Biomedical subjects

C Abboud

Publications and source records attributed to C Abboud.

6 recordsLinked to original sources

PubMed2000

Outcomes of high-dose chemotherapy and autologous stem cell transplant in isolated locally recurrent breast cancer: a multicenter evaluation.

To determine the outcomes of women with isolated loco-regional recurrence (LRR) of breast cancer treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) following conventional therapy, we conducted a retrospective review of 58 patients from five institutions treated between 1990 and 1998. Forty-five patients (78%) had > or = 2 poor prognostic factors (PPF) (defined as disease-free interval preceding LRR < or = 2 years, hormone receptor negative/refractory disease, and incomplete resection). At median follow-up of 14.2 (0.5-72) months, 36 patients (62%) developed progressive disease. Disease progression usually occurred at local (27 patients) vs distant (nine patients) sites. Median time to disease progression following ASCT was 6.1 (1.3-31.4) months. At last follow-up, 23 patients (40%) had expired (all due to disease progression), and 13 (22%) were alive with, and 22 (38%) without progressive disease. By Kaplan-Meier analysis, the estimated median PFS and OS was 20.3 and 29.2 months, respectively. In a multivariate model, complete remission at time of HDCT and estrogen-receptor positive disease were predictive of significantly longer PFS and OS. The survival of this cohort was similar to previous reports of those treated with conventional therapy alone, and to those with distant metastases treated with HDCT. Frequent progression locally, suggests that strategies to improve local disease control are needed.

Adult↗

PubMed1999

Effect of nitric oxide production and oxygen tension on progenitor preservation in ex vivo culture.

Many cell types are capable of expressing inducible nitric oxide synthase (iNOS) in response to cytokines or endotoxin. We detected iNOS mRNA by reverse transcriptase polymerase chain reaction in CD34+ human bone marrow cells after 48-hour incubation with interferon-gamma (IFN-gamma)/tumor necrosis factor alpha (TNF-alpha) and IFN-gamma/lipopolysaccharide. Based on this finding, we examined the effect of nitric oxide (NO) on hematopoiesis and particularly on proliferation and survival of CD34+ marrow cells in in vitro culture. When CD34+ cells were cultured in the presence of an NO donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a dose-dependent inhibition of cell proliferation was observed. Addition of the selective iNOS inhibitor, L-N6-(1-iminoethyl)-lysine hydrochloride (L-NIL) at a dose of 500 microM increased the cell counts by 23% (range 0-89%). The expansion of total CD34+ cell number was 4-fold with a hematopoietic cytokine cocktail compared to 5.2-fold with the addition of L-NIL to this combination. At days 7 and 14 of culture, SNAP induced apoptosis in CD34+ human bone marrow cells detected by an in situ terminal deoxynucleotidyl transferase assay. The apoptosis was partially inhibited with the addition of L-NIL. SNAP also inhibited cell cycling, as evidenced by a 56% decrease in the number of cells in S phase after 5 days of culture in the presence of SNAP. To investigate if NO production was dependent on oxygen tension, J774A mouse macrophage cells were induced with lipopolysaccharide/IFN-gamma, and nitrite production measured by the Griess reaction. Nitrite production was persistently less in 5% compared to 21% oxygen. CD34+ marrow cells from normal donors were also grown under variable oxygen tension, and the cell proliferation in 5% oxygen was significantly greater at both 7 and 14 days of culture. CFU-GM colony growth also was increased in the low oxygen setting. The concentration of various cytokines was measured in CD34+ progenitor culture supernatants, including interleukin (IL)-1 alpha, IL-1 beta and TNF-alpha. SNAP increased IL-1 alpha production by CD34+ cells as well as from light-density bone marrow cells, whereas the effect on IL-1 beta and TNF-alpha production was not significant. Manipulation of oxygen tension and the inhibition of production of reactive oxygen and nitrogen intermediates may have potential to optimize cell expansion and progenitor preservation in ex vivo culture systems.

Animals↗

PubMed1999

Continuous infusion cyclosporine and nifedipine to day +100 with short methotrexate and steroids as GVHD prophylaxis in unrelated donor transplants.

Unrelated donor marrow transplantation is associated with an increased incidence of graft-versus-host disease (GVHD) compared with sibling donor transplants. Forty-one patients undergoing unrelated donor transplants were treated with a GVHD prophylaxis regimen that consisted of continuous infusion cyclosporine from day -1 to 100 days post transplant along with nifedipine, glucocorticoids and short-course methotrexate. The regimen was well-tolerated in this cohort with mostly high risk disease. Fifty-one percent of patients developed acute GVHD, which was grade III-IV in 22% of patients. Six of 22 patients at risk for chronic GVHD developed extensive chronic GVHD, five of whom were adults. In patients <18 years of age, there was a >40% chance of 2 year disease-free survival. Use of continuous infusion cyclosporine with nifedipine as an immunosuppressant and protectant against cyclosporine-induced toxicities in unrelated donor transplants is well-tolerated, and results in acute GVHD incidence favorable to that reported with bolus cyclosporine.

Adolescent↗

PubMed1997

Prolactin receptor messenger ribonucleic acid in normal and neoplastic human pituitary tissues.

We examined the specific cell types in normal human pituitaries that expressed PRL receptor (PRL-R) messenger ribonucleic acid (mRNA) by combined in situ hybridization and immunohistochemistry. The distribution of PRL-R mRNA in 28 pituitary adenomas was examined by in situ hybridization and reverse transcription-PCR in 12 cases of adenomas. In another set of experiments, 34 PRL adenomas from men, women, and bromocriptine-treated patients were analyzed for PRL-R by in situ hybridization. In the normal pituitary, PRL- and LH-producing cells had significantly more mean grain counts per cell and higher percentages of cells positive for PRL-R than GH and TSH cells. PRL-R mRNA was present in all groups of adenomas by in situ hybridization and reverse transcription-PCR. PRL adenomas had a significantly higher density of labeling compared to other adenoma types. Although there was no difference in the levels of PRL-R mRNA in PRL adenomas from men and premenopausal and postmenopausal women, patients treated with bromocriptine before pituitary surgery had significantly lower levels of PRL-R compared to all other groups. These results indicate that in the normal pituitary, PRL and LH cells have the highest level of PRL-R mRNA, whereas PRL adenomas have significantly higher levels of PRL-R mRNA than other types of adenomas, and bromocriptine treatment decreases the levels of PRL-R mRNA in PRL adenomas.

Adenoma↗

PubMed1994

Stem cell factor regulates human melanocyte-matrix interactions.

Stem cell factor (SCF) is hypothesized to play a critical role in the migration of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, c-kit, result in defects in coat pigmentation in mice and in skin pigmentation in humans. In this report we directly show that SCF alters the adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands and regulates integrin expression at the protein level. SCF decreased adhesion of neonatal and fetal cells to collagen IV, and increased attachment of fetal cells to laminin. Attachment of fetal cells to fibronectin was decreased, but was unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes showed that SCF down-regulated the expression of the alpha 2 receptor, and up-regulated the expression of the alpha 3, alpha 5 and beta 1 integrin receptors. SCF down-regulated expression of alpha 2, alpha 5 and beta 1 integrins by fetal melanocytes, and up-regulated expression of the alpha v and alpha 3 integrin receptors. Analysis of melanocyte migration using time-lapse videomicroscopy showed that SCF significantly increased migration of neonatal, but not fetal, melanocytes on fibronectin (FN). We conclude that SCF regulates integrin expression at the protein level and that SCF has pleiotropic effects on melanocyte attachment and migration on ECM ligands. We suggest that this may be one mechanism by which SCF regulates melanocyte migration during development of the skin.

Cell Adhesion↗

PubMed1988

Ectopic ACTH syndrome caused by a bronchial carcinoid tumor responsive to dexamethasone, metyrapone, and corticotropin-releasing factor.

Cushing's syndrome due to bronchial carcinoid tumors that secrete adrenocorticotropin (ACTH) may be difficult to distinguish from pituitary Cushing's disease, since the responses to dexamethasone and metyrapone are sometimes similar. Recently, the ACTH and cortisol responses to ovine corticotropin-releasing factor (oCRF) have been shown to be different in pituitary Cushing's disease than in Cushing's syndrome due to other causes. It is not known if the response to oCRF can distinguish pituitary Cushing's disease from those ACTH-secreting bronchial carcinoid tumors that respond to dexamethasone and metyrapone. A case of Cushing's syndrome due to an ACTH-secreting bronchial carcinoid is described in which the responses to dexamethasone, metyrapone, and oCRF were indistinguishable from the responses observed in pituitary Cushing's disease. A bronchial carcinoid tumor should be considered even when responses to dexamethasone, metyrapone, and oCRF suggest pituitary Cushing's disease.

ACTH Syndrome, Ectopic↗