Faculty Publications

The formation of the primitive endoderm covering the inner cell mass of early mouse embryos can be simulated in vitro by the differentiation of mouse embryonic stem (ES) cells in culture following either aggregation of suspended cells or stimulation of cell monolayers with retinoic acid. The developmentally regulated transcription factors GATA-4 and GATA-6 have determining role in mouse extraembryonic endoderm development. We analyzed the in vitro differentiation of mouse embryonic stem cells deficient of GATA factors and conclude that GATA-4 is required for ES cells to perceive a cell positioning (cell aggregation) signal and GATA-6 is required to sense morphogenic (retinoic acid) signal. The collaboration between GATA-6 and GATA-4, or GATA-6 and GATA-5 which can substitute for GATA-4, is involved in the perception of differentiation cues by embryonic stem cells in their determination of endoderm lineage. This study indicates that the lineage differentiation of ES cells can be manipulated by the expression of GATA factors. Hepatitis C virus (HCV) is a positive strand RNA virus with a narrow host and tissue tropism. It ranks among the most significant of human pathogens, causing inflammation, scarring and cancer of the liver. Recent investigations have shed light on some of the salient molecular features of this virus. These include a requirement for CD81 (a tetraspanin transmembrane protein for viral entry), a novel mechanism for the initiation of RNA synthesis, phosphorylation of a viral protein in the regulation of RNA amplification and virus assembly and, finally, a viral protease suppressing activation of the innate immune response in infected cells. The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti-vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti-epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting. Endoscopy plays a critical role in the management of patients with malignancies involving the gastrointestinal tract. Endoscopic ultrasound has provided essential staging information, made more complete by the ability to perform fine needle aspiration of suspicious lymph nodes. Novel endoscopic resection and ablative techniques are expanding therapeutic choices in premalignant and malignant conditions. Obstruction, virtually anywhere along the length of the gastrointestinal tract, can be relieved with new stents. All of these advances have made the therapeutic gastroenterologist a key member of the team managing patients with tumors of the gastrointestinal tract. The objective of this cross-sectional study was to compare dietary reports from a food frequency questionnaire (FFQ) for US Chinese women with 24-hour recall estimates. The subjects were 56 women recruited through organizations in Philadelphia's Chinese community. Spearman correlations were used to describe FFQ estimates of food servings per month and nutrient intake per day vs estimates from three 24-hour recalls over 1 month. On average, women reported at least weekly consumption of 28 of 96 FFQ food items. The three most frequently consumed were rice (38 times/month), tea (29 times/month), and dark green, leafy vegetables (18 times/month). Comparing reported frequencies of the 28 foods to 24-hour recall estimates, the median Spearman correlation was 0.36. For nutrient estimates, correlations were high (r >0.5) for dietary fiber and calcium; moderate ( r =0.25 to 0.5) for energy, saturated fat, cholesterol, carbohydrates, protein, folic acid, and iron; but poor (r <0.25) for total fat, vitamin C, vitamin A, and carotene. These findings provide some assurance of the FFQ's adequacy for describing US Chinese women's intake of commonly consumed foods and selected nutrients. They also provide a basis for further improvements to, and evaluations of, the FFQ.

The present invention provides novel methods for the treatment of cancer, methods for screening compds. having anti-cancer activity, and methods of assessing cancer progression. In accordance with the present invention, a method of assessing the anti-cancer activity of a KIT tyrosine kinase inhibitor in a biol. sample comprising a tumor cell is provided. In a preferred embodiment, the tumor is a gastrointestinal stromal tumor (GIST) and the KIT tyrosine kinase inhibitor is imatinib, SU11248 (Sugen Pharmaceuticals), or a pharmaceutically acceptable salt thereof. DNA microarrays revealed 148 genes that were differentially expressed between untreated and imatinib-treated human GIST cells, in vitro. One of these genes, Sprouty4A (SPRY4A) a regulator of tyrosine kinase-mediated signaling pathways, was dramatically down- regulated. A biomarker MAFbx was up-regulated in response to imatinib treatment. In addn., imatinib inhibited KIT phosphorylation without affecting the total level of KIT protein. The inventors proposed a method for detg. the efficacy of an anticancer treatment comprising detection of an alteration in phosphorylation of a biomarker (such as decrease in GAB1 phosphorylation). [on SciFinder (R)]