Search PubMed⌕ Search

Biomedical subjects

A Ribas

Publications and source records attributed to A Ribas.

68 records · Page 4Linked to original sources
PubMed1979

Iron toxicity studies of quelamycin.

A previous phase I study demonstrated excessive generalized toxicity (20 of 21 patients) and cardiotoxicity (eight of 21 patients) of single-day intermittent quelamycin (NSC-267703) treatment, and a modified schedule was recommended to overcome this acute toxicity. In the present study, 40 mg/m2 of quelamycin was administered iv on 2 or 3 consecutive days. This 2- or 3-day course was associated with a decrease in the incidence of general symptoms (five of nine patients) and a decrease in cardiotoxicity (none of nine patients). In addition, patients receiving multiple courses of quelamycin were evaluated. Clinical and pathologic findings supported the diagnosis of early hemochromatosis. In conclusion, quelaymcin administration was associated with acute and chronic iron-overloading toxicity. Acute iron toxicity was prevented by the administration of quelamycin at a dose of 40 mg/m2 iv on 3 consecutive days. On the other hand, hemochromatosis was an unexpected finding which requires further investigations before this drug is acceptable for broader studies.

Adolescent↗
PubMedDate not supplied

Characterization of antitumor immunization to a defined melanoma antigen using genetically engineered murine dendritic cells.

A murine model of dendritic cell (DC)-based genetic immunization to a defined human melanoma antigen (Ag), MART-1/Melan-A (MART-1), was developed. The MART-1 gene was stably transfected into the nonimmunogenic mouse fibrosarcoma cell line NFSA that is syngeneic in C3Hf/Sem/Kam (C3H, H-2k) mice to generate the NFSA(MART1) cell line. In vivo protection from a lethal NFSA(MART1) tumor challenge could be generated by DCs transduced with a recombinant adenovirus (AdV) vector expressing MART-1 (AdVMART1). This model has the following characteristics: (a) immunological specificity and memory, (b) comparable protection for varying transduction multiplicities of infection, cell doses, and sites of DC inoculation but, interestingly, worse protection with increasing numbers of vaccinations, (c) the ability to treat small established tumors, (d) an absolute requirement for CD8 and CD4 T cells, (e) generation of MART-1-specific splenic cytotoxic T lymphocytes, and (f) up-regulation of both T helper type 1 and T helper type 2 cytokines. Genetically engineered DCs presenting defined tumor Ags represent an attractive method to generate effective immune responses.

Animals↗
PubMedDate not supplied

Ameboflagellates in bronchial asthma.

OBJECTIVE: To distinguish between the existence of detached ciliary tufts (DCTs) and the possibility of protozoa in the sputum of asthma patients. STUDY DESIGN: One hundred six samples of sputum obtained from 97 patients hospitalized with either asthma or other respiratory diseases were examined blindly. The combination of such criteria as movement, absence of basal plate, existence of red granules, positivity for ultraviolet light and Heidenhain's iron hematoxylin stain (for protozoa) was employed to distinguish between DCTs and true protozoa. RESULTS: The presence of ameboflagellates in sputum has a diagnostic accuracy of 86% in predicting or ruling. out the possibility of acute asthma. CONCLUSION: The presence of ameboflagellate forms is closely related to the existence of bronchial asthma, and these result reflect some etiopathogenic significance in asthma.

Acute Disease↗
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

Antitumor protection using murine dendritic cells pulsed with acid-eluted peptides from in vivo grown tumors of different immunogenicities.

Peptides extracted from tumor cells after mild acid treatment can function as antigenic epitopes when presented by cultured dendritic cells. Peptides were extracted from four tumors syngeneic to C3H mice, three weakly immunogenic tumors (FSA, MCAK, HCA) and one non-immunogenic tumor (NFSA). Dendritic cells pulsed with peptides extracted from the three weakly immunogenic tumors partially protect mice from a tumor challenge with the parental cell line. This protection was evident by a slower rate of tumor appearance and a slower tumor growth curve when compared to control, non-immunized mice. However, vaccination of mice with dendritic cells pulsed with peptides derived from the non-immunogenic cell line NFSA did not elicit a protective response. Neither the route of immunization, the number of immunizations, nor the amount of peptides significantly affected the antitumor protection. Dendritic cells genetically engineered to produce IL-2 did not increase the protective effect of peptide-pulsed dendritic cells. These results suggest that only a partial protection against immunogenic tumors can be achieved when dendritic cells pulsed with acid-eluted tumor peptides are used as antitumor vaccination.

Acids↗
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↗
PubMedDate not supplied

Endothelium-specific expression of an E-selectin promoter recombinant adenoviral vector.

BACKGROUND: E-selectin expression is very low in normal adult blood vessels, but is significantly elevated in newly formed tumor capillaries. We hypothesized that a viral vector which has transcriptional specificity for the tumor vasculature may be a tool for angiogenesis-targeted gene therapy. We therefore designed an adenoviral vector which would only be expressed in cells that transcribe the E-selectin gene. MATERIALS AND METHODS: The E-selectin promoter was inserted into an adenoviral vector driven by the luciferase reporter gene. The resulting AdV-Esel-Luc vector was then used to transduce endothelial cells as well as other cell types, and luciferase activity measured with a luminometric assay. RESULTS: Exposure of transduced endothelial cells to TNF-alpha (tumor necrosis factor-alpha), a known inducer of the E-selectin promoter, generated a 30-fold increase in luciferase expression compared to untreated cells (p = 0.01). Endothelial cells cultured in tumor conditioned media as an in vitro recreation of the tumor environment resulted in even higher induction of luciferase (p = 0.0001). Furthermore, many non-endothelial cell lines expressed minimal levels of luciferase when transduced with the AdV-Esel-Luc vector under identical conditions. CONCLUSIONS: We conclude that the E-selectin promoter can be used in order to confer transcriptional specificity to an adenoviral vector. This transcriptional specificity may in the future enable us to deliver the specific expression of therapeutic genes to the tumor vasculature.

Adenoviridae↗