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Biomedical subjects

O Cussenot

Publications and source records attributed to O Cussenot.

At least 109 records · Page 6Linked to original sources

Oncogene amplifications in early-stage human prostate carcinomas.

Oncogene amplifications are frequently found in solid tumours and are often associated with more aggressively growing forms of human cancer. The proto-oncogenes c-myc, c-erbB2/neu and the 11q13 band are the most frequently amplified regions in adenocarcinomas of various origins. The present study was undertaken to define whether c-myc, int2/FGF3 (11q13 region) and c-erbB2/neu genes are involved in prostate tumorigenesis. Tumours and peripheral lymphocyte DNA from 21 localized early-stage prostatic carcinomas were analysed by Southern-blot electrophoresis for amplification of the c-myc and c-erbB2/neu genes and the 11q13 region (int2/FGF3). We detected no amplification of these 3 oncogenes in our panel.

Biomarkers, Tumor↗

[Natural history and prognostic factors of prostate cancer].

Our present knowledge of the natural history of cancer of the prostate has been acquired from anatomical and clinical observations. They have led to identification of the main prognostic factors of the disease, but as long as the biological and molecular mechanisms implicated in its development remain obscure, our knowledge is incomplete and treatment of its various stages can only be orientated empirically. The main problems which should be resolved by prognostic indications are found at two critical points of the disease: 1) in the case of localised cancer, avoiding radical treatment (surgery or physiotherapy), either for a small, stable tumour discovered by chance (occult cancer) or for an apparently localised tumour but where surgery alone would be ineffective because of a high positive margin or a high metastatic potential; 2) in the case of advanced cancer, to estimate the beneficial effects of early hormonal or nonhormonal treatment on the quality of life and on patient survival. Identification of simple prognostic parameters also aims to reduce the health cost involved in this type of cancer and to increase patient comfort by simplifying initial and subsequent investigations. Prognostic factors include both clinical data and laboratory chemistries. The latter are still the object of numerous and diverse studies involving basic science. The increasing diversity of such studies and preliminary publication without correlated large series has so far precluded judging the reliability of such factors for clinical use. In practice, tumoural volume and stage remain the two factors which can estimate the risk of progression when prostatic cancer is detected microscopically.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Genetic alterations in localized prostate cancer: identification of a common region of deletion on chromosome arm 18q.

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of the TP53 tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.

Alleles↗

Immunocytochemical comparison of cultured normal epithelial prostatic cells with prostatic tissue sections.

By analyzing a culture system of human prostatic epithelial cells (HPEC) and human prostatic fibroblasts (HPF) for expression of several determinants by immunocytochemistry, we have shown that long-term cultures are able to preserve the phenotypic characteristics of the normal tissue from which they are derived. The cytoskeletal elements, prostate-specific proteins, and steroid receptor profiles were compared to those of prostatic epithelium and stroma in situ. When cultured in low serum and low calcium medium, the adult HPEC grew as two layers of cells, the upper one of which retained the differentiation characteristics observed in the luminal fraction of normal prostatic epithelium. This cell type is the likely origin of prostatic neoplasia, with expression of CK8, 18, and 19 but not CK14. Androgen receptors, prostatic-specific antigen, and prostatic acid phosphatase are also expressed in vitro but at lower level than in situ. The lower cell layer expressed most of the same determinants but at a much lower level, suggestive of a stem-cell type. The HPF cultured in RPMI serum supplemented media retained the stromal pattern of the cells observed in situ. Culture systems which conserve the characteristics of their normal counterparts in vivo should provide useful models for studying in vitro genetic and epigenetic factors associated with differentiation and proliferation, but also with tumorigenic progression in the prostatic gland.

Biomarkers↗

Anatomic study of the lumbar region applied to multiplanar imaging techniques: importance and use of oblique vertical sections.

This anatomic study of the lumbar region (as defined by Rouvière [11]) applied to multiplanar imaging techniques was carried out both in the cadaver and in vivo. The cadaver study (5 cases) consisted of anatomic sections (transverse, sagittal, frontal and oblique) and computerised three-dimensional reconstructions after CT studies on subjects injected with colored and radio-opaque latex. The in vivo study (4 cases) used MRI sections and three-dimensional ultrasound sections coupled with the pulsed doppler. The spatially referenced oblique vertical sections revealed the structures from unusual aspects, situating them amidst the retroperitoneal area with the maximum of topographic landmarks. The transposition of these results (obtained by sectional anatomy of the retroperitoneal region) to the new techniques of multiplanar formatting after MRI, ultrasound or CT data acquisition should optimise the investigation of certain retroperitoneal structures by specifying the ideal planes of section for each organ, while diminishing certain artefacts specific to acquisitions in the traditional planes of section. Oblique vertical sections seem eminently suitable for ultrasound location of the suprarenal compartments, study of the renal pedicles and topographic retroperitoneal location. This oblique vertical visualisation constitutes a fundamental resource for the development of video-monitored surgical procedures as it corresponds exactly to the axes of the access routes in percutaneous surgery of the kidney and the adjacent anatomic structures.

Cadaver↗

Computation of eyeball growth by magnetic resonance imaging (26.11.93).

The computation of eyeball growth has a wide field of applications in orbital and ocular pathology. An anatomic and MRI study to compute eyeball growth has been done. The anatomic study was made to determine the best MRI parameters to calculate the ocular surface; then this surface was computed by MRI in the neuro-ocular plane in fetuses and children aged from 0 to 13 years. The curve of eyeball growth shows rapid growth in utero and until 18 months, followed by a phase of slower growth. This method allows measurement in two dimensions, which we find complementary to ultrasound in the antenatal search for certain congenital malformations.

Adolescent↗

Anatomic study of the orbital septum (22.10.93).

The orbital septum separates the intraorbital fat from the palpebral part of the orbicularis oculi m. An anatomic study after injection of colorant into the intraorbital fat allows definition of a fibroadipose layer anterior to the orbital septum. This consists of radial fibers and extraorbital fatty lobules. The septum is derived embryologically from the mesenchyme of the second arch, but the structure of the anterior layer remains controversial. The septum has an important mechanical function in containing the orbital fat and is involved in orbital movements. A knowledge of these different layers facilitates surgical approaches and helps to define the anatomic landmarks in palpebral surgery for conditions such as ptosis and in blepharoplasty.

Anthropometry↗

Distinct androgen 5 alpha-reduction pathways in cultured fibroblasts and immortalized epithelial cells from normal human adult prostate.

All androgen-sensitive peripheral tissues and cells, including the prostate, are commonly believed to possess the ability to metabolize testosterone. We report on the in vitro metabolism of tritiated testosterone performed in immortalized human adult normal prostatic epithelial cells and in human adult normal prostate fibroblastic cells (stromal cells). These two cell types were incubated separately with increasing testosterone concentrations (1 to 50 nM.) for 2 and 4 hours, after which the testosterone metabolic profile was analyzed. Data analysis provided evidence, for the first time, of the existence of two different 5 alpha-reduced metabolic pathways. Stromal cells preferred the androsterone pathway via the oxidative androstenedione formation, whereas epithelial cells preferred the reductive 5 alpha-dihydrotestosterone pathway. These two 5 alpha-reduced metabolites were produced in nearly equal quantities regardless of testosterone concentration or time of incubation. Since interactions between epithelial and stromal cells are involved in the development of the prostate, the availability of defined epithelial and stromal cells suitable for in vitro experiments provides a useful tool for the study of the contribution of androgens to these interactions. The model presented in this study would permit a better evaluation of the intraprostatic regulation of androgen metabolism and the contribution of the anti-5-alpha-reductase drugs to the management of benign prostate hyperplasia.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Exploration and endoscopic treatment of unilateral primary haematuria: is non-specific diffuse pyelitis a real entity?

Chronic unilateral primary haematuria is rare and raises difficult problems of diagnosis and treatment as most of the knowledge in this field has been based on a very limited number of patients. This clinical entity needs critical reevaluation as recent progress in endourological investigations has revealed that lesions other than the classical submucosal haemangioma are just as frequently responsible for unilateral primary haematuria. These endoscopic lesions have generally been poorly defined up to now and our data based on a retrospective review of 8 patients emphasises the persistent gaps in our understanding of the pathophysiology of this disease. Among the lesions responsible for unilateral primary haematuria, diffuse petachiae of the renal pelvis and cavities represent the most frequent endoscopic lesion described in our experience (50% of cases). Histologically, these diffuse lesions correspond to non-specific pyelitis, consisting of simple oedema of the lamina propria. In addition to its diagnostic role, endoscopy can also be used to effectively treat the lesions responsible for unilateral primary haematuria, using either electrocoagulation or nitrate cautery, provided a retrograde approach can be completed by a percutaneous approach, with an overall success rate of 75% of cases with a mean follow-up of 16 months.

Electrocoagulation↗

Endourological treatment of lumbar and iliac ureteral stones. A comparative study of 49 cases.

The efficacy of the Lithoclast has been described extensively in the recent literature. However, to our knowledge, few articles have dealt with the safety of this technique. We present a retrospective study of 49 patients with stones of the lumbar and iliac ureter treated between 1989 and 1992 either by means of the Lithoclast (17 patients), by electrohydraulic shock waves (16 patients), or by trapping the stones in a wire stone basket (16 patients). The success rates were 88% for the Lithoclast and wire stone baskets and 62% for electorhydraulic shock waves. The mean dimensions of the stones were 10 mm for the Lithoclast and electrohydraulic shock wave groups, and 7 mm for the wire stone basket group. Complications consisted of 7 ureteral lesions (2 cases with the Lithoclast, 4 cases with electrohydraulic shock waves and 1 case with the wire stone basket) and 1 stripping of the lower ureter following stone extraction with a wire stone basket, which required open reimplantation. This study demonstrates the efficacy and safety of the Lithoclast for the treatment of large stones of the lumbar and iliac ureter.

Adolescent↗

[Laparoscopic treatment of vesico-ureteral reflux in the pig. Preliminary report].

Laparoscopic urological surgery is currently in a phase of development. In order to evaluate the possibility of treating vesicoureteric reflux by laparoscopy, we performed an elongation of the submucosal ureteric tract via an extravesical approach (Lich-Gregoir) in 4 pigs. After creating a pneumoperitoneum, 4 trocars were introduced into the abdominal cavity. The peritoneum was incised at the level of the iliac vessels and the ureter was released at its middle portion as far as the ureterovesical junction. After coagulation, the detrusor was then incised proximally in relation to the ureterovesical junction, revealing 3 to 4 cm of vesical mucosa. The ureter was buried in the muscular groove, the edges of which were brought together by means of 6 metal staples. In 3 pigs, the bladder and ureter were immediately removed by laparotomy. On macroscopic examination, the staples correctly approximated the muscle layer without transfixing the bladder mucosa or ureter. The patency of the ureter was assessed with a probe. The submucosal tract was sufficiently large, preventing any ureteric compression. In 1 pig, the ureteric meati were incised endoscopically to create reflux. After laparoscopic elongation of the submucosal tract on one side, only the untreated ureter continued to reflux. Correction of vesicoureteric reflux is technically feasible in the pig. Longer studies are necessary before considering the application of this technique to man.

Animals↗

Anatomic basis of laparoscopic surgery in the male pelvis.

Laparoscopic surgery of the male pelvis remains a risky procedure, with around 15% of perioperative complications, as compared to 0.03% in laparoscopic surgery for gynecologic and obstetric conditions. Many of these complications are due to the surgeon's being faced with an unfamiliar anatomic situation in his approach through the laparoscopic operative field. We have added to the data of the literature our anatomic and clinical experience in order to define the anatomic basis of surgical risk in this type of procedure. While dissection lateral to the iliac vessels (surgery of the spermatic cord) is safe, dissection medial to these vessels is more risky because of the confined anatomic relationships and their variations (particularly vascular anomalies and variable relations of the ureter).

Humans↗

Variations in arterial blood supply and the risk of hemorrhage during percutaneous treatment of lesions of the pelviureteral junction obstruction: report of a case of testicular artery arising from an inferior polar renal artery.

Acute hemorrhage during percutaneous surgery on the pelviureteric junction obstruction has been estimated to be 2-3%. Following the experience of peroperative bleeding from a vascular variation, the authors discuss the arterial anomalies of the renal pedicle which may carry the risk of hemorrhage during percutaneous surgery in this region. Arteries in front of or behind the renal pelvis are the cause of ureteropelvic function obstruction in 15-52% of cases and because of their close relationship with the upper urinary tract can complicate the procedure of endopyelotomy. Endourological techniques are inadequate for avoiding the risk of vascular damage during the necessary maneuvers. Inferior polar arteries occur in 9% of the population and their different courses are described. They are not always responsible for the vascular obstruction in the pelviureteric syndrome, and it is the exact determination of this responsibility that makes imaging essential. Arteriography performed in our case allowed embolisation of the damaged inferior polar artery and also showed the anomalous origin of the testicular artery from this polar artery; this appears to be only the second description of this anomaly. This variation is discussed in a review of the literature. In fact the testicular artery has a high or aberrant origin in 20% of cases; in 5-6% of these the origin is from a main or supernumerary renal artery. Origin from an inferior polar artery is exceptional.

Adult↗

Percutaneous extra-anatomic nephrovesical diversion: preliminary report.

We propose a new approach to total ureteric replacement based on the use of a new spiraled composite tube. This tube is inserted percutaneously into the renal pelvis, then tracked subcutaneously and introduced into the bladder via a short incision. The tube is maintained in place by anchoring its spirals along the subcutaneous tract, and only the two silicone extremities are in continuous contact with the urine. We have used this technique for total replacement of the ureter in one renal transplant patient with a follow-up of 8 months and no complication. A longer follow-up is obviously necessary, but this new, minimally invasive approach, using a newly designed tube, would appear to give a new lease of life to an old, abandoned principle.

Adult↗

IGF binding protein-3 secreted by the prostate adenocarcinoma cells (PC-3): differential effect on PC-3 and normal prostate cell growth.

Deregulation of growth in malignant cells has been suggested to be the result of increased secretion by these cells, of autocrine growth factors; alternatively, this deregulation has been assumed to be related to loss of sensitivity by malignant cells to secreted inhibitory molecules. The results of the present publication lend new support to both hypotheses. We recently showed that human prostate adenocarcinoma cells (PC-3 cells) secreted insulin-like growth factor binding proteins (IGFBP) of 45, 34 and 25 kDa. From medium conditioned by dense cultures of PC-3 cells, we have now purified two IGFBPs of M(r) 45 kDa and 34 kDa. The N-amino terminal sequences were determined, and it was shown that they are IGFBP-3. IGFBP-34 appeared to be a deglycosylated form of IGFBP-45. The two IGFBPs had more affinity for IGF-II than for IGF-I. IGFBP-45 and IGFBP-34 were growth-inhibitory factors of chick embryo fibroblasts (CEF): they totally inhibited DNA synthesis stimulated by serum in CEF. Our results point to a clear difference between the effects of these IGFBPs upon growth of normal prostate cells and malignant PC-3 cells. At a concentration of 150 ng/ml, they inhibited growth of normal prostate cells even in the presence of 1 microgram/ml insulin. This suggests that such inhibition was not simply the result of a decrease by the IGFBP of stimulation induced by serum IGF or IGF secreted by the cells. At a concentration of 150 ng/ml, IGFBP did not modify the growth of PC-3 cells. In contrast, it stimulated growth of PC-3 cells when added at a concentration lower than 50 ng/ml (about 1 nM). Our results thus provide new insight concerning the regulation of growth in PC-3 cells.

Adenocarcinoma↗