bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic tumors induced by carbon tetrachloride in transgenic mice carrying a human c‐H‐ras proto‐oncogene without mutations
Authors: Tsunematsu Satoshi , Saito Hidetsugu , Kagawa Tatehiro , Morizane Toshio , Hata Jun‐Ichi , Nakamura Tatsuya , Ishii Hiromasa , Tsuchiya Masaharu , Nomura Tatsuji , Katsuki Motoya 
Published: February 2007

AbstractHepatic tumors were generated in mice by repeated administration of carbon tetrachloride (CCI4). Eight transgenic (Tg) mice carrying a human c‐H‐ras proto‐oncogene (rasH2 line) and 9 non‐Tg mice were killed at 20 weeks. Tg mice developed more tumors than did non‐Tg littermates. Most tumors were neoplastic nodules, but I hepatocellular carcinoma (HCC) was found in a Tg mouse at 20 weeks. Three Tg and 2 non‐Tg mice were kept without further administration of CCI4. Two Tg mice died at 30 weeks of HCC with intra‐abdominal bleeding, and I Tg mouse developed HCC with a mesenteric metastasis at 32 weeks. No HCC was found in 2 non‐Tg mice at 32 weeks. Although mutations at codon 12, 13, and 61 of the H‐ras gene are often found in murine hepatocarcinogenesis, neither the tumors, including one HCC, nor the normal cells revealed any such mutations. These results showed that the unmutated human c‐H‐ras gene facilitates malignant transformation of hepatocytes when continuous liver‐cell death and regeneration is caused by repeated administration of CCI4. © 1994 Wiley‐Liss, Inc.
Correlation between cytopathological results and In situ hybridisation on needle aspiration biopsies of suspected african Burkitt's lymphomas
Authors: Labrecque Louise G. , Lampert Irvin , Kazembe Peter , Philips John , Griffin Beverly E. 
Published: February 2007

AbstractBurkitt's lymphoma (BL) is a very high‐incidence malignancy in sub‐Saharan Africa, where it targets mainly young children. This lymphoma is closely associated with Epstein‐Barr virus (EBV). Diagnosis of BL relies on clinical presentation as well as histological results obtained from biopsies. In this report, 66 new patients from Malawi (one of the southernmost African countries with high‐incidence BL), suspected on clinical grounds to present with BL, had fine needle aspiration biopsies taken, smeared on slides and used for May‐Grünwald Giemsa staining. Duplicate slides were independently assessed for EBV presence and expression by DNA‐DNA and/or RNA‐RNA in situ hybridisation (ISH), using respectively the repetitive viral BamHIW DNA fragment in a biotinylated probe and the small EBV‐encoded RNA EBER I in a digoxigenin‐labelled riboprobe. There was very good correlation between the various techniques in the diagnosis of the lymphomas, showing 67% of clinically suspect cases to be BL. Our report, presenting data on BL in Malawi, illustrates the usefulness of a simple aspiration biopsy in the diagnosis of this malignancy by Giemsa staining and also in both types of ISH.
Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas
Authors: Kuniyasu Hiroki , Yasui Wataru , Yokozaki Hiroshi , Akagi Morihisa , Akama Yoshihiko , Kitahara Kenji , Fujii Kiyomu , Tahara Eiichi 
Published: February 2007

AbstractLoss of heterozygosity (LOH) on the long arm of chromosome 7 was examined using 5 polymorphic marker probes on 98 gastric carcinomas to elucidate a novel locus for development and progression of the tumors. Twenty‐six (32%) of 82 informative cases showed LOH on 7q on at least one locus of 5 loci. Among 5 loci, LOH at D7S95 locus was most frequent, the incidence being 53% in well‐differentiated gastric carcinomas and 33% in poorly differentiated and scirrhous gastric carcinomas respectively. At 3 loci, c‐met, D7S63 and D7S22, the incidence of LOH was about 30% and 10% in well‐differentiated and poorly differentiated gastric carcinoma cases respectively. In contrast, LOH at D7S64 was not detected in any gastric‐carcinoma cases. Deletion mapping of 7q revealed that D7S95 locus was the essential region of LOH. Eight (62%) of 13 cases with LOH at D7S95 locus belonged to the most advanced stage grouping. Furthermore, 6 (75%) of 8 cases with abdominal dissemination showed LOH at D7S95. Therefore, cases with LOH at D7S95 showed significantly worse prognosis than the cases without the LOH in the stage‐III and stage‐IV groups. These findings overall suggest that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.
Topoisomerase I and II activity in human breast, cervix, lung and colon cancer
Authors: McLeod Howard L. , Douglas Fiona , Oates Melanie , Symonds R. Paul , Prakash Drew , Van Der Zee Ate G. J. , Kaye Stanley B. , Brown Robert , Keith W. Nicol 
Published: February 2007

AbstractThe identification of human DNA topoisomerases as cellular targets for active anti‐cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisom‐erase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra‐ and inter‐tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co‐segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase‐directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity.
Parallel assessment of glutathione‐based detoxifying enzymes, O6‐alkylguanine‐dna alkyltransferase and P‐glycoprotein as indicators of drug resistance in tumor and normal lung of patients with lung cancer
Authors: Oberli‐Schrämml Aurelia E. , Joncourt Franziska , Stadler Markus , Altermatt Hans‐Jorg , Buser Kathrin , Ris Hans‐Beat , Schmid Ulrico , Cerny Thomas 
Published: February 2007

AbstractThe levels of several potential indicators of drug resistance were measured in tumor and corresponding normal tissue of 55 untreated patients with lung cancer. The resistance parameters include glutathione (GSH) level, activities of the enzymes glutathione transferase (GST), glutathione peroxidase (GPx) and O6‐alkylguanine‐DNA alkyltransferase (ATase), as well as expression of P‐glycoprotein (Pgp). Median values of GSH, GST and GPx were significantly higher in tumor than in normal tissue of non‐small‐cell lung cancer (NSCLC) or of small‐cell lung cancer (SCLC), whereas ATase was elevated in tumor tissue of NSCLC only. Pgp expression as determined by Western blotting was significantly lower in tumor than in normal tissue of NSCLC. Resistance‐parameter expression did not correlate with stage of disease or age of the patients. We found a negative correlation between smoking intensity and GSH level in normal tissue. Our findings indicate that the fundamental differences in chemo‐sensitivity between SCLC and NSCLC cannot be explained by differences in the GSH‐system or in the expression of Pgp. However, the level of ATase activity may be one of the factors responsible for the difference in chemosensitivity.
Presence of immunoassayable transforming growth factor‐β1 (tgf‐β1) in breast cyst fluid (BCF): Relationship with the intracystic electrolyte and epidermal‐growth‐factor (EGF) content
Authors: Zanard S. , Pensa F. , Torrisi R. , De Franchis V. , Barreca A. , Minuto F. , Boccardo F. 
Published: February 2007

AbstractWe evaluated the presence and distribution of transforming growth factor‐β1 (TGF‐β1) in breast cyst fluid (BCF), and its relationship with intracystic epidermal growth factor (EGF). EGF and TGF‐β1 were determined by radioimmunoassay on 47 BCFs (27 of the Na+/K+ <3 type and 20 of the Na+/K+ >3 type). As expected, EGF levels were inversely correlated with the Na+/K+ ratio, and were consequently higher in Na+/K+ <3 cysts as compared with Na+/K+ >3 cysts, (p < 0.005). By contrast, TGF‐β1 levels were directly correlated with the Na+/K+ ratio (p < 0.01), being higher in Na+/K+ >3 cysts, though not significantly (p = 0.057). A significant negative relationship was found between EGF and TGF‐β1 concentration. When the analysis was performed separately in the 2 cyst sub‐populations, EGF and TGF‐β1 were found to be negatively and significantly correlated in Na+/K+ <3 cysts only (p < 0.01). Our results demonstrate that Na+/K+ <3 cysts contain high levels of EGF, a growth‐stimulating factor, and very low levels of TGF‐β1, a growth‐inhibiting factor. This may provide an explanation for the higher risk of breast cancer observed in women with Na+/K+ <3 cysts. Our results also suggest that EGF accumulation in this type of cysts might be regulated by TGF‐β1.
Enzyme‐Linked immunosorbent assay (ELISA) for IgA and IgG antibodies to epstein‐barr‐virus ribonucleotide reductase in patients with nasopharyngeal carcinoma
Authors: Fones‐Tan A. , Chan S. H. , Tsao S. Y. , Gan L. H. , Tan W. H. , Li B. , Khong P. W. , Gan Y. Y. 
Published: February 2007

Abstract661 bp coding for the carboxyl end of the large sub‐unit of EBV ribonucleotide reductase was cloned into the pMal plasmid vector. Purified recombinant protein was tested in IgG and IgA ELISAs. For the IgG assay, 81 out of 100 NPC patients tested positive, whereas for the IgA assay, 60 tested positive. Among 100 normal individuals, I tested positive for the IgG assay and 9 tested positive for the IgA assay. The IgG assay picked up 6 out of 19 NPC sera which were IFA‐VCA‐ and IFA‐EA‐negative for IgA antibodies. Hence the recombinant ribonucleotide reductase could have good potential as a diagnostic test for NPC or could serve as a complementary test to IFA.
The decreased expression of CD3 ζ chains in cancer patients is not reversed BY IL‐2 Administration
Authors: Farace Françoise , Angevin Eric , Vanderplancke Josiane , Escudier Bernard , Triebel Frédéric 
Published: February 2007

AbstractThe mechanisms underlying the impaired immune response frequently observed in cancer patients are poorly understood. Recently, a decreased expression of the signal‐transducing CD3 ζ chains has been shown to occur in patients with colorectal or renal‐cell carcinoma. Here, we have investigated the expression of the ζ molecule on lymphocytes from patients with advanced cancers including renal‐cell carcinoma (n = 21), hepatic colorectal carcinoma metastases (n = 6), head‐and‐neck squamouscell carcinoma (n = 7) or miscellaneous tumors (n = 7), using flow cytometry analysis of PBMCs with monoclonal antibody specific for the cytoplasmic domain of the ζ chain. The same analysis was also performed with patients undergoing IL‐2 therapy (from 5 days up to 3 months i.v. or s.c). PBMCs from patients (n = 41) showed a significant decrease in expression of the ζ chains as compared to the levels found in lymphocytes from healthy controls (n = 15), which was not reversed by IL‐2 administration. Together, these results suggest that an alteration in the expression of the ζ‐chain‐transducing element in PBMCs may be a common cause of progressive immunosuppression in advanced cancer patients and that IL‐2 is not sufficient to reverse this situation in vivo.
Menstrual and reproductive factors and Gastric‐cancer risk in women
Authors: La Vecchia Carlo , D'Avanzo Barbara , Franceschi Silvia , Negri Eva , Parazzini Fabio , Decarli Adriano 
Published: February 2007

AbstractTo understand possible correlates of the systematically higher gastric‐cancer rates in males than in females, we investigated the role of menstrual, reproductive and hormonal factors in females, using data from a case‐control study conducted in Northern Italy. Cases were 229 post‐menopausal women with incident, histologically confirmed gastric cancer, and controls were 614 post‐menopausal women in hospital for acute, nonneoplastic, non‐digestive‐tract conditions. After allowance for age, education, family history, and selected dietary correlates of stomach cancer, a reduced gastric‐cancer risk was observed in women with later menopause (odds ratio, OR = 0.6, p value for trend <0.05), and longer duration of fertile life (OR = 0.7, but the trend in risk was not significant). The risk of gastric cancer was elevated in multiparous women (OR = 1.7 for 3 and 1.9 for ≥ 4 births as compared to nulliparae). No association was observed with age at menarche, age at first birth, and with number of spontaneous or induced abortions. Ever‐users of oral contraceptives had a non‐significant increased risk (OR = 1.3), and users of oestrogen‐replacement treatment a non‐significant reduced risk (OR = 0.5). Although the association with each factor was moderate, and the interpretation of these findings is not straightforward, these results are compatible with the hypothesis that some role is played by (endogenous and exogenous) female hormones in the process of gastric carcinogenesis.
Linkage analysis in familial melanoma kindreds to markers on chromosome 6p
Authors: Walker Graeme J. , Nancarrow Derek J. , Walters Marilyn K. , Palmer Jane M. , Weber James L. , Hayward Nicholas K. 
Published: February 2007

AbstractMalignant melanoma occurs as a familial cancer in 5%‐10% of cases, where it segregates in a manner consistent with autosomal dominant inheritance. Evidence from cytogenetics, fine mapping studies of deletions in melanomas and recent linkage studies supports the location of a human melanoma predisposition gene on the short arm of chromosome 9. Evidence also exists for a melanoma gene on I p, indicating genetic heterogeneity for melanoma predisposition. Previous studies have also reported findings suggestive of linkage of some melanoma families to the HLA region on the short arm of chromosome 6 (6p), indicating the possibility of even greater heterogeneity. To further define the possible effect of a gene within the HLA region on melanoma susceptibility, we have typed 7 simple tandem repeat polymorphisms (STRPs) from 6p in 16 Australian melanoma kindreds. Maximum 2‐point LOD scores ranged from 1.13 (θ = 0.2) to 2.03 (θ = 0.15) for 4 contiguous markers flanking the HLA complex, and multi‐point analysis gave a peak LOD score of 1.64, 24 centimorgans telomeric to D6S109. However, extended haplotype analysis of these markers showed that a region between D6S105 and HLAF segregated with melanoma in 5/16 families. These results are surprising given that the same cohort of families has previously been shown to be linked to chromosome 9. One interpretation of the current findings is that melanoma susceptibility in some families may result from a gene mapping within the HLA region of chromosome 6p.
P‐glycoprotein expression in the Golgi apparatus of multidrug‐resistant cells
Authors: Molinari Agnese , Cianfriglia Maurizio , Meschini Stefania , Calcabrini Annarica , Arancia Giuseppe 
Published: February 2007

AbstractThe surface and intracellular expression of mdrl‐P‐glycoprotein in parental drug‐sensitive human breast cancer cells (MCF‐7) and their multidrug‐resistant (MDR) variants has been studied by using the monoclonal antibodies (MAbs) MM4.17 and MRK‐16, which recognize 2 different epitopes of the drug efflux pump molecule. Fluorescence microscopic observations showed that P‐glycoprotein, in addition to being located at the cell surface, can also be found in the Golgi apparatus of resistant cells. To confirm this finding, Golgi apparatus and P‐glycoprotein were double‐labelled with wheat‐germ agglutinin (WGA) and MAb MM4.17. Laser scanning confocal microscopy indicated that, in MDR cells, Adriamycin mainly accumulated cytoplasmically in a perinuclear region. This accumulation proved to be modulated by pre‐treatment with verapamil or ATP depletion. Moreover, the vital staining of Adriamycin‐treated MDR cells, performed with the fluorescent lipid N‐{7‐(4‐nitrobenzo‐2‐oxa‐1,3‐diazole)}‐6‐aminocaproyl sphingosine (C6‐NBD‐ceramide), revealed that the anthracyclinic antibiotic was located in the Golgi apparatus. All these results indicate that the drug transporter is located in the Golgi apparatus, in which Adriamycin molecules also accumulate.
A secreted mucin carrying Sialyl‐Lewis a from colon carcinoma cells binds to E‐selectin and inhibits HL‐60 cell adhesion
Authors: Zhang Ke , Baeckström Dan , Hansson Gunnar C. 
Published: February 2007

AbstractSialyl‐Lewis × and a are known as ligands for E‐selectin (ELAM‐I) involved in leukocyte‐endothelial adhesion. L‐Canag (light cancer antigen), secreted by a colon carcinoma cell line COLO 205, is a soluble mucin‐type glycoprotein expressing sialyl‐Lewis a antigens. L‐Canag was purified from spent culture medium by trichloracetic acid precipitation and Superose 6 gel filtration. With a monoclonal antibody against E‐selectin (BBAI) as a positive control, the purified L‐Canag was shown to bind to E‐selectin‐Fc coated into plastic microtiter wells and to the surface of transiently E‐selectin‐transfected COS‐I cells in a Ca2+‐dependent way. Immunofluorescent double labelling showed that both BBAI and L‐Canag stained the same cells and morphological co‐localization on E‐selectin‐transfected COS‐I cells. Like BBAI, L‐Canag can inhibit leukocyte HL‐60 cell adhesion to E‐selectin‐transfected COS‐I cells, and this inhibition can be blocked by a F(ab')2 fragment directed against the sialyl‐Lewis a epitope.
Cellular immune response to human renal‐cell carcinomas: Definition of a common antigen recognized by HLA‐A2‐restricted cytotoxic T‐Lymphocyte (CTL) clones
Authors: Bernhard Helga , Karbach Julia , Wölfel Thomas , Busch Petra , Störkel Stefan , Stöckle Michael , Wölfel Catherine , Seliger Barbara , Huber Christoph , Zum Büschenfelde Karl‐Hermann Meyer , Knuth Alexander 
Published: February 2007

AbstractCytotoxic T lymphocyte (CTL) clones directed against autologous renal‐cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor‐cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4‐ CTL clone MZ1257‐CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257‐RCC was established. No lysis of the autologous EBV‐transformed B lymphocytes (EBV‐B) or K562 cells was observed. A panel of HLA‐A2‐matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross‐reactivity with HLA‐A2‐matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross‐reactive with several HLA‐A2‐positive allogeneic normal kidney cells in culture. The restriction element identified for CTL 5/30 was HLA‐A2, as shown by blocking of cytotoxicity using an anti‐HLA‐A2 monoclonal antibody (MAb) and by resistance of an HLA‐A2‐negative melanoma variant SK29‐MEL. 1.22 against lysis by CTL 5/30. In this report we demonstrate HLA‐A2‐restricted recognition of a T‐cell‐defined antigen on autologous renal‐cancer cells. This antigen is also expressed and recognized in association with HLA‐A2 on normal kidney cells in culture and other HLA‐A2‐positive tumor cells. It may therefore be a normal differentiation antigen to which tolerance is incomplete in the renal‐cell cancer system investigated.
Chimeric transcripts with an open reading frame are generated as a result of translocation to the Pvt‐1 region in mouse B‐cell tumors
Authors: Huppi Konrad , Siwarski David 
Published: February 2007

AbstractSome mouse plasmacytomas exhibit a t(6;15) chromosomal translocation in which the breakpoint resides within the Pvt‐1 locus located 260 kilobases (kb) downstream of c‐myc on mouse chromosome 15. In this report, we show that the Pvt‐1 locus does not exhibit allelic exclusion in that Pvt‐1 transcripts continue to be expressed from the non‐translocated allele in t(6;15) plasmacytomas. From the translocated allele, we find chimeric transcripts containing a short 57‐bp segment of Pvt‐1 (termed Pvt‐1a) spliced directly to the immunoglobulin constant region sequence (lg‐Ck). These short transcripts have replaced a Jk segment with a trytophan residue via RNA splicing and contain a continuous open reading frame (ORF) from Pvt‐1a through Ck. Since this Pvt‐1a/Ck transcript is found in all 3 t(6;15) plasmacytomas examined, regardless of the location of the chromosomal breakpoint, we suggest that the Pvt‐1a/Ck chimera may have a functional role in the development of mouse plasmacytomas.
Association of transforming growth factor alpha (TGFA) and its precursors with malignant change in Barrett's epithelium: Biological and clinical variables
Authors: Brito Maria J. , Filipe M. Isabel , Linehan Jacqueline , Jankowski Janusz 
Published: February 2007

AbstractAdenocarcinomas of the gastro‐esophageal junction (GEJ) and those arising in Barrett's esophagus (BE) are increasing in the West and have a poorer prognosis than distal stomach cancers. This has been attributed mainly to anatomical location, but biological factors such as growth‐regulatory molecules have been implicated. We have investigated the expression of one of these factors, TGFα, and its precursor prepro TGFα in 82 adenocarcinomas of GEJ (32 resected specimens and 50 biopsies) as well as in 48 BE biopsies without tumor, by immunohis‐tochemistry and by Western‐blot analysis. TGFα staining was shown in the cytoplasm and membrane of cells. Western blot confirmed that most immunoreactivity was against mature TGFa (5.6 kDa), but higher‐molecular‐weight bands were also identifiable, suggesting some reactivity with prepro protein. TGFα expression was more extense and intense in intestinal metaplasia and cancer. The tubular histological type of adenocarcinoma was more often positive than the signet‐ring type. Primary tumors with lymph‐node metastases also had increased TGFα expression. We conclude, therefore, that there is differential regulation of the expression of TGFα and its precursors during esophageal tumorigenesis. © 1995 Wiley‐Liss, Inc.