bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leisure‐time physical activity patterns and risk of colon cancer in women
Authors: Wolin Kathleen Y. , Lee I‐Min , Colditz Graham A. , Glynn Robert J. , Fuchs Charles , Giovannucci Edward 
Published: August 2007

AbstractAlthough physical activity has been consistently associated with lower risk of colon cancer, many details of the relationship remain unclear. We assessed the relation between physical activity and risk of colon cancer in 79,295 women aged 40–65 who were free of cancer, ulcerative colitis and Crohn's disease and who reported their leisure‐time physical activity in 1986; 547 cases were identified through 2002. Women who expended more than 21.5 metabolic equivalent hr/week of physical activity had a relative risk (RR) of colon cancer of 0.77 (95% CI 0.58–1.01), compared to women who expended <2 metabolic equivalent hr/week. The association was stronger for distal than proximal tumors. Among women whose only reported activity was walking, there was a decreased risk of colon cancer in women walking 1–1.9 hr/week (RR = 0.69, 95% CI 0.47–1.03) compared to those who did not walk. Results were similar for increased amounts of walking, but there was no evidence of a dose response relation. Among women who participated in moderate or vigorous activity, increasing hours of activity were also associated with a decreased risk of colon cancer (p for trend = 0.01); women exercising >4 hr/week had a 40% lower risk of colon cancer than those exercising <1 hr/week (RR = 0.56, 95%CI 0.33–0.94). Long‐term physical activity was not associated with risk of colon cancer, but the number of cases was small. A significant inverse association exists between physical activity, including that of moderate intensity, such as walking, and risk of colon cancer in women that is more pronounced for distal tumors. © 2007 Wiley‐Liss, Inc.
High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease
Authors: Gravitt Patti E. , Kovacic Melinda Butsch , Herrero Rolando , Schiffman Mark , Bratti Concepcion , Hildesheim Allan , Morales Jorge , Alfaro Mario , Sherman Mark E. , Wacholder Sholom , Rodriguez Ana‐Cecilia , Burk Robert D. 
Published: August 2007

AbstractCervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high‐grade cervical intraepithelial neoplasia or cancer (≥CIN2). To examine disease association with type‐specific viral load for the full‐range of anogenital HPV infections, we conducted cross‐sectional and prospective analyses of ∼2,000 HPV‐infected women from a 10,000‐woman population‐based study in Guanacaste, Costa Rica with 7 years of follow‐up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type‐specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent ≥CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4–83.2) and single non‐16 carcinogenic infections (OR = 9.2, 95% CI = 2.1–39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow‐up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5–213.5) had a strong association between high viral load and incident ≥CIN2; non‐16 carcinogenic high viral load was not associated with incident ≥CIN2 (OR = 0.7, 95% CI = 0.2–1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident ≥CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent ≥CIN2; however HPV16 was uniquely associated with incident ≥CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type‐specific differences observed for incident ≥CIN2. © 2007 Wiley‐Liss, Inc.
Trends in cervical cancer mortality in korea 1993–2002: Corrected mortality using national death certification data and national cancer incidence data
Authors: Shin Hai‐Rim , Park Sohee , Hwang Soon‐Young , Kim Jung‐Eun , Jung Kyu‐Won , Won Young‐Joo , Hwang Seung‐Sik , Yim Seon‐Hee , Choi Kui Son , Park Eun‐Cheol , Park Sang‐Yoon , Kim Jae Weon , Lee Hyo‐Pyo 
Published: August 2007

AbstractCervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993–2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered “uterus, unspecified” deaths previously registered as “cervix, uterine” cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age‐specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age‐standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): −4.05%, 95% CI: −4.88, −3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30–69 years, it increased substantially in women aged ≥70 years (EAPC: 3.62%, 95% CI: 1.92–5.35). Results of this study will provide evidence‐based foundation for the evaluation of the existing cervical cancer‐screening programs. © 2007 Wiley‐Liss, Inc.
Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis
Authors: Lin Jian‐feng , Xu Jun , Tian Hong‐yu , Gao Xia , Chen Qing‐xi , Gu Qi , Xu Gen‐jun , Song Jian‐da , Zhao Fu‐kun 
Published: August 2007

AbstractAlthough serum prostate specific antigen (PSA) is a well‐established diagnostic tool for prostate cancer (PCa) detection, the definitive diagnosis of PCa is based on the information contained in prostate needle biopsy (PNBX) specimens. To define the proteomic features of PNBX specimens to identify candidate biomarkers for PCa, PNBX specimens from patients with PCa or benign prostatic hyperplasia (BPH) were subjected to comparative proteomic analysis. 2‐DE revealed that 52 protein spots exhibited statistically significantly changes among PCa and BPH groups. Interesting spots were identified by MALDI‐TOF‐MS/MS. The 2 most notable groups of proteins identified included latent androgen receptor coregulators [FLNA(7–15) and FKBP4] and enzymes involved in mitochondrial fatty acid β‐oxidation (DCI and ECHS1). An imbalance in the expression of peroxiredoxin subtypes was noted in PCa specimens. Furthermore, different post‐translationally modified isoforms of HSP27 and HSP70.1 were identified. Importantly, changes in FLNA(7–15), FKBP4, and PRDX4 expression were confirmed by immunoblot analyses. Our results suggest that a proteomics‐based approach is useful for developing a more complete picture of the protein profile of PNBX specimen. The proteins identified by this approach may be useful molecular targets for PCa diagnostics and therapeutics. © 2007 Wiley‐Liss, Inc.
Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer
Authors: Merritt Melissa A. , Green Adèle C. , Nagle Christina M. , Webb Penelope M. ,   Australian Cancer Study (Ovarian Cancer) and Australian Ovarian Cancer Study Group
Published: August 2007

AbstractChronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia‐wide case–control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population‐based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01–1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03–1.44 and 1.18, 95% CI 0.81–1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti‐inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. © 2007 Wiley‐Liss, Inc.
Expression of RANTES and MCP‐1 in epithelial cells is regulated via LMP1 and CD40
Authors: Buettner Maike , Meyer Birgit , Schreck Sabine , Niedobitek Gerald 
Published: August 2007

AbstractEpstein‐Barr virus (EBV)‐associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B‐cells, the EBV‐encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF‐κB dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP‐1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF‐κB. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1‐negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP‐1 expression in LMP1‐negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP‐1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment. © 2007 Wiley‐Liss, Inc.
Risk of lung cancer following exposure to carbon black, titanium dioxide and talc: Results from two case–control studies in Montreal
Authors: Ramanakumar Agnihotram V. , Parent Marie‐Élise , Latreille Benoit , Siemiatycki Jack 
Published: August 2007

AbstractThe International Agency for Research on Cancer (IARC) recently evaluated the carcinogenicity of three poorly soluble weakly‐toxic substances: carbon black, titanium dioxide and talc. Though there is evidence of carcinogenity in experimental animals for these substances, the evidence in humans is sparse and equivocal. In the context of two large population based case–control studies of lung cancer carried out in Montreal, we were able to study the possible relationships between the exposure to each of these substances and subsequent risk of lung cancer. We were able to distinguish talc used for industrial purposes from that used for cosmetic purposes. Interviews for Study I were conducted in 1979–1986 (857 cases, 533 population controls, 1,349 cancer controls) and interviews for Study II were conducted in 1996–2001 (1,236 cases and 1,512 controls). Detailed lifetime job histories were elicited, and a team of hygienists and chemists evaluated the evidence of exposure to a host of occupational substances. Lung cancer risk was analysed in relation to each exposure, adjusting for several potential confounders, including smoking. Subjects with occupational exposure to carbon black, titanium dioxide, industrial talc and cosmetic talc did not experience any detectable excess risk of lung cancer. The results are consistent with the recent evaluations of the IARC Monographs. © 2007 Wiley‐Liss, Inc.
Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)
Authors: Kaufmann Andreas M. , Nieland John D. , Jochmus Ingrid , Baur Siegfried , Friese Klaus , Gabelsberger Joseph , Gieseking Friederike , Gissmann Lutz , Glasschröder Birgit , Grubert Thomas , Hillemanns Peter , Höpfl Reinhard , Ikenberg Hans , Schwarz Jörg , Karrasch Matthias , Knoll Anette , Küppers Volkmar , Lechmann Martin , Lelle Ralph J. , Meissner Harald , Müller Rainer T. , Pawlita Michael , Petry Karl Ulrich , Pilch Henryk , Walek Elke , Schneider Achim 
Published: August 2007

AbstractPersistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus‐like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus‐like particles (CVLP) consist of a carboxy‐terminally truncated HPV16L1 protein fused to the amino‐terminal part of the HPV16 E7 protein and self‐assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1‐ and E7‐specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo‐controlled clinical trial has been conducted in 39 HPV16 mono‐infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 μg or 250 μg) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty‐six percent of the responders were also HPV16 DNA‐negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. © 2007 Wiley‐Liss, Inc.
Gene silencing of transcription factor Gli2 inhibits basal cell carcinomalike tumor growth in vivo
Authors: Ji Jingmin , Kump Erwin , Wernli Marion , Erb Peter 
Published: August 2007

AbstractBasal cell carcinoma (BCC) belongs worldwide to the most frequent malignancy among Caucasians. The understanding of the molecular mechanisms of BCC formation, which is a prerequisite for the development of efficient new therapies, is still incomplete. The formation of sporadic BCCs in the skin is associated with uncontrolled hedgehog signaling, and the transcription factor Gli2 has been identified as a key mediator or effector of this signaling. There is indication in the literature that preventing Gli2 function may inhibit BCC formation and growth in vivo; however, the mechanism is unclear and difficult to study in humans. Therefore, we used a mouse tumor allograft model to investigate the role of Gli2 in tumor formation. A constitutively Gli2 expressing mouse tumor cell line was stably transfected with Gli2‐specific shRNA to induce Gli2 gene silencing or with control shRNA. Injecting the Gli2 gene silenced cells into nude mice for tumor formation we detected a strongly retarded tumor growth compared with control tumor cells. Investigating the mechanisms, we found that Gli2 gene silencing has led to the disruption of the tumor structure as demonstrated by staining tumor sections with hematoxylin. Two main reasons for the tumor destruction were identified. We found that apoptosis was markedly increased while vascularization was strongly decreased in these tumors. Thus, important functions of the transcription factor Gli2 in this tumor model are the prevention of apoptosis and the promotion of microvascularization. © 2007 Wiley‐Liss, Inc.
Comparison of nonbreast cancer incidence, survival and mortality between breast screening program participants and nonparticipants
Authors: Phillips Norm , Coldman Andrew 
Published: August 2007

AbstractComparisons of cancer mortality between users and nonusers of screening are potentially biased because of the effects of self‐selection. Previous studies of breast screening have found that individuals likely to participate have lower breast cancer mortality than those unlikely to participate. This study compares the incidence, survival and mortality for all cancer types other than breast between participants and nonparticipants in a service screening mammography program. British Columbian females having their first mammogram between the ages of 40 and 79 and the years 1988 and 2004 were identified as a cohort of “participants”. Person‐years of follow‐up of participants were aggregated by age and year. Nonparticipant person‐years were obtained by subtraction from the total female population. Cancer diagnoses other than breast were identified for participants and nonparticipants. Age, calendar year, and income adjusted relative risks of cancer incidence were estimated from generalized additive models with Poisson errors. Hazard ratios were estimated by Cox regression. Observed cancer mortality in participants was compared with expected mortality generated from nonparticipant incidence and survival rates. Incidence rates of cancer showed a mixed relationship with some elevated, some decreased and others similar to nonparticipant rates. Cancer survival was higher among participants for most cancer types, with an overall hazard ratio of 0.76 (0.73–0.79). Observed mortality in participants was less than expected for most cancers, with an overall mortality ratio of 0.60 (0.58–0.62). The general cancer experience of screening program participants is different from that of the general population. © 2007 Wiley‐Liss, Inc.
Role of high‐molecular weight tropomyosins in TGF‐β‐mediated control of cell motility
Authors: Zheng Qiao , Safina Alfiya , Bakin Andrei V. 
Published: August 2007

AbstractTransforming growth factor beta1 (TGF‐β1) suppresses tumor development at early stages of cancer, but enhances tumor invasion and formation of metastasis. TGF‐β1‐mediated tumor invasion is associated with epithelial to mesenchymal transition (EMT) and matrix proteolysis. The mechanisms of these TGF‐β1 responses in normal and tumor cells are not well understood. Recently, we have reported that TGF‐β1 increases expression of high‐molecular weight tropomyosins (HMW‐tropomyosins) and formation of actin stress fibers in normal epithelial cells. The present study investigated the role of tropomyosin in TGF‐β1‐mediated cell motility and invasion. We found that TGF‐β1 restricts motility of normal epithelial cells although it promotes EMT and formation of actin stress fibers and focal adhesions. Cell motility was enhanced by siRNA‐mediated suppression of HMW‐tropomyosins. TGF‐β1 stimulated migration and matrix proteolysis in breast cancer MDA‐MB‐231 cells that express low levels of HMW‐tropomyosins. Tet‐Off‐regulated expression of HMW‐tropomyosin inhibited cell migration and matrix proteolysis without affecting expression of matrix metalloproteinases. Tropomyosin increased cell adhesion to matrix by enhancing actin fibers and focal adhesions. Finally, tropomyosin impaired the ability of tumor cells to form lung metastases in SCID mice. Thus, these results suggest that HMW‐tropomyosins are important for TGF‐β‐mediated control of cell motility and acquisition of the metastatic potential. © 2007 Wiley‐Liss, Inc.
Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts
Authors: Bell Daphne W. , Kim Sang H. , Godwin Andrew K. , Schiripo Taryn A. , Harris Patricia L. , Haserlat Sara M. , Wahrer Doke C.R. , Haiman Christopher A. , Daly Mary B. , Niendorf Kristin B. , Smith Matthew R. , Sgroi Dennis C. , Garber Judy E. , Olopade Olufunmilayo I. , Marchand Loic Le , Henderson Brian E. , Altshuler David , Haber Daniel A. , Freedman Matthew L. 
Published: August 2007

AbstractThe CHEK2‐1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early‐onset disease; functionally characterized new variants and conducted a population‐based case–control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2‐H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2‐1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early‐onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2‐positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2‐P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low‐penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically‐ and geographically‐selected populations. © 2007 Wiley‐Liss, Inc.