A hygiene experiment in rural Bangladesh.
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Asia↗
Biomedical subjects
R C Leonard
Publications and source records attributed to R C Leonard.
Effect of sodium butyrate and other differentiation inducers on poorly differentiated human ovarian adenocarcinoma cell lines.
We have studied the effects of sodium butyrate, retinoic acid, and dimethyl sulfoxide on two human ovarian carcinoma cell lines PE04 and PE01. PE04 cells, after treatment with sodium butyrate at cytostatic doses (2-3 mM for 4 days), exhibited phenotypic changes including induction of alkaline phosphatase and determinants recognized by the monoclonal antibodies 123C3 and 123A8. These effects are not simply the result of cytostasis as they were not produced by dimethyl sulfoxide or retinoic acid. Other markers are also modified by sodium butyrate including lipid, acid mucin, and glycogen. Retinoic acid modulated expression of lipid and CA125, while dimethyl sulfoxide reduced expression of CA125. Other short chain fatty acids such as propionic acid and valeric acid (in addition to butyric acid) also induced alkaline phosphatase and the determinants recognized by 123C3 and 123A8 in PE04 cells. Other differentiation inducers and cytotoxic agents studied did not induce these markers at cytostatic concentrations. The effects of sodium butyrate (and related short chain fatty acids) thus appear to be relatively specific for this cell line.
Adenocarcinoma↗
Characterization and properties of nine human ovarian adenocarcinoma cell lines.
Four series of cell lines have been derived from patients with ovarian adenocarcinoma. Nine cell lines have been established at one from a solid metastasis. Six lines were derived from the ascites or pleural effusion of patients with poorly differentiated adenocarcinoma: PEO1, PEO4, and PEO6 from one patient, PEA1 and PEA2 from a second, and PEO16 from a third. Three lines (PEO14 and PEO23 from ascites and TO14 from a solid metastasis) were derived from a patient with a well-differentiated serous adenocarcinoma. Each set of cell lines was morphologically distinct. The five cell lines PEO1, PEO4, PEO6, PEA1, and PEA2 had cloning efficiencies on plastic of 1-2% and only a few cells in these lines expressed alkaline phosphatase or vimentin. Only a low percentage of these cells reacted with the monoclonal antibodies 123C3 and 123A8 but most reacted with OC125. Conversely the cell lines PEO14, TO14, PEO23, and PEO16 were characterized by low cloning efficiency values (less than 0.05%), marked expression of alkaline phosphatase and vimentin, and good reaction with 123C3 and 123A8 but not OC125. These four cell lines also exhibited dome formation. Four of the cell lines, PEO1, PEO4, PEO6, and PEO16, have been xenografted into immune-deprived mice and found to be tumorigenic.
Adenocarcinoma↗
Normal G2 chromosomal radiosensitivity and cell survival in the cancer family syndrome.
Recent reports have suggested that elevated chromosomal aberration yields following X-irradiation of skin fibroblasts in the G2 phase of the cell cycle are characteristic of affected members of cancer-prone families. These studies propose that this phenomenon is a consequence of impaired DNA repair and might be a useful predictor of genetic susceptibility to cancer. We have tested G2 chromosomal X-ray sensitivity in skin fibroblasts and peripheral blood lymphocytes from members of a kindred with the cancer family syndrome, a disorder in which susceptibility to colon cancer and other epithelial cancers is inherited in an autosomal dominant pattern. Further, using a cell survival assay, we tested cancer family syndrome skin fibroblasts for sensitivity to four classes of mutagens, including X-rays. In the assays used, skin fibroblasts and lymphocytes from both affected and unaffected family members exhibited responses indistinguishable from normal controls. Karyotypic analysis of lymphocytes and fibroblasts revealed no consistent constitutional cytogenetic abnormality. Thus, affected patients with the cancer family syndrome do not have increased sensitivity to irradiation and chemical mutagens and lack a germ-line chromosomal defect.
Cell Survival↗
Clinical applications of immunocytochemistry in the monitoring of the bone marrow in small cell lung cancer (SCLC).
A panel of monoclonal antibodies (MAbs) has been identified which may be useful in detecting SCLC tumour cells and which does not cross-react significantly with normal marrow elements. Compared with conventional techniques this MAb panel markedly increases detection of micrometastases in the bone marrow especially in limited disease and post-chemotherapy in responding patients. There is a close correlation between immunological positivity and the ability to grow SCLC-like cells for variable periods in serum-free culture. In 4 cases SCLC-like cells have been characterized by electron microscopy or by the establishment of SCLC cell lines in continuous culture. The prognostic importance of pre-treatment detection of marrow involvement is unknown. The implications of post-chemotherapy detection of micrometastases are also uncertain but there may be an association with early systemic relapse which may occur regardless of intervention, including high dose intensification with autologous marrow rescue with primary site and CNS prophylactic irradiation.
Antibodies, Monoclonal↗
Arabinofuranosyl nucleosides induce common fragile sites.
The capacities for fragile site induction of three inhibitors of semiconservative DNA synthesis and DNA repair synthesis, aphidicolin, arabinofuranosyl cytosine, and arabinofuranosyl adenosine were compared. Aphidicolin is known to induce type 4 fragile sites, the largest recognized group of common fragile sites. Although the modes of action of these inhibitors vary, both arabinofuranosyl analogs induce type 4 aphidicolin-sensitive fragile sites. An analysis of variance demonstrates that the three inhibitors are not equally capable of inducing significant breakage (P less than 0.01) at all type 4 fragile sites. Induction of type 4 fragile sites appears to be a general consequence of inhibition of DNA polymerization.
Aphidicolin↗
Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample.
In order to assess the potential of cytogenetic determinations on peripheral blood lymphocytes as a means of monitoring human populations subject to low level occupational and environmental exposures to chemical mutagens and carcinogens, accurate baseline data are required. Accordingly, we have determined mean frequencies of chromosomal aberrations and of sister-chromatid exchanges, their variances, and the sources of this variance in a cohort of 353 healthy employees of the Brookhaven National Laboratory. A detailed protocol was adopted for blood sampling, lymphocyte culture, cytogenetic preparation and scoring in order to minimize variation from these potential sources. Scoring was divided between the Oak Ridge and the Brookhaven groups with duplicate scoring sufficient to evaluate and minimize the effect of any differences between laboratories or between individual scorers. In all, the data include 71,950 cells scored for chromosomal aberrations and 16,898 cells scored for sister-chromatid exchanges. The mean unadjusted frequency of sister-chromatid exchanges was 8.29 +/- 0.08/cell. As reported in other studies, cigarette smoking very significantly influenced sister-chromatid exchange frequencies; in our study the mean for smokers was 9.0 +/- 0.2, while that for non-smokers was 8.1 +/- 0.1/cell. The mean frequency was statistically higher in females than in males, regardless of smoking status. On the other hand, age of the subject did not significantly influence sister-chromatid exchange frequencies. Curiously, the subject's total white cell count did influence sister-chromatid exchange frequency. No other source of variation was found. The frequencies of chromosomal aberrations of all types were determined. The frequency of the most common unequivocal chromatid type, the chromatid deletion, was 0.81 +/- 0.05%, that of the most common unequivocal chromosome type, the dicentric, was 0.16 +/- 0.02%. No statistically significant influence was found of age or sex, nor of any other parameter tested, on the frequency of any chromosomal aberration type, with the single exception of long acentric fragments, often "supernumerary", believed to represent X chromosomes precociously separated at the centromere. Such fragments were significantly more frequent in samples from females than those from males, and showed a significant positive regression on age.
Aneuploidy↗
Chromosomal aberrations and sister-chromatid exchanges in lymphocytes from coke oven workers.
To test whether coke oven workers, an occupational group known to be at increased cancer risk, manifest increased peripheral blood chromosomal aberration frequencies, we obtained samples from a group of 30 steelworker volunteers, who had worked several years at coke oven jobs. Exposure estimates were made using measurements of work place atmospheric coal tar pitch volatiles and work histories. No statistically significant positive regression of chromosomal aberrations on exposure estimates was found. The data from the coke oven workers were also compared with the obtained concurrently and employing precisely the same laboratory protocol from a group of male Brookhaven National Laboratory employees. The coke oven workers as a group were found to have statistically significantly elevated frequencies of chromatid aberrations and of sister-chromatid exchanges.
Aneuploidy↗
Influence of therapy on local control and survival in stage I and II intermediate and high grade non-Hodgkin's lymphoma.
In a consecutive series of 113 patients with localized (Stage I and II) intermediate and high grade non-Hodgkin's lymphoma we have retrospectively analysed patterns of survival and relapse in relation to presenting features and therapy. Two patients were treated by complete surgical excision. Seventy-two were treated by radiotherapy (RT), 19 by chemotherapy (CT) and 20 by combined CT and RT. A number of different chemotherapy combinations were employed. Overall survival for Stage I patients was 68.3% at 5 years and 65.5% at 10 years; for Stage II patients it was 61.2% at 5 years and 52.2% at 10 years. Recurrence-free survival for Stage I patients was 51.4% at 5 years and 42.1% at 10 years; for Stage II patients it was 46.2% at both 5 and 10 years. Local control by radiation was achieved in 59/72 (82%) patients treated with less than 40 Gy and 19/20 (95%) treated with 40 Gy or more. There was no advantage for extended field irradiation when compared with involved field. Eleven of 19 (58%) patients treated by CT alone achieved complete response (CR). For patients responding completely to CT there was no clear advantage for irradiation of originally involved bulky sites. For patients with Stage II and bulky Stage I disease there was a significant (P = 0.05) improvement in recurrence-free survival (RFS) and a trend (P = 0.192) towards improved overall survival for patients treated by CT alone or together with RT compared with RT alone. Independent variables identified by multivariate analysis were age, with better survival for younger patients (P = 0.034) and histopathological group, with better survival for DPDL compared with DH (P = 0.015).
Adolescent↗
Cardiotoxicity of mitozantrone assessed by stress and resting nuclear ventriculography.
Fourteen patients with advanced breast cancer were treated with a combination of vincristine, mitozantrone and prednisolone. Before, during and after cessation of treatment radionuclide assessment of ventricular performance was obtained at rest, in response to cold pressor-induced stress and on recovery from stress. Six of 14 patients (46%) developed abnormalities of left ventricular ejection fraction (LVEF). One patient developed clinical signs of cardiac failure. Mitozantrone is an active agent in the treatment of advanced breast cancer but it can produce cardiotoxicity. In this particular middle-aged population, changes in LVEF occurred over a wide range of cumulative doses. Further investigation is required to determine the nature and prognosis of this iatrogenic toxicity.
Adult↗
Low grade stage I and II non-Hodgkin's lymphoma: results of treatment and relapse pattern following therapy.
Sixty-four patients (37 stage I and 27 stage II) with low grade non-Hodgkin's lymphoma were treated by surgical excision alone (two patients) or with radiotherapy (53 patients), chemotherapy (five patients) or both (four patients). Actuarial survival was 80.7% at 5 years and 77.9% at 10 years. Actuarial recurrence-free survival at 10 years was 49.4% for stage I and 38.0% for stage II patients. Local control was achieved in 52 out of 56 (93%) patients treated with a radiation dose of 30 Gy or greater. There was no advantage for extended compared with involved, field irradiation. A multivariate analysis identified age, sex, stage and disease site as independent prognostic variables for survival.
Adult↗
Non-Hodgkin's lymphoma of the lung.
Non-Hodgkin's lymphoma (NHL) commonly presents with extensive disease involving extranodal tissues. Involvement of the mediastinal and hilar lymph nodes, pleura and lung parenchyma are recognised complications although their incidence is uncertain. However, pulmonary involvement is undoubtedly much less common than involvement at other extra nodal sites. Histologically proven NHL limited to the lung parenchyma, after full staging including computerised tomography and marrow trephines, is extremely rare. We report on two such cases and review the literature.
Female↗
Methylprednisolone, etoposide, vindesine, and chlorambucil (PEEC) alone or alternating with CHOP as initial or salvage therapy for non-Hodgkin's lymphoma.
A novel cytotoxic drug combination, PEEC, has been tested in the initial or salvage treatment of lymphomas. The PEEC combination alone is active in high grade or intermediate grade NHL with two complete and two partial remissions out of four patients so treated. When combined with standard CHOP therapy using an alternating regime, seven out of 11 patients obtained a complete remission and four partial remission. Ten patients were well, off treatment, beyond one year from presentation. The combination was less impressive, however, as salvage therapy with two partial responses in a heavily pre-treated group of nine patients.
Adult↗
Expression of human milk fat globule antigens HMFG1 and HMFG2 on ovarian tumours and lung tumours.
The patterns of reactivity of the monoclonal antibodies HMFG1 and HMFG2 were studied in epithelial ovarian tumours, small cell lung cancer, and non-small cell lung cancer. Twenty primary, paraffin embedded, ovarian tumours were analysed in addition to freshly obtained ascitic fluids (21), a node aspirate (1), solid metastatic tumours (3), and 6 established cell lines. SCLC tumours comprised paraffin embedded bronchial biopsies (31) and metastatic deposits (7) and fresh tissue from bronchial biopsies (3), pleural aspirates (4), bone marrows (5), node aspirates (6), solid metastatic tumour (3), and 4 cultured cell lines. Antigen expression was heterogeneous for all tumour types studied. However, significant differences in antigen expression were noted with the HMFG2 antibody between primary and metastatic lesions from both ovarian and small cell lung cancer groups.
Antibodies, Monoclonal↗
Light-chain isotype-associated B cell suppression in multiple myeloma.
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B-Lymphocytes↗
Phase I study of TCNU, a novel nitrosourea.
TCNU is a chloroethyl nitrosourea based on the endogenous amino acid taurine. This paper reports its first evaluation in man. Eighty-four patients with refractory cancer received 12 dose escalations from 10-150 mg/m2 TCNU administered orally every 6 weeks. Clinical side-effects were predominantly gastro-intestinal but dose-limiting toxicity was thrombocytopenia. Pharmacokinetic monitoring with an HPLC assay sensitive to the nanogram range demonstrated unchanged TCNU in plasma for up to 8 h following administration. The mean half-life was 60 min. Clinical responses were seen in melanoma (four patients), lung cancer (two squamous, one small cell) and one patient each with renal and stomach cancer. These responses, together with the unusual pharmacokinetic profile of TCNU, warrant exploration in disease-orientated phase II studies at a recommended dose of 130 mg/m2 p.o. q 5 weeks.
Adolescent↗
Prognosis in small cell carcinoma of the lung--relationship to human milk fat globule 2 (HMFG2) antigen and other small cell associated antigens.
Forty fixed tissue sections from patients with small cell lung carcinoma (SCCL) have been stained with a panel of 10 monoclonal antibodies using a peroxidase anti-peroxidase method and the incidence of staining has been compared to patient characteristics at presentation and to survival. An inverse association between HMFG2 staining and survival was found with median survival in HMFG2 negative patients 13 months compared to 8 months for HMFG2 positive patients. No such association was found with the other antibodies and no association was found between staining and disease extent or primary versus secondary deposits with this panel of antibodies. Epidermal growth factor receptor was detected in 3/38 presentation biopsies and in these 3 patients mean survival was only 5 months. Further prospective study of HMFG2 as a prognostic indicator in SCCL is suggested.
Antigens, Neoplasm↗
Mitoxantrone versus doxorubicin in combination chemotherapy for advanced carcinoma of the breast.
One hundred fifteen patients with metastatic carcinoma of the breast were treated in a randomized trial of mitoxantrone (Novantrone, Lederle Laboratories, Pearl River, NY) combined with vincristine and prednisolone (VMP) or doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) combined with vincristine and prednisolone (VAP). In 100 evaluable patients, the objective response rates were 35% for VMP and 61% for VAP, the complete response rates being 6% and 13%, respectively. In responding patients, median time to progression was 6.2 months for VMP and 7.9 months for VAP. The median survival whether measured from primary diagnosis, first metastasis, or from the start of chemotherapy was similar for both regimens. Toxicity, particularly alopecia, was appreciably lower in the VMP treated patients, but subclinical cardiotoxicity was seen within the scheduled dosage for both combinations. We conclude that VAP is clearly more active, but clinically more toxic than VMP. There is no survival advantage conferred by the more toxic combination. Cardiac toxicity is a potential hazard with either drug combination.
Antineoplastic Combined Chemotherapy Protocols↗