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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
PubMed2001

Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells.

Reports differ as to whether reconstitution of telomerase activity alone is sufficient for immortalization of different types of human somatic cells or whether additional activities encoded by other "immortalizing" genes are also required. Here we show that ectopic expression of either the catalytic subunit of human telomerase (hTERT) or a temperature-sensitive mutant (U19tsA58) of simian virus 40 large-tumor antigen alone was not sufficient for immortalization of freshly isolated normal adult human mammary fibroblasts and endothelial cells. However, a combination of both genes resulted in the efficient generation of immortal cell lines irrespective of the order in which they were introduced or whether they were introduced early or late in the normal proliferative lifespan of the cultures. The order and timing of transduction, however, did influence genomic stability. Karyotype analysis indicated that introduction of both transgenes at early passage, with hTERT first, yielded diploid cell lines. Temperature-shift experiments revealed that maintenance of the immortalized state depended on continued expression of functional U19tsA58 large-tumor antigen, with hTERT alone unable to maintain growth at nonpermissive temperatures for U19tsA58 large-tumor antigen. Such conditional diploid lines may provide a useful resource for both cell engineering and for studies on immortalization and in vitro transformation.

Adult↗
PubMed2001

Detection of occult metastasis in patients with breast cancer.

The most important factor affecting the outcome of patients with invasive cancer is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary "curative" therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by routinely employed methods (careful pathological, clinical, biochemical, and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention.

Breast Neoplasms↗
PubMed2001

Occult metastasis.

The most important factor affecting the outcome of patients with invasive cancers is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary 'curative' therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by methods routinely employed (careful pathological, clinical, biochemical and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident [1]. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention.

Bone Marrow↗
PubMed2001

Occult metastases in patients with breast cancer.

The presence of occult metastases in the lymph nodes, bone marrow, or both of these compartments may not only define patients who are at higher risk for recurrence and death but also may identify biologically distinct mechanisms of tumor spread (e.g., lymphatic vs. vascular dissemination). Use of techniques to detect occult metastases may also allow the identification of a biologically important population of cells, i.e., those cells constituting the earliest metastatic population of tumor cells. Thus, techniques that identify occult metastases may be valuable in furthering our understanding of the events regulating tumor dissemination.

Bone Marrow Neoplasms↗
PubMed1999

Role of immunohistochemical detection of lymph-node metastases in management of breast cancer. International Breast Cancer Study Group.

BACKGROUND: This study was designed to ascertain whether immunohistochemical methods could improve the detection of metastases in primary breast-cancer patients whose axillary lymph nodes were classified, by conventional methods, as disease free. METHODS: Ipsilateral lymph nodes (negative for metastases by routine histology) from 736 patients (participants in Trial V of the International [Ludwig] Breast Cancer Study) were examined by serial sectioning and staining with haematoxylin and eosin (two sections from each of six levels) and by immunohistochemistry of a single section (with two anticytokeratins AE-1 and CAM 5.2). After median follow-up of 12 years, disease-free and overall survival were estimated by Kaplan-Meier methods. FINDINGS: Occult nodal metastases were detected by serial sectioning and haematoxylin and eosin in 52 (7%) of 736 patients and by immunohistochemistry in 148 (20%). Only two (3%) of 64 invasive lobular or mixed invasive lobular and ductal cancers had node micrometastases, detected by haematoxylin and eosin, compared with 25 (39%) by immunohistochemistry. Occult metastases, detected by either method, were associated with significantly poor disease-free and overall survival in postmenopausal but not in premenopausal patients. Immunohistochemically detected occult lymph-node metastases remained an independent and highly significant predictor of recurrence even after control for tumour grade, tumour size, oestrogen-receptor status, vascular invasion, and treatment assignment (hazard ratio 1.79 [95% CI 1.17-2.74], p=0.007). INTERPRETATION: The immunohistochemical examination of ipsilateral axillary lymph nodes is a reliable, prognostically valuable, and simple method for the detection of occult nodal metastases. Immunohistochemistry is recommended as a standard method of node examination in postmenopausal patients.

Adult↗
PubMed1999

Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours.

The presence of a high number of infiltrating CD1a+ cells in malignant neoplasms has been reported to be associated with an improved prognosis, reduced tumour recurrence and fewer metastases. This study identified a population of CD1a+ cells within the lymphoid cell infiltrate in human ductal breast carcinoma (n = 52), which was significantly different from normal breast tissue, in which only two out of nine cases expressed CD1a+ cells (P = 0.0192). In the majority of cases, the infiltrate was low compared with the number of macrophages and T cells present (results not shown). There was no correlation between the number of CD1a+ cells and tumour grade, with all tumour grades expressing similar numbers of infiltrating CD1a+ cells. There was clear evidence, however, that the CD1a+ cells were closely associated with tumour cells. It is likely that CD1a+ cells have a role in antigen capture and presentation in human tumours, and this study documents the density of CD1a+ cells in a large sample of all histological grades of human breast carcinomas.

Antigens, CD↗
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↗
PubMed1988

The relationship between micrometastases in the bone marrow, histopathologic features of the primary tumor in breast cancer and prognosis.

The pathologic features of the primary tumors in 285 patients with breast cancer at the time of initial presentation, and with no clinical evidence of distant metastases, have been analyzed. The results have been compared with the detection of tumor cells in the bone marrow by use of an immunocytochemical method using antisera raised against the epithelial membrane antigen (EMA). The authors found EMA-positive cells (i.e., tumor cells) in the bone marrow of 77 (27%) patients and a significant association between the presence of such EMA-positive cells in the bone marrow and tumor size (P = 0.006) and peritumoral vascular invasion (P = less than 0.001). A possible relationship with estrogen receptor negativity (P = 0.06) also was noted.

Adult↗