bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake of the neuron‐blocking agent meta‐iodobenzylguanidine and serotonin by human platelets and neuro‐adrenergic tumour cells
Authors: Rutgers M. , Tytgat G. A. M. , Verwijs‐Janssen M. , Buitfnhuis C. , Smets L. A. , Voûte P. A. 
Published: February 2007

AbstractThe adrenomedulla‐imaging agent meta‐iodobenzylguanidine (MIBG) is concentrated by various tumours of neuro‐ectodermal origin. Radio‐iodinated [131I]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [131l]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine‐sensitive uptake of [131I]MIBG was much slower than of [3H]serotonin, but after prolonged incubation high and serotonin‐equivalent uptake levels were observed. Accumulation of MIBG saturated at 10‐ to 100‐fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuro‐adrenergic Uptake‐I in SK‐N‐SH neuroblastoma and PC 12 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PC 12 cells, similarly to that of serotonin in platelets. However, the drug was 100‐fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro‐adrenergic Uptake‐I, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro‐adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet uptake of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro‐adrenergic target cells.
Abnormalities in the p53 gene in tumors and cell lines of human squamous‐cell carcinomas of the head and neck
Authors: Yin Xiao‐Ying , Smith Martin L. , Whiteside Theresa L. , Locker Joseph , Johnson Jonas T. , Herberman Ronald B. 
Published: February 2007

AbstractAbnormalities in the p53 gene were studied in a series of cell lines of human squamous‐cell carcinoma of the head and neck (SCCHN) and in tumor tissues. Restriction‐fragment‐length polymorphism (RFLP), quantitative hybridization and immunochemical analysis of mutant p53 proteins were combined to detect and characterize 3 different phases in the p53 gene alteration: mutation (in 9/9 cases), 17p 13 deletion (9/10 cases) and amplification of the non‐deleted allele (9/31 cases). In SCCHN, deletion of the p53 gene was nearly always accompanied by mutation, only one cell line studied having mutation without deletion. Alterations in the p53 gene are common in SCCHN, and involve a series of genetic events which occur in sequence during tumor progression.
Suppression of tumorigenicity in temperature‐sensitive mutants of embryonal carcinoma cells by induction of cell differentiation at non‐permissive temperature
Authors: Sumi Tetsuro , Sakuda Masayoshi , Nishina Yukio , Kosaka Mitsuko , Nishimune Yoshitakc 
Published: February 2007

AbstractThe temperature‐sensitive (ts) mutants of cell differentiation derived from the mouse teratocarcinoma cell line F9, when exposed to non‐permissive temperature, undergo stem‐cell differentiation concomitant with a transient retardation of cell‐cycle progression. By incubating these mutant strains at non‐permissive temperature, we were able to study the relationship between cell differentiation and tumorigenicity. Upon exposure to non‐permissive temperature, the mutant cells undergo extensive differentiation and lose their ability to initiate tumors in vivo, but retain their in vitro proliferative potential. Our data suggest that the loss of tumorigenicity is not caused by altered proliferative potential, but rather by cell differentiation. We therefore suggest that the loss of proliferative potential and the onset of cell differentiation in teratocarcinoma F9 cells are 2 independent events which can be genetically dissected, and that there is (a) crucial step(s) in the differentiation pathway at which these ts mutant cells lose their tumorigenicity.
Phenotypic properties of cultured tumor cells: Integrin αIIbβ3 expression, tumor‐cell‐induced platelet aggregation, and tumor‐cell adhesion to endothelium as important parameters of experimental metastasis
Authors: Tang Dean G. , Onoda James M. , Steinert Bruce W. , Grossi Irma M. , Nelson Kevin K. , Umuarger Lillian , Diglio Clement A. , Taylor John D. , Honn Kenneth V. 
Published: February 2007

AbstractThe present study was undertaken to investigate the factors involved in determining the metastatic potential of cultured cells derived from solid tumors. We first investigated the effects of cell source and culture conditions on lung colony formation by i.v. injected B16a (B16 amelanotic melanoma) cells and inhibition of tumor colony formation by the thromboxane A2 syn‐thase inhibitor, CGS14854. Prolonged culture resulted in a 10‐fold decrease in the incidence of B16a lung colonies, whereas passage in vivo for 150 days did not affect lung colony formation by tumor cells isolated from enzymatic dispersates by centrifugal elutriation. Cultured BI6a cells maintained at low density (LD) and harvested at low passage (LP) formed significantly more lung colonies than B16a cells harvested at high densities (HD) or high passage (HP). Over‐confluent tumor cells produced even lower number of lung colonies. Lung colony formation by elutriated BI6a cells (i.e., cells freshly isolated from tumor tissue) was consistently inhibited by CGS14854, whereas inhibition of lung colony formation by cultured B16a cells was dependent upon culture conditions. CGS 14854 was ineffective or less effective against HD/HP B16a cells. The differences in lung colony formation between LD, HD and elutriated B16a cells were not due to differential cell‐cycle distribution. Mechanistic studies indicated that LD/LP tumor cells induced aggregation of homologous platelets, whereas HD/HP BI6a cells failed to induce significant platelet aggregation. Aggregation of homologous platelets correlated positively with lung‐colonizing ability. Additionally, LD/LP cells demonstrated higher adhesion to endothelium than HD/HP BI6a cells. Finally, LD/LP BI6a cells expressed higher levels of αIIbβ3 integrins than HD/HP tumor cells, as determined by flow cytometry and immunofluorescence.
FK506 and cyclosporin a regulate proliferation and proto‐oncogene expression in HTLV‐1 ‐associated myelopathy/tropical‐spastic‐paraparesis‐derived T cells
Authors: Natazuka Toshiki , Umemiya‐Okada Tomoyo , Matsui Toshimitsu , Nakao Yoshinobu , Saida Takahiko 
Published: February 2007

AbstractHuman T‐cell‐leukemia‐virus‐type‐1 (HTLV‐I) infection is associated with adult T‐cell leukemia/lymphoma (ATL) and HTLV‐1 ‐associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The T‐cell‐targeting immunosuppressants, FK506 and cyclosporin A (CsA), suppressed proliferation of the HAM/TSP‐derived T‐cell lines, H89–59, H89–79 and H109. FK506 and CsA also reduced expression of the proto‐oncogenes, c‐myc and c‐fos, but not c‐jun and interleukin‐2‐receptor‐α (IL‐2Rα) gene in H109 cells. The growth‐inhibitory effects of FKS06 and CsA were not abrogated by interleukin 2 (IL‐2). These results suggest that the inhibitory effects of FK506 and CsA are independent of IL‐2, and are associated with the reduction of c‐myc and c‐fos gene expression.
Usage of T‐cell receptor Vβ chain genes in fresh and cultured tumor‐infiltrating lymphocytes from human melanoma
Authors: Weidmann Eckhart , Trucco Massimo , Lotze Michael T. , Whiteside Theresa L. , Elder Elaine M. 
Published: February 2007

AbstractTumor‐infiltrating lymphocytes (TIL) freshly obtained from human malignant melanomas as well as the same TIL grown in the presence of interleukin 2 (IL2) were studied for gene expression of the T‐cell receptor (TCR) variable β regions (Vβ). To perform the TCR‐Vβ analysis, total RNA was isolated from TIL and reverse‐transcribed into cDNA, which was then amplified by PCR using 22 different 5′ primers specifically recognizing the sequences of 20 Vβ gene families and a 3′ primer annealing to the constant region of the β chain. The TCR‐α constant region (Cα) gene was co‐amplified as a standard for the calculation of the percentage of each TCR‐Vβ gene expressed. The frequency of individual Vβ regions expressed on TIL was computed from the ratio of cpm Vβ to cpm Ca for each Vβ region in relation to the total of all 22 ratios. With fresh TIL obtained from 8 different melanomas, oligoclonal distribution of Vβ genes expressed on TIL was observed, in comparison with a broader and unrestricted distribution seen with peripheral‐blood T cells of 8 normal individuals. The oligoclonal patterns of Vβ‐gene expression in fresh melanoma TIL were distinct in every tumor. Several of the Vβ‐genes usually expressed in normal PBL were not expressed in fresh TIL. In melanoma TIL cultured in the presence of IL2 and IL4 and in the absence of autologous tumor (AuTu) or antigen‐presenting cells for 23 to 65 days, selection of T‐cell lines expressing a restricted number of Vβ genes occurred. Although in 4/5 TIL cultures this selection involved the Vβ7 gene, no relationship could be established between Vβ gene expression in fresh TIL and that in T‐cell lines outgrowing in long‐term cultures. Selection in culture of CD3+ CD8+ T‐cell lines with Vβ‐gene expression restricted to I or 2 Vβ families did not correlate with the presence or level of AuTu cytotoxicity mediated by these T cells. The results indicate that in TIL cultures random selection of T‐cell lines with reactivity not relevant to AuTu may account for poor expression or loss of AuTu cytotoxicity by most TIL cultured long‐term in the presence of cytokines and in the absence of specific antigenic stimulation.
Monoclonal antibody 4D3 detects small intestinal mucin antigen (SIMA)—Glycoprotein in the serum of patients with colorectal cancer
Authors: Pinczower Gideon D. , Gianello Robert D. , Williams Roderick P. W. , Preston Barry N. , Preston Henry , Linnane Anthony W. 
Published: February 2007

AbstractWe have developed a sensitive ELISA using MAb 4D3 for the detection of a novel epitope on Small Intestinal Mucin Antigen (SIMA) and report here that SIMA is present in the serum of patients with colorectal cancer. SIMA has been shown to occur in tissue from a high proportion of patients with colorectal cancer. SIMA derived from serum was similar to tissue‐derived SIMA: both eluted in the void volume of a Superose 6 column indicating a molecular weight above 5,000 kDa and they exhibited similar buoyant densities on CsCI gradients. The ELISA was most reliable after pre‐treatment of serum with 0.4 M perchloric acid to remove interfering substances. The upper limit for SIMA in normal serum was set as the mean plus 2 standard deviations determined from a group of 97 healthy control subjects. In a samßle of 113 patients with colorectal cancer, SIMA serum levels were elevated in 15% of patients with Dukes' Stage A, 38% with Stage B, 32% with Stage C and 75% with Stage D colorectal cancer. SIMA serum levels were compared with those of the widely used tumor marker, carcino‐embryonic antigen (CEA). The SIMA assay detected a significant number of sera that were not detected by the test for CEA. We propose that SIMA will prove to be a valuable serological tumor marker, in combination with CEA and other tumor markers, for the detection of colorectal cancer.
Increasing incidence of both major histological types of esophageal carcinomas among men in Sweden
Authors: Hansson Lars‐Erik , Sparén Pär , Nyrén Olof 
Published: February 2007

AbstractAlthough a rare tumor form, there is evidence that the incidence of esophageal adenocarcinomas is increasing in Western Europe and the US. The aim of this nationwide population‐based study was to describe the secular trends in the incidence rates of adenocarcinoma and squamous‐cell carcinoma of the esophagus over a 28‐year period from I960 to 1987. The Swedish Cancer Registry, complete to more than 95%, was used to identify the cases. The percentage verified by histology rose from 89% to 98%. The age‐standardized incidence rate of adenocarcinoma increased in males from 0.5 per I05 in 1960–63 to 1.1 per 105 in 1984–87, corresponding to an average annual increase of 1.5%. In females the incidence remained stable around 0.2 per I05. The age‐standardized incidence rate of squamous‐cell carcinoma in males increased from 2.9 to 4.0 per 105, corresponding to an average annual increase of 1.0%. In females the rate decreased from 1.4 to 1.2 per I05, corresponding to an annual average decrease of 0.5%. The male/female ratio was 4.6 for adenocarcinoma and 2.7 for squamous‐cell carcinoma of the esophagus. Since the incidence rates of squamous‐cell carcinoma of the esophagus and of adenocarcinoma seem to be rising, there is a great need for well‐planned analytical epidemiological studies of these tumor locations, taking the histological type into consideration.
Quantitative and qualitative assessment of CA‐125 production by human endometrial epithelial cells: Comparison of eutopic and heterotopic epithelial cells
Authors: Kobayashi Hiroshi , Ida Wakaba , Terao Toshihiko , Kawashima Yoshiro 
Published: February 2007

AbstractWe have established an in vitro system for the culture of epithelial cells (ECs) from human uterine endometrium to examine the production of CA 125 and to characterize the CA‐125 antigen purified from the conditioned media. CA‐125 secretion was higher in heterotopic ECs than in eutopic ECs and it was more significant after heterotopic ECs reached confluence than during the logarithmic growth phase. CA‐125 expression was observed mainly in the G0/G,‐phase. CA‐125 expression on cell membranes did not correlate with the volume of CA 125 released per cell, and there was no amplification of CA‐125 expression in heterotopic EC membranes. Treatment of the purified CA‐125 antigen with 6 M urea yielded a much lower molecular‐mass peak (200 kDa). The results of Western blot indicated the presence of a single polydisperse band of 200 kDa in the conditioned media from eutopic ECs, whereas 2 major CA‐125 isoforms of 200 kDa and 110 kDa, as well as 2 minor forms of 100 kDa and 70 kDa, were observed in the conditioned media of the heterotopic ECs. We conclude that, in heterotopic ECs, the 1 10‐kDa CA‐125 is more prominent than the 200‐kDa antigen, and that the elevation of CA‐125 levels in the conditioned media could be attributed to significantly increased release of I 10‐kDa CA‐125 from heterotopic ECs.
Quercetin induces type‐II estrogen‐binding sites in estrogen‐receptor‐negative (MDA‐MB231) and estrogen‐receptor‐positive (MCF‐7) human breast‐cancer cell lines
Authors: Scambia G. , Mancuso S. , Panici P. Benedetti , De Vincenzo R. , Ferrandina G. , Bonanno G. , Ranelletti F. O. , Piantelli M. , Capelli A. 
Published: February 2007

AbstractWe show that flavonoids positively regulate type‐II estrogen‐binding site (type‐ll EBS) levels both in MCF‐7 (ER‐positive) and in MDA‐MB231 (ER‐negative) breast‐cancer cells. Type‐ll EBS were measured by a whole‐cell assay at 4°C for 2.5 hr using [3H]‐estradiol as tracer. In both cell lines the effect of quercetin (Q) was dose‐related and already evident after 12 hr of Q treatment. The increase of type‐ll EBS levels after Q exposure requires both RNA and protein synthesis, since actinomycin D and cycloheximide completely abolished the stimulatory effect. The ability of flavonoids in inducing type‐ll EBS is well correlated with their relative binding affinity for type‐ll EBS. The flavonoid‐induced enhancement of type‐ll EBS levels is accompanied by increased sensitivity of cancer cells to the inhibitory effect of low Q concentrations. Our data suggest that type‐ll EBS are ligand‐regulated receptors.
Superantigen‐induced cytokines suppress growth of human colon‐carcinoma cells
Authors: Dohlsten Mikael , Sundstedt Anette , Björklund Mariana , Hedlund Gunnar , Kalland Terje 
Published: February 2007

AbstractWe have recently demonstrated that the superantigen staph‐ylococcal enterotoxin A (SEA) conjugated to colon‐carcinoma‐reactive monoclonal antibodies (MAbs) directs T cells to lyse human colon‐carcinoma cells, representing a potential novel tumor therapy. To further analyze the mechanism of anti‐tumor effects of superantigen‐activated T cells, we compared the activity of free and MAb‐conjugated SEA in a long term in vitro co‐culture assay of human peripheral‐blood mononuclear cells (pBMC) and colon‐carcinoma cell lines. Activation of resting T lymphocytes with SEA conjugated to the colon‐carcinoma‐reactive MAb C215 or free SEA resulted in strong inhibition of the growth of all studied colon‐carcinoma cell lines. The growth of WiDr colon‐carcinoma cells was unaffected by the presence of unactivated mononuclear cells, whereas addition of pM concentrations of SEA or C215‐SEA conjugate completely suppressed tumor‐cell growth. The suppressive effect was mediated by both CD4+ and CD8+ T cells and required the presence of MHC‐Class‐ll+ monocytes. The inhibition of tumor‐cell growth was to a large extent mediated by soluble factors present in supernatants from SEA‐ or C215‐SEA‐activated mononuclear cells. Quantitation of cytokine mRNA in SEA‐activated mononuclear cells by the reverse transcriptase‐polymerase chain reaction (RT‐pCR) revealed strong induction of mRNA encoding the cytokines IL‐1α, IL‐1 β, IL‐2, IL‐6, TNF‐α, TNF‐β and IFN‐γ. The use of cytokine‐specific MAb demonstrated that IFN‐γ was of major importance for the tumor‐growth‐inhibitory activity in supernatants of SEA‐activated lymphocytes. Addition of recombinant cytokines to WiDr colon‐carcinoma cells showed that TNF‐α was able to act synergisti‐cally with IFN‐γ to suppress tumor‐cell growth. The local production of tumor‐suppressive cytokines induced by MAb‐targeted superantigens is likely to be of particular relevance for inhibition of the growth of tumor cells not expressing the targeted tumor‐associated antigen.
Carcinogenic potential of some pesticides in a medium‐term multi‐organ bioassay in rats
Authors: Cabral Ricardo , Hasegawa Ryohci , Hoshiya Toru , Hakoi Kazuo , Ogiso Tadashi , Boonyaphiphat Plcumjit , Shirai Tomoyuki , Ito Nobuyuki 
Published: February 2007

AbstractThe carcinogenic potential of 5 pesticides was analyzed using a medium‐term multi‐organ bioassay for carcinogenicity. Male F344 rats were initially treated with 3 known carcinogens (diethylnitrosamine, N‐methyl‐N‐nitrosourea and N‐bis(2‐hydroxypropyl)nitrosamine) during a period of 4 weeks to induce neoplastic changes in a variety of organs, and then given one of 5 pesticides in the diet for a further 16 weeks. Neoplastic and pre‐neoplastic lesions were found in the thyroid, kidney and urinary bladder with propineb, in the forestomach, kidney and thyroid with captan and folpet. The number of glutathione S‐transferase placental‐form‐positive liver‐cell foci was significantly increased in the captan‐ and phosmet‐treated groups. Based on these findings, captan and propineb can be considered as carcinogens and carcinogenicity is suspected for folpet and phosmet. These results are in concordance with reported long‐term carcinogenicity for captan, folpet and propineb. Daminozide was considered not to be carcinogenic. Thus, the present assay of 20 weeks' duration is useful for the prediction of potential carcinogens.
Interaction of human malignant melanoma tumor spheroids with endothelium and reconstituted basement membrane: Modulation by RGDS
Authors: Offner Felix Albert , Feichtinger Hans , Bigalke Iris , Schiefer Johannes , Wirtz Hans Christian , Klosterhalfen Bernd , Kirkpatrick Charles James 
Published: February 2007

AbstractTumor‐cell extravasation involves sequential adhesive interactions with vascular endothelium and the subendothelial basement membrane. We have established a 3‐dimensional model in vitro to simulate these events and to elucidate targets of the anti‐cell‐adhesive synthetic peptide RGDS. Tumor spheroids of the melanoma cell line ST‐ML‐12 served as models of tumor‐cell emboli and were transferred onto human umbilical vein endothelial cells. To imitate the vascular anatomy, the latter were grown on reconstituted basement membranes produced by dextran‐stimulated bovine corneal endothelial cells. RGDS did not affect the homotypic aggregation of the tumor cells and only minimally inhibited the attachment of the spheroids to the reconstituted vessel. A short‐term (20 min) inhibition of adhesion to denuded basement membranes was observed. The attachment was closely associated with damage to the endothelial cells by oxygen‐derived free radicals. RGDS retarded endothelial injury for up to 3 hr. The most prominent effect was observed after penetration of the endothelium. RGDS suppressed the emigration of tumor cells from the attached tumor‐cell cluster in a dose‐ and time‐dependent fashion. After 12 hr, the inhibitory effect progressively declined. This was not due to loss of activity of the peptide, indicating a resistance mechanism in the melanoma cells. On purified components of the basement membrane, RGDS effectively inhibited the initial spheroid attachment to fibronectin and collagen IV but had no effect on attachment to laminin. By contrast, subsequent migration was significantly suppressed on all substrata. Our model permits the study of dynamic cell‐cell and cell‐extracellular‐matrix interactions and indicates that RGDS might predominantly act on early tumor‐cell locomotion after penetration of the endothelium.
In primary human breast carcinomas mutations in exons 5 and 6 of the p53 gene are associated with a high s‐phase index
Authors: Merlo Giorgio R. , Bernardi Amelia , Diella Francesca , Venesio Tiziana , Cappa Alberto P. M. , Callahan Robert , Liscia Daniel S. 
Published: February 2007

AbstractA series of 121 human breast tumors was screened for point mutations in exons 5 through 8 of the p53 gene, by SSCP analysis. On the same tumor samples, the S‐phase index (SPI) was determined by the incorporation of BUdR in fresh tissue. p53 mutations were observed in 29% of the cases. The frequency of point mutations for the individual exons was: exon 5, 10.0%; exon 6, 9.9%; exon 7, 7.1% and exon 8, 5.5%. Two mutations detected by SSCP were confirmed by sequencing the p53 cDNA. The presence of a p53 mutation, irrespective of its location, correlates (p = 0.003) with a high SPI. This association appears to primarily reflect mutations in exon 5 (p = 0.0002) and exon 6 (p = 0.05), since mutations in exons 7 and 8 failed to show any association. These results indicate that mutations in the p53 gene identify highly proliferating tumors, and that the position of the p53 mutation may have different effects upon the proliferative activity of tumor cells in vivo.