tumor suppressor; however in tumor cells, TGF-beta looses anti-proliferative response and become an oncogenic factor. This article reviews current understanding of TGF-beta signaling and different mechanisms that lead to its impairment in various solid tumors and hematological malignancies.