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Biomedical subjects

O Cussenot

Publications and source records attributed to O Cussenot.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays.

Steroid hormones can have profound effects on prostate tumor development making it important to define steroid receptor expression in prostate tissues. For this purpose, androgen receptor (AR) and estrogen receptor (ER alpha and ER beta) expression was quantified in 12 clinically localized and 11 hormone-refractory sporadic prostate tumors, using real-time quantitative reverse transcription-PCR assays. To gain more insight into hormone-responsiveness, estrogen-regulated progesterone receptor (PGR) and androgen-regulated prostatic acid phosphatase (PAP) mRNA levels were also quantified. There is a decrease in expression of ER beta in both clinically localized and hormone-refractory tumors relative to normal prostate tissues. Moreover, hormone-refractory tumors display a decreased expression of ER alpha and an increased expression of AR. There is a positive association between ER alpha, ER beta, and PGR expression (P < 0.0001) and a negative association between AR and the androgen-regulated gene PAP expression in hormone-refractory tumors. Taken together, these data indicate that, although increased expression of the AR gene might play a key role in endocrine treatment failure, it cannot be considered as the sole actor of this unresolved dilemma, and abnormalities in ER alpha and/or ER beta expression may also modulate the growth response of prostate cancer to hormone withdrawal. Our results also suggest that ER alpha and ER beta expression status could be used to identify advanced prostate tumor patients who may respond to antiestrogen therapy.

Acid Phosphatase↗
PubMed2001

In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line.

BACKGROUND: Dog prostate cancer is usually considered to be highly relevant to human prostate cancer. We report the isolation of a new canine prostate cancer epithelial cell line designated DPC-1. METHODS: Primary cultures were established from a canine poorly differentiated prostatic adenocarcinoma. Population doubling time was determined by counting nuclei after cell lysis. Tumorigenicity was assessed in nude mice and in one adult immunodeficient dog. Immunoscintigraphy was performed in both models using a monoclonal antibody (mAb) raised against the [44-62] sequence of human PSMA. RESULTS: DPC-1 cells have a rapid growth in vitro (doubling time, 27 hr) which is not stimulated by androgens. In addition, DPC-1 displays immunoreactivity to human PSA and PSMA. DPC-1 was found to be highly tumorigenic not only in nude mice but also for the first time after orthotopic seeding in an immunodeficient dog. This allograft mimicked, in a compressed form, the aggressive biological behavior of spontaneous dog prostate adenocarcinoma. Immunoscintigraphy using a (131)Iodine-labeled PSMA mAb clearly visualized induced tumors in nude mice and in the dog allograft. CONCLUSIONS: This study suggests that DPC-1 may constitute a powerful model for assessing new diagnostic and/or therapeutic tools in the management of prostate cancer.

Adenocarcinoma↗
PubMed2001

The lateral inframalleolar fat pad: a poorly recognized anatomical structure.

The authors carried out an anatomical histological study of the lateral inframalleolar region in order to improve knowledge of a fat pad of the lateral aspect of the ankle which is not mentioned in most anatomical texts. Twenty-four ankles, from 12 cadavers, free of any local pathology or malformation, were studied. Twenty ankles were dissected, of which, five had samples taken for histological examination. Colored latex was injected into the joint cavities of the last four ankles before anatomical cuts were made in three planes. This study allowed the description of the fat pad which we have called the lateral inframalleolar fat pad (LIMFP). It is oval and made up of a classical unilocular fatty tissue which is clearly distinct from the subcutaneous plane. We have defined its relationships and in particular, the neurovascular ones. The sural nerve which supplies cutaneous sensation to part of the 5th toe runs over the surface of the fat pad. It is accompanied on this part of its course by the short saphenous vein which gives off a medial perforator which traverses the LIMFP. Because of these neurovascular relationships, the LIMFP may play a role in the pathophysiology of neuralgias of the lateral aspect of the 5th toe or of the 4th digital interspace. It should be recognized before any operations on the lower limbs, in particular, before any plastic surgical liposuction, in order to optimize the resection volume to prevent inaesthetic over correction or under corrections which are often confused with residual edema.

Adipose Tissue↗
PubMed2001

Noninvasive detection of genetic instability in cells from prostatic secretion as a marker of prostate cancer.

We present a clinical and molecular study of a series of specific loss of heterozygosity (LOH) indicators which, together with PSA, increase the predictability of cancer in early prostate cancer patients. Considering a positive biopsy as the standard reference, the testing parameters for LOH testing are better than the PSA F/T ratio (<25%), suggesting that this noninvasive approach to detecting early prostate cancer could be very useful as a new tool to optimize the indications for iterative prostate biopsies.

Journal Article↗
PubMed2001

Heterogeneity in genetic susceptibility to prostate cancer.

The incidence of prostate cancer is related to aging. Its increase in the last 10 years, varies from country to country and according to ethnic group, with its greatest incidence among African-American males and the least among Asian males. Only two risk factors have thus far been clearly established for prostate cancer: familial aggregation and ethnic origin. No dietary or environmental cause has yet been identified for prostate cancer. However, some variations in endogenous factors, such as sex steroids or IGF1 circulating levels, may partly explain differences in risk observed between different populations. Genetic polymorphisms of genes encoding for 5alpha-reductase, androgen receptor, or vitamin D receptor have been associated with different degrees of risk for prostate cancer and may explain variations in risk among ethnic groups or within geographic areas. Different studies support the theory that familial prostate cancer may be hereditary and not due to a similar lifestyle. Thus, familial inheritance is a parameter that must be considered when advising screening in high-risk families. Indeed, the relative risk for first-degree relatives of prostate cancer patients can reach 2, 5 and 11 when, respectively, 1, 2 and 3 first-degree relatives are affected. Some familial forms appear to be associated with transmission of a rare, putative, autosomal dominant gene (0.003-0.06 allele frequency) with a high penetrance (88% at age 85). Using this transmission model and linkage analysis, three predisposing loci on chromosome 1: HPC-1 (hereditary prostate cancer 1: 1q24-25), PCaP (predisposing for prostate cancer: 1q42-43) and CAPB (predisposing for prostate and brain tumor: 1p36) and one locus on chromosome 20 (HPC20: 20q13) have been described. Moreover, X-linked transmission has been suggested and related to another predisposing gene locus: HPCX (Xq27-28). It is possible that a large proportion of familial prostate cancer is due not to segregation of a few major gene mutations transmitted according to a monogenic inheritance, but rather to familial sharing of alleles at many loci, each contributing to a small increase in cancer risk.

Journal Article↗
PubMed2001

PCAP is the major known prostate cancer predisposing locus in families from south and west Europe.

To date four prostate cancer predisposing loci have been mapped: HPC1 (Hereditary Prostate Cancer 1) on 1q24-25, PCaP (Predisposing for Cancer Prostate) on 1q42.2-43, CAPB (Cancer Prostate and Brain) on 1p36, and HPCX on Xq27-28. We examined evidence for linkage to those loci in 64 families from south and west Europe. Genotyping of three (six for PCaP) markers encompassing the candidate regions were performed on 221 individuals including 159 affected patients. The resulting data were analysed using both parametric and non parametric linkage methods. No significant evidence of linkage to HPC1, CAPB, or HPCX was found either in the whole population or when pedigrees were stratified according to criteria specific to each locus. By contrast, results in favour of linkage to PCaP locus were observed with maximum multipoint NPL and HLOD scores of 2.8 (P = 0.0026) and 2.65 respectively. Homogeneity analysis performed with multipoint LOD scores gave an estimated proportion of families with linkage to this locus up to 50%. Particularly, families with an earlier age at diagnosis (< or = 65-years-old) contributed significantly to the evidence of linkage with a maximum multipoint NPL score of 2.03 (P = 0.024). Those results suggest that PCaP is the most frequent known locus predisposing to hereditary prostate cancer cases from families from south and west Europe.

Aged↗
PubMed2000

Early-onset hereditary prostate cancer is not associated with specific clinical and biological features.

BACKGROUND: Familial prostate cancer (CaP) accounts for 15-20% of all CaP, and hereditary CaP for 5-10% of patients. Few data are available concerning their clinical and biological features. METHODS: We compared diagnostic modalities, age, clinical stage, PSA, and tumor grade at diagnosis in CaP patients according to familial CaP profile: hereditary (HR) (> or =3 CaP), familial nonhereditary (FNH) (= 2 CaP), and sporadic CaP. Only cases diagnosed after January 1, 1987 (PSA-available period) were included. We considered as informative sporadic (IS) cases those probands with 2+ nonaffected brothers at least 50 years old. Finally, 267 CaP (230 probands and 37 affected brothers) were studied. RESULTS: In multivariate analysis, the only specific parameter significantly associated with HR and FNH CaP was early age at diagnosis; mean ages were 65.3 years (HR), 67 years (FNH), and 70.9 years (IS) (P < 0. 0001). No significant difference was observed concerning clinical stage, PSA, and tumor grade. In addition, diagnostic modalities were similar in the three groups. CONCLUSIONS: Our data confirm the occurrence of early-onset CaP in hereditary families. Although the clinical and biological presentation of HR CaP remains controversial, the lack of specific features observed in our study leads us to conclude that there is no difference in the aggressiveness of the disease in hereditary compared to sporadic CaP.

Aged↗
PubMed2000

Early onset and familial predisposition to prostate cancer significantly enhance the probability for breast cancer in first degree relatives.

Genetic predisposition accounts for >/=10% of all cancer of the prostate (CaP) and is therefore considered a major risk factor, together with age and ethnic origin. Several epidemiological studies have suggested that familial clustering of CaP may be associated with an increased frequency of breast and other cancers among relatives. In order to correlate the incidence of CaP with prevalence of breast and other cancers, we have performed uni- and multi-variate analyses on 691 complete pedigrees including probands, who were consecutive patients with confirmed CaP treated in three French urological departments. We have shown a significantly higher risk (RR = 2.3, p = 0.01) to develop breast cancer in families with multiple than in those with a single CaP. Risk of observing other types of cancer within these families was not significant. We then calculated the breast cancer risk in early onset prostate cancer families, and observed a relative risk that is even more significant (RR = 5.5, p = 0.002). Furthermore, the risk was >30 times that a proband's mother have breast cancer if CaP occurred below 55 years of age, rather than after 75 years (p = 0.003). This study has therefore shown for the first time, the relatively high penetrance for breast cancer in relatives of early onset CaP patients.

Adult↗
PubMed2000

VEGF overexpression in clinically localized prostate tumors and neuropilin-1 overexpression in metastatic forms.

Studies comparing tumor neovascularity with pathological findings suggest that angiogenesis contributes to the pathogenesis of prostate cancer. We have examined 42 primary sporadic prostate tumors at different clinical stages, together with 3 prostate cancer cell lines (DU145, PC3 and LNCaP), for expression of VEGF and the gene encoding the recently identified VEGF165 isoform-specific receptor neuropilin-1, by using a quantitative reverse transcription (RT)-PCR method. We also evaluated the VEGF transcription pattern. Upregulation of VEGF and neuropilin-1 was observed in 12 and 14 tumors, respectively. The VEGF165 isoform was slighly overrepresented in tumors that overexpressed VEGF. VEGF overexpression correlated with stage II disease (p < 0.05); neuropilin-1 overexpression correlated with advanced disease (p < 0. 01) and a high Gleason grade (p < 0.02). Our observations suggest that VEGF expression could be used as a prognostic marker in early-stage prostate tumors, whereas neuropilin-1 overexpression might be a marker of aggressiveness.

Endothelial Growth Factors↗
PubMed2000

htert expression correlates with MYC over-expression in human prostate cancer.

Expression of the telomerase catalytic sub-unit (htert) constitutes a key step in the development of human cancer. Although htert regulation is still unclear, several studies suggest that c-myc may activate its expression. Prostate cancer is one of the most common malignancies among men in Western countries. Since de-regulated expression of myc as well as telomerase activation may contribute to the pathogenicity of this cancer, we investigated this pathway in prostate tumorigenesis. For this purpose, myc- and htert-mRNA expression was quantified in 33 sporadic prostate tumors using a real-time quantitative PCR assay based on TaqMan methodology. myc over-expression was observed in 19 (58%) of 33 tumors, whereas telomerase status evaluated by htert expression was observed in 22 (67%). There was no correlation between myc over-expression or htert expression level and tumor stage or Gleason grade. A significant association (p = 0.0024) was found between myc over-expression and elevated htert expression, indicating that the up-regulation of telomerase activity often observed in prostate tumors might be conferred through transactivation of htert by myc. It is likely that the ability of c-myc protein to stimulate expression of htert and thereby enhance telomerase activity represents an important step in prostate tumorigenesis.

DNA Primers↗
PubMed2000

Telomerase activity as a potential marker in preneoplastic bladder lesions.

OBJECTIVE: To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. PATIENTS AND METHODS: Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. RESULTS: Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable 'telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. CONCLUSION: These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.

Adult↗
PubMed2000

Gene transfer to urethral strictures in rabbits: a preliminary report.

OBJECTIVE: To assess the rationale for virus-mediated gene transfer into the urethra in vivo and in vitro, using a rabbit model, as this is an attractive approach to prevent recurrence after the endoscopic management of urethral strictures. MATERIALS AND METHODS: Primary cultures of rabbit urethral stromal cells were infected with adenoviral and retroviral solutions carrying a nucleus-targeted beta-galactosidase (beta-Gal) reporter gene (respectively 109 and 107 plaque-forming units/mL). In addition, to mimic the human clinical situation, a model was developed of thermally induced stricture in rabbit urethra which produced fibrotic stenosis within 15 days. Using a prototype channelled balloon catheter, these strictures were endoscopically dilated and then instilled with the beta-Gal adenoviral or retroviral constructs. RESULTS: The application of recombinant adenovirus and retrovirus harbouring a nucleus-targeted beta-Gal reporter gene to cultured rabbit urethral stromal cells resulted in a high transduction efficiency of up to 90% and 96%, respectively. Five days after infection, histochemical and immunohistochemical staining of the strictured urethrae showed a 3% rate of transfection targeted to stromal cells within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry, immunohistochemistry and PCR. CONCLUSION: These results represent the first report of endoscopic adenovirus and retrovirus-mediated gene transfer to the urethra. Although at a low rate, transduction reached stromal cells transmurally within the induced strictures and was site-specific.

Adenoviridae↗
PubMed2000

A new prostatic stent for the treatment of benign prostatic hyperplasia in high-risk patients.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of a new prostatic stent (Trestle((R)), Boston Scientific Microvasive) for the treatment of BPH in patients with complete urinary retention and considered to be inoperable. METHODS: The efficacy of the stent was evaluated in terms of return of micturition, level of patient satisfaction, uroflowmetry and residual urine. Any stents removed were examined by infrared spectrophotometry for the presence of crystalline encrustations. RESULTS: From December 1997 to April 1999, 20 stents were inserted under local anaesthesia in 17 patients aged 54-90 years. Stents remained in place for an average of 3.5 months. Two migrations were reported. The mean maximum flow rate was 13.7 ml/s and the mean residual urine was 110 ml. The infrared spectrophotometry study revealed a glycoprotein film on stents in place for 1-6 months, accompanied by uric acid crystals on stents in place for 9 months. CONCLUSION: The Trestle prostatic stent is effective and constitutes a good alternative to surgical treatment in patients with a high operative risk.

Aged↗
PubMed1999

Expression and mutational analysis of the MADR2/Smad2 gene in human prostate cancer.

BACKGROUND: Loss of heterozygosity (LOH) on chromosome arm 18q is common in sporadic prostate cancer and may be involved in cancer development through inactivation of tumor-suppressor genes (TSG). Recent identification, at 18q21.1, of MADR2/Smad2, a key component in transforming growth factor beta (TGFbeta)-family signaling pathways, led us to investigate the role of this gene in prostate tumorigenesis. METHODS: Sporadic primary prostate tumors from 25 patients with clinically localized tumors and 7 with metastatic forms were examined for MADR2/Smad2 mutations by using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis of cDNA, and for gene expression by quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We detected no mutation in MADR2/Smad2 and no abnormal mRNA expression. CONCLUSIONS: Despite recent evidence indicating that MADR2/Smad2 acts as a tumor-suppressor gene, our findings suggest a limited role of this gene in prostate tumorigenesis, at least in the early stages. Another key tumor-suppressor gene may therefore be the main target of the observed LOH at 18q21.1.

Biopsy, Needle↗