tbuckley/cabot-search huggingface dataset:
Splenic diffuse red pulp small B-cell lymphoma displays increased expression of cyclin D3 and recurrent CCND3 mutations
Authors: Soraya Curiel-Olmo, Rufino Mondéjar, Carmen Almaraz, Manuela Mollejo, Laura Cereceda, Roso Marès, Sophia Derdak, Yolanda Campos-Martín, Ana Batlle, Sonia González de Villambrosía, Marta Gut, Julie Blanc, Alexandra Traverse-Glehen, Aurelie Verney, Lucile Baseggio, Francisca I. Camacho, Andrew Wotherspoon, Kostas Stamatopoulos, Aliki Xochelli, Theodora Papadaki, George Kanellis, Maurilio Ponzoni, Monica García-Cosío, Jose P. Vaqué, Sergi Beltrán, Ivo Gut, Miguel Angel Piris, Nerea Martínez
Journal: Blood (2017)
Phosphatidylserine and Oxidized Phosphatidylethanolamine Interact with Protein C Inhibitor (PCI) and Modify Its Activity.
Authors: Julia M. Malleier, Olga Oskolkova, Valery Bochkov, Ingrid Jerabek, Barbora Sokolikova, Thomas Perkmann, Bernd R. Binder, Margarethe Geiger
Journal: Blood (2005)
PUB100 Clinical Outcomes of Non-Small Cell Lung Cancer (NSCLC) Patients with ALK Co-Mutations (EGFR or KRAS) Receiving Tyrosine Kinase Inhibitors (TKI)
Authors: Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Laetitia Mauti, Michael Mark, Patrizia Froesch, Martin Früh
Journal: Journal of Thoracic Oncology (2017)
Risk Factors for Thrombosis in WHO-Defined Early/Prefibrotic Myelofibrosis: An International Study of 264 Patients,
Authors: Veronika Buxhofer-Ausch, Heinz Gisslinger, Juergen Thiele, Bettina Gisslinger, Hans-Michael Kvasnicka, Leonhard Müllauer, Sophie Frantal, Alessandra Carobbio, Francesco Passamonti, Elisa Rumi, Marco Ruggeri, Francesco Rodeghiero, Maria Luigia Randi, Irene Bertozzi, Alessandro M. Vannucchi, Elisabetta Antonioli, Guido Finazzi, Naseema Gangat, Ayalew Tefferi, Tiziano Barbui
Journal: Blood (2011)
P2.01-036 Identification of a Novel Oncogenic Ubiquitin Ligase from a Lung Cancer Epigenome-Wide Association Study (EWAS)
Authors: Christian Faltus, Yassen Assenov, Myrto Barrdahl, Marina Laplana, Olga Bogatyrova, Anika Hüsing, Theron Johnson, Michael Meister, Thomas Muley, Arne Warth, Christoph Plass, Rudolf Kaaks, Angela Risch
Journal: Journal of Thoracic Oncology (2017)
Family caregiver QOL and self-care concerns in lung cancer.
Authors: B. R. Ferrell, M. Grant, M. Koczywas, A. Hurria, M. Loscalzo, G. Juarez, S. Otis-Green, G. Uman, T. Borneman
Journal: Journal of Clinical Oncology (2011)

e19606 Background: Family caregivers play a key role in cancer care and are of significant support in advanced diseases such as lung cancer. This National Cancer Institute funded Program Project (P01) addresses palliative care, quality of life (QOL), and self care for family caregivers in lung cancer. The purpose of this study is to test usual care versus a family caregiver interdisciplinary intervention encompassing a QOL education intervention. Methods: Project 3 of this Program focuses on family caregivers in lung cancer, a group with significant QOL concerns. The study uses a two group, prospective tandem enrollment comparing usual care to a structured palliative care intervention. Family caregivers are followed for 6 months in late stage disease and 12 months in early stage lung cancer. Outcome measures include the Family Caregiver QOL tool, Caregiver Burden tool, Self Care Assessment, Psychological Distress and Caregiver Preparation measures. A Geriatric Core supports this Project to advise on caregiver concerns for the geriatric patient such as burden and caregiving skill acquisition as well as to evaluate the needs of the caregiver. Results: Family caregivers (N=96) were mean age of 57 years, 60% female, 70% spouses/partners, and 40% minority subjects. Sixty percent had chronic illnesses of their own. Key caregiver QOL concerns (0= worst to 10 = best outcomes) included distress of the initial diagnosis (x=1.3), family distress (x=2.89) fear of metastasis (x =3.03) or recurrence (x =3.16) for the patient, living with uncertainty (x =3.68) and distress from the patient’s treatment. Key areas of caregiver burden and stress included time demands, overall stress, needing help navigating health services, and accessing community resources and health information. Conclusions: Findings demonstrate gaps in supporting family caregivers in lung cancer. The next phase of this Program Project tests a comprehensive education intervention for family caregivers and a self care plan for each caregiver. Elements include preparing caregivers in managing symptoms in lung cancer, supporting patients physical, psychological and social concerns and addressing spiritual and end of life care.
Association of VEGF single-nucleotide polymorphisms (SNPs) with response and toxicity in patients treated with bevacizumab.
Authors: M. Sun, G. S. Falchook, J. J. Wheler, D. S. Hong, S. A. Piha-Paul, A. M. Tsimberidou, A. Naing, S. Fu, S. L. Moulder, S. Wen, P. Mueller, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

e13560 Background: Functional polymorphisms modulate the regulation of gene expression or influence the function of the coded protein, and polymorphisms of genes associated with angiogenesis may influence the likelihood of benefit or toxicity from antiangiogenic treatment. Although the ECOG 2100 study demonstrated the predictive value of VEGF polymorphisms in the narrow context of breast cancer patients receiving combination bevacizumab and paclitaxel, it is unknown whether this predictive value of VEGF polymorphisms is more broadly applicable across diverse malignancies or across different bevacizumab treatment combinations. Methods: Archived tissue and PMBCs were collected from 400 patients who were treated on bevacizumab-based clinical trials at our institution. DNA extraction, genotyping, and SNP assay evaluation were performed according to standard protocols. Presence or absence of VEGF SNPs were correlated with response to treatment, defined as partial response, complete response, or prolonged stable disease lasting > 4 months. Presence or absence of VEGF SNPs were also correlated with incidence of bevacizumab-related grade 3 or 4 toxicities. Results: Preliminary analysis of 75 patients, including 21 different tumor types and 6 different bevacizumab combinations, showed a trend of correlation of VEGF polymorphism status with response and toxicity, compared to alternate genotypes. Patients with VEGF-2578 AA demonstrated a trend of improved response rate and prolonged stable disease (38% vs. 17%, p=0.068). Patients with VEGF-1498 TT demonstrated a trend of less bevacizumab-related grade 3 or 4 toxicity (5% vs. 21%, p=0.086). Patients with VEGF-634CC demonstrated a trend of less bevacizumab-related grade 3 or 4 toxicity (9% vs. 16%, p=0.714). Conclusions: These clinical data support the concept that VEGF polymorphisms may be potential biomarkers of efficacy and toxicity for patients treated with bevacizumab combinations, independent of tumor site or histology and independent of bevacizumab combination. Updated results of the 400-patient data set will be presented, including a subanalysis of colorectal cancer patients.
Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy
Authors: Pablo Angulo, Gaurav Kaushik, Dharmalingam Subramaniam, Prasad Dandawate, Kathleen Neville, Katherine Chastain, Shrikant Anant
Journal: Journal of Hematology & Oncology (2017)

Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival. Hence, there is a substantial need for new therapies. The inability to control the metastatic progression of this localized cancer stems from a lack of complete knowledge of the biology of osteosarcoma. Consequently, there has been an aggressive undertaking of scientific investigation of various signaling pathways that could be instrumental in understanding the pathogenesis of osteosarcoma. Here, we review these cancer signaling pathways, including Notch, Wnt, Hedgehog, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT, and JAK/STAT, and their specific role in osteosarcoma. In addition, we highlight numerous natural compounds that have been documented to target these pathways effectively, including curcumin, diallyl trisulfide, resveratrol, apigenin, cyclopamine, and sulforaphane. We elucidate through references that these natural compounds can induce cancer signaling pathway manipulation and possibly facilitate new treatment modalities for osteosarcoma.
AGO-OVAR 14: A retrospective study evaluating the reasons for non-participating in trials in patients with ovarian cancer (OC) treated in coordinating centers of the AGO Ovarian Cancer Study Group
Authors: P. Harter, C. Schade-Brittinger, A. K. Belau, J. Sehouli, S. Loibl, H.-J. Lueck, C. Jackisch, U. Canzler, R. Kimmig
Journal: Journal of Clinical Oncology (2004)

5081 Background: Retrospective analysis suggested that participation in clinical trials is associated with better outcome. However, it is not clear to what extent selection bias contributes to this observation. Methods: This study evaluated the reasons leading to the decision of not participating in clinical trials for OC in 2001. In a retrospective study the 16 AGO study coordination centers documented those pts who were not enrolled in current OC study protocols. Both cohorts, the OVAR-14 pts and pts recruited in prospective trials in the same period were compared. Results: Overall, 273 pts with OC FIGO-stage IIB-IV were enrolled of whom 138 (51%) and 135 (49%) pts were included in OVAR-14 and in prospective clinical trials, respectively. 93/138 pts. (67%) did not meet the inclusion criteria for clinical trials. The most common reasons were a history of 2nd malignancy (24 pts, 17%) and impaired renal function (GFR < 60 ml/min, 39 pts, 28%, of whom 51% had a GFR > 50 ml/min). Further 28 pts (20%) refused participation in a prospective study. 17 pts. (12%) were not recruited although they met the inclusion criteria (investigator's decision). The OVAR-14 pts were older than pts treated in prospective studies (median age 65.8 vs 57.2 yrs.). There were no significant differences with respect to FIGO stage. OVAR-14 pts underwent less radical surgery and more frequent had residual disease of 2 cm or above: 48 pts (34,8%) vs 35 pts (25,9 %) in clinical studies. However, 85/138 pts (62%) were treated with carboplatin-paclitaxel, the standard arm in all AGO studies. Conclusions: Future analysis should reveal if any change in inclusion criteria might increase study participation without compromising safety. Therefore, required GFR was reduced to 50 ml/min in the ongoing AGO trial (OVAR-9). Long-term follow-up should determine whether a history with prior malignancies without relapse should maintain an exclusion criteria in trials for advanced OC. Improving education for both pts and investigators might improve recruitment in clinical trials as well. No significant financial relationships to disclose.
Double outlet right ventricle with severe left ventricular outflow tract obstruction due to small ventricular septal defect and anomalous adherence of the mitral valve to the ventricular septum.
Authors: Yuji Matsuoka, Kaoru Akimoto, Eiichi Sennari, Kunio Hayakawa
Journal: Circulation (1987)

A 1-month-old male infant with a double outlet right ventricle complicated by left ventricular outflow tract obstruction due to a very small ventricular septal defect is described. The atrial septum was intact, but mitral stenosis was present .The characteristic finding in this patient was that the inherently small ventricular septal defect was further narrowed by abnormal adherence of the anterior mitral leaflet to the left ventricular septal surface below the defect . Intracardiac anatomical features other than the adherent mitral valve could be evaluated accurately by two-dimensional echocardiography. Because the atrial septum was intact, balloon atrioseptostomy was not possible. An attempt at surgical creation of an atrial septal defect was unsuccessful, and the patient died immediately after the operation. The autopsy findings of the heart are described, and diagnostic problems and the possibility of radical operation are discussed.
Excessive expression of miR-27 impairs Treg-mediated immunological tolerance
Authors: Leilani O. Cruz, Somaye Sadat Hashemifar, Cheng-Jang Wu, Sunglim Cho, Duc T. Nguyen, Ling-Li Lin, Aly Azeem Khan, Li-Fan Lu
Journal: Journal of Clinical Investigation (2017)

MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner. Rather, dysregulation of Th1 responses and autoimmunity resulted from a perturbed Treg compartment. Excessive miR-27 expression in murine T cells severely impaired Treg differentiation. Moreover, Tregs with exaggerated miR-27-mediated gene regulation exhibited diminished homeostasis and suppressor function in vivo. Mechanistically, we determined that miR-27 represses several known as well as previously uncharacterized targets that play critical roles in controlling multiple aspects of Treg biology. Collectively, our data show that miR-27 functions as a key regulator in Treg development and function and suggest that proper regulation of miR-27 is pivotal to safeguarding Treg-mediated immunological tolerance.
Pilot study of regional hepatic intra-arterial (HIA) paclitaxel in patients (Pts) with breast carcinoma metastatic to the liver
Authors: G. Mavligit, R. Kurzrock, A. Cheung, S. Gupta, D. C. Madoff, M. Wallace, E. Kim, S. A. Curley, G. N. Hortobagyi, L. H. Camacho
Journal: Journal of Clinical Oncology (2006)

10626 Background: Approximately 50% of pts with metastatic breast carcinoma develop hepatic involvement during the course of their disease. Their median survival is 1–14 months (mo). Systemic paclitaxel has good anti-tumor activity against breast carcinoma and is safe. We sought to prospectively determine the safety and anti-tumor activity of HIA paclitaxel therapy. Methods: Ten pts with breast carcinoma and dominant liver metastases received monthly inpatient 24 hr-continuous HIA infusions of paclitaxel at 200 mg/m 2 through intra-arterial catheters placed via percutaneous transfemoral approach. WHO tumor assessment guidelines were used. Results: Nine pts enrolled in this study had infiltrating ductal carcinoma and their median age at the time of treatment was 51 years. The group had received a mean of 3.8 previous treatment regimens including adjuvant regimens. Therapy was well tolerated. Fifty-six courses were delivered. Mean hospital stay was 3 days. No procedure related complications were observed. Most common treatment related toxicities included leukopenia, fatigue, nausea, and vomiting. Three pts attained partial responses (50% decrease in tumors) lasting 6, 7, and 48 months whereas in 4 others disease stabilization lasted 5 to 9 mo. One pt underwent liver resection and remained NED for 48 mo. Eight pts had received prior systemic taxane therapy alone or in combination with other cytotoxics (3 adjuvant; 5 palliative). However, no association between previous taxane exposure and clinical efficacy of this regimen was not established. Conclusions: Hepatic arterial therapy with paclitaxel at this dose and schedule is safe and well tolerated and has reasonable anti-tumor activity against breast carcinoma involving the liver. Previous taxane exposure does not hamper the potential benefit of this approach. This regimen deserves further investigation alone or in combination with targeted strategies in patients with dominant liver involvement from breast carcinoma. No significant financial relationships to disclose.
S40 A retrospective study into the clinical relevance of isolating non-tuberculous mycobacteria in pulmonary samples
Authors: H Burgess, S Cowman, A Jones, R Wilson, MR Loebinger
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> There are in excess of 160 species of non-tuberculous mycobacteria (NTM), the minority of which can cause infection predominantly in patients with an underlying respiratory disease such as bronchiectasis or cystic fibrosis. Isolation of NTM in the respiratory tract does not always signify infection and can represent a transient infection, colonisation or active infection. The American Thoracic Society (ATS) criteria for the diagnosis of NTM infection can be used to help assess clinical relevance and the need to treat patients. A retrospective study was conducted to assess the clinical relevance of different species of NTM isolation. <h3>Methods</h3> A database of microbiology results at a specialist trust was reviewed for patients with positive NTM isolates between January 2005 and December 2010. These patients were assessed against the ATS diagnostic criteria of NTM lung disease. Patient records for those who met the microbiological criteria records were reviewed for demographics, underlying condition and course of infection. Patients were followed up for a minimum of 5 years, or until discharge/death. <h3>Results</h3> Five hundred and fifty-five (555) patients with positive NTM cultures were found, 281 (51%) of whom met the ATS microbiological criteria. 70 (13%) patients met the radiographic criteria and so were likely to have an active infection. This varied by species: <i>M. Avium Complex (MAC)</i> (21%), <i>M. malmoense</i> (20%), <i>M. abscessus</i> (18%) and <i>M. kansasii </i>(17%) were most likely to cause changes on CT, and species such as <i>M. fortuitum</i> (1.6%) and <i>M. gordonae</i> (0%) were less likely. The proportion of patients treated also varied by species, with <i>M. abscessus</i> (45%), <i>M. kansasii</i> (23%) and <i>MAC</i> (20%) most likely to be treated. Five-year mortality for all patients who met the microbiological criteria was 21.4% and was significantly associated with meeting the full ATS criteria, as shown by Figure 1. Five-year survival and the patient’s underlying condition also varied by species. <h3>Conclusions</h3> Clinical relevance of NTM isolation varies by species, clinical symptoms and underlying condition. The decision to treat is influenced by these factors in addition to the ATS criteria.
Smoking, passive smoking, and lung cancer cell types among women in Morocco: Analysis of epidemiologic profiling of 101 cases.
Authors: H. Errihani, S. Ouaouch, H. Abahssain, R. Razine, H. Mrabti, R. Abouqal, M. Ichou, N. Benjaafar, F. A. Zakkouri
Journal: Journal of Clinical Oncology (2011)

7069 Background: In recent years, a rapid increase in lung cancer mortality has been observed among women. The aim of this study was to describe the epidemiological profiling and to analysis the survival of Moroccan women with lung cancer. Methods: The studied sample consisted of women with lung cancer who were admitted to our institution between January 2004 and December 2008. The diagnosis was proved by anatomopathologic analysis of biopsy specimen. Statistical analysis was made by Statistical Package for the Social Science version 13.0 (SPSS). Results: We found 101 women among 1680 cases of lung cancer. The median age was 57 years (range, 24-87). Percentage of never-smokers was 75%, 14% are passive smokers and 11% are smokers. Proportion of non-small cell lung cancer (NSCLC) at stage IV was higher (82%), 16% of cases were at stage III and 2% were at stage II. The proportion of adenocarcinoma (ADK) among never and passive smokers is higher than squamous cell carcinoma (SCC) (69.4% vs 30.6%), while among women who are smokers, the most frequent histological type is SCC (63.6%). The small cell lung cancer (SCLC) is found in 7 cases (6.9%). After 2 months median follow-up (range, 1-24), survival at 6 months of SCC is higher than ADK (44.4% vs 25%; p=0.01). There is no significant difference in progression free survival at 6 months between SCC and ADK (20% vs 25%; p=0.81). The survival of NSCLC at 6 months is 27.7%. Survival at 6 months for SCLC was 0%. The Cox regression analysis showed that smoking and passive smoking are not significantly associated with survival: [HR: 0.62 (95% CI: 0.31, 1.30); p=0.19] and [HR: 0.56 (95% CI: 0.29, 1.08); p=0.08] respectively. ADK is significantly associated with survival [HR: 1.73 (95% CI: 1.05, 2.85); p=0.03]. Brain metastasis is no significantly associated with survival [HR: 1.01 (95% CI: 0.53, 1.93); p=0.97]. There is no significant difference in survival at 6 months between SCC and ADK for subgroup who have never or passive smoked (85 patients): (35% vs 20%; p=0.08). Conclusions: Many Moroccan women affected by lung cancer have never smoked. ADK appears to be the most frequent cell type among never and passive smokers. ADK is significantly associated with poorer survival.
Transcriptosome Profiling of B-CLL Identifies WNT-3A and ROR-1 as an Autocrine Mechanism in Cell Survival.
Authors: James Choi, B. Simons, Chris Riley, T. Klinkhammer, Laurence Cooke, Catherine Spier, R. Sud, Sean Hehn, Harinder Garewal, Daruka Mahadevan
Journal: Blood (2005)
Prognostic significance of multimarker circulating tumor cell analysis in patients with advanced pancreatic cancer.
Authors: A. de Albuquerque, I. Kubisch, D. Ernst, G. Breier, S. Kaul, N. Fersis
Journal: Journal of Clinical Oncology (2011)

e14657 Background: Pancreatic cancer is an aggressive malignancy with mortality levels almost equal to its incidence. Despite remarkable advances having been achieved, the treatment results are still disappointing and there is an urgent need for better prognostic tools. This study aims to develop an accurate immunomagnetic assay followed by the validation of a multimarker panel for circulating tumor cells (CTCs) detection in pancreatic cancer patients. Methods: CTCs were isolated with immunomagnetic separation in a training set of 144 peripheral blood samples from 39 advanced pancreatic cancer patients, using the high affinity antibodies BM7 (MUC1) and VU1D9 (EpCAM) and subsequently analyzed by RT-qPCR for the expression of CK19, MUC1, EpCAM, CEA and Survivin. Specificity and sensitivity of the assay were defined by analysis of blood from 40 healthy volunteers and tumor cells spiking experiments. Progression-free survival was estimated by Kaplan-Meier product limit and compared between groups according to CTCs detection (positive v negative) by log-rank test. Results: Overall positivity of the training set was 49.3% while specificity was 100%. Positivity rates for each individual marker were as follows: 11.8% for CK19, 28.5% for MUC1, 25.7% for EpCAM, 4.2% for CEA and 24.3% for Survivin. CTCs detection was associated with poor prognosis in patients analysed before starting first or second-line therapy (median PFS; 60.7 v 163.6 days in patients with positive CTCs detection and negative CTCs detection, respectively; P <0.0001). Conclusions: The presence of CTCs identified by a panel of markers before treatment is an independent predictor of PFS in patients with pancreatic cancer. Our results highlight the importance of multi-antibody enrichment and the use of a multimarker panel for detection and characterization of CTCs.