tbuckley/cabot-search huggingface dataset:
A phase I study of carboplatin plus oral topotecan in advanced malignancies
Authors: E. Kim, H. Hochster, Y. Novik, A. Chachoua, J. Speyer, F. Muggia
Journal: Journal of Clinical Oncology (2004)

2137 Background: Topotecan given by continuous infusion (CIV) causes less myelosuppression (M) than bolus topotecan; when given orally bid, it may mimic CIV. Tolerance of “topotecan per os” (TPO) with carboplatin (C) was studied in a dose escalation schema. Methods: Patients (pts) with advanced malignancy, PS 0–1, <4 prior regimens, and adequate organ function were eligible. All pts received prior therapy. C AUC 4 D1 and TPO 0.4 mg/m2 or 0.5 mg/m2 bid x 21 days (d) were given every 28d. TPO dosing was interrupted for ANC < 1000 or plts ≤ 75K. Results: The first 7 pts were treated at dose level 1 (0.4mg/m2) and 3 at dose level 2 (0.5mg/m2). Only 11/25 cycles of TPO were given for a full 21d. Reasons for not completing TPO cycles - 7 thrombocytopenia (T), 3 infection (I), 2 progressive disease (PD), 1 adverse event (AE), 1 patient decision. Of 11 complete TPO cycles, 5 subsequent cycles were delayed (3 T, 1 neutropenia (N), 1 I). M was the most serious toxicity, with 3 developing G4 N, 2 febrile neutropenia (FN), and 3 G4 T. In contrast to our prior reports of TPO with either cisplatin or doxil (ASCO 2001 abstract # 2075, mainly ovarian pts), GI toxicity was not dose-limiting (no G3/4 vomiting (V) diarrhea (D)). One partial response (PR) for 22 weeks (wks) and 1 stable disease (SD) for 10 wks were noted (Table 1). Conclusion: C plus TPO had M as the dose-limiting toxicity. In contrast to other TPO regimens, GI toxicity was less severe. We recommend TPO 14d dosing (rather than 21d) when given in combination. Supported by GlaxoSmithKline, NCI core grant # P30 CA16087 Table 1 CTC v 2.0 Common Toxicity Criteria Version 2.0 (or CTC v 2.0) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb GlaxoSmithKline
Fusion Gene Detection Using Whole Transcriptome Analysis in Patients with Chronic Myeloproliferative Neoplasms and Secondary Acute Myeloid Leukemia
Authors: Fiorella Schischlik, Jelena D. Milosevic Feenstra, Elisa Rumi, Daniela Pietra, Bettina Gisslinger, Martin Schalling, Edith Bogner, Heinz Gisslinger, Mario Cazzola, Robert Kralovics
Journal: Blood (2015)
P0568 : TGF-β signaling is activated in patients with chronic hepatitis B and is repressed by SMAD 7 over expression during long term antiviral treatment
Authors: G. Germanidis, N. Argentou, P. Hytiroglou, E. Apostolou, T. Vassiliadis, K. Patsiaoura, P. Sideras, A. Germenis, M. Speletas
Journal: Journal of Hepatology (2015)
Improving influenza virological surveillance in Europe: strain-based reporting of antigenic and genetic characterisation data, 11 European countries, influenza season 2013/14
Authors: Eeva Broberg, Olav Hungnes, Brunhilde Schweiger, Katarina Prosenc, Rod Daniels, Raquel Guiomar, Niina Ikonen, Athanasios Kossyvakis, Francisco Pozo, Simona Puzelli, Isabelle Thomas, Allison Waters, Åsa Wiman, Adam Meijer
Journal: Eurosurveillance (2016)

Influenza antigenic and genetic characterisation data are crucial for influenza vaccine composition decision making. Previously, aggregate data were reported to the European Centre for Disease Prevention and Control by European Union/European Economic Area (EU/EEA) countries. A system for collecting case-specific influenza antigenic and genetic characterisation data was established for the 2013/14 influenza season. In a pilot study, 11 EU/EEA countries reported through the new mechanism. We demonstrated feasibility of reporting strain-based antigenic and genetic data and ca 10% of influenza virus-positive specimens were selected for further characterisation. Proportions of characterised virus (sub)types were similar to influenza virus circulation levels. The main genetic clades were represented by A/StPetersburg/27/2011(H1N1)pdm09 and A/Texas/50/2012(H3N2). A(H1N1)pdm09 viruses were more prevalent in age groups (by years) &lt; 1 (65%; p = 0.0111), 20–39 (50%; p = 0.0046) and 40–64 (55%; p = 0.00001) while A(H3N2) viruses were most prevalent in those ≥ 65 years (62%*; p = 0.0012). Hospitalised patients in the age groups 6–19 years (67%; p = 0.0494) and ≥ 65 years (52%; p = 0.0005) were more frequently infected by A/Texas/50/2012 A(H3N2)-like viruses compared with hospitalised cases in other age groups. Strain-based reporting enabled deeper understanding of influenza virus circulation among hospitalised patients and substantially improved the reporting of virus characterisation data. Therefore, strain-based reporting of readily available data is recommended to all reporting countries within the EU/EEA.
Anatomical Compartments Modulate the Response of Human Hematopoietic Cells to Mitogenic Signaling, In Vivo.
Authors: Linlin Wang, Yasuo Nagasawa, Brent Wood, Ingrid Lintmaer, Wenjin Guo, Michael Harkey, Thalia Papayannopoulou, Cynthia Nourigat
Journal: Blood (2005)
Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial
Authors: J. Quidde, S. Hegewisch-Becker, U. Graeven, C.A. Lerchenmüller, B. Killing, R. Depenbusch, C.-C. Steffens, T. Lange, G. Dietrich, J. Stoehlmacher, A. Reinacher, A. Tannapfel, T. Trarbach, N. Marschner, H.-J. Schmoll, A. Hinke, S.-E. Al-Batran, D. Arnold
Journal: Annals of Oncology (2016)
Therapeutic activity of neutralizing monoclonal antibodies targeting hepatoma-derived growth factor in cancer xenograft models
Authors: L. Mao, H. Ren, Z. Chu, P. Yuan
Journal: Journal of Clinical Oncology (2006)

2517 Background: Hepatoma-derived growth factor (HDGF) is a mitogen for endothelial cells, vessel smooth muscle cells, fibroblasts, as well as some epithelial cells. It is overexpressed in a number of human cancers and its overexpression in tumors strongly correlates with tumor progression, recurrence, and metastasis. We recently showed that down-regulation of HDGF in lung cancer cells reduces tumorigenecity in both in vitro cell and in vivo animal models suggesting HDGF may be of a therapeutic target for cancer. Methods: Recombinant HDGF was used to develop a panel of monoclonal antibodies specifically bind to HDGF. Four antibodies were tested for their therapeutic activity in lung and pancreatic cancer xenograft models. The monoclonal antibodies were administered 250μg/animal (5 mice per group) every 3 days IP when the subcutaneous tumors reached approximately 50 mm3. Results: Two antibodies (C1 and H3) exhibited significant therapeutic activity in A549 lung cancer model whereas H3 also showed a therapeutic effect in MiaPaca-2 pancreatic cancer model. No sign of toxicity in the living animals and histology of major organs were observed in the antibody treated animals. In the A549 model, the mean tumor burden was 960 mm3 for control-IgG treated mice 22 days after tumor inoculation, whereas the mean tumor burdens were 224 mm3 for C1 and 266 mm3 for H3 treated mice (P &lt; 0.05) respectively. In the MiaPaca-2, the mean tumor burden was 994 mm3 for control-IgG treated mice 21 days after tumor inoculation in contrast to 345 mm3 for H3 treated mice (P &lt; 0.05). Consistent with known biologic functions of HDGF, our early morphologic and biomarker analyses suggest that H3 may neutralize tumor cell released HDGF resulting in disruption of tumor stroma and extracellular matrix structures. Conclusions: HDGF is a novel therapeutic target for multiple human cancers and neutralizing monoclonal antibodies targeting HDGF are effective in treating lung and pancreatic cancers in animal models. (Supported by DoD grant DAMD17–01–1-01689–1) No significant financial relationships to disclose.
The Hypoxia-Inducible Factor-1alpha Is Constitutively Upregulated in TP53 Disrupted CLL Cells: A Potential Target to Overcome Fludarabine Resistance
Authors: Valentina Griggio, Candida Vitale, Chiara Riganti, Joanna Kopecka, Michele Dal Bo, Davide Rossi, Gabriele Pozzato, Luca Laurenti, Francesco Zallio, Monia Marchetti, Marina Ruggeri, Paola Omedè, Giovanni Del Poeta, Valter Gattei, Gianluca Gaidano, Mario Boccadoro, Massimo Massaia, Marta Coscia
Journal: Blood (2015)
GW26-e2360 SIRT1 Activities Ameliorate High Glucose Induced Endothelial Cellular Damage and Dysfunction of eNOS in an AMPK-Dependent Manner
Authors: Fei Cai, Cairong Li, Xuezhou Cai, Hang Xie, Weiyao Ding
Journal: Journal of the American College of Cardiology (2015)
Response to crizotinib and gefitinib in a lung adenocarcinoma patient harboring a concurrent EGFR exon 21 mutation and an ALK rearrangement.
Authors: Gabriel Alejandro Bien-Willner, Dong Yang, Christopher M. McCanless, Elizabeth Mambo
Journal: Journal of Clinical Oncology (2016)

e20639 Background: It has been established that activating EGFR mutations in exons 19 and 21, KRAS mutations in codon 12/13 and ALK rearrangements are mutually exclusive events in lung adenocarcinoma. However, recent advances in next generation sequencing technologies have and continue to revolutionize cancer management, and are allowing us to reassess these ideas with data from comprehensive cancer testing. Methods: We report the management of a 57 year old man (non-smoker) with stage IV lung adenocarcinoma with malignant pleural effusions harboring a concomitant EGFR p.L858R mutation and an ALK translocation. Mutational analysis was performed using Molecular Health’s Engineus targeted Profile+ of 613 genes on a pleural effusion sample. ALK rearrangements were evaluated by FISH methods (Personalized Dx, CA). Results: The patient was initially treated with crizotinib and showed objective response for 9 months, with ECOG performance status of 1 prior to progression, at which time the treatment was switched to gefitinib. The decision to attempt crizotinib therapy first was aided by a lack of response to erlotinib in similar cases anecdotally. At present, several months after gefinitib initiation, the patient is stable and continues to be monitored. Conclusions: To our knowledge, this is the first clinical case of a patient with concomitant EGFR mutation and ALK fusion to be treated with ALK inhibitor before EGFR tyrosine kinase inhibitor (TKI). These rare cases continue to challenge current molecular testing algorithms that suggest EGFR testing first and ALK testing only if no EGFR mutations are detected. The management of patients with coexisting mutant EGFR and ALK translocation presents a challenge of what monotherapy should be given first, or whether combination therapy should be administered. In this case, ALK inhibition provided a durable response prior to EGFR inhibition. Since there is no consensus on the treatment of this subgroup, continued reporting of the management of these patients with outcome data is necessary to determine the optimal treatment options in patients with concomitant mutant EGFR and ALK translocation.
Previously Unknown Interactions Between AML1 and MLL Provide Epigenetic Regulation of Gene Expression in Normal Hematopoiesis and in Leukemia
Authors: Gang Huang, Shannon Elf, Xiaomei Yan, Lan Wang, Yan Liu, Goro Sashida, Alex Gural, Silvia Menendez, Jennifer Lee, Youyang Yang, Xinyang Zhao, Stephen D. Nimer
Journal: Blood (2008)
Indication for neoadjuvant chemotherapy in adult patients with high-risk soft-tissue sarcomas
Authors: B. Kasper, E. Kuehl, P. Wuchter, L. Bernd, A. D. Ho, G. Egerer
Journal: Journal of Clinical Oncology (2006)

9578 Background: To determine the efficacy and safety of neoadjuvant chemotherapy for local tumour control and overall survival in patients with high-risk soft-tissue sarcomas (tumour size ≥ 5 cm, G II/III, extracompartimental and deep localisation) we have analyzed the clinical outcome in 25 patients. Methods: Patients with high-risk soft-tissue sarcomas were treated with four cycles of etoposide 125 mg/m 2 /day 1+4, ifosfamide 1500 mg/m 2 /day 1–4 and doxorubicin 50 mg/m 2 /day 1 (EIA regimen) followed by definitive surgery with or without postoperative radiotherapy and adjuvant chemotherapy. 21 patients received chemotherapy in a combined neoadjuvant/adjuvant clinical setting; eighteen of them completed adjuvant chemotherapy. Four patients received chemotherapy in an adjuvant setting only. Results: The objective response rate of neoadjuvant chemotherapy assessable in 21 patients was 43%. Including NED (n = 7) and partial remissions (n = 3), the radiographic response rate was 47.6% with additional 42.9% stable diseases (n = 9). Surgery was performed in two patients before completing the four neoadjuvant chemotherapy cycles because of disease progression. Median overall survival for all patients from the time of first diagnosis was 21.6+ months [range: 8 - 50] and from the start of treatment 20.5+ months [range: 8 - 49]; median progression-free survival after start of treatment was 18.6+ months [range: 1 - 49]. After completion of chemotherapy, R0-resection could be performed in 13 of 21 patients (60%). At completion of entire treatment, 21 of 25 patients (84%) had NED after R0- and R1-resection. Two patients showed no disease progression after R2-resection and are alive with disease (AWD) 21 and 18 months after start of treatment. Two patients died of disease (DOD) ten and eight months after first diagnosis due to metastases. Conclusions: The high proportion of R0-resections supports the idea of a tumour downstaging after neoadjuvant treatment. Our data support the hypothesis that neoadjuvant chemotherapy might be beneficial as an integral part in the treatment strategy of high-risk soft-tissue sarcoma patients. No significant financial relationships to disclose.
GW26-e4611 Male-Specific Association of APC rs383830-T Allele With the Risk of Coronary Heart Disease
Authors: Jinyan Zhong, Xiaowei Zheng, Huadan Ye, Hanbin Cui, Weiping Du, Zhaoxia Zhang, Xiaohong Fei, Shaoyi Lin, Jian Wang, Jia Su, Shiwei Duan, Xiaomin Chen
Journal: Journal of the American College of Cardiology (2015)
Excellent Outcome with Rituximab-CHOP (R-CHOP) Combined with Radiotherapy (RT) in Primary Mediastinal Large B-Cell Lymhoma (PMLBCL).
Authors: Theodoros P. Vassilakopoulos, Maria K. Angelopoulou, Zacharoula Galani, Sotirios Sachanas, Andreas Katsigiannis, Maria N. Dimopoulou, Styliani I. Kokoris, Evridiki Michalis, Evangelia M. Dimitriadou, Marina P. Siakantaris, Flora N. Kontopidou, Christina Kalpadakis, Angelos Sarantopoulos, Pinelopi Korkolopoulou, Paraskevi Roussou, Gerassimos A. Pangalis
Journal: Blood (2005)
Mesenchymal Stem Cells (MSC) Are Not Intrinsically Immune Privileged: Direct Demonstration in TCR Transgenic Mice and by Imaging of Allogeneic Luciferase+ MSC in Immune Competent Vs Immune Deficient Mice
Authors: Lior Zangi, Andreas Beilhack, Robert Negrin, Raanan Margalit, Yair Reisner
Journal: Blood (2008)
Do we need to correct coagulation abnormalities prophylactically in patients with cirrhosis undergoing invasive procedures? a dilemma
Authors: Deepak Amarapurkar, Vaibhav Somani, Apurva Shah
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. Study is supported by Rameshwarji Birla Smarak Kosh. TO THE EDITOR: We read with great interest the recently published study by Lesley et al.1 The researchers compared thromboelastography (TEG) with routine coagulation tests (prothrombin time [PT] and platelet count) to assess the risk of bleeding before invasive procedures in patients with cirrhosis. They concluded that TEG‐guided transfusion strategy leads to a significantly lower use of blood products compared to standard of care (transfusion guided by PT and platelet count) without an increase in bleeding complications in patients with significant coagulopathy. The researchers used preprocedural transfusions as the standard of care, but there is no recommendation for prophylactic transfusion in patients with cirrhosis undergoing invasive procedures. Prophylactic transfusions have not been beneficial; on the contrary, they have been harmful. Given that there was a very low incidence of bleeding in both the groups, Intagliata et al.,2 in a correspondence letter, suggested the need of a study without prophylactic correction of routine coagulation tests. In a multicenter, prospective study of 388 patients with cirrhosis undergoing invasive procedures, we did not use prophylactic transfusion and demonstrated that this strategy is extremely safe. Whenever indicated, any invasive procedures could be safely carried out in patients with cirrhosis without past correction of abnormal routine coagulation tests.3 In the preliminary data of an ongoing prospective study of 60 patients with cirrhosis who underwent invasive procedures, we compared TEG with conventional coagulation tests in all patients; none of the patients in the study received prophylactic correction of abnormal conventional coagulation tests before the invasive procedure or surgery. We found that only 1 patient developed postprocedural clinically significant bleeding.4 A recently published guideline by Nadim et al.5 also recommended against routine prophylactic use of fresh frozen plasma and suggested maintaining platelet counts above 50 × 109/L in the presence of active bleeding. Based on this discussion, we strongly recommend to avoid prophylactic transfusions in patients with cirrhosis undergoing invasive procedures and wait for further studies for the role of TEG in patients with cirrhosis undergoing an invasive procedure.
Adjuvant colon cancer care compliance with level I data and NCCN guidelines in the elderly population.
Authors: Anmol Baranwal, Dinah Faith Q Huff, Marc L. Fishman, Jurgen Kogler, William S. Shimp, Laura Rose Bobolts, Val Fishman, Melissa Armitage, Sharon Davis, Carol Anthony, Anna E. Schorer, Charles L. Bennett, William J. Hrushesky
Journal: Journal of Clinical Oncology (2014)

e14520 Background: Cancer is a disease of old age. Colorectal cancer (CRC) is among the most frequent solid tumors of elderly. Over the past four decades, progressively more efficacious and more toxic adjuvant regimens have evolved. Overall, combinations including oxaliplatin have been among the most efficacious. Older cancer patients often do not tolerate high doses of oxaliplatin. Recently, level I randomized controlled trial data demonstrate that among stage II & III CRC patients over 70 years of age, adjuvant oxaliplatin offers no overall survival advantage while adding toxicity.Oncology Analytics (OA) is a cancer care decision-support corporation comprised of board-certified oncologists, interacting daily with more than 2,800 cancer doctors in the South-Eastern (SE) US, making them aware of relevant level I data and current guidelines. We hypothesized that there has been a significant decline in the requests for oxaliplatin-containing adjuvant chemotherapy for elderly patients with stage II or III colon cancer in the SE United States since these data have appeared and NCCN guidelines have been modified. Methods: From August 2009 to October 2013, adjuvant therapy requests, for stage II or III colon cancer patients were characterized and tabulated. The proportions of patients over 70 years of age, who received or did not receive oxaliplatin were calculated. We used simple linear regression and chi squared analysis to determine time trends for the ratio of oxaliplatin to non-oxaliplatin containing regimens across these four years, and before and after the Sept. 2012 change in NCCN guidelines supporting these data. Results: Over this entire span, the majority of requests for the elderly (71% or 116/164) specified oxaliplatin-containing combinations. The annual proportions of oxaliplatin-containing chemotherapy requests relative to non-oxaliplatin requests did not change meaningfully across these four years (p=0.23), nor before and after the NCCN guidelines change(p=0.54). Conclusions: Neither level I data nor NCCN guideline change have yet altered adjuvant CRC care of the elderly in this region, causing OA to launch a three tiered effort to enhance CRC care quality for the elderly.
Expression of vascular endothelial growth factor (VEGF), p53 in Molecular breast cancer subtypes of pre-menopausal African-American women
Authors: C. U. Ihemelandu, L. D. Leffall, T. J. Naab, W. A. Frederick
Journal: Journal of Clinical Oncology (2007)

21084 Background: Tumor growth and metastasis have been shown to be dependent on angiogenesis. With the current classification of breast tumors into molecular subtypes with distinct prognosis and response to treatment, we sort to analyze the expression of the angiogenesis markers in molecular subtypes and determine their association with clinicopathologic variables of prognostic significance. Methods: A retrospective analysis of women diagnosed with breast cancer from 1998–2005, who had assessable data for ER, PR, and Her-2/neu status. The molecular subtypes were defined as: luminal A, luminal B, basal-like , and Her-2/neu. Results: All molecular breast cancer subtypes overexpressed VEGF, with no statistically significant difference noted between the subtypes: - luminal A (69.8%) basal-like (71.1%), luminal B (70.0%), Her-2/neu (71.0%) (p=.99). Subtypes differed significantly in expression of p53 (p&lt;.000), with the basal-like and Her-2/neu subtypes more likely to be associated with p53 mutations (51.7%) and (54.1%) respectively. No statistically significant association between p53 protein and increased VEGF expression was noted (p=.176) Statistically significant associations between p53 protein and prognostic factors ER (p&lt;.000), PR (p&gt;.000), histologic grade (p&lt;.000), S-phase fraction (p&lt;.001) were noted. A significant inverse correlation was noted between p53 expression and thrombospodin for the age-group &lt;35 years (rho -.810; p=.003). VEGF showed no significant association with the prognostic factors ER, PR, histologic grade and S-phase fraction. A tendency not reaching statistical significance was found between VEGF and angiogenesis (p=.09). A direct correlation between VEGF and thrombospodin was noted in the age- group &lt; 35 years (rho .800; p=.01). Expression of VEGF and thrombospodin did not correlate with survival outcome; however angiogenesis seemed to correlate with survival outcome. Survival outcome was influenced by molecular subtypes with the basal-like and Her-2/neu subtypes having a poorer outcome (p=.01). Conclusions: VEGF expression is not related to p53 status or survival outcome in molecular breast cancer subtypes of pre-menopausal African-American women. No significant financial relationships to disclose.
GW26-e2962 Continuous Angiotensin-(1-7) infusion improves myocardial calcium transient and calcium transient alternans in ischemia-induced cardiac dysfunction rats
Authors: Lichun Wang, Deng Luo, Chufan Luo, Ming Long, Chunyu Deng, Xinxue Liao
Journal: Journal of the American College of Cardiology (2015)
GW26-e1234 A prescription of Jiashen reduces postinfarct left ventricular remodeling via inhibition of TGF-β/Smads signaling pathway
Authors: Yuan Gao, Shiyang Xie, Youping Wang, Bin Li, Xiaoli Nan, Weihong Liu, Mingjun Zhu
Journal: Journal of the American College of Cardiology (2015)
The Feature of δRec-ψJα sjTRECs Level and Frequency of 23 TCR Vβ-Dβ1 sjTRECs in Mononuclear Cells, CD4+ and CD8+ T Cells from Cord Blood and Peripheral Blood of Normal Individuals.
Authors: Yangqiu Li, Qingsong Yin, Shaohua Chen, Lijian Yang, Grzegorz Przybylski, Christian A. Schmidt
Journal: Blood (2006)
Privacy, Propriety, and the United States Television Media: “Watch This Man Die, and Now We Are Going to Sell You Some Detergent”
Authors: Geoffrey Miller, William D. Graf
Journal: The American Journal of Bioethics (2016)

"Privacy, Propriety, and the United States Television Media: “Watch This Man Die, and Now We Are Going to Sell You Some Detergent”." The American Journal of Bioethics, 16(11), pp. 56–57