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Biomedical subjects

D N Carney

Publications and source records attributed to D N Carney.

At least 37 records · Page 2Linked to original sources
PubMed1995

Amplification of the MDM2 gene in human breast cancer and its association with MDM2 and p53 protein status.

The present study reports on the frequency of MDM2 gene amplification and MDM2 protein expression in a series of 100 breast carcinomas and its association with accumulation of the p53 protein. Of the 100 cases, frozen samples for 82 cases were available for Southern blotting. Three of the 82 (4%) demonstrated MDM2 gene amplification of up to 6-fold. Immunohistochemical analysis of the formalin-fixed, paraffin-embedded tumours demonstrated that 7/97 (7%) had nuclear expression for MDM2 in 10-50% of the tumour cells (type 2 staining) and were denoted MDM2+. Two of the MDM2-amplified samples were MDM2+ with one of the two tumours also displaying type 2 p53 nuclear staining. Finally at the protein level, MDM2+ tumours were significantly associated with tumours having low levels of p53 staining (0-10% cells positive) (P = 0.03). We conclude that MDM2 gene amplification occurs at a lower frequency in breast cancer than in non-epithelial tumours. Alterations in MDM2 and p53 may represent alternative pathways in tumorigenesis, but they are not mutually exclusive in all cases.

Blotting, Southern↗
PubMed1995

A germline TaqI restriction fragment length polymorphism in the progesterone receptor gene in ovarian carcinoma.

Clinical outcome in ovarian carcinoma is predicted by progesterone receptor status, indicating an endocrine aspect to this disease. Peripheral leucocyte genomic DNAs were obtained from 41 patients with primary ovarian carcinoma and 83 controls from Ireland, as well as from 26 primary ovarian carcinoma patients and 101 controls in Germany. Southern analysis using a human progesterone receptor (hPR) cDNA probe identified a germline TaqI restriction fragment length polymorphism (RFLP) defined by two alleles: T1, represented by a 2.7 kb fragment; and T2, represented by a 1.9 kb fragment and characterised by an additional TaqI restriction site with respect to T1. An over-representation of T2 in ovarian cancer patients compared with controls in the pooled Irish/German population (P < 0.025) was observed. A difference (P < 0.02) in the distribution of the RFLP genotypes between Irish and German control populations was also observed. The allele distributions could not be shown to differ significantly from Hardy-Weinberg distribution in any subgroup. Using hPR cDNA region-specific probes, the extra TaqI restriction site was mapped to intron G of the hPR gene.

Alleles↗
PubMed1995

Management (chemotherapy/best supportive care) of advanced-stage non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents almost three quarters of all cases of lung cancer. Most NSCLC patients present with either locally advanced inoperable disease, stage IV metastatic disease, or comorbid medical conditions that make them unsuitable for curative resection. Among NSCLC patients in the United States, overall 5-year survival rates range from 10% to 15%. Systemic chemotherapy has had minimal impact on prolonging survival or improving quality of life. Combination chemotherapy regimens containing cisplatin usually produce the best overall response rates. Combination chemotherapy in one study also has been shown to be more efficacious and less expensive than best supportive care. Newer cytotoxic agents, including vinorelbine, gemcitabine, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), docetaxel, and the camptothecins, have shown promise in the treatment of NSCLC. In combination with other effective agents (eg, cisplatin), response rates approaching 50% have been observed. A greater understanding of the biologic properties of lung cancer may help facilitate early detection and chemoprevention in patients at risk.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

The biology of lung cancer.

Lung cancer remains the major cancer killer worldwide. Although advances have been achieved in the past 20 years in understanding the important clinical and prognostic factors for both small cell lung cancer and non-small cell lung cancer, with few exceptions no significant advances have been made in therapeutic results. For patients who have small cell lung cancer, the hope for prolonged survival relates to the sensitivity of the tumor to chemotherapy, with or without radiation therapy. For patients who have non-small cell lung cancer, the only hope for survival is whether the tumor can be surgically excised. Despite only modest advances and responses to systemic treatment for lung cancer, there have been major advances in our understanding of the biologic properties of lung cancer throughout the past decade and a half. The development of numerous cell lines of both major cell subtypes of lung cancer has allowed an in-depth study of its biologic and molecular properties. This paper reviews recent developments in the biology of lung cancer and how these advances may impact on the treatment of patients who have this disease.

Antibodies, Neoplasm↗
PubMed1994

Etoposide in the treatment of elderly/poor-prognosis patients with small-cell lung cancer.

Survival rates for cancer have improved in recent decades, specifically for younger patients. However for those over 65, who account for over half of all cancer patients, mortality rates remain poor. In those with small-cell lung cancer the achievement of cure is possible in only a minority (5-10%). For the elderly and those with extensive disease we have found that the use of oral etoposide offers similar survival rates to more intensive regimens, with minimal side effects and hospitalisation. Thus the expansion of the elderly population mandates for more specific chemotherapeutic approaches in this group.

Adult↗
PubMed1994

Soft tissue and visceral sarcomas in Irish patients. Interim analysis of data obtained by the Dublin Soft Tissue Tumour Panel.

The Dublin Soft Tissue Sarcoma Panel was established in 1989 with a view to achieving a unified approach to diagnosis and management of soft tissue and visceral sarcomas. This interim report presents data on 265 prospectively-evaluated patients and on a separate retrospective series of 126 patients. The patients in the prospective series were treated by 93 different surgical and medical specialists. Tumours presented in all anatomic sites and ranged in size from 0.2 to 60 cm. Leiomyosarcoma was the commonest tumour type. Eighty-nine tumours were inoperable at clinical presentation. There was a consensus panel diagnosis in over 90%, non-neoplastic reactive lesions and primitive round cell tumours being the most difficult cases diagnostically. Management, including onward referral for chemotherapy or radiation therapy, was inconsistent. The 2-year survival figures were: 43% (1989-91) and 37% (1980-88). These findings should provide a basis for the evaluation of coherent treatment strategies for Irish sarcoma patients.

Adolescent↗
PubMed1994

Somatostatin receptor expression in lung cancer.

Experimental evidence suggests that somatostatin analogues may have a role to play in the management of lung tumours. We evaluated membrane preparations of nine small cell lung cancer (SCLC) cell lines and of tumour samples from 3 patients with non-small cell lung cancer (NSCLC), 1 patient with an atypical carcinoid and another with a bronchial carcinoid for the presence of specific binding sites for RC-160, a potent growth inhibitory octapeptide analogue of somatostatin. Specific binding was noted on six of nine SCLC lines. Radio-receptor assay on the cell line NCI H 69 showed evidence of two specific binding sites for RC-160, one with high affinity and the other with low affinity. Binding sites were also found on all five tumour samples. Scatchard analysis indicated the presence of a single class of receptors with high affinity in each case. Histological assessment of the resected specimens before binding assay showed them to be comprised of tumour cells and necrotic tissue, stroma and/or inflammatory cells. Therefore, the specific binding of RC-160 may be to tissues other than the tumour cells. In 3 patients, from whom the tumour samples were obtained, radiolabelled somatostatin analogue scintigraphy using [111In] pentetreotide was performed prior to surgery. In all cases, the radiolabel localised the disease. This study demonstrates the presence of specific binding sites for RC-160 in SCLC. Furthermore, the detection of specific binding in vitro and in vivo in NSCLC and intrapulmonary carcinoids demonstrates that these tumours contain cells which express specific binding sites for somatostatin. These results suggest that RC-160 may have a role to play as a therapeutic agent in lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Scintigraphic imaging of small-cell lung cancer with [111In]pentetreotide, a radiolabelled somatostatin analogue.

Recent work suggests that between 50 and 75% of small-cell lung cancer (SCLC) tumours have specific high-affinity binding sites for somatostatin. This study evaluated the potential role of the radiolabelled somatostatin analogue, [111In]pentetreotide, in the detection and staging of SCLC in patients prior to and after chemotherapy using scintigraphic imaging techniques. Thirteen patients were studied prior to chemotherapy. Following standard staging six patients had limited stage disease and seven extensive disease. [111In]pentetreotide imaging led to the detection of all primary sites of disease, including a primary site of disease not detectable with chest radiograph or computerised tomography (CT) of the thorax. Five of ten metastatic sites detected by standard staging were also imaged. Furthermore, a cerebellar metastasis was detected in a patient thought to have disease confined to the right hemithorax. This was subsequently confirmed with a CT brain scan. Following chemotherapy [111In]pentetreotide imaging detected residual intrathoracic disease in two of three patients with complete remissions by standard staging and in two patients who had had a partial response to chemotherapy. These results suggest that [111In]pentetreotide imaging may have a role to play in the clinical evaluation of patients with SCLC. Specifically, this technique may be of particular value in detecting residual intrathoracic disease in patients thought to be in complete remission by conventional staging methods.

Adult↗
PubMed1994

The diagnostic value of silver nucleolar organizer region assessment in breast cytology.

Benign and malignant breast lesions in cytologic preparations can be difficult to distinguish. The authors applied the silver nucleolar organizer region (AgNOR) technique to cytologic preparations obtained from surgical specimens to evaluate its diagnostic usefulness in making this distinction. Sixty-two benign and 36 malignant lesions were examined. AgNORs were counted and evaluated using a subjective scoring technique to examine AgNOR size, shape, and clustering. The benign lesions had a mean count of 4.44 AgNORs/nucleus (95% CI, 2.4-6.5) and the malignant cases, 9.52 AgNORs/nucleus (95% confidence interval, 7.4-11.7; P < .0005). The median score for benign cases was 7 and for malignant cases, 13 (P < .0001). With a few exceptions, cases with high counts had high scores. The diagnostic accuracy of combined counting and pattern assessment was 90%. The likelihood ratio for correct diagnosis using AgNOR counting was 14:1 and for AgNOR scoring, 13:1.

Breast↗
PubMed1994

Bcl-2 rearrangement in Hodgkin's disease and reactive lymph nodes.

The chromosomal translocation t(14;18)(q32;q21), which involves the bcl-2 oncogene, occurs in most follicular lymphomas. Recent evidence suggests that this translocation occurs in Hodgkin's disease, linking its cellular origin and oncogenesis to follicular non-Hodgkin's lymphomas. Using polymerase chain reaction, the authors examined both Hodgkin's disease (n = 60) and reactive lymph nodes (n = 34) for the presence of bcl-2/JH breakpoint fragments, which are indicative of the t(14;18) chromosomal translocation in the major breakpoint region of the bcl-2 gene. The translocation was detected in approximately 10% of both Hodgkin's disease and nonmalignant reactive lymph node cases. These results suggest the possibility that the translocation may occur in the reactive component of Hodgkin's disease and not in the putative malignant cells, the Reed-Sternberg cells. Furthermore, the detection of the translocation in reactive lymph nodes suggests that it may not be the primary factor in the oncogenesis of follicular lymphoma.

Base Sequence↗
PubMed1994

Comparable prognostic factors and survival in elderly patients with aggressive non-Hodgkin's lymphoma treated with standard-dose adriamycin-based regimens.

We retrospectively analysed the prognostic factors at diagnosis, clinical response, and survival of 192 patients with newly diagnosed aggressive NHL treated in a single institution between 1985 and 1991. Overall, 37.5% (72/192) of patients were 65 years or older (average age 71 years, range 65-85 years), and 62.5% (120/192) were under 65 years of age (average age 45, range 16-64 years). All patients were completely staged and had intermediate- or high-grade NHL. 127 patients were treated on similar regimens with the same chemotherapy dose intensity irrespective of age. Standard-dose m-BACOD (methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, prednisone) or CHOP were used to treat 60/72 (83%) elderly patients and 67/120 (56%) patients less than 65 years. The remaining younger patients were treated with more intensive regimens. There were no significant differences between the groups with regard to stage, histological grade, cell type, elevated LDH, number of extranodal sites, presence of B symptoms, or bulky disease. More elderly patients had a significantly (p < 0.02) poorer performance status (PS), with 42% (25/60) having a PS of 2 or more, compared to 22% (15/67) in those less than 65 years of age. Elderly patients had an inferior complete response rate, 65% versus 76%. However, overall response rates of 95% and 92% were similar. The disease-free survival at 3 years for complete responders in elderly patients was 74% compared to 82% in those under 65. The comparable 3-year overall survival was 59% and 62%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Imaging of bronchial carcinoid tumours with indium-111 pentetreotide.

Neuroendocrine tumours are characterised by the expression of high affinity binding sites for somatostatin. The detection of bronchial carcinoid tumours through scintigraphic imaging is described in two patients using the novel radiolabelled somatostatin analogue indium-111 pentetreotide.

Bronchial Neoplasms↗
PubMed1994

Small cell lung cancer in the elderly.

Mortality rates for patients with lung cancer remain high, despite advances both in our understanding of lung cancer biology and in survival statistics for other types of cancer. Important strategies for improving the figures for lung cancer are identification of subgroups at highest risk for the disease and targeting high-intensity therapy to patients with the greatest chance for cure. In this context, special attention must be given to the elderly population, which accounts for approximately 60% of all cancer cases. Recognizing that close to 13% of the population of the United States can be considered elderly and that this figure is expected to more than double over the next 40 years, the elderly cohort clearly has a significant impact on cancer statistics in general. While approximately 26% of lung cancer patients are potentially curable, the 74% majority has only a remote chance of being cured of their disease. More active therapeutic modalities, with a meaningful effect on survival and quality of life but with more acceptable toxicity than intensive therapy designed for patients with a good chance of cure, are clearly needed for these patients. Several studies have demonstrated that use of oral active agents such as etoposide, alone or in combination with other agents, produce an overall response rate and median survival time similar to those of the more intensive schedules. Once further studies clarify the optimum schedule for use of oral etoposide, it is hoped that its use in combination with other therapeutic agents and/or with radiation therapy will improve the overall response and survival rates among patients at high risk or with poor prognostic factors, such as the elderly.

Age Distribution↗
PubMed1993

Somatostatin and the lung.

Lung carcinoma is the most common cause of death in the western world and is increasing particularly among women. Despite significant developments in our understanding of the molecular biology of this disease our ability to treat the various subtypes of lung cancer has been at a relative standstill for the past decade. Novel approaches to the therapy of lung tumours are required. Recent work has evaluated the potential role of somatostatin and its analogues in the treatment of lung cancer. Experimental evidence has demonstrated that lung tumours, in particular small cell lung cancer (SCLC), may express somatostatin. The significance of this expression has not yet been evaluated. Somatostatin receptors have been demonstrated on between 50-75% of SCLC cell lines and fresh tumour samples studied to date. Using radiolabelled somatostatin analogues SCLC tumours may be detected and localised in patients through scintigraphic imaging techniques. Studies have shown that SCLC cell line clonal proliferation may be inhibited in vitro with somatostatin analogues suggesting that the somatostatin receptors are functional. In-vivo growth inhibition studies have likewise yielded encouraging results with growth inhibition of somatostatin receptor positive SCLC xenografts and receptor negative SCLC and non-small cell lung cancer cell line xenografts. These latter result suggests that somatostatin analogues may inhibit tumour growth by indirect as well as direct means. These findings have laid the ground for formal clinical trials in the future.

Amino Acid Sequence↗
PubMed1993

Angiosarcoma arising from a defunctionalized arteriovenous fistula.

We report a case of angiosarcoma developing in a defunctionalized arteriovenous fistula that had been created for hemodialysis approximately 20 years previously. At presentation the patient had a 30-year history of chronic renal failure and had undergone renal transplantation 10 years previously.

Arteriovenous Shunt, Surgical↗
PubMed1993

Perfluorooctylbromide as a contrast agent for CT and sonography: preliminary clinical results.

OBJECTIVE: Perflubron emulsion is a bromine-based particulate contrast agent that is taken up selectively by the liver and spleen after IV injection. It does not leave the vascular space and also persists in the blood for a longer period than iodinated contrast agents do. We performed a preliminary study to determine the value of the IV perflubron emulsion as a contrast material for CT and sonography. SUBJECTS AND METHODS: To determine the safety and dose response of perflubron emulsion as an IV contrast agent for CT and sonography, 18 cancer patients, 14 of whom had hepatic metastases, were given 0.5-3.0 ml/kg of the emulsion. Sonography and CT of the liver and spleen were performed before and immediately after infusion and then again at 24 hr. RESULTS: A persistent increase in the density of blood, liver, and spleen was observed, where maximal enhancements of 55, 39, and 317 H, respectively, were achieved. Tumor conspicuity increased as metastases enhanced minimally (7 H or less). Peak enhancement of the liver and spleen was delayed to 24 hr with higher doses of perflubron; however, the immediate postinfusion scan allowed the distinction of vessels from hepatic lesions. Sonographically, an increase in tumor echogenicity relative to liver was observed in nine of the 14 subjects, allowing the detection of additional metastases in two. Splenic echogenicity in the near field increased relative to kidney; however, attenuation increased markedly at the time of peak concentration, limiting beam penetration. Similar but milder changes were observed in the liver. Adverse effects occurred in 14 of the subjects; these included lower back pain in six, delayed fever in eight, and malaise in three. CONCLUSION: Perflubron emulsion produced prolonged enhancement of blood, liver, and spleen and increased the conspicuity of liver metastases. However, the side effects encountered could limit its use to a selected population of patients.

Adult↗
PubMed1992

31P MRS as an early prognostic indicator of patient response to chemotherapy.

In this study 31P spectral changes were closely monitored following the initial administration of cytotoxic drugs and related to five parameters of patient response. Pre- and postchemotherapy 31P MRS examinations were performed on 16 patients with large, malignant tumors. These included four tumor types: (i) lymphoma (n = 7), (ii) breast carcinoma (n = 4), (iii) musculoskeletal tumors (n = 4), and (iv) adenocarcinoma (n = 1). A mean of 5 spectra/patient (range 2-10) was performed following the initial chemotherapy. The spectral trends exhibited by 14 of 16 patients reached "points of maximum change," after which they began to revert toward prechemotherapy values. In 2 of 16 patients that did not respond to the initial chemotherapy regimen, no spectral trends were observed. The degree of change of certain spectral parameters, namely, decreases in PME, PME/PDE, PME/PCr, PME/NTP, PDE/PCr, and tumor pH, as well as increases in the ratios Pi/PME and Pi/PDE, were associated with good patient response and separated responders from nonresponders. Pi/PME appears the most promising for discriminating partial from complete responders.

Adult↗