tbuckley/cabot-search huggingface dataset:
Drug-Resistant Brain Metastases: A Role for Pharmacology, Tumor Evolution, and Too-Late Therapy
Authors: Thomas Stricker, Carlos L. Arteaga
Journal: Cancer Discovery (2015)

Two recent studies report deep molecular profiling of matched brain metastases and primary tumors. In both studies, somatic alterations in the brain metastases were frequently discordant with those in the primary tumor, suggesting divergent evolution at metastatic sites and raising questions about the use of biomarkers in patients in clinical trials with targeted therapies.
Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.
Authors: B Zee, B Cole, T Li, G Browman, K James, D Johnston, D Sugano, J Pater
Journal: Journal of Clinical Oncology (1998)

PURPOSE In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). MATERIALS AND METHODS Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. RESULTS The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P &lt; .001). CONCLUSION The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.
Vascular Tissues: Recent Advances in Targeted, Self-Assembling Nanoparticles to Address Vascular Damage Due to Atherosclerosis (Adv. Healthcare Mater. 16/2015)
Authors: Eun Ji Chung, Matthew Tirrell
Journal: Advanced Healthcare Materials (2015)

On page 2408, E. J. Chung and M. Tirrell provide targeted strategies using self-assembling nano-particles for atherosclerosis nanomedicine. The cover image shows recent examples of nano-particles (tobacco mosaic virus in purple, peptide amphiphile micelles in green) within a blood vessel that target early to late stages of atherosclerosis and aim to mitigate the lethality of the disease.
Response to Comment on Shukla et al. Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels. Diabetes Care 2015;38:e98–e99
Authors: Alpana P. Shukla, Louis J. Aronne
Journal: Diabetes Care (2015)

We appreciate the opportunity to respond to Imai et al. (1) regarding our recently published article on the impact of food order on postprandial glucose and insulin levels (2). As we mentioned in our article, the data on this subject are quite limited and we were unable to elaborate on their referenced study due to limitations of word count (3). There are, however, substantial differences in the design and results of the two studies that merit further discussion.

In their study (3), Imai et al. investigated the effect …
Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose–response study of AMG 162 (<i>D</i>enosumab) in patients with <i>R</i>heumato<i>I</i>d arthritis on methotrexate to <i>V</i>alidate inhibitory effect on bone <i>E</i>rosion (DRIVE)—a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial
Authors: Tsutomu Takeuchi, Yoshiya Tanaka, Naoki Ishiguro, Hisashi Yamanaka, Toshiyuki Yoneda, Takeshi Ohira, Naoki Okubo, Harry K Genant, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA). Methods In this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and &lt;5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months. Results Denosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p&lt;0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo. Conclusions Addition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. Trial registration number JapicCTI-101263.
Mitochondrial Quality Control as a Therapeutic Target
Authors: Hagir B. Suliman, Claude A. Piantadosi
Journal: Pharmacological Reviews (2015)

In addition to oxidative phosphorylation (OXPHOS), mitochondria perform other functions such as heme biosynthesis and oxygen sensing and mediate calcium homeostasis, cell growth, and cell death. They participate in cell communication and regulation of inflammation and are important considerations in aging, drug toxicity, and pathogenesis. The cell's capacity to maintain its mitochondria involves intramitochondrial processes, such as heme and protein turnover, and those involving entire organelles, such as fusion, fission, selective mitochondrial macroautophagy (mitophagy), and mitochondrial biogenesis. The integration of these processes exemplifies mitochondrial quality control (QC), which is also important in cellular disorders ranging from primary mitochondrial genetic diseases to those that involve mitochondria secondarily, such as neurodegenerative, cardiovascular, inflammatory, and metabolic syndromes. Consequently, mitochondrial biology represents a potentially useful, but relatively unexploited area of therapeutic innovation. In patients with genetic OXPHOS disorders, the largest group of inborn errors of metabolism, effective therapies, apart from symptomatic and nutritional measures, are largely lacking. Moreover, the genetic and biochemical heterogeneity of these states is remarkably similar to those of certain acquired diseases characterized by metabolic and oxidative stress and displaying wide variability. This biologic variability reflects cell-specific and repair processes that complicate rational pharmacological approaches to both primary and secondary mitochondrial disorders. However, emerging concepts of mitochondrial turnover and dynamics along with new mitochondrial disease models are providing opportunities to develop and evaluate mitochondrial QC-based therapies. The goals of such therapies extend beyond amelioration of energy insufficiency and tissue loss and entail cell repair, cell replacement, and the prevention of fibrosis. This review summarizes current concepts of mitochondria as disease elements and outlines novel strategies to address mitochondrial dysfunction through the stimulation of mitochondrial biogenesis and quality control.
Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a Southwest Oncology Group study.
Authors: K A Margolin, P Y Liu, L E Flaherty, J A Sosman, M J Walker, J W Smith, W S Fletcher, G R Weiss, J M Unger, V K Sondak
Journal: Journal of Clinical Oncology (1998)

PURPOSE The combination of carmustine (BCNU), dacarbazine (DTIC), cisplatin (DDP), and tamoxifen (Tam) has been reported in small series to provide a response rate of 50%, but with significant myelosuppression and risk of thromboembolic complications. We performed this phase II study to assess the antitumor activity and important toxicities of this combination in the cooperative group setting. PATIENTS AND METHODS Seventy-nine eligible patients were treated with BCNU 150 mg/m2/d, every 6 weeks, DTIC 220 mg/m2/d on days 1 to 3 every 3 weeks, DDP 25 mg/m2/d on days 1 to 3 every 3 weeks, and Tam 20 mg orally daily throughout treatment. Treatment cycles were repeated every 6 weeks in responding or stable patients for a maximum duration of 1 year. RESULTS Twelve objective responses were achieved (response rate 15%, 95% confidence interval 8%-25%). Five responses were complete (CR) and seven were partial (PR). The median response duration was 8+ (range, 4-19+) months, (16+ [4-19+] for CR and 8+ [4-11] for PR), and the median survival of the entire group was 9 months. The toxicities were predominantly neutropenia and thrombocytopenia. Four patients developed thromboembolic events. Two patients died while on protocol therapy, one with complications of neutropenia, and the other with disease progression. CONCLUSION The activity of this regimen is in the range reported for single agents or DTIC plus DDP, and the addition of BCNU and Tam appears to increase toxicity. We do not recommend this combination for routine treatment of advanced melanoma or as the control arm in randomized studies of combination therapy.
Profiles of genome complexity identify HORMAD1 as a driver of homologous recombination deficiency and platinum therapy response in triple-negative breast cancer
Authors: A. Grigoriadis, D. Weekes, J.A. Watkins, P. Gazinska, J. Frankum, C. Lord, A. Ashworth, J.M. Ford, M. Telli, A. Tutt
Journal: Annals of Oncology (2015)
Survival and Clinical Outcomes in Surgically Treated Patients With Metastatic Epidural Spinal Cord Compression: Results of the Prospective Multicenter AOSpine Study
Authors: Michael G. Fehlings, Anick Nater, Lindsay Tetreault, Branko Kopjar, Paul Arnold, Mark Dekutoski, Joel Finkelstein, Charles Fisher, John France, Ziya Gokaslan, Eric Massicotte, Laurence Rhines, Peter Rose, Arjun Sahgal, James Schuster, Alexander Vaccaro
Journal: Journal of Clinical Oncology (2015)

Although surgery is used increasingly as a strategy to complement treatment with radiation and chemotherapy in patients with metastatic epidural spinal cord compression (MESCC), the impact of surgery on health-related quality of life (HRQoL) is not well established. We aimed to prospectively evaluate survival, neurologic, functional, and HRQoL outcomes in patients with MESCC who underwent surgical management.One hundred forty-two patients with a single symptomatic MESCC lesion who were treated surgically were enrolled onto a prospective North American multicenter study and were observed at least up to 12 months. Clinical data, including Brief Pain Inventory, ASIA (American Spinal Injury Association) impairment scale, SF-36 Short Form Health Survey, Oswestry Disability Index, and EuroQol 5 dimensions (EQ-5D) scores, were obtained preoperatively, and at 6 weeks and 3, 6, 9, and 12 months postoperatively.Median survival time was 7.7 months. The 30-day and 12-month mortality rates were 9% and 62%, respectively. There was improvement at 6 months postoperatively for ambulatory status (McNemar test, P < .001), lower extremity and total motor scores (Wilcoxon signed rank test, P < .001), and at 6 weeks and 3, 6, and 12 months for Oswestry Disability Index, EQ-5D, and pain interference (paired t test, P < .013). Moreover, at 3 months after surgery, the ASIA impairment scale grade was improved (Stuart-Maxwell test P = .004). SF-36 scores improved postoperatively in six of eight scales. The incidence of wound complications was 10% and 2 patients required a second surgery (screw malposition and epidural hematoma).Surgical intervention, as an adjunct to radiation and chemotherapy, provides immediate and sustained improvement in pain, neurologic, functional, and HRQoL outcomes, with acceptable risks in patients with a focal symptomatic MESCC lesion who have at least a 3 month survival prognosis.
Oncogenic Myc Induces Expression of Glutamine Synthetase through Promoter Demethylation
Authors: Alex J. Bott, I-Chen Peng, Yongjun Fan, Brandon Faubert, Lu Zhao, Jinyu Li, Sarah Neidler, Yu Sun, Nadia Jaber, Dawid Krokowski, Wenyun Lu, Ji-An Pan, Scott Powers, Joshua Rabinowitz, Maria Hatzoglou, Daniel J. Murphy, Russell Jones, Song Wu, Geoffrey Girnun, Wei-Xing Zong
Journal: Cell Metabolism (2015)
Development and validation of the Nancy histological index for UC
Authors: Aude Marchal-Bressenot, Julia Salleron, Camille Boulagnon-Rombi, Claire Bastien, Virginie Cahn, Guillaume Cadiot, Marie-Danièle Diebold, Silvio Danese, Walter Reinisch, Stefan Schreiber, Simon Travis, Laurent Peyrin-Biroulet
Journal: Gut (2015)

<h3>Objective</h3> We developed a validated index for assessing histological disease activity in UC and established its responsiveness. <h3>Methods</h3> Two hundred biopsies were scored. The outcome was the Global Visual Evaluation (GVE). Eight histological features were tested. The Nancy index was developed by multiple linear regression and bootstrap process to create an index that best matched the GVE. Goodness of fit was assessed by the adjusted R squared (adjusted R<sup>2</sup>). The second step was the validation of the index: 100 biopsies were scored for the Nancy index by three pathologists from different centres. Inter-reader reliability was evaluated for each reader. The relationship between the change of the Nancy index and the Geboes index was assessed to assess the responsiveness. <h3>Results</h3> After backward selection with bootstrap validation, 3/8 items were selected: ulceration (adjusted R<sup>2</sup>=0.55), acute inflammatory infiltrate (adjusted R<sup>2</sup>=0.88) and chronic inflammatory infiltrate (adjusted R<sup>2</sup>=0.79). The Nancy index is defined by a 5-level classification ranging from grade 0 (absence of significant histological disease activity) to grade 4 (severely active disease). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.88 (95% CI 0.82 to 0.92) and the index had good inter-reader reliability (ICC=0.86 (0.81 to 0.99)). The correlation between the Nancy index and the Geboes score or the GVE was very good. The index had a good responsiveness with a high correlation between changes in the Geboes score and changes in the Nancy index (0.910 (0.813 to 0.955)). <h3>Conclusions</h3> A three descriptor histological index has been validated for use in clinical practice and clinical trials.
Bridging the Gap: From 2D Cell Culture to 3D Microengineered Extracellular Matrices
Authors: Yanfen Li, Kristopher A. Kilian
Journal: Advanced Healthcare Materials (2015)

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell‐sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell–cell contact, and diffusion. In this review article we explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro‐ and nano‐ fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, techniques for micropatterning in 2D, pseudo‐3D systems, and patterning within 3D hydrogels will be discussed in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues.
Chromosomal Abnormalities in Human Neoplasia
Authors: A A Sandberg, D K Hossfeld
Journal: Annual Review of Medicine (1970)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Circulating Tumor Cells and Recurrence After Primary Systemic Therapy in Stage III Inflammatory Breast Cancer
Authors: Carolyn S. Hall, Mandar Karhade, Barbara A. Laubacher, Henry M. Kuerer, Savitri Krishnamurthy, Sarah DeSnyder, Amber E. Anderson, Vicente Valero, Naoto T. Ueno, Li Yisheng, Su Xiao, Anthony Lucci
Journal: JNCI Journal of the National Cancer Institute (2015)

Inflammatory breast cancer (IBC) is rare and aggressive, with poor survival. While circulating tumor cells (CTCs) predict outcome in non-IBC patients, little data exists regarding their prognostic significance in IBC. This prospective study analyzed blood samples for CTCs from 63 stage III IBC patients to determine if CTCs present after primary systemic chemotherapy predicted relapse. CTC identification was not associated with tumor characteristics, lymph node positivity, or complete pathologic response to systemic therapy. At mean follow-up of 38 months, multivariable analysis demonstrated that detection of one or more CTCs predicted shortened relapse-free (log-rank P = 0.005, hazard ratio [HR] = 4.22, 95% confidence interval [CI] = 1.67 to 10.67, Cox P = 0.002) but not overall survival (log-rank P = 0.54, HR = 1.53, 95% CI = 0.41 to 5.79, Cox P = 0.53). All statistical tests were two-sided. In this study, CTCs after primary chemotherapy identified IBC patients at high risk for relapse.
Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer.
Authors: W K Evans, D Osoba, R Feld, F A Shepherd, M J Bazos, G DeBoer
Journal: Journal of Clinical Oncology (1985)

Seventy-eight patients with evaluable small-cell lung cancer (SCLC) were treated with etoposide (VP-16) and cisplatin after their disease failed to respond to, or relapsed after, induction combination chemotherapy, consisting primarily of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV). Twenty-four patients had limited disease (LD) and 54 had extensive disease (ED). In six (8%) patients, a complete response (CR) was achieved and in 37 (47%), there was a partial response (PR). The median duration of response for responding patients was 22 weeks (range, 4 to 50 weeks) for patients with LD and 18 weeks (range, 4 to 49 weeks) for those with ED. Twelve percent of patients demonstrated stable disease, and 33% of patients had progressive disease on treatment. The median survival times of LD patients achieving a CR or PR were 59 and 34 weeks, respectively, whereas the comparable figures for ED patients were 45 and 23 weeks, respectively. Gastrointestinal toxicity was mild, but myelosuppression, predominantly leukopenia and thrombocytopenia, was common. Mild to moderate nephrotoxicity occurred in 11 patients, but was reversible in all cases. Two febrile episodes occurred during periods of drug-induced neutropenia, but no other significant toxicities were identified. These results provide further evidence that VP-16 and cisplatin is an effective and tolerable combination chemotherapy regimen for SCLC resistant to CAV.
Abstract 16947: Improving Depressive Symptoms among Rural Patients at High Risk for Cardiovascular Disease in the Most Mentally Distressed Area in the Country
Authors: Debra K Moser, Rebecca L Dekker, Gia Mudd-Martin, Misook L Chung, Martha J Biddle, Alison Bailey, Baretta Casey, Susan Westneat, Mary K Rayens, Michael J Novak, Terry A Lennie
Journal: Circulation (2013)

Background: Appalachian Kentucky has the highest rate of mentally unhealthy days in the country. Depressive symptoms are associated with high cardiovascular disease (CVD) risk, and adults with depr...
Identification of Sepsis among Ward Patients
Authors: Michael A. Smyth, Ron Daniels, Gavin D. Perkins
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Sepsis is a systemic response to infection, which may progress to severe sepsis and septic shock (1). It is a global health problem that carries a huge economic burden (2, 3). The last decade has seen a significant drive to improve outcomes for patients with sepsis, with substantial effort focused on intensive care unit (ICU) and emergency department (ED) patients in particular. Recent data have indicated that ward patients who develop sepsis have worse outcomes than ICU or ED patients (4, 5), which has led to efforts to improve sepsis recognition in the ward environment to enable prompt intervention.