Y chromosome molecular analysis was performed using the STS-PCR technique in 50 patients with oligozoospermia. Microdeletions of interval 6 of the Y chromosome were detected in seven patients, in six ...of whom subinterval E was affected. All patients retained the RBM1 and DAZ genes, while in one deletion involved the SPGY gene. The size of the deletion was not apparently related to the severity of the disease. These results suggest the presence of an oligozoospermia critical region on the Y chromosome within subinterval E of interval 6.
Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is active in K-RAS wild type colorectal cancer (CRC). However, initially in responding patients cancer cells ...would become resistant to EGFR inhibition by the activation of alternative growth controlling pathways including the hepatocyte growth factor (HGF)/MET-dependent signal.
mRNA expression profiles of cetuximab-sensitive human GEO colon cancer cells and of their cetuximab-resistant derived GEO-CR cells were analyzed by microarrays. Protein expression levels were evaluated by western blot (WB). Growth factors were measure in the culture medium by Luminex technology. The in vitro antitumor activity of MET inhibitor (METi), was tested in a panel of ten human colon cancer cell lines by MTT assay.
Evaluation of gene expression profile identified a series of genes that were up-regulated in GEO-CR cells possibly involved in acquired resistance to EGFR inhibition. Among these we found several genes involved in the MET pathway. WB analysis detected activated, phosphorylated MET in GEO-CR but not in GEO and in the other colon cancer cell lines tested. We also found in GEO-CR cells up-regulation of EGFR ligands such as transforming growth factor – α (TGFa) and Heparin Binding- Epidermal Growth Factor (HB-EGF). We further observed expression of HGF in GEO-CR cells, supporting HGF/MET autocrine activation following acquired resistance to cetuximab treatment. In fact, the RAS/RAF/MEK/MAPK pathway was constitutively active despite of EGFR inhibition by cetuximab in GEO-CR cells possibly due to HGF-induced MET activation. Treatment with a potent and selective METi was able to overcome cetuximab resistance in GEO-CR cells and causes cell growth inhibition.
These results suggest that autocrine activation of HGF/MET could be a relevant therapeutic target in colorectal cancer patients that become resistant to anti-EGFR treatment.
All authors have declared no conflicts of interest.
Solutions to global problems such as disease detection and control, terrorism, immigration and border control, and illicit drug trafficking require sharing and coordinating information and ...collaboration among government agencies within a country and across national boundaries. This paper presents an approach to achieve information sharing, event notification, enforcement of policies, constraints, regulations, security and privacy rules, and process coordination. The proposed system, designed in collaboration with stakeholders and end users in two Latin American countries, achieves the desired capabilities by integrating a distributed query processor (DQP) that provides form-based and conversational user interfaces, a language translation system, an event server for event filtering and notification, and an event-trigger-rule server. The Web-services infrastructure is used to achieve the interoperation of these heterogeneous component systems. A prototype of the integrated transnational information system is described.
Quality data: what are they? Sforza, V A
Annali dell'Istituto superiore di sanità,
1994, Volume:
30, Issue:
4
Journal Article
Peer reviewed
Nowadays, quality has become a very important factor in almost all areas of endeavour. The data generated from tests for the assessment of potentially toxic chemicals is obviously no exception. It is ...necessary, therefore, that quality systems be developed to ensure that the data generated to support these tests are of good quality. An acceptable quality system should require that, where applicable, the tests be performed according to defined guidelines. Once defined guidelines have been identified for the type of test to be performed, it is then necessary to design a plan which describes how, when, where and by whom the data will be generated. If at all possible, the data should be generated according to written standard procedures which provide for the production of data to the same quality standard. The data should be generated and collected by properly trained staff using data collection systems (paper or electronic media) which ensure the accuracy, reliability and integrity of the data recorded. The data must then be recorded in such a way as to ensure that they are reported completely clearly and accurately. The report, whether it be in the form of scientific article, monograph or formal study report, should present the data in a consistent manner and allow for adequate reconstruction of the events which took place during the test. Finally, the report and the data supporting it should be verified to ensure that the test was carried out according to the relevant guidelines (if used), that the study plan was correctly followed and finally that all data were properly generated and accurately reported in the report.
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