bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-Mediated Blockade of Integrin αvβ6 Inhibits Tumor Progression In vivo by a Transforming Growth Factor-β–Regulated Mechanism
Authors: Koopman Van Aarsen Louise A. , Leone Diane R. , Ho Steffan , Dolinski Brian M. , McCoon Patricia E. , LePage Doreen J. , Kelly Rebecca , Heaney Glenna , Rayhorn Paul , Reid Carl , Simon Kenneth J. , Horan Gerald S. , Tao Nianjun , Gardner Humphrey A. , Skelly Marilyn M. , Gown Allen M. , Thomas Gareth J. , Weinreb Paul H. , Fawell Stephen E. , Violette Shelia M. 
Published: January 2008

Abstract
The αvβ6 integrin is up-regulated on epithelial malignancies and has been implicated in various aspects of cancer progression. Immunohistochemical analysis of αvβ6 expression in 10 human tumor types showed increased expression relative to normal tissues. Squamous carcinomas of the cervix, skin, esophagus, and head and neck exhibited the highest frequency of expression, with positive immunostaining in 92% (n = 46), 84% (n = 49), 68% (n = 56), and 64% (n = 100) of cases, respectively. We studied the role of αvβ6 in Detroit 562 human pharyngeal carcinoma cells in vitro and in vivo. Prominent αvβ6 expression was detected on tumor xenografts at the tumor-stroma interface resembling the expression on human head and neck carcinomas. Nonetheless, coculturing cells in vitro with matrix proteins did not up-regulate αvβ6 expression. Detroit 562 cells showed αvβ6-dependent adhesion and activation of transforming growth factor-β (TGF-β) that was inhibited &gt;90% with an αvβ6 blocking antibody, 6.3G9. Although both recombinant soluble TGF-β receptor type-II (rsTGF-βRII-Fc) and 6.3G9 inhibited TGF-β–mediated Smad2/3 phosphorylation in vitro, there was no effect on proliferation. Conversely, in vivo, 6.3G9 and rsTGF-βRII-Fc inhibited xenograft tumor growth by 50% (n = 10, P &lt; 0.05) and &gt;90% (n = 10, P &lt; 0.001), respectively, suggesting a role for the microenvironment in this response. However, stromal collagen and smooth muscle actin content in xenograft sections were unchanged with treatments. Although further studies are required to consolidate in vitro and in vivo results and define the mechanisms of tumor inhibition by αvβ6 antibodies, our findings support a role for αvβ6 in human cancer and underscore the therapeutic potential of function blocking αvβ6 antibodies. [Cancer Res 2008;68(2):561–70]
MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN
Authors: Yang Hua , Kong William , He Lili , Zhao Jian-Jun , O'Donnell Joshua D. , Wang Jiawang , Wenham Robert M. , Coppola Domenico , Kruk Patricia A. , Nicosia Santo V. , Cheng Jin Q. 
Published: January 2008

Abstract
MicroRNAs (miRNA) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. However, aberrant miRNA expression and its clinicopathologic significance in human ovarian cancer have not been well documented. Here, we show that several miRNAs are altered in human ovarian cancer, with the most significantly deregulated miRNAs being miR-214, miR-199a*, miR-200a, miR-100, miR-125b, and let-7 cluster. Further, we show the frequent deregulation of miR-214, miR-199a*, miR-200a, and miR-100 in ovarian cancers. Significantly, miR-214 induces cell survival and cisplatin resistance through targeting the 3′-untranslated region (UTR) of the PTEN, which leads to down-regulation of PTEN protein and activation of Akt pathway. Inhibition of Akt using Akt inhibitor, API-2/triciribine, or introduction of PTEN cDNA lacking 3′-UTR largely abrogates miR-214–induced cell survival. These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway. [Cancer Res 2008;68(2):425–33]
CSN5 Isopeptidase Activity Links COP9 Signalosome Activation to Breast Cancer Progression
Authors: Adler Adam S. , Littlepage Laurie E. , Lin Meihong , Kawahara Tiara L.A. , Wong David J. , Werb Zena , Chang Howard Y. 
Published: January 2008

Abstract
CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here, we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. [Cancer Res 2008;68(2):506–15]
The Transcriptional Repressor ZEB1 Promotes Metastasis and Loss of Cell Polarity in Cancer
Authors: Spaderna Simone , Schmalhofer Otto , Wahlbuhl Mandy , Dimmler Arno , Bauer Katja , Sultan Aneesa , Hlubek Falk , Jung Andreas , Strand Dennis , Eger Andreas , Kirchner Thomas , Behrens Jürgen , Brabletz Thomas 
Published: January 2008

Abstract
Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program “epithelial-mesenchymal transition” (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression. [Cancer Res 2008;68(2):537–44]
Equol Status Modifies the Association of Soy Intake and Mammographic Density in a Sample of Postmenopausal Women
Authors: Fuhrman Barbara J. , Teter Barbara E. , Barba Maddalena , Byrne Celia , Cavalleri Adalberto , Grant Brydon J. , Horvath Peter J. , Morelli Daniele , Venturelli Elisabetta , Muti Paola C. 
Published: January 2008

Abstract
Only 30% to 50% of people produce the daidzein-metabolite equol after eating soy. We conducted a cross-sectional study of the associations between equol status, intake of soy foods, and mammographic density in a sample of postmenopausal women recruited at a radiology clinic near Buffalo, New York. Participants were 48 to 82 years old, had no history of cancer or breast reduction/augmentation, and no recent use of antibiotics or hormones. Percent density was measured by computer-assisted analysis of digitized images of craniocaudal films. Equol status was assessed using a soy-challenge protocol and usual soy intake by questionnaire. General linear models were used to assess independent and joint effects of equol status and intake of soy on multivariate adjusted percent density (covariates included age, body mass index, parity, age at first birth, and ever use of combined hormone therapy). Of 325 enrolled, 232 (71%) participants completed study assessments and are included in the present analysis. Mean percent density was 34% (±18%). Seventy-five (30%) participants were producers of equol. Forty-three (19%) participants reported regularly eating &gt;1 soy food or supplement/wk. There were no significant independent associations of equol status or soy intake with percent density, but the interaction between these factors was significant (P &lt; 0.01). Among equol producers, those with weekly soy intake had lower percent density (30.7% in weekly consumers of soy versus 38.9% in others; P = 0.08); among nonproducers, weekly soy intake was associated with higher percent density (37.5% in weekly soy consumers versus 30.7% in others; P = 0.03). Results suggest that equol producers and nonproducers may experience different effects of dietary soy on breast tissue. (Cancer Epidemiol Biomarkers Prev 2008;17(1):33–42)
Cigarette Smoking, N-Acetyltransferase 2 Genotypes, and Breast Cancer Risk: Pooled Analysis and Meta-analysis
Authors: Ambrosone Christine B. , Kropp Silke , Yang Jun , Yao Song , Shields Peter G. , Chang-Claude Jenny 
Published: January 2008

Abstract
Approximately 10 years ago, it was noted that smoking increased risk of breast cancer among women with N-acetyltransferase 2 (NAT2) slow acetylation genotypes. This report was followed by a number of studies to address this question. We pooled data from 10 existing studies and also conducted a meta-analysis of 13 studies published from 1996 to October 2006 that were conducted among women, were published in English, and had adequate information on smoking and NAT2 genotyping. Raw data were requested from authors. Unconditional logistic regression was done for pooled analysis, and random effect models was done for meta-analysis. Study heterogeneity was assessed, and sensitivity tests were done when subgroups were excluded from the analysis. In the pooled analysis, there was a significant interaction between smoking, NAT2 genotype, and risk of breast cancer [pack-years (continuous variable, Pinteraction = 0.03)], with higher pack-years significantly associated with an increased risk of breast cancer among women with NAT2 slow genotypes (pooled analysis relative risk, 1.49; 95% confidence interval, 1.08-2.04). These findings were supported by the meta-analysis including all studies; pack-years were significantly associated with risk among slow acetylators in a dose-dependent fashion (meta-analysis relative risk, 1.44; 95% confidence interval, 1.23-1.68 for ≥20 pack-years versus never smokers), but not among rapid acetylators. Similar relationships were noted for smoking status (ever, never) and duration of smoking. Our results show that cigarette smoking is associated with an increase in breast cancer risk among women with NAT2 slow acetylation genotypes. Because slow NAT2 genotypes are present in 50% to 60% of Caucasian populations, smoking is likely to play an important role in breast cancer etiology. (Cancer Epidemiol Biomarkers Prev 2008;17(1):15–26)
Body Mass and Physical Activity and Risk of Gastric Cancer in a Population-Based Cohort Study in Norway
Authors: Sjödahl Krister , Jia Chongqi , Vatten Lars , Nilsen Tom , Hveem Kristian , Lagergren Jesper 
Published: January 2008

Abstract
There is a relation between excess body mass index and overall cancer incidence and mortality, but the relation to noncardia gastric cancer is inconsistent. A high physical activity level decreases the risk of several cancers, but few studies have focused on gastric cancer. We conducted a population-based, prospective cohort study in Nord-Trondelag county in Norway. During 1984 to 1986, all adult residents were invited to participate in a health survey, where body height and weight were measured, and frequency, duration, and intensity of recreational physical activity, together with potential confounding factors, were assessed by questionnaires. New gastric cancers occurring during follow-up in 1984 to 2002 were identified by linkage to the Cancer Registry of Norway. Cox proportional hazards regression models were used to calculate hazard ratios with 95% confidence intervals, adjusted for age, sex, occupation, salt intake, smoking, and alcohol drinking. Follow-up of 73,133 cohort members (88% of all inhabitants) revealed 313 gastric cancers, including 264 noncardia cancers. No statistically significant associations were revealed between different levels of body mass index and risk of noncardia gastric cancer. A statistically significant 50% risk reduction among persons reporting at least a moderate level of recreational physical activity, based on a summary score of physical activity (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9), and a dose-response relation was indicated (P for trend = 0.01). It is concluded that recreational physical activity might have a protective effect against gastric cancer. The sedentary lifestyle gaining ground in western societies might counteract the ongoing decrease in incidence of gastric cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(1):135–40)
Recreational Physical Activity and Cancer Risk in Subsites of the Colon (the Nord-Trøndelag Health Study)
Authors: Nilsen Tom I.L. , Romundstad Pål R. , Petersen Hermod , Gunnell David , Vatten Lars J. 
Published: January 2008

AbstractPhysical activity may reduce colon cancer risk, but the underlying mechanisms remain unclear. Relating physical activity to cancer risk in anatomic segments of the colon may advance our understanding of possible mechanisms. We conducted a prospective study of 59,369 Norwegian men and women who were followed up for cancer incidence and mortality. Cox proportional hazards models were used to estimate multivariably adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). All statistical tests were two sided. During 17 years of follow-up, 736 colon cancers and 294 rectal cancers were diagnosed. Overall, we found an inverse association between recreational physical activity and colon cancer risk, but subsite analyses showed that the association was confined to cancer in the transverse and sigmoid colon. The adjusted HR, comparing people who reported high versus no physical activity, was 0.44 (95% CI, 0.25-0.78) for cancer in the transverse colon and 0.48 (95% CI, 0.31-0.75) for cancer in the sigmoid colon. The corresponding HR for cancer mortality was 0.33 (95% CI, 0.14-0.76) for the transverse colon and 0.29 (95% CI, 0.15-0.56) for the sigmoid colon. For rectal cancer, there was no association with physical activity in these data. In conclusion, the inverse association of recreational physical activity with cancer risk and mortality in the transverse and sigmoid segments of the colon may point at increased colon motility and reduced fecal transit time as possible underlying mechanisms. (Cancer Epidemiol Biomarkers Prev 2008;17(1):183–8)
Relationship between Histamine2-Receptor Antagonist Medications and Risk of Invasive Breast Cancer
Authors: Mathes Robert W. , Malone Kathleen E. , Daling Janet R. , Porter Peggy L. , Li Christopher I. 
Published: January 2008

Abstract
Background: Histamine2-receptor antagonist (H2 blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H2 blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H2 blockers is a potential breast cancer risk factor. The few previous studies evaluating this association have been null but have been limited by small sample sizes, and none have evaluated risk by either histologic type or estrogen receptor/progesterone receptor status.
Methods: Combining data from two population-based case-control studies conducted in western Washington, we assessed the relationship between use of H2 blockers and risk of different types of breast cancer among 1,941 cases and 1,476 controls 55 to 79 years old. Odds ratios and 95% confidence intervals (95% CI) were calculated using polytomous logistic regression.
Results: Current use of H2 blockers overall, cimetidine, and famotidine was not associated with an increased risk of either invasive ductal or invasive lobular breast cancer. Current users of ranitidine had a 2.2-fold (95% CI, 1.1-4.3) increased risk of ductal carcinoma that was confined to a 2.4-fold (95% CI, 1.2-4.9) increased risk of estrogen receptor–positive/progesterone receptor–positive ductal carcinoma.
Conclusions: Use of H2 blockers in general is not associated with an increased risk of breast cancer, although current use of ranitidine may increase risk of hormone receptor–positive ductal carcinoma. Further studies to confirm this finding are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(1):67–72)
Nocturnal Low-Level-Jet-Dominated Atmospheric Boundary Layer Observed by a Doppler Lidar over Oklahoma City during JU2003
Authors: Wang Yansen , Klipp Cheryl L. , Garvey Dennis M. , Ligon David A. , Williamson Chatt C. , Chang Sam S. , Newsom Rob K. , Calhoun Ronald 
Published: January 2008

Abstract
Boundary layer wind data observed by a Doppler lidar and sonic anemometers during the mornings of three intensive observational periods (IOP2, IOP3, and IOP7) of the Joint Urban 2003 (JU2003) field experiment are analyzed to extract the mean and turbulent characteristics of airflow over Oklahoma City, Oklahoma. A strong nocturnal low-level jet (LLJ) dominated the flow in the boundary layer over the measurement domain from midnight to the morning hours. Lidar scans through the LLJ taken after sunrise indicate that the LLJ elevation shows a gradual increase of 25–100 m over the urban area relative to that over the upstream suburban area. The mean wind speed beneath the jet over the urban area is about 10%–15% slower than that over the suburban area. Sonic anemometer observations combined with Doppler lidar observations in the urban and suburban areas are also analyzed to investigate the boundary layer turbulence production in the LLJ-dominated atmospheric boundary layer. The turbulence kinetic energy was higher over the urban domain mainly because of the shear production of building surfaces and building wakes. Direct transport of turbulent momentum flux from the LLJ to the urban street level was very small because of the relatively high elevation of the jet. However, since the LLJ dominated the mean wind in the boundary layer, the turbulence kinetic energy in the urban domain is correlated directly with the LLJ maximum speed and inversely with its height. The results indicate that the jet Richardson number is a reasonably good indicator for turbulent kinetic energy over the urban domain in the LLJ-dominated atmospheric boundary layer.
Genetic variation and recombination of RdRp and HSP 70h genes of Citrus tristeza virus isolates from orange trees showing symptoms of citrus sudden death disease
Authors: Gomes Clarissa PC , Nagata Tatsuya , de Jesus Waldir C , Neto Carlos R Borges , Pappas Georgios J , Martin Darren P 
Published: January 2008

Abstract

Background
Citrus sudden death (CSD), a disease that rapidly kills orange trees, is an emerging threat to the Brazilian citrus industry. Although the causal agent of CSD has not been definitively determined, based on the disease's distribution and symptomatology it is suspected that the agent may be a new strain of Citrus tristeza virus (CTV). CTV genetic variation was therefore assessed in two Brazilian orange trees displaying CSD symptoms and a third with more conventional CTV symptoms.

Results
A total of 286 RNA-dependent-RNA polymerase (RdRp) and 284 heat shock protein 70 homolog (HSP70h) gene fragments were determined for CTV variants infecting the three trees. It was discovered that, despite differences in symptomatology, the trees were all apparently coinfected with similar populations of divergent CTV variants. While mixed CTV infections are common, the genetic distance between the most divergent population members observed (24.1% for RdRp and 11.0% for HSP70h) was far greater than that in previously described mixed infections. Recombinants of five distinct RdRp lineages and three distinct HSP70h lineages were easily detectable but respectively accounted for only 5.9 and 11.9% of the RdRp and HSP70h gene fragments analysed and there was no evidence of an association between particular recombinant mosaics and CSD. Also, comparisons of CTV population structures indicated that the two most similar CTV populations were those of one of the trees with CSD and the tree without CSD.

Conclusion
We suggest that if CTV is the causal agent of CSD, it is most likely a subtle feature of population structures within mixed infections and not merely the presence (or absence) of a single CTV variant within these populations that triggers the disease.
Selective Loss of Somatostatin Receptor 2 in Octreotide-Resistant Growth Hormone-Secreting Adenomas
Authors: Plöckinger Ursula , Albrecht Susann , Mawrin Christian , Saeger Wolfgang , Buchfelder Michael , Petersenn Stephan , Schulz Stefan 
Published: January 2008

Abstract
Objective: The somatostatin analog octreotide preferentially binds to somatostatin receptor (sst) 2A and to a lesser extent to sst5. Although sst2A and sst5 mRNAs are consistently expressed in GH-secreting adenomas, octreotide controls GH secretion only in 65% of acromegalic patients. Hence, we investigated the immunocytochemical expression of sst in a large group of somatotroph tumors.
Methods: Acromegalic patients, cared for in a university referral center, were either operated on without pretreatment (group A, n = 14) or pretreated with octreotide [median (minimum-maximum): dose 1250 (300–1500) μg/d for 5.6 (3–9) months] before surgery (group B, n = 20). In group B octreotide reduced GH secretion by more than 50% in 14 patients (70%) (GH responders). Six patients with less than 50% GH suppression were considered GH nonresponders. We used a panel of extensively characterized antibodies to determine the immunocytochemical sst status in somatotroph adenomas and compared their expression between the groups.
Results: All group A tumors demonstrated immunoreactive sst2A, and all but one had sst5. A similar pattern was found in the GH responders of group B. In contrast, none of the GH nonresponders exhibited detectable sst2A (sst2A: GH responders vs. GH nonresponders, P &lt; 0.0001), whereas sst5 was found in 70%. sst1 and sst3 were detected in 85 and 24% of all cases, independent of previous octreotide treatment.
Conclusions: Our findings suggest that octreotide resistance in GH-secreting adenomas occurs due to a selective loss of sst2A. The persistent expression of sst1 and sst5 receptors suggests that these tumors are potential targets for pan-somatostatin analogs.