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Biomedical subjects

A M Neville

Publications and source records attributed to A M Neville.

At least 19 recordsLinked to original sources
PubMed1992

Factors predicting treatment responsiveness and prognosis in node-negative breast cancer. The International (Ludwig) Breast Cancer Study Group.

PURPOSE: An international trial (formerly Ludwig Trial V) has been conducted in 1,275 subjects to ascertain if perioperative chemotherapy is beneficial for node-negative breast cancer patients and to identify subgroups of patients who benefit from this therapy. PATIENTS AND METHODS: Node-negative breast cancer patients were randomized to receive either one cycle of perioperative chemotherapy or no adjuvant treatment. A detailed pathology review was conducted in 1,203 of the 1,275 patients enrolled. Stepwise Cox regression analysis was used to search for factors either predicting chemotherapeutic responsiveness and/or influencing disease-free survival (DFS). RESULTS: As expected, primary tumor size, grade, and the presence of peritumoral vascular invasion are the most important prognostic factors. Perioperative chemotherapy provides a DFS advantage at 5 years of median follow-up and such treatment is more effective for estrogen receptor-negative than for estrogen receptor-positive tumors, for histologic grade 2 and 3 than for grade 1 tumors, and for patients in whom no axillary lymph node metastases were found even after serial sectioning and review by the Central Pathology Laboratory. CONCLUSION: Hormone receptor status and tumor grade are important factors for predicting responsiveness to perioperative chemotherapy in node-negative breast cancer.

Adult↗
PubMed1991

Detection of tumor antigens with monoclonal antibodies: immunopathology and immunodiagnosis.

The immunocytochemical demonstration, using monoclonal antibodies, of diverse cellular constituents has improved our understanding of many aspects of oncology. This review will focus on this approach to facilitate the detection of human tumors, improve their histological classification and provide functional parameters with potential aetiological, prognostic and/or therapeutic value.

Antibodies, Monoclonal↗
PubMed1990

Functional immunocytopathology and the diagnosis of bone marrow micrometastases.

Immunocytochemical methods offer a new dimension for cytopathology in the diagnosis, prognosis and biology of neoplastic diseases. This concept is illustrated with particular respect to the immunodetection of bone marrow micrometastases and the role of cytologically demonstrable functional parameters in prognosis and therapy planning. A future role for the polymerase chain reaction (PCR) in this diagnostic sphere is proposed.

Biomarkers, Tumor↗
PubMed1990

Characterization of monoclonal antibodies reactive with normal resting, lactating and neoplastic human breast.

Mouse monoclonal antibodies reacting with human mammary gland constituents have been generated and characterized in an attempt to raise breast- or breast-cancer-specific antisera. The immunogens used in these studies included fractionated human milk fat globule membrane, the human breast cancer cell line MCF7 and a crude membrane preparation derived from an axillary nodal metastasis from a patient with breast cancer. Of the antibodies obtained, 8 were characterized and found to bind to different structures in the normal breast. The antibody LICR-LON-LC28 recognizes secretory component and binds strongly to normal resting and lactating breast, but only focally to a minority of breast carcinomas. The antibodies LICR-LON-14.1 and 32.2 react strongly with the lactating breast and recognize kappa- and beta-casein, respectively. Caseins are not produced by breast tumors. The antibodies LICR-LON-TW19.5, H10A and 39.8 all react with carbohydrate epitopes and bind heterogeneously to normal resting breast luminal epithelium and cellular subsets of breast carcinomas. LICR-LON-59.2 and 19.2 react with normal breast myoepithelial cells and the basement membrane, respectively. LICR-LON-59.2 is unusual as a myoepithelial marker in that it stains cells in the majority of breast carcinomas. LICR-LON-19.2 shows extensive reactivity to tumor cell lines in culture but has no reactivity with carcinoma cells from breast biopsies.

Animals↗
PubMed1987

Human breast epithelium in vitro: the re-expression of structural and functional cellular differentiation in long-term culture.

Fragments of human breast epithelium, devoid of all stromal and basal lamina components, which maintain their in vivo topological organisation can be cultured for up to 28 days within a reconstituted rat-tail-derived collagen matrix. These organoids initially undergo a loss of structural and 3-dimensional organisation, typified by loss of lumina formed by epithelial cells, and myosin from myoepithelial cells. Their subsequent reorganisation is dependent on the presence of serum, insulin, hydrocortisone, and cholera toxin in tissue culture medium. After this preliminary phase, a reduction in the concentration of serum, insulin, hydrocortisone, and cholera toxin is necessary to allow the structural differentiation of epithelial and myoepithelial cells. The myoepithelial cells also regain their ability to produce the basal lamina component laminin. The use of bovine-dermal collagen as the matrix, rather than rat-tail-derived collagen is shown to result in more stable organisation and differentiation of the organoids. The successful use of single-cell pellets (derived by trypsinisation of the organoids) in place of organoids in such cultures illustrates that there is no requirement for pre-existing cell/cell contact or topological organisation of cells prior to embedding within the collagen matrix.

Breast↗
PubMed1987

Expression of breast epithelial differentiation antigens in human primary breast cancer.

Monoclonal antibody LICR-LON-M18 is a marker of normal human breast epithelial cell differentiation. The epitope recognized by LICR-LON-M18 is a prominent component of luminal plasma membranes of nonneoplastic resting and lactating human breast epithelial cells but is rarely expressed by human breast carcinomas. With the use of competitive binding-inhibition studies, the immunodominant portion of the LICR-LON-M18 epitope was shown to be the following oligosaccharide sequence [with galactose (Gal) and N-acetylglucosamine (GlcNAc)]: Gal beta 1----4GlcNAc beta 1----. This structure was distinct from Gal beta 1----3GalNac, which was bound by peanut agglutinin (PNA) and was not recognized by LICR-LON-M18 [corrected]. With the use of biochemical techniques, the present data not only confirmed sialylation and consequent "masking" of the LICR-LON-M18 epitope and PNA determinants in human breast carcinomas but also identified the particular groups of glycoproteins involved in this process. These studies provided additional support for the thesis that sialylation of human breast carcinoma glycoproteins represented an enhancement of specific differentiation events normally regulated in the morphogenesis of nonneoplastic human breast epithelium and that specific glycoproteins became masked during the genesis of primary human breast cancer.

Adenocarcinoma, Mucinous↗
PubMed1979

The pathology of adrenocortical neoplasia: a correlated structural and functional approach to the diagnosis of malignant disease.

The structural and functional characteristics of nine functioning adrenocortical tumors (four adenomas and five carcinomas) causing Cushing's syndrome or virilization were studied. All tumors that we considered to show histologic evidence of malignant disease and that subsequently metastasized or recurred also showed in cell culture at least one significant functional or behavioral difference from benign tumors. No single defect was common to all carcinomas, but predominant changes included secretion of precursor steroids, such as 11-deoxycortisol (S) and a blunted or absent response to ACTH. All adenomase examined were normal in these respects in comparison with nondiseased cortical cells in culture. In carcinomas whose functions deviated only minimally from normal the presence of highly differentiated ultrastructural characteristics did not, however, confer a better prognosis.

Adenoma↗
PubMed1978

Aminoglutethimide in treatment of metastatic breast carcinoma.

42 patients with metastatic breast carcinoma were treated with aminoglutethimide, which inhibits adrenal steroid hormone synthesis. Treatment was stopped in 2 patients before response could be assessed; of the other 40, 15 (37.5%) had an objective response, 1 (2.5%) showed a response in bone but not in soft tissue, and 4 (10%) had complete or very great relief of metastatic bone pain but no radiological evidence of improvement. 19 (53%) of 36 patients with bone metastases responded to treatment (15 had X-ray evidence and 4 had pain relief), as did 5 (45%) of 11 patients with soft tissue metastases, 2 (25%) of 8 with malignant marrow infiltration, 1 (14%) of 7 with lung metastases, and none of 13 with liver metastases. Response was commonest in patients who had previously responded to other forms of endocrine therapy. Side-effects, usually mild and transient, occurred in a few patients; the most important were an initial period of somnolence in 9 patients and a rash in 5.

Administration, Oral↗
PubMed1978

The monitoring role of plasma CEA alone and in association with other tumor markers in colorectal and mammary carcinoma.

During the past decade, evidence has accumulated to show that most, if not all, human tumors produce a variety of different factors which, if they pass into the blood and/or urine, may serve as tumor index substances (tumor markers).7 Tumor markers may either be: 1) tumor-derived--i.e., produced by the tumor itself, or 2) tumor-associated--i.e., produced by other tissues in response to the presence of the tumor and its local or distant effects on that tissue. Examples of this latter category include the changes in urinary hydroxyproline output in patients with bone metastases or the altered levels of serum acute phase proteins in neoplasia in general.7 Tumor-derived markers may be produced by either the tumor cell population itself, e.g., CEA, alpha-fetoprotein (AFP), and other oncofetal antigens, inappropriate hormones such as ACTH etc., or by their supporting framework (stroma), e.g., the osteolysins of human breast cancer.3

Breast Neoplasms↗