bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flavaglines: A group of efficient growth inhibitors block cell cycle progression and induce apoptosis in colorectal cancer cells
Authors: Hausott Barbara , Greger Harald , Marian Brigitte 
Published: March 2004

AbstractFlavaglines are flavonol–cinnamate‐derived cyclopenta[b]benzofurans, so far reported only for the genus Aglaia of the plant family Meliaceae. They represent a group of highly bioactive metabolites already known for their strong antileukemic activities. To assess their suitability as chemotherapeutic drugs in colorectal cancer, their cytostatic effects and the underlying mechanisms of action were analyzed in colorectal tumor cell lines. Aglaiastatin was the most active flavagline, inhibiting growth and inducing apoptosis at nanomolar concentrations in SW480 and HT29/HI1 carcinoma cells, while the premalignant adenoma cell lines VACO235 and LT97 as well as the normal intestinal epithelial cell line IEC18 were 1,000 times less sensitive (IC50 > 10 μM). In SW480 cells, aglaiastatin caused cell cycle block in early mitosis, demonstrated by a shift of cell cycle distribution 24 and 48 hr after addition of aglaiastatin and by an increased content of cyclin B after 6 hr together with a decreased level of cyclin A as early as 2 hr after exposure. In addition, induction of apoptosis could be shown by the characteristic morphology of apoptotic nuclei, loss of MMP and downmodulation of bclxl. Strong activation of p38 was observed after 2 hr of exposure, indicating that apoptosis may be induced via a p38‐mediated stress pathway. © 2004 Wiley‐Liss, Inc.
Synergistic effect of lymphotactin and interferon γ‐inducible protein‐10 transgene expression in T‐cell localization and adoptive T‐cell therapy of tumors
Authors: Huang Hui , Xiang Jim 
Published: March 2004

AbstractThe lack of efficient T‐cell infiltration of tumors is a major obstacle to successful adoptive T‐cell therapy. We have previously demonstrated that adenovirus (AdV)‐mediated transgene lymphotactin (Lptn) or IP‐10 expression in tumors can significantly enhance T‐cell tumor infiltration. In this study, active OVA‐specific CD8+ T cells were prepared by coculturing naive OVA‐specific CD8+ T cells from transgenic OT I mice with OVA‐I peptide‐pulsed dendritic cells in vitro. These XCR‐1‐ and CXCR3‐expressing T cells predominantly secreted IFN‐γ and displayed significant killing activity (84% at effector:target cell ratio of 1.5) against OVA‐expressing EG7 tumor cells through perforin‐mediated pathway. Our data also showed that chemokine Lptn and IP‐10 not only can chemoattract, but also stimulate proliferation of CD8+ T cells in vitro, and that a mixture of Lptn and IP‐10 can more efficiently chemoattract CD8+ T cells than either one of them. Furthermore, we demonstrated that the transferred CD8+ T cells detected in group of tumors treated with both AdVLptn and AdVIP‐10 (group a) are around 4 and 2 times more than that in groups of tumors treated with control AdVpLpA (group b) and either AdVIP‐10 (group c) or AdVLptn (group d), respectively. Around 87.5% of mice in group a were tumor‐free compared to the aggressive tumor growth in all 8 mice of group b and 25% or 37.5% cured mice seen in groups c and d (p < 0.05). Thus, our results indicate that enhancement of adoptive T‐cell therapy can be obtained by double tranmsgene Lptn and IP‐10 expression, which facilitates CD8+ T‐cell tumor localization through proliferation and chemoattraction of the transferred CD8+ T cells by in situ chemokine transgene expressions in the tumors. Collectively, our data provide solid evidence of a potent synergy between adoptive T‐cell therapy and adenovirus‐mediated Lptn and IP‐10 gene transfer into tumor tissues, which culminated in the T‐cell tumor localization and eradication of well‐established tumor masses. © 2004 Wiley‐Liss, Inc.
D‐PCa‐2: A novel transcript highly overexpressed in human prostate and prostate cancer
Authors: Weigle Bernd , Kiessling Andrea , Ebner Reinhard , Fuessel Susanne , Temme Achim , Meye Axel , Schmitz Marc , Rieger Michael A. , Ockert Detlef , Wirth Manfred P. , Rieber E. Peter 
Published: March 2004

AbstractIdentification of genes selectively expressed in tumors or individual tissues is a crucial prerequisite for molecular diagnosis and treatment of cancer by addressing molecular targets. By screening an expression database, we identified the novel gene D‐PCa‐2 (Dresden prostate carcinoma 2), which is highly overexpressed in normal prostate tissue and prostate carcinoma (PCa). The corresponding transcript contained an open reading frame of 453 nucleotides encoding a putative protein of 150 amino acids. A large part of exon 8 of the D‐PCa‐2 gene shows strong similarity to the high‐mobility‐group nucleosomal binding protein 2 (HMGN2) cDNA. The highly specific transcription of the D‐PCa‐2 gene in normal and malignant prostate tissues and in a few additional tumors was demonstrated by using multiple tissue dot blot, cancer profiling dot blot and real‐time PCR analyses. Examination of 18 pairs of tumorous and nontumorous prostate tissues from PCa patients by quantitative RT‐PCR revealed D‐PCa‐2 transcripts in all specimens. The potential usefulness of D‐PCa‐2 as a sensitive marker for metastatic prostate carcinoma cells in lymph nodes was demonstrated by the detection of one LNCaP cell in 1 × 105 normal lymph node cells using real‐time RT‐PCR. Examination of 22 lymph nodes from PCa patients either containing metastatic prostate cancer cells or diagnosed as cancer‐free was in full concordance with histopathologic diagnoses. These results validate D‐PCa‐2 as a transcript with high tissue specificity and with a potential application in the diagnosis of PCa. © 2004 Wiley‐Liss, Inc.
Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell‐mediated expansion
Authors: Dhodapkar Kavita M. , Cirignano Barbara , Chamian Francesca , Zagzag David , Miller Douglas C. , Finlay Jonathan L. , Steinman Ralph M. 
Published: March 2004

AbstractBrain tumors carry a poor prognosis, and newer approaches to their therapy are urgently needed. Natural killer T (NKT) cells are distinct innate lymphocytes with antitumor potentials. Defects in NKT cell function have been observed in patients with other forms of cancer. Here we show that both the frequency and interferon‐γ‐producing function of NKT cells are well preserved in adult patients with glioma (n = 9) and comparable to findings in healthy controls (n = 9). These cells can be readily expanded in culture using autologous mature dendritic cells loaded with the NKT ligand, α‐galactosyl ceramide. The expanded NKT cells from glioma patients are functional and, importantly, kill glioma cells in a ligand‐ and CD1d‐dependent manner. Expression of CD1d is detected both on primary glioma cells as well as endothelial cells in infiltrating new blood vessels by immunohistochemistry of glioma tissue sections. These data suggest that targeting NKT cells may provide a novel strategy for immunotherapy of glioma. © 2004 Wiley‐Liss, Inc.
Phenotypic alterations induced by the Hong Kong‐prevalent Epstein‐Barr virus‐encoded LMP1 variant (2117‐LMP1) in nasopharyngeal epithelial cells
Authors: Lo Angela Kwok Fung , Huang Dolly P. , Lo Kwok Wai , Chui Yiu Loon , Li Hoi Ming , Pang Jesse Chung Sean , Tsao Sai‐Wah 
Published: March 2004

AbstractEpstein‐Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), a common cancer in Hong Kong. The EBV‐encoded LMP1 protein is believed to play an important role in cell transformation. We have previously identified a prevalent LMP1 variant (2117‐LMP1) that is expressed in 86% of primary NPC in Hong Kong. In this study, the biologic phenotypes induced by 2117‐LMP1 were compared with those of the prototypic B95.8‐LMP1 in an immortalized nasopharyngeal epithelial cell line, NP69. The 2117‐LMP1 could induce cell proliferation and resistance to apoptosis induced by growth factor deprivation. Expression of 2117‐LMP1 also suppressed expression of p16, p21 and Bax but induced expression of CDK2 and A20. Compared with B95.8‐LMP1, 2117‐LMP1 could induce a higher migration ability in NP69 cells but was less efficient in inducing morphologic changes, anchorage‐independent growth and cell invasion. Relatively weaker ability of 2117‐LMP1 than B95.8‐LMP1 in upregulation of vimentin, VEGF and MMP9 as well as in downregulation of E‐cadherin was observed. 2117‐LMP1 could activate higher level of NF‐κB activity in HEK 293 cells than B95.8‐LMP1. The present study supports a role of 2117‐LMP1 in NPC development by enhancing cell proliferation, cell death inhibition and migration in premalignant nasopharyngeal epithelial cells. Furthermore, our study reveals significant functional differences between 2117‐LMP1 and the prototypic B95.8‐LMP1. Our results provide insights into the pathologic significance of this prevalent LMP1 variant, 2117‐LMP1, in the development of NPC in the Hong Kong population. © 2004 Wiley‐Liss, Inc.
Expression of GLUT‐1 glucose transfer, cellular proliferation activity and grade of tumor correlate with [F‐18]‐fluorodeoxyglucose uptake by positron emission tomography in epithelial tumors of the ovary
Authors: Kurokawa Tetsuji , Yoshida Yoshio , Kawahara Kazumi , Tsuchida Tatsuro , Okazawa Hidehiko , Fujibayashi Yasuhisa , Yonekura Yoshiharu , Kotsuji Fumikazu 
Published: March 2004

AbstractWe evaluated whether tracer FDG uptake, quantified as an SUV by PET in ovarian epithelial tumors, correlates with clinical stage, tumor grade, cell proliferation and glucose metabolism, all of which are biomarkers for response to chemotherapy, prognosis and overall survival in ovarian cancer patients. Seventeen patients suspected of having ovarian cancer by physical examination, tumor marker analysis and anatomic imaging (such as sonography, CT and/or MRI) underwent whole‐body FDG‐PET within the 2 weeks prior to surgery. Seventeen epithelial ovarian tumor specimens (13 malignant tumors, 5 at stage I, 2 at stage II, 6 at stage III; 2 borderline tumors; and 2 benign lesions) were available for pathologic evaluation. They were graded histopathologically, and immunohistochemistry for MIB‐1 (proliferation index marker) and GLUT‐1 was performed. Correlation between FDG uptake and clinical stage, GLUT‐1 expression, MIB‐1 LI and histologic grading score was determined. No positive correlation was observed between FDG uptake and clinical stage (p = 0.14). Intensity of GLUT‐1 expression (r = 0.76, p = 0.001), MIB‐1 LI (r = 0.457, p = 0.014) and histologic grading score (r = 0.692, p = 0.005) showed statistically significant positive correlations with FDG uptake. Stepwise logistic regression analysis revealed that expression of GLUT‐1 transporters was the strongest parameter (r = 0.760, p = 0.0004) by which to predict positive FDG uptake. Therefore, glucose consumption, as determined by analysis of SUVs in FDG‐PET, may be a noninvasive biomarker for ovarian epithelial tumors. © 2004 Wiley‐Liss, Inc.
RASSF1A is a target tumor suppressor from 3p21.3 in nasopharyngeal carcinoma
Authors: Chow Lillian Shuk‐Nga , Lo Kwok‐Wai , Kwong Joseph , To Ka‐Fai , Tsang Kam‐Sze , Lam Ching‐Wan , Dammann Reinhard , Huang Dolly P. 
Published: March 2004

AbstractDeletion on the short arm of chromosome 3 is one of the most important genetic abnormalities in the tumorigenesis of nasopharyngeal carcinoma (NPC). Both physical mapping and functional studies have targeted an NPC‐related tumor suppressor gene(s) to chromosome 3p21.3. We have reported recently that RASSF1A gene, located on a 120‐kb minimal deletion region on 3p21.3, was frequently inactivated by promoter hypermethylation in NPC. We further confirmed that RASSF1A is the critical target tumor suppressor from 3p21.3, with the evidence that loss of expression and aberrant methylation of the other 8 candidate genes/transcripts (HYAL2, FUS1, RASSF1C, BLU, NPRL2, 101F6, PL6 and CACNA2D2) in this 120‐kb region were rare in NPC samples. The contribution of RASSF1A in NPC tumorigenesis was investigated by restoring its expression in a RASSF1A deficient cell line, C666‐1. Transient transfection of wild‐type RASSF1A resulted in marked growth inhibition in NPC cells. Isolated stable clones expressing wild‐type RASSF1A demonstrated retarded cell proliferation in vitro. Soft‐agar assay also showed decreased number and sizes of colony formed in these clones. In vivo nude mice assay demonstrated the dramatic reduction of tumorigenic potential in the RASSF1A‐transfected clones. Our results provide strong evidence to support RASSF1A as a target tumor suppressor gene on 3p21.3 in NPC. © 2004 Wiley‐Liss, Inc.
Women smoking and testicular cancer: One epidemic causing another?
Authors: Pettersson Andreas , Kaijser Magnus , Richiardi Lorenzo , Askling Johan , Ekbom Anders , Akre Olof 
Published: March 2004

AbstractIn many countries the incidence of testicular cancer has increased epidemically, but the aetiology remains obscure. Maternal smoking during pregnancy has been suggested to be a cause, but a satisfactorily valid assessment of the hypothesis is still lacking. To evaluate the epidemiological relevance, we assessed the ecological correlation between female smoking habits and testicular cancer incidence in the Nordic countries. Data on smoking prevalence among women in 5‐year birth cohorts 1910–1940, at 25–29 years of age, were obtained through past studies of smoking habits in Sweden, Denmark, Norway and Finland. Testicular cancer incidence in the presumed offspring birth cohorts 1938–1968, was calculated using data from the respective cancer registries. For comparison, a similar analysis of male smoking and testicular cancer in the presumed offspring cohorts was carried out. The Pearson correlation coefficient between female smoking prevalence and testicular cancer incidence in the generation of the presumed offspring was 0.9 (p < 0.0001) for all countries combined. With the exception of Finland, the country‐specific correlations were of the same magnitude. In multivariate analysis, there was no correlation with male smoking. The strong geographical and temporal correlations between female smoking and testicular cancer indicate that if smoking during pregnancy is a cause of testicular cancer in the offspring, part of the increasing trends could be explained, and more importantly: avoided, by primary prevention. © 2004 Wiley‐Liss, Inc.
Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells
Authors: Wesley Umadevi V. , Tiwari Shakuntala , Houghton Alan N. 
Published: March 2004

AbstractLung cancer is the leading cause of cancer death. Lung cancers produce a variety of mitogenic growth factors that stimulate tumor cell proliferation and migration. The cell surface protease, dipeptidyl peptidase IV (DPPIV), is involved in diverse biologic functions, including peptide‐mediated cellular growth and differentiation. DPPIV is expressed in various normal tissues, including lung tissue, and its expression is lost in many types of human cancers. DPPIV expression and its enzymatic activity are detected in normal bronchial and alveolar epithelium but different histologic subtypes of lung carcinomas lose DPPIV expression. To investigate the role of DPPIV in lung carcinoma, we examined the expression of DPPIV at both mRNA and protein levels in non small cell lung cancer (NSCLC) cell lines and normal human bronchial epithelial cells. DPPIV expression was detectable in normal lung epithelial cells, but was absent or markedly reduced in all NSCLC cell lines at both mRNA and protein levels. Restoration of DPPIV expression in NSCLC cells resulted in profound morphologic changes, inhibition of cell proliferation, anchorage‐independent growth, in vitro cell migration and tumorigenicity in nude mice. DPPIV reexpression also correlated with increased p21 expression, leading to induction of apoptosis and cell cycle arrest in G1 stage. These effects were accompanied by increased expression of cell surface proteins, fibroblast‐activating protein (Fapα) and CD44 that are associated with suppression of tumor growth and metastasis. Thus, DPPIV functions as a tumor suppressor, and its downregulation may contribute to the loss of growth control in NSCLC cells. © 2004 Wiley‐Liss, Inc.
Human mena protein, a serex‐defined antigen overexpressed in breast cancer eliciting both humoral and CD8+ T‐cell immune response
Authors: Di Modugno Francesca , Bronzi Giovanna , Scanlan Matthew J. , Del Bello Duilia , Cascioli Simona , Venturo Irene , Botti Claudio , Nicotra Maria Rita , Mottolese Marcella , Natali Pier Giorgio , Santoni Angela , Jager Elke , Nisticò Paola 
Published: March 2004

AbstractScreening of a cDNA expression library from a primary breast tumor with the autologous patient serum led to the isolation of 6 cDNA clones corresponding to 3 different genes, including a novel gene that maps to chromosome 1 and encodes the human homologue of mouse Mena (hMena, cDNA clone RMNY‐BR‐55), a protein of the Ena/VASP family involved in the regulation of cell motility and adhesion. A cancer‐restricted antibody response against hMena was demonstrated, since 18/93 cancer patient sera, the majority (10/52) from breast cancer, showed anti‐hMena‐specific IgG, while no antibodies were present in healthy donors. When hMena protein expression was analyzed by Western blot and immunohistochemistry, the antigen was overexpressed in the majority of breast cancer cell lines and in 75% of primary breast tumor lesions evaluated. Furthermore, when HLA‐A2‐restricted peptides from the hMena sequence were used to stimulate CD8+ T cells, an hMena‐specific response was found in 9 out of 12 HLA‐A2+ breast cancer patients. In 4 patients, this cell‐mediated immune response was concomitant with antibody response to hMena. Furthermore, an hMena‐specific T‐cell line was established from an HLA‐A2+ breast cancer patient whose primary tumor lesion overexpressed the hMena protein. The present findings highlight the emerging role that overexpression of cytoskeleton regulatory components may have in the induction of a specific antitumor immune response. © 2004 Wiley‐Liss, Inc.
c‐jun NH2‐terminal kinase pathway is involved in constitutive matrix metalloproteinase‐1 expression in a hepatocellular carcinoma‐derived cell line
Authors: Sugioka Yoshihiko , Watanabe Tetsu , Inagaki Yutaka , Kushida Miwa , Niioka Maki , Endo Hitoshi , Higashiyama Reiichi , Okazaki Isao 
Published: March 2004

AbstractTranscription factor c‐Jun serves for cellular proliferation, survival, differentiation and transformation and is recognized as an important factor in cancer development, including hepatocellular carcinoma (HCC). The purpose of present study is to determine the involvement of c‐Jun in matrix metalloproteinase‐1 (MMP‐1) expression, which is previously reported by us to be expressed only in the early stage of human HCC showing stromal invasion. Of 5 human HCC cell lines examined, only HLE cells revealed mRNA and protein expression as well as enzymatic activity of MMP‐1. Transient transfection of an MMP‐1 promoter/luciferase construct (including 4.4 kb full promoter region) into HLE and HCC‐T cells (MMP‐1 nonproducer) showed that high promoter activity was observed only in HLE cells without inducers, and that this promoter activity was still observed when a shorter 0.6 kb proximal promoter construct was transfected. The 0.6 kb promoter region contained 3 AP‐1 sites, and c‐jun mRNA was constitutively expressed in HLE cells without inducers. Furthermore, phosphorylated c‐Jun and c‐Jun NH2‐terminal kinase (JNK) were detected in HLE cells. Promoter activity of the 0.6 kb construct was suppressed with SP600125, a potent inhibitor of JNK, but not with PD98059 and SB203580, potent inhibitors of MEK1/2 and p38, respectively. The inhibitory effect of SP600125 was also observed at protein expression level and in enzymatic activity of MMP‐1. Taken together, this study suggests that the JNK pathway is involved in the expression of MMP‐1 in HCC cells and may represent a new functional role of c‐Jun for HCC development. © 2004 Wiley‐Liss, Inc.
First‐principles pair potentials across the metal–ceramic interface
Authors: Han Xiaoping , Zhang Yue , Xu Huibin 
Published: March 2004

AbstractSystematic approaches are presented to invert the first‐principle binding energy to obtain the pair potentials across the metal/ceramic interfaces. The conformation characteristics of two virtual interface models suitable for the inversion are summarized: (1) the positions of one kind of ceramic ions stay unchanged, but those of the other change; or, (2) there is no change in the relative positions of the ceramic ions to the metal atoms but the positions of two kinds of ceramic ions are all exchanged each other. As an example, we derive the pair potentials of NiZr4+ and NiO2− across the Ni/ZrO2 interface with this method, which exhibit comparable accuracy to the first‐principle results. This provides direct evidence that the interfacial potentials obtained from this method can reasonably describe the general features of bondings across the metal–ceramic interface. The limitation of this method is also discussed. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 968–973, 2004
Ensemble variance in free energy calculations by thermodynamic integration: Theory, optimal “Alchemical” path, and practical solutions
Authors: Blondel Arnaud 
Published: March 2004

AbstractThermodynamic integration is a widely used method to calculate and analyze the effect of a chemical modification on the free energy of a chemical or biochemical process, for example, the impact of an amino acid substitution on protein association. Numerical fluctuations can introduce large uncertainties, limiting the domain of application of the method. The parametric energy function describing the chemical modification in the thermodynamic integration, the “Alchemical path,” determines the amplitudes of the fluctuations. In the present work, I propose a measure of the fluctuations in the thermodynamic integration and an approach to search for a parametric energy path minimizing that measure. The optimal path derived with this approach is very close to the theoretical minimum of the measure, but produces nonergodic sampling. Nevertheless, this path is used to guide the design of a practical and efficient path producing correct sampling. The convergence with this practical path is evaluated on test cases, and compares favorably with that of other methods such as power or polynomial path, soft‐core van der Waals, and some other approaches presented in the literature. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 985–993, 2004
On the applicability of the HSAB principle through the use of improved computational schemes for chemical hardness evaluation
Authors: Putz Mihai V. , Russo Nino , Sicilia Emilia 
Published: March 2004

AbstractFinite difference schemes, named Compact Finite Difference Schemes with Spectral‐like Resolution, have been used for a less crude approximation of the analytical hardness definition as the second‐order derivative of the energy with respect to the electron number. The improved computational schemes, at different levels of theory, have been used to calculate global hardness values of some probe bases, traditionally classified as hard and soft on the basis of their chemical behavior, and to investigate the quantitative applicability of the HSAB principle. Exchange acid‐base reactions have been used to test the HSAB principle assuming the reaction energies as a measure of the stabilization of product adducts. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 994–1003, 2004