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Papers by H. Cortés-funes

cell transplants. cytotoxic therapy and peripheral blood stem morbidity in neutropenic patients g... more cell transplants. cytotoxic therapy and peripheral blood stem morbidity in neutropenic patients given prophylaxis to decrease infection-related Lack of ability of ciprofloxacin-rifampin

The present study looks for the relation between the psychosocial distress experienced by the pat... more The present study looks for the relation between the psychosocial distress experienced by the patient and his family caregiver during the period he is hospitalised. The sample is composed by 94 persons (oncology patients and family caregivers). We have used a sociodemographic questionnaire, the Hospital Anxiety and Depression Scale, the “Quality of life Questionnaire” for general satisfaction and social support and the family APGAR for family functioning. The results indicate that the anxiety of the caregiver is significantly higher than the one of the patient. The family functioning perceived by the patient correlates negatively with the depression and positively with the general satisfaction of the family caregiver. We found a correlation between the age and the depression subscale. In the family caregivers group we confirm that the higher scores in depression appear in ages between 35 and 55. Married patients and caregivers obtain higher punctuation in depression compared to unma...

Journal of Clinical Oncology, 2009

e20600 Background: With the growing number of drugs available for the treatment of cancer, most o... more e20600 Background: With the growing number of drugs available for the treatment of cancer, most of them of oral administration, some aspects of the everyday clinical practice are changing. Interesting is the opinion of the patients (pts) about oral therapy. Methods: We researched differences in preference, tolerance, effectiveness, and safety by means of the delivery of a survey to (pts) who had received oral and intravenous (IV) treatment. One hundred and ninety (pts) were enrolled from September to November 2008. Results: Seventy percent of the (pts) studied were women, the median age at diagnosis was 60 years (range, 28 - 91 years). Fifty percent had gynaecologic tumors; thirty percent digestive; eighteen percent lung cancer and two percent other tumors, with a median of 3 different lines of therapy (range, 1 to 9). Patients preferred the oral route over the IV (76% vs. 20% respectively; P<0.001) and four percent had no preference. Tolerance was better with oral therapy (64%) ...

Annals of Oncology, 1999

J. Crown, B. Coiffier, H. Cortes-Funes, Th. Guillaume, L. Kanz, G. Kvalheim, M. Marty & M. Sy... more J. Crown, B. Coiffier, H. Cortes-Funes, Th. Guillaume, L. Kanz, G. Kvalheim, M. Marty & M. Symann 'St. Vincent's Hospital, Dublin, Ireland; Centre Hospilalier Lvon-Sud, Lyon, France; Hospital Universitario 12 de Octubre, Madrid, Spain; Catholic University of Louvain, Brussels, Belgium; Universitat Tubingen, Tubingen, Germany; The Norwegian Radium Hospital, Oslo, Norway; Hopital Saint-Louis, Paris, France

Annals of Oncology, 1995

A consensus meeting held under the auspices of the European School of Oncology concluded that the... more A consensus meeting held under the auspices of the European School of Oncology concluded that the use of granulocyte growth factors is definitely indicated, or acceptable given existing evidence, in the following circumstances: to alleviate congenital neutropenia; in the mobilisation of peripheral blood progenitor cells for autotransfusion; to encourage engraftment following bone marrow transplantation and in cases of failed engraftment; to support continuation of ganciclovir anti-CMV therapy in certain patients with AIDS, where the switch to foscarnet is contraindicated or where toxicity to foscarnet develops. It was also agreed that there is an overwhelming need for carefully controlled clinical trials in a wide range of indications in which growth factor use may improve outcome. In the majority of tumours, the possible benefit of dose optimisation and intensification, and therefore the role of growth factors in support of such measures has still to be defined. Extramedullary toxicities may in these instances become dose limiting.

Journal of Clinical Oncology, 2000

PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of p... more PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status ≤ 2 and creatinine clearance ≥ 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m2. Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m2 and gemcitabine 1,000 mg/m2 was recommended for phase II,...

Annals of Oncology, 1998

Background: The aim of this study was to determine the clinical activity and toxicity of a novel ... more Background: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m 2 and cisplatin was administered at a dose of 100 mg/m 2 on day 1, every 21 days. Results: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m~/week, and 31 mg/nr/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7-13), 17 patients are still alive and nine have died. The median overall survival is 12 months. Conclusion: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.

Recent Results in Cancer Research, 1980

Quelamycin is triferric doxorubicin, a metallic derivative of adriamycin which, in experimental s... more Quelamycin is triferric doxorubicin, a metallic derivative of adriamycin which, in experimental studies, has been found to have a better therapeutic index than adriamycin and no cardiotoxicity. In Spain, phase I clinical trials carried out in 96 patients with advanced cancer have shown that the drug has low toxicity and considerable antitumor activity, while it is not cardiotoxic, even at cumulative doses of nearly 3 g.

British journal of cancer, Jan 13, 2004

The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresec... more The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC), and outcome parameters were correlated with the expression of thymidine phosphorylase (TP), thymidilate syntetase (TS), vascular endothelial growth factor receptor (VEGFR) 1-3, and microvessel density (MVD). Patients with recurrent or unresectable HNSCC were eligible if they had received prior neoadjuvant chemotherapy, concurrent chemo-radiotherapy, or no prior systemic therapy. Patients received cisplatin (75 mg m(-2) day 1), and capecitabine (2000 mg m(-2) day 1-14) every 3 weeks. A total of 41 patients received 194 cycles. In all, 16 complete responses (39%) and 12 partial responses (29%) were documented, for an overall response rate of 68% (95% CI, 53-80%). Grade 3-4 uncomplicated neutropenia was documented in five subjects. Asthenia, anorexia, hand-foot syndrome, and constipation were the most frequent nonhaematologic event...

Clinical cancer research : an official journal of the American Association for Cancer Research, 2000

To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a... more To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with advanced breast carcinoma in the setting of a multicenter Phase II trial using paclitaxel and doxorubicin. Serum samples were collected from 58 patients with metastatic breast carcinoma before first-line chemotherapy for advanced disease, and the levels of circulating HER2 ECD were measured using an enzyme immunoassay. Immunohistochemistry with anti-HER2 monoclonal antibody CB11 was used to assess the overexpression of HER2 in the primary tumors. When 450 fmol/ml was used as a cutoff, 24 cases (41%) had elevated HER2 ECD levels. Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3; P = 0.032 and P = 0.002, respectively) but not with variables su...

Clinical cancer research : an official journal of the American Association for Cancer Research, 1998

Angiogenin is a protein originally isolated as an inducer of new blood vessel growth, and it has ... more Angiogenin is a protein originally isolated as an inducer of new blood vessel growth, and it has been reported to be an effective substrate for tumor cell adhesion. To understand the role of angiogenin in cancer progression, we evaluated the expression of angiogenin in 459 cases with primary breast carcinoma and in 40 benign breast specimens using an immunoassay. Higher angiogenin concentrations were observed in carcinomas in comparison with fibrocystic disease (mean, 17.3 versus 10.9 ng/mg; P = 0.008), but not with fibroadenomas. We selected 5 ng/mg cytosol protein of angiogenin as the normal cutoff for primary breast carcinoma. Eighty-eight percent of carcinomas expressed elevated angiogenin levels and 12% had low levels. We observed an association between elevated levels of angiogenin and low/ moderate histological grade (P = 0.001) and small tumor size (P = 0.026), but not with age, menopausal status, lymph node status, stage of disease, or hormonal receptor status. With a media...

Seminars in oncology, 1995

From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung can... more From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for t...

British Journal of Cancer, 2004

Revista Española de Cardiología, 1998

Cancer Research, 2012

Background: microRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regu... more Background: microRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. In the present study, we describe miRNA expression in early node-positive BC and identify a 8-miRNA score that could contribute to prognosis assessment. Methods: First, microarray analysis was performed using RNA samples extracted from primary breast cancer. The expression of miRNAs was analyzed by RT-qPCR using the TaqMan Arrays from Applied Biosystems. After a suitable normalization of the 677 miRNAs analyzed, 123 presented a good correlation between their levels of expression in frozen tissue and paraffin tissue. A supervised analysis was done in order to identify MIR that could predict relapse. Results: 172 patients with node-positive chemotherapy-treated early BC were included in the present study. The median age at diagnosis was (53.7) years, 128 cases (74.4%) had positive estrogen receptor, and 163 patients (94,7%) received adjuvant chemotherapy. After a medi...

Revista Clínica Española, 2003

Tumor Biology, 2001

The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by ... more The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by immunoblotting using the monoclonal antibody PAb 1801. Two hundred and five carcinomas (45%) showed positive p53 accumulation and 55% were p53 negative. When comparing p53 positivity and other clinicopathological parameters, significant differences were found with younger age (p = 0.017), premenopausal status (p = 0.003), increasing tumor size (p = 0.026), negative estrogen receptor (p = 0.003) and negative progesterone receptor (p = 0.047), but not with histologic grade, axillary lymph node status, stage or erbB-2 expression. With a median follow-up of 34 months (range 3-70), relapse has occurred in 73 patients. Disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival than patients with p53-negative carcinomas (log-rank test, p = 0.027). A multivariate analysis of disease-free survival showed that p53, tumor size, histologic grade and progesterone receptor had significant independent prognostic value. The immunoblotting technique was controlled with p53 immunohistochemistry in 94 paired samples. We obtained a statistically significant correlation (p = 0.0004) between the two methods. Our results show that the immunoblotting technique offers an alternative approach in evaluating the p53 status of breast biopsy material using cytosolic extracts, and confirm that p53 accumulation is a significant independent indicator of a poor prognosis in operable breast carcinoma.

Leukemia, 2001

Administration of stem cell factor (SCF) has been proven to enhance cytokine-induced mobilization... more Administration of stem cell factor (SCF) has been proven to enhance cytokine-induced mobilization of CD34 ؉ hematopoietic progenitor cells (HPC) into the peripheral blood (PB). The aim of the present study was to explore in a homogeneous group of 22 uniformly treated breast cancer patients: (1) the kinetics of mobilization into PB of both CD34 ؉ and CD34 ؊ cell subsets, including dendritic cells, in sequential samples obtained from day ؉7 up to day ؉12 after mobilization; and (2) the composition of the CD34 ؉ and CD34 ؊ cell subsets present in the two leukapheresis products obtained for each patient. The following CD34 ؉ and CD34 ؊ subsets were analyzed: early CD34 ؉ HPC, erythroid-, myeloid-and B-lymphoid-committed CD34 ؉ precursor cells, mature T, B and NK cells, monocytes, neutrophils, eosinophils, basophils, and dendritic cells (DC) including three subsets of lin ؊ /HLADR ؉ DC (CD16 ؉ , CD33 high and CD123 high). Our results show that the absolute number of PB CD34 ؉ HPC progressively increases from day ؉7 onwards. As far as the CD34 ؊ PB leukocyte subsets are concerned, monocytes (CD14 ؉) displayed the earliest recovery after mobilization predicting neutrophil recovery 1 day in advance. The number of CD34 ؉ HPC collected in a single leukapheresis product was always у1.4 ؋ 10 6 cells/kg body weight. No significant changes were observed between the two leukapheresis sessions either as regards their composition in CD34 ؉ HPC subsets or their CD34 ؊ leukocyte populations except for a higher ratio of both CD34 ؉ erythroid/CD34 ؉ myeloid HPC (0.35 ؎ 0.13 vs 0.30 ؎ 0.13; P ‫؍‬ 0.04) and neutrophils/monocytes (1.58 ؎ 2.1 vs 0.69 ؎ 0.27; P ‫؍‬ 0.009) found for the first leukapheresis. Interestingly, the overall number of dendritic cells (DC) was higher in the second leukapheresis (1.06 ؎ 0.56 vs 1.9 ؎ 0.46; P ‫؍‬ 0.02) due to a selective increase of the CD16 ؉ antigenpresenting cells. In summary, our results show that the combination of cyclophosphamide, G-CSF and SCF is highly effective for stem cell mobilization, with differences observed in the mobilization kinetics of the different hematopoietic cell subsets analyzed. Leukemia (2001) 15, 430-439.

European Journal of Internal Medicine, 2001

cell transplants. cytotoxic therapy and peripheral blood stem morbidity in neutropenic patients g... more cell transplants. cytotoxic therapy and peripheral blood stem morbidity in neutropenic patients given prophylaxis to decrease infection-related Lack of ability of ciprofloxacin-rifampin

The present study looks for the relation between the psychosocial distress experienced by the pat... more The present study looks for the relation between the psychosocial distress experienced by the patient and his family caregiver during the period he is hospitalised. The sample is composed by 94 persons (oncology patients and family caregivers). We have used a sociodemographic questionnaire, the Hospital Anxiety and Depression Scale, the “Quality of life Questionnaire” for general satisfaction and social support and the family APGAR for family functioning. The results indicate that the anxiety of the caregiver is significantly higher than the one of the patient. The family functioning perceived by the patient correlates negatively with the depression and positively with the general satisfaction of the family caregiver. We found a correlation between the age and the depression subscale. In the family caregivers group we confirm that the higher scores in depression appear in ages between 35 and 55. Married patients and caregivers obtain higher punctuation in depression compared to unma...

Journal of Clinical Oncology, 2009

e20600 Background: With the growing number of drugs available for the treatment of cancer, most o... more e20600 Background: With the growing number of drugs available for the treatment of cancer, most of them of oral administration, some aspects of the everyday clinical practice are changing. Interesting is the opinion of the patients (pts) about oral therapy. Methods: We researched differences in preference, tolerance, effectiveness, and safety by means of the delivery of a survey to (pts) who had received oral and intravenous (IV) treatment. One hundred and ninety (pts) were enrolled from September to November 2008. Results: Seventy percent of the (pts) studied were women, the median age at diagnosis was 60 years (range, 28 - 91 years). Fifty percent had gynaecologic tumors; thirty percent digestive; eighteen percent lung cancer and two percent other tumors, with a median of 3 different lines of therapy (range, 1 to 9). Patients preferred the oral route over the IV (76% vs. 20% respectively; P<0.001) and four percent had no preference. Tolerance was better with oral therapy (64%) ...

Annals of Oncology, 1999

J. Crown, B. Coiffier, H. Cortes-Funes, Th. Guillaume, L. Kanz, G. Kvalheim, M. Marty & M. Sy... more J. Crown, B. Coiffier, H. Cortes-Funes, Th. Guillaume, L. Kanz, G. Kvalheim, M. Marty & M. Symann 'St. Vincent's Hospital, Dublin, Ireland; Centre Hospilalier Lvon-Sud, Lyon, France; Hospital Universitario 12 de Octubre, Madrid, Spain; Catholic University of Louvain, Brussels, Belgium; Universitat Tubingen, Tubingen, Germany; The Norwegian Radium Hospital, Oslo, Norway; Hopital Saint-Louis, Paris, France

Annals of Oncology, 1995

A consensus meeting held under the auspices of the European School of Oncology concluded that the... more A consensus meeting held under the auspices of the European School of Oncology concluded that the use of granulocyte growth factors is definitely indicated, or acceptable given existing evidence, in the following circumstances: to alleviate congenital neutropenia; in the mobilisation of peripheral blood progenitor cells for autotransfusion; to encourage engraftment following bone marrow transplantation and in cases of failed engraftment; to support continuation of ganciclovir anti-CMV therapy in certain patients with AIDS, where the switch to foscarnet is contraindicated or where toxicity to foscarnet develops. It was also agreed that there is an overwhelming need for carefully controlled clinical trials in a wide range of indications in which growth factor use may improve outcome. In the majority of tumours, the possible benefit of dose optimisation and intensification, and therefore the role of growth factors in support of such measures has still to be defined. Extramedullary toxicities may in these instances become dose limiting.

Journal of Clinical Oncology, 2000

PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of p... more PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status ≤ 2 and creatinine clearance ≥ 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m2. Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m2 and gemcitabine 1,000 mg/m2 was recommended for phase II,...

Annals of Oncology, 1998

Background: The aim of this study was to determine the clinical activity and toxicity of a novel ... more Background: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m 2 and cisplatin was administered at a dose of 100 mg/m 2 on day 1, every 21 days. Results: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m~/week, and 31 mg/nr/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7-13), 17 patients are still alive and nine have died. The median overall survival is 12 months. Conclusion: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.

Recent Results in Cancer Research, 1980

Quelamycin is triferric doxorubicin, a metallic derivative of adriamycin which, in experimental s... more Quelamycin is triferric doxorubicin, a metallic derivative of adriamycin which, in experimental studies, has been found to have a better therapeutic index than adriamycin and no cardiotoxicity. In Spain, phase I clinical trials carried out in 96 patients with advanced cancer have shown that the drug has low toxicity and considerable antitumor activity, while it is not cardiotoxic, even at cumulative doses of nearly 3 g.

British journal of cancer, Jan 13, 2004

The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresec... more The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC), and outcome parameters were correlated with the expression of thymidine phosphorylase (TP), thymidilate syntetase (TS), vascular endothelial growth factor receptor (VEGFR) 1-3, and microvessel density (MVD). Patients with recurrent or unresectable HNSCC were eligible if they had received prior neoadjuvant chemotherapy, concurrent chemo-radiotherapy, or no prior systemic therapy. Patients received cisplatin (75 mg m(-2) day 1), and capecitabine (2000 mg m(-2) day 1-14) every 3 weeks. A total of 41 patients received 194 cycles. In all, 16 complete responses (39%) and 12 partial responses (29%) were documented, for an overall response rate of 68% (95% CI, 53-80%). Grade 3-4 uncomplicated neutropenia was documented in five subjects. Asthenia, anorexia, hand-foot syndrome, and constipation were the most frequent nonhaematologic event...

Clinical cancer research : an official journal of the American Association for Cancer Research, 2000

To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a... more To test the hypothesis of an association between HER2 and chemotherapy resistance, we performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with advanced breast carcinoma in the setting of a multicenter Phase II trial using paclitaxel and doxorubicin. Serum samples were collected from 58 patients with metastatic breast carcinoma before first-line chemotherapy for advanced disease, and the levels of circulating HER2 ECD were measured using an enzyme immunoassay. Immunohistochemistry with anti-HER2 monoclonal antibody CB11 was used to assess the overexpression of HER2 in the primary tumors. When 450 fmol/ml was used as a cutoff, 24 cases (41%) had elevated HER2 ECD levels. Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3; P = 0.032 and P = 0.002, respectively) but not with variables su...

Clinical cancer research : an official journal of the American Association for Cancer Research, 1998

Angiogenin is a protein originally isolated as an inducer of new blood vessel growth, and it has ... more Angiogenin is a protein originally isolated as an inducer of new blood vessel growth, and it has been reported to be an effective substrate for tumor cell adhesion. To understand the role of angiogenin in cancer progression, we evaluated the expression of angiogenin in 459 cases with primary breast carcinoma and in 40 benign breast specimens using an immunoassay. Higher angiogenin concentrations were observed in carcinomas in comparison with fibrocystic disease (mean, 17.3 versus 10.9 ng/mg; P = 0.008), but not with fibroadenomas. We selected 5 ng/mg cytosol protein of angiogenin as the normal cutoff for primary breast carcinoma. Eighty-eight percent of carcinomas expressed elevated angiogenin levels and 12% had low levels. We observed an association between elevated levels of angiogenin and low/ moderate histological grade (P = 0.001) and small tumor size (P = 0.026), but not with age, menopausal status, lymph node status, stage of disease, or hormonal receptor status. With a media...

Seminars in oncology, 1995

From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung can... more From March 1993 to May 1994, 32 chemotherapy-naive patients with advanced non-small cell lung cancer entered a phase I/II study to determine the maximum tolerated dose and the activity of the paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/cisplatin combination. The 21 men and 11 women had a median age of 59 years (range, 25 to 72 years) and a median performance status of 1 (range, 0 to 2). Histologic types were adenocarcinoma (13 cases), squamous cell carcinoma (10), and large cell carcinoma (nine). Nine patients had stage IIIB disease and 23 had stage IV disease. The first four dose levels of paclitaxel were 135, 175, 200, and 225 mg/m2 given with a fixed cisplatin dose of 100 mg/m2; at level 5, paclitaxel 225 mg/m2 was again given, and the cisplatin dose was increased to 120 mg/m2. Cycles were given every 3 weeks. Paclitaxel was administered as a 3-hour infusion followed by cisplatin, with standard premedication and hyperhydration. The maximum tolerated dose for t...

British Journal of Cancer, 2004

Revista Española de Cardiología, 1998

Cancer Research, 2012

Background: microRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regu... more Background: microRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. In the present study, we describe miRNA expression in early node-positive BC and identify a 8-miRNA score that could contribute to prognosis assessment. Methods: First, microarray analysis was performed using RNA samples extracted from primary breast cancer. The expression of miRNAs was analyzed by RT-qPCR using the TaqMan Arrays from Applied Biosystems. After a suitable normalization of the 677 miRNAs analyzed, 123 presented a good correlation between their levels of expression in frozen tissue and paraffin tissue. A supervised analysis was done in order to identify MIR that could predict relapse. Results: 172 patients with node-positive chemotherapy-treated early BC were included in the present study. The median age at diagnosis was (53.7) years, 128 cases (74.4%) had positive estrogen receptor, and 163 patients (94,7%) received adjuvant chemotherapy. After a medi...

Revista Clínica Española, 2003

Tumor Biology, 2001

The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by ... more The prognostic value of cytosolic p53 protein was evaluated in 458 operable breast carcinomas by immunoblotting using the monoclonal antibody PAb 1801. Two hundred and five carcinomas (45%) showed positive p53 accumulation and 55% were p53 negative. When comparing p53 positivity and other clinicopathological parameters, significant differences were found with younger age (p = 0.017), premenopausal status (p = 0.003), increasing tumor size (p = 0.026), negative estrogen receptor (p = 0.003) and negative progesterone receptor (p = 0.047), but not with histologic grade, axillary lymph node status, stage or erbB-2 expression. With a median follow-up of 34 months (range 3-70), relapse has occurred in 73 patients. Disease-free survival curves showed that patients with p53-positive tumors had a significantly shorter disease-free survival than patients with p53-negative carcinomas (log-rank test, p = 0.027). A multivariate analysis of disease-free survival showed that p53, tumor size, histologic grade and progesterone receptor had significant independent prognostic value. The immunoblotting technique was controlled with p53 immunohistochemistry in 94 paired samples. We obtained a statistically significant correlation (p = 0.0004) between the two methods. Our results show that the immunoblotting technique offers an alternative approach in evaluating the p53 status of breast biopsy material using cytosolic extracts, and confirm that p53 accumulation is a significant independent indicator of a poor prognosis in operable breast carcinoma.

Leukemia, 2001

Administration of stem cell factor (SCF) has been proven to enhance cytokine-induced mobilization... more Administration of stem cell factor (SCF) has been proven to enhance cytokine-induced mobilization of CD34 ؉ hematopoietic progenitor cells (HPC) into the peripheral blood (PB). The aim of the present study was to explore in a homogeneous group of 22 uniformly treated breast cancer patients: (1) the kinetics of mobilization into PB of both CD34 ؉ and CD34 ؊ cell subsets, including dendritic cells, in sequential samples obtained from day ؉7 up to day ؉12 after mobilization; and (2) the composition of the CD34 ؉ and CD34 ؊ cell subsets present in the two leukapheresis products obtained for each patient. The following CD34 ؉ and CD34 ؊ subsets were analyzed: early CD34 ؉ HPC, erythroid-, myeloid-and B-lymphoid-committed CD34 ؉ precursor cells, mature T, B and NK cells, monocytes, neutrophils, eosinophils, basophils, and dendritic cells (DC) including three subsets of lin ؊ /HLADR ؉ DC (CD16 ؉ , CD33 high and CD123 high). Our results show that the absolute number of PB CD34 ؉ HPC progressively increases from day ؉7 onwards. As far as the CD34 ؊ PB leukocyte subsets are concerned, monocytes (CD14 ؉) displayed the earliest recovery after mobilization predicting neutrophil recovery 1 day in advance. The number of CD34 ؉ HPC collected in a single leukapheresis product was always у1.4 ؋ 10 6 cells/kg body weight. No significant changes were observed between the two leukapheresis sessions either as regards their composition in CD34 ؉ HPC subsets or their CD34 ؊ leukocyte populations except for a higher ratio of both CD34 ؉ erythroid/CD34 ؉ myeloid HPC (0.35 ؎ 0.13 vs 0.30 ؎ 0.13; P ‫؍‬ 0.04) and neutrophils/monocytes (1.58 ؎ 2.1 vs 0.69 ؎ 0.27; P ‫؍‬ 0.009) found for the first leukapheresis. Interestingly, the overall number of dendritic cells (DC) was higher in the second leukapheresis (1.06 ؎ 0.56 vs 1.9 ؎ 0.46; P ‫؍‬ 0.02) due to a selective increase of the CD16 ؉ antigenpresenting cells. In summary, our results show that the combination of cyclophosphamide, G-CSF and SCF is highly effective for stem cell mobilization, with differences observed in the mobilization kinetics of the different hematopoietic cell subsets analyzed. Leukemia (2001) 15, 430-439.

European Journal of Internal Medicine, 2001