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N Gross

Publications and source records attributed to N Gross.

At least 37 records · Page 2Linked to original sources
PubMed1998

The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma.

OBJECTIVE: To determine the outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. METHODS: Prospective analysis of 27 eyes in 22 patients with group V retinoblastoma treated with either 2- or 6-cycle chemoreduction and focal treatment methods (argon laser photocoagulation, transpupillary thermotherapy, cryotherapy, and plaque radiotherapy). The need for external beam irradiation and the eventual globe salvage rate were assessed. Median follow-up was 28 months. RESULTS: There were 16 eyes in the 2-cycle chemoreduction treatment group and 11 eyes in the 6-cycle chemoreduction treatment group. No significant difference was noted between the 2 groups with respect to baseline patient and eye findings. After chemoreduction treatment, external beam irradiation was necessary in 12 (75%) of 16 eyes in the 2-cycle chemoreduction treatment group and in 4 (36%) of 11 eyes in the 6-cycle chemoreduction treatment group. There was no statistical difference between the 2- and 6-cycle chemoreduction treatment groups with respect to necessity for external beam irradiation (logistic regression analysis). All 4 eyes in the 2-cycle chemoreduction treatment group and 3 of 12 eyes in the 2-cycle chemoreduction treatment and irradiation group were eventually enucleated, the globe salvage rates being 0% and 75%, respectively. Two of 7 eyes in the 6-cycle chemoreduction treatment group and 1 of 4 eyes in the 6-cycle chemoreduction treatment and irradiation group were enucleated, the globe salvage rates being 71% and 75%, respectively. Except for the 2-cycle chemoreduction treatment group, in which the globe salvage rate was significantly lower (P = .03), there was no difference among the other 3 groups (2-cycle chemoreduction treatment and irradiation, 6-cycle chemoreduction treatment, and 6-cycle chemoreduction treatment and irradiation) with respect to globe salvage (logistic regression analysis). CONCLUSIONS: Local tumor control of group V retinoblastoma is possible with 6-cycle chemoreduction and focal therapy when external beam irradiation is not used. A larger sample size is necessary to determine how often external beam irradiation can be avoided.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Extensive phenotypic analysis of CD34 subsets in successive collections of mobilized peripheral blood progenitors.

The transplantation of mobilized progenitor cells after high-dose chemotherapy shortens haemopoietic engraftment. CD34 cell subsets were examined in 20 consecutive mobilized progenitor cell collections obtained from patients with solid tumours that had not been previously treated. The analysis of CD34 cells was based on the expression of intracellular antigens, surface antigens including CD38, and cell size using multi-dimensional flow cytometry. We also correlated the numbers of stem cell subsets reinfused to haemopoietic recovery. The majority of CD34+ cells expressed CD13 and CD33. A significant proportion was cytoplasmic myeloperoxidase (cMPO) positive. CD34+ MPO+ cells increased significantly in late collections. MPO expression was related to cell size. Cells expressing CD13 also increased in late collections in parallel to CFU-GM count. Small subpopulations of CD34+ CD38+ were committed to B cells, T cells and erythroid cell lineages. A small population expressing the megakaryocytic antigen had a small size and were predominantly CD38-. A minor subpopulation expressed stem cells antigens. These were significantly higher in late collections (CD34+ Thy-1+ and CD34+ CD33-). After mobilization, patients received three cycles of intensive chemotherapy followed by reinfusion of mobilized progenitors (5.45 x 10(6)/kg CD34+ cells, range 3.4-11.88). The numbers of reinfused CD34 cells or the individual subsets did not influence recovery of leucocytes (9 d) or platelets (9 d). In conclusion, the numbers of stem cells and their subsets differed between collections and, in unpretreated patients receiving intensive chemotherapy, there was no delayed engraftment when sufficient numbers of stem cells were reinfused. The recovery period was short and not correlated to any stem cell subsets.

Adult↗
PubMed1998

Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease. Dey Combination Solution Study Group.

Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) potentially can provide increased benefit over single-agent therapy. The objective of this double-blind, randomized, positive-control trial was to determine the effectiveness of an albuterol-ipratropium solution aerosol combination (Dey combination solution, Dey LP, Napa, Calif., USA) compared with solution aerosols of both component medications administered alone in patients with COPD. The trial consisted of a 6-week, 3-period crossover phase followed by a 6-week parallel phase during which patients self-administered study medications by inhalation from a nebulizer. A total of 863 patients were initially randomized to each of the six possible treatment sequences of the three study medications in the crossover phase and received each study medication in turn for a 2-week period. Patients continued to receive the same treatment administered during the last 2-week period of the crossover phase for an additional 6 weeks in the parallel phase. Assessment of 1-second forced expiratory volume (FEV1) curves before and after dosing on the last day of each 2-week period indicated that the combination was superior to either single agent in peak effect and area under the curve up to 8 h after dosing (FEV1-AUC0-8), in both phases of the trial. The use of Dey combination during the crossover phase resulted in 24% more improvement in peak FEV1 than was seen with albuterol alone (p < 0.001), and 37% more than was seen with ipratropium alone (p < 0.001). Similarly, when examining FEV1-AUC0-8, Dey combination resulted in 30% more improvement than was seen with albuterol alone (p < 0.001), and 32% more than was seen with ipratropium alone (p < 0.001). The combination affords a convenient dosing regimen and incorporates enhanced benefit without compromising the safety profile of either component agent.

Adult↗
PubMed1997

Absence of functional CD44 hyaluronan receptor on human NMYC-amplified neuroblastoma cells.

CD44 represents a heterogeneous group of surface glycoproteins, involved in cell-cell and cell-matrix interactions. CD44 is the major receptor for hyaluronate (HA), a component of cell matrices, and most of CD44 known functions are attributed to its ability to recognize HA. We have recently shown that although a majority of human neuroblastomas (NBs), a childhood cancer, express high levels of CD44H, high stages and tumors with amplification of the NMYC proto-oncogene fail to express CD44. Lack of CD44 expression is strongly associated with the presence of NMYC amplification and has been further shown to represent a new feature for predicting risk of disease progression and dissemination. In the present study, we have investigated the role of CD44 expressed by NB cell lines and the possible relationship among the presence of NMYC amplification, functional expression of CD44 receptor, and tumorigenic properties of NB cells. A panel of cell lines with variable NMYC amplification and/or overexpression, as well as clonal and stable NMYC-transfected NB cells, were analyzed for CD44 expression and ability to bind HA. Our results confirmed previous observations that in NB cell lines lack of CD44 is not always related to the presence of NMYC amplification, with a number of cell lines or transfectants with both CD44 expression and NMYC amplification. However, the ability of the CD44 receptor to bind immobilized hyaluronan was restricted to CD44H+ cell lines without NMYC amplification (SH-EP and ACN). The HA-binding function was CD44 dependent and could be specifically blocked by an anti-CD44 antibody. No induction of functional HA binding was obtained with NMYC-amplified cell lines or NMYC transfectants, despite an induced increase of CD44 expression upon differentiation or after tentative activation of the receptor with phorbol esters. Inhibition of N-linked glycosylation with tunicamycin resulted in decreased HA binding of cells bearing an active CD44 receptor. We conclude that NMYC-amplified NB cell lines either do not express CD44 at all or express a nonfunctional receptor, whereas nonamplified cells constitutively express an active receptor. The lack of functional HA binding in NB cells might be partly due to incomplete N-glycosylation. The involvement of NMYC in the regulation of N-linked glycosylation can be suspected.

Antibodies, Blocking↗
PubMed1997

Clinical relevance of CD44 cell surface expression and MYCN gene amplification in neuroblastoma.

This multicentric analysis of tumours obtained from 140 patients with neuroblastoma confirms that the lack of CD44 expression is a highly significant factor of poor prognosis and, as previously published in multivariate analysis of the four factors, i.e. MYCN amplification, CD44 expression, age and tumour stage, CD44 expression and tumour stage were the only independent prognostic factors of event-free survival (Combaret et al., J Clin Oncol 1996, 14, 25-34). Furthermore, CD44 analysis affords significant prognostic discrimination in subgroups of patients with or without MYCN amplified tumours, both in low-stage neuroblastomas and high-grade neuroblastomas. In the subgroup of patients with low-stage neuroblastoma and the stage 4 subgroup, CD44 was the only independent prognostic factor for the prediction of event-free survival in a multivariate analysis. In conclusion, CD44 is one of the most powerful factors for predicting clinical outcome in neuroblastoma at the time of initial staging.

Age Factors↗
PubMed1997

Clinical relevance of TRKA expression on neuroblastoma: comparison with N-MYC amplification and CD44 expression.

TRKA expression was evaluated on 122 untreated neuroblastomas by immunohistochemistry using an antibody with predetermined specificity. This procedure is simple and reliable for protein detection at cellular level in a routine clinical setting. Fourteen tumours were classified as benign ganglioneuroma with a restricted expression of TRKA on ganglion cells; these patients were excluded from the following analysis. A total of 108 tumours were classified as neuroblastoma or ganglioneuroblastoma; 74 expressed TRKA protein, which strongly correlated with low stage, absence of N-MYC amplification, age (<1 year), CD44 expression and favourable clinical outcome. In a univariate analysis including tumour stage, age, histology, N-MYC amplification, CD44 and TRKA expression, all parameters had significant prognostic value. The absence of TRKA expression on CD44-positive or N-MYC non-amplified tumours permits the characterization of a subgroup of patients with intermediate prognosis. However, in a multivariate analysis taking into consideration the prognostic factors mentioned above, CD44 and tumour stage were the only independent prognostic factors for the prediction of patients' event-free survival.

Analysis of Variance↗
PubMed1996

Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.

PURPOSE: In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions. METHODS: Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region. RESULTS: In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage. CONCLUSION: The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.

Antibodies, Monoclonal↗
PubMed1995

Expression of stem cell factor and its receptor by human neuroblastoma cells and tumors.

Bone marrow (BM) is a frequent site of metastasis in children with neuroblastoma (NB). Nonhematopoietic cell lines of the same neuroectodermal origin produce both stem cell factor (SCF) and its receptor, the product of the c-kit protooncogene (c-kit). Because recombinant SCF is likely to be soon clinically tested to accelerate BM recovery after high-dose chemotherapy, a treatment administered to children with disseminated NB, we addressed the question of whether SCF/c-kit complex could play a role in the proliferation and metastasis of NB cells. Northern blot analysis showed SCF mRNA transcripts in 7 of 8 (88%) NB cell lines and c-kit in 1 (13%). Neither c-kit nor SCF could be detected by Western blotting in cell extracts or by surface immunofluorescence and flow cytometry. Soluble SCF protein was detected by enzyme immunoassay at low concentrations in the cell supernatants in the same 7 NB cell lines. Treatment of 4 NB cell lines by SCF +/- cytokines relevant to BM physiology did not induce c-kit antigenic expression or modulate 3H-thymidine uptake. Likewise, the latter was not changed by incubating the cells with anti-c-kit neutralizing antibodies. Immunohistochemical analysis showed weak diffuse or focal staining for SCF and c-kit in few primary or metastatic tumor samples, only once simultaneously. We conclude that NB cell lines usually produce low levels of soluble SCF but do not express c-kit and that both proteins are rarely detected in NB tumors. The SCF/c-kit complex appears to be unlikely to stimulate NB growth or metastasis; thus, recombinant SCF could be safely administered to children with NB.

Cell Division↗
PubMed1995

CD44 expression and modulation on human neuroblastoma tumours and cell lines.

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment and tumour metastasis. A large family of variants or isoforms, generated by alternative splicing of a single gene, has been reported to be involved in the malignant process, by conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumour characterised by an aggressive and metastatic behaviour in advanced stages, with amplification of the MYCN protooncogene. In this report, we show that the CD44 standard molecule was highly expressed in the majority of tumours of stages 1-3, in all stage 4s and ganglioneuromas, but only in a subset of stage 4 tumours. A lack of CD44 expression was observed in all MYCN amplified stage 4 tumours, thus demonstrating a highly significant inverse relationship between MYCN amplification and CD44 expression in neuroblastoma. In addition, the expression of 4 different CD44 isoforms was measured on all specimens and was always found to be negative. Using neuroblastoma cell lines and MYCN expressing transfectants, we show that CD44 expression by neuroblastoma cell lines is not directly related to MYCN amplification, but is associated to the stage of differentiation or lineage, and to the tumorigenic properties of the cells. In addition, CD44 expression can be upmodulated parallel to differentiation or maturation as induced by retinoic acid, bromodeoxyuridine or phorbol ester. In contrast, cytokines such as IFN gamma, TNF alpha, or growth factors such as bFGF, SCF and TGF beta were ineffective in modulating CD44 expression.

Biomarkers, Tumor↗
PubMed1995

Effects of stem cell factor and other bone marrow-derived growth factors on the expression of adhesion molecules and proliferation of human neuroblastoma cells.

Metastasis in children with neuroblastoma (NB) is a poor prognostic factor despite intensive therapy. In the near future, stem cell factor (SCF) is likely to be used clinically to accelerate bone marrow (BM) recovery after high-dose chemotherapy in patients with advanced NB. The high frequency of BM metastases in NB could be secondary to BM-derived human growth factors (HGF) modulating the adhesion, secondary growth (or both) of circulating metastatic NB cells. To test this hypothesis, we studied the in vitro effects on NB cell lines grown in chemically defined medium of SCF, interleukin (IL)-1 beta, IL-3, IL-6, basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) used alone or in combination. The antigenic expression of NB-associated cell adhesion molecules (CAM) HLA class 1, intercellular CAM-1, neural-CAM and CD44 were assayed by monoclonal antibodies and flow cytometry, and DNA synthesis by 3H-thymidine uptake. The expression of CAM was not modulated by SCF or other HGFs. An increase in thymidine uptake was induced by bFGF alone in IMR-32 cells, while SCF and other HGFs had no notable effect. Our results indicate that SCF and other BM-derived HGFs are unlikely to have a generalised effect on the expression of adhesion molecules by NB cells or proliferation. The clinical administration of recombinant human SCF to children with NB should be safe.

Cell Adhesion Molecules↗
PubMed1994

Altered growth and phenotype in clonal mycN transfectants of the SK-N-SH neuroblastoma cell line.

We have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed out-growth of autocrine cells with evidence of an advanced malignant phenotype in a mycN-transfected clonal cell line derived from the single-copy mycN neuroblastoma, SK-N-SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class-I molecules. Clones with high levels of mycN expression had a Schwann/glial-like phenotype with higher surface HLA class-I display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage-independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.

Animals↗
PubMed1994

CD44H expression by human neuroblastoma cells: relation to MYCN amplification and lineage differentiation.

The human CD44 cell surface glycoprotein has been involved in a variety of functions including lymphocyte homing, extracellular cell matrix attachment, and tumor metastasis. Due to the alternative splicing of the single gene, a large family of different variants or isoforms is generated. Several reports have indicated an up-regulation of CD44 variant (v) isoforms in malignant process, conferring metastatic potential to non-metastatic cells. Neuroblastoma is a tumor characterized by an aggressive and metastatic behavior in advanced stages with amplification of the MYCN protooncogene. In this report we show that the CD44 standard molecule is highly expressed in 100% of stage I-III, IVs neuroblastomas and ganglioneuromas but only in a subset of stage IV tumors. In contrast, no expression of CD44 was detected on MYCN amplified stage IV tumors, thus demonstrating a highly significant negative relationship between MYCN amplification and CD44 expression in neuroblastoma. The expression of CD44 on neuroblastoma cultured cell lines was not shown to be related to MYCN amplification but rather linked to the S-type, schwann/glial differentiation lineage. Immunochemical analysis of tumor samples with anti-CD44v3 and -v6 antibodies and Northern blot analysis of mRNA from cell lines with probes spanning exons 4-10 did not reveal any expression of splice variants on neuroblastomas of all stages and cell lines, thus ruling out a major role of these isoforms in neuroblastoma progression and metastasis.

Blotting, Northern↗
PubMed1993

Comparative cost-effectiveness analysis of theophylline and ipratropium bromide in chronic obstructive pulmonary disease. A three-center study.

The charts of 311 patients receiving theophylline (T) and 289 patients receiving ipratropium bromide (IB) for COPD were reviewed to determine the total costs and cost-effectiveness of these 2 agents in 3 different health-care settings. A direct cost-accounting method assessed cost, and a Markov decision-analysis model calculated cost-effectiveness. Costs to treat toxic effects were greater for T versus IB. The types and incidences of toxic effects, by drug, were similar among the three centers. Overall costs for T were $121.40 per patient per therapy-month versus $84.56 per patient per therapy-month for IB, as determined by the cost-accounting method. The marginal cost was $366 for T over IB when extrapolated over 1 year using the Markov model. The Markov model also predicted that patients receiving IB had a greater number of complication-free therapy-months (measurement of effectiveness) than patients receiving T. We conclude that treatment with IB was less costly and more cost-effective than T.

Aged↗
PubMed1992

Differentiation-related expression of adhesion molecules and receptors on human neuroblastoma tissues, cell lines and variants.

The expression of cellular adhesion molecules (CAM) involved in cell adhesion and immune recognition was measured on neuroblastoma tissue samples, on a neuroblastoma (NB) cell line, SK-N-SH, and on 3 phenotypically different variants, SH-SY5Y, SH-EP, SH-IN, representing neuronal, Schwannian/glial or intermediate NB-cell types. Immunohistochemical analysis of CAM expression by NB and related tumors at different stages of differentiation revealed a co-expression of several CAM (ICAM-1/CD54, LFA-3, VLA-2 and HLA-ABC) associated with low stages and more highly differentiated NB tumors and peripheral neuroepitheliomas (PN). In contrast, N-CAM was uniformly expressed on all NB tumors. Flow cytometric analysis of CAM surface expression by SK-N-SH and variant cells revealed highly variable phenotypes. Expression of ICAM-1, LFA-3, VLA-2 and HLA-ABC molecules was associated with the epithelial cell type represented by the SH-EP variant. In contrast, low expression of these molecules and high expression of N-CAM was associated with the neuronal SH-SY5Y cells. Exposure of the NB cells to differentiation inducers (retinoic acid, 5'-bromodeoxyuridine and phorbol esters) and cytokines (tau-interferon, alpha-tumor necrosis factor) resulted in a variable up-regulation of the expression of all CAMs, except N-CAM, regardless of the type of differentiation induced. In an attempt to establish a link between the pattern of expression of CAM on NB cells and their susceptibility to natural killer (NK) or lymphokine-activated killer (LAK) cell lysis, the analysis revealed that NB cells expressing CAM and a differentiated phenotype were less susceptible to NK lysis, but no difference in the sensitivity of the NB cell types to LAK effectors was observed. Treatment of NB target cells with cytokines or PMA decreased their susceptibility to NK and LAK lysis, while induction of differentiation with RA or BUdR resulted in no changes in the sensitivity to NK and LAK lysis. In conclusion, expression of HLA-ABC and several co-regulated CAMs was shown to be associated with a differentiated phenotype in NB, with an overall decreased sensitivity to NK/LAK effector cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Energy demands for walking in dysvascular amputees as related to the level of amputation.

Cardiac function and oxygen consumption were measured in 25 patients who underwent amputation for peripheral vascular disease (PVD), and in five similarly aged control patients with PVD. Five patients at each of the midfoot, Syme's, below-, through-, and above-knee amputation levels and the five controls were measured at rest, normal walking speed, and maximum walking speed on a treadmill. At normal walking speed, all of the patients functioned at approximately 80% of their cardiac capacity. Normal walking speed and cadence decreased and oxygen consumption per meter walked increased with more proximal amputation. The ratio of cardiac function and oxygen consumption at normal walking speed as compared with at rest increased with more proximal amputation, and the capacity to increase walking speed and oxygen consumption lessened. Our results suggest that peripheral vascular insufficiency amputees function at a level approaching their maximum functional capacity. At more proximal amputation levels, the capacity to walk short or long distances is greatly impaired.

Amputation, Surgical↗