bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic protection of repopulating hematopoietic cells with an improved MDR1‐retrovirus allows administration of intensified chemotherapy following stem cell transplantation in mice
Authors: Carpinteiro Alexander , Peinert Stefan , Ostertag Wolfram , Zander Axel R. , Hossfeld Dieter K. , Kühlcke Klaus , Eckert Hans‐Georg , Baum Christopher , Hegewisch‐Becker Susanna 
Published: August 2002

AbstractThis study was undertaken to analyze the hematotoxicity of paclitaxel (Taxol®) and to test whether transduction of repopulating hematopoietic cells with a retroviral vector (SF1m) expressing the human multidrug resistance 1 gene (MDR1) would permit dose intensification following bone marrow transplantation (BMT). While the regimen chosen (8×20 mg/kg i.p. within 12 days) produced a non‐lethal, reversible hematotoxicity in mice with steady‐state hematopoiesis, only 35.3% (6/17) of control mice survived when treated starting 14 days post BMT. In contrast, 83.3% (15/18) of mice transplanted with SF1m‐transduced cells survived, owing to a significant protection against severe acute myelotoxicity (as determined by neutrophil counts, white and red blood cell counts and values for hemoglobin and hematocrit). After recovery from chemotherapy, an increase of myeloid cells that were resistant to colchicine and effluxed the fluorochrome Rhodamine 123 was observed in SF1m‐mice, but not in controls. These results reveal that the lethal, dose‐limiting hematotoxicity of an intensified post‐transplantation chemotherapy with paclitaxel can be prevented by retroviral transfer of the MDR1 gene to a minor proportion of repopulating cells. Our mouse model, mimicking clinically achievable gene transfer rates, thus suggests that bone marrow chemoprotection may widen the therapeutic window and permit an earlier onset of post‐transplantation chemotherapy. © 2002 Wiley‐Liss, Inc.
Cyclin D1 amplification in chromosomal band 11q13 is associated with overrepresentation of 3q21–q29 in head and neck carcinomas
Authors: Jin Yuesheng , Jin Charlotte , Wennerberg Johan , Höglund Mattias , Mertens Fredrik 
Published: August 2002

AbstractEight cytogenetically characterized head and neck squamous cell carcinomas (HNSCCs) with CCND1 amplification in the form of a homogeneously staining region (hsr) in 11q13 were studied by COBRA FISH and FISH with specific probes to identify and characterize chromosomal segments added to the derivative chromosomes 11. In 4 of the tumors, it could be recognized that the material added was derived from the long arm of chromosome 3. The rearrangements were interpreted as der(11)hsr(11)(q13)t(3;11)(q21;q13) in 3 cases and as der(11)hsr(11)(q13)t(3;11)(q14;q13) in 1 case. In the other 4 cases, material from chromosomes 1, 16, or 19 was added to the derivative chromosomes 11. By further FISH analysis with 14 YAC clones spanning 3q13–q21 in the 4 tumors with der(11)hsr(11)t(3;11), it could be shown that they had different breakpoints at the molecular level, excluding the possibility that a particular gene was rearranged by the translocations. More surprisingly, gain of the 3q21–q29 segment was found in all 8 tumors with hsr in 11q13 and loss of 3p was seen in 7 of the tumors. These findings strongly indicate a synergistic effect of CCND1 amplification, loss of distal 11q, 3q gain and 3p deletion in HNSCC development and also suggests a mechanistic link between intrachromosomal amplification at 11q13 and recombination with distal 3q. © 2002 Wiley‐Liss, Inc.
Promoter hypermethylation of the EDNRB gene in nasopharyngeal carcinoma
Authors: Lo Kwok‐Wai , Tsang Yuen‐Shan , Kwong Joseph , To Ka‐Fai , Teo Peter M.L. , Huang Dolly P. 
Published: August 2002

AbstractTo identify the epigenetic changes in nasopharyngeal carcinoma (NPC), we performed methylation‐sensitive restriction fingerprinting (MSRF) analysis on NPC cell lines and xenografts. A 190 bp sequence methylated in NPC tumors was isolated and showed high homology to the 5′ CpG island of the endothelin receptor B (EDNRB) gene. Since the EDNRB gene is commonly inactivated in prostate and bladder cancers, it may be a candidate target gene involved in NPC tumorigenesis. By bisulfite sequencing, we have confirmed that hypermethylation of the 5′ CpG island of EDNRB occurred in both xenografts and all 4 cell lines but not in 2 normal nasopharyngeal outgrowths. RT‐PCR demonstrated that only original EDNRB transcripts, but not the splicing transcripts, were expressed in normal nasopharyngeal epithelial cells. Loss of the original EDNRB expression was consistently found in 2 xenografts and 3 cell lines with dense methylation patterns. Treatment of these 3 cell lines with 5′‐aza‐2′‐deoxycytidine led to re‐expression of the EDNRB transcript and demethylation of its promoter regions. Our results demonstrate that silencing of EDNRB gene expression in NPC is associated with promoter hypermethylation. Using methylation‐specific PCR, we also detected methylation of the 5′ CpG island of EDNRB in 19/21 (90.5%) primary tumors, while no methylation was found in all 6 normal nasopharyngeal epithelia. The high frequencies of promoter hypermethylation suggest that repression of the EDNRB gene may play a role in the development of NPC. © 2002 Wiley‐Liss, Inc.
Cancer risks in first‐generation immigrants to Sweden
Authors: Hemminki Kari , Li Xinjun , Czene Kamila 
Published: August 2002

AbstractWe used the nationwide Swedish Family‐Cancer Database to analyse cancer risks in 613,000 adult immigrants to Sweden. All the immigrants had become parents in Sweden and their median age at immigration was 24 years for men and 22 years for women. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 18 cancer sites using native Swedes as a reference. Data were also available from compatriot marriages. All cancer was decreased by 5% and 8% for immigrant men and women, respectively. However, most of the male increase was due to lung cancer for which male immigrants showed a 41% excess. Among individual cancer sites and immigrant countries, 110 comparisons were significant, 62 showing protection and 48 an increased risk. Most of the differences between the rates in immigrants and Swedes could be ascribed to the variation of cancer incidence in the indigenous populations. Some high immigrant SIRs were 5.05 (n = 6, 95% CI 1.82–11.06) for stomach cancer in Rumanian women and 2.41 (41, 1.73–3.27) for lung cancer in Dutch men. At some sites, such as testis, prostate, skin (melanoma), kidney, cervix and nervous system, the SIRs for immigrants were decreased; in some groups of immigrants SIRs were about 0.20. The highest rates for testicular cancer were noted for Danes and Chileans. Women from Yugoslavia and Turkey had an excess of thyroid tumours. All immigrant groups showed breast, endometrial and ovarian cancers at or below the Swedish level but the differences were no more than 2‐fold. © 2002 Wiley‐Liss, Inc.
Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma
Authors: Rapella Annamaria , Negrioli Anna , Melillo Giovanni , Pastorino Sandra , Varesio Luigi , Bosco Maria Carla 
Published: August 2002

AbstractHuman neuroblastoma (NB) tumors elaborate angiogenic peptides, and enhanced angiogenesis correlates with their aggressive behavior, metastatic spread and poor clinical outcome. Hence, inhibition of angiogenic factor production may represent a potential therapeutic target for NB treatment. There is currently little information regarding the stimuli that control NB production of angiogenic mediators. In this study, we analyzed the effects of hypoxia, a common feature of solid tumors and a major drive to tumor angiogenesis, and of PA, a tryptophan catabolite produced under inflammatory conditions and endowed with several biologic properties, on the production of the angiogenic activator VEGF by advanced‐stage human NB cell lines. We demonstrate that both stimuli are potent inducers of VEGF expression and secretion. VEGF upregulation by PA involved iron chelation because iron sulfate prevented this effect whereas the iron‐chelating agent DFX induced VEGF production. Conversely, the CDK inhibitor Flp completely blocked VEGF induction by hypoxia. This effect occurred as early as 3 hr after stimulation and did not require de novo protein synthesis. Moreover, Flp exerted similar inhibitory activity on VEGF induction by PA or DFX, suggesting that this compound targets an essential step in the signaling pathway that leads to VEGF expression. Our findings demonstrate that PA can modulate angiogenic factor production by tumor cells and establish the importance of Flp as an inhibitor of VEGF production by human NB. © 2002 Wiley‐Liss, Inc.
Vasculogenic mimicry and pseudo‐comedo formation in breast cancer
Authors: Shirakawa Kazuo , Wakasugi Hiro , Heike Yuji , Watanabe Ichiro , Yamada Shigeki , Saito Ken , Konishi Fumio 
Published: August 2002

AbstractTumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC‐9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445–451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560–566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser‐captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT‐PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo‐comedo formation. RT‐PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie‐2, Flt‐1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT‐PCR analysis of 8 specimens from non‐VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5‐year survival (p = 0.071) than the 305 non‐VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis. © 2002 Wiley‐Liss, Inc.
Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells
Authors: Ree Anne Hansen , Engebraaten Olav , Hovig Eivind , Fodstad Øystein 
Published: August 2002

AbstractThe red bone marrow (BM) is an important indicator organ of hematogenous micrometastatic spread of carcinomas. Characterization of biological properties specific for BM micrometastatic cells, however, is technically challenging due to the limited number of target cells usually available for the purpose. This report provides referrals to qualitative gene expression profiling of BM micrometastatic cells enriched by immunomagnetic selection. First, an experimental strategy was used to study regulatory mechanisms involved when BM micrometastatic cells colonize distant organs. The MA‐11 cells, originating from BM micrometastases in a breast cancer patient clinically devoid of overt metastatic disease, were injected into immunodeficient rats. Metastatic MA‐11 cells were subsequently immunoselected from the resulting in vivo lesions. The selected cell populations were compared to the injected cells by differential display analysis, and several genes possibly involved in tumor cell invasion and proliferation were confirmed as differentially expressed among the various MA‐11 cell populations. A direct approach to qualitative gene expression profiling of BM micrometastatic cells was also explored. Carcinoma cells were immunoselected from BM and axillary lymph nodes obtained from breast cancer patients, and the isolated cell populations were compared by differential display analysis. Two candidate genes, identified as factors involved in cellular growth control, appeared as differentially expressed by the target cells from BM. Our study provides detailed information on how to combine an immunomagnetic selection procedure and differential display analysis to reveal gene expression profiles that may characterize BM micrometastatic cells. © 2002 Wiley‐Liss, Inc.
Risk factors for Barrett's esophagus: A case‐control study
Authors: Conio Massimo , Filiberti Rosangela , Blanchi Sabrina , Ferraris Roberto , Marchi Santino , Ravelli Paolo , Lapertosa Gabriella , Iaquinto Gaetano , Sablich Renato , Gusmaroli Riccardo , Aste Hugo , Giacosa Attilio ,   GOSPE
Published: August 2002

AbstractBarrett's esophagus (BE) is an acquired disorder due to chronic gastroesophageal reflux. Environmental factors seem to play an important role in the pathogenesis of BE, especially in Western society. A multicenter case‐control study was carried out between February 1995 and April 1999 in 8 Italian Departments of Gastroenterology gathered in a study group (GOSPE), in order to analyze the influence of some individual characteristics and life‐style habits on the occurrence of BE. Three groups of patients were studied: 149 patients with BE, 143 patients with esophagitis (E) and 308 hospital controls (C) with acute, non‐neoplastic, non‐gastroenterological conditions. The diagnosis of BE was based on endoscopy and histology. E was defined by the Savary classification (grade I–III). Data collection was performed by using a questionnaire that focused on smoking, coffee and alcohol consumption, medical history, drugs history, gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation) and socio‐economic status. Multivariate analysis showed that the frequency of weekly GERD symptoms was significantly associated with both BE and E (p<0.0001), such as the presence of hiatal hernia (p≤0.001). Ulcer was significantly associated with BE (p=0.001). Among patients with E, the risk was directly related to spirits consumption (p=0.03). Patients with GERD symptoms that lasted more than 13 years were more likely to have BE than E (p=0.01). In conclusion, results from our study point out that long‐standing GERD symptoms, hiatal hernia and possibly alcohol consumption are risk factors in the development of the BE and E. © 2002 Wiley‐Liss, Inc.
Inhibition of spontaneous metastases formation by amifostine
Authors: Grdina David J. , Kataoka Yasushi , Murley Jeffrey S. , Hunter Nancy , Weichselbaum Ralph R. , Milas Luka 
Published: August 2002

AbstractAmifostine was investigated for its ability to inhibit spontaneous metastases formation using the well‐characterized murine sarcoma, Sa‐NH. Amifostine was administered intraperitoneally at a dose of 50 mg/kg every other day for 6 days to C3Hf/Kam mice until tumors reached an average size of 8–8.5 mm in diameter. Amifostine was again administered immediately after surgical removal of the tumor‐bearing limbs by amputation, and then once more 2 days later. Twenty‐one days later, animals were evaluated for the presence of spontaneously developed pulmonary metastases. Nontumor‐bearing control animals were sham treated using the same dosing and surgery schedules. Treatment with amifostine appeared to slightly delay tumor growth, that is, 13 vs. 12 days for tumors to reach an average diameter of 8 mm. Amifostine reduced both the incidence of pulmonary metastases formed in experimental animals from 77% to 57% (p < 0.05), and their average number per animal from 12.8 ± 5.4 (SEM) to 2.9 ± 1.1 (SEM). The effect of amifostine exposure on serum levels of the angiogenesis inhibitor angiostatin was also determined using Western blot analysis. Consistent with the antimetastatic effect, exposure of animals to 50 mg/kg of amifostine resulted in a 4‐fold enhanced serum level of angiostatin above control levels. This phenomenon occurred in tumor‐bearing and nontumor‐bearing animals. The effects of amifostine on matrix metalloproteinase (MMP) enzymatic activity was also determined using gelatin zymography. Conditioned growth medium collected from Sa‐NH cells grown to confluency was exposed to various concentrations of SH, i.e., 2‐[(aminopropyl)amino]ethane‐thiol (WR‐1065), the active thiol form of amifostine, for either 30 min or 18 hr. WR‐1065, as a function of increasing dose and time, inhibited the enzymatic activities of MMP‐2 and MMP‐9. At a concentration and time of exposure likely to be achieved in vivo, that is, 40 μM and 30 min, MMP‐2 and MMP‐9 activities were reduced to between 30% and 40% of control values. Consistent with these affects, WR‐1065 was also found to be effective in inhibiting the ability of Sa‐NH cells to migrate through Matrigel membranes. After an 18‐hr exposure under in vitro conditions, WR‐1065 at concentrations of 4, 40 and 400 μM, and 4 mM, inhibited Sa‐NH migration to 11%, 44%, 81% and 97% of control values, respectively. The abilities of amifostine and its active thiol WR‐1065 to stimulate angiostatin production in mice, and to inhibit the MMP enzymatic activities and invasion ability of Sa‐NH cells under in vitro conditions, are consistent with the observed antimetastatic effects exhibited against Sa‐NH tumors growing in vivo. © 2002 Wiley‐Liss, Inc.
Growth inhibition of BEL‐7404 human hepatoma cells by expression of mutant telomerase reverse transcriptase
Authors: Zhang Rugang , Wang Xingwang , Guo Lixia , Xie Hong 
Published: August 2002

AbstractHuman hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia and Africa. Human telomerase reverse transcriptase (hTERT) is expressed in HCC but absent in normal human liver cells, which is consistent with the expression pattern of telomerase. In the present study, expression of a dominant‐negative form of hTERT (DN‐hTERT) resulted in inhibition of telomerase activity and decreased mean telomeric length of BEL‐7404 human hepatoma cells, whereas expression of wild‐type hTERT (WT‐hTERT) and control vector had no such effects. Cell growth was inhibited by this mutant (DN‐hTERT), which was consistent with the changes in telomerase level. Flattened large cells were found in late generations with the DN‐hTERT treatment. When mean telomeric length of DN‐hTERT–transfected cells reached a critical length (about 1.7 kb), apoptosis was induced. Tumorigenicity of DN‐hTERT–expressing cells was eliminated in vivo. These data indicated that hTERT was essential for the growth of hepatoma cells. hTERT can also be used as an important target for anti‐HCC drug screening. © 2002 Wiley‐Liss, Inc.
Reduced sialidase expression in highly metastatic variants of mouse colon adenocarcinoma 26 and retardation of their metastatic ability by sialidase overexpression
Authors: Sawada Masashi , Moriya Setsuko , Saito Seiichi , Shineha Ryuzaburo , Satomi Susumu , Yamori Takao , Tsuruo Takashi , Kannagi Reiji , Miyagi Taeko 
Published: August 2002

AbstractSialidase expression levels are inversely correlated with the metastatic potential of mouse colon adenocarcinoma 26 sublines, as assessed by activity assays and RT‐PCR, irrespective of total and cell surface sialic acid contents. Compared with low metastatic NL4 and NL44 cell lines, the highly metastatic NL17 and NL22 cells exhibit low expression of sialidases, accompanied with higher levels of sialylLex and GM3. To investigate whether these properties of NL17 cells can be altered by sialidase overexpression, we transfected a cytosolic sialidase gene into NL17 cells. The result was markedly inhibited lung metastasis, invasion and cell motility with a concomitant decrease in sialylLex and GM3 levels, in line with the case of spontaneously low metastatic sublines having relatively high endogenous sialidase levels, implying that sialidase level is a determining factor affecting metastatic ability. Treatment of the cells with antibodies against sialylLex and GM3 affected cell adhesion and/or cell motility, providing evidence that desialylation of these molecules, as targets of sialidase, is involved in the suppression of metastasis. © 2002 Wiley‐Liss, Inc.
Beyond bipolar: A three‐dimensional assessment of monetary frameworks
Authors: Kuttner Kenneth N. , Posen Adam S. 
Published: August 2002

AbstractA great deal of attention has been focused recently on the impact of exchange rate regimes, just as previous empirical research examined central bank autonomy and announced targets for domestic monetary policy. To date, however, these three elements of monetary frameworks have been assessed in isolation from one another, and all have been viewed in terms of a unidimensional spectrum of fixity versus flexibility. Using a newly constructed dataset, this paper jointly analyses and compares all three elements' effects on inflation and exchange rate behaviour. The results show that each of the three elements has independent and distinct effects on nominal outcomes. Key findings include: (1) although hard pegs do tend to reduce inflation and attenuate exchange rate fluctuations within some range, they are clearly characterized by large devaluations; (2) central bank autonomy is associated with a more stable exchange rate and lower inflation; and (3) explicit inflation targeting reduces both inflation and its persistence, consistent with the view that inflation targeting increases flexibility through transparency. These results raise the possibility that a combination of central bank autonomy, inflation targeting, and a free float might offer the same benefits as any intermediate exchange rate regime on its own, without the proclivity to occasional large depreciations. Copyright © 2001 Institute for International Economics and Federal Reserve Bank of New York.
The empirics of monetary policy rules in open economies
Authors: Clarida Richard H. 
Published: August 2002

AbstractThis paper uses the empirical framework for formulating and estimating forward looking monetary policy rules developed in Clarida, Gali and Gertler (1998, 1999, 2000, 2001) and Clarida (2000) to assess what we know, don't know, and can't tell about monetary policy making in an open economy with an (implicit) inflation target. Among the issues discussed are: the relationship between structural VAR models of monetary policy and exchange rates and estimates of forward‐looking Taylor rules; the relationship between inflation targeting and leaning against the (exchange rate) wind; why central bankers are averse to even wide‐band target zones; quantifying stresses and costs of a one‐size‐fits‐all monetary policy for the members of a monetary union or currency bloc. Copyright © 2001 John Wiley & Sons, Ltd.
A unifying framework for analysing offsetting capital flows and sterilization: Germany and the ERM
Authors: Brissimis Sophocles N. , Gibson Heather D. , Tsakalotos Euclid 
Published: August 2002

AbstractThis paper provides a unifying framework in which identified offset and sterilization equations can be derived and estimated. The theoretical model suggests that, in the case where the central bank cares about both external and internal goals and capital is less than perfectly mobile, there will be some offsetting capital flows and the central bank will sterilize. Several results from the literature are encompassed as special cases. The equations are estimated for the German experience of the 1980s and the results point to active sterilization by the Bundesbank during this period. Copyright © 2002 John Wiley & Sons, Ltd.