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Montserrat Rue

Publications and source records attributed to Montserrat Rue.

14 recordsLinked to original sources
PubMed2007

Mineral metabolism parameters throughout chronic kidney disease stages 1-5--achievement of K/DOQI target ranges.

BACKGROUND: Dialysis Outcomes and Practice Patterns Study has shown that the proportion of haemodialysis patients with adequate mineral metabolism parameters according to the Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines is very low. The adequacy of such parameters in relation to the recommended ranges in patients with different chronic kidney disease (CKD) stages has not been reported. The objective of this study is to provide an in-depth description of mineral metabolism in the early stages of CKD in a European population, and to compare it with current recommendations for stages 3-5 (K/DOQI guidelines). METHODS: A total of 1836 patients were classified into stages 1-5 according to K/DOQI guidelines. The following clinical and biochemical data were recorded: age, gender, CKD aetiology, presence of diabetes, serum creatinine, creatinine clearance, serum phosphate, calcium, CaxP product and intact parathyroid hormone (PTH). RESULTS: A decrease in 1,25-dihydroxyvitamin D and an increase in PTH are the earliest mineral metabolism alterations in CKD, while serum calcium and phosphate are altered later in the course of CKD. The percentages of patients with serum levels within the recommended K/DOQI guidelines for stages 3, 4 and 5 were as follows: serum calcium: 90.7, 85.6 and 55; serum phosphate: 90.9, 77.1 and 70.3; iPTH 42.4, 24.6 and 46.8 and Ca x P product 99.9, 99.6 and 83.8, respectively. The percentages of patients who had all four parameters within the recommended ranges were 34.9, 18.4 and 21.6 for stages 3, 4 and 5, respectively. CONCLUSION: Mineral metabolism disturbances start early in the course of CKD. The first alterations to take place are a 1,25-dihydroxyvitamin D decrease, a 24 h urine phosphate decrease and a PTH elevation, which show significant level variation when the glomerular filtration rate falls below 60 ml/min. K/DOQI recommended levels for mineral metabolism parameters are difficult to accomplish, in particular for PTH levels.

Adult↗
PubMed2006

Impact of diversity of antibiotic use on the development of antimicrobial resistance.

OBJECTIVES: To evaluate the impact of different antibiotic strategies on acquisition of resistant microorganisms. METHODS: A prospective study was conducted over a 44 month period in a single ICU. Four empirical antibiotic strategies for ventilator-associated pneumonia (VAP) were sequentially implemented. Over the initial 10 months, patient-specific antibiotic therapy was prescribed; then, 4 month periods of prioritization or restriction rotation cycles of various antimicrobial agents were implemented for a total of 24 months; and, finally, during the last 10 months (mixing period) the first-line antibiotic for VAP was changed following a pre-established schedule to ensure maximum heterogeneity. Antibiotic consumption was closely monitored every month, and antimicrobial resistance patterns were regularly assessed. Antimicrobial heterogeneity was estimated using a modified Peterson index (AHI) measuring the ratios for the five most used antibiotics. Colonization by targeted microorganisms and susceptibility patterns were compared with the patient-specific period. RESULTS: Higher diversity of antibiotic prescription was obtained during patient-specific therapy (AHI = 0.93) or mixing periods (AHI = 0.95) than during prioritization (AHI = 0.70) or restriction periods (AHI = 0.68). High homogeneity was associated with increases in carbapenem-resistant Acinetobacter baumannii (CR-Ab) [relative risk (RR) 15.5; 95%CI 5.5-42.8], extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (RR 4.2; 95%CI 1.9-9.3) and Enterococcus faecalis (RR 1.7; 95%CI 1.1-2.9). During the restriction period, incidence of ESBL-producing Enterobacteriaceae and E. faecalis returned to patient-specific rates but CR-Ab remained higher. CONCLUSIONS: Antibiotic prescription patterns balancing the use of different antimicrobials should be promoted to reduce the selection pressure that aids the development of resistance.

Acinetobacter baumannii↗
PubMed2006

Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group.

BACKGROUND: Preliminary studies have shown valspodar (PSC-833: Novartis Pharmaceuticals, East Hanover, NJ) to be a potent inhibitor of multidrug resistance (MDR), one cause of resistance to chemotherapy. An international randomized control study (Phase III) evaluated the use of vincristine, doxorubicin, and dexamethasone (VAD) with (n = 46) and without (n = 48) valspodar in the treatment of patients with recurring or refractory multiple myeloma. METHODS: Patients with documented recurrence or refractory myeloma were stratified based on prior treatment exposure and creatinine and randomized. Because of interaction of valspodar with vincristine and doxorubicin, the doses of these drugs were reduced compared with the VAD-alone arm, and the doxorubicin was further reduced in the last 15 patients when given with valspodar based on pharmacokinetic and toxicity studies. RESULTS: There were no complete or near-complete responses. There were 29% partial responses (PRs) in the VAD-alone arm and 44% with valspodar (P = 0.2). Median progression-free survival was 7 months with VAD alone and 4.9 months with valspodar (P = 0.50). Subjective response was 19% with VAD alone and 17% with valspodar (P = 1.0). Median survival with VAD alone was 18.5 months and 15.3 with the addition of valspodar (P = 0.055). Toxicity of Grade 3 or greater was higher (P < 0.0001) in the valspodar arm (89%) compared with the VAD-alone arm (58%). The reduction of doxorubicin dose reduced toxicity but not significantly (P = 0.11). CONCLUSION: The addition of the MDR-modulating agent valspodar to VAD did not improve treatment outcome. Toxicity was increased in the valspodar-treated group compared with VAD alone.

Administration, Oral↗
PubMed2006

Complementary medicine use before and 1 year following genetic testing for BRCA1/2 mutations.

PURPOSE: We explored change in complementary and alternative medicine (CAM) use by unaffected women and cancer survivors from enrollment into a randomized BRCA1/2 testing program to CAM use 1 year following results disclosure. METHODS: A cohort of 243 high-risk women completed questionnaires at enrollment into a BRCA1/2 randomized trial and 1 year post results disclosure. Uses of several CAMs for cancer prevention were explored, including ingestible, behavioral, and physical modalities. Assessment of the change in CAM use from baseline to 1 year follow-up was conducted using a repeated self-administered questionnaire. Correlates of the number of CAMs used at 1 year were explored using multivariable linear regression models. RESULTS: Among the subset of women who changed their CAM behavior from enrollment to 1 year following BRCA1/2 results disclosure, there was a significantly higher proportion who changed from no CAM use to CAM use among the overall cohort (P=0.01), among women without cancer at enrollment (P=0.003), among women found to be BRCA1/2 carriers (P=0.03), and among women randomized to the genetic counseling intervention arm of the study (P=0.009). Number of CAMs used at 1 year was positively associated with number of CAMs used at baseline, sunscreen use, and BRCA1/2 mutation status. CONCLUSION: High-risk women who have received BRCA1/2 counseling and testing frequently adopt new CAM use in the first year after learning their genetic status. Mutation carriers frequently initiate CAM use after learning their genetic status as part of their cancer preventive regimen. Further studies are warranted to determine the efficacy of CAM-related strategies for cancer prevention.

Adult↗
PubMed2005

FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis.

The FLICE-inhibitory protein (FLIP) plays a key role in the regulation of apoptosis triggered by death ligands. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in some types of tumor but not in others. To assess the possible role of FLIP in apoptosis resistance in endometrial carcinoma, we performed an immunohistochemical study on a tissue microarray composed of 95 endometrial carcinomas. We found positive signals in 43% of the cases, as well as a significant difference in FLIP expression between stage I and II tumors. Moreover, we observed that endometrial carcinoma cell lines Ishikawa and KLE did not undergo apoptosis after TRAIL treatment. Cotreatment of these cells with the inhibitor of transcription actinomycin D resulted in a dramatic decrease in cell viability and induced activation of caspase-8. These events coincided with downregulation of FLIP mRNA and protein. Inhibitors of caspase-8 or overexpression of FLIP completely blocked apoptosis induced by actinomycin D plus TRAIL cotreatment. More importantly, downregulation of endogenous FLIP expression by specific siRNAs sensitized endometrial carcinoma cells to TRAIL-induced apoptosis in the absence of actinomycin D. Taken together, our results suggest for the first time a critical role for FLIP in the regulation apoptosis triggered by TRAIL in endometrial carcinoma cells.

Adenocarcinoma↗
PubMed2005

Immunohistochemical analysis of PTEN in endometrial carcinoma: a tissue microarray study with a comparison of four commercial antibodies in correlation with molecular abnormalities.

The tumor suppressor gene PTEN/MMAC1 is located on chromosome 10q23.3. Inactivation of PTEN, either by mutations, deletions, or promoter hypermethylation, has been identified in a wide variety of tumors. Inactivation of the two alleles of PTEN is required, because it is a tumor suppressor gene. Immunohistochemical staining may be an effective screening method to demonstrate the absence of the protein in tumors exhibiting PTEN inactivation. We studied a tissue microarray, constructed from paraffin-embedded blocks of 95 endometrial carcinomas, 38 of them previously evaluated for alterations in PTEN. We also studied cell blocks obtained from one PTEN-defective endometrial cancer cell line, after transfection with either a plasmid encoding wild-type PTEN or the empty vector. The tumor samples were tested with four different anti-PTEN commercial antibodies: a polyclonal antibody, the monoclonal antibody 28H6, the monoclonal antibody 10P03, and the monoclonal antibody 6.H2.1. Results were correlated with the presence of abnormalities in PTEN, as well as with the immunohistochemical expression of phosphorylated AKT. Antibody 28H6 produced a predominant nuclear staining, while the other three antibodies produced a predominant cytoplasmic staining. There was no significant correlation between the results obtained with the four antibodies. The monoclonal antibody 6.H2.1 was the only one that exhibited a correlation with the presence of molecular alterations in PTEN, and a statistically significant association with immunostaining for phosphorylated AKT (r=-0.249, P=0.037). The monoclonal antibody 10P03 exhibited an association with phospho-AKT that did not have statistical significance. Both 6.H2.1 and 10P03 antibodies stained PTEN-transfected cells, and were negative in the PTEN-deficient cell line blocks. The polyclonal antibody and the monoclonal antibody 28H6 produced positive staining in PTEN-deficient cell line blocks, suggesting nonspecific staining. The results indicate that monoclonal antibody 6.H2.1 may be a suitable alternative for tumors with inactivation of PTEN.

Antibodies, Monoclonal↗
PubMed2005

Survivin expression in endometrial carcinoma: a tissue microarray study with correlation with PTEN and STAT-3.

Evasion of apoptotic cell death plays a key role in cancer development. Survivin is a member of the inhibitor of apoptosis proteins, which also has a role in the control of cell division. Survivin may be overexpressed in some tumors and has been suggested to be related to PTEN, beta-catenin, p53 [all of them frequently abnormal in endometrial carcinomas (ECs)], and STAT-3. A tissue microarray was constructed from paraffin-embedded blocks of 95 ECs, previously studied for microsatellite instability and for alterations in PTEN, k-RAS, and CTNNB-1. Immunohistochemical evaluation included 1) survivin, 2) markers of cell proliferation and apoptosis (Ki67-MIB1 and M 30-neoepitope cytokeratin 18), and 3) proteins involved in cell signaling pathways (PTEN, phospho-AKT, beta-catenin, p53, and STAT-3). Survivin expression was frequent in ECs (75.95%) but did not show any statistical significant correlation with histological type and grade, stage, overall survival, or mitotic and apoptotic indexes. Survivin expression had a statistical significant correlation with decreased PTEN expression (r = -0.383, p = 0.001), increased phospho-AKT (r = 0.70, p < 0.001), and positive STAT-3 immunostaining (r = 0.6, p < 0.001). Survivin expression did not show statistical correlation with either beta-catenin or p53 alterations. The results suggest that increased survivin expression is frequent in ECs and may be dependent on STAT-3 and PI3 K/AKT activation. Because PTEN abnormalities are very frequent in ECs, the results from this study indicate that PTEN may interfere with the process of apoptosis and cell proliferation by promoting survivin expression.

Apoptosis↗
PubMed2004

Initial immunoglobulin M 'flare' after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an Eastern Cooperative Oncology Group Study.

BACKGROUND: The goal of the current study was to characterize the initial upsurge in immunoglobulin M (IgM) levels after treatment with rituximab in patients with Waldenstrom macroglobulinemia (WM). METHODS: As part of a Phase II Eastern Cooperative Oncology Group study, 72 patients were treated with rituximab (375 mg/m(2) weekly for 4 weeks) between April 2000 and January 2002. IgM levels in these patients were measured at five separate time points so that any temporal changes that occurred could be characterized. RESULTS: Of the 54 patients for whom the relevant IgM measurements were available, 29 (54%) experienced an increase in IgM levels between baseline and the first scheduled postbaseline time point. At 2 months, 13 of 22 evaluable patients (59%) continued to have elevated IgM levels, and at 4 months, elevated IgM levels persisted in 4 of 15 evaluable patients (27%). Overall, a nonlinear trend characterized by an initial increase in IgM levels followed by a decrease in these levels was observed (P < 0.0001). CONCLUSIONS: Treating physicians should be aware that an IgM 'flare' may occur in up to 54% of patients treated with rituximab; however, most of these patients experience a decrease in IgM levels within 4 months after the initiation of therapy. Therefore, patients should not be discouraged from continuing to receive this potentially effective therapeutic agent, as responses to rituximab may develop slowly. Longer follow-up will reveal whether patients who experience an upsurge in IgM levels have poorer overall survival or shorter times to progression compared with patients who do not experience this IgM flare. Factors predicting an initial increase in IgM levels could not be identified.

Adult↗
PubMed2004

Abnormalities in the NF-kappaB family and related proteins in endometrial carcinoma.

The NF-kappaB family of transcription factors regulates a wide variety of cellular processes including cell growth, differentiation, and apoptosis. A tissue microarray was constructed from paraffin wax-embedded blocks from 95 endometrial carcinomas (EC), previously studied for microsatellite instability, as well as for alterations in PTEN, k-RAS and beta-catenin. Immunohistochemical evaluation included members of the NF-kappaB (p50, p65, p52, c-Rel, Rel-B) and the IkappaB (IkappaBalpha, IkappaBbeta, IkappaBepsilon, Bcl-3) families, as well as putative targets of NF-kappaB such as Flip, Bcl-xL, Cyclin D1, and oestrogen and progesterone receptors. Results were correlated with the clinical and pathological data. Nuclear immunostaining for members of the NF-kappaB family was frequent in EC (p50, 20%; p65, 16.5-21.9%; p52, 9.3%; c-Rel, 48.9%; Rel-B, 15.7%); and it correlated with negativity for members of the IkappaB family in some cases. There was a statistically significant association between immunoreaction for p50 and p65 (p = 0.006), suggesting activation of the so-called 'classic form' of NF-kappaB, similar to that described in breast cancer. Bcl-3 nuclear immunostaining was detected in 60.7% of cases. The vast majority of p52-positive tumours showed Bcl-3 nuclear immunoreaction (p = 0.038). Immunostaining for putative targets of NF-kappaB was as follows: Bcl-xL, 76.2% (p = 0.001); Flip 43.0%; Cyclin D1, 64.79%. p65 immunostaining correlated with increased immunoreaction for steroid hormone receptors. No correlation was found between NF-kappaB nuclear pattern and the presence of microsatellite instability, or alterations in PTEN, k-RAS, or beta-catenin. These results suggest that the NF-kappaB and IkappaB families of genes may be important in endometrial carcinogenesis, by controlling apoptosis and cell proliferation.

Adenocarcinoma↗
PubMed2004

High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene.

The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.

Acetyltransferases↗
PubMed2004

Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): an Eastern Cooperative Oncology Group Study (E3A98).

Waldenström macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma that strongly expresses CD20 on the cell surface. This study was undertaken to determine the response rate of patients with untreated or previously treated WM to the monoclonal antibody rituximab, which is directed against CD20+ expressed by B-cell lymphomas. Thirty-four untreated and thirty-five previously treated patients received rituximab 375 mg/m2 weekly for 4 consecutive weeks by intravenous infusion on days 1, 8, 15, and 22. Sixty-nine patients were evaluable for response; 19 (27.5%) achieved an objective response and 17 (24.6%) achieved a minor response. The overall response rate was 52.2% (90% CI [41.6%, 62.6%]). Of previously untreated patients 35.3% vs. 20% of previously treated patients achieved an objective response. Median response duration was not significantly different between previously untreated (27 months) and previously treated patients (not reached, P = 0.8). Rituximab produced objective or minor responses in 52.2% of patients and is an active agent in the treatment of WM. Grade 4 toxicity was seen in 11%.

Aged↗
PubMed2003

Clinical and biologic implications of recurrent genomic aberrations in myeloma.

Nonrandom recurrent chromosomal abnormalities are ubiquitous in multiple myeloma (MM) and include, among others, translocations of the immunoglobulin heavy chain locus (IgH). IgH translocations in MM result in the up-regulation of oncogenes, and include more commonly t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23). Based on the recurrent nature of these translocations and their finding since the early stages of the plasma cell (PC) disorders, we hypothesized that they would confer biologic and clinical variability. In addition, deletions of 13q14 and 17p13 have also been associated with a shortened survival. We used cytoplasmic Ig-enhanced interphase fluorescent in situ hybridization to detect deletions (13q14 and 17p13.1), and translocations involving IgH in 351 patients treated with conventional chemotherapy entered into the Eastern Cooperative Oncology Group clinical trial E9486/9487. Translocations were frequently unbalanced with loss of one of the derivative chromosomes. The presence of t(4; 14)(p16;q32) (n = 42; 26 vs 45 months, P <.001), t(14;16)(q32;q23) (n = 15; 16 vs 41 months, P =.003), - 17p13 (n = 37; 23 vs 44 months, P =.005), and - 13q14 (n = 176; 35 vs 51 months, P =.028) were associated with shorter survival. A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and - 17p13), intermediate prognosis (- 13q14), and good prognosis group (all others), with median survivals of 24.7, 42.3, and 50.5 months, respectively (P <.001). This molecular cytogenetic classification identifies patients into poor, intermediate, and good risk categories. More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations.

Adult↗
PubMed2003

Brief physician-initiated quit-smoking strategies for clinical oncology settings: a trial coordinated by the Eastern Cooperative Oncology Group.

PURPOSE: Although tobacco use by cancer patients increases the risk of relapse, diminishes treatment efficacy, and worsens quality of life, about one third of patients who smoked before their diagnosis continue to smoke. Because patients have regular contact with oncologists, the efficacy of a physician-based smoking cessation treatment was evaluated. METHODS: Cancer patients (n = 432) were randomly assigned to either usual care or a National Institutes of Health (NIH) physician-based smoking intervention. The primary outcome was 7-day point prevalence abstinence at 6 and 12 months after study entry. RESULTS: At the 6-month follow-up, there was no significant difference in quit rates between the usual care (11.9%) and intervention (14.4%) groups, and there was no significant difference between the usual care (13.6%) and intervention (13.3%) groups at the 12-month follow-up. Patients were more likely to have quit smoking at 6 months if they had head and neck or lung cancer, began smoking after the age of 16, reported at baseline using a cessation self-help guide or treatment in the last 6 months, and showed greater baseline desire to quit. Patients were more likely to have quit smoking at 12 months if they smoked 15 or fewer cigarettes per day, had head and neck or lung cancer, tried a group cessation program, and showed greater baseline desire to quit. Finally, there was greater adherence among physicians to the NIH model for physician smoking treatment for patients in the intervention versus the usual care group. CONCLUSION: While training physicians to provide smoking cessation treatment to cancer patients can enhance physician adherence to clinical practice guidelines, physician smoking cessation interventions fail to yield significant gains in long-term quit rates among cancer patients.

Adult↗
PubMed2002

Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer.

Estrogen receptor (ER) expression and Her-2 amplification define specific subsets of breast tumors for which specific therapies exist. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. Using microarray analysis and immunohistochemistry, we determined that higher levels of Skp2 are present more frequently in ER-negative tumors than in ER-positive cases. Interestingly, the subset of ER-negative breast carcinomas overexpressing Skp2 are also characterized by high tumor grade, negativity for Her-2, basal-like phenotype, high expression of certain cell cycle regulatory genes, and low levels of p27 protein. We also found that Skp2 expression is cell adhesion-dependent in normal human mammary epithelial cells but not in breast cancer cells and that an inhibition of Skp2 induces a decrease of adhesion-independent growth in both ER-positive and ER-negative cancer cells. Finally, forced expression of Skp2 abolished effects of antiestrogens, suggesting that deregulated Skp2 expression might play a role in the development of resistance to antiestrogens. We conclude that Skp2 has oncogenic potential in breast epithelial cells and is overexpressed in a subset of breast carcinomas (ER- and Her-2 negative) for which Skp2 inhibitors may represent a valid therapeutic option.

Breast Neoplasms↗