tbuckley/cabot-search huggingface dataset:
Metabolic Capability to Induce the Pasteur Effect Mediates Sensitivity of Human Leukemic Cells to Metformin
Authors: Sarah Scotland, Estelle Saland, Lindsay Peyriga, Rémi Peyraud, Elizabeth Micklow, Gwenn Danet-Desnoyers, Stéphane Manenti, Christian Récher, Jean-Charles Portais, Mary Selak, Martin Carroll, Jean-Emmanuel Sarry
Journal: Blood (2011)
Gastric Diffuse Large B-Cell Lymphoma: Analyses of Prognostic Factors and Value of Pretreatment FDG-PET Scan.
Authors: Dai Chihara, Yasuhiro Oki, Shouji Ine, Hiroshi Onoda, Harumi Kato, Hirofumi Taji, Yoshitoyo Kagami, Kazuhito Yamamoto, Yasuo Morishima
Journal: Blood (2009)
Long-term Recurrence and Complications Associated With Elective Incisional Hernia Repair
Authors: Dunja Kokotovic, Thue Bisgaard, Frederik Helgstrand
Journal: JAMA (2016)

Prosthetic mesh is frequently used to reinforce the repair of abdominal wall incisional hernias. The benefits of mesh for reducing the risk of hernia recurrence or the long-term risks of mesh-related complications are not known.To investigate the risks of long-term recurrence and mesh-related complications following elective abdominal wall hernia repair in a population with complete follow-up.Registry-based nationwide cohort study including all elective incisional hernia repairs in Denmark from January 1, 2007, to December 31, 2010. A total of 3242 patients with incisional repair were included. Follow-up until November 1, 2014, was obtained by merging data with prospective registrations from the Danish National Patient Registry supplemented with a retrospective manual review of patient records. A 100% follow-up rate was obtained.Hernia repair using mesh performed by either open or laparoscopic techniques vs open repair without use of mesh.Five-year risk of reoperation for recurrence and 5-year risk of all mesh-related complications requiring subsequent surgery.Among the 3242 patients (mean age, 58.5 [SD, 13.5] years; 1720 women [53.1%]), 1119 underwent open mesh repair (34.5%), 366 had open nonmesh repair (11.3%), and 1757 had laparoscopic mesh repair (54.2%). The median follow-up after open mesh repair was 59 (interquartile range [IQR], 44-80) months, after nonmesh open repair was 62 (IQR, 44-79) months, and after laparoscopic mesh repair was 61 (IQR, 48-78) months. The risk of the need for repair for recurrent hernia following these initial hernia operations was lower for patients with open mesh repair (12.3% [95% CI, 10.4%-14.3%]; risk difference, -4.8% [95% CI, -9.1% to -0.5%]) and for patients with laparoscopic mesh repair (10.6% [95% CI, 9.2%-12.1%]; risk difference, -6.5% [95% CI, -10.6% to -2.4%]) compared with nonmesh repair (17.1% [95% CI, 13.2%-20.9%]). For the entirety of the follow-up duration, there was a progressively increasing number of mesh-related complications for both open and laparoscopic procedures. At 5 years of follow-up, the cumulative incidence of mesh-related complications was 5.6% (95% CI, 4.2%-6.9%) for patients who underwent open mesh hernia repair and 3.7% (95% CI, 2.8%-4.6%) for patients who underwent laparoscopic mesh repair. The long-term repair-related complication rate for patients with an initial nonmesh repair was 0.8% (open nonmesh repair vs open mesh repair: risk difference, 5.3% [95% CI, 4.4%-6.2%]; open nonmesh repair vs laparoscopic mesh repair: risk difference, 3.4% [95% CI, 2.7%-4.1%]).Among patients undergoing incisional repair, sutured repair was associated with a higher risk of reoperation for recurrence over 5 years compared with open mesh and laparoscopic mesh repair. With long-term follow-up, the benefits attributable to mesh are offset in part by mesh-related complications.
Multivariate Analysis Identifies Significant Correlations Between Baseline Biomarkers, DNA Demethylation and Clinical Responses in 122 Patients Treated in a Phase 1/2, Study of Guadecitabine (SGI-110), in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (r/r AML)
Authors: Srikanth Gottipati, Shashank Rohatagi, Woonbok Chung, Pietro Taverna, Hagop M. Kantarjian, Gail J. Roboz, Patricia L. Kropf, Mohammad Azab, Jean-Pierre Issa
Journal: Blood (2015)
P0482 : Improving natural killer cells cytotoxicty and harnessing hepatocyte cancer progression by MIR-486-5P
Authors: A.A. Bassiouni, M.A. Rahmoon, R.A. Youness, A.I. Gomaa, I. Waked, G. Esmat, H.M. El Tayebi, A.I. Abdelaziz
Journal: Journal of Hepatology (2015)
T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy
Authors: Tianjiao Wang, Ye Lu, Avery Polk, Pinki Chowdhury, Carlos Murga Zamalloa, Hiroshi Fujiwara, Koichiro Suemori, Niklas Beyersdorf, Alexandra C. Hristov, Megan S. Lim, Nathanael G. Bailey, Ryan A. Wilcox
Journal: Clinical Cancer Research (2016)

Abstract Purpose: T-cell lymphomas are a molecularly heterogeneous group of non-Hodgkin lymphomas (NHL) that account for a disproportionate number of NHL disease-related deaths due to their inherent and acquired resistance to standard multiagent chemotherapy regimens. Despite their molecular heterogeneity and frequent loss of various T cell–specific receptors, the T-cell antigen receptor is retained in the majority of these lymphomas. As T-cell receptor (TCR) engagement activates a number of signaling pathways and transcription factors that regulate T-cell growth and survival, we examined the TCR's role in mediating resistance to chemotherapy. Experimental Design: Genetic and pharmacologic strategies were utilized to determine the contribution of tyrosine kinases and transcription factors activated in conventional T cells following TCR engagement in acquired chemotherapy resistance in primary T-cell lymphoma cells and patient-derived cell lines. Results: Here, we report that TCR signaling activates a signaling axis that includes ITK, NF-κB, and GATA-3 and promotes chemotherapy resistance. Conclusions: These observations have significant therapeutic implications, as pharmacologic inhibition of ITK prevented the activation of this signaling axis and overcame chemotherapy resistance. Clin Cancer Res; 23(10); 2506–15. ©2016 AACR.
Non-methotrexate based triple drug combination chemotherapy for untreated osteosarcoma
Authors: S. S. Hingmire, S. K. Pai, A. V. Bakshi, R. Bharath, M. Agarwal, A. Puri, U. Dangi, S. Mandhaniya, T. Maksud, P. M. Parikh
Journal: Journal of Clinical Oncology (2007)

20512 Background: Considering the high cost of intensive high-dose methotrexate based chemotherapy, a non-methotrexate based chemotherapy regimen was evaluated in newly diagnosed osteosarcoma patients Methods: A total of 54 patients of newly diagnosed osteosarcoma (2000 to 2005) were included in the study. Chemotherapy protocol included 3 drugs viz. Doxorubicin (20 mg/m 2 on Day1 to Day3), Cisplatin (100 mg/m 2 on Day 1) and Ifosfamide (2000 mg/m 2 on Day1 to Day 5) in combination as A1 cycle - Ifosfamide + Doxorubicin, B1 cycle - Doxorubicin + Cisplatin, C1 cycle - Cisplatin + Ifosfamide. The sequence was repeated as A2, B2 and C2 (total 6 cycles). Surgical excision of primary tumor was done after 3 cycles of chemotherapy Results: The median age at diagnosis was 15.5 years with a slight male preponderance (n=38, 70.4 %). Axial skeleton (maxillary) was affected only in one patient. Lower end of femur was the most common appendicular skeletal site for the primary tumor (n=27, 50 %). Forty two out of 54 (77.8 %) patients had nonmetastatic disease at diagnosis. Lung was the most common site of distant metastasis at diagnosis (11 out of 12 patients). Fifty patients received all 6 chemotherapy cycles as planned. Limb salvage with reconstruction surgery was performed in 35 (64.8 %) patients. Complete (100%) tumor necrosis was seen in 18 (33.3 %) patients. The median duration of follow-up was 16 months. The actuarial disease free and overall survival at 3 years would be 41.4 % and 43.6 % respectively. The incidence of febrile neutropenia was 11.85 % and of grade III/IV thrombocytopenia was 10 % of all chemotherapy cycles. Easily controllable emesis was the commnoest non-hematological toxicity, experienced by 31.5 % of patients. Two patients died due to post chemotherapy neutropenic sepsis. With univariate analysis, complete histological response (100 % tumor necrosis) alone could be identified as independent favorable prognostic factor (3 year OS of 73.6 %, P=0.003). The overall survival outcome was not statistically different in subgroups of sex, age group and pathological tumor size. Conclusions: Non-methotrexate based triple drug combination chemotherapy is an effective treatment option for patients with newly diagnosed osteosarcoma in developing countries like India. No significant financial relationships to disclose.
Tumor Necrosis Factor-α-Converting Enzyme (ADAM17) Mediates GPIbα Shedding from Platelets In Vitro and In Vivo.
Authors: Wolfgang Bergmeier, Crystal L. Piffath, Guiying Cheng, Vandana S. Dole, Yuhua Zhang, Ulrich H. von Andrian, Denisa D. Wagner
Journal: Blood (2004)
Front-Line Treatment of Acute Promyelocytic Leukemia with AIDA Induction Followed by Risk-Adapted Consolidation: Results of the AIDA-2000 Trial of the Italian GIMEMA Group.
Authors: Francesco Lo Coco, Giuseppe Avvisati, Marco Vignetti, Giuseppe Fioritoni, Vincenzo Liso, Felicetto Ferrara, Giuseppe Cimino, Eugenio Gallo, Giuseppe Rossi, Rosario Giustolisi, Francesco Rodeghiero, Nicola Cantore, Tiziano Barbui, Paola Fazi, Antonio Peta, Alberto Bosi, Enrico Madon, Andrea Biondi, Giuseppe Masera, Francesco Nobile, Salvatore Mirto, Maria C. Petti, Franco Mandelli
Journal: Blood (2004)
P177 Cost effectiveness of ambulatory management of spontaneous pneumothorax: Abstract P177 Table 1
Authors: C Pillay, B Shah, M Naeem, R Reddy
Journal: Thorax (2015)

<h3>Introduction</h3> Hospital admissions due to a primary diagnosis of spontaneous pneumothorax (SP) have an annual incidence of 11.2 per 100000.<sup>1</sup> It is estimated there are around 7200 emergency hospital admissions annually for pneumothorax in NHS. We have previously demonstrated pneumothorax patients requiring intercostal drains can be managed safely as outpatients with a Pneumostat device (similar to Heimlich valve).<sup>2</sup> <h3>Methods</h3> All patients with primary spontaneous pneumothorax (PSP) and secondary spontaneous pneumothoraces (SSP) with a good performance status (WHO scale of 0–1) requiring an intercostal drain were eligible for outpatient management. SP patients presenting to hospital between July'14 and June'15 were analysed to see what percentage could be managed on the ambulatory pathway. The number of bed days saved was calculated from the total number of days patients spent in the community with the chest drain. The savings were then extrapolated to whole of NHS. <h3>Results</h3> 50 episodes (in 44 patients) of SP presented to hospital between July'14 and June'15. 36 episodes required a chest drain insertion. 20 of these 36 episodes (55%) were managed on the ambulatory pathway. Based on this approximately 4000 (55% of total NHS admissions) SP patients could be managed in an ambulatory setting annually across NHS. The health care usage (number of attendances at ambulatory care, Chest X-rays and Pneumostat devices used) of patients managed on the ambulatory pathway is listed in table 1. The unit cost of healthcare usage was obtained from the hospital information department and the overall cost of ambulatory care was calculated. The difference between this and the calculated bed day savings established the overall cost savings (Table 1). The potential savings to NHS equate to around £2.8 million based on the calculated average savings of £703/patient. <h3>Conclusion</h3> Ambulatory management of Spontaneous pneumothorax could realise significant savings to the NHS. <h3>References</h3> 1 Gupta D, Hansell A, Nichols T, <i>et al</i>. Epidemiology of pneumothorax in England. <i>Thorax</i> 2000;<b>55</b>(8):666–671 2 Thomas K, Naeem M, Reddy RV. In the pleural zone: P173 ambulatory management of spontaneous pneumothorax. <i>Thorax</i> 2014;<b>69</b>(Suppl 2):A150–A151
Response to: ‘Full-spectrum (FUSE) versus standard forward-viewing colonoscopy in an organised colorectal cancer screening programme’ by Hassan<i>et al</i>
Authors: Benjamin Nulsen, Blair Lewis
Journal: Gut (2016)

We read with great interest the recently published study by Hassan et al ,1 in which the authors randomised 658 faecal immunochemical test-positive patients in Italy to full-spectrum endoscopy (Fuse) or standard forward-viewing endoscopy (SFV). The authors did not identify a difference between Fuse and SFV in several endpoints, including adenoma detection rate (ADR), advanced adenoma detection rate (A-ADR) and mean number of adenomas and proximal adenomas per colonoscopy. These results were surprising given the significantly lower adenoma miss rate (AMR) with Fuse as compared with SFV (7% vs41%) in a previous multicenter, …
Bevacizumab (B), cisplatin (C), and pemetrexed (P) plus maintenance B in chemonaive patients (pts) with advanced nonsquamous non-small cell lung cancer (nsNSCLC): A phase II study.
Authors: Guillermo Lopez-Vivanco, Sergio Carrera, Aintzane Sancho, Ines Marrodan, Eider Azcona, Eluska Iruarrizaga, Itziar Rubio, Alberto Muñoz, Jose Vicente Cardona
Journal: Journal of Clinical Oncology (2012)

e18031 Background: B in combination with platinum doublets followed by continuation maintenance with B prolongs survival and delays progression in chemo-naïve pts with advanced (nsNSCLC). P in combination with C is efficacious in advanced nsNSCLC as frontline treatment. This phase II study aims to evaluate the efficacy and safety of B, C and P plus maintenance B in chemo-naïve pts with advanced nsNSCLC. Methods: Chemo-naïve pts with unresectable stage IIIB or IV nsNSCLC were treated of C (75 mg/m 2 ), P (500 mg/m 2 ), and B (7.5 mg/kg) on day 1 every 21 days up to 6 cycles. Pts with response or stable disease (SD) received maintenance B (7.5 mg/kg) every 21 days until disease progression or unacceptable toxicity. The primary endpoint was median progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety and analysis of K-ras mutations and plasma VEGF levels. Results: From 4/09 to 12/11, 27 pts were enrolled in the study. Data of 21 pts are presented. Median age was 58 years (range 42-74); male/female (%): 81/19; ECOG 0/1 (%): 5/95; adenocarcinoma/large cell carcinoma (%): 95/5. Median follow-up is 4.7 months. 53% of pts received at least 6 cycles of treatment and 20% received up to 12 cycles. Among the 15 pts assessable for response, the ORR was 47% (95% CI, 21-73) and disease control rate was 87%. Median PFS was 6.0 months (95% CI, 1.9-7.5). Grade 3/4 hematologic toxicity was neutropenia (9%/0). Most frequent grade 3/4 non-hematologic toxicities were fatigue (29%/0), venous thrombosis (14%/0), pulmonary embolism (9%/0) and dyspnea (5%/5%). There were no grade 3/4 hemorrhagic events. Data on survival and the analysis of K-ras mutations and VEGF levels will be presented. Conclusions: Treatment with B, C and P plus maintenance B is feasible and effective as front-line treatment of pts with advanced nsNSCLC. These data provide further evidence that B may be used in combination with multiple standard, platinum-based doublets in this setting.
Novel Therapeutic Approach to Improve Hematopoiesis By Targeting Myeloid Derived Suppressor Cells with a Humanized Anti-CD33 Antibody
Authors: Erika A Eksioglu, Karl-Heinz Heider, Bjoern Rueter, Alexis Burnette, Max Wei, Kathy McGraw, Ashley A Basiorka, Parthik Patel, Jeffrey Lancet, Rami Komrokji, Alan F. List, Sheng Wei
Journal: Blood (2014)
Improving nelarabine efficacy in T cell acute lymphoblastic leukemia by targeting aberrant PI3K/AKT/mTOR signaling pathway
Authors: Annalisa Lonetti, Alessandra Cappellini, Alice Bertaina, Franco Locatelli, Andrea Pession, Francesca Buontempo, Camilla Evangelisti, Cecilia Evangelisti, Ester Orsini, Laura Zambonin, Luca Maria Neri, Alberto Maria Martelli, Francesca Chiarini
Journal: Journal of Hematology & Oncology (2016)

Although in recent years, the introduction of novel chemotherapy protocols has improved the outcome of T cell acute lymphoblastic leukemia (T-ALL) patients, refractory and/or relapsing disease remains a foremost concern. In this context, a major contribution was provided by the introduction of the nucleoside analog nelarabine, approved for salvage treatment of T-ALL patients with refractory/relapsed disease. However, nelarabine could induce a life-threatening, dose-dependent neurotoxicity. To improve nelarabine efficacy, we have analyzed its molecular targets, testing selective inhibitors of such targets in combination with nelarabine. The effectiveness of nelarabine as single agent or in combination with PI3K, Bcl2, and MEK inhibitors was evaluated on human T-ALL cell lines and primary T-ALL refractory/relapsed lymphoblasts. The efficacy of signal modulators in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed by flow cytometry, western blotting, and quantitative real-time PCR in T-ALL settings. Treatment with nelarabine as a single agent identified two groups of T-ALL cell lines, one sensitive and one resistant to the drug. Whereas sensitive T-ALL cells showed a significant increase of apoptosis and a strong down-modulation of PI3K signaling, resistant T-ALL cells showed a hyperactivation of AKT and MEK/ERK1/2 signaling pathways, not caused by differences in the expression of nelarabine transporters or metabolic activators. We then studied the combination of nelarabine with the PI3K inhibitors (both pan and dual γ/δ inhibitors), with the Bcl2 specific inhibitor ABT199, and with the MEK inhibitor trametinib on both T-ALL cell lines and patient samples at relapse, which displayed constitutive activation of PI3K signaling and resistance to nelarabine alone. The combination with the pan PI3K inhibitor ZSTK-474 was the most effective in inhibiting the growth of T-ALL cells and was synergistic in decreasing cell survival and inducing apoptosis in nelarabine-resistant T-ALL cells. The drug combination caused AKT dephosphorylation and a downregulation of Bcl2, while nelarabine alone induced an increase in p-AKT and Bcl2 signaling in the resistant T-ALL cells and relapsed patient samples. These findings indicate that nelarabine in combination with PI3K inhibitors may be a promising therapeutic strategy for the treatment of T-ALL relapsed patients.
Association of Uba6-Specific-E2 (USE1) With Lung Tumorigenesis
Authors: Seong-Jin Kim, Tae Hyeong Lee, Sang Hee Nam, Ji-Hong Kim, Sangho Oh, Yeon Sook Cho, Myeong Sup Lee, Sehoon Choi, Peter C. W. Lee
Journal: JNCI Journal of the National Cancer Institute (2016)

The UBA6-specific E2 conjugating enzyme 1 (USE1) ubiquitin enzyme cascade is a poorly characterized arm of the ubiquitin-proteasome system. We investigated whether the UBA6-USE1 enzyme cascade plays a role in lung cancer tumorigenesis.USE1 expression was assessed in tumor-normal paired samples from 106 lung cancer patients by immunoblot. USE1 was stably overexpressed and knocked down in lung cancer cell lines to evaluate cell proliferation, colony formation, and invasion. Xenograft models were used to determine the effects of USE1 on tumor growth (n = 7). Proteomics analysis was used to identify proteins interacting with USE1. The USE1 gene was sequenced in lung cancer patients, and missense mutations of USE1 were generated to evaluate its function. All statistical tests were two-sided.USE1 proteins were frequently overexpressed in lung cancer patients (92.5%) Stable overexpression of USE1 increased cell proliferation ( P = .002), migration ( P < .001), and invasion ( P < .001), whereas knockdown of USE1 reduced cell proliferation ( P < .001), migration ( P = .003), and invasion in lung cancer cells and xenograft models ( P < .001). USE1 was found to have a conserved D-box domain, and the level of the protein was regulated by the anaphase-promoting complex. Several missense mutations in USE1 identified in patients prolong the stability of the protein.USE1 proteins are frequently overexpressed in lung cancer, and missense mutations in USE1 prolong the half-life of the protein, promoting tumor formation. Our findings reveal novel roles for USE1 in lung cancer and the possible use of USE1 as a novel biomarker and therapeutic target for lung cancer treatment.
Abstract A16: Expression of PD-L1 and BCG immunotherapy in non-muscle invasive bladder cancer
Authors: Jun Hyeok Heo, Hyun A. Jin, You Hyun Kang, Ki Hong Kim, Sung Joon Hong, Kyung Seok Han
Journal: Cancer Research (2016)

Abstract Background: Immunotherapy based on BCG has been a standard therapy to prevent recurrence and progression in bladder cancer. Activation of immune checkpoints by binding PD-1 to its ligands, PD-L1, is vital for physiologic regulation of immune system. Tumor cells can co-opt the PD-1 pathway to escape from immunosurveillance mechanism. We investigated expression of immune checkpoints and their effects on T cells in bladder cancer. Methods: A panel of transitional cell carcinoma cell lines (UC-3,T24,KU1919 and 253J) and normal human bladder urothelial cells (SVHUC1) were used to evaluate expression of immune checkpoints. Western blot analysis was used for protein expressions from cell lines and qPCR for RNA expression from human bladder tissues. Human bladder cancer/normal paired tissues were obtained at two time points; surgical resection and then after BCG immunotherapy. Immunohistochemical staining was performed to assess infiltration and distribution of CD4+ and CD8+ T cells in bladder tumor tissues and normal bladder tissues. Immune cells were isolated and T cells were isolated by FACS sorting after immune cell isolation from tumor/normal tissues. Results: PD-L1 proteins were highly expressed in bladder cancer cell lines compared to normal bladder epithelial cell line (SVHUC1). In paired human samples (cancer and normal tissues), PD-L1 were also highly expressed in bladder cancer tissues compared with paired normal tissues. Real time RT-PCR confirmed the high expression of PD-L1 in bladder cancer tissues. Interestingly, normal epithelial tissues regenerated after surgical resection of the tumor and BCG immunotherapy had low PD- after surgical resection and BCG immunotherapy while recurred tumor showed high expression of PD-L1. Isolation of TIL and immunohistochemical staining with CD4/CD8 showed that T cells were more infiltrated in bladder cancer tissues compared to paired normal tissues. Mouse bladder tumor model expressing PD-L1 showed increased CD3+CD4+ T cells and Treg cells. Conclusion: PD-L1 are highly expressed in bladder cancer. CD3+CD4+ T cells and Treg cells are highly infiltrated in human and mouse bladder cancer tissues. Our data suggest that PD-L1 might be involved in tumor recurrence after BCG immunotherapy and might be a novel targets in bladder cancer. Citation Format: Jun Hyeok Heo, Hyun A. Jin, You Hyun Kang, Ki Hong Kim, Sung Joon Hong, Kyung Seok Han. Expression of PD-L1 and BCG immunotherapy in non-muscle invasive bladder cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A16.
Expanded Access Program of Graspa for Treatment of Patients with Acute Lymphoblastic Leukemia Unable to Receive Other Form of L-Asparaginase - a Status Update (NCT02197650)
Authors: Yves Bertrand, Hervé Dombret, Bruno Quesnel, Jean-Louis Stephan, Claudine Schmitt, Severine Lissandre, Maryline Poiree, Christian Recher, Emmanuel Plouvier, Cécile Dumesnil de Maricourt, David Salako, Yann Godfrin, Iman El Hariry
Journal: Blood (2015)
GW26-e2203 Haplotype-Based Case-Control Study of the Human CYP4F2 Gene and Essential Hypertension in the Chinese Han population
Authors: Hong Yang, Zhenyan Fu, Yining Yang, Xiang Ma, Xiaomei Li, Fen Liu, Bangdang Chen, Xiang Xie, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)