bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shedding of the soluble form of CD30 from the Hodgkin‐analogous cell line L540 is strongly inhibited by a new CD30‐specific antibody (Ki‐4)
Authors: Horn‐Lohrens Ottmar , Tiemann Markus , Lange Hans , Kobarg Jörg , Hafner Martin , Hansen Hinrich , Sterry Wolfram , Parwaresch Reza M. , Lemke Hilmar 
Published: February 2007

AbstractThe CD30‐activation marker was detected as the Hodgkin‐associated Ki‐I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30‐specific antibodies (Ki‐2 to Ki‐7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki‐2 to Ki‐7 and the other anti‐CD30 antibodies Ki‐I, Ber‐H2, HeFi‐l, M44, M67, HRS‐I, HRS‐4 and CIO were employed for epitope mapping. The binding of a particular radio‐labeled anti‐CD30 antibody to Hodgkin's‐disease‐derived L540 cells was completed by addition of the various non‐labeled anti‐CD30 antibodies. Three non‐overlapping regions, expressing different antigen‐specific determinants, could be defined on the extracellular part of the CO30 molecule. Cluster A of determinants was recognized by Ki‐2, Ki‐4, Ki‐6 and Ki‐7, Ber‐H2, HRS‐I and HRS‐4, while cluster B was detected by Ki‐I, Ki‐S and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki‐3, M44, HeFi‐l and CIO. Co‐culture experiments of LS40 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki‐I and weakly enhanced by Ki‐2, Ki‐3, Ki‐5 and HeFi‐l, whereas it was almost completely inhibited by Ki‐4 and to a slightly lesser extent by Ber‐H2.
Expression of a B‐cell marker, CD24, on nasopharyngeal carcinoma cells
Authors: Karran Lorainc , Jones Michael , Morley Gary , Van Noorden Susan , Smith Paul , Lampert Irvin , Griffin Beverly E. 
Published: February 2007

AbstractRandom sequencing of clones from a λgt1O cDNA library, made from mRNA expressed in an Epstein‐Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) has revealed the gene transcript of human CD24. The CD24 antigen, a glyco‐sylphosphatidylinositol‐anchored cell surface molecule, has been identified as a B‐cell marker that is lost during cell maturation. We show here that it is expressed on 3 NPC xenografts, previously defined as consisting of poorly differentiated epithelial cells, and on an NPC biopsy. In the case of the former, the level of expression of CD24 corresponds to the EBV load. A B‐lymphoblastoid cell line carrying the same EBV genome as one of the tumours, C15, and an EBV‐negative Burkitt's lymphoma cell line do not display the antigen, but epithelial‐like cells of a laryngeal tumour cell line (Hep2) do express it. Our data suggest that CD24 may be a marker of cell differentiation not only for B cells but also for epithelial cells and may have an indirect association with EBV gene expression.
Vaccination of rabbits with recombinant vaccinia virus carrying the envelope gene of human T‐cell lymphotropic virus type I
Authors: Hakoda E. , Machida H. , Tanaka Y. , Morishita N. , Sawada T. , Shida H. , Hoshino H. , Miyoshi I. 
Published: February 2007

AbstractTwo groups of 3 rabbits each were immunized with either recombinant vaccinia virus, WR‐SFB5env, carrying the human T‐cell lymphotropic virus type I (HTLV‐1) env gene at the site of the hemagglutinin gene of the WR strain, or control vaccinia virus, HA‐WR, lacking the functional hemagglutinin gene. All 6 rabbits responded with anti‐vaccinia virus antibodies. WR‐SFB5env elicited anti‐HTLV‐1 env antibodies but no vesicular stomatitis virus (HTLV‐1) pseudotype neutralizing antibodies in all 3 rabbits. After 10 weeks, the animals were challenged by transfusion of blood from an HTLV‐1‐infected rabbit. Two of the 3 vaccinated rabbits and all 3 control rabbits became infected with HTLV‐1, as indicated by seroconversion and detection of HTLV‐1 proviral sequences by polymerase chain reaction. The rabbit that had been protected from initial challenge became infected with HTLV‐1 upon rechallenge 12 weeks after the first challenge. In view of the proven prophylactic effect of passive immunization against HTLV‐1, our vaccine trial failed because WR‐SFB5env was incapable of inducing neutralizing antibodies against HTLV‐1 in the immunized animals. It remains to be studied whether cell‐mediated immunity such as antibody‐dependent cellular cytotoxicity was involved in the temporary protection of I vaccinated rabbit.
Risk of ocular melanoma in relation to cutaneous and IRIS naevi
Authors: Bataille Veronique , Sasieni Peter , Cuzick Jack , Hungerford John L. , Swerdlow Anthony , Bishop Julia A. Newton 
Published: February 2007

AbstractA case‐control study was set up to assess the risk of eye melanoma in relation to the number and type of cutaneous melanocytic naevi and pigmented lesions of the iris. Cases comprised 211 unselected ocular melanoma patients attending the Ocular Oncology Clinic at Moorfields Eye Hospital, London, during November 1990 to October 1991 and diagnosed after August 1986. Hospital and general practice controls (416) were recruited in the North East Thames Region of the UK. Cutaneous naevi greater than or equal to 2 mm in diameter were counted on the skin. Clinically atypical and congenital naevi were recorded separately. Pigmented lesions of the iris were counted. The relative risk for ocular melanoma increased with numbers of atypical naevi and numbers of common naevi. Ten percent of cases but 3% of controls had at least 100 naevi of 2 mm or greater diameter. Seven percent of cases and 0.4% of controls had 4 or more atypical naevi. Pigmented lesions of the iris were significantly more common in cases than controls. Nine percent of cases had the Atypical Mole syndrome (AMS) phenotype compared with 1% of controls. Six cases had concurrent cutaneous melanoma primaries. We conclude that atypical and iris naevi are important risk factors for eye melanoma and that patients with eye melanoma are at increased risk of cutaneous melanoma. Dermatological examination for the AMS phenotype and cutaneous melanoma should be recommended in eye melanoma patients with large numbers of pigmented lesions of the skin or family history of melanoma.
A case‐control study of hepatitis B and C virus infections in the etiology of hepatocellular carcinoma
Authors: Hadziyannis Stephanos , Tabor Edward , Kaklamani Evangclia , Tzonou Anastasia , Stuver Sherri , Tassopoulos Nicolaos , Mueller Nancy , Trichopoulos Dimitrios 
Published: February 2007

AbstractDuring a 16‐month period in 1991‐1992, blood samples and questionnaire data were obtained from 65 incident cases of hepatocellular carcinoma (HCC) as well as from 2 control groups of hospitalized patients matched on gender and age, which included 65 metastatic liver cancer (MLC) patients and 65 patients hospitalized for eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg and antibody to hepatitis C virus (anti‐HCV) by enzyme immunoassay. The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 18.8 (8.2–43.2) for the presence of HBsAg and 7.7 (1.7–35.1) for anti‐HCV. In the present hospital‐based case‐control study anti‐HCV testing was conducted on recently collected sera, using a second‐generation enzyme immunoassay with confirmation by immunoblot assay. Comparisons with previous work in a similar population demonstrated that, when second‐generation anti‐HCV assays are applied to sera stored for 7–15 years, confirmatory assays or a higher diagnostic cut‐off point may be necessary to ensure that the testing is specific.
Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumours
Authors: Nilsson Ola , Wängberg Bo , Kölby Lars , Schultz Gregory S. , Ahlman Håkan 
Published: February 2007

AbstractTransforming growth‐factor‐α (TGF‐α) is a 50‐amino‐acid polypeptide that binds to the epidermal growth factor (EGF) receptor and stimulates cell growth. It has been suggested that enhanced production of TGF‐α and EGF receptors by tumour cells promote tumour‐cell growth by autocrine mechanisms. In the present study we have investigated the expression of TGF‐α and EGF receptors in human neuroendocrine tumours, including midgut carcinoid tumours, phaeochromocytomas and medullary thyroid carcinomas. TGF‐α expression was demonstrated in biopsies of all tumours examined (n = 30) and EGF receptors in a majority of tumours by Northern analysis and/or immunocy‐tochemistry. Expression of TGF‐α and EGF receptors was also demonstrated in primary cultures of tumour cells. Carcinoid tumours and phaeochromocytomas in culture secreted detectable amounts of TGF‐α into the culture medium (400–700 pM). The amount of secreted TGF‐α could be suppressed by octreotide treatment in individual tumours. Administration of exogenous TGF‐α stimulated carcinoid tumour growth in vitro as determined by the DNA contents of cell cultures. The growth‐stimulatory effect of TGF‐α could be partially blocked by the use of neutralizing anti‐EGF receptor monoclonal antibodies (MAbs). In conclusion, several human neuroendocrine tumours express both TGF‐α and EGF receptors in in vivo and in vitro, suggesting that TGF‐α may regulate tumour‐cell growth by autocrine mechanisms.
Characterization of selected strongly and weakly invasive sublines of a primary human melanoma cell line and isolation of subtractive cDNA clones
Authors: Jacob Karin , Bosserhoff Anja K. , Wach Franz , Knüchel Ruth , Klein Eberhard C. , Hein Rüdiger , Buettner Rcinhard 
Published: February 2007

AbstractInvasion of basement membranes is a key step in systemic spread of tumour cells. To analyze genetic mechanisms involved in this process, we have selected strongly and weakly invasive sublines with stable phenotypes from a primary human melanoma cell line by repeated passage through a reconstituted basement membrane in vitro. The sublines differed approximately 5‐fold in their invasive potential. Invasiveness correlated with better attachment and overexpression of the integrin αv/β3 (vitronectin/laminin‐receptor). Treatment with retinoic acid inhibited proliferation in both sublines and invasion in the weakly invasive cells but stimulated invasion in the strongly invasive subline. Northern‐blot analyses revealed equal levels of mRNA expression regarding collagenase type‐IV and retinoic‐acid receptors but enhanced expression of TIMP‐2 mRNA in weakly invasive cells. The 2 sublines differed significantly in their respective DNA ploidy when compared to the wild‐type Mel Im cell line, suggesting that they represent heterogeneous clones present in the primary tumour. We have started to exploit this in vitro system for tumour heterogeneity to clone genes involved in invasion. By a subtractive cDNA cloning strategy, 12 partial cDNA clones were obtained that are specifically overexpressed in the strongly or weakly invasive subline. These results illustrate that stable genetic alterations lead to heterogeneous subpopulations within primary melanomas which differ in their ability to invade basement membranes and interact with components of the extracellular matrix.
Treatment of Philadelphia‐chromosome‐positive human leukemia in scid mouse model with herbimycin A, bcr‐abl tyrosine kinase activity inhibitor
Authors: Honma Yoshio , Matsuo Yoshinobu , Hayashi Yasuhide , Omura Satoshi 
Published: February 2007

AbstractThe molecular basis of the Philadelphia chromosome (Ph) is a structurally altered c‐abl (bcr‐abl) gene which encodes an abnormally large protein with protein tyrosine kinase activity. Herbimycin A, which effectively reduced intracellular phosphorylation by bcr‐abl tyrosine kinase, preferentially inhibited the growth of Ph‐positive leukemia cell lines. Injection of Ph‐positive and ‐negative leukemia cell lines into mice with severe combined immunodeficiency (SCID) resulted in the death of all mice due to leukemia, although the severity of illness varied according to the cell lines used. Administration of herbimycin A significantly enhanced the survival of mice inoculated with the Ph'‐positive leukemia cell lines tested but barely affected the survival of mice inoculated with the Ph‐negative leukemia cell lines tested. These results suggest that herbimycin A and related compounds may be useful for the treatment of Ph‐positive leukemia. The disease that developed using the Ph‐positive leukemia cell line NALM‐20 resembled human Ph‐positive acute lymphoid leukemia. There was an inverse relationship between the survival time of mice and the number of cells inoculated. The SCID mouse‐NALM‐20 human leukemia chimera would be a good experimental model for screening tyrosine kinase inhibitors as therapeutic agents against Ph‐positive leukemia.
Somatostatin analog RC‐160 inhibits growth of CFPAC‐1 human pancreatic cancer cells in vitro and intracellular production of cyclic adenosine monophosphate
Authors: Qin Yunfcng , Ertl Tibor , Groot Kate , Horvath Judit , Cai Ren‐Zhi , Schally Andrew V. 
Published: February 2007

AbstractThe effect of somatostatin analog RC‐160 on the growth of CFPAC‐I human pancreatic cancer cells in vitro was investigated. RC‐160 effectively inhibited the proliferation of CFPAC‐I cells in culture, inducing a time‐ and dose‐dependent decrease in the number of treated cells. A significant suppression of cell growth was observed after 48 and 72 hr of the exposure to (I μM) RC‐160, the cell number being decreased by 38% and 46%, respectively. RC‐160 was more potent than SS‐14 or SMS201–995 in inhibiting the growth of CFPAC‐I cells, and after 48‐hr treatment the cell number decreased by 49% for RC‐160 compared with 12% for SS‐14 and 27% for SMS201‐995. Binding experiments demonstrated that specific receptors for somatostatin were present on CFPAC‐I cells. SS‐14 showed a high binding affinity for [125I]‐Tyr11‐SS‐14 receptors on CFPAC‐I cells. Scatchard analysis indicated the presence of 2 classes of somatostatin binding sites on the cells, one with high binding affinity and low capacity and the other with low binding affinity and high capacity. RC‐160 could bind to somatostatin receptors on these cells with an affinity similar to SS‐14 but significantly higher than that of SMS201–995. Radioimmunoassay of intracellular cAMP showed that RC‐160 could powerfully inhibit forskolin‐stimulated cAMP production in CFPAC‐I cells. Addition of forskolin to the cultures increased cAMP concentrations in the cellular lysate of treated cells. RC‐160 attenuated or nullified in a dose‐dependent manner the cAMP production stimulated by forskolin. Our observations indicate that somatostatin analog RC‐160 inhibits the proliferation of CFPAC‐I human pancreatic cancer cells in vitro and that this effect may involve the intracellular cAMP pathway.
E‐selectin expression induced by pancreas‐carcinoma‐derived interleukin‐1α results in enhanced adhesion of pancreas‐carcinoma cells to endothelial cells
Authors: Kaji Mitsuhito , Ishikura Hiroshi , Kishimoto Takashi , Omi Makoto , Ishizu Akihiro , Kimura Chisa , Takahashi Toshiyuki , Kato Hiroyuki , Yoshiki Takashi 
Published: February 2007

AbstractCellular adhesion of sialyl‐Lewis‐a(SLea)‐positive pancreas carcinoma to endothelial cells (EC) is augmented by activation of EC via up‐regulated E‐selectin expression on EC. Co‐cultivation of pancreas‐carcinoma cells, PCI‐24, with human umbilical‐vein endothelial cells (HUVEC) for 5 hr at the PCI‐to‐HUVEC ratio of 1:10 induced E‐selectin expression on the endothelial‐cell surface, augmenting SLea‐positive pancreas‐carcinoma cell attachment with HUVEC. Culture supernatants of 6 tested pancreas‐carcinoma cell lines contained soluble, E‐selectin‐inducing factor(s). The E‐selectin‐inducing effect by the supernatants was blocked by the protein‐kinase‐C inhibitor, H7. Antibodies against SLea and E‐selectin but not SLex or ICAM‐I blocked the increased pancreas‐carcinoma‐to‐endothelial attachment. Paraformaldehyde(PFA)‐fixed PCI‐24 cells also induced E‐selectin on vascular endothelial cells upon direct contact with endothelial cells, indicating the presence of a membrane‐bound form. The 6 pancreas‐carcinoma lines all produced IL‐1α mRNA and protein but not IL‐1β or TNF‐α protein and/or mRNA Absorption of IL‐lα from the supernatants by IL‐lα‐specific antibody almost completely abolished E‐selectin‐inducing activity. Anti‐IL‐lα antibody also abolished the E‐selectin‐inducing activity of PFA‐fixed PCI. IL‐1α production by PCI cells was up‐regulated by TNF‐α. These observations suggest that substance(s) produced by pancreas‐carcinoma cells, in this case, IL‐1α, may contribute to pancreas‐carcinoma‐cell colonization in non‐inflamed, distant locations in vivo, by activating vascular endothelial cells.
A mutational hot spot in the p53 gene is associated with hepatoblastomas
Authors: Oda Hideaki , Nakatsuru Yoko , Imai Yasuo , Sugimura Haruhiko , Ishikawa Takatoshi 
Published: February 2007

AbstractHepatoblastomas generally appear in children aged 2 or 3 years old and arise from apparently normal, noncirrhotic liver. To elucidate any possible role of p53 mutations in their genesis, we amplified and sequenced exons 5 to 8 of the p53 gene in 10 cases of hepatoblastoma. Somatic mutations were detected in 9 cases, in eight of which a common point mutation at the firstbase position of codon 157 was found, resulting in an aminoacid substitution of phenylalanine for valine. Two missense mutations in codon 244, and one each in codons 273 and 279, were also found, with 3 hepatoblastomas having double missense mutations. Out of the total of 12 mutations, 11 were G‐to‐T transversions. One was a G‐to‐A transition and guanines were always present on the transcribed strand. Furthermore, p53 overexpression was immunohistochemically observed in 7 out of 9 cases with p53 gene mutations, although the staining pattern was focal and heterogeneous. The findings suggest that particular environmental mutagens may be involved in mutagenesis of the p53 gene in some cases of hepatoblastomas and that p53 mutations at a specific site may play an important role in the genesis of this disease. © 1995 Wiley‐Liss, Inc.
Generation of CD4+ cytotoxic T lymphocytes stimulated by immobilized anti‐CD3 monoclonal antibody and interleukin‐2 in cancer patients
Authors: Tani Masaji , Tammura Hiroshi , Yamaue Hiroki , Mizobata Shizuma , Iwahashi Makoto , Tsunoda Takuya , Noguchi Kohci , Tamai Mikiko , Hotta Tsukasa , Terasawa Hiroshi , Arii Kazuo 
Published: February 2007

AbstractThe proliferation of autologous tumor‐reactive cytotoxic T lymphocytes (CTL), induced by autologous mixed lymphocyte tumor‐cell culture, was remarkably enhanced by activation with immobilized anti‐CD3 monoclonal antibody (MAb) and interleukin‐2 (IL‐2), as compared with IL‐2 alone. The activated CTL exhibited high cytotoxicity against autologous tumor cells. Cytotoxicity against autologous tumor cells was inhibited by anti‐HLA‐DR MAb. In negative selection with immunomagnetic beads, cytotoxicity against autologous tumor cells was inhibited by the elimination of CD4+ cells. The major cell‐surface antigens of the activated CTL were CD3+, CD4+, CD25+, CD45RO+and CD45RA‐, suggesting helper T cells, and the activated CTL produced IL‐2. It is concluded that the CTL activated by immobilized anti‐CD3 MAb and IL‐2 were CD4 cells that had both killer and helper functions. Our findings indicate that adoptive immunotherapy using these activated CTL would be effective in cancer patients. © 1995 Wiley‐Liss, Inc.
Expression of the bcl‐2 gene family in normal and malignant breast tissue: Low bax‐α expression in tumor cells correlates with resistance towards apoptosis
Authors: Bargou Railf C. , Daniel Peter T. , Mapara Markus Y. , Bommert Kurt , Wagener Christian , Kallinich Bianca , Royer Hans D. , Dörken Bcrnd 
Published: February 2007

AbstractWe have studied the expression of the apoptosis‐regulating genes bcl‐2, bcl‐x, bax and APO‐1/fas (CD95) in human breast cancer. The expression pattern of these genes in human breast‐cancer tissues and breast‐cancer‐derived cell lines was compared to that seen in normal breast epithelium and breast epithelial cell lines. No difference with regard to bcl‐2 and bcl‐xL expression was observed between normal breast epithelium and tumor tissue or breast cancer and non‐malignant epithelial cell lines. In contrast, bax‐α, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal cell lines and breast tissue, whereas only weak or no expression could be detected in cancer‐cell lines and malignant tissue. In contrast to malignant cell lines, which express low levels of bax‐α, non‐malignant epithelial cell lines displaying high amounts of bax‐α were highly sensitive to induction of programmed cell death by both serum starvation and APO‐1/fas (CD95) triggering. We therefore propose that dysregulation of apoptosis contributes to the pathogenesis of breast cancer, at least in part, due to an imbalance between anti‐apoptosis genes (such as bcl‐2/bcl‐x) and apoptosis‐promoting genes (bax).
High cell kinetics is associated with amplification of the int‐2, bcl‐1, myc and erbB‐2 proto‐oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers
Authors: Contegiacomo Alma , Pizzi Claudia , De Marchis Laura , Alimandi Maurizio , Delrio Paolo , Palma Ester Di , Petrella Giuseppe , Ottini Laura , French Deborah , Frati Luigi , Bianco Angelo R. , Mariani‐Costantini Renato 
Published: February 2007

AbstractCell kinetics is a predictive parameter of breast‐cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico‐pathological characteristics and genetic alterations at the int‐2, bcl‐1, c‐myc, c‐erbB‐2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor‐proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int‐2 was observed in 11.2%, of bcl‐1 in 9.4%, of c‐myc in 5.7% and of c‐erbB‐2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH + AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph‐node status. Alone, allele loss at the DF‐3 locus was not significantly associated with any of the clinico‐pathological characteristics studied. Alterations at more than one locus, including int‐2/bcl‐1, int‐2/ c‐myc, int‐2/bcl‐1/c‐erbB‐2, and c‐myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series. © 1995 Wiley‐Liss, Inc.