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R E Gallagher

Publications and source records attributed to R E Gallagher.

At least 19 recordsLinked to original sources
PubMed1992

Survey design and observations relating to cancer education funding. Cancer Education Survey II: cancer education in United States medical schools (conducted by The American Association for Cancer Education with the support of the American Cancer Society).

A survey has been conducted of cancer education programs for medical students in United States medical schools by the American Association for Cancer Education with grant support from the Department of Detection and Treatment of the American Cancer Society (formerly the Professional Education Department). Two questionnaires were used, an Educational Resources Questionnaire (ERQ), which 126 of the 128 medical schools completed and returned, and a Faculty and Curriculum Questionnaire (FCQ), which was completed and returned by 1,035 faculty members who had been named as active in undergraduate medical student cancer education by respondents in each school who had been designated by the Dean's Office to complete the ERQ. Overall conclusions included: (1) increased coordination of cancer education activities is a major need in many schools; (2) there is widespread interest in the further development of cancer education objectives; (3) development of a national cancer education curriculum is needed; (4) there is interest in the development of improved instructional materials and methods; (5) development of evaluation methods is needed for cancer education programs; and (6) an ongoing funding process is needed to provide support for interdepartmental coordination of cancer education activities. Cancer prevention and detection topics were ranked above cancer treatment in plans for future curriculum emphasis. More detailed conclusions and recommendations are provided in this publication and three subsequent articles in this issue of the Journal of Cancer Education.

American Cancer Society↗
PubMed1992

Instructional methods and the use of teaching resources in cancer education curricula. Cancer Education Survey II: cancer education in United States medical schools.

The findings on cancer teaching methodology presented in this abstract come from an American Association for Cancer Education (AACE)/American Cancer Society-sponsored survey of American allopathic medical schools in 1989 and 1990 to determine how and how well cancer is presented in the medical school curriculum. Responses were received from 126 institutional and approximately 1,000 faculty respondents. Approximately one-third (368) of faculty respondents indicated the use of specific learning objectives; utilization does vary across disciplines. The lecture remains the dominant form of instructional method. Computers were reported as an instructional modality by only 16% of the faculty respondents. Prepared audiovisual instructional materials appeared to be widely utilized. Use varied from 86% for 35mm slides to 11% for video discs. Faculty favored the development of new teaching materials for ten topic areas ranging from approximately 40% for early detection and prevention to a low of approximately 25% for rehabilitation and continuing care. The survey identified an underutilization of existing outpatient facilities and tumor registries for cancer teaching purposes. The findings give rise to questions concerning the appropriateness of the match between specific instructional goals and the teaching methods employed. Eight recommendations designed to strengthen cancer training are made.

Computer-Assisted Instruction↗
PubMed1992

Cancer prevention education in United States medical schools. Cancer Education Survey II: cancer education in United States medical schools.

The Cancer Education Survey collected data from 126 of 128 US Medical Schools on the current status of cancer-related educational activities for undergraduate medical students. The study was conducted by a Supervisory Committee of the American Association for Cancer Education, with funding from the American Cancer Society. The survey obtained data concerning institutional characteristics in support of undergraduate medical student cancer education, ie, administrative structures, current cancer-related curricula, sources of financial support, and anticipated changes in these characteristics. Institutions were also queried on specific topics of cancer prevention, detection, and diagnosis that might be taught as identifiable areas of instruction for medical students. Three-fourths of the institutions had a lecture on the principles of cancer screening, and, among those, nearly three-fourths classified it as a part of a required course or rotation. Detection of common cancers is taught in virtually all institutions. The least likely cancer prevention lecture topics are related to prevention and cessation of smoking, a well-verified cancer risk. Also, no consistent pattern emerges that might indicate that association with a cancer center imparts to a medical school a greater emphasis on delivery of cancer prevention topics.

American Cancer Society↗
PubMed1992

Changing the cancer curriculum: a curriculum committee's response to the results of the AACE Cancer Education Survey II. Cancer Education Survey II: cancer education in United States medical schools.

The AACE Cancer Education Survey-II offers an unusual opportunity based on data from 125 medical schools and 1,035 experienced cancer educators to effect constructive change with regard to cancer education. The changes suggested include more coordination; integration; and a shift of emphasis to include more on topics of prevention, early diagnosis, tumor biology, rehabilitation, palliative care, and psychosocial issues. Ample opportunities, especially in the ambulatory care arena, exist at most medical schools, and there is a great deal of interest in improving the situation. This article reviews the factors contributing to resistance to change, the data on adult learning, and the major movements and dilemmas facing medical education today. It also discusses some of the external forces like the Liaison Committee on Medical Education (LCME) and foundation support, which are being harnessed to effect change. Given these barriers, forces, and opportunities, the article ends with a possible action plan for an individual, an institution, and national bodies interested in cancer education. The knowledge, skills, values, and attitudes must be defined, taught effectively, and evaluated. It is an opportune time, armed with this useful data, to bring about change in how cancer subjects are taught. The ultimate goal is more knowledgeable and effective practitioners and scientists who can decrease the morbidity and mortality from cancer.

Curriculum↗
PubMed1991

Expression of aberrant O-glycans attached to leukosialin in differentiation-deficient HL-60 cells.

Promyelocytic leukemia HL-60 cells can be induced to differentiate into granulocytic cells by various agents including retinoic acid (RA), dimethyl sulfoxide, and 6-thioguanine (6-TG). Although the induced cells are no longer capable of proliferation, a few cells continue to divide in the presence of inducers, and these cells are resistant to terminal differentiation by these inducers (R. E. Gallagher, D. A. Giangiulio, C-S. Chang, C. J. Glover, and R. L. Felsted, Blood, 68: 1402-1406, 1986). The present study examined the structures of O-glycans attached to leukosialin, a major sialoglycoprotein in HL-60 cells, and the activities of glycosyltransferases involved in O-glycan synthesis. Leukosialin from RA-resistant and 6-TG-resistant HL-60 sublines migrated much more slowly than those from wild-type HL-60 cells when applied to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The dimethyl sulfoxide-resistant HL-60 subline, on the other hand, expressed leukosialin with a molecular weight similar to wild-type HL-60 cells. RA-resistant and 6-TG-resistant HL-60 cells were found to express a significant amount of tetrasaccharides that contain no sialic acid residue, while wild-type HL-60 cells expressed mainly disialosyl hexasaccharides and contained no detectable amount of asialo-oligosaccharides. Furthermore, wild-type HL-60 cells treated with the inducers for 4 days were found to express the same saccharides present in untreated wild-type HL-60 cells, indicating that the altered O-glycans present in RA and 6-TG sublines were not caused by a direct effect of these agents but rather are intrinsically unique to these sublines. To better understand the mechanisms underlying the differences in O-glycans, the activities of four sialyltransferases were measured: Gal beta 1----3GalNAc alpha 2----3sialyltransferase, Gal beta 1----4(3) GlcNAc alpha 2----3sialyltransferase, Gal beta 1----4GlcNAc alpha 2----6sialyltransferase, and GalNAc alpha 2----6sialyltransferase. Among them, Gal beta 1----3GalNAc alpha 2----3sialyltransferase and Gal beta 1----4(3)GlcNAc alpha 2----3sialyltransferase were much lower in the RA- or 6-TG-resistant HL-60 subline than in wild-type HL-60 cells. These findings indicate that the differences in O-glycans are due to the differences in alpha 2----3sialyltransferase activities. These results strongly suggest that O-glycans associated with leukosialin may play some role in HL-60 cell differentiation.

Antigens, CD↗
PubMed1991

Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all trans-retinoic acid.

Two recent reports have described major clinical benefits from all-trans-retinoic acid (tRA) therapy of patients with promyelocytic leukemia (APL). This paper describes the first patient with a blast crisis of chronic myelogenous leukemia (CML-BC) who responded to oral tRA therapy. In vitro marrow studies, including clonogenic assays, immunopheno-typing, cytogenetics and premature chromosome condensation together with chromosome painting provided evidence for the in vivo differentiation and maturation of the malignant cells. The patient achieved a partial remission with reversal of all clinical features of disease, including normalization of peripheral blood counts, complete resolution of fever, fatigue and splenomegaly, and marked maturation of the bone marrow. This response to tRA in CML-BC is unique, and broadens the spectrum of diseases which may respond to retinoids.

Antineoplastic Agents↗
PubMed1989

Human myelogenous leukemia cell line HL-60 cells resistant to differentiation induction by retinoic acid. Decreased content of glycosphingolipids and granulocytic differentiation by neolacto series gangliosides.

We have recently reported that neolacto series gangliosides (NeuAc-nLc) are increased during granulocytic differentiation of human myelogenous leukemia cell line HL-60 cells induced by retinoic acid and that HL-60 cells are differentiated into mature granulocytes when the cells are cultivated with NeuAc-nLc (Nojiri, H., Kitagawa, S., Nakamura, M., Kirito, K., Enomoto, Y., and Saito, M. (1988) J. Biol. Chem. 263, 7443-7446). In contrast to these wild-type-HL-60 cells, HL-60 cells resistant to differentiation induction by retinoic acid showed a markedly decreased content of gangliosides, especially NeuAc-nLc, and did not show any increase in the content of gangliosides when cultivated with retinoic acid. Neutral glycosphingolipids, the precursors of gangliosides, were not accumulated in these resistant cells. When retinoic acid-resistant HL-60 cells were cultivated in the presence of NeuAc-nLc, the cells were found to be differentiated into mature granulocytes on morphological and functional criteria. The differentiation of cells was dependent on the concentration of gangliosides and was accompanied by inhibition of cell growth. Wild-type HL-60 cells differentiated by NeuAc-nLc showed the changes in ganglioside composition, which were similar to those in wild-type HL-60 cells differentiated by retinoic acid; among the gangliosides changed, 2----3 sialylparagloboside and 2----3 sialylnorhexaosylceramide were increased. These findings suggest (a) that the synthesis of particular NeuAc-nLe molecules is an important step for retinoic acid-induced granulocytic differentiation and this step could be bypassed or replaced by exogenous NeuAc-nLc, and (b) that the defective synthesis of particular NeuAc-nLc molecules is responsible for the failure of differentiation induction in retinoic acid-resistant HL-60 cells by retinoic acid.

Cell Differentiation↗
PubMed1989

Variable regulation of sensitivity to retinoic acid-induced differentiation in wild-type and retinoic acid-resistant HL-60 cells.

The initial cell association and metabolic conversion of retinoic acid (RA) by HL-60 cells in serum-free, transferrin/insulin-supplemented, RPMI 1640 medium was greater than or equal to 10-fold greater than in RPMI 1640 medium containing 10% fetal bovine serum (FBS). This was paralleled under the serum-free conditions by 10-fold greater sensitivity to RA-induced differentiation, which was partially reversed by the addition of purified bovine serum albumin to the same concentration present in 10% FBS. In serum-free HL-1 medium, HL-60 cell sensitivity to RA-induced differentiation was approximately 250-fold less than in serum-free RPMI 1640 medium but, in this comparison, there was little difference in RA cell association or metabolism. A greater than 200-fold RA-resistant HL-60 subline had RA cell-association and metabolism rates similar to those of wild-type cells under all culture conditions. No significant qualitative differences in the high performance liquid chromatography elution patterns of polar metabolites were observed under any circumstances. These results indicate that inherent cellular properties, not associated with gross differences in RA uptake or metabolism, primarily determined the relative sensitivity or insensitivity of HL-60 cells to RA-induced differentiation but that RA responsiveness was markedly regulated by extracellular factors, one of which, serum albumin, appeared to act by decreasing the initial cell association and metabolism of RA, whereas other, as yet unidentified exogenous factors, may have acted independently of these functions.

Cell Differentiation↗
PubMed1989

Stability of multiple antigen receptor gene rearrangements and immunophenotype in Hodgkin's disease-derived cell line L428 and variant subline L428KSA.

The Hodgkin's disease (HD) derived cell line L428 and a phorbol ester-selected subline L428KSA, which have been independently passaged in tissue culture for several years, were studied for possible antigen receptor gene and immunophenotypic differences. Multiple but identical alterations of these genes were found, including: the deletion of one and rearrangement of the other immunoglobulin (Ig) heavy chain allele; the rearrangement of one kappa and one lambda light chain allele; and the rearrangement of one T cell receptor (TCR) beta allele. Restriction mapping of the Ig heavy chain locus indicated that rearrangement of the retained allele produced a JH-C gamma 4 fusion product by an isotype switch mechanism. The 14q+ chromosome [t(14q32;?)] present in both cell cultures derived either from translocation 5' (telomeric) to the rearranged JH allele or 3' (centromeric) to the deleted Ig heavy chain allele and did not involve detectable rearrangement of the c-myc, bcl 1, or bcl 2 oncogenes. No differences in the immunophenotype were found between the L428 and L428KSA cells: both expressed leukocyte activation antigens and some determinants associated with myelomonocytic cells but no lymphoid markers. It is postulated that these phenotypic characteristics derived from secondary genetic events/differentiative reprogramming which produced extinction of primary lymphoid characters, including terminal deoxynucleotidyl transferase (TdT) essential to generation of the Ig and TCR gene rearrangements, and expression of an incomplete set of myelomonocytic markers.

Blotting, Southern↗
PubMed1989

Expression of retinoic acid receptor-alpha mRNA in human leukemia cells with variable responsiveness to retinoic acid.

Retinoic acid receptor (RAR)-alpha mRNA expression was studied in a variety of myeloid leukemia cells with variable responsiveness to the induction of terminal differentiation by retinoic acid (RA). Cells from both the wild-type (wt), RA-responsive HL-60 promyelocytic leukemia cell line and a selected greater than or equal to 300-fold RA-resistant subline expressed approximately equal amounts of two RAR-alpha transcripts, 4.0 and 3.1 kb in size. In wt cells, the RAR-alpha did not change during induction of granulocyte differentiation by RA or macrophagic differentiation by 12-0-tetradecanoylphorbol-13-acetate (TPA). Relative to HL-60 cells, other cultured and fresh myeloid leukemia cells expressed 2.5-fold less to equal amounts of the RAR-alpha transcripts. The relative expression in six cases of acute promyelocytic leukemia (APL; two RA-responsive; one, previously treated with 13-cis-RA in vivo, equivocally RA-responsive) and one case of acute myelogenous leukemia (AML) with promyelocytosis (RA unresponsive) was 0.91 +/- 0.14 versus 0.53 +/- 0.14 for eight cases of nonpromyelocytic AML (p congruent to 0.001). Lymphoid leukemia cells expressed 2- to 5-fold less RAR-alpha mRNA. No qualitative variations in the mRNA transcripts were observed, although the 3.1 kb transcript was relatively decreased in three cases. The RAR-alpha gene was not amplified or detectably rearranged in any DNA source, although an apparent EcoRI restriction fragment length polymorphism was observed. It is concluded (a) that the steady-state level of RAR-alpha mRNA is not tightly correlated with natural responsiveness/unresponsiveness or, in some instances, acquired resistance to RA-induced differentiation and (b) that further studies are needed to determine if the mean 1.7-fold higher RAR-alpha mRNA level in APL cells could be an essential factor in the RA-responsiveness of APL cells, as primarily regulated at a different molecular level.

Adult↗
PubMed1988

Cell cycle-dependent reactivity with the monoclonal antibody Ki-67 during myeloid cell differentiation.

The specificity and sensitivity of the monoclonal antibody Ki-67 in identifying proliferating cell compartments was tested with the human promyelocytic leukemia cell line HL-60 using multi-parameter flow cytometry. While correlated measurements of DNA content and Ki-67 immunofluorescence indicated that the antigen was present in all phases of the cell cycle, reactivity with the antibody was highest in proliferating S and G2+M cells. The analysis of the BrdU content of cells sorted on the basis of reactivity with Ki-67 showed a correlation between Ki-67 reactivity and BrdU uptake. In HL-60 cells induced to differentiate with dimethyl sulfoxide (DMSO), the loss of reactivity with Ki-67 paralleled the exit of cells from the cell cycle. This was not observed in DMSO-resistant HL-60 cells. These results validate the usefulness of the Ki-67 antibody for determining the proliferative stage of mammalian cells in culture.

Antibodies, Monoclonal↗
PubMed1987

Effects of interferon and retinoic acid on the growth and differentiation of clonogenic leukemic cells from acute myelogenous leukemia patients treated with recombinant leukocyte-alpha A interferon.

Studies with human myeloid leukemia cell lines indicate that combined interferon (INF) and retinoic acid (RA) have greater effects in inhibiting cell growth and in inducing terminal differentiation than either agent alone. Consequently, we studied the effects of these agents, singly and in combination, on fresh leukemic blast cells obtained from 13 acute myelogenous leukemia (AML) patients, most of whom were subsequently treated with recombinant leukocyte-alpha A interferon (rINF-alpha A). The in-vitro response to rINF-alpha A and RA was assessed in an established myeloid leukemic blast cell clonogenic assay containing conditioned medium from phytohemagglutinin-stimulated lymphocytes. Strong inhibition of colony cell growth (greater than or equal to 50%) was observed in 4/10 cases treated with rINF-alpha A alone, but only at high concentration (greater than or equal to 2500 U/ml) and in 4/10 cases treated with RA alone (5 X 10(-8) M or 5 X 10(-7) M). Combined rINF-alpha A and RA augmented the inhibition of primary or secondary colony cell growth in 5/8 evaluable cases. Stimulation of leukemic cell differentiation was observed in 1/8 cases by rINF-alpha A alone and in 4/7 cases by RA alone. Combined rINF-alpha A and RA enhanced cell differentiation in 4/7 cases. In addition, increased inhibition of clonal cell growth and/or differentiation by RA alone was observed in 2/5 cases following in-vivo rINF-alpha A treatment. These results suggest that treatment with combined rINF-alpha A and RA may be rewarding in some cases of AML.

Cell Differentiation↗
PubMed1986

Evaluating the cancer education program: examining a range of approaches.

The objectives of this article are to provide people who are responsible for cancer education programs with a broadened perspective of the rich array of evaluation strategies available and responsive to the evaluation needs of cancer education programs, and to summarize selected literature resources useful for the development of an evaluation plan. This article reviews limitations found in previous evaluations of medical education programs and provides a descriptive survey of diverse strategies for the evaluation of cancer education programs. The characteristics, requirements, utility, audience, constraints, and resources are presented. Two cancer related case studies are discussed in detail as illustrations of the diversity of strategies available to evaluate cancer education programs.

Evaluation Studies as Topic↗
PubMed1986

Hyposialylation of differentiation-inducer-resistant HL-60 cells.

The total sialic acid concent of retinoic acid (RA)-resistant or 6-thioguanine (6TG)-resistant HL-60 cells was more than tenfold lower and of dimethylsulfoxide (DMSO)-resistant HL-60 cells was approximately twofold lower than that of parental, wild-type (wt) HL-60 cells. Neuraminidase-inaccessible, ie residual cell-associated sialic acid after neuraminidase treatment, was four- to twelvefold lower in the three differentiation-inducer-resistant sublines than in the parent line. Neuraminidase treatment of 125I-labeled surface membrane glycoproteins (SMGs) from wt HL-60 cells converted the two-dimensional gel electrophoretic pattern to one having features in common with RA- and 6TG-resistant cells. However, neuraminidase treatment did not alter the sensitivity of wt HL-60 cells to differentiation induction by RA, hypoxanthine (purine base), or DMSO. These results indicate that differences in peripheral, neuraminidase-accessible sialic acids are important determinants of the gel electrophoretic mobility of the SMGs of the HL-60 line and sublines but are not likely related to the differentiation-resistance mechanism. Further studies are required to determine if hyposialylation of cryptic, neuraminidase-inaccessible sites has functional significance.

Cell Differentiation↗