bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting liver tumors by administering liposomal doxorubicin into the hepatic artery
Authors: Zou Yiyu , Horikoshi Isamu , Ueno Masaharu , Gu Xueqiu , Perez‐Soler Roman 
Published: February 2007

AbstractThe plasma levels, organ distribution, and in vivo anti‐tumor activity of liposomal doxorubicin administered i.v. or i.a. (hepatic) in rats bearing W256 liver tumors were studied. I.a. administration of liposomal doxorubicin resulted in 4‐fold and 1.3‐fold higher liver tumor and liver parenchyma doxorubicin levels, respectively, than i.v. administration, thus suggesting a more preferential distribution of liposomal doxorubicin into the liver tumor with i.a. administration. By contrast, the heart, spleen, and plasma AUCs were decreased 3.8‐, 3.2‐, and 16‐fold, respectively, after i.a. administration. Cumulative urinary excretion at 8 hr was also 14 times lower in animals that received liposomal doxorubicin i.a. In good correlation with these findings, i.a. administration markedly enhanced the anti‐tumor effect of liposomal doxorubicin against liver W256 tumors as measured by tumor growth inhibition 5 days after treatment (‐16% for i.a. administration vs. +89% for i.v. administration, p ⩽ 0.05) and prolongation of survival (ILS: 108% for i.a. administration vs. 26% for i.v. administration, p ⩽ 0.05). Our results show that i.a. administration of liposomal doxorubicin results in preferential distribution of the anti‐tumor agent into the tumor tissue and increased anti‐tumor activity, while increasing the cardioprotective effect of the liposome carrier by decreasing the plasma peak and heart‐tissue levels of the drug.
Alternative splicing of neural‐cell‐adhesion molecule mRNA in human small‐cell lung‐cancer cell line H69
Authors: Moolenaar C. E. C. , Pieneman Cynthia , Walsh Frank S. , Mooi Wolter J. , Michalides Rob J. A. M. 
Published: February 2007

AbstractThe neural‐cell‐adhesion molecule (NCAM) is expressed in all small‐cell lung cancers (SCLC) and in approximately 20% of non‐small‐cell lung tumors (non‐SCLC). These NCAM‐positive lung tumors have a poor prognosis compared with NCAM‐negative tumors. Multiple NCAM protein isoforms are expressed from a single‐copy gene as a result of alternative splicing and/or post‐translational modifications. Therefore, we studied the NCAM isoforms expressed in a human small‐cell lung‐cancer cell line, H69. NCAM mRNA transcripts of 7.2, 6.7, 4.3 and 4.0 were detected in these cells on Northern blots. Since the various NCAM isoforms may have different biological properties, we performed a more precise examination of NCAM mRNAs, using polymerase chain reactions (PCR) with primers flanking the various NCAM exon boundaries. The shortest alternatively spliced sequence that we found was the trinucleotide AAG located between exon 12 and 13 in the so‐called hinge region of the NCAM protein. This AAG trinucleotide was present in the majority of the NCAM mRNAs. A second alternatively spliced 30 nt‐exon VASE (immunoglobulinvariable domain‐like alternatively spliced exon) was present in all NCAM transcript isoforms at the exon 7/exon 8 junction. VASE resulted in the insertion of 10 amino acids into the 4th immunoglobulin‐like loop of the NCAM protein. Within the limits of the PCR methodology, no evidence for the presence of mRNA containing exon 15, encoding the glycosyl‐phosphatidylinositol‐linked (GPI‐linked) NCAM isoform in H69 cells was obtained. Considering that H69 cells express 2 major NCAM protein classes (NCAM‐180 and NCAM‐140), and that the VASE and AAG alternative mRNA splice variants result in minor differences in protein sizes, at least 8 polypeptide isoforms of NCAM might be expressed in H69 cells that contribute to the binding interactions of NCAM.
In vivo anti‐tumor activity of arginine deiminase purified from Mycoplasma arginini
Authors: Takaku Haruo , Takase Megumi , Abe Shin‐Ichiro , Hayashi Hideya , Miyazaki Kaoru 
Published: February 2007

AbstractArginine deiminase (EC 3.5.3.6) was purified to homogeneity from the cell extract of Mycoplasma arginini by molecular‐sieve, anion‐exchange and arginine‐affinity chromatographies. The purified enzyme was composed of 2 identical sub‐units with a molecular weight of 45.000 and had a pl of 4.7. Its Vmax value and Km value for L‐arginine were estimated to be 50 units/mg protein and 0.2 mM, respectively. It exerted maximal enzyme activity at pH 6.0–7.5 and at 50°C. The arginine deiminase was stable at neutral pH. When injected i.v. into mice, the half‐life of the arginine deiminase in blood was about 4 hr. In culture, the enzyme strongly inhibited the growth of 6 kinds of mouse tumor cell lines by depleting L‐arginine in the culture media. When the in vivo growth‐inhibitory activity of arginine deiminase was tested for the 6 tumor cell lines, i.p. administration of the purified enzyme effectively prolonged the survival time of the mice injected with all kinds of the tumor cell lines. Especially, the in vivo growth of a hepatoma cell line, MH134, was completely prevented by the daily administration at a dose of 0.2 mg/mouse for 14 days. These results raise the possibility of the use of the arginine deiminase derived from Mycoplasma arginini as a new anti‐tumor drug.
ANti‐CD3 antibody‐treated mice: In Vivo induction of cytolytic activity and tnf production by lung leukocytes
Authors: Stanňková Jana 
Published: February 2007

AbstractAnti‐CD3 antibody induced non‐MHC‐restricted cytolytic activity in murine spleen cells within 4 hr of incubation in vitro and within 8 hr in vivo after intraperitoneal injection. Interstitial lung leukocytes acquired the capacity to kill both NK‐sensitive and ‐resistant targets within 24 hr after anti‐CD3 injection. In vivo‐stimulated spleen cells produced significantly more IL‐2 and TNF than unstimulated cells. When these cells were restimulated with anti‐CD3 in vitro, a potentiation of TNF production was seen. Interstitial lung leukocytes doubled their TNF production ex vivo after anti‐CD3 injection, and the suppressed TNF production which was seen in lung cells from tumor‐bearing animals was restored after anti‐CD3 stimulation. The TNF production by alveolar macrophages was augmented 5‐fold 48 hr after injection of antibody. Anti‐CD3 antibody also induced significant accumulation of both TNFα and TNFβ mRNA in spleen and lung leukocytes. Pre‐treatment with anti‐TNF antibodies, both in vitro and in vivo, did not eliminate the cytolytic activation of lung and spleen cells. Our data indicate that anti‐CD3 antibodies can induce rapid activation of both cytolytic activity and cytokine production in lung lymphocytes and macrophages.
Immunity to B16 melanoma in mice immunized with IL‐2‐secreting allogeneic mouse fibroblasts expressing melanoma‐associated antigens
Authors: Kim Tae Sung , Russell Stephen J. , Collins Mary K. L. , Cohen Edward P. 
Published: February 2007

AbstractCo‐presentation of weak tumour‐associated antigens along with strongly immunogenic determinants leads to the development of an anti‐tumour immune response in recipients syngeneic with the tumour. Tumour immunity develops in mice immunized with tumour cells modified by the introduction of cDNA for interleukin‐2 (IL‐2). Here, we report the anti‐tumour response following immunization with an IL‐2‐secreting cell construct that expresses tumour‐associated antigens, along with allogeneic major histocompatibility antigens. The construct was prepared by transfecting LM(TK−) mouse fibroblasts (H‐2k) with genomic DNA from B16 melanoma cells syngeneic in C57BL/6J mice (H‐2b). Transfectants expressing melanoma‐associated antigens (MAA) were then infected with an expression‐competent retroviral vector containing a cDNA specifying human IL‐2. Cytotoxicity toward B16 cells was detected for as long as 5 months in both spleen and macrophage cell populations in C57BL/6J mice immunized with the IL‐2‐secreting, cells. Mice immunized with non‐IL‐2‐secreting, MAA‐positive allogeneic cells developed melanoma immunity as well, but to a lesser extent. Immunity to 2 tumour‐cell lines expressing the H‐2d haplotype and to YAC‐I cells was detected in peritoneal macrophages, but not in spleen cells from C57BL/6J mice immunized with the cell construct, indicating that the response to B16 cells was only partially specific. C57BL/6J mice immunized with the IL‐2‐secreting cell construct survived significantly longer, following an injection of viable B16 cells, than mice in various control groups. The contribution of allogeneic antigens to the melanoma immunity was indicated by the failure of mice syngeneic with LM(TK−) cells to develop melanoma immunity following immunization with non‐IL‐2‐secreting, MAA‐positive cell constructs. The formation of IL‐2 partially compensated for the lack of allogeneic antigens.
Hematopoietic growth factors secreted by seven human pleural mesothelioma cell lines: Interleukin‐6 production as a common feature
Authors: Schmitter Doris , Lauber Béatrice , Fagg Barbara , Stahel Rolf A. 
Published: February 2007

AbstractSeven mesothelioma cell lines, established from patients with pleural mesothelioma, exhibited substantial heterogeneity regarding in vitro morphology and growth characteristics. Media conditioned by these cell lines and by MeT5A normal mesothelial cells were examined for (i) colony formation on human bone‐marrow cells, (ii) hematopoietic growth‐factor content and (iii) mitogenic activity on mesothelioma cells. Colony‐stimulating activity was produced only by the ZL34 cell line. Analysis of conditioned media by ELISA revealed that all mesothelioma cell lines constitutively produced IL‐6, while the MeT5A normal mesothelial cells did not; in addition, GM‐CSF and G‐CSF were detected in the supernatant of the ZL34 cell line. Using a 3H‐thymidine incorporation assay, we showed that all mesothelioma cell lines produced mitogenic activity in the culture supernatant, in contrast to the MeT5A normal mesothelial cells. The mitogenic effect of the hematopoietic growth factors detected in mesothelioma culture supernatants was tested on mesothelioma cells and on MeT5A normal mesothelial cells: IL‐6, GM‐CSF and G‐CSF did not stimulate any DNA synthesis. Our results suggest that these hematopoietic growth factors do not act as autocrine growth factors. A common feature of this panel of mesothelioma cell lines is the production of IL‐6; although the biological significance of the aberrant production of cytokines by mesotheliomas remains unclear, IL‐6 might be involved in paraneoplastic syndromes such as thrombocytosis.
Pharmacokinetics and antitumor activity of epirubicin encapsulated in long‐circulating liposomes incorporating a polyethylene glycol‐derivatized phospholipid
Authors: Mayhew E. G. , Lasic D. , Babbar S. , Martin F. J. 
Published: February 2007

AbstractThe antitumor activity of epirubicin (EPI) entrapped in long circulating „Stealth”︁ liposomes containing a polyethylene glycolderivatized phospholipid (S‐EPI) was compared to epirubicin encapsulated in a conventional liposome formulation (L‐EPI) and free epirubicin (F‐EPI) against mouse colon 26 tumor in vivo. Pharmacokinetics of S‐EPI and F‐EPI were also compared in rats. F‐EPI was distributed to tissues within minutes of injection. In contrast, when administered in the S‐EPI formulation, the distribution half‐life of the drug was over 22 hr. S‐EPI also exhibited a reduced clearance compared to F‐EPI, from I I I to < 1.0 ml/hr. S‐EPI inhibited tumor growth more effectively than F‐EPI or L‐EPI by causing tumors to regress and increasing survival of mice. There were 9/10 (S‐EPI) compared to 0/10 (F‐EPI) 120‐day survivors when treatment was started 3 days after tumor implant. When treatment was delayed for 10 days, tumors, which had reached approx. 0.1–0.3 cm3 in volume, regressed in 8/10 animals receiving S‐EPI, whereas in all animals treated with F‐EPI the tumors progressed. L‐EPI was no more effective therapeutically than F‐EPI in this model. The maximum tolerated dose of S‐EPI was higher than that of F‐EPI. The enhanced therapeutic efficacy of S‐EPI is probably related to the extended circulation time of the formulation and its accumulation in tumors.
Harderian gland hyperplasia in c‐mos transgenic mice
Authors: Heath L. A. , Rosenberg M. P. , Thorogood P. , Speight P. , Propst F. 
Published: February 2007

AbstractTransgenic mice carrying the mouse mos proto‐oncogene linked to a retroviral LTR develop hyperplasia of the Harderian glands. Enlargement of the glands is evident as early as 18 weeks after birth, with glands reaching up to 10 times their normal weight. Approximately 65% of the cases of hyperplasia occur bilaterally, and the majority of mice affected are male (66%). Elevated levels of mos expression are found in all Harderian glands of mice from the affected transgenic line, but not in glands of normal mice or a non‐affected transgenic line, indicating that hyperplasia is dependent on mos expression. Histological examination of the tissue reveals a general involvement of the entire gland epithelium in hyperplastic growth, with no evidence of focal or malignant tumours. These observations show that in addition to neu, myc, ras and ret transgenes, mos, a member of the protein‐serine/threonine kinase family of oncogenes, can induce Harderian gland hyperplasia, thus revealing an unusual response by this organ to various classes of oncogenes. Analysis of fos, jun, myc and ets oncogene RNA in mos‐induced hyperplastic Harderian glands shows that there are no consistent changes in the level of expression of these oncogenes, suggesting that mos acts via a mechanism other than by increasing the expression of these genes.
Enzymatic basis of sugar structures of α‐fetoprotein in hepatoma and hepatoblastoma cell lines: Correlation with activities of α1–6 fucosyltransferase and N‐acetylglucosaminyltransferases III and V
Authors: Ohno Masao , Nishikawa Atsushi , Koketsu Masatoshi , Taga Hiroko , Endo Yasuo , Hada Toshikazu , Higashino Kazuya , Taniguchi Naoyuki 
Published: February 2007

Abstractα‐Fetoproteins (AFPs) were purified from 2 hepatoma cell lines (Hep G2 and HuH‐7) and a hepatoblastoma cell line (HuH‐6), and the structures of pyridylaminated (PA) derivatives of their sugar chains were analyzed by HPLC. Simultaneously, the activities of αl‐6 fucosyltransferase (αl‐6FT) and N‐acetylglucosaminyltransferase III (GnT‐III), IV(GnT‐IV) and V(GnT‐V) were assayed in these cell lines. For all 3 cell lines the major sugar chain detected was a fucosylated biantennary structure. Hep G2 cells contained a high level of GnT‐V, which catalyzes the formation of a tri'‐antennary structure, and in fact a substantial percentage of the AFP sugar chains in these cells had the tri'‐antennary structure. αl‐6FT was also high, and fucosylated tri' structures were detected, which suggests that high activities of transferases affect the AFP sugar chains. In HuH‐6 cells, GnT‐III, which catalyzes the formation of bisecting GIcNAc, was elevated. Correspondingly, a fucosylated, bisected biantennary structure was found as a major sugar chain. In the HuH‐7 cell line, the contents of bisecting GIcNAc and tri' structure were low and neither GnT‐III nor GnT‐V was elevated. These data indicate that the sugar structures of AFP in these cell lines correlate well with the activities of αl‐6 FT, GnT‐III and GnT‐V.
Stimulation of human prostatic carcinoma tumor growth in athymic mice and control of migration in culture by extracellular matrix
Authors: Passaniti Antonino , Isaacs John T. , Haney Joseph A. , Adler Scott W. , Cujdik Timothy J. , Long Peter V. , Kleinman Hynda K. 
Published: February 2007

AbstractThe tumorigenicity, migration, growth and invasiveness of certain tumor cells is stimulated by basement membranes. Here we have examined the effect of Matrigel, an extract of basement membrane proteins, on the behavior of several prostate cancer cell lines, testing their growth and invasiveness in vitro and in vivo. Cells of the Tsu‐prI line were more invasive than PC‐3, Du‐145, or LNCaP cells. Peptide inhibitors implicated laminin in the migration and invasion of these cells. When these cells were suspended in Matrigel and injected into nude mice, their growth was greatly enhanced, since large tumors formed in athymic nude mice whereas virtually no tumors were observed in the absence of Matrigel. The growth of a slowly growing line, LNCaP, was increased by exogenous basic fibroblast growth factor when injected with Matrigel. A laminin cell adhesion peptide, YIGSR, was a potent inhibitor of Matrigelstimulated tumor growth implicating cell‐laminin interactions in this process. These results suggest that tumor growth of prostate adenocarcinoma cells may be dependent both on cellular growth factors and on cell‐matrix interactions mediated by laminin which facilitate the development of transplanted tumors in nude mice.
Fibrosis in immune control of mammary‐tumor growth
Authors: Vaage Jan 
Published: February 2007

AbstractIn malignancies, an interruption of growth (dormancy) is sometimes observed. In the immunogenic mammary carcinoma MC2, dormancy followed by regression after a period of growth was observed in 18% of s.c. implants in normal mice. Dormant implants removed for histologic examination were invariably found to be completely surrounded by a highly fibrous stroma. Fibrosis was enhanced in immunized mice, and reduced in immuno‐deficient mice. Surgical disruption of the fibrous capsule around dormant tumors early (19 ± 3 days) in the immune response led more frequently to resumed growth, while later (32 ± 3 days) disruption of the capsule led more frequently to complete regressions. This showed that fibrous capsules that could destroy tumors could also shield them against well‐developed systemic immune mechanisms.
Levels of expression of breast epithelial mucin detected by monoclonal antibody BrE‐3 in breast‐cancer prognosis
Authors: Ceriani Roberto L. , Chan Curtis M. , Baratta Frank S. , Ozzello Luciano , Derosa Carolyn M. , Habif David V. 
Published: February 2007

AbstractTaking into consideration the relationship of breast neoplasia with recent knowledge obtained on the molecular structure and biosynthesis of the breast epithelial mucin, an epitope on this molecule detected by monoclonal antibody (MAb) BrE‐3 was chosen as a marker to study the correlation of expression of the mucin and prognosis in infiltrating ductal carcinomas of the breast. Strong statistical validation was obtained in the use of BrE‐3 in immunohistochemical procedures where scores for the expression of the mucin on paraffin‐embedded sections of the primary breast tumors were studied. Four different immunohistochemical variables measuring levels of expression (intensity or prevalence) in cytoplasm or membrane were obtained for each of 227 patients' breast tumors and subjected to KaplanMeier univariate and Cox proportional‐hazards multi‐variate analysis. Additionally, traditional prognostic variables for breast‐cancer prognosis (grade of differentiation, age, tumor size, axillary‐lymph‐node involvement and estrogen receptors) were subjected to identical analyses. In uni‐variate analysis, low cytoplasmic intensity, high membrane prevalence, and high membrane intensity of mucin expression were each found to be significantly associated with good prognosis in relation to both survival or relapse time. In multi‐variate analysis, all 4 immunohistochemical parameters were significantly associated with both survival and relapse time in these patients. Among the traditional variables, 3 (axillary‐node involvement, grade of differentiation and tumor size) were also found to be statistically significant at the uni‐variate and multi‐variate level. A multi‐variate analysis of the combined immunohistochemical and traditional variables identified the 4 immunohistochemical parameters, tumor size and axillary‐node involvement as having the highest level of association with either survival or relapse time. These variables were then combined and served to define a prognostic model [ILCPS(Comb)], which was found to have the capacity to separate the patient population studied into 4 prognostic groups in terms of survival and 3 groups in terms of relapse. As expected, the ILCPS(Comb) was shown to have a higher level of prognostic association with both survival and relapse than the individual variables themselves, the traditional variables together or the immunohistochemical variables together. Our approach develops a theoretical framework and a statistical model, employing levels of expression of the breast epithelial mucin and 3 traditional variables, which identifies, in terms of prognosis, distinct sub‐populations of patients with infiltrating breast carcinoma with defined risk functions.
A collaborative case‐control study of nutrient intake and pancreatic cancer within the search programme
Authors: Howe G. R. , Ghadirian P. , de Mesquita H. B. Bueno , Zatonski W. A. , Baghurst P. A. , Miller A. B. , Simard A. , Baillargeon J. , de Waard F. , Przewozniak K. , McMichael A. J. , Jain M. , Hsieh C. C. , Maisonneuve P. , Boyle P. , Walker A. M. 
Published: February 2007

AbstractCase‐control studies of pancreatic cancer were conducted in 5 populations with moderate to high rates and differing dietary practices, using a common protocol and questionnaire. Comprehensive diet histories were completed for a total of 802 cases and 1669 controls identified in Adelaide (Australia), Montreal and Toronto (Canada), Utrecht (The Netherlands) and Opole (Poland). Positive associations were observed with intake of carbohydrates and cholesterol, and inverse associations with dietary fiber and vitamin C. These relationships were generally consistent among the 5 studies, and showed statistically significant and generally monotonic dose‐response relationships. The relative risks for highest vs. lowest quintile of intake were estimated for carbohydrates to be 2.57 (95% confidence interval 1.64–4.03), cholesterol 2.68 (1.72–4.17), dietary fiber 0.45 (0.30–0.63), and vitamin C 0.53 (0.38–0.76). The consistency, strength, and specificity of these associations provides evidence for the hypothesis that some or all of these dietary factors may alter the risk of pancreatic cancer.
Induction of growth suppression and modification of gene expression in multi‐drug‐resistant human glioblastoma multiforme cells by recombinant human fibroblast and immune interferon
Authors: Moulton Thomas A. , Jiang Hongping , Guarini Ludovico , Fetell Michael R. , Fisher Paul B. 
Published: February 2007

AbstractThe combination of recombinant human fibroblast (IFN‐β) and immune (IFN‐γ) interferon induces enhanced growth suppression and modifies the antigenic phenotype in parental and multi‐drug‐resistant (MDR) human glioblastoma multiforme (GBM) cells. The present study was conducted to explore the mechanism underlying this cooperative interaction between interferons in inducing growth suppression in MDR‐GBM cells. For this analysis we have utilized 2 MDR‐GBM cell lines which display a differential sensitivity to growth suppression when exposed to IFN‐β or IFN‐γ. GBM‐18‐B3 (MDR) cells are more sensitive to growth inhibition by IFN‐γ than by IFN‐β, whereas GBM‐18‐A3 (MDR) cells are inhibited to a greater degree by IFN‐β than by IFN‐γ. In both cell types, however, growth is suppressed to a greater degree by the combination of interferons than by equivalent concentrations of either type of interferon used alone. Growth suppression induced by the interferons, alone or in combination, was not associated with comparable changes in the steady‐state level of MDRI mRNA. In addition, the anti‐proliferative effect of interferon was similar in GBM‐18 (MDR) cells grown in the presence or absence of colchicine. GBM‐18‐A3 and GBM‐18‐B3 cells differed in their de novo and interferon‐inducible expression levels of IFN‐β‐responsive genes, isg‐15 and isg‐54. In contrast, both cell types responded in a similar manner with respect to expression of the IFN‐γ‐responsive gene, HLA Class II (HLA‐DRβ), and HLA Class I, fibronectin and ICAM‐1, No further increase in expression of any of the genes was observed which was unique to the combination of interferons.