bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction chemotherapy for advanced head and neck cancers: A literature review
Authors: Chang Tsuling Michele
Published: February 2007

Induction chemotherapy before surgery and/or radiotherapy for previously untreated head and neck carcinoma results in greater response rates than chemotherapy for recurrent head and neck carcinomas. Its theoretical advantages are presented. Most studies using induction chemotherapy are nonrandomized, uncontrolled pilot efforts. Multiple‐drug regimens result in greater response rates than single agents, and multiple courses result in greater response rates than single courses. Prognostic factors are discussed. Toxicities are tolerable, except for several reported regimens combining cisplatin, bleomycin, and metho‐trexate. Induction chemotherapy for head and neck cancer is promising and needs further studies with controlled, randomized trials with long‐term follow‐up.
T1‐T2 vocal cord carcinoma: A basis for comparing the results of radiotherapy and surgery
Authors: Mendenhall William M. , Parsons James T. , Stringer Scott P. , Cassisi Nicholas J. , Million Rodney R.
Published: February 2007

This is an analysis of 304 patients with invasive, previously untreated T1‐T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy between October 1964 and December 1984. All patients had a minimum 2‐year follow‐up and 82% had at least 5 years of follow‐up. Patients were excluded from the analysis of local control if they died within 2 years of treatment with the primary site continuously disease‐free. Patients were staged according to the AJCC system and stratified by the surgical procedure that would have been required to resect the tumor. Stage T2 was subdivided into two subsets: T2a (normal mobility) and T2b (decreased mobility). The rates of local control with radiotherapy and the ultimate rates of local control, including patients salvaged surgically for a local recurrence, were as follows: T1, 159 of 171 (93%) and 166 of 171 (97%); T2a, 50 of 65 (77%) and 63 of 65 (97%); and T2b, 31 of 43 (72%) and 38 of 43 (88%). The rate of local control for patients with T1 lesions limited to one cord was not influenced by tumor extension to the anterior commissure. The overall incidence of serious complications was 5 of 304 (1.6%). The 5‐year determinate survival rates were as follows: T1, 130 of 134 (97%); T2a, 43 of 46 (93%); and T2b, 29 of 33 (88%).
Retropharyngeal infiltrating lipoma‐A case report
Authors: Eisele David W. , Landis George H.
Published: February 2007

Infiltrating lipoma is an unusual, benign, slowly growing neoplasm that characteristically infiltrates skeletal muscle and has a propensity for local recurrence if incompletely excised. These tumors rarely occur in the head and neck. A case of infiltrating lipoma of the retropharynx is reported. The clinical, histologic, surgical, and radiologic aspects of the lesion are reviewed. The use of magnetic resonance imaging of this tumor is presented.
Allylic Alcohols as Substrate for Ruthenium‐Catalyzed CC Coupling Allylation Reactions. Preliminary Communication
Authors: Nieves Ignacio Fernández , Schott Danièle , Gruber Stefan , Pregosin Paul S.
Published: February 2007

Allylic alcohols, rather than halides, acetates, or carbonates can be used directly in the Friedel–Crafts‐type coupling with various phenols. The use of a RuIV, rather than a RuII, precursor promotes the formation of one H+ per cycle so that a large excess of acid is never present in the reaction mixture. Consequently, the leaving group in the oxidative addition reaction is H2O, thereby avoiding the production of an unnecessary by‐product.
Phenolic Compounds from Scorzonera tomentosa L.
Authors: Sarı Aynur , Zidorn Christian , Ellmerer Ernst P. , Özgökçe Fevzi , Ongania Karl‐Hans , Stuppner Hermann
Published: February 2007

From the subaerial parts of S. tomentosa L. (Asteraceae), two new dihydroisocoumarins, compounds 1 and 2, a new phthalide, 3, and a new stilbene derivative, 4, were isolated, together with four known compounds, (±)‐hydrangenol (5), (−)‐hydrangenol 4′‐O‐β‐glucoside (6), (±)‐hydramacrophyllol A (7), and (±)‐hydramacrophyllol B (8). All secondary metabolites were identified on the basis of physicochemical, spectroscopic, and mass‐spectrometric data. The known compounds 5–8 were isolated for the first time from this species.
New Iridoid Glycosides from Lamium eriocephalum subsp. eriocephalum
Authors: Yalçın Funda Nuray , Ersöz Tayfun , Avcı Kürşat , Gotfredsen Charlotte H. , Jensen Søren R. , Çalış İhsan
Published: February 2007

Two new iridoid glycosides, eriobioside (1) and lamerioside (2), were isolated from the aerial parts of Lamium eriocephalum subsp. eriocephalum, along with the two known compounds lamiide (3) and ipolamiide (4). Their structures were elucidated by spectroscopic methods (UV, 1D‐ and 2D‐NMR) and by mass spectrometry (HR‐ESI‐MS).
β‐Cyclodextrin‐Supported, Completely Regioselective Ring Opening of Thiiranes with Thiophenol in Water
Authors: Reddy Majjigapu Somi , Surendra Karavadi , Krishnaveni Neelam Srilakshmi , Narender Mendu , Rao Kakulapati Rama
Published: February 2007

Thiolysis of thiiranes I with thiophenols II is performed efficiently in the presence of β‐cyclodextrin in water with high regioselectivity (Scheme, Table).
Estimation of irrigation flow by hydrograph analysis in a complex agricultural catchment in subtropical China
Authors: Tang Jia‐Liang , Zhang Bin , Zepp Harald
Published: February 2007

Estimating the amount of irrigation water is challenging at the catchment scale because of the difficulties in direct measurement and interactions between the flow components. The objectives of the study were to characterize the catchment flows in an agricultural catchment with an irrigation system in subtropical China and to estimate catchment irrigation flow using hydrograph analysis methods. A weighting model and multiple regression models were established to estimate catchment irrigation outflow according to the hydrographs of the inflows and outflows of the catchment. The multiple regression models took into consideration the drainage time of base flow, resulting in better estimation on an event and annual basis. Using the MR‐6d method, the estimated irrigation outflows amounted to 3700 mm, 2600 mm and 2760 mm during 2001, 2002 and 2003 respectively, which covered 70%, 60% and 64% respectively of the total catchment outflows in the corresponding years. Copyright © 2007 John Wiley & Sons, Ltd.
Runoff dependent erosivity and slope length factors suitable for modelling annual erosion using the Universal Soil Loss Equation
Authors: Kinnell P. I. A.
Published: February 2007

Despite revisions and refinements, the Revised Universal Soil Loss Equation (RUSLE), which is the revised version of the Universal Soil Loss Equation (USLE), over predicts small annual soil losses and under predicts large annual soil losses. To some large extent, this results from the equation over estimating small event soil losses and under estimating large event soil losses. Replacing the USLE/RUSLE event erosivity index (EI30) by the product of EI30 and the runoff ratio (QR) significantly reduces the errors in estimating event erosion when runoff is measured, but the USLE‐M, the USLE variant that uses the QREI30 index, requires crop and support practice factors that differ from those used in the RUSLE. The theory which enables the QREI30 index to be used in association with the RUSLE crop and support practice factors is presented. In addition, the USLE/RUSLE approach was developed for conditions where runoff is produced uniformly over a hill slope. A runoff dependent slope length factor that takes account of runoff variations over a hill slope is presented and demonstrated for the situation where runoff from a low runoff producing area passes onto an area where runoff is produced more readily. Copyright © 2007 John Wiley & Sons, Ltd.
Sun exposure and malignant lymphoma: A population‐based case–control study in Germany
Authors: Weihkopf Thomas , Becker Nikolaus , Nieters Alexandra , Mester Birte , Deeg Evelin , Elsner Gine , Blettner Maria , Seidler Andreas
Published: February 2007

Although some causes for malignant lymphoma are known their etiology is not well understood so far. We analyze the relationship between sun exposure and malignant lymphoma in a multicenter, population‐based case–control study. Patients with malignant lymphoma (n = 710, 18–80 years) were prospectively recruited in 6 study regions in Germany. For each case, a gender, region and age‐matched control was drawn from population‐registers. In personal interviews, lifetime holidays spent in sunny climate, outdoor leisure activities and sunbed or sunlamp use were recorded. On basis of job task‐specific supplementary questionnaires, an occupational physician assessed the cumulative working time outside. Odds ratios (OR) and 95%‐confidence‐intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking and alcohol consumption. To increase statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression. We observed a reduced overall lymphoma risk among subjects having spent vacations at sunny climates or frequently used sunbeds or sunlamps. The analysis of lymphoma subentities revealed similar results with the exception of T‐NHL and follicular lymphoma which were positively associated with outdoor leisure activities. While cumulative working time outside appeared unrelated to NHL overall and most subentities, it was negatively associated with follicular lymphoma and weakly positively to HL. This data suggest that exposure to natural and artificial ultraviolet radiation may reduce the OR for lymphoma in this study population. © 2007 Wiley‐Liss, Inc.
Polymorphisms in one‐carbon metabolism and trans‐sulfuration pathway genes and susceptibility to bladder cancer
Authors: Moore Lee E. , Malats Núria , Rothman Nathaniel , Real Francisco X. , Kogevinas Manolis , Karami Sara , García‐Closas Reina , Silverman Debra , Chanock Stephen , Welch Robert , Tardón Adonina , Serra Consol , Carrato Alfredo , Dosemeci Mustafa , García‐Closas Montserrat
Published: February 2007

We have previously reported significant inverse associations between bladder cancer risk and dietary intake of vitamins B2, B6, B12, folate and protein in a hospital‐based bladder cancer case‐control study conducted in Spain (1,150 cases;1,149 controls). Because these dietary factors are involved in the one‐carbon metabolism pathway, we evaluated associations between bladder cancer risk and 33 single nucleotide polymorphisms (SNPs) in 8 genes (CBS, CTH, MTHFR, MTR, MTRR, SHMT1, SLC19A1andTYMS) and interactions with dietary variables involved in this pathway. Two SNPs in theCTHgene were significantly associated with bladder cancer risk. OR (95% CI) for heterozygous and the homozygous variants compared to homozygous wild‐type individuals were: 1.37 (1.04–1.80) IVS3‐66 A > C and 1.22 (1.02–1.45) IVS10‐430 C > T. Because theCTHgene is important for glutathione synthesis, we examined interactions with theGSTM1gene, which codes for glutathione S‐transferase μu. Increased risk for individuals with the IVS10‐430 CT or TT genotype was limited to those with theGSTM1null genotype (p‐interaction = 0.02). No other SNPs were associated with risk of bladder cancer. These findings suggest that common genetic variants in the one‐carbon pathway may not play an important role in the etiology of bladder cancer. However, our results provide some evidence that variation in glutathione synthesis may contribute to risk, particularly among individuals who carry a deletion inGSTM1. Additional work is needed to comprehensively evaluate genomic variation inCTHand related genes in the trans‐sulfuration pathway and bladder cancer risk. © 2007 Wiley‐Liss, Inc.
In vivo and in vitro invasiveness of a rat colon‐cancer cell line maintaining E‐cadherin expression: An enhancing role of tumor‐associated myofibroblasts
Authors: Dimanche‐Boitrel Marie Thearèse , Vakaet Luc , Pujuguet Philippe , Chauffert Bruno , Martin Monique S. , Hammann Arlette , Van Roy Frans , Mareel Marc , Martin François
Published: February 2007

In various cell systems, an inverse relationship was found between expression of E‐cadherin, a molecule involved in the Ca2+‐dependent homophylic cell‐to‐cell attachment of epithelial cells, and the capacity to invade extracellular matrix gels or normal tissues in vitro., DHD/K12/TRb (PROb) cells, maintained as a cell line derived from a rat colon carcinoma, homogeneously expressed. in vitro immunoreactive E‐cadherin, which was functional as shown in cell dissociation‐reassociation assays. PROb cells were found to be non‐invasive in 3 different assays in vitro., However, tumors resulting from a s.c. injection of PROb cells into syngeneic BD‐IX rats were invasive, although PROb cells maintained E‐cadherin expression in the tumors. Cells from a freshly dissociated PROb tumor showed, not only PROb cells but also tumor‐associated myofibrobfasts and were able to cross a Matrigel‐coated filter. PROb tumors were indeed infiltrated by numerous myofibroblasts, mainly located at the invasive edge of the tumor. Cells from an established culture of tumor‐infiltrating myofibroblasts were able to confer upon PROb cells invasiveness through Matrigel‐coated filter or into chick‐heart fragments. PROb cells maintained their capacity to express E‐cadherin after myofibroblast‐enhanced Matrigel invasion. Tumor‐associated myofibroblasts, but not PROb cells, secreted a 72‐kDa collagenase that could play a role in tumor‐cell invasion. These results strongly suggest that cells from the tumor stroma, and more specifically myofibroblasts, may be involved in the invasiveness of epithelial tumor cells in vivo, even when E‐cadherin expression prevents tumor‐cell invasiveness in different in vitro assays.
ErbB‐2 expression in estrogen‐receptor‐positive breast‐tumor cells is regulated by growth‐modulatory reagents
Authors: Taverna Daniela , Antoniotti Susanna , Maggiora Piera , Dati Claudio , de Bortoli Michele , Hynes Nancy E.
Published: February 2007

It has previously been shown that, in the estrogen‐receptor‐positive breast‐tumor cell lines T47D and ZR75.1, the erbB‐2 protein and mRNA content are controlled negatively and positively by, respectively, estrogens and anti‐estrogens. Since estrogens have a positive effect on cell proliferation, while anti‐estrogens inhibit cell growth, the results suggested that there may be an inverse correlation between growth and erbB‐2 expression, We have now examined this matter further. The effect of various growth‐modulatory agents including estrogen (E2), progesterone (Pg), retinoic acid (RA), epidermal growth factor (EGF), insulin (Ins), prolactin (Prl), 12‐O‐tetradecanolyl‐phorbol‐13‐acetate (TPA) and dibutyryl‐3′:5′‐cycfic‐AMP (cAMP) on c‐erbB‐2 promoter activity, RNA and protein expression have been examined. The growth stimulators E2 and EGF both reduced the level of erbB‐2 protein. However, while E2 clearly repressed erbB‐2 transcription, in the case of EGF, neither mRNA nor transcription were decreased. Of the agents which inhibit the growth of T47D and ZR75.1 cells—Pg, Prl, cAMP, RA and TPA—only Pg and cAMP caused an increase in the erbB‐2 protein level. Pg and cAMP positively influenced c‐erbB‐2 promoter activity and RNA amount. TPA and RA also increased promoter activity but neither erbB‐2 mRNA nor protein level was enhanced. The erbB‐2 protein expression in cultures of T47D and ZR75.1 cells at different densities was also analyzed. Both the level of erbB‐2 protein and c‐erbB‐2 promoter activity rose markedly in confluent cultures, suggesting a transcriptional mechanism of control. In conclusion, the data suggest that the effects of various agents on erbB‐2 expression are complex and cannot be explained simply as reflecting the growth state of the cells.
Internalization and intracellular processing of an anti B‐cell lymphoma monoclonal antibody, ll2
Authors: Shih Lisa B. , Lu Helen H.‐Z. , Xuan Hong , Goldenberg David M.
Published: February 2007

The successful clinical experience with antibody LL2 (an IgG2a, anti‐B‐cell lymphoma antibody) in radipimmunodetection and radioimmunotherapy suggests that this antibody may have potential as a carrier of cytotoxic agents. The internalization, cellular trafficking, and catabolism of this antibody in target human Burkitt lymphoma cells (Raji) were investigated. Internalization of intact antibody as well as of the F(ab')2 and Fab' fragments was detected by an FITC‐labeled anti‐mouse second antibody probe, and evaluated by fluorescence microscopy. Internalization of intact IgG (or the fragments) was observed as early as 5 min after incubation at 37°C. Initially, the internalized antibodies were present as micro‐particles inside the cell membrane, and were translocated to the lysosomal compartment within 2 hr. The anatomic location of the internalized antibody, before translocation to the lysosomal compartment, was deduced by comparing the fluorescence images obtained with the antibody to those obtained with fluorescent probes with known cellular distribution in a co‐internalization study. A Golgi‐like compartment was found to be involved in the translocation of the antibody. Cellular catabolism of the bound antibody was studied by using 125I‐labeled antibody on the target cells. At 21 h, 40% of the radioactivity was released into the supernatant as degraded fragments. The observation suggested that the antibody was degraded mainly in the lysosomes, since the degradation was significantly inhibited in the presence of lysosomal inhibitors such as ammonium chloride or leupeptin. Subcellular fractionation of Raji cells after the binding of 125I‐lbeled LL2 indicated that the antibody was translocated to lysosomes as evidenced by SDS‐PAGE. The rate of internalization (K) of LL2, and the re‐expression of the antigen were determined. The rapid Internalization of LL2 and the reexpression of the antigen suggest that this antibody may have potential as a therapeutic immunoconjugate, since it could deliver a higher accumulation of cytotoxic agents into lymphoma cells.
The scid mouse environment causes immunophenotypic changes in human immature T‐cell lines
Authors: Uittenbogaart Christel H. , Anisman Deborah J. , Tary‐Lehmann Magdalena , Vollger Leanne W. , Breit Timo M. , van Dongen Jacques J. M. , Saxon Andrew
Published: February 2007

In order to evaluate whether the SCID mouse can provide the microenvironment for the growth of human immature T‐cell leukemias and if in vivo growth alters their phenotype, we examined the behavior of 3 well‐characterized T‐cell acute lymphoblastic leukemia (T‐ALL)‐derived T‐cell lines which are at different stages of maturation (CEM, SUP‐T3 and MOLT‐4f) after transfer to non‐irradiated SCID mice. All 3 T‐cell lines engrafted and proliferated to form tumors in the mice and showed dissemination patterns in the SCID mouse comparable to those of T‐ALL in man: i.e., human cells were detectable by flow cytpmetry or were cultured from mouse bone marrow, spleen, liver or thymus. CEM, which is the most immature T‐cell line, readily formed tumors after injection of cells. The more mature T‐cell lines, SUP‐T3 and MOLT‐4f, required a longer time period, even after injection of higher cell numbers. Whereas no changes in the configuration of the rearranged T‐cell receptor genes were detected, striking phenotypic changes were observed in all 3 leukemias growing in the SCID mice after injection. SCID‐CEM cells showed an increase in the surface expression of CD3 and CDS and a decrease in the expression of CD1 and CD71 (transferrin‐receptor). SCID‐MOLT‐4f cells showed an increase in CD5 and CD5 expression and a decrease in CD45RA expression. SCID‐SUP‐T3 cells showed increased expression of CD5 and CD45RA. Apparently, the mouse environment caused changes in cell‐surface antigen expression on the T‐ALL‐derived T‐cell lines. Some immunophenotypic changes remained stable during subsequent growth in culture of SUP‐T3 cells, suggesting that maturation of the cell line occurred in vivo. The other cell lines, CEM and MOLT‐4f after undergoing in vivo‐induced changes, reverted to the original immunopheno‐type, suggesting transitory activation in vivo. These data point out the importance of stromal factors in defining growth and maturation of human leukemic cells in vivo, in SCID mice.
In vivo phenotypic characteristics of AKR T‐cell lymphomas with different leukemic potential: Possible role of α4β7 integrin in the progression towards the leukemic phenotype
Authors: Dolcetti R. , Frisan T. , Palmieri G. , Rizzo S. , Maestro R. , Santoni A. , Boiocchi M.
Published: February 2007

The present study was undertaken in order to determine whether the expression of specific surface molecules which mediate immune recognition as well as cell‐cell and cell‐matrix interactions is associated with the leukemic evolution of T‐cell lymphomas. To this end, we have investigated the in vivo phenotypic characteristics and the in vitro natural‐killer(NK)‐cell susceptibility of a group of MCF‐247‐induced AKR/J T‐cell lymphomas with different leukemic potential. We found that in the AKR/J model, the biological aggressiveness of leukemic cells is not dependent upon an escape from host immune surveillance as a consequence of an in vivo down‐regulation of H2‐Kk determinants or a resistance to NK lysis. Moreover, NK susceptibility of AKR/J lymphomas does not seem to correlate with the level of H2‐antigen expression. No obvious correlation was found between the leukemic phenotype and the amount of MEL‐14, LFA‐1, ICAM‐1, Pgp‐1/CD44 and THAM/CD26 antigen expression. An in vivo coordinated up‐regulation of α4 and β7 integrin chains, with the highest levels of expression detected in secondary sites of leukemic infiltration, was observed in the highly leukemic lymphoma NQ22 and, albeit to a lesser extent, in lymphomas with moderate leukemic potential. Conversely, non‐leukemic lymphomas were repeatedly α4‐and β7‐negative. These findings suggest that in the AKR/j system the expression of α4 β7 integrin may contribute to leukemic spreading of T‐cell lymphomas.
The role of protein kinase C isoenzymes in the growth inhibition caused by bryostatin 1 in human A549 lung and MCF‐7 breast carcinoma cells
Authors: Tanwell Caroline S , Gescher Andreas , Bradshaw Tracey D. , Pettit George R.
Published: February 2007

Bryostatin I is a natural product currently under clinical evaluation as an antitumor agent. Like the tumor‐promoting phorbol ester 12‐O‐tetradecanoylphorbol‐13 ‐acetate (TPA) it activates protein kinase C (PKC). Bryostatin I inhibits the growth of the human‐derived A549 lung and MCF‐7 adenocarci‐noma cell lines, but much more weakly than TPA. The hypotheses were tested that differences between cell lines in their response to bryostatin I are related to cellular PKC isotype content, and that differences between TPA and bryostatin I in their effects on cell growth are associated with differential abilities to modulate specific PKC isoenzymes. PKC isozyme profiles were studied by Western‐blot analysis in the cytosol, particulate and nuclear fractions of A549 and MCF‐7 cells. PKCs‐α, −ϵ and −ζ were detected in both cell types with predominant location in the cytosol. Separation of cytosolic PKC isoenzymes in A549 cells by hydroxylapatite column chromatography and determination of PKC activity in fractions yielded a major peak which contained PKC‐α. Exposure of cells to bryostatin I or TPA for 30 min caused the redistribution of PKCs‐α and −ϵ from the cytosol to the particulate and nuclear fractions in a concentration‐dependent fashion. PKC −ϵ was completely down‐regulated by exposure to 10 nM bryostatin I for 18 hr or to TPA for 24 hr. Down‐regulation of PKC‐α was partial at 10 nM and complete at I μM of either agent. Bryostatin I inhibited incorporation of [3H]‐labelled thymidine into cells only transiently, whereas TPA arrested growth for several days in A549 cells and irreversibly in MCF‐7 cells. A549 cells, in which PKC was depleted by exposure to phorbol ester for 9 weeks, were resistant towards bryostatin‐induced inhibition of DNA synthesis. The results suggest that the susceptibility of adenocarcinpma cells towards bryostatin‐induced growth delay are determined by cellular levels of PKCs‐α and/or −ϵ. However, differences between bryostatin I and TPA in their abilities to inhibit cell growth do not seem to be intrinsically related to differences in redistribution or down‐regulation of specific PKC isoenzymes.
TGF‐α can act as morphogen and/or mitogen in a colon‐cancer cell line
Authors: Liu Dan , Gagliardi Giuseppe , Nasim Mansoor M. , Alison Malcolm R. , Oates Tim , Lalani El‐Nasir , Stamp Gordon W. H. , Pignatelli Massimo
Published: February 2007

Transforming growth factor alpha (TGF‐α) has multifunctional biological effects on a variety of mesenchymal and epithelial cells. It is a potent mitogen for a number of normal and transformed cell types, regulates extracellular matrix (ECM) production and promotes breast, kidney and lung morphogenesis. To clarify the role of ECM proteins in the morphogenetic and mitogenic effects of TGF‐α, we have used a human colon carcinoma cell line (SW1222) which expresses EGF receptor. Here we show, that TGF‐α at 1 ng/ml increases the proliferation of SW1222 cells, but only when they are cultured on plastic rather than collagen‐coated plates. Higher concentrations of TGF‐α (10ng/ml) did not increase cell proliferation but significantly enhanced the crypt‐like glandular differentiation when cells were grown in 3‐dimensional collagen gel (p = 0.027). These effects were accompanied by increased expression of α2β1 and α3β1 integrin molecules, which are receptors for extracellular matrix proteins, and by a statistically significant increase in binding of SW1222 cells to type‐1 collagen. The effects of TGF‐α both on binding to type‐1 collagen and on morphological differentiation in 3‐dimensional collagen gel were inhibited by monoclonal antibodies recognizing the α2β1 integrin. These data indicate that the morphogenetic or mitogenic activities of TGF‐α are critically dependent on cellular interactions with extracellular matrix proteins and are primarily mediated by the α2β1 integrin receptor. Inappropriate expression of this growth factor, seen in tumours whose cell‐matrix interactions are greatly impaired, could have deleterious effects on the maintenance of normal tissue architecture and growth control.
Genome amplification of human papillomavirus types 16 and 18 in cervical carcinomas is related to the retention of E1/E2 genes
Authors: Berumen Jaime , Casas Leonora , Segura Erika , Amezcua José L. , Garcia‐Carranca Alejandro
Published: February 2007

The level of amplification (copy number/cell) of HPV16 and HPV18 viral genomes and its correlation with the presence of E1/E2 genes were analyzed in a sample of 42 HPV16‐and 21 HPV18‐positive cervical carcinomas of different clinical stages and histological types. The viral copy number/cell was assessed by dot‐blot hybridization and the presence of E1/E2 genes by PCR and Southern blot. The copy number/cell was significantly lower in HPV18‐positive than in HPV16‐postive tumours (23 ∓ 8 and 457 ∓ 191 respectively). Nearly half of the HPV16s (43%) were distributed similarly to the HPV18s in the ranges of 50 or less copies, having its peak at the group of 1 to 10 copies, whereas the remaining HPV16s (57%) spread over the groups of 51 or more copies, with another peak at the group of 101 to 500. The E1/E2 region was absent in all tumours positive for HPV18 and present in 64% of those positive for HPV16. The HPV16 tumours negative for E1 /E2 had a much lower viral copy number (17 ∓ 12) than the positive ones (582 ∓ 212), thus resembling HPV18‐positive tumours. Viral copy number was negatively correlated with the clinical stage of the tumours and directly associated with the degree of histological differentiation. However, these correlations are primarily attributable to the presence or absence of an intact E1/E2 region.
Verapamil decreases P‐glycoprotein expression in multidrug‐resistant human leukemic cell lines
Authors: Muller Catherine , Bailly Jean‐Denis , Goubin Françoise , Laredo Judith , Jaffrézou Jean‐Pierre , Bordier Christine , Laurent Guy
Published: February 2007

We studied the effect of verapamil on Pgp expression (Pgp) in MDR human leukemia cell lines, K562/ADR and CEM VLB100. In the K562/ADR cell line, addition of verapamil to the culture medium (15μ M concentration) resulted in a 3‐fold decrease in Pgp expression after 72 hr exposure. The effect of verapamil was reversible, and Pgp expression reached the level of untreated controls 24 hr after discontinuation of verapamil. Similar results were obtained with the human vinblastine‐resistant cell line, CEM VLB100. On the contrary, no effect on Pgp expression was observed when the cells were treated with nifedipine or diltiazem (2 other calcium‐channel blockers), even at doses that inhibited cell proliferation. The level of Pgp mRNA in the presence of verapamil was measured by Northern blot and was also decreased 2‐fold (with the maximum reached within 24 hr), suggesting a transcriptional or post‐transcriptional mechanism for verapamil. We further established that the effect of verapamil on Pgp expression led to an increase in DNR and VLB accumulation and cytotoxicity. These results suggest that verapamil acts specifically on Pgp expression in these drug‐selected leukemic cells. The identification of a potentially novel mechanism of action may provide new insights as to how chemosensitization may be more effectively applied in vivo.
Production of IL‐10 by melanoma cells: Examination of its role in immunosuppression mediated by melanoma
Authors: Chen Qiyuan , Daniel Vincent , Maher Darryl W. , Hersey Peter
Published: February 2007

Previous studies have shown that IL‐10 may modulate immune responses towards the humoral arm by inhibiting production of cytokines involved in cell‐mediated responses. In the present studies, we found that mRNA to IL‐10 could be demonstrated in 66% of melanoma cell lines by PCR amplification of reverse‐transcribed mRNA and in supernatant of the cell lines by ELISA. Release into the supernatants increased approximately 2‐fold each day up to 3 days. The MW of 35S‐labelled IL‐10 secreted by melanoma cells was similar to that reported in previous studies. In the present studies we also examined whether IL‐10 may be responsible for some of the immunosuppressive effects of the melanoma cell supernatants observed in previous studies, by testing whether MAbs against IL‐10 could reverse the inhibitory effects of these supernatants. Recombinant IL‐10 and melanoma supernatants were found to inhibit production of TNF‐α, IFN‐γ, IL‐2 and mixed lymphocyte reactions but reversal of these effects of melanoma supernatants by MAbs against IL‐10 was only seen in the case of TNF‐α production. These results extend the range of cell types known to produce IL‐10 and indicate that malignancy of certain cell types may lead to unregulated production of IL‐10 that could have the potential to modulate immune responses against the tumor.
Retinoic acid up‐regulates nuclear retinoic acid receptor‐α expression in human neuroblastoma cells
Authors: Wuarin Laura , Chang Bieshia , Wada Randal , Sidell Neil
Published: February 2007

Retinoic acid (RA) nuclear receptors (RARs) are thought to mediate the cellular and molecular effects of RA on a wide variety of tissues. In most cell types, RARα expression remains relatively constant following exposure to RA, while that of RARβ is rapidly induced. In this study, we show that in human neuroblastoma, a cell type exceptionally sensitive to RA‐induced differentiation, RARα as well as RARβ is markedly up‐regulated by RA treatment. This effect was consistent in all 5 neuroblastoma cell lines tested and was reflected in a 2‐to 5‐fold increase in receptor mRNA levels as assessed by Northern‐blot analysis. Using LA‐N‐5 human neuroblastoma cells, we found that receptor up‐regulation occurred in a time‐and dose‐dependent fashion with increases in both RARα and β mRNA detectable 1–2 hr after the addition of RA. These inductions were not abrogated by cycloheximide, indicating that protein synthesis was not required for the RA responses. Nuclear run‐off experiments combined with Northern‐blot analysis of RARα stability directly demonstrated that the up‐regulation of RARα mRNA levels reflected an increased rate of transcription without changes in message half‐life. These findings, showing direct activation by RA of RARα gene transcription in human neuroblastoma cells, suggest differences in the overall regulation of this receptor from that found in most other RA‐inducible tissue.
The LFA‐1/ICAM cell adhesion pathway is involved in tumor‐cell lysis mediated by bispecific monoclonal‐antibody‐targeted T lymphocytes
Authors: Ferrini Silvano , Sforzini Sabrina , Cambiaggi Anna , Poggi Alessandro , Meazza Raffaella , Canevari Silvana , Colnaghi Maria Ines , Moretta Lorenzo
Published: February 2007

We investigated the role of the LFA‐1 /ICAM, VLA‐4/VCAM‐1 and CD2/LFA‐3 adhesion pathways in the cytolysis of tumor cells mediated by an anti‐EGF‐R/anti‐CD3 bispecific monoclonal antibody (biMAb). The biMAb induced efficient lysis of EGF‐R+ tumor cells (A431, HT‐29, IGROV‐1 and MDA‐MB468) by cytotoxic T lymphocytes (CTL) cultured in IL‐2. Protreatment of effector cells by anti‐LFA‐1α (CDI 1a) and anti‐LFA‐1 β (CD 18) MAbs significantly inhibited cytolysis of all types of EGF‐R+ tumor cells, while anti‐CD2 and anti‐VLA‐4 MAbs were virtually ineffective. We investigated the expression of adhesion‐molecule counter‐receptors on tumor target cells by indirect immunofluorescence. HT‐29, A431 and MDA‐MB 468 tumor cells expressed an ICAM‐1+2−3−VCAM‐1−LFA‐3+ phenotype, while IGROV‐1 was ICAM‐1−2+3−VCAM‐1 −LFA‐3+. Pre‐treatment of A431, HT‐29 and MDA‐MB468 with anti‐ICAM‐1 MAb inhibited cytolysis, further supporting the functional involvement of the LFA‐1 /ICAM adhesion pathway in biMAb‐targeted tumor‐cell lysis. In addition, treatment of target cells with TNFα or IFN‐γ for 24 hr increased the expression of ICAM‐1 in HT‐29, A431 and MDA‐MB468 (ICAM‐2 was induced on IGROV‐1) and also enhanced the sensitivity of these target cells to biMAb‐targeted cytotoxicity. These data suggest that up‐regulation of ICAM‐molecule expression by inflammatory cytokines may increase susceptibility of tumor cells to biMAb‐targeted lysis. Anti‐LFA‐1 MAbs did not significantly inhibit the formation of conjugates between biMAb‐coated T lymphocytes and tumor cells. Co‐aggregation of LFA‐1 molecules with biMAb‐bound CD3 molecules resulted in a more sustained and prolonged increase in the intracellular concentration of. free Ca++ in CD8+ cultured CTL lines. These findings indicate that in T cells targeted by anti‐CD3/anti‐TAA biMAb LFA‐1 may act as a co‐receptor molecule which enhances signal transduction through the CD3/TCR complex.
Clofazimine alters the energy metabolism and inhibits the growth rate of a human lung‐cancer cell line in vitro and in vivo
Authors: Sri‐Pathmanathan Rohendra M. , Plumb Jane A. , Fearon Kenneth C. H.
Published: February 2007

The anti‐leprosy drug Clofazimine is known to inhibit respiratory function and hence energy metabolism in yeast and in transformed fibroblasts. The aim of this study was to examine the effect of Clofazimine on the energy metabolism of a chemoresistant human non‐small‐cell bronchial‐carcinoma cell line (WIL) and to determine whether this agent might inhibit the growth rate of this cell line in vitro and in vivo. Oxidative phosphorylation was estimated in vitro by measuring oxygen consumption polarographically and glycolysis was estimated from lactate production. In cells that had been pre‐treated with an ATP synthetase inhibitor (oligomycin), the addition of Clofazimine resulted in an increase in oxygen consumption similar to that observed with 2,4‐dinitrophenol, a classical inhibitor of oxidative phosphorylation. This inhibition of mitochondrial function was associated with an increase in lactate production. Cellular ATP levels were maintained, possibly indicating a compensatory increase in ATP production via glycolysis. Clofazimine was shown to have a direct cytotoxic effect in vitro with an ID50 of 10.2 μM‐When Clofazimine was administered to athymic mice bearing WIL as a subcutaneous xenograft, tumour growth rate was significantly reduced, so that after 3 weeks, tumour size was one third that of controls (p < 0.01). These results suggest that selective inhibition of tumour energy metabolism with agents such as Clofazimine is a potential novel approach to cancer treatment.
Differential induction of the two early genes c‐jun and c‐fos in weakly and strongly metastatic murine lymphoma cell lines
Authors: Rossi Dunicla , Fumagalli Stefano , Volpi Ludovica , Larizza Lidia
Published: February 2007

Induction of the 2 early‐response genes c‐jun and c‐fos was investigated in the weakly metastatic T‐lymphoma Eb line and the related strongly metastatic lymphomacrophage ESb line to find possible correlations with their different in vitro and in vivo phenotypes. The response of c‐jun was elicited by the protein kinase‐C activators TPA and A23187 in ESb but not in Eb cells. A much lower response of c‐fos was also found in Eb than in ESb cells, in this case by means of scrum and the cAMP elevator forskolin. However, both TPA and the calcium ionophore A23187 were similarly effective in inducing fos‐mRNA in both cell lines. The uncoupling of c‐jun and c‐fos induction in Eb, but not in ESb cells, as well as the uncoupling of c‐fos response to different stimulators, point to a differential activation of these 2 early‐response genes by the main signal transduction pathways in the 2 cell types. The coordinate/uncoordinate availability of the fos/jun heterodimer may confer distinct regulatory patterns on different target genes in ESb/Eb cells. Activation of these genes may underlie the distinct differentiation phenotypes and in vivo behavior of Eb/ESb cells. © Wiley‐Liss, Inc.
Ouabain‐resistant non‐small‐cell lung‐cancer CELL LINE SHOWS COLLATERAL SENSITIVITY TO cis‐diamminedichloroplatinum(II) (CDDP)
Authors: Ohmori Tohru , Nishio Kazuto , Ohta Sei , Kubota Naohiro , Adachi Mitsuru , Komiya Kazuhide , Saijo Nagahiro
Published: February 2007

We have reported that the cellular uptake of cis‐diamminedi‐chloroplatinum(11) (CDDP) was inhibited by an Na+,K+‐adenosine triphosphatase (ATPase) inhibitor, ouabain, in a human non‐small‐cell lung‐cancer cell line, PC‐14, but not in its CDDP‐resistant cell line, PC‐14/CDDP. [3H]Ouabain binding of PC‐14/CDDP was about 50% lower than that of PC‐14. Accordingly, we speculated that a decrease in Na+,K+‐ATPase activity in PC‐14/CDDP might contribute to the decrease in cellular CDDP accumulation. To clarify the relationship between the activity or expression of Na+,K+‐ATPase and cellular CDDP accumulation, we established an ouabain‐resistant non‐small‐cell lung‐cancer cell line (PC‐14/OB300), which showed 1.9‐fold resistance to the cytotoxicity of ouabain. Interestingly, this cell line was 4.2‐fold more sensitive to CDDP than PC‐14. The accumulation of CDDP in PC‐14/OB300 was increased to 2.7‐fold that in PC‐14. This elevation of CDDP accumulation was not considered to be caused by increased passive diffusion, because the accumulation of CDDP in PC‐14/OB300 was also inhibited by ouabain compared to PC‐14. As one of the indices of Na+.K+‐ATPase activity, we determined cellular 86Rb+ influx rates. The 86Rb+ influx rate was 1.5‐fold higher in PC‐14/OB300 and fell to 0.7‐fold in PC‐14/CDDP compared with PC‐14. The mRNA expression of Na+,K+‐ATPase was increased in PC‐14/OB300 and decreased in PC‐ 14/CDDP. There was no difference in cellular [3H]ouabain binding between PC‐14/OB300 and PC‐14. It is passible that Na+,K+‐ATPase of PC‐14/OB300 has a different affinity for ouabain from that of PC‐14. Our results suggest that the enzyme activity or the level of expression of Na+,K+‐ATPase may contribute to the cellular uptake of CDDP and determine the sensitivity to CDDP. © Wiley‐Liss, Inc.
The effect of vitamin and mineral supplementation on esophageal cytology: Results from the linxian dysplasia trial
Authors: Mark Steven D. , Liu Shu Fan , Li Jun Yao , Gail Mitchell H. , Shen Qiong , Dawsey Sanford M. , Liu Fusheng , Taylor Philip R. , Li Bing , Blot William J.
Published: February 2007

The population of Linxian in China has one of the world's highest rates for esophageal/gastric cardia cancer, as well as documented nutritional deficiencies. To determine whether dietary supplementation with a multi‐vitamin multi‐mineral preparation could reduce the risk of esophageal cancer and favorably influence precursor lesions, 3,318 individuals age 40‐69 with cytologically determined grade I or grade 2 esophageal dysplasia were randomly assigned to receive either an active multi‐vitamin multi‐mineral supplement or a placebo. Pills were distributed at monthly visits and incident cancers or deaths were recorded. At 30 and 72 months subsequent to randomization all living participants without a known incident cancer were asked to undergo repeat cytological examination of their esophagus. Based on these procedures participants were classified as having no dysplasia, dysplasia grade I, dysplasia grade 2 or near cancer dysplasia. Diagnoses of cancer were based on the cytology findings plus available histologic, radio‐logic and clinical materials. At the end of the study there was little overall difference in cumulative risk of esophageal cancer between those receiving vitamin/mineral supplementation and those receiving placebo. There was, however, a significant increase in reversion to non‐dysplastic cytology among the group receiving the active treatment. The odds of not having any dysplasia at the two post‐randomization screens was 1.23 times higher in the active treatment group than in the placebo group. Within each treatment group higher categories of dysplasia were associated with higher rates of cancer. © 1994 Wiley‐Liss, Inc.
Expression of MUC1, MUC2, MUC3 and MUC4 mucin mrnas in human pancreatic and intestinal tumor cell lines
Authors: Hollingsworth Michael A. , Strawhecker Judith M. , Caffrey Thomas C. , Mack David R.
Published: February 2007

We examined the steady‐state expression levels of mRNA for the MUC1, MUC2, MUC3 and MUC4 gene products in 12 pancreatic tumor cell lines, 6 colon tumor cell lines, and one ileocecal tumor cell line. The results showed that 10 of 12 pancreatic tumor cell lines expressed MUCI mRNA and that 7 of these 12 lines also expressed relatively high levels of MUC4 mRNA. In contrast, MUC2 mRNA was expressed at only low levels and MUC3 was not detected in the pancreatic tumor cell lines. All 7 intestinal tumor cell lines examined expressed MUC2, and 5 of 7 expressed MUC3; however only one expressed significant levels of MUCI and 2 expressed low levels of M0C4 mRNA. This report of high levels of MUC4 mRNA expression by pancreatic tumor cells raises the possibility that mucin carbohydrate epitopes defined by antibodies such as DuPan 2 may be expressed on a second mucin core protein produced by pancreatic tumor cells. © 1994 Wiley‐Liss, Inc.
Reversal of multidrug resistance by tyrosine‐kinase inhibitors in a non‐P‐glycoprotein‐mediated multidrug‐resistant cell line
Authors: Takeda Yuichiro , Nishio Kazuto , Niitani Hisanobu , Sajio Nagahiro
Published: February 2007

We have already established a human leukemia sub‐line resistant to the growth‐inhibitory effect of TPA (12‐O‐tetradecanoylphorbol 13‐acetate) (K562/TPA) derived from K562. KS62/TPA was found to be a non‐P‐glycoprotein‐mediated multidrug‐ resistant cell line, in which intracellular drug accumulation was not reduced. In K562/TPA, adriamycin (ADM) was distributed mainly in the cytoplasm and was scarcely observed in the nucleus. We determined the relative levels of multidrug‐resistance‐associated protein (MRP), which was recently identified as the novel transporter. The relative levels of MRP in K562/TPA were the same as in K562. Although the catalytic activity of K562/TPA topoisomerase II was about hall that of the parental cells, resistance to other drugs could not be explained by topoisomerase‐II activity. To elucidate the mechanism of drug resistance in K562/TPA, we tried to find chemicals that would reverse the drug resistance. Tyrosine‐kinase inhibitors enhanced the cytotoxicity of anti‐neoplastic drugs against K562/TPA. Therefore we examined the modification of nuclear ADM accumulation in K562/TPA by one of these tyrosine‐kinase inhibitors, genistein. Although the amount of ADM was decreased in the nuclei of K562/TPA cells, it was significantly increased after incubation in the presence of genistein. The formation of DNA single‐strand breaks by ADM. etoposide and ACNU was significantly lower in K562/TPA than in K562, but was significantly increased in the presence of genistein. These results suggest that genistein could overcome drug resistance by enhancing the accumulation of drug into the nuclear fraction of K562/TPA. © 1994 Wiley‐Liss, Inc.
Suppressive effect of recombinant human Cu, Zn‐superoxide dismutase on lung metastasis of murtne tumor cells
Authors: Yoshizaki Naohito , Mogi Yoshihiro , Muramatsu Hirohito , Koike Kazuhiko , Kogawa Katsuhisa , Niitsu Yoshiro
Published: February 2007

The inhibitory effect of recombinant human Cu++Zn++superoxide dismutase (rhSOD) on metastasis of tumor cells in the mouse was investigated. In an experimental pulmonary metastasis model employing Moth A cells as inoculum, significant inhibition of metastasis was obtained by intravenous pre‐ and post‐administration of rhSOD. An inhibitory effect of rhSOD was also observed in a spontaneous pulmonary metastasis model with ILL cells as the inoculum. rhSOD was not observed to have any significant effects on the platelet‐aggregating activity of tumor cells, the adhesiveness of tumor cells to vascular components (endothelial cells, laminin and type‐IV collagen), or the growth of tumor cells either in vitro or in vivo. However, rhSOD suppressed invasion of Meth A and 3LL cells into Matrigel (an artificially reconstituted basement membrane of collagen, laminin and heparan sulfate) in the presence of hypoxanthine and xanthine oxidase, in vitro producers of superoxide. Thus, the present study shows that rhSOD is able to inhibit both experimental and spontaneous pulmonary metastasis, possibly through the suppression of tumor cell invasion into the extracellular matrix. © 1994 Wiley‐Liss, Inc.