bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Genetic Variants in Telomere Pathway Genes and Breast Cancer Risk
Authors: Shen Jing , Gammon Marilie D. , Wu Hui-Chen , Terry Mary Beth , Wang Qiao , Bradshaw Patrick T. , Teitelbaum Susan L. , Neugut Alfred I. , Santella Regina M. 
Published: January 2010

Abstract
Purpose: To explore the etiologic role of genetic variants in telomere pathway genes and breast cancer risk.
Methods: A population-based case-control study, the Long Island Breast Cancer Study Project, was conducted, and 1,067 cases and 1,110 controls were included in the present study. Fifty-two genetic variants of nine telomere-related genes were genotyped.
Results: Seven single nucleotide polymorphisms (SNP) showed significant case-control differences at the level of P &lt; 0.05. The top three statistically significant SNPs under a dominant model were TERT-07 (rs2736109), TERT-54 (rs3816659), and POT1-03 (rs33964002). The odds ratios (OR) were 1.56 [95% confidence interval (95% CI), 1.22-1.99] for the TERT-07 G-allele, 1.27 (95% CI, 1.05-1.52) for the TERT-54 T-allele, and 0.79 (95% CI, 0.67-0.95) for the POT1-03 A-allele. TERT-67 (rs2853669) was statistically significant under a recessive model; the OR of the CC genotype was 0.69 (95% CI, 0.69-0.93) compared with the T-allele. However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P &lt; 0.001 (0.05/52) except for TERT-07. When restricted to Caucasians (94% of the study subjects), a stronger association for the TERT-07 G-allele was observed with an OR of 1.60 (95% CI, 1.24-2.05; P = 0.0002). No effect modifications were found for variant alleles and menopausal status, telomere length, cigarette smoking, body mass index status, and family history of breast cancer risk.
Conclusions: Four SNPs in the TERT and POT1 genes were significantly related with overall breast cancer risk. This initial analysis provides valuable clues for further exploration of the biological role of telomere pathway genes in breast cancer. Cancer Epidemiol Biomarkers Prev; 19(1); 219–28
Lipid Peroxidation and Etheno DNA Adducts in White Blood Cells of Liver Fluke-Infected Patients: Protection by Plasma α-Tocopherol and Praziquantel
Authors: Dechakhamphu Somkid , Pinlaor Somchai , Sitthithaworn Paiboon , Nair Jagadeesan , Bartsch Helmut , Yongvanit Puangrat 
Published: January 2010

Abstract
Chronic infection by the liver fluke Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. To clarify the involvement of oxidative stress and lipid peroxidation–derived DNA damage, etheno (ϵ)-DNA adducts (ϵdA, ϵdC) in WBC and plasma α-tocopherol were measured in samples collected from O. viverrini–infected Thai patients (n = 50) and healthy noninfected volunteers (n = 20). ϵdA and ϵdC levels were three to five times higher (P &lt; 0.001) in infected patients than in controls; O. viverrini infection also increased two to three times in the plasma inflammatory indicators, 8-isoprostane, malondialdehyde, and nitrate/nitrite. Mean plasma α-tocopherol levels were two times lower in patients than in healthy controls (P &lt; 0.001). Two months after a single dose to infected patients of the antiparasitic drug praziquantel, ϵdA and ϵdC levels in WBC were decreased to control level (P &lt; 0.03); plasma 8-isoprostane, malondialdehyde, nitrate/nitrite, and alkaline phosphatase (ALP) were concomitantly lowered. ϵdA and ϵdC levels in WBC were positively correlated with plasma 8-isoprostane, malondialdehyde, and nitrate/nitrite levels and ALP activity, whereas plasma α-tocopherol levels showed inverse correlations. We conclude that chronic O.viverrini infection induces an accumulation of lipid peroxidation–derived DNA damage through oxidative/nitrative stress, which is lowered by the plasma α-tocopherol and by antiparasitic drug therapy. Etheno adducts in WBC and urine should be explored as a risk marker for opisthorchiasis-related cholangiocarcinoma, and to assess the efficacy of preventive and therapeutic interventions. Cancer Epidemiol Biomakers Prev; 19(1); 310–8.
Aspirin and Other Nonsteroidal Anti-inflammatory Drugs in Relation to Hodgkin Lymphoma Risk in Northern Denmark
Authors: Chang Ellen T. , Cronin-Fenton Deirdre P. , Friis Søren , Hjalgrim Henrik , Sørensen Henrik Toft , Pedersen Lars 
Published: January 2010

Abstract
There are few known modifiable risk factors for Hodgkin lymphoma, but the recent finding of an inverse association between routine regular-strength aspirin use and Hodgkin lymphoma risk suggests that aspirin may protect against Hodgkin lymphoma development. To further investigate this association using prospectively collected data, we conducted a population-based case-control study in northern Denmark. A total of 478 incident Hodgkin lymphoma cases were identified in nationwide health-care databases from 1991 to 2008. Ten population controls were matched to each case on age, sex, and county using risk-set sampling. Use of aspirin, selective cyclooxygenase-2 inhibitors, and other nonsteroidal anti-inflammatory drugs (NSAIDs) from 1989 to 2007 was ascertained by linkage to a population-based prescription database. Conditional logistic regression was used to estimate odds ratios for associations between medication use and risk of Hodgkin lymphoma. The odds ratio (95% confidence interval) for ever use (&gt;2 prescriptions) compared with never/rare use (≤2 prescriptions) of low-dose aspirin was 0.7 (0.5-1.2). The association with low-dose aspirin use did not vary appreciably by recentness, duration, or intensity of use. Recent use (&gt;2 prescriptions in the 1-2 years before the index date), short-term use (&lt;7 years), and medium/high-intensity use (≥25% of duration of use covered by prescription) of selective cyclooxygenase-2 inhibitors or other NSAIDs was associated with increased Hodgkin lymphoma risk possibly due to prodromal symptoms among cases. In conclusion, our results provide some evidence of a protective effect of low-dose aspirin, but not other NSAIDs, against Hodgkin lymphoma development.Cancer Epidemiol Biomakers Prev; 19(1);59–64
Cannabidiol Enhances the Inhibitory Effects of Δ9-Tetrahydrocannabinol on Human Glioblastoma Cell Proliferation and Survival
Authors: Marcu Jahan P. , Christian Rigel T. , Lau Darryl , Zielinski Anne J. , Horowitz Maxx P. , Lee Jasmine , Pakdel Arash , Allison Juanita , Limbad Chandani , Moore Dan H. , Yount Garret L. , Desprez Pierre-Yves , McAllister Sean D. 
Published: January 2010

AbstractThe cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor agonist Δ9-tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer in culture and in vivo, and is currently being used in a clinical trial for the treatment of glioblastoma. It has been suggested that other plant-derived cannabinoids, which do not interact efficiently with CB1 and CB2 receptors, can modulate the actions of Δ9-THC. There are conflicting reports, however, as to what extent other cannabinoids can modulate Δ9-THC activity, and most importantly, it is not clear whether other cannabinoid compounds can either potentiate or inhibit the actions of Δ9-THC. We therefore tested cannabidiol, the second most abundant plant-derived cannabinoid, in combination with Δ9-THC. In the U251 and SF126 glioblastoma cell lines, Δ9-THC and cannabidiol acted synergistically to inhibit cell proliferation. The treatment of glioblastoma cells with both compounds led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique. Our results suggest that the addition of cannabidiol to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients. Mol Cancer Ther; 9(1); 180–9
Selective Inhibition of Histone Deacetylases Sensitizes Malignant Cells to Death Receptor Ligands
Authors: Wood Tabitha E. , Dalili Shadi , Simpson Craig D. , Sukhai Mahadeo A. , Hurren Rose , Anyiwe Kika , Mao Xinliang , Suarez Saiz Fernando , Gronda Marcela , Eberhard Yanina , MacLean Neil , Ketela Troy , Reed John C. , Moffat Jason , Minden Mark D. , Batey Robert A. , Schimmer Aaron D. 
Published: January 2010

Abstract
Evasion of death receptor ligand–induced apoptosis represents an important contributor to cancer development and progression. Therefore, molecules that restore sensitivity to death receptor stimuli would be important tools to better understand this biological pathway and potential leads for therapeutic adjuncts. Previously, the small-molecule 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide (that we propose be named droxinostat) was identified as a chemical sensitizer to death receptor stimuli, decreasing the expression of the caspase-8 inhibitor FLIP. However, the direct targets of droxinostat were unknown. To better understand the mechanism of action of droxinostat and highlight new strategies to restore sensitivity to death receptor ligands, we analyzed changes in gene expression using the Connectivity Map after treating cells with droxinostat. Changes in gene expression after droxinostat treatment resembled changes observed after treatment with histone deacetylase (HDAC) inhibitors. Therefore, we examined the effects of droxinostat on HDAC activity and showed that it selectively inhibited HDAC3, HDAC6, and HDAC8 and that inhibition of these HDACs was functionally important for its ability to sensitize cells to death ligands. Thus, we have identified a selective HDAC inhibitor and showed that selective HDAC inhibition sensitizes cells to death ligands, thereby highlighting a new mechanism to overcome resistance to death receptor ligands. Mol Cancer Ther; 9(1); 246–56
8-Amino-Adenosine Inhibits Multiple Mechanisms of Transcription
Authors: Frey Jennifer Ann , Gandhi Varsha 
Published: January 2010

AbstractRoscovitine and flavopiridol suppress cyclin-dependent kinase 7 (CDK7) and CDK9 activity resulting in transcription inhibition, thus providing an alternative mechanism to traditional genotoxic chemotherapy. These agents have been effective in slow or nonreplicative cell types. 8-Amino-adenosine is a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. The objective of the current work was to define mechanisms of action that lead to transcription inhibition by 8-amino-adenosine. 8-Amino-adenosine is metabolized into the active triphosphate (8-amino-ATP) in cells. This accumulation resulted in a simultaneous decrease of intracellular ATP and RNA synthesis. When the effects of established ATP synthesis inhibitors and transcription inhibitors on intracellular ATP concentrations and RNA synthesis were studied, there was a strong correlation between ATP decline and RNA synthesis. This correlation substantiated the hypothesis that the loss of ATP in 8-amino-adenosine–treated cells contributes to the decrease in transcription due to the lack of substrate needed for mRNA body and polyadenylation tail synthesis. RNA polymerase II COOH terminal domain phosphorylation declined sharply in 8-amino-adenosine–treated cells, which may have been due to the lack of an ATP phosphate donor or competitive inhibition with 8-amino-ATP at CDK7 and CDK9. Furthermore, 8-amino-ATP was incorporated into nascent RNA in a dose-dependent manner at the 3′-end resulting in transcription termination. Finally, in vitro transcription assays showed that 8-amino-ATP competes with ATP for incorporation into mRNA. Collectively, we have concluded that 8-amino-adenosine elicits effects on multiple mechanisms of transcription, providing a new class of transcription inhibitors. Mol Cancer Ther; 9(1); 236–45
Notch-1 Inhibition by Withaferin-A: A Therapeutic Target against Colon Carcinogenesis
Authors: Koduru Srinivas , Kumar Raj , Srinivasan Sowmyalakshmi , Evers Mark B. , Damodaran Chendil 
Published: January 2010

Abstract
Notch signaling plays a crucial role in the development of colon cancer; targeting the Notch pathway may sensitize colon cancers to various adjuvant agents. The focus of our current study is to identify natural compounds that target Notch signaling and that might be beneficial for the prevention and treatment of colon cancer. Withaferin-A (WA) is a bioactive compound derived from Withania somnifera, which inhibits Notch-1 signaling and downregulates prosurvival pathways, such as Akt/NF-κB/Bcl-2, in three colon cancer cell lines (HCT-116, SW-480, and SW-620). In addition, WA downregulated the expression of mammalian target of rapamycin signaling components, pS6K and p4E-BP1, and activated c-Jun-NH2-kinase–mediated apoptosis in colon cancer cells. We also established the molecular link between Notch/Akt/mammalian target of rapamycin signaling by complementary approaches (i.e., overexpression of Notch-1 or inhibition of Notch-1 by small interfering RNA). Our results suggest that WA inhibits Notch-mediated prosurvival signaling, which facilitates c-Jun-NH2-kinase–mediated apoptosis in colon cancer cell lines. These results underscore the anticancer activity of WA, which exhibits potential for further development for targeted chemotherapy and/or chemoprevention strategies in the context of colon cancer. Mol Cancer Ther; 9(1); 202–210
Sunitinib Induces Apoptosis and Growth Arrest of Medulloblastoma Tumor Cells by Inhibiting STAT3 and AKT Signaling Pathways
Authors: Yang Fan , Jove Veronica , Xin Hong , Hedvat Michael , Van Meter Timothy E. , Yu Hua 
Published: January 2010

Abstract
Medulloblastomas are the most frequent malignant brain tumors in children. Sunitinib is an oral multitargeted tyrosine kinase inhibitor used in clinical trials as an antiangiogenic agent for cancer therapy. In this report, we show that sunitinib induced apoptosis and inhibited cell proliferation of both a short-term primary culture (VC312) and an established cell line (Daoy) of human medulloblastomas. Sunitinib treatment resulted in the activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase and upregulation of proapoptotic genes, Bak and Bim, and inhibited the expression of survivin, an antiapoptotic protein. Sunitinib treatment also downregulated cyclin E, cyclin D2, and cyclin D3 and upregulated p21Cip1, all of which are involved in regulating cell cycle. In addition, it inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AKT (protein kinase B) in the tumor cells. Dephosphorylation of STAT3 (Tyr705) induced by sunitinib was helped by a reduction in activities of Janus-activated kinase 2 and Src. Additionally, sodium vanadate, an inhibitor of protein tyrosine phosphatases, partially blocked the inhibition of phosphorylated STAT3 by sunitinib. Loss of phosphorylated AKT after sunitinib treatment was accompanied by decreased phosphorylation of downstream proteins glycogen synthase kinase-3β and mammalian target of rapamycin. Expression of a constitutively activated STAT3 mutant or myristoylated AKT partially blocked the effects of sunitinib in these tumor cells. Sunitinib also inhibited the migration of medulloblastoma tumor cells in vitro. These findings suggest the potential use of sunitinib for the treatment of pediatric medulloblastomas. Mol Cancer Res; 8(1); 35–45
Response to Lau's ‘China: Labour Reform and the Challenge Facing the Working Class’
Authors: Minqi Li 
Published: January 2010

In Capital & Class, no. 61 (Spring 1997) we published an article ‘China: Labour Reform and the Challenge Facing the Working Class’, by Raymond Lau which discussed workers' and students' struggles in and around the 1989 democratic movement. In the article below, Li Minqi, who was involved in student democratic activities and in one of the organisations mentioned by Lau, offers a critical response to the author. We also publish Lau's rejoinder. Iread with great interest Raymond W. K. Lau's article, ‘China: Labour Reform and the Challenge Facing the Working Class’, published in Capital & Class, no. 61 (Spring 1997). In fact, I was personally involved in the underground organization which Lau referred to as ‘Wage Workers' Federation’ ( dagongzhe lianhehui). Thus, I can probably help to explain some of Lau's puzzles concerning this organization. I do think Lau's article provides many important insights into and about the conditions of China's working class, and its struggle against capitalist oppression and exploitation. However, I also have some serious disagreements with him, especially on how to evaluate the historical heritage of the Chinese socialist revolution, and how this heritage will impact on the Chinese working class in its current struggle against capitalism. Thus, I would also like to make some comments on these problems.
Are Hot Markets Driven by Hot Resource Shares or Hot Commodities?
Authors: Suchard Jo-An , Woo Li-Anne 
Published: January 2010

Cycles in initial public offer (IPO) underpricing have been historically linked to both the proportion and pricing of resource-based IPOs issued relative to the entire population of IPOs. In addition, IPOs in the less diversified resource sector are exposed to changes in underlying commodity market prices which directly affect firm valuation. However, prior IPO research has largely ignored the various risk factors affecting resource firms. In this paper, we explicitly consider the explanatory power of ‘traditional’ IPO risk factors and augment these with specific risk characteristics associated with the resource sector, such as the underlying changes in resource commodity prices, the nature of activities (exploration versus production), and, the level of commodity diversification. IPO market cycles over the period March 1983 to January 1990 are identified using the switching regression technique of Goldfeld and Quandt (1972). The regression results suggest that for ‘hot’ markets, the level of underpricing is unrelated to any previously identified risk characteristics. Yet in ‘cool’ markets, both the underlying commodity price change, period of subscription, issue size and the proportion of resource to total listing are influential. Interestingly, the level of firm diversification and the nature of resource activity do not systematically affect the level of underpricing.
Patterns of Energy Use in Australian Manufacturing Industry
Authors: Hall P. H. 
Published: January 2010

This paper develops an index of energy productivity and employs it to examine productivity movements across 62 Australian manufacturing industries for the period 1950–1968. Data were not available to permit extension of the analysis beyond 1968. In the empirical part of the paper, the first task is to identify industries which are major energy users. Secondly, the best and worst performers, relative to the average, in terms of energy productivity gain are identified. A line of enquiry into energy productivity is then pursued analogous to that developed by Salter's work on labour productivity and technical change.
Regularities in Australian Share Returns
Authors: Beedles William L. , Dodd Peter , Officer R. R. 
Published: January 2010

The inverse relation between total equity value and return is confirmed for Australian ordinary shares over the 1974–1984 period. We find this so-called size effect to be robust with respect to several technical methodological adjustments. In particular, the pattern persists when we account for: fluctuations in the returns of nominally riskless assets; varying levels of systematic risk of size ranked portfolios; the index selected to represent the common factor in the return generating mechanism; the form of returns, i.e., simple versus continuously compounded; possible initial mispricing of new issues; possible seasoning of new issues; shares that leave the data base for bankruptcy, winding up, or other reasons; the third moment of the return distribution; and the levels of portfolios' unsystematic risks. We do find several economic variables that seem in part to account for the magnitude of the size effect, viz., accounting for: yearly rather than monthly portfolio revision; nonsynchronous trading; and varying transactions charges, volume of information available, and liquidity between large and small firms.
Lost Managers or Industrial Dinosaurs? A Reappraisal of Front-line Management
Authors: Dawson Patrick 
Published: January 2010

A narrow concept of industrial supervision continues to dominate discussion on the future rôle of the supervisor. Although the nature and purpose of workplace supervision has continuously evolved, there remains a general reluctance to accept the significance of these changes. Substantive shifts in supervisory control indicate that there is a far broader range of policy options available in the development of supervision than is currently suggested in the literature. It is therefore important that management understand what constitutes supervision if they wish to be active and constructive shapers rather than passive observers of tomorrow's front-line management. This paper examines the need to reconceptualise supervision and go beyond the simple dichotomy of technical competency and labour regulation. It is argued that the supervisor is neither an “Industrial Dinosaur” nor simply a “Lost Manager”, but a key organisational player whose position should be realigned to meet current organisational needs.