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Biomedical subjects

D N Carney

Publications and source records attributed to D N Carney.

At least 19 recordsLinked to original sources
PubMed2003

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗
PubMed2001

Imaging of primary non-Hodgkin's lymphoma of the liver.

AIM: To describe the radiological findings in primary liver lymphoma, which is a rare entity, presenting usually as a localized liver mass. MATERIALS AND METHODS: We reviewed retrospectively the imaging findings at presentation, of patients in whom a diagnosis of primary liver lymphoma was finally made histologically. The study period covered a 10-year period between January 1990 and December 1999. There were seven patients, all men, with a mean age of 49.6 years. Each patient presented with hepatobiliary disease without peripheral adenopathy. Imaging prior to diagnosis included ultrasonography (seven patients), computed tomography (seven patients) and magnetic resonance imaging (MRI) (two patients). Appearances during and after aggressive chemotherapy were reviewed. RESULTS: Imaging appearances were of either single or multiple liver lesions simulating liver metastases. On ultrasound all foci of primary hepatic lymphoma (PHL) were hypoechoic relative to normal liver. Computed tomography (CT) showed hypoattenuating lesions in all cases, and two cases showed rim enhancement following contrast administration. The MRI appearances were variable, and no pathognomonic feature of PHL was identified, so that histology was required in all patients to establish the diagnosis. CONCLUSIONS: This paper demonstrates the spectrum of findings encountered on various imaging modalities in PHL. We conclude that although PHL is a rare condition, it should always be considered in the differential diagnosis of liver metastases when no primary tumour is apparent.

Adult↗
PubMed2001

Somatostatin, its receptors and analogs, in lung cancer.

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [(111)In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer.

Antineoplastic Agents, Hormonal↗
PubMed1998

New agents in the management of advanced non-small cell lung cancer.

Non-small cell lung cancer accounts for 75% to 80% of the approximately 180,000 new cases of lung cancer that will develop in the Unites States this year. At the time of diagnosis, only 30% to 40% of patients are candidates for curative resection. Even for these patients, the 5-year survival rate ranges from 30% to 70%, indicating that many of these "early stage" patients have micrometastatic disease at the time of initial diagnosis. The remaining approximately 60% of newly diagnosed patients have either locally advanced unresectable disease or stage IV metastatic disease, and the majority of these patients will die of progressive disease before the first anniversary of their diagnosis. Overall, the 5-year survival rate for all newly diagnosed patients with non-small cell lung cancer has improved over the past two decades from 5% to 10% in the United States.

Antineoplastic Agents↗
PubMed1997

BCL-6 and other genomic alterations in non-Hodgkin's lymphoma (NHL).

This study reports on the frequency and disease association pattern of a number of gene rearrangements in a large panel of lymphoid tumours (n = 94). We detected the t(11;14) translocation, involving rearrangement of the BCL-1 locus, in 60% of mantle cell lymphomas. The BCL-2 gene, located at band 18q21, was rearranged in 42% of follicle centre lymphomas (FCL) and in 15% of diffuse large B-cell (DLBC) lymphomas. In this study, 80% of the c-MYC rearrangements were detected in aggressive diffuse lymphoma subsets but, interestingly, 9% of FCL showed involvement of t(8q24) translocation. In our study, rearrangements of the BCL-6 gene at band 3q27 were found in 31% of DLBC lymphomas. Interestingly, 50% of the BCL-6 rearrangement positive lymphoma cases had coexisting gene rearrangements involving all of the aforementioned gene loci. The molecular dissection of these genes will improve our understanding of the genesis of the diverse clinicopathological subtypes.

DNA-Binding Proteins↗
PubMed1997

Overview of chemotherapy for small cell lung cancer.

Small cell lung cancer (SCLC) accounts for 20% to 25% of all lung cancer cases in developing countries. The incidence of and mortality from SCLC continues to increase in these countries, especially in females. Small cell lung cancer is different from other lung cancer histologic types in that it has neuroendocrine features, grows more rapidly, spreads earlier, is more responsive to chemotherapy and radiotherapy, and has a lower cure rate. Because of the propensity to metastasize early, the lack of screening modalities, and the sensitivity to chemotherapy, the cornerstone of treatment is combination chemotherapy, which is indicated in all SCLC patients able to tolerate any therapy. Patients with extensive-stage SCLC generally receive combination chemotherapy alone. Most patients with limited-stage SCLC should be treated with combined modality therapy consisting of chemotherapy and chest radiotherapy. In the rare patient with stage I SCLC and no involved lymph nodes, surgical resection with chemotherapy provides a high rate of long-term survival. Several combinations are used routinely, including the two-drug combination of etoposide with cisplatin or carboplatin, which is used most frequently in the United States. There is no proven role for any type of maintenance therapy, for intensive chemotherapy, or for biological therapies. There have been no major advances in therapy in the last decade, although the recent advent of new active agents, including gemcitabine, provides hope for more effective therapies in future years. This report will review the past literature on SCLC therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Cell culture methods for the establishment of the NCI series of lung cancer cell lines.

More than 200 human small cell lung cancer and non-small cell lung cancer cell lines were established over 15 years mainly by utilizing the serum-free, hormone and growth factor supplemented, defined media HITES and ACL4. Use of modified, established cell culture techniques such as the mechanical spillout method for the releasing of cell aggregates from tumor tissue, ficoll gradient centrifugation for the separation of tumor cells from erythrocytes and tissue debris, and an apparatue consisting of a platinum tubing attached to a suction flask for removal of spent medium have greatly contributed to the success in culturing tumor cells. Characterization of these lung cancer cell lines have extended our knowledge of lung cell biology. Studies elucidating the nutritional requirements of lung cancer cell growth may be helpful for the manipulation of these tumors in patients.

Ascites↗
PubMed1996

Radiolabelled somatostatin analogue scintigraphy in oncology.

Somatostatin analogue scintigraphy represents a new technique employing radiolabelled peptides to detect specific receptor-bearing lesions. 111Indium diethylene-triaminopentaacetic acid-linked octreotide (111In-DTPA-D-Phe1-octreotide), also known as [111In]pentetreotide or OctreoScan, is now established in the management of patients with neueroendocrine gastrointestinal tract and pancreatic tumours, and has proved effective in localizing disease sites in lung, breast and medullary thyroid carcinomas, lymphomas, meningiomas and others. In these conditions (a) the imaging of all disease sites at a single sitting (in a proportion of patients) thereby making further investigations unnecessary, (b) the localization of otherwise unexpected metastatic deposits and (c) the detection of residual disease not found by other means suggest that [111In]pentetreotide may be a useful adjunct in the diagnostic evaluation of patients with somatostatin receptor-bearing tumours.

Breast Neoplasms↗
PubMed1996

Chemotherapy in the management of patients with inoperable non-small cell lung cancer.

Lung cancer remains a major epidemic problem worldwide. The majority of cases are associated with cigarette smoking and the number of people who smoke continues to increase. As a result, the number of lung cancer cases and deaths is expected to increase proportionately over the next decade. The majority of patients who develop lung cancer die of this disease. Non-small cell lung cancer (NSCLC) accounts for 75% of all new cases. The only hope for significant survival depends on surgical resection. At the time of initial presentation, unfortunately, the vast majority of patients are inoperable, either because of advanced disease or because of the presence of comorbid medical conditions such as coronary artery disease. For these reasons, the overall survival rates for patients with NSCLC range from 10% to 15%, figures that have not improved substantially for 20 years. The role of systemic chemotherapy in this population remains debatable for many physicians. Nevertheless, recent studies clearly demonstrate that effective systemic chemotherapy in selected patients can improve survival, quality of life, and performance status. Recently, newer cytotoxic agents, such as vinorelbine, gemcitabine, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), docetaxel, and the camptothecins, have demonstrated their activity in treating patients with NSCLC. When combined with other effective agents, response rates exceeding 50% have been achieved, with median survivals of more than 1 year. The use of these newer agents in combination with well-established agents holds promise for the role of systemic chemotherapy in the future management of patients with early or late-stage NSCLC.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Ovarian carcinoma-associated TaqI restriction fragment length polymorphism in intron G of the progesterone receptor gene is due to an Alu sequence insertion.

Alu sequences, short, repetitive transposable DNA elements, are factors in a number of genetic diseases. We previously identified a germline TaqI RFLP, located in intron G of the human progesterone receptor gene, that showed an association with the incidence of sporadic ovarian carcinoma. Furthermore, the polymorphism was characterized as a small (approximately 300-bp) insertion that was inherited in a Mendelian fashion. Because of its insertional character, we named this polymorphism PROGINS. We report the identification of PROGINS as a 306-bp Alu element of the PV or HS-1 Alu subfamily.

Alleles↗
PubMed1995

Prognostic significance of microvessel density in lymph node negative breast carcinoma.

We evaluated the prognostic value of tumor angiogenesis in node negative breast cancer (NNBC). Paraffin-embedded tissues from 87 patients with NNBC were immunostained for factor VIII-related antigen, using one tissue block representative of the invasive edge of the tumor. Sections were scanned at low power to identify "hotspots" of angiogenesis. Microvessel (MV) counts were performed at x200 magnification, using a grid eyepiece graticule. Within each hot spot, three fields (area of field = 0.22 mm2) were counted and averaged. The highest average for a hot spot and the highest single field value was recorded for each case. Patients were stratified into low and high MV groups and their survival compared. There were no differences in disease-free or overall survival between the two groups whether the highest average or the highest single value was used. Microvessel counts did not correlate with other prognostic features, ie, grade, size, estrogen receptor status, c-erb B-2 or accumulated P53 status. Because of the difficulty in assessing angiogenesis that is heterogenous throughout tumors, MV counting may not be suitable for clinical use as a prognostic factor in NNBC. This problem could be addressed in a prospective study involving more extensive tumor sampling.

Adult↗
PubMed1995

Imaging of small cell carcinoma of the oesophagus.

Four cases of oesophageal small cell carcinoma are described. Radiological features at presentation included oesophageal strictures in association with bulky intrathoracic and intraabdominal lymphadenopathy. The subject is reviewed and the radiologically relevant features are emphasized.

Aged↗
PubMed1995

Carboplatin/etoposide combination chemotherapy in the treatment of poor prognosis patients with small cell lung cancer.

Advances in the treatment of SCLC have been slow but sure over the past decade. It is now recognized that a small subset of patients may be cured of this disease, particularly with combined modality treatment with radiation therapy and systemic chemotherapy. However, perhaps only 25% of all patients will be candidates for this intensive/combined modality approach. Therefore, there is a need to identify effective combination chemotherapy regimens that can be easily administered to the remaining 75% of poor prognosis SCLC patients. Our studies and those of others would suggest that the combination of carboplatin and oral etoposide is a highly effective regimen for the treatment of these patients with results equal to and comparable with more intensive schedules. The ease of administration of this combination with acceptable toxicity would suggest that for such a subset of patients it may be the treatment of choice against which other combination schedules should be compared.

Aged↗