NIR Femtosecond Control of Resonance-Mediated Generation of Coherent Broadband UV Emission

We use shaped near-infrared (NIR) pulses to control the generation of coherent broadband ultraviolet (UV) radiation in an atomic resonance-mediated (2+1) three-photon excitation. Experimental and theoretical results are presented for phase controlling the total emitted UV yield in atomic sodium (Na). Based on our confirmed understanding, we present a new simple scheme for producing shaped femtosecond pulses in the UV/VUV spectral range using the control over atomic resonance-mediated generation of third (or higher order) harmonic.Comment: 14 pages, 4 figure

The metabolic syndrome is not associated with homocysteinemia: The Persian Gulf Healthy Heart Study

Background: It is uncertain whether homocysteine and the metabolic syndrome or its components are related in the general population, as studies investigating the association between homocysteine levels and insulin resistance have shown conflicting results. Methods: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of Iranian men and women aged ≥25 yr, a random sample of 1754 subjects were evaluated for the association of plasma homocysteine levels and the metabolic syndrome using National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria. Total homocysteine levels and high sensitivity C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assays. Results: Subjects with lower HDL-cholesterol and higher blood pressure showed significantly higher homocysteine levels (p=0.001 and p<0.0001; respectively). There was no significant difference in serum levels of homocysteine between subjects with and without the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome did not show a significant association with serum homocysteine levels after adjusting for sex, age, smoking, fruit and vegetable intake pattern, body mass index, and physical inactivity. Concurrent elevated CRP levels and the metabolic syndrome also did not show a significant association with serum homocysteine levels after adjusting for sex, age, and lifestyle cardiovascular risk factors. Conclusions: There was no association between the metabolic syndrome using NCEP-ATPIII criteria and homocysteinemia in this study. These data refute the hypothesis that homocysteine levels are influenced by the metabolic syndrome, at least in general healthy population

Expression prevalence and dynamics of GPCR somatostatin receptors 2 and 3 as cancer biomarkers beyond NET: a paired immunohistochemistry approach

Abstract Somatostatin receptors are clinically validated GPCR biomarkers for diagnosis and treatment of various neuroendocrine tumors (NET). Among the five somatostatin receptors, SST2 and SST3 are associated with apoptosis and cell cycle arrest, making these receptor subtypes better differentiated targets in precision oncology. In this study we performed immunohistochemistry of paired tissue microarrays containing 1125 cores, representing 43 tumor types, each stained for SST2 and SST3. A 12-point immunoreactive scoring (IRS) range was used for interpretation of the staining results. We analyzed the results twice, using the conventional positivity IRS cutoffs ≥ 3 and more stringent ≥ 6. Evaluation of receptors expression dynamics was performed for tumor-nodes-metastases (TNM) defined subgroups (ovarian and hepatocellular adenocarcinomas) as a function of their tumor stage. Our results indicate that two-thirds of tested cores exhibit clinically significant expression of at least SST2 or SST3 (IRS ≥ 6). The expression prevalence of both receptors tends to decline with tumor progression. However, an unexpected upregulation of both SST2 and SST3 reemerged in metastases suggesting conserved receptors genetic potential during tumor life cycle. We suggest that SST2 and SST3 should be further explored as potential biomarkers and therapeutic tools for maximizing the efficiency of somatostatin-based precision oncology of solid tumors beyond NET

Bio-imaging of colorectal cancer models using near infrared labeled epidermal growth factor.

Novel strategies that target the epidermal growth factor receptor (EGFR) have led to the clinical development of monoclonal antibodies, which treat metastatic colorectal cancer (mCRC) but only subgroups of patients with increased wild type KRAS and EGFR gene copy, respond to these agents. Furthermore, resistance to EGFR blockade inevitably occurred, making future therapy difficult. Novel bio-imaging (BOI) methods may assist in quantization of EGFR in mCRC tissue thus complementing the immunohistochemistry methodology, in guiding the future treatment of these patients. The aim of the present study was to explore the usefulness of near infrared-labeled EGF (EGF-NIR) for bio-imaging of CRC using in vitro and in vivo orthotopic tumor CRC models and ex vivo human CRC tissues. We describe the preparation and characterization of EGF-NIR and investigate binding, using BOI of a panel of CRC cell culture models resembling heterogeneity of human CRC tissues. EGF-NIR was specifically and selectively bound by EGFR expressing CRC cells, the intensity of EGF-NIR signal to background ratio (SBR) reflected EGFR levels, dose-response and time course imaging experiments provided optimal conditions for quantization of EGFR levels by BOI. EGF-NIR imaging of mice with HT-29 orthotopic CRC tumor indicated that EGF-NIR is more slowly cleared from the tumor and the highest SBR between tumor and normal adjacent tissue was achieved two days post-injection. Furthermore, images of dissected tissues demonstrated accumulation of EGF-NIR in the tumor and liver. EGF-NIR specifically and strongly labeled EGFR positive human CRC tissues while adjacent CRC tissue and EGFR negative tissues expressed weak NIR signals. This study emphasizes the use of EGF-NIR for preclinical studies. Combined with other methods, EGF-NIR could provide an additional bio-imaging specific tool in the standardization of measurements of EGFR expression in CRC tissues