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D F Hayes

Publications and source records attributed to D F Hayes.

At least 73 records · Page 4Linked to original sources
PubMed1993

Localization of tumor-associated glycoprotein DF3 in normal, inflammatory, and neoplastic lesions of the colon.

BACKGROUND: The expression of DF3 was assessed by a monoclonal antibody in normal, inflammatory, and neoplastic conditions in the large bowel. METHODS: Using immunohistochemistry, expression was examined in formalin-fixed paraffin-embedded biopsy and resection samples of 19 normal colonic mucosal specimens, 49 inflammatory lesions, 34 adenomas, and 38 primary colonic adenocarcinomas. In addition, Western blots of normal colonic mucosa and adenocarcinoma were examined. RESULTS: DF3 expression was detected in 84% of the adenocarcinomas with coarse membrane staining, intense positivity of luminal secretions, and focal cytoplasmic and intracytoplasmic vacuole staining. Nine of 32 areas of transitional mucosa revealed reactivity along apical membranes in crypt cells. Five adenomas containing carcinoma revealed DF3 positivity in the malignant areas only, whereas the remaining 29 were negative. Staining was membrane, luminal, and intracytoplasmic. Two examples of active ulcerative colitis revealed focal reactivity along the apical membrane of crypt cells. No other areas of staining were noted, including 12 cases containing dysplasia. Four of 10 other inflammatory lesions also revealed similar membrane reactivity in crypt cells. Normal colonic mucosa was nonreactive. Examples of normal colonic mucosa were negative for DF3 by Western blot analysis, whereas two carcinoma samples that reacted immunohistochemically were positive. CONCLUSIONS: DF3 is not detectable in normal colonic tissues. It is expressed focally and predominantly along the apical membrane of crypt cells in some inflammatory lesions and in the transitional mucosa of primary adenocarcinomas. Most adenocarcinomas of the colon and adenomas with foci of invasive carcinoma demonstrate reactivity in the cytoplasm and luminal secretions.

Adenocarcinoma↗
PubMed1993

Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes.

BACKGROUND: Alkylating agents administered as single agents or in combination with antimetabolites or anthracyclines delay the appearance of metastases and prolong the survival of breast cancer patients after surgery. PURPOSE: This phase III clinical trial was designed to evaluate the therapeutic efficacy and toxicity of the alkylating agent cyclophosphamide in combination with the antimetabolites methotrexate and fluorouracil adjuvant to breast cancer surgery. METHODS: This study consisted of 255 breast cancer patients (a) with one to three histologically positive axillary lymph nodes and either no detectable primary tumor or operable primary tumors 5 cm or less (T0-T2) (95% of the patients) or (b) with tumors larger than 5 cm (T3) and with negative axillary nodes. Patients were randomly allocated to receive either methotrexate (60 mg/m2) and fluorouracil (600 mg/m2) (MF) intravenously on days 1 and 8 every 28 days for eight cycles or cyclophosphamide (100 mg/m2) orally on days 1-14 plus MF (CMF) every 28 days for the same duration. Median follow-up was 7.8 years, and maximum follow-up was 13 years. RESULTS: There were no statistically significant differences in time to treatment failure or overall survival for patients treated with MF or CMF. At 8 years after completion of treatment, time to treatment failure was 55% (95% confidence interval [CI] = 50%-60%) and 59% (95% CI = 54%-64%) and overall survival was 69% (95% CI = 65%-73%) and 67% (95% CI = 62%-72%) for MF- and CMF-treated patients, respectively. The hazard ratios (MF to CMF) for time to treatment failure and for survival, estimated with a proportional hazards model, were 1.02 (95% CI = 0.69-1.50) and 0.87 (95% CI = 0.56-1.34), respectively. Myelosuppression was significantly greater (P < .0001) in CMF-treated patients during cycles 1-6. Median white blood cell count nadirs were between 4.4 x 10(3)/microL and 3.5 x 10(3)/microL in patients receiving MF and between 3.0 x 10(3)/microL and 2.4 x 10(3)/microL in those receiving CMF. Dose reductions were more frequent in CMF-treated patients, which led to statistically significant differences (P < .0001) in amounts of methotrexate and fluorouracil administered. Primary cancers at other sites occurred in 14 patients (5.5%)--six treated with MF and eight treated with CMF. CONCLUSIONS: Our findings suggest that the addition of cyclophosphamide to adjuvant chemotherapy with MF offers no therapeutic advantage but results in increased myelosuppression. IMPLICATIONS: Future trials will define the possible advantages of antimetabolites in adjuvant therapy. Further information will also become available when results of the ongoing National Surgical Adjuvant Breast and Bowel Project trial comparing adjuvant MF to CMF in node-negative breast cancer patients are presented.

Adult↗
PubMed1993

Tumor markers for breast cancer.

Many antigenic and genetic markers have been proposed for breast cancer, with potential utility in identification, screening, prognosis, detection, or monitoring. Of the available markers, those with the greatest promise in 1993 include the yet-to-be-cloned BrCa1, the p53 tumor suppressor gene, tissue-associated prognostic factors such as HER-2/neu, cathepsin-D, and indicators of angiogenesis, and circulating tumor markers that provide an indication of clinical course, such as CA15-3 and CEA. However, the precise clinical utilities of all of these markers have yet to be determined. It is especially important that the relative independence of the markers in relation to other available markers to determined so as to avoid the unnecessary cost and expense of redundancy. Moreover, it is important that the clinician be aware of the limitations in both sensitivity and specificity of each marker so as not to sensitivity and specificity of each marker so as not to over- or under-interpret the predictive value of any test. With these caveats in mind, judicial application of germ-line, tissue, and soluble tumor markers can improve clinical care of patients at risk for and with breast cancer.

Biomarkers, Tumor↗
PubMed1992

Effects of differentiating agents on cell surface expression of the breast carcinoma-associated DF3-P epitope.

The DF3 antigen is a member of a family of high-molecular-weight glycoproteins aberrantly expressed in human breast carcinomas. Recent work has described the generation of a monoclonal antibody (MAb), designated DF3-P, that reacts with immature, underglycosylated precursors of DF3 antigen. Immunoperoxidase staining studies have demonstrated that MAb DF3-P exhibits selective reactivity with malignant mammary epithelium. Using flow cytometry and live cell radioimmunoassays, the present studies demonstrate that the epitope recognized by MAb DF3-P is expressed on the surface of MCF-7 and other human breast carcinoma cell lines. We also demonstrate that treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate, an agent known to induce a more differentiated mammary cell phenotype, is associated with increased expression of the DF3-P epitope. Similar findings were obtained with sodium butyrate. The results indicate that these agents increase both cell surface DF3-P antigen density and the percentage of DF3-P-positive cells. Immunofluorescence studies performed on chamber slides further demonstrate that MAb DF3-P-reactive cells are detectable in small clones or clusters. Similar studies with 12-O-tetradecanoylphorbol-13-acetate- and butyrate-treated cells demonstrate increases in the size and number of these clusters. Taken together, these results indicate that the DF3-P epitope is expressed on the surface of human breast carcinoma cell lines and that the heterogeneity of this expression is related to the presence of differentiating signals.

Antigens, Neoplasm↗
PubMed1992

Tumor selective reactivity of a monoclonal antibody prepared against a recombinant peptide derived from the DF3 human breast carcinoma-associated antigen.

The DF3 antigen is a member of a family of high molecular weight glycoproteins aberrantly expressed in malignant mammary epithelium. We have generated a monoclonal antibody (MAb), designated DF3-P, against a recombinant DF3/beta-galactosidase fusion protein. Characterization of this MAb has demonstrated reactivity with immature precursors of DF3 antigen and not with the secreted form. These findings are in contrast to those obtained with MAb DF3, a previously described antibody with predominant reactivity against the mature glycoprotein. The finding that deglycosylation of secreted DF3 antigen with neuraminidase and endo-alpha-N-acetylgalactosaminidase is associated with increased MAb DF3-P reactivity provided additional support for the selectivity of this antibody against the protein core. Epitope mapping studies demonstrate that both the DF3-P and DF3 epitopes are located at a TRPAPGS domain in the 20-amino acid tandem repeat. The results of competition studies with synthetic peptides indicate that the proline in this domain is involved in both epitopes, while the potential glycosylation sites at threonine and serine may contribute to the differential reactivity of MAbs DF3 and DF3-P. Taken together, these findings suggest that both antibodies react with a similar epitope that is modified by the presence of carbohydrate moieties. The results of immunoperoxidase staining studies further demonstrate that while MAb DF3-P reacts with formalin-fixed sections of breast carcinomas, this antibody exhibits little if any reactivity with normal mammary epithelium. Selective expression of the DF3-P epitope in malignant breast cells may be useful in identifying this transformed phenotype.

Animals↗
PubMed1992

Immunocytochemical determination of the estrogen-regulated proteins Mr 24,000, Mr 52,000 and DF3 breast cancer associated antigen: clinical value in advanced breast cancer and correlation with estrogen receptor.

The Mr 24,000 and Mr 52,000 estrogen-regulated cytosol proteins, and the breast cancer-associated antigen DF3 have been studied in an immunocytochemical assay. Primary tumor specimens from 119 patients with advanced breast cancer who received endocrine therapy have been studied. Monoclonal antibodies were used for the detection of the proteins in formalin-fixed paraffin-embedded blocks. No correlation between Mr 52,000-positive specimens and the presence of estrogen receptor (ER) could be established (p = 0.87, chi-square test) whereas a statistically significant association between Mr 24,000 (p = 0.0002), DF3 antigen (p = 0.044) and ER was demonstrated. No intercorrelation was found between Mr 24,000 and Mr 52,000 or DF3 (p = 0.63, 0.98 and 0.12 respectively). Clinical response was evaluated for immunocytochemical findings, Mr 24,000 (p = 0.37), Mr 52,000 (p = 0.61) and DF3 (p = 0.68) showed no association whereas ER was statistically correlated (p = 0.00005). Neither overall survival nor disease-free survival correlated to Mr 24,000 (p = 0.18 and 0.75 respectively, logrank test), Mr 52,000 (p = 0.095 and 0.38), or DF3 (p = 0.22 and 0.13) staining, whereas ER-positive tumors did (p = 0.00005). Discrimination between ER-positive responders and ER-positive non-responders was not possible using either Mr 52,000, Mr 24,000 or DF3 staining. Based on our findings we conclude that immunocytochemical staining for Mr 52,000, Mr 24,000 or DF3 cannot be used as a marker to predict response to endocrine therapy in patients with advanced or recurrent breast cancer.

Adult↗
PubMed1991

Lung cancer-associated protein: development and characterization of a new assay that detects a circulating lung cancer marker.

A panel of murine monoclonal antibodies was generated against a high-molecular-weight glycoprotein produced by human lung cancer cells. This lung cancer-associated protein (LCAP) has been shown to circulate in the plasma of patients with lung cancer. Various combinations of MAbs were used in solid-phase enzyme-linked sandwich immunoassays to optimize the detection of LCAP in the plasma of these patients. One of these monoclonal antibodies, designated DF-L1, used both in the solid phase as well as the tracer, was selected to evaluate circulating levels of LCAP in normal subjects and in patients with lung cancer. In 341 normal subjects, the mean LCAP level was 7 units/ml, with 47 (13.8%) and 18 (5.3%) subjects having levels greater than or equal to 15 units/ml and 23 units/ml, respectively. In contrast, 27 of 35 (77.1%) patients with lung cancer had LCAP levels greater than or equal to 23 units/ml. A total of 16 of 19 (84.2%) patients with adenocarcinoma, four of seven (57.1%) patients with squamous cell carcinoma, and four of six (66.7%) patients with small cell carcinoma had levels greater than or equal to 23 units/ml. Moreover, in a small group of patients, serial LCAP levels correlated with clinical course during therapy. The LCAP assay is technically reproducible and unaffected by interfering substances in the blood or by variations in the handling of samples. These results indicate that LCAP is a new and potentially useful marker for the evaluation of patients with lung cancer.

Animals↗
PubMed1991

Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study.

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.

Adult↗
PubMed1990

Detection and characterization of a high molecular weight human lung carcinoma-associated glycoprotein.

We have defined a human lung carcinoma antigen using murine monoclonal antibodies (DF-L1 and DF-L2) prepared against a primary adenocarcinoma of the lung. This antigen is expressed on the surface of human lung carcinoma cell lines and has an apparent Mr of 350,000-420,000. Immunoperoxidase staining has demonstrated expression of the antigen in the cytoplasm and membranes of adenocarcinomas and squamous cell carcinomas but not small cell tumors of the lung. Immunoprecipitation of the antigen following radiolabeling has demonstrated the presence of both protein and carbohydrate. Antigen purified by immunoaffinity was used to study the epitopes defined by monoclonal antibodies DF-L1 and DF-L2. The results indicate that the DF-L1 epitope primarily involves a peptide structure, while the DF-L2 epitope is comprised in part by peptide and O-linked carbohydrate. In contrast, there was no detectable evidence for the presence of N-linked glycosylation. The results also demonstrate that this antigen circulates at elevated levels in patients with carcinoma of the lung. These findings are similar to previous reports of high molecular weight glycoproteins in breast and ovarian carcinomas. Indeed, the present results in lung cancer identify another member of this heterogeneous family of human carcinoma-associated glycoproteins.

Adenocarcinoma↗
PubMed1990

Comprehensive management of disseminated breast cancer.

The management of patients with metastatic breast cancer is best achieved by the judicious use of local and systemic measures that palliate symptoms and improve overall quality of life. When two treatment approaches are known to be equally efficacious, the less toxic should be used. When disease is limited to one or two sites and the patient has an indolent form of the disease, the patient's symptoms are often best palliated with the use of surgery or radiotherapy alone. When multiple sites of disease are evident or the disease is progressing more rapidly, systemic therapy is preferred, and local therapies should be added when the patient is clearly refractory to systemic therapy or when the disease site is unlikely to be adequately palliated with systemic therapy. The use of any of these therapies, including chemotherapy, has a relatively small effect on the median survival of patients with metastatic breast cancer. However, improvements in quality of life are usually greatest with regimens inducing the highest response rates, even when these regimens are associated with greater toxicity. The characteristics of patients likely to respond to endocrine therapy are well defined; in these patients endocrine therapy should be used as the first form of systemic therapy. Among endocrine therapies, the least toxic is used first. The selection of patients for chemotherapy is largely a process of exclusion. When chemotherapy is used, there are a number of different strategies for sequencing chemotherapy that appear to be equally efficacious. In general, patients should be treated with standard doses of drug combinations for a period in excess of 3 months. When used inappropriately, especially in asymptomatic patients, these therapies may actually compromise the patient's quality of life. The use of surgery, radiation therapy, and systemic therapy should be integrated with various types of psychosupport services, especially peer support groups. Patients who want to try new forms of therapy should do so early in the course of the disease when these therapies are most likely to be effective and the patient has the least to lose if the therapy proves ineffective. This is especially true because the use of the most effective regimens at a time when the patient is asymptomatic may mean that the patient is resistant to most or all therapies of proven value when most in need of palliation.

Breast Neoplasms↗