These studies were undertaken to assess the estrogenic and antiestrogenic effects of dietary genistein. To determine estrogenic effects, genistein was mixed into a modified AIN-76 or AIN-93G semipurified diet at 0 (negative control), 150, 375 or 750 microg/g and 17, beta-estradiol at 1.0 microg/g and fed to ovariectomized 70-d-old Sprague-Dawley rats. Estrogenic potency was determined by analyzing uterine weight, mammary gland development, plasma prolactin and expression of uterine c-fos. Dietary genistein (375 and 750 microg/g) increased uterine wet and dry weights (P < 0.05). Mammary gland regression following ovariectomy was significantly inhibited by dietary genistein at 750 microg/g (P < 0.05). Plasma prolactin was significantly greater in ovariectomized rats fed genistein (750 microg/g) compared with comparable rats not receiving genistein. The relative binding affinity of genistein to the estrogen receptor (ER) was 0.01 that of estradiol. Genistein (750 microg/g) induced the uterine expression of c-fos. To evaluate potential antiestrogenic effects, genistein and estradiol were mixed into the modified AIN diets at the doses noted above and fed to ovariectomized rats. Dietary genistein (375 or 750 microg/g) did not inhibit the effects of estradiol on uterine weight, mammary gland development or plasma prolactin. Serum concentration of total genistein (conjugated plus free) in rats fed 750 microg/g was 2.2 micromol/L and free genistein was 0.4 micromol/L. Administration of dietary genistein at 750 microg/g can exert estrogenic effects in the uterus, mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 microg/g) did not antagonize the action of estradiol in estradiol-supplemented ovariectomized rats or in intact rats.

The coherence and dephasing of vibrational motions of molecules constitute an integral part of chemical dynamics, influence material properties, and underpin schemes to control chemical reactions. In the present study, we measure coherent structural dynamics in optically excited N-methyl morpholine by scattering with ultrashort X-ray pulses from the Linac Coherent Light Source. The scattering signals are corrected for the different electron density in the excited electronic state of the molecule compared to the ground state. The experiment maps the evolution of the molecular geometry with femtosecond resolution, showing coherent motion that survives electronic relaxation and appears to persist for longer than previously seen using other methods.

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When a molecule interacts with light, its electrons can absorb energy from the electromagnetic field by rapidly rearranging their positions. This constitutes the first step of photochemical and photophysical processes that include primary events in human vision and photosynthesis. Here, we report the direct measurement of the initial redistribution of electron density when the molecule 1,3-cyclohexadiene (CHD) is optically excited. Our experiments exploit the intense, ultrashort hard x-ray pulses of the Linac Coherent Light Source (LCLS) to map the change in electron density using ultrafast x-ray scattering. The nature of the excited electronic state is identified with excellent spatial resolution and in good agreement with theoretical predictions. The excited state electron density distributions are thus amenable to direct experimental observation.

Purpose: Previously we developed membrane-arrays as a promising tool to detect circulating tumor cells (CTC) with KRAS oncogene in patients with malignancies.This study was conducted to determinate the predictive values of CTCs with KARS mutation by membrane-arrays for metastatic colorectal cancer patients treated with cetuximab plus chemotherapy. Experimental Design: Seventy-six metastatic colorectal cancer patients receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy were enrolled. KRAS mutation status in the peripheral blood of these patients was analyzed using membrane-arrays, and KRAS mutation status in tumors was analyzed by DNA sequencing. Results: Among 76 metastatic colorectal cancer patients, KRAS mutations in tumors and in peripheral blood were identified in 33 (43.4%) and 30 (39.5%) patients, respectively.The detection sensitivity, specificity, and accuracy of membrane-arrays for CTCs with KRAS oncogene were 84.4%, 95.3%, and 90.8%, respectively, and indeed a highly significant correlation to KRAS mutations in tumors (P < 0.0001) was observed. Forty-five (59.2%) patients responded to cetuximab plus chemotherapy, and 41 and 40 were wild-type KRAS in tumors and peripheral blood, respectively (both P < 0.0001). Patients with tumors that harbor wild-type KRAS are more likely to have a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Likewise, patients with CTCs of wild-type KRAS in peripheral blood express a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Conclusions: These findings provide evidence that detection of KRAS mutational status in CTCs, by gene expression array, has potential for clinical application in selecting metastatic colorectal cancer patients most likely to benefit from cetuximab therapy.Colorectal cancer is the second leading cause of cancer-related death in western countries and is the third major cause of cancerrelated death in Taiwan, with >9,000 new cases and 4,000 deaths per year. 12 In the past decade, significant improvements have been made in response rates, progression-free survival (PFS), and overall survival (OS) of metastatic colorectal cancer patients (1 -4). This prominent improvement is mainly due to the recent introduction of new combinations of standard chemotherapy, including 5-fluorouracil/folinic acid, irinotecan, and oxaliplatin, and to the new therapeutic agents targeting molecular events involved in colorectal carcinogenesis such as monoclonal antibodies (mAb) against epidermal growth factor receptor (EGFR) or mAbs against vascular endothelial growth factor. Previous studies (5 -11) showed that the benefits of the anti-EGFR mAb cetuximab among patients with metastatic colorectal cancer are limited to those who have colorectal tumor tissues with wild-type KRAS genes, and KRAS genes with mutations are 12

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A number of metabolites of daidzein and genestein have been synthesized and their biological activities determined. Equol [3], 5,7,4'-trihydroxyisoflavan [5], 4,7,4'-trihydroxyisoflavan [6], dihydrodaidzein [8], and dihydrogenistein [9] were synthesized either from daidzein [1] or genistein [2] by hydrogenation. Similarly, the derivatives 4, 7, and 11 were synthesized from 3, 6, and 10, respectively. During acetylation and nmr experiments, 9 was converted to a novel enol intermediate [10]. Antifungal, antibacterial, mosquitocidal, nematocidal, and topoisomerase inhibition activities of these compounds were evaluated, with equol [3] being the most active of the compounds tested against topoisomerase I.