bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of O6‐methylguanine‐DNA methyltransferase activity on chloroethylnitrosourea chemotherapy in brain tumors
Authors: Mineura Katsuyoshi , Izumi Ichiro , Watanabe Katsuo , Kowada Masayoshi 
Published: February 2007

AbstractChloroethylnitrosoureas (CENUs) alkylate DNA at specific sites and inhibit DNA replication in tumor cells. O6‐Alkylguanine moieties resulting from alkylation of guanine bases are thought to be one of most lethal adducts in living cells. Effectiveness of CENUs is known to relate well with an enzymic activity of the DNA repair enzyme O6‐methylguanine‐DNA methyltransferase (MGMT), which recognizes and removes O6‐alkylguanine. To improve therapeutic results of CENUs, we have measured MGMT activity of human brain tumors and studied the relationship between MGMT activity and clinical responsiveness to 1‐(4‐amino‐2‐methyl‐5‐pyrimidinyl)methyl‐3‐(2‐chloroethyl)‐3‐nitrosourea hydrochloride (ACNU). Thirty‐seven patients with brain tumors were entered into the study. The neoplasms included gliomas, non‐glial tumors, and brain metastases. The MGMT activity of gliomas was significantly lower than that of non‐glial tumors and brain metastases. No significant difference in the enzyme activity was noted between low‐ and high‐grade gliomas. Out of the 22 gliomas 5 tumors indicated a value below 60 fmol/mg, suggestive of a methyl excision repair minus (Mer−) tumor. Two out of 3 evaluable patients with a Mer− tumor responded well to post‐operative ACNU adjuvant chemotherapy. Our results suggest that brain tumors include a certain percentage of Mer− phenotype tumors, and that CENUs such as ACNU should be applied selectively on tumors with a low MGMT activity in order to increase the therapeutic effectiveness. © 1993 Wiley‐Liss, Inc.
Immunohistochemical study of mucin carbohydrates and core proteins in hepatolithiasis and cholangiocarcinoma
Authors: Yamashita Kaneteru , Yonezawa Suguru , Tanaka Sadao , Shirahama Hiroshi , Sakoda Koro , Imai Kohzoh , Xing Pei‐Xiang , McKenzie Ian F. C. , Hilkens John , Kim Young S. , Sato Eiichi 
Published: February 2007

AbstractThe expression of mucin carbohydrates [Tn, sialosyl‐Tn(STn), and T antigens] and core proteins [MUCI‐apomucin‐related antigen (ARA) and MUC2‐ARA] was examined immunohisto‐chemically in tissues from 40 patients with hepatolithiasis and 26 patients with intrahepatic bile‐duct carcinoma. Tn and STn antigens were expressed in most of the carcinomas, and were also often expressed in the atypical bile‐duct epithelium of the patients with hepatolithiasis or carcinoma, whereas they were rarely or never expressed in the normal bile duct, suggesting that they are effective tumor markers. T antigen was less useful as a marker for intrahepatic bile‐duct carcinoma or the atypical epithelium, because it was expressed in normal bile‐duct of some cases. Regarding the expression of ARAs in the carcinomas, non‐invasive bile‐duct cyst adenocarcinomas with favorable prognosis either expressed no MUCI‐ARA with [DF3(‐), MUSE11(‐) and 139H2(‐)] staining pattern or expressed MUCI‐ARA with [DF3(‐), MUSE11(+) and 139H2(+)] staining pattern. However these tumors often expressed MUC2‐ARA with [anti‐MRP(+) and CCP58(+)] staining pattern. In contrast, most invasive non‐papillary cholangiocarcinomas with poor prognosis expressed MUCI‐ARA with [DF3( + ), MUSE 11(+) and 139H2(+)] staining pattern, but expressed no MUC2‐ARA with [anti‐MRP(‐) and CCP58(‐)] staining pattern. These results suggests that different apomucins are produced by bile‐duct cystadenocarcinomas and cholangiocarcinomas with differing prognosis. Furthermore, expression of Tn and STn antigens is a useful indicator of malignancy in the intrahepatic duct. © 1993 Wiley‐Liss, Inc.
Modification of TNF‐α pharmacokinetics in SA‐1 tumor‐bearing mice
Authors: Kus Breda , Serša Gregor , Novaković Srdjan , Urbančič Janja , Štalc Anton 
Published: February 2007

AbstractFibrosarcoma‐SA‐1‐tumor‐bearing mice were treated s.c. in the vicinity of tumors (peri‐tumorally) or intravenously, with recombinant human TNF‐α lacking 1to 3 amino acids from N‐terminal part (TNF‐αNv3). Tumor growth delay, observed after both routes of TNF‐αNv3 application, was statistically significant, though a better anti‐tumor effect was achieved after peri‐tumoral application. TNF‐αNv3 serum levels were determined in these animals and compared with TNF‐αNv3 serum levels in healthy animals, which were treated with TNF‐αNv3 either s.c. or i.v. The peak serum levels of TNF‐αNv3 applied peri‐tumorally/s.c. were significantly higher in tumor‐bearing than in healthy mice, whereas smaller differences in peak serum levels were found after i.v. application, which might correlate with anti‐tumor activity. Whatever the route of application, TNF‐αNv3 elimination from the serum of tumor‐bearing mice was slower than that in healthy animals. Also, comparison of TNF‐αNv3 pharmacokinetic parameters for tumor‐free and sarcoma‐ or melanoma‐bearing mice has demonstrated that the pharmacokinetics of TNF‐αNv3 are modified in tumor‐bearing animals. © 1993 Wiley‐Liss, Inc.
Characterization of cytotoxic activity of saporin anti‐gp185/HER‐2 immunotoxins
Authors: Tecce R. , Digiesi G. , Savarese A. , Trizio D. , Natali P. G. 
Published: February 2007

AbstractThe oncogene HER‐2/neu encodes a trans‐membrane receptor of 185 kDa with tyrosine‐kinase activity. Over‐expression of this molecule has been reported in a significant proportion of human breast and ovarian carcinomas, characterized by a poor clinical prognosis. Two monoclonal antibodies (MAbs), recognizing distinct epitopes of the gp 185 extracellular domain, have been utilized in the present study for the production of immunotoxins (ITs) by conjugation to the type‐1 RIP (ribosome‐inactivating protein) plant toxin saporin 6 (SAP). These ITs have been shown to retain tumor‐specificity and specifically to inhibit protein synthesis in the gp 185HER‐2(+) SK‐BR‐3 breast‐carcinoma cell line with IC50 values lower then I nM. Kinetics of the cytotoxic activity of the ITs are characterized by a slow rate, since incubation times ranging from 24 to 60 hr, depending on the different degree of expression of the receptor, are required to determine > 90% inhibition in the incorporation of radiolabeled leucine. However, the cytotoxic activity of these ITs, as evaluated by a more sensitive clonogenic assay, appears highly potent, since we have observed that 3 to 4 logs of cells are killed upon exposure to the ITs for short times at concentrations ranging from 1 to 5 × 10−8 M. © 1993 Wiley‐Liss, Inc.
Sequential process of blood‐borne lung metastases of spontaneous mammary carcinoma in C3H mice
Authors: Sugino Takashi , Kawaguchi Takanori , Suzuki Toshimitsu 
Published: February 2007

AbstractWe examined the correlation between growth characteristics and the incidence of lung metastases of spontaneous mammary tumors in C3H mice. The growth pattern of the mammary tumors was composed of initial rapid growth, declining growth, and further exponential growth (re‐growth). The “re‐growth” was closely associated with loss of differentiation and progressive increase of the incidence of lung metastases. In addition, we observed the sequential process of blood‐borne lung metastases. The findings involved (i) “passive” intravasation: carcinoma nests encased in newly formed endothelial cells are released into sinusoidal vessels within primary tumors; (ii) “mechanical” arrest and proliferation of multicellular tumor emboli in pulmonary arterioles; (iii) “active” extravasation: carcinoma cells rushed out to the lung parenchyma through the arteriolar walls ruptured by initial minimal penetration of carcinoma cells and intravascular pressure. The results indicate a stable progression in the natural history of C3H mouse mammary carcinomas characterized by growth characteristics, the incidence of lung metastases, and histological change generating a poorly differentiated clone which can successfully complete a sequential process of blood‐borne lung metastasis. © 1993 Wiley‐Liss, Inc.
Complete local tumor remission after therapy with extra‐corporeally applied high‐energy shock waves (HESW)
Authors: Gamarra Fernando , Spelsberg Fritz , Dellian Marc , Goetz Alwin E. 
Published: February 2007

AbstractHigh‐energy shock waves (HESW) have recently been proposed as a means of non‐invasive tumor therapy. Here we report the first successful local treatment of experimental tumors by means of multifocal and repeated application of HESW. The experiments were performed on 29 Syrian golden hamsters bearing amelanotic hamster melanomas in the dorsal skin. HESW, generated electrohydraulically, were applied multifocally to the center and to 5 sites on the margin of the tumors. A group of animals undergoing surgical resection and an untreated group served as controls. Complete remission of local tumor was achieved in more than 90% of the HESW‐treated hamsters and in the same number of surgically treated animals, while untreated tumors continued to grow. Frequency of metastasis was the same in both groups after HESW treatment or surgery. Tumor therapy with multifocally and repeatedly applied HESW was thus as successful as surgery. © 1993 Wiley‐Liss, Inc.
Mouse mammary‐tumor virus activates Fgf‐3/Int‐2 less frequently in tumors from virgin than from parous mice
Authors: Clausse Nathalie , Smith Rosalind , Calberg‐Bacq Claire‐Michelle , Peters Gordon , Dickson Clive 
Published: February 2007

AbstractTumorigenesis by mouse mammary‐tumor virus (MMTV) involves proviral disruption and transcriptional activation of a number of cellular oncogenes, generically termed Int. The frequencies with which different Int genes are activated in different mouse strains can be quite variable, and previous surveys have suggested that insertions at int‐2/Fgf‐3 occur primarily in strains that develop pregnancy‐dependent mammary tumors. To address this issue, we have determined the relative contributions of 5 known Int genes (Wnt‐1, Wnt‐3, Fgf‐3, Fgf‐4 and Int‐3) in mammary tumors from virgin BR6 and multiparous BR6, BALB/cfBR6 and RIII mice. Whereas Fgf‐3 was implicated in 66%, 80% and 92% of the tumors from the respective parous animals, only 20% of the tumors from virgin mice expressed Fgf‐3. This reduced involvement of Fgf‐3 was compensated by proviral insertions in Fgf‐4, Int‐3 and Wnt‐3, but the frequency of Wnt‐1 activation was relatively constant. These data strengthen the link between Fgf‐3 and a pregnancy‐dependent phenotype and suggest that, in the strains analyzed, the frequency of Int‐gene activation was influenced more by the hormonal status than by the genetic background. © 1993 Wiley‐Liss, Inc.
Risk of cancer revealed by follow‐up of families with hereditary non‐polyposis colorectal cancer: A population‐based study
Authors: De Leon Maurizio Ponz , Benatti Piero , Pedroni Monica , Sassatelli Romano , Roncucci Luca 
Published: February 2007

AbstractHereditary non‐polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by susceptibility to large‐bowel cancer, frequently with early onset and localized in the right colon. Several tumours of other sites may also occur with increased frequency in these families. During the period 1984‐1989, 28 families with HNPCC were identified in our Health Care District through a population‐based colorectal cancer registry. Moreover, 61 additional families were selected and classified as having “suspected” HNPCC. The objective of the present study is to report the occurrence of new cases of cancer in the 5‐ to 6‐year follow‐up of individuals at risk of tumour development in either HNPCC or “suspected” families. There were 374 family members at risk in HNPCC and 468 in “suspected” families, contributing, respectively, 2,377 and 2,712 persons/year at risk. Thirty‐four new tumours developed among HNPCC family members vs. 29.3 expected; however, the occurrence of colorectal cancer in this group was significantly higher than expected, and this excess was particularly evident in the age‐groups 41‐50 and 51‐60. In “suspected” HNPCC, 38 new tumours developed vs. 24.5 expected; at variance with the other group, besides colorectal neoplasms, lung, liver and brain tumours also occurred significantly in excess. Moreover, the increased risk was uniformly distributed among different age‐groups. In conclusion, HNPCC family members are at increased risk of developing colorectal cancer, with an earlier onset than the general population; in contrast, high‐risk individuals in “suspected” HNPCC families seem to be prone to a broader neoplastic spectrum, and risk of tumours does not seem to be limited to any particular age‐group.
Quantitation of HTLV‐I provirus among seropositive blood donors: Relation with antibody profile using synthetic peptides
Authors: Matsumura Masayuki , Kushida Shigeki , Ami Yoshihiro , Suga Tetsuya , Uchida Kazuhiko , Kameyama Tsuneo , Terano Akira , Inoue Yukiko , Shiraki Hiroshi , Okochi Kazuo , Sato Hiroyuki , Miwa Masanao 
Published: February 2007

AbstractTo study the pathophysiological state of HTLV‐1 carriers and the quantitative aspect of the risk of HTLV‐1 infection, we measured the absolute amounts of HTLV‐1 provirus in 39 seropositive blood donors. The amount of provirus varied from less than one to more than 104 molecules per 105 peripheral‐blood mononuclear cells (PBMC). The average amount of HTLV‐1 provirus among seropositive blood donors was estimated as 3.7 × 103 molecules per 105 PBMC. The titer of the antibody against only the synthetic peptide (aa 100 to 130) of the gag p19 region of the HTLV‐1 provirus showed a weak but significant correlation with the amount of the provirus.
Analysis of antigens recognized on human melanoma cells by A2‐restricted cytolytic t lymphocytes (CTL)
Authors: Wölfel T. , Hauer M. , Klehmann E. , Brichard V. , Ackermann B. , Knuth A. , Boon T. , Zum büschenfelde K. H. Meyer 
Published: February 2007

AbstractWe have pursued our analysis of potential tumor‐rejection antigens recognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recognized on melanoma cell line SK29‐MEL in association with HLA‐A2. Selection for melanoma‐cell variants resistant to anti‐A CTL revealed that antigen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomitant loss of Aa and Ab in an immunoselected tumor‐cell variant. This variant was also resistant to an autologous CTL clone restricted by HLA‐B45, indicating that this CTL may also recognize a determinant of antigen A. Of 11 allogeneic HLA‐A2 melanoma cell lines that were tested, 5 expressed both Aa and Ab, I expressed only Aa, and I only Ab. None of them was lysed by anti‐B or anti‐C CTL clones. A CTL clone derived from another HLA‐A2‐melanoma patient was found to have exactly the same lytic pattern as the anti‐Ab CTL of the first patient. This suggested that it may be possible to elicit an anti‐Ab response in many HLA‐A2 patients. We conclude that there are at least 2 distinct antigens presented in association with HLA‐A2 that are common to many melanomas and therefore constitute promising targets for specific immunotherapy.
Low doses of radiation induce systemic production of cytokines: Possible contribution to leukemogenesis
Authors: Tartakovsky Boris , Goldstein Orly , Krautghamer Rita , Haran‐Ghera Nechama 
Published: February 2007

AbstractExperiments were conducted to explore the possible effect of low‐dose irradiation on cytokine production in mice. SJL/J and C57BL/6J mice were exposed to 3 Gy and 4 Gy respectively. At various time intervals thereafter, lung‐conditioned media, bone‐marrow‐conditioned media and sera were collected. Interleu‐kin‐6 and macrophage‐colony‐stimulating‐factor activities were tested, lnterleukin‐6 in lung‐conditioned media from both strains was found to be significantly induced by irradiation. Macrophage‐colony‐stimulating‐factor activity was greatly enhanced in sera of irradiated SJL/J mice as well as in bone‐marrow‐conditioned media of both strains. The kinetics of the radiation‐induced interleukin 6 and macrophage‐colony‐stimulating‐factor activity differed in the 2 strains. SJL/J and C57BL/6J mice have been previously shown to be susceptible to low‐dose‐radiation‐induced leukemia. The coleukemogenic effects of both cytokines in 3 different models of experimental leukemogenesis is demonstrated.
Over‐expression of the S13 ribosomal protein in actively growing cells
Authors: Denis Marc G. , Chadeneau Corinne , Lecabellec Marie‐Thérèse , Lemoullac Béatrice , Lemevel Bernard , Meflah Khaled , Lustenberger Patrick 
Published: February 2007

AbstractIn order to define biological markers of aggressiveness, 2 rat colon‐carcinoma cell lines differing by their tumorigenicity were used to clone genes over‐expressed in colon carcinoma as compared with normal epithelial cells. A progressive rat colon‐carcinoma clone (PROb) cDNA library was hybridized with 32P‐cDNA synthesized from mRNA prepared from these PROb cells, or from regressive cells (REGb) derived from the same tumor. Several clones were isolated after the initial screening. The specificity of each clone was confirmed by RNA blotting. One of these (B9) was found to hybridize to an mRNA 30‐fold more abundant in PROb cells than in normal adult rat colon, and was therefore selected for further study. No gene amplification was detected by Southern blot analysis, indicating that the difference in mRNA content was most likely due to an increased transcription of this gene. Sequencing of the cDNA revealed approximately 98% homology with the rat S13 ribosomal protein. The expression level of this gene was determined in a series of rat cell lines with different growth rates. A good correlation was found between these 2 parameters. Our data suggest that the S13 ribosomal‐protein gene can be used to evaluate the growth rate of tumor cells, which might be correlated with their aggressiveness. In an initial trial experiment, S13 ribosomal‐protein mRNA was detected in a series of human colorectal tumors by in situ hybridization. A strong signal was seen in the 4 tumors analyzed.
Evaluation of S9788 as a potential modulator of drug resistance against human tumour sublines expressing differing resistance mechanisms In Vitro
Authors: Hill Bridget T. , van der Graaf Winette T. A. , Hosking Louise K. , De vries Elisabeth G. E. , Mulder Nanno H. , Whelan Richard D. H. 
Published: February 2007

AbstractSignificant activity has been identified using S9788, a triazineaminopiperidine derivative, as a new modulator of multidrug resistance against a series of drug‐resistant human tumour‐cell lines in vitro. Maximal non‐cytotoxic concentrations (i.e., those resulting in ≤ 10% cytotoxicity) of S9788 or verapamil were tested in combination with vinblastine, Adriamycin or vincristine and cytotoxicity was evaluated using a clonogenic assay, or the metabolic dye reduction MTT assay, or by monitoring growth inhibition. Under these conditions, the extent of resistance modulation by verapamil and by S9788 was comparable in the various tumour cell lines tested, although a definite concentration‐dependent modulation was noted with both compounds. The highest dose‐modification factors were noted in the highly vinblastine‐resistant classic multi‐drug‐resistant subline CEM/VLB 100, although resistance reversal was only partial. Resistance modulation by both verapamil and S9788 was noted in 4 drug‐selected resistant sublines and 4 “intrinsically” resistant human tumour cell lines, which all exhibited significant P‐glycoprotein expression. In contrast, in 2 drug‐resistant human tumour sublines (GLC4/ADR and CEM/ VM‐I) characterized by altered topoisomerase‐II activity and proving to be P‐glycoprotein‐negative, no resistance modulation relative to parental cells was observed. These data are consistent with the proposal that resistance modulation is mediated by interaction between S9788 and P‐glycoprotein and support its clinical evaluation in patients with P‐glycoprotein‐positive tumours.
UICC/CRC conference on targeted cancer therapy
Authors: Begent R. H. J. 
Published: February 2007

AbstractSelective delivery of therapy to tumour cells has been a goal of cancer therapy since the beginning of this century. Progress has been slow until recently when a host of technical developments has made effective therapy of cancer appear to be within reach. Different technologies are contributing in several clinical areas. The UICC Committee for Future Prospects in Cancer Therapy and the Cancer Research Campaign held a meeting at the Royal Free Hospital School of Medicine in London to bring together diverse groups working on aspects of targeted cancer therapy.Targeted therapy depends on tumour recognition, a delivery system and a therapeutic modality for tumour killing.
Growth‐regulatory mechanism of two human esophageal‐cancer cell lines in protein‐free conditions
Authors: Iihara K. , Shiozaki H. , Oku K. , Tahara H. , Doki Y. , Oka H. , Kadowaki T. , Iwazawa T. , Inouh M. , Mori T. 
Published: February 2007

AbstractWe investigated the growth‐regulatory mechanism of 2 esophageal squamous‐cancer cell lines, TE2‐NS and TE3‐OS cells, both of which can grow stably in protein‐free conditions in vitro. Protein‐free conditioned media from TE2‐NS and TE3‐OS cells stimulated the growth of these cells. Exogenous epidermal growth factor (EGF), transforming growth factor‐alpha (TGF‐α), insulin‐like growth factor (IGF)‐I and ‐II enhanced cell proliferation by 2.2‐ to 3.8‐fold in protein‐free conditions, as compared with an untreated control. Receptor‐binding assays showed that both TE2‐NS and TE3‐OS cells possessed a single class of high‐affinity binding sites for IGF‐I and 2 classes of binding sites for TGF‐α, as confirmed on the cell membrane by immunochemistry. These results suggest that EGF, TGF‐α and IGFs are candidates for the autocrine growth factor in cancer cells. The addition of inhibitory monoclonal antibodies against TGF‐a and EGFR, but not those against either EGF or IGF‐IR, significantly inhibited growth of the cells. Immunocytochemical staining and ELISA of the conditioned media both confirmed the production of TGF‐α protein, but not EGF protein, in these cell lines. The data for a protein‐free culture system strongly suggested that TGF‐α, but not EGF or IGF, is biologically important as an autocrine growth factor in the growth of these cell lines in vitro.