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Xavier Farré

Publications and source records attributed to Xavier Farré.

8 recordsLinked to original sources
PubMed2004

Expression of the nucleoside-derived drug transporters hCNT1, hENT1 and hENT2 in gynecologic tumors.

Deoxynucleoside analogs are used in the treatment of a variety of solid tumors. Their transport across the plasma membrane may determine their cytotoxicity and thus nucleoside transporter (NT) expression patterns may be of clinical relevance. Lack of appropriate antibodies for use in paraffin-embedded biopsies has been a bottleneck to undertake high-throughput analysis of NT expression in solid tumors. Here we report the characterization of 2 new antibodies raised against the low-affinity equilibrative NTs, hENT1 and hENT2, suitable for that purpose. These 2 antisera, along with a previously characterized antibody that specifically recognizes the high-affinity Na-dependent concentrative NT, hCNT1, have been used to analyze, using a tissue array approach, NT expression in gynecologic cancers (90 ovarian, 80 endometrial and 118 uterine cervix carcinomas). Human CNT1 was not detected in 33% and 39% of the ovarian and uterine cervix carcinomas, respectively, whereas hENT1 and hENT2 expression was significantly retained in a high percentage of tumors (91% and 96% for hENT1, 84% and 98% for hENT2, in ovarian and cervix carcinomas, respectively). Only a few endometrial carcinomas (15%) were found to be negative for hCNT1, but they all retained hENT1 and hENT2 expression. In ovarian cancer, the loss of all 3 NT proteins was a more common event in the clear cell histologic subtype than in the serous, mucinous and endometrioid histotypes. In uterine cervix tumors, the loss of expression of hCNT1 was significantly associated with the adenocarcinoma subtype. In summary, hCNT1 was by far the isoform whose expression was most frequently reduced or lost in the 3 types of gynecologic tumors analyzed. Moreover, NT expression is related to the type of gynecologic tumor and its specific subtype, hCNT1 protein loss being highly correlated with poor prognosis histotypes. Since hCNT1, hENT1 and hENT2 recognize fluoropyrimidines as substrates, but with different affinities, this study anticipates high variability in drug uptake efficiency in solid tumors.

Adenocarcinoma↗
PubMed2004

Power Doppler sonography of invasive breast carcinoma: does tumor vascularization contribute to prediction of axillary status?

PURPOSE: To prospectively compare unenhanced power Doppler sonographic findings of arterial vascularization of invasive breast carcinoma with histopathologic and immunohistochemical parameters and to determine whether tumor arterial vascularization contributes to prediction of axillary node status. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. A total of 97 invasive breast carcinomas were prospectively studied with unenhanced power Doppler sonography before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Sonographic tumor size and number of tumor arteries were correlated with axillary nodal status by means of logistic regression analysis. Tumor microvascularization was immunohistochemically assessed in a subset of 55 carcinomas. Sonographic variables were correlated with tumor arteries with a diameter larger than 300 mum and with the density and area of microvascularization. The kappa statistic and Bland-Altman agreement limits were used to measure agreement between techniques. RESULTS: Good agreement of sonographic and histologic findings regarding number of tumor arteries (kappa= 0.66, P < .001) and tumor size (P = .012) was observed. Multivariate analysis showed an independent relationship between probability of axillary metastasis, number of tumor arteries (P = .016), and sonographic tumor size (P = .035). A predictive model of axillary status was developed. The receiver operating characteristic curve was used to determine 0.2324 as the score to classify axillary nodal status. This score indicated high sensitivity (96.1%), low specificity (53.0%), and high negative predictive value (96.1%). CONCLUSION: The number of arteries in invasive breast carcinoma detected with unenhanced power Doppler sonography and sonographic tumor size are independent predictors of axillary nodal status; these variables could contribute to reliable prediction of absence of axillary involvement on the basis of a mathematic model.

Adult↗
PubMed2003

PTOV-1, a novel protein overexpressed in prostate cancer, shuttles between the cytoplasm and the nucleus and promotes entry into the S phase of the cell division cycle.

PTOV1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer. The PTOV1 protein consists of two novel protein domains arranged in tandem, without significant similarities to known protein motifs. By immunohistochemical analysis, we have found that PTOV1 is overexpressed in 71% of 38 prostate carcinomas and in 80% of samples with prostate intraepithelial neoplasia. High levels of PTOV1 in tumors correlated significantly with proliferative index, as assessed by Ki67 immunoreactivity, and associated with a nuclear localization of the protein, suggesting a functional relationship between PTOV1 overexpression, proliferative status, and nuclear localization. In quiescent cultured prostate tumor cells, PTOV1 localized to the cytoplasm, being excluded from nuclei. After serum stimulation, PTOV1 partially translocated to the nucleus at the beginning of the S phase. At the end of mitosis, PTOV1 exited the nucleus. Transient transfection of chimeric green fluorescent protein-PTOV1 forced the entry of cells into the S phase of the cell cycle, as shown by double fluorescent imaging for green fluorescent protein and for Ki67, and also by flow cytometry. This was accompanied by greatly increased levels of cyclin D1 protein in the transfected cells. These observations suggest that overexpression of PTOV1 can contribute to the proliferative status of prostate tumor cells and thus to their biological behavior.

Adenocarcinoma↗
PubMed2003

Autologous elastic cartilage for laryngoplasty: histologic evaluation in a rabbit model.

A wide range of materials have been used to achieve medialization of the paralyzed vocal fold. Recently, medialization techniques using autologous cartilage have been described, but little information is available on cartilage integration and viability in this situation. In this prospective, experimental, controlled study, right vocal fold paralysis was surgically induced in 30 New Zealand rabbits. An autologous auricular cartilage transplant was inserted in the vocal fold in 15 animals. In the control group, only the laryngeal nerve was sectioned. Each group was divided into two groups with follow-ups of 6 weeks and 6 months, respectively. Histologic studies revealed no inflammatory reaction against the cartilage transplants. There were no differences in the transplant surfaces in the 6-week and 6-month groups. The results show tissue integration and a low level of initial transplant resorption that stabilizes with time. Autologous auricular cartilage appears to be an appropriate material for type I thyroplasty procedures because of the low absorption rate.

Animals↗
PubMed2002

Alterations of cell cycle-regulatory genes in prostate cancer.

Deregulated proliferation is one of the main events in neoplastic transformation, and this has prompted increased attention being given to the understanding of the mechanisms involved in cell cycle regulation and its alterations. The 'retinoblastoma pathway', a key effector controlling G1-S phase transition, includes several oncogenes and tumour suppressor genes which display a wide range of abnormalities with potential usefulness as markers of evolution or treatment response in prostate cancer. Among these, the existence of p53 mutations seems to predict resistance to radiotherapy or systemic treatment, and p16 overexpression or p27 downregulation seems to serve as markers of poor evolution. The well-established existence of a critical hormonal role in prostate carcinogenesis coupled with the relationship of androgenic activity and regulation of several cell cycle modulators forces cell cycle control in the prostate to be envisioned as a highly complex steroid-influenced system, which will undoubtedly have critical implications in the future management of prostate cancer patients.

Carcinoma↗
PubMedDate not supplied

Low p27 expression predicts biochemical relapse after radical prostatectomy in patients with clinically localised prostate cancer.

OBJECTIVE: To assess the prognostic value of p27 protein expression in clinically localised prostate cancer with respect to biochemical recurrence after radical prostatectomy. PATIENTS AND METHODS: Fifty-two patients (median age 63 years) with prostate cancer were treated by radical prostatectomy in an 18-month period. Data recorded: preoperative PSA level, histopathological Gleason grade, pathological stage and status of surgical margins. p27 expression was evaluated in this group of tumors by immunohistochemistry (positivity was defined as > or = 30% positive cells). Biochemical relapse (BR) was defined by a serum PSA level > or = 0.3 ng/ml. RESULTS: Twenty-two out of 47 patients (47%) with available follow-up showed a low p27 protein expression. p27 expression did not correlate with pathological stage, Gleason score, serum PSA levels or the status of the surgical margins. Patients presented with BR during the follow-up (risk of BR (RBR) at 36 months: 40%). Patients with low p27 expression showed a higher RBR than the others (RBR 36-month 59% vs. 18%, respectively; p = 0.02). In a multivariate analysis, only p27 along with stage maintained the predictive value for biochemical relapse. CONCLUSION: p27 expression is a promising prognostic factor in prostate cancer, since it has proved to be a predictor of biochemical relapse.

Aged↗