tbuckley/cabot-search huggingface dataset:
Growth factor receptors and cell cycle proteins as new molecular prognosis markers in high-grade undifferentiated pleomorphic sarcoma (HGUPS).
Authors: C. Serrano, S. Simonetti, C. M. Valverde, R. Morales, C. Suarez, T. Moline, J. Carles, S. Ramon y Cajal, C. Romagosa
Journal: Journal of Clinical Oncology (2011)

10077 Background: HGUPS represent a recently renamed subgroup that accounts for approximately 5% of adult soft tissue sarcomas. Apart from its known cytogenetic complexity, there is still a lack of in the understanding of its molecular biology. PI3K-AKT and MAPK growth-factor signalling are considered two major mechanisms of proliferation in sarcomas. Disturbances in cell cycle genes may also play a crucial role. New biomarkers in such group of tumors are an unmet medical need. Methods: We retrospectively analyzed clinical data from 37 pts with surgically resected stage II and III HGUPS. Immunohistochemical staining in formalin-fixed and paraffin-embedded tissue was done in all cases for 4EBP1, p4EBP1, pS6K, pEIF4G, EIF4E, pEIF4E, pERK, p16 and ki-67. The levels of expression were evaluated as percentage and intensity of stained cells (Hscore). p16 and ki-67 were evaluated as a percentage. Results: Pts characteristics were: median age 72 (32-96); gender: 20M/15F/2Unk; median tumor size 9 cm (2-30); Grade 2, 6 pts (16%), Grade 3, 27 pts (73%), Unknown 4 pts (10%); stage IIA 11 pts (30%), stage IIB 3 pts (8%), stage III 22 pts (59%); 21 pts received adjuvant radiotherapy (57%) and 13 adjuvant chemotherapy (35%). Low pERK (Hscore<50) and high p16 (>40%) and ki-67 (>40%) expression were significantly associated with shortened time to relapse (TTR) (p=0.014, p=0.035 and p=0.002) and overall survival (OS) (p=0.022, p=0.013 and p=0.000) in the univariate analysis. High levels of p4EBP1 (Hscore>30) showed a nonsignificative trend towards short TTR (p=0.129). Low pERK expression was also associated with early relapse at 1 and 3 years (p=0.047 and p=0.037) and a trend towards greater likelihood of metastases (p=0.089). In the multivariate analysis, p4EBP1 (p=0.001) and pERK (p=0.001) were independent prognosis factors of TTR (p=0.001 and p=0.001) and OS (p=0.014 and p=0.005). High Ki67 levels were associated only with less OS (p=0.001). Conclusions: pERK, p4EBP1 and Ki67 are prognosis factors of HGUPS. We have found a strong correlation with TTR and OS. Signalling through MAPK and p4EBP1 pathway might therefore be a critical targetable option in HGUPS pts.
The interval of endoscopic variceal ligation: The shorter the better?
Authors: Gin‐Ho Lo
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. TO THE EDITOR: I read with interest the article by Sheibani et al. regarding the treatment interval of endoscopic variceal ligation to prevent variceal rebleeding.1 The researchers demonstrated that 1‐week ligation intervals led to more‐rapid variceal eradication than 2‐week intervals without an increase in complications and without a reduction of rebleeding. The researchers thus suggested that ligation intervals may be individualized based on patient and physician preferences. Though interesting, several points need further clarification. In the current trial, 1‐week ligation intervals showed clearly that variceal eradication could be achieved more rapidly than 2‐week ligation intervals. Apart from this superiority, 1‐week ligation intervals could encounter more ligation‐induced ulcer bleeding (9% vs. 4%), more dysphagia or chest pain (9% vs. 2%), and more patients with postponed ligation session as compared with 2‐week ligation intervals, though these differences were not statistically significant. Moreover, variceal rebleeding rates within 12 weeks were 13% in the 1‐week group and 9% in the 2‐week group. The incidence of ligation‐induced esophageal ulcers was not shown in the current study. Our previous trial showed that postligation ulcers occurred in 57% of the 2‐week group as compared with 11% in the 4‐week group.2 Akin to the current study, the variceal obliteration was also more rapidly achieved in the 2‐week ligation interval group than the 4‐week ligation interval group and similar rebleeding rate in both treatment groups. Based on these two studies, it appears that short ligation intervals such as 1‐2 weeks may be associated with rapid variceal obliteration as well as mild increase of complications, but without benefit in the reduction of rebleeding. Currently, the combination of banding ligation and beta‐blockers has been recommended as the first choice to prevent variceal bleeding.3 Given that the utmost goals of prevention variceal rebleeding are to reduce rebleeding episodes and enhance survival, the policy of adopting ligation interval as short as 1 week to achieve rapid variceal obliteration becomes unbeneficial as well as unjustified.
Is the Memorial Sloan-Kettering Cancer Center breast cancer nomogram feasible on Turkish breast cancer patients? Analysis of 740 patients.
Authors: L. Yeniay, E. B. Carti, C. A. Karaca, U. Yararbas, O. Zekioglu, M. Kapkac
Journal: Journal of Clinical Oncology (2011)

e11551 Background: By applying the nomogram developed by Van Zee, we aimed to assess the feasibility of the the nomogram as well as to study the predictive factors affecting SLN and non-SLN involvement in our patients group. Methods: Documents of 740 clinically node negative, early invasive breast cancer patients whom had well-done SLN biopsy between 2003 and 2010 were examined retrospectively. SLN involvement prediction score for each patient was calculated by using the nomogram. Furthermore, by using nonsentinel lypmh node prediction nomogram, prediction scores for non-SLN involvement were calculated for each patients who underwent axillary dissection owing to positive SLN. SPSS version 13 was used for statistical analyses. Results: Mean age was 51.7 (19-85). Mean follow-up duration was 29.5 months. Mean SLN number was 2.7 (1-9). On univariate analysis, age, tumor size, histological type, progesteron receptor status, presence of p53 mutation, nuclear grade, multifocality, presence of lymphovascular invasion and number of resected positive and negative SLN were found to be associated with SLN involvement. Among the studied prognostic factors; only, the number of resected positive and negative SLNs and presence of lymphovascular invasion were found to be correlated with non-SLN metastase (Table). When the scores of MSKCC nomogram calculated for each patient, the ROC curve score for SLN and non-SLN involvement was 0.749 (p<0.0001) and 0.660 (p<0.0001) respectively. Conclusions: This is the first validating report using the nomogram from Turkey. Our study showed that using the nomogram for predicting SLN involvement and also for non-SLN involvement, which were both developped by the MSKCC group, was feasible for our patients. Predictive factors for SLN and non-SLN involvement (p<0.05 was significant). SLN involvement (p) Non-SLN involvement (p) Age 0.002 0.277 Tumor size <0.0001 0.754 Histologic type 0.046 0.965 Progesteron receptor status 0.02 0.227 p53 mutation 0.042 0.278 Nuclear grade 0.024 0.097 Multifocality 0.04 0.4 Lymphovascular invasion <0.0001 <0.0001 Number of resected positive and negative SLN 0.021 0.021
Outcome of Lower Risk Non Del 5q MDS after Failure of Erythropoiesis Stimulating Agents (ESA), and Impact of Post-ESA Treatment on Survival: A Retrospective European Study
Authors: Sophie Park, Jean-François Hamel, Andrea Toma, Charikleia Kelaidi, Maria Campelo Diez, Valeria Santini, Enrico Balleari, Jennifer Schemenau, Rosa Sapena, Katharina Goetze, Catharina Mueller-Thomas, Odile Beyne-Rauzy, Aspasia Stamatoullas, Ioannis Kotsianidis, Agnes Guerci, Dominique Bordessoule, Pascale Cony-Makhoul, Stéphane Cheze, Eric Wattel, Christian Rose, Norbert Vey, Ulrich Germing, Guillermo Sanz, François Dreyfus, Pierre Fenaux
Journal: Blood (2015)
Allogeneic Transplantation from an HLA-Matched Family Donor in First Complete Remission of Acute Myeloid Leukemia Had an Adverse Impact on Quality of Life in Patients Followed for at Least Five Years after Treatment: A Survey of the German AML Intergroup on 525 Patients.
Authors: Dorle Messerer, Jutta Engel, Jörg Hasford, Markus Schaich, Silke Soucek, Gerhard Ehninger, Christina Sauerland, Thomas Büchner, Dietger W. Niederwieser, Rainer Krahl, Jürgen Krauter, Irina Schäfer, Arnold Ganser, Claire Schleich, Hartmut Döhner, Richard F. Schlenk
Journal: Blood (2005)
Breast cancer (BC) care and outcomes in Latin America and the Caribbean (LAC).
Authors: N. Justo, N. E. Wilking, B. Jönsson
Journal: Journal of Clinical Oncology (2011)

202 Background: The global BC Care and Outcomes Report revealed ample differences in BC care and outcomes exist across continents, exposing the need for regionally focused studies. Aim: Provide an overview of the burden of BC and of BC care and outcomes in LAC and identify the major challenges Methods: Review of literature (PubMed, LILACS, SCIELO), public databases (Globocan 2002 and 2008, CEPALSTAT, DIRAC, PAHO, WHOSYS, etc) and conference presentations (ASCO, ISPOR). Local experts and patient organizations were surveyed. Current BC epidemiology in LAC, countries’ risk profiles and future trends, disease burden and available resources, patterns of care and treatment access (case studies), and outcomes (such as mortality-to-incidence ratios - MIRs) were analyzed and compared (Sweden as benchmark). Results: BC exhibits the highest annual incidence (114,900 cases) and mortality (37,000 deaths) of all cancers in LAC and is expected to double by 2030. Age is the main risk factor. Heavy burden is due to younger age at diagnosis. Poor outcomes are partly due to late diagnosis. Availability of specialized surgeons, waiting times, node clearance policy and access to breast reconstruction vary widely across countries and between public and private settings. Radiotherapy equipment is insufficient, except in Uruguay, Chile, and Venezuela. All modern systemic therapies are available, but some not widely diffused due to their costs. Palliative care is developing but, despite great efforts, problems persist. BC MIRs have improved, albeit unevenly, over time. Conclusions: Inequalities in access to diagnosis and treatment, fragmented organization and management of BC care and poor uptake of evidence-based best practices result in high morbidity and associated societal costs. [Table: see text]
Eculizumab Therapy of Adult TA-TMA: A High Response Rate Is Associated with a High Infection-Related Mortality
Authors: Stephan R Bohl, Stephanie Harsdorf, Stefan Schoensteiner, Phyllis Schwarzwaelder, Katrina Scholl, Verena Wais, Lars Bullinger, Hartmut Döhner, Florian Kuchenbauer, Donald Bunjes
Journal: Blood (2016)
The natural history and effect of adjuvant therapy on resected AJCC stage I-II lymph node-negative pancreatic cancer.
Authors: Shaun McKenzie, Bin Huang, Thomas Tucker, Patrick McGrath, Dennie V. Jones, Philip Desimone, Mark Evers
Journal: Journal of Clinical Oncology (2012)

264 Background: Previous investigation has suggested that early stage, lymph node negative pancreatic adenocarcinoma (PAC) has a relatively good prognosis and adjuvant therapy provides little benefit over surgery alone. The purpose of our trial was to evaluate patients with stage I-II PAC receiving surgical resection to determine their clinical characteristics, overall outcome, and the impact of adjuvant therapy on survival. Methods: Utilizing the population-based registry data from the Kentucky Cancer Registry (KCR) we identified patients with lymph node negative, AJCC I-II, PAC who underwent pancreatic resection during the years of 1995-2008. Patients were further stratified by receipt of surgery alone versus surgery with adjuvant chemotherapy or chemoradiation. Clinical and pathologic data included patient demographics, tumor characteristics, and lymph node status. Kaplan-Meier and Cox-regression survival analyses were performed. Results: During the study period, 203 patients meeting criteria were identified from the KCR. Median survival (MS) for the entire cohort was 21.7 months. The majority of patients were &gt;70 years old, Caucasian, had well or moderately differentiated tumors and tumors &lt;5cm. 46% (n=94) and 54% (n=109) of patients had stage I and II disease respectively. When stratified by surgery only (n=119, 59%) versus adjuvant therapy (n=84, 41%), only younger age predicted receipt of adjuvant therapy (p=0.002). Adjuvant therapy provided no benefit over surgery alone regardless of stage (stage I MS: 21.5 vs. 24.7 months, p=0.97 and stage II MS: 24.2 vs. 18.0, p=0.13, respectively). By multivariate analysis, only tumor size &gt;5cm predicted worse survival (HR 2.32, CI 1.21-4.45, p=0.012). Age, stage, adjuvant therapy, differentiation, and lymph node retrieval had no impact on survival. Conclusions: Our data indicate that the survival for surgically resected early stage, lymph node negative pancreatic adenocarcinoma remains poor and is not improved by the addition of adjuvant chemotherapy. These findings should be considered when designing future adjuvant therapy trials for this deadly disease.
Significance of Missing Inhibitory KIR Ligands in Nonmyeloablative, HLA-Haploidentical (Haplo) BMT with Posttransplantation High-Dose Cyclophosphamide (PT/Cy)
Authors: Yvette L. Kasamon, Leo Luznik, M. Sue Leffell, Hua-ling Tsai, Heather J. Symons, Javier Bolaños-Meade, Gary Rosner, Lawrence E. Morris, Pamela A. Crilley, Richard J. Jones, Ephraim J. Fuchs
Journal: Blood (2011)
Predictive value of KIT immunohistochemical staining for KIT mutations in patients with gastrointestinal stromal tumors (GIST): A systematic review.
Authors: Nay Min Tun, Gina M. Villani
Journal: Journal of Clinical Oncology (2012)

30 Background: Immunohistochemical staining for KIT (CD117) is used as part of diagnostic tool for GIST. Approximately 95% of GIST are known to be positive for CD117. Studies have shown that not all CD117-positive GIST carry KIT mutations nor does CD117 negativity rule out KIT or PDGFRA mutations. We performed a systematic review to investigate the positive and negative predictive values of KIT immunostaining for KIT mutations in GIST. Methods: A Medline search of the MeSH terms “KIT mutation” and “GIST” and “prevalence” yielded 54 articles from year 1999 to 2011. English language studies on GIST with data available for KIT immunostaining as well as KIT gene mutations were included. Studies lacking data on either CD117 positivity or KIT mutations were excluded. Immunostaining was done using Dako polyclonal rabbit antibody or PKCh monoclonal mouse antibody in eligible studies. Denaturing high-pressure liquid chromatography (DHPLC) was used to screen mutations in majority of eligible studies, and ABI Prism Genetic Analyzer to sequence DNA. Results: 6 studies including 708 CD117-positive GIST patients were eligible for analysis of positive predictive value of KIT immunostaining for KIT mutations and 5 studies including 47 CD117-negative GIST patients for negative predictive value. Many studies were excluded due to insufficient data on CD117 positivity or KIT mutational analysis. 72.8% of CD117-positive GIST tumors carried KIT mutations (exon 11 62.2%, exon 9 10.2%, exon 13 1.8% and exon 17 1%), and 4.1% harbored PDGFRA mutations. In contrast, 74.5% of CD117-negative GIST tumors did not have KIT mutations. 25.5% of CD117-negative GIST harbored KIT exon 11 mutations (no mutations in exon 9, 13 or 17 were observed). In addition, 30% of CD117-negative GIST were found to have PDGFRA mutations. Conclusions: PDGFRA mutations were found to be 7 times more common in CD117-negative than in CD117-positive GIST (30% vs. 4.1%). Over half (55.5%) of CD117-negative GIST carried KIT exon 11 or PDGFRA mutations. We recommend mutational analysis in all tumors clinically suspected of GIST and that are CD117-negative for two reasons: 1. in order to make a diagnosis, and 2. to help tailor therapy.
Mutation Analysis in 200 Cases of Newly Diagnosed Myelodysplastic Syndrome By Next Generation Sequencing: Association with Established Prognostic Variables and IPSS-R
Authors: Kankana Ghosh, Parsa Hodjat, Priyanka Priyanka, Beenu Thakral, Keyur P. Patel, Mark Routbort, Rashmi Kanagal-Shamana, C. Cameron Yin, Zhuang Zuo, Raja Luthra, Tariq Muzzafar
Journal: Blood (2015)
Shift to Anti-Fibrinolysis on the Administration of L-Asparaginase (L-Asp) during Induction Therapy for Pediatric Acute Lymphoblastic Leukemia (ALL)
Authors: Takashi Ishihara, Keiji Nogami, Tomoko Matsumoto, Yasufumi Takeshita, Akitaka Nomura, Satoshi Ochi, Toshiaki Ishida, Yoshiyuki Kosaka, Akihisa Sawada, Masami Inoue, Midori Shima
Journal: Blood (2016)
A Phase II Study of CC-5013 Treatment for Myelofibrosis with Myeloid Metaplasia: A Preliminary Report.
Authors: Ayalew Tefferi, William J. Hogan, Alexandra P. Wolanskyj, Trudy A. Shaw, Gayle E. Reyes, Antje Hoering, Rebecca F. McClure, Ruben A. Mesa
Journal: Blood (2004)
A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma
Authors: Sergio Fernández-Pello, Fabian Hofmann, Rana Tahbaz, Lorenzo Marconi, Thomas B. Lam, Laurence Albiges, Karim Bensalah, Steven E. Canfield, Saeed Dabestani, Rachel H. Giles, Milan Hora, Markus A. Kuczyk, Axel S. Merseburger, Thomas Powles, Michael Staehler, Alessandro Volpe, Börje Ljungberg, Axel Bex
Journal: European Urology (2016)
Evaluation of a prostate brachytherapy technique designed to reduce short- and long-term urinary dysfunction: 5-year results of a multi-institutional comparative cohort study.
Authors: J. A. Talcott, A. L. Zietman, I. D. Kaplan, J. A. Clark, A. V. D'Amico
Journal: Journal of Clinical Oncology (2011)

70 Background: To evaluate a novel prostate brachytherapy technique designed to reduce short- and long-term urinary dysfunction by sharply reducing periurethral prostate radiation (XBT), we compared urinary outcomes of XBT patients to those of 2 groups treated with standard technique (SBT) in a prospective 5-year cohort study. Methods: We surveyed newly diagnosed, untreated patients patients with clinically localized prostate cancer before brachytherapy to gather demographic, clinical and quality of life information, with follow-up at 1, 3, 12, 24, 36, 48 and 60 months after treatment. XBT patients were treated at Brigham and Women's Hospital. SBT was given at Beth Israel-Deaconess or Metrowest Hospital, which used the same technique, or at Massachusetts General Hospital. Results: Of 263 enrolled patients who completed at least 3-month follow-up, including 73 XBT patients and 190 SBT patients, 99 at 1 site (SBT 1 ) and 91 at the other (SBT 2 ), 167 (63%) had completed 5-year follow-up as of September 2010. XBT patients were younger and reported more baseline urinary obstruction/irritation, but the treatment groups were otherwise similar before treatment. Urinary obstruction/irritation was increased for 24 months. XBT patients reported lower increases which resolved earlier. SBT 2 patients initially reported greater urinary dysfunction than SBT 1 patients, but the problem resolved after changing technique to better localize the urethra. Urinary incontinence appeared to rise at 60 months after SBT but not XBT. Of patients who reported complete pretreatment urinary control, 33% of SBT vs. 15% of XBT patients reported some incontinence (p=0.08). Conclusions: Sharply reduced periurethral radiation suppresses post-treatment increases in urinary obstruction/irritation and may reduce long-term urinary incontinence. No significant financial relationships to disclose.
Effects of equivalent weight loss, with or without exercise, on sex hormones related to breast cancer risk in postmenopausal women: The SHAPE-2 trial.
Authors: Anne Maria May, Willemijn van Gemert, Petra Peeters, Job van der Palen, Jantine Schuit, Evelyn Monninkhof
Journal: Journal of Clinical Oncology (2014)

1504 Background: Physical activity is a known protective factor for postmenopausal breast cancer. Exercise intervention studies suggest that physical activity influences breast cancer related sex hormone levels mainly through concordant weight loss. The aim of this study is to investigate whether there is an additional beneficial effect of exercise beyond the effect of weight loss. Methods: After a 5-week run-in period, 243 inactive, overweight and postmenopausal women were randomly allocated to either a diet group (n=97), exercise group (n=98) or stable weight control group (n=48). The aim of both intervention groups was to lose 5-6 kilograms weight. The diet group followed an energy restricted diet. The exercise group participated in a 16-week endurance and strength training program (4 hrs/wk) and were prescribed a small caloric intake restriction. Primary outcomes were assessed at baseline and after 16 weeks, and included serum levels of estron, (free) estradiol, androstenedione, (free) testosterone and sex hormone binding globulin (SHBG). Results: Both the diet and exercise group achieved the aimed weight loss (-4.9 kg and -5.5 kg, respectively), while the control group remained stable (+0.06 kg). Compared with control, all estrogens decreased significantly in the exercise group, while in the diet group only free estradiol was significantly decreased (p<0.05). Also, compared with diet, the exercise group showed more favorable effects on all estrogens (p≤0.05). For androgens, only the exercise group showed beneficial effects on free testosterone compared with control (p=0.01) and diet (p=0.07). Positive effects on SHBG were significant in both intervention groups (p<0.0001) and larger in the exercise group compared with diet (p=0.07). Conclusions: Exercise induced weight loss resulted in stronger favorable effects on breast cancer related hormones and SHBG, than diet induced weight loss, demonstrating the importance of exercise for postmenopausal breast cancer risk reduction. Clinical trial information: NCT01511276.
Targeting Immune Suppressive Microenvironment By Immune Checkpoint Blockade in Multiple Myeloma
Authors: Gullu Topal Gorgun, Kristen Cowens, Steven Paula, Mehmet Kemal Samur, Hiroto Ohguchi, Ahaana Singh, Randie E White, Giada Bianchi, Rikio Suzuki, Shohei Kikuchi, Takeshi Harada, Naoya Mimura, Yu-Tzu Tai, Teru Hideshima, Jacob P. Laubach, Noopur Raje, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson
Journal: Blood (2014)
Central Nervous System (CNS) Involvement with Multiple Myeloma (MM) – Longterm Survival Can Be Achieved with Radiation, Intrathecal (IT) Chemotherapy, and Immunomodulatory Agents (IMiDs),
Authors: Christine Chen, Ahmed M. Rabea, Esther Masih-Khan, Chia-Min Chu, Vishal Kukreti, Suzanne Trudel, Rodger E. Tiedemann, Donna E. Reece
Journal: Blood (2011)
Elevated Basal Autophagy in SF3B1 Mutated Myelodysplastic Syndromes: Relationship with Survival Outcomes and Therapeutic Implications
Authors: Valeria Visconte, Kevin R. Kelly, Steffan T. Nawrocki, Yingchun Han, Hetty E. Carraway, Anjali S. Advani, Jaroslaw P. Maciejewski, Heesun J Rogers, Mikkael A. Sekeres, Jennifer S. Carew
Journal: Blood (2015)
Reply to "Neutrophils are not required for resolution of acute gouty arthritis in mice"
Authors: Christiane Reinwald, Christine Schauer, Janka Zsófia Csepregi, Deborah Kienhöfer, Daniela Weidner, Marie Malissen, Attila Mocsai, Georg Schett, Martin Herrmann, Markus Hoffmann
Journal: Nature Medicine (2016)
Johnson &amp; Johnson is ordered to pay $1bn over faulty hip implants
Authors: Owen Dyer
Journal: BMJ (2016)

A federal jury in Dallas has ordered Johnson & Johnson to pay $1.041bn (£0.82bn; €0.98bn) in compensation and punitive damages after it found in favour of six plaintiffs who claimed that the company’s DePuy medical devices subsidiary deliberately hid flaws in its Pinnacle metal-on-metal artificial hips from doctors and patients.

All six plaintiffs needed revision surgery to replace the devices and to repair injuries that included tissue death and bone erosion. The Dallas hearing was a test case, the third of seven “bellwether” cases intended to establish liability and to guide compensation in 8900 claims pending from other Pinnacle …