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Biomedical subjects

F Calero

Publications and source records attributed to F Calero.

At least 19 recordsLinked to original sources
PubMed2005

Breast cancer prognosis determined by gene expression profiling: a quantitative reverse transcriptase polymerase chain reaction study.

PURPOSE: We sought to reproduce with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) the results obtained with a 70-gene expression profile that has been described previously in breast cancer. PATIENTS AND METHODS: Frozen breast cancer samples from patients who were operated on were used to isolate tumor RNA. Ninety-six patients with stage I to II disease were included. Median age was 57 years (range, 27 to 80 years). Forty-eight patients had lymph node-negative and 48 lymph node-positive disease. qRT-PCR amplifications were performed and the results were correlated with clinical data. RESULTS: After a minimum follow-up of 5 years, 25 patients had a relapse. The gene profile divided patients into two groups with poor and good prognosis. Significant differences with regard to grade of differentiation, size and hormone receptors were seen between the two groups. The gene profile was significantly associated with relapse-free survival and overall survival in the whole group of 96 patients. Multivariate analysis showed that only lymph node status and gene profile were significantly correlated to overall survival. CONCLUSION: qRT-PCR reproduced the results obtained with microarrays for a prognostic gene profile in women with early-stage breast cancer.

Adult↗
PubMed2004

[Steroid-responsive nephrotic syndrome in IgA nephropathy].

A 46-year-old male, smoker of half a packet a day and an alcohol intake of 80 grams a day, with an unremarkable medical history, was referred to our service in the year 1988 for a study of nephrotic syndrome. He presented normal renal function, without either microhematuria nor hypertension. In blood analysis an albuminemia of 10 g/l and proteinuria of 22 g/d was observed. A first renal biopsy was carried out which indicated minimal change disease. Steroid treatment was started, as a result the nephrotic syndrome disappeared and the blood analysis normalized. Later he had 4 new outbreaks, all of them steroid-responsive. In 1992 a second renal biopsy was performed after the fourth outbreak and the presence of mild renal failure, that this time indicated a IgA nephropathy. Steroid treatment was tried again, and this time cyclophosphamide was added to try to reduce steroid doses. This result in normalization of renal function and decrease of proteinuria to 2 g/d. The patient remained stable until 1996 when the fifth outbreak occurred, again with mild renal failure and proteinuria in nephrotic range. Therefore a third renal biopsy was performed, that confirmed the presence of IgA nephropathy, but now with signs of histological progression of the disease. Following this, he presented five outbreaks in 3 years, all of them steroid-responsive, with decrease of proteinuria although without renal function normalization. In the year 2000, at his tenth outbreak of nephrotic syndrome it was decided to add cyclosporine to the steroid treatment, achieving the stability of the patient, without further outbreaks until now, with proteinuria of 1.6 g/d and C. creat. 59 ml/min.

Biopsy↗
PubMed2001

A screening for high copy suppressors of the sit4 hal3 synthetically lethal phenotype reveals a role for the yeast Nha1 antiporter in cell cycle regulation.

A screening for multicopy suppressors of the G(1)/S blockage of a conditional sit4 hal3 mutant yielded the NHA1 gene, encoding a Na(+),K(+)/H(+) antiporter, composed of a transmembrane domain and a large carboxyl-terminal tail, which has been related to cation detoxification processes. Expression of either the powerful Saccharomyces cerevisiae Ena1 Na(+)/H(+)-ATPase or the Schizosaccharomyces pombe Sod2 Na(+)/H(+) antiporter, although increasing tolerance to sodium, was unable to mimic the Nha1 function in the cell cycle. Mutation of the conserved Asp residues Asp(266)-Asp(267) selectively abolished Na(+) efflux without modifying K(+) efflux and did not affect the capacity of Nha1 to relieve the G(1) blockage. Mutagenesis analysis revealed that the region near the carboxyl-terminal end of Nha1 comprising residues 800-948 is dispensable for sodium detoxification but necessary for transport of K(+) cations. Therefore, this portion of the protein contains structural elements that selectively modulate Nha1 antiporter functions. This region is also required for Nha1 to function in the cell cycle. However, expression of the closely related Cnh1 antiporter from Candida albicans, which also contains a long carboxyl-terminal extension, although allowing efficient K(+) transport does not relieve cell cycle blockage. This indicates that although the determinants for Nha1-mediated regulation of potassium transport and the cell cycle map very closely in the protein, most probably the function of Nha1 on cell cycle is independent of its ability to extrude potassium cations.

Amino Acid Sequence↗
PubMed2001

The prognostic significance of P-cadherin in infiltrating ductal breast carcinoma.

We have immunohistochemically investigated P-cadherin (P-CD) expression in a series of 210 infiltrating ductal carcinomas (IDC) in an attempt to assess the biological and prognostic relevance of P-CD in patients harboring IDCs. Although only 74/210 (35%) of IDCs expressed P-CD in >5% of tumor cells (P-CD-positive carcinomas), categorical analyses revealed that P-CD-positive IDCs were larger (26 +/- 21 cm versus 22 +/- 11 cm, P =.0568), of higher histological grade (P =.0001), and had more lymph node metastases (P =.0327) than P-CD-negative breast carcinomas. In addition, P-CD-positive tumors were negative for estrogen (P =.0001) and progesterone receptors (P =.0001) and showed reduced E-cadherin expression (P =.0276) more frequently than P-CD-negative tumors. Univariate analysis carried out in 171 patients demonstrated that P-CD expression was also an indicator of poor prognosis (chi(2) = 8.292, P =.004), extent of lymph node metastasis (chi(2) = 20.854, P =.0000), histological grade (chi(2) = 12.908, P =.0016), and negative progesterone receptors (chi(2) = 4.116, P =.042). However, only histological grade and nodal metastases emerged as independent prognostic markers in the multivariate analysis. These results suggest that although P-CD expression may be involved in the progression of IDCs, its value as an independent prognostic factor remains to be established.

Adult↗
PubMed2001

Effect of angiotensin II receptor blockade on renal disease progression in patients with non-diabetic chronic renal failure.

BACKGROUND: The aim of the present study was to investigate the effect of losartan on the progression of renal function in non-diabetic patients with chronic renal failure in an open, prospective, follow-up study of 1 year. METHODS: Twenty-nine hypertensive patients (14 females and 15 males; mean age 63 years.) with non-diabetic chronic renal failure of several causes received losartan 50 mg/day (plus other antihypertensive agents if needed) and were followed-up prospectively during 13+/-1 months. Eighteen patients received angiotensin-converting enzyme inhibitors plus other antihypertensive drugs at baseline. Patients had been followed-up for 44+/-4 months prior to the treatment with losartan. The rate of progression of renal insufficiency was evaluated as the slope of the reciprocal of serum creatinine vs time in months. RESULTS: Blood pressure, creatinine clearance and urinary protein excretion at baseline and after 1 year of treatment with losartan were: 149+/-3/90+/-1 vs 142+/-2/84+/-1 mmHg (P<0.01/P<0.05), 29+/-3 vs 29+/-3 ml/min (P=NS), and 1.7+/-0.4 vs 1.2+/-0.2 g/24 h (P=0.11, NS). Serum creatinine at baseline, and after 6 months and 1 year of treatment with losartan was: 3.18+/-0.24, 3.24+/-0.27 (P=NS vs baseline) and 3.49+/-0.32 mg ml (P<0.05 vs baseline). The rate of progression of renal disease before and after 1 year of treatment with losartan was -0.0039+/-0.0058 vs -0.0012+/-0.0073 mg/month (P<0.01). Changes in proteinuria after 1 year of treatment with losartan correlated with the change in renal disease progression (r=-0.519, P<0.01). CONCLUSIONS: The rate of progression of renal function in patients with non-diabetic chronic renal failure is slowed down after 1 year of treatment with losartan. The results of this preliminary study suggest that AT1 receptor blockade treatment offers renoprotection in this subset of patients, although these results need to be confirmed in appropriate controlled trials.

Angiotensin Receptor Antagonists↗
PubMed2000

Factors influencing collection and engraftment of CD34+ cells in patients with breast cancer following high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation.

Although autologous PBPC transplantation is being used increasingly for the treatment of breast cancer, there are few data on factors influencing mobilization and engraftment in these patients. We have analyzed these factors in 70 patients with advanced or metastatic breast cancer undergoing autologous PBPC transplantation. All patients were mobilized after stimulation with G-CSF, and a median of 3.16 x 10(6)/kg CD34+ cells (range 0.75-23.33) were infused. All patients received conditioning with a combination of cyclophosphamide, thiotepa, and carboplatin, and postinfusion G-CSF was administered to 60 patients. The median times to reach 0.5 x 10(9)/L and 1 x 10(9)/L neutrophils were 10 and 11 days, respectively. The median times to obtain 20 x 10(9)/L and 50 x 10(9)/L platelets were 12 and 18 days, respectively. An analysis of factors that influence CD34+ cell collection was performed by linear regression. Previous radiation therapy and increasing age were associated with lower numbers of CD34+ cells collected. Those variables that could influence the tempo of engraftment were examined by multivariate analysis using Cox regression models. The number of CD34+ cells infused was found to influence both neutrophil and platelet recovery. The use of G-CSF after transplant, accelerated neutrophil recovery, and having more than six cycles of previous chemotherapy was an unfavorable factor for recovering >50 x 10(9)/L platelets.

Adult↗
PubMed2000

Trk1 and Trk2 define the major K(+) transport system in fission yeast.

The trk1(+) gene has been proposed as a component of the K(+) influx system in the fission yeast Schizosaccharomyces pombe. Previous work from our laboratories revealed that trk1 mutants do not show significantly altered content or influx of K(+), although they are more sensitive to Na(+). Genome database searches revealed that S. pombe encodes a putative gene (designated here trk2(+)) that shows significant identity to trk1(+). We have analyzed the characteristics of potassium influx in S. pombe by using trk1 trk2 mutants. Unlike budding yeast, fission yeast displays a biphasic transport kinetics. trk2 mutants do not show altered K(+) transport and exhibit only a slightly reduced Na(+) tolerance. However, trk1 trk2 double mutants fail to grow at low K(+) concentrations and show a dramatic decrease in Rb(+) influx, as a result of loss of the high-affinity transport component. Furthermore, trk1 trk2 cells are very sensitive to Na(+), as would be expected for a strain showing defective potassium transport. When trk1 trk2 cells are maintained in K(+)-free medium, the potassium content remains higher than that of the wild type or trk single mutants. In addition, the trk1 trk2 strain displays increased sensitivity to hygromycin B. These results are consistent with a hyperpolarized state of the plasma membrane. An additional phenotype of cells lacking both Trk components is a failure to grow at acidic pH. In conclusion, the Trk1 and Trk2 proteins define the major K(+) transport system in fission yeast, and in contrast to what is known for budding yeast, the presence of any of these two proteins is sufficient to allow growth at normal potassium levels.

Amino Acid Sequence↗
PubMed1999

The Schizosaccharomyces pombe Pzh1 protein phosphatase regulates Na+ ion influx in a Trk1-independent fashion.

We have previously shown that fission yeast encodes a PPZ-like phosphatase, designated Pzhl, which is an important determinant of cation homeostasis. pzh1 delta mutants display increased tolerance to Na+ ions, but they are hypersensitive to KC1 [Balcells, L., Gómez, N., Casamayor, A., Clotet, J. & Ariño, J. (1997) Eur. J. Biochem. 250, 476-483]. We have immunodetected Pzh1 in yeast extracts and found that this phosphatase is largely associated with particulate fractions. Cells defective in Pzh1 do not show altered efflux of Na+ or Li+ ions, but they accumulate these cations more slowly than wild-type cells. K+ ion content of pzh1 delta cells is about twice that of wild-type cells, and this can be explained by decreased efflux of K+. Therefore, Pzh1 may regulate both Na+ influx and K+ efflux in fission yeast. To test the possible relationship between K+ uptake, Na+ tolerance and Pzh1 function, we deleted the trk1+ gene, which encodes a putative high-affinity transporter of K+ ions. trkl delta mutants grew well even at relatively low concentrations of KCl and did not show significantly altered content or influx of K+ ions. However, they showed a Na(+)-sensitive phenotype which was greatly intensified by deletion of the sod2+ gene (which encodes the major determinant for efflux of Na+ ions), and clearly ameliorated by deletion of the pzh1 phosphatase, as well as by moderate concentrations of KCl in the medium. These results suggest that Trk1 does not mediate the effect of Pzh1 on NaCl tolerance and that fission yeast contains efficient systems, other than Trk1, for uptake of K+ ions.

Biological Transport↗
PubMed1999

Biochemical and genetic analyses of the role of yeast casein kinase 2 in salt tolerance.

Saccharomyces cerevisiae cells lacking the regulatory subunit of casein kinase 2 (CK-2), encoded by the gene CKB1, display a phenotype of hypersensitivity to Na(+) and Li(+) cations. The sensitivity of a strain lacking ckb1 is higher than that of a calcineurin mutant and similar to that of a strain lacking HAL3, the regulatory subunit of the Ppz1 protein phosphatase. Genetic analysis indicated that Ckb1 participates in regulatory pathways different from that of Ppz1 or calcineurin. Deletion of CKB1 increased the salt sensitivity of a strain lacking Ena1 ATPase, the major determinant for sodium efflux, suggesting that the function of the kinase is not mediated by Ena1. Consistently, ckb1 mutants did not show an altered cation efflux. The function of Ckb1 was independent of the TRK system, which is responsible for discrimination of potassium and sodium entry, and in the absence of the kinase regulatory subunit, the influx of sodium was essentially normal. Therefore, the salt sensitivity of a ckb1 mutant cannot be attributed to defects in the fluxes of sodium. In fact, in these cells, both the intracellular content and the cytoplasm/vacuole ratio for sodium were similar to those features of wild-type cells. The possible causes for the salt sensitivity phenotype of casein kinase mutants are discussed in the light of these findings.

Adenosine Triphosphatases↗
PubMed1998

Hematopoietic cell transplantation using plasma and DMSO without HES, with non-programmed freezing by immersion in a methanol bath: results in 213 cases.

A simplified cryopreservation method for bone marrow (BM) and peripheral blood progenitor cells (PBPC) was utilized in hematopoietic cell transplantation of 213 patients with hematological or solid neoplasms after ablative chemotherapy (187 with peripheral blood progenitor cells and 26 with bone marrow). Cells were cryopreserved, after addition of autologous fresh plasma with DMSO, without HES, by freezing to -80 degrees C in a methanol bath and non-programmed freezer. For the patients autotransplanted with PBPC, the median period necessary for recovery of more than 0.5 x 10(9)/l granulocytes was 11 days (range 6-44), and 15 (8-204) days were required to obtain more than 20 x 10(9)/l platelets. For the patients autotransplanted with BM, the median period necessary to recover >0.5 x 10(9)/l granulocytes was 12 days (range 9-33), and 24 (12-57) days to obtain more than 20 x 10(9)/l platelets. These results support this method as being very effective in achieving high-quality cryopreservation. The procedure, which uses a non-programmed freezer, simplifies and reduces enormously the cost of the technical measures currently in use, enabling its adoption in almost any clinical oncological institution.

Adolescent↗
PubMed1997

Pontomedullary efferent projections of the ventral respiratory neuronal subsets of the rat.

The pontomedullary trajectories of projections efferent from the ventral respiratory cell group were anterogradely labelled after discrete injections of Fluoro Ruby into three morphophysiologically identified subdivisions (Bötzinger complex, rostral inspiratory, and caudal expiratory cell groups). The anterogradely labelled varicosities were located in a variety of areas involved in cardiorespiratory function: other subdivisions of the ventral respiratory cell group, the parabrachial (medial, central, and external lateral), Kölliker-Fuse, and lateral paragigantocellular nuclei, A5, and perifacial areas. Although the target areas were similar for the three studied subdivisions, some differences of the location and densities of labelled varicosities were found. Anterogradely labelled fibre bundles were found bilaterally after all of the tracer injections. Three caudally efferent bundles passed through the ventral respiratory cell group, dorsal medullary, and paramedian reticular nuclei. A labelled fibre bundle also took an ascending route through the ventral respiratory cell group: it surrounded the facial nucleus, and then followed two different pathways, one coursing towards forebrain areas and the other to the parabrachial and Kölliker-Fuse complex. Bundles of efferent axons decussated mainly at medullary levels and to a lesser extent in the pons. In the contralateral medulla and pons these labelled fibre bundles followed pathways similar to those observed ipsilaterally. The three ventral respiratory neuronal subsets sent axonal projections through similar tracts, but within them they were topographically organized. The present data are discussed with respect to the circuitry involved in the mechanisms of cardiorespiratory and other visceral functions.

Animals↗
PubMed1994

Primary tubal carcinoma.

Fourteen patients were studied in a retrospective review of malignancies of the fallopian tube in the Maternity Section of La Paz Hospital, Madrid, over a period of 19 years. Three patients were excluded at reassessment. Adenocarcinoma was the most common histological type. Eight patients have survived but one of them has had a relapse. None were diagnosed prior to surgery. A comparative study of survival and stage, muscular invasion and grade of cellular differentiation was performed. It is concluded that the best results are obtained when adjuvant treatment with polychemotherapy containing platinum is used.

Adenocarcinoma↗
PubMed1992

[Influence of chronic renal failure and of its treatment on serum erythropoietin].

BACKGROUND: In order to know the influence of dialysis treatment in erythropoietin production, serum erythropoietin (Ep) has been studied in patients with anemia due to chronic renal failure (CRF). METHODS: Thirty six of them in hemodialysis (HD), 10 in continuous ambulatory peritoneal dialysis (CAPD) and 18 in predialysis stage (PD) and their results were compared to two control groups, including 72 healthy controls (HC) and the second one 89 iron deficiency anemia patients (ID). RESULTS: Patients had lower Hb and Ep levels than the other groups. Although Ep was higher in CAPD and PD. Ep levels were similar to HC values, and lower than ID levels. It could be demonstrated any correlation between Hb and Ep in CRF patients, however a negative exponential correlation was demonstrated in ID patients between Hb and Ep (r = -0.83; p less than 0.00001). In summary, Ep is higher in CAPD and in PD than in HD, but the levels are lower than they should be expected. CONCLUSIONS: These data confirm an Ep production failure in most of IRC patients and it seems likely that Ep treatment could be effective to treat the anemia of CRF.

Anemia↗
PubMed1992

Epirubicin: clinical toxicity during the phase II program in endometrial and cervical cancer.

We have evaluated the clinical toxicity of Epirubicin 80 mg/m2 i.v., every 3 weeks in 58 patients with FIGO III-IV endometrial adenocarcinoma or squamous uterine cervix carcinoma. The median age of the whole group was 59 years (37-77); 37 patients were previously treated with radiotherapy and two with cisplatin based chemotherapy. The median KI at entry was 80. A total of 308 courses of chemotherapy were administered with a median of 5 per patient. Overall toxicity data shows that this dose level is associated with mild haematological toxicity with only two cases having grade 3 (WHO) leukopenia. Nine patients suffered emesis in spite of prophylactic therapy and were classified as grade 3. One case presented grade four diarrhoea but the relation with the antineoplastic treatment was uncertain. One woman with hepatic dysfunction at entry had grade 3 leukopenia, developed pneumonia and died. The median total cumulative dose of EPI was 360 mg/m2 (160-880) with 19 cases exposed to cumulative doses higher than 550 mg/m2. Congestive heart failure was not observed. Our data confirm the safety of EPI at these dose levels and suggest the possibility of developing new trials with higher doses of this anthracycline analog.

Adult↗
PubMed1991

Epirubicin in advanced endometrial adenocarcinoma: a phase II study of the Grupo Ginecologico Español para el Tratamiento Oncologico (GGETO).

27 patients with FIGO stage III-IV endometrial adenocarcinoma were entered in a phase II trial evaluating activity and safety of epirubicin given at 80 mg/m2 intravenously every 3 weeks. 2 complete remissions (including a pathological one) and 5 partial responses were observed for a response rate of 26% (95% confidence interval 11-46). The median time to progression and median survival for all treated patients was 6 and 9.5 months, respectively. Treatment was well tolerated. Haematological toxicity was mild. The median total cumulative dose of epirubicin was 480 mg/m2 (160-880) and cardiac toxicity was not observed. Further studies with higher doses of epirubicin in combination with other active drugs are indicated.

Adenocarcinoma↗
PubMed1991

Single agent epirubicin in squamous cell cervical cancer. A phase II trial.

Thirty consecutive patients with FIGO stage III-IV, squamous cell uterine cervix cancer were entered in a phase II trial evaluating activity and safety of epirubicin when given at a dose of 80 mg/m2 i.v., every 3 weeks. Two complete responses (including a pathological complete remission) plus 3 partial responses were observed among 27 evaluable patients with a response rate of 18.5% (95% confidence limits = 7.6%-36.4%). The median time to progression and median survival for all treated patients were 3 and 8 months respectively. Treatment was well tolerated. Haematological toxicity was mild. WHO grade 4 toxicity was not observed. The median total cumulative dose of epirubicin was 360 mg/m2 (80-840 mg/m2). Congestive heart failure was not noted. Further studies in cervical cancer with higher doses of epirubicin as single agent or in combination with other nonmyelotoxic drugs are indicated.

Adult↗
PubMed1990

Hb O Padova in a Spanish Family.

Haematological and biochemical aspects of a new family with heterozygous Hb O Padova [alpha 30(B11) Glu----Lys] is described. This variant has been found on a screening programme of abnormal haemoglobin in cord blood. It was separated by cellulose acetate, isoelectric focusing, citrate agar, DEAE-cellulose chromatography and by cation exchange high-performance liquid chromatography. The heat stability and the functional properties were found to be normal. This is the third family with Hb O Padova reported, all from the Mediterranean region.

Amino Acids↗