bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer
Authors: Xia Peng , An Han-Xiang , Dang Cheng-Xue , Radpour Ramin , Kohler Corina , Fokas Emmanouil , Engenhart-Cabillic Rita , Holzgreve Wolfgang , Zhong Xiao Yan 
Published: December 2009

Abstract

Background
Alterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA). We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters.

Methods
Peripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu protein.

Results
The content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023). Reduced mtDNA was found often in post menopausal cancer group (P = 0.024). No difference in mtDNA content, in regards to age (p = 0.564), lymph node involvement (p = 0.673), ER (p = 0.877), PR (p = 0.763), and Her-2/neu expression (p = 0.335), was observed.

Conclusion
Early detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer.
Early detection of influenza outbreaks using the DC Department of Health's syndromic surveillance system
Authors: Griffin Beth Ann , Jain Arvind K , Davies-Cole John , Glymph Chevelle , Lum Garret , Washington Samuel C , Stoto Michael A 
Published: December 2009

Abstract

Background
Since 2001, the District of Columbia Department of Health has been using an emergency room syndromic surveillance system to identify possible disease outbreaks. Data are received from a number of local hospital emergency rooms and analyzed daily using a variety of statistical detection algorithms. The aims of this paper are to characterize the performance of these statistical detection algorithms in rigorous yet practical terms in order to identify the optimal parameters for each and to compare the ability of two syndrome definition criteria and data from a children's hospital versus vs. other hospitals to determine the onset of seasonal influenza.

Methods
We first used a fine-tuning approach to improve the sensitivity of each algorithm to detecting simulated outbreaks and to identifying previously known outbreaks. Subsequently, using the fine-tuned algorithms, we examined (i) the ability of unspecified infection and respiratory syndrome categories to detect the start of the flu season and (ii) how well data from Children's National Medical Center (CNMC) did versus all the other hospitals when using unspecified infection, respiratory, and both categories together.

Results
Simulation studies using the data showed that over a range of situations, the multivariate CUSUM algorithm performed more effectively than the other algorithms tested. In addition, the parameters that yielded optimal performance varied for each algorithm, especially with the number of cases in the data stream. In terms of detecting the onset of seasonal influenza, only "unspecified infection," especially the counts from CNMC, clearly delineated influenza outbreaks out of the eight available syndromic classifications. In three of five years, CNMC consistently flags earlier (from 2 days up to 2 weeks earlier) than a multivariate analysis of all other DC hospitals.

Conclusions
When practitioners apply statistical detection algorithms to their own data, fine tuning of parameters is necessary to improve overall sensitivity. With fined tuned algorithms, our results suggest that emergency room based syndromic surveillance focusing on unspecified infection cases in children is an effective way to determine the beginning of the influenza outbreak and could serve as a trigger for more intensive surveillance efforts and initiate infection control measures in the community.
Assessing exposure, uptake and toxicity of silver and cerium dioxide nanoparticles from contaminated environments
Authors: Gaiser Birgit K , Fernandes Teresa F , Jepson Mark , Lead Jamie R , Tyler Charles R , Stone Vicki 
Published: December 2009

Abstract
The aim of this project was to compare cerium oxide and silver particles of different sizes for their potential for uptake by aquatic species, human exposure via ingestion of contaminated food sources and to assess their resultant toxicity. The results demonstrate the potential for uptake of nano and larger particles by fish via the gastrointestinal tract, and by human intestinal epithelial cells, therefore suggesting that ingestion is a viable route of uptake into different organism types. A consistency was also shown in the sensitivity of aquatic, fish cell and human cell models to Ag and CeO2 particles of different sizes; with the observed sensitivity sequence from highest to lowest as: nano-Ag > micro Ag > nano CeO2 = micro CeO2. Such consistency suggests that further studies might allow extrapolation of results between different models and species.
Knowledge, use and ecology of golden thistle (Scolymus hispanicus L.) in Central Spain
Authors: Polo Sandra , Tardío Javier , Vélez-del-Burgo Ainhoa , Molina María , Pardo-de-Santayana Manuel 
Published: December 2009

Abstract

Background
This paper assesses the current ethnobotanical knowledge, use and management of Scolymus hispanicus L. in two localities of Central Spain and the relation with its natural abundance. It also addresses the influence of sociodemographic factors such as age, gender and time living in the village in the variation of knowledge and practice levels.

Methods
During 2007 and 2008, 99 semi-structured interviews and a questionnaire were made to a random stratified sample by sex and age, asking them about their traditional knowledge and practices (use and gathering) of Scolymus hispanicus. A knowledge and practice (KP) index was created based on the answers to the questionnaire.

Results and Discussion

Scolymus hispanicus is still gathered and consumed by 20% and 35% of the informants, respectively. According to the KP index, the knowledge and practice level is similar in both villages. Age and time living in the village are the factors that better explain the variability in the KP level. People living for more than ten years in the village and those older than 60 years have the highest knowledge level, whereas the younger than 19 the lowest.

Conclusions
Our data suggests that the prevalence of ethnobotanical knowledge and uses depends more on the cultural importance of the plant and the transmission of such popular knowledge than on the resource's abundance.
Late treatment with imatinib mesylate ameliorates radiation-induced lung fibrosis in a mouse model
Authors: Li Minglun , Abdollahi Amir , Gröne Hermann-Josef , Lipson Kenneth E , Belka Claus , Huber Peter E 
Published: December 2009

Abstract

Background
We have previously shown that small molecule PDGF receptor tyrosine kinase inhibitors (RTKI) can drastically attenuate radiation-induced pulmonary fibrosis if the drug administration starts at the time of radiation during acute inflammation with present but limited effects against acute inflammation. To rule out interactions of the drug with acute inflammation, we investigated here in an interventive trial if a later drug administration start at a time when the acute inflammation has subsided - has also beneficial antifibrotic effects.

Methods
Whole thoraces of C57BL/6 mice were irradiated with 20 Gy and treated with the RTKI imatinib starting either 3 days after radiation (during acute inflammation) or two weeks after radiation (after the acute inflammation has subsided as demonstrated by leucocyte count). Lungs were monitored and analyzed by clinical, histological and in vivo non-invasive computed tomography as a quantitative measure for lung density and lung fibrosis.

Results
Irradiation induced severe lung fibrosis resulting in markedly reduced mouse survival vs. non-irradiated controls. Both early start of imatinib treatment during inflammation and late imatinib start markedly attenuated the development of pulmonary fibrosis as demonstrated by clinical, histological and qualitative and quantitative computed tomography results such as reduced lung density. Both administration schedules resulted in prolonged lifespans. The earlier drug treatment start resulted in slightly stronger beneficial antifibrotic effects along all measured endpoints than the later start.

Conclusions
Our findings show that imatinib, even when administered after the acute inflammation has subsided, attenuates radiation-induced lung fibrosis in mice. Our data also indicate that the fibrotic fate is not only determined by the early inflammatory events but rather a complex process in which secondary events at later time points are important. Because of the clinical availability of imatinib or similar compounds, a meaningful attenuation of radiation-induced lung fibrosis in patients seems possible.
Long-Term Follow-Up of Cisplatin Combination Chemotherapy in Patients With Disseminated Nonseminomatous Germ Cell Tumors: Is a Postchemotherapy Retroperitoneal Lymph Node Dissection Needed After Complete Remission?
Authors: Ehrlich Yaron , Brames Mary J. , Beck Stephen D.W. , Foster Richard S. , Einhorn Lawrence H. 
Published: December 2009

Purpose Controversy arises regarding the optimal management of patients with nonseminomatous germ cell tumor (NSGCT) who achieve a serologic and radiographic complete remission (CR) to systemic chemotherapy. Some authors recommend postchemotherapy retroperitoneal lymph node dissection (PC-RPLND), whereas others omit surgery and observe these patients. In an attempt to address this question, we report the long-term follow-up of patients treated at Indiana University who were observed without PC-RPLND. Patients and Methods This is a retrospective analysis of patients with NSGCT who achieved a CR to first-line chemotherapy and were monitored without further therapy. CR was defined as normalization of serum tumor markers and resolution of radiographic disease (residual mass < 1 cm). Results One hundred forty-one patients were identified. Five patients (4%) had less than 2 years of follow-up. After a median follow-up of 15.5 years, 12 patients (9%) experienced relapse. Of these 12 patients, eight patients currently have no evidence of disease (NED), and four patients died of disease. The estimated 15-year recurrence-free survival (RFS) and cancer-specific survival rates were 90% and 97%, respectively. The estimated 15-year RFS for good-risk patients (n = 109) versus intermediate- or poor-risk patients (n = 32) was 95% and 73% (P = .001), respectively. Six patients (4%) experienced recurrence in the retroperitoneum, of whom two patients died of disease. Five patients had late relapse (range, 3 to 13 years), including two patients in the retroperitoneum. All five patients currently have NED. Conclusion Patients obtaining a CR after first-line chemotherapy can be safely observed without PC-RPLND. Relapses are rare and potentially curable with further treatment.
Multicenter, Phase II Study of Decitabine for the First-Line Treatment of Older Patients With Acute Myeloid Leukemia
Authors: Cashen Amanda F. , Schiller Gary J. , O'Donnell Margaret R. , DiPersio John F. 
Published: December 2009

Purpose Older patients with acute myeloid leukemia (AML) have limited treatment options because of the lack of effectiveness and the toxicity of available therapies. We investigated the efficacy and toxicity of the hypomethylating agent decitabine as initial therapy in older patients with AML. Patients and Methods In this multicenter, phase II study, patients older than 60 years who had AML (ie, > 20% bone marrow blasts) and no prior therapy for AML were treated with decitabine 20 mg/m2 intravenously for 5 consecutive days of a 4-week cycle. Response was assessed by weekly CBC and bone marrow biopsy after cycle 2 and after each subsequent cycle. Patients continued to receive decitabine until disease progression or an unacceptable adverse event occurred. Results Fifty-five patients (mean age, 74 years) were enrolled and were treated with a median of three cycles (range, one to 25 cycles) of decitabine. The expert-reviewed overall response rate was 25% (complete response rate, 24%). The response rate was consistent across subgroups, including in patients with poor-risk cytogenetics and in those with a history of myelodysplastic syndrome. The overall median survival was 7.7 months, and the 30-day mortality rate was 7%. The most common toxicities were myelosuppression, febrile neutropenia, and fatigue. Conclusion Decitabine given in a low-dose, 5-day regimen has activity as upfront therapy in older patients with AML, and it has acceptable toxicity and 30-day mortality.
Phase I/II Trial of Metronomic Chemotherapy With Daily Dalteparin and Cyclophosphamide, Twice-Weekly Methotrexate, and Daily Prednisone As Therapy for Metastatic Breast Cancer Using Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor Levels As Markers of Response
Authors: Wong Nan Soon , Buckman Robert A. , Clemons Mark , Verma Shailendra , Dent Susan , Trudeau Maureen E. , Roche Kathie , Ebos John , Kerbel Robert , DeBoer Gerrit E. , Sutherland Donald J.A. , Emmenegger Urban , Slingerland Joyce , Gardner Sandra , Pritchard Kathleen I. 
Published: December 2009

Purpose Preclinical studies indicate that metronomic chemotherapy is antiangiogenic and synergistic with other antiangiogenic agents. We designed a phase I/II study to evaluate the safety and activity of adding dalteparin and prednisone to metronomic cyclophosphamide and methotrexate in women with measurable metastatic breast cancer (MBC). Patients and Methods Patients received daily dalteparin and oral cyclophosphamide, twice-weekly methotrexate, and daily prednisone (dalCMP). The primary study end point was clinical benefit rate (CBR), a combination of complete response (CR), partial response (PR), and prolonged stable disease for ≥ 24 weeks (pSD). Secondary end points included time to progression (TTP), duration of response, and overall survival (OS). Biomarker response to treatment was assessed by using plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptors (sVEGFRs) –1 and –2. Results Forty-one eligible patients were accrued. Sixteen (39%) had no prior chemotherapy for MBC; 15 (37%) had two or more chemotherapy regimens for MBC. Toxicities were minimal except for transient grade 3 elevation of liver transaminases in 11 patients (27%) and grade 3 vomiting in one patient (2%). One patient (2%) had CR, six (15%) had PR, and three (7%) had pSD, for a CBR of 10 (24%) of 41 patients. Median TTP was 10 weeks (95% CI, 8 to 17 weeks), and median OS was 48 weeks (95% CI, 32 to 79 weeks). VEGF levels decreased but not significantly, whereas sVEGFR-1 and -2 levels increased significantly after 2 weeks of therapy. There was no correlation between response and VEGF, sVEGFR-1, or sVEGFR-2 levels. Conclusion Metronomic dalCMP is safe, well tolerated, and clinically active in MBC.
Favorable Prognostic Impact of NPM1 Mutations in Older Patients With Cytogenetically Normal De Novo Acute Myeloid Leukemia and Associated Gene- and MicroRNA-Expression Signatures: A Cancer and Leukemia Group B Study
Authors: Becker Heiko , Marcucci Guido , Maharry Kati , Radmacher Michael D. , Mrózek Krzysztof , Margeson Dean , Whitman Susan P. , Wu Yue-Zhong , Schwind Sebastian , Paschka Peter , Powell Bayard L. , Carter Thomas H. , Kolitz Jonathan E. , Wetzler Meir , Carroll Andrew J. , Baer Maria R. , Caligiuri Michael A. , Larson Richard A. , Bloomfield Clara D. 
Published: December 2009

Purpose To analyze the prognostic significance of NPM1 mutations, and the associated gene- and microRNA-expression signatures in older patients with de novo, cytogenetically normal acute myeloid leukemia (CN-AML) treated with intensive chemotherapy. Patients and Methods One hundred forty-eight adults age ≥ 60 years with de novo CN-AML, enrolled onto Cancer and Leukemia Group B protocols 9720 and 10201, were studied at diagnosis for NPM1, FLT3, CEBPA, and WT1 mutations, and gene- and microRNA-expression profiles. Results Patients with NPM1 mutations (56%) had higher complete remission (CR) rates (84% v 48%; P < .001) and longer disease-free survival (DFS; P = .047; 3-year rates, 23% v 10%) and overall survival (OS; P < .001; 3-year rates, 35% v 8%) than NPM1 wild-type patients. In multivariable analyses, NPM1 mutations remained independent predictors for higher CR rates (P < .001) and longer DFS (P = .004) and OS (P < .001), after adjustment for other prognostic clinical and molecular variables. Unexpectedly, the prognostic impact of NPM1 mutations was mainly observed in patients ≥ 70 years. Gene- and microRNA-expression profiles associated with NPM1 mutations were similar across older patient age groups and similar to those in younger (< 60 years) patients with CN-AML. These profiles were characterized by upregulation of HOX genes and their embedded microRNAs and downregulation of the prognostically adverse MN1, BAALC, and ERG genes. Conclusion NPM1 mutations have favorable prognostic impact in older patients with CN-AML, especially those age ≥ 70 years. The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups.
Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation
Authors: Yu Chun-Feng , Peng Wen-Ming , Oldenburg Johannes , Hoch Jochen , Bieber Thomas , Limmer Andreas , Hartmann Gunther , Barchet Winfried , Eis-Hübinger Anna Maria , Novak Natalija 
Published: December 2009

AbstractSignals involved in the commitment of Th17 differentiation are of substantial interest for our understanding of antimicrobial defense mechanisms and autoimmune disorders. Various ways in which myeloid dendritic cells modulate Th17 differentiation have been identified. However, although plasmacytoid dendritic cells (PDCs) are regarded as important players in antiviral/antimicrobial host defense and autoimmune diseases, a putative modulatory role of PDCs in Th17 differentiation has not yet been elucidated in detail. We demonstrated that PDCs are capable of promoting Th17 differentiation in response to TLR7 stimulation. Further, both the differentiation of Th17 cells from naive T cells and the amplification of Th17 effector functions of memory T cells are promoted by PDCs after TLR7 activation. Our data are of strong clinical relevance because TLR7 activation in PDCs might represent one of the missing links between innate and adaptive immune mechanisms and contribute to the amplification of Th17-driven autoimmune disorders as well as viral host defense.
Lactic Acid and Acidification Inhibit TNF Secretion and Glycolysis of Human Monocytes
Authors: Dietl Katrin , Renner Kathrin , Dettmer Katja , Timischl Birgit , Eberhart Karin , Dorn Christoph , Hellerbrand Claus , Kastenberger Michael , Kunz-Schughart Leoni A. , Oefner Peter J. , Andreesen Reinhard , Gottfried Eva , Kreutz Marina P. 
Published: December 2009

Abstract
High concentrations of lactic acid (LA) are found under various pathophysiological conditions and are accompanied by an acidification of the environment. To study the impact of LA on TNF secretion, human LPS-stimulated monocytes were cultured with or without LA or the corresponding pH control. TNF secretion was significantly suppressed by low concentrations of LA (≤10 mM), whereas only strong acidification had a similar effect. This result was confirmed in a coculture model of human monocytes with multicellular tumor spheroids. Blocking synthesis of tumor-derived lactate by oxamic acid, an inhibitor of lactate dehydrogenase, reversed the suppression of TNF secretion in this coculture model. We then investigated possible mechanisms underlying the suppression. Uptake of [3-13C]lactate by monocytes was shown by hyphenated mass spectrometry. As lactate might interfere with glycolysis, the glycolytic flux of monocytes was determined. We added [1,2-13C2]glucose to the culture medium and measured glucose uptake and conversion into [2,3-13C2]lactate. Activation of monocytes increased the glycolytic flux and the secretion of lactate, whereas oxygen consumption was decreased. Addition of unlabeled LA resulted in a highly significant decrease in [2,3-13C2]lactate secretion, whereas a mere corresponding decrease in pH exerted a less pronounced effect. Both treatments increased intracellular [2,3-13C2]lactate levels. Blocking of glycolysis by 2-deoxyglucose strongly inhibited TNF secretion, whereas suppression of oxidative phosphorylation by rotenone had little effect. These results support the hypothesis that TNF secretion by human monocytes depends on glycolysis and suggest that LA and acidification may be involved in the suppression of TNF secretion in the tumor environment.
Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells
Authors: Su Xinming , Ye Jian , Hsueh Eddy C. , Zhang Yanping , Hoft Daniel F. , Peng Guangyong 
Published: December 2009

AbstractAlthough Th17 cells play critical roles in the pathogenesis of many inflammatory and autoimmune diseases, their prevalence among tumor-infiltrating lymphocytes (TILs) and function in human tumor immunity remains largely unknown. We have recently demonstrated high percentages of Th17 cells in TILs from ovarian cancer patients, but the mechanisms of accumulation of these Th17 cells in the tumor microenvironment are still unclear. In this study, we further showed elevated Th17 cell populations in the TILs obtained from melanoma and breast and colon cancers, suggesting that development of tumor-infiltrating CD4+ Th17 cells may be a general feature in cancer patients. We then demonstrated that tumor microenvironmental RANTES and MCP-1 secreted by tumor cells and tumor-derived fibroblasts mediate the recruitment of Th17 cells. In addition to their recruitment, we found that tumor cells and tumor-derived fibroblasts produce a proinflammatory cytokine milieu as well as provide cell–cell contact engagement that facilitates the generation and expansion of Th17 cells. We also showed that inflammatory TLR and nucleotide oligomerization binding domain 2 signaling promote the attraction and generation of Th17 cells induced by tumor cells and tumor-derived fibroblasts. These results identify Th17 cells as an important component of human TILs, demonstrate mechanisms involved in the recruitment and regulation of Th17 cells in tumor microenvironments, and provide new insights relevant for the development of novel cancer immunotherapeutic approaches.