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Biomedical subjects

D N Carney

Publications and source records attributed to D N Carney.

At least 91 records · Page 5Linked to original sources
PubMed1989

The biology of lung cancer. A review.

Advances in the understanding of the biology of lung cancer have progressed rapidly over the last decade. It is clear that considerable heterogeneity exists both in small-cell and non-small-cell lung cancer tumours with common properties being shared by both cell types. To further understand the prognostic and clinical significance of these biological properties it is clear that in future clinical trials of both tumour types these properties should be taken into consideration.

Biomarkers, Tumor↗
PubMed1989

Ovarian carcinoma.

Considerable advances have been made in understanding the biological properties and improvements in treatments in ovarian carcinoma over the past decade. Even for patients with advanced disease at the time of presentation, cytotoxic chemotherapy with or without radiotherapy had had a major impact upon overall survival. However few patients are cured of their disease when they present at an advanced stage and in the years ahead considerable pressure will be brought on the use of alternative modalities of therapy and the detection of ovarian carcinoma at a much earlier stage if these improvements are to be maintained. The use of monoclonal antibodies and other biological response modifiers such as interferons or the use of compounds to overcome drug resistance may lead to further improvements in patient survival.

Combined Modality Therapy↗
PubMed1988

Demonstration of Chromogranin A in human neuroendocrine cell lines by immunohistology and immunoassay.

We have used immunohistology and radioimmunoassay procedures to study Chromogranin A (CgA) in human neuroendocrine tumor cell lines, especially small cell lung cancers (SCLC). By immunohistology, CgA could be detected in 11 of 18 classical SCLC cell lines, in a medullary thyroid carcinoma (MTC) cell line, and in only one of 13 variant- or non-SCLC cell lines. By radioimmunoassay, CgA could be detected in the cells and culture media of all of the classical SCLC cell lines tested. Many of the classical SCLC cell lines also produced calcitonin (CT). These studies demonstrate that CgA production is a common feature of SCLC cell lines, especially those with neuroendocrine characteristics.

Calcitonin↗
PubMed1988

Quantitative description of classic and variant small cell lung cancer cell lines by nuclear image cytometry.

Six small cell lung cancer (SCLC) cell lines were examined using nuclear image analysis to find features characteristic of the classic and the variant type of SCLC. On the basis of their biochemical and biological properties three of these cell lines have been shown to represent the classic types, and three represent the variant type of SCLC. Using a combination of the image-derived run length, density, and geometric features, it was possible to distinguish between the classic and variant SCLC cell lines. The results of this study may be of help in assessing photometric features for the separation of the classic and variant subtypes of SCLC in solid tumors. Because of differences in treatment and prognosis between these two subtypes, such a separation may be of clinical value.

Carcinoma, Small Cell↗
PubMed1988

Levels of neuron-specific enolase after chemotherapy do not predict a response in small cell lung cancer.

Neuron-specific enolase (NSE) was measured in serum samples of 35 patients with small cell lung cancer and 10 control patients. The samples were collected during 10 days after the first course of chemotherapy, in order to investigate whether changes of NSE had a predictive value of tumour response. Three patterns of change of NSE were observed. Pattern 1 showed an increase of serum NSE with a maximum value more than 1.5 times the pretreatment level (n = 17); pattern 2 involved no increase at all or less than 1.5 times the pretreatment level (n = 14); pattern 3 showed a continuous decrease (n = 5). No relationship between the three patterns of change and the tumour response was observed. Only an NSE level less than 10 ng/ml at the time of start of the second course predicted a major response.

Carcinoma, Small Cell↗
PubMed1988

Neurotensin binds with high affinity to small cell lung cancer cells.

Several small cell lung cancer cell lines bound 125I-neurotensin with high affinity. Radiolabeled neurotensin bound with high affinity (Kd = 4 nM) to a single class of sites (2300/cell) using cell line NCI-H209. Binding was time dependent and reversible. Pharmacology studies indicated that the C-terminal of neurotensin was important for the high affinity binding activity. Because high concentrations of neurotensin and its receptors are associated with small cell lung cancer, neurotensin may function as a regulatory peptide in this disease.

Binding, Competitive↗
PubMed1988

Desmosomal plaque proteins are preserved in all grades of breast cancer. An immunohistochemical study utilizing monoclonal antibodies to desmoplakin.

Using a monoclonal antibody specific for desmoplakin, we evaluated 52 breast carcinomas, 25 normal tissues, 10 benign breast lesions, and 14 nonepithelial tumors. Carcinomas were classified as ductal or lobular, and they were graded histologically according to degree of malignancy and differentiation. Nonepithelial tumors were negative for desmoplakin. All carcinomas stained positively. Desmosomal staining occurred along epithelial cell borders as discrete, punctate granules. Staining intensity was similar in infiltrating carcinomas, in situ carcinomas, benign breast lesions, and normal breast epithelium. Our study demonstrates that most infiltrating breast carcinomas retain abundant desmoplakin, regardless of tumor grade, degree of differentiation, or tumor type (duct or lobular). Although altered desmosomal structure may be important, our findings suggest that loss of desmosomes is not necessary for tumor invasion or metastasis. Desmosomes have a characteristic staining pattern that is easy to interpret, and monoclonal antibodies to desmoplakin may prove useful as markers for distinguishing undifferentiated carcinomas from nonepithelial cancers.

Antibodies, Monoclonal↗
PubMed1988

Bombesin: a potent mitogen for small cell lung cancer.

While advances in the diagnosis and staging of SCLC have been made over the past decade, overall therapeutic results remain essentially unchanged. However, during this time period there have been major advances in understanding the biology of this tumor cell type. The recognition of considerable heterogeneity among SCLC cells may be of prognostic importance, while the demonstration of specific growth factors, including bombesin, for this tumor type may open up new means for endocrine therapy of lung carcinoma in vivo. Over the next 5-10 yr, studies of clinical trials using specific antibodies or analogs of bombesin-like growth factors in patients with SCLC will define more clearly the role of BLI and GRP in patients with this disease.

Animals↗
PubMed1988

Spontaneous changes in intermediate filament protein expression patterns in lung cancer cell lines.

The usefulness of cell lines in the study and prediction of the clinical behaviour of lung cancer is still a matter of debate. However, lung tumour cell cultures have been of value in investigations concerning molecular and cell biological aspects of these neoplasms. Especially in the examination of characteristics specific for the main types of differentiation (squamous cell carcinoma, adenocarcinoma, small cell carcinoma), in vitro studies have been most important. Twenty eight lung cancer cell lines were cultured for up to four years, and were examined at regular intervals for their intermediate filament protein (IFP) expression patterns using a panel of cytokeratin (CK) and neurofilament (NF) antibodies. These studies showed that the classic type of small cell lung cancer (SCLC) cell lines contain CKs 8, 18, and occasionally CK 19, while the variant-type SCLC cell lines generally express no CKs but can contain NFs. Non-SCLC cell lines, such as squamous cell carcinoma and adenocarcinoma cell lines, contain CKs 7 (in most cases), 8, 18 and 19. In one variant SCLC cell line and in one adenocarcinoma cell line CKs 4, 10 and 13, characteristic of squamous cell differentiation, were found. Although most cell lines have remained stable with respect to growth characteristics and IFP expression patterns, five lung cancer cultures exhibited a transition from one cell type to another, paralleled by changes in IFP expression. Progressions from classic to variant SCLC cell lines have been observed, next to conversions from variant SCLC to cell lines re-expressing cytokeratins. In some cases this resulted in a coexpression of CKs and NFs within a cell line and even within individual tumour cells. These results strongly support the earlier finding that CK expression in SCLC cell lines is a reliable marker for the classic type of differentiation, while the absence of CKs and the presence of NFs marks the variant type of differentiation. Our results are discussed in view of previous histological findings.

Carcinoma, Small Cell↗
PubMed1988

BN/GRP-like peptides and receptors in small cell lung cancer.

BN/GRP-like peptides are produced in high concentrations in SCLC cell lines and in low concentrations in beta-lymphoblastoid cell lines. The BN/GRP-like peptides are secreted from SCLC cell line NCI-H345 by stimuli which elevate the intracellular cAMP levels. These stimuli include theophylline, PHI, secretin and VIP. Also, elevated plasma levels of BN/GRP-like peptides are found in patients with extensive SCLC. In these patients the levels of BN/GRP-like peptides can be increased further approximately 5-fold after secretin infusion. Because SCLC cells make and secrete BN/GRP-like peptides, they may function as regulatory peptides in this disease.

Carcinoma, Small Cell↗
PubMed1988

Small cell lung cancer cell lines: pure and variant types can be distinguished by their extracellular matrix synthesis.

Variant subclasses of cell lines derived from small cell lung cancers have previously been characterized, having distinctive biochemical, morphological and growth properties compared to the classic lines. Both types of small cell lung cancer express features suggesting that they are derived from neuroectodermal cells. We compared the capacity of these two types of lung cancer cell lines to synthesize the extracellular matrix glycoproteins, fibronectin and laminin, and also analysed a few other non-small cell lung cancer lines, as controls. We found that the cell lines of the pure type did not produce laminin or fibronectin, whereas the cell lines of the variant type synthesized laminin, and the non-small cell lung cancer lines produced either laminin or fibronectin. These findings suggest that the variant form of small cell lung cancer may be derived from a primitive neuroectodermal cell, with both neural and epithelial features, whereas the classic type is derived from a more mature cell with predominantly neuronal features. The differences in extracellular matrix synthesis, and laminin in particular, may explain some of the in vitro and in vivo characteristics of the tumour.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Lung cancer biology.

Advances in the understanding of the biology of lung cancer have progressed rapidly over the past decade while treatment results have remained essentially unchanged. It is clear that the knowledge of the heterogeneity of lung cancer cell types in respect of growth properties, biomarker expression, oncogene expression, and antigen expression needs to be applied in the clinic; and their role in predicting response to cytotoxic therapy and survival needs prospective evaluation. In addition the application of cell lines in screening for tumor-specific cytotoxic agents should provide for a more rational approach for drug selection in future clinical trials. Finally the development of magnetic resonance spectroscopy may also play a role both in further understanding the biology of lung cancer, and in the clinical assessment of tumor sensitivity in vivo. More recent data using DNA probes specific for the cytogenetic deletion on chromosome 3, previously identified in only SCLC, suggests that this deletion 3p 14-23 is common to most, if not all, cell types of lung cancer. This adds further to the hypothesis that a common stem cell exists from which all histologic types of lung cancer arise.

Antigens, Neoplasm↗
PubMed1987

Levels of high energy phosphates in human lung cancer cell lines by 31P nuclear magnetic resonance spectroscopy.

Human lung cancers are divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on established criteria. SCLC differs from NSCLC by the expression of biomarkers, including creatine kinase-BB isoenzyme (EC 2.7.3.2). Subtypes of SCLC are referred to as classic and variant, both of which have elevated levels of creatine kinase-BB isoenzyme. We, therefore, applied 31P nuclear magnetic resonance spectroscopy to cell lines of classic SCLC, variant SCLC, and NSCLC human tumors, using continuous perfusion to identify any differences in the detectable levels of intracellular high-energy phosphate compounds. The spectra indicate that only the variant SCLC cells maintain high levels of phosphocreatine. Additionally, the classic SCLC cells express elevated levels of a diphosphodiester. Neither phosphocreatine nor diphosphodiesters are found in the NSCLC cell spectra.

Adenosine Triphosphate↗