tbuckley/cabot-search huggingface dataset:
The sooner the better: Analysis of proactive palliative medicine consultation in the medical intensive care unit amongst patients with stage IV malignancy.
Authors: Shanna R Levine, Earle I Bridget, Wendy S.A. Edwards
Journal: Journal of Clinical Oncology (2014)

78 Background: Palliative care has been shown to improve quality of life and prolong median survival in patients with advanced cancer. Sadly, patients are still suffering at the end of their lives perhaps secondary to aggressive hospital care. ICU use in the last month of life increased from 24.3% to 29.2% over the last study decade. Our objective was to evaluate and quantify outcomes, including survival, of patients with active stage IV malignancy admitted to an urban university affiliated hospital MICU who had a palliative medicine consult. Methods: A retrospective chart review of patients from 04/2013 - 04/2014 admitted to the MICU with active stage IV malignancy identified via a validated proactive case finding trigger tool. The trigger was based on eight criteria, one of which being active stage IV malignancy. The MICU census was reviewed biweekly. Data collected included pain and symptom relief, clarification of goals of care, length of stay, and disposition (hospice, rehabilitation facility, home and death). Results: Four hundred sixty eight patients were assessed. One hundred and twenty two patients met 1 of the 8 criteria, and 24 patients met the inclusion criteria for review. Three patients were not seen due to attending and/or family preference. Thirty eight percent of patients had improved symptoms and management control, 42% had clarification of goals of care and medically appropriate decision making, and 42% experienced psychosocial spiritual counseling. Eight patients died during their hospital stay, 4 were transferred to inpatient hospice facilities, 3 to rehabilitation facility, 2 went home and the remainder was “other”. The average length of stay of patients seen by palliative care was 20 days compared to 31 days for patients not seen by the palliative team. Conclusions: Nearly 40% of patients with active stage IV malignancy admitted to the MICU died during their hospital stay. We believe this study illuminates the futility of ICU care in this patient population. Consultation from the palliative medicine team using a proactive trigger tool can be beneficial to allow for better symptom control, clarification of goals and psychosocial counseling.
Distinct Associations Between UGT1A1 Gene Promoter Polymorphism and Hyperbilirubinemia in Korean CML Patients Treated with Nilotinib and Radotinib
Authors: Soo-Hyun Kim, Soo Young Choi, Sung-Eun Lee, Yun Jeong Oh, Hae Lyun Yoo, Eun-Jung Jang, Mi-yeon Choi, Moon-mi Jang, Hyeoung Joon Kim, Jae-Yong Kwak, Hawk Kim, Young-Rok Do, Dong-Wook Kim
Journal: Blood (2014)
Doppler-Ultrasonography with perfusion software and contrast medium injection as an early evaluation tool of gastro intestinal stromal tumor (GIST) treated by imatinib: Results of a prospective study
Authors: N. Lassau, M. Lamuraglia, J. Leclère, S. Bonvalot, D. Vanel, C. Robert, A. Roche, T. Tursz, J. Y. Blay, A. Le Cesne
Journal: Journal of Clinical Oncology (2004)

9048 Background: To evaluate Doppler-Ultrasonography with perfusion software and contrast agent injection (DUPSCA) as a predictor of tumor response to imatinib (Gleevec® ) in positive c-Kit GIST. Methods: Patients (pts) with advanced GIST treated by imatinib (French BFR14 trial) were prospectively included in a monocentric imaging trial. DUPSCA was performed with a sonograph Aplio using a perfusion software (Toshiba) before imatinib administration (d0), on day1, 7, 14, 60, and then every 3 months (m). The percentage of contrast uptake was evaluated at each tumor site by two radiologists. Results obtained by DUPSCA were compared to CT scans (every 2 m for 6 m and then every 3 m). Results: To date, 21 pts (40 target lesions) underwent 117 DUPSCA examinations. At 2 months 19 lesions in 15 pts have a CT scan good response (GR) (according to tumor volume and necrosis) and 8 lesions in 5 pts have a poor response (PR). There was no significant difference of volume between these 2 groups at d1, 7, 14 and 60. The mean percentage of contrast uptake decreased from 62% at d0 to 27% at d7 (p=4.10−6) to 12% at d14 (p= 3.10−7) for GR target lesions versus 45% to 38% to 42% at d0, d7(p=0.3) and d14 (p=0.8) respectively in PR target lesions. Conclusions: UDPSCA is a new, simple, non invasive and reproductible imaging technique that allows an early and accurate evaluation of imatinib activity and may be anticipates the secondary resistance to (Gleevec® ). Final results will be presented during next ASCO. No significant financial relationships to disclose.
Corrigendum to “Transgenic ω -3 PUFA enrichment alters morphology and gene expression profile in adipose tissue of obese mice: potential role for protectins” [Metab Clin Exp 64 (2015) 666–676]
Authors: Phillip J. White, Patricia L. Mitchell, Michael Schwab, Jocelyn Trottier, Jing X. Kang, Olivier Barbier, André Marette
Journal: Metabolism (2015)
Purging of Mammary Carcinoma Cells During Ex Vivo Culture of CD34+ Hematopoietic Progenitor Cells With Recombinant Immunotoxins
Authors: A. Spyridonidis, M. Schmidt, W. Bernhardt, A. Papadimitriou, M. Azemar, W. Wels, B. Groner, R. Henschler
Journal: Blood (1998)
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2)-induced apoptosis in human leukemia cells proceeds through generation of reactive oxygen species and inactivation of Akt
Authors: Joo-In Park, Sung-Won Shin, Chi-Yeon Seo, Hoon Han, Jong-Young Kwak
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2271 

Recent studies showed that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand for PPARγ, inhibits cell growth. However, the exact mechanisms underlying this effect are still being explored. The effect of 15d-PGJ2-induced apoptosis was examined in human leukemia cells in relation to mitochondrial injury, oxidative damage, and perturbations in signaling pathways. 15d-PGJ2 induced apoptosis in these cells in a dose-dependent manner associated with release of mitochondrial proteins (cytochrome c, Smac/DIABLO, and AIF), generation of reactive oxygen species (ROS), down-regulation of XIAP, and inactivation of Akt. Enforced activation of Akt by a constitutively active myristylated Akt construct prevented 15d-PGJ2-mediated mitochondrial injury, XIAP down-regulation, and apoptosis, but not ROS generation. Conversely, 15d-PGJ2 lethality was potentiated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Collectively, these findings suggest a hierarchical model of 15d-PGJ2-related apoptosis induction in human leukemia cells in which 15d-PGJ2-induced oxidative injury represents a primary event resulting in Akt inactivation, leading to XIAP down-regulation, mitochondrial injury, and apoptosis. These results also suggest that 15d-PGJ2 may have therapeutic relevance in the treatment of human leukemia cells including K562 cells, and the inhibition of Akt phosphorylation through ROS production may contribute to 15d-PGJ2-induced apoptosis in human leukemia cell lines.    This study was supported by the Korea Science and Engineering Foundation through the Medical Science and Engineering Research Center for Cancer Molecular Therapy at Dong-A University.
Challenges in pulmonary fibrosis: 6 {middle dot} Problematic granulomatous lung disease
Authors: J L Myers, H D Tazelaar
Journal: Thorax (2007)

Granulomatous inflammation in lung biopsies is a relatively non-specific finding that can occur in a range of inflammatory and neoplastic conditions. This review focuses on the patterns of granulomatous inflammation that can cause diffuse lung disease, highlighting histopathological features helpful in differential diagnosis.
Tumor VEGF expression and serum VEGF levels are independent prognostic factors in curatively resected gastric cancer patients
Authors: M. Pera, O. Vidal, J. Elizalde, A. Soriano, A. Volant, A. Palacin, R. Molina, A. Castells, J. Pique, J. Metges
Journal: Journal of Clinical Oncology (2006)

4021 Background: Increased serum and/or tumor vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) have been shown to predict poor survival in several neoplasms, but their prognostic value in gastric cancer (GC) remains unknown. Methods: Serum VEGF (S-VEGF) and uPA concentrations were measured by commercially available ELISA in 20 healthy controls and 97 GC patients (70% I-II stages) before an R0 gastric resection. Tumor expression of VEGF and uPA were assessed by immunohistochemistry. Additional variables, including demographic, histological and therapeutic data were also evaluated. Univariate (Kaplan-Meier, log-rank test) and multivariate (Cox regression) analyses were performed to select prognostic factors regarding survival and tumor recurrence. Results: S-VEGF, but not uPA levels were significantly higher in GC patients than in controls. After a mean follow-up of 47 ± 3 months, the probability of cancer-related survival at 2, 5, and 10 years was 86%, 69% and 59%, respectively. Univariate analysis identified tumor VEGF expression (p=0.001) and high (&gt; 289 pg/ml) S-VEGF levels (p=0.045), along with pTMN stage, grade of curability, perineural invasion, lymph node ratio, and extent of lymphadenectomy as variables associated with cancer-related survival. The mean disease-free survival was 20 ± 3 months, the probability of tumor recurrence being 78%, 62% and 62% at 2, 5 and 10 years, respectively. Prognostic variables for recurrence were the same as those identified for survival. Multivariate analysis identified tumor VEGF expression and high S-VEGF levels as independent prognostic survival factors. Conclusions: After a long follow-up, tumor VEGF expression and S-VEGF levels are independent prognostic factors for recurrence and survival in curatively resected gastric cancer patients. Such markers for increased angiogenic activity might help to identify patients at high risk of recurrence that could mostly benefit from adjuvant therapies. It is tempting to speculate that trials assessing the potential benefit of a.ntiangiogenic agents might be particularly warranted in patients with resected GC and a highly angiogenic phenotype. No significant financial relationships to disclose.
Abstract 18707: Do Patients with Heart Failure and Atrial Fibrillation Adhere to Warfarin After Hospital Discharge? Findings from the Get With The Guidelines-Heart Failure Registry and Medicare Linked Database
Authors: Zubin Eapen, Xiaojuan Mi, Gregg C Fonarow, Paul A Heidenreich, Lesley H Curtis, Adrian F Hernandez, Sana M Al-Khatib
Journal: Circulation (2012)

Background: Prescribing warfarin at hospital discharge in patients with heart failure (HF) and atrial fibrillation (AF) without contraindications is recommended. Post-discharge adherence and long-term persistence to warfarin therapy among patients with HF and AF has not been fully described. Methods: We identified patients with HF and AF who were ≥65 years, without contraindications to warfarin therapy, and discharged home from hospitals in the GWTG-HF Registry from 1/2006-12/2009. We used linked Medicare prescription drug event data to measure adherence. Main outcome measures were prescription at discharge, outpatient prescription claim within 90 days, discontinuation, and adherence measured with the medication possession ratio. We used the cumulative incidence function to estimate rates of initiation and discontinuation. Results: Among 2691 eligible patients, 1856 (69.0%) were prescribed warfarin at discharge (Table). Within 90 days, 84.5% of eligible patients who had a discharge prescription filled a prescription for the therapy, compared with 12.3% of eligible patients without a discharge prescription (P&lt;0.001). The median medication possession ratio over 1 year of follow-up was significantly higher among patients who were prescribed warfarin therapy at discharge (0.78 vs. 0.63) than among those not prescribed therapy (P&lt;0.001). Among 1,631 patients who filled a prescription within 90 days of discharge, 7.1% discontinued therapy within 1 year. Conclusions: Approximately one-third of eligible patients with HF/AF and no reported contraindication to anticoagulation were not prescribed warfarin therapy at discharge from an HF hospitalization. Eligible patients without a discharge prescription seldom initiated therapy as outpatients. Most patients who were prescribed warfarin at discharge filled the prescription within 90 days and remained on therapy; yet even among these patients, opportunities to improve adherence remain. .
Conflicts of interest are bound to increase as GPs co-commission more primary care services, report warns
Authors: Gareth Iacobucci
Journal: BMJ (2015)

Controls for managing conflicts of interests in clinical commissioning groups (CCGs) in England are variable in their robustness and will be increasingly tested as groups commission more general practice services, the National Audit Office (NAO) has warned.

A new report produced for the Department of Health, NHS England, and Monitor found that almost all CCGs in England had put in place legislative requirements set out in the Health and Social Care Act 2012 to help them prevent and manage conflicts of interest.1

But, where CCGs reported information about their current processes for managing conflicts, the NAO reported that “the adequacy of those controls had varied.” It added that new arrangements enabling CCGs to co-commission primary care services from GPs “are likely to significantly increase the number and scale of conflicts of interest.”

In an analysis conducted in February 2015 the NAO found that 117 of England’s …
A review of the “symptom burden” for patients attending an oncology day ward
Authors: S. J. Asghar, M. M. Kehoe, J. Ryan, I. Haidar, G. D. Leonard, J. S. Fleming
Journal: Journal of Clinical Oncology (2008)

20722 Background: Cancer and its treatment pose a significant symptom burden to patients. Chemotherapy related side-effects may be the prime focus in patients attending an oncology day ward with less emphasis on other symptoms. To optimise the quality of life of patients attending an oncology day ward we sought to evaluate, from a patient’s perspective, all symptoms including chemotherapy side effects, functional status, and well being. Methods: Selected patients were electively attending our oncology day ward for chemotherapy. All such patients were administered the EORTC QLQ-C30 questionnaire incorporating seven multi-item scales; Three functional scales (physical, role and social, cognitive and emotional), three symptom scales (fatigue, pain and associated, others mostly gastrointestinal), and a global health and quality of life (QoL) scale. The study was carried out during two separate weeks. There were no changes to patient selection in the intervening period. Results: A total of 70 patients participated in this study. Almost 60% of patients reported no problem with physical functioning, emotional and cognitive functioning (58.54%), 45.9% of patients reported no limitation to their social/role functioning. More than 70% reported satisfactory pain control and no trouble with appetite loss, nausea/vomiting, diarrhoea or constipation. Over all 62.5% patients rated their health and quality of life as good to excellent and14% as average. Fatigue was found to be the most significant symptom issue (67%). Of this 67%, one third of the patients reported significant fatigue i.e. very tired, weak, and needing to rest most of the time. Conclusions: Fatigue was the most reported symptom while the other QoL indices were maintained. Fatigue has a profound impact on functioning in the cancer patient and this should be addressed in an oncology day ward setting. Use of QoL scales may facilitate the early detection of potentially underestimated symptoms. No significant financial relationships to disclose.
Colorectal cancer expression of chemokine receptor CXCR4 promotes liver metastasis
Authors: J. Kim, H. Takeuchi, L. Foshag, A. Bilchik, D. S. B. Hoon
Journal: Journal of Clinical Oncology (2004)

3582 Background: Chemokines released from organs provide homing signals to specific receptor-bearing cells, conferring migrational and invasive properties to those cells. Our hypothesis is CXCR4 expression by colorectal cancer (CRC) cells facilitates metastasis to the liver. Methods: Premalignant and malignant CRC lesions (n=90: adenoma, n=4; AJCC stages I/II, n=33; AJCC stages III/IV, n=24; liver metastases, n=29) were identified from a CRC patient database. Microarray screening mRNA analysis was performed on 6 CRC tissue specimens from different stages. Initially, these gene expression arrays were performed for profiling known chemokine receptors. Specific gene mRNAs identified by the arrays were then verified by quantitative real-time PCR (qRT) analysis in 86 patients with CRC using paraffin-embedded tissues (n=49) and frozen tissues (n=37). Subset analysis of stage I/II patients was conducted to determine whether chemokine receptor expression levels correlated with local or distant metastasis (LDM). Results: Microarray analysis revealed expression of several chemokine receptors. CXCR4 was prominent and, thus, further assessed for differential gene expression. Comparison of CXCR4 expression levels by qRT in stage I/II CRC vs. liver metastases, primary stage III/IV CRC vs. liver metastases, and primary stage I-IV CRC vs. liver metastases revealed significant upregulation of CXCR4 expression in liver metastases in all comparisons (Chi-Square; p=0.025, p=0.032, and p=0.010, respectively). Subset analysis of stage I/II patients revealed that 30% (n=3/10) of patients with high CXCR4 expression developed LDM, whereas, no patients with low expression (n=0/23) developed LDM during a mean follow-up of 39 months (p=0.022). Conclusions: SDF-1, which is the ligand for CXCR4, is highly expressed in liver and may promote homing of CXCR4 (+) CRC cells. Therefore, our study suggests CXCR4 expression on CRC cells is a potential factor for facilitating metastasis. Furthermore, our study suggests the potential metastatic disposition of CRC cells with high CXCR4 expression in stage I/II patients. No significant financial relationships to disclose.
THE EFFECTS OF DRUGS ON ENZYME SYSTEMS
Authors: F.EDMUND HUNTER, OLIVER H. LOWRY
Journal: Pharmacological Reviews (1956)

It is hoped the foregoing may illustrate not only the complexities of drug-enzyme interactions but also the richness of the possibilities for selective interference with enzyme systems by foreign agents. At the present time, most of the successful drugs are developed empirically or through synthesis of congeners of pre-existing successful types. One wishes for a rational approach which would permit the deliberate development of new drugs specifically to affect particular enzymes. There have been many attempts to develop drugs on a rational basis. Perhaps these attempts will be more successful in the near future. But it must be admitted that the total enzyme matrix of the living organism is more complex and subtle than formerly visualized. Although new information concerning enzymes and their sensitivity to inhibition is being obtained at a constantly accelerated rate, each increment of knowledge also shows the goal to be a little further away than it had appeared to be.
Abstract P3-06-13: Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – The SpheroNEO study
Authors: Kathrin ML Halfter, Nina Ditsch, Hans-Christian Kolberg, Holger Fischer, Tanja Hauzenberger, Franz Edler von Koch, Ingo Bauerfeind, Gunter von Minckwitz, Ilona Funke, Alexander Crispin, Barbara Mayer
Journal: Cancer Research (2015)

Abstract (1) PURPOSE The aim of the prospective trial was to determine if cell survival in a breast cancer spheroid model following cytostatic treatment in vitro predicts treatment response in breast cancer patients receiving equivalent neoadjuvant therapy. (2) PATIENTS AND METHODS Three-dimensional spheroids were directly generated from fresh tumor biopsy samples of 78 patients eligible for neoadjuvant therapy. Cell survival in vitro, as well baseline clinical and pathological characteristics were correlated with the outcome following treatment of each patient to determine the factor(s) most highly associated with pathological complete response (pCR i.e.ypT0/ypN0) at surgery. (3) RESULTS Cell survival after treatment in the breast cancer spheroid model proved to be a sensitive and specific predictor for pCR in individual breast cancer patients. A mean cell survival of 21.8% was found in the breast cancer spheroid model for 22 patients with pCR versus 63.8% in 56 patients without pCR (P = .001). A receiver operator characteristic analysis determined an area under the ROC curve of 0.86 (95% CI: 0.77 to 0.96) for cell survival compared to classic factors i.e. negative hormone receptor and positive Her2/neu status, and age ≤ 50 years at primary diagnosis (AUC = 0.80, 95% CI: 0.70 to 0.90). A cutoff of 35% cell survival was proposed, which grouped patients according to likelihood for pCR. Out of the 32 patients with values below this threshold, 21 patients (65.6%) and one patient (2.2%) with a cell survival greater than 35% achieved pCR respectively; (sensitivity 95.5% (95% CI: 0.86 to 1.00); specificity 80.4% (95% CI: 0.70 to 0.91)).The specificity was improved to 81% (95% CI: 58 to 95%) if the patient was treated per-protocol. A positive correlation was also found between cell survival in vitro and residual tumor size (P = .021), indicating the possibility of the model to predict degree of response. (4) CONCLUSION The breast cancer spheroid model is a valuable predictor for treatment outcome in patients undergoing neoadjuvant chemotherapy for primary breast cancer. Preclinical selection of the most efficient drugs is a prerequisite to improve pCR. Citation Format: Kathrin ML Halfter, Nina Ditsch, Hans-Christian Kolberg, Holger Fischer, Tanja Hauzenberger, Franz Edler von Koch, Ingo Bauerfeind, Gunter von Minckwitz, Ilona Funke, Alexander Crispin, Barbara Mayer. Prospective cohort study using the breast cancer spheroid model as a predictor for response to neoadjuvant therapy – The SpheroNEO study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-13.
Abstract 17547: Renal Sympathetic Denervation Shows No Ill Effects on Renal Function While Inducing a Sudden and Persisting Reduction in Ambulatory Blood Pressure Profiles
Authors: Henning Lemm, Sebastian Dietz, Alexander Vogt, Daniel Holzapfel, Michael Buerke, Silke Markau, Matthias Girndt, Karl Werdan, Alexander Plehn
Journal: Circulation (2012)

Renal sympathetic denervation (RDN) is indicated for treatment-resistant arterial hypertension (systolic pressure ≥160 mmHg on ≥3 antihypertensive drugs). A radiofrequency catheter induces controlled thermal sympathetic nerve destruction in the renal arteries resulting in lowered sympathetic tone and blood pressure. We assumed that the lowered blood pressure may influence renal function. Ambulatory 24 hour blood pressure profiles, blood & urine samples and renal artery resistive indices were taken prior, the day after, 3 & 6 months after the procedure respectively. Samples were analysed for renal function parameters (creatinine, creatinine clearance, urea, albuminuria, beta-2-micro- & alpha-2-macroglobulin). All patients underwent bilateral RDN. All data were statistically analysed with repeated measures ANOVA and Greenhouse-Geisser correction if indicated. All results as mean ± SEM. In 132 patients (80 males; 64 with type II diabetes; 26 with known CAD; age 63.33 ± 0.80 yrs; BMI 31.79 ± 0.49) RR dropped ...