tbuckley/cabot-search huggingface dataset:
Analysis of single nucleotide polymorphisms (SNPs) of cytidine deaminase (CDA) and xeroderma pigmentosum group D (XPD) genes for the prediction of clinical response to gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC) patients
Authors: E. Vasile, E. Giovannetti, C. Tibaldi, V. Mey, S. Nannizzi, L. Landi, I. Stasi, R. Danesi, M. Del Tacca, A. Falcone
Journal: Journal of Clinical Oncology (2006)

7219 Background: Detection of genomic differences predictive of drug response may allow to customize chemotherapy to the characteristics of individual patients. Gemcitabine alone or in combination with cisplatin are two of the most common regimens used in the treatment of advanced NSCLC. We investigated the correlation between selected SNPs of genes encoding enzymes involved in the activity of gemcitabine and cisplatin, including CDA, XPD and ERCC1, and the response to chemotherapy. Methods: Forty advanced NSCLC chemo-naïve patients were enrolled into the study; 16 patients, aged &gt; 70 years, were treated with gemcitabine; 24 patients, aged &lt; 70 years, were treated with cisplatin plus gemcitabine. SNPs CDA A79C, XPD A751C, XPD G312A and ERCC1 C118T were analyzed with the ABI PRISM 7900HT Sequence Detection System using TaqMan probe-based assay in DNA obtained from peripheral blood samples. Statistical analysis was performed using Pearson χ 2 test, Kaplan-Meier curve and log rank test. Results: Up to now 31 patients, 11 treated with gemcitabine and 20 with cisplatin plus gemcitabine, are evaluable for response with RECIST criteria; correlation between response and genotype are showed in the table. Actuarial progression free survival (PFS) was longer in patients treated with gemcitabine ± cisplatin with CDA A79A genotype than in others (respectively 11.0 vs 2.5 months, p = 0.0092), while no correlation was found between the SNPs of XPD and ERCC1 and PFS in patients receiving cisplatin and gemcitabine. Conclusions: CDA A79A genotype resulted predictive of response and longer PFS in NSCLC patients treated with gemcitabine ± cisplatin. There was also a trend toward significant correlation between XPD A751A and better response in cisplatin-treated patients, while the SNPs in XPD 312 and ERCC1 118 were not associated with response to chemotherapy. [Table: see text] No significant financial relationships to disclose.
The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements
Authors: Claudio Procaccini, Fortunata Carbone, Dario Di Silvestre, Francesca Brambilla, Veronica De Rosa, Mario Galgani, Deriggio Faicchia, Gianni Marone, Donatella Tramontano, Marco Corona, Carlo Alviggi, Antonio Porcellini, Antonio La Cava, Pierluigi Mauri, Giuseppe Matarese
Journal: Immunity (2016)

Human CD4(+)CD25(hi)Foxp3(+)CD127(-) Treg and CD4(+)CD25(-)Foxp3(-) Tconv cell functions are governed by their metabolic requirements. Here we report a comprehensive comparative analysis between ex vivo human Treg and Tconv cells that comprises analyses of the proteomic networks in subcellular compartments. We identified a dominant proteomic signature at the metabolic level that primarily impacted the highly-tuned balance between glucose and fatty-acid oxidation in the two cell types. Ex vivo Treg cells were highly glycolytic while Tconv cells used predominantly fatty-acid oxidation (FAO). When cultured in vitro, Treg cells engaged both glycolysis and FAO to proliferate, while Tconv cell proliferation mainly relied on glucose metabolism. Our unbiased proteomic analysis provides a molecular picture of the impact of metabolism on ex vivo human Treg versus Tconv cell functions that might be relevant for therapeutic manipulations of these cells.
Suicide and Ambient Temperature in East Asian Countries: A Time-Stratified Case-Crossover Analysis
Authors: Yoonhee Kim, Ho Kim, Yasushi Honda, Yue Leon Guo, Bing-Yu Chen, Jong-Min Woo, Kristie L. Ebi
Journal: Environmental Health Perspectives (2015)

BackgroundA limited number of studies suggest that ambient temperature contributes to suicide; these studies typically focus on a single nation and use temporally and spatially aggregated data.ObjectiveWe evaluated the association between ambient temperature and suicide in multiple cities in three East Asian countries.MethodsA time-stratified case-crossover method was used to explore the relationship between temperature and suicide, adjusting for potential time-varying confounders and time-invariant individual characteristics. Sex- and age-specific associations of temperature with suicide were estimated, as were interactions between temperature and these variables. A random-effects meta-analysis was used to estimate country-specific pooled associations of temperature with suicide.ResultsAn increase in temperature corresponding to half of the city-specific standard deviation was positively associated with suicide in most cities, although average suicide rates varied substantially. Pooled country-level effect estimates were 7.8% (95% CI: 5.0, 10.8%) for a 2.3°C increase in ambient temperature in Taiwan, 6.8% (95% CI: 5.4, 8.2%) for a 4.7°C increase in Korea, and 4.5% (95% CI: 3.3, 5.7%) for a 4.2°C increase in Japan. The association between temperature and suicide was significant even after adjusting for sunshine duration; the association between sunshine and suicide was not significant. The associations were greater among men than women in 12 of the 15 cities although not significantly so. There was little evidence of a consistent pattern of associations with age. In general, associations were strongest with temperature on the same day or the previous day, with little evidence of associations with temperature over longer lags (up to 5 days).ConclusionsWe estimated consistent positive associations between suicide and elevated ambient temperature in three East Asian countries, regardless of country, sex, and age.CitationKim Y, Kim H, Honda Y, Guo YL, Chen BY, Woo JM, Ebi KL. 2016. Suicide and ambient temperature in East Asian countries: a time-stratified case-crossover analysis. Environ Health Perspect 124:75–80; http://dx.doi.org/10.1289/ehp.1409392
Response of Walker 256 Carcinosarcoma Cells to 12-&lt;italic&gt;O&lt;/italic&gt;-Tetradecanoylphorbol 13-Acetate: Possible Regulation by Endogenous Cyclooxygenase Metabolites
Authors: J Varani, P Perone
Journal: JNCI Journal of the National Cancer Institute (1985)

Walker 256 carcinosarcoma cells (Walker cells) maintained in suspension culture responded to stimulation with 12-O-tetradecanoylphorbol 13-acetate [(TPA) CAS: 16561-29-8] by becoming temporarily adherent to the substratum. Both the control and treated cells produced very low levels of cyclooxygenase metabolites as detected by radioimmunoassay procedures. Levels of prostaglandin F2α, 6-keto prostaglandin F1α (6-keto PGF1α) (a prostacyclin metabolite), and thromboxane B2 were virtually the same as background, and prostaglandin E2 (PGE2) levels were only slightly higher. Studies employing high-performance liquid chromatography also failed to detect significant quantities of cyclooxygenase products in the supernatants from either the control or the stimulated Walker cells. Although the Walker cells maintained in culture failed to produce significant amounts of cyclooxygenase metabolites, they produced much greater amounts of these products, particularly PGE2 and 6-keto PGF1α when they were maintained as an ascites tumor. Concomitant with the production of these metabolites was a loss in responsiveness to TPA in the adherence assay. Upon reestablishment in culture, the cells gradually reacquired the ability to respond to TPA. Over the same period, synthesis of cyclooxygenase products was curtailed. If the cells taken from ascites tumors were incubated with indomethacin so as to inhibit the production of cyclooxygenase metabolites, they rapidly regained responsiveness to TPA. These findings suggest that stimulus-coupled responses in the Walker cells may be regulated, at least in part, through the production of endogenous cyclooxygenase metabolites.
Income is an independent risk factor for worse asthma outcomes
Authors: Juan Carlos Cardet, Margee Louisias, Tonya S. King, Mario Castro, Christopher D. Codispoti, Ryan Dunn, Linda Engle, B. Louise Giles, Fernando Holguin, John J. Lima, Dayna Long, Njira Lugogo, Sharmilee Nyenhuis, Victor E. Ortega, Sima Ramratnam, Michael E. Wechsler, Elliot Israel, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2017)
A Malignant Trophoblastic Cell Line: High Rates of DNA Synthesis Measured by a Rapid Disc Method&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robert O. Hussa, Roland A. Pattillo, John C. Garancis, Anna C. F. Ruckert, Richard F. Mattingly
Journal: JNCI Journal of the National Cancer Institute (1970)

A filter disc method was used to measure incorporation of thymidine-methyl-3H into DNA in cultured choriocarcinoma cells (BeWo cell line) and in other tumors and tissues actively synthesizing DNA. This rapid, simple method was as precise as other techniques. The rate of thymidine-methyl-3H incorporation into DNA in BeWo was at least 10 times greater than the rate in rapidly growing solid tissues (normal human placenta, normal human fetal liver, regenerating rat liver, and rapidly growing rat hepatoma), but did not differ significantly from the rate in HeLa cells. The number of cells per unit weight in BeWo was 1½–2½ times less and the cellular DNA content 2–5 times greater than in all other tissues examined, which indicated the larger size of these undifferentiated embryonic cells. Incubation of BeWo cells with actinomycin D inhibited DNA synthesis, and caused dose-dependent necrosis as observed by electron microscopy. Thus BeWo is an ideal, homogeneous cell line with which to investigate the action of chemotherapeutic agents on DNA synthesis and cell viability in malignant cells.
Hemoglobin increase in advanced/metastatic lung cancer patients receiving multicycle chemotherapy and weekly darbepoetin alfa: An initial ongoing experience
Authors: M. R. Migliorino, L. De Petris, O. Martelli, A. Mancuso, R. Di Salvia, F. De Marinis
Journal: Journal of Clinical Oncology (2004)

8250 Background: Recombinant human erythropoietin (rHuEpo) is efficient in treating chemotherapy-induced anemia, increasing mean hemoglobin (Hgb) levels by 1 g/dl at 4 weeks (w) (Gabrilove, JCO 2001). Darbepoetin alfa, a novel erythropoiesis stimulating protein, has a lower receptor-binding affinity than rHuEPO, due to its higher sialic acid-containing carbohydrate content, but a longer serum half-life, that should confer it a greater and faster in vivo potency at 2 and 4 w (Egrie, Exp Hematol 2003). Aim of this ongoing study was to evaluate whether in the treatment of anemic lung cancer patients, darbepoetin alfa had the same efficacy as that expected from rHuEpo. Methods:From July till October 2003, 24 patients with advanced-metastatic NSCLC receiving chemo- (22 pts) or radiotherapy (2 pts), mean age 64 yrs, ECOG 0–1, were treated for treatment-induced anemia with darbepoetin alfa, 150 mcg/w s.c. for 4 w. The treatment was started at Hgb levels ≤10.5 g/dl, or at Hgb >10.5 g/dl, but with a Hgb reduction ≥1.5 g/dl after the beginning of chemotherapy. Hgb response was assessed at 2 and 4 w of treatment. Results:Mean Hgb change was 0.54 g/dl and 1.14 g/dl at 2 and 4 w respectively. Eight/24 and 13/24 pts had a Hgb increase ≥1 g/dl at 2 and 4 w respectively, while 6/24 pts had a major response, with an increase ≥2g/dl at 4 w. Twenty-two patients were therefore stratified according to the schedule of chemotherapy they were receiving (platinum- vs non-platinum-based [59% vs 41%], oral vs i.v. [27% vs 73%]) and to pre-treatment vs no-pre-treatment with rHuEPO (27% vs 73%), and then correlated with the response to darbepoetin therapy (t-test). No statistical differences between the groups were observed. Conclusions: Compared with data from historical studies, in our cluster of patients darbepoetin alfa was equiactive with rHuEpo at 4 weeks, showing a similar rate of early responses at 2 w. Moreover, no significant differences in response were observed for those patients who were receiving less anemia-inducing treatments, such as non-platinum-based therapy or oral therapy (vinorelbine 4 pts, ZD-1839 2 pts). No significant financial relationships to disclose.
Demonstration of Antibodies in Patients' Sera, Directed Against Nonspecific Cross-reacting Antigen
Authors: S. von Kleist
 3, M. King, K. Havemann
Journal: JNCI Journal of the National Cancer Institute (1978)

Nonspecific cross-reacting antigen (NCA), which strongly cross-reacts with carcinoembryonic antigen, was demonstrated to be an autoantigen. Antibodies directed against NCA were shown in different groups of patients, but high titers (greater than 1/64) were found only in cancer patients. A correlation between tumor mass, antigen load, and antibody titer apparently existed. Sera obtained from patients preoperatively and postoperatively differed significantly (P greater than 0.01) in the sense that titers were high only in sera sampled after the patients were treated. Nevertheless, the formation of these antibodies cannot be considered a cancer-specific phenomenon because of their existence also in patients with nonmalignant diseases.
In vivo perspective study about the effects of weekly low dose administration of zoledronic acid (ZA) on angiogenesis
Authors: D. Santini, B. Vincenzi, F. Battistoni, S. Galluzzo, L. Rocci, F. Uzzalli, O. Venditti, C. Grilli, G. Dicuonzo, G. Tonini
Journal: Journal of Clinical Oncology (2007)

3558 Purpose: Recent data have demonstrated in preclinical tumor models an antiangiogenic and antitumor activity of low weekly doses of ZA. As a consequence, the purpose of this study was to confirm these data, evaluating in cancer patients the modifications in angiogenic cytokines levels following repeated weekly low doses of ZA. Experimental Design: 26 consecutive cancer patients with bone metastases treated, for the first time, with four weekly doses of 1 mg of ZA followed by standard doses (4 mg every 28 days) were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) at different time points: just before and after 1, 7, 14, 21, 28, 56 and 84 days following the first disphosphonate infusion. Results: Basal serum VEGF median levels were significantly decreased just after 7 days (-29.7%) (with only one weekly infusion) (P=0.038), This significant decrease of circulating VEGF levels persisted 14(-33.2%), 21 (-39.4%), 28(-31.8%), 56(-33.6%) and 84(-27.9%) days after the first infusion (respectively, P=0.002, P=0.001, P=0.008, P=0.002, P=0.014). Conclusions: This study confirms, for the first time in humans, that weekly low doses of zoledronic acid could have antiangiogenic properties through a significant and long lasting decrease of VEGF serum levels. No significant financial relationships to disclose.
Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve
Authors: Jacob P. Dal-Bianco, Elena Aikawa, Joyce Bischoff, J. Luis Guerrero, Jesper Hjortnaes, Jonathan Beaudoin, Catherine Szymanski, Philipp E. Bartko, Margo M. Seybolt, Mark D. Handschumacher, Suzanne Sullivan, Michael L. Garcia, Adam Mauskapf, James S. Titus, Jill Wylie-Sears, Whitney S. Irvin, Miguel Chaput, Emmanuel Messas, Albert A. Hagège, Alain Carpentier, Robert A. Levine
Journal: Journal of the American College of Cardiology (2016)
Algorithm to rule out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multicentre study
Authors: Christian Jansen, Christopher Bogs, Wim Verlinden, Maja Thiele, Philipp Möller, Jan Görtzen, Jennifer Lehmann, Michael Praktiknjo, Johannes Chang, Aleksander Krag, Christian P Strassburg, Sven Francque, Jonel Trebicka
Journal: Gut (2016)

Recently, the UK guidelines on variceal bleeding 1 and other reports have introduced
Discrepancies in three commercial prognostic breast cancer assays used in adjuvant chemotherapy decisions.
Authors: Ashrei Y Bayewitz, Jeffrey Gary Schneider, Lorna Ogden, George Turi
Journal: Journal of Clinical Oncology (2014)

84 Background: OT (Oncotype DX), MS (Mammostrat) and MP (Mammaprint) are three prognostic measures of breast cancer recurrence risk. All three were retrospectively validated in large patient cohorts and are now used when deciding on risk-reducing adjuvant chemotherapy. Our objective was to directly compare these three assays and their potential for differential effects on adjuvant chemotherapy decision making. Methods: We have previously reported that OT reduces adjuvant chemotherapy utilization, whereas MS did not exhibit this same net tendency in identical patients. In this study, we performed MP assays in 31 ER+ N0 breast cancer patients for which we already had OT and MS results. Decision analysis was applied to determine changes in management that would be most likely depending on which assay was used to guide decision making. Results: Our decision analysis demonstrated that in a substantial proportion of breast cancer patients, each of the three assays led to changes in adjuvant treatment decisions compared with what would have been chosen based upon conventional criteria alone. OT changed the decision in 55% of patients, and MS and MP would have changed those decisions in 45% and 65% of patients, respectively. In two-by-two paired analyses, treatment decisions would have differed in 61% of cases for OT versus MS; 29% for OT versus MP and 38% for MS versus MP. OT had the greatest tendency to eliminate adjuvant chemotherapy use (in 55% of patients versus MS and in 22% of patients versus MP), whereas MS had the greatest tendency to increase chemotherapy use (in 55% of patients versus OT and 35% versus MP). Conclusions: In this study of 31ER+ N0 breast cancer patients, three commercially available prognostic assays (OT, MS and MP) often yielded discordant risk category results. Our decision analysis suggests that these discordant results may frequently lead to different chemotherapy choices based upon which assay had been selected to guide decision making.
Efficacité et complications de la résection par mucosectomie des adénomes duodénaux
Authors: V Lépilliez, T Ponchon, B Napoléon, A Wassouf, B Parmentier, JC Saurin
Journal: Endoscopy (2006)

L'adénome duodénal a une prévalence faible en dehors de la polypose adénomateuse familiale. Seules de petites séries de traitement endoscopique de ces lésions ont été publiées. Nous présentons une série importante réalisée dans 2 centres universitaires lyonnais.
Pharmacogenetic analysis of UGT1A1, UGT1A6, UGT1A7 and thymidylate synthase in a phase II study of capecitabine plus irinotecan in patients with metastatic colorectal cancer
Authors: L. E. Carlini, N. J. Meropol, Y.-M. Chen, C. McGarry, T. Hill, P. Gold, R. L. Blanchard
Journal: Journal of Clinical Oncology (2004)

3623 Background: Capecitabine (CAP) and irinotecan (IR) are used in the treatment of colorectal cancer (CRC). SN-38, the active metabolite of IR, is metabolized by several UDP-glucuronosyltransferases including UGT1A1, UGT1A6, and UGT1A7. Although UGT1A1 genotype has previously been correlated with IR toxicity, the association between other UGT genotypes and IR response or toxicity has not been determined. CAP is a prodrug of 5-fluorouracil (5FU) that inhibits thymidylate synthase (TS). Although genetic polymorphisms in TS have been associated with antitumor response to 5FU, such relationships are not well established with CAP. The objective of this study was to evaluate the impact of genetic polymorphisms in UGT1A1, UGT1A6, UGT1A7, and TS on response and toxicity in patients with CRC treated with CAP/IR. Methods: 67 chemotherapy-naïve patients (pts) with measurable metastatic CRC were treated with IR (100–125 mg/m2 intravenously on days 1 and 8), plus CAP (orally 900-1000 mg/m2 twice daily on days 2–15). DNA was genotyped using Pyrosequencing, dye terminator sequencing, and GeneScan technologies. Results: The overall response rate was 42% (RECIST Criteria). 26 pts (39%) had CTC grade 3–4 diarrhea, and 7 pts had grade 3–4 neutropenia (10%). Low activity UGT1A7 genotypes, UGT1A7*2/*2 (6 pts) and *3/*3 (7 pts), were significantly associated with antitumor response (p=.005, 11 of 13 patients) and lack of toxicity (p=0.01, only 1 of 13 patients exhibited severe toxicity). There were no statistically significant associations between UGT1A1, UGT1A6 or TS genotypes and toxicity or antitumor response. Conclusions: These data suggest, for the first time, that UGT1A7 genotype may be a useful predictor of response and toxicity in patients with CRC treated with irinotecan-based therapy. Specifically, patients with genotypes associated with low metabolic capacity may be particularly likely to exhibit an antitumor response with little toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Labs Roche Labs Roche Labs Roche Labs Roche Labs
Cyclic Nucleotide Phosphodiesterase and Protein Activator in Human Cancer Cell Lines and Brown-Pearce Carcinoma
Authors: Yung Pin Liu, Vernon G. Wong, Bruce A. Chabner
Journal: JNCI Journal of the National Cancer Institute (1977)

3′:5′-Cyclic-AMP phosphodiesterase (EC 3.1.4.17) and the activating factor of cyclic nucleotide phosphodiesterase were detected in cultured human cell lines from patients with lymphoblastic leukemia and retinoblastoma and in the Brown-Pearce (rabbit) carcinoma. The homogenate of lymphoblasts contained levels of the activating factor in excess of that required to produce maximal activation of the endogenous phosphodiesterase. The activating factor found in these malignant cells appears to be similar to the calcium-binding protein activator of bovine brain phosphodiesterase on the basis of the molecular weight obtained from gel filtration, electrophoretic patterns, calcium requirement for the activity, and the effect of calcium on the proteolysis. In addition, the tumor-derived activator was able to restore the activity of activator-deficient phosphodiesterase from the bovine brain.