Plant-Based Diet and IGF-1 Modulation on HER2-Positive Breast Cancer: A Lifestyle Medicine Nutrition Approach in Oncology.

Breast cancer is the second most common type of cancer in women worldwide, where nutritional intervention should be part of a multidisciplinary lifestyle approach in oncology, promoting therapeutic success. Insulin-like growth factor 1 (IGF-1), along with estrogen, can promote the development of neoplastic cells in breast tissue. Cancers that develop under IGF-1 stimulation are often resistant to therapy. This case report describes a 47-year-old woman, body mass index 27.4 kg/m2, with HER2-positive breast cancer, as well as elevated blood glucose, total cholesterol, and low-density lipoprotein cholesterol. Soon after her breast cancer diagnosis, she transitioned from a Western pattern diet (WPD) to a predominantly whole-food, plant-based diet (PWFPBD) for 1035 days, followed by 232 days of PWFPBD plus night fasting for 16 hours per day. IGF-1 decreased 22.38%, glycemia and total cholesterol decreased by -55.06% and -36.00% at the end of the first intervention and went up by 6.25%, and 3.87%, respectively, at the end of the second intervention. A PWFPBD, with or without 16-hour overnight fasting, seems to modulate plasma levels of IGF-1 on a 47-year-old woman diagnosed with breast cancer, type HER2-positive. Future research, should explore the physiologic and pathophysiological mechanisms and clarify whether this dietary strategy, may be clinically useful in preventing HER2-positive breast cancer.

NASA's Satellite Laser Ranging Systems for the 21st Century.

For over 40 years, NASA's global network of satellite laser ranging (SLR) stations has provided a significant percentage of the global orbital data used to define the International Terrestrial Reference Frame (ITRF). The current NASA legacy network is reaching its end-of-life and a new generation of systems must be ready to take its place. Scientific demands of sub-millimeter precision ranging and the ever-increasing number of tracking targets give aggressive performance requirements to this new generation of systems. Using lessons learned from the legacy systems and the successful development of a prototype station, a new network of SLR stations, called the Space Geodesy Satellite Laser Ranging (SGSLR) systems, is being developed. These will be the state-of-the-art SLR component of NASA's Space Geodesy Project (SGP). Each of SGSLR's nine subsystems has been designed to produce a robust, kilohertz laser ranging system with 24/7 operational capability and with minimal human intervention. SGSLR's data must support the aggressive goals of the Global Geodetic Observing System (GGOS), which are 1 millimeter (mm) position accuracy and 0.1 mm per year stability of the ITRF. This paper will describe the major requirements and accompanying design of the new SGSLR systems, how the systems will be tested, and the expected system performance.

Matrix metalloproteinases: biologic activity and clinical implications.

Tumor progression is a complex, multistage process by which a normal cell undergoes genetic changes that result in phenotypic alterations and the acquisition of the ability to spread and colonize distant sites in the body. Although many factors regulate malignant tumor growth and spread, interactions between a tumor and its surrounding microenvironment result in the production of important protein products that are crucial to each step of tumor progression. The matrix metalloproteinases (MMPs) are a family of degradative enzymes with clear links to malignancy. These enzymes are associated with tumor cell invasion of the basement membrane and stroma, blood vessel penetration, and metastasis. They have more recently been implicated in primary and metastatic tumor growth and angiogenesis, and they may even have a role in tumor promotion. This review outlines our current understanding of the MMP family, including the association of particular MMPs with malignant phenotypes and the role of MMPs in specific steps of the metastatic cascade. As scientific understanding of the MMPs has advanced, therapeutic strategies that capitalize on blocking the enzymes have rapidly developed. The preclinical and clinical evolution of the synthetic MMP inhibitors (MMPIs) is also examined, with the discussion encompassing important methodologic issues associated with determining clinical efficacy of MMPIs and other novel therapeutic agents.

The combination of Pit-1 and Pit-1T have a synergistic stimulatory effect on the thyrotropin beta-subunit promoter but not the growth hormone or prolactin promoters.

Pit-1 is a pituitary-specific transcription factor with protein expression limited to thyrotrope, somatotrope, and lactotrope cells of the anterior pituitary gland. We have recently described a thyrotrope-specific variant isoform of Pit-1, called Pit-1T, which contains an additional 14 amino acids in the activation domain generated by an alternate 3'-splicing choice. Pit-1T, in the presence of Pit-1, stimulates the thyrotropin beta-subunit (TSH beta) promoter in a thyrotrope-derived cell that lacks all Pit-1 isoform proteins. Three laboratories have identified another Pit-1 splice variant, called Pit-1 beta, which contains an additional 26 amino acids in the activation domain that is generated by a similar 3'-alternate splice choice. Pit-1 beta has been shown to stimulate the GH promoter, but not the PRL or TSH beta promoters. In this report, we evaluate the effect of the three Pit-1 isoforms (Pit-1, Pit-1T, and Pit-1 beta) on the GH, PRL, and TSH beta promoters when introduced into different cell types. The combination of Pit-1 and Pit-1T had a synergistic stimulatory effect on the TSH beta promoter, but not on the PRL or GH promoters in a thyrotrope-derived cell line that lacks all Pit-1 protein isoforms (alpha TSH cells). When added to GH3 cells, which lack only the Pit-1T isoform, Pit-1T selectively stimulated the TSH beta promoter and not the GH or PRL promoters, suggesting that the thyrotrope-specific Pit-1T exhibits a promoter-specific effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Pit-1 in regulating mouse TSH beta promoter activity in thyrotropes.

TSH beta gene expression is restricted to pituitary thyrotropes. Since Pit-1 is present in these cells, we characterized Pit-1 RNA and protein in thyrotropes, and tested its function in regulating TSH beta promoter activity. We demonstrate that both TtT-97 thyrotropic tumors and pituitaries contain four Pit-1 transcripts of 3.2, 2.6, 2.4, and 1.9 kb, respectively. Only two transcripts of 2.7 and 2.1 kb were detected in alpha TSH cells, a thyrotrope derived cell that no longer expresses TSH beta. Western analysis revealed Pit-1 protein in TtT-97 cells but not in alpha TSH cells. DNase I protection assays localized Pit-1 binding to three areas of the mouse TSH beta promoter. However, basal TSH beta promoter activity was minimally stimulated when alpha TSH cells or TtT-97 thyrotropes were co-transfected with mouse Pit-1 and a mTSH beta luciferase construct. These studies suggest that Pit-1 is not limiting for cell-specific expression of the TSH beta gene in thyrotrope-derived cells and implies that additional thyrotropic factors are likely required.

Coupling optical waveguides by tapers.

The coupling of single-mode optical waveguides through the use of expanding and contracting tapers is examined theoretically. In particular, the problems of angular and transverse misalignments of an input and output taper are investigated along with the effects of the taper itself. A tradeoff is found to exist, that is, widening the guide by means of a taper leads to less critical coupling tolerances for transverse displacements, but tighter tolerances for angular misalignment. Similar considerations apply to large core singlemode fibers.