tbuckley/cabot-search huggingface dataset:
Efficacy and safety of everolimus with early reduction or elimination of tacrolimus in 719 de novo liver transplant recipients: 12 month results of a phase iii, randomized, controlled study
Authors: Faouzi Saliba, Paolo De Simone, Frederik Nevens, Luciano De Carlis, Herold Metselaar, Susanne Beckebaum, Sven Jonas, Debra Sudan, Lutz Fischer, John J Fung, Hai Jiang, Guido Junge
Journal: Hepatology (2011)
Nano-immunoassay profiling of ERK and MEK isoforms in fine-needle aspirates of solid tumors.
Authors: A. C. Fan, J. Dermody, C. Kong, N. Zhang, A. D. Colevas, D. W. Felsher
Journal: Journal of Clinical Oncology (2010)

2564 Background: We have developed the use of a highly sensitive microfluidic nano-immunoassay system (NIA) to analyze proteins in as little as 4 nanoliters of lysate from clinical specimens. We previously reported use of NIA to measure proteins in hematopoietic clinical specimens (Fan et al, Nature Medicine 2009). Now, we present results that NIA can be used to obtain reproducible and distinct signatures of phosphorylated and unphosphorylated ERK and MEK isoforms in fine-needle aspirates (FNAs) of solid tumor and nontumor clinical specimens. Methods: NIA uses isoelectric focusing to separate proteins so that multiple isoforms of a protein can be measured simultaneously and relative abundance of the isoforms can be calculated. We first developed protocols to process FNA specimens for reproducible NIA analysis of solid tumors, then performed NIA analysis of ERK1/2 and MEK1 profiles in 200 specimens of paired tumor and nontumor FNAs. Over 20 proteomic parameters were measured, including unphosphorylated, single- and multiple- phosphorylated isoforms, and calculated percentages of each isoform for each protein. Samples were run in triplicate. ANOVA was used for biostatistical analysis. Results: Across all tumor types, the mean coefficient of variance for technical replicates was less than 5%. We found that transport time up to 60 minutes on ice did not significantly alter the ERK and MEK profiles (p values for each parameter= NS for 0 minutes vs. 60 minutes). Preliminary analysis of the squamous cell tumor and nontumor profiles suggests that different ratios of phosphorylated and unphosphorylated ERK1/2 and MEK1 isoforms can distinguish FNAs from tumor or nontumor specimens. Notably, measurements of single isoforms alone can not resolve the two groups. Conclusions: Our studies demonstrate that NIA can be used to precisely and reliably measure differences in total and relative abundance of ERK and MEK isoforms in solid tumors. We are currently incorporating NIA proteomic analysis in correlative studies for prospective clinical trials. NIA may be a promising novel technology for new diagnostic and biomarker studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Biosciences Cell Biosciences
The factors affecting objective response in patients with advanced malignant tumor treated with H101, an E1B-55kD deleted oncolytic adenovirus
Authors: H. Xia, R. Zhao, W. Hu, Z. Li, G. Hu, F. Hu
Journal: Journal of Clinical Oncology (2006)

13166 Background: H101 is E1B-55kD deleted oncolytic adenovirus which can selectively replicate in tumor cells. Previous phase I/II clinical trials have shown that H101 has certain anti-tumor effects and is safe when applied to patients by intratumoral injection. The aim of this study is to identify the factors affecting tumor response in patients with advanced malignant tumor treated with H101. Methods: All patients in H101 phase II clinical trial were retrospectively reviewed. They were treated with either H101 alone (group A) or H101 combined with conventional chemotherapy (group B). H101 was administrated by intratumoral injection at the dosage of 5×10 11 viral particles, once a day for 5 consecutive days. The objective response was evaluated according to WHO criteria and the adverse events were recorded. All information required for this study was retrieved from the database of H101 phase II clinical trial. Chi square test and stepwise multivariable regression were used for statistic analysis with a significant level of p&lt;0.05. Results: There were 106 evaluable patients in this study, 54 in group A (36 males and 18 females, age: 36–78 years), 52 in group B (35 males and 17 females, age: 18–76 years). The diagnoses of these patients include head &amp; neck cancer (54), breast cancer (13) and others (39). All were in the advanced stage of the disease, and refractory or resistant to chemo and radio therapy. The objective response rate was higher in group B (23.1%) as compared to group A (16.7%). In patients with response (CR or PR), 62.5% of them experienced fever after the injection of H101, in contrast, only 18.9% of the patients without response did so. The difference was statistically significant (p&lt;0.01). In the stepwise multivariable regression analysis, tumor response was used as dependent variable, and the independent variables included demographic data, clinical and pathologic type of the tumor, and treatment regimen. The result revealed that tumor response was positively correlated with the fever after H101 injection (p&lt;0.01). Conclusions: H101 has certain anti-tumor efficacy in patients with advanced malignancies, which might be enhanced by the fever after H101 injection and/or combining with chemotherapy. [Table: see text]
PD-1 expression and its impact on survival in localized clear cell renal cell carcinoma.
Authors: Rishi Robert Sekar, Michelle A. DiMarco, Dattatraya Patil, Adeboye O. Osunkoya, Brian P. Pollack, Gabriel Sica, Viraj A. Master
Journal: Journal of Clinical Oncology (2016)

568 Background: Programmed cell death protein 1 (PD-1) immune checkpoint inhibitors have been shown to have activity in advanced renal cell carcinoma (RCC), prompting research into PD-1 as a potential biomarker. In this study, we evaluate tumor PD-1 expression and its prognostic value in patients with localized clear cell RCC. Methods: Patients that underwent nephrectomy for localized clear cell RCC (T1-T3) with &gt;4 years of follow-up were queried from our nephrectomy database. Tissue blocks with tumor and adjacent benign renal parenchyma were selected for analysis. Immunohistochemical staining for PD-1 was performed on tumor specimens using anti-PD-1 clone NAT105 (Abcam). Focusing on immune cells, PD-1 positivity was defined as &gt;1% expression and graded in 10% increments. The relationship between PD-1 positivity, FNG, and TNM stage was evaluated using Pearson’s chi-square test. The impact of PD-1 positivity on overall and recurrence-free survival was evaluated using the Kaplan-Meir method. Results: Fifty-three patients were included in the study. The distribution of PD-1 expression in 10% increments can be seen in Table. No statistically significant correlation was found between PD-1 positivity, TNM stage and FNG (chi-square test; p=0.15, p=0.62, respectively). No statistically significant differences in overall or recurrence-free survival were found between positive and negative PD-1 expression groups (log-rank; p=0.32, p=0.43, respectively). Conclusions: Our data show that primary tumor PD-1 expression varies widely in patients with clear cell RCC and that PD-1 positivity does not correlate with commonly reported histopathological features such as TNM stage and FNG. Further, PD-1 positivity does not have a significant impact on overall and recurrence-free survival. These findings contrast with previous studies of PD-1 expression in RCC, suggesting that further research into the role of PD-1 in tumor progression as well as methods of case/tissue block selection and PD-1 quantification is needed. [Table: see text]
Intensive Induction Is Beneficial for High Risk Younger Patients with Aggressive B-Cell Lymphoma, While Frontline ASCT Brings No Benefit: Final Analysis of MegaCHOP-BEAM and MegaCHOP-ESHAP-BEAM Studies.
Authors: Robert Pytlik, David Belada, Katerina Kubackova, Tomas Kozak, Milada Jankovska, Jan Pirnos, Ingrid Bolomska, Ingrid Vasova, Tomas Papajik, Alena Sykorova, Hana Siffnerova, Michaela Hamouzova, Pavel Klener, Marek Trneny
Journal: Blood (2006)
Geoffrey William Hinchley
Authors: Richard Neville Walker
Journal: BMJ (2016)

Born the second of four children in Barrow in Furness, Geoffrey William Hinchley (“Geoff”) excelled both academically and athletically at Barrow Boys Grammar School. At medical school he was a popular member of his year, the sporty “archetypal northerner,” who ran the student bar at a profit and coauthored an anthology of rugby songs of enduring notoriety. His best remembered nickname, “Sluice,” commemorated his prowess with a yard of ale; another—“Soup Dragon”—derived from his enunciation, which was surprisingly soft for someone so confident and outgoing.

In nature expansive and convivial, Geoff was the life and soul of the party and the heart of many a serious political or philosophical discussion, usually over pints in his local pub. But he was entirely serious about his career.

After a brief stint as a house physician in Jersey, Geoff held a succession of roles at Charing Cross, latterly as a lecturer in anatomy and as senior house officer in accident and emergency medicine. There then followed senior house officer positions in orthopaedics, thoracic surgery, general surgery, and urology at Mount Gould and Derriford hospitals in Plymouth before a brief, but glamorous, interlude as ship’s doctor aboard the luxury cruise liner Ocean Pearl . It was during this time that Geoff witnessed at first hand the …
Frequent Expression of Cancer/Testis Antigens CT7 and LAGE-1 in Advanced Stage Multiple Myeloma: Are They Possible Targets for Immunotherapy?.
Authors: Valeria Cristina da Costa Andrade, Gisele Wally Braga Colleoni, Andre L. Vettore, Roberta Spetic Felix, Manuella S.S. Almeida, Fabricio Carvallho, Mihoko Yamamoto, Marco Antonio Zago
Journal: Blood (2006)
The PI3K/Akt Pathway Is an Important Regulator of Homing and Adhesion in Waldenstrom’s Macroglobulinemia.
Authors: Xavier Leleu, Hai Ngo, Judy Runnels, Costas Pitsillides, Joel Spencer, Anne-Sophie Moreau, Evdoxia Hatjiharisi, Xiaoying Jia, Garrett O’Sullivan, Steven Treon, Teru Hideshima, Charles Lin, Kenneth Anderson, Irene Ghobrial
Journal: Blood (2006)
Placental Growth Factor: a Novel, Stromal-Derived Target in Human CML.
Authors: Sonja Loges, Thomas Schmidt, Christa Maes, Bart Jonckx, Maria Kleppe, Kim De Keersmaecker, Marc Tjwa, Thomas Schenk, Karolien Anne Beel, Christiane DeWolf-Peeters, Geert Carmeliet, Jan Cools, Richard E Clark, Peter Vandenberghe, Tim H Brummendorf, Tessa Holyoake, Andreas Hochhaus, Peter Carmeliet
Journal: Blood (2009)
Prof. Almaz A. Aldashev (1953–2016)
Authors: Martin R. Wilkins, Nicholas W. Morrell
Journal: European Respiratory Journal (2016)

Almaz Aldashev was a man of his people. He was never more happy than when travelling through his native mountains, talking, eating and singing with his fellow Kyrgyz, drinking kumis, fishing in streams, and sleeping in yurts.

He was born on November 1, 1953 in Frunze (now known as Bishkek), then capital of Kyrgyzstan and part of the Union of Soviet Socialist Republics (USSR). His father, Abdulkhai Aldashev, was professor of veterinary science at the National Agrarian University, as well as a member of the Writers' Association of Kyrgyzstan (now the Kyrgyz Republic). His mother, Fatima, devoted herself entirely to raising five children. Together, they stimulated and nurtured Almaz's broad education and deep understanding of his country's cultural history.

Almaz spent his undergraduate years in Moscow. In 1980, he became a research assistant in the high-altitude laboratory in Kyrgyzstan, sparking a career-long interest in hypoxia-induced pulmonary hypertension. He was awarded his PhD by the Moscow Academy of Sciences in 1983 on “Receptors, intracellular signalling and hypoxic proteins at high-altitude pulmonary hypertension”. He was soon Head of the Laboratory of Molecular and Cell Biology within the Institute of Cardiology in Bishkek, and in 2002, he became Director of the Institute of Molecular Biology and Medicine. His scientific leadership was recognised internationally …
Macrophage Metabolism Controls Tumor Blood Vessel Morphogenesis and Metastasis
Authors: Mathias Wenes, Min Shang, Mario Di Matteo, Jermaine Goveia, Rosa Martín-Pérez, Jens Serneels, Hans Prenen, Bart Ghesquière, Peter Carmeliet, Massimiliano Mazzone
Journal: Cell Metabolism (2016)
GMC closes inquiry into troubled Aberdeen hospital
Authors: Bryan Christie
Journal: BMJ (2016)

A lengthy investigation by the UK General Medical Council into the conduct of senior doctors at Aberdeen Royal Infirmary has concluded without any action being taken.

The inquiry was prompted by two critical reports issued in late 2014 by Healthcare Improvement Scotland and the Royal College of Surgeons of England into problems at the hospital, the largest in the NHS Grampian area. The reports found serious …
Putting the Health of Communities and Populations First
Authors: Lynn R. Goldman, Shiriki K. Kumanyika, Nirav R. Shah
Journal: JAMA (2016)

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Molecular markers in colon cancer have a stage specific prognostic value. results of the translational study on the petacc 3-eortc 40883-sakk 60-00 trial
Authors: A Roth, Sabine Tejpar, P Yan, R Fiocca, D Klingbiel, M Delorenzi, D Dietrich, R Labianca, D Cunningham, Eric Van Cutsem, F Bosman
Journal: Annals of Oncology (2009)
Cancer patients have unrealistic expectations of taking part in trials, UK study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

More than 80% of UK cancer patients considering participating in a phase I drug trial do so anticipating clinical benefit, a study has found. Researchers at the Royal Marsden NHS Foundation Trust and the Institute of Cancer found that about half of patients expected to see their tumour shrink and that one in 10 hoped for a cure, even after consultation with specialists.

But response rates in such trials, which are usually reserved for patients with cancers that no longer respond to standard treatments, are typically far lower, ranging from 4% to 20%, and the median survival time of such patients is only six months, the researchers noted.

Phase I …
Detection of EGFR-activating mutations from plasma DNA as a potent predictor of survival outcomes in FASTACT 2: A randomized phase III study on intercalated combination of erlotinib (E) and chemotherapy (C).
Authors: Tony Mok, Yi Long Wu, Jin Soo Lee, Chong-Jen Yu, Virote Sriuranpong, Wei Wen, Julie Tsai, Matt Truman, Barbara Klughammer, Lin Wu
Journal: Journal of Clinical Oncology (2013)

8021 Background: Biomarker analysis of tumor from FASTACT 2 confirmed predictive power of EGFR mut on the benefit of intercalated combination of E and C as 1st line in advanced NSCLC (T. Mok, ESMO 2012). However, only limited tumor were available. Recent development allowed us to detect EGFR mut in cell-free DNA from plasma (pEGFRmut). In this study, we studied the concordance between pEGFRmut and EGFR mut in tumor (tEGFRmut), and the role of pEGFRmut as predictor of PFS and OS. Methods: Retrospective EGFR mut testing of FFPET and plasma from FASTACT 2 were performed with two allele-specific PCR assays, cobas EGFR_FFPET test and cobas EGFR_blood test (in development). Both tests are designed to detect EGFR activating mut (exon 19 deletions, L858R, G719X). One FFPET section was used for tissue test and 2-ml plasma was used for blood test. Results: Among 268 tumors from 451 enrolled pts, 90% (241/268) were analyzable. 40% (96/241) harbored at least one activating EGFR mut. All 427 plasmas from 451 enrolled pts were analyzable. 32% (136/427) were positive for EGFR activating mut. The concordance of two tests from 224 matched tissue and plasma samples was summarized below. Using tissue as comparator, the sensitivity of plasma test was 76% (68/89) and the specificity of plasma test was 96% (130/135) respectively. Positive and negative predictive values for EGFR activating mut were 93% (68/73) and 86% (130/151) respectively. Median PFS of patients with pEGFRmut treated with intercalated combination versus chemotherapy alone was 13.8 vs. 6.1 m (HR=0.21 p&lt;0.0001), and for pEGFR wild-type, 6.7 vs. 6.0 m (HR=0.80, p=0.06). Median OS of patients with pEGFRmut treated with intercalated combination versus chemotherapy alone was 32.4 vs. 19.0 m (HR=0.51, p=0.0035), and for pEGFR wild-type, 16.1 vs 13.3 m (HR=0.89, p=0.39). Conclusions: cobas EGFR_blood test can be used to reliably detect EGFR mutations in plasma. pEGFRmut is a potent predictor of survival outcomes in FASTACT 2. Clinical trial information: NCT00883779/ MO22201/CTONG0902. [Table: see text]
Baseline demographics of the randomized, placebo-controlled, double-blind, phase III RADIANT-4 study of everolimus in nonfunctional gastrointestinal (GI) or lung neuroendocrine tumors (NET).
Authors: James C. Yao, Roberto Buzzoni, Carlo Carnaghi, Nicola Fazio, Simron Singh, Edward M. Wolin, Jiri Tomasek, Markus Raderer, Harald Lahner, Du Hung Lam, Helene Cauwel, Juan W. Valle, Gianfranco Delle Fave, Eric Van Cutsem, Jonathan R. Strosberg, Margot Et Tesselaar, Yasuhiro Shimada, Do-Youn Oh, Matthew Kulke, Marianne E. Pavel
Journal: Journal of Clinical Oncology (2015)

276 Background: NET are malignant tumors arising from neuroendocrine cells throughout the body. Everolimus (EVE), a mammalian target of rapamycin inhibitor, is approved for the treatment of advanced, well-differentiated pancreatic NET. There is an unmet medical need in GI and lung NET; targeted therapies, such as everolimus, are of particular interest. Methods: Patients with advanced nonfunctional NET of GI or lung origin with progressive disease (PD) within the past 6 months were randomized (2:1) to EVE 10 mg/d or placebo, both with best supportive care. Concomitant use of somatostatin analogue (SSA) was not allowed during the study, except for control of emergent carcinoid symptoms not manageable by standard therapy. Patients were stratified based on tumor sites, prior SSA exposure, and WHO performance status (PS) at baseline. Primary endpoint was progression-free survival (PFS) as assessed by central radiology review using modified RECIST 1.0 criteria. Primary analysis is planned after ~176 PFS events. Crossover to open label EVE after progression would not be allowed prior to the primary analysis. Overall survival was the key secondary endpoint. Results: Recruitment is completed. Of 388 patients screened, 302 were randomized (planned, 285). Median age was 63 years, 53% were females, and majority of them (76.2%) were white. The most common tumor sites were lung (29.8%), ileum (23.5%), and rectum (13.2%). WHO PS was 0 in 219 (72.5%) patients and 1 in 82 (27.2%) patients; 52% had received SSA prior to study entry. As of Sep 16, 2013, 173 (57.3%) patients remain on treatment, 127 (42.1%) discontinued treatment and 2 (0.7%) were not treated. PD (24.2%) and adverse events (10.6%) were the most common reasons for treatment discontinuation. Results of primary analysis are expected by early 2015. Conclusions: RADIANT-4 is the first phase III study to assess the efficacy and safety of EVE in patients with nonfunctional NET of GI or lung origin. Non-crossover design and prospective stratification of the population based on known prognostic factors should minimize confounding in the estimation of the treatment effect. Clinical trial information: NCT01524783.
Case 21-1963
Authors: Bernard M. Jacobson, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of CaseA sixty-year-old woman was referred to the hospital because of pain in the back.The patient had been in good health until one month before admission, when aching pain between the scapulas developed three days after she had raked leaves. The pain became persistent and extended over the right anterior and lateral portions of the chest and down to the posterior iliac crests. It was aggravated by motion and coughing and was partially relieved by codeine.During the three weeks before entry numerous ecchymoses appeared over the trunk and extremities, and a blood-streaked nasal discharge and a . . .
Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial
Authors: W. Shi, T. Jiang, P. Nuciforo, C. Hatzis, E. Holmes, N. Harbeck, C. Sotiriou, L. Peña, S. Loi, D.D. Rosa, S. Chia, A. Wardley, T. Ueno, J. Rossari, H. Eidtmann, A. Armour, M. Piccart-Gebhart, D.L. Rimm, J. Baselga, L. Pusztai
Journal: Annals of Oncology (2016)