bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapy of human T‐cell acute lymphoblastic leukaemia in severe combined immunodeficient mice with two different anti‐CD7‐saporin immunotoxins containing hindered or non‐hindered disulphide cross‐linkers
Authors: Flavell David J. , Boehm Deborah A. , Okayama Keiko , Kohler Janice A. , Flavell Sopsamor N. U. 
Published: February 2007

AbstractA SCID mouse model of human T‐ALL has been used to determine the in vivo therapeutic efficacy of two anti‐CD7‐saporin immunotoxins constructed with either a hindered (HB2‐SMPT‐Sap) or non‐hindered (HB2‐SPDP‐Sap) disulphide bond between antibody and saporin. Groups of 10 SCID mice were injected intravenously (i.v.) with 2 × 106 human T‐ALL HSB‐2 cells followed seven days later by i.v. injection with either a single dose or with 3 doses of HB2‐SPDP‐Sap or HB2‐SMPT‐Sap given on alternate days. Control groups received equivalent sham injections of PBS or molar equivalent amounts of unconjugated HB2 antibody + saporin. Animals receiving a single dose of HB2‐SMPT‐Sap showed better survival than animals receiving a single dose of HB2‐SPDP‐Sap but the difference was not shown to be significant by log‐rank analysis. When given as a triple dose both immunotoxins performed similarly. Comparison of single‐dose with triple‐dose IT therapy revealed that the therapeutic effect of a triple dose of HB2‐SPDP‐Sap was significantly better than that of single dose, but this was not the case with HB2‐SMPT‐Sap. Pharmacokinetic studies of HB2‐SPDP‐Sap and HB2‐SMPT‐Sap in normal and HSB‐2 leukaemia bearing SCID mice failed to reveal any difference in clearance rates for these two IT's. We conclude from these studies that there is no therapeutic advantage to be gained from constructing the HB2‐Sap IT with a hindered disulphide bond in this particular model of human T‐ALL.
Different characteristics of hepatoid and non‐hepatoid α‐fetoprotein‐producing gastric carcinomas: An experimental study using xenografted tumors
Authors: Aizawa Kikuo , Motoyama Teiichi , Suzuki Satoshi , Tanaka Norio , Yabusaki Hiroshi , Tanaka Shinsuke , Muto Ichiro , Tanaka Otsuo , Hatakeyama Katsuyoshi 
Published: February 2007

AbstractThe characteristics, including metastatic potential, of 5 xenografts of α‐fetoprotein (AFP)‐producing gastric carcinomas in nude mice, designated TSG1, TSG3, TSG11, TSG17 and TSG20, were examined. Of these xenografts, TSG1, TSG11 and TSG20 were regarded as hepatoid adenocarcinomas based on their morphological resemblance to hepatocellular carcinoma, frequent immunoreactivity for liver‐cell markers, and excessive production of AFP with a high concanavalin A (Con‐A)‐binding property of hepatic type. On the other hand, TSG3 and TSG17 tumors showed the features of poorly differentiated medullary adenocarcinoma with scattered AFP‐positive cells consistent with low AFP levels in mouse sera, and negative immunoreactivity for other liver‐cell markers. Ultrastructurally, these tumors were composed of undifferentiated cells with a little adenocarcinomatous differentiation. Moreover, the AFP produced by TSG3 and TSG17 tumors had an extremely high Con‐A non‐bound fraction (80% to 90%), which was different from that of the hepatic or yolk‐sac types. Therefore, both TSG3 and TSG17 tumors were regarded as non‐hepatoid, poorly differentiated adenocarcinomas which could be differentiated from any types of AFP‐producing gastric carcinoma. Furthermore, cells from hepatoid adenocarcinoma strains (TSG1, TSG11 and TSG20) injected into the spleens of nude mice produced liver metastases in all the mice examined, whereas cells from non‐hepatoid carcinoma strains (TSG3 and TSG17) produced few or no liver metastases. Our data show that some non‐hepatoid AFP‐producing gastric carcinomas have lower liver‐metastasizing potential than hepatoid AFP‐producing gastric carcinomas.
Hypermethylation of replicating hepatic DNA following N‐methyl‐N‐nitrosourea administration
Authors: Kanduc Darja , Aresta Antonella , Farber Emmanuel 
Published: February 2007

AbstractChanges in the degree of methylation of cytosine in DNA are considered to be mechanistically important in modulating gene expression. To gain a better understanding of the relationship(s) linking onco‐proliferative processes and enzymatic DNA methylation, a study has been carried out on the hepatic DNA methylation pattern during DNA replication following partial hepatectomy (PH), mitogen treatment and N‐methyl‐N‐nitrosourea (MNU) administration in rats. The following results were obtained: (i) DNA hypomethylation was seen during DNA synthesis, with each of the 3 stimuli, namely MNU administration, partial hepatectomy, and hepatomitogen treatment; (ii) the level of DNA hypomethylation was not quantificatively related to the extent of DNA replication as measured by incorporation of [3H]thymidine into hepatic DNA: (iii) MNU administration under conditions conducive to carcinogenic development, i.e. during the S phase of compensatory cell proliferation, caused hypermethylation of replicating hepatic DNA, as shown by Hpall and Mspl restriction patterns.
Inhibition of the metastatic spread and growth of B16‐BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitor
Authors: Chirvi Renato G. S. , Garofalo Angela , Crimmin Michael J. , Bawden Lindsay J. , Stoppacciaro Antonella , Brown Peter D. , Giavazzi Raffaella 
Published: February 2007

AbstractThe synthetic matrix metalloproteinase inhibitor batimastat was tested for its ability to inhibit growth and metastatic spread of the B16‐BL6 murine melanoma in syngeneic C57BL/6N mice. Intraperitoneal administration of batimastat resulted in a significant inhibition in the number of lung colonies produced by B16‐BL6 cells injected i.v. The effect of batimastat on spontaneous metastases was examined in mice inoculated in the hind footpad with B16‐BL6 melanoma. The primary tumor was removed surgically after 26‐28 days. Batimastat was administered twice a day from day 14 to day 28 (pre‐surgery) or from day 26 to day 44 (post‐surgery). With both protocols, the median number of lung metastases was not significantly affected, but there was a significant reduction in the weight of the metastases. Finally, the effect of batimastat was examined on s.c. growth of B16‐BL6 melanoma. Batimastat administered daily, starting at day of tumor transplantation, resulted in a significant growth delay, whereas treatment starting at advanced stage tumor only reduced tumor growth marginally. Our results indicate that a matrix metalloproteinase inhibitor can not only prevent the colonization of secondary organs by B16‐BL6 cells but also limit the growth of solid tumors.
Transformation and tumor progression are frequently associated with expression of the α3/β1 heterodimer in solid tumors
Authors: Bartolazzi Armando , Cerboni Cristina , Nicotra Maria R. , Mottolese Marcella , Bigotti Aldo , Natali Pier G. 
Published: February 2007

AbstractThe ability of tumor cells to interact with the extracellular matrix (ECM) is functionally mediated by a variety of receptor molecules among which the integrins are a well‐characterized family of mediators. In this study we have investigated immuno‐histochemically the in vivo expression of the α/β1 promiscuous receptor for ECM constituents in a variety of human solid malignancies. Although the receptor appears to undergo changes in distribution patterns, its expression is maintained in a high percentage of primary (76%) and metastatic (82%) tumors. Furthermore, the comparative immunohistochemical evaluation of α/β1 and its ligands, in a selected number of tumors of different histotypes, demonstrated that the expression of this integrin correlates with the presence of at least one ligand, either around nests of neoplastic cells or at the epithelial‐stromal interface. The highly conserved expression of α/β1 shown in this study suggests that this receptor may play a role in tumor growth at the primary as well as at the metastatic site.
Clonal analysis of human gynecologic cancers by means of the polymerase chain reaction
Authors: Sawada Masumi , Azuma Chihiro , Hashimoto Kazumasa , Noguchi Shinzaburo , Ozaki Masami , Saji Fumitaka , Tanizawa Osamu 
Published: February 2007

AbstractClonality of human gynecologic cancers was analyzed in small DNA samples prepared from cryostat sections, by means of the polymerase chain reaction (PCR). The method used for clonal analysis was based on restriction fragment length polymorphism of the X‐chromosome‐linked phosphoglycerokinase (PGK) gene and on the differential methylation of the PGK gene due to random inactivation of 1 of 2 X‐chromosomes by methylation in females. Among 52 gynecologic cancers tested, 25 were found to be heterozygous for the BstXI polymorphism of the PGK gene. All the 25 gynecologic cancers (4 cervix, 11 endometrium, 7 ovary and 3 fallopian tube) analyzed by the PCR‐based method were monoclonal in origin while adjacent normal tissues were polyclonal. When DNA samples were prepared from widely separated sites of tumors and/or metastatic lesions, every sample was found to be monoclonal, and the same allele of the PGK gene was inactivated in each case. These results demonstrate that clonal analysis by PCR offers a good method for studying clonality in small DNA samples prepared from cryostat sections of tumors. This method could be applied to distinguish between benign and malignant gynecologic lesions.
Polyclonal uses of T‐cell receptor (TCR)α and β genes for cytotoxic T lymphocytes in human metastatic melanoma: possible involvement of TCRα in tumor‐cell recognition
Authors: Seito Dai , Morita Tatsuo , Masuoka Kazuhiro , Maeda Tomoyuki , Saya Hideyuki , Itoh Kyogo 
Published: February 2007

AbstractIdentification of genetic structure and diversity of T‐cell receptor (TCR)α and β genes for cytotoxic T lymphocytes (CTLs) infiltrating human cancers is important for the better understanding of molecular mechanisms of host defense at tumor sites. cDNAs of TCRα and β genes of 22 different melanoma‐specific CTL clones established from the tumor‐infiltrating lymphocytes of 2 patients were sequenced for analysis of their genetic structure and diversity. Vα7.2‐Jα10‐Cα was found in 4 of 22 clones, 2 of which also used the same β‐chain. The other 20 clones showed different combinations of α and β use. At deduced amino‐acid levels, 7 of 9 clones from one patient used a threonine residue at the 26th position in the complementarity‐determining region (CDR)1 of TCRα. Eight of 13 clones used a threonine at the 99th or a serine residue at the 100th position in CDR3 of TCRα. CTL clones with the same or different TCRα showed the same or different patterns of cytotoxicity, respectively. These results suggest that CTLs usually do not demonstrate clonal expansion at tumor sites of metastatic melanoma's but rather that polyclonal T cells capable of binding to multiple melanoma determinants through CDR3 of TCRα accumulate in the tumor.
A K‐ras 13GLY → ASP mutation is recognized by HLA‐DQ7 restricted T cells in a patient with colorectal cancer. Modifying effect of DQ7 on established cancers harbouring this mutation?
Authors: Fossum Beate , Breivik Jarle , Meling Gunn Iren , Iii Tobias Gedde‐Dahl , Hansen Torbjørn , Knutsen Ingebjørg , Rognum Torleiv O. , Thorsby Erik , Gaudernack Gustav 
Published: February 2007

AbstractWe have characterized and described in detail 2 CD4+ T‐lymphocyte clones (TLC) from a colonic cancer patient. These TLC specifically recognize a K‐ras‐derived peptide carrying the 13Asp mutation commonly found in adenocarcinomas of the colon. The TLC were independently derived, as they carried 2 different T‐cell receptors. The TLC recognized partly overlapping epitopes within the 13Asp peptide, presented by HLA‐DQ7 molecules, suggesting that this molecule might confer some protective immunity against the mutation. On the basis of analysis of 251 colonic carcinomas, the presence of HLA‐DQ7 did not seem to protect against the establishment of carcinomas carrying the 13Asp mutation, since the frequency of the DQ7 haplotype was not decreased among patients having this mutation. A modifying effect of DQ7 on the development of carcinomas with a 13Asp mutation was, however, observed, resulting in fewer tumours reaching advanced Dukes stages when DQ7 was present.
Pyrimidine nucleotide metabolism in human colon carcinomas: Comparison of normal tissues, primary tumors and xenografts
Authors: Luccioni C. , Beaumatin J. , Bardot V. , Lefrançois D. 
Published: February 2007

AbstractThe activities of 5 enzymes involved in the pyrimidine metabolism were measured in xenografts of 8 human colon adenocarcinomas and in the corresponding primary tumors and normal tissues. The enzymes studied were thymidine kinase, thymidine phosphorylase, uridine kinase, uridine phosphorylase and thymidylate synthase. With the exception of the phosphorylases in one tumor, all enzyme activities were higher in primary tumors than in the corresponding normal tissues. The average activities of thymidine kinase and thymidylate synthase were of the same order of magnitude in xenografts and in primary tumors. The uridine metabolizing enzymes tend to have a higher activity in xenografts than in primary tumors. The most consistent and significant change was a sharp decrease in thymidine phosphorylase activity in xenografts as compared to primary tumors. Whether or not the difference in thymidine phosphorylase activity between xenografts and primary tumors is related to the contribution of non‐cancerous cells in primary tumors remains to be determined. However, these results raise questions concerning the representativeness of xenografts with reference to primary tumors and suggest that care should be taken in the application of this model.
Interferon gamma‐induced reduction in erbB‐2 tyrosyl phosphorylation in human ovarian carcinoma cells
Authors: Mishra Shirkant , Hamburger Anne W. 
Published: February 2007

AbstractInterferon, which inhibits growth of ovarian cancer cells in vivo and in vitro, decreases expression of erbB‐2 protein in ovarian carcinoma cell lines. We now show that interferon‐γ (IFN‐γ) also decreases constitutive tyrosine phosphorylation of erbB‐2 and inhibits erbB‐2 kinase activity in an ovarian cancer cell line. SK‐OV3 ovarian cancer cells, which over‐express erbB‐2, were treated with IFN‐γ for 0‐72 hr. Immunoblot analysis revealed that IFN decreased the levels of tyrosyl phosphorylated erbB‐2 24 hr after IFN treatment. Protein levels of erbB‐2 were not changed until 72 hr post‐treatment. Tyrosine kinase (TK) activity of immunoprecipitated erbB‐2 for an exogenous substrate was decreased in IFN‐treated cells. Total cellular protein tyrosine phosphatase (PTPase) activity for the epidermal growth factor receptor was not changed by IFN treatment. Our results suggest that the decreased levels of tyrosyl phosphorylated proteins observed after IFN treatment in SK‐OV3 cells may be due to inhibition of erbB‐2 kinase activity.
Suppression of multi‐drug resistance gene expression in the mouse liver by 1,4‐bis[2,(3,5‐dichloropyridyloxy)]benzene
Authors: Russell Alison L. , Henderson Colin J. , Smith Gillian , Roland Wolf C. 
Published: February 2007

AbstractP‐glycoproteins encoded by the (multi‐drug resistance) mdr genes play a central role in the resistance of tumor cells to a wide range of anti‐cancer drugs. Modulation of P‐glycoprotein function could therefore provide a means of sensitising tumor cells to chemotherapy. Studies in this context have centred around the use of compounds which antagonise the P‐glycoprotein membrane transport system. To investigate the possibility of modulating P‐glycoprotein expression at a transcriptional level, we investigated the effects of hormonal factors and cytochrome P450‐inducing agents on hepatic expression of murine mdr I, mdr 2 and mdr 3. Hepatic mdr 2 and mdr 3 expressions were significantly suppressed in hypophysectomised animals, indicating that pituitary hormones activate the hepatic expression of these genes. Many of the foreign compounds and anti‐cancer drugs tested did not significantly induce mdr 1, 2 or 3 expression. However, it was of particular interest that a potent cytochrome P450 inducer, 1,4‐bis[2‐(3,5‐dichloropyridyloxy)]benzene, almost completely suppressed hepatic mdr 2 and 3 expressions.
Vaccination with ant‐idiotype antibodies mimicking a renal cell carcinoma‐associated antigen induces tumor immunity
Authors: Uemura Hirotsugu , Beniers Antonius J. M. C. , Okajima Eigoro , Debruyne Frans M. J. , Oosterwijk Egbert 
Published: February 2007

AbstractWe have previously isolated and characterized 6 different internal image mouse monoclonal anti‐idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Abl), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31,44,51, 71,82 and 91) demonstrated specificity for the combining site of AbI, and appeared to recognize 2 partly overlapping idiotopes on AbI. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti‐tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2‐fold increase in antigen‐specific anti‐anti‐idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen‐positive cell lysates, and all Ab3 sera contained immunoglobulin resembling AbI (Abl), as shown by competitive AbI ‐antigen binding assays. Fine‐specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Abl binding pocket. Treatment of RCC‐challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH‐91‐immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3‐NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti‐tumor effects in immune‐competent animals.
Abnormalities of the adenomatous polyposis coli gene in human oral squamous‐cell carcinoma
Authors: Uzawa Katsuhiro , Yoshida Hidehiko , Suzuki Hiroyoshi , Tanzawa Hideki , Shimazaki Jun , Seino Susumu , Sato Kenichi 
Published: February 2007

AbstractRecent studies have suggested that abnormalities in the adenomatous polyposis coir gene (APC gene) are associated with the development not only of familial adenomatous polyposis coli (FAP) but also of cancers in digestive organs. In order to elucidate whether abnormalities of the APC gene could contribute to the development of oral squamous‐cell carcinoma (SCC), genomic DNAs from tumors and normal tissues of 24 unrelated Japanese patients were examined by using PCR‐SSCP (polymerase chain reaction single‐strand conformation polymorphism) and sequence analyses. Five novel nudeotide substitutions of the APC gene in tumor tissues were identified in 3 patients with oral SCC (12.5%), resulting in 3 amino‐acid replacements or a truncation of the APC gene product. We also examined 24 tumor and 24 normal tissue samples for loss of heterozygosity (LOH) at exon 11 of the APC gene by PCR‐LOH assay. In this analysis, 45.8% of samples were informative and LOH was detected in 72.7% of informative cases. The frequency of LOH in oral SCC was similar to that previously reported in esopha‐geal SCC. These results suggest that abnormalities in the APC gene are associated with the development of human oral SCC.
PEG‐IL‐2 therapy of advanced cancer in the guinea pig. Impact of the primary tumor and beneficial effect of cyclopphosphamide
Authors: Balemans Lianne T. M. , Steerenberg Peter A. , Koppenhagen Frank J. , Kremer Bas H. A. , De Mulder Pieter H. M. , Claessen Anke M. E. , Scheper Rik J. , Otter Willem Den 
Published: February 2007

AbstractThe efficacy of tumor therapy using polyethylene‐glycolmodified interleukin‐2 (PEG‐IL‐2), alone or in combination with cyclophosphamide, was studied in advanced metastatic disease in the guinea pig. Line 10 (L10) tumor cells appeared in the axillary lymph node only 7 days after intradermal tumor‐cell inoculation, and lymph‐node leukocytes were almost completely replaced by tumor cells on day 28. Local treatment of the intradermally growing L10 hepatocarcinoma in the guinea pig with a relatively low dose of PEG‐IL‐2 resulted in regression of the primary tumor and prevention of lymph‐node metastases. Therapy was completely curative (4 out of 5 animals) when started on day 7 or 14 after tumor‐cell inoculation. When started on day 21, therapy was effective in only some (2 out of 5 cured) of the treated animals. Anti‐tumor effects against the primary tumor and against lymph‐node metastases were observed only after intratumoral (i.t.) administration of PEG‐IL‐2. Injection of the agent into or near lymph‐node metastases in the absence of the primary tumor had no curative effect. In PBS/BSA‐treated control animals the primary tumor and metastases grew progressively. In the treatment of far advanced metastatic disease, the combination of i.t. administration of PEG‐IL‐2 and i.p. injection of cyclophosphamide (Cy) resulted in improved anti‐tumoral effects (5/5 guinea pigs were cured) when compared with monotherapy using either agent (one and none out of 5 animals cured, respectively). PBS/BSA heated controls showed progressive tumor‐growth. We conclude that large primary tumors and lymph‐node metastases can be treated effectively with PEG‐IL‐2. The i.t. route of administration is of major importance in the treatment of metastases, since administration of PEG‐IL‐2 near or into the lymph node had no therapeutic effect. Combination of PEG‐IL‐2 therapy with systemic injections of Cy significantly improved the curative effects of the treatment of advanced metastatic cancer.
Establishment of a human small‐cell lung‐cancer subline resistant to okadaic acid
Authors: Takeda Yuichiro , Nishio Kazuto , Kubota Naohiro , Miura Kaoru , Morikage Toshihiko , Ohmori Tohru , Kudoh Shoji , Niitani Hisanobu , Saijo Nagahiro 
Published: February 2007

AbstractOkadaic acid (OA), a specific protein phosphatase inhibitor, has various biological functions. To elucidate the mechanism of OA resistance, we have established a small‐cell lung‐cancer subline (H69/OA100) resistant to the growth‐inhibitory effect of OA; this was done by using the parental cell line (H69) and increasing the concentration of OA. H69/OA100 was about 8 times more resistant to OA than H69. Intracellular retention of the fluorescent OA derivative in H69/OA100 was the same as that in H69. The catalytic activity of protein phosphatase from H69/OA100 was significantly reduced compared with that from H69. The protein phosphatase from H69/OA100 was 3.6 times more resistant to OA than that from H69. We examined the effect of OA on the activity of the immunoprecipitated protein phosphatase type 1 (PPI) and type 2A (PP2A) from the 2 cell lines. The PPI and PP2A from H69/OA100 showed more resistance to OA than those from H69. We next examined the effect of OA on the cell cycle of H69 and H69/OA100. In H69, G2/M block was observed at an OA concentration of 30 ng/ml whereas in H69/OA100, no G2/M block was observed at concentrations up to 100 ng/ml OA. We finally evaluated the amount of p34cdc2 kinase expression and the phosphorylation status of p34cdc2. There was no difference in p34cdc2 expression between H69 and H69/OA100 at several concentrations of OA. However, dephosphorylation of p34cdc2 was observed at 30 ng/ml OA in H69, but not in H69/OA100 up to 100 ng/ml OA. These data suggest that the resistance to OA and the resistance of the cell‐cycle block to OA in H69/OA100 might be due to alteration of protein phosphatase activity.