bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease‐associated casein kinase I δ mutation may promote adenomatous polyps formation via a Wnt/β‐catenin independent mechanism
Authors: Tsai I‐Chun , Woolf Margaret , Neklason Deborah W. , Branford William W. , Yost H. Joseph , Burt Randall W. , Virshup David M. 
Published: November 2006

AbstractThe Wnt signaling pathway is critical for embryonic development and is dysregulated in multiple cancers. Two closely related isoforms of casein kinase I (CKIδ and ϵ) are positive regulators of this pathway. We speculated that mutations in the autoinhibitory domain of CKIδ/ϵ might upregulate CKIδ/ϵ activity and hence Wnt signaling and increase the risk of adenomatous polyps and colon cancer. Exons encoding the CKIϵ and CKIδ regulatory domains were sequenced from DNA obtained from individuals with adenomatous polyps and a family history of colon cancer unaffected by familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer (HNPCC). A CKIδ missense mutation, changing a highly conserved residue, Arg324, to His (R324H), was found in an individual with large and multiple polyps diagnosed at a relatively young age. Two findings indicate that this mutation is biologically active. First, ectopic ventral expression of CKIδ(R324H) in Xenopus embryos results in secondary axis formation with an additional distinctive phenotype (altered morphological movements) similar to that seen with unregulated CKIϵ. Second, CKIδ(R324H) is more potent than wildtype CKIδ in transformation of RKO colon cancer cells. Although the R324H mutation does not significantly change CKIδ kinase activity in an in vitro kinase assay or Wnt/β‐catenin signal transduction as assessed by a β‐catenin reporter assay, it alters morphogenetic movements via a β‐catenin‐independent mechanism in early Xenopus development. This novel human CKIδ mutation may alter the physiological role and enhance the transforming ability of CKIδ through a Wnt/β‐catenin independent mechanism and thereby influence colonic adenoma development. © 2006 Wiley‐Liss, Inc.
Body size, hormone therapy and risk of breast cancer in Asian–American women
Authors: Wu Anna H. , Yu Mimi C. , Tseng Chiu‐Chen , Pike Malcolm C. 
Published: November 2006

AbstractHistorically, breast cancer rates have been low in Asia but rates have increased substantially in Asian–Americans for reasons that are not well understood. The authors conducted a population‐based case–control study of breast cancer in Los Angeles County, which included 1,277 (450 Chinese, 352 Japanese, 475 Filipinos) women with incident, histologically confirmed breast cancer and 1,160 control subjects (486 Chinese, 311 Japanese, 363 Filipinos). A detailed in‐person interview was conducted, which included questions on menopausal hormone therapy (HT) use, height, weight in each decade of life and reproductive factors. Breast cancer risk increased with increasing recent weight in postmenopausal women (p trend = 0.015). There was a significant 16% (95% CI = 2–35%) increase in risk per 10 kg of body weight in postmenopausal women. In both premenopausal and postmenopausal women, risk increased with increasing waist to hip ratio; this remained statistically significant after adjustment for recent weight in all subjects combined (p trend = 0.042). The increased risk associated with high recent weight in postmenopausal women was more apparent for women with high waist to hip ratio (p trend = 0.013). Use of HT was a significant risk factor; risk increased 26% per 5 years of current use of estrogen and progestin therapy (p trend = 0.017). The increased risk associated with high body weight was observed irrespective of HT use. Use of HT and high body size might have contributed to the rapid increase of breast cancer in Asian–Americans. © 2006 Wiley‐Liss, Inc.
Identification of HLA‐A24 restricted shared antigen recognized by autologous cytotoxic T lymphocytes from a patient with large cell carcinoma of the lung
Authors: Sugaya Masakazu , Takenoyama Mitsuhiro , Shigematsu Yoshiki , Baba Tetsuro , Fukuyama Takashi , Nagata Yoshika , Mizukami Makiko , So Tetsuya , Ichiki Yoshinobu , Yasuda Manabu , So Tomoko , Hanagiri Takeshi , Sugio Kenji , Yasumoto Kosei 
Published: November 2006

AbstractThe aim of the present study was to elucidate the tumor‐specific cellular immunological responses occurring in a patient with large cell carcinoma of the lung who had no evidence of recurrence following surgical resections of both a primary lung lesion and a metastatic adrenal lesion. We analyzed an autologous tumor‐specific cytotoxic T lymphocytes (CTL clone F2b), which were HLA‐A*2402 restricted from regional lymph node lymphocytes. The F2b possessed T cell receptor (TCR) using the Vα5 and Vβ7 gene segment. The existence of precursor CTL (pCTL) against autologous tumor cells (A904L) was analyzed using CTL clone‐specific PCR. Lymphocytes with the same TCR as F2b were detected in the primary tumor tissue, regional lymph node and the peripheral blood collected from the patient 3 years after the operation. Using the F2b, we identified a cDNA clone encoding the tumor antigen using cDNA expression cloning method. The gene was found to encode splicing variant of the Tara gene. Finally, we identified the 9‐mer Ag peptide, using constructions of mini‐genes. The F2b recognized 3 out of 7 HLA‐A24 positive allogeneic tumor cell lines and in 1 out of 7 HLA‐A24 negative allogeneic tumor cell lines when transfected with HLA‐A24. This peptide is therefore considered to be potentially useful for performing specific immunotherapy in a significant proportion of lung cancer patients bearing HLA‐A24. © 2006 Wiley‐Liss, Inc.
Pyrazolo–pyrimidine‐derived c‐Src inhibitor reduces angiogenesis and survival of squamous carcinoma cells by suppressing vascular endothelial growth factor production and signaling
Authors: Donnini Sandra , Monti Martina , Castagnini Cinzia , Solito Raffaella , Botta Maurizio , Schenone Silvia , Giachetti Antonio , Ziche Marina 
Published: November 2006

AbstractSrc tyrosine kinase family cooperates with activated growth factor receptors to regulate growth, invasion and metastasis. The authors examined the influence of a novel c‐Src inhibitor, 1l, derived from 4‐amino‐substituted‐pyrazolo–pyrimidines, on tumor angiogenesis and on the angiogenic output of squamous carcinoma cells, A431 and SCC‐4. The effect of 1l was assessed on growth and microvessel density in A431 tumors and its effect compared with the established c‐Src inhibitor PP‐1. The effects of c‐Src inhibition were investigated on vascular endothelial growth factor (VEGF) expression and activity in tumor cells grown in vivo and in vitro, as well as on VEGF mediated signaling and on endothelial cell functions. Nanomolar concentrations of 1l decreased tumor volume promoted by A431 implanted in nude mice, without affecting in vitro cell tumor survival. This effect was related to 1l inhibition of VEGF production, and secondary to an effect on tumor microvessel density. The rabbit cornea assay confirmed that 1l markedly decreased neovessel growth induced by VEGF. In cultured endothelial cells, 1l inhibited the VEGF‐induced phosphorylation on tyr416 of c‐Src, resulting in a reduced cell proliferation and invasion. Consistently, 1l dowregulated endothelial nitric oxide synthase, MAPK‐extracellular receptor kinase 1–2 (ERK1‐2) activity and matrix metalloproteinases (MMP‐2/MMP‐9), while the tissue inhibitors of metalloproteinases (TIMP2/TIMP‐1) were upregulated. These results demonstrate that nM concentrations of c‐Src kinase inhibitors (1l and PP‐1), by reducing the production of VEGF released by tumor cell and its endothelial cell responses, have a highly selective antiangiogenesis effect, which might be useful in combination therapies. © 2006 Wiley‐Liss, Inc.
Dietary polyphenolic phytochemicals—promising cancer chemopreventive agents in humans? A review of their clinical properties
Authors: Thomasset Sarah C. , Berry David P. , Garcea Giuseppe , Marczylo Timothy , Steward William P. , Gescher Andreas J. 
Published: November 2006

AbstractEpidemiological and preclinical evidence suggests that polyphenolic phytochemicals exemplified by epigallocatechin gallate from tea, curcumin from curry and soya isoflavones possess cancer chemopreventive properties. Whilst such naturally occurring polyphenols have been the subject of numerous mechanistic studies in cells, information on their clinical properties, which might help assess their promise as human cancer chemopreventive agents, is scarce. Therefore, we present a review of pilot studies and trials with a cancer chemoprevention‐related rationale, in which either healthy individuals or patients with premalignant conditions or cancer received polyphenolic phytochemicals. The review identifies trial design elements specifically applicable to polyphenolic phytochemicals. The available evidence for tea polyphenols tentatively supports their advancement into phase III clinical intervention trials aimed at the prevention of progression of prostate intraepithelial neoplasia, leukoplakia or premalignant cervical disease. In the case of curcumin and soya isoflavones more studies in premalignacies seem appropriate to optimise the nature and design of suitable phase III trials. The abundance of flavonoids and related polyphenols in the plant kingdom makes it possible that several hitherto uncharacterised agents with chemopreventive efficacy are still to be identified, which may constitute attractive alternatives to currently used chemopreventive drugs. © 2006 Wiley‐Liss, Inc.
Loss of chromosomal integrity drives rat mammary tumorigenesis
Authors: Goepfert Thea M. , Moreno‐Smith Myrthala , Edwards David G. , Pathak Sen , Medina Daniel , Brinkley W.R. 
Published: November 2006

AbstractBreast cancer incidence varies with diet and other environmental influences, including carcinogen exposure. However, the effects of carcinogens on cell growth control pathways are poorly understood. Here, we have examined processes that are activated in the mammary glands of rats treated with 1‐methyl‐1‐nitrosourea (MNU). This synthetic carcinogen was used to study events occurring during mammary tumor initiation and development. In female Wistar‐Furth rats, given 1 dose of MNU beginning at 50 days of age, 84% of the rats developed tumors by 46 weeks of age (latency 13–15 weeks). Changes in the gland occurred as early as 1‐day post‐MNU. Cells exhibited DNA damage, leading to chromosomal instability, supernumerary centrosomes and higher levels of Aurora A; these events correlated with the appearance of preneoplasia in the glands. In mammary tumors, elevated numbers of centrosomes coincided with genomic instability. Tumors were transplanted into syngeneic hosts and subsequent tumor generations displayed the same marker chromosomes in mostly aneuploid metaphases with hyperdiploid numbers of chromosomes, suggesting that clonality and aneuploidy were passed on from one generation to the next. Collectively, these data suggest that the carcinogen MNU induces changes resulting in genetic instability detectable before hyperplasia and tumors develop in the rat mammary gland. © 2006 Wiley‐Liss, Inc.
Carbohydrate intake, glycemic index and glycemic load in relation to risk of endometrial cancer: A prospective study of Swedish women
Authors: Larsson Susanna C. , Friberg Emilie , Wolk Alicja 
Published: November 2006

AbstractThe associations of carbohydrate intake, glycemic index and glycemic load with endometrial cancer risk were examined among 61,226 participants of the Swedish Mammography Cohort who were cancer‐free at enrollment between 1987 and 1990 and completed a food frequency questionnaire. During a mean follow‐up of 15.6 years, through June 2005, 608 incident cases of endometrial adenocarcinoma were diagnosed. We observed no overall association between carbohydrate intake, glycemic index or glycemic load and incidence of endometrial cancer; the rate ratios (RRs) for the highest versus the lowest quintile were 1.12 (95% CI, 0.85–1.47) for carbohydrate intake, 1.00 (95% CI, 0.77–1.30) for glycemic index and 1.15 (95% CI, 0.88–1.51) for glycemic load. However, among obese women (body mass index, BMI ≥30 kg/m2), endometrial cancer incidence was nonsignificantly elevated in the top versus bottom quintiles of carbohydrate intake (RR, 1.68; 95% CI, 0.86–3.29) and glycemic load (RR, 1.57; 95% CI, 0.82–2.99). In a subanalysis of women who completed a follow‐up questionnaire in 1997, which collected information on physical activity, carbohydrate intake and glycemic load were positively related to endometrial cancer risk among overweight women (BMI ≥25 kg/m2) with low physical activity. In this subgroup, the multivariate RRs comparing extreme quartiles were 1.90 (95% CI, 0.84–4.31) for carbohydrate intake and 2.99 (95% CI, 1.17–7.67) for glycemic load. Results from this cohort study suggest that a high carbohydrate intake and a high glycemic load may increase the risk of endometrial cancer among overweight women with low physical activity. © 2006 Wiley‐Liss, Inc.
SV40 and human cancer: A review of recent data
Authors: Shah Keerti V. 
Published: November 2006

AbstractAn unknown proportion of formalin‐inactivated poliovirus vaccine lots administered to millions of US residents between 1955 and 1963 was contaminated with small amounts of infectious simian virus 40 (SV40), a polyomavirus of the rhesus macaque. It has been reported that mesothelioma, brain tumors, osteosarcoma and non‐Hodgkin lymphoma (NHL) contain SV40 DNA sequences and that SV40 infection introduced into humans by the vaccine probably contributed to the development of these cancers. The Immunization Safety Review Committee of the Institute of Medicine (IOM) reviewed this topic in 2002. The present review of recent studies showed that the earlier results describing the recovery of SV40 DNA sequences from a large proportion of the above tumors were not reproducible and that most studies were negative. Contamination with laboratory plasmids was identified as a possible source of false positive results in some previous studies. The low‐level immunoreactivity of human sera to SV40 was very likely the result of cross‐reactivity with antibodies to the SV40‐related human polyomaviruses BKV and JCV, rather than of authentic SV40 infection. SV40 sero‐reactivity in patients with the suspect tumors was no greater than that in controls. In epidemiologic studies, the increased incidence of some of the suspect tumors in the 1970s to 1980s was not related to the risk of exposure to SV40‐contaminated vaccines. In summary, the most recent evidence does not support the notion that SV40 contributed to the development of human cancers. © 2006 Wiley‐Liss, Inc.
CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC‐EURGAST study
Authors: Palli Domenico , Masala Giovanna , Del Giudice Giuseppe , Plebani Mario , Basso Daniela , Berti Duccio , E. Numans Mattijs , Ceroti Marco , Peeters Petra H.M. , de Mesquita H. Bas Bueno , Buchner Frederike L. , Clavel‐Chapelon Francoise , Boutron‐Ruault Marie‐Christine , Krogh Vittorio , Saieva Calogero , Vineis Paolo , Panico Salvatore , Tumino Rosario , Nyrén Olof , Simán Henrik , Berglund Goran , Hallmans Goran , Sanchez Maria‐Jose , Larrãnaga Nerea , Barricarte Aurelio , Navarro Carmen , Quiros Jose R. , Key Tim , Allen Naomi , Bingham Sheila , Khaw Kay Tee , Boeing Heiner , Weikert Cornelia , Linseisen Jakob , Nagel Gabriele , Overvad Kim , Thomsen Reimar W. , Tjonneland Anne , Olsen Anja , Trichoupoulou Antonia , Trichopoulos Dimitrios , Arvaniti Athina , Pera Guillem , Kaaks Rudolf , Jenab Mazda , Ferrari Pietro , Nesi Gabriella , Carneiro Fatima , Riboli Elio , Gonzalez Carlos A. 
Published: November 2006

AbstractHelicobacter pylori (H. pylori), atrophic gastritis, dietary and life‐style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case–control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992–1998, provided life‐style and dietary information and a blood sample (360,000; mean follow‐up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually‐matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 μg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti‐H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4‐fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2–5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3–12.6); on the other hand, a ten‐fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0–40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites. © 2006 Wiley‐Liss, Inc.
MTHFR C677T and colorectal cancer risk: A meta‐analysis of 25 populations
Authors: Hubner Richard A. , Houlston Richard S. 
Published: November 2006

AbstractThe common functional methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the risk of colorectal cancer (CRC), but data from published studies with individually low statistical power are conflicting. To clarify the role of MTHFR C677T genotype in CRC, we considered all available studies in a meta‐analysis. Studies reporting on MTHFR C677T genotype and CRC were searched in PubMed up to April 2006. The principle prior hypothesis was that homozygosity for MTHFR 677TT would be associated with reduced risk of CRC. Data were available for 29,931 subjects, including 12,243 with CRC, from 25 independent populations. Compared to the homozygous CC genotype, the MTHFR 677TT genotype was associated with a reduced risk of CRC (odds ratio (OR): 0.83; 95% confidence interval (CI): 0.75–0.93; p = 0.001). There was some heterogeneity among the results of individual studies, but this was not statistically significant (heterogeneity p = 0.12; I2 = 25.8%). Heterozygosity for MTHFR 677 did not influence CRC risk (OR: 0.99; 95% CI: 0.94–1.04). These findings indicate that individuals homozygous for the MTHFR 677TT genotype are at moderately reduced risk of CRC, and support the proposal that common genetic variation in the MTHFR gene contributes to CRC susceptibility, probably accounting for at least 9% of the total incidence. © 2006 Wiley‐Liss, Inc.
Prediction of metastasis from low‐malignant breast cancer by gene expression profiling
Authors: Thomassen Mads , Tan Qihua , Eiriksdottir Freyja , Bak Martin , Cold Søren , Kruse Torben A. 
Published: November 2006

AbstractPromising results for prediction of outcome in breast cancer have been obtained by genome wide gene expression profiling. Some studies have suggested that an extensive overtreatment of breast cancer patients might be reduced by risk assessment with gene expression profiling. A patient group hardly examined in these studies is the low‐risk patients for whom outcome is very difficult to predict with currently used methods. These patients do not receive adjuvant treatment according to the guidelines of the Danish Breast Cancer Cooperative Group (DBCG). In this study, 26 tumors from low‐risk patients were examined with gene expression profiling. An intermediate risk group of 34 low‐malignant T2 tumors that fulfilled all other low‐risk criteria than tumor size was included to increase statistical power. A 32‐gene classifier, HUMAC32, was identified and it predicted metastases with 80% sensitivity and 77% specificity. The classifier was also validated in an independent group of high‐risk tumors resulting in comparable performance of HUMAC32 and a 70‐gene classifier developed for this group. Furthermore, the 70‐gene signature was tested in our low‐ and intermediate‐risk samples. The results demonstrated high cross‐platform consistency of the classifiers. Higher performance of HUMAC32 was demonstrated among the low‐malignant cancers compared with the 70‐gene classifier. This suggests that although the metastatic potential to some extend is determined by the same genes in groups of tumors with different characteristics and risk, expression‐based classification specifically developed in low‐risk patients have higher predictive power in this group. © 2006 Wiley‐Liss, Inc.
Dietary zinc, copper and selenium, and risk of lung cancer
Authors: Mahabir Somdat , Spitz Margaret R. , Barrera Stephanie L. , Beaver Shao Hua , Etzel Carol , Forman Michele R. 
Published: November 2006

AbstractZinc, copper and selenium are important cofactors for several enzymes that play a role in maintaining DNA integrity. However, limited epidemiologic research on these dietary trace metals and lung cancer risk is available. In an ongoing study of 1,676 incident lung cancer cases and 1,676 matched healthy controls, we studied the associations between dietary zinc, copper and selenium and lung cancer risk. Using multiple logistic regression analysis, the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for all subjects by increasing quartiles of dietary zinc intake were 1.0, 0.80 (0.65–0.99), 0.64 (0.51–0.81), 0.57 (0.42–0.75), respectively (p trend = 0.0004); similar results were found for men. For dietary copper, the ORs and 95% CI for all subjects were 1.0, 0.59 (0.49–0.73), 0.51 (0.41–0.64), 0.34 (0.26–0.45), respectively (p trend < 0.0001); similar reductions in risk and trend were observed by gender. Dietary selenium intake was not associated with risk, except for a significant inverse trend (p = 0.04) in men. Protective trends (p < 0.05) against lung cancer with increased dietary zinc intake were also found for all ages, BMI > 25, current smokers, pack‐years ≤30, light drinkers and participants without emphysema. Increased dietary copper intake was associated with protective trends (p < 0.05) across all ages, BMI, smoking and vitamin/mineral supplement categories, pack‐years ≤30 and 30.1–51.75 and participants without emphysema. Our results suggest that dietary zinc and copper intakes are associated with reduced risk of lung cancer. Given the known limitations of case–control studies, these findings must be interpreted with caution and warrant further investigation. © 2006 Wiley‐Liss, Inc.