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Biomedical subjects

D N Carney

Publications and source records attributed to D N Carney.

At least 145 records · Page 8Linked to original sources
PubMed1984

Diagnosis and significance of liver metastases in small cell carcinoma of the lung.

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.

Actuarial Analysis↗
PubMed1984

Elevated serum creatine kinase BB levels in patients with small cell lung cancer.

Clinical tumor specimens and cultures of small cell lung cancer (SCLC) produce 10- to 100-fold higher quantities of the BB isoenzyme of creatine kinase (CK-BB) (EC 2.7.3.2) than did other types of lung cancer. Serum CK-BB levels were evaluated in 105 newly diagnosed, previously untreated patients with SCLC. All patients were thoroughly staged, including 42 patients with limited-stage and 63 patients with extensive-stage disease. Serum CK-BB was elevated (greater than 10 ng/ml) in 27 patients (26%) (range, 11 to 522 ng/ml; median, 40 ng/ml). Only 1 of 42 patients with limited disease had an elevated serum CK-BB, while 26 of 63 (41%) of patients with extensive disease did. When patients were subgrouped according to the number of metastatic sites detected in pretreatment staging, a significant association between the presence of an elevated serum CK-BB and the number of metastatic sites was observed (p less than 0.005). No association between the presence of metastatic disease in a specific site and an elevated serum CK-BB could be detected. After adjusting for the number of metastatic sites, survival among patients with a normal pretreatment CK-BB was significantly better than in patients with an elevated CK-BB (p = 0.014). Sequential serum CK-BB determinations in 33 patients revealed an excellent correlation between clinical response to therapy and serum CK-BB levels. Continuous SCLC cell lines established from 13 patients in this study all expressed high levels of CK-BB. These data suggest that serum CK-BB determinations may be of value in estimating the extent of tumor dissemination, assigning prognosis, and monitoring response to therapy in patients with SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Heterogeneity in the radiation survival curves and biochemical properties of human lung cancer cell lines.

Human lung cancers of distinct histology exhibit different responses to radiation therapy in vivo. For examination of the basis of this phenomenon, the radiation survival curves and levels of relevant enzymes were determined in 16 lung cancer cell lines derived from tumors of different histology. These included lines from 5 adenocarcinomas, 7 small cell tumors, 3 variant small cell tumors, and 1 large cell tumor. These findings were compared to those obtained with the use of a normal skin fibroblast cell line. Whether cloned in liquid culture or soft agarose, cell lines had similar radiation survival curves. These curves were consistent with the apparent in vivo radiation responsiveness of the tumors. Although considerable heterogeneity in radiation survival curves was observed among the cell lines, cells from large cell lines and small variant lines had pronounced shoulders and extrapolation numbers (n) from 5.6 to 14. In contrast, cells from small cell lines and adenocarcinoma cell lines were more "sensitive" (-n values of 1-3.3). In these cell lines, levels of DNA polymerase beta, glutathione (GSH), GSH transferase, GSH reductase (NAD(P)H), gamma-glutamyltransferase did not correlate with radiation parameters of sensitivity. DNA polymerase beta and GSH levels were, however, higher than those in a line of normal skin fibroblasts. These cell lines may be useful in identifying the basis of the variable responsiveness of human lung cancer cells to ionizing radiation.

Cell Line↗
PubMed1984

Therapy for multiple myeloma with alternating non-cross-resistant chemotherapy combinations: heterogeneity of tumor responsiveness.

Thirty-five previously untreated patients with multiple myeloma were treated with a 60-week course of alternating, potentially non-cross-resistant chemotherapy combinations (melphalan and prednisone; vincristine, cyclophosphamide, doxorubicin, and prednisone; and carmustine, melphalan, and prednisone), alternating every 15 weeks in an attempt to prevent the development of drug resistance. The overall objective response rate (greater than 50% decrease in M protein) was 60% and six patients (17%) had a complete disappearance of the M protein. After 60 weeks, chemotherapy was discontinued in 17 responding or stable patients until relapse occurred from 4 to 39 months later (median, 12 months). Patients relapsing late (greater than 12 months after discontinuation of therapy) responded more frequently than those relapsing earlier to the reinstitution of the same chemotherapy program. The overall response rate and the actuarial median survival of 26 months in the 35 patients do not differ from the results reported recently with nonalternating combinations given until clinical tumor progression. The failure of this study to prolong survival by using alternating regimens may be due to (a) the likely possibility that the initial two regimens are not actually non-cross-resistant in most myeloma patients, and (b) the long interval between the alternating regimens, particularly in the face of the low response rate to the initial regimen of melphalan and prednisone.

Adult↗
PubMed1984

Continuous culture and soft agarose cloning of multiple human breast carcinoma cell lines in serum-free medium.

We tested the ability of a serum-free medium containing insulin, transferrin, 17 beta-estradiol, dexamethasone, triiodothyronine, prostaglandin F2 alpha, and fibronectin (HBCA medium) to support the continuous growth and passage of five human breast carcinoma cell lines on a collagen matrix. Doubling times of the cell lines (20 to 44 hr) were similar in HBCA and serum-supplemented media. The gross morphology of the cell lines was not altered in the serum-free medium. Insulin, transferrin, and the collagen matrix were the most essential factors required for optimal growth of the cell lines. Estradiol appeared to stimulate the growth of cell lines, both with and without estrogen receptors. HBCA medium supplemented with low concentrations of bovine serum albumin, Fraction V (0.5%, v/v), supported the clonal growth of three cell lines in soft agarose with colony-forming efficiencies superior to that observed with standard serum-supplemented medium. Deleting estradiol from HBCA medium reduced the colony-forming efficiency of the three cell lines. HBCA medium may be useful in studying hormonal regulation and improving the in vitro growth of human breast cancer.

Breast Neoplasms↗
PubMed1984

Analysis of human small cell lung cancer differentiation antigens using a panel of rat monoclonal antibodies.

The antigen expression of human small cell lung cancer (SCLC) was studied using a panel of 21 independent rat monoclonal antibodies. The panel was selected by isolating hybridomas producing antibodies reactive with two SCLC lines but not with autologous B-lymphoblastoid lines. The antibodies were then tested in radiobinding assays against a panel of 17 SCLC lines, 13 non-small cell lung cancer lines, 6 SCLC necropsy specimens, 13 neuroectodermal lines (melanomas, neuroblastomas, glioblastomas), 15 other human lines, the glycolipid extracts of SCLC, human meconium, and human red blood cells. Using immunohistochemical assays, 14 of the antibodies were tested against normal lung, liver, and kidney, and lung cancer biopsies and xenografts. These analyses revealed the following: (a) SCLC elicited predominantly immunoglobulin M antibodies despite hyperimmunization; (b) the 21 antibodies displayed distinct binding and immunohistochemical phenotypes, indicating that they recognized many different epitopes; (c) 14 of the 21 antibodies reacted with glycolipid determinants; (d) the 21 determinants were expressed on over 80% of SCLC cell lines, necropsy samples, and xenografts; (e) the determinants were also expressed on normal adult bronchial epithelium, proximal tubules of adult kidney, and in a few instances on other normal cell types; (f) the antigens were expressed less frequently on nonsmall cell lung cancer samples but did not clearly distinguish SCLC from non-small cell lung cancer; (g) biochemical and morphological variants of SCLC exhibiting more malignant and undifferentiated behavior and containing greatly amplified c-myconcogenes failed to express several determinants or expressed them at lower levels; (h) and finally, while many human cell lines failed to express the antigens including human melanoma and glioblastoma lines, human neuroblastoma lines frequently did express the SCLC antigens. These detailed studies utilizing a panel of distinct monoclonal antibodies define a series of antigens on the surface of the majority of SCLC undescribed previously.

Animals↗
PubMed1983

High-dose methotrexate with leucovorin rescue in patients with unresectable non-small cell carcinoma of the lung.

Thirty-one patients with unresectable non-small cell carcinoma of the lung (19 adenocarcinoma, 7 large cell carcinoma, 4 squamous cell carcinoma, 1 mixed histology) were treated with one of two intravenous infusion schedules of high dose methotrexate with leucovorin rescue. First, 14 patients received methotrexate in escalating doses from 1.5 to 12 g/m2 over 6 hours followed immediately with leucovorin 15 mg/m2 for 12 doses every 6 hours; there were no complete or partial responses among these 14 patients. Then, 17 patients were treated with a loading bolus of 50 mg/m2 intravenous methotrexate followed by a 30-hour continuous infusion of 1.5 g/m2. Leucovorin 15 mg/m2 every 6 hours for 12 doses was begun at the end of the infusion. There were 3 partial responses among the 17 patients in this group. The results demonstrate that both 6- and 30-hour infusions of high-dose methotrexate regimens can be given safely to middle aged adult patients, but the overall 10% response rate does not appear to be significantly different than the results with standard-dose methotrexate.

Adenocarcinoma↗
PubMed1983

Treatment of extensive stage small cell bronchogenic carcinoma. Effects of variation in intensity of induction chemotherapy.

Forty-nine consecutive previously untreated patients with extensive stage small cell bronchogenic carcinoma were treated with cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, etoposide (VP-16-213) 125 mg/m2, and vincristine 1.4 mg/m2 (maximum 2 mg) as induction chemotherapy. Thirty-four patients were given high-intensity therapy, receiving these drugs on both Days 1 and 8 of two or three 21-day induction courses. Fifteen other patients were treated with moderate intensity, receiving these drugs only on Day 1 of two 21-day induction courses. The number and intensity of induction courses were determined by the time of entry into the study. There were 31 complete or partial remissions among the 33 evaluable patients treated with high-intensity therapy (94 percent), including eight complete remissions (24 percent), whereas there were 11 responses (73 percent) including three complete responses (20 percent) among the 15 patients treated with moderate-intensity therapy. There was no marked tendency for the patients in the high-intensity group to have a more favorable response to the induction chemotherapy (p = 0.22), and survival experience was very similar in the two groups (p = 0.92). Overall median survival was 12 months. Within the high-intensity group, there was no significant difference between patients receiving two or three courses of induction therapy with respect to response (p = 0.97) or survival (p = 0.32). There were six induction deaths in the high-intensity induction group (18 percent) and one induction death in the moderate-intensity group (7 percent) (p = 0.59). In addition to the expected hematologic and infectious complications, there were unexpectedly high frequencies of mucositis, reversible congestive heart failure, and severe peripheral neuropathy in patients treated with high-intensity induction. Only two patients, both in the high-intensity group, were alive and free of disease at 24 months. Increasing the intensity of induction chemotherapy with these drugs did not significantly improve response or survival in extensive stage small cell bronchogenic carcinoma.

Adult↗
PubMed1983

Fatal hypereosinophilia with chromosome 15q- in a patient with multiple primary and familial neoplasms.

A man with large-cell carcinoma of the lung, cerebral meningioma, occult adenocarcinoma of the prostate, and follicular adenoma of the thyroid developed symptomatic, rapidly progressive hypereosinophilia with abnormalities of eosinophil ultrastructure and bone marrow karyotype (45,X,15q22-). Although the patient's eosinophilia defied strict classification as idiopathic hypereosinophilic syndrome (HES), simple tumor-associated eosinophilia, or eosinophilic leukemia, it appeared to be incited by the lung cancer and quickly acquired malignant independence. The family had an excess of prostate cancer and lymphoproliferative neoplasms.

Adenocarcinoma↗
PubMed1983

Calcitonin secretion by continuous cultures of small cell carcinoma of the lung: incidence and immunoheterogeneity studies.

A study was made of immunoreactive calcitonin (iCT) secretion by continuous cultures of small cell carcinoma of the lung (SCCL). Using an antiserum region specific for the midportion of the molecule, 9/12 cultures were found to secrete iCT. Gel filtration studies were performed on both supernatant fluid (SF) and cell pellet (CP) extract from a culture secreting high levels of iCT. Multiple iCT fractions were found in the SF with the major fraction being of high molecular weight (MW). In contrast, the CP had apparently monomeric CT as its principal iCT fraction. These studies demonstrate frequent iCT secretion by SCCL cultures and significant disparities between the iCT moieties found extra- and intracellularly.

Animals↗
PubMed1983

Hormone supplemented media for cloning human breast cancer: increased colony formation without alteration of chemosensitivity.

We tested the ability of hormones and growth factors to enhance the colony formation in soft agarose of breast carcinoma using two human breast carcinoma cell lines, MCF-7 and MDA-MB231, MCF-7 could clone in a basal medium supplemented only by insulin, transferrin, prostaglandin F2 alpha, and fibronectin. Combining oestradiol, dexamethasone, insulin, transferrin, and triiodothyronine with a basal medium supplemented with 5% (v/v) foetal bovine serum (FBS) increased colony forming efficiency (CFE) two-to three-fold over the best obtained in serum supplemented medium without hormones. While optimal CFE was seen in the hormonally supplemented medium plus 5% FBS, clonal anchorage independent growth could also be obtained without serum for both cell lines by substituting 0.5-1% (v/v) bovine serum albumin (BSA) for FBS. Although CFE was enhanced with the addition of hormones, they did not substantially alter the in vitro chemosensitivity patterns of the cell lines to 8 cytotoxic drugs. Hormonally-supplemented medium with 5% FBS increased the CFE of a small number of fresh specimens of human breast cancer compared with medium supplemented with serum alone. The systematic study of requirements for the in vitro growth of human breast cancer may improve drug sensitivity testing by increasing our ability to grow this neoplasm in culture.

Antineoplastic Agents↗
PubMed1983

Small-cell carcinoma of lung: reinduction therapy after late relapse.

Some patients with small-cell carcinoma of lung can be expected to achieve long-term disease-free survival. However, relapses may occur even after 2 years. Information on the treatment of these patients is sparse, although response rates to "salvage" therapy in patients with progressive disease while receiving treatment are poor. We report six patients who had relapses after more than 2 years in complete remission. Five patients were retreated with chemotherapy including some or all of the drugs in the initial treatment, and four had responses with a median duration of 10 months (range, 2 to 18 months). Thus retreatment with chemotherapy similar to the initial treatment can occasionally achieve second responses persisting up to 1 year or longer. The high incidence of patients who have relapses after 2 years confirms previous data on relatively slow growth rates in small-cell carcinoma.

Adult↗
PubMed1983

In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variants.

The in vitro response to radiation and chemotherapeutic drugs of cell lines established from 7 patients with small cell (SC) lung cancer were tested using a soft agarose clonogenic assay. Five cell lines retained the typical morphological and biochemical amine precursor uptake decarboxylation characteristics of SC, while two cell lines had undergone "transformation" to large cell (LC) morphological variants with loss of amine precursor uptake decarboxylation cell characteristics of SC. The radiation survival curves for the SC lines were characterized by D0 values ranging from 51 to 140 rads and extrapolation values (n) ranging from 1.0 to 3.3. While the D0 values of the radiation survival curves of the LC variants were similar (91 and 80 rads), the extrapolation values were 5.6 and 11.1 In vitro chemosensitivity testing of the cell lines revealed an excellent correlation between prior treatment status of the patient and in vitro sensitivity or resistance. No correlation was observed between in vitro chemosensitivity and radiation response. These data suggest that transformation of SC to LC with loss of amine precursor uptake and decarboxylation characteristics is associated with a marked increase in radiation resistance (n) in vitro. The observation of a 2- to 5-fold increase in survival of the LC compared to the SC lines following 200 rads suggests that the use of larger daily radiation fractions and/or radiation-sensitizing drugs might lead to a significantly greater clinical response in patients with LC morphology. This clinical approach may have a major impact on patient response and survival.

Antineoplastic Agents↗
PubMed1983

Monoclonal antibodies that distinguish non-small cell from small cell lung cancer.

Two murine IgG2Ak monoclonal antibodies (703D4, 704A 1) were produced and characterized after immunization with a human large cell lung cancer line (NCI-H 157). These antibodies detect different epitopes on 31 kilodalton [35S]methionine incorporating protein(s). Radiobinding and immunohistochemical studies show these antibodies bind to most (11/13) human non-small cell lung cancer (adenocarcinoma, epidermoid, and large cell), but not to small cell lung cancer (0/11) tumors tested. The epitopes these antibodies recognized are also expressed on human melanomas (7/8), two other tumors (osteogenic sarcoma, renal cell carcinoma), but not on many other human tumors (breast, colon, neuroblastoma, lymphoid), and not on a panel of normal adult human tissues. Because the antigen(s) are preserved after fixation and because of their ability to distinguish lung cancer types from each other and normal tissues, they should be of clinical, as well as of biologic interest.

Animals↗