tbuckley/cabot-search huggingface dataset:
Targeting HER2 in patients with HER2-negative metastatic breast cancer with elevated serum levels of the HER2 extracellular domain and/or HER2-positive circulating tumor cells in the clinical routine
Authors: C.M. Kurbacher, A. Quade, G. Kunstmann, S. Herz, J.A. Kurbacher, M.A. Warm
Journal: Annals of Oncology (2015)
New insights into the prognostic value of Ki-67 labeling index in patients with triple-negative breast cancer.
Authors: Shuang Hao, Shao Zhimin
Journal: Journal of Clinical Oncology (2014)

e12031 Background: The clinical-pathological importance of Ki-67 labeling index (LI) in breast cancers has been intensely studied; however, the prognostic relevance in triple negative (TN) subtype has not been demonstrated. The aim of this analysis was to investigate the relevance of Ki-67 LI and age for the identification of triple-negative breast cancer (TNBC) subtype. Methods: A total of 571 female TNBC patients operated and diagnosed at our institution from January 2002 to June 2011 were categorized by Ki-67 LI and diagnosed age. Kaplan-Meier method and the log-rank test were used for survival analysis. Cox proportional hazards models were fit to determine the association of Ki-67 LI and diagnosed age with breast-cancer specific survival (BCSS) outcomes. A varying-coefficient Cox model was used to describe the effect of Ki-67 on the BCSS outcomes changing with diagnosed age after adjustment for disease characteristics. Results: Of the 571 patients, median age and Ki-67 LI were 50 years and 35%, and median follow-up time of 44.5 months (range 2.2–139.1). The 5-year BCSS was 83%. Based on the analysis results, there was no prognostic significance in Ki-67 LI in all patients. When analyzing age of diagnosis as a continuous variable, the hazard ratio (HR) of Ki-67 LI>35% to Ki-67 LI≤35% of breast cancer-specific mortality (BCSM) increased in a S-shaped curve with increasing diagnosed age up to about 50 years old and remained higher risks for high Ki-67 LI. When focused on the patients being diagnosed at age≤50 years, the BCSS was 84% , respectively, with an adjusted HR low Ki-67 LI vs. high of 0.36 (95 % CI 0.14–0.99, P=0.04). However, in the patients being diagnosed at age>50 years, low Ki-67 LI revealed to have a better prognosis (adjusted P=0.22, >0.05). Based on the data from the large cohort of a clinical cancer registry, it was demonstrated that Ki-67 LI has different significance in patients of different age groups. Conclusions: Lower proliferation measured by Ki-67 has poor prognosis relevance in TNBC of patients diagnosed≤50 years old, which is different with Luminal A subtype. Further validation of the clinical significance of Ki-67 LI need to be demonstrated, which is essential for this group of breast tumors.
Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer
Authors: Shanshan Zhao, Milan S. Geybels, Amy Leonardson, Rohina Rubicz, Suzanne Kolb, Qingxiang Yan, Brandy Klotzle, Marina Bibikova, Antonio Hurtado-Coll, Dean Troyer, Raymond Lance, Daniel W. Lin, Jonathan L. Wright, Elaine A. Ostrander, Jian-Bing Fan, Ziding Feng, Janet L. Stanford
Journal: Clinical Cancer Research (2016)

Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential.
Addition of verapamil to overcome drug resistance in multiple myeloma: preliminary clinical observations in 10 patients.
Authors: L H Trümper, A D Ho, G Wulf, W Hunstein
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.10.1578 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2778486 Addition of verapamil to overcome drug resistance in multiple myeloma: preliminary clinical observations in 10 patients. L H TrümperxL H TrümperSearch for articles by this author , A D HoxA D HoSearch for articles by this author , G WulfxG WulfSearch for articles by this author , W HunsteinxW HunsteinSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.10.1578 PDF "Addition of verapamil to overcome drug resistance in multiple myeloma: preliminary clinical observations in 10 patients.." Journal of Clinical Oncology, 7(10), pp. 1578–1579© 1989 by American Society of Clinical Oncology
Differential effect of clozapine on weight: a controlled study
Authors: J R Bustillo, R W Buchanan, D Irish, A Breier
Journal: American Journal of Psychiatry (1996)

This study examined whether clozapine induces more weight gain than haloperidol and whether weight gain is related to clinical improvement.The weight and symptoms of 39 outpatients with schizophrenia who were randomly assigned to double-blind treatment with either clozapine or haloperidol were assessed. The weight and symptoms of 33 of the patients who chose to take clozapine during a 1-year follow-up after the study ended were also assessed.The patients treated with clozapine gained significantly more weight over baseline (7%) than the haloperidol-treated patients (1%). Weight gain was not significantly correlated with improvements in either positive or negative symptoms. Fifty-eight percent of the patients followed for 1 year gained at least 10% over their baseline weight.Weight gain is an important side effect of clozapine and is unrelated to the drug's differential antipsychotic efficacy.
Survival outcomes of patients with metastatic germ cell tumor (mGCT) treated from 1998 to 2012: The Indiana University (IU) experience.
Authors: Nabil Adra, Kimberly Peihsi Ku, Maitri Kalra, Sandra Althouse, Nasser H. Hanna, Lawrence H. Einhorn, Costantine Albany
Journal: Journal of Clinical Oncology (2016)

491 Background: Patients with mGCT’s treated between 1975-1990 were classified by the International Germ Cell Cancer Collaborative Group (IGCCCG) into good, intermediate, and poor risk. This study attempts to identify prognostic factors in a contemporary cohort of patients with mGCT treated at IU. Methods: Retrospective analysis of all patients with GCT seen at IU from 1998-2012. 1,341 consecutive patients with mGCT were identified of whom 615 patients received initial chemotherapy at IU and were eligible for analysis. All patients in this cohort were treated with cisplatin-based combination chemotherapy. Kaplan-Meier methods were used for analysis of 5 year progression free survival (PFS) and overall survival (OS). Results: Median age was 29. Median follow up time 5 years. Good, intermediate, and poor risk disease had median AFP of 8, 1822, 291 and median hCG of 8, 5000, 12837 respectively. 89 (14%) patients had seminoma and 526 (86%) had non-seminomatous GCT (NSGCT). Primary site was testis/retroperitoneal in 565 (92%) and mediastinum in 48 (8%). The 5 year PFS and OS for patients with poor risk excluding primary mediastinal NSGCT (PMNSGCT) was 52% and 78% respectively. In contrast, 5 year PFS and OS for patients with PMNSGCT was 49% and 58% respectively. The results comparing outcomes of patients in IGCCCG versus patients at IU are depicted in the table below. Conclusions: In this contemporary retrospective dataset from Indiana University there was improvement in OS for men with poor risk mGCT, possibly due to improved salvage chemotherapy. Only patients with PMNSGCT continue to have poor outcomes and pose a therapeutic challenge due to lack of effective salvage therapy. [Table: see text]
P62 Bacterial translocation in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: implication in haemodynamic alterations and mortality
Authors: M Montes de Oca, M Coello Mercedes, S C M Jose, R Claudio, T Alberto, V Antonio, F G Clotilde, C Sara, G G J Antonio
Journal: Gut (2010)

Introduction  Hepatitis C virus (HCV)-related liver disease follows an accelerated course in patients with human immunodeficiency virus (HIV) co-infection. Liver fibrosis progression to cirrhosis is faster in HIV/HCV coinfected individuals than in HCV-monoinfected subjects. Immunosuppression (lower CD4 cell count), markers of severe liver disease (Child Pugh score) and the absence of HAART are independent predictors of liver-related mortality in patients with end-stage liver disease coinfected with HIV and HCV. However, the intrinsic mechanisms through which HIV infection have an influence in the worse prognosis of these patients remain unknown. Among the possible mechanisms involved in the evolution of both HIV and HCV infection in coinfected patients, we suggest that microbial translocation may contribute to the accelerated course of liver damage in HCV-HIV patients through the activation of immune system.  Aim  Analysis of the influence of portal hypertension on intestinal permeability in HIV-infected patients with hepatitis C virus (HCV)-related cirrhosis, as well of the prognostic significance of consequent macrophage activation.  Method  20 HIV-monoinfected patients, seventy patients with HIV-HVC co-infection, twenty of them with compensated and fifty with decompensated cirrhosis, and twenty healthy controls were evaluated for intestinal permeability and bacterial translocation (lipopolysaccharide-binding protein (LBP)), macrophage activation (soluble CD14 (sCD14), soluble tumour necrosis factor receptor 55 Kd (sTNFRI), and interleukin 6 (IL-6)), and activation of the renin-angiotensin-aldosterone axis. Patients with decompensated cirrhosis were followed during a median period of 429 days.  Results  LBP concentration was significantly increased in HIV monoinfected patients when compared with healthy controls. Patients with decompensated cirrhosis, but not those with compensated liver disease, show increased LBP levels when compared with HIV monoinfected patients. Patients with increased LBP concentration showed elevated sCD14, sTNFRI and IL-6 levels. 22 patients died, by a liver-related cause, during the follow-up and two more suffered liver transplantation. The mortality at 1 and 2 years was 36 and 56 %. Child-Pugh index, CD4 T cell count, plasma aldosterone and serum IL-6 concentrations independently predicted liver-related mortality.  Conclusion  The increased intestinal permeability, observed in patients with monoinfection by HIV, is significantly higher in those with concomitant portal hypertension. Parameters indicative of macrophage activation, such as IL-6, in addition of immuno-depression, liver function markers and haemodynamic derangement (plasma aldosterone concentration) influence the survival of HIV-HCV co-infected patients with decompensated cirrhosis.
Immunotherapy of Cancer Visualized by Live Microscopy: Seeing Is Believing
Authors: Alvaro Teijeira, Iñaki Etxeberria, Mariano Ponz-Sarvise, Ignacio Melero
Journal: Clinical Cancer Research (2016)

The success of immunotherapy of cancer depends on several cellular events in the tumors that can be visualized by live microscopy strategies in experimental models. Taking advantage of advanced microscopy techniques, Lehmann and colleagues explore in this issue of CCR the mechanism of action of a novel bispecific mAb (TCB-CEA) that targets membrane-bound CEA and CD3ε. Clin Cancer Res; 22(17); 4277-9. ©2016 AACRSee related article by Lehmann et al., p. 4417.
Randomized Controlled Trial of Two Different Dosing Regimens of Palifermin to Prevent Mucositis In Multiple Myeloma Patients Receiving One-Day Administration of High-Dose Melphalan
Authors: Nicole M.A. Blijlevens, Maarten E de Chateau, Gergely Krivan, Werner Rabitsch, Arpad Szomor, Robert Pytlik, Agneta Lissmats, Hans Erik Johnsen, Tapani Ruutu, Hermann Einsele, Dietger W Niederwieser
Journal: Blood (2010)
Consensus conference: Osteoporosis
Authors: O L Bijvoet
Journal: JAMA (1984)

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Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome
Authors: Leslie B. Gordon, Monica E. Kleinman, Joe Massaro, Ralph B. D’Agostino, Heather Shappell, Marie Gerhard-Herman, Leslie B. Smoot, Catherine M. Gordon, Robert H. Cleveland, Ara Nazarian, Brian D. Snyder, Nicole J. Ullrich, V. Michelle Silvera, Marilyn G. Liang, Nicolle Quinn, David T. Miller, Susanna Y. Huh, Anne A. Dowton, Kelly Littlefield, Maya M. Greer, Mark W. Kieran
Journal: Circulation (2016)

Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation.Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial.No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial.Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid.URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.
Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis
Authors: Moisés Selman, Carlos López-Otín, Annie Pardo
Journal: European Respiratory Journal (2016)

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal disease of unknown aetiology. A growing body of evidence supports that IPF represents an epithelial-driven process characterised by aberrant epithelial cell behaviour, fibroblast/myofibroblast activation and excessive accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The mechanisms involved in the abnormal hyper-activation of the epithelium are unclear, but we propose that recapitulation of pathways and processes critical to embryological development associated with a tissue specific age-related stochastic epigenetic drift may be implicated. These pathways may also contribute to the distinctive behaviour of IPF fibroblasts. Genomic and epigenomic studies have revealed that wingless/Int, sonic hedgehog and other developmental signalling pathways are reactivated and deregulated in IPF. Moreover, some of these pathways cross-talk with transforming growth factor-β activating a profibrotic feedback loop. The expression pattern of microRNAs is also dysregulated in IPF and exhibits a similar expression profile to embryonic lungs. In addition, senescence, a process usually associated with ageing, which occurs early in alveolar epithelial cells of IPF lungs, likely represents a conserved programmed developmental mechanism. Here, we review the major developmental pathways that get twisted in IPF, and discuss the connection with ageing and potential therapeutic approaches.
Decision making for older adults with advanced cancer: Patient and family member perspectives.
Authors: Susan Elizabeth Hickman, Michael T. Weaver, Barbara Habermann, Paul R. Helft
Journal: Journal of Clinical Oncology (2014)

101 Background: The National Cancer Institute and palliative care guidelines emphasize the importance of family member perspectives in end-of-life decision-making for patients with advanced cancer. However, only a handful of studies have examined what role family members play in decisions to continue or discontinue disease-directed therapy. Methods: Thirty-four dyads consisting of a patient (PT) aged 65 and older with metastatic lung, pancreatic, or esophageal cancer and a family member (FM) filled out surveys about goals of care, discussions with the treating oncologist, communication conflict, and decisional uncertainty. Results: Most PTs (60%) understood their cancer was metastatic, and 86% reported they were currently receiving chemotherapy. PTs and FMs (82%) had a shared understanding about current goal of treatment and were more likely to report discussions with the treating oncologist about reasons to continue chemotherapy (90%) than discussions about reasons to discontinue it (53%) (McNemar’s S = 7.0, DF = 1, exact p =.016). However, only a minority of PTs and FMs (26.5%) agree on the preferred course of treatment. FMs (59%) were more likely than PTs (24%) to prefer a course of treatment focused on palliation rather than extending life (Bowker’s S=9.3, DF=3, p=.026). Many patients (44%) were unsure of their preferences. Patients who perceived higher levels of communication conflict with their family reported more decisional uncertainty about their preferred treatment option (r =.49, p =.02). Conclusions: Patients and family members largely share in their understanding of the current treatment goal and recall of discussions with the oncologist about treatment options. However, family members tend to prefer a course of treatment focused on comfort compared to patients, who prefer a course of treatment that extends life as much as possible even if it means having more side effects, pain, or discomfort. Patients who report conflicted communication with family members are more uncertain about their decisions. Findings suggest a need for increased discussion about goals of care and treatment alternatives with advanced cancer patients and their family members.
L718Q Mutation as New Mechanism of Acquired Resistance to AZD9291 in EGFR -Mutated NSCLC
Authors: Melissa Bersanelli, Roberta Minari, Paola Bordi, Letizia Gnetti, Cecilia Bozzetti, Anna Squadrilli, Costanza Anna Maria Lagrasta, Lorena Bottarelli, Ganna Osipova, Enrica Capelletto, Marco Mor, Marcello Tiseo
Journal: Journal of Thoracic Oncology (2016)

AZD9291 (osimertinib) is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) with impressive tumor responses in EGFRT790M-mutated NSCLC.1 The selectivity of AZD9291 for EGFR T790M depends on its covalent interaction with cysteine 797 in the adenosine triphosphate-binding cleft. Mutation at the EGFR C797 codon, such as the missense variant C797S, has been demonstrated as the principal mechanism of acquired resistance to third-generation EGFR TKIs.2 Little is known about alternative mechanisms.
FISHing in the dark: How the combination of FISH and conventional karyotyping improves the diagnostic yield in CpG‐stimulated chronic lymphocytic leukemia
Authors: Adrian M. Dubuc, Matthew S. Davids, Mirela Pulluqi, Olja Pulluqi, Kevin Hoang, Jesus M. Hernandez‐Sánchez, Cathy Schlich, Jesus M. Hernández‐Rivas, Jennifer R. Brown, Paola Dal Cin
Journal: American Journal of Hematology (2016)

Despite significant advances in molecular genetic approaches, fluorescence in situ hybridization (FISH) remains the gold standard for the diagnostic evaluation of genomic aberrations in patients with chronic lymphocytic leukemia (CLL). Efforts to improve the diagnostic utility of molecular cytogenetic testing have led to the expansion of the traditional 4-probe CLL FISH panel. Not only do these efforts increase the cost of testing, they remain hindered by the inherent limitations of FISH studies - namely the inability to evaluate genomic changes outside of the targeted loci. While array-based profiling and next generation sequencing (NGS) have critically expanded our understanding of the molecular pathogenesis of CLL, these methodologies are not routinely used by diagnostic laboratories to evaluate copy number changes or the mutational profile of this disease. Mitogenic stimulation of CLL specimens with CpG-oligonucleotide (CpG-ODN) has been identified as a reliable and reproducible means of obtaining a karyotype, facilitating a low-resolution genome-wide analysis. Across a cohort of 1255 CpG-ODN-stimulated CLL specimens, we describe the clinical utility associated with the combinatorial use of FISH and karyotyping. Our testing algorithm achieves a higher diagnostic yield (∼10%) through the detection of complex karyotypes, well-characterized chromosomal aberrations not covered by the traditional CLL FISH panel and through the detection of concurrent secondary malignancies. Moreover, the single cell nature of this approach permits the evaluation of emerging new clinical concepts including clonal dynamics and clonal evolution. This approach can be broadly applied by diagnostic laboratories to improve the utility of traditional and molecular cytogenetic studies of CLL. Am. J. Hematol. 91:978-983, 2016. © 2016 Wiley Periodicals, Inc.