bluuebunny/crossref_metadata_2025_split huggingface dataset:
Children with endemic Burkitt lymphoma are deficient in EBNA1‐specific IFN‐γ T cell responses
Authors: Moormann Ann M. , Heller Kevin N. , Chelimo Kiprotich , Embury Paula , Ploutz‐Snyder Robert , Otieno Juliana A. , Oduor Margaret , Münz Christian , Rochford Rosemary 
Published: September 2008

AbstractEndemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial Africa and is linked to Epstein–Barr virus (EBV) and Plasmodium falciparum coinfections early in life. Epstein–Barr nuclear antigen 1 (EBNA1) is the sole viral latent antigen expressed in BL tumors. Loss of EBNA1‐specific immune surveillance could allow eBL emergence. Therefore, EBNA1‐specific T cell responses were analyzed by IFN‐γ ELISPOT in Kenyan children with eBL and compared to healthy children with divergent malaria exposure. Significantly fewer children with eBL, 16% (7/44) had EBNA1‐specific IFN‐γ responses in contrast to healthy children living in a malaria holoendemic area or in an area with sporadic malaria transmission, 67% (40/60) and 72% (43/60) responders, respectively (p < 0.003). Children with eBL maintained IgG1 dominated antibody responses to EBNA1 similar to healthy children suggesting a selective loss of IFN‐γ secreting EBNA1‐specific T cells in the presence of intact humoral immunity. CD8+ T cell responses to EBV lytic and latent antigens not expressed in the tumors were similarly robust in eBL patients compared to healthy children. In addition, CD4+ T cell responses to a malaria protein, merozoite surface protein 1, were present in lymphoma patients. This study demonstrates a selective loss of EBNA1‐specific T cell responses in children with eBL and suggests a potential immunotherapeutic target for this EBV‐associated lymphoma. © 2008 Wiley‐Liss, Inc.
The presence of a methylation fingerprint of Helicobacter pylori infection in human gastric mucosae
Authors: Nakajima Takeshi , Yamashita Satoshi , Maekita Takao , Niwa Tohru , Nakazawa Kazuyuki , Ushijima Toshikazu 
Published: September 2008

AbstractAberrant DNA methylation is deeply involved in human cancers, but its inducers and targets are still mostly unclear. Helicobacter pylori infection was recently shown to induce aberrant methylation in gastric mucosae, and produce a predisposed field for cancerization. Here, we analyzed the presence of target genes in methylation induction by H. pylori and the mechanism for the gene specificity. Noncancerous gastric mucosae were collected from 4 groups of individuals (with and without a gastric cancer, and with and without current H. pylori infection; N = 11 for each group), and methylation of promoter CpG islands of 48 genes that can be methylated in gastric cancer cell lines was analyzed by methylation‐specific PCR. In total, 26 genes were consistently methylated in individuals with current or past infection by H. pylori, whereas 7 genes were not methylated at all. In addition, 14 genes were randomly or intermediately methylated in individuals with gastric cancers and the remaining 1 gene was methylated in all the cases. The methylation‐susceptible genes had significantly lower mRNA expression levels than the methylation‐resistant genes. H. pylori infection did not induce mRNA and protein expression of DNA methyltransferases; DNMT1, DNMT3A or DNMT3B. Gene specificity was present in the induction of aberrant DNA methylation by H. pylori infection, and low mRNA expression, which could precede methylation, was one of the mechanisms for the gene specificity. These findings open up the possibility that a methylation fingerprint can be used as a novel marker for past exposure to a specific carcinogenic factor. © 2008 Wiley‐Liss, Inc.
Effects of sunitinib on tumor hemodynamics and delivery of chemotherapy
Authors: Czabanka Marcus , Vinci Mara , Heppner Frank , Ullrich Axel , Vajkoczy Peter 
Published: September 2008

AbstractCurrent clinical protocols favor a combination of antiangiogenic/antivascular compounds with classical chemotherapy. However, it remains unclear to what extent an antiangiogenic/antivascular therapy influences the delivery of chemotherapy. Therefore, the aim of the present study was to characterize the effects of the antiangiogenic tyrosine kinase inhibitor sunitinib on tumor microhemodynamics and delivery of chemotherapy. SF126 tumor cells were implanted subcutaneously into nude mice and were analyzed repeatedly by intravital microscopy. Treatment with sunitinib was initiated 7 days after implantation. To assess the effects of sunitinib on tumor vasculature and hemodynamics, we analyzed total and functional vessel densities, microvascular diameter, and microvascular blood flow rate. To study the delivery of chemotherapy, autofluorescent doxorubicin was systemically administered and its vascular delivery to the tumor tissue was quantified. Histological analysis included endothelial cell proliferation, pericyte coverage of tumor vessels, and tumor cell proliferation. Sunitinib significantly suppressed tumor growth by both antivascular and antiangiogenic effects. However, a number of tumor vessels escaped antiangiogenic therapy. Interestingly, in these surviving blood vessels sunitinib treatment resulted in an increased microvascular blood flow rate resulting in an improved delivery of chemotherapy via these blood vessels. Besides its potent antiangiogenic and antivascular efficacy, sunitinib treatment results in improved microhemodynamics and blood flow in tumor blood vessels that escape therapy leading to an improved vascular delivery of chemotherapy. These results provide the basis for a potential chemosensitizing effect of sunitinib. © 2008 Wiley‐Liss, Inc.
Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the U.S. Agricultural Health Study
Authors: Koutros Stella , Lynch Charles F. , Ma Xiaomei , Lee Won Jin , Hoppin Jane A. , Christensen Carol H. , Andreotti Gabriella , Freeman Laura Beane , Rusiecki Jennifer A. , Hou Lifang , Sandler Dale P. , Alavanja Michael C.R. 
Published: September 2008

AbstractImazethapyr, a heterocyclic aromatic amine, is a widely used crop herbicide first registered for use in the United States in 1989. We evaluated cancer incidence among imazethapyr‐exposed pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed pesticide applicators in the U.S., enrolled from 1993–1997. Among the 49,398 licensed pesticide applicators eligible for analysis, 20,646 applicators reported use of imazethapyr and 2,907 incident cancers developed through 2004. Imazethapyr exposure was classified by intensity‐weighted lifetime exposure days calculated as [years of use × days per year × intensity level]. Poisson regression analysis was used to evaluate the relationship between imazethapyr exposure and cancer incidence. We found significant trends in risk with increasing lifetime exposure for bladder cancer (p for trend 0.01) and colon cancer (p for trend 0.02). Rate ratios (RRs) were increased by 137% for bladder cancer and 78% for colon cancer when the highest exposed were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic cancers or melanoma. These findings provide new evidence that exposure to aromatic amine pesticides may be an overlooked exposure in the etiology of bladder and colon cancer. The use of imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans. Published 2008 Wiley‐Liss, Inc.
Up‐to‐date cancer survival: Period analysis and beyond
Authors: Brenner Hermann , Hakulinen Timo 
Published: September 2008

AbstractSince its introduction in 1996, period analysis has been shown to be useful for deriving more up‐to‐date cancer survival estimates, and the method is now increasingly used for that purpose in national and international cancer survival studies. However, period analysis, like other commonly employed methods, is just a special case from a broad class of design options in the analysis of cancer survival data. Here, we explore a broader range of design options, including 2 model‐based approaches, for deriving up‐to‐date estimates of 5‐ and 10‐year relative survival for patients diagnosed in the most recent 5‐year interval for which data are available. The performance of the various designs is evaluated empirically for 20 common forms of cancer using more than 50‐year long time series of data from the Finnish Cancer Registry. Period analysis as well as the 2 model‐based approaches, one using a “cohort‐type model” and another using a “period‐type model”, all performed better than traditional cohort or complete analysis. Compared with “standard period analysis”, the cohort‐type model further increased up‐to‐dateness of survival estimates, whereas the period‐type model increased their precision. While our analysis confirms advantages of period analysis over traditional methods in terms of up‐to‐dateness of cancer survival data, further improvements are possible by flexible use of model‐based approaches. © 2008 Wiley‐Liss, Inc.
Oviduct‐specific glycoprotein is a molecular marker for invasion in endometrial tumorigenesis identified using a relevant mouse model
Authors: Wang Hong , Joshi Ayesha , Iaconis Lori , Solomon Garron J. , Xiang Zhaoying , Verhage Harold G. , Douglas Wayne , Ronnett Brigitte M. , Ellenson Lora Hedrick 
Published: September 2008

AbstractThe light microscopic distinction between complex atypical hyperplasia (CAH) and invasive endometrioid carcinoma (UEC) on endometrial sampling is problematic and often has significant clinical implications. Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. We used the previously described Pten+/−; Mlh1−/− mouse model. DNA was isolated from microdissected lesions (CAH and carcinoma) and analyzed for LOH and mutations of Pten and additional candidate genes. To identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. The majority of CAHs and carcinomas, arising in this model showed biallelic inactivation of Pten mediated through LOH or intragenic mutation of the wild‐type allele suggesting that complete loss of Pten is insufficient for the development of carcinoma. The global gene expression studies detected increased expression of oviduct‐specific glycoprotein (OGP) in carcinoma as compared with CAHs. This finding was validated using immunohistochemical staining in a collection of primary human UECs and CAHs. Our studies identify a molecular marker for invasive endometrial cancer that may have clinical significance, and highlight the usefulness of this mouse model in not only understanding the genetic underpinnings of endometrial carcinoma, but as a tool to develop clinically relevant biomarkers. © 2008 Wiley‐Liss, Inc.
Promoter hypermethylation of the ADAM23 gene in colorectal cancer cell lines and cancer tissues
Authors: Choi Jin‐Sung , Kim Kyung‐Hee , Jeon You‐Kyung , Kim Sung‐Hee , Jang Sang‐Geun , Ku Ja‐Lok , Park Jae‐Gahb 
Published: September 2008

AbstractPromoter hypermethylation of the ADAM23 gene, which is normally involved in cell‐to‐cell and cell‐to matrix adhesion, has been reported in pancreatic, breast and brain cancer, and recently the role of this gene was examined in gastric cancer. In this study, we analyzed ADAM23 expression in colorectal cancer cell lines and examined its methylation by methylation‐specific PCR (MSP) and bisulfate‐modified DNA sequencing analysis. Methylated cells were treated with 5‐aza‐2′‐deoxycytidine to restore the ADAM23 expression. We then examined ADAM23 methylation status in colorectal cancer tissues and their corresponding normal tissues. We found that ADAM23 was aberrantly silenced or expressed at very low levels in 28 of the 32 (88%) colorectal cancer cell lines. MSP analysis showed that ADAM23 was methylated in 29 of 32 (91%) colorectal cancer cell lines and attenuated expression of ADAM23 was found to be related to hypermethylation in its promoter region. Moreover, the CpG dinucleotide methylation threshold of 70–90% was found to be required for complete silencing. In addition, when some cell lines without ADAM23 expression were treated with 5‐aza‐2′‐deoxycytidine, ADAM23 was reexpressed. In colorectal cancer tissues, the promoter region of ADAM23 was hypermethylated in 36 of 76 (47%). These results demonstrated that ADAM23 may be down‐regulated by aberrant promoter hypermethylation during the progression of colorectal cancer. © 2008 Wiley‐Liss, Inc.
At what costs will screening with CT colonography be competitive? A cost‐effectiveness approach
Authors: Lansdorp‐Vogelaar Iris , van Ballegooijen Marjolein , Zauber Ann G. , Boer Rob , Wilschut Janneke , Habbema J. Dik F. 
Published: September 2008

AbstractThe costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost‐effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN‐colon microsimulation model to estimate the costs and life‐years gained of screening persons aged 50–80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp ≥6 mm and (iv) a suspected polyp ≥10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life‐years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps ≥6 mm. For this strategy to be as cost‐effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39–47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10‐yearly colonoscopy, where we compared to different intervals of colonoscopy screening. © 2008 Wiley‐Liss, Inc.
Increased frequency of hematopoietic malignancies in relatives of patients with lymphoid neoplasms: A French case–control study
Authors: Villeneuve Sara , Orsi Laurent , Monnereau Alain , Berthou Christian , Fenaux Pierre , Marit Gerald , Soubeyran Pierre , Huguet Françoise , Milpied Noël , Leporrier Michel , Hemon Denis , Troussard Xavier , Clavel Jacqueline 
Published: September 2008

AbstractLymphoid neoplasms (LNs), including non‐Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), lymphoproliferative syndrome (LPS) and multiple myeloma (MM), are among the most frequent cancers (∼17,000 new cases per year in France), after those related to smoking. LNs were investigated using the data from the ENGELA study. ENGELA is a multicenter hospital‐based case–control study that was carried out in France over the period September 2000–December 2004. In all, 822 cases (397 NHL, 149 LH, 168 SLP and 108 MM) and 752 controls were included and described 5,481 and 5,188 first‐degree relatives, respectively. A positive association with a familial history of hematopoietic cancer was observed for LN (OR = 1.7 [1.0–2.8]) overall and for LPS (OR = 3.2 [1.4–6.8]). The associations with HL (OR = 10.4 [2.0–53.8]) and NHL (OR = 2.4 [1.0–5.9]) were stronger for men. The associations were also stronger when the disease had been diagnosed before the relatives were aged 45 years. The results mainly support the involvement of genetic factors and suggest that at least some of those factors may be sex‐linked. However, the slight overrepresentation of affected spouses among the cases might also support the responsibility of environmental factors. © 2008 Wiley‐Liss, Inc.
A novel peptide from human apolipoprotein(a) inhibits angiogenesis and tumor growth by targeting c‐Src phosphorylation in VEGF‐induced human umbilical endothelial cells
Authors: Yi Zheng‐Fang , Cho Sung‐Gook , Zhao Hui , Wu Yuan‐yuan , Luo Jian , Li Dali , Yi Tingfang , Xu Xun , Wu Zirong , Liu Mingyao 
Published: September 2008

AbstractMany angiogenesis inhibitors are derived from large plasma proteins. Previous studies showed that the Kringle5‐like domain (termed KV) in human apolipoprotein (a) is a potential antiangiogenic factor. However, its active region and the underling molecular mechanism remain elusive. Here, we identified an 11‐amino acid peptide (named KV11) as the key region for the antiangiogenic function of the KV domain of apolipoprotein (a). We demonstrate that KV11 inhibits angiogenesis in vitro by suppressing human umbilical vein endothelial cell migration and microtubule formation. KV11 inhibits angiogenesis in chicken chorioallantoic membrane assays and mouse corneal micropocket angiogenesis assays in vivo. KV11 peptide shows no effect on tumor cell growth or proliferation, but significantly inhibits tumor growth in SCID mouse xenograft tumor model (p < 0.01) by preventing tumor angiogenesis. We elucidate that KV11 peptide suppresses angiogenesis and tumor progression by targeting the c‐Src/ERK signaling pathways. Together, these studies provide the first evidence that KV11 from apolipoprotein KV domain has anti‐angiogenesis functions and may be an anti‐tumor drug candidate. © 2008 Wiley‐Liss, Inc.
Hydrazine, methylhydrazine and methylhydrazine sulfate carcinogenesis in swiss mice. failure of ammonium hydroxide to interfere in the development of tumors
Authors: Toth Bela 
Published: September 2008

AbstractSolutions of hydrazine as 0.001%, methylhydrazine as 0.01%, methylhydrazine sulfate as 0.001%, and ammonium hydroxide as 0.3, 0.2 and 0.1% were administered continuously in the drinking water of 5‐ and 6‐week‐old randomly bred Swiss mice for their entire lifetime. Similarly ammonium hydroxide as a 0.1% solution was given to 7‐week‐old inbred C3H mice. Hydrazine and methylhydrazine sulfate significantly increased the incidence of lung tumors in Swiss mice, while methylhydrazine enhanced the development of this neoplasm by shortening its latent period. The ammonium hydroxide treatments in Swiss and C3H mice were, however, without carcinogenic effect, and did not inhibit the development of breast adenocarcinomas in C3H females, which are characteristic of these animals.The present study thus proves for the first time the carcinogenicity of methylhydrazine, provides further evidence of the tumor‐inducing capability of hydrazine by itself and negates the possibility that the metabolite of hydrazine, ammonium hydroxide, could interfere in the development ofneoplasia.
Evidence for a clonal origin of head and neck tumors
Authors: Fialkow Philip J. , Martin George M. , Klein George , Clifford Peter , Singh Surjit 
Published: September 2008

AbstractAccording to the inactive‐X hypothesis only one of the two genes at X‐linked loci is active in somatic cells of females. Thus, in women heterozygous for the A and B genes at the X‐linked glucose‐6‐phosphate dehydrogenase (G‐6‐PD) locus, single cells or clones of cells show either type A or type B enzyme. Similarly, pure tumors with a clonal origin arising in G‐6‐PD heterozygotes exhibit only type A or B enzyme, while those with multiple cell origin may show both A and B enzymes. The G‐6‐PD types of normal and neoplastic tissue were determined in 28 patients with tumors of the head and neck who were heterozygous at the G‐6‐PD locus. Normal tissues contained two enzyme types. Only one tumor from the 11 patients with anaplastic carcinoma of the nasopharynx was pure enough (i. e., with a relatively small number of non‐tumor cells) to allow firm conclusions. This tumor had a single enzyme phenotype and this is compatible with a clonal origin. Single enzyme phenotypes were also found in the two benign tumors and in single cases of plasmacytoma, melanoma, neuroblastoma and reticulum‐cell sarcoma. The data from three cases of carcinoma of the palate and from single cases of carcinoma of an ectopic salivary gland and the thyroid gland respectively are also compatible with a clonal origin. Only one relatively pure tumor had a double enzyme phenotype, but even in this case, the evidence for a multiple cell origin is not convincing. Thus, the data in this and other studies suggest that at least one step in the development of most human neoplasms occurs in a single cell, i. e., the mature tumors have a clonal origin.
Effect of local radiotherapy on the antibody levels against ebv‐induced early and capsid antigens (ea and vca) in patients with certain malignant tumours
Authors: Einhorn N. , Henle G. , Henle W. , Klein G. , Clifford P. 
Published: September 2008

AbstractAntibodies to tumour‐related and EBV‐associated intracellular antigens were studied in 14 cases of Burkitt's lymphoma, 50 of nasopharyngeal carcinoma, 10 of maxillary carcinoma and 95 cases of other tumours, all of whom received radiotherapy in Nairobi. For up to 1 month after radiotherapy the cases of Burkitt's lymphoma recorded an increase in antibodies to early antigens (EA) amounting to, on average, about one titre step (p<0.001). During the same interval there was a small but significant increase in antibodies to viral capsid antigen (VCA) (mean 0.6 titre step; p<0.001). The patients with nasopharyngeal and maxillary carcinoma, too, showed a small but statistically significant increase in antibodies to VCA 2‐6 months after radiotherapy (p<0.01 and 0.001, respectively), but no increase in antibodies to EA. On the contrary, in nasopharyngeal carcinoma patients there was a significant decrease in antibodies to EA 2‐3 months after radiotherapy. In the group of other tumours there was no evidence of a change in antibodies to the intracellular antigens studied during any of the relevant intervals.
Properties of a murine sarcoma virus isolated from a tumor arising in an nzw/nzb f1 hybrid mouse. II. physical and biological characteristics
Authors: Gazdar Adi F. , Sarma Padman S. , Bassin Robert H. 
Published: September 2008

AbstractThe properties of a potent murine sarcoma virus (MSV), which was isolated after in vivo passage of a spontaneous tumor arising in an NZW/NZB F1 hybrid mouse, are described. The agent had the morphological and growth characteristics of a type C virus, and contained the group‐specific (gs) antigen of the murine leukemia‐sarcoma viruses. The virus induced discrete, focal lesions of transformed cells in mouse tissue‐culture cells. Focus formation usually followed a “two‐hit” titration pattern, and sarcoma virus preparations contained a large excess of an accompanying non‐transforming type C virus. The MSV was stable when stored at — 70° C; it was ether‐sensitive and had a buoyant density of 1.16g/cm3 when centrifuged in sucrose density gradients. These properties are similar to those of the Moloney (M‐MSV), Harvey (H‐MSV), and Kirsten (Ki‐MSV) isolates of MSV. When inoculated into hamsters, the new strain of MSV rapidly induced sarcomas. While the viruses produced by hamster and mouse tumors both contained the murine gs antigen, the host range of the MSV was altered by hamster passage. It failed to induce focal lesions in mouse and hamster cells, and did not induce sarcomas or leukemias when injected into newborn mice and hamsters. The antigenic properties and infectivity of the virus produced by hamster tumor cells were significantly different from the properties of the hamster leukemia pseudotype viruses obtained from hamster tumors induced by the other strains of MSV.