bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preexisting epithelial diversity in normal human livers: A tissue-tethered cytometric analysis in portal/periportal epithelial cells
Authors: Isse Kumiko , Lesniak Andrew , Grama Kedar , Maier John , Specht Susan , Castillo-Rama Marcela , Lunz John , Roysam Badrinath , Michalopoulos George , Demetris Anthony J. 
Published: November 2012

Abstract

Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the canals of Hering and/or metaplasia of preexisting mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high-resolution whole-slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes preexist in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. “Virtually digested” WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g., scatterplots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. The results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bipotential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa.

Conclusion:

Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable preexistent hybrid epithelial diversity in normal human liver. This computationally enabled tissue analysis approach offers much broader potential beyond the results presented here.
Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis
Authors: Huang Chiung-Kuei , Lee Soo Ok , Lai Kuo-Pao , Ma Wen-Lung , Lin Tzu-Hua , Tsai Meng-Yin , Luo Jie , Chang Chawnshang 
Published: November 2012

Abstract

Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been considered as an alternative therapy, replacing liver transplantation in clinical trials, to treat liver cirrhosis, an irreversible disease that may eventually lead to liver cancer development. However, low survival rate of the BM-MSCs leading to unsatisfactory efficacy remains a major concern. Gender differences have been suggested in BM-MSCs therapeutic application, but the effect of the androgen receptor (AR), a key factor in male sexual phenotype, in this application is not clear. Using two liver cirrhosis mouse models induced by CCl4 or thioacetamide, we showed that targeting AR in the BM-MSCs improved their self-renewal and migration potentials and increased paracrine effects to exert anti-inflammatory and anti-fibrotic actions to enhance liver repair. Mechanism dissection studies suggested that knocking out AR in BM-MSCs led to improved self-renewal and migration by alteration of the signaling of epidermal growth factor receptor and matrix metalloproteinase 9 and resulted in suppression of infiltrating macrophages and hepatic stellate cell activation through modulation of interleukin (IL)1R/IL1Ra signaling. Therapeutic approaches using either AR/small interfering RNA or the AR degradation enhancer, ASC-J9®, to target AR in BM-MSCs all led to increased efficacy for liver repair.

Conclusion

: Targeting AR, a key factor in male sexual phenotype, in BM-MSCs improves transplantation therapeutic efficacy for treating liver fibrosis.
Salvage chemoimmunotherapy with rituximab, ifosfamide and etoposide (R‐IE regimen) in patients with primary CNS lymphoma relapsed or refractory to high‐dose methotrexate‐based chemotherapy
Authors: Mappa Silvia , Marturano Emerenziana , Licata Giada , Frezzato Maurizio , Frungillo Niccolò , Ilariucci Fiorella , Stelitano Caterina , Ferrari Antonella , Sorarù Mariella , Vianello Fabrizio , Baldini Luca , Proserpio Ilaria , Foppoli Marco , Assanelli Andrea , Reni Michele , Caligaris‐Cappio Federico , Ferreri Andrés J. M. 
Published: November 2012

AbstractDespite a high proportion of patients with primary CNS lymphoma (PCNSL) experiences failure after/during first‐line treatment, a few studies focused on salvage therapy are available, often with disappointing results. Herein, we report feasibility and activity of a combination of rituximab, ifosfamide and etoposide (R‐IE regimen) in a multicentre series of patients with PCNSL relapsed or refractory to high‐dose methotrexate‐based chemotherapy. We considered consecutive HIV‐negative patients ≤75 years old with failed PCNSL treated with R‐IE regimen (rituximab 375 mg/m2, day 0; ifosfamide 2 g/m2/day, days1–3; etoposide 250 mg/m2, day 1; four courses). Twenty‐two patients (median age 60 years; range 39–72; male/female ratio: 1:4) received R‐IE as second‐line (n = 18) or third‐line (n = 4) treatment. Eleven patients had refractory PCNSL, and 11 had relapsing disease. Twelve patients had been previously irradiated. Sixty (68%) of the 88 planned courses were actually delivered; only one patient interrupted R‐IE because of toxicity. Grade 4 hematological toxicity was manageable; a single case of grade 4 non‐hematological toxicity (transient hepatotoxicity) was recorded. Response was complete in six patients and partial in three (overall response rate = 41%; 95%CI: 21–61%). Seven patients were successfully referred to autologous peripheral blood stem cell collection; four responders were consolidated with high‐dose chemotherapy supported by autologous stem cell transplant. At a median follow‐up of 24 months, eight responders did not experience relapse, two of them died of neurological impairment while in remission. Six patients are alive, with a 2‐year survival after relapse of 25 ± 9%. We concluded that R‐IE is a feasible and active combination for patients with relapsed/refractory PCNSL. This regimen allows stem cell collection and successful consolidation with high‐dose chemotherapy and autologous transplant. Copyright © 2012 John Wiley & Sons, Ltd.
Cell‐based selection provides novel molecular probes for cancer stem cells
Authors: Sefah Kwame , Bae Kyung‐Mi , Phillips Joseph A. , Siemann Dietmar W. , Su Zhen , McClellan Steve , Vieweg Johannes , Tan Weihong 
Published: November 2012

AbstractCancer stem cells (CSC) represent a malignant subpopulation of cells in hierarchically organized tumors. They constitute a subpopulation of malignant cells within a tumor mass and possess the ability to self‐renew giving rise to heterogeneous tumor cell populations with a complex set of differentiated tumor cells. CSC may be the cause of metastasis and therapeutic refractory disease. Because few markers exist to identify and isolate pure CSC, we used cell‐based Systematic Evolution of Ligands by EXponential enrichment (cell‐SELEX) to create DNA aptamers that can identify novel molecular targets on the surfaces of live CSC. Out of 22 putative DNA sequences, 3 bound to ∼90% and 5 bound to ∼15% of DU145 prostate cancer cells. The 15% of cells that were positive for the second panel of aptamers expressed high levels of E‐cadherin and CD44, had high aldehyde dehydrogenase 1 activity, grew as spheroids under nonadherent culture conditions, and initiated tumors in immune‐compromised mice. The discovery of the molecular targets of these aptamers could reveal novel CSC biomarkers.
Clinical and immunologic responses in melanoma patients vaccinated with MAGE‐A3‐genetically modified lymphocytes
Authors: Russo Vincenzo , Pilla Lorenzo , Lunghi Francesca , Crocchiolo Roberto , Greco Raffaella , Ciceri Fabio , Maggioni Daniela , Fontana Raffaella , Mukenge Sylvain , Rivoltini Licia , Rigamonti Gianluigi , Mercuri Santo Raffaele , Nicoletti Roberto , Maschio Alessandro Del , Gianolli Luigi , Fazio Ferruccio , Marchianò Alfonso , Florio Annabella Di , Maio Michele , Salomoni Monica , Gallo‐Stampino Corrado , Fiacco Matteo Del , Lambiase Antonio , Coulie Pierre G. , Patuzzo Roberto , Parmiani Giorgio , Traversari Catia , Bordignon Claudio , Santinami Mario , Bregni Marco 
Published: November 2012

AbstractCancer vaccines have recently been shown to induce some clinical benefits. The relationship between clinical activity and anti‐vaccine T cell responses is somewhat controversial. Indeed, in many trials it has been documented that the induction of vaccine‐specific T cells exceeds the clinical responses observed. Here, we evaluate immunological and clinical responses in 23 MAGE‐A3+ melanoma patients treated with autologous lymphocytes genetically engineered to express the tumor antigen MAGE‐A3 and the viral gene product thymidine kinase of the herpes simplex virus (HSV‐TK). HSV‐TK was used as safety system in case of adverse events and as tracer antigen to monitor the immune competence of treated patients. The increase of anti‐TK and anti‐MAGE‐A3 T‐cells after vaccination was observed in 90 and 27% of patients, respectively. Among 19 patients with measurable disease, we observed a disease control rate of 26.3%, with one objective clinical response, and four durable, stable diseases. Three patients out of five with no evidence of disease (NED) at the time of vaccination remained NED after 73+, 70+ and 50+ months. Notably, we report that only patients experiencing MAGE‐A3‐specific immune responses showed a clinical benefit. Additionally, we report that responder and non‐responder patients activate and expand T cells against the tracer antigen TK in a similar way, suggesting that local rather than systemic immune suppression might be involved in limiting clinically relevant antitumor immune responses.
The αVβ3/αVβ5 integrin inhibitor cilengitide augments tumor response to melphalan isolated limb perfusion in a sarcoma model
Authors: ten Hagen Timo L.M. , Seynhaeve Ann L.B. , de Wiel‐Ambagtsheer Gisela aan , de Bruijn Ernst A. , van Tiel Sandra T. , Ruegg Curzio , Meyring Michael , Grell Matthias , Goodman Simon L. , Eggermont Alexander M.M. 
Published: November 2012

AbstractIsolated limb perfusion (ILP) with melphalan and tumor necrosis factor (TNF)‐α is used to treat bulky, locally advanced melanoma and sarcoma. However, TNF toxicity suggests a need for better‐tolerated drugs. Cilengitide (EMD 121974), a novel cyclic inhibitor of alpha‐V integrins, has both anti‐angiogenic and direct anti‐tumor effects and is a possible alternative to TNF in ILP. In this study, rats bearing a hind limb soft tissue sarcoma underwent ILP using different combinations of melphalan, TNF and cilengitide in the perfusate. Further groups had intra‐peritoneal (i.p.) injections of cilengitide or saline 2 hr before and 3 hr after ILP. A 77% response rate (RR) was seen in animals treated i.p. with cilengitide and perfused with melphalan plus cilengitide. The RR was 85% in animals treated i.p. with cilengitide and ILP using melphalan plus both TNF and cilengitide. Both RRs were significantly greater than those seen with melphalan or cilengitide alone. Histopathology showed that high RRs were accompanied by disruption of tumor vascular endothelium and tumor necrosis. Compared with ILP using melphalan alone, the addition of cilengitide resulted in a three to sevenfold increase in melphalan concentration in tumor but not in muscle in the perfused limb. Supportive in vitro studies indicate that cilengitide both inhibits tumor cell attachment and increases endothelial permeability. Since cilengitide has low toxicity, these data suggest the agent is a good alternative to TNF in the ILP setting.
A novel non‐invasive digital imaging method for continuous biomass monitoring and cell distribution mapping in photobioreactors
Authors: Uyar Basar 
Published: November 2012

AbstractBackgroundIn this study, a simple, non‐invasive, non‐destructive digital imaging method was developed to determine the cell biomass concentration and distribution in photobioreactors. For this purpose, images of a panel type photobioreactor containing Rhodobacter capsulatus as a model photosynthetic microorganism were captured with a digital camera and processed to obtain RGB color information.ResultsAcquired photobioreactor images were processed to quantify cell concentration, blue color component was shown to be suitable for estimating the cell concentration accurately. In a batch reactor, the biomass change over time was tracked efficiently by the proposed method as verified by mass and spectrophotometric analysis. Cell distribution profile in the photobioreactor was revealed by further analyses of the selected captured images. It was shown that cells were denser at the bottom part of the photobioreactor, and the concentration gradient increased over time during the batch runs.ConclusionThis research suggests that image analysis technique may be used as a simple method for continuous and online monitoring of cell concentration in photobioreactors. The research also demonstrated that a cell distribution map in the photobioreactor can be constructed to reveal non‐homogeneity. © 2012 Society of Chemical Industry
Degradation of short chain polychlorinated paraffins by a new isolate: tests in pure culture and sewage sludge
Authors: Lu Mang 
Published: November 2012

AbstractBACKGROUNDShort chain chlorinated paraffins SCCPs are priority hazardous substances classified by the European Water Framework Directive and have been detected in sewage sludge of wastewater treatment plants worldwide. However, studies on the biodegradation of SCCPs presented in sewage sludge are very scarce.RESULTSIn this study, a bacterial strain that can utilize SCCPs as a sole source of carbon and energy was isolated from soil. This strain was identified as Pseudomonas sp. N35. The efficacy of SCCP degradation by strain N35 was tested in pure culture and sewage sludge microcosms containing 66.1 mg kg–1 SCCPs. The results showed that 57.5% of chloride was released into the medium as chloride ions in pure culture within 20 days. Mesophilic temperature and near‐neutral pH were most favorable for SCCP degradation. The addition of low concentrations of glucose, Tween‐80 and acetone (20 mg L–1) enhanced SCCP degradation. Bioaugmentation resulted in 73.4% removal of SCCPs in the sludge microcosm after 30 days of treatment.CONCLUSIONBioaugmentation with specific strains may be of great significance in bioremediation of SCCP‐containing sewage sludge.© 2012 Society of Chemical Industry
Multiphasic contrast‐enhanced MRI: Single‐slice versus volumetric quantification of tumor enhancement for the assessment of renal clear‐cell carcinoma fuhrman grade
Authors: Vargas Hebert Alberto , Delaney Holly G. , Delappe Eithne M. , Wang Ya , Zheng Junting , Moskowitz Chaya S. , Tan Yongqiang , Zhao Binsheng , Schwartz Lawrence H. , Hricak Hedvig , Russo Paul , Akin Oguz 
Published: November 2012

AbstractPurpose:To assess the association between clear‐cell carcinoma pathology grade at nephrectomy and magnetic resonance imaging (MRI) tumor enhancement.Materials and Methods:The Institutional Review Board approved this retrospective study and waived the informed consent requirement. In all, 32 patients underwent multiphase contrast‐enhanced MRI prior to nephrectomy. MRI tumor enhancement was measured using two approaches: 1) the most enhancing portion of the tumor on a single slice and 2) volumetric analysis of enhancement in the entire tumor. Associations between pathological grade, tumor size, and enhancement were evaluated using the Kruskal–Wallis test and generalized logistic regression models.Results:No significant association between pathology grade and enhancement was found when measurements were made on a single slice. When measured in the entire tumor, significant associations were found between higher pathology grades and lower mean, median, top 10%, top 25%, and top 50% tumor enhancement (P < 0.001–0.002). On multivariate analysis the association between grade and enhancement remained significant (P = 0.041–0.043), but tumor size did not make an additional contribution beyond tumor enhancement alone in differentiating between tumor grades.Conclusion:There is significant association between tumor grade and enhancement, but only when measured in the entire tumor and not on the most enhancing portion on a single slice. J. Magn. Reson. Imaging 2013;37:1160–1167. © 2012 Wiley Periodicals, Inc.
Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by chemoradiation and total mesorectal excision: Initial experience
Authors: Nougaret Stephanie , Fujii Shinya , Addley Helen C. , Bibeau Frederic , Pandey Himanshu , Mikhael Hisham , Reinhold Caroline , Azria David , Rouanet Philippe , Gallix Benoit 
Published: November 2012

Purpose:To evaluate rectal cancer volumetry in predicting initial neoadjuvant chemotherapy response.Materials and Methods:Sixteen consecutive patients who underwent neoadjuvant chemotherapy (CX) before chemoradiotherapy (CRT) and surgery were enrolled in this retrospective study. Tumor volume was evaluated at the first magnetic resonance imaging (MRI), after CX and after CRT. Tumor volume regression (TVR) and downstaging were compared with histological results according to Tumor Regression Grade (TRG) to assess CX and CRT response, respectively.Results:The mean tumor volume was 132 cm3 ± 166 before and 56 cm3 ± 71 after CX. TVR after CX was significantly different between patients with poor histologic response (TRG1/2) and those with good histologic response (TRG3/4) (P = 0.001). An optimal cutoff of TVR >68% (area under the curve [AUC]: 0.9, 95% confidence interval [CI]: 0.65–0.98, P = 0.0001) to predict good histology response after CX was assessed by receiver operating characteristic curve. According to previous data and this study, we defined 70% as the best cutoff values according to sensitivity (86%), specificity (100%) of TVR for predicting good histology response. In contradistinction, MRI downstaging was associated with TRG only after CRT (P = 0.04).Conclusion:Our pilot study showed that MRI volumetry can predict early histological response after CX and before CRT. MRI volumetry could help the clinician to distinguish early responders in order to aid appropriate individually tailored therapies. J. Magn. Reson. Imaging 2013;38:726–732. © 2012 Wiley Periodicals, Inc.
Effects of age and gender on neuroanatomical volumes
Authors: Inano Sachiko , Takao Hidemasa , Hayashi Naoto , Yoshioka Naoki , Mori Harushi , Kunimatsu Akira , Abe Osamu , Ohtomo Kuni 
Published: November 2012

AbstractPurpose:To investigate age‐related differences, gender differences, and age‐by‐gender interactions on the volumes of 18 neuroanatomical structures, with a large sample at a single institution.Materials and Methods:A total of 861 normal subjects (mean age = 56.1 ± 9.8 years, age range = 24.0–84.8 years) were included in this study. All subjects were scanned at 3.0 T. Measurement of the 18 neuroanatomical volumes was performed with FreeSurfer v. 4.5. Differences in volumes of neuroanatomical structures were tested using analysis of covariance with intracranial volume‐normalized volume as the dependent variable, and independent variables of age, sex, age × sex, age × age, age × age × sex, and scanner. Nonsignificant higher‐order terms were removed sequentially from the model. A P value of < 0.0028 (=0.5/18) was considered to indicate a statistically significant difference.Results:All neuroanatomical volumes, except for the caudate nucleus, pallidum, and 4th ventricle, were significantly related to age (linearly or quadratically). Significant gender differences were found in all neuroanatomical volumes, except for cerebral white matter, cerebellar cortex, caudate nucleus, and amygdala. No neuroanatomical volume showed a significant interaction between age (age × age) and gender.Conclusion:Our results showed age and gender effects on neuroanatomical volumes, and indicate no gender difference in the aging process of neuroanatomical volumes. J. Magn. Reson. Imaging 2013;37:1072–1076. © 2012 Wiley Periodicals, Inc.
Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease
Authors: Ubhi Kiren , Rockenstein Edward , Vazquez‐Roque Ruben , Mante Michael , Inglis Chandra , Patrick Christina , Adame Anthony , Fahnestock Margaret , Doppler Edith , Novak Philip , Moessler Herbert , Masliah Eliezer 
Published: November 2012

AbstractAlzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid‐β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic‐like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro‐nerve growth factor (NGF), NGF, brain‐derived neurotrophic factor (BDNF), neurotropin (NT)‐3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro‐NGF were increased in saline‐treated hAPP tg mice. In contrast, CBL‐treated hAPP tg mice showed levels of pro‐NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL‐treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75NTR immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline‐treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro‐NGF/NGF balance and a concomitant protection of cholinergic neurons. © 2012 Wiley Periodicals, Inc.