bluuebunny/crossref_metadata_2025_split huggingface dataset:
BASIC MORPHOGENETIC SYSTEM MODELING SHAPE CHANGES OF MIGRATING CELLS: HOW TO EXPLAIN FLUCTUATING LAMELLIPODIAL DYNAMICS
Authors: ALT WOLFGANG , TRANQUILLO ROBERT T. 
Published: November 2004

Migration of cells as leukocytes (white blood cells) or keratinocytes (outer epidermic cells) plays an important role in the response of (human) organisms to infections or injuries. When placed on two-dimensional substrata, these cells show extensive protrusions of so-called lamellipods, mostly around the whole cell periphery, inducing characteristic shape changes of the cell outline and subsequent translocation of the cell body. In order to explain the observed lamellipodial dynamics we investigate a "circular" model describing radial extension, L(t, x), of the cell periphery and density, a(t, x), of the underlying cortical polymer layer, consisting of actin and myosin filaments, as well as their contractile activity and their tangential transport velocity v(t, x). The resulting differential equations constitute a system of a non-local hyperbolic transport equation for a on the unit circle combined with a parabolic equation for L. Linear stability analysis as well as numerical simulations provide characteristic "morphogenetic behavior" of this model system, typically showing spatio-temporal patterns with one, two or more protrusions. One important feature of this morphogenetic system on the unit circle is the simple fact that stationary patterns might appear, but are stable only up to rotational shifts. This feature becomes effective, if we introduce stochastic perturbations of the PDE system, e.g. by adding a spatio-temporally correlated Gauss process to the rate term for actin assembly (thought to be induced by fluctuations of bound chemo-receptors which diffuse in the cell membrane). Then, depending on the choice of parameters, typical protrusion patterns transiently appear, or remain but are shifted circumferentially. Characteristic spatio-temporal auto-correlation results for these "model cells" can be compared to corresponding statistical results for "real cells".
DNA damage in bronchial epithelial and mesothelial cells with and without associated crocidolite asbestos fibers
Authors: Nygren Jonas , Suhonen Satu , Norppa Hannu , Linnainmaa Kaija 
Published: November 2004

AbstractMesothelioma is induced almost exclusively by exposure to asbestos fibers. We have investigated whether the induction of DNA damage in human bronchial epithelial BEAS 2B cells and human mesothelial MeT 5A cells by crocidolite asbestos (2 μg/cm2) requires the presence of asbestos fibers in the cells. DNA damage was measured microscopically by the Comet assay, and the presence of fibers in the same cells was assessed using bright‐field illumination. After treatment times of 6–72 hr, damage levels were, on the average, two times higher in cells with fibers than in cells without fibers. It was further found that DNA damage decreased with time in BEAS 2B cells both with and without fibers. No decrease in damage with time was seen in MeT 5A cells, suggesting that these mesothelial cells repair the initial damage poorly, lack induction of protective systems, or constantly produce high levels of damaging species. Our results indicate that crocidolite‐treated human mesothelial MeT 5A and bronchial epithelial BEAS 2B cells show an elevated level of DNA damage if they contain a fiber. In comparison with epithelial BEAS 2B cells, mesothelial MeT 5A cells have more DNA damage after the crocidolite treatment and the damage is more persistent. Environ. Mol. Mutagen., 2004. © 2004 Wiley‐Liss, Inc.
PTCH polymorphism is associated with the rate of increase in basal cell carcinoma numbers during follow‐up: Preliminary data on the influence of an exon 12‐exon 23 haplotype
Authors: Strange Richard C. , El‐Genidy Noha , Ramachandran Sudarshan , Lovatt Tracy J. , Fryer Anthony A. , Smith Andrew G. , Lear John T. , Ichii‐Jones Fumiyo , Jones Peter W. , Hoban Paul R. 
Published: November 2004

AbstractAfter first presentation with a basal cell carcinoma (BCC), patients demonstrate interindividual diversity in the rate of development of further BCCs (number/year of follow‐up). The mechanism for this variation is unknown. In this study, we evaluated whether PTCH variants mediate this phenomenon. We used negative binomial regression analysis to identify associations between BCC numbers/year and host characteristics, parameters of exposure to ultraviolet radiation (UVR), and PTCH exon 121686 C/T, intron 152560+9 G/C, and exon 233944 C/T genotypes and haplotypes in 279 BCC cases who presented with an initial tumor on the head/neck. PTCH genotypes were not significantly associated with BCCs/year, although cases with two copies of the C1686‐C3944 haplotype developed significantly fewer BCCs/year than those without this haplotype (rate ratio = 0.44; 95% CI = 0.27–0.71). Cases with one copy of T1686‐T3944 developed more BCCs/year (rate ratio = 2.46; 95% CI = 1.27–3.97) than those without the haplotype. We found no significant associations between BCCs/year and the other PTCH haplotypes studied. We reexamined the association of C1686‐C3944 with BCCs/year in a model that included UVR exposure parameters (sunburning in childhood, sunbathing score, intermittency of exposure between 40 and 60 years of age, exposure in hours/year) and skin type, gender, and age at first presentation. The association between C1686‐C3944 and BCCs/year remained significant (rate ratio = 0.44; 95% CI = 0.26–0.73 for two copies of the haplotype). The data show that allelic variation in PTCH contributes to the rate of development of BCC. Environ. Mol. Mutagen., 2004. © 2004 Wiley‐Liss, Inc.
Histone deacetylase inhibitors suppress telomerase reverse transcriptase mrna expression in prostate cancer cells
Authors: Suenaga Mitsuhiro , Soda Hiroshi , Oka Mikio , Yamaguchi Akihiko , Nakatomi Katsumi , Shiozawa Ken , Kawabata Shigeru , Kasai Takashi , Yamada Yasuaki , Kamihira Shimeru , Tei Chuwa , Kohno Shigeru 
Published: November 2004

AbstractTelomerase activity is involved in cellular immortality. We have recently demonstrated that telomerase activity is closely associated with cell proliferation in prostate cancers. Telomerase is composed primarily of the catalytic subunit (hTERT) and the RNA template (hTERC), and hTERT expression is regulated by several factors such as c‐MYC and p21Waf1. Histone deacetylase (HDAC) inhibitors are known to modulate transcription and exhibit antiproliferative effects on cancer cells. The present study was designed to evaluate the effects of HDAC inhibitors on hTERT mRNA expression in prostate cancer cells. LNCaP and PC‐3 cells were treated with HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB); mRNA expression and telomerase activity were evaluated by RT‐PCR and the TRAP assay, respectively. In LNCaP cells, hTERT mRNA expression was suppressed at 1 and 3 hr after treatment with 1 μM TSA and 4 mM NaB, respectively, followed by inhibition of telomerase activity. The inhibition of hTERT mRNA expression preceded suppression of cell proliferation. In PC‐3 cells, TSA and NaB also inhibited cell proliferation, hTERT mRNA expression and telomerase activity. In both cell lines, TSA and NaB had no effect on hTERC expression, or on expression of c‐myc and p21Waf1 mRNA. These effects of TSA and NaB were unlikely to be consequences of cell cycle arrest, apoptosis, or cell differentiation. Thus, HDAC inhibitors down‐regulated telomerase activity via suppression of hTERT mRNA expression. Our study identified a novel mechanism for the antiproliferative effects of HDAC inhibitors on prostate cancer cells. © 2001 Wiley‐Liss, Inc.
Extra‐cellular thiol metabolism in clones of human metastatic melanoma with different gamma‐glutamyl transpeptidase expression: Implications for cell response to platinum‐based drugs
Authors: Paolicchi Aldo , Lorenzini Evelina , Perego Paola , Supino Rosanna , Zunino Franco , Comporti Mario , Pompella Alfonso 
Published: November 2004

AbstractThiol redox status can affect important functions both intracellularly and extracellularly. The plasma membrane enzyme γ‐glutamyl transpeptidase (GGT), which plays a crucial role in cellular handling of thiols, is often expressed in malignant tumors, including melanoma, although its expression levels may vary widely among different tumors or cells of the same tumor. In an attempt to better understand the functional significance of GGT overexpression, we have examined the relationships between intra‐ and extra‐cellular thiol metabolism and GGT expression. Intra‐ and extra‐cellular distribution of glutathione and other low mol. wt. thiols and disulfides was investigated in two different Me665/2 human melanoma clones that originated from the same metastasis, but exhibiting high (2/60 clone) and low (2/21 clone) GGT activity. Intracellular content of glutathione was lower in GGT‐rich 2/60 cells, in spite of high GGT expression. A lower utilization of extracellular cystine was also observed in these cells. In both clones, a direct secretion of cysteine in the extracellular medium was detected, which was independent of GGT‐mediated catabolism of extracellular glutathione. Substantial amounts of glutathione, GSSG and glutathione‐cysteine disulfide were accumulated extracellularly only in the case of GGT‐poor 2/21 cells, while the same event was apparent in 2/60 cells only after the following inhibition of GGT activity. When exposed to the trinuclear platinum compound BBR 3464 or hydrogen peroxide, which are very reactive for sulfur‐containing nucleophiles, the 2/60 clone showed higher sensitivity than the 2/21 clone to both agents. These results suggest that the clone‐specific balance between transport of sulfur aminoacids and GGT activity results in profound differences in the capability of each clone to modify the thiol redox status of the extracellular milieu. The finding may have important implications in tumor cell behavior with particular reference to chemosensitivity, since thiols are recognized factors in modulation of cell sensitivity to platinum‐based anticancer drugs. © 2002 Wiley‐Liss, Inc.
Identification of bradykinin receptors in clinical cancer specimens and murine tumor tissues
Authors: Wu Jun , Akaike Takaaki , Hayashida Kazuyuki , Miyamoto Yoichi , Nakagawa Takenobu , Miyakawa Kazuhisa , Müller‐Esterl Werner , Maeda Hiroshi 
Published: November 2004

AbstractBradykinin (BK) has multiple pathophysiologic functions such as induction of vascular permeability and mitogenesis, and it triggers the release of other mediators such as nitric oxide in inflammatory and cancer tissues. To explore the pathophysiologic roles of BK in tumor, we examined the distribution of BK B2 receptors in human adenocarcinoma (lung, stomach), lymphoma (lymph node), hepatoma, squamous cell carcinoma (lung) and carcinoid (duodenum), and in mouse colon adenocarcinoma 38 (C‐38) and sarcoma 180 (S‐180) tumor tissues. Immunohistochemical staining of tumor tissues with an anti‐BK B2 receptor antibody, or autoradiography with the B2 receptor antagonist [125I]HOE 140 (D‐Arg‐[Hyp Thi D‐Tic Oic8]‐BK) and the B2 receptor agonist [3H]BK indicated the presence of B2 receptors in all human tumor cells and murine S‐180 and C‐38 cells. Specific binding of [3H]HOE 140 was observed in S‐180 cells with a Kd of 2.1 nM. Binding of [125I]HOE 140 to S‐180 cells was competed by an excess amount (20–100 times) of nonradiolabeled HOE 140 or BK, but not by BK B1 receptor agonist des‐Arg9‐BK. These results provide direct evidence that the BK B2 receptor is expressed in human cancer and experimental murine tumors, which suggests a potential role for BK in inducing pathologic signal transduction in cancer growth and progression, nitric oxide production and vascular permeability enhancement in tumors. BK antagonists may thus have applications in the modulation of cancer growth and in paraneoplastic syndromes. © 2001 Wiley‐Liss, Inc.
Sun exposure and interaction with family history in risk of melanoma, Queensland, Australia
Authors: Siskind Victor , Aitken Joanne , Green Adèle , Martin Nicholas 
Published: November 2004

AbstractSun exposure is the main environmental risk factor for melanoma, but the timing of exposure during life that confers increased risk is controversial. Here we provide the first report of the association between lifetime and age‐specific cumulative ultraviolet exposure and cutaneous melanoma in Queensland, Australia, an area of high solar radiation, and examine the association separately for families at high, intermediate and low familial melanoma risk. Subjects were a population‐based sample of melanoma cases diagnosed and registered in Queensland between 1982 and 1990 and their relatives. The analysis included 1,263 cases and relatives with confirmed cutaneous melanoma and 3,111 first‐degree relatives without melanoma as controls. Data on lifetime residence and sun exposure, family history and other melanoma risk factors were collected by a mailed questionnaire. Using conditional multiple logistic regression with stratification by family, cumulative sun exposure in childhood and in adulthood after age 20 was significantly associated with melanoma, with estimated relative risks of 1.15 per 5,000 minimal erythemal doses (MEDs) from age 5 to 12 years, and 1.52 per 5 MEDs/day from age 20. There was no association with sun exposure in families at high familial melanoma risk. History of nonmelanoma skin cancer (relative risk [RR] = 1.26) and multiple sunburns (RR = 1.31) were significant risk factors. These findings indicate that sun exposure in childhood and in adulthood are important determinants of melanoma but not in those rare families with high melanoma susceptibility, in which genetic factors are likely to be more important. © 2002 Wiley‐Liss, Inc.
Cu/Zn superoxide dismutase plays a role in angiogenesis
Authors: Marikovsky Moshe , Nevo Nava , Vadai Ezra , Harris‐Cerruti Catherine 
Published: November 2004

AbstractEndothelial cells produce oxygen radicals spontaneously and this process is augmented by hypoxia/reoxygenation. Cu/Zn superoxide dismutase (SOD‐1) is an important enzyme in cellular oxygen metabolism. To determine whether alterations in SOD‐1 activity affect angiogenesis we used transgenic SOD‐1 (Tg‐SOD) mice with elevated level of SOD‐1. Angiogenesis induced subcutaneously by bFGF in Tg‐SOD mice was 3‐fold higher than in control non‐transgenic (ntg) mice. Oral administration of disulfiram (DSF), an inhibitor of SOD‐1, inhibited angiogenesis in Tg‐SOD mice as well as in CD1 nude mice. Effects of DSF on cultured cells were also tested. Application of DSF to cultured bovine capillary endothelial (BCE) cells caused inhibition of DNA synthesis and induction of apoptosis. These effects were prevented by addition of antioxidants, further indicating involvement of reactive oxygen species. DSF also reduced the level of glutathione and the production of H2O2 in BCE cells. Moreover, PC12‐SOD cells with elevated SOD‐1 were less sensitive to DSF treatment then control cells. These data indicate that the effects of DSF are mediated by inhibition of SOD‐1 activity. Tumor development is known to largely depend on angiogenesis. We found that oral administration of DSF to mice caused significant inhibition of C6 glioma tumor development and marked reduction (by 10–19‐fold) in metastatic growth of Lewis lung carcinoma. The data suggest a role for SOD‐1 in angiogenesis, establish DSF as a potential inhibitor of angiogenesis and raise the possibility that attenuating SOD‐1 activity may be important in treatment of angiogenesis‐dependent pathologies. © 2002 Wiley‐Liss, Inc.
Changes in lung‐cancer mortality trends in Spain
Authors: Franco José , Pérez‐Hoyos Santiago , Plaza Pedro 
Published: November 2004

AbstractSeveral changes in smoking patterns over the past decades in Spain can be expected to result in a shift in lung‐cancer mortality rates. We examined time trends in lung‐cancer mortality from 1973–1997 using a log‐linear Poisson age‐period‐cohort model. The standardized lung‐cancer mortality rate for men almost doubled, from 31.4 per 100,000 in 1973 to 58.6 in 1997, with an average annual increase of 2.7%. Mortality increased for male generations born until 1952 as a consequence of the increasing cigarette smoking in successive birth cohorts. However, the slight downward trend observed for the 2 youngest generations suggests a more favorable outcome of the lung‐cancer epidemic among Spanish males in the coming years, if this trend continues. For women, mortality rates were 5 to 9 times lower than those for men, 6.3 per 100,000 in 1973 and 6.4 in 1997. However, the increasing mortality among younger generations born since 1942 reflects the rise in the prevalence of smoking women during the last decades and can be expected to spread to older age groups as a cohort effect, indicating the early phase of the smoking‐related lung‐cancer epidemic among Spanish females. The decreasing mortality trend observed in women until the late 1980s could be attributed to a lower exposure to environmental tobacco smoke at home as a result of a significant reduction in the prevalence of smoking men. © 2002 Wiley‐Liss, Inc.
Expression of cancer/testis antigens in cutaneous T cell lymphomas
Authors: Häffner Andreas C. , Tassis Anatoli , Zepter Karoline , Storz Monique , Tureci Oezlem , Burg Günter , Nestle Frank Oliver 
Published: November 2004

AbstractCancer/testis‐antigens (CTA), a novel and expanding family of immunogenic proteins detected by serological screening of recombinant cDNA expression libraries, encompass promising candidate targets for T‐cell based immunotherapy. We screened kryo‐preserved tissue of cutaneous T cell lymphoma (CTCL, n=36) such as mycosis fungoides (MF, n=17), pleomorphic cutaneous T‐cell lymphoma (n=8) and Sezary's syndrome (SS, n= 11) as well as a non‐malignant entity (small plaques parapsoriasis, SPP, n=5), for the expression of CTA by RT‐PCR and Northern blot hybridization. From a panel of eleven CTA (MAGE‐1, MAGE‐C1, MAGE‐3, BAGE, GAGE, SSX‐1, SSX‐2, SSX4, SCP‐1, NY‐ESO‐1 and TS85) (HOM‐Tes‐85), mRNA expression could be detected for SCP‐1 in 8/17 MF and 6/8 pleomorphic CTCL patients but was completely absent in small plaques parapsoriasis. SS patients had a more heterogeneous antigen expression pattern: Gage (1/11), MAGE‐1 (3/11), MAGE‐3 (6/11), MAGE‐C1 (5/11), NY‐ESO‐1 (7/11) and TS85 (5/11), with expression of MAGE‐3 confirmed by immunohistochemistry. CTA could provide defined targets for antigen‐based vaccination in a high percentage of cases with CTCL. SCP‐1 might serve as an additional diagnostic indicator in early and clinically indistinct lesions suspicious for cutaneous T‐cell lymphoma. © 2001 Wiley‐Liss, Inc.
K‐ras mutation in helicobacter pylori‐associated chronic gastritis in patients with and without gastric cancer
Authors: Hiyama Toru , Haruma Ken , Kitadai Yasuhiko , Masuda Hiroshi , Miyamoto Masaki , Tanaka Shinji , Yoshihara Masaharu , Shimamoto Fumio , Chayama Kazuaki 
Published: November 2004

AbstractMutations of an oncogene, K‐ras, are associated with the development and progression of many types of human cancer. To elucidate the significance of K‐ras mutations in gastric carcinogenesis, we examined K‐ras mutations in gastric cancers and in Helicobacter pylori‐associated chronic gastritis (H. pylori‐CG), which is associated with an increased risk for the gastric cancer development. Specimens of gastric cancer and H. pylori‐CG were obtained from 64 gastric cancer patients with H. pylori‐CG, 99 cancer‐free H. pylori‐CG patients and 30 H. pylori‐negative healthy subjects. K‐ras mutations were examined by polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP), followed by DNA sequencing analysis. K‐ras mutations were detected in 4 of 48 (8.3%) gastric cancers, in 10 of 163 (6.1%) H. pylori‐CG and none of the 30 H. pylori‐negative healthy subjects. In the gastric cancer patients, mutated K‐ras was detected in differentiated type cancers but not in any of the undifferentiated type cancers. K‐ras mutations in H. pylori‐CG were significantly more frequent in gastric cancer patients than in cancer‐free patients (10.9% vs. 3.0%, p = 0.044). In addition, K‐ras mutations in H. pylori‐CG were significantly more frequent in patients with K‐ras mutated gastric cancer than in patients with K‐ras unmutated gastric cancer (50.0% vs. 3.7%, p = 0.037). These data suggest that the genetic mechanism(s) of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric cancer and that K‐ras mutations may be involved in the early stages of gastric carcinogenesis of the differentiated type. © 2001 Wiley‐Liss, Inc.
Changes in cell shape and anchorage in relation to the restriction point
Authors: Martinsson Hanna‐Stina , Zickert Peter , Starborg Maria , Larsson Olle , Zetterberg Anders 
Published: November 2004

AbstractThe restriction point (R) separates the G1 phase of continuously cycling cells into two functionally different parts. The first part, G1‐pm, represents the growth factor dependent post‐mitotic interval from mitosis to R, which is of constant length (3–4 h). The second part, G1‐ps, represents the growth factor independent, pre‐S phase interval of G1 that lasts from R to S and that varies in time from 1 to 10 h. G1‐pm cells rapidly exit (within 1 h) from the cell cycle and enter G0 as a response to serum withdrawal. The finding that R occurs at a set time after mitosis indicates that R may be related to the metabolic and/or structural changes that the cell underwent during the previous mitosis. We have recently shown that phosphorylation of the retinoblastoma tumor suppressor protein (pRb) is not the molecular mechanism behind R, as has been suggested previously. Here, we present an alternative explanation for R. In the present study, we applied a single cell approach using time‐lapse analysis, which revealed that upon serum starvation the G1‐pm cells rapidly underwent a transient change in cell shape from flat to spherical before exiting to G0. Platelet derived growth factor (PDGF) counteracted this change in shape and also prevented exit to G0 to the same extent. Furthermore epidermal growth factor (EGF) and insulin like growth factor (IGF‐1), which only partially counteracted this change, only partially counteracts exit to G0. These data clearly indicate a direct link between change in cell shape and exit to G0 in G1‐cells that have not passed R. © 2004 Wiley‐Liss, Inc.