A serum substitute that can support the continuous growth of mammary tumor cells.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D H Moore
Publications and source records attributed to D H Moore.
A method for the continuous cultivation of mammary epithelium.
Explore the source record for details and available documents.
Animals↗
On the frequency of chromosome exchanges in a control population measured by chromosome painting.
Chromosome painting has been shown to be a valid and rapid method for quantifying structural chromosome rearrangements in human lymphocytes. The method is particularly useful for detecting stable aberrations which are difficult and expensive to quantify with classical methods. The inherent stability of translocations has enabled them to be used as a biodosimeter for chronic and temporally displaced exposure to radiation. Translocations may also be useful for quantifying chronic exposure to other environmental agents which may result in an accumulation of cytogenetic damage with age. Most exposures are chronic and occur at low rates, and conventional cytogenetic methods such as dicentric analysis are not expected to be informative. To understand the extent to which age and lifestyle factors impact the frequency of stable aberrations, we have performed chromosome painting on metaphase-arrested lymphocytes cultured from 47 healthy adults ranging in age from 19 to 77 years, and from umbilical cord blood obtained from eight healthy full-term infants. All subjects had previously been screened to eliminate those who had received significant occupational or accidental exposure to radiation or chemicals, and none had received chemo- or radiotherapy. Due to the infrequent occurrence of stable aberrations in peripheral lymphocytes, we analyzed the equivalent of more than 1100 metaphase cells from each of these 55 people. An average of one cell in 130 (0.77%) was observed to have a translocation or a stable insertion. A significant relationship between stable aberrations and the square of the age is apparent (R2 = 0.69, Y = 0.0615 + 0.000304 age2; p < 0.00001). These results support the hypothesis that stable aberrations accumulate with time, and are likely to integrate adverse environmental exposure.
Adult↗
Long-term health effects of low dose exposure to nerve agent.
Possible long-term toxic effects of nerve agents have been investigated using sensitive toxicological screens and extensive toxicity studies in various animal models. Data on humans have been obtained from controlled studies and accidental exposures. Studies in the area of 'low dose' exposure to nerve agents are currently being performed.
Accidents↗
The risk of nodal metastasis in early adenocarcinoma of the uterine cervix.
A functional and widely accepted definition of microinvasive cervical adenocarcinoma remains elusive. The purpose of this study was to determine at which depth of invasion the likelihood of lymph node metastasis or disease recurrence was so small that conservative surgery could be considered appropriate. Charts of patients with adenocarcinoma of the cervix (ACC) who underwent radical hysterectomy and pelvic lymphadenectomy (n = 98) at Indiana University Medical Center from 1987 to 1998 were retrospectively reviewed. Patients with stage IA1-IB1 lesions were included in the study. Patients treated with preoperative radiotherapy were excluded. Pathologic parameters evaluated included histologic type, depth of stromal invasion (DOI), and the presence of lymphatic vascular space invasion, or lymph node metastases. The patient median age was 39 years (20-65). The median time of follow-up was 30 months (4-124). Lymph node metastases were found in ten patients and 11 developed recurrences. The precise DOI could be measured in 84 patients. Of the 48 patients with cancers with a DOI </= 5 mm, none had involved parametria or nodes; whereas eight of the 36 with a DOI > 5 mm had nodal metastases (P = 0.00069). None of these 48 patients with a tumor DOI </= 5 mm developed a recurrence whereas six of the 36 patients with a tumor DOI > 5 mm developed recurrent disease (P = 0.0048). The risk of nodal metastases and recurrence is so low in patients with ACC and DOI </= 5 mm that for patients with such depth documented on conization with negative margins pelvic lymphadenectomy may be omitted.
Adenocarcinoma↗
The utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer.
The objective of this study was to evaluate the ability of a preoperative serum CA125 to predict whether optimal debulking (OD) could be achieved for patients with stage III and IV epithelial ovarian cancer (EOC). The records of consecutive patients who underwent primary surgery for EOC at Indiana University Hospital between January 1997 and January 2003 were reviewed. Eligibility criteria included FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative CA125, and an operative note clearly defining volume of residual disease. The Medcalc software statistical package was used to generate a receiver-operating characteristic (ROC) curve. Two hundred and eighty-nine cases of stage III/IV EOC were identified, of which 164 met the eligibility criteria. Serum CA125 </=400 was associated with OD >/=75% of the time. Conversely, OD was achieved in </=40% of patients with CA125 >/=4500. The area under the ROC curve for CA125 was .670. The OD rate for those with and without ascites was 49% and 79%, respectively (P < 0.001). In a multivariate analysis using CA125, age, and ascites, the area under the curve was 0.686. We conclude that preoperative serum CA125 did not reliably predict OD in patients with stage III-IV EOC.
Adenocarcinoma↗
Breast cancer: etiology and possible prevention.
Explore the source record for details and available documents.
Animals↗
Function and distribution of acetyl- and butyrylcholinesterase in canine tracheal smooth muscle.
The total cholinesterase activity in canine tracheal smooth muscle was found to consist of butyrylcholinesterase and acetylcholinesterase in a ratio of 3:1. Most of the acetyl- and butyrylcholinesterase sites were distributed on the muscle surface; the remaining hydrolytic sites were associated with internal structures. Intracellular acetylcholinesterase staining was associated with the perinuclear envelope, sarcoplasmic reticulum and Golgi apparatus. Intracellular butyrylcholinesterase was associated with the perinuclear envelope, sarcoplasmic reticulum and the contractile filaments. Inhibition of acetylcholinesterase by the selective agent 1,5,bis(allyl-dimethylammoniumphenyl)-pentane-3-one dibromide (BW 284C51) led to a parallel leftward shift in the concentration-response curve for bath-applied acetylcholine. A similar shift was observed in the frequency-response curve for neurally released acetylcholine. Inhibition of butyrylcholinesterase by the selective agent tetraisopropyl-pyrophosphoramide potentiated the response to bath-applied and neurally released acetylcholine; the potentiation was limited to acetylcholine concentrations greater than or equal to 1 microM and frequencies greater than or equal to 10 Hz. It is concluded that both acetyl- and butyrylcholinesterase participate in the hydrolysis of acetylcholine in canine tracheal smooth muscle. The role of acetylcholinesterase is evident over the entire range of concentrations (1 nM to 100 microM) and frequencies (1 to 90 Hz) examined, whereas the role of butyrylcholinesterase is confined to the higher end of the concentration and frequency ranges used.
Acetylcholinesterase↗
Factors affecting HPRT mutant frequency in T-lymphocytes of smokers and nonsmokers.
The frequency of thioguanine-resistant, hypoxanthine phosphoribosyltransferase-deficient lymphocytes in the peripheral blood of human subjects was used to study the genotoxic effects of smoking. Sixty-two nonsmokers and 58 smokers, aged 19 to 45 years with average ages of 30 and 32 years, respectively, and with no other known exposures, were studied using an in vitro assay of the frequency of mutant lymphocyte clones. Analysis of variance explained 68% of the variation in the mutant frequencies. Mutant frequency was dependent upon lymphocyte cloning efficiency, length of smoking history, age, and interactions between these variables. Four nonsmokers and three smokers had high mutant frequencies that were not explained by these variables. Mutant frequencies were inversely related to lymphocyte cloning efficiencies; the effect was twice as great for smokers as for nonsmokers. The time-dependent effect of smoking dominated, with mutant frequency increasing 10%/year of smoking as compared with an independent 1%/year of age. Smoking had a greater effect on young smokers' lymphocytes. Heterogeneity of mutant frequency among both smokers and nonsmokers and its implications for use of lymphocyte mutation assays as biomarkers are discussed.
Adult↗
Increased thymidine kinase and thymidylate synthase activities in human epithelial ovarian carcinoma.
BACKGROUND: Thymidylate synthase (dTMP synthase, EC 2.1.1.45) is responsible for the de novo biosynthesis of thymidylate (dTMP) whereas thymidine kinase (TdR kinase, EC 2.7.1.21) is the salvage enzyme which leads to the production of dTMP even in presence of d TMP synthase inhibition. The current study was undertaken to compare the steady-state activities of d TMP synthase and TdR kinase in extracts of human epithelial ovarian carcinoma and normal ovaries. MATERIAL AND METHODS: Tissue extracts of epithelial ovarian carcinomas and normal ovaries were analyzed for activities of d TMP synthase (by a method that measures released 3H2O) and TdR kinase (by polyethyleneimine impregnated (PEI) cellulose plate radioassay), methods established in this laboratory. RESULTS: The dTMP synthase activity (mean +/- S.E.) in extracts of ovarian carcinomas (N = 11) was 0.198 +/- 0.069 and in extracts of normal ovaries (N = 12) it was 0.025 +/- 0.0004 nmol/hr/mg protein. By contrast, TdR kinase activity in extracts of ovarian carcinoma (N = 13) was 27.7 +/- 8.5 compared to 1.0 +/- 0.3 nmol/hr/mg protein in extracts of normal ovaries (N = 15). CONCLUSION: The observed 140-fold higher TdR kinase activity suggests that DNA synthesis may continue despite inhibition of dTMP synthase with current schedules of 5-fluorouracil (5-FU) and leucovorin. The addition of azidothymidine, a competitive inhibitor of TdR kinase, to 5-FU and leucovorin might be a rational biochemical strategy to employ in patients with refractory ovarian carcinoma.
Adult↗
The apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme is elevated in premalignant and malignant cervical cancer.
The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease (APE) is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA-binding capability of JUN and FOS, HeLa AP-1, and numerous other transcription factors, including Myb, members of the CREB family and nuclear factor-kappa B. Although previously presumed to be ubiquitously expressed at comparable levels in all tissues and cell types, recent evidence has shown APE to vary significantly in its expression between tissues and even within tissues. To further characterize APE expression at various stages of cervical neoplasia, we investigated the levels of APE protein expression using immunohistochemistry in normal cervix, pre-invasive and invasive squamous lesions of the cervix, as well as in cervical cancer cell lines. We report here that the APE protein is predominantly expressed in the nuclei of cells from both primary tumors and cervical cell lines, but the level of APE protein is significantly and dramatically elevated in cervical cancer tissue. These results implicate the use of anti-APE antibodies as an effective reagent in the early detection of premalignant and malignant cancer of the cervix. These findings are suggestive that the increase of a DNA repair enzyme in cancerous cells may allow these cells to be refractive to chemotherapy.
Antibody Specificity↗