bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAF interactions with raft‐like buoyant complexes, better than TRAF rates of degradation, differentiate signaling by CD40 and EBV latent membrane protein 1
Authors: Ardila‐Osorio Hector , Pioche‐Durieu Catherine , Puvion‐Dutilleul Francine , Clausse Bernard , Wiels Joëlle , Miller William , Raab‐Traub Nancy , Busson Pierre 
Published: August 2004

AbstractThe CD40 receptor and the Epstein‐Barr virus oncoprotein LMP1 are both members of the TNF‐receptor family and share several signaling mediators, including TRAF2 and TRAF3. Depending on the cell lineage and stage of maturation, LMP1 and CD40 can have synergistic, antagonist or unrelated effects. Previous publications have suggested that both TRAF2 and TRAF3 move into lipid rafts upon LMP1 expression or CD40 activation, whereas their proteolysis is only enhanced by CD40. However CD40‐induced proteolysis of TRAF2 has only been reported in murine cells, and there are conflicting data regarding translocation of TRAF2 into lipid rafts. We therefore investigated TRAF2 and TRAF3 modifications induced by CD40 and LMP1 signaling in a panel of human cell lines of lymphoid and epithelial origins. Upon CD40 stimulation, a marked redistribution of TRAF2 into the buoyant raft fraction was observed in all cell lines and was often associated with a similar redistribution of TRAF3. In contrast, only TRAF3 was redistributed into the raft fraction upon LMP1 expression. Moreover parallel changes in subcellular distribution of TRAF2 and TRAF3 were recorded by electron microscopy. A significant decrease in TRAF2 and TRAF3 concentrations triggered by CD40 ligation was observed in only 1 cell line and there was no evidence that this decrease was required for the negative feed‐back on JNK activation. TRAF2 redistribution into raft‐like complexes thus appears as the most significant event distinctive of CD40 and LMP1 signaling. On the other hand, the parallel influence of CD40 and LMP1 on TRAF3 redistribution is consistent with functional similarities between the CD40‐TRAF3 and LMP1‐TRAF3 axes.
Occupational risk factors for low grade and high grade glioma: Results from an international case control study of adult brain tumours
Authors: Schlehofer Brigitte , Hettinger Iris , Ryan Philip , Blettner Maria , Preston‐Martin Susan , Little Julian , Arslan Annie , Ahlbom Anders , Giles Graham G. , Howe Geoffrey R. , Ménégoz Francoise , Rodvall Ylva , Choi Won N. , Wahrendorf Jürgen 
Published: August 2004

AbstractThe majority of suspected occupational risk factors for adult brain tumours have yet to be confirmed as etiologically relevant. Within an international case‐control study on brain tumours, lifelong occupational histories and information on exposures to specific substances were obtained by direct interviews to further investigate occupational risk factors for glioma. This is one of the largest studies of brain tumours in adults, including 1,178 cases and 1987 population controls from 8 collaborating study centres matched for age, gender and centre. All occupational information, was aggregated into 16 occupational categories. In a pooled analysis, odds ratios (OR), adjusted for education, were estimated separately for men and women and for high‐grade glioma (HGG) and low‐grade glioma (LGG), focusing especially on 6 categories defined a priori: agricultural, chemical, construction, metal, electrical/electronic and transport. For men, an elevated OR of glioma associated with the category “metal” (OR = 1.24, 95% CI 0.96–1.62) was seen, which appeared to be largely accounted for by LGG (OR = 1.59, 95% CI 1.00–2.52). For the other 5 occupational categories, no elevated risks for glioma were observed. For women the only noteworthy observation for the 6 a priori categories was an inverse association with the “agriculture” category (OR = 0.60, 95% CI 0.36–0.99). Apart from the 6 major categories, women working in food production or food processing (category “food”) showed an increased OR of 1.95 (95% CI 1.04–3.68). None of the 20 substance groups was positively associated with glioma risk. Although some other point estimates were elevated, they lacked statistical significance. The results do not provide evidence of a strong association between occupational exposures and glioma development.
Inhibition of leukemic cell growth by a novel anti‐cancer drug (GUT‐70) from calophyllum brasiliense that acts by induction of apoptosis
Authors: Kimura Shinya , Ito Chihiro , Jyoko Naoto , Segawa Hidekazu , Kuroda Junya , Okada Masayuki , Adachi Souichi , Nakahata Tatsutoshi , Yuasa Takeshi , Filho Valdir Cechinel , Furukawa Hiroshi , Maekawa Taira 
Published: August 2004

AbstractDuring our search for cancer chemopreventing compounds derived from plant sources, we discovered that the natural product GUT‐70, isolated from the stem bark of Calophyllum brasiliense collected in Brazil, significantly inhibits the growth of leukemic cells. GUT‐70, characterized as a tricyclic coumarin, 5‐methoxy‐2,2‐dimethyl‐6‐(2‐methyl‐1‐oxo‐2‐butenyl) ‐10‐propyl‐2H,8H‐benzo[1,2‐b;3,4‐b′]dipyran‐8‐one (C23H26O5), inhibited all 6 human leukemic cell lines evaluated, including the P‐glycoprotein overexpressing cell line, in a concentration and time‐dependent manner with IC50 values from 2–5 μM. Furthermore, GUT‐70 did not inhibit colony formation by normal hematopoietic progenitors up to 30 μM and also did not inhibit the proliferation of normal human hepatocytes up to 30 μM. GUT‐70 activated the caspase 2, 3, 8 and 9, and induced the apoptosis in leukemic cells, which was inhibited by caspase inhibitors. GUT‐70 induced anti‐leukemic effects independent of the p53‐p2lWAFl/CIP1 pathway and increased the overall expression of p27KIP1 and p57KIP2, to stop the cell cycle at the G1/S transition. Thus, a novel anti‐cancer drug, GUT‐70 isolated from the stem bark of C. brasiliense induces caspase‐mediated and p53‐independent apoptosis to overcome multidrug resistance and may become a potent leukemia therapeutics.
Alcohol consumption and risk of prostate cancer in middle‐aged men
Authors: Schoonen W. Marieke , Salinas Claudia A. , Kiemeney Lambertus A.L.M. , Stanford Janet L. 
Published: August 2004

AbstractAlcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal milieu and contains chemical substances such as flavonoids (red wine), which may alter tumor cell growth. Data from a population‐based case‐control study in King County, WA, were utilized to evaluate the association of alcohol consumption with prostate cancer in middle‐aged men. A total of 753 newly diagnosed prostate cancer cases, 40–64 years of age, participated in the study. Seven hundred three control subjects, frequency matched to cases by age, were selected through random digit dialing. All participants completed an in‐person interview on lifetime alcohol consumption and other risk factors for prostate cancer. Logistic regression models were used to estimate odds ratios (OR) and assess significance (95% confidence intervals [CI]). All tests of statistical significance were two‐sided. No clear association with prostate cancer risk was seen for overall alcohol consumption. Each additional glass of red wine consumed per week showed a statistically significant 6% decrease in relative risk (OR = 0.94; 95% CI = 0.90–0.98), and there was evidence for a decline in risk estimates across increasing categories of red wine intake (trend p = 0.02). No clear associations were seen for consumption of beer or liquor. Our present study suggests that consumption of beer or liquor is not associated with prostate cancer. There may be, however, a reduced relative risk associated with increasing level of red wine consumption. Further research is needed to evaluate the potential negative association between red wine intake and prostate cancer risk.
Aberrant promoter methylation of human DAB2 interactive protein (hDAB2IP) gene in lung cancers
Authors: Yano Masaaki , Toyooka Shinichi , Tsukuda Kazunori , Dote Hideaki , Ouchida Mamoru , Hanabata Tetsuro , Aoe Motoi , Date Hiroshi , Gazdar Adi F. , Shimizu Nobuyoshi 
Published: August 2004

AbstractThe human DOC‐2/DAB2 interactive protein gene (hDAB2IP) is a novel member of the Ras GTPase‐activating gene family that is known to act as a tumor suppressor gene and is inactivated by methylation in prostate and breast cancers. We established previously a methylation‐specific PCR (MSP) for the promoter region (m2a and m2b regions) of hDAB2IP and examined hDAB2IP methylation status in breast cancers. We analyzed the methylation and expression status of hDAB2IP in lung cancers. The methylation status of hDAB2IP was examined in lung cancer cell lines using bisulfite sequencing and MSP. Expression was examined using conventional and real‐time RT‐PCR, and methylation was found to be inversely correlated with expression, confirming that the MSP can also be used to examine hDAB2IP methylation status in lung cancers. Aberrant methylation was detected at the m2a region in 19 of 47 lung cancer cell lines (40%) and 26 of 70 primary tumors (37%) and at the m2b in 16 lines (34%) and 25 of 70 tumors (36%). Gene expression was restored in methylated cell lines supplemented with 5‐aza‐2′‐deoxycytidine, confirming that methylation was responsible for downregulation. We also examined the relationship between hDAB2IP methylation and clinico‐pathological features of the lung cancers and found that hDAB2IP methylation was associated with advanced disease stage. Our results demonstrate that hDAB2IP methylation is frequently present in lung cancers and plays a key role in hDAB2IP silencing. hDAB2IP methylation could be used as a biomarker for disease stage, reflecting the degree of clinico‐pathological malignancy of lung cancer.
Xenogeneic immunization in mice using HER2 DNA delivered by an adenoviral vector
Authors: Gallo Pasquale , Dharmapuri Sridhar , Nuzzo Maurizio , Maldini Daniele , Iezzi Manuela , Cavallo Federica , Musiani Piero , Forni Guido , Monaci Paolo 
Published: August 2004

AbstractThe protective efficacy of xenogeneic vaccination with DNA encoding the HER2 oncogene was evaluated in BALB/c mice transgenic for the transforming form of the neu oncogene, which spontaneously develops carcinomas in all mammary glands. Intramuscular injection of either plasmid DNA followed by electrical stimulation (pVIJ‐HER2 with ES) or an adenoviral vector (Ad5‐HER2), both expressing the HER2 oncogene, was tested. Immunization using pVIJ‐HER2 with ES elicited a cell‐mediated response that was much lower than that elicited by the immunization with Ad5‐HER2, as measured by the frequency of IFN‐γ‐secreting spleen cells. The dominant T‐cell epitope of the HER2 protein product (p185) in the BALB/c (H‐2d) genetic background was identified. While the T‐cell response elicited was only partially crossreactive with the corresponding rat epitopes because of sequence variations (89% similarity), a cytotoxic T‐lymphocyte activity against the rat immunodominant epitope was also evident. The Ad5‐HER2 vaccination induced also antibodies against p185, which crossreacted with the rat protein homolog. Both T‐ and B‐cell responses slowly declined with time. Vaccination with Ad5‐HER2 at 6 and 9 weeks of age delayed incidence and reduced multiplicity of tumors in neu transgenic mice.
CD95L mediates tumor counterattack in vitro but induces neutrophil‐independent tumor rejection in vivo
Authors: Igney Frederik H. , Behrens Christian K. , Krammer Peter H. 
Published: August 2004

AbstractMany tumors express CD95L (CD178, FasL, APO‐1L) and may thus kill tumor‐infiltrating lymphocytes, a phenomenon called tumor counterattack. However, presently it is not clear whether tumor counterattack is a relevant immune escape mechanism. To characterize the effect of CD95L expression of tumor cells on tumor‐specific T cells, we established an in vitro system with TCR tg T cells and a model tumor antigen. Preactivated antitumor T cells were able to kill CD95L− and CD95L+ tumor cells. CD95L+ tumor cells killed activated T cells in vitro and inhibited the expansion of cytotoxic antitumor T cells in mixed lymphocyte tumor reactions. In vivo CD95L expression led to delayed tumor growth or complete tumor rejection. Neutrophils were not responsible for the delayed growth of the CD95L+ tumors tested. In mice with neutrophils deficient for important cytotoxicity mechanisms (p47phox−/− or iNOS−/− mice), CD95L+ tumors grew similarly as in wild‐type mice. Incidence and growth rate of CD95L+ tumors in mice injected with a neutrophil‐depleting or an isotype control antibody was the same. In CD95‐deficient lpr mice, tumor growth was not altered as compared to wild‐type mice. Taken together, CD95L mediated tumor counterattack in vitro, but led to neutrophil‐independent tumor rejection in vivo.
Influence of glutathione S‐transferase pi and p53 expression on tumor frequency and spectrum in mice
Authors: Gate Laurent , Majumdar Rajrupa S. , Lunk Alexandra , Tew Kenneth D. 
Published: August 2004

AbstractThe role of glutathione S‐transferase π (GSTπ) in tumor development has been previously suggested; however the exact function of this enzyme in carcinogenesis remains unclear. GSTπ has been identified as a modulator of cell signaling by interacting with and inhibiting c‐Jun N‐terminal kinase (JNK). This kinase has been in turn described as a regulator of p53 stability and transcriptional activity. To study the possible interaction between GSTπ and p53, we crossed GSTπ‐deficient animals with p53−/− mice. Double knock out animals were viable but developed tumors within 6 months of age; the life span of these animals was however similar to that of GSTπ+/−/p53−/− and GSTπ+/+/p53−/−. Mice heterozygous for p53 lived significantly longer than the p53−/− animals and developed tumors much later, and the expression of GSTπ did not significantly modify the life span of the animals. In contrast, in a wild‐type p53 background, GSTπ−/− mice developed tumors with a significantly higher frequency than heterozygous and wild‐type animals with a median tumor free life span 20 weeks shorter. In addition, in p53+/+ background, one third of the GSTπ−/− animals developed lung adenomas, while less than 10% of GSTπ+/− and GSTπ+/+ presented such tumors. GSTπ expression did not alter the expression of tumorigenesis markers such as COX‐2 or ornithine decarboxylase in response to phorbol ester. Furthermore, GSTπ‐deficient mouse embryo fibroblasts were more sensitive to H2O2‐induced apoptosis. P53−/− cells, independent of GSTπ status, were more sensitive to UV and other DNA damaging agents than their wild‐type counterparts. These results suggest that GSTπ may play a protective role in the development of spontaneous tumors.
Mutant BRCA1 alleles transmission: Different approaches and different biases
Authors: de la Hoya Miguel , Meijers‐Heijboer Hanne , Fernández Juan Manuel , Díez Orland , Osorio Ana , Alonso Carmen , van Leeuwen Inge , Díaz‐Rubio Eduardo , Cornelisse Cees , Benítez Javier , Devilee Peter , Caldés Trinidad 
Published: August 2004

AbstractRecently, a non‐random transmission of BRCA1 mutant alleles to the off‐spring of carriers has been suggested. If confirmed by further studies, the finding will have important implications both for risk assessment and the understanding of BRCA1 biology. However, these kind of analysis are not easy to perform due to several ascertainment biases inherent to the identification of BRCA1 carriers. In this report we propose different approaches to overcome such biases and we present additional data supporting a non‐random transmission of BRCA1 mutant alleles.
Lack of prognostic implications of HER‐2/neu abnormalities in 345 stage I nonsmall cell carcinomas (NSCLC) and 207 stage I–III neuroendocrine tumours (NET) of the lung
Authors: Pelosi Giuseppe , Del Curto Barbara , Dell'Orto Patrizia , Pasini Felice , Veronesi Giulia , Spaggiari Lorenzo , Maisonneuve Patrick , Iannucci Antonio , Terzi Alberto , Lonardoni Alessandro , Viale Giuseppe 
Published: August 2004

AbstractHER‐2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER‐2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage nonsmall cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER‐2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I‐III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER‐2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high‐level amplification (HER‐2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous‐cell carcinoma and 1 large‐cell neuroendocrine carcinoma (LCNEC), and low‐level amplification (HER‐2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous‐cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER‐2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER‐2/neu gene amplification or protein overexpression.
A recombinant humanized anti‐insulin‐like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti‐epidermal growth factor receptor therapy against human cancer xenografts
Authors: Goetsch Liliane , Gonzalez Alexandra , Leger Olivier , Beck Alain , Pauwels Petrus J. , Haeuw Jean François , Corvaia Nathalie 
Published: August 2004

AbstractInteraction of insulin‐like growth factor receptor I (IGF‐IR) with its ligands has been reported to induce cell proliferation, transformation and blockade of cell apoptotic functions. IGF‐IR is overexpressed on numerous tumor cell types and its blockade could be of importance for anti‐cancer therapy. We have generated a humanized anti‐IGF‐IR antibody h7C10 that blocksin vitroIGF‐I and IGF‐II‐induced cell proliferation of MCF‐7 breast cancer cells. Analysis of the IGF‐I transduction cascade demonstrated that the humanized anti‐IGF‐IR antibody and its murine parental form block IGF‐I‐induced tyrosine phosphorylation, both its β‐chain and IRS‐1 tyrosine phosphorylation. This presumably leads to cell cycle arrest and, consequently, growth inhibition. Treatment of nude mice bearing either human breast cancer cells (MCF‐7) or non small lung cancer cells (A549) with h7C10, or its murine parental form 7C10, inhibited significantly tumor growth. An almost complete inhibition of A549 tumor growth was observed when mice were treated with the anti‐IGF‐IR antibody combined with either a chemotherapeutic agent, Vinorelbine or an anti‐epidermal growth factor receptor (EGFR) antibody, 225. Combined therapy prolonged significantly the life span of mice in an orthotopicin vivomodel of A549; the combination of the anti‐IGF‐IR antibody with an anti‐EGFR antibody was superior to the Vinorelbine combination. The present results indicate that the humanized anti‐IGF‐IR antibody h7C10 has a great potential for cancer therapy when combined with either a chemotherapeutic agent or an antibody that targets other growth factor receptors, such as the epidermal growth factor receptor.
Overexpression of a hybrid gene consisting of the amino‐terminal fragment of urokinase and carboxyl‐terminal domain of bikunin suppresses invasion and migration of human ovarian cancer cells in vitro
Authors: Takei Yuji , Mizukami Hiroaki , Saga Yasushi , Kobayashi Hiroshi , Suzuki Mika , Matsushita Takashi , Ozawa Keiya , Suzuki Mitsuaki 
Published: August 2004

AbstractA Kunitz‐type protease inhibitor, bikunin, is known to suppress the invasion and metastasis of cancer cells. HI8, a carboxyl‐terminal domain of bikunin, is an active site of this glycoprotein. To increase its affinity for cancer cells, we constructed a chimeric gene, ATF‐HI8, and investigated the anti‐invasive and anti‐migratory activity of ATF‐HI8 on ovarian cancer cells. ATF‐HI8‐expressing plasmid and ATF‐expressing plasmid were introduced into the highly invasive and metastatic ovarian cancer cell line HRA. The properties of the established cell line (HRA/ATF‐HI8) were compared to those of the HRA/ATF and the HRA/luciferase (HRA/LUC, control) cell lines in terms of cell proliferation, invasion and migration. As a result, (i) there were no differences in cell proliferation between HRA/ATF‐HI8 and HRA/LUC; (ii) the invasion and migration of HRA/ATF‐HI8 cells were significantly inhibited compared to those of HRA/LUC cells; (iii) the migration, but not the invasion, of HRA/ATF cells was significantly inhibited compared to that of HRA/LUC. These results indicate that the overexpression of ATF‐HI8 inhibits the invasion and migration of ovarian cancer cells without affecting cell proliferation and suggest that HI8 is involved in the anti‐invasive and the anti‐migratory activities, and the addition of ATF brought about the increase in the anti‐migratory activity of HI8. The above findings suggest the applicability of therapeutic strategies targeting the inhibition of peritoneal invasion and dissemination of ovarian cancer by the use of the chimeric gene ATF‐HI8.
Epidermal growth factor receptor (EGFR) downstream molecules as response predictive markers for gefitinib (Iressa®, ZD1839) in chemotherapy‐resistant non‐small cell lung cancer
Authors: Han Sae‐Won , Hwang Pil Gyu , Chung Doo Hyun , Kim Dong‐Wan , Im Seock‐Ah , Kim Young Tae , Kim Tae‐You , Heo Dae Seog , Bang Yung‐Jue , Kim Noe Kyeong 
Published: August 2004

AbstractGefitinib has shown meaningful antitumor activity with tolerable toxicity in chemotherapy‐refractory NSCLC in previous studies. Moreover, EGFR expression failed to show a correlation with response. In an attempt to identify predictive markers of response, we have investigated the tumoral expression of key signaling molecules of EGFR (EGFR, p‐EGFR, p‐Akt, p‐Erk, p‐STAT3) by immunohistochemistry and analyzed their correlations with response. Of 65 patients who received gefitinib (250 mg/day) for chemotherapy‐refractory NSCLC, there were 14 partial responses (21.5%), 21 stable diseases (32.3%) and 21 progressive diseases (32.3%). Median durations of overall survival and time to progression were 6.7 months and 2.8 months, respectively. Immunohistochemistry was performed in 34 patients with evaluable tissue specimens. EGFR was overexpressed (2+ or 3+) in 32.4% and p‐EGFR was positive in 26.5%. The expressions of p‐Akt, p‐Erk and p‐STAT3 were positive (1+ or 2+) in 50%, 38.2% and 79.4%, respectively. The EGFR expression was not correlated with p‐EGFR or the downstream molecules. EGFR or p‐EGFR status did not correlate with response. Positive expression of p‐Erk was significantly associated with poor response (38.1% in −, 14.3% in 1+, 0% in 2+; p = 0.046). Furthermore, tumors with positive p‐Akt and negative p‐Erk nuclear expression exhibited the best response (60%), whereas there was no response in the opposite [p‐Akt (−), p‐Erk (+)] cases. Intense nuclear staining of p‐Akt (2+) was associated with prolonged TTP (HR 0.25, 95% confidence interval [CI] 0.08–0.79, p = 0.018) and OS (HR 0.16, 95% CI 0.04–0.62, p = 0.008). These results support the assumption that gefitinib responsiveness might be predicted by activated EGFR downstream molecules such as p‐Akt and p‐Erk.