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A de la Taille

Publications and source records attributed to A de la Taille.

At least 19 recordsLinked to original sources
PubMed2006

Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells.

beta-Catenin, a component of the Wnt signaling pathway, is a coactivator of human androgen receptor (hAR) transcriptional activity. Here, we show that Wnt signaling also influences androgen-mediated signaling through its ability to regulate hAR mRNA and protein in prostate cancer (PCa) cells. Three functional LEF-1/TCF binding sites lie within the promoter of the hAR gene as shown by CHIP assays that captured beta-catenin-bound chromatin from Wnt-activated LNCaP cells. Chimeric reporter vectors that use the hAR gene promoter to drive luciferase expression confirmed that these LEF-1/TCF binding elements are able to confer robust upregulation of luciferase expression when stimulated by Wnt-1 or by transfection with beta-catenin and that dominant-negative TCF or mutations within the dominant TCF-binding element abrogated the response. Semi-quantitative and real time RT-PCR assays confirmed that Wnt activation upregulates hAR mRNA in PCa cells. In contrast, hAR protein expression was strongly suppressed by Wnt activation. The reduction of hAR protein is consistent with evidence that Wnt signaling increased phosphorylation of Akt and its downstream target, MDM2 that promotes degradation of hAR protein through a proteasomal pathway. These data indicate that the hAR gene is a direct target of LEF-1/TCF transcriptional regulation in PCa cells but also show that the expression of the hAR protein is suppressed by a degradation pathway regulated by cross-talk of Wnt to Akt that is likely mediated by Wnt-directed degradation of the B regulatory subunit of protein phosphatase, PP2A.

Binding Sites↗
PubMed2005

[Can IPSS be modified or replaced to evaluate BPH in daily practice?].

Despite all the national and international recommendations, few doctors use IPSS to diagnose and monitor patients suffering from benign prostatic hypertrophy. The purpose of this article is to re-examine the Literature on the various methods that may improve evaluation of patients suffering from BPH ranging from a direct integration of the specific discomfort caused by each symptom to the use of visual analog scales (VAS). Concerning VAS, there seems to be a strong correlation between the IPSS score and the score by VAS for the evaluation of symptoms, discomfort and quality of life. The improvements in symptoms following medical treatment are shown in a parallel manner by the IPSS and VAS. Additional complementary studies on a broad population of patients are necessary before proposing this new tool for the diagnosis and follow-up of patients suffering from BPH.

Humans↗
PubMed2003

[Urologic complications of radiotherapy].

Radiation therapy is commonly used to treat pelvic or retroperitoneal cancers but has some impact on genito-urinary system: short-term side effects are frequent with usually a completed regression. However, the incidence of major complications is about 12% and is probably underestimated due to a long delay between radiation therapy and diagnosis of some adverse events such as ureteral strictures or fistula. Clinical follow-up must absolutely include an early diagnosis and treatment of radiation therapy complications such as renal dysfunction, ureteral stricture, ureteral fistula, chronic bladder injury, bladder fistula, urethral stricture, infertility or erectile dysfunction.

Female↗
PubMed2003

A preoperative clinical prognostic model for non-metastatic renal cell carcinoma.

OBJECTIVE: To develop a model to predict the outcome before surgery for non-metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: The records of 660 patients with non-metastatic RCC, operated at three European medical institutes, were reviewed. Univariate and multivariate analyses were used to assess the clinical and pathological variables affecting disease-free survival. RESULTS: The median (range) follow-up was 42 (2-180) months; the disease recurred in 110 patients (16%). The 2- and 5-year overall survival was 87% and 54%, respectively. Five variables were significant in the univariate analysis, i.e. clinical presentation, clinical and pathological size, tumour grade and stage (P < 0.05). The preoperative variables, e.g. clinical presentation and clinical tumour size, were retained from the multivariate model. A recurrence risk formula (RRF) was constructed from this model, as (1.28 x presentation (asymptomatic = 0; symptomatic = 1) + (0.13 x clinical size)). Using this equation, the 2- and 5-year disease-free survival was 96% and 93% for an RRF of < or = 1.2 and 83% and 68% for an RRF of > 1.2. CONCLUSION: A formula was developed which, independent of stage, can be used to predict the rate of treatment failure in patients who undergo nephrectomy for non-metastatic RCC. The RRF might be useful for more accurate sub-grouping of good-prognosis patients, and for counselling patients before surgery, their personalized follow-up or adjuvant treatment once available.

Adult↗
PubMed2003

The androgen receptor in hormone-refractory prostate cancer: relevance of different mechanisms of androgen receptor signaling (Review).

The last decade has brought increased awareness to prostate cancer as a significant health problem. Prostate cancer is very heterogeneous in its etiology and progression, but androgen signaling appears to be a common key element in its development and progression. Blocking of androgen signaling results in a decrease in tumor volume as well as a decline in serum PSA in the majority of patients with prostate cancer. Today, endocrine therapy involves androgen depletion by orchiectomy or by treatment with LHRH-analoga as well as blockade of the androgen receptor (AR) with anti-androgens. However, during these treatments almost all tumors relapse to a hormone-insensitive state. The mechanisms that lead from initially androgen-sensitive to androgen-unresponsive tumor cell growth have been partly elucidated by new insights into the molecular mechanisms of androgen receptor signaling over the past several years. In addition to androgen receptor mutations that broaden the ligand-specificity of the AR, androgen-independent transactivation of the AR by peptide growth factors such as epidermal growth factor and insulin-like growth factor-I has been discovered. Furthermore, analysis of proteins that interact with the AR led to the isolation of coactivator proteins that mediate transcriptional activation by the AR. The following review will discuss the elements involved in androgen receptor signaling and summarize the present knowledge of their biological and clinical relevance in advanced prostate cancer.

Cell Division↗
PubMed2002

Predictive factors of radiation therapy for patients with prostate specific antigen recurrence after radical prostatectomy.

OBJECTIVE: To assess the efficacy of salvage/adjuvant radiation therapy (RT) for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). PATIENTS AND METHODS: Between 1997 and 2001, 52 patients were treated in our institution with RT for PSA recurrence after RP. The mean (range) delay between RP and RT was 30.5 (0.16-105.6) months. Eighteen patients received no hormonal therapy before RT. The failure of RT was defined as three consecutive increases in PSA levels with intervals of > or = 6 weeks. RESULTS: Within a mean (range) follow-up of 27.7 (6-69) months, 18 patients presented with biochemical progression. The 3-year biochemical progression-free survival was 51%. Using univariate analysis, an age < 65 years (P = 0.0262), a Gleason score on the RP specimen of > or = 8 (P = 0.0024), stage pT3 (P = 0.02), a detectable nadir PSA after RT (P < 0.001) and the absence of hormonal therapy (P = 0.0359) were associated with a lower biochemical progression-free survival. However, only the Gleason score (P = 0.0395) and nadir serum PSA after RT (P = 0.028) remained independent predictive factors on multivariate analysis. CONCLUSION: Half of the present patients treated with RT for an isolated high serum PSA level after RP were free of biochemical relapse at 3 years of follow-up. RT may be proposed to selected patients with mild morbidity. However, definitive evidence of the beneficial effect of adjuvant RT for patients with PSA recurrence after RP awaits the conclusion of randomized clinical trials.

Aged↗
PubMed2001

Reduction of wild type p53 function confers a hormone resistant phenotype on LNCaP prostate cancer cells.

BACKGROUND: The protein encoded by the p53 gene is required for some forms of apoptosis and loss or mutations in this gene are found with increased frequency in advanced and hormone resistant human prostate cancers. In order to better appreciate whether reduction of wildtype p53 function in prostate cancer cells might contribute to the development of therapeutic-resistance by these cells, we created stable variants of the androgen-responsive, wild type p53-expressing human prostate cancer cell line, LNCaP, by transfection with expression vectors designed to reduce expression or function of wildtype p53 in them. These cells were then tested for their ability to form tumors in castrated male nude mice. METHODS: A conditional eukaryotic expression vector (under tetracycline regulation) expressing antisense p53 cDNA was constructed and either directly transfected into LNCaP cells or tranduced into these cells using recombinant retroviruses containing the vector. Stably transfected/transduced cells (LNCaP/Asp53) were evaluated by Western blot analysis for the ability of doxycycline to reduce p53 protein expression and for their ability to form tumors in castrated male nude mice treated or untreated with doxycycline. Additionally, we derived an LNCaP subline (LNCaP/DD) stably expressing a dominant-negative form of p53 and tested these cells for their ability to form tumors in castrated male nude mice. RESULTS: LNCaP/Asp53 cells showed reduced expression of p53 protein when cultured in a medium containing doxycycline and tested sublines were able to efficiently form tumors in castrated male nude mice only when the mice were treated with doxycycline. LNCaP/DD cells were readily able to form tumors in castrated male nude mice whereas parental LNCaP cells or control-transfected LNCaP cells were not. CONCLUSION: Loss of wildtype p53 function can contribute to the phenotype of hormone resistance of prostate cancer cells.

Animals↗
PubMed2001

[Cancer of the prostate: influence of nutritional factors. General nutritional factors].

OBESITY: Studies attempting to establish an epidemiological link between body mass index and the risk of cancer of the prostate have been contradictory. ENERGY INTAKE: No straightforward relationship between energy intake and cancer of the prostate has been identified. FAR INTAKE: According to epidemiology studies, there is a correlation between high-fat diet and the incidence of cancer of the prostate. It has thus been demonstrated that men whose diet contains more than 30 to 40% fat have a higher risk of developing cancer of the prostate than those whose diet contains less than 30% fat. In addition, high-fat diets favor progression of tumors in elderly subjects. ROLE OF SATURATED FAT: Saturated fat has been implicated most often in the development of cancer of the prostate, high intake being correlated with shorter survival after diagnosis of cancer.

Age Factors↗
PubMed2001

[Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants and trace elements].

CANCER OF THE PROSTATE AND VITAMINS: Four vitamins have been studied, vitamins A, E, D and C. the results of these studies have been contradictory. Vitamin A and vitamin E would have a protective effect. ANTIOXIDANTS: Carotenes have an activity similar to that of vitamin A. Beta-carotene was positively associated with risk of cancer of the prostate in one study while two others were unable to demonstrate any relationship. Lycopene, the red color in fruits and vegetables, particularly tomatoes, would contribute to a lower risk of prostate cancer. TRACE ELEMENTS: Cadmium would increase the risk of cancer while selenium would have a protective effect. However studies concerning selenium carry certain methodological biases.

Aged↗
PubMed2001

[Cancer of the prostate: influence of nutritional factors. A new nutritional approach].

FIBERS: A group of vegetarian subjects have been shown to have a lower risk of cancer of the prostate than a control group. But the exact role of food fiber remains to be determined because plant foods also have an antioxidant effect on their own. PLANT PRODUCTS AND EXTRACTS: A compound called PD SPEC has been showed to have antitumor effects both in vitro and in vivo. Evaluated in patients with a cancer escaping hormone control, the clinical response was a lower level of prostate specific antigen (PSA). SOYBEANS: Several studies have demonstrated the interesting properties of soybeans. No study has however been able to demonstrate the optimal dose per day. A prospective study is currently under way using a 40 g/day dose. OVERALL NUTRITIONAL APPROACH: Several studies are being conducted using a proposed diet where 15% of the total energy intake comes from fat (associated with a low saturated/unsaturated ratio), high fiber content (18 g/100 kcal) and 40 g daily soybean protein. Although large-scale studies with rigorous methodology are lacking, an overall nutritional approach could be an interesting strategy for the management of cancer of the prostate.

Animals↗
PubMed2001

Biomarker analysis demonstrates a hypoxic environment in the castrated rat ventral prostate gland.

Within the first 24 h after castration of an adult male rat, the vascular system of the ventral prostate gland undergoes a degenerative process that drastically reduces blood flow to the tissue. Since the vascular degeneration precedes the loss of the prostatic epithelium (by apoptosis), we have proposed that the onset of epithelial cell apoptosis in this tissue is caused by an ischemic/hypoxic environment resulting from the loss of blood flow. In order to further evaluate the extent to which ischemia/hypoxia might be a factor in apoptosis of the prostate epithelium after castration, we analyzed for biomarkers of cellular hypoxia in rat ventral prostates during the first 3 days following castration. Ventral prostate tissues removed from hypoxyprobe-1-treated adult male rats (uncastrated controls; surgically castrated for 24, 48 or 72 h, or sham-castrated for equivalent times) were directly analyzed for evidence of hypoxia by in situ immunohistochemical evaluation of hypoxyprobe-1 adduct formation in the prostate cells. Protein extracts from these tissues were also tested for expression of the 120 kDa hypoxia-inducible factor-1-alpha (HIF-1-alpha) protein as well as for expression of mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) proteins using a Western blot assay. The tyrosine phosphorylation status of the latter signaling molecules was also evaluated by Western blotting using anti-tyrosine phosphate antibodies. Our results showed that epithelial cells of the rat ventral prostate stained positively for hypoxyprobe-1 adducts at all times after castration, whereas cells in control tissues were unstained by this procedure. In addition, the prostatic expression of HIF-1-alpha protein was increased approximately 20-fold at 48 h after castration compared to control tissues. Finally, although prostatic MAPK and JNK protein expression was unaltered during the early period after castration, phosphorylation of the JUN kinase protein was significantly elevated, indicating that this stress-activated cellular signaling pathway becomes more active subsequent to castration. These results support our proposal that early castration-induced degeneration and constriction of the vascular system of the rat ventral prostate gland leads to reduced oxygenation of prostatic epithelial cells and the activation of hypoxic cellular signaling in these cells through upregulation of HIF-1-alpha expression and stimulation of the JUN kinase signaling pathway.

Animals↗
PubMed2001

[PC SPES in prostatic cancer: critical review of the literature].

PC SPES is a mixture of Chinese plants or plant extracts available on unrestricted sale since 1996 in the treatment of prostate cancer. Each of its components has been individually demonstrated to have an antitumour action anti-neoplastic in various in vitro or in vivo models. Its favourable action on hormone-resistant prostate cancer, demonstrated in studies with only a short follow-up, led to a certain publicity concerning this product, and its unrestricted sale together with the possibility of purchasing this product in other countries by Internet have led to the use of this product by some patients in France without medical advice or follow-up. This article presents a critical review of the results of this product in prostate cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2001

[Tendinopathy associated with fluoroquinolones: individuals at risk, incriminated physiopathologic mechanisms, therapeutic management].

The use of fluoroquinolones in urology has grown considerably over recent years. Unfortunately, although these molecules are not associated with severe life-threatening complications, they have nevertheless been associated with tendon lesions responsible for functional disability. The frequency of these complications is probably underestimated. There is a variable lag-time (3 to 5 days) between introduction of the antibacterial and onset of pain. The symptom most frequently reported is pain over the tendon affected and the tendons most frequently affected are those submitted to high constraints. Bilateral lesions are present in 66% of cases. Although Pefloxacin is associated with the highest frequency of tendon complications (2.7% versus 0.2-0.3% for other fluoroquinolones), the duration of treatment appears to be important in every case, with a peak frequency after a fortnight of treatment. Although these complications were considered for a long time to be associated with patients presenting certain risk factors (age, steroid therapy, renal failure), they can also occur suddenly, in young adult sportsmen or non-sportsmen, with no known tendon disease. Several hypotheses have been proposed to explain the development of these cases of tendinopathy: immuno-allergic mechanisms, direct toxicity of the molecule on collagen fibres, cell-mediated oxidative aggression, or tendon necrosis due to vascular mechanisms. The outcome remains favourable in 75% of cases of tendinitis and in 49% of cases for tendon rupture. Contraindications must therefore be identified and the duration of treatment must be adapted, as the functional handicap can be long and particularly severe.

Anti-Infective Agents↗
PubMed2000

Blood-based RT-PCR assays of MN/CA9 or PSMA: clinical application in renal cancer patients.

OBJECTIVES: To report a survey of blood-based RNAs obtained from common groups of control and renal cancer patients for expression of both MN/CA9 and prostate-specific membrane antigen (PSMA) messenger RNAs. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) assays for MN/CA9 and PSMA were performed on RNAs extracted from 81 blood samples (59 patients with renal cancer, 7 with benign tumors, and 15 control volunteers). The results of these assays were statistically analyzed to determine whether a positive result (individually or combined) correlates with any tumor characteristics. RESULTS: Neither MN/CA9 nor PSMA amplification products were detected in the RNAs from peripheral blood samples of the 15 control volunteers and from the 7 patients with benign renal tumor (sensitivity 100%). MN/CA9 alone was detected in 11 (19%) of 59 samples and PSMA alone in 12 (20%) of 59 samples from patients with renal cancer. PSMA positivity was significantly correlated with vascular invasion of the primary tumor. Expression of one or both of these molecular tumor markers was detected in 21 (36%) of 59 renal cancer patients. When combined, the results of the MN/CA9 and PSMA RT-PCR tests were found to be highly associated with vascular invasion in nephrectomy specimens (sensitivity 67%, specificity 77%, odds ratio = 6.89, P = 0.002). CONCLUSIONS: Combination of RT-PCR assays for MN/CA9 and PSMA provides a sensitive blood test for molecular detection of clear cell carcinoma of the kidney and its potential for vascular invasion. Further testing of this assay will be required to evaluate its efficacy in the diagnosis, screening, and follow-up of patients with kidney cancer.

Adult↗
PubMed2000

Salvage cryotherapy for recurrent prostate cancer after radiation therapy: the Columbia experience.

OBJECTIVES: Cryotherapy of the prostate represents a potential treatment for localized recurrent prostate cancer after radiation therapy. We report our experience and evaluate the predictive factors for prostate-specific antigen (PSA) recurrence. METHODS: Between October 1994 and April 1999, 43 patients underwent salvage cryoablation. All patients had biopsy-proven recurrent prostate cancer without seminal vesicle invasion, negative bone scans, and negative lymph node dissection. Patients had received 3 months of combined hormonal therapy before cryosurgery. Biochemical recurrence-free survival (bRFS) was defined as a PSA value less than 0.1 ng/mL. RESULTS: Complications included incontinence (9%), obstruction (5%), urethral stricture (5%), rectal pain (26%), urinary infection (9%), scrotal edema (12%), and hematuria (5%). The mean follow-up was 21.9 months (range 1.2 to 54). Twenty-six patients (60%) reached a serum PSA nadir less than 0.1 ng/mL, 16 (37%) had a PSA less than 4 ng/mL, and 1 (3%) had a PSA less than 10 ng/mL. The bRFS rate was 79% at 6 months and 66% at 12 months. The bRFS rate was higher for patients who had an undetectable postcryotherapy PSA than for patients who did not reach a PSA less than 0. 1 ng/mL (73% versus 30%, P = 0.0076). Using multivariate analysis, a PSA nadir greater than 0.1 ng/mL was an independent predictor of PSA recurrence. CONCLUSIONS: Current salvage cryotherapy of the prostate can result in undetectable serum PSA levels with low morbidity. Our data support the current safety and efficacy profile. We believe that cryotherapy is a viable option in the treatment of patients who have biopsy-proven local failure after radiation therapy for prostate cancer. Further refinements in technique and equipment may enhance cryosurgical results.

Aged↗
PubMed2000

Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer: two case reports.

PURPOSE: Herbal therapies are unconventional treatments that have been used for several different diseases. PC-SPES is an herbal mixture, composed of eight different herbs (chrysanthemum, isatis, licorice, Ganoderma lucidum, Panax pseudo-ginseng, Rabdosia rubescens, saw palmetto, and scutellaria), which has been used as an alternative in the treatment of prostate cancer. We report two cases of hormone-refractory prostate cancer patients, who showed a favorable response to therapy with this herbal combination, controlling the progression of the disease. METHODS: We report two cases of biopsy proven prostate cancer patients with metastatic disease, treated with total androgen blockade, progressing to an androgen-independent status. These patients were offered traditional therapies for hormone-resistant prostate cancer, and they chose to take PC-SPES. The follow-up as well as their evolution are described. RESULTS: PC-SPES extract decreased the prostate-specific antigen (PSA) value for both patients from an initial value of 100 and 386 ng/mL to 24 and 114 ng/mL after 1 year and 4 months, respectively, remaining stable until now. No gynecomastia or hot flashes were observed in these patients and the treatment was well tolerated. CONCLUSION: PC-SPES has shown a strong estrogenic in vitro and in vivo activity as an alternative tool in the management of prostate cancer patients. These cases suggest that PC-SPES might have some potential activity against hormone-independent prostate cancers.

Aged↗
PubMed2000

Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer.

PURPOSE: We investigate the potential use of the phytotherapeutic PC-SPES to treat human prostate cancer, and evaluate its in vivo and in vitro activity, and clinical efficacy. MATERIALS AND METHODS: PC-SPES was evaluated for its ability to induce apoptosis on prostate cancer cell lines LNCaP, PC3 and DU145. The effect of oral PC-SPES on growth of PC3 tumors present in male immunodeficient mice was studied. A total of 30 male nude mice were divided in 5 groups. In groups 1 control and 2 full dose therapy was started the same day of the tumor injection. In groups 3 control, 4 half dose and 5 full dose PC-SPES therapy was initiated 1 week after tumor injection. A total of 69 patients with prostate cancer were treated with 3 capsules of 320 mg. PC-SPES daily. Serum prostate specific antigen (PSA) responses and side effects were evaluated. RESULTS: All of the cultured prostate cancer cell lines had a significant dose dependent induction of apoptosis following exposure to an alcoholic PC-SPES extract. Immunodeficient mice xenografted with the PC3 cell line had reduced tumor volume compared with sham treated controls when they were treated with a PC-SPES extract from the time of tumor cell implantation (931 +/- 89 versus 1,424 +/- 685 mm.3, p not significant) but not when the treatment was begun 1 week after tumor cell implantation. The testis, prostate, bladder and seminal vesicles of the treated mice were significantly reduced in weight compared with the sham treated animals. Of the patients with prostate cancer 82% had decreased serum PSA 2 months, 78% 6 months and 88% 12 months after treatment with PC-SPES. Side effects in the treated patient population included nipple tenderness in 42% and phlebitis requiring heparinization in 2%. CONCLUSIONS: An extract of the phytotherapeutic agent PC-SPES proved to be active in inducing apoptosis of hormone sensitive and insensitive prostate cancer cells in vitro, and in suppressing the growth rate of a hormone insensitive prostate cancer cell line in vivo. The overwhelming majority of patients with prostate cancer treated with the agent experienced a decrease in serum PSA but also demonstrated a side effect profile comparable to estrogen treatment.

Aged↗