bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predominant mRNA class in HPV16‐infected genital neoplasias does not encode the e6 or the E7 protein
Authors: Bohm S. , Wilczynski S. P. , Pfister H. , Iftner T. 
Published: February 2007

AbstractHuman papillomavirus (HPV) type 16 is strongly implicated in the development of progressive neoplasias of the uterine cervix. Its oncogenic potential is decisively determined by the activity of the early gene products E6 and E7. To look for changes in the expression of these genes during tumour progression we cloned subgenomic fragments of HPV 16 into RNA expression vectors, which allowed the generation of 35S‐labelled riboprobes specific for distinct mRNA classes. Four constructs were made to differentiate between transcripts starting upstream of the E6 ORF or the E1 ORF, and one probe was specific for unspliced E6/E7 region transcripts. Five other constructs were used to identify transcripts covering the E1, E2, E4, L1 and L2 regions. With the help of these constructs, we analyzed by in situ hybridization 2 low‐grade intraepithelial neoplasias of the vulva, I high‐grade neoplasia of the cervix as well as 4 vulvar and 3 cervical carcinomas. Transcripts from the E1, E2, E4, L1 and L2 region that were consistently detected in the differentiated layers of benign lesions were variably expressed in precancers and carcinomas. None of the investigated cases revealed detectable amounts of unspliced E6/E7 transcripts with a coding potential for a full‐length E6 protein. In benign lesions, the E7 transcripts were confined to isolated nuclei of differentiated cells, whereas high‐grade lesions and invasive cancers showed elevated levels of equally distributed E7‐specific signals in the cytoplasm of all tumour cells. The most abundant transcripts observed in intraepithelial neoplasias and in invasive cancers appear to initiate within ORF E7 and therefore have no coding potential for full‐length E6 and E7 proteins. Our data show that the actual level of E7‐specific transcripts in cancers is lower than anticipated from earlier studies using an ORF E6/E7‐specific probe that hybridizes with the 5′‐ends of the abundant mRNA class.
Enhanced expression of LFA‐3 on human T‐cell lines and leukemic cells carrying human T‐cell‐leukemia virus type 1
Authors: Imai Toshio , Tanaka Yoshikazu , Fukudome Kenji , Takagi Shin , Araki Koichi , Yoshie Osamu 
Published: February 2007

AbstractPreviously, we studied the surface expression of LFA‐1 (CD 11 a/CD 18) and ICAM‐1 (CD54) in a panel of 16 human T‐cell lines and found that those carrying HTLV‐1 pro‐viruses expressed high levels of ICAM‐1. Enhanced expression of ICAM‐1 was also seen in fresh leukemic cells from ATL patients. In the present study, we systematically examined the surface expression of 19 different cell‐adhesion molecules (CAMs) (the immunoglobulin superfamily, the homing receptors, the integrins, etc.) in a panel of 20 human T‐cell lines (6 HTLV‐1‐negative lines and 14 HTLV‐1‐positive lines). The surface expression of LFA‐3 (CD58) was constantly enhanced in HTLV‐1‐positive T‐cell lines except for MT‐1, an ATL‐derived cell line, which was devoid of a number of CAMs including ICAM‐1. LFA‐3 proteins and mRNA were found at strongly increased levels in HTLV‐1 ‐positive T‐cell lines.
Uncoordinate induction and differential regulation of hla class‐I and class‐II expression by γ‐interferon in differentiating human neuroblastoma cells
Authors: Ponzoni Mirco , Guarnaccia Francesco , Corrias Mariavaleria , Cornaglia‐Ferraris Paolo 
Published: February 2007

AbstractRecombinant γ‐interferon (IFN‐γ) has recently been shown to be one of the most effective inducers of neuroblastoma (NB) cell differentiation. Since increasing evidence indicates that expression of MHC class‐I and class‐II antigens by tumour cells is important for immunorecognition and cell targeting, we tested whether induction of NB cell differentiation by IFN‐γ is followed by expression of HLA class‐I and class‐II molecules. LAN‐5 human NB cell line completely lacks HLA class‐I antigens. Their expression was induced in a dose‐dependent manner by IFN‐γ. HLA class‐II molecules are also absent on LAN‐5 cells, but only DP antigens were dose‐dependently induced by IFN‐γ, while DR and DQ molecules were unaffected by the treatment. To confirm and extend the immunological data to all the class‐II molecules, we performed Northern blot analysis, observing that DPα mRNA was induced in a dose‐ and time‐dependent manner. DOβ and DZα genes were also induced peaking after 3 days of IFN‐γ treatment. DRβ and DQβ genes, which were not induced by IFN‐γ, gave a normal pattern of enzyme restriction by Southern blot. To get an insight into the regulation of HLA class‐II gene expression in the neuronal model, we measured the decline of the steady‐state HLA class‐II mRNA. DOβ mRNA rapidly returned to baseline level after removing IFN‐γ, while the decay rates of DPα and DZα mRNA were very slow. This might indicate different regulation at the post‐transcriptional level for DOβ mRNA with respect to DPα and DZα mRNA. To strengthen these findings we evaluated the half‐lives of the mRNA after IFN‐γ induction by means of actinomycin D treatment. HLA‐DOβ mRNA had a shorter half‐life, while DZα and DPα had a longer decay rate. Finally, we report that treatment of LAN‐5 cells with cycloheximide did not alter the rate of transcription of the HLA‐DPα gene, suggesting that no protein factor(s) is/are needed to maintain DPα gene expression.
Decreasing the level of translation initiation factor 4E with antisense rna causes reversal of ras‐mediated transformation and tumorigenesis of cloned rat embryo fibroblasts
Authors: Rinker‐Schaeffer Carrie W. , Graff Jeremy R. , De Benedetti Arrigo , Zimmer Stephen G. , Rhoads Robert E. 
Published: February 2007

AbstractTransformation of cloned rat embryo fibroblasts (CREF) with the T24‐ras oncogene results in loss of contact inhibition, growth in soft agar and tumor formation in nude mice. Previously we showed that in such cells (CREF T24), the phosphorylation rate of protein synthesis initiation factor 4E (elF‐4E) is increased, correlating with an increase in the general rate of protein synthesis. In the present study, we have expressed antisense RNA complementary to elF‐4E mRNA in CREF T24 cells using a stably integrated vector. Cells expressing antisense RNA (CREF T24/AS) contained 30‐50% of the normal level of elF‐4E and exhibited many of the properties of untransformed cells. CREF T24 had a spindle‐shaped, refractile appearance, whereas CREF T24/AS grew in ordered, parallel patterns and exhibited contact inhibition similar to untransformed CREF. The rates of growth and protein synthesis in CREF T24/AS were decreased compared to CREF T24 but were not as low as in CREF. The efficiency of growth in soft agar was 11‐fold lower for CREF T24/AS compared with CREF T24. The latency period for tumor formation in nude mice was increased from 8 days for CREF T24 to 17‐27 days for CREF T24/AS and various clonal lines derived from them. Cell lines established from these CREF T24/AS‐derived tumors were shown to have partially regained the elF‐4E levels characteristic of CREF T24. These results demonstrate that many of the phenotypic alterations associated with ras‐induced malignant transformation can be reversed by a moderate reduction of the translational initiation capacity and therefore may be mediated through a translational mechanism.
Circumvention of tamoxifen resistance by the pure anti‐estrogen ICI 182, 780
Authors: Hu X. F. , Veroni M. , de Luise M. , Wakeling A. , Sutherland R. , Watts C. K. W. , Zalcberg J. R. 
Published: February 2007

AbstractBoth primary and acquired resistance to the growth‐inhibitory effects of anti‐estrogens (e.g., tamoxifen) limits the clinical usefulness of these drugs in the treatment of breast cancer. The new, steroidal anti‐estrogen ICI 182,780 was tested for its ability to inhibit the proliferation of a tamoxifen‐resistant variant of the parental MCF‐7 human breast‐cancer cell line. Two cell lines cloned from the MCF‐7 line were used for these experiments: a tamoxifen‐sensitive line, MCF 5‐21, and a tamoxifen‐resistant line, MCF 5‐23. Compared with tamoxifen, ICI 182,780 appeared to be 150 and 1540 times more effective in inhibiting cell growth in the 5‐21 and 5‐23 sub‐lines respectively. ICI 182,780 completely circumvented tamoxifen resistance at a concentration of (5 to 10) × 10−9 M in this model. Based on IC50 concentrations, the 5‐23 line was 22‐fold more resistant to tamoxifen than the 5‐21 line, but only 2‐fold more resistant to ICI 182, 780, reducing relative resistance by 10‐fold in the resistant line. There were no differences in ER parameters between the 2 lines. ER numbers/cell were: 40500 and 34800 and the KD 0.48 and 0.15 × 10−9 M in the 5‐21 and 5‐23 cells respectively. In the 5‐23 cells, the concentrations of ICI 182, 780 and tamoxifen resulting in a 50% inhibition of 3 H‐estradiol binding were 2.3 × 10−8 M and 1 × 10−6 M, respectively (cf. estradiol 0.89 × 10−9 M). Thus, one potential mechanism for the increased effectiveness of ICI 182,780 may relate to the increased affinity of this drug for the estrogen receptor as compared with tamoxifen.
Breath hydrogen and methane in populations at different risk for colon cancer
Authors: Marchand Loïc Le , Wilkens Lynne R. , Harwood Patricia , Cooney Robert V. 
Published: February 2007

AbstractResults from laboratory and clinical studies have suggested that fermentation in the large bowel may play a protective role against colon cancer. Hydrogen and methane are end‐products of colonic fermentation that are absorbed into the bloodstream and excreted via expired air in the breath. Thus, breath levels of hydrogen and methane have been used as markers for this process. Breath levels of these gases were compared among 10 ethnic and sex groups that exhibit marked differences for colon cancer risk in Hawaii. Four end‐expiratory breath samples were used to characterize daily excretion of hydrogen and methane in a population‐based sample of 244 men and women. There was no significant difference in breath hydrogen or methane by sex or age. Hawaiians produced significantly more hydrogen than Filipinos, and Hawaiians and Caucasians more methane than the 3 Asian groups. These differences did not correlate with risk of colon cancer among these ethnic populations.
Association between expression of sialosyl‐Tn antigen and intestinalization of gastric carcinomas
Authors: Kushima Ryoji , Jancic Snezana , Hattori Takanori 
Published: February 2007

AbstractWe examined immunohistochemically the expression of sialosyl‐Tn antigen (STN) in 137 primary gastric carcinomas. In the non‐neoplastic mucosa, STN was expressed in all goblet cells, most absorptive cells and Paneth cells of intestinalized tubules, whereas it was not seen in the gastric mucosa proper. We evaluated the association between the mucin‐histochemical findings of intramucosal carcinomas and the STN‐expression. STN was expressed in 8 of 20 undifferentiated‐type carcinomas, all of which were mucin‐histochemically of the gastric type. STN was expressed in 25 of 51 differentiated‐type carcinomas, among which it was expressed in 3 of 12 gastric‐type, 11 of 17 intestinal‐type and 11 of 22 mixed‐type adenocarcinomas. The extent of STN expression in the intestinal‐type adenocarcinomas was significantly higher than in gastric‐type adenocarcinomas and undifferentiated‐type carcinomas, and that seen in mixed‐type adenocarcinomas was significantly higher than in the gastric‐type adenocarcinomas. We also examined STN expression in early and advanced carcinomas. As the depth of carcinoma invasion progressed, the extent of STN expression was significantly higher and its incidence was significantly higher. Our findings suggest that STN expression reflects intestinalization of the gastric mucosa, and that a kind of intestinal metaplasia occurs in progressing gastric carcinoma cells.
Hodgkin's disease: The protective effect of childbearing
Authors: Kravdal ØYstein , Hansen Svein 
Published: February 2007

AbstractRegister and census data for complete cohorts of Norwegian men and women born between 1935 and 1974 were used to examine the relationship between reproductive factors and the incidence of Hodgkin's disease (HD). Among 1.3 million men and 1.3 million women under observation, 695 male and 441 female cases of HD were diagnosed during the period of follow‐up. Our hazard model estimates showed that women, at a given age and in a given birth cohort, have an HD incidence inversely related to current parity. A clear relationship was found only for the nodular sclerosis subtype. In men, the risk of HD development was higher than that in childless women, and there was no parity effect. The lower HD incidence among high‐parity women could not be ascribed to their lower social status. Presumably, there is a still unidentified protective factor associated with the biology of childbearing, the effect of which possibly wears off with increasing length of time since childbirth. In addition, there are indications of a net effect of age at entry into motherhood, which may explain part of the estimated parity effect.
Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal‐associated proteins
Authors: Itoh Fumio , Ikuta Shigeo , Hinoda Yuji , Arimura Yoshiaki , Ohe Mutsumi , Adachi Masaaki , Ariyama Takeshi , Inazawa Johji , Imai Kohzoh , Yachi Akira 
Published: February 2007

AbstractWe have investigated the mRNA expression of 2 human protein tyrosine phosphatases with sequence homology to cytoskeletal proteins, PTPHI and PTPMEG. Northern‐blot analysis of PTPHI using poly (A)+ RNA from normal human colon tissue showed a low‐abundance message of 4.3 kb. Reverse‐transcriptase/polymerase‐chain reaction (RT‐PCR) was therefore used to detect it in a wide variety of cell lines including 9 colorectal, 5 gastric, 5 hepatic and 6 hematopoietic tumor cells. PTPHI mRNA was not detected only in Colo 320 cells over‐expressing c‐myc mRNA, among the colorectal cancer cell lines examined. When Colo 320 cells were incubated with 5 mM sodium butyrate for 5 days, PTPH I mRNA became detectable, concomitant with the marked decrease in the expression level of c‐myc mRNA. Moreover, the chromosomal localization of PTPHI gene was investigated by fluorescence in situ hybridization. Interestingly, PTPHI gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists.
Effect of somatostatin analog RC‐160 and bombesin/gastrin releasing peptide antagonist RC‐3095 on growth of PC‐3 human prostate‐cancer xenografts in nude mice
Authors: Pinski Jacek , Schally Andrew V. , Halmos Gabor , Szepeshazi Karoly 
Published: February 2007

AbstractNude mice bearing xenografts of the androgen‐independent human prostate‐cancer cell line PC‐3 were treated for 4 weeks with somatostatin analog RC‐160, bombesin/gastrin‐releasing peptide (GRP) antagonist (RC‐3095), or the combination of both peptides. In the first experiment, treatment was started when the tumors measured approximately 10 mm3. Tumor volumes and weights were reduced by about 40% by RC‐160 or RC‐3095 administered by s.c. injections at doses of 100 μg/day/ animal and 20 μg/day/animal respectively. The combination of RC‐3095 with RC‐160 did not further potentiate suppression of tumor growth, but histologically the ratio of apoptotic and mitotic indices was significantly higher in the groups treated with the combination than in the other groups. Serum gastrin levels were significantly reduced in all treated groups. Therapy with RC‐160 or the combination also significantly decreased serum growth‐hormone levels. Specific high‐affinity binding sites for bombesin, somatostatin and epidermal growth factor (EGF) were found on the tumor membranes. Receptors for EGF were significantly down‐regulated by treatment with RC‐3095, RC‐160 and a combination of both analogs. Tumors from mice treated with RC‐160 showed a significant increase in maximal binding capacity for somatostatin as compared with control tumors, demonstrating the absence of down‐regulation. In the second experiment, treatment was started when the tumors were well developed and measured approximately 90 mm3. No significant reduction in volume, weight and growth rate of tumors was found in the groups treated with RC‐160 or RC‐3095. Our results suggest that somatostatin analog RC‐160 and bombesin/GRP antagonist RC‐3095 can inhibit the growth of androgen‐independent prostate cancer when the therapy is started at an early stage of tumor development.
p53 protein accumulation and gene mutations in human glioma cell lines
Authors: Anker Lars , Ohgaki Hiroko , Ludeke Barbara I. , Herrmann Hans‐Dietrich , Kleihues Paul , Westphal Manfred 
Published: February 2007

AbstractMutations in, and aberrant expression of, the p53 tumor suppressor gene were assessed in 17 cell lines derived from human malignant brain tumors (glioblastoma multiforme). Ex‐ons 5 through 8 were screened by single strand conformational polymorphism analysis (SSCP), followed by direct DNA sequencing. Mutations were found in 6 of 17 glioma cell lines, i.e., at a frequency similar to that found in primary malignant gliomas. Loss of the wild type allele was observed in 4 of the mutated cell lines. Two cell lines had the same mutation (CGG → TGG; Arg → Trp) in codon 248. Five of 6 mutations were transitions, 4 of which occurred at CpG dinucleotides. In one cell line a 10‐bp deletion at the intron 4/exon 5 junction was found. Five of 6 glioma cell lines contained a mutation identical to that in the respective primary tumor despite prolonged in vitro culture (140‐221 passages). Thus, the acquisition of p53 mutations during culture appears to be infrequent. Two cell lines derived from heterozygous tumors maintained the wild type p53 allele during long term culture. p53 protein levels were assessed by immunofluorescence cytochemistry and immunoprecipitation followed by Western blot analysis and revealed elevated levels of the p53 protein, although to a variable extent, in all cell lines with p53 mutations. A marked p53 protein accumulation was also observed in two cell lines lacking p53 mutations in exons 5 through 8, indicating that a prolonged half life of the gene product is not solely dependent on an aberrant coding sequence. The remaining cell lines had either low levels or no detectable p53 protein; one of the latter contained a gross rearrangement of the p53 gene. Our results suggest that with respect to p53 gene status, glioma cell lines usually resemble the original tumors and may, therefore, be suitable for studying the biological changes associated with p53 mutations in glial tumors.
Allogeneic blood transfusion reduces murine pulmonary natural killer (NK) activity and enhances lung metastasis of a syngeneic tumour
Authors: Clarke P. Jane , Burton Robert C. , Wood Kathryn J. 
Published: February 2007

AbstractA model was established whereby CS7BL/6 (B6) blood injected i.v. into C3H mice 7 days prior to i.v. injection of syngeneic UV‐2237 tumour cells significantly increased the number of pulmonary metastases counted 21 days later as compared with levels observed in mice treated with saline, C3H or NZW blood or SRBC. This regimen of B6 allogeneic blood transfusion of C3H mice also significantly depressed splenic and pulmonary NK activity as assayed by lysis of 51Cr YAC‐1 in vitro and by clearance of 111In YAC‐1 in vivo respectively. Anti‐asialo GMI treatment, which depletes NK activity in vivo, and Poly I:C treatment, which enhances NK activity in vivo, were associated with significantly increased and decreased pulmonary metastasis of UV‐2237, respectively, in C3H mice. Depletion of CD4+ and CD8+ T cells had no effect. Cyclophosphamide pretreatment which, among other effects, depletes NK cells, significantly increased pulmonary metastasis of UV‐2237 in C3H mice. This was corrected by adoptive transfer of normal C3H spleen cells but not spleen cells from anti‐asialo GM 1 ‐treated C3H mice or B6‐blood‐transfused C3H mice. Furthermore, a 1:1 mixture of normal C3H spleen cells with spleen cells from B6‐blood‐transfused C3H mice also failed to reconstitute the cyclophosphamide‐pre‐treated C3H mice. We conclude that allogeneic blood transfusion augments pulmonary metastasis of the UV‐2237 sarcoma in C3H mice and that the mechanism involves suppression of NK activity.
Patterns of allele losses suggest the existence of five distinct regions of loh on chromosome 17 in breast cancer
Authors: Kirchweger Regina , Zeillinger Robert , Schneeberger Christian , Speiser Paul , Louason Geneviève , Theillet Charles 
Published: February 2007

AbstractChromosome 17 is a frequent target during breast‐cancer formation and progression. It has been shown to be affected by allele losses at multiple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of breast tumors. To this end we analyzed 151 pairs of tumor and cognate lymphocyte DNAs by Southern blotting with 5 RFLP or VNTR probes and by PCR at 8 CA repeat polymorphic loci for LOHs. Moreover, we studied DNA amplification of the evi2, erbB2, thra1, gcsf and rara genes. Data presented here point strongly to the existence of 5 distinct regions of allele losses on chromosome 17:2 on 17p, 3 on 17q. Of the 2 regions on 17p, one involves tp53 while the second is located more distally toward the telomere. LOH was found in 45.9% and 58.8% respectively. The 3 regions on 17q are located: (i) on the proximal portion of the long arm band q21, corresponding to the brcal region; (ii) in a central region defined by the marker D17S74; (iii) on the distal part of 17q (band q25) characterized by losses of the marker D17S24. Each of these regions presented respectively allele losses in 47.5%, 33.3% and 40.8% of the informative tumors. Whereas some tumors presented patterns of LOH consistent with the loss of a complete chromosomal arm or of large portions of the chromosome, a high proportion of the analyzed tumors showed interstitial losses. Amplifications were found in 15% of the tumors and were centered around erbB2. An altered chromosome 17 (bearing an LOH or a DNA amplification) was found in more than 80% of the breast tumor set analyzed here and multiple anomalies affecting this chromosome were often detected in the same sample.
The effect of GM‐CSF and G‐CSF on the growth of human osteosarcoma cells in vitro and in vivo
Authors: Thacker J. Dean , Dedhar Shoukat , Hogge Donna E. 
Published: February 2007

AbstractThe human osteosarcoma cell line, MG63, responds both to GM‐CSF and to G‐CSF in vitro. To assess the significance of these observations to tumor growth in vivo, MG63 cells were engineered by retroviral infection to produce human GM‐CSF or G‐CSF. These retrovirally infected cells become autostimulatory as measured by increased [3H]‐thymidine incorporation (3‐to 7‐fold) and anchorage‐independent colony formation (7‐to 10‐fold) as compared with uninfected MG63 cells or cells infected with control (neor) retrovirus. The increased proliferation induced by exogenous GM‐CSF or G‐CSF on uninfected MG63 cells in both assays could be completely inhibited by anti‐GM‐CSF or anti‐G‐CSF antibodies, while the same antibodies only partially abrogated proliferation by the growth‐factor‐producing cells. None of 34 nude or SCID mice developed tumors when injected s.c. with uninfected or neor‐virus‐infected cells. In contrast, all 30 mice injected with GM‐CSF‐or G‐CSF‐producing MG63 cells developed tumors which were G418‐resistant and factor‐producing. Tumor cell DNA showed a polyclonal retroviral integration pattern indistinguishable from that in the DNA of cells injected into mice. Tumors that formed following injection of a mixture of G418‐resistant, GM‐CSF‐producing cells and cells infected with virus containing only the hygror gene contained hygromycin‐resistant cells in the same proportion as was present in the original cell mixture. These data indicate that GM‐CSF and G‐CSF can support the growth of an osteosarcoma cell line both in vitro and in vivo whether the factor is supplied by autocrine production or from exogenous sources.