bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation of RASSF1A, RASSF2A, and HIN-1 Is Associated with Poor Outcome after Radiotherapy, but not Surgery, in Oral Squamous Cell Carcinoma
Authors: Huang Kuo-Hao , Huang Shiang-Fu , Chen I-How , Liao Chun-Ta , Wang Hung-Ming , Hsieh Ling-Ling 
Published: June 2009

Abstract
Purpose: Radiotherapy is the standard adjuvant treatment for oral squamous cell carcinoma (OSCC). The Ras/PI3K/AKT pathway is the major mechanism associated with radioresistance. To evaluate the potential significance on the outcome of radiotherapy in OSCC of the Ras/PI3K/AKT pathway with respect to methylation of negative regulators, we examined the methylation status of genes known to be involved in Ras/PI3K/AKT pathway and aberrantly methylated in human cancers together with the mutation status of K-ras/H-ras.
Experimental Design: PCR–denaturing high-performance liquid chromatography was used to examine the methylation status of the RASSF1A, RASSF2A, PTEN, and HIN-1 genes, and PCR-RFLP was used to determine the mutation status of K-ras/H-ras in 482 OSCCs. Associations between mutation, methylation, clinicopathologic parameters, and outcome were evaluated.
Results: The frequencies of K-ras/H-ras mutation and promoter methylation of the RASSF1A, RASSF2A, PTEN, and HIN-1 genes were 6.6%, 22.4%, 27.8%, 1.2%, and 7.3%, respectively. A combination of RASSF1A and RASSF2A methylation was found to be significantly associated with poor disease-free survival (DFS). Furthermore, a gene dosage effect of the activated Ras/PI3K/AKT signal on DFS was observed in patients treated with radiotherapy after surgery but not in patients treated with surgery alone. The Ras/PI3K/AKT pathway was activated in 140 primary OSCCs among 286 patients treated with radiotherapy after surgery and methylation of RASSF1A/RASSF2A (75.7%) was the most common mechanism.
Conclusion: Our study indicates that epigenetic silencing of tumor suppressor genes involved in the Ras/PI3K/AKT pathway plays an important role in OSCC radioresistance and this provides a rationale for exploring novel treatment strategies.
Restoration of p53 Pathway by Nutlin-3 Induces Cell Cycle Arrest and Apoptosis in Human Rhabdomyosarcoma Cells
Authors: Miyachi Mitsuru , Kakazu Naoki , Yagyu Shigeki , Katsumi Yoshiki , Tsubai-Shimizu Satoko , Kikuchi Ken , Tsuchiya Kunihiko , Iehara Tomoko , Hosoi Hajime 
Published: June 2009

Abstract
Purpose: Seventy to eighty percent of rhabdomyosarcoma (RMS) tumors retain wild-type p53. The tumor suppressor p53 plays a central role in inducing cell cycle arrest or apoptosis in response to various stresses. p53 protein levels are regulated by MDM2 through ubiquitin-dependent degradation. In this study, we evaluated whether nutlin-3, a recently developed small-molecule antagonist of MDM2, has an effect on p53-dependent cell cycle arrest and apoptosis in cultured human RMS cell lines.
Experimental Design: Five RMS cell lines with different p53 statuses and MDM2 expression levels were treated with nutlin-3. Gene expression patterns, cell viability, cell cycle, and apoptosis after nutlin-3 treatment, and antitumor activity of combination treatment with vincristine or actinomycin D were assessed.
Results: Significant p53 activation was observed in wild-type p53 cell lines after nutlin-3 treatment. p53 activation led to cell cycle arrest in parallel with increased p21 expression. Furthermore, these cell lines underwent p53-dependent apoptosis, concomitant with elevation of proapoptotic genes and activation of caspase-3. The effect of nutlin-3 was almost the same in terms of half maximal inhibitory concentration and apoptosis whether or not MDM2 was overexpressed. Nutlin-3 did not induce either cell cycle arrest or apoptosis in p53 mutant cell lines. A combination of vincristine or actinomycin D with nutlin-3 enhanced the antitumor activity in RMS cell lines with wild-type p53.
Conclusions: Nutlin-3 effectively restored p53 function in both normal MDM2 expression and MDM2 overexpression RMS cell lines with wild-type p53. p53 restoration therapy is a potential therapeutic strategy for refractory RMS with wild-type p53.
Antitumor Effects and Biomarkers of Activity of AZD0530, a Src Inhibitor, in Pancreatic Cancer
Authors: Rajeshkumar N.V. , Tan Aik Choon , De Oliveira Elizabeth , Womack Chris , Wombwell Helen , Morgan Shethah , Warren Madhuri V. , Walker Jill , Green Tim P. , Jimeno Antonio , Messersmith Wells A. , Hidalgo Manuel 
Published: June 2009

Abstract
Purpose: To determine the efficacy of AZD0530, an orally active small molecule Src inhibitor, in human pancreatic cancer xenografts and to seek biomarkers predictive of activity.
Experimental Design: Sixteen patient-derived pancreatic cancer xenografts from the PancXenoBank collection at Johns Hopkins were treated with AZD0530 (50 mg/kg/day, p.o.) for 28 days. Baseline gene expression profiles of differently expressed genes in 16 tumors by Affymetrix U133 Plus 2.0 gene array were used to predict AZD0530 sensitivity in an independent group of eight tumors using the K-Top Scoring Pairs (K-TSP) method.
Results: Three patient tumors of 16 were found to be sensitive to AZD0530, defined as tumor growth &lt;50% compared with control tumors (100%). Western blot and/or immunohistochemistry results showed that AZD0530 administration resulted in the down-regulation of Src, FAK, p-FAK, p-paxillin, p-STAT-3, and XIAP in sensitive tumor xenografts compared with control tumors. The K-TSP classifier identified one gene pair (LRRC19 and IGFBP2) from the 16 training cases based on a decision rule. The classifier achieved 100% and 83.3% of sensitivity and specificity in an independent test set that consists of eight xenograft cases.
Conclusions: AZD0530 treatment significantly inhibits the tumor growth in a subset of human pancreatic tumor xenografts. One gene pair (LRRC19 and IGFBP2) identified by the K-TSP classifier has high predictive power for AZD0530 sensitivity, suggesting the potential for this gene pair as biomarker for pancreatic tumor sensitivity to AZD0530.
Identifying the Safety Profile of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Anticipation of a Phase I Clinical Trial in Patients with Recurrent Ovarian Cancer
Authors: Matthews Kellie , Noker Patricia E. , Tian Baohong , Grimes Sheila D. , Fulton Ronna , Schweikart Karen , Harris Raymond , Aurigemma Rose , Wang Minghui , Barnes Mack N. , Siegal Gene P. , Hemminki Akseli , Zinn Kurt , Curiel David T. , Alvarez Ronald D. 
Published: June 2009

Abstract
Purpose: The purpose of this study was to evaluate the biodistribution and toxicity of Ad5.SSTR/TK.RGD, an infectivity-enhanced adenovirus expressing a therapeutic suicide gene and somatostatin receptor type 2 (for noninvasive assessment of gene transfer with nuclear imaging) in advance of a planned phase I clinical trial for recurrent ovarian carcinoma.
Experimental Design: Cohorts of Syrian hamsters were treated i.p. for 3 consecutive days with Ad5.SSTR/TK.RGD or control buffer with or without the prodrug ganciclovir (GCV) and euthanized on day 4, 19, or 56. Tissue and serum samples were evaluated for the presence of virus using qPCR analysis and were assessed for vector-related tissue or laboratory effects.
Results: Levels of Ad5.SSTR/TK.RGD in blood and tissues outside of the abdominal cavity were low, indicating minimal systemic absorption. GCV did not affect Ad5.SSTR/TK.RGD biodistribution. The mean Ad5.SSTR/TK.RGD viral level was 100-fold lower on day 19 than day 4, suggesting vector elimination over time. Animals in the Ad5.SSTR/TK.RGD ± GCV cohort had clinical laboratory parameters and microscopic lesions in the abdominal organs indicative of an inflammatory response. Toxicity in this dose cohort seemed to be reversible over time.
Conclusions: These studies provide justification for planned dosing of Ad5.SSTR/TK.RGD for a planned phase I clinical trial and insights regarding anticipated toxicity.
GATA4 and GATA5 are Potential Tumor Suppressors and Biomarkers in Colorectal Cancer
Authors: Hellebrekers Debby M.E.I. , Lentjes Marjolein H.F.M. , van den Bosch Sandra M. , Melotte Veerle , Wouters Kim A.D. , Daenen Kathleen L.J. , Smits Kim M. , Akiyama Yoshimitsu , Yuasa Yasuhito , Sanduleanu Silvia , Khalid-de Bakker Carolina A.J. , Jonkers Daisy , Weijenberg Matty P. , Louwagie Joost , van Criekinge Wim , Carvalho Beatriz , Meijer Gerrit A. , Baylin Stephen B. , Herman James G. , de Bruïne Adriaan P. , van Engeland Manon 
Published: June 2009

Abstract
Purpose: The transcription factors GATA4 and GATA5 are involved in gastrointestinal development and are inactivated by promoter hypermethylation in colorectal cancer. Here, we evaluated GATA4/5 promoter methylation as potential biomarkers for noninvasive colorectal cancer detection, and investigated the role of GATA4/5 in colorectal cancer.
Experimental Design: Promoter methylation of GATA4/5 was analyzed in colorectal tissue and fecal DNA from colorectal cancer patients and healthy controls using methylation-specific PCR. The potential function of GATA4/5 as tumor suppressors was studied by inducing GATA4/5 overexpression in human colorectal cancer cell lines.
Results: GATA4/5 methylation was observed in 70% (63/90) and 79% (61/77) of colorectal carcinomas, respectively, and was independent of clinicopathologic features. Methylation frequencies in normal colon tissues from noncancerous controls were 6% (5 of 88, GATA4; P &lt; 0.001) and 13% (13 of 100, GATA5; P &lt; 0.001). GATA4/5 overexpression suppressed colony formation (P &lt; 0.005), proliferation (P &lt; 0.001), migration (P &lt; 0.05), invasion (P &lt; 0.05), and anchorage-independent growth (P &lt; 0.0001) of colorectal cancer cells. Examination of GATA4 methylation in fecal DNA from two independent series of colorectal cancer patients and controls yielded a sensitivity of 71% [95% confidence interval (95% CI), 55-88%] and specificity of 84% (95% CI, 74–95%) for colorectal cancer detection in the training set, and a sensitivity of 51% (95% CI, 37–65%) and specificity of 93% (95% CI, 84-100%) in the validation set.
Conclusions: Methylation of GATA4/5 is a common and specific event in colorectal carcinomas, and GATA4/5 exhibit tumor suppressive effects in colorectal cancer cells in vitro. GATA4 methylation in fecal DNA may be of interest for colorectal cancer detection.
High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma
Authors: Anagnostou Valsamo K. , Bepler Gerold , Syrigos Konstantinos N. , Tanoue Lynn , Gettinger Scott , Homer Robert J. , Boffa Daniel , Detterbeck Frank , Rimm David L. 
Published: June 2009

Abstract
Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTOR in carcinogenesis, its prognostic potential in lung cancer has not been investigated. Here, we quantitatively assessed mTOR protein expression in two large data sets to investigate the impact of mTOR expression on patient survival.
Experimental Design: Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess mTOR expression in a training cohort of 167 lung cancer patients. An independent cohort of 235 lung cancer patients (from a second institution) was used for validation.
Results: Tumors expressed mTOR in the cytoplasm in 56% and 50% of the cases in training and validation cohorts, respectively; mTOR expression was not associated with standard clinical or pathologic characteristics. Patients with high mTOR expression had a longer median overall survival compared with the low expressers (52.7 versus 38.5 months; log rank P = 0.06), which was more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively).
Conclusions: mTOR expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTOR into clinical decisions.
A Mitochondrial Target Sequence Polymorphism in Manganese Superoxide Dismutase Predicts Inferior Survival in Breast Cancer Patients Treated with Cyclophosphamide
Authors: Glynn Sharon A. , Boersma Brenda J. , Howe Tiffany M. , Edvardsen Hege , Geisler Stephanie B. , Goodman Julie E. , Ridnour Lisa A. , Lønning Per E. , Børresen-Dale Anne-Lise , Naume Bjorn , Kristensen Vessela N. , Chanock Stephen J. , Wink David A. , Ambs Stefan 
Published: June 2009

AbstractPurpose: Manganese superoxide dismutase protects against oxidative damage and modulates the efficacy of chemotherapeutic drugs. A functional single-nucleotide polymorphism in codon 16 of SOD2 (rs4880), which encodes manganese superoxide dismutase, results in a substitution of valine by alanine (Val16Ala). We hypothesized that this single-nucleotide polymorphism affects breast cancer survival of patients receiving chemotherapy.Experimental Design: Two patient populations from the United States (n = 248) and Norway (n = 340) were genotyped for Val16Ala. Kaplan-Meier survival and Cox proportional hazards regression analyses were used to examine the relationship between Val16Ala and disease-specific survival.Results: Val16Ala was significantly associated with breast cancer outcome in both patient populations. Carriers of the Ala allele had inferior survival rates in the multivariate analysis [hazard ratio (HR), 2.44 and 95% confidence interval (95% CI), 1.11-5.37 in U.S. cohort; HR, 1.91 and 95% CI, 1.06-3.45 in Norway cohort for Ala/Ala versus Val/Val]. In an analysis of the combined cohorts, this association was significant for patients receiving adjuvant therapy (HR, 2.47; 95% CI, 1.46-4.19), but not for patients without it (HR, 1.47; 95% CI, 0.57-3.74). After further stratification by type of chemotherapy, the effect of the Ala allele was mostly restricted to cyclophosphamide-containing chemotherapy regimens (HR, 22.0; 95% CI, 5.22-92.9; Ala/Ala versus Val/Val).Conclusion: The Val16Ala polymorphism affects survival of patients receiving cyclophosphamide-containing chemotherapy. The findings provide the first evidence pointing toward a mechanism for cyclophosphamide resistance in breast cancer patients.
Eribulin: Rediscovering Tubulin as an Anticancer Target
Authors: Jimeno Antonio 
Published: June 2009

Abstract
Eribulin mesylate (E7389) is a synthetic analog of the marine macrolide halichondrin B, which acts as a novel microtubule modulator with a distinct mechanism of action. Two eribulin mesylate phase 1 studies exploring weekly and 3-weekly schedules are reported in this issue. These trials show linear pharmacokinetics, a toxicity profile consisting in neutropenia and fatigue, and early hints of antitumor activity. In this commentary we give a brief historical perspective of the halichondrins and put into context eribulin mesylate as a novel tubulin modulator.
The Role of Redaction Criticism in the Evaluation of a Textual Variant: Another Look at 1QIsaª XXXII 14 (38:21–22)
Authors: Stromberg Jacob 
Published: June 2009

AbstractWith the discovery of the Dead Sea Scrolls, new emphasis has been placed on the extent to which the last stages of the formation of the Hebrew Bible have been preserved in early manuscripts. It is very widely held that such manuscript evidence comes in 1QIsaª XXXII 14. Here, Isa 38:21–22, which commentators suspected were secondary long before the discovery of the scrolls, are written in a secondary hand partly down the margin. This has led to the conclusion that 1QIsaª preserves an earlier unexpanded form of this passage. In this study, I argue that, despite the validity of this approach and attractiveness of this specific case, 1QIsaª XXXII 14 more likely reflects an omission. It will be seen that a redactional analysis of Isa 38, informed by the parallel in 2 Kgs 20, illuminates the text-critical evaluation of 1QIsa&ordf XXXII 14.
Economic Crisis, Henryk Grossman and the Responsibility of Socialists
Authors: Kuhn Rick 
Published: June 2009

AbstractHenryk Grossman's discussion of economic crises was designed to complement his Leninist understanding of politics. For Grossman, as for Marx, the fundamental contradiction of capitalist production is between the unlimited scope for expanding the output of use-values and restrictions imposed by the framework of producing profits. The increasing weight of capitalists' outlays on dead compared to living labour, which is the only source of new value, gives rise to the system's tendency to break down and, hence, to economic crises. Deep financial crises can only be understood in the context of developments in production and particularly movements in the rate of profit. The initial widespread hostility to Grossman's development of Marxist economics can mainly be explained in terms of the logics of Social-Democratic and Stalinist politics. In contrast to dominant views on the Left today, the Marxist tradition in which Grossman stood places the construction of organisations capable of assisting the working class' conquest of political power at the heart of the responsibility of socialists. Grossman's political practice expressed his understanding of the close relationship between capitalism's breakdown tendency and the importance of building a revolutionary party.
Apocalyptic Sublime: On the Brighton Photo-Biennial
Authors: Edwards Steve 
Published: June 2009

AbstractBased on an account of the Brighton Photo-Biennial Memory of Fire: The War of Images and Images of War, curated by Julian Stallabrass in late 2008, this essay considers the photographic coverage of the recent imperialist interventions in the Middle East. Taking its cue from Stallabrass's event, it reflects on the decline of documentary and photojournalism since the Vietnam War and the current attenuated politics of the media. It argues that the problem of the sublime extends beyond the current genre of 'aftermath'-photography and asks what might constitute a more cognitively adequate politics of the image.
Financialised Capitalism: Crisis and Financial Expropriation
Authors: Lapavitsas Costas 
Published: June 2009

AbstractThe current crisis is one outcome of the financialisation of contemporary capitalism. It arose in the USA because of the enormous expansion of mortgage-lending, including to the poorest layers of the working class. It became general because of the trading of debt by financial institutions. These phenomena are integral to financialisation. During the last three decades, large enterprises have turned to open markets to obtain finance, forcing banks to seek alternative sources of profit. One avenue has been provision of financial services to individual workers. This trend has been facilitated by the retreat of public provision from housing, pensions, education, and so on. A further avenue has been to adopt investment-banking practices in open financial markets. The extraction of financial profits directly out of personal income constitutes financial expropriation. Combined with investment-banking, it has catalysed the current gigantic crisis. More broadly, financialisation has sustained the emergence of new layers of rentiers, defined primarily through their relation to the financial system rather than ownership of loanable capital. Finally, financialisation has posed important questions regarding finance-capital and imperialism.
Firing Back: Against the Tyranny of the Market 2: Global Turbulence: Social Activists' and State Responses to Globalization: Globalization and Inequality: Neoliberalism's Downward Spiral: Anti-Capitalism: A Marxist Introduction
Authors: Westra Richard 
Published: June 2009

AbstractThis article reviews a cross-section of the globalisation-literature written prior to the unfolding economic crisis of 2007. It assesses the literature in terms of its apprehending of changes in capitalism and the prospects for social change that are envisioned.
Gramsci storico. Una lettura dei 'Quaderni del carcere'
Authors: Filippini Michele 
Published: June 2009

AbstractThe review article reconstructs the reception of Gramsci's writings in Italy from the postwar-period to the present. Compared to the Italian debate that has given little attention to Gramsci's writings, except for in some periods such as the 1970s, Gramsci's fortune has continued to grow internationally. Recent Italian contributions, such as the book of Alberto Bugio, Grasmci storico, criticised in this review, remain indebted to an historicist approach that does not allow a use of Gramscian categories as an optic for interpreting and enacting the transformation of the present. The analysis concentrates on concepts such as 'passive revolution', 'fascism', 'Taylorism' and 'bureaucracy'.
Reconstruction and Perceptual Experience: Further Thoughts on Psychoanalytic Listening
Authors: Schwaber Evelyne Albrecht 
Published: June 2009

Freud's monumental shift to the fantasy theory heralded the view that “it is psychical and not material reality” which is our sole domain of inquiry. Yet despite theoretical agreement and cogent technical admonitions against concerning ourselves with absolute or “external” truth, psychoanalytic listening betrays a stance in which the analyst attunes to a reality other than that of the patient's inner world, assuming the position of arbiter—even if a silent one—of what is or is not “distorted” in the patient's perceptual experience. The central impact of perception as a significant component of the patient's inner experience—past and present—goes unattended. Clinical examples from differing theoretical persuasions are reviewed to demonstrate this occurrence. An alternative mode of listening is considered which assumes an underlying shift in outlook, suspending any notion that we can “know” what is “correct” in the patient's perception, while sharpening attunement to its clinical impact—as may be evidenced by a shift in affect or state, a turn of phrase, or the transient appearance of a symptom or old behavior. It is argued that such a stance will lead to a more singular focus on the patient's psychic reality, permitting the emergence of a deepening realm of psychic phenomena, enhancing the capacity of self-observation, and richly facilitating the reconstructive process.
Journal of the American Psychoanalytic Association: A Retrospective (1953–1972)
Authors: Frosch John 
Published: June 2009

In this article, as Editor Emeritus, I review the early evolution of the Journal. It began with the Bulletin, of which I was Editor. It became necessary to give more attention and space to the publication of group discussions and panels. The early days of the Journal were characterized at times by internecine strife of a personal, political, and scientific nature. My ability to deal with this situation was hampered by my lack of knowledge, and even an amateurish quality concerned with editing a journal, although I had had considerable experience in editing The Annual Survey of Psychoanalysis. Out of the realization of the impact of this strife on the scientific activities of the Journal, grew the firm determination to emphasize the role of the Editor and the Journal as free from the political fluctuations that characterized the Association from time to time. This was essential in establishing freedom from pressure, and autonomy insofar as the scientific activities of the Journal were concerned. It was indicated especially in setting up the criteria for selection of papers, so as to create a climate of fairness and objectivity. These criteria are stated in the article. How the various problems mentioned above were dealt with is described in this contribution.