tbuckley/cabot-search huggingface dataset:
The Epidemiologic Necropsy
Authors: George G. Rhoads
Journal: JAMA (1987)

<h3>To the Editor.—</h3> It was good to see a lead article in<i>JAMA</i><sup>1</sup>highlighting the value of routine necropsy not only for teaching purposes, but also for the data on the occurrence of incidental disease that such examinations can provide. I was surprised, however, that the authors did not bemoan the falling autopsy rate that is reducing the epidemiologic value of such data. Extrapolation of their figures suggests that the autopsy will be dead at Yale University as early as 1990! There are several reasons why the<i>prevalence</i>rates for "surprise" cases of lung cancer at autopsy are not comparable to the<i>incidence</i>rates from a tumor registry. The proportion of cases that are undiagnosed prior to autopsy is somewhat arbitrary since it depends on the thoroughness of the diagnostic effort in life. There might well be more "surprises" in smaller, service-oriented hospitals than in larger, academic ones. Moreover,
Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials
Authors: Benjamin M. Ellingson, Robert J. Harris, Davis C. Woodworth, Kevin Leu, Okkar Zaw, Warren P. Mason, Solmaz Sahebjam, Lauren E. Abrey, Dana T. Aftab, Gisela M. Schwab, Colin Hessel, Albert Lai, Phioanh L. Nghiemphu, Whitney B. Pope, Patrick Y. Wen, Timothy F. Cloughesy
Journal: Neuro-Oncology (2016)

The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM. Included were 497 patients with recurrent GBM from 4 data sources: 2 single-center sites (University of Toronto, University of California Los Angeles) and 2 phase II multicenter trials (AVF3708G, Bevacizumab ± Irinotecan, NCT00345163; XL184-201, Cabozantinib, NCT00704288). T1 subtraction maps were used to define volume of contrast enhancing tumor, including central necrosis. Cox multivariable and univariate analyses were used to evaluate the relationship between tumor volume prior to second- or third-line therapy and OS. Both continuous measures of baseline tumor volume and tumors dichotomized into large (≥15cc) and small (<15cc) tumors were significant predictors of OS (P<.0001), independently of age and treatment. Univariate analysis demonstrated significant OS differences (P<.05) between large (≥15cc) and small (<15cc) tumors in patients under all therapeutic scenarios. Only patients treated with cabozantinib who previously failed anti-angiogenic therapy did not show an OS dependence on baseline tumor volume. Baseline tumor volume is a significant prognostic factor in recurrent GBM. Clinical trial treatment arms must have a balanced distribution of tumor size, and tumor size should be considered when interpreting therapeutic efficacy.
Progression and Outcome in Patients with Biclonal Gammopathies
Authors: Trey Carlton Mullikin, S. Vincent Rajkumar, Angela Dispenzieri, Morie A Gertz, Martha Q Lacy, Francis Buadi, Prashant Kapoor, Jerry A. Katzmann, Dirk Larson, Robert Kyle, Shaji Kumar
Journal: Blood (2014)
Combination Chemotherapy with Pentostatin, Cyclophosphamide and Rituximab Induces High Rate of Remissions Including Complete Responses and Achievement of Minimal Residual Disease in Previously Untreated B-Chronic Lymphocytic Leukemia.
Authors: Neil E. Kay, Susan M. Geyer, Thomas Lin, Timothy G. Call, Diane F. Jelinek, Nancy D. Bone, Gordon W. Dewald, Nyla L. Heerema, Renee Tschumper, L. Smith, Michael R. Grever, John C. Byrd
Journal: Blood (2004)
Inactivation of the putative ubiquitin-E3 ligase PDLIM2 in classical Hodgkin and anaplastic large cell lymphoma
Authors: K D Wurster, F Hummel, J Richter, M Giefing, S Hartmann, M-L Hansmann, S Kreher, K Köchert, D Krappmann, W Klapper, M Hummel, S-S Wenzel, G Lenz, M Janz, B Dörken, R Siebert, S Mathas
Journal: Leukemia (2016)

Apart from its unique histopathological appearance with rare tumor cells embedded in an inflammatory background of bystander cells, classical Hodgkin lymphoma (cHL) is characterized by an unusual activation of a broad range of signaling pathways involved in cellular activation. This includes constitutive high-level activity of nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), activator protein-1 (AP-1) and interferon regulatory factor (IRF) transcription factors (TFs) that are physiologically only transiently activated. Here, we demonstrate that inactivation of the putative ubiquitin E3-ligase PDLIM2 contributes to this TF activation. PDLIM2 expression is lost at the mRNA and protein levels in the majority of cHL cell lines and Hodgkin and Reed–Sternberg (HRS) cells of nearly all cHL primary samples. This loss is associated with PDLIM2 genomic alterations, promoter methylation and altered splicing. Reconstitution of PDLIM2 in HRS cell lines inhibits proliferation, blocks NF-κB transcriptional activity and contributes to cHL-specific gene expression. In non-Hodgkin B-cell lines, small interfering RNA-mediated PDLIM2 knockdown results in superactivation of TFs NF-κB and AP-1 following phorbol 12-myristate 13-acetate (PMA) stimulation. Furthermore, expression of PDLIM2 is lost in anaplastic large cell lymphoma (ALCL) that shares key biological aspects with cHL. We conclude that inactivation of PDLIM2 is a recurrent finding in cHL and ALCL, promotes activation of inflammatory signaling pathways and thereby contributes to their pathogenesis.
A phase II trial of postoperative radiotherapy (RT), cisplatin, and panitumumab in patients with high-risk, resected locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Authors: R. L. Ferris, A. P. Kotsakis, D. E. Heron, S. Kim, U. Duvvuri, G. J. Kubicek, J. R. Grandis, J. T. Johnson, A. Argiris
Journal: Journal of Clinical Oncology (2010)

TPS262 Background: Postoperative RT plus cisplatin has emerged as standard treatment for high risk, resected SCCHN patients. The epidermal growth factor receptor (EGFR) is a poor prognostic factor and important therapeutic target. The EGFR-specific antibody, panitumumab, has promising chemo- and radiosensitizing properties in phase I experience in SCCHN. We incorporated panitumumab into postoperative RT and cisplatin. Methods: Patients are treated 3-7 weeks after surgical resection without gross residual tumor of pathologic stage III or IVa SCCHN of the oral cavity, larynx, or hypopharynx. We excluded a) T3N0 larynx and b) any T1N1, if there were no high risk pathologic features (<1 mm margins extracapsular spread, perineural or angiolymphatic invasion, or >2 positive lymph nodes). Patients received no other prior therapy for SCCHN and have ECOG performance status of 0-1. Treatment consists of standard RT (60-66 Gy with daily fractions in 6-7 weeks) concurrent with weekly panitumumab 2.5 mg/kg IV and weekly cisplatin (30 mg/m2 IV). Carboplatin (AUC 1.5 weekly) can be subsequently substituted for cisplatin toxicities. In this one-arm phase II study the primary endpoint is the progression-free survival at 2 years with a planned sample size of 47 patients. We assume that postoperative radiation and cisplatin alone would result in 2- year PFS of 50%, and that addition of panitumumab will increase it to 70%. Secondary endpoints are overall survival, event-free survival, and toxicities. Correlative studies will investigate several EGFR-related and immune biomarkers in tumor and blood samples obtained prior and after therapy. Correlation of biomarkers with 2-year PFS include, a) EGFR and downstream pathway activation, b) FcγR polymorphisms, and c) serum cytokine profiles. Specific EGFR and angiogenesis biomarkers will be analyzed using reverse phase protein microarrays (RPPA), using baseline archival tumor tissue. Pretreatment and posttreatment serum specimens will be used for cytokine/chemokine and immune biomarkers. Fourteen patients have been enrolled in this ongoing study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Merck Amgen, PGxH Biosciences
Gfi1 as a Regulator of Hematopoietic Differentiation.
Authors: H. Leighton Grimes, Chinavenmeni S. Velu, Shane Horman, Aditya Chaubey, Tristan Bourdeau, Haiming Xu, Jinfang Zhu, William Paul, Clemencia Colmenares, David A. Williams, Brian Gebelein
Journal: Blood (2008)
Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma
Authors: Antonio Palumbo, Asher Chanan-Khan, Katja Weisel, Ajay K. Nooka, Tamas Masszi, Meral Beksac, Ivan Spicka, Vania Hungria, Markus Munder, Maria V. Mateos, Tomer M. Mark, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Andrew Spencer, Pieter Sonneveld
Journal: New England Journal of Medicine (2016)

Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival.A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P=0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3% and 32.9%, respectively), anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, respectively). Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 98.2% of these patients, they occurred during the first infusion.Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone. (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT02136134.).
Online Intervention for Prevention of Major Depression<b>—Reply</b>
Authors: David Daniel Ebert, Claudia Buntrock, Pim Cuijpers
Journal: JAMA (2016)

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Celebrating the New
Authors: Kimberly Callan
Journal: Journal of the National Comprehensive Cancer Network (2008)

Celebrating the NewAn old saying my mother was fond of using suggests that for every door closed, a new one is opened.However optimistic that may be for doors, it is certainly true of years, with each end bringing an inevitable, and usually welcome, beginning.That welcome is especially true for many of us at JNCCN this year, and as we celebrate the new year, we cannot help but be mindful of important losses in 2007.After Christopher Desch, NCCN Medical Director and new co-
Efficacy of an mHealth intervention to stimulate physical activity in COPD patients after pulmonary rehabilitation
Authors: Sigrid N.W. Vorrink, Helianthe S.M. Kort, Thierry Troosters, Pieter Zanen, Jan-Willem J. Lammers
Journal: European Respiratory Journal (2016)

Physical inactivity in patients with chronic obstructive pulmonary disease (COPD) is associated with poor health status and increased disease burden. The present study aims to test the efficacy of a previously developed mobile (m)Health intervention to improve or maintain physical activity in patients with COPD after pulmonary rehabilitation. A randomised controlled trial was performed in 32 physiotherapy practices in the Netherlands. COPD patients were randomised into intervention or usual care groups. The intervention consisted of a smartphone application for the patients and a monitoring website for the physiotherapists. Measurements were performed at 0, 3, 6 and 12 months. Physical activity, functional exercise capacity, lung function, health-related quality of life and body mass index were assessed. 157 patients started the study and 121 completed it. There were no significant positive effects of the intervention on physical activity (at 0 months: intervention 5824±3418 steps per weekday, usual care 5717±2870 steps per weekday; at 12 months: intervention 4819±2526 steps per weekday, usual care 4950±2634 steps per weekday; p=0.811) or on the secondary end-points. There was a significant decrease over time in physical activity (p&lt;0.001), lung function (p&lt;0.001) and mastery (p=0.017), but not in functional exercise capacity (p=0.585). Although functional exercise capacity did not deteriorate, our mHealth intervention did not improve or maintain physical activity in patients with COPD after a period of pulmonary rehabilitation.
Transitional cell carcinomas of the upper urothelial tract: A retrospective analysis
Authors: F. Merlin, T. Sava, A. B. Porcaro, C. Ghimenton, M. Frisinghelli, P. Manno, C. Griso, M. A. Bassetto, L. Comunale, G. L. Cetto
Journal: Journal of Clinical Oncology (2004)

4740 Background: Transitional cell carcinomas (TCC) of the renal pelvis and ureter are relatively uncommon. The aim of this study was to investigate prognostic factors for relapse and patterns of bladder recurrence after surgery. Methods: 55 patients (pts) with upper urinary tract TCC treated surgically between 1988 and 2002 were retrospectively reviewed. Prognostic factors, relapse, bladder recurrence and survival were analysed. Results: We observed a median age of 66 (33–83) years, a male predominance (75%) and renal pelvis site of primitive disease (67%) more frequently. Eleven pts (20%) had a synchronous ureteral and pelvicalyceal tumours, while 15% of pts had diagnosis of muscle-invasive bladder tumours synchronous. At diagnosis 7 pts had metastatic disease. 29% of pts had subsequently bladder involvement after a median time of 16 (1–142) months. Distant relapsed occurred in 25% of pts, mainly lymph nodes and lung metastasis (but also bone and soft tissue), with a median time to relapse of 6 (1–23) months. 34.5% of pts died of disease. T, N and Grading confirmed to be the most important prognostic factors while vascular invasion seems reflect T stage (it was present only in T3 and T4 pts); age and gender had no prognostic importance in our series. 81% of the pts were heavy smokers, while no hereditary factors were detected. Interestingly 16% of our pts developed subsequently a non TCC second tumour. Conclusions: In our series T, N and G are the only important prognostic factors. Relapse occurred soon and usually as pulmonary and lymph nodes metastases. Frequently, 44% in our pts, there is a synchronous or metachronous bladder TCC: median time is 16 months, but some pts had bladder recurrence after many years from nephroureterectomy. Therefore a strict follow-up should be performed in this pts. No significant financial relationships to disclose.
Interactions of graphene with mammalian cells: Molecular mechanisms and biomedical insights
Authors: Bo Zhang, Peng Wei, Zhixiang Zhou, Taotao Wei
Journal: Advanced Drug Delivery Reviews (2016)

Carbon-based functional nanomaterials have attracted immense scientific interest from many disciplines and, due to their extraordinary properties, have offered tremendous potential in a diverse range of applications. Among the different carbon nanomaterials, graphene is one of the newest and is considered the most important. Graphene, a monolayer material composed of sp2-hybridized carbon atoms hexagonally arranged in a two-dimensional structure, can be easily functionalized by chemical modification. Functionalized graphene and its derivatives have been used in diverse nano-biotechnological applications, such as in environmental engineering, biomedicine, and biotechnology. However, the prospective use of graphene-related materials in a biological context requires a detailed comprehension of these materials, which is essential for expanding their biomedical applications in the future. In recent years, the number of biological studies involving graphene-related nanomaterials has rapidly increased. These studies have documented the effects of the biological interactions between graphene-related materials and different organizational levels of living systems, ranging from biomolecules to animals. In the present review, we will summarize the recent progress in understanding mainly the interactions between graphene and cells. The impact of graphene on intracellular components, and especially the uptake and transport of graphene by cells, will be discussed in detail.
Case 24-2016
Authors: Hasan Bazari, William E. Palmer, Jason M. Baron, Katrina Armstrong
Journal: New England Journal of Medicine (2016)

A 66-year-old man presented with malaise, weakness, hypercalcemia, and acute kidney injury. CT of the abdomen and pelvis revealed no evidence of cancer; CT of the chest revealed a sclerotic lesion of the eighth rib. Additional tests were performed, and a diagnosis was made.
P0529 : Anti capsid drugs HAP12 and AT130 target HBV core protein nuclear functions
Authors: L. Belloni, G.A. Palumbo, L. Lupacchini, L. Li, S. Reddy Chirapu, L. Calvo, M.G. Finn, U. Lopatin, A. Zlotnick, M. Levrero
Journal: Journal of Hepatology (2015)
A phase II study of biweekly carboplatin (Cb) and gemcitabine (G) with bevacizumab (B) as first-line treatment in patients with advanced, inoperable stage IIIb/IV non-squamous non-small cell lung cancer (NSCLC).
Authors: S. Bommakanti, T. Larson, A. Dudek, J. Koopmeiners, P. Kumar
Journal: Journal of Clinical Oncology (2010)

e18091 Background: Cb and G is an active platinum doublet used as first line therapy in advanced, inoperable lung cancer. The addition of B to a platinum doublet has shown improved efficacy. A combination of Cb and G is known to generate a high frequency of thrombocytopenia. Therefore, we developed a biweekly schedule that resulted in low thrombocytopenia rates and better tolerance. This study evaluated the efficacy and safety of Cb and G combined with B. Methods: This was a single arm phase II study in non- squamous NSCLC. A 14-day treatment cycle was given with a maximum of 6 cycles per patient.B was to continue until disease progression. G 2,000 mg/m2 and Cb with AUC = 3 was administered with B 10 mg/kg on day 1. The primary endpoint was progression-free survival (PFS) > 4 months with the power 85% at one-sided 0.05 significant level. Results: 36 patients were enrolled in this study from 3/2007 to 11/2009. A total of 301 cycles were administered, with a median number of cycles 6 (range 2 to 30). Grades 3-5 toxicities that occurred in at least 10 percent of patients included grade 3 hypertension (n = 7), and grade 4 PE (n = 4). There were no CR, 17 (47%) PR, 14 (39%) SD, 3 (8%) DP, and 2 (6%) unknown. Median PFS was 5.3 months (95% CI: 4.44, 7.71). Estimate of 6 month PFS was .404 (95% CI: 0.263, 0.620) and 12 month PFS was 0.197 (95% CI: 0.094, 0.410). Median overall survival (OS) was 15.2 months (95% CI: 11.6, Inf). Estimate of 6 month OS was 0.879 (95% CI: 0.775, 0.998) and 12 month OS was .594 (95% CI: 0.429, 0.821). Conclusions: Study met its primary endpoint. The regimen was well tolerated despite six patients having grade IV non-hematologic toxicities, resulting in early study termination. No significant financial relationships to disclose.
Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease
Authors: Hila Milo Rasouly, Sudhir Kumar, Stefanie Chan, Anna Pisarek-Horowitz, Richa Sharma, Qiongchao J. Xi, Yuriko Nishizaki, Yujiro Higashi, David J. Salant, Richard L. Maas, Weining Lu
Journal: Kidney International (2016)