tbuckley/cabot-search huggingface dataset:
Abstract 4: ABT-263 is effective in a subset of non-small cell lung cancer cell lines
Authors: Aoi Kuroda, Keiko Ohgino, Hiroyuki Yasuda, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Tetsuo Tani, Shigenari Nukaga, Ichiro Kawada, Katsuhiko Naoki, Kenzo Soejima, Tomoko Betsuyaku
Journal: Cancer Research (2015)

Abstract Rationale: ABT-263 (Navitoclax) is one of the BH3 mimetics targeting anti-apoptotic B-cell lymphoma-2 (Bcl-2) family proteins such as Bcl-2, Bcl-XL, and Bcl-w, thereby inducing apoptosis. It has been reported that the response to ABT-263 is associated with expressions of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein. Given its effectiveness as a single agent in preclinical studies, ABT-263 is currently being evaluated in clinical trials for small cell lung cancer (SCLC) and leukemia. However, the efficacy of ABT-263 in non-small cell lung cancer (NSCLC) has not been fully evaluated. We examined the effect of ABT-263 on cell proliferation of NSCLC cell lines and investigated the underlying mechanisms. Methods: The following 9 NSCLC cell lines were examined: SK-LU-1, A549, H358, Calu3, H3122, H1975, H460, H441, and BID007. The effects of ABT-263 in NSCLC cell lines were evaluated by MTS assay. Apoptosis was examined by flowcytometry using staining for annexin V and propidium iodide (PI), and also western blotting for cleaved PARP. Quantitative RT-PCR was carried out to assess the mRNA expression levels of anti-apoptotic genes and pro-apoptotic genes. Immunoprecipitation and western blotting were performed to compare the levels of anti-apoptotic and pro-apoptotic proteins between the sensitive and resistant cell lines. In addition, knockdown of Mcl-1 was performed by siRNA. Results: By screening 9 NSCLC cell lines using MTS assay, we found Calu3 and BID007were sensitive to ABT-263. We also confirmed that apoptosis was induced only in the ABT-263 sensitive lines but not in the ABT-263 resistant cell lines after ABT-263 treatment. However, the expression levels of Bcl-2 family proteins, including Mcl-1, did not differ significantly among the ABT-263 sensitive and resistant cell lines. Unlike the results in previous reports regarding SCLC, Mcl-1 was not decreased in the sensitive cell lines. The ABT-263 resistant cell lines became sensitive to ABT-263 after knockdown of Mcl-1 by siRNA, while the ABT-263 sensitive cell lines maintained the same sensitivity. Conclusion: We found that Calu3 and BID007 were sensitive to ABT-263. In the sensitive NSCLC cell lines, ABT-263 induces apoptosis irrespective of Mcl-1 expression levels. Citation Format: Aoi Kuroda, Keiko Ohgino, Hiroyuki Yasuda, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Tetsuo Tani, Shigenari Nukaga, Ichiro Kawada, Katsuhiko Naoki, Kenzo Soejima, Tomoko Betsuyaku. ABT-263 is effective in a subset of non-small cell lung cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4. doi:10.1158/1538-7445.AM2015-4
SUPPLEMENT 2250
Authors: L NICHOLLS
Journal: BMJ (1948)

Before the war Malaya was prosperous owing to the export of large quantities of rubber, tin, and coconut produce.The imports consisted largely of food, consumer goods, machinery, and motor vehicles.Food Available in 1949 The staple article of diet of the population of Malaya was rice; about two-thirds of the rice consumed in the country was imported from Burma, Thailand, and to a lesser extent from .jndo-China and other countries of the Far East.In 1940 the principal imports of foods of vegetable origin were: rice, 646,076 tons; wheat flour and prepared cereals, 91,243 tons; pulses (dhals, peas, and beans), 36,304 tons; and sugar, &13,935 tons.The population of Malaya may be estimated at between 5t and 6 million persons.Taking the figure of 6 millions, a calculation of these imported foods in terms of calories daily per head of the population gives the following: lb. per Head per Year Calories per Head Daily Rice.240 1,000 Wheat and other cereals .. 33 140 Pulses .13'50 Sugar .42-180 Total... 1,370The foodstuffs of animal origin that were imported and used in Malaya appear impressive at first sight: 25,117 head of cattle; 212,281 pigs, sheep, or goats; 1,365,972 poultry; over one hundred million eggs; 1,145,765 cases of condensed milk; and 1,209,626 lb. of dried milk.But these do not give mores 4han 30 calories daily per head of the population.During 1940, therefore, foodstuffs to the value of about 1,400 calories daily per head were imported into Malaya.After the outbreak of war in Europe a drive was started to produce more food, and some progress was made before the Japanese invaded Malaya.The estimates of the Agricultural Department for 1940 indicate that 812 calories daily per head were obtainable from foods, other than oils, grown in the Kcountry.The amount of fish and meat available would have been about 100 calories in value.There was ample oil in the form of coconut products and red palm oil.Thus a conservative estimate of the calories per head daily available in 1940 is: imported foodstuffs, 1,400; rice grown locally, 560; roots, bananas, etc., 202; garden vegetables, 50; fish and meat, 100; oils, at least 250.Total, 2,562 calories.JThe rice, roots, banana, and garden vegetable figures are Agricultural Department estimates.The Food Position under the Japanese The quantity of rice and other foodstuffs imported during the Japanese occupation is not known.But the havoc of war had prevented cultivation in vast areas of Burma, the greatest
Abstract 13414: Impact of Atorvastatin on Development of New-onset Diabetes Mellitus in Asian Population: Three-year Clinical Follow up Results
Authors: Yoonjee Park, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Raghavender Goud Akkala, Sun ki Lee, Ji Bak Kim, Sung Il Im, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2013)

Background: Although statin therapy is beneficial for vascular diseases, the relationship between specific statin therapy and the incidence of new-onset diabetes mellitus (DM) remains uncertain. We...
Abstract 1844: Increased Mortality And Perioperative Complications In Patients After Previous Elective Percutaneous Coronary Interventions Undergoing Coronary Artery Bypass Surgery
Authors: Nikolaos Bonaros, Diana Hennerbichler, Hannes Alber, Alfred Kocher, Otmar Pachinger, Guenther Laufer, Johannes Bonatti
Journal: Circulation (2007)

Introduction. The number of patients with previous Percutaneous Coronary Interventions (PCI) referred to Coronary Artery Bypass Grafting (CABG) is continuously increasing. The relationship between previous elective PCI and the perioperative outcome after CABG remains undetermined. The aim of the study was to investigate whether patients referred to CABG after previous elective PCI have an increased perioperative risk. Methods. Between January 2002 and May 2007, 4412 consecutive patients underwent first-time open heart surgery at our department. After excluding patients with a history of emergent PCI, we isolated 306 patients after previous elective PCI during the last 24 months before CABG (Group 1). Those patients were compared to 452 consecutive patients without history of previous PCI, who underwent CABG during the same period and who were matched for age, gender and preoperative risk factors (Group 2). Both groups were compared in terms of 30-day mortality, Major Adverse Cardiac Events (MACEs), and perioperative complications. Results. Both groups were comparable concerning preoperative linear EuroSCORE (Group 1: 4.83±0.18, Group 2: 4.72±0.14, p=0.63). Patients with previous elective PCI before CABG had increased perioperative mortality (Group 1: 3.3% vs Group 2: 1.9%, p&lt;0.001) and MACEs (Group 1: 7.9% vs 4.3%, p&lt;0.001). This fact was associated with a worse logistic perioperative outcome (Group 1: 1.26±0.39, Group 2: 2.33, p=0.044). In addition, the incidence of bleeding complications (Group 1: 5.9% vs Group 2: 3.8%, p=0.017) and the number of blood products (Group 1: 1.70±0.31 vs 0.61±0.17, p&lt;0.001) used were higher in patients of the Group 1. A higher incidence of acute renal failure (Group 1: 5.9% vs 2.7%, p=0.025) and renal replacement therapy (Group 1: 3.6% vs Group 2: 1.7%, p=0.03) was observed in patients of the same group. Conclusions. Patients with previous elective PCI before referral to CABG have a worse perioperative outcome in terms of mortality, MACE and perioperative complications as compared to patients with no history of PCI.
Nitroprusside in Critically Ill Patients with Aortic Stenosis
Authors: Pradeep K. Agarwal, Rekha Kumari
Journal: New England Journal of Medicine (2003)

regarding the use of nitroprusside in patientswith severe aortic stenosis and severe left ventricularsystolic dysfunction is encouraging. However, we donot agree with the authors that nitroprusside is asafe drug. It has a very narrow therapeutic win-dow and requires close monitoring. Nitroprusside-induced cyanide intoxication may be fatal.
Synergistic interaction between all-trans retinoic acid, Herceptin, and tamoxifen in BT-474 human breast cancer cells.
Authors: Debbie C. Koay, Michael P. Digiovanna
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2205 

HER-2/neu and estrogen receptor (ER) play critical roles in breast cancer. HER-2/neu and ER are validated therapeutic targets; the anti-HER-2/neu antibody Herceptin and the antiestrogen tamoxifen are effective drugs targeting these two receptors. Retinoids have also been shown to inhibit breast cancer growth. We find that all-trans retinoic acid (atRA) downregulates phosphorylation of HER-2/neu and decreases ER activity in BT-474 human breast cancer cells. We thus hypothesize that treatment with atRA and simultaneous targeting of HER-2/neu and/or ER may synergistically inhibit growth of breast cancer cells. We find that combining atRA with Herceptin, tamoxifen, or both results in strong synergistic growth inhibition of BT-474 breast cancer cells. To elucidate the molecular mechanisms underlying this synergistic growth inhibition, we examined the effects of these various drug combinations on cell cycle and apoptosis. We find that atRA, Herceptin, and tamoxifen all lead to an enhanced accumulation of cells in G0/G1 phase coupled with a reduction of cells in S phase of cell cycle. Furthermore, while neither atRA, Herceptin, tamoxifen, nor the Herceptin/tamoxifen combination induce apoptosis, the combination of atRA with Herceptin or with the Herceptin/tamoxifen combination does induce apoptosis. These findings suggest that there are synergistic interactions between atRA, Herceptin, and tamoxifen. Treatment with atRA and simultaneous inhibition of HER-2/neu and/or ER signaling may translate into improved therapy for breast cancer patients.
川崎病并发严重肾功能不全、液气胸、重度贫血一例
Authors: 孙少勇, 姚莉, 孙桂林, 马艳华
Journal: BMJ (2011)

患儿男,5个月,因发热7 d、呼吸困难5 d、加重1 d于2008年3月29日入院.患儿7 d来持续发热,体温最高39.5℃,不伴寒战;近5 d患儿出现呼吸困难,呼吸增快,50～60次/min,伴鼻扇及三凹征,吃奶少;近1 d呼吸困难加重,伴呻吟,口周发绀,曾在当地医院按肺炎、心力衰竭治疗5 d,给予头孢哌酮舒巴坦钠及去乙酰毛花苷(西地兰)治疗,因病情加重,转入我院.追问病史,患儿于发病第3天出现皮疹,双眼结膜稍充血。
Global vaccine initiative creates inequity, analysis concludes
Authors: Gavin Yamey
Journal: BMJ (2001)

An analysis of the operation of the Global Alliance for Vaccines and Immunization (GAVI), the private-public venture launched last year with a $750m (£500m) donation from the Bill and Melinda Gates Foundation, has concluded that it overemphasises high tech vaccines, lacks sustainability and transparency, and relies too heavily on private sector funding.

The alliance, whose founding partners include the World Health Organization, Unicef, the World Bank, and some national governments, aims “to fulfil the right of every child to be protected against vaccine-preventable diseases of public health concern” (www.vaccinealliance.org).

The analysis, by Dr Anita Hardon, …
Glucose Metabolism of the Isolated Eccrine Sweat Gland
Authors: Kenzo Sato, Richard L. Dobson
Journal: Journal of Clinical Investigation (1973)

This paper attempts to further clarify the characteristics of Mecholyl- or epinephrine-stimulated glucose metabolism in the isolated monkey eccrine sweat gland with special emphasis on its relationship to increased sodium transport. The Mecholyl- or epinephrine-stimulated glucose metabolism (as estimated by either lactate or (14)CO(2) production or both) is seen only in the secretory coil and not in the duct. It is markedly suppressed in the absence of glucose, Na(+), or K(+). It is inhibited by ouabain (10(-3) M) and partially suppressed in a low-sodium (40 mM), high-potassium (100 mM) medium.2,4-dinitrophenol (10(-4) M) reverses ouabain-induced inhibition of lactate and (14)CO(2) production but only partially reverses inhibition induced by Na(+) + K(+) deprivation, indicating that metabolic inhibition by ouabain is secondary to the inhibition of sodium transport. There is no synergism between Mecholyl and epinephrine. The absence of any significant inhibitory effects by acetazolamide (Diamox) or HCO(3) (-)-free media suggests that H(+) transport may not be important in sweat gland function. In contrast to a report by Wolfe et al., human eccrine sweat glands show considerable oxidative activity ((14)CO(2) production of 0.42-0.72 nmol/gland/h). These observations are discussed in terms of the linkage between sweat gland energy metabolism and sodium transport.
Fortnightly Reviews: Failure to thrive
Authors: H Marcovitch
Journal: BMJ (1994)

points * Failure to thrive may be the end point of any combination of a nutritional disorder, poor growth, and psychosocial deprivation * Normal short children do not need investi- gation.The clues might be very low birth weight, low mid-parental height, normal growth velocity, and no observable illness * Growth charts are an essential part of child health surveillance but need careful interpre- tation.It is not axiomatic that a healthy child should grow along a particular centile line * Hospital admission is rarely necessary and may be counterproductive.Day attendance, for investigation and observation of child-parent interaction, may be more valuable Box 1-Differential diagnoses in children who may be failing to thrive * Normal child of short stature 0 Severe developmental delay * Idiosyncratic growth pattern 0 Chronic infection (urinary tract, lung) * Breast feeding failure * Gastrointestinal disorders * Formula feed errors 0 Metabolic disease * Non-organic failure to thrive 0 Congenital heart disease * Breast feeding failure * Errors in artificial feeding * Inability to feed optimally, as in impaired mental or motor development or owing to anomalies such as cleft palate * Chronic illness (for example, congenital heart disease,"9 cirrhosis, chronic renal failure, chronic or recurrent urinary tract infection) * Bizarre diets2' (for example, unorthodox health beliefs, Munchausen syndrome by proxy) * Chronic subdural haematoma (likely to be due to non-accidental injury)
Complement Activation in Paroxysmal Nocturnal Hemoglobinuria (PNH) Causes Oxidative Damage Which May Affect Response to Eculizumab
Authors: Michela Sica, Annamaria Pellecchia, Margherita Berardi, Lucia Gargiulo, Tolulase A Olutogun, Giovanni Caocci, Giorgio La Nasa, Maria De Angioletti, Lucio Luzzatto, Rosario Notaro
Journal: Blood (2014)
Abstract 15228: Hyperleptinemia Exacerbates High Fat Diet-mediated Atrial Remodeling and Fibrillation
Authors: Yuki Ebata, Akira Fukui, Hidekazu Kondo, Shotaro Saito, Ichitaro Abe, Kohei Aoki, Tetsuji Shinohara, Yasushi Teshima, Tetsunori Saikawa, Naohiko Takahashi
Journal: Circulation (2014)

Introduction: Obesity is an independent risk factor of atrial fibrillation (AF). Although serum leptin levels have been reportedly up-regulated in subjects with obesity and metabolic syndrome (leptin resistance), the relation of hyperleptinemia and AF remains to be solved. Hypothesis: We tested the hypothesis whether hyperleptinemia could exacerbate high-fat-diet (HFD)-mediated AF. Methods: Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob mice (Ob) were treated either with normal-fat-diet (NFD) or 60% HFD. Eight weeks later, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed. The effect of leptin antagonist (LAnt) was also examined using osmotic mini-pump in WT-HFD mice. Results: 1) HFD increased body weight and plasma leptin concentration in WT mice (both p&lt;0.01). 2) Masson trichrome staining revealed that heterogeneous interstitial LA fibrosis was evident in WT-HFD, which was not observed in Ob-HFD (p&lt;0.05). Up-regulation of collagen1, α-SMA, TNF-α, and MCP-1 mRNA levels observed in WT-HFD mice LA, was attenuated in Ob-HFD mice. 3) While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, it induced AF less frequently (1/8, 12.5%) in Ob-HFD mice (p&lt;0.01). 4) In isolated perfused heart experiments, interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (p&lt;0.05). 5) Western immunoblotting revealed up-regulated expressions of phosphorylated-calmodulin kinase II (p-CamKII) and Na+-Ca2+ exchanger in WT-HFD mice (both p&lt;0.01). However, these changes were attenuated in Ob-HFD mice. 6) LAnt treatment for 4 weeks attenuated the AF inducibility assessed by transesophageal burst pacing (8/8 vs 2/8, p&lt;0.05). Conclusions: Our findings suggest that hyperleptinemia (leptin resistance) plays an essential role in HFD-mediated atrial remodeling and AF. Inhibition of leptin or leptin signaling may become a novel therapeutic target to prevent obesity-related AF.
Alpha-fetoprotein-L3: Useful or Useless for Hepatocellular Carcinoma?
Authors: M Kudo
Journal: Liver Cancer (2013)

Alpha-fetoprotein-L3: Useful or Useless for Hepatocellular Carcinoma?Japan is the only country where alpha-fetoprotein (AFP)-L3 can be measured in the routine clinical setting.Since AFP-L3 examination has been covered by health insurance in Japan for over 10 years, it is now routinely measured during general medical checkups for patients with chronic liver disease.To increase the specificity of AFP, the AFP-L3 glycoform can be used as a measure of cancerous changes in the AFP composite carbohydrate moiety.The most frequently used cut-off value is 10% [1], which gives a positive rate of 0/71 (0.0%), 1/90 (1.1%), 0/13 (0.0%), 0/14 (0.0%), and 18/82 (22.0%) for chronic hepatitis, hepatic cirrhosis, dysplastic nodules, early hepatocellular carcinoma, and advanced hepatocellular carcinoma, respectively.This yields a sensitivity of 18.8% and a specificity of 99.4%.Therefore, although AFP-L3 has high specificity, due to its low sensitivity, it is considered to be of limited use in screening.It is possible, however, to diagnose a marginally higher number of patients with advanced hepatocellular carcinoma [2].Furthermore, as AFP-L3 may be elevated during hepatic failure, interpretation should be made with caution.AFP-L3 dynamics are largely related to the degree of biological malignancy of hepatocellular carcinoma [2,3].Results of pathological investigations conducted on patients who have undergone hepatic resection showed that those with infiltrative growth, capsular invasion, septum formation, portal vein infiltration, and hepatic vein infiltration were significantly more likely to have AFP-L3-positive (>10%) cancer [4].To investigate cases of hepatocellular carcinoma for which therapeutic intervention was given and in which tumor markers were measured chronologically, an investigation was conducted prior to therapeutic intervention with a group of 196 AFP-L3-positive (>10%) patients and a group of 645 AFP-L3-negative patients.When the overall survival rate was compared between the AFP-L3-positive and negative groups, the latter group showed more favorable survival than the former group (p < 0.001).When the AFP-L3 dynamics before and at six months after treatment were compared, 599 cases remained negative, 113 remained positive, 83 underwent conversion from positive to negative (negative conversion), and 46 underwent conversion from negative to positive (positive conversion).When survival rates were investigated, the constantly negative and negative conversion groups had more favorable survival rates than the constantly positive and positive conversion group.In other words, even though there are AFP-L3-positive cancers with poor prognosis and a
Abstract A42: Paracrine regulation of the pancreatic cancer epigenome
Authors: Mara H. Sherman, Eric Collisson, Michael Downes, Ronald M. Evans
Journal: Cancer Research (2015)

Abstract Development of pancreatic ductal adenocarcinoma (PDAC) follows an increasingly well-defined series of genetic events in the pancreatic epithelium. Less well understood are the steps orchestrating the exuberant desmoplasia that accompanies every case of PDAC. This accumulation of stromal components arises from and is maintained by the reciprocal interactions between genetically altered tumor cells and adjacent stroma. Pancreatic stellate cells (PSCs) are myofibroblast-like cells activated by tissue damage and implicated in wound healing. Recent work suggests that PSCs are key primary drivers of the desmoplastic reaction that characterizes the disease, possibly through their established secretory capacity. We wished to explore the paracrine effects of PSC secreted factors on gene expression in pancreatic cancer cells. To investigate the global gene expression changes induced by stromal factors, PDAC cell lines were grown in “a-stromal” or “stromal” conditions. The addition of structural and diffusible PSC-derived factors significantly altered expression of thousands of genes in the cancer genome, suggesting that these factors exert genome-wide effects on the epigenetic state to so broadly affect transcription level. Stromal inputs lead to broad hyperacetylation of histones in the PDAC epigenome, particularly on gene-activating lysines on histone tails. These epigenetic events coincided with induction of genes implicated in anabolic metabolism, the glycosylation pathway, and inflammation. The gene expression changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental cues characteristic of PDAC. As epigenome modification results in changes in gene expression through the functions of readers, we tested a small molecule inhibitor of a family of epigenetic readers for the capacity to inhibit gene expression changes downstream of stromal factors. Paracrine induction of pro-growth and inflammatory genes was inhibited by this small molecule, suggesting that acetyl-lysine readers serve as key transducers of stromal inputs to drive alterations in gene expression in pancreatic cancer cells. Inhibition of acetyl-lysine sensing reduced pancreatic tumor growth and associated inflammation in vivo, with significant reduction in expression of genes implicated in macromolecule biosynthesis and tumor-permissive immune regulation. This work supports further investigation of epigenetic modulators, in combination with targeted drugs or immunotherapeutic approaches, for the treatment of PDAC. Citation Format: Mara H. Sherman, Eric Collisson, Michael Downes, Ronald M. Evans. Paracrine regulation of the pancreatic cancer epigenome. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A42.