Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer.

Until now, no molecular parameter has been available for predicting the metastatic potential of prostate tumours, which leaves their outcome uncertain despite an apparent benign histology or early stage. Abnormal expression of adhesion molecules, such as E-cadherin, can be contributing factors for increased invasiveness and metastatic potential. Histological analysis for E-cadherin expression was carried out on paraffin-embedded tumour tissues. Tumour metastatic potential was indirectly evaluated by detecting circulating prostate cells (CPC), using reverse transciptase-polymerase chain reaction (RT-PCR) and prostate-specific membrane antigen (PSMA) as a target. Patients were followed-up for a median of 14 months (range 10--19 months) after surgery with serum prostate-specific antigen (PSA) level measurement. Interestingly, 23 of 44 localised tumours exhibited aberrant E-cadherin expression. Prior to primary surgery, PSMA RT-PCR detected the spread of prostate cells to the blood in 24 patients. Statistical analysis showed that abnormal E-cadherin expression in the tumours was the only variable that was independently correlated with prostate cell dissemination in the blood (P<0.0001). In logistic regression analysis, abnormal E-cadherin expression was a significant independent predictor for a later biological relapse. This impaired adhesion status was clearly correlated with a haematogenous spread of the primary tumour cells. It could therefore be an objective way to restrict the indications for radical surgery to patients not presenting with this feature.

Blood-borne RT-PCR assay for prostasin- specific transcripts to identify circulating prostate cells in cancer patients.

OBJECTIVE: The aim of this study was to establish the specific detection of prostasin-expressing prostate cells in the blood of patients with prostate cancer. PATIENTS AND METHODS: A prostasin-specific RT-PCR assay was developed and optimized using limiting dilutions of cell line LNCaP mixed with normal blood specimens. Then, it was used to examine peripheral blood samples from 96 patients with prostate cancer (localized carcinoma, n = 69, metastatic, n = 27). Specificity was assessed by examination of 86 negative controls (healthy individuals, n = 47, benign prostate hyperplasia, n = 17, nonprostate cancer patients, n = 22). RESULTS: All 86 control samples failed to amplify the specific 546-bp prostasin PCR products. Blood samples from 35 out of 96 (36%) prostate cancer patients were found positive. In metastatic patients, 63% (17/27) scored positive whereas in localized adenocarcinoma prostasin primers detected prostate cells in 26% (18/69). CONCLUSION: Our results that approximately 30% of patients with localized prostate cancer scored positive for prostasin-specific RT-PCR confirm that the hematogenous spillage of prostate cells is an early event in the natural history of prostate cancer. As none of our negative controls were found positive, we conclude that blood-borne RT-PCR amplification of prostasin transcripts may lead to an earlier diagnosis of disseminated disease in patients with organ-confined carcinoma. The clinical significance of prostate cell detection and the potential applications of this new tool aside or along prostate-specific antigen or prostate-specific membrane antigen RT-PCR require longer-term follow-up.

Molecular expression of PSMA mRNA and protein in primary renal tumors.

Human prostate-specific membrane antigen (PSMA), a 100-kDa integral transmembrane glycoprotein, is considered to be a highly specific marker of the prostate gland, and has successfully been used as a marker of circulating prostatic epithelial cells. Extended PSMA homology has been demonstrated with a cDNA found in rat cerebral and renal tissues. In this study, we aimed to evaluate the expression of PSMA mRNA in a variety of human renal cancer tissues (n = 20) and cell lines (n = 12). Using reverse transcriptase-polymerase chain reaction, DNA sequencing, blottings, and specific anti-PSMA labelling with CYT 351 antibody, we identified PSMA mRNA and protein in normal and in neoplastic renal tissue. The sequence of the polymerase-chain-reaction products is identical to that of PSMA cDNA derived from prostate tissue. Immunological staining with the CYT 351 reveals that PSMA is expressed mainly in tubular cells. Since PSMA does not appear to be restricted to prostatic tissue, this novel biomarker may prove useful in the staging of renal cancer and in the search for the hematogenous spread of renal cells.

[Vertical transmission of the human T-cell leukemia virus in an endemic area. An epidemiological study in children from 0 to 5 years in Gabon]. / Etude de la transmission verticale du human T-cell leukemia virus en zone d'endémie. A travers une enquête épidémiologique chez les enfants de 0 à 5 ans au Gabon.

A seroepidemiological survey was conducted in a representative population of children aged 0-5 in Gabon. Breast-feeding appears to an important mode of HTLV vertical transmission. Owing to other epidemiological data in population of gabonese adults allow us to think that breast-feeding related transmission and sexual transmission seem to occur in equal proportion in the global HTLV transmission in that area of endemicity.

[The association of acute polyradiculoneuritis, transitory diabetes insipidus and pregnancy. Apropos of a case and review of the literature]. / Association polyradiculonévrite aiguë, diabéte insipide transitoire et grossesse. A propos d'un cas et revue de la littérature.

This is the first report of the association of transitory diabetes insipidus with acute infective polyneuritis (landry Guillain-Barre Syndrome) occurring in pregnancy. The authors try to establish the inter-relationship between each pathological condition and pregnancy. Polyneuritis in its severe form does not seem to increase the risk of prematurity significantly. The severe forms of more generalised neurological condition as compared with the more limited condition has been noted in the literature but it is not possible to state how pregnancy effects the outcome. Plasma exchange procedures are now possible in pregnant women and the benefits of this treatment have been illustrated in severe forms of polyneuritis. There is difficulty still in selecting what criteria are sufficient to start on a therapy that is not without risk. Finally, the association between transitory diabetes insipidus and pregnancy has been reviewed in the literature and a description is given of the many physiopathological mechanisms associated with it. Diabetes insipidus is rarely found in pregnancy. All authors describe a placental factor with these troubles. The most recent theories suggest that prostaglandins and placental vasopressin are implicated. Treatment is suggested and consists of DDAVP (deamino 8-d-arginine vasopressin), which seems to be the most effective. Close collaboration between the obstetrician, the recovery services and the paediatrician is necessary to get the best results for this very severe pathological condition occurring in pregnancy.

Evaluation of the teratogenic potential of three aliphatic nitriles in the rat.

Acetonitrile (ACN), adiponitrile (ADN), and propionitrile (PN), were evaluated for embryotoxic and teratogenic potential in rats. Mated Sprague-Dawley rats were administered one of the three nitriles by gavage on gestation Days 6-19, inclusive. Daily dosage levels (mg/kg body wt) were: ACN at 0, 125, 190, and 275; ADN at 0, 20, 40, and 80; PN at 0, 20, 40, and 80. There was evidence of maternal toxicity in each of the high dose groups treated with ACN, ADN, or PN. Some maternal effects also were seen with ADN at the middle dosage. Embryotoxic effects were observed at the highest dosage tested for ACN and middle and high dose levels for PN. Slight fetotoxicity was observed at the highest dosage for ADN. No teratogenic effects were observed at any dosage level with ACN, ADN, or PN.

[Idiopathic aneurysm of the left ventricle. Apropos of 4 cases operated on with success]. / Anévrysme idiopathique du ventricule gauche. A propos de 4 cas opérés avec succès.

Over a period of 3 years, 4 cases of idiopathic left ventricular aneurysm, 3 white females and one coloured male aged 34, 53, 29 and 47 years respectively, were observed. All presented with paroxysmal ventricular or supraventricular tachycardia, which, in one case, was severe enough in itself to justify surgery. On angiography, large left ventricular aneurysms bordering the mitral annulus and responsible for moderate mitral regurgitation in two patients were demonstrated. Aneurysmectomy was only possible in 2 cases, the other two having pericardial adhesions with a risk of uncontrollable haemorrhage during dissection being managed by suture of the neck of the aneurysm. The surgical results were very satisfactory, especially with respect to the arrhythmias with a follow-up of 48, 24, 15 and 9 months respectively. In a review of the literature, 93 cases of idiopathic left ventricular aneurysm were analysed, less than 20 of which have been managed surgically. Left ventricular aneurysms seem to be large fibrotic structures located at the border of the mitral, or, less commonly, below the aortic annulus. It is important to differentiate them from congenital left ventricular diverticuli which are usually located at the apex, have muscular walls and are therefore contractile. The aetiology of these aneurysms is unknown: the possible role of myocardial infarction may be excluded as the coronary arteries are always normal on angiography and at autopsy. The relatively young age of the patients is also an argument against this hypothesis. Other suggested causes such as syphilis, tuberculosis, Chagas' disease, non-specific myocarditis, sarcoidosis and thoracic trauma may also be excluded. Surgery seems to be indicated in cases complicated by resistant arrhythmias, peripheral embolism or when the aneurysm increases rapidly in size.