bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Cryogenian (Neoproterozoic) glacial and post-glacial successions at the southern margin of the Congo Craton, northern Namibia: facies, palaeogeography and hydrocarbon perspective
Authors: Bechstädt Thilo , Jäger Hartmut , Spence Guy , Werner Georg 
Published: October 2009

Abstract
The geological paradox of at least two Neoproterozoic glacial intervals at tropical latitudes intercalated within carbonates remains an unsolved puzzle. Several conceptual models have been proposed to explain these apparent rapid swings between climatic extremes and the associated isotopic changes in sea-water chemistry. In Oman, post-glacial transgressive sedimentary successions represent important hydrocarbon source rocks. Source rock characteristics of Neoproterozoic post-glacial successions in other parts of the world (even if not directly correlatable) are, therefore, of special economic interest.
This paper concentrates on the Ghaub Formation diamictite interval in northern Namibia and the major environmental change in the aftermath of the assumed glaciation. The relationship of the post-glacial sediments with the underlying different types of cap carbonate and diamictite successions is discussed, and a model of the succession of events is presented. The palaeotopography, caused mostly by ongoing tectonic activity including uplift on the scale of thousands of metres, strongly influenced the petroleum system created and played an important role for the hydrocarbon prospectivity of this post-glacial succession. Tectonic activity on the shelf of the southern margin of the Congo Craton was repeated, and different sub-basins were created before, during and after the Ghaub glaciation. The newly formed relief was flooded, and the different sub-basins were affected by restricted circulation for quite some time. This general scenario bears many similarities to the late Ordovician–early Silurian petroleum system, also formed during post-glacial sea-level rise.
A New Hybrid Algorithm for Variational Inclusions, Generalized Equilibrium Problems, and a Finite Family of Quasi-Nonexpansive Mappings
Authors: Cholamjiak Prasit , Suantai Suthep 
Published: October 2009

AbstractWe proposed in this paper a new iterative scheme for finding common elements of the set of fixed points of a finite family of quasi-nonexpansive mappings, the set of solutions of variational inclusion, and the set of solutions of generalized equilibrium problems. Some strong convergence results were derived by using the concept of "Equation missing"-mappings for a finite family of quasi-nonexpansive mappings. Strong convergence results are derived under suitable conditions in Hilbert spaces.
Coincidence Theorems for Certain Classes of Hybrid Contractions
Authors: Singh SL , Mishra SN 
Published: October 2009

AbstractCoincidence and fixed point theorems for a new class of hybrid contractions consisting of a pair of single-valued and multivalued maps on an arbitrary nonempty set with values in a metric space are proved. In addition, the existence of a common solution for certain class of functional equations arising in dynamic programming, under much weaker conditions are discussed. The results obtained here in generalize many well known results.
CXC Receptor-1 Silencing Inhibits Androgen-Independent Prostate Cancer
Authors: Shamaladevi Nagarajarao , Lyn Dominic A. , Escudero Diogo O. , Lokeshwar Bal L. 
Published: October 2009

Abstract
The CXC receptor-1 (CXCR1) is a coreceptor for interleukin-8 (IL-8) and is expressed on both normal and tumor cells. The function of CXCR1 in prostate cancer was investigated by silencing its expression, using RNA interference. We established stable cell colonies of PC-3 cells, depleted of CXCR1, using lentiviral plasmids (pLK0.1puro) generating small hairpin RNA (shRNA) against CXCR1 mRNA. Stable shRNA transfectants (PLK1–PLK5) that express significantly reduced CXCR1 mRNA (≥90% down) and protein (≥43% down) or vector-only transfectants (PC-3V) were characterized. PLK cells showed reduced cell proliferation (down, ≥66%), due to cell cycle arrest at G1-S phase, decreases in Cyclin D1, CDK4, phosphorylated Rb, and extracellular signal-regulated kinase 1/2 levels compared with those in PC-3V cells. CXCR1 depletion lead to increases in spontaneous apoptosis by mitochondria-mediated intrinsic mechanism and increases in proapoptotic proteins (BAD, 40%; BAX, 12%), but decreases in antiapoptotic proteins (BCL2, down 38%; BCLxL, 20%). PLK2 cells grew as slow-growing tumors (decrease of 54%), compared with that of PC3V tumors in athymic mice. Ex vivo analyses of PLK2 tumor tissues showed reduced expression of Cyclin D1 and vascular endothelial growth factor, and increased apoptosis activity. Other IL-8–expressing prostate cancer cell lines also exhibited similar phenotypes when CXCR1 was depleted by CXCR1 shRNA transfection. In contrast to these cells, CXCR1 depletion had little effect on IL-8 ligand–deficient LNCaP cells. RNA interference rescue using mutated CXCR1 plasmids reversed the silencing effect of PLK2, thus demonstrating the specificity of phenotypic alteration by CXCR1 shRNA. These studies establish that CXCR1 promotes IL-8–mediated tumor growth. [Cancer Res 2009;69(21):8265–74]
Epigenetic Inactivation of the Circadian Clock Gene BMAL1 in Hematologic Malignancies
Authors: Taniguchi Hiroaki , Fernández Agustin F. , Setién Fernando , Ropero Santiago , Ballestar Esteban , Villanueva Alberto , Yamamoto Hiroyuki , Imai Kohzoh , Shinomura Yasuhisa , Esteller Manel 
Published: October 2009

Abstract
Disruption of circadian rhythms, daily oscillations in biological processes that are regulated by an endogenous clock, has been linked to tumorigenesis. Normal and malignant tissues often show asynchronies in cell proliferation and metabolic rhythms. Cancer chronotherapy takes biological time into account to improve the therapy. However, alterations of the circadian clock machinery genes have rarely been reported in human cancer. Herein, we show that the BMAL1 gene, a core component of the circadian clock, is transcriptionally silenced by promoter CpG island hypermethylation in hematologic malignancies, such as diffuse large B-cell lymphoma and acute lymphocytic and myeloid leukemias. We also describe how BMAL1 reintroduction in hypermethylated leukemia/lymphoma cells causes growth inhibition in colony assays and nude mice, whereas BMAL1 depletion by RNA interference in unmethylated cells enhances tumor growth. We also show that BMAL1 epigenetic inactivation impairs the characteristic circadian clock expression pattern of genes such as C-MYC, catalase, and p300 in association with a loss of BMAL1 occupancy in their respective promoters. Furthermore, the DNA hypermethylation–associated loss of BMAL1 also prevents the recruitment of its natural partner, the CLOCK protein, to their common targets, further enhancing the perturbed circadian rhythm of the malignant cells. These findings suggest that BMAL1 epigenetic inactivation contributes to the development of hematologic malignancies by disrupting the cellular circadian clock. [Cancer Res 2009;69(21):8447–54]
Enhanced Antitumor Activity Induced by Adoptive T-Cell Transfer and Adjunctive Use of the Histone Deacetylase Inhibitor LAQ824
Authors: Vo Dan D. , Prins Robert M. , Begley Jonathan L. , Donahue Timothy R. , Morris Lilah F. , Bruhn Kevin W. , de la Rocha Pilar , Yang Meng-Yin , Mok Stephen , Garban Hermes J. , Craft Noah , Economou James S. , Marincola Francesco M. , Wang Ena , Ribas Antoni 
Published: October 2009

Abstract
Tumors grow in the presence of antigen-specific T cells, suggesting the existence of intrinsic cancer cell escape mechanisms. We hypothesized that a histone deacetylase (HDAC) inhibitor could sensitize tumor cells to immunotherapy because this class of agents has been reported to increase tumor antigen expression and shift gene expression to a proapoptotic milieu in cancer cells. To test this question, we treated B16 murine melanoma with the combination of the HDAC inhibitor LAQ824 and the adoptive transfer of gp100 melanoma antigen-specific pmel-1 T cells. The combined therapy significantly improved antitumor activity through several mechanisms: (a) increase in MHC and tumor-associated antigen expression by tumor cells; (b) decrease in competing endogenous lymphocytes in recipient mice, resulting in a proliferative advantage for the adoptively transferred cells; and (c) improvement in the functional activity of the adoptively transferred lymphocytes. We confirmed the beneficial effects of this HDAC inhibitor as a sensitizer to immunotherapy in a different model of prophylactic prime-boost vaccination with the melanoma antigen tyrosinase-related protein 2, which also showed a significant improvement in antitumor activity against B16 melanoma. In conclusion, the HDAC inhibitor LAQ824 significantly enhances tumor immunotherapy through effects on target tumor cells as well as improving the antitumor activity of tumor antigen-specific lymphocytes. [Cancer Res 2009;69(22):8693–9]
Metabolic Approaches to Treatment of Melanoma
Authors: Hersey Peter , Watts Ralph Neal , Zhang Xu Dong , Hackett John 
Published: October 2009

Abstract
Purpose: Lactate dehydrogenase (LDH) levels in blood of patients with melanoma have proven to be an accurate predictor of prognosis and response to some treatments. Exclusion of patients with high LDH levels from many trials of new treatments has created a need for treatments aimed at patients with high LDH levels. This article reviews the metabolic basis for the association of LDH with prognosis and the treatment initiatives that may be successful in this patient group.
Experimental Design: Review of current literature on the topic.
Results: A number of new treatment initiatives based on manipulation of metabolic pathways in melanoma cells are now available and await evaluation in well-designed clinical trials.
Conclusions: Different cancers may require different metabolic approaches for effective treatment. In view of the high rate of glycolysis in most melanoma cells, approaches based on inhibition of acid excretion from the cells seem particularly attractive. (Clin Cancer Res 2009;15(21):6490–4)
Tumor-Derived Tissue FactorBearing Microparticles Are Associated With Venous Thromboembolic Events in Malignancy
Authors: Zwicker Jeffrey I. , Liebman Howard A. , Neuberg Donna , Lacroix Romaric , Bauer Kenneth A. , Furie Barbara C. , Furie Bruce 
Published: October 2009

Abstract
Purpose: Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factorbearing microparticles in plasma contribute to cancer-associated thrombosis.
Experimental Design: We developed impedance-based flow cytometry to detect, quantitate, and size microparticles in platelet-poor plasma. We evaluated the number of tissue factorbearing microparticles in a cohort of cancer patients of different histologies (N = 96) and conducted a case-control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared with 60 cancer patients of similar age, stage, sex, and diagnosis without known VTE, as well as 22 patients with an idiopathic VTE.
Results: Tissue factorbearing microparticles were detected in patients with advanced malignancy, including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factorbearing microparticles were associated VTE in cancer patients (adjusted odds ratio, 3.72; 95 confidence interval, 1.18-11.76; P = 0.01). In cancer patients without VTE, a retrospective analysis revealed a 1-year cumulative incidence of VTE of 34.8 in patients with tissue factorbearing microparticles versus 0 in those without detectable tissue factorbearing microparticles (Gray test P = 0.002).The median number of tissue factorbearing microparticles in the cancer VTE cohort (7.1 104 microparticles/L) was significantly greater than both the idiopathic VTE and cancerno VTE groups (P = 0.002 and P = 0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which coexpressed the epithelial tumor antigen, MUC-1.
Conclusion: We conclude that tumor-derived tissue factorbearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis. (Clin Cancer Res 2009;15(22):683040)
NKG2D Ligand Expression in Human Colorectal Cancer Reveals Associations with Prognosis and Evidence for Immunoediting
Authors: McGilvray Roger W. , Eagle Robert A. , Watson Nicholas F.S. , Al-Attar Ahmad , Ball Graham , Jafferji Insiya , Trowsdale John , Durrant Lindy G. 
Published: October 2009

Abstract
Purpose: NKG2D (natural killer group 2, member D) binds to cellular ligands of the MIC and ULBP/RAET family. These ligands have restricted expression in normal tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands is thought to be important in carcinogenesis but its prognostic effect has not been investigated in such a large cohort.
Experimental Design: In our study, 462 primary colorectal tumors were screened for the expression of all MIC/ULBP/RAET proteins and NK cell infiltration. Tumor microarray technology was used for the purpose of this investigation.
Results: NKG2D ligands were expressed by the majority of colorectal tumors; however, the level of expression varied considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus 62 months) showed improved patient survival. Tumors expressing high levels of MIC and RAET1G showed improved survival of 77 months over tumors that expressed high levels of one ligand or low levels of both. High-level expression of all ligands was frequent in tumor-node-metastasis stage I tumors, but became progressively less frequent in stages II, III, and IV tumors. Expression of MIC was correlated with NK cellular infiltration.
Conclusion: The observations presented are consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced their expression of NKG2D ligands. The combination of MIC and tumor-node-metastasis stage was found to be the strongest predictor of survival, splitting patients into eight groups and suggesting prognostic value in clinical assessment. Of particular interest were stage I patients with low expression of MIC who had a similar survival to stage III patients, and may be candidates for adjuvant therapy. (Clin Cancer Res 2009;15(22):69937002)
Altered Tissue 3′-Deoxy-3′-[18F]Fluorothymidine Pharmacokinetics in Human Breast Cancer following Capecitabine Treatment Detected by Positron Emission Tomography
Authors: Kenny Laura M. , Contractor Kaiyumars B. , Stebbing Justin , Al-Nahhas Adil , Palmieri Carlo , Shousha Sami , Coombes R. Charles , Aboagye Eric O. 
Published: October 2009

Abstract
Purpose: We showed in preclinical models that thymidylate synthase (TS) inhibition leads to redistribution of the nucleoside transporter, ENT1, to the cell membrane and hence increases tissue uptake of [18F]fluorothymidine (FLT). In this study, we assessed for the first time the altered pharmacokinetics of FLT in patients following administration of capecitabine, a drug whose mode of action has been reported to include TS inhibition.
Experimental Design: We analyzed 10 lesions from six patients with breast cancer by positron emission tomography before and after treatment with capecitabine. Although drug treatment did not alter tumor delivery pharmacokinetic variables (K1 and permeability product surface area) or blood flow, tumor FLT retention variables increased with drug treatment in all but one patient.
Results: The baseline average standardized uptake value at 60 minutes, rate constant for the net irreversible transfer of radiotracer from plasma to tumor (Ki), and unit impulse response function at 60 minutes were 11.11 × 10−5 m2/mL, 4.38 × 10−2 mL plasma/min/mL tissue, and 4.93 × 10−2/min, respectively. One hour after capecitabine administration, the standardized uptake value was 13.55 × 10−5 m2/mL (P = 0.004), Ki 7.40 × 10−2 mL plasma/min/mL tissue (P = 0.004), and impulse response function was 7.40 × 10−2/min (P = 0.002). FLT pharmacokinetics did not change in normal tissues, suggesting that the effect was largely restricted to tumors (P = 0.55).
Conclusions: We have identified FLT positron emission tomography retention parameters that could be used in future early clinical studies to measure the pharmacodynamics of TS inhibitors, as well as for identifying patients who are unlikely to benefit from TS inhibition. (Clin Cancer Res 2009;15(21):6649–57)
Rituximab-Mediated Cell Signaling and Chemo/Immuno-sensitization of Drug-Resistant B-NHL Is Independent of Its Fc Functions
Authors: Vega Mario I. , Huerta-Yepez Sara , Martinez-Paniagua Melisa , Martinez-Miguel Bernardo , Hernandez-Pando Rogelio , González-Bonilla Cesar R. , Chinn Paul , Hanna Nabil , Hariharan Kandasamy , Jazirehi Ali R. , Bonavida Benjamin 
Published: October 2009

AbstractPurpose: Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined with chemotherapy, is used in the treatment of non–Hodgkin's lymphoma (NHL). Rituximab binds to CD20 and inhibits intracellular survival/growth pathways leading to chemo/immunosensitization of tumor cells in vitro. The contribution of rituximab Fc-FcR interaction in signaling is not known. This study examined the role of Fc-FcR interactions in rituximab-induced signaling using rituximab (Fab')2 fragments as well as rituximab devoid of the CH2 Fc-binding domain (CH2−).Experimental Design: Rituximab (CH2−) and rituximab (Fab')2 were tested for their activity on B-NHL cell lines. Cell signaling and sensitization to chemotherapy and immunotherapy were examined. The in vitro studies were validated in mice bearing tumor xenografts.Results: Although the modified antibodies were defective in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity functions, they retained all other biological activities such as inhibition of cell proliferation, induction of cell aggregation, and apoptosis induction. In addition, similar to rituximab, the modified antibodies inhibited the activity of cell survival/growth pathways and their associated transcription factors (e.g., NF-κB, YY1, SP-1), and signal transducers and activators of transcription 3 (STAT-3), and downregulated the expression of antiapoptotic gene products, such as Bcl-2/Bclxl, which regulate drug resistance. The modified antibodies, similar to rituximab, sensitized resistant B-NHL cells to both CDDP and Fas ligand–induced apoptosis. Furthermore, treatment of nude mice bearing Raji tumor cell xenografts with the combination of rituximab (Fab')2 or rituximab and CDDP resulted in similar and significant inhibition of tumor growth.Conclusion: These findings reveal that rituximab-mediated inhibition of intracellular signaling pathways and leading to chemo/immuno-sensitization of resistant B-NHL is Fc independent. (Clin Cancer Res 2009;15(21):6582–94)
Serum Molecular Signatures of Weight Change during Early Breast Cancer Chemotherapy
Authors: Keun Hector C. , Sidhu Jasmin , Pchejetski Dmitry , Lewis Jacqueline S. , Marconell Helena , Patterson Michael , Bloom Steven R. , Amber Vian , Coombes R. Charles , Stebbing Justin 
Published: October 2009

Abstract
Purpose: Weight gain in women receiving chemotherapy for breast cancer is associated with a higher risk of recurrence but its mechanisms are poorly understood.
Experimental Design: To investigate this, we assessed the metabolic, cytokine, and appetite-related peptide alterations during adjuvant chemotherapy for early breast cancer in postmenopausal women, and correlated these with body mass measurements. Specifically, we performed global metabolic profiling using 1H-nuclear magnetic resonance spectroscopy of sequential sera, examined ghrelin immunoreactivity, RIAs for GLP-1 and peptide YY, and electrochemiluminescent cytokine analyses (tumor necrosis factor-α and interleukin-6) on sequential samples.
Results: In those who gained &gt;1.5 kg, several metabolite levels were positively associated with weight gain, specifically lactate, which was 63.5% greater in patients with increased body weight during chemotherapy compared with those with no weight gain (P &lt; 0.01; the prespecified primary end point). A strong correlation (r = 0.7, P &lt; 0.001) was detected between the rate of weight change and serum lactate levels, and on average, lactate levels exhibited the greatest metabolic response to chemotherapy, increasing by up to 75%. Normalized levels of peptide YY were also observed to be elevated in patients not gaining weight posttreatment (+30% compared with −7% for the weight gain group; P &lt; 10−4). Baseline lactate, alanine, and body fat were all prognostic for weight gain (area under the receiver operator characteristic curves, &gt;0.77; P &lt; 0.05). No associations were observed between any other parameter and weight gain, including cytokine levels.
Conclusions: Metabonomics identifies excess energy expenditure pathways perturbed during chemotherapy for breast cancer, and establishes a significant association between serum lactate, body fat, and substantive weight gain during chemotherapy. (Clin Cancer Res 2009;15(21):6716–23)
Enhancing Cancer Vaccine Efficacy via Modulation of the Tumor Microenvironment
Authors: Disis Mary L. 
Published: October 2009

Abstract
The development of therapeutic cancer vaccines is impacted by immunosuppressive elements in the tumor microenvironment. Most immunogenic cancer proteins are “self,” therefore, peripheral tolerance contributes substantially to tumor immune escape. Transforming growth factor β (TGFβ) actively modulates both inflammation and tolerance induction. Combining vaccination with agents that disarm TGFβ will enhance vaccine efficacy. (Clin Cancer Res 2009;15(21):1–3) (Clin Cancer Res 2009;15(21):6476–8)
Has Quantitative Multimodal Imaging of Treatment Response Arrived?
Authors: Yankeelov Thomas E. , Gore John C. 
Published: October 2009

Abstract
Although there have been dramatic increases in the range and quality of information available from noninvasive imaging methods, their application in clinical trials has been limited. One promising approach is to apply imaging techniques in preclinical studies designed to mimic a corresponding clinical trial in order to inform that trial. (Clin Cancer Res 2009;15(21):6473–5)
Estrogenic Promotion of ErbB2 Tyrosine Kinase Activity in Mammary Tumor Cells Requires Activation of ErbB3 Signaling
Authors: Liu Bolin , Ordonez-Ercan Dalia , Fan Zeying , Huang Xiaoping , Edgerton Susan M. , Yang XiaoHe , Thor Ann D. 
Published: October 2009

AbstractIncreasing evidence suggests molecular interactions between erbB2 and other receptor tyrosine kinases, and estrogenic compounds and their cognate receptors. We have recently reported that downregulation of erbB3 abrogates erbB2-mediated tamoxifen resistance in breast cancer cells. On the basis of these data, we hypothesized that erbB3 may play a major role connecting these two sentinel pathways. Interactions were studied using mammary/breast cancer cell lines from wild-type rat c-neu gene transgenic mice and humans. Estradiol promoted cell proliferation and activated erbB2/neu tyrosine kinase, Akt, and mitogen-activated protein kinase signaling exclusively in mammary and breast epithelial cell lines with coexpression of both erbB2 and erbB3. Estradiol action was independent of the transgene promoter (MMTV-LTR) activity, both in vitro and in vivo, as well as c-neu transgene or endogenous erbB2 gene expression. Estrogen induction of cell growth promotion, erbB2/neu activation, and downstream signaling was abrogated by blockade of estrogen receptor (ER) with the pure ER antagonist ICI 182,780 or knockdown of erbB3 expression via specific siRNA. These data suggest that activation of both ER and erbB2/erbB3 signaling is requisite for estrogen-induced mitogenesis and erbB2/neu tyrosine kinase activation.(Mol Cancer Res 2009;7(11):1882–92)