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Biomedical subjects

R Stroup

Publications and source records attributed to R Stroup.

11 recordsLinked to original sources
PubMed2001

Independent association of angiogenesis index with outcome in prostate cancer.

New molecular factors have been characterized that are associated with the prognosis of prostate carcinoma patients, including p53 status and angiogenesis. We reported recently that mutant p53 (mp53) was associated with decreased expression of an endogenous inhibitor of angiogenesis, thrombospondin-1 (TSP-1), and increased microvessel density in melanoma and breast cancer. In this study, we performed a similar analysis on primary prostate carcinoma to determine whether these factors were associated with each other or patient outcomes. Paraffin-embedded specimens of 98 cases of primary prostate carcinoma were obtained and examined to confirm tissue diagnosis and Gleason scores. Carcinoma-specific levels of p53, TSP-1, and tumor angiogenesis were determined using semiquantitative immunohistochemistry (IHC) methods. Acquisition of mp53 was significantly associated with decreased TSP-1 (P = 0.002) and increased angiogenesis (P < 0.0001). An angiogenesis index integrating mp53, TSP-1, and angiogenesis (CD31) scores was found to be an independent predictor of survival in univariate and multivariate analyses that included Gleason score, clinical stage, and patient age. Further validation of the angiogenesis index in prostate carcinoma may provide a new tool to stratify patient risk.

Adenocarcinoma↗
PubMed1998

Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin.

To determine whether multidrug resistance (MDR1) P-glycoprotein (Pgp) expression correlated with clinical MDR1-related drug resistance, we established a protocol for quantitative measurement of Pgp expression and in vitro drug resistance in doxorubicin resistant MCF7 breast cancer cell lines and 359 freshly resected specimens of breast carcinoma. Pgp expression was detected with 4E3, UIC2, and JSB-1 monoclonal antibodies using flow cytometry and immunohistochemistry (IHC). Pgp function was determined using PSC833 in a drug resistance-reversal assay and with a three-dimensional agarose-based extreme drug resistance assay. MCF7 calibrator cell lines expressed Pgp, which was functional and in proportion to the degree of drug resistance. Flow cytometry, UIC2 shift assays, IHC scores, and determination of absorbance products by image analysis were all highly correlated (r > 0.9). Overall Pgp expression increased from 11% in untreated patients to 30% in patients who had previously received chemotherapy. Compared with Pgp-negative tumors, a significant increase in doxorubicin and Taxol resistance was seen for breast cancers that expressed Pgp, regardless of prior treatment. A strong correlation between the degree of Pgp expression and in vitro resistance to Taxol and doxorubicin (but not to 5-fluorouracil) was found when either IHC scores or image analysis-based methods were used to quantify Pgp expression (n = 185, P < 0.0001). The degree of Pgp expression strongly correlated with the degree of drug resistance in the clinical specimens studied. These data suggest that (a) Pgp contributes to clinical MDR1-related drug resistance, and (b) both intrinsic and acquired expression of Pgp in breast cancer may contribute in part to therapeutic failure and relapse.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Antigenic phenotypes of hairy cell leukemia and monocytoid B-cell lymphoma: an immunohistochemical evaluation of 66 cases.

Using a large panel of antibodies on multi-tumor block sections of routinely processed, paraffin-embedded fixed tissue, we compared the antigenic phenotype of 42 clinically, morphologically, and immunologically well-characterized cases of hairy cell leukemia (HCL) with 24 cases of monocytoid B-cell lymphoma (MBCL) selected from the Monocytoid B-Cell Lymphoma Registry at the City of Hope National Medical Center. The predominant antigenic phenotype of hairy cells was CD45 (leukocyte common antigen)+, CD45Ra (4KB5, MB1, MT2)+, L26+, CDw75 (LN1)+, CD74 (LN2)+, LN3+, MB2+, CD45RO (UCHL1)-, MT1-, CD15 (Leu-M1)-, neuron-specific enolase (NSE)-, epithelial membrane antigen-, and CD30 (Ber-H2)-. The immunophenotype of neoplastic monocytoid B lymphocytes was essentially identical to that of the hairy cells, with one exception: the neoplastic monocytoid B lymphocytes were stained by epithelial membrane antigen in seven cases. An interesting observation was the staining by anti-muscle-specific actin of the neoplastic cells of MBCL in 53% of cases, but of none of the cases of HCL. The results of our study (1) indicate that HCL and MBCL can be immunophenotyped reliably on fixed tissue samples, (2) further confirm the proposed lineage relationship between these two lymphoproliferative disorders, and (3) indicate that decalcification of bone marrow biopsies does not adversely affect the immunoreactivity of hematopoietic-associated antigens.

Antigens, Neoplasm↗
PubMed1991

Malignant histiocytosis X. A distinct clinicopathologic entity.

Histiocytosis X (HX) is characterized morphologically by a proliferation of Langerhans' cells (LC), and most often has an indolent, chronic course. To determine whether a distinct clinicopathologic entity of malignant histiocytosis X exists, the authors examined tissues from 31 patients with HX and divided them into four categories. Group A (19 patients) was characterized morphologically by benign-appearing LC and had an indolent course. The male:female (M:F) ratio was 10:9, and the mean age was 21 years (range, 2 months to 60 years). The immunophenotype of this group was S-100+, vimentin+, LN-2+, LN-3+, lysozyme-, LCA-, Leu-M1-. Group B (three patients) had benign-appearing LC, yet had an aggressive clinical course. All patients were male, with a mean age of 47 years (range, 3 years to 72 years). Organs involved included the liver, spleen, heart, thymus, lung, kidney, and pancreas. The immunophenotype was the same as for Group A. Group C (two patients) had atypical and malignant appearing LC, yet a relatively benign clinical course. The ages were four and 65 years, with one female and one male patient. In both patients, the cells were S-100+, vimentin+, LN-2+, LN-3+, and LCA-. Group D (seven patients) was characterized by atypical and malignant-appearing LC and an aggressive clinical course. The mean age was 25 years (range, congenital to 54 years) with one female and six male patients. Organs involved were the thymus, lungs, spleen, liver, kidney, brain, heart, pancreas, stomach, and muscle. Birbeck granules were found in two patients, and the one patient on which fresh tissue was available was CD1+. The typical immunophenotype was S-100+, vimentin+, LN-2+, LN-3+, Leu-M1-, lysozyme-. The results of our study indicate that (1) a distinct clinical entity of malignant HX, characterized morphologically by malignant-appearing LC and clinically by male predominance, atypical organ involvement, and an aggressive clinical course, does exist; and (2) the morphologic appearance of the LC is an imperfect predictor of the clinical severity of HX.

Adolescent↗
PubMed1990

Surface immunoglobulin-positive lymphoblastic lymphoma. A report of three cases.

Lymphoblastic lymphomas (LBL) are a morphologically homogeneous group of non-Hodgkin's lymphomas which are indistinguishable in tissue sections from acute lymphoblastic leukemia (ALL). Although initial immunologic studies of LBL suggested that these lymphomas are of the T-cell phenotype, investigations have recently described patients with LBL having pre-B-cell, "common" ALL, and natural killer cell phenotypes. The authors recently reported detailed immunophenotypic characteristics in 36 cases of LBL, including a single case of LBL with a surface immunoglobulin-positive B-cell phenotype. Three additional patients with LBL whose cells expressed monoclonal serum immunoglobulins are presented here. In addition, the neoplastic lymphocytes expressed several B-cell-associated antigens. The tumor cells in the single case tested were TdT-negative. Despite the unusual immunologic phenotype, the morphologic features in all three cases were characteristic of LBL. In addition to the previously reported single case, to the authors' knowledge these are the only reported cases of a previously unrecognized variant of LBL: surface immunoglobulin-positive, B-cell LBL.

Adolescent↗
PubMed1989

Relationship between eosinophil density and T-cell activation markers in lymph nodes of patients with Hodgkin's disease.

Hodgkin's disease (HD) is characterized morphologically by a variable infiltration of tissues by eosinophilic granulocytes. The lesions also contain numerous T cells, predominantly of the CD4+ immunophenotype. To investigate whether the presence or absence of tissue eosinophilia is related to the immunophenotype of the T cells, we studied 43 cases of HD (28 nodular sclerosing, ten mixed cellularity, and five unclassifiable) for the relative numbers of lymphocytes positive for CD2, CD3, CD4, CD5, CD8, CD25, CD38, T9, TQ1, HLA-DR, and beta F1, and for the number of eosinophils in tissue sections. By univariate and multivariate analysis, we determined that there was an inverse relationship between the number of eosinophils and the presence of TQ1+ (P less than .0005) and CD25+ (P less than .0005) lymphocytes. In addition, we observed that TQ1 stained the Reed-Sternberg cells in these lesions. We also determined that the T cells expressed HLA-DR more frequently in the nodular sclerosis subtype than in other subtypes of HD (P less than or equal to .0001). We therefore conclude that the degree of tissue eosinophilia in the lymph nodes of patients with HD may be explained, at least in part, by the immunophenotype of the T cells present in the affected lymph nodes.

Antibodies, Monoclonal↗
PubMed1987

Rearrangement of kappa-chain and T-cell receptor beta-chain genes in malignant lymphomas of "T-cell" phenotype.

Detection of immunoglobulin gene rearrangements by molecular hybridization is considered to be a highly sensitive approach to the evaluation of clonality of B-cell-derived neoplasms. Like monoclonal surface immunoglobulin in B cells, which serves as a reliable immunophenotypic marker for clonality, rearrangement of the genes encoding immunoglobulin light chains has been accepted as a reliable genotypic marker for the presence of a clonal expansion of B lymphocytes. The authors now report 3 cases of non-Hodgkin's lymphoma that were immunologically classified as having a T-cell phenotype and in which, in addition to rearrangements of the T-cell receptor beta-chain gene, a rearrangement of an immunoglobulin light-chain gene was clearly identified by Southern blot hybridization. The results demonstrate that the data obtained by molecular hybridization should be interpreted with caution when the immunogenetic findings do not correlate with immunophenotypic expression, and that the results of molecular genetics studies should be interpreted in conjunction with morphologic and immunologic findings.

Aged↗
PubMed1983

Factors affecting expression of glycolipid tumor antigens: influence of ceramide composition and coexisting glycolipid on the antigenicity of gangliotriaosylceramide in murine lymphoma cells.

Gangliotriaosylceramide (Gg3Cer) was previously described as a tumor-associated antigen in murine L5178Y lymphoma [Young, W. W., Jr., and Hakomori, S., Science (Wash. D.C.), 211: 487-489, 1981]. This paper describes the major factors affecting the expression of Gg3Cer at the surface of various clones of L5178Y lymphoma. Of 26 sublines that were recloned, six cell lines showing different degrees of Gg3Cer expression at the cell surface were used for analysis of the glycolipid composition as related to its cell surface antigenicity. Three remarkable correlations between glycolipid composition and the antigenicity of Gg3Cer have been found: (a) high-expressor sublines were characterized by a large proportion of a unique molecular species of Gg3Cer having alpha-hydroxypalmitic acid in its ceramide moiety in striking contrast to low expressors which did not contain this molecular species; (b) low expressors contained a large quantity of ganglio-N-tetraosylceramide (Gg4Cer) and NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal beta 1 leads to 4Glc beta 1 leads to 1 Cer (GM1b) gangliosides, whereas these glycolipids were almost absent in high-expressor clones; and (c) nonexpressors, which were converted from the high expressors in vivo through immunotherapy with the monoclonal antibodies to Gg3Cer, contained a large quantity of ganglio-N-tetraosylceramide and NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal beta 1 leads to 4Glc beta 1 leads to 1Cer. The nonexpressors should have an induced enzyme system to metabolize Gg3Cer to ganglio-N-tetraosylceramide and NeuAc alpha 2 leads to 3Gal beta 1 leads to 3GalNAc beta 1 leads to 4Gal beta 1 leads to 4Glc beta 1 leads to 1Cer. Three factors, i.e., ceramide composition, coexisting glycolipids, and an antibody-dependent glycolipid change, are therefore important in determination of glycolipid antigenicity and antigen modulation by antibodies. The ceramide composition may affect glycolipid organization in membranes, and the coexisting glycolipid having a longer carbohydrate chain may mask the accessibility of antibody to the antigenic glycolipid. The antigenic modulation by the action of the antibody in vivo may be based on activation of a new glycosyltransferase.

Animals↗