tbuckley/cabot-search huggingface dataset:
Investigation of infiltrating regulatory T lymphocytes in tumor areas in oral cancer lesions
Authors: I. Sukhotska, L. García-Alonso, R. Sirera, G. Sarrión, E. Jantus Lewintre, M. Gil, A. Cabrera, A. Berrocal, J. Bagán, C. Camps
Journal: Journal of Clinical Oncology (2009)

e22070 Background: HLA-G is a human non-classical MHC molecule, mainly expressed in the trophoblast whose main function is to suppress immunologic activity that allows maternal tolerance to phoetus. On the other hand, infiltrating regulatory T lymphocytes (Treg) could promote peripheral inmunotolerance fo oncogenic transformation. Methods: We performed real-time PCR in frozen oral cancer specimens from untreated patients who had undergone surgical resection (n=22) and in normal oral mucosa from healthy subjects (n=10). Samples were processed for mRNA extraction and quantification of gene expression was expressed as relative concentration by an endogenous gene. To asses the presence of infiltrating Treg we analysed CTLA-4, Foxp-3, IL-10, TGF-beta, CD4, CD8, CXCR4, CD127 and CD25 and also we determined HLA-G levels. We correlate the expression of immunologic mediators with clinical variables. Results: Patients presented squamous carcinomas of the tongue (n=12) or gum (n=10) and stages ranged from I to IV (stage I=4; II=9; III=4; IV=5). 10 patients presented well-differentiated lesions and the other 12 moderately-differentiated cells. Eight patients received post- surgery chemo and radiotherapy. Our results show that tumor samples had significant higher expression of the CTLA-4, Foxp-3, TGF-beta and CD127 genes than normal tissue. However, those data showed no correlation between the levels of expression and clinico-pathologic variables. When patients were grouped according to tumor size, there was a trend in the way that bigger tumoral lesions expressed relative higher amounts of Treg. By contrast we could not observe an increase of the expression of HLA-G in patients. Conclusions: Our results reveal that there is an increase in the expression of Treg in oral cancer patients. These Treg in tumoral tissues might contribute to the impairment of immunological rejection of the neoplasic transformation. Conversely we have not been able to demonstrate tumoral expression of HLA-G as a strategy to escape from immunosurveyance. Further analysis of this cells and their function is important in order to develop new therapeutic strategies. No significant financial relationships to disclose.
Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis
Authors: Jie Zhang, Fenglong Xie, Huifeng Yun, Lang Chen, Paul Muntner, Emily B Levitan, Monika M Safford, Shia T Kent, Mark T Osterman, James D Lewis, Kenneth Saag, Jasvinder A Singh, Jeffrey R Curtis
Journal: Annals of the Rheumatic Diseases (2016)

To compare the coronary heart disease risk among patients with rheumatoid arthritis (RA) initiating common biologic disease-modifying antirheumatic drugs of different mechanisms.We conducted a retrospective cohort study of patients with RA enrolled in Medicare, a public health plan covering >90% of US residents 65 years or older, from 2006 to 2012 who (1) initiated a biologic, (2) had complete medical and pharmacy coverage for at least 12 months before biologic initiation and (3) were free of coronary heart disease at the time of initiation. We compared the incidence rates (IRs) of (1) acute myocardial infarction (AMI) and (2) a composite outcome of AMI or coronary revascularisation and used multivariable adjusted Cox regression models to examine the associations between the type of biologic and the two outcomes.We identified 47 193 eligible patients with RA with mean age 64 (SD 13) years; 85% were women. Crude IRs for AMI ranged from 5.7 to 8.8 cases per 1000 person-years (PYs). AMI risk was significantly elevated among antitumour necrosis factor (anti-TNF) initiators overall (adjusted HR (aHR) 1.3; 95% CI 1.0 to 1.6) and individually among etanercept (aHR 1.3; 95% CI 1.0 to 1.8) and infliximab (aHR 1.3; 95% CI 1.0 to 1.6) compared with abatacept initiators. Crude IRs for the composite outcome ranged from 7.6 to 14.5 per 1000 PYs. Tocilizumab initiators were at reduced risk of the composite outcome compared with abatacept initiators (aHR 0.64, 95% CI 0.41 to 0.99).Findings from this observational study of patients with RA suggested that anti-TNF biologics may be associated with higher AMI risk compared with abatacept.
Molecular targeting in acute myeloid leukemia (AML) therapy: APcK110 is a new inhibitor of c-Kit activity in AML blasts
Authors: S. Faderl, W. Bornmann, D. Maxwell, Z. Peng, Q. Van, Z. Liu, S. Verstovsek, A. Ferrajoli, H. M. Kantarjian, Z. Estrov
Journal: Journal of Clinical Oncology (2007)

7019 Background: Tyrosine kinases (TK) are important for most cellular functions and require stringent control and regulation. C- Kit, a TK and transmembrane receptor for stem cell factor, plays a crucial role in hematopoiesis. Mutations of c-Kit can contribute to AML pathophysiology and have been associated with shorter survival and higher relapse risk following standard AML therapy. On the other hand, responses have been observed following TK inhibitor therapy such as imatinib. Identification of c-Kit or its pathways in AML leukemogenesis and development of new compounds targeting these mutations may therefore hold promise for therapy. Methods: APcK110 is the result of a structure-based design of c-Kit inhibitors and was derived of a set of compounds with favorable IC 50 values in a c-Kit kinase assay. Here we present results of the activity and mechanism of action of APcK110. We used the mastocytosis cell line HMC1.1 carrying an activating c-Kit mutation and two AML lines (OCIM2 and OCI/AML3) as well as primary samples from patients with AML. Results: We demonstrate that: (1) APcK110 inhibits proliferation of all three cell lines in a dose dependent fashion using an MTT assay. Inhibition of proliferation is most significant in the SCF-dependent cell line OCI/AML3; (2) inhibition of OCIM2 cells (SCF-responsive) by APcK110 can be enhanced when adding SCF suggesting recruitment of c-Kit-dependent signaling components and increased activity of the c-Kit inhibitor under these circumstances; (3) APcK110 is a more potent inhibitor of OCI/AML3 proliferation than imatinib and dasatininb; (4) using Western immunoblotting, APcK110 decreases levels of phospho-Akt, phospho-Stat3 and 5 in a time- and dose-dependent fashion demonstrating activity of APcK110 on c-Kit downstream signaling pathways; (5) APcK110 induces apoptosis by cleavage of caspase 3 and PARP; (6) APcK110 inhibits proliferation of primary AML cells in a clonogenic assay, but does not affect proliferation of normal controls. Conclusions: APcK110 is a potent inhibitor of AML cell lines and primary samples from patients with AML. Activation of c-Kit or downstream pathways increases activity of APcK110. APcK110 and similar compounds should be evaluated in clinical trials of patients with AML. No significant financial relationships to disclose.
Role of surgery in patients with stage IIIA non-small cell lung cancer (NSCLC): Lessons learned from a tertiary referral cancer center experience.
Authors: C. Aggarwal, B. Egleston, L. Li, H. Borghaei, R. Mehra, N. Somaiah, A. Turaka, W. J. Scott, C. J. Langer, G. R. Simon
Journal: Journal of Clinical Oncology (2010)

7066
Changes in γ-Glutamyltransferase Activity During &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenylacetamide-Induced Rat Hepatocarcinogenesis&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: E R Capouya, R Lindahl
Journal: JNCI Journal of the National Cancer Institute (1983)

Changes in gamma-glutamyltransferase (GGT) activity throughout the course of rat hepatocarcinogenesis induced by brief dietary exposure to N-2-fluorenylacetamide (2-FAA) followed by promotion with dietary phenobarbital (PB) were studied. By examination of changes in total GGT activity and its histochemical localization, the effects of initiator and promoter on this enzyme can be clearly differentiated. Both 2-FAA and PB increase total GGT activity in grossly normal liver, PB causing a tenfold greater increase than that caused by 2-FAA. Although the elevation of GGT activity in livers of rats sequentially treated with 2-FAA-PB was not additive or synergistic, the course of increase was distinct from that of either 2-FAA- or PB-caused changes in activity, suggesting that 2-FAA and PB interact to alter the GGT phenotype of sequentially treated animals. GGT activity in neoplasms induced by either 2-FAA or 2-FAA-PB was highly variable, i.e., from nearly basal levels to those 170-fold greater than basal. Lesions induced by 2-FAA without PB promotion had elevated GGT, indicating that PB is not required to produce GGT-positive neoplasms by this protocol. Histochemically, changes in GGT activity occurred in both hepatocytes and nonhepatocyte cell populations in a characteristic, treatment-dependent manner, well-correlated with total GGT activity. Treatment with 2-FAA, especially that with 2-FAA-PB, induced primarily focal and nodular GGT activity patterns. PB alone produced no GGT-positive foci, but it did cause GGT-positive ductular proliferation. Continued PB exposure produced a GGT activity pattern which clearly defined the interlobular regions of the liver; no similar staining pattern was seen in either 2-FAA-treated or 2-FAA-PB-treated livers. These results indicate that an initiator and one of its promoters, combined and individually, alter GGT activity in a characteristic manner over the course of hepatocarcinogenesis. Moreover, the effects of the promoter on GGT activity are dependent on whether or not prior exposure to initiator has occurred.
Analysis of drug delivery and outcome differences in platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC)
Authors: D. Z. Radosavljevic, I. Kezic, S. Jelic, Z. Tomasevic, I. Golubicic
Journal: Journal of Clinical Oncology (2006)

17120 Background: Dose intensity (DI) is the dominant treatment design variable with respect to the degree of therapeutic response while total dose (TD) correlates best with the duration of response in an incurable patient population. To further explore the nature of the relationship of response to treatment (RR) and stable disease (SD) with median survival in advanced NSCLC, we performed an analysis of dose intensity and total dose of platinum compounds in first-line treatment of advanced NSCLC. Methods: Individual patient data from three phase 2/3 studies conducted at the Institute for Oncology and Radiology of Serbia from 1990 to 2001 were reviewed to perform an analysis of DI and TD for responding patients (CR+PR) and stable disease ones (SD). All patients were treated with cisplatin (120 mg/m 2 ) or carboplatin (500 mg/m 2 and thereafter AUC 6) based doublets or triplets, every four weeks (second-generation regimens). Results: 109 case records were analyzed, 93 patients received cisplatin-based and 16 carboplatin-based regimens. For responding patients (N=36) median DI of cisplatin was 29.84 mg/m 2 /wk (range 24.17–36.42) and for stable disease patients (N = 57) median DI was 29.94 mg/m 2 /wk (range 27.11–40.91). Wilcoxon rank sum test p = 0.28. In percentage, responders had DI of 0.985 of planned dose, and stabilizations had DI 0.99 of planned dose. Regarding TD, responders received median of 577.5 mg/m 2 of cisplatin (236.1–1070) while stable disease patients received median of 475 mg/m 2 (231.3–929.4), Wilcoxon p=0.0045. Median survival for responders was 9.5 months and for SD patients 6.0 months (log-rank test, p = 0.021). For carboplatin-receiving patients (N = 16) median DI was 122.85 mg/m 2 /wk (111.91–141.04) and median TD 1900.30 mg/m 2 /wk (1000–3000). Conclusions: Received DI of cisplatin was the same for responders and stable disease patients, but responders received more drug than stable-disease patients and lived significantly longer. The optimal duration of treatment for stable disease patients as probably the most frequent advanced NCSLC population requires careful consideration, especially while we are still in the era of platinum-based chemotherapy. No significant financial relationships to disclose.
Reducing unscheduled attendances at hospital due to lung cancer via a rapid access flexible clinic
Authors: Hannah Morgan, Luke Hodgson, Richard Lee, Sarah Doffman
Journal: European Respiratory Journal (2011)

Brighton and Sussex University Hospitals (BSUH) comprises two acute hospitals in SE England. The lung cancer MDT sees 250 new cases/year. Regional and UK outcomes have been historically poor for 1 & 5 year survival with high numbers presenting late.  Data suggests that lung cancer had the highest rate of unscheduled admissions & the greatest number of inpatient bed days compared with other cancer sites in the Trust.  We present a review of admissions in 2010, including stage at presentation/route to diagnosis and the impact of introducing a flexible clinic through which patients with a known diagnosis can self-trigger an appointment or rearrange their existing appointment.  During 2010 there were 110 patients admitted as an unscheduled emergency, 83 (75%) through A&E.  33 patients (30%) were newly diagnosed and of those 26 patients (24%) had metastatic disease at presentation (Stage IV).  Within the flexible clinic 22 patients triggered an appointment and thereby avoiding an emergency unscheduled attendance. There was a 20% reduction overall in lung cancer admissions in 2010 compared with 2008/9. 107 clinic appointments were cancelled following a telephone contact with the patient facilitating capacity for rapid access referrals: 96 of these were cancelled as the patients were asymptomatic.   Conclusions:  1. Introduction of the flexible clinic has reduced overall admissions by 20%. 2. A high proportion of patients were diagnosed with advanced disease whilst an inpatient. 3. Greater awareness of the symptoms of lung cancer may reduce late presentation. 4. Greater uptake of the flexible clinic may further reduce unscheduled admissions with lung cancer.
Phase II study of a combination of S-1 and weekly paclitaxel in patient with advanced or recurrent gastric cancer
Authors: Y. Ueda, H. Yamagishi, D. Ichikawa, J. Morii, N. Kakihara, T. Yamashita, H. Aragane, H. Nishi, A. Chigusa, J. Sakamoto
Journal: Journal of Clinical Oncology (2006)

14033 Background: Based on the results of our phase I study on a combination of S-1 (tegafur, oxonic acid, and CDHP) and weekly paclitaxel (PTX) for advanced or recurrent gastric cancer (ARGC) (Ueda et al, ASCO 2004), we conducted a multi-center phase II study to prospectively evaluate efficacy, QOL, and toxicity of S-1 plus weekly PTX in patients with ARGC. Methods: Eligibility included patients with histologically-proven ARGC, 20–80 years old, having a ECOG performance status (PS) of 0–2 and adequate organ functions, and having received no prior chemotherapy except postoperative adjuvant therapies without taxanes. S-1 was given orally at a dose of 80 mg/m 2 /day for 14 consecutive days (days 1–14) followed by a 2-week rest. PTX was administered weekly as a 1-hour intravenous infusion on days 1, 8, and 15. This treatment was repeated every 4-weeks as one cycle. Results: Fifty-four patients with measurable lesions (RECIST) were enrolled between Feb. 2004 and Nov. 2005. Histologically, a half of the patients had differentiated type and the other patients had undifferentiated type adenocarcinoma. The median age was 61 (range, 38–78). Three-fourths were male patients. The PS was 0/1/2 in 47/6/1 patients respectively. Thirty nine were primary cases and 15 were recurrent cases after gastrectomy. Treatment was terminated in two patients for toxicities and in one patient for refusal during the first cycle; thus compliance of 94.4%. A total of 254 cycles were administered (median 4.7, range 2–14), and 45 patients were assessable efficacy and toxicity until Dec. 2005. In these 45 assessable patients, 2 CRs and 27 PRs were obtained, resulting in an overall response rate of 64.4%. Twelve pts (26.7%) had stable disease, and 4 pts (8.9%) progressed. The tumor control rate was 91.1%. Conclusions: The combination of S-1 and weekly PTX is highly active for ARGC, and can be given safely with good tolerance and convenience profile. It is a candidate for the standard regimen and expected to contribute to better prognosis and QOL in ARGC patients. No significant financial relationships to disclose.
Dissociative symptoms in a substance abuse population
Authors: G E Dunn, A M Paolo, J J Ryan, J Van Fleet
Journal: American Journal of Psychiatry (1993)

This study was intended to examine the extent of dissociative experiences that exist within a substance abuse population and to determine how demographic and clinical variables affect these experiences.A total of 265 male veterans being treated on an inpatient substance abuse unit completed a standard test battery that included the MMPI-2, the Shipley-Hartford Institute of Living Scale, and the Dissociative Experiences Scale. Additional demographic and clinical information was obtained from the patients' medical records.Over 41% of the cohort had scores on the Dissociative Experiences Scale that suggested the need for further evaluation of a dissociative disorder. A stepwise multiple regression analysis revealed that level of psychological discomfort, IQ, and race accounted for more than 24% of the variance in Dissociative Experiences Scale scores.Substance abuse populations may need to be routinely screened for dissociative symptoms just as they are for depression and anxiety.
On theory integration: Toward developing affective components within cognitive architectures
Authors: Justin M. Olds, Julian N. Marewski
Journal: Behavioral and Brain Sciences (2015)

In The Cognitive-Emotional Brain, Pessoa (2013) suggests that cognition and emotion should not be considered separately. We agree with this and argue that cognitive architectures can provide steady ground for this kind of theory integration and for investigating interactions among underlying cognitive processes. We briefly explore how affective components can be implemented and how neuroimaging measures can help validate models and influence theory development.
WITHDRAWN: The antitumor efficacy of docetaxel is enhanced by encapsulation in novel amphiphilic polymer cholesterol-coupled TPGS micelles
Authors: Yanzhi Song, Qingjing Tian, Chaoyang Lai, Mengjing Wang, Jia Shi, Yihui Deng
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
A phase II study of maintenance therapy with temsirolimus (TEM) after response to first-line docetaxel (TAX) chemotherapy in castration-resistant prostate cancer (CRPC).
Authors: U. Emmenegger, S. S. Sridhar, C. M. Booth, R. Kerbel, S. R. Berry, Y. Ko
Journal: Journal of Clinical Oncology (2010)

TPS246 Background: TAX chemotherapy is the standard of care for first-line cytotoxic therapy of CRPC. However, a number of questions remain regarding the optimal use of TAX following maximal response. Aside from intermittent TAX chemotherapy, maintenance therapy with well- tolerated cytotoxic or cytostatic agents could be one strategy used to prolong the treatment response and chemotherapy-free interval without significantly compromising quality of life. The mammalian target of rapamycin (mTOR) serine/threonine protein kinase is involved in many aspects of CRPC, and mTOR inhibitors have demonstrated significant anti-prostate cancer activity in preclinical testing. Methods: This nonrandomized, open-label, multicenter phase II trial studies maintenance therapy with the mTOR inhibitor temsirolimus (TEM) in patients that have responded to TAX chemotherapy. Eligible CRPC patients must have received between 6 to 8 cycles of first-line TAX chemotherapy (75 mg/m2 q3weeks plus prednisone 5 mg po bid) with documented treatment response by PSA (>50% decline from baseline) or RECIST criteria. They will be administered weekly TEM (25 mg iv) until treatment failure, i.e., objective (RECIST) or symptomatic disease progression. Assuming an increase in time to treatment failure (the primary endpoint of this trial) from 3 to 6 months by using TEM, a type I error rate of 0.05, a power of 80% and a 15% drop-off rate, 30 patients will be enrolled. Secondary clinical endpoints include safety (NCI-CTCAE v3.0) and quality of life (FACT-P and PPI) assessments, changes in PSA doubling time and time to PSA progression, objective tumor response rate (RECIST) and overall survival. Correlative studies on serum/plasma and peripheral blood mononuclear cell lysates will assess surrogate markers of mTOR inhibition (e.g., phospho-p70S6 kinase), cellular and molecular markers of the postulated antiangiogenic effects of TEM (e.g., circulating endothelial (progenitor) cells, vascular endothelial cell growth factor), and markers of intratumoral hypoxia/pH (e.g., osteopontin, carbonic anhydrase IX, as potential predictive markers of treatment benefit). No significant financial relationships to disclose.
Abstract 11771: Both Semi-Quantitative and Quantitative Assessment of Positron Emission Tomography Strongly Predicts Outcomes in Patients Being Evaluated for Cardiac Sarcoidosis
Authors: Vladyslava Bazylevska, Herman H Feringa, Samala Venkata, Raymond R Russell, Daniel Jacoby, Lavanya Bellumkonda
Journal: Circulation (2014)

Background: 18F-FDG positron emission tomography (PET) along with 82Rubidium radiotracer imaging is a non-invasive semi-quantitative technique that aids in the diagnosis of cardiac sarcoidosis. More recently, quantitative analysis using standardized uptake values (SUV) has shown that higher SUV indicates greater degree of active inflammation. This study evaluated the prognostic value of positive PET results on clinical outcome and assessed SUV in relation to PET interpretation and its prognostic value. Methods: We retrospectively analyzed 83 patients with proven or suspected cardiac sarcoidosis, referred for PET imaging between 2009-2013. Baseline characteristics and follow-up events were obtained by medical chart review. Outcomes included death, SCD, heart transplant, drop in EF (&gt;10%), new VT, and ICD discharge. Automated software was used to obtain pixel-based counts from which SUV was calculated. Results: During follow-up, composite endpoints occurred in 23 patients (28%). In multivariate analysis, semi-quantitative assessment of abnormal myocardial FDG uptake was a significant predictor of adverse clinical outcome (HR=3.01, 95% CI=1.06-8.59). This association remained significant in subgroup analysis of Japanese Ministry of Health and Welfare Criteria (JMHC) negative patients (HR=6.96, 95% CI=1.18-40.9). In quantitative assessment, SUV heterogeneity as expressed by the absolute difference in maximum and minimum myocardial SUV value of &gt;0.56 most accurately represented abnormal myocardial FDG uptake (ROC area under the curve 0.82). This was also an independent significant predictor of adverse outcome (HR=3.77, 95% CI=1.15-12.4). Conclusions: Patients with abnormal FDG uptake are 3 times more likely to have adverse outcomes. Abnormal FDG uptake remains a very strong predictor of outcomes in those with negative JMHC. A difference between maximal and minimal SUV of &gt;0.56 g/ml most accurately represents abnormal FDG uptake by semi-quantitative assessment and also predicts adverse outcome. Both semi-quantitative and quantitative assessment of myocardial FDG uptake can be important to clinicians to identify those patients at highest risk for adverse events.