bluuebunny/crossref_metadata_2025_split huggingface dataset:
The changing importance of prognostic factors in breast cancer during long‐term follow‐up
Authors: Lipponen P. , Aaltomaa S. , Eskelinen M. , Kosma V.‐M. , Marin S. , Syrjänen K. 
Published: February 2007

AbstractA cohort of 464 breast‐cancer patients were followed up for over 10 years and the clinical, histological and morphometric factors were related to survival within different time periods during follow‐up. Tumor diameter, axillary lymph‐node status (pN), tubule formation and the fraction of intraductal growth as determined from the primary tumor biopsy specimen had prognostic value up to 5 years. Histological grade, morphometric nuclear factors and the M/V index had only short‐term prognostic value immediately after the primary therapy. In axillary lymph‐node‐negative (ANN) tumors tubule formation, intraductal growth, tumor necrosis and tumor diameter had prognostic value during the first 3 postoperative years. In axillary lymph‐node‐positive (ANP) tumors, tumor diameter, intraductal growth and tubule formation had long‐term prognostic value whereas the M/V index had prognostic value only for 1 postoperative year. Tumor diameter, axillary lymph‐node status, tubule formation and the proportion of intraductal growth also had independent long‐term prognostic value in a multivariate analysis and accordingly these factors can categorize breast‐cancer patients into prognostic groups after several years of follow‐up. In contrast, mitotic frequency loses its prognostic power within 2 postoperative years, while morphometric nuclear factors and histological grade have no practical prognostic value after 1 year of follow‐up.© 1992 Wifey‐Liss, Inc.
Risk factors for gallbladder cancer: A polish case‐control study
Authors: Zatonski Witold A. , La Vecchia Carlo , Przewozniak Krzysztof , Maisonneuve Patrick , Lowenfels Al B. , Boyle Peter 
Published: February 2007

AbstractA population‐based case‐control study of gallbladder cancer was conducted in the south‐west of Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer. A total of 73 cases and 186 controls were interviewed using a questionnaire including demographic and socio‐economic factors, education, smoking, alcohol, tea and coffee consumption, and past medical history. A validated diet history was used to estimate the daily intake of calories, fats, carbohydrates, proteins, cholesterol, fibres and vitamins C and E. Gallbladder disease was the major determinant of subsequent gallbladder cancer: 41 cases (56%) vs. 15 (8%) controls had a past history of gallbladder disease, corresponding to an odds ratio (OR) of 12.5 (95% confidence interval, 5.8 to 26.6), and the OR was 12.1 for gallbladder problems dating back 20 years or more in the past. There was an inverse relationship with education, the OR being 0.3 (95% CI 0.1 to 1.2) for 13 years of education or more vs. less than 7. Gallbladder cancer risk was positively associated with total calorie intake, with ORs of 1.4, 1.5,4.1 for the 3 upper quartiles compared with the lowest one (trend, p < 0.01). Weaker direct associations were observed for proteins, carbohydrates and cholesterol. There was some suggestion of inverse associations with fibre intake, and a more consistent one with vitamins C and E. These results further quantify the role of gallstones, and suggest that total calorie intake and other dietary factors potentially linked with benign gallbladder conditions are involved in the aetiology of gallbladder cancer. © 1992 Wifey‐Liss, Inc.
Two antigens detected on human ocular melanomas with the mouse monoclonal antibodies 2/10sn and 10/12SN
Authors: Safi Nour , Kantor Raphe R. S. , Atkinson Barbara , Moratz Chantal , Wilt Allen R. , Pancake Sam , Reba Richard , Mathieson Bonnie J. , Desgrez Alex 
Published: February 2007

AbstractSeven human ocular melanoma cell lines were established in vitro and 3 of these, GU‐4, LLN‐40 and its subline C17‐11, were characterized. Mice were immunized with these ocular melanoma cell lines, and 2 hybridomas producing monoclonal IgG1antibodies (MAb) were produced. MAb 2/10SN recognizes a 44‐kDa monomeric protein, whereas MAb 10/12SN reacts with an 83/65‐kDa heterodimeric protein. These melanoma‐associated antigens (MAA) are detected at high concentrations in the cytoplasm of ocular melanoma cells. However, cell‐surface labelling techniques suggest that these MAA are also associated with the cell‐surface membrane. These 2 ocular MAA are also expressed by several skin melanoma cell lines. Immunohistochemical studies have localized these antigens to ocular and skin melanomas, to sweat ducts and basal squamous cells in normal skin, with limited expression in several other normal tissues and some carcinomas. Biodistribution studies in nude mice with human ocular melanomas have demonstrated good localization of 125I‐labeled MAb 2/10SN at the tumor sites. Therefore, these 2 MAbs, 2/10SN and 10/12SN, recognize MAA which appear to be unique and may prove useful for imaging purposes. © 1992 Wifey‐Liss, Inc.
Potentiation by novobiocin of the cytotoxic activity of etoposide (VP‐16) and teniposide (VM‐26)
Authors: Rappa Germana , Lorico Aurelio , Sartorelli Alan C. 
Published: February 2007

AbstractThe coumermycin antibiotic novobiocin, which interacts with the nuclear enzyme topoisomerase II, produced supra‐additive toxicity to WEHI‐3B D+ leukemia cells at clinically achievable concentrations, when combined with teniposide (VM‐26) or etoposide (VP‐16). Simultaneous exposure of cells to both agents was required for maximum efficacy of the combination. Novobiocin also produced supra‐additive toxicity to A549 human lung carcinoma cells when combined with VM‐26 or VP‐16. At concentrations above the peak plasma levels achievable in patients, novobiocin lost its potentiating activity. Exposure of WEHI‐3B D+ cells to novobiocin did not modify the cytotoxicity produced by the topoisomerase II inhibitor m‐AMSA, whereas, in contrast, novobiocin antagonized the cytotoxicity of m‐AMSA in A549 cells. Although it has been suggested that inhibitors of the syntheses of DNA and RNA interfere with the cytotoxic activity of the epipodophyllotoxins, maximum potentiation of the cytotoxicities of VP‐16 and VM‐26 occurred at novobiocin concentrations that decreased the rates of synthesis of both DNA and RNA in WEHI‐3B D+ cells by about 50%. The number of DNA‐topoisomerase‐ll covalent complexes stabilized by VM‐26 in WEHI‐3B D+ cells was greatly increased when cells were exposed simultaneously to VM‐26 and novobiocin for 1 hr, but not when cells were treated with m‐AMSA and novobiocin for the same period of time. Novobiocin did not affect the amount of covalent complexes produced by VM‐26 in isolated nuclei, suggesting that the potentiating activity of novobiocin was not due to its direct interaction with the nuclear topoisomerase II enzyme. Our findings suggest that therapeutic levels of novobiocin may be capable of enhancing the clinical activities of VP‐16 and VM‐26. © 1992 Wifey‐Liss, Inc.
Polyethylene‐glycol‐modified interleukin‐2 is superior to interleukin‐2 in locoregional immunotherapy of established guinea‐pig tumors
Authors: Mattijssen Vera , Balemans Lianne T. M. , Steerenberg Peter A. , de Mulder Pieter H. M. 
Published: February 2007

AbstractPolyethylene glycol‐modified recombinant human interleukin‐2 (PEG‐IL‐2) represents a cytokine with prolonged circulatory half‐life and increased antitumor activity as compared to recombinant interleukin‐2 (rIL‐2) after systemic administration. We studied whether PEG‐IL‐2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line‐10 tumor cells into the flanks of strain‐2 guinea‐pigs results in a fast‐growing tumor and regional lymph‐node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5‐6 animals were treated with repeated intratumoral and perilymphatic rIL‐2 or PEG‐IL‐2 injections. PEG‐IL‐2 caused significant growth inhibition of both the primary tumor and the regional lymph‐node metastases at lower doses and with less frequent administration than rIL‐2. The best schedule for PEG‐IL‐2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (ρ < 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG‐IL‐2 treatment rejected a rechallenge with line‐10 tumor cells, whereas no cures were seen after rIL‐2 injections. PEG‐IL‐2 therefore appears to be a valuable substance for intratumoral immunotherapy. © 1992 Wifey‐Liss, Inc.
Insulin‐like growth‐factor‐binding protein gene expression and protein production by human tumour cell lines
Authors: Reeve Julie G. , Kirby Lemuel B. , Brinkman Ad , Hughes Stephanie A. , Schwander Jurg , Bleehen Norman M. 
Published: February 2007

AbstractThe secretion of insulin‐like growth‐factor‐binding proteins (IGFBPs) and expression of the genes encoding IGFBP‐I, IGFBP‐2 and IGFBP‐3 have been studied in a panel of cell lines derived from breast carcinomas, Wilms' tumour, neuroblastoma, retinoblastoma, colon carcinoma, liver adenocarcinoma, Burkitt's lymphoma and a non‐small‐cell lung carcinoma. All cell lines, with the exception of the Burkitt's lymphoma cell line, secreted IGFBPs, as detected by affinity labelling. A 34‐kDa BP was present in the conditioned media of all IGFBP‐secreting cell lines, whereas BPs ranging from 18 kDa to 53 kDa were variably secreted. All IGFBP‐secreting cell lines expressed the IGFBP‐2 gene as determined by Northern blot analysis. The Wilms' tumour, the neuroblastoma and the retinoblastoma cell line expressed the IGFBP‐2 gene only. All other cell lines, with the exception of the Burkitt's lymphoma, expressed the IGFBP‐2 gene and, in addition, either the IGFBP‐I gene and/or the IGFBP‐3 gene. IGFBP‐I gene expression could be detected by reverse transcriptase polymerase chain reaction only. IGFBP‐3 gene expression was detected by Northern blot analysis, but transcripts were less abundant than IGFBP‐2 mRNAs. These findings indicate that the expression of multiple BP genes and the secretion of BPs may be a common property of tumour cells. © 1992 Wifey‐Liss, Inc.
Reduced tumorigenicity of fibrosarcomas which constitutively generate il‐1α either spontaneously or following il‐1α gene transfer
Authors: Douvdevani Amos , Huleihel Mahmoud , Zöller Margot , Segal Shraga , Apte Ron N. 
Published: February 2007

AbstractInterleukin‐I (IL‐I) is a major immunoregulatory/proinflammatory cytokine which also affects fibroblast proliferation and function and therefore it was of interest to investigate whether its constitutive expression influences the in vivo tumorigenic potential of transformed fibroblastoid cell lines. Here we report on a strong correlation between the constitutive expression of IL‐1α and reduced tumorigenicity, using various series of oncogene‐transformed NIH/3T3‐derived cell lines which produce the cytokine spontaneously or upon gene transfer, following transfection with the IL‐1α cDNA. Reduced tumorigenicity of the constitutive IL‐1α producing cell lines was manifested either by inability to grow in animals or by regressions of initially growing tumors, within 2 to 3 weeks from cell inoculation. In contrast, mice inoculated with non‐IL‐1‐producing cell lines developed progressive tumors which ultimately killed the animals. Clones obtained from a non‐IL‐1‐producing met‐transformed cell line shifted from a progressive to a regressive phenotype, following transfection with an IL‐1α‐encoding gene, inserted into an appropriate expression vector, resulting in constitutive expression of the cytokine. The effects of constitutive IL‐1 expression on tumor development were observed both in histocompatible (NFS/N) and partially allogeneic (BALB/c) mice; however, they were more pronounced in the allogeneic environment. Fibrosarcomas which are non‐IL‐1 producers induced progressive tumors in both strains of mice at the same growth rate. The differences between the growth characteristics of the fibrosarcomas in histocompatible vs. partially allogeneic mice suggest that IL‐1 exerts adjuvant‐like effects which increase the immunogenicity of tumor‐cell antigens, and they also argue against the possibility that an IL‐1‐mediated local non‐specific inflammatory response is the major effector mechanism of tumor rejection. Indeed, in subsequent studies we shall report on the importance of specific cellular immune responses, especially cytotoxic T lymphocytes (CTLs), in the eradication of constitutive IL‐1‐producing fibrosarcomas. Thus, our findings may serve as the basis for novel immunotherapy strategies aimed at the induction of IL‐1 expression by cells comprising the neoplasm or alternatively by local application of the cytokine in the vicinity of the tumor. © 1992 Wifey‐Liss, Inc.
Prevalence and expression of human papillomavirus in tonsillar carcinomas, indicating a possible viral etiology
Authors: Snijders Peter J. F. , Cromme Frans V. , Van Brule Adriaan J. C. Den , Schrijnemakers Henri F. J. , Snow Gordon B. , Meijer Chris J. L. M. , Walboomers Jan M. M. 
Published: February 2007

AbstractThe presence of human papillomavirus (HPV) DNA was assessed in biopsies of tonsillar carcinomas (n = 10) and cases of tonsillitis (n = 7), serving as controls, by general‐primer‐mediated PCR (GP‐PCR). All carcinomas appeared HPV‐positive, whereas all cases of tonsillitis were HPV‐negative. Additional type‐specific PCR for HPV 6, 11, 16, 18, 31 and 33 revealed that 4 carcinomas contained HPV 16 DNA, 4 contained HPV 33 DNA and I contained an HPV 16/33 double infection. False positivity was excluded by additional Southern blot analysis of type‐specific PCR‐positive samples (n = 4). Further characterization of GP‐PCR products by sequence analysis revealed that 2 carcinomas contained still uncharacter‐ized HPV genotypes; one of these also contained HPV 33 DNA and one was negative by type‐specific PCR. Application of RNA PCR revealed expression of HPV 16 or HPV 33 E7 encoding spliced E6*l transcripts in all tonsillar carcinomas (n = 4) examined. Additional non‐radioactive RNA in situ hybridization performed on 3 biopsies revealed the presence of HPV 16 or HPV 33 E7 transcripts exclusively localized within the carcinoma cells, whereas stroma stained negative. These findings strongly support a role for certain HPV types in the pathogenesis of tonsillar carcinomas.
Colon cancer in argentina. I: Risk from intake of dietary items
Authors: Iscovich J. M. , L'Abbé K. A. , Castelleto R. , Calzona A. , Bernedo A. , Chopita N. A. , Jmelnitzsky A. C. , Kaldor J. 
Published: February 2007

AbstractA case‐control study has been conducted to investigate the relationship between dietary components and risk of colon cancer in the La Plata area of Argentina. Cases are 110 patients newly diagnosed with colon cancer in 10 major hospitals between 1985 and 1986. Two neighbourhood controls per case were individually matched by age, sex and place of residence. Personal interviews elicited information on frequency of consumption of 140 food items during the 5‐year period up to 6 months prior to interview. Risk is analyzed by quartiles of individual food items and groups of items. Multivariate conditional logistic regression modelling indicates that consumption of eggs is associated with increased risk for colon cancer (odds ratios by quartile: 1.0, 1.58, 2.02, 4.66), as are some dairy products (ORs of 1.93 for the highest quartile of consumption of cheese). Intake of vegetables, fish and poultry is associated with statistically significant decreasing risk (ORs of 0.075, 0.39 and 0.39, for the highest categories of consumption of vegetables, fish and poultry, respectively). The risk for red meat does not consistently increase as consumption increases. Risks are not altered by the inclusion of potential confounders such as education or body mass index. These findings confirm those of several previous studies and are of particular interest, since the Argentinean diet typically includes a high intake of red meat.
An analysis of autologous T‐cell anti‐tumour responses in colon‐carcinoma patients following active specific immunization (ASI)
Authors: Patel B. T. , Lutz M. B. , Schlag P. , Schirrmacher V. 
Published: February 2007

AbstractAs part of a phase‐II clinical trial of post‐operative active specific immunization (ASI) with virus‐modified autologous tumour cells (AuTu) in colorectal carcinoma patients, we have analyzed in vitro anti‐AuTu immune responses with lymphocytes isolated from the peripheral blood (PBL) of 5 treated patients. The PBL of 3 “responder patients”, those who developed a positive DTH reaction to AuTu, when stimulated in standard in vitro autologous lymphocyte tumour‐cell cultures (ALTC), showed cytotoxic anti‐AuTu reactivity only in association with natural‐kilIer‐cell(NK)‐like activity. We removed nonspecific cytotoxic cells (CD56‐positive) from PBL of colon carcinoma or melanoma patients and positively selected T cells with strong CD8 staining (CD8hi) using FACS. Following in vitro stimulation, specific cytotoxic T cells (CTL) directed against either autologous EBV‐transformed B cells (AuEBV‐B) or autologous melanoma cells were identified in the CD8hi T‐cell population. However, even using this novel technique, no specific CTL against autologous colon carcinoma cell lines were detected in PBL from ASI‐treated patients (2 DTH responders and 2 DTH non‐responders). If AuTu‐specrfic CTL precursors existed in these blood samples, their frequency must have been very low (less than 1 in 8 × 104 CD8 positive T cells). Sorted CD4 T cells from these patients, in the presence of autologous antigen‐presenting cells, showed no specific anti‐tumour proliferative response, and in one instance we observed inhibition of proliferation in the presence of tumour cells.
A prospective study of transmission by transfusion of HTLV‐I and risk factors associated with seroconversion
Authors: Manns Angela , Wilks Rainford J. , Murphy Edward L. , Haynes Grace , Figueroa J. Peter , Barnett Marge , Hanchard Barrie , Blattner William A. 
Published: February 2007

AbstractTo evaluate the risk of transfusion‐related transmission of HTLV‐I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV‐I serological screening assay. This information would prove useful in formulating strategies for blood‐donor screening. We followed 118 pre‐transfusion HTLV‐l‐negative transfusion recipients at monthly intervals posttransfusion for I year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV‐I seroconversion was estimated and risk‐factor data associated with seroconversion among 66 HTLV‐l‐exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV‐l‐positive cellular blood components, 0/12 recipients of positive non‐cellular donor units and 0/52 recipients of HTLV‐l‐negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immunosuppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood‐borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV‐I transmission and that screening of donor blood effectively prevents HTLV‐I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood‐donor screening for HTLV‐I is not possible.
Inhibitory effects of human interferons on the immortalization of HUMAN, but not rabbit, T lymphocytes by human T‐lymphotropic virus type‐I (HTLV‐I)
Authors: Oka Takashi , Iwata Jun , Furihata Mutsuo , Sonobe Hiroshi , Miyoshi Isao , Ohtsuki Yuji 
Published: February 2007

AbstractThe effects of human interferon (IFN)‐α, ‐β, and ‐γ on the immortalization of human and rabbit lymphocytes by human T‐lymphotropic virus type‐l (HTLV‐I) have been investigated. The immortalization of human peripheral‐blood lymphocytes co‐cultured with lethally X‐ray‐irradiated HTLV‐l‐producer cells, MT‐2, was blocked in the presence of more than 40 u/ml human recombinant IFN‐α or more than 200 u/ml human natural type IFN‐fi. However, rhlFN‐γ did not block immortalization by HTLV‐I even at higher doses. On the other hand, the presence of high doses of hlFN‐α, ‐β, or ‐γ did not exhibit any biological effect on the immortalization of rabbit peripheral‐blood lymphocytes co‐cultured with lethally X‐ray‐irradiated MT‐2 cells. Integration of the full length of HTLV‐I genome was detected in every transformant by Southern blot analysis. All cell lines established were CD4+/CD8÷ T‐lymphocytes, except for one cell line of CD4+/CD8+. Morphologically intact HTLV‐I production was observed by electron microscopy in these cells. Our results indicate that HTLV‐I released under the strongly suppressed condition in the presence of IFNs remains active and able to immortalize T lymphocytes. It is also suggested that immortalization of human T lymphocytes by HTLV‐I can be inhibited by the antiviral state induced by the treatment with low doses of hlFN‐α and ‐β, whereas immortalization of rabbit T lymphocytes is not inhibited because of the species specificity of hlFNs.
Modifications of an immunodominant peptide antigen induce different anti‐polyoma tumor responses in two separate mouse strains
Authors: Reinholdsson‐Ljunggren Git , Dalianis Tina 
Published: February 2007

AbstractAn immunodominant polyoma peptide antigen MT162‐176 was modified with regard to amino acid (aa) composition in an attempt to analyze its immunogenicity in detail. Twelve modifications of peptide MT 162‐176, 3 overlapping peptides and 9 peptides with point mutations, were synthesized and used for immunizations of (A.CA x C57BL/6)F1 and CBA mice against the syngeneic polyoma tumors SECA and SEBA All 3 overlapping peptides MT 162‐176, MT165‐174 and MT 170‐176, were immunogenic in (A.CA x CS7BL/6)F1 mice against SECA, indicating that possibly more than one immunogenic epitope may be recognized within the MT 162‐176 sequence. In CBA mice, the 2 peptides covering the C‐terminal half were immunogenic against SEBA, while the N‐terminal peptide was possibly somewhat less efficient. The peptides with aa point mutations induced different anti‐tumor responses in the 2 mouse strains. In CBA mice, only one mutant, MT162‐176.28, was immunogenic. For (A.CA x C57BI)F1 3 different mutants, MTI62176.29, MTI62‐I76.35 and MTI62‐I76.36 were immunogenic against SECA, while the remaining 6 had lost their activity. These results suggest that a different emphasis of recognition of peptide MT 162‐176 exists with regard to the 2 mouse strains examined. Furthermore, different immunization procedures were tested. We found that repeated immunizations with peptide without Freund's adjuvant was the most efficient. © 1992 Wiley‐Liss, Inc.