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Nicolas Mottet

Publications and source records attributed to Nicolas Mottet.

At least 19 recordsLinked to original sources
PubMed2006

DNA-methylation-dependent alterations of claudin-4 expression in human bladder carcinoma.

The expression pattern of tight junction (TJ) proteins is frequently disrupted in epithelial tumors. In particular, isoform- and organ-specific alterations of claudins have been detected in human cancers, highlighting them as interesting tools for the prognosis or treatment of various carcinomas. However, the molecular mechanisms responsible for these alterations are seldom identified. Here, we analyzed the expression and localization of claudins 1, 4, and 7 in human bladder carcinoma. Claudin-4 expression was significantly altered in 26/39 tumors, contrasting with the rare modifications detected in the expression of claudins 1 and 7. Overexpression of claudin-4 in differentiated carcinomas was followed by a strong downregulation in invasive/high-grade tumors, and this expression pattern was associated to the 1-year survival of bladder tumor patients. A CpG island was identified within the coding sequence of the CLDN4 gene, and treatment with a methyl-transferase inhibitor restored expression of the protein in primary cultures prepared from high-grade human bladder tumors. In addition, claudin-4 expression correlated with its gene methylation profile in healthy and tumoral bladders from 20 patients, and downregulation of claudin-4 expression was detected in the urothelium of mice overexpressing DNA methyl transferase 3a (Dnmt3a). Delocalization of claudins 1 and 4 from TJs was observed in most human bladder tumors and in the bladder tumor cell line HT-1376. Although the CLDN4 gene was unmethylated in these cells, pharmacological inhibition of methyl transferases re-addressed the two proteins to TJs, resulting in an increase of cell polarization and transepithelial resistance. These biological effects were prevented by expression of claudin-4-specific siRNAs, demonstrating the important role played by claudin-4 in maintaining a functional regulation of homeostasis in urothelial cells. Results of this study indicate that the TJ barrier is disrupted from early stages of urothelial tumorigenesis. In addition, we identified hypermethylation as the mechanism leading to the alteration of claudin-4 expression, and maybe also localization, in bladder carcinoma.

Animals↗
PubMed2006

Optimizing outcomes and quality of life in the hormonal treatment of prostate cancer.

We review the effectiveness of androgen-deprivation therapy (ADT) in the management of prostate cancer, and the effect that this treatment has on a patient's quality of life (QoL), based on discussions held at a European symposium on the management of prostate cancer. The overall QoL is reduced in asymptomatic men, and there are known decreases in cognitive function, self-esteem, libido and sexual function. Hot flashes are also a frequent problem. Prolonged ADT can lead to osteoporosis and subsequently fractures. Various effective methods exist to manage and minimize these side-effects; some are specific to the side-effect, whereas other more general methods include lifestyle changes, specific drugs and added hormonal manipulations. Intermittent ADT for patients taking luteinizing hormone-releasing hormone agonists offers a promising method to reduce adverse effects, and possibly increases the time to androgen independence. Initial studies indicate that prostate-specific antigen-based progression with intermittent ADT is similar to that seen with continuous ADT, but there is a reduction in side-effects, leading to an improvement in QoL.

Androgen Antagonists↗
PubMed2006

Using prostate-specific antigen screening and nomograms to assess risk and predict outcomes in the management of prostate cancer.

We review the role of prostate-specific antigen (PSA) and the importance of patient education in the management of prostate cancer, based on discussions held at a European symposium on managing prostate cancer. Although PSA is the most widely used serum marker for detecting prostate cancer and for monitoring treatment responses, its use as a diagnostic marker is controversial due to concerns of over-diagnosis and low specificity. PSA isoforms, as well as PSA doubling time, might improve the specificity for earlier prostate cancer detection and can be used as surrogate markers for treatment efficacy. Patients can differ considerably in the importance they place on health-related quality of life aspects and fear of cancer progression. Consequently, there needs to be active, educated discussion of risk and outcomes between physicians and patients. Risk assessment tools, e.g. validated nomograms, enable clinicians to improve their decision analysis and form the basis for subsequent discussion of treatment options between the physician and patient, thereby enabling informed consent and appropriate decision-making.

Humans↗
PubMed2006

Gemcitabine and cisplatin after radical cystectomy for bladder cancer in an adjuvant setting: feasibility study from the Genito-Urinary Group of the French Federation of Cancer Centers.

The impact of adjuvant chemotherapy in locally advanced bladder cancer is still not fully established. Between January 2000 and November 2001, 30 patients entered the trial to receive four cycles of a combination of gemcitabine 1,250 mg/m on day 1 and day 8 and cisplatin 70 mg/m on day 1, repeated every 3 weeks. Histologic diagnoses included pT2-pT3-pT4 tumors and/or pN1-pN2. Combination treatment with gemcitabine and cisplatin was considered feasible if 70% of the patients received a relative dose intensity of each drug of more than 90%. Twenty-seven patients received four cycles of combination treatment. The relative dose intensity of cisplatine and gemcitabine was 96 and 88%, respectively. No toxic death occurred. We conclude that giving four cycles of the gemcitabine-cisplatin regimen in the adjuvant setting after cystectomy is feasible with a manageable toxicity and a high relative dose intensity. Whether this approach may increase survival is currently assessed in a randomized trial.

Adult↗
PubMed2006

Subcutaneous interleukin-2 and interferon-alpha in metastatic renal cell carcinoma: results of a French regional experience in Languedoc.

OBJECTIVES: To assess the efficacy and toxicity of an immunotherapy regimen combining subcutaneous (SC) interleukin-2 (IL-2) and interferon-alpha (IFN) in patients with metastatic renal cell carcinoma (MRCC). METHODS: The present study included 86 patients with MRCC. Data on treatment toxicity and efficacy (responses rates and overall survival) were collected on a hospital database. Treatment consisted of 6-week cycles repeated every 2 months for a maximum of 3 cycles. Each cycle included SC IL-2 20 x 10 MIU/m2 3 times/wk on weeks 1 and 4; 5 x 10 MIU/m2 3 times/wk on weeks 2, 3, 5, and 6, in combination with IFN 6 x 10 MIU/m2 once weekly on weeks 1 and 4; and 3 times/wk on weeks 2, 3, 5, and 6. RESULTS: Seventy (82%) and 71 (83%) patients received more than 80% of the planned doses of IL-2 and IFN during the first cycle, respectively. Ten patients had to stop therapy before the end of the first cycle because of excessive toxicity (7 patients) or rapidly progressive disease (3 patients). Only 17 (28%) proceeded to the second cycle. Main toxicities included fever and asthenia in 86 (100%) patients, nausea/emesis in 83 (96%) patients, skin disorders in 69 (80%) patients, hypotension in 56 (65%) patients, and diarrhea in 50 (58%) patients. Sixty-seven (78%) patients developed at least one episode of grade 3 toxicity. Objective responses were observed in 13 patients, including 4 complete and 9 partial responses (15%; 95% confidence interval, 9.5-20.5%). After a median follow-up of 45 months, the median time to progression was 4 months (range, 1-41) and the median survival was 14 months (range, 1-89). CONCLUSIONS: Only a small subset of patients with MRCC is likely to benefit from treatment with IL-2 and IFN. As toxicity is significant, the refinement of predictive variables for sensitivity to immunotherapy is mandatory.

Adult↗
PubMed2005

[Should the contralateral testis be systematically biopsied after orchidectomy for unilateral germ cell tumour of the testis?].

Intratubular neoplasia (ITN) of the testis is a precursor of germ cell tumour, apart from spermatocytic seminoma. It is often detected in testicular tissue adjacent to germ cell tumours, but is less common in the contralateral testis. Early diagnosis of ITN by testicular biopsy would allow earlier, conservative management. However, this approach remains highly controversial except in very specific indications.

Biopsy↗
PubMed2004

[Conservative surgery for testicular tumours].

The management of testicular tumours is based on inguinal orchidectomy, but conservative surgery is possible in some situations. The indication for conservative surgery is based on clinical assessment, precise analysis of good quality ultrasound images and testicular marker assays. It must be performed according to a strict operative protocol. Conservative surgery may be indicated in the case of teratoma in prepubescent boys, suspicion of epidermal cyst or Leydig cell tumour in adults. Finally, the presence of a germline tumour in a patient with a solitary testis can also be an indication for this type of procedure by observing particularly rigorous imperatives: very motivated patient, absence of hypogonadism, remaining parenchyma representing more than 25% of the initial parenchyma, systematic screening for and treatment of an associated carcinoma in situ by radiotherapy or radical surgery, rigorous and prolonged subsequent surveillance. Only strict compliance with these rules in a very well informed and compliant patient can allow partial orchidectomy to be performed in complete safety, allowing maintenance of endogenous testicular activity.

Humans↗
PubMed2004

[Penile tumors].

Explore the source record for details and available documents.

Humans↗
PubMed2003

Prostatic tissual distribution of alfuzosin in patients with benign prostatic hyperplasia following repeated oral administration.

OBJECTIVES: The blood and prostatic concentrations of alfuzosin were determined in patients with benign prostatic hyperplasia (BPH). METHODS: 12 patients scheduled for BPH surgery were treated with alfuzosin 5 mg twice daily prior to surgery in an open trial. Seven doses were given over a 4-day period. Blood samples were drawn before the first and the last intake (day 3). On day 4 (surgery day), a blood and prostate tissue sample were taken simultaneously 12 hours after the last drug intake. RESULTS: Mean trough blood levels were 6.0+/-4.6 ng/ml and 5.8+/-3.7 ng/ml on day 3 and day 4, respectively, indicating a stable alfuzosin concentration. The mean prostate concentration on day 4 was 12.3+/-5.6 ng/g. Alfuzosin prostate and blood concentrations at 12 hours post dosing on day 4 were significantly correlated (r=0.804, p=0.0016); the prostate-blood ratio was 2.4+/-0.7. CONCLUSIONS: Oral administration of alfuzosin leads to a high diffusion of the drug into the prostate of BPH patients.

Administration, Oral↗