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Biomedical subjects

J Albanell

Publications and source records attributed to J Albanell.

53 records · Page 3Linked to original sources
PubMed1997

PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner.

PD153035 is reported to be a specific and potent inhibitor of the epidermal growth factor (EGF) receptor tyrosine kinase and, to a lesser degree, of the closely related HER2/neu receptor. We show that PD153035 inhibits EGF-dependent EGF receptor phosphorylation and suppresses the proliferation and clonogenicity of a wide panel of EGF receptor-overexpressing human cancer cell lines. EGF receptor autophosphorylation in response to exogenous EGF was completely inhibited at PD153035 concentrations of >75 nM in cells overexpressing the EGF receptor. In contrast, PD153035 only reduced heregulin-dependent tyrosine phosphorylation in HER2/neu-overexpressing cell lines at significantly higher concentrations (1400-2800 nM). PD153035 exposure did not affect the expression of either EGF receptors or HER2/neu. PD153035 caused a dose-dependent growth inhibition of EGF receptor-overexpressing cell lines at low micromolar concentrations, and the IC50 in monolayer cultures was less than 1 microM in most cell lines tested. At doses of up to 2.5 microM, the IC50 for HER2/neu-overexpressing cells was not reached. In colony-forming assays, the PD153035 growth-inhibitory activity in cultures driven by endogenous (autocrine) ligand was correlated with EGF receptor number, with higher activity in cells expressing higher numbers of EGF receptors and only minimal activity in cells expressing normal numbers of EGF receptors but high HER2/neu levels. PD153053 also abolished all growth effects mediated by the addition of exogenous EGF; this condition could be reversed upon removal of the compound. Cotreatment with C225, an anti-EGF receptor-blocking monoclonal antibody, further enhanced the antitumor activity of PD153035, suggesting mechanisms of action for C225 other than competition with ligand binding. This latter finding also suggests that combined anti-EGF receptor strategies may be of enhanced benefit against tumors with high levels of EGF receptor expression.

Adenocarcinoma↗
PubMed1996

Telomerase activity is repressed during differentiation of maturation-sensitive but not resistant human tumor cell lines.

The effects of induced differentiation on telomerase activity were examined in human acute promyelocytic leukemic (NB4) and human embryonal carcinoma (NTERA-2) cells exposed to all-trans-retinoic acid or hexamethylene bisacetamide. Retinoic acid treatment of NB4 and NTERA-2 cells, and hexamethylene bisacetamide treatment of NTERA-2 cells caused a decline in telomerase activity in differentiation-sensitive but not in resistant clones of these cell lines. Changes in telomerase activity as measured by the PCR-based telomeric repeat amplification protocol assay were noted by 24-72 h of exposure to the inducer, suggesting that its regulation may precede terminal differentiation. The degree of telomerase activity decline was greater in NB4 cells than in NTERA-2 cells, probably reflecting in part a more mature state of NB4 cells after 5 days of exposure to the inducer. Mixing of protein extracts from treated and untreated cells did not suggest the presence of diffusible telomerase inhibitors. Expression of the RNA component of telomerase was also examined in NB4 cells, and its decline correlated with the reduced telomerase activity measured by the telomeric repeat amplification protocol assay during induced differentiation of these tumor cells. Taken together, these findings indicate that telomerase is a regulated enzyme system during induced human tumor cell differentiation, showing an inverse relationship between the degree of differentiation and telomerase activity. These models will be be useful to study the regulation and role of telomerase during induced differentiation of human tumor cells.

Acetamides↗
PubMed1996

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

Actuarial Analysis↗
PubMed1996

Five-day course of granulocyte colony-stimulating factor in patients with prolonged neutropenia after adjuvant chemotherapy for breast cancer is a safe and cost-effective schedule to maintain dose-intensity.

PURPOSE: To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS: Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS: None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION: A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.

Adult↗
PubMed1996

[Preliminary results of a phase II randomized controlled trial comparing M-VAC and M-CAVI in patients with bladder cancer (T2-4 N0-1 M0)].

OBJECTIVES: The combination of carboplatin, methotrexate and vinblastine (M-CAVI) is an active and well-tolerated regimen for patients with bladder cancer who are ineligible for cisplatin-based regimens. We have prospectively randomized patients with locally advanced (T2-4 N0 M0) or locoregional (Tx N1 M0) bladder cancer suitable for subsequent surgical treatment to M-VAC or M-CAVI chemotherapy. METHODS: M-CAVI consisted of carboplatin (300 mg/m2 on day 1 and later adjusted to 4.5 mg/dl/min according to Calvert's formula), methotrexate (30 mg/m2 on days 1, 15 and 22) and vinblastine (3 mg/m2 on days 1, 15 and 22). After 3-4 cycles, the patients were assessed for surgical resection. RESULTS: To date, 60 patients have been included. There were 58 completely evaluable patients, 27 were randomized to M-VAC and 31 to M-CAVI. The overall response rates were similar for M-VAC (48%; confidence interval 95%, 26%-67%) and M-CAVI (45%; confidence interval 95%, 28%-62%). The pathological complete responses were similar for the M-VAC and M-CAVI regimens for both the group with locally advanced (27% vs 39%, p = NS) and locoregional (14% vs 14%, p = NS) bladder cancer. The median actuarial survival for the M-VAC treated group was 23 months and 18 months for the M-CAVI. M-VAC therapy was statistically significantly associated with more events of granulocytopenic fever, grade 2-3 nausea and vomiting, grade 2 alopecia and grade 3-4 mucositis. CONCLUSIONS: The results achieved in the 60 patients included in the study indicate that M-CAVI is better tolerated than M-VAC, although both treatment regimens have similar overall response rates, pathological response rates and survival in patients with locally advanced and locoregional bladder cancer.

Adolescent↗
PubMed1995

Phase II trial of an all-oral regimen of tegafur and folinic acid in patients with previously treated metastatic breast cancer.

BACKGROUND: Tegafur is an antimetabolite slowly metabolized to 5-fluorouracil in vivo. Protracted administration of oral tegafur is active in metastatic breast cancer, with reported response rates ranging from 29 to 44%. The addition of folinic acid could improve the efficacy of tegafur by means of biochemical modulation. METHODS: A prospective Phase II trial in patients with pretreated metastatic breast cancer was performed. The regimen consisted of oral tegafur (750 mg/m2/day) and oral folinic acid (45 mg/day) for 21 days, recycling at day 28. RESULTS: Twenty-five patients were included. Eight partial responses were observed for an objective response rate of 32% (95% confidence intervals for response, 23-41%). The median duration of response was 7 months. According to WHO criteria, 24% of patients experienced grade 3 mucositis and 12% grade 3 diarrhea, but no other significant toxicities were observed. Twenty-eight percent of patients required dose reductions for toxicity. CONCLUSIONS: A significant response rate with oral tegafur and folinic acid in patients with heavily pretreated breast cancer was found. This all-oral regimen, which could be safely administered on an outpatient basis, deserves further evaluation to define the role of folinic acid on the activity of tegafur in metastatic breast cancer.

Administration, Oral↗
PubMed1995

Malignant lymphoproliferative diseases in HIV-seropositive patients. A study of 40 cases at a single institution in Spain.

We identified 40 patients with malignant lymphoproliferative diseases (MLD) and HIV infection (seropositive) at a single Spanish university hospital. Thirty-two patients had non-Hodgkin's lymphoma (NHL), 6 primary central nervous system lymphoma (PCL) and 8 patients Hodgkin's disease (HD). Median age at presentation was 32 years. Four histopathological groups had distinct presenting clinical features: in 93% of the Burkitt-type lymphomas, the lymphoma itself was the AIDS defining criterion, while high and intermediate grade NHL other than Burkitt-like tended to have a more advanced HIV infection, demonstrated by antecedent AIDS criteria in 58% of these patients and a median CD4 positive cell count of 291 mm3; HD occurred in some patients without previous opportunistic infections (7/8 patients) but with median CD4 cells of 105 mm3; PCL occurred in a terminal stage of HIV infection, in patients with a low performance status, and frequent antecedent AIDS criteria. Objective response to chemotherapy could be seen in 62% of NHL patients and 100% of HD. Survival was adversely related to an antecedent diagnosis of AIDS, low performance status, and a primary localization in the central nervous system. Overall median survival was 5 months, but patients without the mentioned three adverse prognostic factors had a median survival of 10 months.

Actuarial Analysis↗
PubMed1992

Carboplatin, methotrexate, and vinblastine in patients with bladder cancer who were ineligible for cisplatin-based chemotherapy.

BACKGROUND: A Phase II trial with a new regimen of methotrexate, carboplatin, and vinblastine (M-CAVI) was conducted for patients with bladder cancer who could not receive cisplatin-based chemotherapy. METHODS: Treatment consisted of methotrexate (30 mg/m2) on days 1, 15, and 22; carboplatin (300 mg/m2) on day 2; and vinblastine (3 mg/m2) on days 2, 15, and 22, scheduled at 28-day intervals. The dosage of carboplatin was adjusted for creatinine clearance. Twenty-five patients with metastatic (n = 9) or locally advanced or locoregional bladder cancer with a poor prognosis (n = 16) were treated with M-CAVI. Fifteen patients had abnormal serum creatinine levels, 4 had a low performance status, 3 had cardiac disease, and 3 were older than 70 years old. RESULTS: Among 23 patients assessable for clinical response, the response rate was 48%. The median duration of response for metastatic disease was 7 months. Among nine patients assessable for pathologic response, there were two complete responses and three partial responses. The toxic effects have been moderate. CONCLUSIONS: M-CAVI is an active and well-tolerated regimen that can be used in patients with bladder cancer who are ineligible to receive cisplatin-based chemotherapy.

Adult↗
PubMed1992

[Bladder neoplasm in a patient with panarteritis nodosa treated with cyclophosphamide].

Cyclophosphamide is used both in the treatment of malignant and non-malignant diseases. Urinary neoplasms secondary to its use have been described. We discuss the case of a patient with panarteritis nodosa treated with cyclophosphamide during 63 months, with a total dose of 210 grams, and that showed a bladder neoplasm 8 years after beginning of the treatment. In patients receiving a total dose of cyclophosphamide over 85 grams, a follow-up of ten years minimum should be performed aimed to the early detection of secondary neoplasms.

Adrenal Cortex Hormones↗
PubMed1992

[Spinal cord compression as a primary manifestation of occult thyroid carcinoma].

Metastatic disease is the first clinical manifestation of differentiated thyroid carcinoma (DTC) in less than 5% of cases. Bone metastases as the first sign of DTC are associated with a poor prognosis, both for being resistant to treatment and for complications due to them. Spinal cord compression is a rare development in DTC, which may present late in the course of the disease. An initial presentation of DTC with a spinal cord compression is an extremely rare condition.

Adenocarcinoma↗
PubMed1990

[Treatment with interferon of systemic Langerhans-cell histiocytosis in an adult].

We report an adult patient with systemic Langerhans' cell histiocytosis (LHX), who was refractory to multiple chemotherapy courses and in whom a partial clinical and biological 3-month remission was achieved with alpha-2-interferon. The patient's response was associated with an increase in the rate of natural killer cells and to a return to normal of the H/S T-lymphocyte ratio. Immunological abnormalities have been reported in this condition, and it is now accepted that the most important one is a decrease in suppressor lymphocytes. However, it is not known whether these abnormalities are endogenous or exogenous. The experience with modifiers of the biological response for the treatment of LHX is scanty, but the probable immunological pathogenesis of the condition justifies a therapeutic trial of those agents in patients not responding to conventional therapy.

Adult↗
PubMedDate not supplied

Early results of the value of p53 in predicting survival in a homogeneous cohort of patients with invasive bladder cancer treated with a neoadjuvant carboplatin-based regimen (M-CAVI).

AIMS AND BACKGROUND: Several reports on prognostic factors for infiltrating-bladder cancer have given controversial results. We assessed the prognostic value of p53 nuclear overexpression together with known prognostic factors for survival in patients with invasive T2-4 N0 M0 bladder cancer treated with neoadjuvant chemotherapy. STUDY DESIGN: Thirty-five paraffinized tumor samples from initial transurethral resection of patients with bladder cancer were analyzed immunohistochemically to detect overexpression of p53 protein. Patients were treated with 3 to 4 cycles of neoadjuvant methotrexate, carboplatin, and vinblastine (M-CAVI) and then underwent radical cystectomy. Prechemotherapy, treatment, and postchemotherapy factors were analyzed for correlation with survival by univariate and multivariate analysis. Fifty-seven percent of tumors were positive for p53 protein, 71.5% had grade III-IV tumors, and 72% had organ-confined disease. The median follow-up was 20 months (range 5-71+). RESULTS: By univariate analysis, the significant pretreatment factors were initial tumor (T) stage (P < 0.0001) and the male sex (P = 0.03). Five postchemotherapy variables were found significant: surgery performed according to protocol (P = 0.003), overall clinical (P = 0.004), and overall pathologic (P = 0.02) response to therapy, postchemotherapy pathologic stage (P = 0.0002), and tumor status after surgery (P = 0.0006). By multivariate analysis, the initial prechemotherapy T stage was the only factor that demonstrated independent significance. CONCLUSIONS: Although the median follow-up of the study is still too short, in this group of patients treated with a neoadjuvant carboplatin-based regimen, a classical variable (prechemotherapy T stage) rather than p53 nuclear overexpression was an independent prognostic factor for survival. Further follow-up will be required to assess the value of p53 overexpression as a prognostic factor in invasive bladder cancer patients treated with neoadjuvant carboplatin-based chemotherapy.

Aged↗
PubMedDate not supplied

Node-negative breast cancers with p53(-)/HER2-neu(-) status may identify women with very good prognosis.

BACKGROUND: The contribution of p53 and HER-2/neu to the management of node-negative breast cancer (NNBC) could be improved by combining their results. MATERIAL AND METHODS: We studied paraffin-embedded primary tumors for p53 (BP-53-12-1) (n=57) and HER2/neu (pAB1) (n=63) from NNBC patients. The results were grouped in a negative (p53(-)/neu(-)) versus a positive group (one or both overexpressed). The association between both groups (negative and positive) and clinicopathologic parameters, S-phase fraction and DNA ploidy, and patients' outcome, was analyzed. RESULTS: In 28% of the tumors p53 was overexpressed, and HER2/neu in 11%. Sixty-five percent (37 out of 57) were p53(-)/neu(-), and 35% overexpressed one (31.5%) or both (3.5%) oncoproteins. Significant correlations were found between p53(-)/neu(-) tumors and age greater than 50 (p=0.003), S-phase fraction lower than 7 (p=0.03), and positive estrogen receptor contents (p=0.049). Actuarial 5-year disease-free and overall survival for p53(-)/neu(-) tumors were 88% and 97%, respectively, versus 50% and 66%, for tumors overexpressing one or both oncoproteins (p=0.004).

Age Factors↗