bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Levels of Nrf2 Determine Chemoresistance in Type II Endometrial Cancer
Authors: Jiang Tao , Chen Ning , Zhao Fei , Wang Xiao-Jun , Kong Beihua , Zheng Wenxin , Zhang Donna D. 
Published: June 2010

Abstract
Type II endometrial cancer, which mainly presents as serous and clear cell types, has proved to be the most malignant and recurrent carcinoma among various female genital malignancies. The transcription factor Nrf2 was first described as having chemopreventive activity. Activation of the Nrf2-mediated cellular defense response protects cells against the toxic and carcinogenic effects of environmental insults by upregulating an array of genes that detoxify reactive oxygen species and restore cellular redox homeostasis. However, the cancer-promoting role of Nrf2 has recently been revealed. Nrf2 is constitutively upregulated in several types of human cancer tissues and cancer cell lines. Furthermore, inhibition of Nrf2 expression sensitizes cancer cells to chemotherapeutic drugs. In this study, the constitutive level of Nrf2 was compared in different types of human endometrial tumors. It was found that Nrf2 was highly expressed in endometrial serous carcinoma (ESC), whereas complex hyperplasia and endometrial endometrioid carcinoma (EEC) had no or marginal expression of Nrf2. Likewise, the ESC-derived SPEC-2 cell line had a higher level of Nrf2 expression and was more resistant to the toxic effects of cisplatin and paclitaxel than the Ishikawa cell line, which was generated from EEC. Silencing of Nrf2 rendered SPEC-2 cells more susceptible to chemotherapeutic drugs, whereas it had a limited effect on Ishikawa cells. Inhibition of Nrf2 expression by overexpressing Keap1 sensitized SPEC-2 cells or SPEC-2–derived xenografts to chemotherapeutic treatments using both cell culture and severe combined immunodeficient mouse models. Collectively, we provide a molecular basis for the use of Nrf2 inhibitors to increase the efficacy of chemotherapeutic drugs and to combat chemoresistance, the biggest obstacle in chemotherapy. Cancer Res; 70(13); 5486–96. ©2010 AACR.
Cancer Stem Cells and Self-renewal
Authors: O'Brien Catherine Adell , Kreso Antonija , Jamieson Catriona H.M. 
Published: June 2010

Abstract
The cancer stem cell (CSC) or cancer-initiating cancer (C-IC) model has garnered considerable attention over the past several years since Dick and colleagues published a seminal report showing that a hierarchy exists among leukemic cells. In more recent years, a similar hierarchical organization, at the apex of which exists the CSC, has been identified in a variety of solid tumors. Human CSCs are defined by their ability to: (i) generate a xenograft that histologically resembles the parent tumor from which it was derived, (ii) be serially transplanted in a xenograft assay thereby showing the ability to self-renew (regenerate), and (iii) generate daughter cells that possess some proliferative capacity but are unable to initiate or maintain the cancer because they lack intrinsic regenerative potential. The emerging complexity of the CSC phenotype and function is at times daunting and has led to some confusion in the field. However, at its core, the CSC model is about identifying and characterizing the cancer cells that possess the greatest capacity to regenerate all aspects of the tumor. It is becoming clear that cancer cells evolve as a result of their ability to hijack normal self-renewal pathways, a process that can drive malignant transformation. Studying self-renewal in the context of cancer and CSC maintenance will lead to a better understanding of the mechanisms driving tumor growth. This review will address some of the main controversies in the CSC field and emphasize the importance of focusing first and foremost on the defining feature of CSCs: dysregulated self-renewal capacity. Clin Cancer Res; 16(12); 3113–20. ©2010 AACR.
The Difficulty of Targeting Cancer Stem Cell Niches
Authors: LaBarge Mark A. 
Published: June 2010

Abstract
Normal stem cell niches typically are identified by their distinctive anatomical features and by association with tissue-specific stem cells. Identifying cancer stem cell (CSC) niches presents a special problem because there are few if any common anatomical features among tumors, and the physical phenotypes that reportedly describe the CSCs as entities may be subject to the host's microenvironment, sex, and tumor stage. Irrespective of a niche's location, the occupant's phenotype, or the precise molecular composition, all niches must do basically the same thing: maintain the activities in a stem cell that define it as such. Therefore, a potentially successful strategy, both for elaborating a molecular and cellular portrait of a CSC niche, and for therapeutically targeting them, is to identify components in the tumor microenvironment that are required for maintaining the functions of self-renewal, differentiation, and quiescence in the face of cytotoxic therapeutic regimens. Clin Cancer Res; 16(12); 3121–9. ©2010 AACR.
Targeting Wnt Signaling: Can We Safely Eradicate Cancer Stem Cells?
Authors: Takahashi-Yanaga Fumi , Kahn Michael 
Published: June 2010

Abstract
The Wnt signaling pathways have been conserved throughout evolution and regulate cell proliferation, morphology, motility, and fate during embryonic development. These pathways also play important roles throughout adult life to maintain homeostasis of tissues including skin, blood, intestine, and brain by regulating somatic stem cells and their niches. Aberrant regulation of the Wnt pathway leads to neoplastic proliferation in these same tissues. It has been suggested that Wnt signaling is also involved in the regulation of cancer stem cells (CSC), because there are many similarities in the signaling pathways that regulate normal adult stem cells and CSC. In this Perspective, we have focused on the Wnt/β-catenin signaling pathway, which is the most intensively studied and best characterized Wnt signaling pathway. We provide an overview on the function of the Wnt/β-catenin signaling pathway in CSC, and the possibility of the development of novel therapeutics to target this pathway. Clin Cancer Res; 16(12); 3153–62. ©2010 AACR.
Development of an Integrated Genomic Classifier for a Novel Agent in Colorectal Cancer: Approach to Individualized Therapy in Early Development
Authors: Pitts Todd M. , Tan Aik Choon , Kulikowski Gillian N. , Tentler John J. , Brown Amy M. , Flanigan Sara A. , Leong Stephen , Coldren Christopher D. , Hirsch Fred R. , Varella-Garcia Marileila , Korch Christopher , Eckhardt S. Gail 
Published: June 2010

Abstract
Background: A plethora of agents is in early stages of development for colorectal cancer (CRC), including those that target the insulin-like growth factor I receptor (IGFIR) pathway. In the current environment of numerous cancer targets, it is imperative that patient selection strategies be developed with the intent of preliminary testing in the latter stages of phase I trials. The goal of this study was to develop and characterize predictive biomarkers for an IGFIR tyrosine kinase inhibitor, OSI-906, that could be applied in CRC-specific studies of this agent.
Methods: Twenty-seven CRC cell lines were exposed to OSI-906 and classified according to IC50 value as sensitive (≤1.5 μmol/L) or resistant (&gt;5 μmol/L). Cell lines were subjected to immunoblotting and immunohistochemistry for effector proteins, IGFIR copy number by fluorescence in situ hybridization, KRAS/BRAF/phosphoinositide 3-kinase mutation status, and baseline gene array analysis. The most sensitive and resistant cell lines were used for gene array and pathway analyses, along with shRNA knockdown of highly ranked genes. The resulting integrated genomic classifier was then tested against eight human CRC explants in vivo.
Results: Baseline gene array data from cell lines and xenografts were used to develop a k-top scoring pair (k-TSP) classifier, which, in combination with IGFIR fluorescence in situ hybridization and KRAS mutational status, was able to predict with 100% accuracy a test set of patient-derived CRC xenografts.
Conclusions: These results indicate that an integrated approach to the development of individualized therapy is feasible and should be applied early in the development of novel agents, ideally in conjunction with late-stage phase I trials. Clin Cancer Res; 16(12); 3193–204. ©2010 AACR.
Biobehavioral, Immune, and Health Benefits following Recurrence for Psychological Intervention Participants
Authors: Andersen Barbara L. , Thornton Lisa M. , Shapiro Charles L. , Farrar William B. , Mundy Bethany L. , Yang Hae-Chung , Carson William E. 
Published: June 2010

AbstractPurpose: A clinical trial was designed to test the hypothesis that a psychological intervention could reduce the risk of cancer recurrence. Newly diagnosed regional breast cancer patients (n = 227) were randomized to the intervention-with-assessment or the assessment-only arm. The intervention had positive psychological, social, immune, and health benefits, and after a median of 11 years the intervention arm was found to have reduced the risk of recurrence (hazard ratio, 0.55; P = 0.034). In follow-up, we hypothesized that the intervention arm might also show longer survival after recurrence. If observed, we then would examine potential biobehavioral mechanisms.Experimental Design: All patients were followed; 62 recurred. Survival analyses included all 62. Upon recurrence diagnosis, those available for further biobehavioral study were accrued (n = 41, 23 intervention and 18 assessment). For those 41, psychological, social, adherence, health, and immune (natural killer cell cytotoxicity, T-cell proliferation) data were collected at recurrence diagnosis and 4, 8, and 12 months later.Results: Intent-to-treat analysis revealed reduced risk of death following recurrence for the intervention arm (hazard ratio, 0.41; P = 0.014). Mixed-effects follow-up analyses with biobehavioral data showed that all patients responded with significant psychological distress at recurrence diagnosis, but thereafter only the intervention arm improved (P values &lt; 0.023). Immune indices were significantly higher for the intervention arm at 12 months (P values &lt; 0.017).Conclusions: Hazards analyses augment previous findings in showing improved survival for the intervention arm after recurrence. Follow-up analyses showing biobehavioral advantages for the intervention arm contribute to our understanding of how improved survival was achieved. Clin Cancer Res; 16(12); 3270–8. ©2010 AACR.
Continuous Docetaxel Chemotherapy Improves Therapeutic Efficacy in Murine Models of Ovarian Cancer
Authors: De Souza Raquel , Zahedi Payam , Moriyama Eduardo H. , Allen Christine J. , Wilson Brian C. , Piquette-Miller Micheline 
Published: June 2010

AbstractOvarian cancer is known as the silent killer for being asymptomatic until late stages. Current first-line treatment consists of debulking surgery followed by i.v. chemotherapeutics administered intermittently, which leads to insufficient drug concentrations at tumor sites, accelerated tumor proliferation rates, and drug resistance, resulting in an overall median survival of only 2 to 4 years. For these reasons, more effective treatment strategies must be developed. We have investigated a localized, continuous chemotherapy approach in tumor models of human and murine ovarian cancers using the antineoplastic agent docetaxel. We show here that continuous docetaxel therapy is considerably more efficacious than intermittent therapy, resulting in a greater decrease in tumor burden and ascites fluid accumulation. Immunohistochemical analyses show that continuous chemotherapy abrogates tumor cell proliferation and angiogenesis to the tumor microenvironment, leading to greater tumor cell death than intermittent docetaxel therapy. Overall, our results show greater therapeutic advantages of continuous over intermittent chemotherapy in the treatment of ovarian cancer. Mol Cancer Ther; 9(6); 1820–30. ©2010 AACR.
Cyclooxygenase-Deficient Pancreatic Cancer Cells Use Exogenous Sources of Prostaglandins
Authors: Omura Noriyuki , Griffith Margaret , Vincent Audrey , Li Ang , Hong Seung-Mo , Walter Kimberly , Borges Michael , Goggins Michael 
Published: June 2010

Abstract
Genes that are differentially expressed in pancreatic cancers and under epigenetic regulation are of considerable biological and therapeutic interest. We used global gene expression profiling and epigenetic treatment of pancreatic cell lines including pancreatic cancer cell lines, pancreatic cancer–associated fibroblasts, and cell lines derived from nonneoplastic pancreata. We examined expression and epigenetic alterations of cyclooxygenase-1 (COX-1) and COX-2 in pancreatic cancers and normal pancreas and performed proliferation, knockdown, and coculture experiments to understand the role of stromal sources of prostaglandins for pancreatic cancers. We identify COX-1 as a gene under epigenetic regulation in pancreatic cancers. We find that COX-1 expression is absent in many pancreatic cancer cells and some of these cancers also lack COX-2 expression. Suspecting that such cancers must rely on exogenous sources of prostaglandins, we show that pancreatic cancer stromal cells, such as fibroblasts expressing COX-1 and COX-2, are a likely source of prostaglandins for pancreatic cancer cells deficient in COX. Knocking down the prostaglandin transporter multidrug resistance–associated protein-4 in fibroblasts suppresses the proliferation of cocultured pancreatic cancer cells lacking COX. Pancreatic cancers that lack COX can use exogenous sources of prostaglandins. Blocking multidrug resistance–associated protein-4 may be a useful therapeutic strategy to deplete COX-deficient pancreatic cancers of prostaglandins. Mol Cancer Res; 8(6); 821–32. ©2010 AACR.
Cancer-Associated Fibroblasts Derived from EGFR-TKI–Resistant Tumors Reverse EGFR Pathway Inhibition by EGFR-TKIs
Authors: Mink Sheldon R. , Vashistha Surabhi , Zhang Wenxuan , Hodge Amanda , Agus David B. , Jain Anjali 
Published: June 2010

Abstract
Epidermal growth factor receptor (EGFR) plays a critical role in oncogenesis, which makes it an attractive target for pharmacologic inhibition. Yet, EGFR inhibition with tyrosine kinase inhibitors (TKI) does not result in a measurable and sustainable clinical benefit in a vast majority of tumors. This emphasizes the need for further investigations into resistance mechanisms against EGFR-TKIs. We previously reported the generation of an in vivo adenocarcinoma model of EGFR-TKI–acquired resistance that was devoid of the known mechanisms of resistance. Using this same xenograft model, we now show that the tumor stroma plays an important role in limiting responsiveness to EGFR-TKIs. EGFR-TKI–resistant tumors display increased surface expression of CD44hi/CD24lo and markers of epithelial to mesenchymal transition (EMT), SNAI1, and N-cadherin. An in vivo green fluorescent protein–tagging approach reveals that the tumor stroma of the EGFR-TKI–resistant tumors is distinct in that 24% of its cancer-associated fibroblast (CAF) population is composed of EMT-derived tumor cells that represent the in vivo escape from EGFR-TKIs. We further show that EMT subpopulation–harboring CAFs isolated from the EGFR-TKI–resistant tumors are tumorigenic and express the biomarker of gefitinib resistance, epithelial membrane protein-1. Finally, we provide evidence that paracrine factors secreted from the EGFR-TKI–resistant CAFs mitigate the EGFR-TKI–mediated blockade of pEGFR and pMAPK in cocultured tumor cells, regardless of their EGFR mutational status. This is the first demonstration that the tumor stroma is modified with acquisition of EGFR-TKI resistance and that it further contributes in promoting drug resistance. Mol Cancer Res; 8(6); 809–20. ©2010 AACR.
Meat Processing and Colon Carcinogenesis: Cooked, Nitrite-Treated, and Oxidized High-Heme Cured Meat Promotes Mucin-Depleted Foci in Rats
Authors: Santarelli Raphaëlle L. , Vendeuvre Jean-Luc , Naud Nathalie , Taché Sylviane , Guéraud Françoise , Viau Michelle , Genot Claude , Corpet Denis E. , Pierre Fabrice H.F. 
Published: June 2010

Abstract
Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 × 2 × 2 × 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high-heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P &lt; 0.05). This nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make nonpromoting processed meat. Cancer Prev Res; 3(7); 852–64. ©2010 AACR.
Lakī and Kurdish
Authors: Shahsavari Faramarz 
Published: June 2010

AbstractThis paper aims at verifying the traditional set of phonetic changes, defined by D. N. Mackenzie as the main distinctive feature of the Kurdish dialects, with regard to Lakī having yet no clear affiliation in the Iranian dialectology. It is usually considered to be a dialect of Kurdish, sometimes a transitional dialect between Kurdish and Luri, and even a separate idiom.
The Dialect of Jowshaqan Part One: Phonology, Morphology and Syntax
Authors: Borjian Habib 
Published: June 2010

AbstractThis article presents the grammar of Jowshaqani, a Central Iranian dialect. Like other members of this group, Jowshaqani has its own peculiarities; for instance, it has a rich inventory of personal pronouns distinguished by gender in the 3rd person singular, as do verb endings: nen ate “he comes”, néna atea “she comes”, etc. The past tenses of transitive verbs are inflected ergatively, with the agential affixes, which float through the sentence yielding complex syntactic structures.
Some Notes on the Caspian Energy and Ethnic Conflicts in the Caucasus
Authors: Mousavi Mohammad 
Published: June 2010

AbstractIn the past two decades, the transportation of Caspian oil and gas resources to the international markets has been one of the most controversial and pressing issues in regional politics. Possibly, this is due to the fact that it is more than just an economic problem, having also a visible security and geopolitical aspect. Hence, pipeline competition has fuelled both rivalry and cooperation among existing and potential transit countries. Particularly, the routes through the Caucasus are the most problematic, as the transit corridors through Russia, Azerbaijan Republic, Georgia, and further Turkey have faced with various ethnic conflicts in these countries. In the 1990s, these conflicts played a crucial role in increasing the risk of Caspian oil transit through the Caucasus and Russia. The ethnicities in this region have used the pipeline politics more as a bargaining chip vis-à-vis their central governments for a better position, and less as a pretext for separation. The international political environment, such as the September 11 attack on the U.S. soil and the following global “war on terror” led by the United States, have already undermined such ethnic bargaining power against the governments and have shifted the separatist trends to an inferior position. This paper is a brief re-examination of the situation concerning the energy transit and the ethnic conflicts in the region.
Monitoring of low molecular weight heparin anticoagulation during haemodialysis with a Sonoclot Analyzer
Authors: Schött Ulf , Nilsson Lars Göran , Broman Marcus , Engström Martin 
Published: June 2010

Objectives: Sonoclot was used in this study to monitor low molecular weight heparin (LMWH) during haemodialysis. Material and Methods: Two different intravenous doses (standard / half-dose) of dalteparin were studied in eight patients. Blood was sampled for coagulation analyses with Sonoclot, thrombin-antithrombin (TAT) and anti-Xa. A visual fibrin deposition score (VFS) in the venous drip chamber was also evaluated. Results: All patients completed their dialysis. There was a progressive increase in TAT levels, which correlated to the dalteparin dose. Significant differences (p<0.05) were found for TAT, VFS and Sonoclot celite-activated clotting time (SonACT) between the different LMWH dosages. TAT and Sonoclot correlated to each other, but not to the VFS. SonACT was significantly increased at two hours, with the high dalteparin dose compared to the lower dose. Conclusion: Both Sonoclot and TAT failed to predict the VFS. No patient had any clinical clotting events and all dialyses were completed successfully.
Preoperative therapeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study
Authors: Dronkers JJ , Lamberts H. , Reutelingsperger IMMD , Naber RH , Dronkers-Landman CM , Veldman A. , van Meeteren NLU 
Published: June 2010

Objective: Investigation of the feasibility and preliminary effect of a short-term intensive preoperative exercise programme for elderly patients scheduled for elective abdominal oncological surgery. Design: Single-blind randomized controlled pilot study. Setting: Ordinary hospital in the Netherlands. Subjects: Forty-two elderly patients (>60 years). Interventions: Patients were randomly assigned to receive a short-term intensive therapeutic exercise programme to improve muscle strength, aerobic capacity, and functional activities, given in the outpatient department (intervention group; n =22), or home-based exercise advice (control group; n=20). Main measures: Parameters of feasibility, preoperative functional capacity and postoperative course. Results: The intensive training programme was feasible, with a high compliance and no adverse events. Respiratory muscle endurance increased in the preoperative period from 259 ± 273 to 404 ± 349 J in the intervention group and differed significantly from that in the control group (350 ± 299 to 305 ± 323 J; P<0.01). Timed-Up-and-Go, chair rise time, LASA Physical Activity Questionnaire, Physical Work Capacity and Quality of Life (EORTC-C30) did not reveal significant differences between the two groups. There was no significant difference in postoperative complications and length of hospital stay between the two groups. Conclusion: The intensive therapeutic exercise programme was feasible and improved the respiratory function of patients due to undergo elective abdominal surgery compared with home-based exercise advice.