tbuckley/cabot-search huggingface dataset:
Impact of the double expression of MYC and BCL2 on outcomes of localized primary gastric diffuse large B-cell lymphoma patients in the rituximab era
Authors: A Kawajiri, D Maruyama, A M Maeshima, J Nomoto, S Makita, H Kitahara, K-i Miyamoto, S Fukuhara, T Suzuki, W Munakata, K Tajima, J Itami, H Taniguchi, Y Kobayashi, K Tobinai
Journal: Blood Cancer Journal (2016)

Impact of the double expression of MYC and BCL2 on outcomes of localized primary gastric diffuse large B-cell lymphoma patients in the rituximab era
CCR2 Influences T Regulatory Cell Migration to Tumors and Serves as a Biomarker of Cyclophosphamide Sensitivity
Authors: Pierre-Louis Loyher, Juliette Rochefort, Camille Baudesson de Chanville, Pauline Hamon, Géraldine Lescaille, Chloé Bertolus, Maude Guillot-Delost, Matthew F. Krummel, François M. Lemoine, Christophe Combadière, Alexandre Boissonnas
Journal: Cancer Research (2016)

The CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4+ T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2+ Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen-specific cells in the dLN, where they displayed an activated immunosuppressive phenotype. Notably, in mouse models, low-dose cyclophosphamide treatment preferentially depleted CCR2+ Treg, enhancing priming of tumor-specific CD8+ T cells. In the MMTV-PyMT transgenic mouse model of breast cancer and in oral squamous cell carcinoma patients, tumor development was associated with decreased blood frequency and inversely increased tumor frequency of CCR2+ Tregs. Our results define a novel subset of CCR2+ Treg involved in tumoral immune escape, and they offer evidence that this Treg subset may be preferentially eradicated by low-dose cyclophosphamide treatment. Cancer Res; 76(22); 6483-94. ©2016 AACR.
Lapatinib and sunitinib on glioma cell migration through implication of growth factor with integrins.
Authors: H. Kalofonos, K. Dimitropoulos, E. Giannopoulou, U. Kyriakopoulou, A. A. Argyriou
Journal: Journal of Clinical Oncology (2010)

e12527 Background: Malignant gliomas are the most common and aggressive primary brain tumors. Sunitinib is an oral, small-molecule, multi-targeting receptor tyrosine kinase inhibitor (TKI), including platelet-derived growth factor receptors (PDGFR) and vascular endothelial growth factor receptors (VEGFR). Lapatinib is an ATP-competitive dual TKI for epidermal growth factor receptor (EGFR) and HER2/neu (ErbB-2). The aim of this study was to assess the antitumor effect of sunitinib and lapatinib applied either alone or in combination on two glioma cell lines. We previously showed that sunitinib and lapatinib have an antiproliferative effect in U87 and M059K glioma cell lines. In the current setting, we focused on the effect of each agent in cell migration. Furthermore, we sought to evaluate the effect of lapatinib in the formation of EGFR-integrin β1 complex, as well as the effect of sunitinib in the VEGFR-integrin β3 and PDGFR-integrin β3 complexes formation. Methods: U87 and M059K cells were cultured as recommended by ATCC. Migration assays were performed in chambers, using uncoated polycarbonate membranes. Immunoprecipitation and western blot analysis were used for studying the complex formation of EGFR, PDGFR and VEGFR with integrins. The protein localization was evaluated through immunofluorescence assay. Results: We found that both agents administered either alone or in combination, reduced the ability of U87 and M059K cells to migrate 4 h after their application. The time course study of the effect of lapatinib on EGFR-integrin β1 complex revealed an inhibition in complex formation up to 30 min after the application of the agent. Likewise, sunitinib inhibited complex formation of VEGFR-integrin β3 and PDGFR-integrin β3 complexes within 2h after its application. The previously-described interruption of complexes formation was confirmed with an immunofluorescence assay. The experiments with M059K cells are still ongoing. Conclusions: The preliminary results of our study are the first to support the implication of an anti-EGFR agent, lapatinib and a multi-targeted agent, sunitinib in glioma cells migration, through a mechanism implying interruption of growth factor-integrin complexes formation. No significant financial relationships to disclose.
A prospective multicenter study of guanylyl cyclase C (GCC), quantified by the reverse transcriptase-polymerase chain reaction (qRT-PCR), as a prognostic marker of occult metastases in lymph nodes of pN0 colorectal cancer patients
Authors: S. A. Waldman, T. Hyslop, S. Schulz, K. Nielsen, J. Haaf, C. Bonaccorso, Y. Li, A. Barkun, D. Weinberg
Journal: Journal of Clinical Oncology (2008)

11011 Background: Patients with pN0 colorectal cancer have a ∼25% risk of disease recurrence reflecting, in part, under-diagnosis of lymph node metastases at staging. Improved methods that predict recurrence would identify patients who could benefit from adjuvant chemotherapy. GCC, expressed selectively by intestinal cells and universally in colorectal tumors, is a marker whose detection in lymph nodes could enhance staging. Methods: At staging, 356 patients with pN0 colorectal cancer from 9 hospitals were enrolled. Fresh lymph nodes >5 mm were bisected for histopathology and GCC qRT-PCR. Three hundred patients provided lymph nodes, of which 261 provided tissues with sufficient mRNA for analysis. Categorical GCC expression, normalized to beta-actin, was estimated in 2,452 lymph nodes from these patients, who were followed to assess time to recurrence. Results: Median follow-up of patients was 45 months (range 1–75 months). Of the 261 patients, 13% (34 patients) had lymph nodes free of occult metastases by GCC qRT-PCR and all but 2 remained free of disease (5.8% raw recurrence rate). Conversely, 20.7% (47 patients) with lymph nodes containing occult metastases by GCC qRT-PCR developed recurrent disease (p=0.029, log-rank test). In multivariable Cox models, controlling for T stage, tumor location, lymphovascular invasion, and tumor differentiation, occult metastases in lymph nodes by GCC qRT-PCR was the most powerful independent predictor of recurrence (adjusted Hazard Ratio=4.51, p=0.039, 95%CI=1.07, 18.90). Conclusions: GCC qRT-PCR identifies occult metastases in lymph nodes that independently predict time to recurrence in pN0 colorectal cancer patients. Thus, GCC may serve as a prognostic and predictive marker, identifying pN0 patients at minimum risk for disease recurrence and, conversely, who might benefit from adjuvant chemotherapy, respectively. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Targeted Diagnostics and Therapeutics, Inc. Targeted Diagnostics and Therapeutics, Inc. Targeted Diagnostics and Therapeutics, Inc.
Romiplostim for the Treatment of Adults with Primary Immune Thrombocytopenia (ITP) in Routine Clinical Practice – Interim Results From a Large, European, Observational Study
Authors: Dominik Selleslag, Ann Janssens, Hans Wadenvik, Michael Steurer, Philippe Quittet, Georgia Kaiafa, Tomas Kozak, Helen Papadaki, Jean-François Viallard, Kerry Dillingham, Georg Kreuzbauer
Journal: Blood (2012)
A phase I and pharmacokinetic (PK) study of continuous daily administration of P1446A-05, a potent and specific oral Cdk4 inhibitor.
Authors: Desiree Hao, Quincy Chu, Stephen Welch, Cindy Y. F. Yau, Jennifer L. Spratlin, Patricia Tang, Mary J. MacKenzie, Carol A. Townsley, Diane Arndt, Laureen Johnson, Daniela Trapsa, Pamela Degendorfer, Sujay Kulkarni, Gajendra Jawlekar, Poornima Dhobe, Amit M. Oza
Journal: Journal of Clinical Oncology (2012)

3013 Background: P1446A-05 is a novel oral inhibitor of Cdk4-D1, Cdk1-B, and Cdk9-T, and has been shown to inhibit tumor growth both in vitro and in vivo. Pharmacodynamic studies demonstrate that activation of Cdk1 reappears within 48 hours after P1446A-05 is withdrawn, suggesting the need for prolonged administration hence, we sought to evaluate the feasibility, safety and tolerability of a continuous daily schedule of P1446A-05 in patients (pts) with advanced malignancies. Methods: P1446A-05 was given at escalating doses of 75, 150, 250, 350 and 500mg. Samples were collected for PK at multiple time points over 24 hours on cycle 1 day 1 and 15, as well as at single time points on cycle 1 day 8, 22 and cycle 2 day 1. Results: Thirty-nine pts (median age=63 years, 51% male, 51% ECOG PS=1) collectively received more than 100 cycles of P1446A-05. The majority of drug-related toxicities were ≤Grade 2, the most common of which were diarrhea (n=54), nausea/vomiting (n=27/17), fatigue (n=22) and anorexia (n=16). Two pts developed study-drug related diarrhea with hypokalemia/elevated creatinine and died during cycle 1. Dose-limiting toxicities (DLT) at 500mg (Table) led to subsequent de-escalation and expansion of the 350mg cohort. A total of 24 pts were treated at 350mg; only one patient experienced dose-limiting diarrhea. PK data are summarized below. Accumulation ratios across dose levels suggest moderate accumulation with continuous dosing. Nine pts achieved stable disease (SD) for at least 2 cycles. One pt with alveolar soft tissue sarcoma, whose disease was progressing at enrollment, remains on treatment with SD after 11 cycles. Conclusions: The recommend phase II dose of P1446A-05 is 350mg. Further phase II studies at this dose will be conducted with potential enrichment strategies. [Table: see text]
Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume
Authors: Martin Kolb, Luca Richeldi, Jürgen Behr, Toby M Maher, Wenbo Tang, Susanne Stowasser, Christoph Hallmann, Roland M du Bois
Journal: Thorax (2016)

<h3>Rationale</h3> There is no consensus as to when treatment for idiopathic pulmonary fibrosis (IPF) should be initiated. Some physicians prefer not to treat patients with preserved lung volume. <h3>Objective</h3> To investigate whether patients with IPF and preserved lung volume receive the same benefit from nintedanib as patients with more impaired lung volume. <h3>Methods</h3> Post hoc subgroup analyses of pooled data from the two replicate phase III INPULSIS trials by baseline FVC % predicted (≤90%, &gt;90%). <h3>Results</h3> At baseline, 274 patients had FVC &gt;90% predicted and 787 patients had FVC ≤90% predicted. In patients treated with placebo, the adjusted annual rate of decline in FVC was consistent between patients with FVC &gt;90% predicted and FVC ≤90% predicted (−224.6 mL/year and −223.6 mL/year, respectively). There was no statistically significant difference between these subgroups in the effect of nintedanib on annual rate of decline in FVC, change from baseline in St George9s Respiratory Questionnaire total score or time to first acute exacerbation. In patients with baseline FVC &gt;90% predicted and ≤90% predicted, respectively, the adjusted annual rate of decline in FVC with nintedanib was −91.5 mL/year (difference vs placebo: 133.1 mL/year (95% CI 68.0 to 198.2)) and −121.5 mL/year (difference vs placebo: 102.1 mL/year (95% CI 61.9 to 142.3)). Adverse events associated with nintedanib were similar in both subgroups. <h3>Conclusions</h3> Patients with IPF and preserved lung volume (FVC &gt;90% predicted) have the same rate of FVC decline and receive the same benefit from nintedanib as patients with more impaired lung volume. <h3>Trial registration number</h3> NCT01335464 and NCT01335477.
The effects of performance status one week before hospital admission on the outcomes of critically ill patients
Authors: Fernando G. Zampieri, Fernando A. Bozza, Giulliana M. Moralez, Débora D. S. Mazza, Alexandre V. Scotti, Marcelo S. Santino, Rubens A. B. Ribeiro, Edison M. Rodrigues Filho, Maurício M. Cabral, Marcelo O. Maia, Patrícia S. D’Alessandro, Sandro V. Oliveira, Márcia A. M. Menezes, Eliana B. Caser, Roberto S. Lannes, Meton S. Alencar Neto, Maristela M. Machado, Marcelo F. Sousa, Jorge I. F. Salluh, Marcio Soares
Journal: Intensive Care Medicine (2016)
Kras mutation reflects the different cholangiocytes pheno- and genotype in intrahepatic cholangiocarcinoma
Authors: Komuta Mina, Chris Verslype, Sara Vander Borght, Vincent Vandecaveye, Werner Van Steenbergen, Wim Laleman, Jacques Pirenne, Raymond Aerts, Frederik Nevens, Baki Topal, Tania Roskams
Journal: Hepatology (2012)
Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti–tumor necrosis factor agents versus classic therapies: Prospective meta-analysis of Psonet registries
Authors: Ignacio Garcia-Doval, Arnon D. Cohen, Simone Cazzaniga, Ilan Feldhamer, Antonio Addis, Gregorio Carretero, Carlos Ferrándiz, Robert S. Stern, Luigi Naldi
Journal: Journal of the American Academy of Dermatology (2016)
Angiopoietin‐like protein 1 antagonizes MET receptor activity to repress sorafenib resistance and cancer stemness in hepatocellular carcinoma
Authors: Hsin‐An Chen, Tsang‐Chih Kuo, Chi‐Feng Tseng, Jui‐Ti Ma, Shu‐Ting Yang, Chia‐Jui Yen, Ching‐Yao Yang, Shian‐Ying Sung, Jen‐Liang Su
Journal: Hepatology (2016)

Angiopoietin‐like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis. However, little is known about the effects of ANGPTL1 on sorafenib resistance and cancer stem cell properties in hepatocellular carcinoma (HCC) and the mechanism underlying these effects. Here, we show that ANGPTL1 expression positively correlates with sorafenib sensitivity in HCC cells and human HCC tissues. ANGPTL1 significantly decreases epithelial‐mesenchymal transition (EMT)‐driven sorafenib resistance, cancer stemness, and tumor growth of HCC cells by repressing Slug expression. ANGPTL1 directly interacts with and inactivates MET receptor, which contributes to Slug suppression through inhibition of the extracellular receptor kinase/protein kinase B (ERK/AKT)‐dependent early growth response protein 1 (Egr‐1) pathway. ANGPTL1 expression inversely correlates with Slug expression, poor sorafenib responsiveness, and poor clinical outcomes in HCC patients. Conclusion: ANGPTL1 inhibits sorafenib resistance and cancer stemness in HCC cells by repressing EMT through inhibition of the MET receptor−AKT/ERK−Egr‐1−Slug signaling cascade. ANGPTL1 may serve as a novel MET receptor inhibitor for advanced HCC therapy. (H epatology 2016;64:1637‐1651)
Pulmonary mucosa-associated lymphoid tissue lymphoma revisited
Authors: Emilie Catherinot, Elisabeth Longchampt, Agnès Ferroni, Elisabeth Rivaud, Pierre Cahen, Louis-Jean Couderc
Journal: European Respiratory Journal (2016)

We read with great interest the review of Borie et al. [1] on pulmonary lymphoma of the mucosa-associated lymphoid tissue (MALT). We agree with the hypothesis that chronic antigen stimulation of microbial origin may lead to the development of pulmonary MALT lymphoma. Indeed, MALT lymphoma has been associated with various chronic infections in extrapulmonary localisations. This link has previously been demonstrated between Helicobacter pylori infection and gastric MALT lymphoma, and suggested with Campylobacter jejuni , Chlamydia psittaci and Borrelia burgdorferi with small intestine lymphoma, ocular annexa lymphoma and cutaneous lymphoma, respectively. Similarly a link has recently been suggested between infection with Achromobacter xylosoxidans and pulmonary MALT lymphoma [2]. Our results do not suggest a link between mycobacteria and pulmonary MALT lymphoma: high-speed sequencing is needed <http://ow.ly/xXXm301AQ6r>
Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders.
Authors: Douglas Buckner Johnson, Nikhil I. Khushalani, Igor Puzanov, Tejaswi Mudigonda, Howard Kaufman, Jeffrey Alan Sosman, Janice M. Mehnert, Joseph Clark
Journal: Journal of Clinical Oncology (2015)

9019 Background: Ipilimumab (Ipi) is a cornerstone of metastatic melanoma therapeutics. Since Ipi toxicities are largely immune-related, clinicians may withhold therapy in patients (pts) with pre-existing autoimmune disorders (AD). We assessed whether pts with AD treated with Ipi experienced exacerbation of their AD, excessive immune-related adverse events (irAEs), and optimal clinical activity. Methods: We retrospectively reviewed records from 12 pts with metastatic melanoma and pre-existing AD treated with Ipi from 4 centers. We characterized baseline AD symptoms, prior management, and disease course on therapy. We also assessed rates of classical Ipi-related irAEs, and subsequent clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Results: Of 12 pts, 5 had baseline rheumatoid arthritis, 3 had psoriasis/psoriatic arthritis, 1 had systemic lupus erythematosus, 1 had Crohn's disease, 1 had transverse myelitis, and 1 had sarcoidosis. Ten (83%) had previously received corticosteroids or other systemic therapy for their AD, including 5 ongoing at the time of Ipi initiation (low-dose prednisone in 2 pts and hydroxychloroquine in 3). Following Ipi, 6 pts (50%) had symptomatic worsening or flares of their AD; all resolved with short courses of corticosteroids and none required additional immune suppression. Grade 3-5 irAEs were observed in 5 pts (42%) including colitis (n = 2), hypophysitis (n = 2), and acute angle glaucoma (n = 1). One treatment-related death occurred, presumably from colitis and possibly hypophysitis (no laboratory confirmation) following dose 3 of Ipi. ORR was 17% (2/12 pts); median OS and PFS were and 22.0 and 3.0 months, respectively. One pt experienced a durable complete response. Conclusions: This is the largest study of Ipi in pts with autoimmune disorders. Ipi was associated with moderate tolerability and clinical activity in this cohort of pts with mild to moderate pre-existing AD. Clinicians should monitor pts closely for irAEs and AD flares. Larger retrospective and prospective studies are ongoing to characterize this cohort further.
Liver transplantation for advanced hepatocellular carcinoma
Authors: Hae Won Lee, Kyung-Suk Suh
Journal: Clinical and Molecular Hepatology (2016)

There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future. Keywords: Carcinoma; Hepatocellular; Transplantation, Liver; Selection Criteria; Expanded criteria; Biomarker
Upper gastrointestinal (GI) motility is affected by hypoallergenic feed composition
Authors: Nathalie Rommel, Margot Selleslagh, Rosan Meyer, Michalis Papadopoulos, Gloria Dominquez, Claire De Koker, Robert Dziubak, Sofie Verschueren, Charlotte Scheerens, Eveline Deloose, Lukas Van Oudenhove, Taher Omari, Jan Tack, Neil Shah
Journal: Allergy (2013)
Inability to Tolerate Standard Therapy Is a Major Reason for Poor Outcome In Older Adults with Acute Lymphoblastic Leukemia (ALL): Results From the International MRC/ECOG Trial
Authors: Jonathan I Sive, Georgina Buck, Adele Fielding, Hillard M. Lazarus, Mark R. Litzow, Selina Luger, David I. Marks, Andrew McMillan, Susan M Richards, Jacob M. Rowe, Martin S. Tallman, Anthony H. Goldstone
Journal: Blood (2010)
Nyha classification, creatinine and oral anticoagulation are independent risk factors for adverse outcome in patients with Eisenmenger’s syndrome
Authors: Alexander Van De Bruaene, Marion Delcroix, Agnes Pasquet, Julie De Backer, Michel De Pauw, Robert Naeije, Jean-Luc Vachiéry, Bernard Paelinck, Marielle Morissens, Werner Budts
Journal: Circulation (2010)
Evaluation of speech outcomes in oral and oropharyngeal cancers
Authors: R. C. Dwivedi
Journal: Journal of Clinical Oncology (2009)

e17039 Background: The aim of the study was to review the literature on oral and oropharyngeal cancers for speech outcomes over the last 8 years. Study design: Systematic review of published studies between 2000 and 2008. Methods: A comprehensive literature search for speech outcomes was performed on PUBMED/MEDLINE, EMBASE, CINAHL, and Science citation index from 2000 to 2008 using the key words- speech, voice, articulation, acoustic analysis etc in oral and oropharyngeal cancers. The reference lists from the selected relevant articles were also inspected and any other pertinent publications were added to the final review. Articles published in all languages on human subjects, and all types of studies were included. Sixty eight articles satisfied the inclusion criterion and their findings were tabulated, analysed and evaluate based on the modality used for evaluation - questionnaire evaluation (QE), perceptual evaluation (PE) and acoustic analysis (AE). Results: 39/68 studies used questionnaires; 30/68 used PE and 2/68 used acoustic analysis. Questionnaires with PE were used in 5 studies. Thirty three/ 68 were retrospective, 28/68 prospective and 7/68 were cross-sectional studies. The finds suggest that the Frequency and quality of abnormal phonation depends on postoperative deficits. Oral (vs. oropharyngeal) cancers, advanced (vs. early), associated comorbidities (vs. without comorbidities), flap reconstruction (vs. primary closure), irradiated (vs. non-irradiated) and Mandibulotomy (vs. without mandibulotomy) have poor speech outcome. Preservation of Tip of tongue and FOM, lateral type excision, smaller excision, greater tongue mobility, primary closure and younger patients have better speech outcome. Conclusions: No validated scoring system for PE has been used; QE needs to be done with speech/ dysarthria specific questionnaires. Most studies suffered because of their retrospective nature, single modality evaluation, small sample size and short duration of follow-up. There is a clear paucity of acoustic analysis studies in oral and oropharyngeal literature and further longitudinal studies are needed. No significant financial relationships to disclose.
Case 50-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Judah Folkman, Jaime Prat
Journal: New England Journal of Medicine (1980)

Presentation of CaseA three-year-old girl from Bogotá, Colombia, was admitted to the hospital because of an abdominal mass.She was delivered by cesarean section of an uncomplicated, full-term second pregnancy and was in good health until six weeks before entry, when she began to have night sweats. Two weeks before admission abdominal pain, anorexia, fever, and a sore throat developed; a physician made a diagnosis of laryngitis. Abdominal pain recurred, and she complained of bilateral shoulder pain and persistent pain in the throat. During the week before entry she appeared pale and yellow. Four days before admission she entered . . .
A New Flowcytometry-Based Method to Discriminate Malignant From Normal Stem Cells in CML.
Authors: Jeroen J.W.M. Janssen, Wendy Deenik, Karlijn G.M. Smolders, Monique Terwijn, Angele Kelder, J. J. Cornelissen, Gerrit-Jan Schuurhuis, Gert J. Ossenkoppele
Journal: Blood (2009)