bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laboratory determination of chemotherapeutic drug resistance in tumor cells from patients with leukemia, using a fluorometric microculture cytotoxicity assay (FMCA)
Authors: Larsson Rolf , Kristensen Jörgen , Sandberg Charlotta , Nygren Peter 
Published: February 2007

AbstractAn automated fluorometric microculture cytotoxicity assay (FMCA) based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein was employed for chemotherapeutic‐drug‐sensitivity testing of tumor‐cell suspensions from patients with leukemia. Fluorescence was linearly related to cell number, and reproducible measurements of drug sensitivity could be performed using fresh or cryopreserved leukemia cells. A marked heterogeneity with respect to chemotherapeutic drug sensitivity was observed for a panel of cytotoxic drugs tested in 43 samples from 35 patients with treated or untreated acute and chronic leukemia. For samples obtained from patients with chronic lymphocytic and acute myelocytic leukemia, sensitivity profiles for standard drugs corresponded to known clinical activity and the assay detected primary and acquired drug resistance. Individual in vitro/in vivo correlations indicated high specificity with respect to the identification of drug resistance. The results suggest that the FMCA may be a simple and rapid method for in vivo‐representative determinations of chemotherapeutic drug resistance in tumor cells obtained from patients with leukemia.
Effects of sandostatin and castration on pancreatic carcinogenesis in rats and hamsters
Authors: Meuers M. , Woutersen R. A. , van Garderen‐Hoetmer A. , Barker G. H. , de Jong F. H. , Foekens J. A. , Klijn J. G. M. 
Published: February 2007

AbstractThe effects of treatment with the somatostatin analogue Sandostatin, separately and in combination with surgical castration, on the development of azaserine‐induced lesions in rat pancreas and N‐nitrosobis(2‐oxopropyl)amine (BOP)‐induced lesions in hamster pancreas were investigated. The animals were divided in 4 groups and treated as follows: (a) controls, injected s.c. with saline solution (0.9% NaCI); (b) orchiectomy directly after the last treatment with carcinogen; (c) Sandostatin (SMS 201–995) subcutaneously; (d) orchiectomy followed by treatment with Sandostatin. No significant suppressive effects on plasma EGF or IGF‐I concentrations were noted after Sandostatin treatment, but plasma gastrin levels decreased slightly in the rats, not in the hamsters. In rats, Sandostatin treatment enhanced rather than inhibited growth of acidophilic atypical acinar cell nodules. In hamster pancreas, by contrast, Sandostatin inhibited the development of putative pre‐neoplastic ductular lesions. There was no interaction between treatment with Sandostatin and surgical castration. It was concluded that Sandostatin, when administered prophylactically, has an inhibitory effect on the growth of putative pre‐neoplastic ductular, but not acinar, lesions.
Establishment and characterization of a thymic carcinoma cell line (Ty‐82) carrying t(15;19)(ql5;p13) chromosome abnormality
Authors: Kuzume T. , Kubonishi I. , Takeuchi S. , Takeuchi T. , Iwata J. , Sonobe H. , Ohtsuki Y. , Miyoshi I. 
Published: February 2007

AbstractA new human cell line, designated Ty‐82, was established from the pleural effusion of a 22‐year‐old woman with undifferentiated thymic carcinoma. This cell line consisted of primitive cells that were positive for α‐naphthyl butyrate esterase and acid phosphatase. The cells were shown to express epithelial membrane antigen, but were completely negative for cytokeratin, carcinoembryonic antigen, glial fibrillary acidic protein, desmin, S‐100 protein, lysozyme, Leu‐7, HLA‐DR (la), leukocyte common antigen, Ki‐I antigen, T‐cell antigens, B‐cell antigens, myelomonocyte antigens, and Epstein‐Barr‐virus nuclear antigen. Electron microscopy showed that the cells were highly anaplastic, with no sign of cellular differentiation to any lineages. The Ty‐82 cell line was found to have a karyotype of 46, XX, t( 15; 19)(q 15;p 13), being identical to that of the patient's tumor cells. Four of 5 nude mice inoculated sub‐cutaneously with Ty‐82 cells developed tumors which displayed a histological picture similar to the original tumor. Thymic carcinoma is a recently recognized entity, and its cellular and clinical behavior are poorly understood. The newly established thymic carcinoma cell line would provide a useful tool for the better understanding of this rare disease.
Biphasic effect of camp‐elevating agents on ICAM‐1 expression stimulated by retinoic acid and interferonγ
Authors: Bouillon Marlène , Fortier Michel A. , Boulianne Robert , Audette Marie 
Published: February 2007

AbstractIncubation of the human glioma cell line HS 683 in the presence of IFN‐7 or retinoic acid strongly stimulates the cell‐surface expression of the intercellular adhesion molecule ICAM‐I. We have investigated the role of the cAMP‐mediated signal transduction pathway in this process and report that pharmacological agents which increased the intracellular levels of cAMP exhibited a biphasic action on ICAM‐1 expression in human glioma cell line HS 683. Treatment for I hr with 25 (μM forskolin or 1 mM) isobutylmethylxanthine, or for 12 hrwith 100 ng/ml pertussis toxin or 50 fig/ml cholera toxin transiently stimulated ICAM‐1 expression with a maximal level of expression 8 hr post treatment, after which time ICAM‐1 expression returned to the basal level. On the other hand, such pre‐ treatments inhibited the inducing effects of either retinoic acid or IFN‐γ. Indeed, 24 hr after treatment with cAMP‐elevating agents, both the retinoic‐acid‐ and the IFN–γ‐induced ICAM‐1 expression were inhibited by 60 to 80%, with a maximal 90 to 100% inhibition 72 hr post treatment. This inhibition of the cell‐surface expression of ICAM‐1 was confirmed at the mRNA level. The intracytoplasmic levels of cAMP were also quantified following treatments with forskolin, retinoic acid or IFN–γ. In response to forskolin, cAMP levels increased 30‐fold within 5 min, whereas a 10‐fold increase occurred 60 min following treatment with 10 μM retinoic acid. lnterferonγ, in contrast, did not induce cAMP accumulation. These results were also correlated with an in vitro activation of adenylyl cyclase activity by retinoic acid and inhibition of this activity by IFN‐γ, in a dose‐dependent and a GTP‐dependent manner. Our results suggest that the suppression of IFN‐γ‐induced ICAM‐1 expression, obtained upon pre‐treatment with cAMP‐elevating agents, is due to direct antagonism with IFN‐γ action on adenylyl cyclase. However, the inhibition of retinoic‐acid‐induced ICAM‐1 expression cannot be explained by the same mechanisms. The timing of adenylyl cyclase stimulation and cAMP accumulation, as well as the levels of cAMP accumulation, are probably involved in this inhibition. Our results also emphasize the fact that the induction of ICAM‐1 expression is a multi‐step process implicating different transductional signals among which cAMP might be involved as a second messenger.
The relationship between multi‐drug resistance and resistance to natural‐killer‐cell and lymphokine‐activated killer‐cell lysis in human leukemic cell lines
Authors: Treichel Robin S. , Olken Sarah 
Published: February 2007

AbstractResults concerning a possible link between susceptibility to natural‐cell‐mediated immune cytolysis and the multi‐drug resistance (MDR) phenotype are conflicting. We evaluated in human acute lymphocytic leukemia the relationship between acquired drug resistance and susceptibility to cytolysis mediated by endogenous, interferon‐activated, and interleukin‐2‐ activated natural cytotoxic celts. Eight human leukemia drug‐ resistant/sensitive cell line pairs were evaluated; drug‐resistant sub‐lines included those selected for primary resistance to adriamycin, etoposide, teniposide, vincristine, and vinblastine. A majority of P‐glycoprotein‐positive MDR sub‐lines displayed slight but statistically significant resistance to endogenous and/or interferon‐activated natural‐killer(NK)‐cell‐mediated lysis, as compared with the drug‐sensitive parental type. P‐glycoprotein‐ negative sub‐lines displayed variable NK susceptibility; within this group, the variants selected for primary etoposide resistance were more susceptible to NK cytolysis than parental cells. Results of cold‐target‐inhibition experiments suggest that altered NK susceptibility does not arise solely from modulation of NK target recognition and adherence structures. IL2‐activated killer (LAK) cells lysed both drug‐sensitive and drug‐resistant lines. Two MDR lines selected for primary etoposide resistance displayed enhanced LAK susceptibility. In contrast, the 2 variants selected for resistance to adriamycin exhibited partial resistance to LAK‐mediated killing, which could be overcome at high effector‐to‐target ratios. Our results support the development of interleukin‐2/LAK immunotherapy for the treatment of leukemias with acquired drug resistance.
Isolation and characterization of a monoclonal antibody, K1, reactive with ovarian cancers and normal mesothelium
Authors: Chang Kai , Pastan Ira , Willingham Mark C. 
Published: February 2007

AbstractWe have isolated a new monoclonal antibody (MAb), K1, that reacts with an epitope on the surface of human ovarian carcinoma cells. This antibody was generated by immunization of mice with periodate‐treated human ovarian carcinoma (OVCAR‐3) cells. These mice had been previously made tolerant with normal human kidney membranes. Spleen lymphocytes from these mice were selected prior to fusion using a panning purification method on living OVCAR‐3 cells. Initial screening of surface‐reactive clones was performed in a single day using immunofluorescence on living OVCAR‐3 cells, and secondary screening was performed using immunoperoxidase histochemistry on cryostat sections of normal human tissues and human tumors. The K1 clone was subcloned and identified as an IgM isotype, but was subsequently isotype‐switched to lgGIK using a panning selection method. When evaluated by immunohistochemistry, the antigen reactive with K1 was found in many ovarian non‐mucinous tumors, as well as in squamous tumors of the esophagus, and cervical cancer. The only normal adult human tissues showing uniform reactivity with K1 were the mesothelia of the peritoneal, pleural and pericardial cavities. There was also limited reactivity with epithelia of the trachea, tonsil and Fallopian tube. A similar tissue reactivity for K1 was found in tissues from cynomolgus monkeys. K1 reacted with many of the same tissues and tumors as the previously identified antibody OC125, but several lines of evidence indicate that K1 reacts with a different epitope and probably a different molecule, when compared to OC125. This evidence included assays employing immunofluorescence competition, double‐ label immunofluorescence, and solid‐phase and live‐cell radioim‐ munoassays. Since our data indicate that the antigen reactive with the K1 antibody is a new molecular species, we have named the antigen CAKI. Unlike the shed antigen CA125, CAKI was only cell‐associated and was not found in the supernatant of cultured OVCAR‐3 cells or in the blood of ovarian cancer patients. The K1 antibody may be useful as a targeting agent for therapy and in the diagnosis of ovarian carcinoma, as well as some other human cancers.
Allelic loss on chromosome 22 correlates with histopathological predictors of recurrence of meningiomas
Authors: Sanson Marc , Richard Stéphane , Delattre Olivier , Poliwka Marc , Mikol Jacqueline , Philippon Jacques , Thomas Gilles 
Published: February 2007

AbstractMeningiomas are common tumors of the nervous system. Although usually benign, they may exhibit variable degrees of aggressiveness. Their probability of recurrence after subtotal resection has been correlated with several histological parameters. Independently, a loss of chromosome 22, as evidenced either by cytogenetics or by somatic loss of alleles, has been observed in about half of the cases studied. In 34 meningiomas we have examined the relationship between loss of chromosome 22 alleles and 6 histological predictors of recurrence. Significant correlations were found for 3 of these, i.e. prominent nucleoli (p < 0.002), microscope count of mitoses (p < 0.05) and nuclear pleomorphism (p < 0.02). Correlation with the other 3, i.e. sheeting of cells, vascularity and micronecrosis, did not reach significance. Total tumor score, defined by the sum of the individual scores for these 6 parameters, was strongly correlated to allelic loss (p < 0.0001). Thus, the loss of chromosome 22 alleles, which possibly contribute to the inactivation of tumor‐suppressor gene(s), might be a potent genetic marker of the aggressiveness of meningiomas.
Different fatty‐acid profiles in phosphoinositides from human fibroblastic meningiomas with or without chromosome 22 monosomy
Authors: Bordoni Alessandra , Hrelia Silvana , Biagi Pier Luigi , Berra Bruno 
Published: February 2007

AbstractThe fatty‐acid composition of phosphoinositides derived from 13 human fibroblastic meningiomas, divided according to the presence or the absence of monosomy of chromosome 22, was analyzed. Phosphoinositides were separated into their 3 main components: phosphatidylinositol, phosphatidylinositol‐4‐phosphate, and phosphatidylinositol‐4,5‐bisphosphate. In all the tumors, regardless of cytogenetic differences, remarkable differences were detected, between phosphatidylinositol and phosphatidylinositol‐4‐phosphate or phosphatidylinositol‐4,5‐bisphosphate. In meningiomas with 22 monosomy, there was a significant decrease in the relative amount of arachidonate in all the phosphoinositide fractions; this situation might determine diminished down‐regulation of the corresponding diacylglycerol, derived by the phospholipase‐C‐stimulated hydrolysis of phosphoinositides, and, consequently, different protein‐kinase‐C stimulation.
Human T‐cell leukemia virus type I(HTLV‐I) infection of T cells bearing T‐cell receptor γδ: Effects of HTLV‐I infection on cytotoxicity
Authors: Yasukawa Masaki , Inatsuki Akira , Yakushijin Yoshihiro , Kobayashi Yuzuru 
Published: February 2007

AbstractIn order to clarify the cellular tropism of human T‐cell leukemia virus type I (HTLV‐I) and the effects of HTLV‐I infection on T‐cell functions, we investigated the infectiousness of HTLV‐I on T cells bearing T‐cell receptor (TCR) γδ and functional alterations of the HTLV‐I‐infected TCR‐γδ+ T cells. CD3+CD4−CD8−TCR‐γδ+ T‐cell clones which possessed cytotoxicity were co‐cultured with a HTLV‐I‐producing T‐cell line. After several weeks, integration of HTLV‐I proviral DNA in TCR‐γδ+ T cells was detected by Southern blot analysis. During the continuous culture of HTLV‐I‐infected TCR‐γδ+ T‐cell clones, 2 distinct phases were observed in terms of cytotoxic activity and expression of the CD3‐TCR‐γδ complex. Early after HTLV‐I infection, TCR‐γδ+ T cells lost their spontaneous cytotoxicity, but this was restored by the addition of lectin. At this time, no differences were observed in the expression of various surface molecules between HTLV‐I‐infected and uninfected parent cells, except for increased expression of CD25 on HTLV‐I‐ infected cells. At about 30 weeks after HTLV‐I infection, the cytotoxicity of HTLV‐I‐infected cells was almost completely lost, even in the presence of lectin, and expression of the CD3‐TCR‐γδ complex on the cell surface was markedly decreased. Concomitant with the decreased expression of CD3‐ TCR‐γδ complexes, a decrease in the elevation of cytoplasmic Ca2+ concentration induced by anti‐CD3 and anti‐TCR monoclonal antibodies (MAbs) was also observed. Our present findings thus show that HTLV‐I can infect TCR‐γδ+ T cells, and that consequently their functions are profoundly affected through 2 distinct phases.
Increased phosphorylation of nuclear phosphoproteins in human lung‐cancer cells resistant to cis‐diamminedichloroplatinum(II)
Authors: Nishio Kazuto , Sugimoto Yoshikazu , Kasahara Kazuo , Fujiwara Yasuhiro , Nishiwaki Shinji , Fujiki Hirota , Ohata Masahiro , Saijo Nagahiro 
Published: February 2007

AbstractA novel non‐phorbol‐ester‐like tumor promoter, okadaic acid (OA) has been shown to be an inhibitor of protein phosphatase I and IIA and, thus, to cause an “apparent activation” of protein kinase C (PKC). We previously showed that cis‐diamminedichloroplatinum(II) (CDDP)‐resistant cells, PC‐9/CDDP, were cross‐ resistant to OA and that the cross‐resistance was not due to the increased efflux of OA. We hypothesized that the phosphorylation status of some cellular proteins might be important in CDDP‐resistancc. No significant difference in PKC activity or total protein phosphatase activity measured in vitro was seen between PC‐9 and PC‐9/CDDP cells, nor in their sensitivity to inhibition by OA, nor in the amount of phosphorylation of whole cells or TCA‐insoluble material. By SDS‐PAGE after incubation of intact cells with 32P, we detected a marked increase, compared to PC‐9 cells, in phosphorylation of the nuclear proteins of MW 32 and 20 kDa in CDDP‐resistant PC‐9/CDDP cells with no apparent difference in protein content. When phosphorylation of nuclear proteins observed in PC‐9/CDDP cells was analyzed by 2‐dimensional SDS‐PAGE, the 32‐kDa protein had a PI of about 4.5. The 32‐kDa and 20‐kDa bands were increased in a dose‐dependent manner by CDDP treatment. On the other hand, no increase in phosphorylation of these proteins was observed in parental PC‐9 cells. These results demonstrate a marked difference in the phosphorylation status of specific nuclear proteins between parental and CDDP‐resistant cell lines, which may be related to CDDP‐resistance.
Interleukin‐1 produced by tumorigenic fibroblasts influences tumor rejection
Authors: Zöller Margot , Doudevani Amos , Segal Shraga , Apte Ron N. 
Published: February 2007

AbstractOncogene‐transformed BALB/c‐3T3 fibroblasts which spontaneously or upon immune‐activation with cytokines and lipopolysaccharide (LPS) generate IL‐I α, were tested for their tumorigenicity as well as their interaction with natural immune defense by NK cells and macrophages. Oncogene‐transformed fibroblasts were weakly tumorigenic, since not all mice developed tumors despite application of high doses of tumor cells. This was independent of the immune status of the host. However, in the immunocompetent host those transformed fibroblast lines which spontaneously produced IL‐I α grew only transiently and then regressed. After induction of IL‐I α production, a decrease in the rate of tumor take was noted and the rate of regression of developing tumors was increased. Regression of IL‐I‐producing transformed fibroblasts was strongly reduced but not completely abolished in sublethally irradiated mice. This indicated that IL‐I production may predominantly influence T‐cell‐mediated defense, but some influence on non‐ adaptive immunity could not be excluded a priori. IL‐I production did not influence susceptibility of transformed fibroblasts towards NK cells and macrophages. However, IL‐I‐producing transformed fibroblasts were most potent stimulators of NK cells and macrophages, the stimulatory effect being locally restricted. In conclusion, IL‐I producing, oncogene‐transformed fibroblasts which generated the cytokine constitutively or upon immune‐activation, were rejected from the tumor‐bearing host following initial growth. Fibroblast‐induced local activation of NK cells and macrophages was shown to play some role in tumor graft rejection. The influence of IL‐I production of transformed fibroblasts on T‐cell‐mediated defense is addressed in the accompanying report.
Characterization of epithelial phenotypes in mortal and immortal human breast cells
Authors: Paine Terry Maloney , Soule Herbert D. , Pauley Robert J. , Dawson Peter J. 
Published: February 2007

AbstractWe have previously described the mortal human breast epithelial culture MCF‐10M, that was derived from fibrocystic breast tissue, was cultivated in medium with low calcium content for over 2 years, and spontaneously gave rise to the immortal MCF‐10 cell line. The emergence of immortalized cells, characterized by growth in conventional calcium levels, from mortal cells has proven to be a reproducible event. Here we report the establishment of a second immortal line from MCF‐10M, designated MCF‐10‐2, and establishment of the MCF‐12 immortal line after long‐term cultivation of MCF‐12M mortal cells from reduction mammoplasty tissue. DNA fingerprinting demonstrated the independent, human origin and lineage of the MCF‐10‐2 and MCF‐12 cell lines. Both lines require cortisol and EGF for maximal growth. The expression in these cultures of in vivo breast epithelial phenotypes was analyzed using 2‐dimensional gel Western blots and immunoper‐ oxidase staining with antibodies to cytokeratins and polymorphic epithelial mucin. MCF‐10M and MCF‐12M retain the cytokeratin profile of the luminal cell (7, 8, 18, 19), and also express cytokeratin 14, found predominantly in basal cells. The immortal lines express a similar profile, except that cytokeratin 19, a component of the fully differentiated luminal cell, is not expressed in the more uniform population seen in MCF‐10 and MCF‐12, but is retained in the morphologically mixed, less‐ selected population of MCF‐10‐2. Epitopes on the polymorphic epithelial mucin, recognized by antibodies HMFG 1, HMFG 2 and SM‐3, were detected in the mortal cultures and in the immortal lines, indicating the occurrence of both normal and abnormal mucin processing. MCF‐10, MCF‐10‐2 and MCF‐12 cells do not form tumors in nude mice, but appear to organize as duct‐like structures before regressing in the 5th week post injection.
Induction of IL‐4 secretion by the radiation leukemia virus (RadLV): Role in autocrine growth stimulation of RadLV infected pre‐leukemic cells
Authors: Yefenof Eitan , Ela Catherine , Kotler Moshe , Vitetta Ellen S. 
Published: February 2007

AbstractIntrathymic inoculation of radiation‐leukemia virus (RadLV) into C57BL/6 mice induces a population of pre‐leukemic (PL) T cells which progress into clonal, mature thymic lymphomas after a latency period of 3 to 5 months. In order to understand how PL cells are retained in the thymus for a prolonged period of time we determined whether RadLV infected cells secrete and/or respond to a T‐cell growth factor that may be involved in the long‐term maintenance of a thymic PL‐cell pool. We have previously found that in vitro proliferation of RadLV‐infected PL cells is IL‐4‐dependent. Here we show that RadLV induces IL‐4 secretion and IL‐4 receptor (IL‐4R) expression in normal thymic lymphocytes. RadLV‐infected PL thymocytes express IL‐4R and secrete IL‐4. Their IL‐4 secretion could be enhanced if incubated in the presence of RadLV and this enhancement was inhibited by anti‐RadLV antibodies. Several RadLV‐induced lymphoma lines secreted IL‐4 and/or expressed IL‐4R, but these features were not essential for their continuous growth. The results suggest that RadLV induces IL‐4‐dependent autocrine growth which maintains a population of PL T cells in the thymus. Transition from a PL state to overt thymic lymphoma involves emancipation of a PL cell from IL‐4 dependency.