Biomedical subjects

J Estapé

Publications and source records attributed to J Estapé.

At least 19 recordsLinked to original sources

PubMed1998

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma.

p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II + III) (P = 0.017) and poor tubule formation (P = 0.002), and was significantly less frequent in lobular carcinomas (P = 0.0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation.

Blotting, Western↗

PubMed1998

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

PURPOSE: We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS: From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS: After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION: Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

Adenocarcinoma↗

PubMed1997

Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status.

Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which are altered in some breast carcinomas. However, the possible cooperation between CCND1 and Rb, as well as the influence and coincidence of their abnormalities in the proliferative capacity of mammary carcinoma cells in vivo, is still unknown. In order to assess both the significance of the CCND1 gene and Rb alterations in breast carcinomas and their relationship with the proliferative capacity of the tumours and other clinico-pathological factors, CCND1 mRNA expression was studied in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which were also studied immunohistochemically, Rb expression was analysed in the same cases by immunohistochemistry, whereas the proliferative activity of the carcinoma was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19 tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical expression, ten carcinomas had few positive cells, and 19 were absolutely negative. CCND1 mRNA and protein overexpression was associated with oestrogen receptor (ER) expression by the tumour. Interestingly, lack of ER expression was associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No association was observed between CCND1 mRNA or protein overexpression and tumour proliferation or other clinico-pathological parameters. Loss of Rb expression was observed in 26 per cent of the tumours. This abnormality was significantly associated with increased mean S-phase (P = 0.017) and decreased CCND1 mRNA expression in non-overexpressed tumours, supporting in vivo the postulated regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up-regulation is not associated with increased proliferative activity in breast carcinomas, whereas its expression might be regulated in vivo by hormones and Rb. Loss of Rb expression is significantly associated with an increased proliferation of tumour cells, suggesting an important role in the progression of a subset of breast carcinomas, regardless of CCND1 abnormalities.

Blotting, Northern↗

PubMed1997

Phase II trial of cisplatinum and etoposide in brain metastases of solid tumors.

Fourteen patients with brain metastases (BM) of solid tumors received intravenous cisplatinum, 40 mg/m2/day and etoposide, 150 mg/m2/day, for 3 days every 3 weeks. Primary tumors were lung (8 patients), breast (4), colon (1), and stomach (1). Two patients responded (1 complete response in a poorly differentiated lung cancer patient and 1 partial response in a breast cancer patient). The overall response rate was 14%, with a median survival of 6 months. Main toxicity was grade 3-4 neutropenia that occurred in 36% of patients. There were no toxic-related deaths. Chemotherapy as a single therapeutic regimen seems not to be an effective treatment for BM from relatively resistant solid tumors. Moreover, it produces rather high, although not life-threatening, hematologic toxicity.

Adult↗

PubMed1996

Neoadjuvant and adjuvant chemotherapy in the multidisciplinary treatment of oral cancer stage III or IV.

We performed a retrospective analysis on the effect of initial induction chemotherapy with two courses of cisplatin (each course 120 mg/m2 cisplatin on day 1, then 20 mg/m2 bleomycin (alone) per day for 5 days with 4 weeks between courses) in 75 consecutive patients with advanced cancer of the oral cavity or lip. Further local therapy consisted of surgery or radiation, depending on tumour location. In 18 resected patients adjuvant chemotherapy was added. This consisted of carboplatin, 400 mg/m2 on day 1 then ftorafur alone, 500 mg/m2/day for 30 consecutive days, repeated every month for 4 consecutive months. Among the patients treated in the neoadjuvant setting, complete response was observed in 10 out of 75 patients (13%), and partial response in a further 50 patients (67%) (partial plus complete rate 80%). Of all the patients, 43% in stage III and 26% in stage IV were long-term survivors. Improved survival was observed in surgical patients where adjuvant postoperative chemotherapy was added (P < 0.025). The main toxic effect was vomiting, observed in 71 patients. We noted a low rate of stomatitis (4%) and an important hearing loss (12%). Neoadjuvant and adjuvant cisplatin-based chemotherapy as part of a multidisciplinary approach have a high overall response rate and low toxicity, and should increase survival in cancer of the oral cavity or lip.

Adult↗

PubMed1996

Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3.

To evaluate the utility of c-erbB-2, carcinoembryonic antigen (CEA) and CA 15.3 in the early diagnosis of recurrence, serial serum determinations of these antigens were performed in 200 patients (follow-up 1-4 years, mean 2.2 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Eighty-nine patients developed metastases during follow-up. C-erbB-2, CEA and CA 15.3 were elevated (> 20 U ml-1, > 10 ng ml-1 or > 60 U ml-1 respectively) before diagnosis in 28%, 30% and 47% of the 89 patients with recurrence, with a lead time of 4.5 +/- 2.4, 4.9 +/- 2.4 and 4.8 +/- 2.4 months respectively. Tumour marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver metastases. When patients with locoregional recurrences were excluded, sensitivity improved: 31% (c-erbB-2), 33% (CEA) and 56% (CA 15.3), with 76% having at least one of the three tumour markers. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (8/10, 80%) than in those without overexpression (1/30, 3.3%) (P = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PR+ patients (CA 15.3, P < 0.0001) or in PR- patients (c-erbB-2, P = 0.009). Specificity of the tumour markers was 100% for all three markers (111 NED patients). In conclusion, c-erbB-2 is a useful tool for early diagnosis of metastases, mainly in those patients with c-erbB-2 overexpression in tissue. Using all three markers simultaneously it is possible to increase the sensitivity in the early diagnosis of recurrence by 11.2%.

Bone Neoplasms↗

PubMed1996

Calcium supplementation and ototoxicity in patients receiving cisplatin.

We have studied the effect on ototoxicity of maintaining serum calcium concentration by calcium gluconate infusion in cancer patients receiving high-dose cisplatin in a randomized study in two groups: 11 patients received calcium gluconate, 4 mg kg-1 i.v. infusion during cisplatin therapy; 11 other patients without any calcium supplementation served as controls. All of them received the first course of chemotherapy, based on cisplatin, 120 mg m2 with a hydration schedule. An audiogram was performed in each patient just before cisplatin and repeated after 1 day and 3 weeks. Mean total calcium concentration in control patients before and after chemotherapy was 2.2 +/- 0.14 (95% confidence interval 1.9-2.5) and 2.0 +/- 0.13 (95% CI 1.7-2.24) mmol 1(-1) respectively (P = 0.0004) and for ionized calcium 1.22 +/- 0.52 (95% CI 0.21-2.23) and 1.11 +/- 0.07 (95% CI 0.97-1.25) mmol 1(-1) respectively (P = 0.0005). Serum magnesium levels were maintained or increased by magnesium supplementation. Although there was no change in serum total or ionized calcium, or serum magnesium in the calcium infusion group, no differences in hearing loss between the groups were observed. High-dose cisplatin chemotherapy for cancer patients induces an acute decrease of serum total calcium and serum ionized calcium and audiometric changes. Maintenance of calcium serum levels by calcium gluconate infusion did not protect against ototoxicity in those patients.

Adolescent↗

PubMed1996

Treatment of multiple myeloma in elderly people: long-term results in 178 patients.

The purposes of the present study have been to analyse the presenting features, response to therapy and survival of myeloma patients aged 70 years or more, in comparison to younger patients. From January 1985 to December 1989, 487 patients with multiple myeloma (MM) were randomized to receive melphalan and prednisone (MP) versus alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, BCNU, adriamycin, and prednisone (VBAP). The subset of 178 patients who were 70 or more years is the subject of this study, whereas the 309 patients younger than 70 years were used as a control group. The presenting features and response to chemotherapy of older patients were no different to those of the younger population. However, the survival of elderly patients was significantly shorter (median 23.4 vs. 33.5 months, p < 0.001). The overall response rate to MP in older patients was 50% (28% objective plus 22% partial response) compared with 61% (44% objective plus 17% partial response) to combination chemotherapy (p = not significant). Myelosuppression was moderate in both arms, although MP produced a higher degree of thrombocytopenia. There were no significant differences in survival between patients given MP versus VCMP/ VBAP (median, 20 vs. 27 months, p = 0.2). Response to treatment was associated with a significantly longer survival. Older patients with symptomatic myeloma tolerate chemotherapy and should be offered treatment.

Age Factors↗

PubMed1996

Six-year follow-up of primary small cell carcinoma of the esophagus showing a complete response: a case report.

Six-year follow-up of a case of small cell carcinoma of the esophagus showing a complete response is reported. The small cell pattern appeared intermingled with areas of invasive squamous cell carcinoma and carcinoma in situ. A neoadjuvant polychemotherapy regimen was used, followed by radiation therapy and adjuvant chemotherapy. This therapeutic combination resulted in complete response of the disease, as confirmed by computed tomography, endoscopy and biopsy. The patient is currently still alive, 6 years after the diagnosis, without any sign of relapse. A review of the literature reveals that this patient has survived longer than any others with this disease after treatment by chemoradiotherapy. The authors suggest that this therapy should be considered for patients with limited small cell carcinoma of the esophagus.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas: long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative Group for the Study of Hematological Malignancies Treatment, Spanish Society of Hematology).

From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.

Adult↗

PubMed1996

Detection of circulating neoplastic cells by reverse-transcriptase polymerase chain reaction in malignant melanoma: association with clinical stage and prognosis.

PURPOSE: Circulating melanoma cells can be detected in peripheral blood by means of tyrosinase mRNA amplification by reverse-transcriptase polymerase chain reaction (RT-PCR). We conducted a prospective study to evaluate the clinical significance of the presence of circulating neoplastic cells in the blood of patients with malignant melanoma (MM). METHODS: A sensitive RT-PCR assay was used to detect tyrosinase mRNA in the peripheral blood of patients with stages I to IV melanoma. Healthy subjects or patients with other malignancies were used as negative controls. RESULTS: Ninety-one assessable patients were included in the study. There was a statistically significant association between RT-PCR positivity and clinical stage. Circulating melanoma cells were detected in 36% of patients with localized disease (stages I and II), in 45% of patients with regional nodal involvement (stage III), and in 94% of patients with metastatic disease (stage IV) (P < .001). In stage II-III patients who were RT-PCR-positive for mRNA tyrosinase in blood, the recurrence rate and disease-free survival were significantly worse than patients who were RT-PCR-negative. In multivariate analysis, RT-PCR was an independent prognostic factor for recurrence in patients with nonmetastatic disease (P = .002). CONCLUSION: The detection of circulating melanoma cells in peripheral blood by RT-PCR correlated with the clinical stage of patients with melanoma and was an independent prognostic factor for recurrence. Further studies are warranted to better assess the significance of this test in the evaluation of prognosis, early detection of relapse, and in monitoring the effectiveness of systemic therapy.

Adult↗

PubMed1996

Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated.

PURPOSE: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS: From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS: Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION: The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.

Adult↗

PubMed1994

Chronic oral etoposide in advanced breast cancer.

Chronic oral etoposide has shown activity in some metastatic refractory tumors. To test its activity in previously treated metastatic breast cancer patients, we started a study in 18 consecutive patients given etoposide orally at 50 mg/m2 daily for 21 days. A partial response was observed in 4 of 18 patients (22%); of the responding patients, 3 had visceral metastases and 1 had multiple bone metastases. Leukopenia of grade 3 or 4 was the main hematological toxic effect (23% of patients) and alopecia was the most important nonhematological toxicity. Chronic oral etoposide shows some activity in pretreated patients with metastatic breast cancer, with tolerance being good and toxicity, acceptable. Further studies of this drug given as first-line chemotherapy or in combination with other drugs can establish all its potential activity in this cancer.

Administration, Oral↗

PubMed1994

Age and clinical characteristics of 1433 patients with lung cancer.

A review has been conducted of 1433 patients treated by the Lung Cancer Unit of our hospital to assess the association of age with clinical characteristics of patients with lung cancer. The factors evaluated were tobacco, stage of disease, treatment and survival of patients treated surgically. A comparison was made of patients aged 65 or less with those over 65. There was a similar prevalence of smokers in both age groups. The stage of disease at time of diagnosis was similar (33% of the patients aged 65 or less were Stage I or II versus 37% of the older patients). The distribution by histological type showed significant differences (p < 0.05) with a higher percentage of squamous carcinoma in the younger group (54% versus 44%). Surgery was performed in 30% of the patients aged 65 years or less but only in 19% of the older cases (p < 0.05). Among those patients treated surgically there was no difference in the survival of younger and older patients.

Aged↗

PubMed1994

Carboplatin plus ftorafur as a palliative treatment in locally advanced cancer of the oral cavity and lip.

Forty consecutive patients with local advanced cancer of the oral cavity and lip, heavily pretreated, were palliated with two courses of carboplatin, 400 mg/m2 intravenously once a month plus ftorafur, 500 mg/m2 daily per os for 30 days. Previous treatment consisted of surgery (17 patients), radiation therapy (23 patients), and chemotherapy with cisplatin plus bleomycin (15 patients). The main sites of primary tumor were the tongue (12 patients), hard palate (6 patients), retromolar area (6 patients), tonsils (6 patients), perioral skin and lip (5 patients), and floor of the mouth (5 patients). Complete response was observed in 3 patients, and partial response in 7. Symptomatic improvement was observed in 56% of the cases. Median duration of response was 9 months. Median survival was 7 months. The main toxic effects were nausea (39 cases), vomiting (35 cases), and thrombocytopenia (4 cases). We conclude that carboplatin plus ftorafur has a role as palliative chemotherapy in cancer of the oral cavity and lip in heavily pretreated patients when local therapies are not suitable.

Adult↗

PubMed1994

TAG-72, CA 19.9 and CEA as tumor markers in gastric cancer.

Serum levels of CEA, CA 19.9 and TAG-72 were measured in 79 patients with active gastric cancer, 47 with treated gastric cancer and no clinical evidence of the disease and 33 with benign gastric disease. In the patients with active gastric cancer TAG-72 was increased in 47%, CA 19.9 in 46% and CEA in 33%. The sensitivity of these markers was related to the stage of the disease, although upon comparison of stages I-II and III-IV significant difference was observed only for TAG-72. The combined use of two of the markers increased the sensitivity compared with the use of only one. The results suggest that the combination of TAG-72 and CA 19.9 may be useful in the post surgical management of patients with gastric cancer.

Antigens, Neoplasm↗

PubMed1993

[Cerebral metastasis of melanoma: study of 48 patients].

BACKGROUND: Malignant melanoma is a frequent cause of cerebral metastases (CM). In the present study the characteristics of primitive melanomas of patients with CM, their forms of clinical presentation and treatment were analyzed. METHODS: A retrospective study of the patients with melanoma and CM diagnosed between 1982 and 1991 was carried out. RESULTS: Out of 786 patients with melanoma 48 were identified with CM. In 65% of the melanoma originated in cutaneous areas BANS (of bad prognosis). The median thickness of the tumor (Breslow's index) was of 3.6 mm. The median period of latency between diagnosis of the melanoma and the detection of CM was 22 months. Although recent hemorrhage of the CM was observed in the cranial computerized tomography in 20 of the 48 patients, only 7 presented clinical symptoms of ictus. In 23 patients the CM were the only evidence of metastases of the melanoma. The median survival was one month in the patients treated with only dexamethasone, 3.5 months in the chemotherapy group, 2.5 months for the group given radiotherapy and 6 months for those undergoing surgery. CONCLUSIONS: Most of the patients with cerebral metastasis had a primitive melanoma with criteria of bad prognosis. The presence of hemorrhage in computerized tomography did not always correlate with clinical symptoms of ictus. Surgical treatment must be considered in patient with sole cerebral metastasis without evidence of distant disease.

Adult↗

PubMed1993

Positive results of adjuvant mitomycin-C in resected gastric cancer: a randomised trial on 134 patients.

In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a randomised trial on 134 patients in two arms: a control one with no further treatment after surgery versus a treatment arm given mitomycin-C (MMC), 20 mg/m2 intravenously one day every 6 weeks for four courses, starting before the sixth week after surgery. The median follow-up was 105 months. In the control arm, 49 out of 66 patients died due to recurrence, versus 40 out of 68 patients in treatment arm. Actuarial survival curve was statistically significant (P < 0.025) in favour of the treatment group. Liver metastases were lower in adjuvant group than in the control group (8/68 versus 19/66). Toxicity was mild. Main toxic effects were thrombocytopenia, leukopenia, nausea and vomiting. A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed. In that particular case MMC was given after surgery. We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery, improves survival rate in gastric cancer resected patients.

Adult↗