bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐metastatic vaccination of tumor‐bearing mice with il‐2‐gene‐inserted tumor cells
Authors: Porgador Angel , Gansbacher Bernd , Bannerji Rajat , Tzehoval Esther , Gilboa Eli , Feldman Michael , Eisenbach Lea 
Published: February 2007

AbstractIL‐2 gene was introduced through retroviral vectors into the highly malignant and poorly immunogenic 3LL‐D122 clone. Both high and low D122‐11‐2 secretors showed elimination of tumorigenicity in syngeneic immune‐competent mice; however, in nude mice only the high IL‐2 secretor showed reduced tumorigenicity as compared with parental D 122 cells. Also, following intravenous inoculation, only the high IL‐2 secretor showed reduced generation of metastases, whereas the low IL‐2 secretors were as highly metastatic as parental cells. These results seem to indicate that low levels of IL‐2 secreted by tumor cells are sufficient to activate T cells, while higher levels are needed in order to activate non‐T‐cell effectors. D122‐IL‐2 secretors induced high levels of anti‐tumor CTL, while their sensitivity to the lytic activity of these CTL was similar to the sensitivity of D122 cells, thus indicating that the elevation of immunogenicity of IL‐2 secretors was essentially due to the secreted IL‐2. In accordance with CTL induction, pre‐immunization with IL‐2 secretors protected mice against subsequent challenge of parental cells. Moreover, immunization in an “immunotherapy protocol” i.e., vaccination of mice carrying an established tumor of parental D122 cells with inactivated D122‐IL‐2 infectants, almost completely eliminated the generation of lung metastases by D122 cells, thus providing a rationale for the use of IL‐2 gene transferred tumor cells as a modality for treatment of metastasis.
Cellular and In Vivo characterization of the MCR rat mammary tumor model
Authors: Gutzwiller Alois , Regenass Urs , Matter Alex , Lydon Nicholas B. 
Published: February 2007

AbstractThe slowly growing, transplantable MCR‐83 rat mammary tumor is estrogen‐dependent and non‐metastasizing. A rapidly growing, estrogen‐independent, metastasizing subline (MCR‐86) was subsequently isolated in vivo. We have established and characterized cell lines from both MCR rat mammary tumors. MCR cell lines and tumors were studied in vivo and in vitro. Analysis of DNA from tumors and cell lines showed that mutations had not occurred in codons 12, 13 and 61 of the Ha‐ras and Ki‐ras genes. Additionally, dominant transforming activity could not be detected by DNA transfection using NIH 3T3 focus‐forming assay. No gene amplification was detected for either the EGF‐receptor or c‐erbB‐2 genes. Differences in the tyrosine phosphorylation patterns were found between the 2 MCR cell lines. Addition of serum to starved cells resulted in the tyrosine phosphorylation of a 120‐kDa protein, which was elevated in the MCR‐86. The lack of ras activation in the MCR tumors differentiates this model from the widely studied, chemically induced rodent mammary tumors. In addition, the differences in the cellular phosphotyrosine patterns between MCR‐83 and MCR‐86 suggests the occurrence of alterations in signalling pathways that involve tyrosine protein kinases.
Co‐amplification of c‐myc/pvt‐1 in immortalized mouse b‐lymphocytic cell lines results in a novel pvt‐1/aj‐l transcript
Authors: Huppi Konrad , Siwarski David , Shaughnessy John D. , Frederic Mushinski J. 
Published: February 2007

AbstractIn a series of mouse pvt‐I cDNA clones prepared from an immortalized B‐cell line that contains an amplified c‐myc/pvt‐I region, we have identified a unique cDNA, AJ‐I, which contains 57 bp of pvt‐I sequence (pvt‐la) spliced to a novel sequence of 2.1 kb. We report here that this 3′ segment (termed AJ‐IX) maps more than 60 kb telomeric to pvt‐la and is encoded by novel locus (AJ‐I) on mouse chromosome 15. The AJ‐IX probe detects a transcript that is expressed only in normal mouse brain and testis. Several mast‐cell tumors, Ly‐I+ B‐lymphocytic cell lines and a neuroblastoma also display abundant levels of AJ‐IX‐specific mRNA. However, splicing of pvt‐la to AJ‐IX found exclusively in Ly‐I+ B‐cell lines that contain amplified c‐myc/pvt‐I. We conclude that some feature in the generation of this amplicon facilitates the synthesis of a pvt‐I/AJ‐IX chimeric mRNA that may play a role in immortalization of these Ly‐I+ B‐cell lines.
Persistence of plasmin‐mediated pro‐urokinase activation on the surface of human monocytoid leukemia cells In Vitro
Authors: Tapiovaara Hannele , Stephens Ross W. , Vaheri Antti 
Published: February 2007

AbstractHuman leukemia cell lines, unlike those from adherent tumors, have been shown to continuously activate the prourokinase (pro‐u‐PA) they produce. In the present study we found that, in normal cell‐culture conditions in 10% FCS the plasminogen activation cascade works continuously on monocytoid leukemia cells, which expressed plasmin activity and active u‐PA on their cell surface. This plasmin catalyzed the conversion of the produced pro‐u‐PA to active 2‐chain urokinase (tcu‐PA), and was derived from bovine serum plasminogen the activity of cell‐bound tcu‐PA. Plasmin generation was abolished and pro‐u‐PA accumulated in cell cultures that were grown for several days, either in the presence of serum thoroughly depleted of plasminogen, or in the presence of I mM tranexamic acid. Plasmin generated on the cell surface was found to be present in 2 enzymatically active fragments, of 85,000 and Mr 50,000, which were slowly released into the growth medium. These fragments could activate pro‐u‐PA serum‐free growth medium. Most of the bound plasmin could be washed off cells with 10 mM tranexamic acid, but complete removal of plasmin from the cell surface required washing of the cells with acid‐glycine pH 3.0.
Action of a cd24‐specific deglycosylated ricin‐a‐chain immunotoxin in conventional and novel models of small‐cell‐lung‐cancer xenograft
Authors: Zangemeister‐Wittke Uwe , Lehmann Hans‐Peter , Waibel Robert , Wawrzynczak Edward J. , Stahel Rolf A. 
Published: February 2007

AbstractThe therapeutic efficacy of an immunotoxin, SWA II‐SPDB‐dg.ricin A chain, recognizing the leukocyte‐differentiation antigen CD24, was evaluated against SCLC cell lines in tissue culture and in 2 nude‐mouse models. The first model used conventional S.C. solid‐tumor xenografts. The second used small tumor‐cell deposits established in S.C. implanted sponge matrices and allowed us to directly estimate the killing efficiency of the immunotoxin under experimentally defined conditions in vivo. It also mimics the clinical setting of disseminated tumor cells which form the basis of residual disease in SCLC. The cytotoxic potency of SWAII‐SPDB‐dg.ricin A chain was demonstrated in tissue culture by the inhibition of 3H‐leucine incorporation and by the selective elimination of CD24‐positive tumor cells in clonogenic assays. In nude mice, SWAII‐SPDB‐dg.ricin A chain was cleared from the blood circulation with biphasic kinetics: an initial (α phase of 1 hr and a second β phase of 20.5 hr. Following i.v. injection of a dose equivalent to 30% of the LD50, the immunotoxin delayed the growth of SW2 solid‐tumor xenografts by 16 days. The therapeutic efficacy of SWAII‐SPDB‐ dg.ricin A chain was further demonstrated by the selective elimination of clonogenic SW2 cells from small tumor‐cell deposits established in sponge matrices. Regrowth of the solid tumors after the initial response and the clonogenic activity in the sponge‐derived cell population were mediated by CD24‐positive cells, excluding the selection of CD24‐negative mutants during immunotoxin therapy.
Accumulated allelic losses in the development of invasive urothelial cancer
Authors: Habuchi Tomonori , Ogawa Osamu , Kakehi Yoshiyuki , Ogura Keiji , Koshiba Masahiro , Hamazaki Shuji , Takahashi Rei , Sugiyama Taketoshi , Yoshida Osamu 
Published: February 2007

AbstractTo investigate the roles of allelic loss in the development of urothelial cancer, loss of heterozygosity was examined on 7 chromosomal arms in 49 cases of urothelial cancer of various grades and stages. Loss of heterozygosity was found on alleles in order of frequency as follows: 9q (21/38, 55%), 11p (20/44, 45%), 17p (18/42,43%), 13q (10/39,26%), 3p (8/41, 20%), 10q 2/29, 7%) and 1p (1/36, 3%). lnvasive (high‐grade or ≥pT2) tumors showed the loss of 17p (13/16,81%) and the loss of 13q (7/16, 44%) with significantly higher frequencies than non‐invasive (grade 1‐2 ≤pTI ) tumors. Although the loss of 3p and the loss of 11p were also more frequently associated with the invasive phenotypes, the loss of 11p was detected in a considerable number (9 of 26,35%) of non‐invasive tumors. Our results indicate that the loss of 11p might generally occur at an earlier stage before the loss of 3p, 13q or 17p in tumor progression. Since no correlation was found between the loss of 9q and the tumor grade or stage, this genetic alteration appears to be unrelated to invasiveness, and could be one of the initial events in tumorigenesis. Although accumulated allelic losses of 3p, 11p, 13q and 17p are considered to be involved in the development of the invasive type of urothelial cancers, these multiple genetic alterations may have already occurred in some pathologically non‐invasive urothelial cancers. Furthermore, there appears to be some variation in the pattern of cumulative allelic loss.
Mother‐to‐child transmission of human T‐lymphotropic virus type I (HTLV‐I): An extended follow‐up study on children between 18 and 22‐24 years old in Okinawa, Japan
Authors: Ueda Kohji , Kusuhara Koichi , Tokugawa Ken , Miyazaki Chiaki , Okada Kenji , Maeda Yoshiaki , Shiraki Hiroshi , Fukada Kenji 
Published: February 2007

AbstractThe significant difference observed between the seroprevalence of HTLV‐I in adults and in children is as yet unexplained. To evaluate a hypothetical explanation of the existence of seroconversion cases of „seronegative carriers”︁ for this phenomenon, 21 of 55 children who had been born to seropositive mothers and who remained seronegative until the age of 18 years were further followed up at the ages of 22 and/or 24 years. None of the 21 seronegative children born to seropositive mothers seroconverted, either at 22 years or at 24 years. In addition, the polymerase‐chain‐reaction (PCR) technique could not prove the existence of the HTLV‐I provirus genome in peripheral mononuclear cells (PBMC) of 10 of these children. Our results fail to prove the possibility of viral latency of HTLV‐I in mother‐to‐child transmission. Therefore, the hypothetical seroconversion of „seronegative carriers”︁ after adulthood can not be an explanation.
Down‐regulation of integrated Epstein‐Barr virus nuclear antigen 1 and 2 genes in a burkitt lymphoma cell line after lymphoblastoid cells somatic cell fusion with autologous EBV‐immortalized
Authors: Wolf Jurgen , Pawlita Michael , Klevenz Britta , Frech Barbara , Freese Ulrich‐Karl , Müller‐Lantzsch Niko , Diehl Volker , Hausen Harald Zur 
Published: February 2007

AbstractEpstein Barr virus (EBV) latent gene expression was analyzed in somatic cell hybrids between an EBV‐positive Burkitt lymphoma (BL) cell line (BL 60) and an autologous EBV‐immortalized lymphoblastoid cell line (LCL, IARC 277). The EBV genomes carried by the parental cell lines differ in sequence and in their physical state. The BL 60 EBV genome is integrated into the host cell genome whereas the LCL IARC 277 carries exclusively episomal EBV molecules. The hybrid cells contain both EBV genomes and display the differentiation phenotype of the parental LCL with regard to growth characteristics and cell‐surface antigen expression in vitro and in vivo. While the EBNA 1 and EBNA 2 gene expression of the LCL‐derived EBV is maintained in these hybrid cells, the BL‐60‐derived EBNA 1 and EBNA 2 genes are transcriptionally down‐regulated. Mapping of the genomic region surrounding the latent Cp promoter of the BL‐60‐derived EBV revealed an extensive deletion upstream of the Cp promoter including the enhancer element in the ori P region, the origin of latent viral replication (ori P), the coding sequences for the EBV latent membrane protein (LMP) and the EBV terminal protein (TP), and suggested that one viral‐cellular junction sequence is located near the Cp promoter. Integration of EBV into the host cell genome together with the extensive deletion might be causally related with the altered latent gene expression pattern after introduction of a lympho‐blastoid host‐cell background by somatic cell fusion. Down‐regulation of the BL‐60‐derived EBNA genes could be due to loss of regulatory sequences in the BL‐derived EBV necessary for EBNA 1 and EBNA 2 transcription in the lymphoblastoid hybrid cells, but not in the parental BL cells.
Molecular and cellular heterogeneity of wilms' tumor
Authors: Velasco Susana , D'Amico Domenico , Schneider Nancy R. , Timmons Charles , Chappell Elizabeth , Lee Daniel , Nisen Perry D. 
Published: February 2007

AbstractWe developed a Wilms' tumor‐cell culture system to investigate the molecular basis of nephrogenesis and oncogenesis. Several distinct fractions of cells were isolated and characterized from the same tumor specimen. The cells exhibited striking differences in morphology, immunocytochemical staining profiles and cytogenetics. One fraction contained cells with features of epithelium; other cell fractions resembled partially differentiated mesenchyme (blastema or stroma). While the Wilms' tumor‐suppressor gene WTI was not altered, loss of heterozygosity (LOH) and an insertion in intron I of the p53 tumor‐suppressor gene occurred in the tumor and the cultured cell types. LOH for RB was detected only in the cultured cells. These findings are consistent with a model of tumor initiation in a pluripotent cell that is able to undergo subsequent differentiation along multiple different lines and which mimics normal nephrogenesis.
Production of interleukin‐1β and interleukin‐6 in hepatoblastoma
Authors: Schweinitz Dietrich Von , Hadam Martin R. , Welte Karl , Mildenberger Hermann , Pietsch Torsten 
Published: February 2007

AbstractThrombocytosis and fever are frequent symptoms in children with hepatoblastoma. Interleukin‐6 (IL‐6) has been shown to mediate thrombocytosis and an acute‐phase reaction including fever. We therefore investigated samples from I4 untreated patients with hepatoblastoma for this cytokine and in addition for interleukin‐I α (IL‐Iα), interleukin‐Iβ (IL‐Iβ) and tumor necrosis factor‐α (TNF‐α), all of which are known to induce IL‐6 production. High serum levels of IL‐6 were only found in 3/I4 patients; the other cytokines were not detectable. In contrast, I2/I4 tumors produced substantial amounts of IL‐6 in primary cell culture, while IL‐Iβ was found in 3/I4 supernatants; IL‐Iα and TNF‐α were always negative. Immunoenzymatic staining of fresh tumors revealed that IL‐6 is not produced by the tumor cells, but rather by surrounding fibroblasts and endothelial cells. In tumor cells only IL‐Iβ, but neither IL‐Iα, TNF‐α nor IL‐6, could be detected. In co‐culture experiments with fibroblasts and endothelial cells, addition of hepatoblastoma cells enhanced IL‐6 production. Including an IL‐I receptor antagonist abolished this effect incompletely. Our results suggest that tumor cells in hepatoblastoma induce IL‐6 production in surrounding fibroblasts and endothelial cells by virtue of their endogenous secretion of IL‐Iβ and supposedly some other, as yet unidentified, mediator.
Cholecystectomy and colorectal cancer: Evidence from a cohort study on diet and cancer
Authors: Goldbohm R. Alexandra , van den Brandt Piet A. , van't Veer Pieter , Dorant Elisabeth , Sturmans Ferd , Hermus Rudolph J. J. 
Published: February 2007

AbstractThe association between cholecystectomy and subsequent risk for colorectal carcinoma was investigated in a prospective cohort study on diet and cancer (n = 120,852), which is being conducted in the Netherlands from 1986 onwards among 120,852 men and women, aged 55 to 69. After a follow‐up period of 3.3 years, 478 incident cases of colorectal cancer (258 men and 220 women) were identified in the cohort, 64 of whom reported at baseline to have undergone previous gall‐bladder surgery (21 men and 43 women). After adjustment for age and familial history of large‐bowel cancer, the relative rate (RR) for colorectal cancer in subjects who had undergone cholecystectomy compared with those who had not was 1.81 in men (p=0.02) and 1.47 in women (p=0.05). Additional adjustment for parity, Quetelet index, alcohol intake and other dietary variables resulted in a RR of 1.78 in men and 1.51 in women. In women, the highest RR was detected in the right colon (RR = 1.89), whereas in men, no site within the large bowel accounted specifically for the increased relative rate. In both men and women, the rate appeared to increase from approximately 6 years after cholecystectomy onward. According to the TNM stage of the disease, cholecystectomized patients were not detected at an earlier stage than the other patients. It is concluded that in this study the positive association between colorectal cancer and cholecystectomy cannot be explained by detection bias or ascertainment bias and is not confounded by risk factors for gallstone disease or dietary factors.
Orthodox jews have a lower incidence of malignant melanoma. A note on the potentially protective role of traditional clothing
Authors: Vardi Gil , Modan Baruch , Golan Rachel , Novikov Ilya , Shafir Raphael 
Published: February 2007

AbstractThe incidence of malignant melanoma (MM) in orthodox and non‐orthodox Jews in Israel during the years 1970‐1982 was compared through an assessment of incidence rates in the orthodox and non‐orthodox neighborhoods in the city of Jerusalem and by a comparison of the rates in 2 cities on the outskirts of Tel Aviv, one of which has a strongly orthodox population. Within the city of Jerusalem the incidence of MM for the European‐American born in the orthodox neighborhoods was significantly lower than in the rest of the city in males, and of borderline significance in females. A similar pattern was seen upon comparison of the orthodox city of Bnei Brak to its neighbor city, Givatayim. The findings are consistent with the role of sun exposure in the etiology of malignant melanoma.
Relation between autoradiographically measured blood flow and ATP concentrations obtained from imaging bioluminescence in tumors following hyperthermia
Authors: Dellian Marc , Walenta Stefan , Kuhnle Gerhard E. H. , Gamarra Fernando , Mueller‐Klieser Wolfgang , Goetz Alwin E. 
Published: February 2007

AbstractThe effects of moderate local hyperthermia (43.3°C/30 min) on regional blood flow and regional ATP distribution in the amelanotic hamster melanoma A‐Mel‐3 were investigated by high‐resolution techniques. Blood flow and ATP concentrations were measured simultaneously in treated and untreated tumors and in adjacent tissues by means of (14C)‐lodoantipyrine autoradiography and quantitative imaging bioluminescence in consecutive tissue sections at 3, 12 and 24 hr following treatment. Digital image processing and the use of a special algorithm allowed the regional interrelationship of the 2 parameters to be quantified. Measurements revealed a great heterogeneity of blood flow and ATP between and within the tumors. A pronounced reduction of blood flow and ATP in tumors was observed after hyperthermia in comparison to untreated controls. The adjacent tissue remained mostly unaffected. However, a weakly positive relationship between the 2 parameters was obtained when variables were averaged in tumors or groups. At the microregional level, the untreated tumor tissue revealed a significant, positive correlation between nutritional blood flow and ATP concentrations. This local correlation was reduced and changed with time after treatment indicating different time courses of the parameters. Hyperthermia induced a sudden decrease in blood flow, later associated with a decline in ATP. A slight recovery of both parameters was observed 24 hr after hyperthermia. The results indicate that the metabolic status of the tumor cell is critically dependent on nutritional blood flow but also on the energy requirement of the individual tumor.
P‐glycoprotein and alterations in the glutathione/glutathione‐peroxidase cycle underlie doxorubicin resistance in HL‐60‐R, a subclone of the HL‐60 human leukemia cell line
Authors: Raghu Ganapathirama , Pierre‐Jerome Mario , Dordal Margaret S. , Simonian Philip , Bauer Kenneth D. , Winter Jane N. 
Published: February 2007

AbstractHL‐60‐R, a multi‐drug‐resistant (MDR) subclone of the human leukemia cell line HL‐60, was selected in continuous culture in doxorubicin (DOX) in the absence of mutagenic agents. When compared to the parent line HL‐60, HL‐60‐R showed greater relative resistance to vinblastine than to etoposide, or to the selecting agent DOX. Co‐exposure to verapamil, a known modulator of MDR, partially increased its sensitivity to DOX and vinblastine. The HL‐60‐R cell line stained positively with the P‐glycoprotein‐specific monoclonal antibody (MAb), C219, whereas the HL‐60 parent was negative. Southern analysis showed 32‐fold amplification of the mdr I gene in HL‐60‐R, whereas slot‐blot analysis demonstrated 70‐fold over‐expression of the specific mdrI message in HL‐60‐R compared to HL‐60. Northern blot analysis revealed the presence of 2 species of messenger RNA of sizes 5.1 kb and 4.5 kb. No transcripts were detectable in the parent. Flow cytometric analysis showed significantly reduced cellular retention of DOX as well as rapid efflux from the drug‐resistant cell line. HL‐60‐R proved to be nearly 4 times more resistant to hydrogen peroxide than its parent, and 1,000 times more resistant to inhibition of cellular glutathione synthesis by D,L‐buthionine sulfoxirnine (BSO). Verapamil modulated DOX resistance in HL‐60‐R incompletely but, in the presence of glutathione depletion, nearly completely reversed DOX resistance. Elevated levels of glutathione and glutathione‐peroxidase activity were demonstrated, thereby implicating enhanced activity of the glutathionel/glutathione‐peroxidase cycle as an additional basis for its resistance to DOX. These findings suggest that an enhanced capacity for detoxifying oxyradicals may contribute to anthracycline resistance in acute leukemia.
Calcium intake and 28‐year gastro‐intestinal cancer mortality in dutch civil servants
Authors: Slob Ingrid C. M. , Lambregts Johannes L. M. C. , Schuit Albertine J. , Kok Frans J. 
Published: February 2007

AbstractThe association between calcium intake and gastrointestinal cancer mortality was investigated in a 28‐year follow‐up study. Data were obtained from a general health examination in 1953–1954 among Dutch civil servants and their spouses, aged 40 to 65 years. Information from 2,591 participants was used for this study. Risk analyses were performed using logistic regression models with the highest quintile of calcium intake as reference. No statistically significant relation between calcium intake and gastrointestinal cancer mortality is observed, although the risk estimate for women with the lowest calcium intake is substantial. Odds ratios (OR) were adjusted for age, energy intake and dietary fiber. After inclusion of other potential confounders to the models (body‐mass index and smoking habits), the results hardly differed. Both men and women who died of colorectal cancer had a lower mean calcium intake compared to the rest of the population. For women this was statistically significant. Our results suggest that a low calcium intake may be related to gastrointestinal cancer mortality among women of this study population.