bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐idiotype vaccine against Hodgkin's lymphoma: Induction of B‐ and T‐cell immunity across species barriers against cd30 antigen by murine monoclonal internal image antibodies
Authors: Pohl C. , Renner C. , Schwonzen M. , Sieber M. , Lorenz P. , Pfreundschuh M. , Diehl V. 
Published: February 2007

AbstractMurine monoclonal antibody HRS‐4 (Ab,), which defines the cell‐bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti‐idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS‐4 were shown to be anti‐idiotypic Ab2β carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS‐4 and effectively inhibited binding of HRS‐4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH‐coupled Ab2β 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH‐coupled 14G9 and 9G10 exhibited a statistically significant (p < 0.01) delayed‐type hyper‐sensitivity reaction against CO30 expressing Hodgkin‐derived L540‐cells. We conclude from these data that Ab2β* 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30‐specific T‐cell‐ and B‐cell‐mediated immune response in mice and even across species barriers in rabbits. These CD30 anti‐id antibodies may hold promise for use as vaccines against CD30‐antigen‐expressing lymphomas.
Enhancement by thyroxine of experimental carcinogenesis induced in rat colon by azoxymethane
Authors: Iishi Hiroyasu , Tatsuta Masaharu , Baba Miyako , Okuda Shigeru , Taniguchi Haruo 
Published: February 2007

AbstractThe effect of thyroxine (T4) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon mucosa were investigated in Wistar rats. Rats were given AOM by injection once a week for 10 weeks, together with T4 in depot form until the end of the experiment. Administration of T4 resulted in a significant increase in the incidence of colon tumors in week 35. However, it did not influence the histological appearance of the colon tumors or the histological types and depths of involvement of colon adenocarcinomas. Furthermore, it caused a significant increase in the labeling index of the colon during, but not after, AOM treatment. Our findings indicate that T4 enhances the development of colon tumors, which may be related to its effect in increasing proliferation of epithelial cells in the colon mucosa during administration of the carcinogen.
Differential expression of myogenic regulatory genes, MyoD1 and myogenin, in human rhabdomyosarcoma sublines
Authors: Hosoi Hajime , Sugimoto Tohru , Hayashi Yasuhide , Inaba Toshiya , Horii Yoshihiro , Morioka Hiroyuki , Fushiki Shinji , Hamazaki Minoru , Sawada Tadashi 
Published: February 2007

AbstractA cell line (SCMC‐MM‐1) was established from a human abdominal tumor that was initially diagnosed as a malignant mesenchymoma by histological, immunohistochemical and clinical criteria. The cell line was composed of 2 morphologically and immunohistochemically distinct cell types, one with a small polygonal phenotype (P‐type), characterized by the immune‐staining of vimentin and the presence of a few electron‐microscopically visible organelles, and the other with a giant tubular phenotype (T‐type), characterized by the immunostaining of desmin, α‐sarcomeric actin and skeletal‐muscle myosin, and the presence of thick and thin myofilaments and Z‐line materials. The parental cell line was cloned into 2 sublines, a P‐type clone (SCMC‐MM‐1‐19P) and a T‐type clone (SCMC‐MM‐1–1T), which shared both 2q37 and 11p15 translocations, the characteristic chromosomal aberrations for rhabdomyosar‐coma, with the parental SCMC‐MM‐I cell line. Northern‐blot analyses of the myogenic regulatory genes, including MyoDI and myogenin, demonstrated the expression of MyoDI in both of these sublines. Myogenin was very weakly expressed in the SCMC‐MM‐1–19P subline, but strongly expressed in the SCMC‐MM‐1–1T subline. Chromosomal and myogenic‐regulatory‐gene analyses revealed that both of these sublines were rhabdomyo‐sarcoma cell lines. Furthermore, the regulatory‐gene analyses indicated that these 2 sublines represented 2 distinct differentiation stages of myoblasts, and that MyoD1 and myogenin could serve as the lineage marker and the differentiation marker, respectively, of human rhabdomyosarcoma.
Relationships of DNA ploidy, S‐phase fraction and hormone receptor status to tumor stage in breast cancers detected by population screening
Authors: Stål Olle , Brisfors Ann , Carstensen John , Ferraud Lilianne , Hatschek Thomas , Nordenskjöld Bo 
Published: February 2007

AbstractCellular DNA content was analyzed by flow cytometry and estrogen and progesterone receptors by an immuno‐biochemical method (EIA) in a consecutive series of 807 frozen breast‐cancer samples. Before the beginning of the study, a mammography screening program had been introduced in the region where the tumors were diagnosed. Forty percent of the tumors were judged as DNA diploid, of which 86% were ER‐positive. The proportion of ER‐positive tumors among non‐diploids was significantly lower, or 73% (p < 0.001). S‐phase fraction (SPF) was estimated in 691 cases (86%), with an overall mean of 8.4%. DNA ploidy as well as ER and PR status were independently related to SPF. Unlike the results obtained in most older series, the biological variables correlated significantly with tumor staging factors such as lymph‐node status and tumor size. Patients with nodal involvement, especially those with 4 positive nodes or more, more often had tumors which were receptor‐negative, DNA aneuploid and of high S‐phase rate. Large tumor size was significantly related to lower frequencies of receptor positivity and strongly related to DNA aneuploidy and high S‐phase fraction. Multiple linear regression analysis showed that these relationships were mainly due to the associations of SPF with the other variables. S‐phase fraction was the only independent factor predicting nodal status, while DNA ploidy in addition to SPF was associated with tumor size. In fact, DNA ploidy (p < 0.001), ER and PR status (p < 0.001, p = 0.002), nodal status (p = 0.04) and tumor size (p < 0.001) were all independently related to SPF.
Anti‐tumor and immunomodulatory activity of intraperitoneal IFN‐γ in ovarian carcinoma patients with minimal residual tumor after chemotherapy
Authors: Colombo N. , Peccatori F. , Paganin C. , Bini S. , Brandely M. , Mangioni C. , Mantovani A. , Allavena P. 
Published: February 2007

AbstractEight patients with epithelial ovarian carcinoma persisting after chemotherapy, selected for having a residual tumor no larger than I cm in diameter, were treated intra‐peritoneally (i.p.) with recombinant interferon‐γ twice weekly for 3 months. Toxicity consisted of fever and malaise in all patients and a transient rise in hepatic enzyme levels in 3 patients. The cytotoxic function of peripheral blood and peritoneal tumor‐associated lymphocytes (TAL) and macrophages (TAM), was studied using cell lines as targets. I.p. IFN‐γ augmented the cytotoxic activity of lymphocytes and mononuclear phagocytes: stimulation was more marked and more frequently observed with TAL and occasionally TAM than with blood effectors, suggesting preferential modulation at the site of tumor growth and IFN administration. Surgical laparotomy revealed that I patient had a complete response, 2 a partial response and 2 had stable disease, while 3 patients had progressive disease. In this small series of patients there was no obvious, strict correlation between immunomodulation by IFN‐γ and clinical response. These results indicate that, in contrast to its lack of activity in advanced ovarian carcinoma, IFN‐γ has definite immunomodulatory and antitumor activity in the presence of limited tumor burden.
In vitro response of human small‐cell lung‐cancer cell lines to chemotherapeutic drugs; no correlation with clinical data
Authors: Smit E. F. , de Vries E. G. E. , Timmer‐Bosscha H. , de Leij L. F. H. M. , Oosterhuis J. W. , Scheper R. J. , Weening J. J. , Postmus P. E. , Mulder N. H. 
Published: February 2007

AbstractThree cell lines derived from small‐cell lung carcinoma (SCLC) tumors of patients who had no clinical response after treatment with a multi‐drug regimen were compared to 3 cell lines derived from tumors of patients who, upon treatment, showed a complete clinical response. These 2 groups of cell lines were considered to represent the in vitro counterparts of the 2 extremes of the clinical spectrum of sensitivity for chemotherapeutic drugs in small‐cell lung cancer. To assess whether the in vivo (in)sensitivity of a tumor to a certain drug regimen is retained in vitro, the cell lines were tested for drug sensitivity using the microtiter‐well tetrazolium assay and the results were compared with the in vivo data. No correlation was found. Since in vitro models using cell lines are based on the assumption that a cell line reflects the properties of the tumor from which it is derived, several additional parameters such as MAb staining against different SCLC‐associated antigens and DNA content were analyzed in the biopsies and the cell lines. The results showed that selection of discrete tumor‐cell populations in vitro occurs. Results of in vitro chemosensitivity testing for individual SCLC patients should be interpreted with caution.
Transformed rat pancreatic islet‐cell lines established by BK virus infection in vitro
Authors: Haukland Hanne Husom , Vonen Barthold , Traavik Terje 
Published: February 2007

AbstractSingle‐cell suspensions of primary rat pancreatic islet cells were infected with BK virus (BKV) prototype (Gardner) and the naturally occurring BKV strain (TU), isolated from human urine. These viral strains have different sequences in their non‐coding control regions which contain promoter‐enhancer elements and origin of DNA replication. Uninfected cell cultures disintegrated within 3 weeks, while a varying number of virus‐infected cultures were immortalized and a majority exhibited focal areas of 2‐dimensional growth. A significantly higher proportion of the BKV (TU)‐ than of the BKV (Gardner)‐infected cultures were immortalized. Large tumor (T) antigen expression was evident in virus‐infected cultures from day 4 post infection (p.i.), while insulin secretion decreased steadily during the first weeks of culture. Two cell lines were established from BKV (TU)‐infected cultures. Line 5A4 was contact‐inhibited, growing as a dense monolayer, while 6A3 demonstrated foci of 2‐dimensional growth. Both cell lines have retained their morphology and T‐antigen expression for approximately 130 passages. At high passages a low level of intracellular insulin, but no secretion into media, was detected. Based on standard biological tests (reduced serum requirements, growth at low cell density, anchorage‐independent growth and tumor induction in nude mice) both cell lines have a fully transformed phenotype, but 6A3 appears to be more malignantly transformed. Since both cell lines were established simultaneously from the same primary cells with the same virus batch, they provide an opportunity to study the transforming mechanisms of BKV in a relative context.
Some approaches to improve the therapeutic effectiveness of adoptive chemoimmunotherapy with spleen cells from melphalan‐treated BALB/C mice bearing a large MOPC‐315 tumor
Authors: Weiskirch Larry M. , Mokyr Margalit B. 
Published: February 2007

AbstractSpleen cells from BALB/c mice that are in the process of eradicating a large MOPC‐315 tumor following low‐dose L‐PAM therapy (L‐PAM TuB spleen cells) were previously shown to be capable of bringing about the complete regression of a large (15 to 20 mm) s.c. MOPC‐315 tumor in a substantial percentage of T‐cell‐deficient (athymic nude) mice that had been treated with low‐dose L‐PAM (adoptive chemo‐immunotherapy; ACIT). Here we show that aggressive depletion of CD4+ T‐cells by treatment both of spleen‐cell donors and of recipients with anti‐L3T4 monoclonal antibody (MAb) greatly improved the therapeutic effectiveness of L‐PAM TuB spleen cells in ACIT. In the light of the apparent importance of cytotoxic T‐lymphocytes (CTLs) for tumor eradication in low‐dose L‐PAM‐treated MOPC‐315‐tumor bearers, it is interesting that treatment of L‐PAM TuB spleen‐cell donors with anti‐L3T4 MAb was found to result in the generation of enhanced splenic anti‐MOPC‐315 cytotoxicity. Although most athymic nude mice in which the tumor had apparently completely regressed following ACIT remained tumor‐free, approximately 1/3 of the mice relapsed. However, a substantial percentage of the relapsing mice were rescued by a low dose of L‐PAM, which was not effective in causing tumor regression in athymic nude mice bearing a comparably large tumor if the mice had not been subjected previously to ACIT. Almost all athymic nude mice that had been „cured”︁ of a large MOPC‐315 tumor by ACIT but did not resist a subsequent MOPC‐315 tumor challenge were rescued by low dose L‐PAM. Thus, the therapeutic effectiveness of L‐PAM TuB spleen cells in ACIT may be improved by aggressive depletion of CD4+ T‐cells, suggesting that a low dose of L‐PAM, which leads to the acquisition of potent splenic‐tumor‐eradicating immunity in BALB/c mice bearing a large MOPC‐315 tumor, does not eliminate completely (or possibly not at all) the inhibitory activity of CD4+ T‐cells. In addition, athymic nude mice that are not endowed with fully protective tumor‐eradicating immunity following ACIT still have a substantial residual anti‐tumor immune potential that can be exploited to bring about eradication of a large tumor burden following low‐dose L‐PAM therapy.
An organoid culture assay (OCA) for determining the drug sensitivity of human tumors
Authors: Köpf‐Maier P. , Kolon B. 
Published: February 2007

AbstractA model for testing chemotherapeutic agents in vitro is described. It is based on an organoid culture method which allows human carcinomas to grow in vitro and to maintain many typical in vivo properties, including 3‐dimensional architecture, growth of multiple cell types, expression of morphological differentiation and formation of histotypical structures. The preservation of drug sensitivity and resistance under the conditions of our organoid culture assay (OCA) was demonstrated by investigating 3 strains of a human hypopharynx carcinoma which differed by different sensitivity to cisplatin in in vivo conditions. These differences were retained in vitro and the modified neutral‐red (NR) assay was especially suitable for revealing drug‐induced cytotoxic damage in OCA. On the basis of our findings, the following approach is proposed for the in vitro testing of cytostatic drugs before they are administered to patients. (1) Removal of carcinomas from patients; (2) dense cell suspensions of these carcinomas to be dropped on membrane filters at the air‐medium interface, resulting in growth of solid nodules of organized carcinoma tissues; (3) addition of cytostatic drugs to the growth medium for 2 or 3 days; (4) detachment and bisection of the culture nodules; (5) determination of viable cells by NR uptake and total cell mass by the sulforhodamin B (SRB) assay; (6) determination of quotient NR:SRB absorbance, related as percentage to control value: this indicates the fraction of viable cells and gives a measure of the cytotoxic injury caused by the applied cytotoxic drug. Thus, the OCA seems to be suitable for defining the patterns of drug sensitivity and resistance of individual human carcinomas in vitro within a few days.
The use of molecular genetic markers to demonstrate the effect of organ environment on clonal dominance in a human renal‐cell carcinoma grown in nude mice
Authors: Staroselsky Alexander N. , Radinsky Robert , Fidler Isaiah J. , Pathak Sen , Chernajovsky Yuti , Frost Philip 
Published: February 2007

AbstractTransduction of the SNI2C human renal‐cell carcinoma line with the neoR gene produces a genetically „tagged”︁ cell population within which individual clones can be identified if they dominate the tumor during its growth in vivo. We used this technique to determine whether the clones that dominate the primary local tumor and its metastases are the same or different when the tumor is growing in different organ sites in nude mice. The results show that clonal dominance is influenced by the organ environment in which the primary tumor grows, i.e., distinct clones dominated in the kidney, colon and subcutaneous sites. In addition, tumors grown in the orthotopic site (kidney) were all populated by the same dominant clones, and each distant visceral metastasis retained the same clonality. SNI2C neoR‐cells grown in an epithelial, ectopic site (colon) produced tumors with uniquely different dominant clones, and their visceral metastases retained the dominant pattern expressed by the parent tumor from which they were derived. In contrast, SNI2C tumors growing subcutaneously showed a random pattern of clonal dominance in both their primary and metastatic sites. Parallel cytogenetic analyses could not demonstrate these patterns. We conclude that the organ environment significantly influences clonal dominance of human renal carcinoma and that tumor injection into orthotopic sites may produce a more reproducible selection of dominant clones.
Modulation by staurosporine of phorbol‐ester‐induced effects on growth and protein kinase C localization in a549 human lung‐carcinoma cells
Authors: Bradshaw Tracey D. , Gescher Andreas , Pettit George R. 
Published: February 2007

Abstract12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and bryostatin I are activators of protein kinase C (PKC). TPA is a potent inhibitor of the growth of A549 cells, while bryostatin I exerts a weak antiproliferative effect upon this cell line. We tested the hypothesis that the PKC inhibitor staurosporine (STAU) can interfere with the effects of TPA or bryostatin I on A549 cells. STAU alone arrested A549 cell growth effectively with an IC50 of 0.65 nM as determined by cell counting after incubation for 96 hr. It also caused the release of lactate dehydrogenase from cells with an IC50 of 18.4 nM. On incubation with cells for up to 8 hr, STAU (100 nM) alone did not reduce thymidine incorporation into cells. However, it partially abrogated the inhibition of DNA synthesis caused by TPA or bryostatin 1(10 nM). The IC50 for inhibition by STAU of the activity of PKC purified from A549 cells was 6.1 nM. Localization and levels of PKC were studied by Western blot and phorbol ester receptor binding analyses. STAU (100 nM) did not prevent the TPA‐induced rapid redistribution of PKC to the cell membrane, but instead increased it by 25%. The PKC downregulation caused by TPA was not reduced in the presence of STAU. The results suggest that (i) PKC activation is involved in growth inhibition caused by TPA or bryostatin I in A549 cells, and (ii) subcellular localization or levels of PKC can be pharmacologically manipulated even under conditions of inhibited kinase function.
Presence of IGF‐I In human midgut carcinoid tumours—an autocrine regulator of carcinoid tumour growth?
Authors: Nilsson Ola , Wängberg Bo , Theodorsson Elvar , Skottner Anna , Ahlman Håkan 
Published: February 2007

AbstractThe presence of IGF‐I and IGF‐I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF‐I‐positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF‐I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co‐distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF‐I. Reverse‐phase HPLC of tumour extracts demonstrated a major IGF‐I‐immunoreactive component eluting in the position of rhlGF‐I, but also 2 other more hydrophobic forms. Conditioned serum‐free media from primary cultures of carcinoid tumors contained detectable amounts of IGF‐I, indicating a spontaneous release of IGF‐I from tumour cells into the culture medium. Levels of IGF‐I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF‐I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF‐I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF‐I every 3–4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF‐I and that some of the tumours also have IGF‐I receptors. We therefore suggest that IGF‐I may act as an autocrine or paracrine regulator of carcinoid tumour‐cell growth.
MHC‐restricted responses of CD8+ AND CD4+ T‐cell clones from regional lymph nodes of melanoma patients
Authors: Chen Qiyuan , Hersey Peter 
Published: February 2007

AbstractRegional lymph‐node (LN) lymphocytes may constitute an important defence against the spread of human melanoma beyond regional LNs. The present study was directed to clonal analysis of lymphocytes cultured either directly from the LNs or after stimulation in cultures with autologous melanoma (MLTC). T‐cell clones derived from MLTC reactions had either CD4+ or CD8+ phenotypes. Inhibition studies with monoclonal antibodies (MAbs) suggested that the CD8+ cytotoxic T‐cell (CTL) clones had MHC‐class‐I‐restricted cytotoxic activity against the autologous and a proportion of HLA‐class‐I‐compatible allogeneic melanomas. The pattern of cytotoxicity against a panel of HLA‐typed melanoma cells and inhibition by (polyclonal) HLA‐typing sera suggested the CD8+ CTL were restricted by HLA‐A3. The CD4+ T‐cell clones had weak cytotoxic activity which appeared restricted by HLA‐DR2. T cells cultured from unstimulated lymphocytes were all CD4+. One of the clones exhibited cytotoxic activity against both the autologous and HLA‐DR2‐compatible allogeneic melanoma cells, whereas another 2 had cytotoxic activity only against a HLA‐DR2‐compatible allogeneic melanoma established from a primary melanoma. IL‐2 production by a 4th non‐cytotoxic clone had similar specificity. These results suggest that HLA‐A3 and DR2 may act as restricting elements in recognition of melanoma antigens by T cells from LNs and that they may have recognized at least 2 different antigens on the melanoma cells.
Glycolipids carrying Ley are preferentially expressed on small‐cell lung cancer cells as detected by the monoclonal antibody MLuC1
Authors: Leoni Flavio , Colnaghi Maria I. , Canevari Silvana , Ménard Sylvie , Colzani Elsa , Facheris Patrizia , Figini Mariangela , Miotti Silvia , Magnani John L. 
Published: February 2007

AbstractThe monoclonal antibody MLuCI, which reacts strongly with a high percentage of small‐cell lung cancers (SCLC), as well as with various human carcinomas, has been used to immunochemically characterize the recognized epitope (CaMLuCI). To this aim 3 different approaches were adopted: (I) immunoblotting/ immunostaining of extracts from various tumor‐cell lines; (2) inhibition of binding by purified oligosaccharides; (3) direct binding to oligosaccharide‐protein conjugates. All of these experiments indicate that CaMLuCI is present on the Ley blood‐group structure heterogeneously expressed on various glycoproteins and glycolipids. The expression of the glycoconjugates carrying Ley was then analyzed on breast and lung cancers and on their normal counterparts. Our overall results suggest that SCLC produce Ley‐active glycolipids in higher amounts compared to other tumors of the same or of a different oncotype, as well as normal lung cells, thus indicating an SCLC‐specific modification of the glycosylation pathways.