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R A Stahel

Publications and source records attributed to R A Stahel.

At least 127 records · Page 7Linked to original sources
PubMed1988

Monoclonal antibodies against mesothelial membrane antigen discriminate between malignant mesothelioma and lung adenocarcinoma.

Monoclonal antibodies (MAbs) were generated by immunizing mice with the mesothelioma cell line SPC111 and selected by indirect immunofluorescence on viable cells. Indirect immunofluorescence staining and radioimmunoassays demonstrated selective binding of the antibodies ME1 and ME2 with the surface membrane of mesothelioma, but not with lung adenocarcinoma cell lines. Lung small-cell carcinoma cell lines were unreactive, while staining was seen in a proportion of lung squamous-cell carcinoma cell lines. The antibodies were unreactive with other cell lines, including breast, colon, ovarian, and renal-cell carcinoma, leukemia, and lung fibroblast. The antibodies stained normal mesothelial cells, but were unreactive with normal bronchial epithelial cells in primary cultures, or peripheral blood cells. Immunohistochemical staining of cryostat sections of tumor tissues confirmed the ability of the antibodies to distinguish between mesothelioma and lung adenocarcinoma. All 12 mesothelioma tissues, but none of 9 lung adenocarcinomas or large-cell carcinomas, stained with the MAbs. Staining of malignant mesothelioma tissues was very homogeneous. Some lung squamous-cell carcinomas and breast carcinomas were stained focally by both, and some ovarian carcinomas by one antibody. Solid-phase radioimmunoassays demonstrated antigen sensitivity to chymotrypsin digestion and binding competition between the antibodies. The antibodies ME1 and ME2 identify a surface membrane antigen with preferential expression on normal and malignant mesothelial cells. They distinguish malignant mesothelioma from lung adenocarcinoma on cryostat sections and promise to be useful tools in biological studies of mesothelial cells.

Adenocarcinoma↗
PubMed1988

[Immunotherapy of tumors using interleukin-2 and lymphokine-activated killer cells].

The tolerance and effectiveness of an interleukin-2 analog (rIL-2) in combination with lymphokine activated killer (LAK) cells has been studied. 14 patients with metastatic solid tumors, including 8 renal cell carcinomas, 3 melanomas and 3 extragonadal germ cell tumors refractory to standard therapy, were treated for a 3-week period. rIL-2 was administered as a bolus at 30,000 U/kg every 8 hours on days 1-5 and days 12-19. Leukapheresis was done on days 8-12, and lymphocytes were incubated with rIL-2 for 3-4 days in vitro and reinfused on days 12, 13, and 15. rIL-2 dose and schedule were adjusted according to toxicity. The major side effects were constitutional symptoms and a capillary leak syndrome with hypotension and impaired renal function. Partial responses were documented in 2/8 renal cell carcinomas and 1/3 melanomas. The response durations were 1, 5 and 6 months.

Adult↗
PubMed1987

Characterization of an epithelial and a tumor-associated human small cell lung carcinoma glycoprotein antigen.

The small cell carcinoma (SCC) antigens recognized by LAM2 and LAM8 antibody were characterized by comparison of their tissue expression and analysis of their biochemical composition. LAM2, but not LAM8 antigen could be demonstrated in lipid extracts of SCC cells. By immunohistochemical staining the SCC antigen LAM2 was shown to be an epithelial type membrane antigen. Immunoblotting experiments and competition solid phase radioimmunoassays showed LAM2 antigen to be a native conformation of a glycoprotein with major bands at Mr 100,000-120,000 and a minor band at Mr 210,000. L-Fucose was a dominant part of the epitope which appeared to be closely related to the carbohydrate epitope of the blood group antigen H(O). The tumor-associated membrane antigen LAM8 was shown to be a glycoprotein with major bands at Mr 90,000-135,000 and a minor band at Mr 200,000. Neuraminic acid was the predominant part of the carbohydrate epitope. LAM8 antibody recognized a structure in the saliva of Lea positive probands, but untreated and neuraminidase-treated SCC extracts were unreactive with anti-Lea antibody. Anti CA 19-9 (sialo-Lea antigen) and LAM2 antibodies did not compete for LAM8 binding in direct radioimmunoassays. The sialo-GP90-135 antigen recognized by LAM8 antibody therefore is likely to represent a novel tumor antigen.

Antibodies, Monoclonal↗
PubMed1986

Cytotoxic murine monoclonal antibody LAM8 with specificity for human small cell carcinoma of the lung.

The reactivity of the murine immunoglobulin monoclonal antibody LAM8 directed against a membrane antigen of human small cell carcinoma (SCC) of the lung was investigated on human cell lines and tissues. Indirect immunofluorescence staining, radioimmunoassays, and cytotoxicity assays showed LAM8 antibody to selectively react with SCC but not with non-SCC lung cancer cell lines and extrapulmonary tumor cell lines. Unlike other SCC antibodies, including those we have previously described, highly preferential reactivity with SCC tissues was also demonstrated by immunoperoxidase staining of deparaffinized formalin-fixed tissue sections. Membrane and cytoplasmic staining was seen in of 9 of 12 SCC tissues. No significant staining was seen in non-SCC lung cancer and a wide range of other tumors, including mesothelioma and bronchial carcinoids. Significant LAM8 reactivity was also absent in normal tissues of all major organs. Few tumors and epithelial tissues, including bronchial epithelium had rare LAM8 positive cells which were always less than 2% of the entire cell population. In vitro treatment with antibody and human complement was highly cytotoxic to SCC cells, but had not effect on bone marrow progenitor cells. Immunoblotting of membrane extracts separated on sodium dodecyl sulfate-polyacrylamide gels showed the LAM8 antigen to have a band of an approximate molecular weight of 135,000 and a cluster of bands with approximate molecular weights of 90,000. This reactivity was lost after incubation of the extracts with periodate. LAM8 antibody shows a highly preferential reactivity with SCC cell lines and formalin-fixed paraffin-embedded SCC tissues and is selectively cytotoxic to cells expressing LAM8 antigen.

Antibodies, Monoclonal↗
PubMed1985

Selective cytotoxicity of murine monoclonal antibody LAM2 against human small-cell carcinoma in the presence of human complement: possible use for in vitro elimination of tumor cells from bone marrow.

LAM2 is a murine IgM monoclonal antibody (MAb) which binds strongly to the cell membrane of human lung small-cell carcinoma (SCC) and squamous-cell carcinoma but not to normal bone-marrow cells. The cytotoxicity of this antibody in the presence of human complement was investigated in vitro by chromium release and clonogenic assays. The optimal treatment conditions included incubation with antibody for 30 min at 37 degrees C followed by 3 additions of human complement 30 min apart. Cell lysis ranged from 94 to 98% in 4 SCC cell lines at antibody dilutions of 1:100: a lower level of lysis (60%) occurred in a lung squamous-cell carcinoma cell line. The cytotoxic effect was strictly complement-dependent. No cytotoxic effect was seen with other human cell lines including lung adenocarcinoma, lung large-cell carcinoma, myeloid leukemia, and lymphoblastic leukemia. No lysis was seen with nucleated marrow cells from healthy volunteers. Normal marrow cells in excess did not inhibit SCC cell lysis. Incubation with antibody and complement resulted in a 100-fold reduction of colony formation of SCC cells, but did not reduce the number of colonies of marrow-cell precursors, including CFU-GEMM, BFU-E, and CFU-C. The selective cytotoxicity of LAM2 antibody to SCC, but not to normal bone-marrow cells, suggests that this antibody may be useful for the in vitro elimination of SCC cells from the bone marrow.

Animals↗
PubMed1985

Murine monoclonal antibody LAM2 defines cell membrane determinant with preferential expression on human lung small-cell carcinoma and squamous-cell carcinomas.

Murine monoclonal antibodies (MAbs) were generated against a human undifferentiated lung carcinoma cell line. The hybridoma designated LAM2 produced an IgM kappa MAb with reactivity to the cell membrane. Indirect immunofluorescence staining and radioimmunoassay showed LAM2 antibody to react preferentially with lung small-cell carcinoma (SCC) cell lines and squamous-cell carcinoma (SQC) cell lines. LAM2 antibody also stained primary cultures of normal bronchial epithelial cells, but was unreactive with human erythrocytes and nucleated marrow cells. Indirect immunofluorescent staining with LAM2 antibody was performed on frozen sections of human tumor tissues and normal tissues. LAM2 antibody stained all 8 SCC carcinomas, 4 of 5 SQC of the lung and head and neck region, and 2 or 4 lung large-cell carcinomas. No staining was seen on lung adenocarcinomas, breast carcinomas, ovarian carcinomas, renal cell carcinomas, colon carcinomas, or mesotheliomas. Staining was present on sections of normal bronchus, but not on normal lung parenchyma, liver, kidney, adrenal or skin. While LAM2 antibody was highly reactive with all SCC examined, its antigenic determinant was not expressed in other cell lines and tumors of presumed neuroectodermal origin, including neuroblastoma, melanoma, and bronchial carcinoid. Radioimmunoprecipitation showed the antigen defined by LAM2 antibody to have two major bands of approximate molecular weights of 45,000 and 125,000. The selective reactivity of LAM2 antibody with SCC and SQC, but not with most other tumor tissues and normal tissues, makes it a good candidate for use in clinical diagnosis and possibly serotherapy.

Antibodies, Monoclonal↗
PubMed1985

Cytoskeleton-associated proteins: their role as cellular integrators in the neoplastic process.

The cytoskeleton (CSK) of eukaryotic cells is composed of a complex interconnected network of filaments which is important in a wide variety of cellular functions including changes in cell shape, cell motility, mitosis, anchorage-dependent growth, and the localization of cellular organelles such as mitochondria, polyribosomes, and secretory granules. The various proteins comprising the cytoskeleton include actin in microfilaments, tubulin in microtubules, and the heterogeneous group of intermediate filament proteins that are associated with different cell types (keratin in epithelial cells, vimentin in fibroblasts, desmin in muscle cells, glial filament protein in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins are closely associated with the cytoskeleton and influence its organization. In neoplastic cells, the expression of these different CSK proteins, especially the intermediate filament proteins, reflects their morphologic and functional differentiation. The carcinomas contain keratin; identification of individual keratin components may allow further sub-classification of carcinomas which is consistent with their tissue of origin. The sarcomas of muscle origin contain desmin. Vimentin is found primarily with cells of mesenchymal origin, but may coexist with other intermediate filament proteins in other tumors. One example is the coexistence of keratin and vimentin in tumors, such as mesotheliomas, which are derived from epithelial cells of embryonic origin. Glial fibrillary acidic protein is the most specific marker for glial tumors. Tumors of neural origin are characterized by the presence of neurofilament subunits. Therefore, analysis of CSK composition would be useful in diagnosis of clinical specimens and aid in studies of lineage relationships of neoplasms. Although no consistent differences in cytoskeletal structure between neoplastic and normal cells have been identified so far, the presence of more subtle biochemical alterations in the cytoskeletal structure of neoplastic cells that contributes to malignant behavior has not been ruled out. Since the cytoskeletal network plays an important role in cell shape and cell locomotion, which in turn are thought to be involved in growth control, invasion, and metastasis, further work is directed at identifying the various alterations in cytoskeletal architecture that may influence the malignant behavior of neoplastic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Actin Cytoskeleton↗
PubMed1985

Use of SM-1 monoclonal antibody and human complement in selective killing of small cell carcinoma of the lung.

SM-1 is a murine monoclonal antibody strongly reactive with a cell membrane antigen of small cell carcinoma (SCC) of the lung but unreactive with the membrane of most other carcinomas and normal tissues including normal bone marrow. We have found that in the presence of human complement, SM-1 antibody is highly cytotoxic to SCC cells. Using three treatments with antibody and complement, more than 99% of SCC cells in culture were lysed, as determined by the chromium release and clonogenic assays. Similar efficiency of SCC cell lysis was observed when one SM-1 antibody treatment was followed by three treatments with human complement. In contrast, there was little antibody-dependent lysis of non-small cell lung cancer cells, other carcinomas, and leukemia cell lines. The amount of chromium released from normal bone marrow cells treated with SM-1 antibody and complement was minimal and was mainly due to the effect of complement alone. Clonogenic assays, including colony-forming unit-granulocytic/monocytic, erythroid burst-forming unit, and colony-forming unit-granulocytic/erythroid/monocytic/megakaryocytic, also showed no significant SM-1 antibody-dependent cytotoxicity on normal bone marrow precursors. Since SM-1 antibody is selectively cytotoxic to SCC cells in the presence of human complement, it is a potentially useful agent for the selective eradication of tumor cell contamination in marrows of patients with metastatic small cell lung cancer and possibly for in vivo serotherapy.

Antibodies, Monoclonal↗
PubMed1985

Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody.

A murine monoclonal antibody against a surface antigen of small-cell carcinoma of the lung (SM1 antibody) was investigated for its use in detecting bone marrow metastasis. Bone marrow cells of healthy volunteers and of patients with small-cell carcinoma of the lung (SCCL) were examined for reactivity with SM1 antibody and indirect immunofluorescence and the results compared to conventional histochemical staining (Wright-Giemsa stain of bone marrow aspirates and hematoxylin-eosin stains of bone marrow biopsies). No SM1 reactivity was found in marrow cells of eight healthy volunteers. Thirty-six samples from 33 patients with SCCL were examined; tumor involvement was found in 69% by SM1 antibody and in 16% by histochemical stains. All bone marrow samples from patients with SCCL that were unreactive with SM1 antibody also showed no evidence of tumor involvement by histochemical stains. Samples of 29 patients were investigated at initial staging; SM1 reactive cells were found in 50% of 16 patients with limited disease and in 77% of 13 patients with extensive disease. Overall, the proportion of patients recognized to have disseminated disease at diagnosis was increased from 45% to 72% by monoclonal antibody staining. Indirect immunofluorescence with SM1 antibody allows detection of bone marrow metastasis of SCCL that cannot be seen by conventional morphology and can identify disseminated disease in patients otherwise staged limited disease.

Animals↗
PubMed1985

Selective cytotoxicity of the SM1 monoclonal antibody towards small cell carcinoma of the lung.

A murine monoclonal antibody, SM1, is strongly reactive with the surface membrane of small cell carcinoma of the lung. SM1 antibody is unreactive with most other cancers and various normal tissues including bone marrow cells. We now find that SM1 antibody is selectively cytotoxic to small cell carcinoma (SCC) in vitro. The antibody is present in high titers in supernatant fluids or ascites obtained by i.p. injection of SM1 hybridoma cells into pristaned BALB/c mice. The cytotoxic effect of the antibody is reduced to one-half maximal activity only at dilutions greater than 1:40,000. The efficiency of tumor cell lysis is greatly enhanced by repeated treatments with antibody and complement. Using three treatments with antibody and complement, 99.9% of SCC cells are lysed, as determined by the chromium release. Similar efficiency of SCC cell kill was observed by clonogenic assays. SM1 antibody produces no significant antibody-dependent lysis of cell lines derived from non-SCC lung carcinomas and leukemia cells. The results from chromium release assay and clonogenic assays also indicate that the effect of SM1 antibody and complement on bone marrow cells is minimal and could be accounted for by the effect of complement alone.

Antibodies, Monoclonal↗
PubMed1984

Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide, BCNU and VP-16 in small cell carcinoma of the lung and a review of current literature.

Four patients with limited disease small cell carcinoma of the lung were treated with high-dose cyclophosphamide (120 mg/kg over days 1 and 2), BCNU (400 mg/m2 over days 1 and 2) and VP-16 (200 mg days 1-5) used as intensification treatment after conventional chemotherapy. To ameliorate hematopoietic toxicity, autologous bone marrow cells collected and cryopreserved prior to treatment were reinfused on day 8. In three patients clinical response was evaluable. Two achieved a complete remission: one died without evidence of tumor after 3 months; the other had a regional relapse after 6 months. One patient who had progression of disease on conventional chemotherapy was refractory to high-dose treatment. Three patients developed diffuse interstitial pneumonitis 3 weeks after treatment and two died of respiratory failure. High-dose intensification chemotherapy with autologous marrow reinfusion may complement the effects of standard combination chemotherapy in small cell carcinoma of the lung. The current status of this approach is reviewed.

Adult↗
PubMed1983

[Systemic mycoses in hematologic neoplasms].

Between July 1973 and June 1981 systemic fungal infections were found in 27 of 270 autopsies of patients with hematologic malignancies: in 16 aspergillosis, in 6 candidiasis, in one aspergillosis and candidiasis, and in 4 mucormycosis. The frequency increased from 6% during the first 6 years to 25% during the last 2 years (p = 0.025). Fever despite antibiotics and new pulmonary infiltrates were the major symptoms. In only 6 of 16 patients did microbiological findings support the clinically suspected diagnosis. Systemic fungal infections were the principal cause of death in 12 patients. Because of the difficulty of establishing the diagnosis, empiric antimycotic therapy should be started promptly on clinical suspicion in patients with neutropenia and fever despite antibiotics.

Amphotericin B↗
PubMed1982

[Idiopathic splenomegaly: the preliminary stage of a malignant lymphoma? Report on 2 cases].

Two patients with splenomegaly and a mild degree of hypersplenism are presented. Both underwent diagnostic splenectomy and in both the histologic examination of the spleen disclosed follicular lymphoid hyperplasia. The clinical picture and histologic findings were compatible with the diagnosis of idiopathic splenomegaly. 33 months after splenectomy a non-Hodgkin lymphoma was diagnosed in one patient. The literature on idiopathic splenomegaly is reviewed and the high incidence of non-Hodgkin lymphoma in the follow-up of such patients is pointed out.

Adult↗
PubMed1982

Surgical resection of residual tumor after chemotherapy in non-seminomatous testicular cancer.

Fifteen patients with disseminated non-seminomatous testicular cancer, 13 of whom had advanced disease, underwent surgery for residual tumor after induction chemotherapy. Complete remissions were achieved in 7 of 9 patients with mediastinal or pulmonary metastases and in 2 of 6 patients with retroperitoneal metastases. Patients with alpha-fetoprotein (AFP) levels over 10(4) ng/ml at diagnosis and/or a positive AFP preoperatively failed to achieve complete remission. Complete remissions were obtained in all 8 patients who had resection of necrosis, mature teratoma, immature teratoma or mature teratoma with malignant foci, but in only 1 of 7 patients who had resection of embryonal carcinoma or yolk sac tumor with other components. Of 9 patients with complete remission, 8 have remained free of disease after a median follow-up time of 29 months (range 6-66 months) and one had a contralateral non-seminomatous testicular cancer removed after 60 months. In addition to being therapeutically successful, the combined use of chemotherapy followed by surgery for residual tumor may lead to a better understanding of the influence of chemotherapy on the biology of testicular carcinoma.

Adult↗