tbuckley/cabot-search huggingface dataset:
Palliative systemic chemotherapy with gemcitabine (GEM) and 5-fluorouracil (5-FU) as 24h-infusion in patients with advanced inoperable biliary tract cancer (UICC stage IV)
Authors: S. Kersten, A. Wein, H. Albrecht, U. Reulbach, G. Maennlein, K. Wolff, N. Ostermeier, W. Hohenberger, E. G. Hahn, F. Boxberger
Journal: Journal of Clinical Oncology (2009)

e15633 Background: Due to the late diagnosis of biliary tract carcinomas in an advanced tumor stage, the application of palliative chemotherapy frequently remains as a possible treatment option. The aim of this study is to evaluate the efficacy and toxic side effects of a chemotherapy schedule consisting of GEM combined with 5-FU in patients (pts.) with metastatic biliary tract cancer. Methods: Evaluation of 35 pts. based on our prospective tumor registry data; essential inclusion criteria: histologically proven adeno-carcinoma, UICC stage IV, chemonaivity; all the pts. were presented in the interdisciplinary tumorboard of Erlangen University and were primarily non-curatively-resectable (n = 35); evaluation period: 11/1998 - 09/2008; treatment schedule: 1.000 mg/m 2 of GEM as a 0.5h-infusion (inf.) combined with 2.000 mg/m 2 of 5-FU as a 24h-inf. via port catheter on day 1, 8, 15 qd 22. Results: Median age: 64 years; men/women: n=18/17; ECOG 0/1/2: n=10/21/4; localisation: intrahepatic bile ducts: n=19, extrahepatic bile ducts: n=11; gall bladder: n=4; metastases: liver: 91.4%, lymph nodes: 51.4%, peritoneum: 28.8%, bones: 8.6%, intestine: 8.6%, skin: 2.9%, lungs: 2.9%; chemotherapy applications: total number: 486, average value/patient: 13.9; CA 19–9 elevated yes/no: n=13/22 (37.1%/62.9%); CEA elevated yes/no: n=15/9 (42.9%/25.7%, not evaluable: 11); higher grade toxicity (III or IV): leukocytopenia III: 14.3%, thrombocytopenia III: 2.9%, weariness III: 2.9%, diarrhea III: 5.7%, diarrhea IV: 2.9%, vomiting IV: 2.9%, pain III: 5.7%, ascites III: 5.7%, infections III: 2.9%, thromboembolia IV: 2.9%, elevated bilirubin value III: 1.7%, grade IV: 8.3%; deep leg vein thrombosis: 15%; median TTP: 5.1 months (95% CI: 2.9 - 7.2); median overall survival: 10.4 months (95% CI: 7.9 - 12.9); 6-months-/1-year-/2-year-survival rate: 65.7%/45.7%/17.1%; response rate: PR: n=5 (14.3%), SD: n=18 (51.4%), PD: n=7 (20%), not evaluable: n=5 (14.3%); tumor control (PR/SD): n=23 (65.7%); median follow-up: 10.4 months. Conclusions: Combination chemotherapy with weekly GEM as a 0.5h-inf. and 5-FU as a 24h-inf. on an out-patient basis is an effective palliative treatment schedule with solely low grade toxicity. No significant financial relationships to disclose.
575. High Content Analysis of CRISPR-Cas9 Gene-Edited Human Embryonic Stem Cells
Authors: Jared Carlson-Stevermer, Madelyn Goedland, Benjamin Steyer, Arezoo Movaghar, Meng Lou, Lucille Kohlenberg, Ryan Prestil, Krishanu Saha
Journal: Molecular Therapy (2016)

Gene-edited human cells are important resources for drug target identification, regulatory science, regenerative medicine and basic biology. Recently, use of the CRISPR-Cas9 system drastically cut the time required to produce gene-edited cell lines down to a few months. Targeted gene disruption in a population of human cells followed by selection and next-generation sequencing can identify drug targets, however many of these methods destroy all mutant clones, so a subsequent gene-editing experiment is required to obtain living mutant cells for downstream analysis. Overall, there is a need to increase the speed, multiplexing and precision in generating CRISPR-Cas9 mutants. ArrayEdit, a simple approach utilizing surface-modified multiwell plates containing one-pot transcribed single-guide RNAs (see Figure), separates thousands of edited cell populations for automated, live, high-content imaging and analysis. The approach lowers the time and cost of gene editing and produces edited human embryonic stem cells at high efficiencies. Edited genes can be expressed in both pluripotent stem cells and differentiated cells from all three major germ layers. This allows for the real-time observation of mutations causing phenotypic differences that can be measured in in vitro tissues and organoids during culture as opposed to defined end points. The live cell and tissue assays on ArrayEdit are compatible with standard screening platforms and a variety of human cell types, thus permitting robust and sensitive detection of differences in proliferation, differentiation and other downstream effects of gene editing. This preclinical platform adds important capabilities to observe editing and selection in situ within complex structures generated by human cells, ultimately enabling optical and other molecular perturbations in the editing workflow that could refine the specificity and versatility of gene editing.
Very Elderly Patients with Chronic Phase-Chronic Myeloid Leukemia on Imatinib: No Impact of Concomitant Drugs on Complete Cytogenetic Response
Authors: Alessandra Iurlo, Roberto Latagliata, Cristina Bucelli, Dario Ferrero, Fausto Castagnetti, Massimo Breccia, Elisabetta Abruzzese, Daniele Cattaneo, Carmen Fava, Antonella Gozzini, Mario Annunziata, Mario Tiribelli, Patrizia Pregno, Fabio Stagno, Paolo Vigneri, Francesco Cavazzini, Gianni Binotto, Giovanna Mansueto, Sabina Russo, Franca Falzetti, Enrico Montefusco, Gabriele Gugliotta, Cristiana Gasbarrino, Ada D'Addosio, Laura Cortesi, Michele Cedrone, Antonella Russo Rossi, Paolo Avanzini, Mauro Endri, Antonio Spadea, Francesca Celesti, Gianfranco Giglio, Alessandro Isidori, Monica Crugnola, Elisabetta Calistri, Federica Sorà, Giovanna Rege-Cambrin, Simona Sica, Luigia Luciano, Ester Maria Orlandi, Monica Bocchia, Mauro Tettamanti, Giuliana Alimena, Giuseppe Saglio, Gianantonio Rosti, Alessandro Nobili, Pier Mannuccio Mannucci, Agostino Cortelezzi
Journal: Blood (2015)
Significance of hypersensitivity reactions in the outpatient infusion unit: Retrospective study in JCHO Kyushu hospital
Authors: Kyoko Tomoda, Tsuyoshi Muta, Ayako Ono, Chinatsu Makiyama, Gen Hirano, Akitaka Makiyama, Kenichi Aoki, Ryosuke Ogawa, Shuyo Umeda, Akihiko Uchiyama
Journal: Annals of Oncology (2015)
Combined Chemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) for Relapsed or Untreated Progressive Chronic Lymphocytic Leukemia (CLL). A Single Center Experience.
Authors: Santiago Pavlovsky, Carolina Pavlovsky, Laura Pardo, Sandra Sapia, Isolda I. Fernandez, Mariana Juni
Journal: Blood (2005)
A Multi‐Biomarker Disease Activity Score and the Choice of Second‐Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure
Authors: Karen Hambardzumyan, Saedis Saevarsdottir, Kristina Forslind, Ingemar F. Petersson, Johan K. Wallman, Sofia Ernestam, Rebecca J. Bolce, Ronald F. van Vollenhoven
Journal: Arthritis & Rheumatology (2016)

Objective To investigate whether the Multi‐Biomarker Disease Activity (MBDA) score predicts optimal add‐on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX‐IRs). Methods We analyzed data from 157 MTX‐IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28‐ESR] &gt;3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28‐based response to each second‐line treatment was analyzed at randomization with the Breslow‐Day test for 2 × 2 groups, using both validated categories (low [&lt;30], moderate [30–44], and high [&gt;44]) and dichotomized categories (lower [≤38] versus higher [&gt;38]). Results Among the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab ( P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively ( P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively ( P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab. Conclusion In patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post‐MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.
Wearable, yes, but able…?: it is time for evidence-based marketing claims!
Authors: Billy Sperlich, Hans-Christer Holmberg
Journal: British Journal of Sports Medicine (2016)

With great interest, we1 have been following the growing popularity of non-invasive wearable sensor technology as a way to increase physical performance, assist recovery or monitor health. These sensors, integrated into clothing worn on the body, are often referred to as ‘wearables’ or ‘wearable technology’.

The popularity of the wearables is mainly due to three recent advances: (1) miniature sensor technology,1 (2) telemetric transfer and (web-based) storage of personal data and (3) extension of battery life. According to a worldwide survey of fitness trends, wearable technology appears set to be the number 1 trend in 2017,2 with expected sales for some wearables in the range of 1.5–2.6 billion US$.2

We believe that this type of technology will be a central tool in the fitness and health industry, provided some fundamental issues …
Treatment of Relapsed or Refractory Non-Hodgkin’s Lymphoma (NHL) or Hodgkin’s Disease (HD) with High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation (HSCT) Using a Novel Mitoxantrone-Containing Preparative Regimen.
Authors: Leslie Andritsos, Wendy Suhre, Mark Nahirny, Ellen Chase, Michael Carroll, Jennifer Christian, Thomas P. Miller, Andrew M. Yeager
Journal: Blood (2006)
Familial Atrial Septal Defect and Atrioventricular Conduction Disturbance Associated With a Point Mutation in the Cardiac Homeobox Gene CSX/NKX2-5 in a Japanese Patient
Authors: Toru Hosoda, Issei Komuro, Ichiro Shiojima, Yukio Hiroi, Miki Harada, Yuji Murakawa, Yasunobu Hirata, Yoshio Yazaki
Journal: Circulation (1999)

Atrial septal defect (ASD) is the most common form of congenital cardiac defect in humans. Recently, point mutations in the cardiac homeobox gene CSX/NKX2-5 have been reported to cause the autosomal dominant form of familial ASD. Notably, all the affected patients exhibit atrioventricular conduction disturbance and some of them died suddenly. The first case of familial ASD with a mutation of the CSX/NKX2-5 gene in a Japanese patient is reported here. Identification of CSX/NKX2-5 mutations in ASD patients would be very important because the existence of such mutations may predict sudden cardiac death. (Jpn Circ J 1999; 63: 425 - 426)
Thromboembolic events (TEE) in children and young adults with sarcoma
Authors: I. Paz-Priel, L. Long, D. Bernstein, C. L. Mackall, L. J. Helman, A. S. Wayne
Journal: Journal of Clinical Oncology (2004)

8524 Background: Adults with malignancy are at increased risk for thromboembolic events (TEE). However, data on TEE in pediatric patients with cancer are limited. Methods: To ascertain the risk and clinical features of TEE in pediatric sarcoma patients, we reviewed records on 119 consecutive patients with sarcoma treated from 10/80 to 07/02. Results: Median patient age was 18 years (range 4–32). Twenty-two TEE were diagnosed in 18/119 (15.1%) patients. Incidence by diagnosis was Ewing's sarcoma 7/61 (11.5%), osteogenic sarcoma 2/20 (10%), rhabdomyosarcoma 4/24 (16.7%) and other sarcomas 5/14 (35.7%). TEE developed in 12/51 (23.5%) patients with metastases at presentation vs. 6/68 (8.8%) with local disease (p=0.028). Thromboses were detected at presentation in 13/22 (59.1%), during the initial treatment cycle in 4/22 (18.2%), and at recurrence in 5/22 (22.7%). Ten (45.5%) events were asymptomatic (detected on routine imaging or autopsy). Sites of thromboses were deep veins of the extremities 10/22 (45.5%), pulmonary embolism 4/22 (18.2%), inferior vena cava (IVC) 4/22 (18.2%), superior vena cava 1/22 (4.5%), right atrium 2/22 (9.1%), and superior sagittal sinus 1/22 (4.5%). TEE were associated with tumor compression in 8/22 (36.4%) and with indwelling venous catheters in 3/22 (13.6%). A lupus anticoagulant was detected in 2 of 4 patients evaluated. Initial treatment included standard heparin in 9/22 (40.9%), low molecular weight heparin in 4/22 (18.2%), thrombolysis in 3/22 (13.6%), and IVC filter placement in 4/22 (18.2%). Conclusions: Thromboembolism is common in children and young adults with sarcomas. Thromboses are frequently detected around the time of oncologic presentation, may be asymptomatic, and appear to be associated with a higher disease burden including metastasis and local tumor compression. Pediatric patients with sarcoma should be monitored closely for TEE. No significant financial relationships to disclose.
Comparison of four alternative national universal anterior cruciate ligament injury prevention programme implementation strategies to reduce secondary future medical costs
Authors: Dion A Lewis, Brent Kirkbride, Christopher J Vertullo, Louisa Gordon, Tracy A Comans
Journal: British Journal of Sports Medicine (2016)

Background/aim Anterior cruciate ligament (ACL) injury is a common and devastating sporting injury. With or without ACL reconstruction, the risk of knee osteoarthritis (OA) and permanent disability later in life is markedly increased. While neuromuscular training programmes can prevent 50–80% of ACL injuries, no national implementation strategies exist in Australia. The aim of this study was to compare the ability of four alternative national universal ACL injury prevention programme implementation strategies to reduce future medical costs secondary to ACL injury. Methods A Markov economic decision model was constructed to estimate the value in lifetime future medical costs prevented by implementing a national ACL prevention programme among four hypothetical cohorts: high-risk sport participants (HR) aged 12–25 years; HR 18–25 years; HR 12–17 years; all youths (ALL) 12–17 years. Results Of the four programmes examined, the HR 12–25 programme provided the greatest value, averting US$693 of direct healthcare costs per person per lifetime or US$221 870 880 in total. Without training, 9.4% of this cohort will rupture their ACL and 16.8% will develop knee OA. Training prevents 3764 lifetime ACL ruptures per 100 000 individuals, a 40% reduction in ACL injuries. 842 lifetime cases of OA per 100 000 individuals and 584 TKRs per 100 000 are subsequently averted. Numbers needed to treat ranged from 27 for the HR 12–25 to 190 for the ALL 12–17. Conclusions The HR 12–25 programme was the most effective implementation strategy. Estimation of the break-even cost of health expenditure savings will enable optimal future programme design, implementation and expenditure.
Abstract 1004: Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer
Authors: Sheeja Aravindan, Satish Kumar Ramraj, Faizan H. Khan, Terence S. Herman, Somasundaram T. Somasundaram, Natarajan Aravindan
Journal: Cancer Research (2015)

Abstract Background: Identifying the drug-deliverables that target autophagy is crucial to finding a cure for pancreatic cancer (PC), as activated autophagy is associated with poor patient outcomes. Our recent studies recognized the anti-PC potential of an antioxidant-rich collection of seaweed polyphenols and identified potential compounds for the treatment of PC. Accordingly, we investigated whether such compounds could regulate autophagy in therapy-resistant PC cells in vitro and in residual PC in vivo. Results: Human Panc-3.27 and MiaPaCa-2 cells were exposed to FIR with/without polyphenol from Spatoglossum asperum (SA-EA), Padina tetrastromatica (PT-EA), or Hormophysa triquerta (HT-EA). The cells were subjected to QPCR to examine transcriptional alterations in the following autophagy functional regulators: ATG3, ATG5, ATG7, ATG5, LC3A, LC3B, Beclin, Myd88, HMGB1, Rage, and TLRs 1-9. Using a clinically relevant mouse model of residual PC, we use tissue microarray (TMA) and immunohistochemistry (IHC) procedures to investigate the potential of polyphenol(s) to target ATG3, ATG5, ATG12, LC3A, LC3B, BECN1, and survivin after clinical radiotherapy. Radiation significantly increased the transcription of autophagy functional regulators in both lines. Seaweed polyphenols completely suppressed all investigated regulators in both lines. TMA-IHC analysis revealed the complete regulation of ATG3, ATG5, 12, LC3A, LC3B, BECN1, and survivin in residual PC following SA-EA, PT-EA, and HT-EA treatment. Conclusions: These data demonstrate the autophagy blue print in therapy-resistant PC cells for the first time. Moreover, the data strongly suggest that the selected polyphenols could serve as effective adjuvants for current PC treatment modalities and may inhibit tumor relapse by comprehensively targeting therapy-orchestrated autophagy in residual cells. Citation Format: Sheeja Aravindan, Satish Kumar Ramraj, Faizan H. Khan, Terence S. Herman, Somasundaram T. Somasundaram, Natarajan Aravindan. Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer. [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 1004. doi:10.1158/1538-7445.AM2015-1004
125. Engineered Nucleases-Mediated In Situ Correction of a Genetic Defect By Homologous Recombination Into the Native Locus
Authors: Maria Carmela Latella, Francesca Miselli, Giandomenico Turchiano, Claudio Mussolino, Javier Cudeiro, Fernando Larcher, Alessandra Recchia
Journal: Molecular Therapy (2015)

Engineered nucleases specific for genomic targets are extensively used to generate DSBs that increase the rate and efficiency of homologous recombination (HR). We seek to determine the efficacy of nucleases in a clinical relevant genetic defect. The genetic defect we are addressing as model to test the nucleases-mediated genome editing technology is the junctional epidermolysis bullosa (JEB), a family of severe skin adhesion disorders due to autosomal recessive mutations in the LAMB3 gene coding for the laminin-332 heterotrimer, a key component of the dermal-epidermal junction. Recently, we provided proof of principle that ZFN-mediated, AAVS1-targeted GFP addition can be achieved in human keratinocytes and in long-term repopulating epithelial stem cells in a validated preclinical model of xenotransplantation of human skin equivalents on immunodeficient mice. This project aims at the demonstration of a successful in situ correction of the LAMB3 gene in primary keratinocytes from Herlitz JEB patients. Recently TALEN-based gene correction for dystrophic EB has been reported. Similarly, we have developed a genome editing approach for JEB. In particular we have designed TALENs specific for the second intron of LAMB3 gene and a HR cassette including a splicible LAMB3 cDNA (from exon 3 to the end of the gene). In particular immortalized JEB keratinocytes were transfected with TALEN mRNAs and infected with an IDLV vector carrying the HR cassette. The in situ gene correction has been evaluated by site-specific PCR and knock-in expression of the corrected LAMB3 gene on bulk population. We then assessed targeting efficiency and specificity by extensive molecular analyses of single-cell clones isolated by limiting dilution from the TALENs/IDLV-treated immortalized JEB population. We isolated 256 clones and expanded 69 of them. Sixteen out of 69 clones showed an in vitro adhesion advantage, hosted the HR cassette correctly integrated into the predetermined locus, expressed the corrected LAMB3 gene and produced the laminin-332 protein. In parallel, CRISPR-Cas9 nuclease has been designed on the same locus to compare the transduction efficiency and cleavage activity and to translate the knock-in targeting platform to primary JEB keratinocytes.
Abstract 1299: Tumor-infiltrating B cells are predictive of human lung squamous cell survival
Authors: Sara Centuori, Samuel Kim, Cecil Gomes, Charles Putnam, David Mount, Linda Garland, Jesse Martinez
Journal: Cancer Research (2015)

Abstract Recent studies in human lung squamous cell carcinoma (SqCC) have shown that upregulation of B cell-associated genes strongly correlate with patient survival. More than any genetic factor (immunologic or otherwise) CD79A, a pan-B cell marker, was found to have the strongest predictive value. Expression of this marker was capable of identifying short (&amp;lt; 2 years) and long (&amp;gt; 6 years) term lung SqCC survivors, with greater than 80% accuracy. These data suggest that the presence of CD79A-expressing tumor-infiltrating B (TIL-B) cells may be contributing to patient outcome. The aim of this study was to characterize CD79A+ TIL-B cells in SqCC patient samples and evaluate their role in lung SqCC survival. We evaluated human lung cancer specimens from long and short term survivors for the presence of CD79A+ TIL-B cells by immunofluorescence and found that their presence directly correlates with survival time. Further analysis showed that CD79A expression found in tumors of long term survivors (&amp;gt;6 years) co-localizes with CD20 staining but not CD138 staining, indicating that the cells responsible for producing a survival signature are not plasma cells. These data indicate that CD79A+ TIL-B cells are contributing to the generation of an efficient immune response in lung SqCC and may be doing so through non-humoral functions. Citation Format: Sara Centuori, Samuel Kim, Cecil Gomes, Charles Putnam, David Mount, Linda Garland, Jesse Martinez. Tumor-infiltrating B cells are predictive of human lung squamous cell survival. [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 1299. doi:10.1158/1538-7445.AM2015-1299