tbuckley/cabot-search huggingface dataset:
An examination into quality of life as a prognostic survival indicator. Results of a meta-analysis of over 10,000 patients covering 30 EORTC clinical trials
Authors: C. Quinten, C. Coens, M. Mauer, S. Comte, M. Sprangers, C. S. Cleeland, D. Osoba, K. Bjordal, A. Bottomley
Journal: Journal of Clinical Oncology (2008)

9516 Background: While individual studies have suggested baseline QOL (Quality of Life) to be prognostic, results have been contradictory and very few large sample size pooled analyses have been undertaken which could confirm the prognostic value of QOL. Our study aimed to examine if QOL, as assessed by one standardized measure, can predict survival when pooled across a large sample of patients with different disease sites. Such information will provide a rationale to stratify for QOL factors in future clinical trials. Methods: A total of 30 European Organization for Research and Treatment of Cancer (EORTC) Randomized Controlled Trials (RCT) were selected for inclusion in our study, where patients had completed a baseline QOL assessment using the EORTC QLQ-C30 and with survival data. HRQOL parameters were evaluated on a set of 15 standard scales. Clinical data included age (≤60 vs >60), gender, distant metastasis, World Health Organization (WHO) performance status (WHO 0–1 vs WHO 2–3) and site were included. Prognostic significance was assessed using Cox proportional hazard models. Bootstrap re-sampling was applied to check the stability of the models. Results: In the pooled analysis, seven QOL endpoints were prognostic; physical functioning (HR=0.992; p<.0001), emotional functioning (HR=1.002; p<0.0142), global health status (HR=0.994; p<.0001), dyspnoea (HR=1.006; p=<.0001), appetite loss (HR=1.007; p=0.0001), constipation (HR=1.002; p=0.0001) and financial difficulties (HR=0.997; p=<.0001). When the analysis was adjusted for clinical variables, physical functioning (HR=0.994; p<.0001), cognitive functioning (HR=1.003; p=0.0105), global health status (HR=0.996; p=0.0006), fatigue (HR=0.997; p=0.0160), nausea and vomiting (HR=1.005; p=0.0004), pain (HR=1.003; p=0.0003), dyspnoea (HR=1.006; p<.0001), and appetite loss (HR=1.005; p<.0001) were prognostic. Conclusions: Our results indicate QOL data are prognostic, and our large sample of patients from RCT gives confidence to the results. Whilst these findings vary by disease site, generally QOL data can help add insight to predicting survival in cancer patients. No significant financial relationships to disclose.
Janet Christina Easton
Authors: Judith Easton Ramsay, Julian M Simpson
Journal: BMJ (2016)

Janet Christina Brash was born in a tenement flat in Scotstoun, Glasgow. Her mother had worked in service as a housekeeper in Kent in England; her father, from Glasgow, had been a delivery boy who would eventually become a bank manager. In the late 1940s Janet was awarded a bursary to attend Glasgow University’s medical school. After qualifying she took a job south of the border in Hexham and passed the fellowship examination for the Faculty of Anaesthetists of the Royal College of Surgeons, the then new examination …
GW26-e4505 Type 2 Ryanodine Receptor Hyperphosphorylation Plays a Role in the Development of Hypertensive Heart Failure
Authors: Kangyin Chen, Tigang Huang, Tong Liu, Yong-Jian Li, Xin Zhou, Wei Cai, Guangping Li, Yuming Li
Journal: Journal of the American College of Cardiology (2015)
Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study
Authors: RA Nash, R Etzioni, R Storb, T Furlong, T Gooley, C Anasetti, FR Appelbaum, K Doney, P Martin, J Slattery
Journal: Blood (1995)
Piracy of COX-2/PGE2/EP receptor pathway by Kaposi's sarcoma–associated herpes virus (KSHV): A potential Achilles’ heel of KSHV-related diseases.
Authors: A. G. Paul, N. Sharma-Walia, B. Chandran
Journal: Journal of Clinical Oncology (2011)

8062 Background: KSHV is etiologically associated with Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL). KS is the most common and aggressive AIDS-defining malignancy and PEL accounts for 4% of all AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) with a median survival of approximately six months. Our earlier studies demonstrated that COX-2 inhibition by NSAIDs down-regulated major KSHV latency gene LANA-1 and exogenous PGE2 reversed this effect. Here, we examined the role of COX-2/PGE2/EP receptor pathway in KSHV related diseases. Methods: In the first part of the study, we examined the role of COX-2 in PEL using nimesulide, a well-known COX-2 specific NSAID and human PEL cell lines. In the second part of the study, we investigated the role of COX-2/PGE2/EP receptors in KS pathogenesis using KS lesions, KSHV-latently infected cells, and a 293 based promoter assay. Results: In the first part, our data demonstrates that nimesulide is efficacious in inducing proliferation arrest in different PEL cell lines. Nimesulide induced sustained cell death and G1 arrest in BCBL-1 and down-regulated KSHV latent genes LANA-1 and vFLIP. Consequently, nimesulide treatment activated p53/p21 by blocking LANA-1/p53 interaction, down-regulated p-Akt, p-GSK-3b, VEGF-C, syndecan-1, aquaporin-3, VDR, and cell cycle proteins cyclins E/A, and cdc25C. In the second part, COX-2, PGE2 and its receptors (EP1-4) were detected in KS lesions with the strong staining of COX-2/EP2/EP4. In latently KSHV infected endothelial cells, expression of COX-2/EP receptors and PGE2 secretion were up-regulated and EP receptor antagonists down-regulated LANA-1 expression as well as Ca2+, p-Src, p-PI3K, p-PKCζ/λ, and p-NF-κB and their pharmacological inhibition down-regulated exogenous PGE2 and EP receptor agonists induced the LANA-1 promoter activity. Conclusions: Overall, our data for the first time provides a comprehensive molecular framework linking COX-2 with PEL pathogenesis. Furthermore, our data for the first time implicate the inflammatory EP receptors in any form of herpes virus latency and uncovered the chemotherapeutic potential of nimesulide in treating PEL.
Abstract B47: The role of ZNF217 in the development of breast cancer chemoresistance
Authors: Christopher Suarez, Sunil S. Badve, Laurie E. Littlepage
Journal: Clinical Cancer Research (2015)

Abstract Breast cancer is the second leading cause of cancer related deaths with an estimated 232,340 new cases and 39,620 deaths in 2013. Despite 93% of patients being diagnosed with local or regional stage disease, most patient deaths result from metastasis as a result of recurrent disease after the development of therapeutic resistance. Developing a better understanding of the molecular mechanisms of therapeutic resistance is critical to help identify novel therapeutics that overcome metastasis, resistance, and death. We previously identified the transcription factor ZNF217 as a prognostic indicator for breast cancer patients. ZNF217 is overexpressed in breast cancer and numerous other cancers, and this overexpression promotes reduced survival, increased metastasis, and reduced response to therapy. We found that Znf217 overexpression promotes an increase in cancer phenotypes, including self-renewal capacity, invasion, and metastasis. We next determined if Znf217 overexpression in vivo contributed to chemotherapy resistance. We treated mice overexpressing Znf217 or vector with a combination therapy of microtubule inhibitor epothilone B, adriamycin, and cyclophosphamide (EAC). The mice that overexpressed Znf217 had increased tumor volume and decreased survival compared to control mice. Mice overexpressing Znf217, that were treated with EAC, developed a significant increase in tumor volume over control mice within 21 days of EAC treatment. This confirmed that mice overexpressing Znf217 developed resistance to the EAC chemotherapy. To overcome breast cancer chemoresistance caused by ZNF217 overexpression, we identified triciribine as a drug that kills cells that overexpress ZNF217. We found that triciribine treatment inhibited tumor burden in vivo in tumors that overexpressed Znf217 and also had synergy with doxorubicin in human xenografts. We now are confirming these results using patient-derived tumor xenografts to compare therapeutic response of human tumors with high versus low levels of ZNF217 expression. Utilizing animal models that overexpress ZNF217 will allow us to identify combination therapies that are able to overcome resistance. In addition, these studies will provide an ideal model system to search for mechanistic insight into the process of developing therapeutic resistance. Citation Format: Christopher Suarez, Sunil S. Badve, Laurie E. Littlepage. The role of ZNF217 in the development of breast cancer chemoresistance. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B47.
Horse chestnut seed extract for the treatment of arm lymphedema
Authors: P. R. Hutson, R. R. Love, J. F. Cleary, S. A. Anderson, L. Vanummersen, S. L. Morgan-Meadows, E. A. Doran
Journal: Journal of Clinical Oncology (2004)

8095 Background: Lymphedema of the arm occurs frequently as a consequence of surgical and radiation damage to the major lymphatics during lymph node dissection (LND) and adjuvant treatment of breast cancer. Usual lymphedema treatments are massage, compression sleeves and wraps; there are no drug treatments currently available in the USA. This is an interim report of our use of Horse chestnut seed extract (HCSE) for the treatment of arm lymphedema in breast cancer survivors. HCSE is widely used in Europe for venous and lymphatic disorders, and is postulated to act by decreasing capillary and interstitial permeability. Methods: In this double-blind, randomized, and placebo-controlled study, eligible subjects with stable arm lymphedema receive placebo or HCSE (50mg escins) twice daily PO for three months, followed by a 1 month washout. Eligible subjects have affected : unaffected arm edema ratios of ≥ 1.1 to 1 by bioelectric impedance, and significant response was empirically set as a 15% decrease in arm ratios. Arm edema is measured concurrently with serial tape measurements, water displacement, and bioelectric impedance. Subjective assessments include the FACT-B QOL instrument and a 16-item experimental lymphedema questionnaire. Results: 25 subjects (of 68 sought) are evaluable at 3 months. 24 patients are at intermediate assessment points and accrual continues. One patient developed progression of known breast cancer metastases; one developed minor, reversible dizziness and tolerated 50% dose reduction. There are no statistically significant differences in the amount of lymphedema at 3 months by any of the measurement techniques. Small changes in arm volume are not reflected by correlative changes in the scores of the QOL instruments. Conclusions: HCSE at doses commonly used for treating CVI or varicose veins is well tolerated in breast cancer survivors with lymphedema. This interim analysis does not demonstrate significant objective or subjective benefit of HCSE in reducing arm lymphedema. QOL questionnaires need improvement to identify issues that more specifically reflect the impact of lymphedema. Funded by the Susan G. Komen Breast Cancer Research Foundation (BCTR 0100506). No significant financial relationships to disclose.
A Case of Vasovagal Syncope with Convulsions. The Effects of Midodrine Hydrochloride.
Authors: Sen Koyama, Taku Matsubara, Yoshifusa Aizawa, Mitsuru Ohshima, Toshio Yamaguchi, Yuko Yamazaki, Yutaka Igarashi, Yusuke Tamura, Masaru Yamazoe, Tohru Izumi, Akira Shibata, Yasuki Tanaka, Kenichi Watanabe
Journal: Circulation (1992)

A 42-year-old female had suffered from repeated syncope. She had vasovagal syncope with convulsions from vasodilatation and cardiac standstill which lasted for 9.8 sec. The 60 degrees head-up tilt test, nitroglycerin injection and isoproterenol infusion provoked vasovagal reaction. Although a beta blocker was not effective in preventing tilt-induced hypotension and bradycardia, midodrine hydrochloride (alpha-1 stimulant) or atropine prevented it. In this patient, insufficient constriction of capacitance vessels might have played an important role in activation of an inhibitory reflex from cardiopulmonary mechanoreceptors which caused hypotension and bradycardia.
Development and clinical testing of a device for functional bronchoscopy
Authors: Lutz Freitag, Kaid Darwiche
Journal: European Respiratory Journal (2011)

We have developed a universal interface that enables to observe and process physiological data during flexible bronchoscopy. Various sensors for measuring flows, pressures, CO2 and other gas concentrations, pulse oximetry and optical spectra are built into a block that is placed next to the patient9s head. It also contains an emphysema valve simulator. Sensing catheters are guided through the working channel of the bronchoscope. Curves and values are displayed on the video-screen, superimposed over the endo-image. All are stored and processed in real time. So far, the system has been used in more than 150 patients. Measuring mouth air-flow while observing the larynx enables to validate vocal chord dysfunction at rest and during exercise. Internal flow and pressure measurements combined with airway planimetry are useful to identify and quantify malacias. Examples are shown demonstrating bronchoscopy guided lobar lung function tests with measurement of collateral ventilation, lobar gas exchange and perfusion. Together with the built-in valve simulator it facilitates individually tailored endoscopic emphysema treatment. Using the optical catheter, auto-fluorescence and drug-induced fluorescence of the mucosa is measured for cancer detection and photodynamic therapy.  The simultaneous measurement of physiological data and the bronchoscopic image broadens the application of bronchoscopy, helps to solve diagnostic puzzles and has proven to be extremely useful for endoscopic treatment planning.
Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis
Authors: Franck Housseau, Shaoguang Wu, Elizabeth C. Wick, Hongni Fan, Xinqun Wu, Nicolas J. Llosa, Kellie N. Smith, Ada Tam, Sudipto Ganguly, Jane W. Wanyiri, Thevambiga Iyadorai, Ausama A. Malik, April C. Roslani, Jamunarani S. Vadivelu, Sara Van Meerbeke, David L. Huso, Drew M. Pardoll, Cynthia L. Sears
Journal: Cancer Research (2016)

IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as γδ T cells, become available under inflammatory conditions, but their contributions to cancer development are unclear. In this study, we modeled Th17-driven colon tumorigenesis by colonizing Min(Ap) (c+/-) mice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), to investigate the link between inflammation and colorectal cancer. We found that ablating Th17 cells by knocking out Stat3 in CD4(+) T cells delayed tumorigenesis, but failed to suppress the eventual formation of colonic tumors. However, IL17 blockade significantly attenuated tumor formation, indicating a critical requirement for IL17 in tumorigenesis, but from a source other than Th17 cells. Notably, genetic ablation of γδ T cells in ETBF-colonized Th17-deficient Min mice prevented the late emergence of colonic tumors. Taken together, these findings support a redundant role for adaptive Th17 cell- and innate γδT17 cell-derived IL17 in bacteria-induced colon carcinogenesis, stressing the importance of therapeutically targeting the cytokine itself rather than its cellular sources. Cancer Res; 76(8); 2115-24. ©2016 AACR.
Predictors of use of sentinel lymph node biopsy (SNB) in a population-based cohort of breast cancer (BC) patients (pts)
Authors: M. L. Tao, J. Malin, P. Ganz, J. Adams, D. Tisnado, S. Hickey, K. Kahn
Journal: Journal of Clinical Oncology (2004)

6006 Background: Clinical trials testing the validity of SNB in BC will not mature for several years, yet SNB has already been adopted as routine in many settings. Using a population-based cohort of new-onset BC pts in Los Angeles County, we examined the use and patient-, hospital-, and provider-level predictors of use of SNB and SNB-only (i.e. without completion dissection). Methods: From 4/1/00 to 11/30/00, we identified 1716 eligible new onset BC pts and all their available breast-related procedures using population-based tumor registry rapid case ascertainment (RCA). Of these, 1105 (64%) had any axillary excisional procedure. We excluded 138 with mastectomy as the first therapeutic procedure, leaving 967 in the RCA cohort. 489 of these pts provided additional information about their surgeons (self-report cohort). Multivariate logistic regression of SNB and separately of SNB-only was used to assess the influence of patient (age, race-ethnicity) and hospital (ownership, teaching, total bed number, and participation in SNB-clinical-trial) variables. Surgeon BC case volume (BCV) and gender were also examined for the self-report cohort. We adjusted for clustering of pts within hospitals (and within providers for the self-report cohort). Results: Use of SNB and SNB-only were prevalent (RCA cohort: 42% and 22%; self-report cohort: 46% and 23%). Odds ratios for use of SNB were lower for Blacks (0.35**), Hispanics (0.53*), older pts (0.97**), and pts not in a clinical-trial-hospital (5.8**). Odds ratio for use of SNB-only were also lower for smaller (1.004**) and teaching hospitals (0.22*). Results were similar for the self-report cohort. Surgeon BCV also predicted receipt of SNB and SNB-only. (OR 1.04–1.07**). Conclusions: Despite the absence of completed trials assessing the validity of SNB in the community, dissemination of the procedure has been extensive. Minority and elderly patients appear to be receiving SNB and SNB-only at rates lower than others. These data suggest observed disparities in care may occur as early as the initial diffusion of a new technology. * p ≤ 0.05; ** p ≤ 0.01 Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration National Cancer Institute
Less than a third of NHS employees think their organisation has enough staff
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Just under a third of NHS employees believe that there are enough staff in their workplaces to enable them to do their jobs properly, according to the 2015 NHS Staff Survey.1

The figure from the annual survey—published by NHS England and Picker Europe—was consistent with the 29% who agreed with the statement last year.

The poll was carried out between September and December 2015 and found that 73% of NHS staff worked extra hours in 2015, the highest percentage for five years. This compared with 71% in 2014 and a low …
Angptl-4 Is Upregulated Under Inflammatory Conditions In The BM Of Mice, Expands Myeloid Progenitors and Accelerates Reconstitution Of Platelets After Myelosuppressive Therapy
Authors: Anne Schumacher, Till Braunschweig, Bernd Denecke, Tim H. Brümmendorf, Patrick Ziegler
Journal: Blood (2013)
Efficacy and Safety Of Lenalidomide Plus Low-Dose Dexamethasone In Chinese Patients With Relapsed and Refractory Multiple Myeloma (RRMM) and Renal Impairment: MM-021 Subgroup Analysis
Authors: Li Yu, Xin Du, Jie Jin, Zhen Cai, Fangping Chen, Xiao Li, Depei Wu, Fanyi Meng, Huisheng Ai, MMed, Jingshan Zhang, Honeylet Wortman-Vayn, Jay Mei, Jianmin Wang, Jian Hou
Journal: Blood (2013)
A study of surveillance mammography (SM) of the contralateral breast (CLB) following total mastectomy (TM) for breast cancer (BC)
Authors: M. C. Gainford, K. I. Pritchard, L. Paszat
Journal: Journal of Clinical Oncology (2005)

6048 Background: Following a diagnosis of primary BC, SM is recommended at yearly intervals. However, there has never been a direct evaluation of SM. Methods: This is an observational case-cohort study. Endpoints include the clinical outcome following detection of contralateral breast cancer (CLBC) by SM; stage of tumor, type of surgery (TM or breast conserving surgery (BCS)), and the percentage that develop subsequent distant metastases. The underlying population consisting of all women with a new diagnosis of invasive BC that had a TM within four months of diagnosis between 07/91 and 12/93 in Ontario, Canada was identified from the Ontario Cancer Registry (OCR). The OCR was linked to administrative databases and a clinical database formed from chart review to ascertain dates of SM, dates of surgeries and to obtain pathological confirmation of CLBC and tumor stage by TNM system. Cases were a stratified random sample of women who had subsequent CLB surgery following TM. The sub-cohort was a random sample of those who had a TM as their initial treatment regardless of the outcome. Current minimum follow-up is seven years and the maximum twelve. Results: To date 26 confirmed metachronous CLBC have been identified; 15% (4/26, T2 x 4) had CLBC detected by both palpation and SM; 15% (4/26, T1 x 1, T2 x 3) were detected by palpation alone and 70% (18/26, Tis x 5, T1 x 12, T2 x 1) were detected by SM alone. Following a diagnosis by SM, 67% of cases had a subsequent TM and 22% developed subsequent metastatic disease. Conclusions: Twenty eight percent of SM detected lesions appear to be in situ disease. The majority of CLBC detected by SM had subsequent TM. This study is ongoing and further data will be collected to investigate the outcomes of SM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Biomira, Ortho- Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca, Aventis, Pfizer, Pharmacia AstraZeneca, Aventis
Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG
Authors: Deborah T. Blumenthal, Thierry Gorlia, Mark R. Gilbert, Michelle M. Kim, L. Burt Nabors, Warren P. Mason, Monika E. Hegi, Peixin Zhang, Vassilis Golfinopoulos, James R. Perry, Do Hyun Nam, Sara C. Erridge, Benjamin W. Corn, René O Mirimanoff, Paul D. Brown, Brigitta G. Baumert, Minesh P. Mehta, Martin J. van den Bent, David A. Reardon, Michael Weller, Roger Stupp
Journal: Neuro-Oncology (2017)

Radiation with concurrent and adjuvant (6 cycles) temozolomide (TMZ) is the established standard of postsurgical care for newly diagnosed glioblastoma (GBM). This regimen has been adopted with variations, including extending TMZ beyond 6 cycles. The optimal duration of maintenance therapy remains controversial. We performed pooled analysis of individual patient data from 4 randomized trials for newly diagnosed GBM. All patients who were progression free 28 days after cycle 6 were included. The decision to continue TMZ was per local practice and standards, and at the discretion of the treating physician. Patients were grouped into those treated with 6 cycles and those who continued beyond 6 cycles. Progression-free and overall survival were compared, adjusted by age, performance status, resection extent, and MGMT methylation. A total of 2214 GBM patients were included in the 4 trials. Of these, 624 qualified for analysis 291 continued maintenance TMZ until progression or up to 12 cycles, while 333 discontinued TMZ after 6 cycles. Adjusted for prognostic factors, treatment with more than 6 cycles of TMZ was associated with a somewhat improved progression-free survival (hazard ratio [HR] 0.80 [0.65–0.98], P = .03), in particular for patients with methylated MGMT (n = 342, HR 0.65 [0.50–0.85], P < .01). However, overall survival was not affected by the number of TMZ cycles (HR = 0.92 [0.71–1.19], P = .52), including the MGMT methylated subgroup (HR = 0.89 [0.63–1.26], P = .51). Continuing TMZ beyond 6 cycles was not shown to increase overall survival for newly diagnosed GBM.