tbuckley/cabot-search huggingface dataset:
Cancer-related distress and unmet needs among newly diagnosed and longer-term cancer survivors from a community-based distress screening program.
Authors: Joanne S. Buzaglo, Melissa F Miller, Victoria Kennedy, Margaret Longacre, Mitch Golant, Patricia A. Robinson
Journal: Journal of Clinical Oncology (2016)

220 Background: As survival rates increase among cancer patients, quality of life needs become more salient. Cancer Support Source (CSS) is a distress screening, referral and follow up program that uses a validated distress screening tool and referral algorithm to link cancer patients to resources tailored to their needs. The objective of this study was to describe psychosocial concerns and unmet needs at different times since cancer diagnosis. Methods: English speaking cancer survivors (n = 905) across 26 affiliates of a nationwide cancer support organization participated in the CSS program by first completing a screening tool, including a 4 item depression subscale. Participants rated the level of concern (0 to 4) about 15 items and identified the help they wanted for each item (talk with a member of your health care team and/or connect you with online resources). We used regression analysis, adjusting for age, to examine differences by time since diagnosis ( &lt; 1 y; ≥ 1 y) in level of distress; type of concerns (rated ≥ 2); and items selected to talk with the health care team. Results: The sample was 78% female, 10% Latino, 9% Black, and median age 57 y. 41% were breast cancer survivors, 6% lung, and 6% colorectal. More than half were within 1 y of their diagnosis (61%, n = 507); 39% ≥ 1 y (n = 331). Those newly diagnosed ( &lt; 1 y) had significantly higher levels of distress (p = 0.011); increased risk for depression (p = 0.007); and more likely to be concerned about changes in work, school, or home life; body image; feeling nervous or afraid; worry about the future; and making a treatment decision (p &lt; 0.05). Among those who indicated that an item was a concern, newly diagnosed patients were significantly more likely to want to talk to their health care team about pain; financial worries; exercising; feeling lonely or isolated; feeling nervous or afraid; and worry about the future (p &lt; 0.05). Conclusions: These findings suggest that patients are more distressed and more likely to want to talk about their psychosocial needs within the first year of a cancer diagnosis. Future research should evaluate efforts to provide tailored resources within the first year of a diagnosis when distress levels are highest.
Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth muscle in patients with severe asthma
Authors: L. Chachi, M. Abbasian, A. Gavrila, A. Alzahrani, O. Tliba, P. Bradding, A. J. Wardlaw, C. Brightling, Y. Amrani
Journal: Allergy (2016)

Background The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. Methods Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR. Immunohistochemistry and flow cytometry assays were used to assess the expression of the protein phosphatase PP5 in endobronchial biopsies and ASM cells. Results The production of CCL11 and CCL5 by TNF-α was insensitive to both fluticasone and dexamethasone in ASM cells from severe asthmatic compared to that in healthy subjects. Fluticasone-induced GRα nuclear translocation, phosphorylation at serine 211 and expression of GC-induced leucine zipper (GILZ) were significantly reduced in ASM cells from severe asthmatics compared to responses in healthy subjects. Levels of PP5 were increased in ASM cells from severe asthmatics and PP5 knockdown using siRNA restored fluticasone repressive action on chemokine production and its ability to induce GRα nuclear translocation and GRE-dependent GILZ expression. In vivo PP5 expression was also increased in the ASM bundles in endobronchial biopsies in severe asthmatics. Conclusions PP5-dependent impairment of GRα function represents a novel mechanism driving GC insensitivity in ASM in severe asthma.
Association of IgG4‐Related Disease With History of Malignancy
Authors: Zachary S. Wallace, Carly J. Wallace, Na Lu, Hyon K. Choi, John H. Stone
Journal: Arthritis & Rheumatology (2016)

Objective IgG4‐related disease (IgG4‐RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4‐RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4‐RD patients who have a history of malignancy preceding the clinical onset of IgG4‐RD. This study was undertaken to characterize IgG4‐RD in the setting of previous malignancy diagnosis. Methods We identified IgG4‐RD patients with a history of invasive malignancy from a well‐defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age‐ and sex‐matched controls for each case and calculated the odds of malignancy among those with IgG4‐RD compared to controls, using conditional logistic regression. Results The mean ± SD age at IgG4‐RD onset was 50.3 ± 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4‐RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1–3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was &gt;3‐fold higher in IgG4‐RD patients (95% CI 1.6–6.2). Conclusion Our findings suggest that, in a subset of patients with IgG4‐RD, malignancy may be associated with subsequent IgG4‐RD development. Potential explanations include shared risk factors for both IgG4‐RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4‐RD, and an increased risk of IgG4‐RD resulting from cancer treatment.
Prevalence and management of anemia in patients with non-myeloid tumors undergoing systemic therapy.
Authors: J. Steegmann, J. Sanchez, R. Colomer, M. Vaz, J. López Jiménez, I. Jalón, M. Provencio, A. González Martín, M. Pérez
Journal: Journal of Clinical Oncology (2010)

e19658 Background: The European Cancer Anemia Survey revealed that, despite a high prevalence of anemia (hemoglobin (Hb)<12 g/dL) in cancer patients (pts) undergoing chemotherapy (CT), few receive treatment. The present study aimed to provide data on anemia prevalence and management in Spain. Methods: Observational, cross-sectional study performed in 2008 in 21 Spanish hospitals. Eligible pts were ≥18 years, with non-myeloid malignancies and treated with systemic therapy (CT, hormonal therapy (HT) or immunotherapy (IT)). Data on clinical characteristics, cancer and anemia therapy, and Hb levels were collected at inclusion and for the previous 4 weeks. Anemia was defined as Hb<12 g/dL. Results: The study included 214 pts with a median age of 63 years (range 20-91), 58% women, 73% with solid tumors, and 79% with advanced disease. CT was used in 91% of pts (of whom 26% received platinum compounds), HT in 8.5%, and IT in 8.5%. Median Hb levels were 12 g/dL (7.4-16.1), with 48% (95% confidence interval: 45-59) of pts presenting anemia (of whom 13% were <10 g/dL and 31% were symptomatic). There was a trend towards higher prevalence of anemia in women (52% vs 42%, p=0.14) and in solid tumors (52% vs 37%, p= 0.09). No association was found between anemia and age, tumor stage or type, nor cancer therapy type. A higher prevalence was observed in pts with CT (51% vs 20%, p=0,01), platinum-based CT (70% vs 47%, p=0.01) or palliative CT (61% vs 39%, p=0.003). The use of anemia treatments in the last 4 weeks in pts with anemia was as follows: 62% did not receive any treatment, 24% received ESAs, 14% received iron supplementation and 8.7% received transfusion. Conclusions: In the Spanish hospital setting, approximately half of pts with non-myeloid tumors undergoing systemic therapy suffer anemia. Our analysis indicates that more than fifty percent of anemic pts do not receive treatment. Study supported with an educational grant of AMGEN S.A. No significant financial relationships to disclose.
Cflar Genetic Variant Resulting In Alternate Splicing Determines Isoform Specific Production Of H-Cflar Protein and Is Predictive Of Cellular Cytoxicity Of Triptolide In Hapmap Lymphoblast and AML Cell Lines
Authors: Lata Chauhan, Brooke Fridley, Feldberg Tanya, Taraswi Mitra Ghosh, Neha Bhise, Jatinder Lamba
Journal: Blood (2013)
P2-207: Results of induction chemoradiotherapy followed surgery in patients with locally advanced non-small cell lung cancer
Authors: Sureyya Sarihan, Sena Kurt, Eda B. Yilmaz, Turkkan Evrensel, Sami Bayram, Cengiz Gebitekin, Saduman B. Adim, Lutfi Ozkan
Journal: Journal of Thoracic Oncology (2007)
P1-086: Utility of Multi-planer Reformation (MPR) CT Images of Small Peripheral Lung Cancers
Authors: Kana Oiwa, Haruhiro Saito, Kouzou Yamada, Humihiro Oshita, Kenei Nakazato, Hisatoshi Asano, Kazuo Masui, Yasuhumi Katou, Hiroyuki Ito, Haruhiko Nakayama, Kazumasa Noda, Yoichi Kameda, Hiroshi Inoue
Journal: Journal of Thoracic Oncology (2007)
Clinical and biomarker evaluations of sunitinib in patients (pts) with advanced well-differentiated grade 3 (G3) and poorly differentiated neuroendocrine neoplasms (PD-NEN).
Authors: Chantal Dreyer, Anne Couvelard, Thomas Walter, Catherine Lombard Bohas, Patricia Niccoli, Jean-François Seitz, Olivia Hentic, Anna Pellat, Thierry Andre, Camille Couffignat, Nathalie Lobbe, France Mentre, Pierre Bedossa, Pascal Hammel, Sandrine J. Faivre, Magalie Zappa, Philippe B. Ruszniewski, Eric Raymond
Journal: Journal of Clinical Oncology (2016)

274 Background: Angiogenesis is extensively developed in well-differentiated pancreatic neuroendocrine tumors (PNET) where sunitinib was showed to prolong progression-free survival leading to FDA and EMA approval. However, clinical experience in pts with well-differentiated G3 &amp; PD-NEN remains limited. Methods: This prospective phase II trial evaluate potential biomarkers correlating with sunitinib activity in pts with advanced well differentiated G3 or PD-NEN. Sunitinib was given at the dose of 37.5 mg/d as a continuous daily dosing until progression or unacceptable toxicity. Evaluation of activity was based on RECIST1.1. Safety was evaluated according to NCI-CTCAEv4. Pharmacokinetics (PK) of sunitinib and SU12662 (main active metabolite) were evaluated. Tumor biomarkers (PDGFR-b, VEGFR2, Carbonic Anhydrase 9, Ki67 and p-AKT) were evaluated in tumor tissues, quantified in tumor cells and stroma (vessels, fibroblasts) using immunohistochemistry and correlated with response by RECIST. Results: Among 31 pts (M/F: 18/13, median age 61), 13 pancreatic, 5 gastric, 5 rectal, 4 colonic, and 4 other G3 &amp; PD-NEN were entered. 27 pts had previous treatment with chemotherapy (mainly platinum/VP16). Among 26 pts evaluable for safety and activity, 7 pts (23%, 95%CI: 6.9%-39.3%), including 3 pts classified as well-differentiated G3 neoplasms) experienced partial responses and tumor stabilizations (clinical benefit). Safety and PK exposure to sunitinib and SU12662 in those pts was consistent with that experienced in PNET. Among the above evaluated tumor biomarkers, only Ki67 correlated with sunitinib activity. The median Ki67 was 20% and 77.5% in pts with CB versus non-responders (p=.002), respectively. ROC curves showed correlations between lower Ki67 in tumors and sunitinib activity (OR:0.9; IC95%:0.831-0.9, p=.039). With a threshold value of Ki67 of 47%, sensitivity and specificity were 80%, the predictive positive value was 67% and the negative predictive value was 86%. Conclusions: In pts with well-differentiated G3 &amp; PD-NEN, sunitinib showed evidence of activity that was more pronounced in pts with Ki67&lt;47%. Clinical trial information: NCT01215578.
Abstract 427: Host and tumoral CXCR2 signaling contributes to tumor growth
Authors: Danielle Carroll, James Harper, Karen McDaid, Ruth Franks, Catherine Eberline, Jane Kendrew, Richard Sainson, Judith Anderton, Chris Rossant, Karen Coffman, Ching Ching Leow, Ivan Inigo, Mitchell Reville, Jacintha Shenton, Lesley Young, Simon Barry
Journal: Cancer Research (2015)

Abstract Chemokines are essential mediators of leukocyte migration and inflammation. Additionally they play an important role in tumour growth. The G-protein coupled receptor, CXCR2, and its ligands (CXCL 1,2,3,5,6,7 and IL8) have been shown to promote tumour initiation and growth, chemo-resistance, angiogenesis and immune cell infiltration (neutrophil, myeloid derived suppressor cells (MDSCs) and macrophages) into the tumour microenvironment. However the contribution of host and tumour CXCR2 has not been elucidated. We have developed both murine and human specific anti-CXCR2 antibodies alongside a humanised CXCR2 transgenic mouse to address the contribution of host and tumour CXCR2 signalling to tumour growth and maintenance. In pre-clinical tumours, granulocytic cells (neutrophils and MDSCs) within the tumour increase with size, in parallel with alteration in cell numbers observed within the spleen, peripheral blood and bone marrow. Inhibition of host CXCR2 has a dramatic impact on peripheral neutrophil levels, as well as their ability to become activated. In pre-clinical tumour models, inhibition of CXCR2 results in tumour growth inhibition. Contribution of host or tumour cells to the effect of CXCR2 blockade was model dependent. In the EL4 murine lymphoma model, only inhibition of host/peripheral CXCR2 was able to impact tumour growth. Whereas, in other murine syngeneic models (CT26 and B16), both host and tumour CXCR2 play a role in tumour growth. This was further demonstrated in an NSCLC patient derived xenograft, where the contribution of tumour CXCR2 was stronger than the host. Collectively our data show that CXCR2 inhibition (alone or in combination) has potential to influence growth of a number of tumour types. Future work is focused on understanding the mechanisms underlying the effects of CXCR2 inhibition, which remain key to developing it as an effective anti-cancer therapeutic. Citation Format: Danielle Carroll, James Harper, Karen McDaid, Ruth Franks, Catherine Eberline, Jane Kendrew, Richard Sainson, Judith Anderton, Chris Rossant, Karen Coffman, Ching Ching Leow, Ivan Inigo, Mitchell Reville, Jacintha Shenton, Lesley Young, Simon Barry. Host and tumoral CXCR2 signaling contributes to tumor growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 427. doi:10.1158/1538-7445.AM2015-427
Prevalence and risk factors for sexual dysfunction in gynecologic tumors survivors.
Authors: A. Tagliapietra, L. Gaba, C. Castelo-Branco, A. Torrents, P. Gascon, L. Vidal Boixader
Journal: Journal of Clinical Oncology (2010)

e19622 Background: Oncologic treatments for gynecological tumors are known to cause deleterious effects on sexual health. Relatively little attention has been focused on studying sexual dysfunction in these women despite it negatively impact on their quality of life. Methods: Women with all types of gynecological tumors were asked to participate in the survey. All participating patients had finished treatment for at least 6 months and were free of disease. Sexual function was assessed by the validated spanish version of the Female Sexual Function Index (FSFI), a 19-item self-report measure of six separate domains consisting of desire disorder, arousal disorder, orgasmic disorder, sexual pain disorder, vaginal lubrication and global sexual and relationship satisfaction. Scores below 24 were considered as indicators of sexual dysfunction. Results: 50 women with ovarian (n=25), endometrial (n=10) and cervical cancer (n=15) answered the questionnaire. Mean age was 51.4 years (28-70). Thirt-three patients (74%) reported sexual dysfunction. Median FSFI score was 15.15 (4.3-23.45). Lower FSFI scores corresponded to desire and vaginal lubrication disorder. No associations were found between sexual dysfunction and tumor type, stage, time from the diagnosis, previous chemotherapy, hormonotherapy and menopause at the time of the diagnosis. Lower levels of education, depression, previous radiotherapy treatment, vaginal dryness and lack of stable partner were predictors of worse sexual functioning. Conclusions: Our survey confirms the extend of impaired sexual functioning among gynecologic tumors survivors. Although numbers are small, certain factors may predict for patients at higher risk to present with sexual dysfunction and help to anticipate problems and develop guided therapy. No significant financial relationships to disclose.
Preliminary results from case-control study confirm Zika virus causes microcephaly
Authors: Susan Mayor
Journal: BMJ (2016)

Zika virus in utero is causally associated with microcephaly in infants, showed preliminary results from the first case-control study to investigate whether Zika virus infection during pregnancy can result in microcephaly.1

The Brazilian Ministry of Health requested that a study be undertaken to investigate the causes of the microcephaly epidemic after declaring it a national public health emergency in November 2015. It was assumed that the relation between Zika virus and microcephaly was causal, …
6-month angiographic and 18-month clinical results of the multicenter randomized DEBIUT (Drug Eluting Balloon In BIfUrcations Trial)
Authors: Anouar Belkacemil, Pierfrancesco Agostoni, Christophe Dubois, Jo Dens, Christophe Naber, Hendrik Nathoe, Tom Adriaenssens, Pieter Doevendans, Eric Belle, Chunlai Shao, Pieter Stella
Journal: Journal of the American College of Cardiology (2011)
Molecular characterisation of a factor VIII specific IgG4 monoclonal antibody derived from a hemophilia A patient with inhibitor
Authors: Marc Jacquemin, BG Desqueper, Abdellah Benhida, Luc Vander Elst, Marc Hoylaerts, M Bakkus, K Thielemans, Jozef Arnout, Kathelijne Peerlinck, Jean Guy Gilles, Jozef Vermylen, Jean-Marie Saint-Remy
Journal: Blood (1997)
P1-036: Characteristics of non-small cell lung cancer in patients under 40: a National Cancer Database (NCDB) Analysis 1998-2004
Authors: Vamsidhar Velcheti, Pooja Chitneni, Boone Goodgame, Daniel Morgensztern, Feng Gao, Maria Baggstrom, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2007)
Management of prisoners with autism is not perfect but is improving
Authors: Alexandra H Lewis, Clare Hughes, Mo Foster, Kim Turner
Journal: BMJ (2016)

Ashworth draws welcome attention to the difficulties experienced by autistic prisoners.1

The Autism Act placed a duty on the government to produce strategies to help autistic people. These contained actions for the criminal justice system (CJS) and the Ministry of Justice to set up a cross government group.

The National Offender Management Service commissioned the National Autistic Society (NAS) to conduct a …
Matrix Metalloproteinase-7 Is a Urinary Biomarker and Pathogenic Mediator of Kidney Fibrosis
Authors: Dong Zhou, Yuan Tian, Ling Sun, Lili Zhou, Liangxiang Xiao, Roderick J. Tan, Jianwei Tian, Haiyan Fu, Fan Fan Hou, Youhua Liu
Journal: Journal of the American Society of Nephrology (2016)

Matrix metalloproteinase-7 (MMP-7), a secreted zinc– and calcium–dependent endopeptidase, is a transcriptional target of canonical Wnt/ β -catenin signaling. Because Wnt/ β -catenin is activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various kidney disorders had markedly elevated urinary levels of MMP-7. Furthermore, urinary MMP-7 levels closely correlated with renal fibrosis scores in patients. In mice, knockout of MMP-7 ameliorated the fibrotic lesions and expression of matrix genes induced by obstructive injury. Genetic ablation of MMP-7 also preserved E-cadherin protein expression and substantially reduced the expression of total and dephosphorylated β -catenin and the de novo expression of vimentin and fibroblast-specific protein 1 in renal tubules of obstructed kidneys. In vitro , MMP-7 proteolytically degraded E-cadherin in proximal tubular cells, leading to β -catenin liberation and nuclear translocation and induction of β -catenin target genes by a mechanism independent of Wnt ligands. Finally, pharmacologic inhibition of MMP-7 immediately after obstructive injury reduced renal fibrosis in vivo . These results suggest that MMP-7 not only can serve as a noninvasive biomarker but also is an important pathogenic mediator of kidney fibrosis.
Prognostic Factors for Survival of Elderly Patients with Acute Myeloid Leukemia after Intensive Chemotherapy: Validation of 3 Popular Prognostic Models
Authors: Ebru Koca, Aysun Halacoglu, Umit Yavuz Malkan, Deniz Arica, Sema Karakus, Hakan Goker, Ibrahim C. Haznedaroglu, Nilgun Sayinalp, Yahya Buyukasik
Journal: Blood (2014)
The health of the nation.
Authors: J Ashton
Journal: BMJ (1991)

ISBN 978-1-906837-78-5 Cover design: lukejefford.com E ach day seems to bring fresh warnings of the pressuresbearing down on the NHS. As resources fail to keep trackof demand, the principle of universal healthcare is under threat as never before. Excessive waiting times, the rationing of new drugs, ambulances queuing up outside A&E, staff shortages, the list goes on. What has brought the NHS to the precarious position it now finds itself in? And what might be done to ensure in future that care goes to those who need it, when they need it?
Follow up to 10 years and pathologic complete response (pCR) after neoadjuvant chemotherapy in locally advanced breast cancer patients treated from 2005 to 2010: a monocentric experience
Authors: E.S. Traverso, C. Cosentino, E. Bennicelli, F. Tava, P. Tava, M.F. Cosimi, C. Simoni
Journal: Annals of Oncology (2015)