bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of type a and b tumor necrosis factor (TNF) receptors on melanoma cells can be regulated by dbc‐AMP and IFN‐γ
Authors: Carrel Stefan , Hartmann Françoise , Salvi Suzanne , Albrecht Hugo , Schreyer Magali , Rimoldi Donata 
Published: February 2007

AbstractLocal administration of high‐dose r‐TNFα with IFNγ in the limbs of melanoma patients has proved to be a very promising treatment. To understand the role played by the effect of TNF on melanoma cells in tumor destruction, we have investigated the expression of TNF‐receptors in melanoma cells using monoclonal antibodies specific for the type‐A (75‐kDa) and the type‐B (55‐kDa) TNF receptors. Flow cytometric analysis of cultured melanoma cells indicated the presence of both types of receptor. Quantificative differences in the relative levels of receptors were observed for different cells lines, although the type‐B receptor was generally more strongly expressed. Similar results were obtained by immunohistochemistry on cryosections from tumor samples. Positive staining of variable intensity was observed for the type‐B TNF‐receptor in a high percentage of tumor cells. The type‐A TNF‐receptor was also detected, but with a weaker staining. The total TNF‐binding activity of cultured melanoma cells, as measured by binding of 125l‐labeled TNFα, was up‐regulated between 2‐ and 4‐fold by incubation of cells with activators of protein kinase A or IFNγ. Treatment of cultured melanoma cells with dbc‐AMP resulted in a selective induction of type‐A TNF‐receptors, without affecting the type‐B receptor level. In contrast, IFN‐y was able to induce either type of receptor in a cell‐line‐dependent fashion. Addition of TNFγ to melanoma cells induced the activation of the nuclear transcription factor KB, as measured in an electrophoretic mobility shift assay, thus indicating the biological significance of the TNF‐receptors on these cells. © 1995 Wiley‐Liss Inc.
MRP gene overexpression in a human doxorubicin‐resistant SCLC cell line: Alterations in cellular pharmacokinetics and in pattern of cross‐resistance
Authors: Binaschi Monica , Supino Rosanna , Gambetta Romolo A. , Giaccone Giuseppe , Prosperi Ennio , Capranico Giovanni , Catalog Ignazio , Zunino Franco 
Published: February 2007

AbstractThe development of non‐P‐glycoprotein‐mediated multidrug resistance is a frequent event among lung‐cancer cell lines. In an attempt to understand the underlying mechanisms of this phenotype, we have selected a multi‐drug‐resistant subline (POGB/DX) in vitro for doxorubicin resistance. The original cell line (POGB) was established in vitro from a non‐treated patient with a small‐cell lung cancer. POGB/DX cells were crossresistant to other drugs, associated with MDR phenotype. In contrast, they were not resistant to taxol, camptothecin or melphalan, but were instead hypersensitive to 5‐fluorouracil. Although expression of the mdr‐l gene was not detected in POGB/DX cells, cellular pharmacokinetics showed a reduced drug accumulation and altered intracellular localization in the POGB/DX cell line. This defect in drug accumulation was associated with overexpression and amplification of the MRP gene. Interestingly, verapamil, a known modulator of P‐glycoprotein function, was able to reverse drug resistance and to increase drug accumulation. In Northern‐blot analysis no differences in expression of topoisomerase I and II (α and β), DNA polymerase β, or HSP70 and HSP60 genes were observed between POGB and POGB/DX. Coupled to lack of changes in expression of known resistance factors, over expression of MRP and modulation by verapamil strongly support a role for this gene product in the development of drug resistance in this SCLC cell system. This study provides evidence that (a) altered cellular pharmacokinetics is related to MRP expression; (b) MRP‐mediated phenotype is characterized by a specific pattern of cross‐resistance, which does not involve taxol; and (c) verapamil may be effective in modulating the function of the MRP gene product. © 1995 Wiley‐Liss Inc.
Identification of a novel peptide derived from the melanocyte‐specific gp100 antigen as the dominant epitope recognized by an HLA‐A2.1‐restricted anti‐melanoma CTL line
Authors: Barker Alexander B. H. , Schreurs Marco W. J. , Tafazzul Gaalda , De Boer Annemiek J. , Kawakami Yutaka , Adema Gosse J. , Figdor Carl G. 
Published: February 2007

AbstractCytotoxic T lymphocytes (CTL) reactive with human melanoma tumor cells occasionally display cross‐reactivity with normal melanocytes. Previously, we identified the melanocyte lineage‐specific antigen gp100 that is expressed by both melanoma cells and normal melanocytes, as a target antigen for tumor‐infiltrating lymphocytes derived from a melanoma patient (TIL 1200). Here, we demonstrate that the oligoclonal HLA‐A2.1‐restricted TIL 1200 line is reactive with 2 distinct peptides derived from the gpl00 protein. Apart from the peptide corresponding to gpl00 amino acids 457–466, we identified the gpl00 peptide 154–162 as a second epitope recognized by TIL 1200. A 100‐fold lower concentration of this novel gpl00 peptide was required for target‐cell sensitization compared to peptide 457–466, indicating that the 154–162 peptide is the dominant gpl00 epitope for TIL 1200. Together with the recently described gpl00 280–288 epitope, 3 distinct CTL epitopes have now been identified in gpl00, all presented in the context of HLA‐A2.1. Therefore, gpl00 is an attractive target antigen in the development of immuno‐therapeutic protocols against melanoma. © 1995 Wiley‐Liss Inc.
Interferon‐α/β can impede development of carcinogen‐induced squamous‐cell tumors in the esophagus of C57B1 mice
Authors: Fagerberg Jan , Rubio Carlos , Gresser Ion , Kuylenstierna Richard , Munck‐Wikland Eva , Strander Hans 
Published: February 2007

AbstractThe effect of treatment with murine interferon‐α/β preparations on diethylnitrosamine‐induced squamous‐cell tumors in the esophagus of C57B1 mice was investigated. Diethylnitrosamine was administered in the drinking water for 18 weeks. Interferon was given intraperitoneally during the same 18 weeks or from the end of the period of carcinogen exposure until termination of the experiment. In mice given interferon and diethylnitrosamine synchronously, a significantly lower tumor index (number of tumors/cm of esophageal mucosa) was observed as compared to all control groups. Treatment with interferon after the administration of the carcinogen was terminated had no effect on the appearance of tumors. These data suggest that interferon therapy can exert certain effects on carcinogenesis. © 1995 Wiley‐Liss Inc.
Socioeconomic factors and human cancer
Authors: Tomatis Lorenzo 
Published: February 2007

AbstractIn spite of the many attempts made at various periods of human history to arrive at an equalitarian society by reducing differences between the rich and the poor and by redistributing wealth, social inequalities have not disappeared and even seem to be increasing worldwide. Inequalities in health represent some of the social inequalities present in our society and are one of their most convincing indices. In industrialized countries, it has been consistently shown that total incidence of and mortality from cancer are higher in less favored socioeconomic groups, mainly due to increased rates at certain sites. The differences observed between socioeconomic groups within industrialized countries are similar, although not identical, to those prevailing between industrialized and developing countries. Occupational risks are becoming a very serious problem in developing countries, largely as a consequence of the transfer of hazardous industries from highly industrialized countries where certain industries are judged to be unacceptable. A similar double standard is applied toward tobacco advertising and sales in the industrialized and developing countries. © 1995 Wiley‐Liss Inc.
Multiple births and risk of breast cancer
Authors: Dietz Amy Trentham , Newcomb Polly A. , Storer Bany E. , Longnecker Matthew P. , Mittendorf Robert 
Published: February 2007

AbstractData from a large, multicenter, population‐based case‐control study were analyzed to investigate the relation between multiple birth pregnancies and subsequent breast‐cancer risk in the gravidas. Women less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, western Massachusetts, Maine and New Hampshire. Controls aged less than 65 years were selected randomly from lists of licensed drivers, and controls aged between 65 and 74 were selected randomly from lists of Medicare beneficiaries. Information on reproductive history and other factors was obtained by means of telephone interviews. After excluding nulliparous women, 5,880 case subjects and 8,217 controls remained for analysis. Multiple birth pregnancies occurred in 146 cases and 218 controls. Adjusted for the number of full‐term pregnancies and other confounders, the odds ratio (OR) for any multiple birth pregnancy was 0.94 (95% confidence interval, 0.75 to 1.17). The null association between multiple birth pregnancies and breast cancer remained if the mother's first pregnancy or last pregnancy resulted in a multiple birth. In addition, no trend in risk emerged for age at first multiple birth or time since last multiple birth. While other investigators have suggested biological mechanisms to explain both protective and detrimental effects of multiple births and subsequent development of breast cancer, this study does not support either assertion. © 1995 Wley‐Liss, Inc.
Correlation between the sensitivity or resistance to IL‐2 and the response to cyclophosphamide of 4 tumors transplantable in the same murine host
Authors: Greco Giampaolo , Gabriele Lucia , Rozera Carmela , Venditti Massimo , Belardelli Filippo , Proietti Enrico 
Published: February 2007

AbstractWe have studied the anti‐tumor response to cyclophosphamide (CTX) in DBA/2 mice transplanted s.c. with 4 tumors exhibiting different responses to IL‐2: ESb lymphoma and Friend leukemia cells (non‐responsive or poorly responsive, respectively), pI I‐R‐Eb and Eb lymphoma cells (both highly responsive to IL‐2). CTX injections on days 7, 14 and 21 resulted in a significant anti‐tumor response in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no anti‐tumor effect was observed in mice injected with Eb or pI I‐R‐Eb cells. All 4 tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide, an in vitro active analogue of CTX. To define the host mechanisms responsible for the lack of an anti‐tumor effect of CTX in mice transplanted with IL‐2‐responsive tumors, we studied several aspects of the spontaneous or IL‐2‐induced anti‐tumor response in mice transplanted with pI I‐R‐Eb cells. Injection of monoclonal antibodies (MAbs) to IFN‐γ completely abolished the anti‐tumor effects of IL‐2. Using a Winn assay, clear‐cut anti‐tumor activity was found in spleen cells from mice transplanted with the IL‐2‐responsive tumors. This activity was abolished by CTX, which also abrogated the anti‐tumor response to IL‐2 in mice injected with pI I‐R‐Eb cells. Our results indicate an inverse correlation between sensitivity to IL‐2 and response to CTX and emphasize the importance of initial host‐tumor interaction in determining the type of response to IL‐2 or CTX. © 1995 Wiley‐Liss, Inc.
Pharmacokinetics and anti‐tumor activity of vincristine encapsulated in sterically stabilized liposomes
Authors: Allen Theresa M. , Newman Mary S. , Woodle Martin C. , Mayhew Eric , Uster Paul S. 
Published: February 2007

AbstractVincristine is used clinically for the treatment of various types of cancer. Recent significant therapeutic improvements obtained by entrapping anthracyclines in sterically stabilized liposomes raised the question whether the therapeutic index of vincristine can be similarly increased by formulation into such long‐circulating liposomes. Encapsulation of vincristine in sterically stabilized liposomes (SL‐VCR) prolonged the drug's distribution phase plasma half‐life in rats from 0.22 to 10.5 hr. There was no significant difference in LD50 (⪋ 2.5 mg/kg, i.v.), but mice given sublethal doses of SL‐VCR experienced significantly less weight loss than those given the same dose of free drug. Compared to free drug, SL‐VCR was most effective against i.p. or s.c. implanted tumors. However, i.v. tumor inoculation nullified the therapeutic advantage of encapsulation. A single i.v. 2 mg/kg dose of SL‐VCR increased the life span of mice bearing i.v. implanted P388 cells by only 44%, while the life span of i.p. P388 implanted mice was increased by 199%. In an s.c. implanted murine colon carcinoma, multiple doses of free drug did little to slow the growth of the tumors, but SL‐VCR was able to produce long‐term survivors in several dose regimens. These results indicate that prolonged circulation time increases the therapeutic index of VCR entrapped in liposomes against s.c. or i.p. implanted tumors, but does not improve the drug's activity against rapidly growing i.v. disseminated leukemias. © 1995 Wiiey‐Liss, Inc.
Composition of ether‐linked sub‐classes of glycerophospholipids in clones with a different metastatic potential isolated from a murine fibrosarcoma line (T3 cells)
Authors: Fallani Anna , Mannori Gianna , Ruggieri Salvatore 
Published: February 2007

AbstractAn increase of ether‐linked sub‐classes of choline and ethanol‐amine glycerophospholipids has been shown in different types of tumor cells, and correlated with some of their specific biological parameters. In the present study, we examined the composition of ether‐linked lipids in a series of clones with a different lung‐colonizing potential isolated in our laboratory from a highly metastatic fibrosarcoma line (T3 cells). We found good correlation between the metastatic potential of T3 isolates and increased proportions of both alkylacyl and alkenylacyl subclasses in choline glycerophospholipids (CGP). Moreover, propagation of a weakly metastatic T3 clone in tissue culture led to the emergence of a sub‐clone which expressed high metastatic potential together with a high level of alkylacyl and alkenylacyl CGP. No differences were found in the alkylacyl and alkenylacyl‐ethanolamine glycerophospholipids (EGP) between the strongly and weakly metastatic T3 clones. We discuss the accumulation of alkylacyl and alkenylacyl CGP in metastatic cells for its possible role in metastatic diffusion by generation of platelet‐activating factor (PAF). © 1995 Wiley‐Liss, Inc.
Differential effects of verapamil and quinine on the reversal of doxorubicin resistance in a human leukemia cell line
Authors: Bennis Sanae , Ichas François , Robert Jacques 
Published: February 2007

AbstractWe studied the restoration of doxorubicin accumulation and sensitivity by verapamil and quinine in a variant of the human erythroleukemia cell line K562 selected for resistance to doxorubicin and presenting a multidrug‐resistance (MDR) phenotype. Verapamil was able to completely restore doxorubicin accumulation in the resistant cells to the level obtained in sensitive cells, but only partially reversed doxorubicin resistance. Quinine, in contrast, had a relatively weak effect on doxorubicin accumulation but was able to completely restore doxorubicin sensitivity in the resistant cells. In addition, verapamil was able to decrease azidopine binding to P‐glycoprotein, whereas quinine was not. Quinine also modified the intracellular tolerance to doxorubicin, which suggests that it is able to modify drug distribution within the cells. Confocal microscopy revealed that verapamil and quinine were able to restore nuclear fluorescence staining of doxorubicin in resistant cells; since this was obtained for quinine without significant increase of doxorubicin accumulation, this observation confirms that quinine acts principally on doxorubicin redistribution within the cells, allowing the drug to reach its nuclear targets. When used in association, verapamil and quinine reversed doxorubicin resistance in a synergistic fashion. We conclude that verapamil and quinine do not share the same targets for reversal of MDR in this cell line; whereas verapamil directly interferes with P‐glycoprotein and mainly governs drug accumulation, quinine has essentially intracellular targets involved in drug redistribution from sequestration compartments. © 1995 Wiley‐Liss Inc.
Engineering high affinity humanized anti‐p185HER2/anti‐CD3 bispecific F(ab′)2 for efficient lysis of p185HER2 overexpressing tumor cells
Authors: Zhu Zhenping , Lewis Gail D. , Carter Paul 
Published: February 2007

AbstractWe previously constructed a humanized anti‐p185HER2/anti‐CD3 bispecific antibody variant, BsF(ab′)2 v1 which retargets the cytotoxic activity of human T cells in vitro against human breast tumor cells which overexpress the p185HER2 product of the HER2/neu (c‐erbB‐2) protooncogene. Subsequently we identified an improved anti‐CD3 variant, v9, which binds to T cells with approx. 100‐fold higher affinity than the original variant, v1. Here we demonstrate that BsF(ab′)2 v9 is more potent than BsF(ab′)2 v1 in stimulating the proliferation of both resting peripheral blood lymphocytes (PBL) and IL‐2‐activated, long‐term cultured T lymphocytes (ATL). In addition, at low concentrations (0.01‐1 ng/ml) BsF(ab′)2 v9 is much more efficient than BsF(ab)2 v1 in directing lysis of p185HER2‐overexpressing tumor cells by IL‐2 activated PBL. In contrast, at higher concentration BsF(ab′)2 v9 and BsF(ab′)2 v1 have similar potency in retargeted cytotoxicity. At BsF(ab′)2 v9 concentrations of ⩾ 1 ng/ml the susceptibility of p185HER2‐expressing tumor cells to lysis is apparently independent of the level of p185HER2 expression. At lower concentrations of BsF(ab′)2 v9 and/or lower ratios of effector to target cells the extent of lysis is reduced, in some cases improving the selectivity of lysis of high p185HER2 expressors over low expressors. Thus selection of a high affinity anti‐CD3 arm is likely important in the design of BsF(ab′)2 for retargeting the cytotoxicity of T cells to tumors. The dose of BsF(ab′)2 v9 in any future clinical evaluation will require optimization to maximize anti‐tumor efficacy whilst minimizing potential toxicity against normal tissue expressing p185HER2. © 1995 Wiley‐Liss Inc.
Identification of differentially expressed genes in T‐lymphoid malignancies in an animal model system
Authors: Starkey Cindi R. , Levy Laura S. 
Published: February 2007

AbstractThe molecular events characterizing lymphoid malignancy have been examined in an animal model system, specifically, the retroviral induction of leukemia and lymphoma in the domestic cat following infection with feline leukemia virus (FeLV). Genes differentially expressed in FeLV‐induced lymphomas were isolated using a strategy of differential hybridization. Six genes were identified which demonstrate a higher level of expression in an FeLV‐induced feline thymic tumor as compared with normal thymus. The differentially expressed genes encode the feline homologues of ribosomal proteins S3a, S4, S17, and L41, elongation factor‐1α, and cytochrome oxidase sub‐unit 1. Northern‐blot analysis and quantification by phosphorimaging demonstrates that these genes are expressed at levels from 1.5‐to 3.1‐fold higher in J5–1 thymic tumor as compared with normal thymus. Expression of the selected ribosomal protein mRNA was further examined in a series of human and feline tissues, including normal tissues, malignant tumors and cell lines. Our data reveal that elevation of the selected ribosomal protein mRNA is associated with all FeLV‐induced thymic lymphomas examined. The differentially expressed ribosomal protein mRNA accumulates in a balanced manner in thymic lymphomas. By contrast, the elevation in ribosomal protein mRNA levels is not associated uniformly with hematopoietic malignancy, T‐lymphoid malignancy, solid tumors or actively proliferating cells. Rather, the elevation appears to be a uniform and distinctive feature of T‐cell malignancy of this particular type. The elevated expression of these genes may be causally related to the neoplastic process. © 1995 Wiley‐Liss Inc.
Cinnamic acid: A natural product with potential use in cancer intervention
Authors: Liu Lei , Hudgins W. Robert , Shack Sonsoles , Yin Mu Quan , Samid Dvorit 
Published: February 2007

AbstractCinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA‐A3, class‐1 major histocompatibility antigen). Further molecular analysis indicated that the anti‐tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation‐inducers with potential use in cancer intervention. © 1995 Wiley‐Liss Inc.
Interleukin‐11 protects the clonogenic stem cells in murine small‐intestinal crypts from impairment of their reproductive capacity by radiation
Authors: Potten Christopher S. 
Published: February 2007

AbstractThe rapidly proliferating gastrointestinal mucosa is one of the major limiting tissues in cancer therapy. Because of its short transit time and high sensitivity to radiation and chemotherapeutic drugs, damage is rapidly manifested. Protection of the important stem cells in the tissue could be achieved, in principle, by appropriate prior manipulation with cytokines or growth factors which might make them more resistant to the cytotoxic treatment, for example, by putting them out of cycle. Such strategies might reduce some of the adverse side‐effects of cancer treatment and improve the quality of life of patients, while possibly allowing an escalation of therapeutic dose. The functional capacity of stem cells has been studied for many years using a microcolony assay technique which measures the regenerative capacity of the clonogenic stem cells in crypts. These cells determine the survival of crypts which themselves determine whether or not the mucosal integrity is maintained and ultimately whether the animal or patient survives. Here, we demonstrate that treatment with interleukin‐11 for 2 days prior to radiation exposure can significantly increase the number of surviving crypts. Treatment with IL‐11 both before (for 2 days) and after irradiation (for 3 days) produces a slightly enhanced protection. Up to about 4 times more crypts survive at the highest radiation dose after either of these treatment schedules. These studies may provide a radiobiological explanation for the increased survival of animals when IL‐11 is administered during SFU and radiation exposures. © 1995 Wiley‐Liss Inc.