bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the antibodies against human papillomavirus 16 E4 and E7 proteins with cervical cancer positive for human papillomavirus DNA
Authors: Onda Takashi , Kanda Tadahito , Zanma Soichi , Yasugi Toshiharu , Watanabe Sumie , Kawana Takashi , Ueda Kuniaki , Yoshikawai Hiroyuki , Taketani Yuji , Yoshiike Kunito 
Published: February 2007

AbstractOccurrence of the antibodies against human papillomavirus (HPV) 16 proteins E4 and E7 is specifically but independently associated with cervical cancer. To correlate HPV DNA and antibody data, we examined the biopsy specimens and sera, by polymerase chain reaction (PCR) and by ELISA, respectively, from 51 patients with cervical cancer (including 3 recurrent cases) and 22 with cervical intra‐epithelial neoplasia. Consensus primers for the LI region were used for PCR and bacterially expressed, purified fusion protein HPV‐16 E4 and non‐fusion protein HPV‐16 E7 were used for ELISA. HPV‐16 DNA and other HPV types were detected in 17 and 25, respectively, out of 51 cases of cervical cancer. Ten out of the 17 HPV‐ 16‐DNA‐ positives were positive either for anti‐E4 or for anti‐E7: positivities for anti‐E4, for anti‐E7, and for both were 6/17, 5/17 and 1/17 respectively. Three anti‐E7‐positives consisted of those for HPV‐33, ‐52 and ‐58 DNA, suggesting that limited cross‐reaction occurred between the HPV types. Among the HPV‐ 16‐DNA‐positive cases of cancer, lymph‐node or distant metastasis was recorded more frequently in the seropositives than in the seronegatives. Our results show that the HPV‐16 anti‐E4 or anti‐E7 occurs in some, but not in all, of the HPV‐16‐DNA‐positive cases, and support the hypothesis that the presence of the HPV‐16 antibodies can be used as a marker for possible metastasis.
Ectopic production of heparin‐binding growth factors and receptors for basic fibroblast growth factor by rat mammary epithelial cell lines derived from malignant metastatic tumours
Authors: Fernig David G. , Barraclough Roger , Ke Youqiang , Wilkinson Mark C. , Rudland Philip S. , Smith John A. 
Published: February 2007

AbstractA rat mammary (Rama) epithelial cell line, Rama 704, derived from normal rat mammary gland does not possess any detectable cell‐surface receptors for basic fibroblast growth factor (bFGF), produces a barely detectable level of bFGF mRNA and does not contain detectable levels of bFGF‐like activity. Similar results have been obtained with the Rama 37 epithelial cells derived from benign tumours. However, 4 independently isolated epithelial cell lines derived from malignant rat mammary tumours and their metastases possess receptors for bFGF and contain between 2 ng and 9 ng heparin‐binding, growth‐stimulatory activity per 106 cells. The weakly metastatic Rama 600 cells possess high‐ and low‐affinity receptors for bFGF, (KD 20 pM and 8 nM, respectively), while the moderately metastatic Rama 800 cells possess only high‐affinity receptors (KD 40 pM). The moderately metastatic C18PLN and 267LU cells, derived from metastases arising from benign Rama 37 cells which had been transfected with DNA from the malignant Rama 800 cells, also possess only high‐affinity receptors (KD 36 pM and 80 pM, respectively). Our results show that within the Rama system there is a correlation between the appearance of heparin‐binding growth factors and of high‐affinity but not low‐affinity receptors for bFGF with the malignant phenotype.
The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma
Authors: Naredi Peter L. J. , Lindnér Per G. , Holmberg Stig B. , Stenram Unne , Peterson Anders , Hafström Larsolof R. 
Published: February 2007

AbstractThe influence of TNF α on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF α on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF‐α exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF a was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF‐α administration with the 133Xe‐washout technique. The passage of microspheres through the tumour vascular bed (non‐entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF‐α administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF α in vitro was tested. A reduction of tumour blood flow was observed in TNF‐α‐treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF‐α groups as compared with controls. There was no significant change in non‐entrapment for the TNF‐a‐treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF a had no effect on the viability of the cloned hepatoma cell line in vitro.
The effect of hypoxia on acquired drug resistance and response to epidermal growth factor in chinese hamster lung fibroblasts and human breast‐cancer cells in vitro
Authors: Kalra R. , Jones A‐M. , Kirk J. , Adams G. E. , Stratford I. J. 
Published: February 2007

AbstractProlonged hypoxia induced transient drug resistance in Chinese hamster lung fibroblasts. Previously hypoxic cells were resistant to adriamycin and resistant to etoposide. Complete recovery of etoposide sensitivity was observed following re‐aeration for 24 hr. A change in P‐glycoprotein expression was unlikely to contribute to the resistance caused by hypoxia, since adriamycin resistance was not reversed by verapamil. However, alteration in the plasma membrane structure may be involved, since previously hypoxic cells were resistant to extracellular superoxide radical generated by the addition of xanthine/ xanthine oxidase. In contrast, adriamycin sensitivity was not altered by hypoxia in 3 human breast‐cancer cell lines. MDA‐468 and MCF‐7/Adr differed in their response to EGF, independent of the presence of hypoxia. These results suggest that hypoxic‐stress‐induced drug resistance is not generalized.
Mutation and expression of the p53 gene in malignant melanoma cell lines
Authors: Weiss Jürgen , Schwechheimer Karl , Cavenee Webster K. , Herlyn Meenhard , Arden Karen C. 
Published: February 2007

AbstractThree monoclonal antibodies (MAbs) against p53 protein (PAb 24o, DO‐I and Pab1801) were used to define the immunophenotype of 13 melanoma cell lines. Immunoreactions could be detected in 12 out of 13 cell lines by using the indirect immunofluorescence technique. In 7 of these the majority of cells displayed cytoplasmic staining whereas positive nuclei were detected in only a few cells. Two cell lines had predominantly nuclear reactivity, while the remaining 3 cell lines showed signals in both locations. Despite identical nuclear staining patterns, the 3 MAbs produced qualitatively distinct cytoplasmic immunoreactions. PAb240 and DO‐ I, which showed similar staining frequencies, appeared more sensitive in the detection of p53 protein than did PAb 1801. Immunoprecipita‐tions of lysates from each of the cell lines with MAbs DO‐I and 1801 (which bind to both wild‐type and mutant p53 species) detected 53–kDa proteins, whereas PAb240 (which recognizes the mutant conformation of the protein in this type of assay) detected 53–kDa proteins in only 4 cell lines. Nucleotide sequencing of exons 5 to 9 of TP53 in these latter cell lines showed that each has homozygous point mutations in the locus, whereas in the others no TP53 alterations were found. Three of the 4 mutations were C‐to‐T transversions, alterations possibly caused by damage from UV‐light. Our findings indicate that immunostaining with p53 antibodies, although common in malignant melanoma, results from the presence of mutant p53 protein in about 30% of the cases tested. Neither immunostaining with PAb240 nor the patterns of intracellular distributions of the signals are sufficient to detect TP53 mutations.
p53 Mutation in gastric cancer: A genetic model for carcinogenesis is common to gastric and colorectal cancer
Authors: Uchino Shinya , Noguchi Masayuki , Ochiai Atsushi , Saito Takao , Kobayashi Michio , Hirohashi Setsuo 
Published: February 2007

AbstractMutation of the p53 tumour‐suppressor gene in exons 5 through 8 was examined in 118 cases of gastric cancer (59 early gastric cancers and 59 advanced gastric cancers) using PCR‐SSCP (polymerase‐chain‐reaction‐single‐strand‐conformation polymorphism) analysis and direct sequencing. In early gastric cancer, mutations were found in 15 of 41 (37%) cases of the cohesive type, i.e., papillary adenocarcinoma, well to moderately differentiated tubular adenocarcinoma, and poorly differentiated adenocarcinoma with solid nests or focal tubular structures, but were not detected in 18 cases of the noncohesive type, i.e., signet‐ring‐cell carcinoma and poorly differentiated adenocarcinoma growing in a scattered manner. In advanced gastric cancer, 25 of 59 (42%) cases of the cohesive type had p53 mutation. No significant association was found between p53 mutation and other histopathological parameters such as macroscopic classification, lymph‐node involvement and depth of tumour invasion. Fifteen of 25 (60%) mutations in the advanced gastric‐cancer group were accompanied by allele loss at the p53 gene locus. Eighty‐three percent of mutations in early gastric cancer and 52% of mutations in advanced gastric cancer showed G:C‐to‐A:T transition, almost exclusively at CpG dinucleotide mutational hot spots, indicating that the spectrum of p53 mutation was similar to that of colorectal cancer. These data suggest that the p53 mutation occurs selectively in gastric cancer of the cohesive type from the intramucosal cancer stage.
Endocrine cells in colorectal adenocarcinomas: Incidence, hormone profile and prognostic relevance
Authors: De Bruïne A. P. , Wiggers Th. , Beek C. , Volovics A. , Von Meyenfeldt M. , Arends J. W. , Bosman F. T. 
Published: February 2007

AbstractThe occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial‐cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA‐positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA‐positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon‐like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA‐positive tumors tended to be more aggressive than CGA‐negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar‐cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin‐producing tumors showed intermediate behavior.
Vase mini‐exon usage by ncam is not restricted to tumours of neuroectodermal origin
Authors: Patel K. , Culverwell A. , Rossell R. J. , Kemshead J. T. , Phimister E. 
Published: February 2007

AbstractThe neural cell adhesion molecule (NCAM) plays an important role in normal development. Many variants of NCAM are generated through post‐transcriptional and post‐translational modifications. These variants are tissue‐specific and their expression is developmentally regulated. NCAM is also re‐expressed in a number of human tumours, including neuroblastoma, rhabdomyosarcoma, Wilms' tumour and Ewing's sarcoma. We have characterized the NCAM variants associated with rhabdomyosarcoma. Polysialylated NCAMs are present in this tumour and, after neuraminidase treatment, they resolve into 2 bands of 140 and 120 kDa. These data were corroborated by Northern‐blot analysis where mRNA species of 6.7 and 5.5 kb are detected. These mRNA code for the 140‐ and 120‐kDa NCAM proteins respectively. PCR analysis shows that the previously described VASE mini‐exon is also present in NCAM found in rhabdomyosarcoma. The VASE mini‐exon, spliced at exon 7–8 junctions, has previously been detected in neural and heart NCAM, as well as in NCAMs found in human small‐cell lung carcinoma (SCLC). DNA sequencing confirmed that the VASE mini‐exon in rhabdomyosarcoma is identical to that found in neuroblastoma and SCLC.
Development of an anti‐idiotypic antibody reactive with an antibody defining the epitope R P A P in the muc‐1 epithelial mucin core
Authors: Bashford Jill L. , Adrian Robins R. , Price Michael R. 
Published: February 2007

AbstractC595 is a murine lgG3 monoclonal antibody (MAb) raised against human urinary mucin. C595 antibody binds to the protein core of the MUC‐1 mucin (the polymorphic epithelial mucin, PEM) which is elevated in tissue and secretions from human breast carcinomas. The antibody defines the tetrameric epitope, R P A P. In the present study, a syngeneic antiidiotypic MAb, 911, was raised in BALB/c mice against the C595 antibody. This lgG2a anti‐idiotypic antibody blocked the binding of C595 to its mucin core antigen. In turn, pre‐blocking of C595 with a 20 amino‐acid mucin core peptide specifically inhibited binding of 911 antibody to C595. Cross‐reactivity of antibody 911 was only observed against the IgM MAb, 789/91, which has the same minimum antibody‐binding epitope as C595, namely, RPAP. Syngeneic and xenogeneic anti‐sera against 911 antibody displayed increased binding to heptameric peptide sequences containing the motif, R P A(P). The anti‐idiotypic antibody 911 therefore appears to recognize a site within or close to the binding site of the C595 antibody and thus carries an internal image of the parental mucin epitope. Consequently, the 911 idiotypic network offers a promising model system to investigate the mechanism of anti‐idiotype‐induced tumour immunity.
De‐regulation of endogenous retrotransposons in mouse mammary carcinomas of diverse etiologies
Authors: Asch Bonnie B. , Asch Harold L. , Stoler Daniel L. , Anderson Garth R. 
Published: February 2007

AbstractOf the several families of endogenous retrovirus‐like elements present in the mouse genome, only mouse mammary tumor virus has been analyzed for its role in mammary carcino‐genesis. Very little is known about the expression and activities of other retro‐elements in normal and malignant mammary epithelium. We have begun investigating the possible involvement of the 3 retrotransposons, intracisternal A particles (IAPs), murine‐leukemia‐virus‐related (MuLVr) elements, and VL30 sequences, in neoplastic progression of the mammary gland in BALB/c mice. The purpose of the present study was to determine which of these elements was active in primary mammary carcinomas induced by chemical, hormonal and viral agents. Each of these cancers had aberrant expression of at least one of the latter retrovirus‐like components. IAP and/or MuLVr sequences were over‐expressed 3 to 100‐fold in most of the tumors as compared with normal mammary tissue, whereas VL30 expression was markedly decreased by 5‐ to 35‐fold in almost all of the neoplasms. Our results thus demonstrate that substantial changes in the expression of one or more of these 3 families of endogenous retrotransposons are triggered during mouse mammary tumorigenesis, regardless of etiology. Direct involvement of lAPs and MuLVr elements in neoplastic progression by transposition and insertional mutagenesis in the genome of several hematopoietic cell types has already been demonstrated. Their elevated expression in many mammary carcinomas suggests that these retrotransposons may also be potential participants in some pathways of mouse mammary carcinogenesis.
CD30‐antigen‐specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: Potential use for the treatment of hodgkin's lymphoma
Authors: Pohl Christoph , Denfeld Ralf , Renner Christoph , Jung Wolfram , Bohlen Heribert , Sahin Ugur , Hombach Andreas , van Lier René , Schwonzen Martin , Diehl Volker , Pfreundschuh Michael 
Published: February 2007

AbstractCross‐linking of specific tumor antigens with the T‐cell‐associated CD3 and CD28 antigens can increase IL‐2 secretion, proliferation and antigen‐specific cytotoxicity in resting T cells. This cross‐linking can be achieved effectively by bispecific monoclonal antibodies (BiMAb) with specificity for both the tumor antigen and CD3 or CD28 antigen, respectively. To take advantage of the enhanced activation of CD3 pre‐activated T cells by additional activation via the CD28 antigen, BiMAb OKT3/HRS‐3 with reactivity to both CD3 and the Hodgkin's‐lymphoma‐associated CD30 antigen and the BiMAb 15E8/ HRS‐3 with reactivity to both CD28 and CD30 antigen were generated by hybridoma fusion. Resting T cells, represented by Jurkat cells (CD3+ /CD28+) were specifically activated to produce IL‐2 by co‐cultivation with an EBV‐transformed B‐cell line (LAZ509, CD30+/CD19+) only in the presence of the CD30/ CD28 cross‐linking BiMAb and an additional cross‐linking anti‐CD3/CDI9 BiMAb (OKT3/6A4). Neither the cross‐linking BiMAbs alone nor any combination of the monospecific parental MAbs induced a comparable IL‐2 production by Jurkat cells in the presence of LAZ509. In addition, using a combination of these BiMAbs, an antigen‐dependent cytotoxicity was induced by targeting APC‐depleted peripheral blood lymphocytes to CD30+ L540 cells. T cells, previously specifically activated by CD3/CD30 in the presence of CD30 antigen, were cytotoxic to CD30+ cell lines only after incubation with BiMAb anti‐CD28/ CD30. Neither of the BiMAbs nor any of the parental antibodies induced a comparable effect. Our results indicate that such BiMAbs may offer a new approach for specific immunotherapy of Hodgkin's lymphoma, which takes advantage of cytokine secretion and cytotoxicity of activated T cells.
An in vitro model of ovarian epithelial carcinogenesis: Changes in cell‐cell communication and adhesion occurring during neoplastic progression
Authors: Hoffman Anton G. , Burghardt Robert C. , Tilley Roger , Auersperg Nelly 
Published: February 2007

AbstractTo investigate the cellular mechanisms of ovarian epithelial carcinogenesis, a series of progressively transformed rat ovarian surface epithelial (ROSE) cell lines were developed and studied. Transfection of primary ROSE cells and an immortalized ROSE line (ROSE 199) with the pSV3neo plasmid (SV40 T‐antigen) yielded transformed lines which retained epithelial morphology. In vivo selection of these pSV3neo cell populations resulted in further phenotypic transformation. Transfection of ROSE 199 with pSV2neo/c‐H‐rosEJ (rasEJ p21) resulted in a malignant line which appeared fibroblast‐like and formed invasive sarcomas both in athymic mice and in immunocompetent rats. Gap junctional intercellular communication (GJIC) and cell‐cell adhesion were studied in this series of ROSE lines. Both c‐H‐rasEJ‐transformation and in vivo selection resulted in a significant reduction of GJIC between adjoining cells and a transition of in vitro migration as continuous epithelial sheets to the dissociation of individual cells. This apparent shift in cell adhesiveness was associated with reduced expression of the E‐cadherin adhesion molecule. Our data suggest that neoplastic progression of the ovarian surface epithelium may be associated with concomitant reductions in GJIC, E‐cadherin expression and functional adhesiveness.
An in vitro model of intra‐epithelial expansion of transformed urothelial cells
Authors: Rebel Johanna M. J. , De Boer Willem I. , Thijssen Cornelia D. E. M. , Vermey Marcel , Zwarthoff Ellen C. , Van Der Kwast Theo H. 
Published: February 2007

AbstractReplacement of normal urothelium by pre‐cancerous epithelium may explain the high recurrence rate of human bladder cancer. An in vitro model was designed in order to study the mechanisms of expansion of transformed urothelial cells at the expense of normal urothelium. For this purpose, mouse bladder explants were allowed to expand on a transparent porous membrane. Subsequently, cell sheets of the non‐tumorigenic mouse urothelial cell line NUC‐5, the tumorigenic mouse urothelial cell line NUC‐5 Py and the human bladder‐carcinoma cell line T24 were inoculated adjacent to the primary explant. Daily measurements of the outgrowth of the bladder explant were performed, and all cultures were terminated on day 24. At this time the post‐confluent primary urothelial cell outgrowths still showed proliferative activity, as demonstrated by bromodeoxyuridine incorporation. In due course the non‐tumorigenic NUC‐5 cells were replaced by the bladder outgrowth. T24 and NUC‐5 Py cells were able to inhibit the bladder outgrowth, or even infiltrate or replace the explant. This was confirmed by immunohistochemistry with (species‐specific) anti‐cytokeratin antibodies and by microscopic evaluation of cross‐sections of the porous membrane. This co‐cultivation model appears to be suitable for the in vitro study of the mechanisms of intra‐epithelial expansion of transformed urothelial cell lines.
M‐CSF gene transduction in multidrug‐resistant human cancer cells to enhance anti‐P‐glycoprotein antibody‐dependent macrophage‐mediated cytotoxicity
Authors: Heike Yuji , Sone Saburo , Yano Seiji , Seimiya Hiroyuki , Tsuruo Takashi , Ogura Takeshi 
Published: February 2007

AbstractA human macrophage‐colony‐stimulating‐factor(M‐CSF) gene inserted into an expression vector (pRc/CMV‐MCSF) was transfected into multidrug‐resistant (MDR) human ovarian cancer cells (AD 10) to induce secretion of human M‐CSF into the medium. The M‐CSF level in the culture medium of the transfected cells reached 100 ng/ml after 7 days, and the ability of the cells to secrete M‐CSF was stable for at least 3 months. Transfection of the M‐CSF gene did not result in any change in expression of MDRI (P‐glycoprotein), proliferation or chemosensitivity of the cells from those of the parent cells. There was also no difference between the transfected and the parent cells in susceptibility to NK cell‐ or interleukin‐2‐activated killer‐cell‐mediated cytotoxicity. Human blood monocytes that had been incubated for 4 days in medium with the culture supernatant of MH‐AD 10 cells exhibited higher ADCC activity than untreated monocytes against MDRI‐positive cancer cells. This effect of the supernatant of AD 10 cells was completely abolished by its treatment with a monoclonal anti‐M‐CSF antibody (MAb). When transfected human MDR cells were injected into nude mice, an inverse correlation was seen between the ability of the cells to produce M‐CSF and their tumorigenicity. Thus, gene modification of MDR cancer cells seems hopeful as a therapeutic method for enhancing anti‐MDRI ‐MAb‐dependent macrophage‐mediated cytotoxicity against human MDR cancer cells.