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  • 1
    ISSN: 0730-2312
    Keywords: Lung neoplasms ; oncogenes ; drug therapy ; mortality ; pathology ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We identified 126 tumor cell lines established from patients with small cell cancer at the NCI-Navy Medical Oncology Branch from 1977 through 1992. Extensive clinical information was available on 96 patients from whom these cell lines were established. These patients comprised approximately one fourth of the 407 patients treated on prospective therapeutic clinical trials during the same time period. The proportion of tumor cell lines established from previously untreated patients with both limited and extensive stage small cell lung cancer increased during the 16 years of the study (P = 0.008). MYC family DNA amplification was present in 16 of 44 (36%) tumor cell lines established from previously treated patients compared to 7 of 52 (11%) of tumor cell lines established from untreated patients (P = 0.009). MYC DNA amplification in tumor cell lines established from patients previously treated with chemotherapy continued to be associated with shortened survival (P = 0.001). The initiation of a policy to obtain tumor tissue for the purpose of selecting chemotherapeutic agents given to individual patients was associated with an increase in the proportion of patients from whom tumor cell lines could be established for both extensive and limited stage patients (P = 0.001 and 0.05, respectively). © 1996 Wiley-Liss, Inc.
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  • 2
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 24-31 
    ISSN: 0730-2312
    Keywords: lung cancer cell lines ; cell culture techniques ; SErum-free ; defined medium ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: More than 200 human small cell lung cancer and non-small cell lung cancer cell lines were established over 15 years mainly by utilizing the serum-free, hormone and growth factor supplemented, defined media HITES and ACL4. Use of modified, established cell culture techniques such as the mechanical spillout method for the releasing of cell aggregates from tumor tissue, ficoll gradient centrifugation for the separation of tumor cells from erythrocytes and tissue debris, and an apparatue consisting of a platinum tubing attached to a suction flask for removal of spent medium have greatly contributed to the success in culturing tumor cells. Characterization of these lung cancer cell lines have extended our knowledge of lung cell biology. Studies elucidating the nutritional requirements of lung cancer cell growth may be helpful for the manipulation of these tumors in patients. © 1996 Wiley-Liss, Inc.
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  • 3
    ISSN: 0730-2312
    Keywords: non-small cell lung cancer ; small cell lung cancer ; drug resistance ; cell survival ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Clinical protocols for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) were devised to prospectively select individualized chemotherapy based on in vitro drug sensitivity testing (DST) of cell lines derived from the patient's SCLC tumor cell lines or the patient's fresh NSCLC tumor. DST data derived from SCLC tumor cell lines were available for 33/115 (29%) patients. The DST-selected chemotherapy regimen was administered to 21 (18%) patients, or 64% of patients with DST. In SCLC, the DST-selected chemotherapy was administered either during weeks 13-24 following 12 weeks of etoposide/cisplatin, or at relapse after complete response to etoposide/cisplatin. Several parameters of in vitro drug sensitivity were significantly associated (two-sided P 〈 0.05) with clinical response to primary therapy and also with response to the DST-selected chemotherapy regimen, but were not associated with survival (P = 0.24). Five patients treated with their DST-selected chemotherapy attained a complete or partial response, compared to 5 of 68 who received an empiric regimen (P = 0.057). A total of 36/165 (22%) NSCLC patients had DST successfully completed. These results directed management for 21/96 (22%) patients who eventually received chemotherapy, or 58% of patients with DST. Response to chemotherapy for the patients treated prospectively with their DST-selected chemotherapy regimen (2/21; 9%) was not significantly different than the response rate for patients treated empirically with etoposide/cisplatin (10/69; 14%) in the absence of in vitro results to direct chemotherapy (P = 0.73). There was no difference in survival by treatment group for the NSCLC patients. The correlation between in vitro and clinical response was not significant for any individual drug or for all drugs considered together, illustrating the poor predictive value of in vitro testing with currently available chemotherapy in NSCLC. © 1996 Wiley-Liss, Inc.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 2 (1974), S. 558-581 
    ISSN: 0091-7419
    Keywords: Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Internal dialysis techniques have been used to examine the influence of external and internal cations on Ca efflux from ATP-depleted squid axons. The main observation is that Ca efflux is promoted by external Na and inhibited by internal Na. The Na0 -dependent Ca efflux appears to be a function of [Na]03, and is also affected by the membrane potential; a 25 mV depolarization may cause as much as an e-fold decrease in Ca efflux. These data are consistent with a counter-transport exchange of 3Na+-for-1Ca2+. A Ca0-dependent Ca efflux has also been observed; it is prominent in Na sea water or Le sea water, and is markedly diminished in choline sea water. This flux is consistent with the idea of a Ca-Ca exchange diffusion process. Taken together, the Na0 - and the Ca0 -dependent Ca effluxes fit a two-site model for carrier-mediated Ca transport; one site binds two Na+ or one Ca2+, while the second site can bind either one Na+ or one Li+. The data reported here suggest that both sites must be filled on the inward journey, but that only the Ca-binding site need be occupied on the outward journey of the carrier. A mechanism of this type could derive sufficient energy from the Na and voltage gradients to maintain a [Ca2+]0/[Ca2+]i concentration ratio of about 104 in the absence of ATP. The present experiments do not, however, rule out the possible participation of a metabolically driven Ca transport mechanism in vivo.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 6 (1977), S. 599-616 
    ISSN: 0091-7419
    Keywords: plants ; polysaccharides ; elicitors ; phytoalexins ; Rhizobium ; nitrogen-fixation ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Plants are resistant to almost all of the microorganisms with which they come in contact. In response to invasion by a fungus, bacterium, or a virus, many plants produce low molecular weight compounds, phytoalexins, which inhibit the growth of microorganisms. Phytoalexins are produced whether or not the invading microorganism is a pathogen. The production of phytoalexins appears to be a widespread mechanism by which plants attempt to defend themselves against pests. Molecules of microbial origin which trigger phytoalexin accumulation in plants are called elicitors. Structural polysaccharides from the mycelial walls of several fungi elicit phytoalexin accumlation in plants. Approximately 10 ng of the polysaccharide elicits the accumulation in plants of more than sufficient amounts of phytoalexin to stop the growth of microorganisms in vitro. The best characterized elicitors have been demonstrated to be β-1,3-glucans with branches to the 6 position of some of the glucosyl residues. Oligosaccharides, produced by partial acid hydrolysis of the mycelial wall glucans, are exceptionally active elicitors. The smallest oligosaccharide which is still an effective elicitor is composed of about 8 sugar residues.Bacteria also elicit phytoalexin accumulation in plants, but the Rhizobium symbionts of legumes presumably have a mechanism which allows them to avoid either eliciting phytoalexin accumulation or the effects of the phytoalexins if they are accumulated. The lectins of legumes bind to the lipopolysaccharides of their symbiont, but not of their non-symbiont, Rhizobium. It is not known whether the lectin-lipopolysaccharide interaction is involved with the establishment of symbiosis. However, evidence will be presented that suggests that lectins are, in fact, enzymes capable of modifying the structurs of the lipopolysaccharides of their symbiont, but not of their non-symbiont, Rhizobium. It will also be shown that the lipopolysaccharides isolated from different Rhizobium species and from different strains of individual Rhizobium species have different sugar compositions. Thus, the different strains of a single Rhizobium species are as different from one another as the different species of Salmonella and other gram-negative bacteria. This conclusion is substantiated by experiments demonstrating that antibodies to the lipopolysaccharide from a single Rhizobium strain can differentiate that strain from other strains of the same species as well as from other Rhizobium species. The role in symbiosis of the strain-specific O-antigens is unknown.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 1 (1973), S. 382-384 
    ISSN: 0091-7419
    Keywords: Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cyclic AMP appears to regulate cell growth. Cyclic AMP levels are high in normal chicken embryo fibroblasts and drop to very low levels when the cells are transformed by the Bryan high-titer strain of Rous sarcoma virus. Cells infected with a temperature-sensitive mutant of the virus have normal levels of cyclic AMP at the nonpermissive (nontransforming temperature), but when the cells are shifted to the permissive (transforming) temperature the cyclic AMP levels rapidly fall to values that are found in transformed cells. Studies on the adenylate cyclase and cyclic AMP phosphodiesterase in normal and transformed chicken embryo fibroblasts have shown that the adenylate cyclase is greatly decreased in the transformed cells whereas the phosphodiesterase is increased. The decrease in adenylate cylcase activity is the result of an increase in the Km of the substrate and a loss of a magnesium ion activator site. The increase in phosphodiesterase activity is the result of an increase in total phosphodiesterase activity and a decrease in the negative cooperativity of plasma membrane bound phosphodiesterase. Thus the fall in cyclic AMP levels that occurs on transformation can be correlated with changes in the activity of adenylate cyclase and cyclic AMP phosphodiesterase.
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  • 7
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 4 (1976), S. 233-240 
    ISSN: 0091-7419
    Keywords: Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cells dissociated from the R3230AC mammary adenocarcinoma from intact and diabetic rats were examined for insulin binding and glucose transport. The Kd for insulin binding, ∼ 10-10 M, was similar in all tumors studied. However, the apparent number of receptor sites per cell increased in cells from diabetic rats. Kinetic analysis of 3-0-methyl glucose (3-OMG) entry showed both diffusional and passive carrier characteristics. Insulin (4 × 10-9 M) in vitro did not affect diffusional entry, whereas the hormone altered the passive carrier system, as reflected by an increase in Km and Vmax. Insulin decreased initial velocity of glucose transport at 4-6 mM glucose levels but increased initial velocity of glucose transport at 20 mM glucose. An explanation of the role of insulin on tumor growth in vivo from effects on glucose transport in vitro is proposed.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 10 (1979), S. 265-275 
    ISSN: 0091-7419
    Keywords: membrane hydration ; membrane-bound water ; ANS fluorescence ; infrared spectra ; water-membrane interactions ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Bound water is a major component of biological membranes and is required for the structural stability of the lipid bilayer. It has also been postulated that it is involved in water transport, membrane fusion, and mobility of membrane proteins and lipids. We have measured the fluorescence emission of membrane-bound 1-anilino-8-naphthalenesulfonate (ANS) and the infrared spectra of membranes, both as a function of hydration. ANS fluorescence is sensitive to polarity and fluidity of the membrane-aqueous interface, while infrared absorption is sensitive to the hydrogen bonding and vibrational motion of water and membrane proteins and lipids. The fluorescence results provide evidence of increasing rigidity and/or decreasing polarity of the membrane-aqueous interface with removal of water. The membrane infrared spectra show prominent hydration-dependent changes in a number of bands with possible assignments to cholesterol (vinyl CH bend, OH stretch), protein (amide A, II, V), and bound water (OH stretch). Further characterization of the bound water should allow its incorporation into current models of membrane structure and give insight into the role of membrane hydration in cell surface function.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 14 (1980), S. 255-266 
    ISSN: 0091-7419
    Keywords: cytodifferentiation ; dexamethasone ; methylisobutylxanthine ; fetal calf serum ; retinoic acid ; preadipocytes ; adipose conversion ; Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The role of retiinoic acid in modulating the differentiation of 3T3-L2 fibroblasts into adipocytes has been examined. Results indicate that the retinoid is capable of effectively inhibiting the degree of adipose conversion which is brought about by treatment of preadipocytes with 1-methyl-3-isobutylxanthine plus dexamethasone. Morphological and enzymatic (fatty acid synthetase activity) expression of the adipose phenotype are both inhibited more than 90% by 10-6 M retinoic acid. The inhibition is concentration dependent with retinoic acid levels as low as 10-11 M capable of reducing adipose conversion by 20%. Retinoic acid must be administered simultaneously with the triggering agents to be effective. Exposure of nongrowing preadipocytes to retinoic acid does not alter the ability of the cells to differentiate in response to a subsequent treatment with methylisobutylxanthine plus dexamethasone. Further, the inhibition is reversible. Cultures in which methylisobutylxanthine plus dexamethasone triggered differentiation has been blocked by addition of retinoic acid (10-6M) will readily undergo adipose conversion in response to a second treatment with methylisobutylxanthinthine plus dexamethasone in the absence of the retioid. Similar inhibition of differentiation was found when cultures were treated with drugs in medium supplemented with either newborn calf serum or fetal calf serum. However, the extent to which methylisobutylxanthine plus dexamethasone are able to promote differentiation in these cells is considerably greater in medium containing fetal calf serum.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Supramolecular Structure 2 (1974), S. 138-149 
    ISSN: 0091-7419
    Keywords: Life Sciences ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The formation of fibrin gels involves many operations which are fundamental to other assembly schemes, including limited proteolysis, spontaneous associations, and covalent stabilization. Despite a quarter century of intensive effort by a large number of laboratories, the orientation of the fundamental units in the gel is not known, nor, for that matter, is the arrangement of the subunit chains within the parent fibrinogen molecule. In this article some symmetry considerations are discussed in light of the geometry of the starting molecules and conditions necessitated by the covalent stitching which occurs after gel formation. Only a dimeric molecule in which the twofold symmetry axis coincides with a minor axis of an elongated fibrinogen molecule satisfies all the conditions.
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