tbuckley/cabot-search huggingface dataset:
Impact of a dedicated supportive care center telephone triaging program (SCCTP) for patients with advanced cancer.
Authors: Lindsey E Pimentel, Sriram Yennurajalingam, Gary B. Chisholm, Tonya Edwards, Maria Guerra-Sanchez, Maxine Grace Jaucian De La Cruz, Marieberta Vidal, Kimberson Tanco, Eduardo Bruera
Journal: Journal of Clinical Oncology (2013)

54 Background: Due to high symptom burden in advanced cancer patients, ongoing symptom management for outpatient palliative care patients is vital. More patients are receiving outpatient care; Yet, most palliative care patients receive less than 2 follow ups. Nurse telephone care can improve quality of life in these patients. Our aim was to determine frequency and care provided by Supportive Care Center Telephone Program (SCCTP) in advanced cancer patients. Methods: 400 consecutive patients who utilized palliative care service, 200 from outpatient Supportive Care Center (SCC) and 200 from inpatient Palliative Care (IPC), were followed for 6 months starting 3/2012 to examine call frequency and reason and outcomes including pain and other symptoms [Edmonton Symptom Assessment Scale (ESAS) and Memorial Delirium Assessment Scale (MDAS)] associated with utilization of SCCTP. We also examined the effect of SCCTP interventions on pain, ESAS and counseling needs. Results: 375 patients were evaluable. Median age 59 years, 53% female, 70% white. Most frequent cancer type were gastrointestinal (20%, p &lt; 0.0001) for IPC and thoracic (23%, p &lt;0.0001) for SCC. SCC patients had higher prevalence of CAGE positivity (28% SCC vs 11% IPC, p &lt;0.0001), ESAS SDS(p=0.0134), depression(p=0.0009), anxiety(p=0.0097) and sleep(p=0.0015); MDAS scores were significantly higher in IPC (p&lt;0.0001).115/400 patients (29%) utilized SCCTP. 96/115 outpatients (83%) used the SCCTP vs 19/115 IPC (17%). Common reasons for calls were pain (24%), pain medication refills (24%) and counseling (12%). Of 115 phone calls, 340 recommendations were made; 43% (145/340) were regarding care at home; 56% of these recommendations were regarding opioids. Patients who utilized SCCTP had worse pain(p=0.0059), fatigue(p=0.0448), depression(p=0.0410), FWB(p=0.0149) and better MDAS scores(p=0.0138) compared to non-utilizers. Conclusions: There was more frequent SCCTP use by outpatients than inpatients. Most common reason for utilization was pain control. Frequently, recommendations were made to continue symptom management at home. Patients who utilized SCCTP had worse pain, fatigue, depression, well-being scores and better delirium scores.
Tissue biomarkers (BIOM) in colon cancer (COC): The translational study on the randomized phase III trial comparing infused irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) to 5-FU/FA in stage II-III COC patients (pts)
Authors: A. D. Roth, S. Tejpar, P. Yan, R. Fiocca, D. Dietrich, G. Bodoky, R. Labianca, D. Cunningham, E. Van Cutsem, F. Bosman
Journal: Journal of Clinical Oncology (2007)

4022 Background and Aims: PETACC 3 is a large adjuvant trial with 3,005 COC pts. The value of BIOM in COC in adjuvant setting is still a matter of debate because of lack of large data sets. We took advantage of PETACC 3 to assess P53, SMAD4, thymidylate synthetase (TS), telomerase (HTERT) expressions, UGT1A1 genotype, KRAS and BRAF mutations, microsatellite instability (MSI), 18q and 8p LOH with regard to their prognostic and predictive value and their individual interactions on a very large homogeneous cohort of COC pts. In addition we investigated the association between UGT1A1 genotype and occurrence of diarrhoea and Gd 4 neutropenia. Methods: 1,564 formalin fixed paraffin embedded (FFPE) tissue blocks of PETACC 3 pts were prospectively collected and 5–20μ sections cut. DNA from normal (Nor) and tumoral (Tu) tissue was extracted after section microdissection. P53, SMAD4, TS and HTERT were assessed by immunohistochemistry (IHC); MSI was typed with 10 markers, KRAS exon 2 and BRAF exon 15 mutations by allele specific real time PCR on Tu DNA; 18q and 8p LOH by typing multiple SNPs by pyrosequencing on Nor/Tu DNA; UGT1A1 genotypes by PCR and fragment sizing on Nor DNA. Prognostic/predictive value of each BIOM is analysed by Cox regression for disease free survival and by logistic regression for specific toxicity. Associations between any 2 categorized BIOM and between each BIOM and each known prognostic variable are tested by chi-square tests. Results: DNA of 1405 pts was extracted and successfully analyzed in 97.1% for KRAS, 98.6% for BRAF, 94% for 18q LOH, 93.6% for MSI, 86% for UGT1A1, 8p LOH is still ongoing. Of 1530 pts slides IHC analysis was successful in 94.5% for P53, 94.2% for SMAD4, 82.9% for TS, 53.9% for HTERT. The clinical database was made available in Nov 06 and statistical analysis started on Dec 11th 2006. Conclusion: This is the largest multicenter centrally coordinated tissue BIOM study performed in COC to date. The high success rate of analysis shows that large prospective BIOM studies can be performed on routine FFPE material. Final results on the prognostic/predictive value of each molecular BIOM will be available at the meeting. No significant financial relationships to disclose.
Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury
Authors: G Serviddio, F Bellanti, R Tamborra, T Rollo, N Capitanio, A D Romano, J Sastre, G Vendemiale, E Altomare
Journal: Gut (2008)

<h3>Background:</h3> The mechanisms of progression from fatty liver to steatohepatitis and cirrhosis are not well elucidated. Mitochondrial dysfunction represents a key factor in the progression of non-alcoholic steatohepatitis (NASH) as mitochondria are the main cellular site of fatty acid oxidation, ATP synthesis and reactive oxygen species (ROS) production. <h3>Aims:</h3> (1) To evaluate the role of the uncoupling protein 2 in controlling mitochondrial proton leak and ROS production in NASH rats and humans; and (2) to assess the acute liver damage induced by ischaemia–reperfusion in rats with NASH. <h3>Methods:</h3> Mitochondria were extracted from the livers of NASH humans and rats fed a methionine and choline deficient diet. Proton leak, H<sub>2</sub>O<sub>2</sub> synthesis, reduced glutathione/oxidised glutathione, 4-hydroxy-2-nonenal (HNE)–protein adducts, uncoupling protein-2 (UCP2) expression and ATP homeostasis were evaluated before and after ischaemia–reperfusion injury. <h3>Results:</h3> NASH mitochondria exhibited an increased rate of proton leak due to upregulation of UCP2. These results correlated with increased production of mitochondrial hydrogen peroxide and HNE–protein adducts, and decreased hepatic ATP content that was not dependent on mitochondrial ATPase dysfunction. The application of an ischaemia–reperfusion protocol to these livers strongly depleted hepatic ATP stores, significantly increased mitochondrial ROS production and impaired ATPase activity. Livers from patients with NASH exhibited UCP2 over-expression and mitochondrial oxidative stress. <h3>Conclusions:</h3> Upregulation of UCP2 in human and rat NASH liver induces mitochondrial uncoupling, lowers the redox pressure on the mitochondrial respiratory chain and acts as a protective mechanism against damage progression but compromises the liver capacity to respond to additional acute energy demands, such as ischaemia–reperfusion. These findings suggest that UCP2-dependent mitochondria uncoupling is an important factor underlying events leading to NASH and cirrhosis.
儿童血压的测量——理论上应该列为常规，实际工作中却少有行动
Authors: Chris, Colin, Michie, 张扬红
Journal: BMJ (2009)

儿童应当测量血压的理论尽管已经众所周知，但临床上很少付诸行动。虽然有综述称“测量血压已经成为儿科常规查体的一个重要部分，可实际情况并非如此。在美国和澳大利亚，就诊于急诊科的儿童只有5．3％～66％测量过血压24，而英国约为9％。急诊科给就诊的成年人测量血压已经成为习惯，为什么对儿童就做得不够呢？
Circulating cancer cells (CCC) in non-small cell lung cancer (NSCLC): incidence and preliminary observations on prognostic significance and potential for individualized therapy
Authors: M. J. Edelman, S. Bisaccia, R. Smith, S. Lesko, Z. P. Lum, P. O. P. Ts’o
Journal: Journal of Clinical Oncology (2005)

7205 Background: There is a need to improve our ability to monitor the status of NSCLC during therapy as well as to determine relapse. In addition, there is a need to more rationally select therapeutics based upon the molecular characteristics of the tumor. Repetitive biopsy of NSCLC is not feasible. CCC are present in a range of malignancies and have been documented to correlate with disease activity. In addition, cells can be stained for markers of chemotherapeutic sensitivity including ERCC1, beta tubulin III and RRM1. Methods: Patients with Stage III or IV NSCLC undergoing therapy were evaluated utilizing the BloodBiopsy system. 20 cc. of blood was drawn and are isolated utilizing a negative selection technique which involves density gradient centrifugation and immunomagnetic cell sorting to to remove RBC and WBC. Cells are then stained with a pan anti-cytokeratin fluorescently labeled antibody cocktail and counted utilizing atutomated immunofluorescence microscopy. Three fluorescent labeled monoclonal antibody markers can be assessed. Digital images can be quantitatively analyzed. Preliminary evaluations with blood spiked with NSCLC cell lines were performed. Results: 24 patients were evaluated with at least one determination, 14 had two or more determinations. Stage III A or B (without effusion) = 8, Stage IIIB (effusion) or IV = 16. 16M, 9F. Median age = 61 years. 19 79%(95% CI = 58%–93%) demonstrated CCC at some point in their disease, 12 50% (95%CI = 29%–71%) at baseline. When present, the number of cells detected varied from 1–11 (mean=4, median =2). There was no clear correlation between presence/absence and number of CCC and outcome, but the numbers are small. In vitro marker studies utilizing the system have been successfully performed and pt samples are now being analyzed. Conclusions: 1. Circulating cancer cells are present in the majority of patients with locally advanced (Stage III a and nodal IIIb) and advanced (IIIb (effusion) and IV) NSCLC. 2. It is unclear whether CCC correlate with disease activity. 3. It is feasible to analyze these cells for putative markers of drug sensitivity. Supported in part by NCI SBIR Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CCC Diagnostics CCC Diagnostics
Ifosfamide: an active drug in the treatment of adenocarcinoma of the pancreas.
Authors: P J Loehrer, S D Williams, L H Einhorn, R Ansari
Journal: Journal of Clinical Oncology (1985)

From April 1982, until February 1984, 29 patients with biopsy-proven and measurable adenocarcinoma of the pancreas were treated with ifosfamide. Ifosfamide was administered at a dose of 1.25 to 1.5 g/m2 daily for five consecutive days with courses repeated every three weeks. If no serious toxicity was noted, subsequent dosages were escalated to a maximum of 2.0 g/m2/d. In addition, N-acetylcysteine (NAC) (8 to 12 g/d) was administered (in divided daily doses days 1 through 7) as a urothelial protective agent. Nausea and vomiting occurred in the majority of the treated patients. Other toxicities noted were mild myelo-suppression, CNS toxicity, and one case of acute renal failure. One complete response (CR) and five partial responses (PR) were observed in 27 evaluable patients (CRs and PRs = 22%). Ifosfamide has definite activity against pancreatic adenocarcinoma. Doses greater than 1.2 g/m2 for days 1 through 5 can be administered without significant toxicity in the majority of patients. Further trials with ifosfamide alone and/or with other agents are warranted.
Fluid Shear Stress Attenuates Tumor Necrosis Factor-α–Induced Tissue Factor Expression in Cultured Human Endothelial Cells
Authors: Yutaka Matsumoto, Yohko Kawai, Kiyoaki Watanabe, Kazuo Sakai, Mitsuru Murata, Makoto Handa, Shin Nakamura, Yasuo Ikeda
Journal: Blood (1998)
Abstract B2-21: Identification of somatic RNA splicing alterations in human cancers
Authors: Angela N. Brooks, Yawei Ge, Kevin Chau, Samuel S. Freeman, Gordon Saksena, Chandra Sekhar Pedamallu, Matthew Meyerson
Journal: Cancer Research (2015)

Abstract Recent whole-exome sequencing studies have found that somatic mutations frequently occur in splicing factors across multiple cancer types, supporting the need to systematically and globally characterize splicing alterations across human cancers. Somatic alterations that affect RNA processing of cancer genes may be caused by multiple mechanisms, including mutations in splicing factors, mutations in cis-acting splice sites and other regulatory sequences, alterations in methylation, or alterations in chromatin structure. For a global look at somatic RNA splicing alterations, we are applying the Cancer Outlier Profile Analysis (COPA) approach on ~7,000 cancer transcriptomes from 12 tumor types in The Cancer Genome Atlas (TCGA) and investigating the underlying somatic mutations that cause these splicing alterations using matched whole-exome, whole-genome, and methylation data from these samples. To identify and quantify alternative splicing in RNA-Seq data, including unannotated splicing events, we have further developed a computational pipeline called JuncBASE. To distinguish between cancer-specific splicing alterations and normal transcriptome variation, we are utilizing ~700 RNA-Seq libraries from healthy individuals from the Genotype-Tissue Expression (GTEx) project. COPA analysis of outlier splicing events in lung adenocarcinomas and glioblastomas successfully identified known altered splicing events in MET and EGFR, respectively, that are caused by DNA level somatic mutations. The genomic mechanisms for novel somatic splicing events in known cancer genes such as FGFR3, as well as genes previously uncharacterized in cancer genomes, are currently being investigated. To identify splicing events that may be novel somatic driver alterations, these events have been profiled using RNA-Seq data from the Cancer Cell Line Encyclopedia and are being used as biomarkers to identify genetic vulnerabilities in high-throughput shRNA screens. This work will have a significant impact on the identification of somatic splicing events that contribute to cancer pathogenesis. Citation Format: Angela N. Brooks, Yawei Ge, Kevin Chau, Samuel S. Freeman, Gordon Saksena, Chandra Sekhar Pedamallu, Matthew Meyerson. Identification of somatic RNA splicing alterations in human cancers. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-21.
Response of insulin-like growth factor I and renal hemodynamics to a high- and low-protein diet in the rat.
Authors: R Hirschberg, J D Kopple
Journal: Journal of the American Society of Nephrology (1991)

An increase in plasma insulin-like growth factor I (IGF-I) levels by growth hormone injection or IGF-I infusion can raise renal plasma flow and glomerular filtration rate. However, it is not known whether a more physiological stimulus for IGF-I will also increase IGF-I in the kidney and whether the increase in renal or serum IGF-I is correlated with the increase in renal plasma flow and glomerular filtration rate. Male rats were pair fed either a high-protein (36% protein, N = 9) or a low-protein but isocaloric diet (9% protein, N = 9) for 10 to 14 days. Renal plasma flow and glomerular filtration rate were then estimated by clearance measurements, and IGF-I was measured in extracted serum, liver, renal cortical tissue, and glomeruli. Body weight gain and combined kidney weight were higher in high-protein rats as compared with low-protein animals (0.86 +/- 0.02 SEM versus 0.77 +/- 0.02 g/100 g body wt; P less than 0.05), but liver weights were not different. Serum, liver, and glomerular IGF-I levels were also higher in the high-protein rats as compared with the low-protein animals (serum, 1.12 +/- 0.03 versus 0.80 +/- 0.06 U/mL, P less than 0.05; liver, 183 +/- 17 versus 117 +/- 16 mU/g wet wt, P less than 0.05; glomeruli, 7.43 +/- 0.73 versus 4.81 +/- 0.59 mU/mg of protein, P less than 0.05). In contrast, the renal cortical IGF-I levels were not different in high-protein versus low-protein rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 206: A New MicroRNA Family Regulating Cardiac Autophagy and Hypertrophy
Authors: Thomas Thum, Shashi K Gupta, Ahmet Ucar, Jan Fiedler, Leon DeWindt, Stefan Engelhardt, Johann Bauersachs, Kamal Chowdhury
Journal: Circulation Research (2012)

Pathologic growth of cardiomyocytes and derailed autophagy are major determinants for the development of heart failure, one of the leading medical causes of mortality worldwide. Here, we show the microRNA (miRNA)-212/132 family to regulate hypertrophy and autophagy in cardiomyocytes. Hypertrophic stimuli lead to the upregulation of miR-212 and miR-132 expression in cardiomyocytes, which are both necessary and sufficient to drive the hypertrophic growth of cardiomyocytes. MiR-212/132 null mice are protected from pressure-overload induced heart failure, whereas cardiomyocyte-specific overexpression of the miR-212/132 family leads to pathological cardiac hypertrophy, heart failure and lethality in mice. Mechanistically, both miR-212 and miR-132 directly target the anti-hypertrophic and pro-autophagic FoxO3 transcription factor and overexpression of these miRNAs leads to hyperactivation of pro-hypertrophic calcineurin/NFAT signalling and impaired autophagic response upon starvation. Pharmacologic miRNA inhibition by antagomir injection rescues cardiac hypertrophy and heart failure in mice, offering a possible therapeutic approach for cardiac failure.
P-071 Single-center experience with first-line S-1 plus cisplatin chemotherapy for locally advanced unresectable and metastatic gastric and gastroesophageal junction adenocarcinoma in a Caucasian population
Authors: Á. Petrányi, M. Farkas, É. Végh, G. Lakatos, G. Demeter, G. Bodoky
Journal: Annals of Oncology (2015)
Abstract 308: Controlling Methylglyoxal To Prevent The Development Of Diabetic Cardiomyopathy
Authors: Branka Vulesevic, Ali Ahmadi, Ross Milne, Erik Suuronen
Journal: Circulation Research (2013)

Hyperglycemia caused by diabetes leads to increased glucose oxidation and mitochondrial generation of superoxide. One of the most abundant by-products of glucose oxidation is methylglyoxal (MG). MG has been implicated in the development of diabetic complications. Diabetic cardiomyopathy, characterized by systolic and diastolic dysfunction, has a complex etiology, including the accumulation of MG-formed advanced glycation end products (AGEs). Methylglyoxal is detoxified by the activities of the enzymes glyoxalase 1 (GLO1) and glyoxalase 2. We have developed a mouse line that carries a transgene encoding human GLO1 (hGlo1) under the control of the preproendothelin promoter. The hGlo1 transgene has been shown to reduce MG-derived AGEs in tissues of streptozotocin (STZ)-induced hyperglycemic mice. We have also shown that over-expression of hGlo1, solely in the bone marrow, can rescue defective post-ischemic revascularization in STZ-treated mice. In this present study, the hGlo1 mice have been used to test the hypothesis that reduced MG levels can offset the development of diabetic cardiomyopathy. Diabetes was induced by intraperitoneal injection of STZ; 4 and 8 weeks post-STZ treatment, echocardiography of the wild type (WT) diabetic group showed systolic dysfunction. At 4 weeks of hyperglycemia, the ejection fraction (EF) was 54% and fraction shortening (FS) 37%. In contrast, cardiac function in the GLO1 diabetic mice as well as non-diabetic controls remained normal over time. Both the EF and FS were significantly lower in WT diabetic mice at 4 weeks post STZ-treatment compared to the control mice (p=0.02 and p=0.04, respectively). Western blots of heart tissue collected after 8 weeks of diabetes showed a significant increase in the expression of RAGE (receptor for AGE) in WT diabetic mice compared to other groups (p=0.038). Heart tissue collected from GLO1 diabetic and non-diabetic mice had increased GLO1 activity by 1.7-fold compared to the non transgenic mice. These results suggest that MG contributes to the development of diabetic cardiomyopathy and that reducing methylglyoxal levels could be a potential therapeutic target for prevention.
Clinical impact of low-burden BCR-ABL1 mutations detectable by amplicon deep sequencing in Philadelphia-positive acute lymphoblastic leukemia patients
Authors: S Soverini, C De Benedittis, C Papayannidis, K Machova Polakova, C Venturi, D Russo, P Bresciani, A Iurlo, M Mancini, A Vitale, S Chiaretti, R Foà, E Abruzzese, F Sorà, A Kohlmann, T Haferlach, M Baccarani, M Cavo, G Martinelli
Journal: Leukemia (2016)
Proposed Guidelines for Future Vitamin D Studies
Authors: Rudruidee Karnchanasorn, Horng-Yih Ou, Ken C. Chiu
Journal: JAMA Internal Medicine (2016)

To the Editor The recent article by Hansen et al1 described a randomized clinical trial on the treatment of vitamin D insufficiency in postmenopausal women. This is a topic of great interest to us, and we would like to express some serious concerns regarding the conclusions drawn by Hansen et al.
The acceptance of “one to one” peer survivor counseling in patients with ovarian cancer.
Authors: D. Lerner, L. T. Chuang, A. Moulton, J. Rahaman, E. Rodriguez-Dumont, P. R. Dottino
Journal: Journal of Clinical Oncology (2010)

e19602 Background: “One to one” peer survivor counseling is a unique social support program offered to patients diagnosed with ovarian cancer at Mount Sinai Hospital. A peer survivor is made available to the patient at the time of diagnosis to provide support and guidance through the treatment. Our study is conducted to determine the acceptance of peer survivor counseling. Methods: A retrospective chart review of 161 consecutive patients presented for surgical management of ovarian cancers to the Gynecologic Oncology service at Mount Sinai Hospital between July 2003 and June 2007. Results: Complete data was available for 151 women, 105 patients (69.5%) were offered “one to one” peer survivor counseling. Ninety-four women (91.2%) accepted counseling and participated in the program. The median age of the participants was 59 (range 28–85) years old, 14 (14.8%) patients with stage I-II and 80 (85.1%) patients with stage III-IV disease. Majority of the participants (89.3%) spoke English as a primary language and (81.9%) of participants were Caucasian. Among the Caucasian population 89% accepted the offer for the “one to one” peer survivor counseling compared to 100% acceptance rate in non-Caucasian population (p= 0.3). In the Caucasian population that accepted counseling 35% were single, widowed or divorced compared to 58.8% in the non-Caucasian population (p= 0.1), a difference with a trend towards statistical significance. Conclusions: “One to one” peer survivor counseling is highly accepted by patients with newly diagnosed ovarian cancer. Acceptance appears to be higher in the non-Caucasian populations. This difference maybe attributed to increased need for social support in single, widowed and divorced patients. Further investigation is ongoing to determine the impact on quality of at our institution. No significant financial relationships to disclose.
The Syndrome of the Sea-Blue Histiocyte
Authors: Murray N. Silverstein, Ralph D. Ellefson, Edgar J. Ahern
Journal: New England Journal of Medicine (1970)

Nine patients had a syndrome characterized by the presence of a sea-blue histiocyte and splenomegaly. Lipid analysis of liver from the most recent patient revealed accumulations of specific glycosphingolipids and phospholipids. Urinary mucopolysaccharide excretion was increased, and there was a suggestion of mucopolysaccharide storage in the hepatic parenchymal cells. Clinically, patients with the disease may have a relatively benign course, with mild purpura secondary to thrombocytopenia, or may have progressive hepatic cirrhosis, hepatic failure and death. The name "syndrome of the sea-blue histiocyte," the striking morphologic feature of the disease, is suggested for these cases.