tbuckley/cabot-search huggingface dataset:
Eosinophilic pneumonias
Authors: V. Cottin, J.‐F. Cordier
Journal: Allergy (2005)

Eosinophilic pneumonias (EP) encompass a wide spectrum of lung diseases characterized by peripheral blood eosinophilia (&gt;1 × 10 9 eosinophils/l) and/or alveolar eosinophilia (&gt;25%). Blood eosinophilia may be lacking, as in the early phase of idiopathic acute EP, or in patients already taking oral corticosteroids. EP may present with varying severity, ranging from almost asymptomatic infiltrates to the acute respiratory distress syndrome necessitating mechanical ventilation. Possible causes of EP must be thoroughly investigated, especially drugs and the variety of parasitic infections (considering history of travel or residence in areas of endemic parasitic infection). However, chronic EP remains idiopathic in many cases. When present, extrathoracic manifestations lead to suspect Churg–Strauss syndrome (CSS) or the hypereosinophilic syndrome (HES), the prognosis of which is dominated by cardiac involvement. Apart from the treatment of specific causes when possible, corticosteroids remain the cornerstone of symptomatic treatment for eosinophilic disorders, usually with a dramatic response, but frequent relapses when tapering or after stopping the treatment. The adjunction of immunosuppressants to corticosteroids is necessary in patients with CSS and poor prognosis factors. Imatinib has recently proven effective in the treatment of the myeloproliferative variant of the HES.
Health-related quality of life measures in melanoma patients receiving pulsed high-dose intravenous interferon alpha 2b (IFNα2b)
Authors: P. Mohr, A. Hauschild, U. Trefzer, K. Neuber, A. Enk, K. Raas, H. Gogas, T. Kuechler, M. Weichenthal
Journal: Journal of Clinical Oncology (2007)

8536 Background: Major problems of high-dose interferon (HDI) in patients with malignant melanoma (MM) result from side effects and impairment of quality of life (QoL). Up to now it is unclear whether intraveneous (iv), subcutaneous (sc), or both components of HDI treatment are necessary for the efficacy in adjuvant treatment of MM. The adjuvant phase III DeCOG MM-ADJ-5 trial evaluates efficacy, safety, and tolerability of pulsed high-dose intravenous IFNa2b. In this prospective, randomized trial, 3 courses of IFNa2b 20 Mio IU/m 2 iv on 5 days a week for 4 weeks repeated every 4 months are compared to the standard HDI regimen. The higher iv dosage produces more toxicity, but for a shorter period of time, since patients in the pulsed treatment arm are 9 months off treatment as compared to the conventional sc treatment with 10 Mio IU/m 2 three times a week given for 11 months after 4 weeks of iv therapy. Methods: With a planned recruitment of 600 patients, an interim analysis of QoL has been performed after half of the patients completed treatment. EORTC QLQ- C30 questionnaire modified for interferon side effects was obtained before therapy, and at 4, 16, 24, and 40 weeks of treatment. The global QoL items were obtained weekly by a visual analogue scale over the whole year of treatment. Additionally, the side effects were scored using CTC- AE toxicity levels, and dose modifications were recorded. Results: A total of 300 patients were evaluated. After 4 weeks of initial iv HDI treatment the global QoL score decreased similarly in both treatment groups (35% vs. 41%). Four weeks after the initial iv pulse, the global QoL score completely recovered in the experimental arm (104%). In the conventional HDI, QoL remained reduced by an average 22% during the whole subcutaneous treatment phase. During the second and third iv-pulse in the experimental arm, QoL again decreased and completely recovered thereafter. Overall, the cumulative QoL score measured for 12 months treatment was significantly in favour of the pulsed regimen (+16% AuC value). Conclusions: Patients under pulsed adjuvant HDI treatment experience significantly less impairment of QoL and may therefore have a higher rate of completing the scheduled dosage. [Table: see text]
Antigen-Presenting Cells in the Skin
Authors: Sakeen W. Kashem, Muzlifah Haniffa, Daniel H. Kaplan
Journal: Annual Review of Immunology (2017)

Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen-sensing, -processing, and -presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation. Skin APCs are a highly heterogeneous population with functionally specialized subsets that are developmentally imprinted and modulated by local tissue microenvironmental and inflammatory cues. This review explores recent advances that have allowed for a more accurate taxonomy of APC subsets found in both mouse and human skin. It also examines the functional specificity of individual APC subsets and their collaboration with other immune cell types that together promote adaptive T cell and regional cutaneous immune responses during homeostasis, inflammation, and disease.
Mutator Genes UDG and AID Appear To Be Normal in Class-Switch Deficient and Clonally Homogeneous Waldenstrom’s Macroglobulinemias Having Either Germline or Hypermutated Clonotypic IgH VDJ.
Authors: Jitra Kriangkum, Brian J. Taylor, Erin R. Strachan, Steven P. Treon, Michael J. Mant, Tony Reiman, Andrew R. Belch, Linda M. Pilarski
Journal: Blood (2004)
Carboplatin and paclitaxel versus cisplatin, paclitaxel and doxorubicin for frontline chemotherapy of advanced ovarian carcinoma (AOC): A Hellenic Cooperative Oncology Group Study
Authors: G. Aravantinos, G. Fountzilas, H. P. Kalofonos, D. V. Skarlos, P. Kosmidis, I. Grimani, N. Pavlidis, D. Bafaloukos, D. Pectasides, M. A. Dimopoulos
Journal: Journal of Clinical Oncology (2006)

5074 Background: Carboplatin combined with paclitaxel are considered treatment of choice as initial chemotherapy for AOC. We compared this combination with a regimen combining cisplatin plus paclitaxel and doxorubicin. In the pre-taxane era the addition of doxorubicin to the cisplatin-based regimens appeared to improve survival. Therefore, there was a significant interest in assessing the role of a taxane/platinum/ anthracycline combination therapy in a randomized study. Methods: Patients with AOC after the initial cytoreductive surgery were stratified according to the FIGO stage and the presence of residual disease and randomized to either 6 courses of paclitaxel 175 mg/m 2 as 3h infusion plus carboplatin 7AUC (group A) or paclitaxel at the same dose plus cisplatin 75 mg/m 2 plus doxorubicin 40 mg/m 2 and G-CSF (Lenograsim) 0.263 mg sc from day 7 to day 11 (group B). Primary endpoint was overall survival (OS). At alpha = 5%, 400 patients were required, to detect with power of 80%, a ±15% difference to a baseline survival rate of 50% at the 3-year time point. Results: Intent to treat analysis was performed on 432 patients (group A: 210, B: 222). The treatment groups were well balanced in terms of major patient and tumor characteristics. 70% of the patients had stage III and 23% stage IV disease. Significantly more patients developed febrile neutropenia in group B (p = 0.01). No other significant differences were observed in terms of severe toxicity and no difference was found between the two groups in complete and overall response rate. With a median follow up of 44 months, median survival was 37.2 months in group A and 45.2 months in group B (p = 0.33). Conclusions: Both regimens are well tolerated and effective as first line chemotherapy of AOC. Combination of cisplatin, paclitaxel and doxorubicin does not seem to improve survival as compared with the standard carboplatin/paclitaxel regimen. No significant financial relationships to disclose.
Use of Crispr/Cas Genome Editing in Ba/F3 Cells to Generate the Fip1l1-Pdgfra and Nup214-Abl1 Fusion Genes
Authors: Marlies Vanden Bempt, Charles E de Bock, Nicole Mentens, Olga Gielen, Ellen Geerdens, Sofie Demeyer, Jan Cools
Journal: Blood (2014)
Abstract 3626: Expression of BARD1 splice variant impairs homologous recombination and can predict PARP1 inhibitor therapy in colorectal cancer
Authors: Ozkan Ozden, Faraz Bishehsari, Jessica Bauer, Seung Hyua Baik, Barbara Jung
Journal: Cancer Research (2015)

Abstract Background &amp; Aims: BRCA1 associated RING domain protein 1 (BARD1) stabilizes BRCA1 protein by forming a heterodimeric RING-RING complex. Its alterations impact function of BRCA1, disabling HR (homologous recombination) repair leading to sensitivity to PARP-1 inhibition in cancer. In colorectal cancer (CRC), we observed expression of BARD1 splice variants (SVs) and loss of full-length is associated with poor prognosis despite wild type expression of BRCA1. Here, we examined the roles of BARD1 SV and its therapeutic impact on PARP-1 inhibition, oxaliplatin and irinotecan sensitivity in CRC cell lines. Methods: A panel of CRC cell lines was treated with PARP-1 inhibitor, ABT888, and HR proficiency assessed via RAD51 foci formation. BARD1 splice variant (SV B1/4) transcription was determined via real-time PCR, and protein expression assessed via immunoblotting. Tumorigenesis of CRC cells expressing SV B1/4 and wild type BARD1 was measured by epithelial-mesenchymal transitions (EMT), colony formation abilities, and migration assays. Results: Caco-2 CRC cells were significantly more sensitive to PARP-1 inhibition when compared to the other CRC cell lines. This sensitivity was not associated with loss of BRCA1 or full-length BARD1 expression but rather with expression of BARD1 SV 1/4. Caco-2 showed significantly impaired HR response following PARP-1 inhibition with ABT888 and characterized by decreased RAD51 foci formation. Exogenous expression of the BARD1 SV B1/4 in SW480 cells exhibits a more transformed phenotype, decreased RAD51 foci formation, reduced BRCA1 E3 ubiquitin ligase activity, and increased sensitivity to PARP-1 inhibitor. Addition of irinotecan to ABT888 pre-treated cells created higher specificity and sensitivity with respect to killing of SV B1/4 expressing SW480 cells. Further immunofluorescence and confocal microscopy studies are underway to investigate the effect of BARD1 SV B1/4 on BRCA1 homologous recombination DNA repair function. Conclusions: Expression of BARD1 SV might be a potential biomarker for therapeutic sensitivity to PARP-1 inhibitors in treatment of CRC. Citation Format: Ozkan Ozden, Faraz Bishehsari, Jessica Bauer, Seung Hyua Baik, Barbara Jung. Expression of BARD1 splice variant impairs homologous recombination and can predict PARP1 inhibitor therapy in colorectal 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 3626. doi:10.1158/1538-7445.AM2015-3626
P0614 : Key HBsAg mutations significantly correlate with HCC, hamper HBsAg secretion and promote cell proliferation in vitro
Authors: M. Surdo, R. Salpini, N. Warner, M.F. Cortese, C. Mirabelli, D. Colledge, S. Soppe, M. Pollicita, R. Longo, S. Romano, G. Cappiello, A. Spanò, P. Trimoulet, H. Fleury, J. Vecchiet, N. Iapadre, A. Barlattani, A. Bertoli, T. Mari, C. Pasquazzi, G. Missale, C. Sarrecchia, E. Orecchini, A. Michienzi, M. Andreoni, S. Francioso, M. Angelico, F. Ceccherini-Silberstein, S. Locarnini, C.-F. Perno, V. Svicher
Journal: Journal of Hepatology (2015)
Tumor response to chemotherapy as a surrogate endpoint of survival in advanced non-small cell lung cancer (NSCLC): Results of an individual patients data meta-analysis
Authors: P. Bruzzi, M. Sormani, M. Tiseo, L. Boni, R. Rosell, A. Ardizzoni
Journal: Journal of Clinical Oncology (2007)

7548 Background: In order to assess the validity of objective response to chemotherapy (CT) as a surrogate endpoint of survival in advanced non-small cell lung cancer (NSCLC), we applied the four Prentice criteria to the data collected in the CISCA meta-analysis, comparing the efficacy of carboplatin and cisplatin in the first-line treatment of advanced NSCLC. Methods: Nine trials including 2,968 patients (pts) were analyzed in the CISCA meta-analysis. The prognostic effect of tumor response on survival was analyzed setting a landmark at two months after randomization (time of response recording), in order to eliminate early death from the analysis. After this landmark correction, pts included in the validation analysis were 2,525 with complete data on tumor response and survival. Results: Cisplatin-based CT was associated with a significantly higher tumor response rate compared with carboplatin-based CT (OR = 1.39; 95% CI: 1.18–1.64; p &lt; 0.001). Carboplatin regimens also led to a numerically higher risk of death as compared to cisplatin (HR = 1.06; 95% CI: 0.98–1.16; p = 0.15). Tumor response was a highly significant predictor of survival (HR = 0.50; 95% CI: 0.46–0.55; p &lt; 0.001). When tumor response was introduced in the Cox model (as a four level variable), the hazard ratio in favour of cisplatin treatment changed from 1.06 to 1.004 (95% CI: 0.922–1.093; p = 0.94), indicating that no residual effect of the cisplatin treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of cisplatin CT was a result of the increase in response rate. The median survival time of patients with complete and partial response was 19.5 months (95% CI: 11.5–27.5 months) and 14.0 months (95% CI: 13.1–14.9 months), respectively; whereas, the median survival time of patients with no response was 7.8 months (95% CI: 7.5–8.1 months). Conclusions: These results support the hypothesis that the achievement of an objective response to CT in advanced NSCLC is associated with a survival benefit. The potential role of objective response as a surrogate endpoint for survival in CT trials of advanced NSCLC warrants further investigation. No significant financial relationships to disclose.
LIVER TRANSPLANTATION IN POLYCYSTIC LIVER DISEASE : EXCELLENT SURVIVAL AND IMPROVEMENT OF QUALITY OF LIFE
Authors: Loes van Keimpema, Frederik Nevens, Rene Adam, Robert J. Porte, Panagiotis Fikatas, Thomas Becker, Preben Kirkegaard, Herold J. Metselaar, Joost P. Drenth
Journal: Hepatology (2009)
Effect of antioxidants on STAT3, cell survival gene products, apoptosis and chemoresistance in lung cancer cells
Authors: A. K. Pathak, M. Bhutani, R. Pathak, A. Mohan
Journal: Journal of Clinical Oncology (2006)

20067 Background: We had earlier demonstrated that antioxidants (beta carotene, vitamins C and E) enhance the apoptotic effect of paclitaxel and carboplatin in vitro and there was a suggestion that when used as an adjunct to the above chemotherapeutic agents in patients with NSCLC, they might enhance the efficacy of the latter. To elucidate the mechanism underlying the synergistic effect between antioxidants and chemotherapy, in the present study we evaluated the effect of antioxidants on STAT3 activation in NSCLC cells. Since this transcription factor has been shown to regulate multiple oncogenic pathways, including pathways regulating tumor cell survival, we further studied how STAT3 modulation relates to apoptosis and downstream apoptosis regulatory proteins. Methods: H520 cells were treated with antioxidants. STAT3 proteins were assessed by western blotting and their nuclear localization was evaluated by immunocytochemistry. Antiapoptotic proteins (survivin, Bcl-2, Bcl-xl and cyclin D1) were evaluated by Western blotting. To assess the interaction, cells were treated with chemotherapy (Paclitaxel and Carboplatin) with or without antioxidants and the effect was assessed by Live &amp; Dead assay, MTT assay and flowcytometry. Results: Antioxidants inhibited STAT3 phosphorylation in a dose and time dependent manner before the initiation of cell death and depleted the nuclear pool of STAT3. This effect was specific since there was no effect on STAT5 phosphorylation and was reversible since STAT 3 reverted back to its constitutively activated state after the removal of antioxidants. Antioxidants suppressed the expression of antiapoptotic proteins Bcl -2, Bcl-xl, cyclin D1 and survivin. This resulted in the inhibition of proliferation of cells and induction of apoptosis as evident on caspase 3 activation and PARP cleavage. Antioxidants arrested the cells in G0/G1 phase of cell cycle making them more vulnerable to the cytotoxic effects of chemotherapy. This synergy was evident on live and dead assay. Conclusions: Our results demonstrate that antioxidants are potent inhibitors of STAT3 phosphorylation and can have a potential role as an adjunct to chemotherapy in lung cancer. No significant financial relationships to disclose.
O-0012 Prognostic Factors of Overall Survival (OS) in Previously Treated Advanced Gastric Cancer (AGC): Analysis of the Phase 3 Granite-1 Trial
Authors: Eric Van Cutsem, Yasuo Hamamoto, Jeeyun Lee, Atsushi Ohtsu, Shukui Qin, Timothy Price, Rui-Hua Xu, Eun-Kee Song, Feng Bi, Olivier Bouché, Alain Feliu, Tonia Nesheiwat, Rosemary Delaney, Joann Chen, Chiara Costantini, Syed Rizvi, Tarek Sahmoud, Tashiko Doi
Journal: Annals of Oncology (2012)
Salvage gastrectomy for unresectable advanced gastric cancer after combination chemotherapy with docetaxel, cisplatin, and S-1.
Authors: Kei Hosoda, Keishi Yamashita, Shinichi Sakuramoto, Hiroaki Mieno, Katsuhiko Higuchi, Hiomitsu Moriya, Natsuya Katada, Shiro Kikuchi, Masahiko Watanabe
Journal: Journal of Clinical Oncology (2013)

e15113 Background: The prognosis for patients with unresectable advanced gastric cancer treated with chemotherapy alone is extremely poor. We have evaluated the safety and efficacy of salvage gastrectomy following chemotherapy with docetaxel, cisplatin, and S-1 (DCS) in patients with unresectable advanced gastric cancer. Methods: We evaluated 30 patients with unresectable advanced gastric adenocarcinoma whose lesions were down-staged by DCS chemotherapy and who underwent salvage gastrectomy with lymph node dissection from 2006 to 2012, when visible lesions were judged resectable. We retrospectively reviewed their medical records to identify factors that would influence overall survival. Results: Of the 30 patients, 17 had extra-regional lymph node metastases, 5 had liver metastases, 9 had peritoneal dissemination and 6 had pancreatic head invasion prior to DCS chemotherapy. Of the 30 patients, 23, 3, and 4 underwent R0, R1, and R2 resection, respectively. No in-hospital deaths or reoperations occurred. Pathological evaluation of primary tumors revealed grades 3, 2, 1b, 1a, and 0 tumor regression in 4, 9, 7, 7, and 2 patients, respectively. Median progression-free survival was 19 months.Two-year progression-free survival and overall survival rates were 45% and 65%, respectively. Of 17 patients with target tumors, 15 had partial responses, making the overall response rate 88%. The most common grade 3/4 hematologic toxicity was neutropenia (56%); all treatment-related toxicities were resolved, and no patient died of toxicity-related causes. Univariate analysis showed that R1/2 surgery (p&lt;0.001), diffuse type histology (p=0.054), histological grade 0/1a/1b following chemotherapy (p&lt;0.033), ypN3 (p&lt;0.001) and yply2/3 (p=0.003), were significantly prognostic of reduced overall survival. A multivariate proportional hazard model found that ypN3 (p=0.003) was the sole independent prognostic factor. Conclusions: Salvage gastrectomy after DCS chemotherapy was safe and effective in patients with unresectable advanced gastric cancer. Lymph node metastasis after chemotherapy was significantly prognostic of poor prognosis, suggesting the need for further treatment.
The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules
Authors: Freidrich M. Cruz, Jeff D. Colbert, Elena Merino, Barry A. Kriegsman, Kenneth L. Rock
Journal: Annual Review of Immunology (2017)

To monitor the health of cells, the immune system tasks antigen-presenting cells with gathering antigens from other cells and bringing them to CD8 T cells in the form of peptides bound to MHC-I molecules. Most cells would be unable to perform this function because they use their MHC-I molecules to exclusively present peptides derived from the cell's own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC-I through a process called cross-presentation. How this important task is accomplished, its role in health and disease, and its potential for exploitation are the subject of this review.
P0877 : HCVRNA levels assessed at early stages of sofosbuvir/ribavirin dual therapy identify relapse patients
Authors: B. Maasoumy, J. Vermehren, C. Berkowski, B. Bremer, G. Cloherty, D. Perner, M.P. Manns, S. Zeuzem, M. Cornberg, H. Wedemeyer, C. Sarrazin
Journal: Journal of Hepatology (2015)
Pulmonary vascular cell dysfunction in chronic thromboembolic pulmonary hypertension: a role of c-reactive protein?
Authors: Rozenn Quarck, Marijke Wynants, E Alfaro-Moreno, M. Rosario Sepulveda, Frank Wuytack, Dirk Van Raemdonck, Bart Meyns, Marion Delcroix
Journal: Cardiovascular Research (2010)
Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index
Authors: Claudia Pagliari
Journal: JAMA Pediatrics (2016)

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