p140Cap dual regulation of E-cadherin/EGFR cross-talk and Ras signalling in tumour cell scatter and proliferation.

The adaptor protein p140Cap/SNIP is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Here, by gain and loss of function approaches in breast and colon cancer cells, we report that p140Cap immobilizes E-cadherin at the cell membrane and inhibits EGFR and Erk1/2 signalling, blocking scatter and proliferation of cancer cells. p140Cap-dependent regulation of E-cadherin/EGFR cross-talk and cell motility is due to the inhibition of Src kinase. However, rescue of Src activity is not sufficient to restore Erk1/2 phosphorylation and proliferation. Indeed, p140Cap also impairs Erk1/2 phosphorylation by affecting Ras activity, downstream to the EGFR. In conclusion, p140Cap stabilizes adherens junctions and inhibits EGFR and Ras signalling through the dual control of both Src and Ras activities, thus affecting crucial cancer properties such as invasion and growth. Interestingly, p140Cap expression is lost in more aggressive human breast cancers, showing an inverse correlation with EGFR expression. Therefore, p140Cap mechanistically behaves as a tumour suppressor that inhibits signalling pathways leading to aggressive phenotypes.

A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model.

The Src family tyrosine kinases are key modulators of cancer cell invasion and metastasis and a number of Src kinase inhibitors are currently in clinical development for the treatment of solid tumours. However, there is growing evidence that Src is also upregulated at very early stages of epithelial cancer development. We have investigated the role of Src in mouse skin, which is one of the most tractable models of epithelial homoeostasis and tumorigenesis. We found that Src protein expression and activity was regulated during the normal hair cycle and was increased specifically during the proliferative anagen phase and also in response to the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). AZD0530, a selective Src inhibitor, prevented the TPA-induced proliferation of basal keratinocytes both in vivo and in vitro. Moreover, treatment with AZD0530 reduced papilloma formation following the well-established 7,12-dimethylbenz(a)anthracene/TPA skin carcinogenesis protocol but did not inhibit the subsequent proliferation of the papillomas. Furthermore, AZD0530 did not alter the malignant conversion of papillomas to squamous cell carcinoma suggesting a role for Src in early tumour development in the skin carcinogenesis model, rather than at later stages of tumour progression. Src expression and activity were also seen in human actinic keratoses that are hyperproliferative pre-malignant skin lesions, indicating that Src may also play a role in the early stages of human skin tumour development. Thus, Src inhibitors such as AZD0530 may therefore have chemopreventative properties in patients with hyperproliferative epidermal disorders.

Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression.

Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies.

[Mycetoma of the neck and the nape of the neck due to Madurella mycetomatis. Apropos of a case in Mauritania]. / Mycétome du cou et de la nuque à Madurella mycetomatis. A propos d'un cas mauritanien.

Fungous mycetoma of the nape of the neck due to Madurella mycetomatis is an unusual localisation (four cases in mondial literature) and severe affection. This reports deals with a case occurred after traumatism. Despite five months of itraconazole and chirurgical treatment, the therapeutic escape was evident.

[Vital prognosis in acute pancreatitis. Study of 5 clinicobiological indices]. / Pronostic vital dans la pancréatite aiguë. Etude de 5 indices clinico-biologiques.

The values of the Acute Physiology and Chronic Health Enquiry (Apache II) and the Simplified Acute Physiology Scores (SAPS) were compared with Ranson and Imrie scores to predict death after acute pancreatitis. Fifty-five (ten deaths) patients were evaluated. Patients who died had a mean score greater than those who survived. The accuracy of all scores was similar after 48 hours. The ICU (Intensive Care Unit) available at the time of admission may facilitate the early selection of patients for appropriate management.

[Celioscopic appendectomy. Results in 137 consecutive patients]. / Appendicectomie coelioscopique. Résultats chez 137 malades consécutifs.

Between September 1990 and August 1992, laparoscopic appendicectomy was attempted in 137 patients: 98 females and 39 males (sex-ratio: 2.5:1) with a mean age of 31 years (range: 15-85). The patients were operated on by 9 surgeons. Laparoscopic appendicectomy was possible in 120 patients (87.6%). In 19 patients the procedure was converted into open surgery. The main causes of unsuccessful laparoscopic procedures were: retrocaecal appendix (n = 5) and injury of appendiceal artery (n = 4). The rate of unsuccessful procedures was 31% in retrocaecal appendix and 9.4% in the other cases (P < 0.02). In exclusively laparoscopic procedures, the mean operating time was 63 (2.9) minutes. It was 49 (3) minutes for experienced surgeons and 69 (3.3) for other surgeons (P < 0.05). Histological examination of the appendix revealed inflammatory signs in 97 specimens (71%). There were no wound infections after successful laparoscopic appedicectomy. One female patient developed an abscess in the pouch of Douglas. The median postoperative hospital stay was 3 days (range: 1-16). These results suggest that laparoscopic appendicectomy is a safe technique, with low morbidity allowing short postoperative hospital stay.

Evaluation of a cancer prevention and detection continuing education program for nurses.

To stay relevant and continue to meet the needs it was created to meet, a 15-year-old continuing education program in cancer prevention and detection for nurses has found change a constant. The process it has followed in evaluation--identifying goals, gathering and analyzing data, and reporting the results--can be compared with the nursing process in which feedback prompts changes and initiates the evaluation process all over again. The most recent part of the program's ongoing evaluation involved 70 nurses enrolled in a three-week continuing education program in which the nurses were pretested and posttested to measure cognitive gain in nine content areas covered in classroom and clinical instruction. Paired t test scores showed overall that students' scores improved significantly, increasing a mean of 18% across all categories. These results indicate that students are gaining knowledge, and measures of skills, improving on those already in place, are being added in what is only the latest modification of a program shaped by feedback from students, faculty, and research.

[Renocolonic fistula complicating vesicorenal reflux and xanthogranulomatous pyelonephritis in a 20-month-old child]. / Fistule réno-colique compliquant un reflux vésico-rénal et une pyélonéphrite xanthogranulomateuse chez un enfant de 20 mois.

A case of vesico-renal reflux with xanthogranulomatous pyelonephritis complicated with a renocolic fistula in a 20 months old child is reported. Imaging in this case was crucial for the diagnosis and the work up; it included ASP, renal ultrasound, UIV retrograde cystography and CT. The treatment consisted in a right ureteronephrectomy after fistula's section.