bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Proteomic Analysis of Advanced Serous Ovarian Cancer Using Reverse Phase Protein Array: TGF-β Pathway Signaling Indicates Response to Primary Chemotherapy
Authors: Carey Mark S. , Agarwal Roshan , Gilks Blake , Swenerton Kenneth , Kalloger Steve , Santos Jennifer , Ju Zhenlin , Lu Yiling , Zhang Fan , Coombes Kevin R. , Miller Dianne , Huntsman David , Mills Gordon B. , Hennessy Bryan T. 
Published: May 2010

Abstract
Purpose: Using reverse phase protein array, we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage, high-grade serous ovarian cancer.
Experimental Design: Tumor samples were obtained from 45 patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples, and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by reverse phase protein array. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization and Cox regression to test for the association between protein expression and progression-free survival. A significance level of P ≤ 0.05 was used.
Results: The mean age at diagnosis was 56.8 years. epidermal growth factor receptor, YKL-40, and several transforming growth factor β (TGF-β) pathway proteins [c-jun–NH2–kinase (JNK), JNK phosphorylated at residues 183 and 185, plasminogen activator inhibitor 1, Smad3, TAZ] showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, epidermal growth factor receptor (P &lt; 0.02), JNK (P &lt; 0.01), and Smad3 (P &lt; 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGF-β pathway proteins was unlikely because of false discovery (P &lt; 0.007; Bonferroni adjusted).
Conclusion: TGF-β pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. Clin Cancer Res; 16(10); 2852–60. ©2010 AACR.
Identification of a Quantitative MINT Locus Methylation Profile Predicting Local Regional Recurrence of Rectal Cancer
Authors: de Maat Michiel F.G. , van de Velde Cornelis J.H. , Benard Anne , Putter Hein , Morreau Hans , van Krieken J. Han J.M. , Meershoek Klein-Kranenbarg Elma , de Graaf Eelco J. , Tollenaar Rob A.E.M. , Hoon Dave S.B. 
Published: May 2010

Abstract
Purpose: Risk assessment for locoregional disease recurrence would be highly valuable in preoperative treatment planning for patients undergoing primary rectal tumor resection. Epigenetic aberrations such as DNA methylation have been shown to be significant prognostic biomarkers of disease outcome. In this study, we evaluated the significance of a quantitative epigenetic multimarker panel analysis of primary tumors to predict local recurrence in rectal cancer patients from a retrospective multicenter clinical trial.
Experimental Design: Primary tumors were studied from patients enrolled in the trial who underwent total mesorectal excision for rectal cancer (n = 325). Methylation levels of seven methylated-in-tumor (MINT) loci were assessed by absolute quantitative assessment of methylated alleles. Unsupervised random forest clustering of quantitative MINT methylation data was used to show subclassification into groups with matching methylation profiles.
Results: Variable importance parameters [Gini-Index (GI)] of the clustering algorithm indicated MINT3 and MINT17 (GI, 20.2 and 20.7, respectively) to be informative for patient grouping compared with the other MINT loci (highest GI, 12.2). When using this two-biomarker panel, four different patient clusters were identified. One cluster containing 73% (184 of 251) of the patients was at significantly increased risk of local recurrence (hazard ratio, 10.23; 95% confidence interval, 1.38-75.91) in multivariate analysis, corrected for standard prognostic factors of rectal cancer. This group showed a significantly higher local recurrence probability than patients receiving preoperative radiation (P &lt; 0.0001).
Conclusion: Quantitative epigenetic subclassification of rectal cancers has clinical utility in distinguishing tumors with increased risk for local recurrence and may help tailor treatment regimens for locoregional control. Clin Cancer Res; 16(10); 2811–8. ©2010 AACR.
Efficacy, Biodistribution, and Pharmacokinetics of CD22-Targeted Pegylated Liposomal Doxorubicin in a B-cell Non–Hodgkin's Lymphoma Xenograft Mouse Model
Authors: Tuscano Joseph M. , Martin Shiloh M. , Ma Yunpeng , Zamboni William , O'Donnell Robert T. 
Published: May 2010

Abstract
Purpose: Non–Hodgkin's lymphoma (NHL) is the sixth most common cause of cancer death in the U.S. Pegylated liposomal doxorubicin (PLD) is a liposomal form of doxorubicin (DXR) that causes less toxicity than does free DXR. To further enhance efficacy and decrease toxicity, we conjugated HB22.7, an anti-CD22 monoclonal antibody to PLD, thus creating CD22-targeted immunoliposomal PLD (IL-PLD).
Experimental Design: In vitro cytotoxicity of IL-PLD and PLD was assessed in CD22-positive and CD22-negative cell lines. Biodistribution, myelotoxicity, and plasma pharmacokinetics were measured in NHL xenograft–bearing mice treated with IL-PLD or PLD. Survival, tumor volume, and toxicity (WBC counts, body weights) were assessed in mice receiving a single dose (8, 12, or 16 mg DXR/kg) or three doses (8 mg DXR/kg/dose) of IL-PLD; controls were PLD, free DXR, PLD plus unconjugated HB22.7, IL-null (HB22.7-conjugated empty liposome), and nontreated mice.
Results: IL-PLD improved cytotoxicity over PLD only in CD22-positive cells. IL-PLD displayed similar pharmacokinetics and toxicities as PLD. Tumor DXR accumulation was greater and tumor/normal tissue ratios were similar (spleen) or greater (kidney, lung, and liver) in mice treated with IL-PLD versus PLD. IL-PLD reduced tumor volume more effectively than PLD at all doses; the three-dose regimen was superior. The three-dose regimen was used in confirmatory studies, which showed that IL-PLD produced significantly greater tumor volume reduction and enhanced survival versus PLD.
Conclusion: IL-PLD has increased efficacy without increased toxicity compared with PLD. This suggests that IL-PLD may be an improved form of DXR-based therapy of NHL. Clin Cancer Res; 16(10); 2760–8. ©2010 AACR.
Graft-versus-Leukemia Antigen CML66 Elicits Coordinated B-Cell and T-Cell Immunity after Donor Lymphocyte Infusion
Authors: Zhang Wandi , Choi Jaewon , Zeng Wanyong , Rogers Shelby A. , Alyea Edwin P. , Rheinwald James G. , Canning Christine M. , Brusic Vladimir , Sasada Tetsuro , Reinherz Ellis L. , Ritz Jerome , Soiffer Robert J. , Wu Catherine J. 
Published: May 2010

Abstract
Purpose: The target antigens of graft-versus-leukemia that are tumor associated are incompletely characterized.
Experimental Design: We examined responses developing against CML66, an immunogenic antigen preferentially expressed in myeloid progenitor cells identified from a patient with chronic myelogenous leukemia who attained long-lived remission following CD4+ donor lymphocyte infusion (DLI).
Results: From this patient, CML66-reactive CD8+ T-cell clones were detected against an endogenously presented HLA-B*4403–restricted epitope (HDVDALLW). Neither CML66-specific antibody nor T-cell responses were detectable in peripheral blood before DLI. However, by 1 month after DLI, CD8+ T cells were present in peripheral blood and at 10-fold higher frequency in marrow. Subsequently, plasma antibody to CML66 developed in association with disease remission. Donor-derived CML66-reactive T cells were detected at low levels in vivo in marrow before DLI by ELISpot and by a nested PCR-based assay to detect clonotypic T-cell receptor sequences but not in blood of the patient pre-DLI nor of the graft donor.
Conclusions: CD4+ DLI results in rapid expansion of preexisting marrow-resident leukemia-specific donor CD8+ T cells, followed by a cascade of antigen-specific immune responses detectable in blood. Our single-antigen analysis thus shows that durable posttransplant tumor immunity is directed in part against nonpolymorphic overexpressed leukemia antigens that elicit coordinated cellular and humoral immunity. Clin Cancer Res; 16(10); 2729–39. ©2010 AACR.
Overexpression of miR-21 Promotes an In vitro Metastatic Phenotype by Targeting the Tumor Suppressor RHOB
Authors: Connolly Erin C. , Van Doorslaer Koenraad , Rogler Leslie E. , Rogler Charles E. 
Published: May 2010

Abstract
Metastasis is a multistep process that involves the deregulation of oncogenes and tumor suppressors beyond changes required for primary tumor formation. RHOB is known to have tumor suppressor activity, and its knockdown is associated with more aggressive tumors as well as changes in cell shape, migration, and adhesion. This study shows that oncogenic microRNA, miR-21, represses RHOB expression by directly targeting the 3′ untranslated region. Loss of miR-21 is associated with an elevation of RHOB in hepatocellular carcinoma cell lines Huh-7 and HepG2 and in the metastatic breast cancer cell line MDA-MB-231. Using in vitro models of distinct stages of metastasis, we showed that loss of miR-21 also causes a reduction in migration, invasion, and cell elongation. The reduction in migration and cell elongation can be mimicked by overexpression of RHOB. Furthermore, changes in miR-21 expression lead to alterations in matrix metalloproteinase-9 activity. Therefore, we conclude that miR-21 promotes multiple components of the metastatic phenotype in vitro by regulating several important tumor suppressors, including RHOB. Mol Cancer Res; 8(5); 691–700. ©2010 AACR.
Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies
Authors: Nagel Inga , Szczepanowski Monika , Martín-Subero José I. , Harder Lana , Akasaka Takashi , Ammerpohl Ole , Callet-Bauchu Evelyne , Gascoyne Randy D. , Gesk Stefan , Horsman Doug , Klapper Wolfram , Majid Aneela , Martinez-Climent José A. , Stilgenbauer Stephan , Tönnies Holger , Dyer Martin J. S. , Siebert Reiner 
Published: May 2010

Abstract
Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis.
Glucocorticoids promote survival of anti-inflammatory macrophages via stimulation of adenosine receptor A3
Authors: Barczyk Katarzyna , Ehrchen Jan , Tenbrock Klaus , Ahlmann Martina , Kneidl Jessica , Viemann Dorothee , Roth Johannes 
Published: May 2010

AbstractActive resolution of inflammation is a previously unrecognized process essential for tissue homeostasis. Monocytes play a pivotal role in the generation as well as resolution of inflammation. Glucocorticoids (GCs) are widely used anti-inflammatory agents. We demonstrate that GCs exhibit antiapoptotic effects in monocytes resulting in differentiation to an anti-inflammatory phenotype. The molecular basis of this novel antiapoptotic effect is a prolonged activation of the extracellular signal regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway resulting in inhibition of caspase activities and expression of antiapoptotic genes via activation of c-Myc. We identified up-regulation and activation of A3 adenosine receptor (A3AR) as the initial trigger of this antiapoptotic pathway. In summary, we deciphered a novel molecular pathway promoting survival of anti-inflammatory monocytes. Specific activation of A3AR or its downstream signaling pathways may thus be a novel strategy to modulate inflammation in autoimmune disorders with fewer side effects via induction of inflammatory resolution rather than immunosuppression.
Patterning of mutually interacting bacterial bodies: close contacts and airborne signals
Authors: Čepl Jaroslav J , Pátková Irena , Blahůšková Anna , Cvrčková Fatima , Markoš Anton 
Published: May 2010

Abstract

Background
Bacterial bodies (colonies) can develop complex patterns of color and structure. These patterns may arise as a result of both colony-autonomous developmental and regulatory processes (self-patterning) and environmental influences, including those generated by neighbor bodies. We have studied the interplay of intra-colony signaling (self-patterning) and inter-colony influences in related clones of Serratia rubidaea grown on rich media.

Results
Colonies are shaped by both autonomous patterning and by signals generated by co-habitants of the morphogenetic space, mediating both internal shaping of the body, and communication between bodies sharing the same living space. The result of development is affected by the overall distribution of neighbors in the dish. The neighbors' presence is communicated via at least two putative signals, while additional signals may be involved in generating some unusual patterns observed upon encounters of different clones. A formal model accounting for some aspects of colony morphogenesis and inter-colony interactions is proposed.

Conclusions
The complex patterns of color and texture observed in Serratia rubidaea colonies may be based on at least two signals produced by cells, one of them diffusing through the substrate (agar) and the other carried by a volatile compound and absorbed into the substrate. Differences between clones with regard to the interpretation of signals may result from different sensitivity to signal threshold(s).
Role of myosin light chain kinase in intestinal epithelial barrier defects in a rat model of bowel obstruction
Authors: Wu Chi-Chin , Lu Yen-Zhen , Wu Li-Ling , Yu Linda C 
Published: May 2010

Abstract

Background
Bowel obstruction is a common cause of abdominal emergency, since the patients are at increased risk of septicemia resulting in high mortality rate. While the compartmentalized changes in enteric microfloral population and augmentation of bacterial translocation (BT) have already been reported using experimental obstruction models, alterations in epithelial permeability of the obstructed guts has not been studied in detail. Myosin light chain kinase (MLCK) is actively involved in the contraction of epithelial perijunctional actinomyosin ring and thereby increases paracellular permeability. In the current study we attempt to investigate the role of MLCK in epithelial barrier defects using a rat model of simple mechanical obstruction.

Methods
Wistar rats received intraperitoneal injection of ML-7 (a MLCK inhibitor) or vehicle at 24, 12 and 1 hrs before and 12 hrs after intestinal obstruction (IO). The distal small intestine was obstructed with a single ligature placed 10 cm proximal to the ileocecal junction in IO rats for 24 hrs. Sham-operated rats served as controls.

Results
Mucosal injury, such as villous blunting and increased crypt/villus ratio, was observed in the distal small intestine of IO rats. Despite massive enterocyte shedding, intestinal villi were covered with a contiguous epithelial layer without cell apoptosis. Increased transmural macromolecular flux was noticed in the distal small intestine and the proximal colon after IO. The bacterial colony forming units in the spleen and liver of IO rats were significantly higher than those of sham controls. Addition of ML-7 ameliorated the IO-triggered epithelial MLC phosphorylation, mucosal injury and macromolecular flux, but not the level of BT.

Conclusions
The results suggest that IO-induced premature enterocytic sloughing and enhanced paracellular antigenic flux were mediated by epithelial MLCK activation. In addition, enteric bacteria may undergo transcytotic routes other than paracellular paths to cross the epithelium.
Effective in vivo and ex vivogene transfer to intestinal mucosa by VSV-G-pseudotyped lentiviral vectors
Authors: Matsumoto Hiroshi , Kimura Takahiro , Haga Kazunori , Kasahara Noriyuki , Anton Peter , McGowan Ian 
Published: May 2010

Abstract

Background
Gene transfer to the gastrointestinal (GI) mucosa is a therapeutic strategy which could prove particularly advantageous for treatment of various hereditary and acquired intestinal disorders, including inflammatory bowel disease (IBD), GI infections, and cancer.

Methods
We evaluated vesicular stomatitis virus glycoprotein envelope (VSV-G)-pseudotyped lentiviral vectors (LV) for efficacy of gene transfer to both murine rectosigmoid colon in vivo and human colon explants ex vivo. LV encoding beta-galactosidase (LV-β-Gal) or firefly-luciferase (LV-fLuc) reporter genes were administered by intrarectal instillation in mice, or applied topically for ex vivo transduction of human colorectal explant tissues from normal individuals. Macroscopic and histological evaluations were performed to assess any tissue damage or inflammation. Transduction efficiency and systemic biodistribution were evaluated by real-time quantitative PCR. LV-fLuc expression was evaluated by ex vivo bioluminescence imaging. LV-β-Gal expression and identity of transduced cell types were examined by histochemical and immunofluorescence staining.

Results
Imaging studies showed positive fLuc signals in murine distal colon; β-Gal-positive cells were found in both murine and human intestinal tissue. In the murine model, β-Gal-positive epithelial and lamina propria cells were found to express cytokeratin, CD45, and CD4. LV-transduced β-Gal-positive cells were also seen in human colorectal explants, consisting mainly of CD45, CD4, and CD11c-positive cells confined to the LP.

Conclusions
We have demonstrated the feasibility of LV-mediated gene transfer into colonic mucosa. We also identified differential patterns of mucosal gene transfer dependent on whether murine or human tissue was used. Within the limitations of the study, the LV did not appear to induce mucosal damage and were not distributed beyond the distal colon.
A new method to detect loss of heterozygosity using cohort heterozygosity comparisons
Authors: Green Michael R , Jardine Paul , Wood Peter , Wellwood Jeremy , Lea Rod A , Marlton Paula , Griffiths Lyn R 
Published: May 2010

Abstract

Background
Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort.

Methods
DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes.

Results
Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions.

Conclusions
We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.
Shamba Maisha: A pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients
Authors: Pandit Jay A , Sirotin Nicole , Tittle Robin , Onjolo Elijah , Bukusi Elizabeth A , Cohen Craig R 
Published: May 2010

Abstract

Background
HIV/AIDS negatively impacts poverty alleviation and food security, which reciprocally hinder the rapid scale up and effectiveness of HIV care programs. Nyanza province has the highest HIV prevalence (15.3%), and is the third highest contributor (2.4 million people) to rural poverty in Kenya. Thus, we tested the feasibility of providing a micro-irrigation pump to HIV-positive farmers in order to evaluate its impact on health and economic advancement among HIV-positive patients and their families.

Methods
Thirty HIV-positive patients enrolled in the Family AIDS Care and Education Services (FACES) program in Kisumu, Kenya were provided a micro-financed loan to receive an irrigation pump and farming guidance from KickStart, the developer of the pump. Economic data, CD4 counts, household health and loan repayment history were collected 12 months after the pumps were distributed.

Results
Mean annual family income increased by $1,332 over baseline. CD4 counts did not change significantly. Though income increased, only three (10%) participants had paid off more than a quarter of the loan.

Conclusions
We demonstrated the feasibility of an income-generating micro-irrigation intervention among HIV-positive patients and the collection of health and economic data. While family income improved significantly, loan repayment rates were low- likely complicated by the drought that occurred in Kenya during the intervention period.