tbuckley/cabot-search huggingface dataset:
Acute allergic reactions to infusion chemotherapy in outpatient office practice
Authors: M. Mundia, S. Ali, M. F. Ali, D. Devlin, F. Nezhat, A. G. Mundia
Journal: Journal of Clinical Oncology (2009)

e20722 Background: Outpatient chemotherapy/biotherapy in oncologist's offices are being utilized in greater numbers, increasing the risks of acute allergic reactions. Methods: The clinical charts of patients receieving prolonged infusion chemotherapy/biotherapy treatments (1–3 hours of infusion) in a community oncologist's office setting were reviewed to determine the rate(risk), management and outcome of severe acute allergic reactions. Results: From January 2007 to December 2008, there were 1453 patient infusions conducted. 653 infusions in 2007 and 800 in 2008. All patients were premedicated with antiemetics, H2 blockers if indicated and dexamethasone. In addition starting 2008 patients also recieved diphenhydramine 25mg. There were total of 15 aute allergic reactions. 10 patients with respiratory symptoms(cough/dysponea/wheezing), 3 patients developed anaphylactic reactions, and 2 patients developed rash. Chemotherapy infusions were promptly discontinued and appropriate resusitative measures instituted. The drugs to which reactions occured included 6 to docetaxel, 3 paclitaxel, 3 carboplatin. and 3 oxaliplatin. All patients responded to resusitative measures which included IV fluids, oxygen, subcutaneous epinephrine, IV dexamethasone, and IV diphenhydramine. None required assisted ventilation or cardio version. All patients were discharged home after 1 to 3 hours of observation. Conclusions: Acute allergic reactions to anticancer therapy must be anticipated in all cases. Appropraite preventive protocols and prompt response will minimize the morbidity and eliminate mortality. No significant financial relationships to disclose.
Carcinogenic Effect of Dipropylnitrosamine and Compounds Related by β-Oxidation2
Authors: J. Althoff, F. W. Krueger, U. Mohr
Journal: JNCI Journal of the National Cancer Institute (1973)

Dipropylnitrosamine injected subcutaneously once weekly for life into Syrian golden hamsters caused a 100% tumor incidence in the respiratory system. The β-hydroxylated compound (2-hydroxypropyl) propylnitrosamine and the β-oxidized compound (2-oxopropyl) propylnitrosamine, administered by the same route and frequency, showed the same effects. Methylpropylnitrosamine injected subcutaneously once weekly for life led to similar results. From these findings it was assumed that, in addition to α-hydroxylation, metabolism by β-hydroxylation might be associated with the carcinogenic effect of dipropylnitrosamine.
Contraception at Risk
Journal: New England Journal of Medicine (2013)

Certain physiological and pathological conditions in women require choice of a contraceptive method that will not aggravate the condition or exacerbate known side effects. IUDs and oral contraceptives (OCs) are not appropriate for the immediate postpartum. Low dose progestins appear best suited and can be started on the 5th day after delivery. IUDs and high dose discontinuous progestins are the best choices for the menopausal period, but contraindications to them must be respected. Contraception with a dominant progestational climate is required in case of benign breast disease. Low dose progestins may cause luteal insufficiency and low dose combined OCs may allow endogenous estradiol secretion poorly balanced by the progestin. All progestin-dominant formulations and discontinuous 19-norsteroids may be used. 19-norsteroids appear suitable for women with breast cancer because of their antiestrogenic activity. High dose progestins are advisable for women with precancerous or cancerous endometrial pathology. Estrogens should be avoided in such cases. Cervical cancer has never been proven to be hormonodependent, and at present the use of hormonal contraception in cervical dysplasia is not contraindicated except after pelvic radiation for invasive cancer. Use of the IUD has the same indications as for the general population after lesions have been treated. In cases of hyperlipidemia, low doses of continuously administered 19-norsteroids cause a decline of high density lipoprotein (HDL) cholesterol but are considered to be without longterm metabolic effects. The new progestin desogestrel does not diminish HDL cholesterol. Many cases of hyperlipidemia and hypercholesterolemia contraindicate OCs at the usual dose and require mechanical contraception, although low dose progestins may be considered. Derivatives of 17-hydroxyprogesterone are without effects on lipid metabolism but are less reliable. No contraceptive method is fully satisfactory for diabetics. Hormonal contraception is risky because of possible metabolic and vascular effects. Low dose progestins have the fewest side effects but are often poorly tolerated. IUDs are often used for diabetics despite possible increased risks of infection and failure. Hypertensive women should not use combined OCs or high-dose 19-norsteroids, but low dose progestins carry no risk of hypertension. Women at vascular risk are advised to use IUDs if no specific contraindications are found. Otherwise low-dose progestins are an acceptable choice. Low dose progestins are often the only possibility for cardiac patients. Nonhypertensive women with renal insufficiency can use OCs under careful supervision if there are no contraindications. Combined OCs are contraindicated when there is any disturbance of hepatic function, but low dose progestins or mechanical means are acceptable. Chronic use of certain drugs which act as enzymatic inductors is incompatible with hormonal contraception.
Recognizing religion's dark side: Religious ritual increases antisociality and hinders self-control
Authors: Nicholas M. Hobson, Michael Inzlicht
Journal: Behavioral and Brain Sciences (2016)

Abstract The target article develops an account of religious prosociality that is driven by increases in self-control. We suggest this account is incomplete. Although religion might increase prosociality to the in-group, it decreases it to the much larger out-group. Rituals, for example, lead to out-group derogation. We also challenge the link between religion and improved self-control, offering evidence that religion hinders self-control.
A role for pre-mNK cells in tumor progression
Authors: Carolyn Rosinsky, Paul Andrew Antony
Journal: Journal for ImmunoTherapy of Cancer (2016)

The innate and adaptive immune systems have evolved together to fight infection and cancerous tissues. The innate immune system emerges first with the adaptive immune system following, both ostensibly being bridged by dendritic cells (DC). Recently cells have emerged that possess characteristics of both innate and adaptive immune cell qualities, termed interferon-producing killer dendritic cells (IKDCs). These cells have an indistinct origin that is not well understood. They appear to have more NK cell attributes than DC but purportedly can regulate the immune system similar to immunoregulatory NK cells. Because of this, they have been renamed pre-mNK cells (pre-mature NK cells). We argue in this commentary that pre-mNK cells may contribute to cancer recurrence.
P33 Treatment with Toll-like receptor 4 antagonist restores the inflammatory cellular immune dysfunction in acetaminophen induced acute liver failure mice
Authors: N Shah, M Montes de Oca, D Dhar, M Jover-Cobos, N Alun Davies, R Mookerjee, R Jalan
Journal: Gut (2010)

Introduction  Acute liver failure (ALF) is a rare, catastrophic syndrome commonly caused by acetaminophen (APAP) that results in the death of about 40% patients. In addition to liver dysfunction, its outcome is critically dependent upon the severity of inflammation. Paradoxically, infection complicates the outcome of patients with ALF. Toll-like receptor 4 (TLR4) plays an important role in the innate immune response recognising and mediating pro-inflammatory cytokine release.  Aim  The aims of this study were to characterise the cellular immune response in APAP induced ALF in mice and to determine whether treatment with a specific TLR4 antagonist (STM28) restores cellular immune dysfunction.  Method  CD1 (n=18) mice were studied (Sham, n=6; APAP (500 mg/kg IP), n=6; and APAP (500 mg/kg IP) plus STM-28, 20 ug prior to and after 6 h, n=6). The mice were sacrificed after 8 h. Peripheral blood was stained with fluorochrome-labelled antibodies specific for peripheral blood myeloid cells, dendritic cells (plasmacytoid and myeloid, expression of CD86 in myeloid); monocytes (resident and inflammatory); total granulocytes and neutrophils; CD4/CD8 T-cells and the expression of CD25 in CD4T cell populations; B cells and NK cells. Flow cytometric analysis was performed on a FACS Canto II. Biochemistry was measured spectrophotometrically.  Results  Compared with sham animals, ALF was associated with widespread and profound abnormalities in cellular immune responses which were significantly improved in the group treated with TLR4 antagonist after APAP administration; significant improvement was observed in (STM28 vs APAP): total myeloid cells (39% vs 57%, p=0.0002), neutrophils (21% vs 37%, p=0.005), total granulocytes (28% vs 48%, p=0.0016), monocytes (6% vs 11%, p=0.0009) and resident monocytes, which are able to differentiate into macrophage (7% vs 15%, p=0.01). No significant differences were observed in subtypes of myeloid and plasmocytoid dendritic cells (54% vs 56% and 15% vs 10%, respectively), T-lymphocytes (16% vs 14%), B cells (7% vs 6%) and NK cells (1% vs 1%). These decrease in cellular inflammatory response was associated with a significant reduction in markers of liver injury (ALT: p  Conclusion  The results of this study suggest profound cellular immune dysfunction in APAP induced ALF mice which have a predominant pro-inflammatory phenotype. This dysfunction can be significantly improved by treatment with a TLR4 antagonist. This restoration of immune dysfunction is associated with significantly less liver injury indicating that TLR4 antagonism may have important therapeutic potential in APAP induced ALF.
Body mass index predicts discontinuation due to ineffectiveness and female sex predicts discontinuation due to side-effects in patients with psoriasis treated with adalimumab, etanercept or ustekinumab in daily practice: a prospective, comparative, long-t
Authors: J. Zweegers, J.M.P.A. van den Reek, P.C.M. van de Kerkhof, M.E. Otero, A.L.A. Kuijpers, M.I.A. Koetsier, W.P. Arnold, M.A.M. Berends, L. Weppner-Parren, P.M. Ossenkoppele, M.D. Njoo, J.M. Mommers, P.P.M. van Lümig, R.J.B. Driessen, W. Kievit, E.M.G.J. de Jong
Journal: British Journal of Dermatology (2016)

Predictors for successful treatment are important for personalized medicine. Predictors for drug survival of biologics in psoriasis have been assessed, but not split for different biologics or for the reason of discontinuation.To compare long-term drug survival between the outpatient biologics adalimumab, etanercept and ustekinumab in patients with psoriasis, and to elucidate predictors for overall survival and drug discontinuation due to ineffectiveness and side-effects for each biologic separately.Ten years of data were extracted from the prospective, multicentre, long-term BioCAPTURE registry. Kaplan-Meier survival analyses and confounder-corrected multivariate Cox regression analysis for drug survival (MCR-DS) were performed to compare drug survival between biologics. To elucidate the predictors for different reasons of discontinuation for each biologic, univariate Cox regression analyses and multivariate Cox regression analyses for predictors (MCR-P) with backward selection were performed.In total, 526 treatment episodes - 186 adalimumab, 238 etanercept and 102 ustekinumab - were included covering 1333 treatment years. MCR-DS showed a significantly higher overall survival for ustekinumab compared with adalimumab and etanercept. MCR-P showed that higher body mass index (BMI) was a predictor for discontinuation due to ineffectiveness for etanercept and ustekinumab and that female sex was a predictor for discontinuation due to side-effects for adalimumab, etanercept and ustekinumab.Ustekinumab has the highest confounder-corrected long-term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side-effects in all three outpatient biologics.
FBW7 (F-box and WD Repeat Domain-Containing 7) Negatively Regulates Glucose Metabolism by Targeting the c-Myc/TXNIP (Thioredoxin-Binding Protein) Axis in Pancreatic Cancer
Authors: Shunrong Ji, Yi Qin, Chen Liang, Run Huang, Si Shi, Jiang Liu, Kaizhou Jin, Dingkong Liang, Wenyan Xu, Bo Zhang, Liang Liu, Chen Liu, Jin Xu, Quanxing Ni, Paul J. Chiao, Min Li, Xianjun Yu
Journal: Clinical Cancer Research (2016)

Abstract Purpose: FBW7 functions as a tumor suppressor by targeting oncoproteins for destruction. We previously reported that the oncogenic mutation of KRAS inhibits the tumor suppressor FBW7 via the Ras–Raf–MEK–ERK pathway, which facilitates the proliferation and survival of pancreatic cancer cells. However, the underlying mechanism by which FBW7 suppresses pancreatic cancer remains unexplored. Here, we sought to elucidate the function of FBW7 in pancreatic cancer glucose metabolism and malignancy. Experimental Design: Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we analyzed the correlation between SUVmax and FBW7 expression in pancreatic cancer tissues. The impact of FBW7 on glucose metabolism was further validated in vitro and in vivo. Finally, gene expression profiling was performed to identify core signaling pathways. Results: The expression level of FBW7 was negatively associated with SUVmax in pancreatic cancer patients. FBW7 significantly suppressed glucose metabolism in pancreatic cancer cells in vitro. Using a xenograft model, MicroPET/CT imaging results indicated that FBW7 substantially decreased 18F-fluorodeoxyglucose (18F-FDG) uptake in xenograft tumors. Gene expression profiling data revealed that TXNIP, a negative regulator of metabolic transformation, was a downstream target of FBW7. Mechanistically, we demonstrated that TXNIP was a c-Myc target gene and that FBW7 regulated TXNIP expression in a c-Myc–dependent manner. Conclusions: Our results thus reveal that FBW7 serves as a negative regulator of glucose metabolism through regulation of the c-Myc/TXNIP axis in pancreatic cancer. Clin Cancer Res; 22(15); 3950–60. ©2016 AACR.
Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients
Authors: Gonzalo Hernández, Concepción Vaquero, Paloma González, Carles Subira, Fernando Frutos-Vivar, Gemma Rialp, Cesar Laborda, Laura Colinas, Rafael Cuena, Rafael Fernández
Journal: JAMA (2016)

Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that conditioned high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy. However, conclusive data about reintubation are lacking.To determine whether high-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy for preventing reintubation in mechanically ventilated patients at low risk for reintubation.Multicenter randomized clinical trial conducted between September 2012 and October 2014 in 7 intensive care units (ICUs) in Spain. Participants were 527 adult critical patients at low risk for reintubation who fulfilled criteria for planned extubation. Low risk for reintubation was defined as younger than 65 years; Acute Physiology and Chronic Health Evaluation II score less than 12 on day of extubation; body mass index less than 30; adequate secretions management; simple weaning; 0 or 1 comorbidity; and absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, and prolonged mechanical ventilation.Patients were randomized to undergo either high-flow or conventional oxygen therapy for 24 hours after extubation.The primary outcome was reintubation within 72 hours, compared with the Cochran-Mantel-Haenszel χ2 test. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis and multiorgan failure, ICU and hospital length of stay and mortality, adverse events, and time to reintubation.Of 527 patients (mean age, 51 years [range, 18-64]; 62% men), 264 received high-flow therapy and 263 conventional oxygen therapy. Reintubation within 72 hours was less common in the high-flow group (13 patients [4.9%] vs 32 [12.2%] in the conventional group; absolute difference, 7.2% [95% CI, 2.5% to 12.2%]; P = .004). Postextubation respiratory failure was less common in the high-flow group (22/264 patients [8.3%] vs 38/263 [14.4%] in the conventional group; absolute difference, 6.1% [95% CI, 0.7% to 11.6%]; P = .03). Time to reintubation was not significantly different between groups (19 hours [interquartile range, 12-28] in the high-flow group vs 15 hours [interquartile range, 9-31] in the conventional group; absolute difference, -4 [95% CI, -54 to 46]; P = .66]. No adverse effects were reported.Among extubated patients at low risk for reintubation, the use of high-flow nasal cannula oxygen compared with conventional oxygen therapy reduced the risk of reintubation within 72 hours.clinicaltrials.gov Identifier: NCT01191489.
Prognostic and predictive value of vascular endothelial growth factor and soluble flt-1 and kdr levels in the sera of small cell lung cancer patients
Authors: Z. Ustuner, P. Saip, V. Yasasever, B. Ozturk, B. Vural, U. Ozbek, E. Topuz
Journal: Journal of Clinical Oncology (2007)

21152 Background: Small cell lung cancer (SCLC) has a rapid growth rate, and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre and post treatment serum VEGF and its receptors Flt-1 and Kdr levels in SCLC patients have impact on clinical outcome is unknown. Methods: From February 2001- January 2003, 39 consecutive patients (34 male, 5 female) with histologically proven SCLC were enrolled into the study. The patients were staged as limited and extensive according to the Veterans Administration Lung Group (VALSG). Pre treatment (n:39) and post treatment (n:25) serum samples of the same patients after 3 months of treatment were collected. The levels of VEGF and its receptors Flt-1 and kdr are measured in the serum by quantitative sandwich enzyme immunoassay technique. Statistical analysis was performed using the SPSS 10.0 pocket program. Results: The median pretreatment serum VEGF, Flt-1, and Kdr levels were 1,200 pg/ml (range, 1,414.3±956.2 pg/ml), 85 pg/ml (range, 97.8±70.7 pg/ml), and 11,550 pg/ml (range, 14,481±6,267 pg/ml) respectively. The pretreatment serum VEGF, Flt-1, and Kdr concentrations were not different in limited and extensive stages. We detected a poor but positive correlation between VEGF and Kdr (r=0.46, p=0.003). Pretreatment low serum VEGF value (&lt;728.5 pg/ml) and good response to treatment were found as good prognostic factors in multivariate analysis. Surveillance of serum VEGF and Flt-1, Kdr values did not correlate with clinical parameters. Conclusions: Serum VEGF was found to be a significant and independent prognostic factor in SCLC patients. We showed a limited association between serum levels of VEGF and Kdr. Whether the levels of serum VEGF and its receptors Flt-1 and kdr have value in detecting treatment modalities of SCLC needs further studies. No significant financial relationships to disclose.
Brief Communication : Nonspecific Inhibition of DNA Repair by Promoting and Nonpromoting Phorbol Esters 2
Authors: R. Langenbach, C. Kuszynski
Journal: JNCI Journal of the National Cancer Institute (1975)

The effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and its nonpromoting structural analogue, 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate (Me-TPA), on N-acetoxy-2-acetylaminofluorene-elicited DNA repair and replicative DNA synthesis was measured in normal human fibroblasts. Both esters inhibited DNA repair synthesis, and Me-TPA was nearly as effective as TPA. In addition, TPA inhibited replicative DNA synthesis. These findings showed that inhibition of DNA repair synthesis may not be a major factor in the mechanisms of action of tumor promoters.
Treatment of Skin Ulcers Secondary to Sneddon Syndrome With Alprostadil (Prostaglandin E1)
Authors: Cristina Collantes-Rodríguez, David Jiménez-Gallo, Cintia Arjona-Aguilera, Lidia Ossorio-García, Mario Linares-Barrios
Journal: JAMA Dermatology (2016)

Treatment of Skin Ulcers Secondary to Sneddon Syndrome With Alprostadil (Prostaglandin E1)Sneddon syndrome (SS) is a rare noninflammatory systemic vascular disease that clinically presents with cerebrovascular disease and racemous livedo. 1 This condition is characterized by obstructive vasculopathy of cutaneous microcirculation, which can lead to the development of painful skin ulcers.
Fas-Independent and Nonapoptotic Cytotoxicity Mediated by a Human CD4+ T-Cell Clone Directed Against an Acute Myelogenous Leukemia–Associated DEK-CAN Fusion Peptide
Authors: Hideki Ohminami, Masaki Yasukawa, Shin Kaneko, Yoshihiro Yakushijin, Yasuhito Abe, Yoshihito Kasahara, Yasushi Ishida, Shigeru Fujita
Journal: Blood (1999)
The EGF Receptor Promotes the Malignant Potential of Glioma by Regulating Amino Acid Transport System xc(<b>—</b>)
Authors: Kenji Tsuchihashi, Shogo Okazaki, Mitsuyo Ohmura, Miyuki Ishikawa, Oltea Sampetrean, Nobuyuki Onishi, Hiroaki Wakimoto, Momoko Yoshikawa, Ryo Seishima, Yoshimi Iwasaki, Takayuki Morikawa, Shinya Abe, Ayumi Takao, Misato Shimizu, Takashi Masuko, Motoo Nagane, Frank B. Furnari, Tetsu Akiyama, Makoto Suematsu, Eishi Baba, Koichi Akashi, Hideyuki Saya, Osamu Nagano
Journal: Cancer Research (2016)

Extracellular free amino acids contribute to the interaction between a tumor and its microenvironment through effects on cellular metabolism and malignant behavior. System xc(-) is composed of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Here, we show that the EGFR interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake, as well as increased glutamate, which promotes matrix invasion. Imaging mass spectrometry also revealed that brain tumors formed in mice by human glioma cells stably overexpressing EGFR contained higher levels of reduced glutathione compared with those formed by parental cells. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells, as well as tumor growth and invasiveness. Our findings establish a new functional role for EGFR in promoting the malignant potential of glioma cells through interaction with xCT at the cell surface. Cancer Res; 76(10); 2954-63. ©2016 AACR.