bluuebunny/crossref_metadata_2025_split huggingface dataset:
Msh2 deficiency increases susceptibility to benzo[a]pyrene‐induced lymphomagenesis
Authors: Zienolddiny Shanbeh , Ryberg David , Svendsrud Debbie H. , Eilertsen Einar , Skaug Vidar , Hewer Alan , Phillips David H. , te Riele Hein , Haugen Aage 
Published: December 2005

AbstractDNA mismatch repair (MMR) is essential for repair of single‐base mismatches and insertion/deletion loops. MMR proteins also participate in cellular response to DNA damaging agents such as various alkylating agents. Mice deficient in the MMR gene Msh2 develop tumors earlier after exposure to alkylating agents when compared to unexposed mice. The interaction between the MMR system and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (B[a]P) has not been investigated in vivo. Here, we show that treatment of Msh2‐deficient mice with B[a]P enhances susceptibility to lymphomagenesis. Carrying at least one intact copy of the Msh2 gene had a protective effect. B[a]P treatment only induced lymphomas in 3 of the 40 (7.5%) mice with at least one intact copy of the Msh2 gene as compared to 13 of the 17 (76.5%) Msh2‐deficient mice and occurs only after a much longer time period. The B[a]P‐DNA adduct levels measured in lung, liver, spleen and forestomach of B[a]P‐treated Msh2−/− mice were not significantly different from B[a]P‐treated Msh2+/+ mice. In summary, the results suggest that B[a]P accelerates lymphomagenesis in Msh2‐deficient mice. Furthermore, Msh2 deficiency does not have any significant effect on B[a]P‐DNA adduct levels. © 2005 Wiley‐Liss, Inc.
Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis
Authors: Malafa Mokenge P. , Fokum Frida D. , Andoh Jennifer , Neitzel Leslie T. , Bandyopadhyay Sucharita , Zhan Rui , Iiizumi Megumi , Furuta Eiji , Horvath Elizabeth , Watabe Kounosuke 
Published: December 2005

AbstractProstate cancer is a major cause of cancer death and morbidity in western countries. However, because of its intrinsic nature of chemoresistance, there is only limited systemic therapy available for the patients. Vitamin E (VE) has been under intensive study as a chemopreventive agent for various types of cancers. Preclinical studies suggest that vitamin E succinate (VES) is the most effective antitumor analogue of VE, yet there are scarce studies of VES in prostate cancer. In this study, we investigated the effects of VES on a panel of prostate cancer cells, and a xenograft model of prostate cancer. Our results indicate that VES significantly inhibited proliferation and induced apoptosis of prostate cancer cell lines in a dose and time dependent manner. The results of microarray analysis followed by real‐time RT‐PCR and inhibitor analyses indicated that the VES‐induced apoptosis is mediated by caspase‐4 in prostate tumor cells. In our animal model of prostate cancer in SCID mouse, daily injection of VES significantly suppressed tumor growth as well as lung metastases. These results suggest a potential therapeutic utility of VES for patients with prostate cancer. © 2005 Wiley‐Liss, Inc.
Animal models for the study of squamous cell carcinoma of the upper aerodigestive tract: A historical perspective with review of their utility and limitations. Part A. Chemically‐induced de novo cancer, syngeneic animal models of HNSCC, animal models of transplanted xenogeneic human tumors
Authors: Smith Lee P. , Thomas Giovana R. 
Published: December 2005

AbstractUnderstanding the complex histological, genetic and molecular changes that lead to malignant transformation of squamous epithelia of the head and neck will likely guide the development of methods for improved diagnosis, monitoring and treatment of head and neck squamous cell carcinoma (HNSCC). The development and use of animal models that closely mimic the histopathology and molecular pathogenesis of HNSCC in humans would greatly expand the research possibilities and provide a means of testing potential therapeutic agents. However, many available animal models of HNSCC fall short of this objective. In order for investigators to select the appropriate model to answer scientific questions, it is important to understand the benefits and limitations of available animal models for the study of HNSCC. The purpose of this work is to give an overview of the most pertinent animal models of HNSCC, and to discuss future directions of research in this field. © 2005 Wiley‐Liss, Inc.
Extra‐tumoral breast tissue in breast cancer patients: Variations with steroid contraceptive use
Authors: Vamre Tone B. Aaman , Stalsberg Helge , Thomas David B. ,   The WHO Collaborative Study of Neoplasia and Steroid Contraceptives
Published: December 2005

AbstractThe association between oral contraceptive (OC) use and benign breast changes in extra‐tumoral breast tissue was studied histologically in 1,503 breast cancer patients from The WHO Collaborative Study of Neoplasia and Steroid Contraceptives. The occurrence of ductal hyperplasia, ductal atypia, sclerosing adenosis, cysts, apocrine metaplasia, apocrine hyperplasia, apocrine atypia, adenosis, lobular atypia, duct ectasia, calcifications, inflammatory reaction, lactational metaplasia and a high epithelial‐stromal ratio was graded semi‐quantitatively. Prevalence odds ratio (POR) for each histologic variable was calculated by logistic regression analyses. Patients who had ever used OC had lower occurrence of ductal hyperplasia than never users (POR 0.72 (95% CI 0.52–0.99)). Current use and more than 8 years of use was also associated with a lower prevalence of ductal hyperplasia (POR 0.40 (0.20–0.81) and POR 0.33 (0.17–0.64), respectively). Age > 35 years at first use was associated with increased prevalence of ductal carcinoma in situ (POR 2.15 (1.05–4.40)), but not of atypical ductal hyperplasia. Our results show that the effects of OC use on ductal hyperplasia in non‐neoplastic breast tissue of breast cancer patients are similar to what others have found in patients with benign breast disease only. The increased prevalence of extra‐tumoral ductal carcinoma in situ in breast cancer patients who started OC use at high age may possibly be explained by a longer preinvasive phase in these patients. © 2005 Wiley‐Liss, Inc.
Contact of high‐invasive, but not low‐invasive, melanoma cells to native collagen I induces the release of mature cathepsin B
Authors: Klose Anke , Wilbrand‐Hennes Astrid , Zigrino Paola , Weber Ekkehard , Krieg Thomas , Mauch Cornelia , Hunzelmann Nicolas 
Published: December 2005

AbstractMetastasis of malignant tumor cells involves cell–cell and cell–matrix interactions, which regulate the expression and localization of proteolytic enzymes. In the present study, we investigated the expression and localization of the lysosomal cysteine proteinase cathepsin B and its natural inhibitors cystatin A, B and C in high‐ (MV3), intermediate‐ (SKmel28) and low‐invasive (SKmel23, WM164) human melanoma cell lines grown on plastic or in contact with monomeric or fibrillar collagen type I. Neither the transcript levels of cathepsin B nor those of the natural inhibitors, cystatin B and C, were altered by the interaction of melanoma cells with collagen type I. However, protein expression and cellular localization of cathepsin B and its inhibitors were markedly affected. In contrast to low‐invasive cells, high‐invasive cells constitutively released procathepsin B when cultured on plastic. In addition, contact of invasive cells with fibrillar collagen type I resulted in the release of both mature forms of the protease. Perturbation studies using inhibitory antibodies against the β1 subunit of the integrin receptor indicated a role for the β1 integrin receptor family in the regulation of cathepsin B release. Cystatin B protein expression was much lower in high‐invasive cells in both culture conditions, when compared to low‐invasive cells. Cystatin C expression was comparable in all cells, but cell contact to fibrillar collagen type I induced its expression. These results strongly implicate a pivotal role of cell–matrix interactions for the regulation of cathepsin B localization and activity in melanoma cells. © 2005 Wiley‐Liss, Inc.
BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non‐mucinous colorectal cancer
Authors: Tanaka Hirofumi , Deng Guoren , Matsuzaki Koji , Kakar Sanjay , Kim Grace E. , Miura Soichiro , Sleisenger Marvin H. , Kim Young S. 
Published: December 2005

AbstractMucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non‐mucinous CRC are not known. Activating mutations of BRAF and KRAS and their relationship with MSI and CIMP were examined in 83 sporadic CRC specimens (26 mucinous and 57 non‐mucinous CRC). MSI, CIMP, BRAF and KRAS mutation were observed in 17, 24, 25 and 36% of the tumors, respectively. BRAF mutation was highly correlated with MSI (p < 0.001) and CIMP (p < 0.001). A higher incidence of MSI (27% vs. 12%), CIMP (38% vs. 18%, p < 0.05) and BRAF mutation (46% vs. 16%, p < 0.01) was observed in mucinous CRC. KRAS mutation (27% vs. 40%) was observed more frequently in non‐mucinous CRC. Significantly higher percentages of mucinous CRC (54%, p < 0.05) had MSI or CIMP or BRAF mutations. Concordant occurrence of 2 or more of these alterations was observed in 39% of mucinous CRC and only 11% of non‐mucinous CRC (p < 0.01). The more frequent occurrence and closer association among MSI, CIMP and BRAF mutation in mucinous CRC observed in our study further supports the idea that its pathogenesis may involve distinct genetic and epigenetic changes. © 2005 Wiley‐Liss, Inc.
Cancer risk among Finnish food industry workers
Authors: Laakkonen Aarne , Kauppinen Timo , Pukkala Eero 
Published: December 2005

AbstractOccupational cancer risks suggested among food industry workers are inconclusive. The objective of our study was to assess associations between different cancers and working in the food industry in Finland. The carcinogenic exposures are mainly inhalatory, and we were therefore interested in respiratory cancers in particular. We followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person‐years during 1971–95. The 1970 Census data on occupations were linked with data on subsequent incident cancer cases. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated for each occupation using the economically active population as the reference. A total of 2,526 incident cancer cases were observed. Elevated risks were observed among male food industry workers for pancreatic (SIR = 1.50, CI = 1.13–1.96) and kidney cancers (1.51, 1.16–1.94). With respect to specific occupations, there was an excess of lung cancer among female bakers (1.38, 1.01–1.85) and laryngeal cancer among male grain millers (2.60, 1.05–5.36). Occupational exposure is unlikely to be a major risk factor for cancer among Finnish workers employed in typical food industry occupations. © 2005 Wiley‐Liss, Inc.
Alcohol consumption and mammographic density in a multiethnic population
Authors: Maskarinec Gertraud , Takata Yumie , Pagano Ian , Lurie Galina , Wilkens Lynne R. , Kolonel Laurence N. 
Published: December 2005

AbstractThis report examined the association between alcohol intake and breast cancer risk as assessed by mammographic densities in a multiethnic population. Information for this analysis was available from 2 previous investigations: a nutritional intervention study (The Breast, Estrogens, and Nutrition Study; BEAN) with 217 premenopausal women and a nested case‐control study within The Multiethnic Cohort (MEC) with 1,250 primarily postmenopausal women. On the basis of self‐reported alcohol intake from a validated food frequency questionnaire, women were categorized into abstainers (<1 drink/month), low (<1 drink/day) and high (≥1 drink/day) alcohol consumers. On average, 3 mammograms were available per woman. Using mixed models, we calculated mean percent densities for each alcohol consumption category while adjusting for covariates. Mean alcohol intakes for women in the BEAN study and for cases and controls in the MEC study were 2.0, 2.7 and 1.8 drinks/week, respectively. Overall, the difference in densities between abstainers and the highest alcohol intake category was only 1–2% and the differences were not statistically significant. However, the difference was 3–5% for women aged 55–65 years and for breast cancer cases. In postmenopausal women without hormone replacement therapy (HRT), breast density increased by 2% for each higher alcohol intake category. Breast densities were also elevated for high alcohol consumers on estrogen‐only therapy as compared to abstainers and low consumers, whereas combined HRT use was associated with higher mammographic densities independent of alcohol use. In conclusion, despite the low alcohol intake in our population, alcohol consumers had higher percent breast densities than did abstainers. The larger difference in some subgroups suggests that women with certain characteristics may be more susceptible to the influence of alcohol on breast density than others. © 2005 Wiley‐Liss, Inc.
Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival
Authors: Yeh Yao‐Tsung , Hou Ming‐Feng , Chung Yueh‐Fang , Chen Yi‐Jiun , Yang Sheau‐Fang , Chen Da‐Chung , Su Jinu‐Huang , Yuan Shyng‐Shiou F. 
Published: December 2005

AbstractPhosphorylation/activation of c‐jun NH2‐terminal kinase (JNK) has an ambivalent role, pro‐proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p‐JNK) in breast cancer is mostly undefined. In this study, we analyzed the expression of p‐JNK, as well as p‐ERK1/2 and p‐38, in the pair of cancer and noncancer breast tissues, by using immunoblotting techniques. These results were further correlated with the clinicopathological characteristics and overall survival. Decreased p‐JNK1/2 expression in cancer tissues was observed in 48.5% of breast infiltrating ductal carcinoma (IDC) cases and was correlated significantly with the increased tumor grade and the decreased age at diagnosis (p = 0.030 and 0.029). Interestingly, the Kaplan–Meier survival curve showed that the decreased p‐JNK1/2 expression was associated with a better overall survival of IDC (p = 0.004). The expression of p‐JNK1/2 was positively correlated with p‐p38 (p = 0.002), but not p‐ERK1/2. Furthermore, co‐expressed p‐JNK1/2 and p‐p38 was associated with a poor overall survival of IDC (p = 0.007). In conclusion, our results indicate that the aberrant p‐JNK1/2 expression and the co‐expressed p‐JNK1/2 and p‐p38 in breast tissues may play a role in the carcinogenesis of breast IDC. © 2005 Wiley‐Liss, Inc.
CYP17 MspA1 polymorphism and risk of biliary tract cancers and gallstones: A population‐based study in Shanghai, China
Authors: Hou Lifang , Xu Jianfeng , Gao Yu‐Tang , Rashid Asif , Zheng Síqun Lilly , Sakoda Lori C. , Shen Ming‐Chang , Wang Bing‐Sheng , Deng Jie , Han Tian‐Quan , Zhang Bai‐He , Meyers Deborah A. , Fraumeni Joseph F. , Hsing Ann W. 
Published: December 2005

AbstractBiliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile duct and ampulla of Vater, are rare but highly fatal malignancies. Other than gallstones, little is known about the risk factors for biliary tract cancers. Endogenous estrogens are thought to play a role in the etiology of gallstones and gallbladder cancer, since both conditions predominate in females and are associated with parity and obesity. In view of reports linking the CYP17 MspA1 polymorphism to high circulating levels of estrogens and a predisposition to other hormonally related cancers, we examined the relationship between CYP17 MspA1 variants and risk of biliary disease in a population‐based case‐control study in Shanghai. The study included 446 cancer cases (254 gallbladder, 139 extrahepatic bile duct, 53 ampullary cancers), 929 biliary stone cases (691 gallbladder, 238 bile duct) and 818 population controls. Genomic DNA from peripheral blood lymphocytes was used for genotyping. Relative to those with the A2/A2 genotype, A1 carriers (A1/A1 and A1/A2 genotypes) had an increased risk of gallbladder cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1–2.1). In addition, women with the A1 allele and high parity (≥3) had a 3‐fold risk of gallbladder cancer (OR = 3.3, 95% CI = 1.6–6.9), compared to those with the A2/A2 genotype and lower parity, with the highest risk seen for those also having biliary stones (OR = 4.6, 95% CI = 1.8–11.7, Pinteraction = 0.04). The A1 allele was not associated with a higher risk of gallstones except among those with body mass index (BMI) greater than 25 kg/m2 (OR = 3.1, 95% CI = 2.0–4.8, Pinteraction = 0.02) and among those with a history of diabetes (OR = 2.5, 95% CI = 1.4–4.3, Pinteraction = 0.09). No clear relation was seen between the CYP17 polymorphism and cancers of the bile duct or ampulla of Vater. The association of the CYP17 MspA1 polymorphism with an increased risk of gallbladder cancer, as well as biliary stones among overweight and diabetic individuals, suggests an interplay between genetic and hormonal risk factors in gallbladder disease. © 2005 Wiley‐Liss, Inc.
Monitoring of disseminated tumor cells in bone marrow in high‐risk breast cancer patients treated with high‐dose chemotherapy
Authors: Drageset Vilde , Nesland Jahn M. , Erikstein Bjorn , Skovlund Eva , Sommer Hilde , Anker Gun , Wist Erik , Lundgren Steinar , Bergh Jonas , Kvalheim Gunnar 
Published: December 2005

AbstractThe present study aimed to investigate the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients before and after high‐dose adjuvant chemotherapy with or without progenitor stem‐cell support. One hundred and eighteen high‐risk stage II breast cancer patients entering the Scandinavian Study Group multicenter trial were randomized to 9 cycles of tailored and dose‐escalated FEC (5‐flurouracil, epirubicin, cyclophosphamide) or 3 cycles of standard FEC followed by high‐dose chemotherapy. Bone marrow (BM) samples at diagnosis and 6 months after completion of chemotherapy were assessed for the presence of cytokeratin positive (CK+) cells. Before treatment, 29% of the patients were CK+ (21% in the dose‐escalated group and 36% in the high‐dose‐group). Six months after treatment, 17% of the patients were CK+ (17 and 16% respectively). Of the 95 patients who were evaluated 6 months after treatment, 60% were consistently CK−. CK+ cells in BM was evaluated as a prognostic and predictive marker and compared to other defined prognostic factors of the primary tumor. Monitoring BM changes at the time of diagnosis and 6 months posttreatment is an independent predictive factor for breast‐cancer‐specific survival (BCS) (p = 0.001). Those who have consistent CK negative (−) BM findings constitute a group of patients with good prognosis. Our results suggest that changes in CK+ cells in BM before and after chemotherapy can be used clinically as a surrogate maker to predict outcome in breast cancer patients. © 2005 Wiley‐Liss, Inc.
Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers
Authors: Jung Barbara , Smith E. Julieta , Doctolero Ryan T. , Gervaz Pascal , Alonso Julio C. , Miyai Katsumi , Keku Temitope , Sandler Robert S. , Carethers John M. 
Published: December 2005

AbstractHigh‐frequency microsatellite unstable (MSI‐H) colon tumors develop as a consequence of mutations at repetitive sequences in target genes. TGFBR2 and ACVR2, encoding TGFβ superfamily receptors, and the proapoptotic gene BAX are frequent targets for frameshift mutation. We analyzed the effect of these mutations on survival and histology in 2 separate cohorts. Forty‐eight MSI‐H Dukes B2 colon tumors from a cohort of 172 patients had mutations in TGFBR2, BAX and ACVR2 correlated with patient survival. Further, 54 population‐based MSI‐H colon cancers of all stages from a cohort of 503 patients had mutations correlated with tumor stage, grade and size. Of 44 amplifiable MSI‐H Dukes B2 tumors, 70% harbored TGFBR2, 63% BAX and only 4.5% ACVR2 mutations. While mutation alone did not influence survival, concomitant mutation of TGFBR2 and BAX was associated with an improved prognosis in Dukes B2 patients (p = 0.05). ACVR2 mutations were more frequent in the second, population‐based cohort (stage II: 32.5%, p < 0.05). While no target gene mutation correlated with stage in this cohort, poor histological grade and large tumor volume were associated with mutant ACVR2, but not TGFBR2 or BAX mutations, and likely accounts for the lower prevalence of ACVR2 mutations in the first, well‐differentiated Dukes B2 cohort. Because target gene mutations did not correlate with stage, they likely occur early in the pathogenesis of MSI‐H cancers. Mutations in TGFBR2 and BAX may improve survival in MSI‐H Dukes B2 patients, and mutations of ACVR2 may augment histological changes consistent with poor tumor grade that is characteristic of MSI‐H colon cancers, and increase tumor size. © 2005 Wiley‐Liss, Inc.
Cancer incidence in a cohort of Ontario and Quebec women having bilateral breast augmentation
Authors: Brisson Jacques , Holowaty Eric J. , Villeneuve Paul J. , Xie Lin , Ugnat Anne‐Marie , Latulippe Louis , Mao Yang 
Published: December 2005

AbstractThe possibility that women, who receive breast implants for cosmetic purposes, have increased long‐term risks of developing cancer continues to be debated. The objective of our study was to prospectively examine cancer incidence among women who received breast implants. A cohort was assembled of 24,558 women, 18 years of age and older, who underwent bilateral cosmetic breast augmentation, and 15,893 women who underwent other cosmetic procedures in Ontario or Quebec between 1974 and 1989. These plastic surgery patients were selected from the same clinics as the implant population. Incident cancers were identified by linking to Canadian registry data up to December 31, 1997. In total, 676 cancers were identified among women who received breast implants compared to 899 expected based on general population rates (standardized incidence ratio (SIR) = 0.75; 95% confidence interval (CI) = 0.70–0.81). Overall cancer incidence rates among women who received breast implants were similar to that of the other plastic surgery patients (relative risk (RR) = 0.91, 95% CI = 0.81–1.02). However, women who received breast implants had lower breast cancer rates than the plastic surgery patients (RR = 0.64, 95% CI = 0.53–0.79). No increased risks were observed among the implant population for any of the other cancer sites examined. Comparisons involving only women who received breast implants found no association between long‐term breast cancer incidence and implant site (submuscular vs. subglandular), fill (saline vs. silicone) or envelope (polyurethane‐coated or not). In conclusion, women undergoing cosmetic breast augmentation do not appear to be at an increased long‐term risk of developing cancer. © 2005 Wiley‐Liss, Inc.