Biomedical subjects

D M Nanus

Publications and source records attributed to D M Nanus.

58 records · Page 4Linked to original sources

PubMedDate not supplied

B-lymphoproliferative disorders: a proposed unified pathogenetic pathway.

The clinical features of lymphoproliferative diseases associated with paraproteinemia are briefly reviewed and correlated with current immunologic concepts in an effort to clarify the pathophysiology of B-lymphocyte disorders. B-lymphocyte maturation proceeds in a predictable manner from the Pre-B cell to the formation of idiotype specific plasma cells and memory B-lymphocytes. The immunoglobulin isotype produced by the mature plasma cell is determined by a site specific process of gene switching which proceeds from mu to alpha production. Lymphoproliferative diseases are the result of disordered B cell maturation and their clinical features can be explained by identifying the locus of the maturational defect.

Adult↗

PubMedDate not supplied

Renal cell carcinoma.

Renal cell carcinoma (RCC) is characterized by (a) lack of early warning signs, which results in a high proportion of patients with metastases at the time of diagnosis; (b) protean clinical manifestations; and (c) resistance to radiotherapy and chemotherapy. The estimates of new diagnoses and deaths from kidney cancer in the United States during 1996 are 30,600 and 12,000, respectively. RCC occurs nearly twice as often in men as in women. The age at diagnosis is generally older than 40 years; the median age is in the midsixties. The incidence of RCC has been rising steadily. Between 1974 and 1990, there was a 38% increase in the number of patients who had a diagnosis of RCC. This increase was accompanied by a significant improvement in 5-year survival. Both trends are likely the result of improved diagnostic capability. Newer radiographic techniques, including ultrasonography, computed tomography, and magnetic resonance imaging, are detecting kidney tumors more frequently and at a lower disease stage, when tumors can be resected for cure. Surgical treatment is the only curative therapy for localized RCC. Radical nephrectomy remains the mainstay of surgical management, but techniques are being modified. These modifications include partial nephrectomy and resection of vena caval thrombi. In highly selected cases, surgical resection of locally recurrent RCC or of disease at a solitary metastatic site is associated with long-term survival. Metastatic RCC is highly resistant to the many systemic therapies that have been extensively investigated. A minority of patients achieve complete or partial response to interferon, interleukin-2, or both. Response can be dramatic but is rarely durable. Because most patients do not achieve response, these agents are not considered effective treatments for RCC, but the response in some patients indicates the need for continued research on their use. Identification of new agents with better antitumor activity against metastases remains a high priority in clinical investigation of therapy for this refractory disease.

Antineoplastic Agents↗

PubMedDate not supplied

Expression of the retinoblastoma gene product in renal tumors.

BACKGROUND: Alterations in the retinoblastoma (Rb) gene and its protein product have been detected in numerous solid tumor malignancies. Loss of Rb function is believed to contribute to neoplastic transformation or to the development of metastases. To define the role of Rb in renal cancer, we analyzed renal tumor specimens for molecular alterations in the Rb gene and for lack of Rb protein expression, and correlated the results to clinicopathological characteristics. MATERIALS AND METHODS: Thirteen renal cancer cell lines, 62 primary renal tumors, and 5 metastatic renal cancers were studied by Southern blot analysis for defects in the Rb gene, and by immunohistochemistry for Rb protein expression. Results were correlated with histopathological parameters and patient survival. RESULTS: Structural alterations in the Rb gene were not detects in any of the renal cancer cell line or primary renal tumors studied. A rearranged Rb gene was observed in 1/5 metastatic tumor specimens. Western blot analyses revealed a truncated Rb protein in one of 13 renal cancer cell lines; immunohistochemical analysis revealed Rb protein in all papillary and oncocytic tumors, and in 39/44 non-papillary tumors. Rb expression patterns did not correlate with pathological stage, histological grade or the development of metastatic disease. CONCLUSION: Molecular alterations of the Rb gene are infrequent (<2%) in renal cancers, and Rb protein is present in the majority of primary (92%) and metastatic (100%) renal tumors. Loss of Rb expression does not appear to significantly contribute to malignant transformation or progression of renal cancers.

Adenocarcinoma↗

PubMedDate not supplied

Expression of the kidney-associated differentiation glycoprotein gp160 and resistance to the antitumor effects of interferon alpha in renal cell carcinomas.

BACKGROUND: Alpha interferon (IFN-alpha) is commonly used to treat patients with advanced renal cell carcinoma (RCC). We previously reported that resistance of RCCs to IFN-alpha in vitro correlated with the expression of a cell-surface glycoprotein of 160,00 kD molecular weight (gp160) which we subsequently identified as aminopeptidase A. MATERIALS AND METHODS: To directly test the role of gp160/APA in IFN-resistance, we stably introduced the gp160/APA cDNA into IFN-sensitive SK-RC-49 cells resulting in the expression of an enzymatically active gp160/APA protein. In addition, to determine if gp160/APA expression could function as a marker of IFN-resistance in vivo, we assessed gp160/APA protein levels in autologous normal kidney and primary renal cancer specimens from 29 patients half of which were randomized to receive adjuvant IFN-alpha therapy following nephrectomy. RESULTS: Four clones which possessed varying amounts of gp160/APA specific enzyme activity were assayed for sensitivity to the antiproliferative effects of IFN-alpha. All four clones exhibited sensitivity to IFN-alpha similar to that observed with parental SK-RC-49 cells. The analysis of tumor tissue detected no significant difference between the mean level of gp160/APA in tissue from control and IFN-alpha treated patients (1.33 A.U. versus 0.9981 A.U., p = 0.23); however, the mean gp160/APA level was significantly less in tumor tissue (mean = 1.15 A.U.) compared to normal tissue (mean = 2.15 A.U.; p < 0.00001). Within the IFN-alpha treated group, tumor gp160/APA levels did not correlate with the development of metastases or survival (p = 0.469). CONCLUSIONS: These data indicate that gp160/APA does not directly convey IFN-resistance to RCC cells and suggest that expression of gp160/APA in primary RCCs does not predict the benefit of IFN-alpha therapy.

Aged↗