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Biomedical subjects

A Estabrook

Publications and source records attributed to A Estabrook.

27 records · Page 2Linked to original sources
PubMed1985

Immunoreactivity and biodistribution of indium-111-labeled monoclonal antibody to a human high molecular weight-melanoma associated antigen.

The anti-human, high molecular weight-melanoma associated antigen (HMW-MAA) MoAb 225.28S was chelated with 111In and then tested for its in vitro reactivity with cultured human melanoma cells and for its biodistribution in human melanoma bearing nude mice. In vitro studies showed that the radiolabeled antibody reacted specifically with cultured melanoma cells. However, binding of DTPA to the monoclonal antibody reduced its titer with cultured melanoma cells from 1:1024 to 1:512. Further labeling of the DTPA-antibody conjugate with 111In caused an additional reduction of its titer to 1:128. Injection of the radiolabeled monoclonal antibody into nude mice resulted in the accumulation of significantly (p less than 0.001) higher radioactivity in melanoma tissue than in nude mice injected with either [111In] chloride or 111In-labeled antibody to human acid phosphatase. The specificity of the distribution of the radiolabeled antibody in nude mice also was indicated by its poor localization in lesions other than melanoma (e.g., human prostate carcinoma and chronic abscess). The localization of antibody in liver and kidney was also high, although lower than that achieved in tumor. These results indicate that 111In-labeled monoclonal antibodies to human tumor associated antigens may be useful for localizing malignant lesions. However, there is a need to improve labeling and/or purification of antibody in order to decrease renal and hepatic activity.

Animals↗
PubMed1983

Antigenic modulation of pan-T-cell and T-cell subset-specific markers.

The time course and extent of antigenic modulation induced by monoclonal antibodies OKT3, OKT4, OKT8, BE2, and BE3 was investigated. OKT3-induced antigenic modulation could be detected as early as after 3-hr incubation with the antibody and almost total removal of the OKT3-reactive antigen was seen by 42 hr. This modulation did not decrease the expression of T-cell antigens detected by OKT4 and OKT8. OKT3-modulated cells reexpressed the antigen after 42-hr incubation in OKT3-free media. BE3 (homologue of OKT1) also caused modulation of its surface antigen after 24-hr incubation. In contrast, OKT4 did not induce modulation even after 42-hr incubation with high concentrations of OKT4 antibody. Approximately 43% of the OKT8-reactive lymphocytes could be induced to modulate this antigen. A tumor-associated antigen present on neoplastic lymphocytes from patients with cutaneous T-cell lymphoma, recognized by monoclonal antibody BE2, also was not induced to modulate. These results suggest that antigenic modulation and the fate of the modulated antibody may be of importance to immunotherapeutic applications of these reagents.

Animals↗
PubMed1982

Diagnosis of cutaneous T cell lymphoma by use of monoclonal antibodies reactive with tumor-associated antigens.

Two murine monoclonal antibodies (BE1 and BE2), produced by using leukemic helper T cells from a patient with cutaneous T-cell lymphoma (CTCL) as immunogens, reacted selectively with CTCL lymphocytes and some transformed cultured lymphocytes, as determined by radioimmunoassay (RIA) and indirect immunofluorescence (IIF). BE1 reacted significantly (P less than or equal to 0.001) with leukemic CTCL lymphocytes and with CTCL cells from infiltrated lymph nodes (RIA, mean +/- SD = 776 +/- 275 cpm), as compared with background counts (263 +/- 68). BE1 binding to normal blood mononuclear cells (RIA, mean +/- SD = 283 +/- 58 cpm) was indistinguishable from background. BE1 also reacted with Epstein-Barr virus (EBV)-transformed B-cell lines (RIA, mean +/- SD = 794 +/- 230) and some long-term T-cell lines. BE1 did not react with the majority of lymphoid cell lines or tumor cell lines tested. BE1 also did not react with any normal tissues screened by IIF. BE1 precipitated a molecule from CTCL cells that, under reducing conditions, has two components with molecular mass of 27,200 and 25,800 D. BE2 also reacted significantly (P less than or equal to 0.001) with CTCL cells from two of four patients (RIA, mean +/- SD = 519 +/- 113 cpm). The binding of BE2 to normal mononuclear cells was indistinguishable from background (309 +/- 38 cpm). BE2 also reacted with an antigen present on EBV-B-cell lines (RIA, mean +/- SD = 654 +/- 194) and MOLT 3 and HUT 78 T-cell lines. BE2 reacted with an antigen expressed on a subpopulation of lymphocytes from five of eight patients with B-cell CLL studied by IIF (mean +/- SD = 18 +/- 6). Other long-term T-cell lines and tumor cell lines studied by IIF were unreactive with BE2. BE2 did not react with any of the normal tissues studied. BE2 precipitated a molecule (78,000 D) from CTCL cells and EBV-B cells with a single component under reducing conditions. Immunoperoxidase-labeled BE1 and BE2 reacted with CTCL cells in frozen sections of infiltrated lymph nodes and skin. In addition, BE1 and BE2 reacted with blood lymphocytes from 16 of 21 patients whose CTCL had otherwise been considered localized to skin. These two monoclonal antibodies react with tumor antigens associated with CTCL and appear to be useful in the diagnosis of this disorder.

Antibodies, Monoclonal↗
PubMedDate not supplied

Fine needle aspiration biopsy of intramammary neurilemoma.

A case of benign neurilemoma (schwannoma) arising in the breast is presented, including the fine needle aspiration (FNA) biopsy findings. The aspirate yielded a cellular smear composed of clusters of spindle-shaped cells showing minimal atypia. The absence of mitotic figures and breast epithelium suggested a benign neoplasm. The final diagnosis was established on the excised mass by histopathologic study and the use of special stains. The utility and pitfalls of FNA biopsy in diagnosing this rare entity are discussed.

Aged↗
PubMedDate not supplied

Increased surface expression and shedding of tumor associated antigens by human breast carcinoma cells treated with recombinant human interferons or phorbol ester tumor promoters.

In the present study we have evaluated the effect of recombinant interferons, including leukocyte (IFN-alpha A), fibroblast (IFN-beta) and immune (IFN-gamma), and the tumor promoting agent 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of tumor associated antigens (TAA) and class II HLA-DR antigens on human breast carcinoma cell lines. The effect of these agents on the shedding of a high molecular weight tumor associated glycoprotein, BCA-225, was also determined. All three interferons and TPA enhanced the expression of the Mr 180,000 carcinoembryonic antigen (CEA) and CEA-related TAA recognized by monoclonal antibody B1.1 in both T47D and MCF-7 human breast carcinoma cell lines. The three types of interferons and TPA differed in their absolute TAA-augmenting ability, even in single-cell subclones derived from MCF-7 cells and previously shown to display a differential susceptibility to IFN-alpha augmentation of B1.1 expression. In general, IFN-gamma was more effective than IFN-alpha, IFN-beta or TPA in augmenting the expression of TAA, CEA and BCA-225, and HLA-DR expression in T47D and MCF-7 cells. Differences were also apparent in the ability of the three interferon preparations and TPA to induce shedding of BCA-225 in T47D and MCF-7 cells and their subclones. As observed with TAA expression, IFN-gamma was the most effective preparation in inducing TAA shedding. IFN-gamma also induced the expression and the shedding of BCA-225 by a subclone of T47D cells, T47D cl 17, which normally displays a reduced expression of BCA-225 and does not spontaneously shed this TAA without exposure to IFN-gamma. Recombinant leukocyte interferon (IFN-alpha A) also enhanced BCA-225 expression on T47D cells grown as xenografts in nude mice in vivo. The results of the present study emphasize the complexity of potential antigenic responses which can be induced in human breast carcinoma cells when they are exposed to biological response modulators, including different types of interferon, and tumor promoting agents, such as TPA. This investigation also indicates that both classes of agents can differentially augment expression and/or shedding of TAA by specific breast carcinoma cell lines as well as subclones derived from the same breast carcinoma cell line.

Antibodies, Monoclonal↗
PubMedDate not supplied

Carcinogen-DNA adducts in human breast tissue.

Breast cancer is the second leading cause of cancer death among American women. Known risk factors account for only approximately one-third of the 182,000 new cases diagnosed each year in the United States. There is both concern and debate over the contribution of environmental exposures related to lifestyle, occupation, and ambient pollution, particularly in high risk areas such as Long Island, NY and the rest of the northeastern United States. Biomarkers such as carcinogen-DNA adducts can help to explore the role of environmental risk factors for breast cancer by documenting DNA damage from specific carcinogens directly in human tissue. In this pilot study, a total of 31 breast tissue samples were analyzed by the 32P-postlabeling method for carcinogen-DNA adducts characteristic of complex mixtures of aromatic compounds (such as polycyclic aromatic hydrocarbons) and tobacco smoke. The samples included tumor and tumor-adjacent tissues from 15 women with breast cancer and normal tissue samples from 4 women undergoing breast reduction. Among the breast cancer cases, the mean aromatic/hydrophobic-DNA adduct level in all tissues assayed was 5.3 +/- 2.4 (SD) adducts/10(8) nucleotides compared to 2.3 +/- 1.5 among the samples from the noncancer patients. Breast tissue (tumor and/or nontumor) from 30% (5 of 15) of women with breast cancer displayed a pattern of adducts (referred to as a diagonal zone of radioactivity) associated previously, in studies of other tissues, with exposure to tobacco smoke. The 5 positive samples were from current smokers; tissue samples from the 8 nonsmoking cases did not show this characteristic pattern (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗