tbuckley/cabot-search huggingface dataset:
PTU-053 Is procollagen III aminopeptide a good predictor of liver fibrosis in patients with psoriasis on methotrexate therapy?
Authors: K Walsh, S Riley, Y C Lim, A Dhar
Journal: Gut (2010)

<h3>Introduction</h3> The prevalence of hepatotoxicity in long-term methotrexate therapy is around 0–4%. The British Association of Dermatology recommends procollagen III aminopeptide (PIIINP) level monitoring to identify patients at risk of hepatotoxicity with a view to liver biopsy while North American guidelines recommend liver biopsy based on cumulative dose of methotrexate. <h3>Methods</h3> 1. To correlate the accuracy of abnormal PIIINP level to predict liver fibrosis in patients receiving long-term methotrexate for psoriasis. 2. To assess adherence to the British Association of Dermatology guidance for PIIINP monitoring. The histology database (SNOMED) was interrogated for a 5-year period (1 January 2003 to 31 December 2007) to find all patients whose liver biopsies had been reported to show fibrosis, and patients with psoriasis identified. Case notes were reviewed for all psoriasis patients on long-term methotrexate. Levels of PIIINP, cumulative methotrexate dosage, comorbidities, drug history, alcohol intake, liver histology and clinical decision following liver biopsy (continuation or stoppage of methotrexate) were recorded. <h3>Results</h3> 578 liver biopsies during this period yielded 38 patients receiving methotrexate. 7 patients had methotrexate for another condition and were excluded; a further nine were excluded due to lack of case notes or repeat biopsies for follow-up. 22 patients with psoriasis had liver biopsies while on methotrexate treatment, of which 18 had elevated PIIINP levels above recommended threshold for liver biopsy and four patients had clinician decided biopsies. The mean cumulative dose of methotrexate to first biopsy was 3.86 g (range 0.69 g–9.25 g). The mean time to first biopsy was 4.2 years (range 1.1–10.1 years). 2 patients had PIIINP levels above 8 μg/l, one of which had grade 2 fibrosis on biopsy; the remaining 16 had PIIINP between 4.2 and 8 μg/l and two had Grade 2 fibrosis in this group. Liver histology (n=21): 15 patients had steatosis, three patients had grade 2 and one patient had Grade 1 fibrosis and two patients had normal liver histology. Clinical Outcome: four patients with fibrosis had methotrexate stopped as a result of the biopsy findings and the rest were continued (80%). <h3>Conclusion</h3> 19/21 (90%) patients with abnormal PIIINP had abnormal liver histology, but only 19% had fibrosis sufficient to discontinue treatment. PIIINP therefore did not correlate well with liver fibrosis. Newer non-invasive methods such as Fibroscan® may assess fibrosis better in this group of patients and need to be studied.
Abstract 2266: CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling
Authors: Bingya Liu, Ming-de Zang, Jian-fang Li, Li-ping Su, Zheng-gang Zhu, Min Yan
Journal: Cancer Research (2015)

Abstract CEACAM6 is a glycosylphosphatidylinositol (GPI)-linked immunoglobulin superfamily member that is implicated in a variety of human cancers. In our previous study, we reported that CEACAM6 was overexpressed in gastric cancer (GC) tissues and promoted cancer metastasis. The purpose of this study is to determine the role of CEACAM6 in tumor angiogenesis and vasculogenic mimicry (VM). We found that overexpression of CEACAM6 promoted tubular formation of human umbilical vein endothelial cells (HUVECs) and VM formation in GC. While opposing results were achieved in CEACAM6 knock-down groups. Interestingly, we found that mosaic vessels formed by HUVECs and GCs were observed in vitro by 3D-culture. Moreover, overexpression of CEACAM6 in GCs promoted tumor growth, VEGF secretion and VM structures in vivo. In accordance with these observations, we found that phosphorylation of FAK and phosphorylation of paxillin were up-regulated in CEACAM6-overexpressing GCs, and FAK inhibitor Y15 could reduce tube and VM formation. These findings suggest that CEACAM6 promotes tumor angiogenesis and VM may via FAK signaling, and CEACAM6 maybe a new potential target for cancer anti-vascular treatment. Citation Format: Bingya Liu, Ming-de Zang, Jian-fang Li, Li-ping Su, Zheng-gang Zhu,Min Yan. CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2266. doi:10.1158/1538-7445.AM2015-2266
Leukemic Dendritic Cells Expand Central Memory T Lymphocytes From HCT Donors Able to React against the Original Leukemia in Vitro and In Vivo.
Authors: Monica Casucci, Serena Kimi Perna, Attilio Bondanza, Zulma Magnani, Massimo Bernardi, Alessandro Crotta, Cristina Tresoldi, Katharina Fleischhauer, Elena Provasi, Maurilio Ponzoni, Federico Caligaris-Cappio, Fabio Ciceri, Claudio Bordignon, Alessandro Cignetti, Chiara Bonini
Journal: Blood (2009)
<i>IDH</i> mutation status impact on in vivo hypoxia biomarkers expression: New insights from a clinical, nuclear imaging, and immunohistochemical study in 34 patients with glioma.
Authors: P. Metellus, C. Colin, D. Taieb, E. Guedj, I. Nanni-Metellus, B. Coulibaly, C. Colavolpe, S. Fuentes, H. Dufour, M. Barrie, O. L. Chinot, L. Ouafik, D. Figarella-Branger
Journal: Journal of Clinical Oncology (2011)

2078 Background: Mutations in the gene encoding isocitrate dehydrogenase enzyme isoforms 1 (IDH1) and 2 (IDH2) have recently been identified in a large proportion of glial tumors of the CNS, but their mechanistic role in tumor development and progression remains unclear. Here, we assessed the actual impact of IDH1 and IDH2 mutations in patients harboring WHO grade 2 and 3 gliomas. Methods: We sequenced IDH1 at codon 132 and IDH2 at codon 172 in 34 patients with WHO grade 2 and 3 gliomas who benefited from a preoperative 18F-FDG positron emission tomography (PET). Immunohistochemical expression of Hypoxia Inducible Factor alpha (HIF-1 a), Carbonic Anhydrase IX (CAIX) and Glucose Transporter 1 (GLUT1) along with the R132HIDH1 mutation was assessed in all cases as well as 1p19q deletion status and p53 expression. Results: HIF-1α expression was found in 15% of IDH-mutated compared to 14.3% of IDH-nonmutated tumors (P=0.954). Also, GLUT-1 positive staining was found in 5.% of IDH-mutated and in 7.1% of IDH-nonmutated tumors (P=0.794). Finally, CA-IX expression was found in 15% of IDH-mutated and in 7.1% of IDH-nonmutated tumors (P=0.484). The combined expression of these three hypoxic markers was found in 2 WHO grade 3 tumors, one of which was IDH-mutated whereas the other was IDH-nonmutated (P=0.794). In IDH-mutated tumors, the median SUVmax ratio was 2.24 vs. 2.15 in IDH-nonmutated tumors (P=0.775). Conclusions: Together, these data suggest the absence of correlation between IDH mutation status and in vivo hypoxic biomarkers expression in WHO grade 2 and 3 gliomas.
662. Mesenchymal and Induced Pluripotent Stem Cells: General Insights and Clinical Perspectives
Authors: Helena D. Zomer, Atanasio S. Vidane, Natalia N. Gonçalves, Daniele S. Martins, Carlos E. Ambrósio
Journal: Molecular Therapy (2015)

Mesenchymal stem cells (MSC) have awakened a great deal of interest in regenerative medicine due to their plasticity, immunomodulatory and anti-inflammatory properties. They are easy in yield and can be acquired through non-invasive methods from adult tissues. Besides, are non-tumorigenic and are extensively studied. In the other hand, induced pluripotent stem (iPS) cells can be derived directly from adult cells through gene reprogramming. The new iPS technology avoids the embryo destruction or manipulation to generate pluripotent cells, therefore, are exempt of ethical implication surrounding embryonic stem cell use. The pre-differentiation of iPS cells can assure the safety of future approaches. Both MSC and iPS cells can be used to autologous cell transplantations without the risk of immune rejection and represent a great opportunity to future therapies. In this we discussed the therapeutic perspectives using mesenchymal and induced pluripotent stem cells and used the rabbit mouse of fat tissue stem cell and use it for IPs production. Perpectives and negatives highlights of this protocols will open venue for stem cell labs to produce safe different cell types using the rabbit model.
Manslaughter trials ignore systemic failures
Authors: Robin E Ferner
Journal: BMJ (2016)

Donaldson’s important editorial describes the haphazard way in which doctors come to face charges of gross negligence manslaughter.1 Police investigation can be triggered by complaints from relatives, hospital authorities, or coroners.2 We do not know the true numbers of cases that are investigated by the police, referred to the Crown Prosecution Service, or subsequently prosecuted—the Crown Prosecution Service does not recognise …
Cost-Effectiveness Analysis of Oral Iron Chelation Therapy with Deferasirox (Exjade®, ICL670) Versus Infusional Chelation Therapy with Deferoxamine in Patients with Transfusion-Dependent Myelodysplastic Syndrome.
Authors: Thomas E. Delea, Simu K. Thomas, Jean-Francois Baladi, Pradyumna D. Phatak
Journal: Blood (2005)
544. Targeted Gene Delivery To the Enteric Nervous System: α-Synuclein Impairs Colonic Motility
Authors: Matthew J. Benskey, Matthew J. Benskey, Nathan C. Kuhn, Nathan C. Kuhn, James J. Galligan, James J. Galligan, Joanna Garcia, Joanna Garcia, William W. Hauswirth, William W. Hauswirth, Christian Mueller, Sanford L. Boye, Fredric P. Mnafredsson
Journal: Molecular Therapy (2015)

The enteric nervous system (ENS) is a division of the autonomic nervous system that coordinates the control of gastrointestinal (GI) function. Several diseases are associated with abnormalities of the ENS, for example, GI dysfunction is one of the most common non-motor complaints associated with Parkinson's disease (PD). GI pathology affects virtually every level of the GI tract, primarily presenting as decreased colonic motility. Recent studies have demonstrated that the protein, α-synuclein (α-syn), forms large inclusion within neurons of the ENS, suggesting that α-syn pathology within the ENS may play a role in the etiology of GI dysfunction in PD. To determine if α-syn expression within neurons of the ENS is sufficient to produce GI dysfunction, we aimed to overexpress human wildtype α-syn within the ENS using direct injections of adeno associated virus (AAV) to the descending colon. However, as there have been no focused investigations into the targeted transduction of the ENS using AAV, we first examined the efficiency and tropism of transduction using several AAV serotypes. Rats received direct injections (6 × 5ml) of either AAV 1, 2, 5, 6, 8 or 9 expressing green fluorescent protein (GFP) into the descending colon. Transduction occurred in neurons and enteric glia within the myenteric and submucosal plexuses of the ENS. AAV6 and AAV9 showed the highest levels of transduction, with AAV9 primarily transducing neurons, and AAV6 transducing neurons as well as enteric glia. Transduction efficiency scaled with titer and time, to plateau at 4-weeks post injection at a titer of 6.25×1012 viral genomes (vg)/ml. Following characterization of AAV transduction in the ENS, it was determined that AAV9 demonstrated the highest levels of neuronal transduction, and was selected to deliver the α-syn transgene to the ENS. Adult male rats received direct injections (6 × 5ml at 1×1013vg/ml) of AAV9 expressing either human wildtype α-syn or a GFP control transgene into the descending colon. Four weeks post-surgery, colonic motility was assayed by quantifying the time necessary to transit and excrete a bead through 5cm of the descending colon. Animals that received AAV-α-syn had significantly impaired colonic motility, with a mean colonic transit time of 171.5 ± 43.4 minutes compared to animals that received AAV-GFP with a mean colonic transit time of 15 ± 6.8 minutes. Here we present a thorough characterization of the transduction profile of AAV in the ENS following direct injection to the descending colon. Further, using AAV to deliver human α-syn to neurons of the ENS, colonic motility was significantly decreased.
PO07TREATMENT OF AGGRESSIVE PITUITARY TUMOURS WITH TEMOZOLOMIDE
Authors: Francesca Solda, Neil Kitchen, Joan Grieve, Michael Powell, Stephanie E. Baldeweg, Naomi Fersht
Journal: Neuro-Oncology (2015)

INTRODUCTION: The management of aggressive pituitary tumours is challenging and conventional treatments are unable to provide long-term tumour control. In the salvage setting, Temozolomide (TMZ) has shown promising results both in reducing tumour size and hormone hypersecretion. METHOD: We present two patients, case 1 with a rapidly growing atypical prolactinoma and case 2 with a clinically non-functioning pituitary carcinoma with a spinal metastasis, treated with TMZ (200mg/m2, d1-d5/28 days, 12 and 6 cycles respectively) at tumour progression after multiple treatment approaches. RESULTS: TMZ provided good control of disease in both cases in parallel with reduced serum prolactin in case 1. Treatment was well tolerated with minimal toxicity. Tumour recurrence was observed 36 months after treatment termination in case 1 and the patient received stereotactic radiosurgery. Eight months after the termination of TMZ, case 2 is asymptomatic with controlled disease. CONCLUSION: TMZ was effective in the management of two aggressive pituitary tumours that failed to respond to conventional treatments. Prospective controlled studies are needed to define optimal treatment dose and duration and uniform criteria to select patients who will benefit from TMZ.
High Resolution HLA Typing by Sequencing for HLA-A, B, C, DR, DQ in 115 Unrelated Cord Blood/Patient Pairs- Does It Improve Outcomes after Cord Blood-Transplantation?.
Authors: Gesine Koegler, Juergen Enczmann, Vanderson Rocha, Eliane Gluckman, Peter Wernet
Journal: Blood (2004)
137. Viral Hitchhiking to Increase Therapeutic Potential: Autonomously Packaged Elements (APEs)
Authors: Kyle J. Hill, Alexander D. Swain, Margaret J. Lange, Donald H. Burke
Journal: Molecular Therapy (2015)

Human Immunodeficiency Virus (HIV) preferentially packages its own RNA genome and various RNA transcripts (tRNA-Lys3, 7SL, aptamers, etc.) with a broad range of consequences. For example, genome and tRNA are required for viral life cycle (positive impact on viral fitness), various cellular RNAs such as 7SL appear to "hitchhike" with no obvious essential roles (neutral), and aptamers that bind RT exert their influence by co-packaging with the viral proteins (inhibitory). While the mechanisms that promote selective incorporation of these transcripts have not been fully described, it is generally accepted that RNA secondary structures allow the RNA to associate with viral proteins during packaging. Identification of these RNA secondary structures would allow for exploitation of a range of packaging mechanisms to drive RNA incorporation for therapeutic purposes. We therefore applied a novel in vivo selection to identify RNAs specifically associated with incorporation into virus particles. We have previously demonstrated that multiple RNA aptamers selected against HIV Reverse Transcriptase (RT) are incorporated into the budding virus– potentially through interactions with the RT– and that they effectively reduce infectivity. To identify conserved features of highly efficient aptamer packagers, we have developed a cell-based protocol for the selection of Autonomously Packaging Elements (APEs). Pre-enriched RNA aptamer libraries were transfected into virus producing cells where we exploit the intracellular viral life cycles to perform the selection of APEs. We inserted an aptamer library downstream of a CMV promoter and co-transfected the library with HIV proviral plasmids. This generated pseudotyped virus particles containing the packaged RNA aptamers, while the cells retain the non-packaged RNA. By reverse transcribing the packaged RNA component, then amplifying and re-inserting it into the expression vector and iteratively transfecting fresh producer cells, we increase packaging competition and aptamer specificity. Subsequent High-Throughput Sequencing and computational analysis will allow us to probe the sequence and structural requirements of APEs. Individual aptamers will be evaluated for their packaging affinity and ability to inhibit viral replication in cell culture. Expanding on this selection scheme by swapping out the RT in the transfection with a panel of divergent RTs is expected to identify aptamer motifs which target evolutionarily conserved RT residues. Application of the APE selection system to an extended viral panel utilizing a range of starting libraries allows for nearly limitless variability in selection output.
Imatinib Mesylate Is Superior to Allogeneic Hematopoietic Stem Cell Transplantation As the First-Line Therapy for Patients with Chronic Myeloid Leukemia in the Early Chronic Phase
Authors: Qian Jiang, Lan-Ping Xu, Dai-Hong Liu, Kai-Yan Liu, Bin Jiang, Xiao-hui Zhang, Yu Wang, Shan-Shan Chen, Xiao-Dong Mo, Xiang-Yu Zhao, Huan Chen, Yu-Hong Chen, Wei Han, Hao Jiang, Ya-Zhen Qin, Yan-Rong Liu, Yue-yun Lai, Hong-Xia Shi, Meng Lv, Xiao Jun Huang
Journal: Blood (2011)
Abstract 1274: Hallmark of immune responses to multiple tumor-associated antigens (TAAs) in immunodiagnosis of hepatocellular carcinoma (HCC) and other solid tumors
Authors: Liping Dai, Pei Li, Weihong Liu, Chenglin Luo, Eng M. Tan, Jianying Zhang
Journal: Cancer Research (2015)

Abstract The immune system of the patient with cancer is a sensitive sensor of alterations in structure and/or function of participants in tumorigenesis pathways and is capable of making immune responses in the form of autoantibodies to tumor-associated antigens (TAAs). A hallmark of this immune response is the production of autoantibodies of multiple specificities indicating the activation of more than one tumorigenesis pathway. Novel autoantibodies appear prior to or coincident with clinical detection of transformation to cancer. Activation of more than one tumorigenesis pathway expressed as multiple autoantibodies to TAAs is a finding consistent with the synthetic lethality paradigm where mutation of more than one gene or in the case of cancer, more than one tumorigenesis pathway is required for malignant transformation. After analyzing 321 sera from patients with different type of cancer for autoantibodies to seven selected TAAs including p53, c-myc, cyclin B1, p62, KOC, IMP1 and Survivin, 34% of the sera had autoantibody to one TAA and 20% had two to six autoantibodies simultaneously. In a recent study, we have used a mini-array of 14 selected TAAs as an approach in the immunodiagnosis of HCC, and found that 68% of the sera contained one or more than one antibodies against these TAAs. In addition, this TAA array can identify 43.8% of HCC patients who had normal AFP levels in serum. Some autoantibodies appeared de-novo concurrent with conversion to malignancy. Many novel target antigens besides the above have been identified and shown to be participants in tumorigenesis. The immune system response to TAAs is a repository of information on partners in the synthetic lethality paradigm. Our study can also support the hypothesis that a customized TAA array used for detecting anti-TAA autoantibodies can constitute a promising and powerful tool for immunodiagnosis of HCC and other solid tumors. Citation Format: Liping Dai, Pei Li, Weihong Liu, Chenglin Luo, Eng M. Tan, Jianying Zhang. Hallmark of immune responses to multiple tumor-associated antigens (TAAs) in immunodiagnosis of hepatocellular carcinoma (HCC) and other solid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1274. doi:10.1158/1538-7445.AM2015-1274
Treatment Outcome with Imatinib-Based Maintenance Therapy in Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukaemia (Ph+ALL) Ineligible for Allogeneic Stem Cell Transplantation (SCT).
Authors: Heike Pfeifer, Barbara Wassmann, Sylvia Wystub, Lydia Wunderle, Joerg Chromik, Patrick Brueck, Andreas Hochhaus, Anja Binckebanck, Dieter Hoelzer, Oliver Ottmann
Journal: Blood (2007)
Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer
Authors: M. M-Rabet, O. Cabaud, E. Josselin, P. Finetti, R. Castellano, A. Farina, E. Agavnian-Couquiaud, G. Saviane, Y. Collette, P. Viens, A. Gonçalves, C. Ginestier, E. Charafe-Jauffret, D. Birnbaum, D. Olive, F. Bertucci, M. Lopez
Journal: Annals of Oncology (2016)
Vascular targeted photodynamic treatment is effective in low risk prostate cancer, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

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Treatment strategy for borderline resectable pancreatic cancer with artery involvement.
Authors: Seiko Hirono, Manabu Kawai, Ken-Ichi Okada, Motoki Miyazawa, Atsushi Shimizu, Yuji Kitahata, Masaki Ueno, Shinya Hayami, Shunsuke Yamaguchi, Katsunari Takifuji, Tsukasa Hotta, Masaki Nakamura, Kenji Matsuda, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2015)

373 Background: It has been still controversial to perform surgical resection with borderline resectable pancreatic cancer with artery involvement (BR-A), because an aggressive surgery leads to high morbidity and mortality with low R0 rate for the BR-A patients. In this study, we evaluated whether or not neoadjuvant therapy followed by surgical resection improves survival benefits for BR-A patients. Methods: There were 138 patients with BR-A among 330 pancreatic cancer patients underwent surgical resection at Wakayama Medical University Hospital. We compared clinicopathological factors between 38 BR-A patients with neoadjuvant therapy followed by surgical resection and 100 BR-A patients with upfront surgery to evaluate the clinical impacts of neoadjuvant therapy. Results: The overall survival (OS) of BR-A patients was significantly shorter than that of the patients with borderline resectbale pancreatic cancer with portal vein/ superior mesenteric vein (PV/SMV) involvement (n=76) and resectable pancreatic cancer (n=105) who underwent surgical resection (median OS: 13.6 vs. 20.6 months, P&lt;0.001). The OS of BR-A patient with neoadjuvant therapy followed by surgical resection was significantly longer than those with upfront surgery (median OS: 20.2 vs. 12.9 months, P=0.047). Multivariate analysis showed that older age (P=0.027), pathological PV/SMV invasion (P=0.031), moderated or poor differentiated tumor (P=0.008), positive lymph node ratio ³a0.1 (P=0.018), and no postoperative adjuvant chemotherapy (P&lt;0.001) were independent poor prognostic factors for BR-A patients. Conclusions: Neoadjuvant treatment might bring the clinical benefits for BR-A patients, and it is important to develop the appropriate regimen of neoadjuvant therapy and postoperative adjuvant therapy for longer survival in BR-A patients. Clinical trial information: 000003795.
Human Hematopoietic Stem Cells and Leukemic Cells Form Cadherin-Catenin Based Junctional Complexes with Mesenchymal Stromal Cells
Authors: Patrick Wuchter, Rainer Saffrich, Wolfgang Wagner, Frederik Wein, Mario Stephan Schubert, Volker Eckstein, Anthony D. Ho
Journal: Blood (2008)