bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALDH2 genotype‐associated differences in the acute effects of alcohol on P300, psychomotor performance, and subjective response in healthy young Korean men: a double‐blind placebo‐controlled crossover study
Authors: Shin Hee‐Young , Shin Il‐Seon , Yoon Jin‐Sang 
Published: March 2006

AbstractBackgroundThis study investigated the acute effects of alcohol on neurophysiological and psychomotor functions and the subjective response in healthy young Korean men according to the mitochondrial aldehyde dehydrogenase (ALDH2) genotype.MethodA total of 24 males, half with ALDH2*1/*1 (active form) and the rest with ALDH2*1/*2 (inactive form), were selected through genotyping. In a double‐blind placebo‐controlled crossover design, each subject consumed either a 0.5 g/kg dose of alcohol or a placebo on two separate occasions, 1 week apart. The blood alcohol concentrations (BACs), P300 of event‐related potential, psychomotor performance, and perceived feelings were assessed.ResultsAlthough the BACs were similar between the two groups, the effects of alcohol on P300 were greater overall in subjects with ALDH2*1/*2 than in subjects with ALDH2*1/*1. Psychomotor performance was more impaired after alcohol ingestion in subjects with ALDH2*1/*2 than in subjects with ALDH2*1/*1. The subjective response after alcohol ingestion was more negative in subjects with ALDH2*1/*2, compared to subjects with ALDH2*1/*1.ConclusionsThese results suggest that the ALDH2 polymorphism is an important factor in determining the effects of alcohol on various psychobehavioral functions. Copyright © 2006 John Wiley & Sons, Ltd.
Cyclooxygenase‐2 (cox‐2) expression is an independent predictor of prostate cancer recurrence
Authors: Cohen Brian L. , Gomez Pablo , Omori Yohei , Duncan Robert C. , Civantos Francisco , Soloway Mark S. , Lokeshwar Vinata B. , Lokeshwar Bal L. 
Published: March 2006

AbstractLack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase‐2 (COX‐2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX‐2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty‐three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow‐up: 95 months). COX‐2 expression was determined by IHC, using an anti‐COX‐2 antibody. Three individuals scored the staining independently, as high‐ or low‐expression. COX‐2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62‐months follow‐up, COX‐2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at ≥ 100‐months follow‐up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX‐2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX‐2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX‐2 expression had the highest probability of recurrence (Kaplan‐Meier analysis). COX‐2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process. © 2006 Wiley‐Liss, Inc.
Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer
Authors: Newton Tanya R. , Parsons Peter G. , Lincoln Douglas J. , Cummings Margaret C. , Wyld David K. , Webb Penelope M. , Green Adele C. , Boyle Glen M. 
Published: March 2006

AbstractThe majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically‐confirmed late‐stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow‐up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation‐2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7‐fold increased risk of dying (95% CI 1.9–29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. © 2006 Wiley‐Liss, Inc.
Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients
Authors: Ikuerowo Stephen O. , Kuczyk Markus A. , Mengel Michael , van der Heyde Eyck , Shittu Olayiwola B. , Vaske Bernhard , Jonas Udo , Machtens Stefan , Serth Jürgen 
Published: March 2006

AbstractCyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long‐term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p = 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p = 0.02) and pN (p = 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long‐term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p = 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni‐ and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. © 2006 Wiley‐Liss, Inc.
Aflatoxin‐B exposure does not lead to p53 mutations but results in enhanced liver cancer of Hupki (human p53 knock‐in) mice
Authors: Tong Wei‐Min , Lee Ming‐Kei , Galendo Dominique , Wang Zhao‐Qi , Sabapathy Kanaga 
Published: March 2006

AbstractHepatocellular carcinoma (HCC) is a common human malignancy that is often associated with risk factors such as aflatoxin‐B1 (AFB1) exposure and Hepatitis‐B virus infection in developing countries. There is a strong correlation between these risk factors and mutation of the tumor‐suppressor gene p53 at codon 249. In vitro experiments have also shown that treatment of human liver cells with AFB1 results in p53 mutations. A tumor‐promoting role for mutant p53 was demonstrated using transgenic mice models, in which HCC development was accelerated upon AFB1‐exposure. However, wild‐type mice in which AFB1 alone was used to induce liver cancers have failed to recapitulate p53 mutations, raising the possibility that mouse DNA context may not be appropriate for the generation of AFB1‐induced p53 mutations. We have now tested this hypothesis using the Hupki mice (human p53 knock‐in) in which the mouse DNA‐binding domain has been replaced by the homologous human p53 segment. Mice were followed for 80 weeks after AFB1 injection for survival and HCC formation. Hupki mice were found to be more susceptible to AFB1 than wild‐type mice. Moreover, only 19% of wild‐type mice developed HCCs compared to 44% in Hupki mice. However, none of the liver tumors and normal tissues from Hupki mice contained any mutations in the DNA‐binding domain of p53. These findings suggest that the human DNA context of the p53 gene alone may not be the sole determinant of AFB1‐induced mutagenesis. Furthermore, humanized p53 appears not to be as effective as murine p53 in the mouse cellular environment in preventing malignant transformation. © 2006 Wiley‐Liss, Inc.
Sex differences in risk of lung cancer: Expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts
Authors: Mollerup Steen , Berge Gisle , Bæra Rita , Skaug Vidar , Hewer Alan , Phillips David H. , Stangeland Lodve , Haugen Aage 
Published: March 2006

AbstractIt is controversial whether women have a higher lung cancer susceptibility compared to men. We previously reported higher levels of smoking‐related bulky DNA adducts in female lungs. In a pilot study (27 cases), we also found a higher level of female lung cytochrome P4501A1 (CYP1A1) gene expression. In the present extended study we report on the pulmonary expression of several genes involved in polycyclic aromatic hydrocarbon bioactivation in relation to sex, smoking and DNA adducts. CYP1A1, CYP1B1, aryl hydrocarbon receptor and microsomal epoxide hydrolase gene expression was measured by quantitative real‐time reverse transcriptase‐PCR in 121 normal lung tissue samples. The expression of CYP1A1 and CYP1B1 was significantly higher among current smokers compared to ex‐smokers and never‐smokers. Among current smokers, females had a 3.9‐fold higher median level of CYP1A1 compared to males (p = 0.011). CYP1B1 expression was not related to sex. Lung DNA adducts (measured by 32P‐postlabeling) were highly significantly related to CYP1A1 (p < 0.0001) irrespective of smoking‐status. Our results are consistent with the hypothesis that CYP1A1 plays a significant role in lung DNA adduct formation and support a higher susceptibility to lung cancer among females. © 2006 Wiley‐Liss, Inc.
Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF‐7 human breast cancer xenografts
Authors: Saarinen Niina M. , Power Krista , Chen Jianmin , Thompson Lilian U. 
Published: March 2006

AbstractIn several epidemiological studies, a phytoestrogen‐rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial. In postmenopausal mammary cancer xenograft model, flaxseed (FS), a rich source of plant lignans, reduced breast cancer growth, while soy protein (SP), a rich source of isoflavones, enhanced it. The intake of phytoestrogens is increasing particularly among postmenopausal women, emphasizing the importance of elucidating their interactive effects on breast cancer. Our study determined the effect of FS and SP diets, alone and in combination, on the established human breast cancer MCF‐7 tumor growth in ovariectomized athymic nude mice. Tumor bearing mice were divided into 4 groups and fed for 25 weeks either the basal diet (BD), or BD supplemented with 10% FS, 20% SP or 10% FS and 20% SP. After estrogen deprivation, FS regressed the tumor size similar to that of control. SP initially regressed the tumors but starting at week 13, the tumors regressed significantly less than in control and 43% of the tumors were regrowing until the end of the experiment and were significantly larger in size than in control. The combination of SP with FS reduced the tumor growth similar to that of control, as suggested also by the reduced tumor cell proliferation index. In conclusion, dietary FS did not stimulate the growth of estrogen responsive MCF‐7 cancers in ovariectomized mice, while long‐term consumption of SP did. Furthermore, FS reduced the tumor growth stimulating effect of SP to the same level as control, suggesting tumor growth attenuating effect of FS. © 2006 Wiley‐Liss, Inc.
N7‐methyldeoxyguanosine levels in DNA isolated from cervical cytology samples are associated with smoking
Authors: Harrison Kathryn L. , Khan Noreen S. , Dey Paola , Povey Andrew C. 
Published: March 2006

AbstractSmoking has been associated, in epidemiological studies, with an increased risk of cervical neoplasia. This may be in part due to the presence of tobacco‐specific nitrosamines in cervical mucous of smokers, which may result in carcinogenic DNA damage. We have thus examined whether cervical DNA contains alkylation damage arising from exposure to methylating agents (N7‐methyldeoxyguanosine, N7‐MedG). DNA was extracted from cervical cytology samples and N7‐MedG levels were measured using an immunoslotblot assay. Ninety percentage of the DNA samples were alkylated and N7‐MedG levels (mean, 95% CI) in ever‐smokers (1.27, 0.90–1.81 μmol/mol dG) were significantly higher than those in nonsmokers (0.42, 0.20–0.91 μmol/mol dG: p = 0.005). N7‐MedG adduct levels were significantly correlated with number of cigarettes smoked per day and pack years of cigarette smoking in current smokers. There was no association with N7‐MedG levels and cervical intraepithelial neoplasia status, age, parity or contraception use. Our study suggests that cervical DNA contains alkylation damage that can arise from exposure to cigarette smoke. © 2006 Wiley‐Liss, Inc.
The burden of cancer attributable to alcohol drinking
Authors: Boffetta Paolo , Hashibe Mia , La Vecchia Carlo , Zatonski Witold , Rehm Jürgen 
Published: March 2006

AbstractWe estimated the number of cancer cases and deaths attributable to alcohol drinking in 2002 by sex and WHO subregion, based on relative risks of cancers of the oral cavity, pharynx, esophagus, liver, colon, rectum, larynx and female breast obtained from recent meta‐ and pooled analyses and data on prevalence of drinkers obtained from the WHO Global Burden of Disease project. A total of 389,100 cases of cancer are attributable to alcohol drinking worldwide, representing 3.6% of all cancers (5.2% in men, 1.7% in women). The corresponding figure for mortality is 232,900 deaths (3.5% of all cancer deaths). This proportion is particularly high among men in Central and Eastern Europe. Among women, breast cancer comprises 60% of alcohol‐attributable cancers. Although our estimates are based on simplified assumptions, the burden of alcohol‐associated cancer appears to be substantial and needs to be considered when making public health recommendations on alcohol drinking. © 2006 Wiley‐Liss, Inc.
Second primary malignancies among patients with soft tissue tumors in Sweden
Authors: Ji Jianguang , Hemminki Kari 
Published: March 2006

AbstractSurvival from soft tissue tumors (STTs) has been improved because of the successful treatment. One of the late sequelae in STT survivors is the development of a second malignancy. The present study aimed at quantifying risks for second malignancies in patients with STTs, and risks for second STTs after other primary malignancies. Adjusted standardized incidence ratios (SIRs), calculated from the Swedish Family‐Cancer Database, were used as a measure of risk. Among 6,671 primary STT patients, a total of 650 second malignancies occurred. Besides second STTs, other cancer sites with an increased SIR were the nervous system, endocrine glands, skin (melanoma and squamous cell carcinoma) and prostate; the risk for non‐Hodgkin lymphoma (NHL) was also increased. The overall risk of second malignancies decreased in the following order: fibrosarocma (1.63) > myxosarcoma (1.48) > leiomyosarcoma (1.44) > liposarcoma (1.21). An increased risk of second STTs after primary cancers of the bone, ovary, nervous system, cervix, thyroid gland, skin, endometrium, breast, upper aerodigestive tract, and after Hodgkin disease, NHL and leukemia was also noted. This study showed that the incidence of second primary malignancies in patients with STTs was increased, but the SIRs varied among specific cancer sites. Besides therapeutic effects, the associations between STTs and bone and nervous system tumors suggested that cancer syndromes, such as neurofibromatosis type 1 and Li–Fraumeni syndrome, may partly explain the excesses. The associations of STTs with cancers of the skin (squamous cell carcinoma and melanoma) and with NHL may be related to immunodeficiency. © 2006 Wiley‐Liss, Inc.
RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas
Authors: Shibata David , Mori Yuriko , Cai Kun , Zhang Li , Yin Jing , Elahi Abul , Hamelin Richard , Wong Yick F. , Lo Wing K. , Chung Tony K.H. , Sato Fumiaki , Karpeh Martin S. , Meltzer Stephen J. 
Published: March 2006

AbstractThe recently described gene, RAB32, is a ras proto‐oncogene family member that encodes an A‐kinase‐anchoring protein. RAB32 has been found to be frequently hypermethylated in microsatellite instability‐high (MSI‐H) colon cancers. We sought to determine the prevalence of RAB32 hypermethylation in gastric and endometrial adenocarcinomas, the 2 other major tumor types in which MSI‐H is common. Moreover, we delineated the association of RAB32 hypermethylation with microsatellite instability (MSI) and hMLH1 hypermethylation. MSI status and hypermethylation of the RAB32 and hMLH1 genes were studied in paired primary normal and tumor tissues from 48 patients with gastric cancer. An additional 80 endometrial cancer patients were studied for RAB32 methylation and MSI status. Thirteen (27%) of 48 gastric cancers demonstrated evidence of RAB32 hypermethylation. MSI status was determined in 46 of the tumors, with 7 (100%) of 7 MSI‐H tumors, 1 (33%) of 3 MSI‐low (MSI‐L) tumors and 4 (11%) of 36 microsatellite‐stable (MSS) tumors found to harbor RAB32 hypermethylation. RAB32 methylation was significantly associated with intestinal type histology and concomitant hMLH1 hypermethylation in gastric cancer. In contrast, RAB32 methylation occurred in only 1 of 80 endometrial cancers, including 20 MSI‐H, 8 MSI‐L and 52 MSS tumors. Hypermethylation of hMLH1 was noted in 16 (20%) of 80 endometrial tumors. We conclude that although RAB32 methylation is rare in endometrial cancers, it is strongly associated with hMLH1 hypermethylation and MSI in gastric adenocarcinomas. Given its similar involvement in colon cancer, RAB32 inactivation may represent a component of the oncogenic pathway of microsatellite‐unstable gastrointestinal adenocarcinomas. © 2006 Wiley‐Liss, Inc.
Chenodeoxycholic acid stimulates the progression of human esophageal cancer cells: A possible mechanism of angiogenesis in patients with esophageal cancer
Authors: Soma Toshiya , Kaganoi Junichi , Kawabe Atsushi , Kondo Kan , Tsunoda Shigeru , Imamura Masayuki , Shimada Yutaka 
Published: March 2006

AbstractBile acids are known to promote the growth of gastrointestinal cancer. However, the underlying mechanism remains unclear. We examined whether bile acids induce tumor growth via the cyclooxygenase (COX)‐2 angiogenic pathway. In vitro, esophageal squamous cell carcinoma (ESCC) cells and esophageal adenocarcinoma cells were studied. Production of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) in response to treatment with chenodeoxycholic acid (CDCA) was assessed by enzyme‐linked immunosorbent assay (ELISA). COX‐2 protein and VEGF protein were measured by immunoblot analysis, and COX‐2 activity was measured by ELISA. In vivo, CDCA was administered to ESCC cell‐bearing mice. Tumor tissues were analyzed immunohistochemically, and microvessel density was evaluated. Clinically, 134 patients with ESCC who underwent esophagectomy were studied. In vitro, CDCA induced the production of PGE2 and VEGF in dose‐ and time‐dependent manners, and these effects were attenuated by a selective COX‐2 inhibitor, mitogen‐activated protein kinases inhibitor, or epidermal growth factor receptor inhibitor. CDCA‐induced COX‐2 in the cell lysate increased the secretion of VEGF into the culture medium. In vivo, CDCA markedly enhanced tumor growth and increased vascularization. Clinically, patients whose tumors expressed both COX‐2 and VEGF had poor outcomes. Our results suggest that bile acids, important constituents of duodenal fluid, stimulate the development of human esophageal cancer by promoting angiogenesis via the COX‐2 pathway. © 2006 Wiley‐Liss, Inc.
Subtype HPV38b[FA125] demonstrates heterogeneity of human papillomavirus type 38
Authors: Hazard Kristina , Eliasson Linda , Dillner Joakim , Forslund Ola 
Published: March 2006

AbstractThe human papillomaviruses (HPVs) exist as more than 100 distinct types. While variants of HPV are common, only few HPV subtypes have been reported. HPV type 38 has been proposed to be associated with nonmelanoma skin cancer (NMSC), with reported prevalences of up to 55%. A subtype of HPV38 was cloned, completely sequenced and found to have a 96% sequence similarity to prototype HPV38 in the L1 open reading frame. The presence of prototype HPV38 and HPV38b[FA125] was examined in paired biopsies of tape‐stripped skin lesions and healthy skin from 269 immunocompetent patients by real‐time PCR. Prototype HPV38 and HPV38b[FA125] were present in seven (3%) and five (2%) lesions, respectively, in viral loads ranging from one copy per 150 cells to one copy per 70,000 cells. In summary, we found that HPV38 is heterogeneous and is one of so far only few HPVs that contain subtypes. The heterogeneity needs to be considered in studies of the biology of this virus. © 2006 Wiley‐Liss, Inc.