bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serologic mapping and biochemical characterization of the carcinoembryonic antigen epitopes using fourteen distinct monoclonal antibodies
Authors: Kuroki Masahide , Greiner John W. , Simpson Jean F. , Primus F. James , Guadagni Fiorella , Schlom Jeffrey 
Published: February 2007

AbstractA series of 14 monoclonal anti‐carcinoembryonic antigen (CEA, Mr 180,000) antibodies (MAbs) that show a strong degree of selective reactivity for human colon carcinomas versus normal adult tissues were used to construct a serological map of the CEA molecule. The MAbs were generated using extracts of colon carcinomas as immunogen and are thus given a COL designation. None of the 14 COL‐MAbs tested were reactive with purified non‐specific cross‐reacting antigen (NCA, Mr 55,000) from normal lung, although some showed reactivity to human granulocytes. All the COL‐MAbs tested were reactive with normal fecal antigen‐2 (NFA‐2, Mr170,000); however, many of the COL‐MAbs demonstrated a higher affinity constant to CEA than to NFA‐2. Cross‐competition radioimmunoassays classified the 14 COL‐MAbs into 5 groups. The chemical nature of the COL‐binding domains was tested using chemically or enzymatically treated CEA; all reacted with periodate‐treated CEA and deglycosy‐lated CEA, indicating that the COL‐reactive epitopes appear to be of a proteinaceous nature. Heat treatment, reduction, alkylation, pepsin digestion or pronase treatment of CEA, however, gave differential results with respect to COL binding. Antibody titration experiments were carried out to define differential reactivities to colorectal carcinoma versus NCA‐containing granulocyte extracts; these results were compared with results obtained using several anti‐CEA MAbs that have been used in clinical trials. Granulocyte binding and biochemical studies showed that the COL MAbs may distinguish as many as 7 to 10 CEA epitopes.
Human tumor‐infiltrating lymphocyte (TIL) cytotoxicity facilitated by anti‐T‐cell receptor antibody
Authors: Schoof Deric D. , Jung Sung‐Eun , Eberlein Timothy J. 
Published: February 2007

AbstractLong‐term growth of tumor‐infiltrating lymphocytes (TIL) in high concentrations of rlL‐2 is required for generation of therapeutic numbers of cells for adoptive immunotherapy of human cancer. Under these conditions rlL‐2 promotes both anti‐tumor cytotoxicity and lymphocyte growth from tumors of several histological types. In a series of 16 consecutive tumors, studies of TIL‐mediated cytotoxicity against different tumor targets were characterized by an initial strong tumor‐non‐specific cytotoxicity. With time, TIL bulk cultures became non‐cytotoxic against all targets (median time = 38 days). Non‐cytotoxic TIL bulk populations were capable of mediating strong cytotoxic responses if pre‐treated with anti‐T‐cell antigen receptor antibody (TcR) before addition to targets. TIL populations were not, however, uniformly susceptible to anti‐TcR‐mediated cytotoxicity. Anti‐TcR‐mediated cytotoxicity was confined to CD8+ bulk populations (defined as populations with a CD4/CD8 ratio <l), with virtually no cytotoxicity observed in CD4+ populations (CD4/CD8 ratio >2), (p < 0.01). Both CD4 and CD8 populations expressed TcR antigen reactive with anti‐TcR antibody. These results indicate that, despite poor in vitro anti‐tumor cytotoxicity in short‐term assays, CD8+ TIL are fully competent cytotoxic effector cells when subjected to strong activation signals via the TcR complex. In addition, these results imply that adoptively transferred CD4+ populations of TIL have in vivo biologic functions quite distinct from those of CD8+ populations and, further, that disparate clinical outcomes could reasonably be expected from the adoptive transfer of either population alone.
Cancer incidence among spouses of patients with colorectal cancer
Authors: Mellemgaard Anders , Jensen Ole Møller , Lynge Elsebeth 
Published: February 2007

AbstractThe risk of colorectal cancer was examined among spouses of approximately 10,000 colorectal cancer patients. A total of 8,095 spouses were identified, and cancer cases in this cohort were sought in the Danish Cancer Registry. No excess risk was found for colorectal cancer as such. The data were also anal/zed by subsite of the large bowel for the index cases and for the spouses, respectively. The estimated relative risks were in general close to unity, the only exception being the risk of right‐sided colon cancer among husbands of index cases with left‐sided colon cancer, RR = 2.17 (p < 0.05). The absence of excess risk was noted regardless of the duration of marriage. The risk of other cancers with a presumed etiology similar to that of colorectal cancer (cancer of the uterine corpus, breast, prostate and biliary tract) was also close to expected values.
in situ oestrone synthesis in normal breast and breast tumour tissues: Effect of treatment with 4‐hydroxyandrostenedione
Authors: Reed M. J. , Owen A. M. , Lai L. C. , Coldham N. G. , Ghilchik M. W. , Shaikh N. A. , James V. H. T. 
Published: February 2007

AbstractAn isotopic infusion technique has been used in an attempt to determine the contribution that local, in situ, oestrone synthesis makes to the oestrogen content of breast tumours. 3H‐Androstenedione and 14C‐oestrone were infused into women with advanced breast cancer for 12 hr before operation. At surgery, normal breast and breast tumour biopsy samples were obtained and 3H‐androstenedione, 3H‐oestrone derived from 3H‐androstenedione and 14C‐oestrone were isolated and measured. DNA polymerase α activity, a marker of cellular proliferation, was also measured to examine whether local synthesis of oestrone exerted a biological effect. The study was repeated after patients had been treated with the aromatase inhibitor, 4‐hydroxyandrostenedione, before undergoing further surgery for removal of their tumours. In 4/6 tumours examined, in situ synthesis of 3H‐oestrone from 3H‐androstenedione accounted for the major part (84.3 ± 9.0%) of the 3H‐oestrone detected, while no significant in situ synthesis occurred in 2 other tumours. Although treatment with 4‐hydroxyandrostenedione did not significantly alter the uptake of 3H‐androstenedione or 14C‐oestrone into breast tissues, in situ formation of 3H‐oestrone was only detected in one tumour sample after treatment. DNA polymerase α activity decreased in 4/6 tumours after treatment with 4‐hydroxyandrostenedione. Overall, however, there was no significant correlation between the level of 3H‐oestrone formed in situ and DNA polymerase α activity (r = 0.38, NS). It is concluded that in some, but not all, breast tumours in situ formation of oestrone can make an important contribution to the oestrogen content of breast tumours.
Polymorphism of the c‐Ha‐ras‐1 proto‐oncogene in sporadic and familial breast cancer
Authors: Barkardóttir Rósa B. , Jóhannsson Óskarth , Arason Adalgeir , Gudnason Vilmundur , Egilsson Valgardur 
Published: February 2007

AbstractTwo studies on breast cancer patients are described. Our aim was to examine whether the combined frequency of rare c‐Ha‐ras‐l alleles in cancer patients was raised. Firstly, the c‐Ha‐ras‐l locus in 56 breast cancer patients and 48 controls was examined for restriction fragment length polymorphism (RFLP) by Southern blot analysis of leukocyte DNA. Four predominant allelic fragments were found in both groups together with a variety of rare alleles. The 2 groups did not differ significantly in overall distribution of c‐Ha‐ras‐l alleles. Rare alleles combined were about as frequent in cases (7.1 %) as in controls (6.3%). Secondly, 53 members of 3 families having a high incidence of breast cancer were c‐Ha‐ras‐l genotyped. None of 10 affected members was found to carry a rare c‐Ha‐ras‐l allele. The only c‐Ha‐ras‐l allele common to 11 affected members was a 6.8‐kb allele which is found in 72% of the controls. Furthermore, this allele was found with equal frequency in affected and non‐affected family members.
Tumor blood flow: The principal modulator of oxidative and glycolytic metabolism, and of the metabolic micromilieu of human tumor xenografts in vivo
Authors: Kallinowski F. , Schlenger K. H. , Kloes M. , Stohrer M. , Vaupel P. 
Published: February 2007

AbstractWe have investigated therapeutically relevant pathophysiological parameters of human breast and lung cancer xenografts in nude rats. All lung cancers and one breast cancer exhibited rapid growth and high blood flow values paralleled by high metabolic rates. The tissue of these tumors was well oxygenated up to very advanced growth stages. Xenografts from other breast cancer cell lines grew much more slowly, were poorly perfused, and exhibited low metabolic rates. Here, tumor hypoxia and tissue acidosis were evident. These results indicate that significant differences in the metabolic micromilieu can be detected in human tumors; these are due to varying perfusion rates and may be partly responsible for failure to obtain tumor control in individual patients.
Fibronectin/laminin and their receptors in aberrant growth control in FR3T3 cells transformed by ha‐ras oncogene and epidermal growth factor gene
Authors: Chakrabarty Subhas , Jan Yih , Levine Alan , McClenic Brian , Varani James 
Published: February 2007

AbstractFR3T3 cells transfected with either the Ha‐ras oncogene or the epidermal‐growth‐factor (EGF) gene demonstrate the transformed phenotype as indicated by in vitro and in vivo criteria. We have examined non‐transformed FR3T3 cells as well as Ha‐ras‐oncogene‐transformed and EGF‐gene‐trans‐formed cells for expression of cell surface fibronectin and cell surface laminin. Fibronectin was absent from the surface of the Ha‐ras‐oncogene‐transformed cells but present on both the EGF‐gene‐transformed cells and the non‐transformed FR3T3 cells. Laminin was present on the cell surface in all 3 lines. The lack of surface fibronectin on the Ha‐ras‐oncogene‐transformed cells was associated with reduced fibronectin production as indicated by immunoblotting of whole cell extracts and by ELISA. Concomitantly, there was a significant reduction of fibronectin binding by the Ha‐ras‐oncogene‐transformed cells as compared to their EGF‐gene‐transformed and non‐transformed counterparts. The Ha‐ras‐oncogene‐transformed cells demonstrated reduced cell‐substrate adhesiveness relative to the other two cell lines, as indicated by rates of attachment and spreading on plastic culture dishes in the presence of bovine serum albumin. They also demonstrated reduced adhesiveness in response to fibronectin but not laminin. Taken together, our results suggest that aberrant expression of fibronectin/fibronectin receptors is associated with Ha‐ras‐oncogene‐induced transformation. In contrast, transformation by the EGF gene does not appear to involve aberrant expression of fibronectin/ fibronectin receptors.
Relationship between tumorigenicity and the dosage of lymphoma‐ vs. Normal‐parent‐derived chromosome 15 in somatic cell hybrids between lymphoma cells with rearranged pvt‐1 gene and normal cells
Authors: Uno Masatsune , Wirschubsky Zwi , Wiener Francis , Klein George 
Published: February 2007

AbstractSomatic cell hybrids were generated between YACUT, a doubly drug‐resistant subline of YAC‐I (a Moloney‐virus‐induced T‐cell lymphoma of strain A/Sn origin with 2 pro viral insertions near the pvt‐1 locus) and normal diploid fibroblasts of CBAT6T6 origin. Three independent fusions were performed. Three uncloned hybrid cultures and 9 independently‐derived clones were tested for tumorigenicity by the inoculation of graded cell numbers into syngeneic hosts. One of 3 uncloned hybrid cultures and 3 of 9 clones were weakly tumorigenic (take incidence 0%), and 1 of 3 uncloned hybrid cultures and 6 clones were highly tumorigenic (take incidence >80%). One weakly tumorigenic hybrid and 3 weakly tumorigenic clones carried 3 copies of the tumor‐derived chromosome 15 and 2 copies of the normal fibroblast‐derived t(l4;l5) chromosomes. In contrast, 2 highly malignant hybrid clones lost one copy of the normal‐fibroblast‐derived t(14;15), but contained increased numbers (3.44‐4.44) of the tumor‐derived chromosome 15. Four tumorigenic segregants selected from the weakly tumorigenic fibroblast hybrids by in vivo inoculation showed the same cytogenetic change as the highly tumorigenic hybrid clones, in that the ratio of the normal:tumor‐derived chromosomes 15 changed from 1.18‐1.55 to 4.11‐5.71. Tumorigenicity was thus associated with a modified balance between the tumor vs. the normal‐parent‐derived 15‐chromosomes. Instead of the usual 3:2 ratio, the tumor‐derived 15‐chromosomes increased disproportionately, whereas the relative number of the normal‐parent‐derived 15‐chromosome decreased, as a rule. These results suggest that amplification of the lymphoma‐derived chromosome 15 favors tumorigenicity, but that this effect is counteracted by some influence emanating from the normal‐parent‐derived homologous chromosome.
Efficacy of two‐route chemotherapy using cis‐diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, in combination with angiotensin II for rat liver tumor
Authors: Hasuda Keitaro , Kobayashi Hiroaki , Aoki Ken , Taniguchi Shun'ichiro , Baba Tsuneo 
Published: February 2007

AbstractTo improve the therapeutic effects of conventional TRC using i.a. CDDP plus simultaneous i.v. STS in a rat liver tumor, we made use of the AT‐II‐induced hypertension method, in combination with TRC. The decrease in tumor area (‐15%), measured 8 days after the TRC using CDDP 12 mg/ kg i.a. plus i.v. post‐administration (5 min later) of STS 1,264 mg/kg, was much greater than that (+13%) seen in the conventional TRC, but BUN level was elevated (44.9 mg/dl). AT‐II (15 μg/kg) administered i.a. simultaneously with CDDP normalized the BUN level (20.3 mg/dl) and further decreased (‐15% to ‐31%) the tumor area (modified TRC). The modified TRC also exhibited a higher anti‐tumor effect than did CDDP 3 mg/kg with AT‐II i.a. (5%) at a similar BUN level (22.2 mg/dl). Loss of body weight, decrease in WBC count and changes in serum transaminases of rats treated with the modified TRC were tolerable. The improved therapeutic effect of the modified TRC was explained as follows: during AT‐ll‐induced hypertension, (1) CDDP delivery to the tumor was increased by 150% and (2) CDDP delivery to the kidney was decreased by 35%. The latter effect of AT‐II made feasible the post‐administration of STS to CDDP.
A survey of the human T‐cell lymphotropic virus type I (HTLV‐I) in South‐Western Colombia
Authors: Maloney Elizabeth M. , Ramirez Hernan , Levin Arthur , Blattner William A. 
Published: February 2007

AbstractTo evaluate altitude of birthplace and residence as factors associated with geographic clustering of HTLV‐I infection in Colombia, we sampled a total of 670 current residents of the South Pacific coastal lowland and of upland regions (Cali and environs) of the Valle and Cauca Provinces, located at an altitude of 3,100 ft. Among the 255 lowland study subjects, 4.3% had antibody against HTLV‐I, compared to 0.9% of the 415 upland study subjects. A hypothesis emerging from this study is that the lower socio‐economic status of lowland residents and associated diseases, particularly untreated syphilis and other sexually transmitted diseases, may explain the increased HTLV‐I seropositivity rates in this population.
Epidermal growth factor receptors in spontaneous ovarian granulosa cell tumors of swr‐derived mice
Authors: Tennent Barbara J. , Beamer Wesley G. , Shultz Leonard D. , Adamson Eileen D. 
Published: February 2007

AbstractEpidermal growth factor (EGF) receptor binding properties were examined in spontaneous ovarian granulosa cell (GC) tumors from SWR and SWR‐derived strains of mice. EGF binding was measured at room temperature in tissue ho‐mogenates from GC tumors and normal ovaries from adult randomly cycling mice. GC tumor tissue displayed significantly increased EGF binding and 2 receptor populations (Rl and R2). Normal ovarian tissue appeared to have only one receptor population with a dissociation constant (Kd) similar to the Rl (high‐affinity) receptor in GC tumors. In subsequent experiments, GC tumor and normal granulosa cells from immature mice were analyzed in primary cultures for EGF binding, immunofluorescence microscopy for receptors, and cell proliferation. After 24 hr in culture, the GC tumors bound 10‐fold more EGF/ug protein than did normal granulosa cells. GC tumor cells, but not normal granulosa cells, showed specific immunofluorescence when reacted with a polyclonal antibody to mouse EGFR. During 96 hr in culture, GC tumor cells, but not normal cells, showed a significant proliferative response to EGF. In conclusion, the EGF binding capacity is markedly increased in GC tumor cells and the proliferation data suggest that this growth factor supports tumor growth in the SWR model system.
Intraperitoneal and subcutaneous xenografts of human ovarian carcinoma in nude mice and their potential in experimental therapy
Authors: Massazza Gabriella , Tomasoni Antonella , Lucchini Valeria , Allavena Paola , Erba Eugenio , Colombo Nicoletta , Mantovani Alberto , D'Incalci Maurizio , Mangioni Costantino , Giavazzi Raffaella 
Published: February 2007

AbstractHuman ovarian carcinomas (HOC) were established s.c. and i.p. in nude mice and the biological characteristics were investigated for 4 xenografts. HOC8 and HOC 18, derived respectively from a primary tumor of the ovary and a pleural effusion (from 2 different patients) were established s.c. in nude mice. HOC10 and HOC22, derived from the ascites of 2 patients, were directly established as ascites after i.p. injection in nude mice. The s.c. and i.p. growth behavior of the 4 HOC lines was investigated. HOC18, HOC8 and HOC22 cells produced progressively growing tumor after s.c. injection but HOC10 ascites would not grow s.c. The cell suspension derived from HOC18 only produced carcinomatosis upon i.p. injection, while HOC8 cells produced both ascites and carcinomatosis. The 2 ascites HOC10 and HOC22 produced ascites in nude mice, but only HOC22 formed i.p. carcinomatosis. Histopathological characteristics of the patients' primary tumors persisted in nude mice, regardless of the site of tumor implantation. DNA histograms of the xenografts closely matched the patients' tumors and remained stable at different passages. Cisplatin, adriamycin and cyclophosphamide given i.v. were tested against HOC8 and HOC18 growing s.c. and HOC22 and HOC10 growing i.p. HOC8 showed a significant response to DDP and almost no sensitivity to ADR and CTX. HOC18 showed only moderate growth delay with all 3 drugs. Mice bearing HOC10 and HOC22 ascites had a prolonged survival time after DDP and ADR treatment.
Rabbit blastocoelic fluid regulation of tumor‐cell proliferation in vitro
Authors: Lambert Raymond D. , Gosselin Sylvie , Pothier Francois , Morin Cybele , Veilleux Raymonde , Roy Michel , Fortier Michel A. 
Published: February 2007

AbstractTo determine whether rabbit blastocoelic fluid could inhibit tumor‐cell proliferation, day‐9 and day‐12 embryonic fluids, together with autologous and homologous sera, were collected from pregnant or pseudopregnant rabbits and tested against 13 different cell lines and on human carcinoma cells in primary culture. An inhibitory effect on cell proliferation was observed in the presence of blastocoelic fluids, but not with homologous or heterologous sera. This suppression was higher with samples collected at day 12 than at day 9 of pregnancy. No such inhibition could be detected on one‐cell rabbit embryos or on freshly prepared uterine stromal or myometrial cells. In addition, the inhibitory activity on tumor cells was completely reversible upon removal of the fluids. Incorporation of 3H‐thymidine, 3H‐uridine and 35S‐methionine revealed that, in the presence of blastocoelic fluids, both DNA and RNA syntheses were rapidly inhibited. Inhibition of protein synthesis did not occur before 24 hr of treatment. We conclude that rabbit blastocoelic fluid suppresses the proliferation of tumor cells via inhibition of RNAand DNA synthesis by a process which may involve the expression of growth suppression gene(s).
Inhibition by cysteamine of hepatocarcinogenesis induced by N‐nitrosomorpholine in sprague‐dawley rats
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako 
Published: February 2007

AbstractThe effect of cysteamine (2‐aminoethanethiol hydrochloride) on hepatocarcinogenesis induced by N‐nitrosomor‐pholine (NNM) was investigated in male Sprague‐Dawley rats. Rats received alternate‐day s.c. injections of cysteamine, and beginning in experimental week 3 were given drinking water containing NNM for 8 weeks. Pre‐neoplastic and neoplastic lesions staining positive for gamma‐glutamyl transpeptidase (GGT) or glucose‐6‐phosphate dehydrogenase (G6PD) were examined by histochemical techniques. In week 18, quantitative histological analysis showed that prolonged administration of cysteamine resulted in a significant reduction in the number of GGT‐positive and G6PD‐positive hepatic lesions. Histologically, hepatocellular carcinomas were significantly fewer and smaller in GGT‐positive and G6PD‐positive lesions in rats treated with cysteamine than in untreated rats. Administration of cysteamine also caused a significant decrease in the liver norepinephrine concentration and in the labelling indices of pre‐neoplastic lesions and the surrounding liver. Our findings indicate that cysteamine inhibits hepatocarcinogenesis; this may be related to its reducing effect on norepinephrine concentration in the liver and its subsequent inhibition of cell proliferation in neoplastic lesions and surrounding hepatocvtes.
Two different anti‐erythroid monoclonal antibodies in immunodiagnosis of human leukemias: A comparative study
Authors: Tupitsyn N. N. , Mechetner E. B. , Baryschnikov A. Ju. , Drozdova T. S. , Frenkel M. A. , Ievleva E. S. , Kiselev A. V. , Perilov A. A. , Peterson I. S. , Probatova N. A. , Protasova A. K. , Rozinova E. N. , Tonevitsky A. G. , Volkova M. A. 
Published: February 2007

AbstractTo date, only anti‐glycophorin‐A monoclonal antibodies (MAbs) have been widely used as anti‐erythroid probes in the diagnosis of leukemias. We have examined blood, bone‐marrow and lymph‐node samples from 474 patients, adults and children, with different hemopoietic malignancies, using a panel of MAbs including 2 anti‐erythroid MAbs directed to glycophorin‐A and an antigen of erythroblasts, Ag‐Eb. MAb HAE9 directed against a human epitope of Ag‐Eb has earlier been shown to be highly specific for immature erythroid cells. Of all the patients, 2.7% demonstrated glycophorin‐A expression on blast cells, while anti‐Ag‐Eb MAb HAE9 reacted positively with cells from 6.0% of patients. Samples from 31 of 474 (6.5%) patients expressed one or both erythroid markers. Our results indicate that MAb HAE9 may be useful, in combination with anti‐glycophorin‐A MAbs, as an anti‐erythroid probe for immunophenotyping human leukemias.