tbuckley/cabot-search huggingface dataset:
Comparative Effects of Selected Drug Combinations on the Growth of a Human Pancreatic Carcinoma Cell Line (MIA PaCa-2)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G Fountzilas, H Gratzner, L O Lim, A A Yunis
Journal: JNCI Journal of the National Cancer Institute (1986)

The inhibitory effect of several drug combinations on the growth of the human pancreatic carcinoma cell line MIA PaCa-2 was studied in relation to drug-scheduling interval in vitro. All drug exposures were for 1 hour. The sequential exposure of cells to 1.5×10−8M vincristine (VCR) or vindesine (VDS) followed by 2×10−8M 1,2-dihydroxy-9,10-anthracenedione (DHAD) or 3×10−7M adriamycin (ADR) had at best an additive effect, demonstrated by isobologram analysis, when the two drugs were given 6 hours apart. Flow cytometry (FCM) analysis after exposure of the cells to the priming drug alone, i.e., VCR or VDS, showed an accumulation of cells in S-phase. The exposure of MIA PaCa-2 cells to 1.6×10−5M 5-fluorouracil (FUra) followed by 2×10−8M DHAD or 3×10−7M ADR had an additive (with DHAD) or synergistic (with ADR) effect when the two drugs were given simultaneously and a synergistic effect with either drug when they were given 2, 6, or 24 hours apart. FCM analysis after exposure to FUra alone showed a rapid S-phase accumulation appearing within 6 hours and increasing further after 24 hours. Sequential exposure of cells to 1.5×10−8M VCR and 1.6×10−5M FUra had a synergistic effect, regardless of the sequence or the time interval between the two drugs.
HCP-07THE INFLUENCE OF PERIOPERATIVE SEIZURE PROPHYLAXIS ON SEIZURE RATE AND HOSPITAL QUALITY METRICS AFTER GLIOMA SURGERY
Authors: Michael Dewan, Gabrielle White-Dzuro, Philip Brinson, Reid Thompson, Lola Chambless
Journal: Neuro-Oncology (2015)

BACKGROUND: Seizures represent one of the most common and feared perioperative complications following brain tumor surgery.Despite conflicting evidence regarding efficacy, prophylactic antiepileptic drugs (AED) are frequently administered in an effort to reduce seizure incidence and improve patient and hospital reported outcomes.The authors address this question by examining an institutional glioma population.METHODS: Patients with glioma undergoing craniotomy for resection between 1998 and 2014 were enrolled into our institutional tumor registry.Perioperative seizures were considered those occurring within 14 days of the index surgery.Student t-test and multivariate logistic regression were used to analyze differences in means between continuous and categorical variables, respectively.RESULTS: Among 347 patients undergoing craniotomy for glioma resection, 299 (86.2%) were administered prophylactic AED post-operatively.Levetiracetam was the preferred agent, utilized in 73.7% of subjects.Sixteen (5.3%) patients receiving prophylactic AED suffered a perioperative seizure, compared to 1 (2.1%) not on prophylaxis (p ¼ 0.62).Among the 17 patients that suffered a perioperative seizure, only 6 (35%) had a prior history of seizure.Mean hospital length of stay (LOS) was similar between both groups: 3.29 (AED) vs. 3.54 (no AED) days, p ¼ 0.626.Similarly, there was no difference in ICU LOS among patients receiving (2.25 days) and not receiving (2.64 days) seizure prophylaxis, p ¼ 0.38.The prophylaxis group had a similar rate of 90-day ED visits as the non-prophylaxis group: 12.0 vs. 17.0%,p ¼ 0.341.However, patients administered seizure prophylaxis were less likely to be readmitted within 90 days of the index surgery (21.9 vs. 35%, p ¼ 0.041).CONCLUSIONS: To the authors' knowledge this is the first study specifically evaluating the influence of perioperative seizure prophylaxis on emerging hospital quality metrics including length of stay and readmission.Interestingly, while associated with lower rates of readmission, perioperative AED administration fails to reduce the risk of post-operative seizures or hospital and ICU LOS.
Stromal-Based Signatures for the Classification of Gastric Cancer
Authors: Mark T. Uhlik, Jiangang Liu, Beverly L. Falcon, Seema Iyer, Julie Stewart, Hilal Celikkaya, Marguerita O'Mahony, Christopher Sevinsky, Christina Lowes, Larry Douglass, Cynthia Jeffries, Diane Bodenmiller, Sudhakar Chintharlapalli, Anthony Fischl, Damien Gerald, Qi Xue, Jee-yun Lee, Alberto Santamaria-Pang, Yousef Al-Kofahi, Yunxia Sui, Keyur Desai, Thompson Doman, Amit Aggarwal, Julia H. Carter, Bronislaw Pytowski, Shou-ching Jaminet, Fiona Ginty, Aejaz Nasir, Janice A. Nagy, Harold F. Dvorak, Laura E. Benjamin
Journal: Cancer Research (2016)

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. ©2016 AACR.
Peripherally inserted central venous catheters (PICCs) in cancer patients placed by specialist nurses. A prospective observational study of 817 consecutive catheterizations
Authors: M. Muroni, F. Oleari, S. Bontini, C. Gozzo, O. Grassi, L. Cappucciati, G. Cremona, M.R. Cordani, L. Cavanna
Journal: Annals of Oncology (2015)
The DART Study: Part 1 results from the dalantercept plus axitinib dose escalation and expansion cohorts in patients with advanced renal cell carcinoma (RCC).
Authors: Martin Henner Voss, Elizabeth R. Plimack, Brian I. Rini, Michael B. Atkins, Robert Alter, Rupal Satish Bhatt, J. Thaddeus Beck, Musa Mutyaba, Kristen M. Pappas, Dawn Wilson, Xiaosha Zhang, Matthew L. Sherman, Shuchi Sumant Pandya
Journal: Journal of Clinical Oncology (2015)

4567 Background: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis involved in blood vessel maturation and stabilization. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in dual angiogenic blockade and augmented inhibition of tumor growth in RCC xenograft models. Dalantercept (Dal) is an ALK1 receptor-fusion protein that acts as a ligand trap and has demonstrated monotherapy activity with an acceptable safety profile in a completed Phase 1 study. Methods: Part 1 of this study evaluated the safety, tolerability, and preliminary activity of escalating dose levels of Dal plus standard dose axitinib in pts with advanced RCC. 3-6 pts each received 0.6, 0.9, or 1.2 mg/kg Dal SC Q3W and axitinib 5 mg PO BID. Key eligibility: predominantly clear cell RCC, 1 prior VEGFR TKI, ≤ 3 prior tx. Results: As of January 16, 2015, a total of 29 pts were enrolled. During dose escalation, 15 pts were enrolled in 3 cohorts (n = 6, 4, 5) at dose levels of 0.6, 0.9 and 1.2 mg/kg, respectively. There were no DLTs. The 1.2 mg/kg dose level was expanded to include 9 more pts and edema events including peripheral edema (n = 8), fluid overload (n = 1), and ascites (n = 1) were reported. The 0.9 mg/kg dose level was then expanded to include 5 more pts. This dose level was well tolerated (4 pts with grade 1 edema, 1 pt with pleural effusion and no ascites), and selected for Part 2. AEs ( > 30%) regardless of attribution included: fatigue, diarrhea, dysphonia, peripheral edema, nausea, decreased appetite, epistaxis, hypertension, arthralgia, creatinine rise, cough, and hand-foot rash. There were no grade 4/5 related adverse events. 28 pts were evaluable by RECIST v1.1. The ORR was 25% (n = 7). Disease control (PR+SD) at 6 months was 57% (n = 16). The preliminary median PFS is 8.3 months for all dose levels combined. The mPFS at the 0.9 mg/kg dose level has not been reached. Conclusions: The combination of dalantercept and axitinib is well tolerated and has shown encouraging activity in pts who have received prior VEGF, mTOR, and immune therapies. Part 2 of this study will randomize 130 pts to dalantercept + axitinib vs. placebo + axitinib and is actively accruing patients. Clinical trial information: NCT01727336.
Blood eosinophil count: a biomarker of an important treatable trait in patients with airway disease
Authors: Ian D. Pavord, Alvar Agusti
Journal: European Respiratory Journal (2016)

Inhaled corticosteroids (ICS) are widely used to treat patients with chronic obstructive pulmonary disease (COPD). Their main impact is to reduce the risk of exacerbations; in contrast to long-acting bronchodilators their effects on symptoms and lung function are small and insufficient to use as a guide of treatment efficacy. As a result, ICS are applied in a "risk-directed" fashion, with treatment directed at patients deemed to be at risk of exacerbations because of a past history of events, and/or poor lung function [1]. A better, more precise strategy would be to apply treatment in a targeted fashion according to a biomarker indicating the likelihood that corticosteroid treatment will have a positive effect on the outcome of interest ( i.e. reduction in exacerbations or decline in lung function). Blood eosinophil count can identify eosinophilic airway inflammation, a "treatable trait" of COPD <http://ow.ly/Xn098>
PCSK9 Association With Lipoprotein(a)
Authors: Hagai Tavori, Devon Christian, Jessica Minnier, Deanna Plubell, Michael D. Shapiro, Calvin Yeang, Ilaria Giunzioni, Mikael Croyal, P. Barton Duell, Gilles Lambert, Sotirios Tsimikas, Sergio Fazio
Journal: Circulation Research (2016)

Rationale: Lipoprotein(a) [Lp(a)] is a highly atherogenic low-density lipoprotein–like particle characterized by the presence of apoprotein(a) [apo(a)] bound to apolipoprotein B. Proprotein convertase subtilisin/kexin type 9 (PCSK9) selectively binds low-density lipoprotein; we hypothesized that it can also be associated with Lp(a) in plasma. Objective: Characterize the association of PCSK9 and Lp(a) in 39 subjects with high Lp(a) levels (range 39–320 mg/dL) and in transgenic mice expressing either human apo(a) only or human Lp(a) (via coexpression of human apo(a) and human apolipoprotein B). Methods and Results: We show that PCSK9 is physically associated with Lp(a) in vivo using 3 different approaches: (1) analysis of Lp(a) fractions isolated by ultracentrifugation; (2) immunoprecipitation of plasma using antibodies to PCSK9 and immunodetection of apo(a); (3) ELISA quantification of Lp(a)-associated PCSK9. Plasma PCSK9 levels correlated with Lp(a) levels, but not with the number of kringle IV-2 repeats. PCSK9 did not bind to apo(a) only, and the association of PCSK9 with Lp(a) was not affected by the loss of the apo(a) region responsible for binding oxidized phospholipids. Preferential association of PCSK9 with Lp(a) versus low-density lipoprotein (1.7-fold increase) was seen in subjects with high Lp(a) and normal low-density lipoprotein. Finally, Lp(a)-associated PCSK9 levels directly correlated with plasma Lp(a) levels but not with total plasma PCSK9 levels. Conclusions: Our results show, for the first time, that plasma PCSK9 is found in association with Lp(a) particles in humans with high Lp(a) levels and in mice carrying human Lp(a). Lp(a)-bound PCSK9 may be pursued as a biomarker for cardiovascular risk.
Added value of molecular assay Xpert MTB/RIF compared to sputum smear microscopy to assess the risk of tuberculosis transmission in a low-prevalence country
Authors: O. Opota, L. Senn, G. Prod'hom, J. Mazza-Stalder, F. Tissot, G. Greub, K. Jaton
Journal: Clinical Microbiology and Infection (2016)

<h2>Abstract</h2> Airborne precautions are required at hospital admission for patients with suspected pulmonary tuberculosis. The isolation is maintained until 3 serially collected sputum smears are acid-fast bacilli negative, a time- and labor-intensive method with limited sensitivity and specificity, which has a great impact on patient flow management. We evaluated the possibility of replacing the result of microscopy by the semiquantitative result of the molecular point-of-care test Xpert MTB/RIF to assess patients' transmission risk to quickly guide airborne isolation decisions in low-endemic countries. The performance of the Xpert MTB/RIF, used as a first-line test, was compared to the results of microscopy for specimens (<i>n</i>=242) collected from May 2010 to December 2014 in Lausanne, Switzerland. The sensitivity and specificity of Xpert MTB/RIF were 91.5% (65/71) and 99.6% (170/171), respectively, vs. 64.8% (46/71) and 94.2% (161/171) for microscopy. Samples with negative Xpert MTB/RIF were all smear negative for <i>Mycobacterium tuberculosis</i> (negative predictive value, 100%). The semiquantitative results of Xpert MTB/RIF—high, medium, low or very low—were found to correlate with acid-fast bacilli detection: positive predictive value of 100% (6/6), 96.5% (27/28), 52.2% (12/23) and 11.1% (1/9) respectively. Finally, when including clinical criteria, we identified 11 smear-negative but Xpert MTB/RIF–positive patients with a significant transmission potential. In conclusion, our data support the introduction of an Xpert MTB/RIF–based strategy as a replacement of smear microscopy for a faster and more accurate management of tuberculosis patients' transmission risk in a low-prevalence country.
The effects of Gosha-jinki-gan on oxaliplatin-related neurotoxicity: A prospective randomized study
Authors: M. Nishioka, M. Shimada, N. Kurita, T. Utsunomiya, T. Iwata, K. Yoshikawa, J. Higashijima
Journal: Journal of Clinical Oncology (2009)

e15056 Background: Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but sensory neurotoxicity is its dose-limiting toxicity. The OPTIMOX (stop and go) approach offers a reasonable strategy, but preventive agent is not established. It is reported that Gosha-jinki-gan (a blended herbal medicine) is recently considered as an effective agent for the neurotoxicity of taxanes and for vibration sensation in patients with diabetic neuropathy. Patients and Methods: From 2007, 32 patients treated with modified FOLFOX6 for advanced or unresectable colorectal cancer were randomized. Fifteen patients received oral administration of 7.5 g/day of Gosha-jinki-gan (G group) every days from first course and 17 patients (Control group) did not. Neurotoxicities were evaluated every course according to DEB-NTC (Neurotoxicity Criteria of DEBIOPHARM) and NCI-CTCAE Ver.3.0 using self-check sheet. Results: The median number of cycles of per patient of G group was 14 (range, 4–26), and that of C Group was 9 (range, 1–20). Cumulative dose of oxaliplatin of two groups was 1,190 mg/m2 (G group) and 765 mg/m2 (C Group). Peripheral neurotoxicity evaluated by DEB-NTC in Group G was grade 0 in 0 patients (0%), grade 1 in 11 (73%), grade 2 in 4 (27%) and grade 3 in 0 (0%) and, in C group, respectively, 1 (6%), 6 (35%), 7 (41%), 3 (18%). According to NCI-CTCAE, neurotoxicity was lower in G group than that of C group. Fifteen patients in G group were evaluated by RECIST criteria with a PR rate of 66.7%, SD rate of 20.0% and PD rate of 13.3%. Seventeen patients in C group were evaluated by RECIST criteria with a PR rate of 52.9%, SD rate of 35.3% and disease control rate of 11.8%. Conclusion: Gosha-jinki-gan is effective for preventing oxaliplatin-induced neuropathy in advanced or unresectable colorectal cancer patients. [Table: see text]
Randomized double-blind placebo-controlled international trial of abago-vomab maintenance therapy in patients with advanced ovarian cancer after complete response to first-line chemotherapy: The Monoclonal Antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abago-vomab (MIMOSA) trial.
Authors: J. Pfisterer, J. S. Berek, A. Casado, K. Cwiertka, T. Pinter, A. Pluzanska, E. Pujade-Lauraine, G. Scambia, J. B. Vermorken, C. Simonelli, M. Bertolotti, A. Capriati, P. Sabbatini
Journal: Journal of Clinical Oncology (2011)

LBA5002 Background: Abagovomab, a murine monoclonal anti-idiotypic antibody directed against CA125, has been shown to induce an active immune response against CA125 tumor-associated antigen in advanced ovarian cancer patients. Methods: Abagovomab (A) has been tested in a randomized (2:1) double-blind, placebo (P) controlled, multicenter phase II/III trial in patients with FIGO stage III/IV ovarian cancer after complete response to platinum-taxane first-line chemotherapy. A (2 mg/1 ml) or P was given subcutaneously every 2 weeks for 6 weeks (induction phase); then every 4 weeks (maintenance phase) until recurrence, or up to 21 months after the last patient had been randomized. Primary endpoint is progression-free survival (PFS); secondary endpoints are OS and immunological response. An estimated 870 patients, with a mean follow-up of 18 months, were needed to observe at least 535 recurrences, which provides a power &gt;90% in rejecting the null hypothesis of equality between A and P on PFS according to a hazard ratio (HR) of 1.33, in which median P PFS time is 18 months, significance level (a) 5% (two-sided), and the overall dropout rate 10%. Primary analysis was run on PFS in the ITT population. The design included a prospective stratification in randomization for the following prognostic factors: FIGO stage (III-IV); tumor size after debulking (residual tumor &lt;1 cm, &gt;1 cm); and CA125 serum level after the third cycle (&lt;35 U/ml, &gt;35 U/ml). The Cox proportional hazards model was used for adjusting the primary analysis. Results: 888 patients were enrolled by December 2008, 593 in A arm and 295 in P arm. The median follow-up was 28.1 months and the mean number treatment administrations was 18. Baseline characteristics were balanced between arms. Overall tolerability profile was consistent with previous A studies. Median (95% CI) PFS was 13.24 (10.612-13.602) months for A arm and 13.21 (10.612-16.000) months for P arm; HR=1.099 (0.919-1.315); p=0.301. Conclusions: Treatment with A did not translate into a prolonged PFS.
Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18–64 years old
Authors: Ganesh Raghu, Shih-Yin Chen, Qiang Hou, Wei-Shi Yeh, Harold R. Collard
Journal: European Respiratory Journal (2016)

We sought to present the epidemiology of idiopathic pulmonary fibrosis (IPF) in adults 18–64 years old in the USA. From adults aged 18–64 years in a large administrative claims data in 2004–2010, patients with IPF were identified using diagnosis codes. We estimated annual incidence and cumulative prevalence of IPF over time, and examined potential risk factors for the IPF diagnosis. The annual cumulative prevalence increased steadily in the first few years (from 13.4 cases per 100 000 persons in 2005 to 18.2 cases in 2010 per 100 000 persons), which is likely due to a methodological reason, while the annual incidence of IPF decreased over time (from 7.9 cases per 100 000 person-years in 2005 to 5.8 cases in 2010 per 100 000 person-years). The overall decrease was mainly driven by a decreasing trend in the younger patients (aged 18–44 years), while the incidence in older patients remained stable. Consistent trends were observed in subgroups defined by previously published more restrictive algorithms for diagnosis. Older age and male sex were associated with a higher incidence of disease (p&lt;0.05). In US adults younger than 65 years, we observed a decreasing incidence of IPF over time which may partially explain the plateau of cumulative prevalence in the last few years of our data.
Disease, treatment, and outcome differences between men and women with follicular lymphoma in the United States
Authors: Chadi Nabhan, Xiaolei Zhou, Bann‐Mo Day, Keith Dawson, Andrew D. Zelenetz, Jonathan W. Friedberg, James R. Cerhan, Brian K. Link, Christopher R. Flowers
Journal: American Journal of Hematology (2016)

We aimed to comprehensively study sex differences in disease and patients' characteristics, treatment and outcomes in patients with follicular lymphoma (FL) in the United States (USA) utilizing the National LymphoCare Study registry (2004–2014). Among evaluable males ( n = 1277) and females ( n = 1375) with FL, females less commonly received anthracyclines and were more likely to receive rituximab monotherapy. Overall response rates were comparable between sex groups. With a median follow‐up of 8.1 years, male sex emerged as an adverse factor for PFS (HR, 0.84, 95% CI, 0.72–0.97). Lymphoma‐related mortality (HR, 0.46; 0.23–0.93) and overall survival (HR, 0.63; 0.41–0.97) favored females aged ≤60 years. There are subtle differences in outcomes between male and female FL patients diagnosed and treated in the contemporary era. These data represent the largest prospective analysis of FL patients in the USA based on sex and can aid design of clinical trials for this disease. Am. J. Hematol. 91:770–775, 2016. © 2016 Wiley Periodicals, Inc.
Survival Of AML Patients Relapsing After Allogeneic Stem Cell Transplantation: A Center For International Blood and Marrow Transplant Research Study
Authors: Nelli Bejanyan, Daniel J. Weisdorf, Hailin Wang, Brent R. Logan, Steven M. Devine, Marcos de Lima, Donald W. Bunjes, Mei-Jie Zhang
Journal: Blood (2013)