bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical detection of P‐glycoprotein in human tumor cells with a low degree of drug resistance
Authors: Broxterman Henricus J. , Pinedo Herbert M. , Kuiper Catharina M. , Van Der Hoeven Jacobus J. M. , De Lange Pieter , Quak Jasper J. , Scheper Rik J. , Keizer Hiskias G. , Schuurhus Gerrit Jan , Lankelma Jan 
Published: February 2007

AbstractWe report the immunohistochemical detection of the 170–180 kDa multi‐drug‐resistance‐related P‐glycoprotein in human tumor cells with a low level of resistance. A series of human squamous lung cancer cell lines with increasing levels of resistance to doxorubicin (DOX) was developed and stained for P‐glycoprotein, using the JSB‐lMAb. Subline SW1573/50A with a 4‐ to 6‐fold cross‐resistance to daunorubicin (DNR) and vincristine (VCR) showed rather uniform positive staining for P‐glycoprotein apparently at cytoplasmic sites. Only in cells with higher degrees of resistance (> 10‐fold) could plasmamembrane‐associated P‐glycoprotein be made visible. DNR efflux was increased in SW1573I50A as compared to the parent line SWl573 (52 and 70% DNR were retained during 3 min efflux respectively). Verapamil partially reversed DNR and VCR resistance in SWl573/50A. Cells obtained from a metastasized renal cell carcinoma and cultured in vitro stained in a similar way to SWl573/50A and showed some sensitivity to verapamil modulation of VCR cytotoxicity. Our results suggest that weakly resistant cancer cells obtained from patients can be routinely detected with JSB‐l on cytospins, and Implicate that in such weakly resistant cells P‐glycoprotein may be present, while plasma membrane expression is not yet readily detectable.
Induction of tumor‐cell lysis by bi‐specific monoclonal antibodies recognizing renal‐cell carcinoma and cd3 antigen
Authors: Van Duk J. , Warnaar S. O. , Van Eendenburg J. D. H. , Thienpont M. , Braakman E. , Boot J. H. A. , Fleuren G. J. , Bolhuis R. L. H. 
Published: February 2007

AbstractBi‐specific monoclonal antibodies (MAbs) were developed by somatic hybridization of 2 mouse hybridomas, one producing MAb against the G250 renal‐cell carcinoma (RCC)‐associated antigen and the other against the T‐cell antigen CD3 (OKT3). The dual specificity of the hybrid MAb produced by these so‐called quadromas was analyzed by immunohisto chemistry on tissue sections and by cytotoxicity assays with relevant target and effector cells. The bi‐specific MAb could induce TCRαβ/CD3+ and TCRγδ/CD3+ cloned lymphocytes to kill RCC cells. A noteworthy finding was that the TCRαβ and γδ lymphocyte clones showed different triggering abilities. The specificity of target‐cell lysis by the cytotoxic T cells (CTL) was dictated by the specificity of the G250 MAb. Control bi‐specific MAb, recognizing a cell‐surface structure not involved in T‐cell activation, did not induce lysis. Several lgG subclass switch variants of the G250 hybridoma, i.e., lgG1, 2a, and lgE, were used for somatic hybridization with the OKT3 hybridoma (lgG2a. Except for lgE, all lgG subclass combinations could equally induce cytolysis. Induction of cytolysis was inhibited only by excess OKT3 MAb. Comparison of 2 bi‐specific MAb preparations of the same combination (lgG2a/1), produced by 2 quadromas derived from the same parental hybridomas after identical purification procedures, produced different amounts of bispecific MAb.
Restriction fragment length polymorphism of the l‐myc gene and susceptibility to metastasis in renal cancer patients
Authors: Kakehi Yoshiyuki , Yoshida Osamu 
Published: February 2007

AbstractWe examined Southern blot analyses of normal and tumor DNAs from 50 patients with sporadic renal cancer, using the human L‐myc oncogene fragment as a hybridization probe. Our purpose was to study the relationship between the restriction fragment length polymorphism (RFLP) of the L‐myc and the frequencies of metastases. There was no individual difference in patterns of L‐myc RFLP between normal and tumor‐tissue DNAs digested with EcoRI. The patients were classified into 3 genetic types according to the polymorphic patterns defined by the 2 alleles [10‐kilobase (kb) and 6.6‐kb fragments]. The relative ratios of the 3 genotypes in the renal cancer patients were similar to those seen in healthy Japanese. However, of 16 patients who exhibited distant organ metastases at the time of surgery, only one was a 10‐kb fragment homozygote. The incidence of distant metastases in 10‐kb homozygotes was significantly lower than that in 6.6‐kb homozygotes plus heterozygotes (p = 0.06). These results basically correspond to the previous findings in the lung cancer patients, and suggest that L‐myc RFLP is a widely applicable genetic marker to predict prognosis in cancer patients.
Computer‐assisted image analysis of silver staining in normal and leukemic bone marrow
Authors: Arden K. C. , Bucana C. D. , Johnston D. A. , Pathak S. 
Published: February 2007

AbstractComputer‐assisted image analysis was used to quantitate the amount of silver staining in interphase nuclei of bone marrow cells from acute lymphocytic leukemia (ALL) patients. When we compared the data obtained for the interphase nuclei with that obtained for the metaphase spreads, we found a strong correlation between the fraction of bone‐marrow metaphases stained positively with silver, the average number of silver‐positive nucleolus organizer regions per metaphase, and the amount of silver staining in the interphase nuclei. Computer‐assisted image analysis of interphase nuclei can be used, therefore, to differentiate normal from ALL bone‐marrow samples.
Lack of correlation between peripheral blood lymphokine‐activated killer (lak) cell function and clinical response in patients with advanced malignant melanoma receiving recombinant interleukin 2
Authors: Ghosh A. K. , Dazzi H. , Thatcher N. , Moore M. 
Published: February 2007

AbstractA phase‐1/II study of recombinant interleukin 2 (rIL‐2) was performed in 31 melanoma patients. The first dose of rIL‐2 was given intrasplenically followed 4 hr later by an i.v. dose and 3 further i.v. doses on alternate days. Three courses of treatment were planned at 3‐week intervals. The maximum tolerated single dose was 11 × 106 Cetus U/m2. Haematological and immunological data were available on 20 patients. Post‐treatment response to rIL‐2 therapy was evident from (i) a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound at 4–7 days (2 times pre‐treatment values); (ii) an increase in the number of IL‐2 receptor‐positive lymphocytes (4–15 times pre‐treatment values); (iii) an increase in the number of “positive” patients with cytotoxic (anti‐K562) peripheral blood mononuclear cells (PBMC) from 30% to 80%; (iv) amplified killing of K562 by positive patients in relation to pre‐treatment values; and (v) the induction of PBMC cytotoxicity (in 45% of patients) against the NK‐resistant, LAK‐sensitive target, Mel 1. Partial clinical responses to rIL‐2 treatment were observed in 4 patients, but these were not reflected in the PBMC LAK activity or the other parameters examined.
Evidence of enhancement of the ras oncogene protein product (p21) in a spectrum of human tumors
Authors: De Biasi F. , Del Sal G. , Horan Hand P. 
Published: February 2007

AbstractUsing a direct binding liquid competition radioimmunoassay, the amount of the ras oncogene protein product, p21, was quantitated in a variety of human tumors and adjacent apparently normal tissues. In 48 of 50 matched tumor and normal tissue biopsy specimens from 50 patients, more ras p21 was detected in the tumor than in its normal counterpart. Twenty‐five of 28 breast tumors demonstrated more ras p21 than the average of the values obtained for fibroadenomas. Furthermore, in 17 of the 19 cases studied, over 20% more ras p21 was observed in breast carcinomas compared with their respective normal counterparts. More ras p21 was also demonstrated in the majority of tumors of the stomach, lung, colon and bladder compared with their respective adjacent normal tissues. Our data therefore indicate that ras p21 expression is quantitatively enhanced in many human tumors originating from several different tissue types.
Co‐regulation of metastatic and transforming activity of normal and mutant ras genes
Authors: Egan Sean E. , Broere James J. , Jarolim Lenka , Wright Jim A. , Greenberg Arnold H. 
Published: February 2007

AbstractWe have analyzed the metastatic properties of NIH‐3T3 cells transformed by H‐ras activated through over‐expression and/or mutation. Our results reveal that elevated expression of H‐ras proto‐oncogene can induce the complete metastatic phenotype. Cells transformed by the proto‐oncogene have a lower metastatic potential than those transformed by a mutated ras gene. ras oncogenes activated through alterations in codon 12 which encode p21 molecules with impaired GTPase activity, or in codon 59 which produce p21 molecules that release bound guanine nucleotides faster, or in codon 61 which produce p21 having impaired GTPase activity and altered nucleotide release properties, are all able to induce the metastatic phenotype. Leucine‐61‐activated oncogenes with an additional mutation in codons 116, 117 or 119, resulting in a reduced affinity for guanine nucleotides, are also capable of inducing metastatic behavior. These data indicate that ras genes which are capable of transforming are also capable of inducing the full metastatic phenotype in NIH‐3T3 cells. This suggests that both phenotypes are induced through an increase in p21‐GTP concentration in ras‐transformed cells. This established model for ras‐mediated transformation can also explain the qualitative and quantitative regulation of metastatic behavior by ras.
Use of the membrane invasion culture system (mics) as a screen for anti‐invasive agents
Authors: Welch Danny R. , Lobl Thomas J. , Seftor Elisabeth A. , Wack Peter J. , Aeed Paul A. , Yohem Karin H. , Seftor Richard E. B. , Hendrix Mary J. C. 
Published: February 2007

AbstractThe Membrane Invasion Culture System (MICS) assay was adapted for relatively rapid screening of compounds and used to identify anti‐invasive drugs that inhibit human and murine tumor cell migration through a reconstituted basement membrane in vitro. Cell lines demonstrating low and high invasive and metastatic potentials were tested with all compounds for tumoricidal effects prior to evaluation in MICS at non‐cytotoxic doses. The effect on invasive potential in the MICS assay was determined in 3 categories: (1) 48 hr drug pre‐treatment prior to seeding in the MICS (exceptions: 90 min pre‐treatment with pertussis toxin and, for some studies, continuous exposure for 2‐7 days); (2) peptide or prostaglandins 2 hr after seeding and attachment to the membranes in MICS followed by continuous exposure; and (3) cells receiving neither drug nor peptide treatment and serving as controls in each MICS chamber. Since invasion involves cellular motility and deformability, some cytoskeleton disrupting agents were selected. Of these, vincristine, colcemid and colchicine inhibited invasion but taxol did not. Pre‐treatment with cAMP agonists produced conflicting results: dibutyryl cAMP and 8‐(4‐chloro‐phenylthio) cAMP resulted in 50% and 38% reduction in invasion, respectively, whereas 8‐bromo cAMP stimulated invasive potential by 30%. Forskolin and cholera toxin both significantly reduced invasiveness. Pre‐treatment with 5‐azacytidine and araC, to consider the role of methylation and proliferations decreased invasive ability. Anti‐metastatic drugs such as γ‐interferon and razoxane inhibited invasive potential but to varying degrees. Treatment of cells with prostaglandins E2, F2α, A2, and D2 were ineffectual; however, indomethacin mildly inhibits invasion (< 30%). With respect to the cell surface and metastatic potential, pre‐treatment with tunicamycin did not alter invasiveness; whereas pre‐treatment with swainsonine blocked invasion by approximately 50% at 0.3 μg/ml. The inhibition caused by swainsonine was enhanced (to 92%) if cells were continuously exposed to drug and was reversible. Several RGD‐containing peptides which inhibit attachment to various substrates did not modify invasion in the MICS if added after cell attachment was completed. The peptide which inhibits laminin attachment, CDPGYIGSR, inhibited invasion by 48%. Two peptides from the fibrinogen gamma chain were mildly inhibitory and peptides from TGF‐α inhibited invasion >60%. Collectively, these results demonstrate the potential utility of the MICS for prescreening compounds for anti‐invasive potential, and ultimately anti‐metastatic therapy.
Actions of medroxyprogesterone acetate on the efficacy of cytotoxic drugs: Studies with human breast cancer cells in culture
Authors: Shaikh Naeem A. , Owen Alison M. , Ghilchik Margaret W. , Braunsberg Hannelore 
Published: February 2007

AbstractHuman breast cancer cells (MCF‐7) showed increased responses to methotrexate and vincristine after a 48‐hr pretreatment with medroxyprogesterone acetate. The effect of the hormone, which was detectable at concentrations of between 10 and 100nm, was independent of its growth‐inhibitory action. These findings confirm a previous clinical study and have important implications with regard to the management of advanced breast cancer.
Protection against chemically induced skin tumorigenesis in sencar mice by tannic acid
Authors: Das Mukul , Bickers David R. , Mukhtar Hasan 
Published: February 2007

AbstractTannic acid, a naturally occurring dietary polyphenol, was evaluated as a possible anticarcinogen in an initiation‐and‐promotion skin tumorigenesis protocol. In the 2‐stage tumor protocol in SENCAR mice, using DMBA, BP and MNU as the initiating agents followed by twice‐weekly applications of TPA as tumor promotor, tannic acid was found to be an effective inhibitor of tumor formation whether the tumor data are considered as cumulative number of tumors, percentage of mice with tumors or tumors/mouse. After 9 weeks of TPA application, the number of tumors/mouse in the groups receiving DMBA, BP and MNU were 32.10 ± 3.18, 3.70 ± 0.55 and 2.00 ± 0.53, respectively, whereas the corresponding numbers in the DMBA, BP and MNU groups receiving prior applications of tannic acid were 11.50 ± 2.38, 0.35 ± 0.15 and 0.35 ± 0.13, respectively. These results suggest that tannic acid may prove useful in reducing the risk of chemically‐induced skin tumorigenesis.
Over‐expression of MDR gene with no dna amplification in a multiple‐drug‐resistant human ovarian carcinoma cell line
Authors: Bénard Jean , Silva Jacqueline Da , Teyssier Jean‐Raymond , Riou Guy 
Published: February 2007

AbstractHuman ovarian adenocarcinoma cells IGROVI were induced to become resistant in vitro to Vincristine (VCR) by continuous and discontinuous stepwise exposure to the drug. Both sublines exhibited similar indexes of resistance (approx. 800). The acquisition of VCR resistance was associated with changes of morphology and with cross‐resistance to Adriamycin, VP16 and actinomycin D. Addition of verapamil enhanced sensitivity of resistant cells to VCR. This multi‐drug‐resistant (MDR) phenotype was associated with high levels of human MDR, gene transcripts (25‐ to 100‐fold). In contrast to other reports, no significant amplification of the locus could be observed. Reactivity with MRK16, a monoclonal antibody (MAb) directed against the MDR 170 kDa protein, was found to be related to the level of MDR1 transcription. In addition, both OVI/VCR sublines exhibited a marked loss of tumorigenicity. Besides the chromosomal markers of OVI/p, the two resistant sublines revealed a common cytogenetic rearrangement: a deletion of the short arm of one chromosome II: del(11)(p12). We suggest that the acquisition of this marker might be associated with the non‐tumorigenic phenotype of OVI/VCR‐resistant sublines.
Carcinogenicity of iron in conjunction with a chlorinated environmental chemical, hexachlorobenzene, in c57bl/10scsn mice
Authors: Smith Andrew G. , Cabral Jose R. P. , Carthew Philip , Francis Jean E. , Manson Margaret M. 
Published: February 2007

AbstractPre‐loading of C57BL/10ScSn mice with iron greatly sensitizes them to the induction of hepatic porphyria caused by hexachlorobenzene (HCB) (Smith and Francis, 1983). HCB will also cause liver tumours in experimental animals. Elevated liver iron stores are implicated in the development of some human liver cancers. To determine whether iron overload will potentiate the hepatocarcinogenicity of HCB, male C57BL/10ScSn mice received a single dose of iron‐dextran complex or the dextran carrier and were then fed HCB in the diet (0.01%) for up to 18 months. A very clear potentiation by iron of liver tumour incidence occurred. Of the mice which received HCB, but no iron, for 12 months a low incidence of liver hyperplastic nodules was observed, whereas preadministration of iron increased the incidence. After 18 months, all surviving mice initially given iron followed by HCB developed advanced hepatic nodules and 90% had hepatocellular carcinomas. No tumours were seen in animals that only received HCB. Nodules were not seen in iron‐dosed mice receiving control diet, but another novel observation was that these animals developed porphyria by 6 months. Although iron enhanced tumour formation in the presence of HCB, the foci, nodules and carcinomas formed all excluded iron. Preliminary studies with the DBA/2 strain suggested that these mice were considerably less susceptible to potentiation by iron.
In vivo localization of a bispecific antibody which targets human t lymphocytes to lyse human colon cancer cells
Authors: Barr Ian G. , Miescher Sylvia , Fliedner Vladimir Von , Buchegger Franz , Barras Catherine , Lanzavecchia Antonio , Mach Jean‐Pierre , Carrel Stefan 
Published: February 2007

AbstractA bispecific MAb was derived from the fusion of a hybridoma producing MAb CD3 with a hybridoma producing MAb L‐Dl (which is directed against a 41‐kDa glycoprotein expressed in most gastro‐intestinal and pancreatic carcinomas). Bispecific antibody molecules were isolated from parental antibody molecules by the use of hydroxylapatite‐HPLC and shown to target human cytolytic T lymphocytes, irrespective of their original specificity, to specifically lyse human colon carcinoma cells. Localization studies in vivo using nude mice bearing human colon carcinoma xenografts showed significant accumulation of the HPLC‐purified 125l‐labelled bispecific antibodies into the tumor compared to 131l‐labelled control CD3 antibody.
Tumor prevention by a xanthate compound in experimental mouse‐skin tumorigenesis
Authors: Fürstenberger G. , Amtmann E. , Marks F. , Sauer G. 
Published: February 2007

AbstractThe antiviral and antitumoral compound tricyclodecan‐9‐yl‐xanthogenate (D609), which is an inhibitor of protein kinase C activation, has been used for tumor prevention in vivo. When applied chronically together with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in the classic initiationpromotion mouse‐skin model, D609 prevented tumor induction in a dose‐dependent manner. At the concentration that inhibited tumor formation by 97%, no toxic effects were detected and the TPA‐induced hyperplasia remained unaffected. As D609 failed to prevent the activity of a chronically applied carcinogen, it is concluded that the observed tumor prevention achieved with D609 is tumor‐promotion‐specific and is not due to killing of tumor cells.
Growth‐inhibitory activity of interferon‐beta against human colorectal carcinoma cell lines
Authors: Wong Vicky L. Y. , Rieman Dave J. , Aronson Lori , Dalton Barbara J. , Greig Russell , Anzano Mario A. 
Published: February 2007

AbstractRecombinant human interferon beta (rIFN‐β) inhibited in a time‐ and dose‐dependent manner the proliferation of 18/18 human colon carcinoma cell lines in monolayer culture and 8/9 lines in a soft agar assay but had no effect on 4 human fibroblast cell lines. Maximal inhibition of cell proliferation by rIFN‐β required repetitive treatment (every 2 days) with lymphokine (50 units/ml). Furthermore, the inhibitory activity of rIFN‐β was neutralized by polyclonal antibodies against natural IFN‐β. In contrast to rIFN‐β, rIFN‐α was inactive against all colon cell lines tested, and rIFN‐γ, with the exception of HT‐29 cells, was similarly ineffective. These data demonstrate that rIFN‐β is a potent growth inhibitor of colon carcinoma cells in vitro, and suggest that studies on its mechanism of action may lead to a better understanding of the regulation of colon tumor cell proliferation.
Minimal dose and time protection by lindane (γ‐isomer of 1,2,3,4,5,6 hexachlorocyclohexane) against liver tumors induced by aflatoxin b1
Authors: Angsubhakorn Subhkij , Bhamarapravati Natth , Pradermwong Apichat , Im‐Emgamol Nipa , Sahaphong Somphong 
Published: February 2007

AbstractThis study was carried out in order to investigate the minimal exposure to lindane (LD, 99.72% gamma isomer of 1,2,3,4,5,6 hexachlorocyclohexane), a chlorinated hydrocarbon insecticide, required to protect against liver tumor induced by aflatoxin B1 (AFB1). Materials fed to Buffalo strain rats were as follows: LD 100 ppm; AFB1 I ppm, LD 100 ppm plus AFB1 1 ppm; and control basal diet. The experimental animals were clinically observed and then serially killed at 1, 3, 5, 10, 15 and 82 weeks. Concurrent administration of LD with AFB1 to rats for more than 3 weeks totally inhibited the incidence of AFB1‐induced hepatocellular carcinomas by week 82. Only 1 of 20 rats (5%) fed the same regimen for 1 week developed liver tumors. Animals given 1 ppm AFB1 singly for 15 weeks had a high liver tumor incidence (31.5%). No animals developed liver tumors in LD‐treated and control groups. LD may inhibit AFB1‐induced liver tumors by stimulating hepatic metabolism and excretion of AFB1 so that less carcinogen is available to liver tissue.
Altered restriction pattern of the putative DNA binding domain of estrogen receptor or related genes in primary human meningiomas
Authors: Vacca A. , Fazio V. M. , Gandini O. , Oppido P. , Delfini R. , Frati L. , Gulino A. 
Published: February 2007

AbstractWe analyzed by restriction mapping the genomic organization of the estrogen receptor gene in several primary human brain tumors in order to investigate the possible relationships between the development of these tumors and gonadal steroid hormones. In 5 out of 23 meningiomas the Eco RI restriction of genomic DNAs revealed 6 invariant normal fragments of 6.5, 4.8, 3.8, 3.1, 2.7 and 1.7 kb, plus 2 additional variant fragments of either 8.6 or 2.5 kb. More detailed analysis showed that these variant bands hybridized with a probe specific for the middle region of the estrogen receptor cDNA, coding for the DNA‐binding domain of the receptor. This abnormal restriction pattern was found only in these meningiomas and not in other brain tumors or DNAs obtained from peripheral blood lymphocytes.