tbuckley/cabot-search huggingface dataset:
Impact of performance status (PS) on oncologists' decision to administer chemotherapy (CTX) and overall survival (OS).
Authors: Arpit Rao, Eric R Siegel, Rangaswamy Govindarajan
Journal: Journal of Clinical Oncology (2014)

e17580 Background: PS is a well-known prognostic marker for patients with malignancy (M). Patients with poor PS (ECOG PS ≥2) are not included in clinical trials. It is unclear whether this subset gets CTX in clinical practice, and if so, how that affects their OS. Methods: A retrospective intent-to-treat analysis was performed on subjects with metastatic cancer presenting to a teaching hospital between 1/1/2007 and 12/31/2009. Index encounter (IE) was the visit in which a decision on CTX was made. Patients with more than one type of M or with M for which TNM staging was unavailable were excluded. OS was computed as the time in months from the IE to the date of death or last contact. PS groups were compared via log-rank test, and Cox regression and Kaplan-Meier methods were used for survival analysis. Results: 150 patientswere included in the analysis. 82 (55%) had good PS (GPS) and 68 (45%) had poor PS (PPS). Decision to give CTX was made on 74/82 (90%) patients with GPS versus 47/68 (69%) with PPS (p = 0.001). Age, gender and race were comparable between the groups (Table). Non-small cell lung cancer (19/150; 13%), breast cancer (15/150; 10%) and colon cancer (11/150; 7%) were the most common encountered malignancies. 134 deaths were observed during 2,148.9 total months of follow-up. Hazard ratio for OS in PPS group treated with CTX was 0.79 (P=0.38) Conclusions: In clinical practice, oncologists recommended CTX to a significant proportion of patients with PPS. There appeared to be no statistically significant difference in OS due to CTX in this group. Since a large number of subjects with PPS are offered chemotherapy and due to the difference in sites of malignancies with variable prognosis, a larger multi institutional analysis to evaluate this further is warranted. GPS PPS P value PS group, N 82 68 No. (%) of subjects receiving CTX 74 (90) 47 (69) 0.001 Age in years Median (range) 60 (16–81) 60 (30–88) 0.43 Males, N (%) 39 (49) 41 (51) 0.12 Race, N (%): White Black Other 59 (72) 19 (23) 3 (4) 53 (78) 14 (21) 1 (2) 0.62
A Distinct Low Lung Function Trajectory from Childhood to the Fourth Decade of Life
Authors: Cristine E. Berry, Dean Billheimer, Isaac C. Jenkins, Zhenqiang J. Lu, Debra A. Stern, Lynn B. Gerald, Tara F. Carr, Stefano Guerra, Wayne J. Morgan, Anne L. Wright, Fernando D. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Low maximally attained lung function increases the risk of chronic obstructive pulmonary disease irrespective of the subsequent rate of lung function decline.Objectives: We aimed to determine if there were individuals with a distinct, persistently low lung function trajectory in the CRS (Tucson Children’s Respiratory Study).Methods: The CRS, an ongoing birth cohort study, enrolled 1,246 participants between 1980 and 1984. Latent class linear mixed effects modeling of the ratio of FEV1 to FVC was used to identify distinct lung function trajectories among participants with two or more spirometry measurements between ages 11 and 32 years.Measurements and Main Results: Among 599 participants with 2,142 observations, a model with two distinct trajectories (a low trajectory [n = 56; 9.3%] and a normal trajectory) fit the data significantly better than a model with only one trajectory (P = 0.0007). As compared with those with a normal trajectory, participants with a persistently low trajectory were more likely to have a history of maternal asthma (20.0% vs. 9.9%; P = 0.02); early life lower respiratory illness caused by respiratory syncytial virus (41.2% vs. 21.4%; P = 0.001); and physician-diagnosed active asthma at age 32 years (43.9% vs. 16.2%; P < 0.001). Individuals with a persistently low trajectory also demonstrated lower lung function as measured by average maximal expiratory flow at functional residual capacity during infancy and at age 6 years.Conclusions: A distinct group of individuals in a nonselected population demonstrates a persistently low lung function trajectory that may be partly established at birth and predisposes them to chronic obstructive pulmonary disease later in life.
GOLM1 Modulates EGFR/RTK Cell-Surface Recycling to Drive Hepatocellular Carcinoma Metastasis
Authors: Qing-Hai Ye, Wen-Wei Zhu, Ju-Bo Zhang, Yi Qin, Ming Lu, Guo-Ling Lin, Lei Guo, Bo Zhang, Zhen-Hai Lin, Stephanie Roessler, Marshonna Forgues, Hu-Liang Jia, Lu Lu, Xiao-Fei Zhang, Bao-Feng Lian, Lu Xie, Qiong-Zhu Dong, Zhao-You Tang, Xin Wei Wang, Lun-Xiu Qin
Journal: Cancer Cell (2016)
Investigating Synthetic Lethality Between mTOR Hyperactivation and Cap-Dependent mRNA Translation In a Receptor Tyrosine Kinase Driven Model Of Acute T-Cell Leukemia
Authors: Adrian Schwarzer, Helmut Holtmann, Celina Schauerte, Nomme Benn, Jan Völkel, Sabine Knöß, Johannes Zuber, Zhixiong Li, Axel Schambach, Christopher Baum
Journal: Blood (2013)
A Phase 1 Trial Of Reolysin Alone In Patients With Refractory Or Relapsed Multiple Myeloma
Authors: Douglas W. Sborov, Gerard Nuovo, Andrew Stiff, Thomas Mace, Gregory Lesinski, Don M. Benson, Yvonne A Efebera, Ashley E. Rosko, Flavia Pichiorri, Craig C Hofmeister
Journal: Blood (2013)
P-224 A Novel Method of Quantification of Cu2+ Level as the Antioxidative Status Evaluation in Colon Neoplasm
Authors: S.H. Kim, H.J. Chun, I.K. Yoo, J.M. Lee, H.S. Choi, B. Keum, E.S. Kim, Y.T. Jeen, H.S. Lee, C.D. Kim
Journal: Annals of Oncology (2015)
Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis
Authors: Andrea Schietinger, Mary Philip, Varintra E. Krisnawan, Edison Y. Chiu, Jeffrey J. Delrow, Ryan S. Basom, Peter Lauer, Dirk G. Brockstedt, Sue E. Knoblaugh, Günter J. Hämmerling, Todd D. Schell, Natalio Garbi, Philip D. Greenberg
Journal: Immunity (2016)
Phase I study of docetaxel and temsirolimus in refractory solid tumors.
Authors: T. N. Mwandoro, F. Gao, A. C. Lockhart, R. Suresh, B. R. Tan, A. Wang-Gillam, P. M. Fracasso, J. Picus
Journal: Journal of Clinical Oncology (2010)

e13149 Background: Temsirolimus (CCI-779) is an ester analog of rapamycin and a selective inhibitor of the mammalian target of rapamycin (mTOR). Temsirolimus blocks the signals of at least two separate downstream pathways that control the translation of specific mRNAs required for cell cycle progression from G1 to S. In preclinical studies, mTOR inhibitors have demonstrated synergistic cytotoxic effects with taxanes providing the rationale for this phase I combination study. Methods: This is an open-label, dose-escalation study to determine the maximum tolerated dose (MTD), incidence, and severity of toxicities, and antitumor activity of temsirolimus administered weekly in combination with docetaxel administered every 3 weeks in patients with refractory solid malignancies. Results: Twenty patients have been enrolled in this ongoing trial. Patient demographics were 11 males/9 females, median age 50 (range: 27-72), and median ECOG score: 1 (0:6, 1:11, 2:2). Tumor histologies were colon (4), pancreas (4), rectum (3), gallbladder (2), non-small cell lung cancer (1), endometrium (1), neuroendocrine (1), esophagus (1), stomach (1), pharynx (1), small intestine (1). One out of 4 patients in cohort 1, and 0 out of 7 patients in cohort 2 were able to complete cycle 1 without doses being held or reduced. Therefore, eligibility criteria and treatment plans were revised and the 1A dose cohort was explored. Treatment in this cohort has been tolerated and patients are now being enrolled into the PK cohort. Conclusions: Enrollment continues to the MTD/phase II dose (50/15) cohort to clarify pharmacokinetic relationships between docetaxel and temsirolimus. Dose level Dose (docetaxel/ temsirolimus)mg/m2 # Pts Toxicities ≥ grade 3 Bestresponse 1 60/15 4 Diarrhea, neutropenia, hyperglycemia 1 SD 3 PD 2 60/25 7 Diarrhea, mucositis ALT 3 SD 2 PD 2 NE 1A 50/15 9 Neutropenia, platelet, fatigue, diarrhea 1uPR 4 SD 2 PD 2 NE Abbreviations: SD, stable disease; PD, progressive disease; NE, not evaluable; uPR, unconfirmed partial response. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Amgen, Merck, sanofi-aventis, Taxalog, Wyeth
Sensitive Troponin I Assay in Patients With Suspected Acute Coronary Syndrome
Authors: Jeffrey D. Clough
Journal: JAMA (2011)

To the Editor: Dr Mills and colleagues demonstrated a significant reduction in myocardial infarction (MI) and death in patients with suspected acute coronary syndrome (ACS) through use of a lower-threshold troponin assay. One surprising finding was a modest increase in use of recommended therapies in patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL during the implementation phase, which would be expected to result in reduced events. In fact, revascularization rates were stable despite more than a doubling in coronary angiography. Aspirin, -blocker, and angiotensin-converting enzyme inhibitor use did not differ between the phases. Although more statins were prescribed at discharge in the implementation phase, a similar difference was present on admission, suggesting possible baseline differences between these nonrandomized samples. The most striking difference was in clopidogrel use, 31% in the validation phase vs 61% in the implementation phase. If the outcome difference between the 2 groups was driven by clopidogrel, this would be a substantially greater benefit than demonstrated in prior studies. For example, the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial showed a 2.1% absolute risk reduction in death from cardiovascular causes, nonfatal MI, or stroke over 12 months (9.3% in clopidogrel group vs 11.4% in placebo group) for patients with ACS without ST-segment elevation compared with an 18% difference in death or recurrent MI at 12 months (39% in validation cohort vs 21% in implementation cohort) in the report by Mills et al. Determination of the rates of clopidogrel use in patients who did or did not have an event would be interesting. In addition, other than the presence of cardiac risk factors and interventions, little is known about the population. Given the high overall mortality rates and low rates of revascularization despite angiography, many patients may have had noncardiac medical issues, and the results may be due to higher attention to underlying coronary artery disease in a population with comorbid illnesses. This is supported by the low rates of use of recommended therapies. For instance, only 47% of validation phase patients with peak troponin concentrations of 0.05 to 0.19 ng/mL were taking a -blocker at discharge when 69% of these patients carried a diagnosis of ischemic heart disease prior to admission. It would be useful to know the number of patients who underwent stress testing, the percentage diagnosed with ischemic heart disease, other discharge diagnoses, and creatinine levels as alternate explanations for elevated troponin levels. Jeffrey D. Clough, MD, MBA Seth S. Martin, MD Matthew W. Cope, MD
Profiling response to carmustine/bevacizumab in recurrent glioblastoma.
Authors: Leonardo Rojas, Andres F. Cardona, Beatriz Wills, Oscar Arrieta, Carlos A. Vargas, Hernan Carranza, Jorge M. Otero, Nicolas Useche, Sonia Bermudez, Enrique Jimenez, Fernando Hakim, Carmen Balana
Journal: Journal of Clinical Oncology (2016)

2059 Background: The prognosis for patients (pts) with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Angiogenesis is crucial for glioblastoma (Gb) growth, and anti-vascular endothelial growth factor agents are widely used in recurrent Gb pts. Following the results of BELoB trial we explored the efficacy of carmustine plus bevacizumab considering the prognostic value of several biomarkers. Methods: This retrospective study included 59 adult pts with histologically confirmed Gb who were treated with carmustine (BCNU 80 mg/m2 days 1-3 every 8 weeks) in combination with bevacizumab (10 mg/kg every 15 days) as a second line regimen. Response rate (RR), 6-month progression free survival (PFS6), progression-free survival (PFS) and overall survival (OS) were assessed according to CD133 mRNA expression, MGMT methylation (pMGMT) and IDH1/2, p53 and EGFRvIII mutation status. Results: The median age was 43-yo (23-70 years), 35 patients were male (59%), 78% of cases were treated with debulking surgery and 22% had undergone biopsy. The median follow-up was 18.6 months (95%CI 6.4-36), overall RR to BCNU/Bev combination was 54%, median PFS was 8,6 months (IC95% 2.4-14.7) and median OS was 27.1 months (IC95% 23.3-28.6). IDH1/2 mutations were found in 30%, pMGMT in 56%, p53 mutations in 29%, EGFRvIII in 24% and high CD133 mRNA expression in 57%. The variables that positively affected PFS were PS (p = 0.015), IDH+ (p = 0.05) and pMGMT+ (p = 0.009). Similarly, OS was significantly modified by the extent of surgical intervention (p = 0.005) and pMGMT+ (p = 0.05). Multivariate analysis showed that pMGMT and age affected OS in the study population (p = 0.018 and 0.04, respectively). The most frequent grade 3 or severe toxicities were hypertension (13 [22%]), fatigue (7 [12%]), thrombocytopenia (5 [8.4%]), deep vein thrombosis/pulmonary embolism (3 [5.0%]), and infections (2 [3.3%]). Conclusions: Combination of carmustine with Bev is well tolerated and may derive benefit in recurrent Gb. pMGMT and age were associated with good prognosis.
P0252 : Identification of the apical sodium bile salt transporter (ASBT) as a novel molecular target to enhance the sensitivity of cholangiocarcinoma to chemotherapy
Authors: E. Lozano, R.I. Macias, M.J. Monte, O. Briz, F. Jimenez, S. Jimenez, B. Castaño, R. Al-Abdulla, F. Al-Aqil, A. Hernandez, J.M. Banales, M.A. Serrano, J.J. Marin
Journal: Journal of Hepatology (2015)
Extracellular lipid-free apolipoprotein E inhibits HCV replication and induces ABCG1-dependent cholesterol efflux
Authors: Emilie Crouchet, Mathieu Lefèvre, Eloi R Verrier, Marine A Oudot, Thomas F Baumert, Catherine Schuster
Journal: Gut (2016)

<h3>Objective</h3> The HCV life cycle and the lipid metabolism are inextricably intertwined. In the blood, HCV virions are associated with lipoproteins, forming lipoviroparticles (LVPs), which are the most infectious form of the virus. Apolipoprotein E (apoE), a key LVP component, plays an essential role in HCV entry, assembly and egress. ApoE is also a cell host factor involved in lipoprotein homeostasis. Although the majority of apoE is associated with lipoproteins, a lipid-free (LF) form exists in blood. However, the role of LF-apoE in both lipid metabolism and HCV life cycle is poorly understood. <h3>Design</h3> In this study, using the cell culture-derived HCV model system in human hepatoma Huh7.5.1 cells and primary human hepatocytes (PHH), we investigated the effect of LF-apoE on the early steps of HCV life cycle and on the lipid metabolism of hepatic cells. <h3>Results</h3> A dose-dependent decrease in HCV replication was observed when Huh7.5.1 cells and PHH were treated with increasing amounts of LF-apoE. We showed that LF-apoE acts on HCV replication independently of previously described apoE receptors. We observed that LF-apoE induced a marked hepatic cholesterol efflux via the ATP-binding cassette subfamily G member 1 (ABCG1) protein that in turn inhibits HCV replication. LF-apoE also increases both apolipoprotein AI and high-density lipoprotein production. <h3>Conclusions</h3> Our findings highlight a new mechanism in lipid metabolism regulation and interaction of the lipid metabolism with the HCV life cycle, which may be important for viral pathogenesis and might also be explored for antiviral therapy.
Similar Efficacy of Thalidomide-Based and Bortezomib-Based Regimens In the First Relapse of 209 Multiple Myeloma Patients Previously Untreated with Novel Drugs
Authors: Marta Krejci, Evzen Gregora, Ivan Spicka, Vlastimil Scudla, Jan Straub, Jiri Minarik, Zdenek Adam, Andrea Krivanova, Ludek Pour, Lenka Zahradova, Jiri Mayer, Roman Hajek
Journal: Blood (2010)
False Suggestion of Malignant Transformation of Benign Bone Tumor by 18F-FDG PET/CT
Authors: Yu-Ren Chen, Yu-Cheng Kuo, Cheng-Nan Hsu, Te-Chun Hsieh, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2016)

A 68-year-old man underwent serial F-FDG PET/CT scan follow-up for lung cancer. Then 5.5 years after the initial F-FDG PET/CT scan, the presumed benign bone tumor in the left clavicle showed markedly increased FDG uptake during follow-up; in contrast, the Tc-MDP bone scan paradoxically exhibited no apparent interval change since last bone scan 5.5 years earlier. He underwent a CT-guided biopsy, and the pathological diagnosis was benign fibrous histiocytoma. The result was consistent with the lack of progression in Tc-MDP bone scan, whereas the F-FDG PET/CT scan gave a false-positive impression of malignant transformation.
The Influence Of Dietary Restriction On Quality Of Life In The Patients With Hematological Malignancies Who Received Chemotherapy: A Single-Institution Study
Authors: Nozomi Hamada, Fumihito Tajima, Masumi Sakuno, Kumiko Tanabe, Rika Hasegawa, Michiyo Fuse, Toshio Kawatani, Tetsuo Yamamoto, Masae Higashimori
Journal: Blood (2013)
Phase I study of the oral CDK-TRKA inhibitor PHA-848125 in recurrent malignant glioma (MG).
Authors: A. Benouaich-Amiel, E. Mazza, C. Massard, P. Gaviani, F. Fiorentini, A. Scaburri, M. A. Pacciarini, E. Calvo
Journal: Journal of Clinical Oncology (2010)

2087 Background: Mutations in growth factor receptors signaling and in Rb pathway characterize MG pathogenesis. PHA-848125 (PHA) is a dual CDK/TRKA oral inhibitor, able to cross the blood brain barrier. It induces autophagy, is active as single agent in glioma models subcutaneously and intracranially implanted and produces a clear therapeutic gain in combination with temozolomide (TMZ) or TMZ + radiotherapy. Methods: Phase I part in adult patients (pts) (13 glioblastoma [GBM], 5 astrocytoma, 3 oligodendroglioma, 1 meningioma) with KPS ≥ 70, not taking enzyme-inducing antiepileptic drugs (EIAEDs), to determine the recommended dose for phase II (RP2D) and dose-limiting toxicity (DLT) of PHA, given orally once daily for 14 days in a 3-week cycle (cy). Cohorts of 3-6 pts received PHA at dose levels of 18 (5 pts), 36 (4 pts), 54 (8 pts) and 72 (5 pts) mg/m2/day. Results: 22 pts were treated for a total of 53 cys (median 3, range 1-6): side effects were dose- dependent and mainly on liver function, starting from 36 mg/m2, with bilirubin and transaminase elevations of grade (gr) 2-3, and becoming dose-limiting at 72 mg/m2. Other effects were gr 1-2 tremors, diarrhea, nausea and vomiting and mild hematologic toxicity (occasionally severe). Two DLTs occurred at 72 mg/m2: one gr 4 PLT decrease and one prolonged gr 3 ALT elevation. The RP2D was defined as 54 mg/m2 (8 pts, 21 cys), its toxicity consisting mainly in reversible tremors (2 pts, max gr 2) and in transaminase elevations (5 pts, max gr 3). Two pts remained on study for 6 cys. PK data indicate that exposure proportionally increased with dose, with Cmax at 2.5h (median) and half-life of 30-40 h. Day 14/day 1 AUC (0- 24h) ratio was around 3. At RP2D, day 14 AUC (0-24h) was 15.4 μ M·h (CV: 34%) and Cmax 0.86 μ M. Phase II part in recurrent GBM is ongoing (8 pts treated, 1 pt progression-free at 6 months). A 6-pt cohort treated with EIAEDs is also underway. Conclusions: PHA shows mild/moderate, reversible and manageable toxicity at the RP2D of 54 mg/m2. Transaminase elevation is dose limiting. Side effects are in line with the already known toxicity pattern, with a more pronounced effect on liver with this 14-day on/7-day off schedule. PK data are predictable and highly reproducible across studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Accelera, Nerviano Medical Sciences
Status Epilepticus and Brain Atrophy
Authors: Andrew J. Cole
Journal: JAMA Neurology (2016)

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TGFΒ-induced transcription in cancer
Authors: Gaia Cantelli, Eva Crosas-Molist, Mirella Georgouli, Victoria Sanz-Moreno
Journal: Seminars in Cancer Biology (2016)

The Transforming Growth Factor-beta (TGFβ) pathway mediates a broad spectrum of cellular processes and is involved in several diseases, including cancer. TGFβ has a dual role in tumours, acting as a tumour suppressor in the early phase of tumorigenesis and as a tumour promoter in more advanced stages. In this review, we discuss the effects of TGFβ-driven transcription on all stages of tumour progression, with special focus on lung cancer. Since some TGFβ target genes are specifically involved in promoting metastasis, we speculate that these genes might be good targets to block tumour progression without compromising the tumour suppressor effects of the TGFβ pathway.
Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques
Authors: Xiao Li, Cong Wang, Hui Tan, Leilei Cheng, Guobing Liu, Yi Yang, Yanzhao Zhao, Yiqiu Zhang, Yanli Li, Chunfu Zhang, Yan Xiu, Dengfeng Cheng, Hongcheng Shi
Journal: Biomaterials (2016)
Validity of diagnostic codes for identifying cutaneous squamous cell carcinoma in The Health Improvement Network
Authors: Z.C. Chiesa Fuxench, A.B. Troxel, J.M. Gelfand
Journal: British Journal of Dermatology (2016)

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), collectively referred to as “non-melanoma skin cancer (NMSC)”, are the most common cancers worldwide.1,2 Despite their considerable public health burden, there are substantial gaps in the epidemiological study of these malignancies as they are not commonly included in cancer registries.3,4

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68Ga-PSMA PET/MR Showing Intense PSMA Uptake in Nodular Fasciitis Mimicking Prostate Cancer Metastasis
Authors: Martin Henninger, Tobias Maurer, Charlotte Hacker, Matthias Eiber
Journal: Clinical Nuclear Medicine (2016)

The recently introduced PSMA PET has developed as a powerful imaging tool for staging of prostate cancer. This case showed an intense uptake of Ga-PSMA in a soft-tissue mass of the rectus femoris muscle. Histopathology revealed the diagnosis of fasciitis nodularis. Therefore, it advises caution particularly in patients with solitary and atypical located lesions as they might not be indicative for metastatic prostate cancer, but eventually be caused by different conditions.