Androgen inducibility of Fgf8 in Shionogi carcinoma 115 cells correlates with an adjacent t(5;19) translocation

Fgf8 (fibroblast growth factor 8) was initially cloned from a mouse mammary tumor cell line derived from the androgen-dependent Shionogi carcinoma 115. The androgen-inducible expression of Fgf8 in this tumor controls its androgen-dependent phenotype, thus stimulating interest in this gene as a possible factor in human prostate cancer and other androgen-sensitive cancers. However, apart from Shionogi carcinoma 115, the androgen inducibility of Fgf8 is controversial. In the present study, having not detected androgen-inducible expression of Fgf8 in other mouse mammary cell lines or mouse prostate, we examined the Shionogi carcinoma 115-derived S115 cell line for mouse mammary tumor virus (MMTV) insertions or other nearby DNA rearrangements that might explain the androgen inducibility of Fgf8 in these cells. Southern blotting did not detect MMTV insertions near Fgf8 but did reveal a specific DNA rearrangement 3.7 kb upstream of Fgf8 in S115 cells and in other cells (SC115) independently derived from Shionogi carcinoma 115. Spectral karyotyping of S115 cells and sequencing of the cloned rearrangement junctions indicate that Fgf8 is involved in a t(5;19) translocation. The chromosome 5 sequence joined to Fgf8 is immediately adjacent to Smr2 (submaxillary gland androgen-regulated protein 2) and includes Muc10 (mucin 10), two genes that we show are testosterone inducible in S115 cells, suggesting that the androgen-dependent expression of Fgf8 in Shionogi carcinoma 115 and derivative cells results from this translocation. Together, these results suggest that androgen inducibility is not an inherent property of the Fgf8 gene, which has implications regarding this gene's proposed role in the etiology of hormone-responsive cancers.     

Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members

BACKGROUND/AIMS: Sedation rates may vary among countries, depending on patients' and endoscopists' preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). METHODS: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives' endoscopy units. RESULTS: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders' endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available 'in most of the endoscopy units' in 46% (13/28) of the countries. Though they were available in 91% of the national representatives' endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. CONCLUSIONS: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.     

Evaluation of 2 whole-slide imaging applications in dermatopathology

Digitization of glass slides holds great promise for increasing workflow efficiency, but current applications have not gained widespread acceptance. Applications to date have not taken into consideration pathologists' workflow patterns, and as a result many find navigation cumbersome and interpretation more challenging when compared to glass slides. We observed 3 dermatopathologists evaluate a set of cases using 2 digital applications, one of which used a novel navigation method developed in-house. We then compared their approach to the digital slides with the gold standard traditional microscopy with glass slides. Common diagnoses were identified in 3 categories: inflammatory, nonmelanocytic, and melanocytic lesions. Forty-five cases were selected representing these diagnoses. Digital slides were captured on a commercially available scanner. Sign-out was performed with a commercial viewer as well as with the in-house application. Sessions were captured on video and reviewed. Time to examine each slide, time spent at each magnification, and diagnostic concordance were measured. Average time spent per slide was least with the microscope (23 seconds) as compared with the in-house (34 seconds) or the vendor application (38 seconds). This difference was most significant in the least complex cases. Pathologists reported difficulty interpreting mitotic figures, neutrophil lobules, and eosinophil granules by digital slides. These results suggest that current applications for viewing digital slides do not yet provide a more efficient means of evaluating dermatopathology cases and reinforce the need for improvement in both the capture process and the presentation of digital slides, with particular attention paid to the interface and navigation.     

Relationship of stable integration of herpes simplex virus-2 BglII N subfragmentXho2 to malignant transformation of human papillomavirus-immortalized cervical keratinocytes

Transfection of the right end Xho2 subfragment of BglII N of herpes simplex virus-2 (HSV-2) into human genital keratinocytes immortalized by human papillomavirus (HPV) type 16 or 18 resulted in invasive and noninvasive indolent cystic squamous carcinomas when cells were injected into immunocompromised mice. Retention and expression of the right end portion of the BglII N fragment correlated with malignancy, as the corresponding HSV-2 sequences were integrated and transcribed in the tumorigenic cell lines. HPV-immortalized cells alone were not tumorigenic. In contrast, previous results have shown that using the entire BglII N region can malignantly transform HPV-immortalized cells, although HSV2 DNA was not retained. Together, these observations localize the transforming activity of BglII N to Xho2 and suggest that the remaining sequences have an inhibitory effect on stable integration. The Xho2 sequence is 2480 bp long and contains an open reading frame (ORF) extending from nucleotides 559 to 1797. The ORF encodes a putative protein of 412-aa with a m.w. of 42–43 kDa and is highly homologous to U_L43 of HSV-1. The correlation of tumorigenicity with stable integration and expression of Xho2 DNA in HPV-immortalized cells indicates that HSV-2 should be investigated further for a possible role in cervical cancer. Int. J. Cancer 76:865–871, 1998.© 1998 Wiley-Liss, Inc.+ This article is a US Government work and, as such, is in the public domain in the United States of America.