bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the impacts of cigarette taxes on youth smoking participation, initiation, and persistence: empirical evidence from Canada
Authors: Sen Anindya , Wirjanto Tony 
Published: October 2009

AbstractIn response to the widespread availability of illegal contraband, the federal and five provincial governments in Canada implemented a 40–60% reduction to cigarette excise taxes in February 1994. We exploit this unique and discrete policy shock by estimating the effects of cigarette taxes on youth smoking with data from the 1992–1996 Waterloo Smoking Prevention Program, 1991 General Social Survey, 1994 Youth Smoking Survey, 1996–1997 and 1998–1999 National population Health Surveys, and the 1999 Canadian Tobacco Use Monitoring Survey. Empirical estimates yield daily and occasional participation elasticities from −0.10 to −0.14, which is consistent with findings from recent U.S.‐based research. A key contribution of this research is in the analysis of lower taxes on a panel of 591 youths from the Waterloo Smoking Prevention Program, who did not smoke in 1993, but 43% of whom confirm smoking participation following the tax reduction. Employing these data reveals elasticities from −0.2 to −0.5, which suggest that even significant and discrete changes in taxes might have limited impacts on the initiation and persistence of youth smoking. Copyright © 2009 John Wiley & Sons, Ltd.
Investment in antiviral drugs: a real options approach
Authors: Attema Arthur E. , Lugnér Anna K. , Feenstra Talitha L. 
Published: October 2009

AbstractReal options analysis is a promising approach to model investment under uncertainty. We employ this approach to value stockpiling of antiviral drugs as a precautionary measure against a possible influenza pandemic. Modifications of the real options approach to include risk attitude and deviations from expected utility are presented. We show that risk aversion counteracts the tendency to delay investment for this case of precautionary investment, which is in contrast to earlier applications of risk aversion to real options analysis. Moreover, we provide a numerical example using real world data and discuss the implications of real options analysis for health policy. Suggestions for further extensions of the model and a comparison with the expected value of information analysis are put forward. Copyright © 2009 John Wiley & Sons, Ltd.
Role of CXC chemokine ligand 13 in oral squamous cell carcinoma associated osteolysis in athymic mice
Authors: Pandruvada Subramanya N.M. , Yuvaraj Sambandam , Liu Xiang , Sundaram Kumaran , Shanmugarajan Srinivasan , Ries William L. , Norris James S. , London Steven D. , Reddy Sakamuri V. 
Published: October 2009

AbstractOral squamous cell carcinomas (OSCC) are malignant tumors with a potent activity of local bone invasion; however, the molecular mechanisms of tumor osteolysis are unclear. In this study, we identified high level expression of chemokine ligand, CXCL13 and RANK ligand (RANKL) in OSCC cells (SCC1, SCC12 and SCC14a). OSCC cell‐conditioned media (20%) induced osteoclast differentiation which was inhibited by OPG in peripheral blood monocyte cultures indicating that OSCC cells produce soluble RANKL. Recombinant hCXCL13 (10 ng/ml) significantly enhanced RANKL‐stimulated osteoclast differentiation in these cultures. Trans‐well migration assay identified that CXCL13 induces chemotaxis of peripheral blood monocytes in vitro which was inhibited by addition of anti‐CXCR5 receptor antibody. Zymogram analysis of conditioned media from OSCC cells revealed matrix metalloproteinase‐9 (MMP‐9) activity. Interestingly, CXCL13 treatment to OSCC cells induced CXCR5 and MMP‐9 expression suggesting an autocrine regulatory function in OSCC cells. To examine the OSCC tumor cell bone invasion/osteolysis, we established an in vivo model for OSCC by subcutaneous injection of OSCC cells onto the surface of calvaria in NCr‐nu/nu athymic mice, which developed tumors in 4–5 weeks. μCT analysis revealed numerous osteolytic lesions in calvaria from OSCC tumor‐bearing mice. Histochemical staining of calvarial sections from these mice revealed a significant increase in the numbers of TRAP‐positive osteoclasts at the tumor‐bone interface. Immunohistochemical analysis confirmed CXCL13 and MMP‐9 expression in tumor cells. Thus, our data implicate a functional role for CXCL13 in bone invasion and may be a potential therapeutic target to prevent osteolysis associated with OSCC tumors in vivo.
GSTT1andGSTM1polymorphisms and myelodysplastic syndrome risk: a systematic review and meta‐analysis
Authors: Dahabreh Issa J. , Giannouli Stavroula , Gota Vaia , Voulgarelis Michael 
Published: October 2009

AbstractGlutathione‐S‐transferace polymorphisms may make hematopoietic lineage cells susceptible to genotoxicity following exposure to heavy metals or benzene. We conducted a systematic review and meta‐analysis to define the effect ofGSTM1andGSTT1null polymorphisms on MDS risk. We searched the PubMed and SCOPUS databases to identify peer‐reviewed published case‐control studies investigating the association betweenGSTT1and/orGSTM1null genotypes and development of MDS. Between‐study heterogeneity was assessed using Cochran's Q statistic and the I2statistic. Odds ratios from individual studies were pooled using fixed and random effects models. Thirteen studies were considered eligible for theGSTT1meta‐analysis (1471 cases, 1907 controls) and 10 were considered eligible for theGSTM1meta‐analysis (1161 cases, 1668 controls). For theGSTT1polymorphism, there was moderate between study heterogeneity (pQ= 0.01; I2= 52.3%) and the null genotype was significantly associated with increased risk of MDS development, random effects OR = 1.43 (95% CI, 1.09–1.89);p= 0.01. For theGSTM1polymorphisms there was moderate between‐study heterogeneity (p= 0.07; I2= 43.1%) and the random effects OR = 1.02 (95% CI, 0.82–1.28) was non‐significant (p= 0.85). TheGSTT1null genotype is a significant risk factor for MDS development. Gene‐environment interactions need to be further explored.
Differential activation of cell death and autophagy results in an increased cytotoxic potential for trifluorothymidine compared to 5‐fluorouracil in colon cancer cells
Authors: Bijnsdorp Irene V. , Peters Godefridus J. , Temmink Olaf H. , Fukushima Masakazu , Kruyt Frank A. 
Published: October 2009

AbstractTrifluorothymidine (TFT) is part of the oral drug formulation TAS‐102. Both 5‐fluorouracil (5‐FU) and TFT can inhibit thymidylate synthase and be incorporated into DNA. TFT shows only moderate cross‐resistance to 5‐FU. Therefore, we examined whether mechanistic differences in cell death could underlie their different modes of action in colorectal cancer cell lines (WiDR, Lovo92 and Colo320). Drug cytotoxicity was determined by SRB‐ and clonogenic assays, cell death by flow cytometry (PI and annexin V), caspase cleavage by Western blotting and activity assays and in vivo activity in the hollow fiber assay. The IC50 values of TFT were 1‐6 fold lower than for 5‐FU, and clonogenic survival was less than 0.9% at 3 μM TFT, while 2–20% of the cells still survived after 20 μM 5‐FU. In general, TFT was a more potent inducer of apoptosis than 5‐FU, although the contribution of caspases varied between the used cell lines and necrosis‐like cell death was detected. Accordingly, both drugs induced caspase (Z‐VAD) independent cell death and lysosomal cathepsin B was involved. Activation of autophagy recovery mechanisms was only triggered by 5‐FU, but not by TFT as determined by LC3B expression and cleavage. Inhibition of autophagy by 3‐MA in 5‐FU exposed cells reduced cell survival. Also, in vivo TFT (as TAS‐102) caused more cell death than a 5‐FU formulation. We conclude that TFT and 5‐FU induce cell death via both caspase‐dependent and independent mechanisms. The TFT was more potent than 5‐FU, because it induces higher levels of cell death and does not elicit an autophagic survival response in the cancer cell lines. This provides a strong molecular basis for further application of TFT in cancer therapy.
p38delta/MAPK13 as a diagnostic marker for cholangiocarcinoma and its involvement in cell motility and invasion
Authors: Tan Felicia Li‐Sher , Ooi Aikseng , Huang Dachuan , Wong Jing Chii , Qian Chao‐Nan , Chao Cora , Ooi London , Tan Yu‐Meng , Chung Alexander , Cheow Peng‐Chung , Zhang Zhongfa , Petillo David , Yang Ximing J. , Teh Bin Tean 
Published: October 2009

AbstractCholangiocarcinoma (CC) and hepatocellularcarcinoma (HCC) are two main forms of liver malignancies, which exhibit differences in drug response and prognosis. Immunohistotochemical staining for cytokeratin markers has been used to some success in the differential diagnosis of CC from HCC. However, there remains a need for additional markers for increased sensitivity and specificity of diagnosis. In this study, we have identified a p38 MAP kinase, p38δ (also known as MAPK13 or SAPK4) as a protein that is upregulated in CC relative to HCC and to normal biliary tract tissues. We performed microarray gene expression profiling on 17 cases of CC, 12 cases of adjacent normal liver tissue, and three case of normal bile duct tissue. p38δ was upregulated in 16 out of 17 cases of CC relative to normal tissue. We subsequently performed immunohistochemical staining of p38δ in 54 cases of CC and 54 cases of HCC. p38δ staining distinguished CC from HCC with a sensitivity of 92.6% and a specificity of 90.7%. To explore the possible functional significance of p38δ expression in CC, we examined the effects of overexpression and knockdown of p38δ expression in human CC cell lines. Our results indicate that p38δ is important for motility and invasion of CC cells, suggesting that p38δ may play an important role in CC metastasis. In summary, p38δ may serve as a novel diagnostic marker for CC and may also serve as a new target for molecular based therapy of this disease.
Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein‐Barr virus‐positive epithelial malignancies and mediates enhanced cell death
Authors: Hui K.F. , Chiang Alan K.S. 
Published: October 2009

AbstractIn Epstein‐Barr virus (EBV)‐associated malignancies, the virus is harbored in every tumor cell and persists in tightly latent forms expressing a very limited number of viral latent proteins. Induction of EBV lytic cycle leads to expression of a much larger number of viral proteins, which may serve as potential therapeutic targets. We found that 4 histone deacetylase inhibitors, trichostatin A (TSA), sodium butyrate (SB), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), all significantly induced EBV lytic cycle in EBV‐positive gastric carcinoma cells (AGS/BX1, latency II) but only weakly induced in Burkitt lymphoma cells (AK2003, latency I) and did not induce in lymphoblastoid cells (LCLs, latency III). Interestingly, SAHA potently induced viral lytic cycle in AGS/BX1 cells at micromolar concentrations (evidenced by 8‐fold increase in viral DNA replication, strong expression of viral lytic proteins and production of infectious virus particles) and mediated enhanced cell death of EBV‐positive AGS/BX1 cells when compared with that of EBV‐negative AGS cells, possibly related to cell cycle arrest at G2/M phase. Furthermore, SAHA effected strong induction of EBV lytic cycle in nasopharyngeal carcinoma but not in NK lymphoma cells (both expressing EBV latency II pattern), indicating preferential viral lytic induction in epithelial rather than lymphoid malignancies. In conclusion, SAHA is found to be a potent EBV lytic cycle inducing agent, which warrants further investigation into its potential application as a novel virus‐targeted drug for treatment of EBV‐associated epithelial malignancies.
Direct and indirect contribution of bone marrow‐derived cells to cancer
Authors: Guest Ian , Ilic Zoran , Ma Jun , Grant Denise , Glinsky Gennadi , Sell Stewart 
Published: October 2009

AbstractStromal‐epithelial interactions may control the growth and initiation of cancers. Here, we not only test the hypothesis that bone marrow‐derived cells may effect development of cancers arising from other tissue cells by forming tumor stroma but also that sarcomas may arise by transformation of stem cells from the bone marrow and epithelial cancers may arise by transdifferentiation of bone marrow stem cells to epithelial cancers. Lethally irradiated female FVB/N mice were restored with bone marrow (BM) transplants from a male transgenic mouse carrying the polyoma middle T‐oncoprotein under the control of the mouse mammary tumor virus promoter (MMTV‐PyMT) and followed for development of lesions. All of 8 lethally irradiated female FVB/N recipient mice, restored with BM transplants from a male MMTV‐PyMT transgenic mouse, developed Y‐chromosome negative (Y−) cancers of various organs surrounded by Y+ stroma. One of the female FVB/N recipient mice also developed fibrosarcoma and 1, a diploid breast adenocarcinoma containing Y chromosomes. In contrast, only 1 of 12 control female mice restored with normal male BM developed a tumor (lymphoma) during the same time period. These results indicate not only that the transgenic BM‐derived stromal cells may indirectly contribute to development of tumors in recipient mice but also that sarcomas may arise by transformation of BM stem cells and that breast cancers arise by transdifferentiation of BM stem cells, presumably by mesenchymal‐epithelial transition.
Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC)
Authors: Albinger‐Hegyi Andrea , Stoeckli Sandro J. , Schmid Stephan , Storz Martina , Iotzova Guergana , Probst‐Hensch Nicole M. , Rehrauer Hubert , Tinguely Marianne , Moch Holger , Hegyi Ivan 
Published: October 2009

AbstractProteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix. However, they have an important role in the tumour development as well as in tumour progression. To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT‐PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total). Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001). High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001). Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037). In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival. In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC. Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies.
Is therapeutic plasma exchange indicated for patients with gemcitabine‐induced hemolytic uremic syndrome?
Authors: Gore Ethan McCaleb , Jones Benjamin Scott , Marques Marisa B. 
Published: October 2009

AbstractAtypical hemolytic uremic syndrome (aHUS) has been described as an uncommon complication of gemcitabine. In this review, we discuss the diagnosis of gemcitabine‐induced aHUS (GiHUS) and the published experience with therapeutic plasma exchange (TPE). To illustrate GiHUS, we present a patient who developed hypertension and peripheral edema while receiving gemcitabine and subsequently was found to have thrombocytopenia, hemolytic anemia, renal failure, and normal ADAMTS‐13 activity. Although laboratory parameters improved on suspending gemcitabine, they worsened after reinstitution of the drug. Thrombocytopenia and hemolysis ceased once the drug was permanently discontinued without therapeutic plasma exchange (TPE). The pathological characteristics of GiHUS suggest damage of the glomeruli endothelial lining, leading to occlusion by fibrin‐rich thrombi. Among 26 patients described in the literature not treated with TPE, 56% recovered from GiHUS, whereas only 30% of 18 patients treated with TPE did. The difference in recovery rate may have been confounded by the severity of GiHUS as suggested by the rate of dialysis in each group: 10/26 (38%) patients who did not receive TPE were dialyzed compared with 11/18 (61%) of those who had plasma exchange. Thus, although the currently available evidence is not decisive for use or non use of TPE, we suggest that the most important therapeutic intervention in GiHUS is discontinuation of the drug. Apheresis medicine specialists should be aware of this specific type of aHUS and provide treatment advice based on the currently available evidence. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.
Postdonation platelet counts are safe when collecting platelets with the Trima Accel using a postdonation platelet count target of ≥50,000 platelets/μL
Authors: Alex Jessie , Roberts Beverly , Raife Thomas 
Published: October 2009

AbstractIn December 2007, the FDA issued a guidance document recommending that apheresis cell separators be configured with a postdonation platelet count target of ≥100,000 platelets/μL. Currently, our Trima Accel apheresis cell separators are configured with a postdonation platelet count target of ≥50,000 platelets/μL. To determine the safety of our current procedure, we analyzed the postdonation platelet counts of 115 donors collected using our current procedure. All of 115 donors had postdonation platelet counts ≥100,000 platelets/μL. On the basis of predonation platelet counts, we calculated that raising the postdonation target platelet count to ≥100,000 platelets/μL would have disqualified 19 out of 225 potential platelet products. We conclude that the current postdonation platelet count target of ≥50,000 platelets/μL is safe for donors collected using the Trima Accel. Efforts to reduce the incidence of TRALI are creating challenges for the platelet supply. Increasing the postdonation platelet count target to ≥100,000 platelets/μL will reduce productivity in apheresis platelet collection and may not enhance donor safety. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.
Targeted inhibition of the EGFR pathways enhances Zn‐BC‐AM PDT‐induced apoptosis in well‐differentiated nasopharyngeal carcinoma cells
Authors: Koon Ho‐Kee , Chan Pui‐Shan , Wong Ricky Ngok‐Shun , Wu Zhen‐Guo , Lung Maria Li , Chang Chi‐Kwong , Mak Nai‐Ki 
Published: October 2009

AbstractEpidermal growth factor receptor (EGFR), a receptor often expressed in nasopharyngeal carcinoma (NPC) cells, is one of the recently identified molecular targets in cancer treatment. In the present study, the effects of combined treatment of Zn‐BC‐AM PDT with an EGFR inhibitor AG1478 were investigated. Well‐differentiated NPC HK‐1 cells were subjected to PDT with 1 µM of Zn‐BC‐AM and were irradiated at a light dose of 1 J/cm2 in the presence or absence of EGFR inhibitor AG1478. Specific protein kinase inhibitors of downstream EGFR targets were also used in the investigation. EGFR, Akt, and ERK were found constitutively activated in HK‐1 cells and the activities could be inhibited by the EGFR inhibitor AG1478. A sub‐lethal concentration of AG1478 was found to further enhance the irreversible cell damage induced by Zn‐BC‐AM PDT in HK‐1 cells. Pre‐incubation of the cells with specific inhibitors of EGFR (AG1478), PI3k/Akt (LY294002), or MEK/ERK (PD98059) before light irradiation were found to enhance Zn‐BC‐AM PDT‐induced formation of apoptotic cells. The efficacy of Zn‐BC‐AM PDT can be increased through the inhibition of EGFR/PI3K/Akt and EGFR/MEK/ERK signaling pathways in NPC cells. Combination therapy with Zn‐BC‐AM PDT and EGFR inhibitors may further be developed for the treatment of advanced NPC. J. Cell. Biochem. 108: 1356–1363, 2009. © 2009 Wiley‐Liss, Inc.
Stability and individual change in depressive symptoms among mothers raising young children with ASD: maternal and child correlates
Authors: Carter Alice S. , Martínez‐Pedraza Frances de L. , Gray Sarah A. O. 
Published: October 2009

AbstractMothers raising children with Autism Spectrum Disorders (ASD) evidence elevated depressive symptoms, but symptom stability has not been examined. Mothers (N=143) of toddlers with ASD (77% boys) were enrolled and assessed when their children were 18 to 33 months old and followed annually for 2 years. Multilevel modeling revealed no significant change in group depressive symptom level, which was in the moderately elevated range (Intercept=13.67; SE=.96). In contrast, there was significant individual variation in change over time. Child problem behaviors and delayed competence, maternal anxiety symptoms and angry/hostile mood, low parenting efficacy and social supports, and coping styles were associated with depression severity. Only maternal anxiety and parenting efficacy predicted individual change. Many mothers do not appear to adapt, supporting the need for early intervention for maternal well‐being. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1–11, 2009.
Energy transfer in master equation simulations: A new approach
Authors: Barker John R. 
Published: October 2009

AbstractCollisional energy transfer plays a key role in recombination, unimolecular, and chemical activation reactions. For master equation simulations of such reaction systems, it is conventionally assumed that the rate constant for inelastic energy transfer collisions is independent of the excitation energy. However, numerical instabilities and nonphysical results are encountered when normalizing the collision step‐size distribution in the sparse density of states regime at low energies. It is argued here that the conventional assumption is not correct, and it is shown that the numerical problems and nonphysical results are eliminated by making a plausible assumption about the energy dependence of the rate coefficient for inelastic collisions. The new assumption produces a model that is more physically realistic for any reasonable choice of collision step‐size distribution, but more work remains to be done. The resulting numerical algorithm is stable and noniterative. Testing shows that overall accuracy in master equation simulations is better with this new approach than with the conventional one. This new approach is appropriate for all energy‐grained master equation formulations. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 748–763, 2009