tbuckley/cabot-search huggingface dataset:
Abstract 100: G-Protein Coupled Estrogen Receptor1 Prevents Mitochondria Inner Membrane Protein (Mitofilin) Degradation after Ischemia/Reperfusion
Authors: Tanoya L Harris, Bjorn Olde, Fredrik L Leeb-Lundberg, Jean C. Bopassa
Journal: Circulation Research (2014)

We recently found that estrogen treatment delays the mitochondrial permeability transition pore opening and reduces ROS production after ischemia/reperfusion, suggesting that estrogen promotes mitochondrial integrity. As mitochondrial inner membrane protein (mitofilin) has been found to control mitochondrial cristae morphology and function, we investigated whether estrogen effect on mitochondrial integrity after ischemia/reperfusion involved regulation of mitofilin via activation of G-Protein Coupled Estrogen Receptor1 (GPER1). Isolated hearts from male WT (C57BL/6NCrL), and GPER1-/- mice were perfused using Langendorff technique, with and without estrogen (40 nM). Hearts were subjected to 20 min global ischemia followed by 10 min reperfusion. Mitochondria were isolated, and 2D-DIGE followed by mass spectrometry was performed. Mitofilin expression level was confirmed using Western blot analysis in mitochondrial fractions. Mitofilin distribution was visualized using confocal microscopy in isolated cardiomyocytes, and its spatial organization in mitochondria was imaged using high resolution fluorescence microscopy. Electron microscopy was used to observe mitochondrial cristae morphology. We obtained 52 unique proteins of interest, in which mitofilin was identified. Immunoblot analysis confirmed the increased in mitofilin level with estrogen treatment as compared to control in WT but not in GPER1 KO. Cardiomyocyte images revealed as observed in non-ischemic myocytes that estrogen treatment conserved mitofilin distribution in the peri-membrane and T-tubules, while only peri-membrane mitofilin was more visible in control group. High resolution microscopy showed a better spatial organization of mitofilin in single mitochondria with estrogen treatment compared to control, in which mitofilin was almost absent. Electron microscopy showed that mitochondrial morphology was conserved in estrogen-treated group as cristae were well organized compared to control, in which cristae were disrupted. These data indicate that estrogen action induces regulation of mitofilin expression during ischemia/reperfusion. Estrogen effect on mitofilin may contribute to improved mitochondrial integrity and function.
Early switching from morphine to methadone plus acetaminophen in the analgesia of oncologic patientes: A randomized, double-blind, placebo-controlled study
Authors: D. I. Cubero, W. J. David Filho, A. del Giglio
Journal: Journal of Clinical Oncology (2009)

e20579 Background: The objective of this study is to evaluate the efficacy of methadone as substitute for morphine and to investigate if the addition of acetaminophen could reduce the time to attain an equianalgesic methadone dose and to improve the level of analgesia of oncologic patients. Methods: Fifty patients in regular use of morphine with a stable dose for at least 1 week were submitted to the sudden change of this opioid for methadone and randomized in a double blind way to receive acetaminophen (750 mg PO every 6 hours) or placebo for a 7-day period. Data regarding level of pain and side effects were collected and a quality of life questionnaire (QLQ-C30) was applied. Results: Substitution of morphine for methadone resulted in improvement of the toxicity profile with reduction in obstipation (p &lt; 0.001) and xerostomia (p = 0.03). There was improvement in the Numeric Pain Scale (p = 0.03) as well as a significant improvement in the functional level and symptomatology according to the QLQ-C30 questionnaire. Addition of acetaminophen did not reflect improvement in analgesia and also reduction in time of stabilization of methadone doses. At the end of the study most patients (70.8%, p 0.001) preferred to continue with methadone instead of returning to morphine. Conclusions: Early switching from morphine to methadone showed to be safe and efficient in the reduction of side effects improvement of analgesia allowing a comfortable dosage at a lower cost. In this scenario the association with acetaminophen did not reflect improvement of analgesia or reduction in time for equianalgesia. No significant financial relationships to disclose.
Screening for Depression
Authors: Jill Jin
Journal: JAMA (2016)

Albert L. Siu, MD, MSPH; and the US Preventive Services Task Force (USPSTF); Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Linda Ciofu Baumann, PhD, RN, APRN; Karina W. Davidson, PhD, MASc; Mark Ebell, MD, MS; Francisco A. R. García, MD, MPH; Matthew Gillman, MD, SM; Jessica Herzstein, MD, MPH; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; Douglas K. Owens, MD, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH
P-114 A phase II trial of bevacizumab and erlotinib as second line therapy for advanced hepatocellular carcinoma
Authors: A. Kaseb, H. Al-Shamsi, J. Morris, M. Iwasaki, L. Xiao, R. Abdelwahab, K. Raghav, M. Hassan, H. Hassabo, R. Wolff
Journal: Annals of Oncology (2015)
Prophylatic cranial irradiation (PCI) in patients (Pts) with stage IV metastatic melanoma (MM) receiving concurrent biochemotherapy (cBCT) and maintenance biotherapy (MBT)
Authors: P. Boasberg, D. R. Minor, O. Hamid, J. S. Weber, R. Wollman, C. M. Anderson, S. J. O’Day
Journal: Journal of Clinical Oncology (2008)

20009 Background: CNS metastases occur in 40–50% of responders to cBCT. In an effort to reduce CNS progression we tested Temozolomide (TMZ) and PCI in cBCT responders. Methods: AJCC stage IV MM Pts without CNS metastases were treated initially with cBCT substituting TMZ at 150mg/m2/day × 4 days for DTIC (O’Day et al JCO: 17:2752, 1999). Study endpoint was a reduction in the incidence of CNS metastases (33% historical vs. 20% goal) at 12 months. Pts who achieved stable disease or better on cBCT received CNS consolidation with TMZ (75mg/m2/day × 4 weeks) and concurrent PCI (36 Gy in 18 fractions,5days/week). Pts then received MBT for 24 months or until clinically significant progression (ASCO: 20:352a #1405, 2001). Results: 69 Pts have enrolled with 3 CR, 27 PR, and 8 SD to induction cBCT (4 Pts non-evaluable for response - Gr IV toxicity). 68 Pts. have been followed for 12 months. Of all Pts 16 of 68 (24%) have developed CNS metastases (4 Pts CNS only) at 12 months. 34 of the 38 PCI eligible Pts (7 M1a, 11 M1b, 20 M1c) received PCI (2 refused, 2 Gr IV toxicity). Of the PCI recipients 5 (15%) developed CNS metastases prior to 12 months with 2 additional CNS relapses after 12 months. Of cBCT progression Pts (2 M1a, 7 M1b, 18 M1c) 9 of 27 (33%) developed CNS metastases prior to 12 months with 2 additional relapses after 12 months. The median survival of all Pts treated with cBCT was 12 months (14 months for PCI eligible Pts and 8 months for PCI ineligible Pts). Conclusions: There was a trend (24% actual vs. 33% historical) in the reduction of CNS metastases at 12 months for all Pts. Although the primary endpoint (20%) was not met, there was a low incidence of CNS metastases in PCI recipients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Merck, Novartis, Schering-Plough
Gene expression patterns of oncogenic signaling pathways provide a novel approach to targeted therapeutics in advanced non-small cell lung cancer (NSCLC)
Authors: A. Potti, A. Bild, H. Dressman, M. Kelley, D. Harpole, J. Nevins
Journal: Journal of Clinical Oncology (2007)

7503 Gene expression profiles reflect unique aspects of individual tumors and may characterize tumor heterogeneity in NSCLC. We used gene expression signatures that reflect the deregulation of major oncogenic signaling pathways (Ras, PI3 kinase, Akt, Src, β-catenin, E2F, and Myc) to identify patterns of pathway activation in 118 samples from patients with recurrent (n = 69) and metastatic (n = 49) NSCLC. These individuals, in particular, the patients with metastatic disease are likely to be resistant to standard chemotherapy pointing to the need for alternative therapeutic options. As one approach to this challenge, we used Affymetrix expression data to identify patterns of pathway deregulation in patients with advanced (recurrent/metastatic) disease and compared them to our previously described data on early stage NSCLC (n = 91). Unique to the recurrent and metastatic disease cohorts, a majority of the tumors (greater than 80%) had deregulation of multiple signaling pathways. In particluar, NSCLC tumors with deregulated Src and Myc pathways had a much worse prognosis than those with deregulated Ras and Akt pathways [median survival: 15.5 months vs. 55.3 months, hazard ratio: 2.6, p &lt; 0.01]. Further, using cell proliferation assays, we have shown that the predicted deregulation of Ras, Src and PI3K pathways was directly proportional (p &lt; 0.01, log rank test) to the sensitivity of NSCLC cell lines (n = 17) to agents that specifically target these pathways, suggesting that an ability to profile the status of oncogenic pathways in a tumor sample provides an opportunity to better characterize the oncogenic process in patients with recurrent and advanced NSCLC. More importantly, such a strategy provides a novel approach to targeted therapeutics in NSCLC by guiding the appropriate use of pathway specific inhibitors. Finally, data on gene expression patterns involving other signatures representing unique cancer biology relevant to NSCLC (e.g. hypoxia, chromosomal instability, and angiogenesis) will be also be presented. No significant financial relationships to disclose.
Effect of YangWeiKangLiu Granules on peripheral blood T-lymphocyte cell rDNA transcription activity and Fas expression in gastric cancer patients metastasis
Authors: J. Li, G.-Z. Sun, H.-S. Lin
Journal: Journal of Clinical Oncology (2005)

4275 Background: Gastric cancer is one of the common malignant tumors in China. Besides radiotherapy or/and chemotherapy, TCM also plays a important role in preventing gastric cancer from relapse and metastasis. The study is to investigate the effect of artistically composed chinese medicinal herbs, YangWeiKangLiu Granules, on peripheral blood T-lymphocyte cell rDNA transcription activity and Fas expression in gastric cancer patients metastasis. Methods: The transcrition activity of rDNA in T-lymphocyte was determined by KL-2 immune imaging system, and the Fas expression in peripheral T-lymphocyte was analyzed by flow cytometry. Results: The area of Ag-NORs increased signicantly determined by KL-2 immune imaging systerm in the patiens treated by YangWeiKangLiu Granules (P<0.01), and the Fas expression in peripheral T-lymphocyte was much lower analyzed with flow cytometry in the same patients. (P<0.01). Conclusions: YangWeiKangLiu Granules could improve the cell-mediated immune function through decreasing the apoptosis of T-lymphocyte in gastric cancer patients. No significant financial relationships to disclose.
Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life
Authors: H Bower, T M-L Andersson, M Björkholm, P W Dickman, P C Lambert, Å R Derolf
Journal: Blood Cancer Journal (2016)

We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997-2005 and 2006-2011 the most pronounced increase was for those aged 61-70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13-0.19) to 0.28 (95% CI: 0.23-0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1-41.8) years in 1975 and 19.5 (95% CI: 16.4-22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7-14.0) and 12.0 (95% CI: 11.3-12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61-70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers.
Observations on the Pathogenesis of Experimental Skin Tumors. A Study of the Mechanism by Which Papillomas Develop
Authors: Richard Siegler, M. L. Duran-Reynals
Journal: JNCI Journal of the National Cancer Institute (1962)

Methyleholanthrene applied over the site of dermal vaccinial infection in the skin of cortisone-treated mice results in a tumor effect which is more rapid and severe than that seen after the application of methyleholanthrene alone. Because of the rapidity of this enhanced reaction and the sharp localization of the ensuing tumors, the actual physical mechanism of papilloma formation can be followed. The pathological changes are depicted by sequential photographs, and the development of the papilloma is presented. The immediate effect of the treatment is to destroy surface epithelium and hair follicles. It is from regenerating epithelium that papillomas arise by an orderly sequential process, elongate, and sequester. Malignant tumors arose from the atrophic neighboring epithelium and not directly from the papillomas.
Another MSF clinic is bombed in Yemen
Authors: Owen Dyer
Journal: BMJ (2015)

The aid agency Medecins Sans Frontieres has reported that an airstrike by the Saudi led coalition has hit one of its clinics in Yemen, in the southern city of Taiz. Nine people were wounded, including two medical staff, and two of the wounded people are in a critical condition.1

The bombing was the second by the Saudi led coalition of an MSF facility in Yemen in a matter of weeks. The organisation’s hospital in the northern city of Saada was hit on 26 October.

It is the fourth air attack on MSF facilities around the world in two difficult months for the agency, which began …
FDG-PET SUVmax is an independent prognostic indicator in patients with non-small cell lung cancer
Authors: Laura-Jane Smith, Neal Navani, Paul Bassett, Irfan Kayani, Ashley Groves, Sam Janes
Journal: European Respiratory Journal (2011)

Background:  FDG-PET is a commonly used non-invasive tool for diagnosis and staging of lung cancer, the leading cause of cancer death.SUVmax has been suggested to be an independent prognostic factor in patients with operable non-small-cell lung cancer (NSCLC).However, PET-CT is not recommended in patients with advanced disease.   Aim:  Evaluate the utility of SUVmax of the primary lesion as an independent predictor of overall survival in patients with NSCLC, including advanced disease.   Methods:  Retrospective analysis of 47 patients (29 male, median age 69 years) with NSCLC (stage I 38%, stage II 9%, stage III 34%, stage IV 18%) who underwent FDG-PET at diagnosis.Cox regression analysis was applied to examine the effect of SUVmax on survival.This was then adjusted for stage, treatment, age, sex and histology.   Results:  There was a significant difference in survival between patients who had a low vs high SUVmax, hazard ratio 3.31 (p=0.006), such that an increase in SUVmax of the primary of 5 points conferred a hazard ratio of 1.49 (p=0.013).  This relationship was maintained when multiple factors were adjusted for, with a hazard ratio for an increase in SUVmax of the primary of 5 points of 2.8 (p=0.03).   Conclusion:  FDG-PET provides additional information about prognosis in NSCLC, independent of stage at presentation.The relationship between SUVmax of the primary and survival is maintained, even in patients with advanced disease.
Good usage of epoetin alpha biosimilar: A subanalysis of the orheo study.
Authors: Mauricette Michallet, Pierre Soubeyran, Elisabeth Luporsi, Jean-Emmanuel Kurtz, Helene Albrand
Journal: Journal of Clinical Oncology (2014)

217 Background: Chemotherapy-induced anaemia (CIA) is a frequent complication of patients with cancer. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was a post-marketing, observational, multicentre study conducted in France that evaluated the changes in haemoglobin (Hb) level in patients with solid tumours, lymphoma or myeloma, treated with an epoetin alfa biosimilar (EAB) (Retacrit, Hospira Inc.). In this subanalysis of the ORHEO study, we compare the usage of EAB in relation to the dosage recommendations of the European Organisation for Research and Treatment of Cancer (EORTC) guidelines, regarding two criteria: efficacy and safety profile. Methods: Patients with CIA receiving chemotherapy for solid tumours (breast, lung, colorectal), lymphoma or myeloma, and prescribed EAB were monitored at the start of the EAB therapy (D0), at 3 months (M3) and 6 months (M6). Hb response was defined as achievement of target Hb without blood transfusions in the preceding 3 weeks and during treatment or Hb ≥10 g/dL orHb increase ≥1 g/dL since inclusion. The prescribed dosage of EAB according to body weight and the tolerability of EAB at that recommended dosage were analysed at each time point. Results: Data from 2310 patients were analysed. Throughout the study 43.8% of patients received the recommended dose of EAB as determined by their weight. Overall, the percentage of responders was 81.6% at M3 and 86.5% at M6. Responses to treatment (meeting predefined Hb target levels) at M6 were similar whether or not EAB was prescribed at the recommended dose throughout the study. A similar proportion of patients receiving the recommended dose of EAB reported adverse events (AEs) at M6 compared with patients who did not receive the recommended dose (9.9% vs 9.0%). Overall, the incidence of thromboembolic events was 3.5% over the duration of the study (M3 2.4%; M6 1.5%). Conclusions: Of the 2310 patients with CIA included in this analysis, less than half (43.8%) received the recommended dose of EAB over the six-month course of the study. The majority of patients had a similar response to therapy regardless of dose. The frequency of overall AEs at M6 did not vary depending on dose. Clinical trial information: NCT02140736.
Left and Right Ventricular Wall Motion Abnormalities In Thalassemia Major Patients
Authors: Antonella Meloni, Gaetano Giuffrida, Cristina Paci, Leonardo Sardella, Alessandra Quota, Pier Paolo Bitti, Lucia De Franceschi, Cristina Salvatori, Valentina Vinci, Vincenzo Positano, Massimo Lombardi, Alessia Pepe
Journal: Blood (2013)
Nasopharyngeal Cancer Among Young People in the United States: Racial Variations by Cell Type
Authors: Mark H. Greene, Joseph F. Fraumeni, Robert Hoover
Journal: JNCI Journal of the National Cancer Institute (1977)

U. S. mortality and incidence statistics for nasopharyngeal cancer showed a fourfold excess risk of sarcomas in white children under age 10, and a fourfold to sevenfold excess of carcinomas in teen-age blacks. Mortality from nasopharyngeal carcinomas in young people was greater in the South than in the North, with the excess mortality in blacks linked to rural residence and low socioeconomic status. These and other characteristics of nasopharyngeal carcinoma in young persons suggested that environmental (perhaps infectious) agents are involved in this age group. These patterns contrasted with nasopharyngeal carcinomas developing after age 25, when the rates predominated in Chinese Americans. Nasopharyngeal cancer in the United States had three age peaks, with racial and epidemiologic distinctions that seemed to reflect different etiologies.
Epidemic Kaposi’s sarcoma in Italy, a country with intravenous drug users as the main group affected by HIV infection
Authors: U. Tirelli, E. Vaccher, A. Lazzarin, D. Errante, E. Alessi, I. Crosato, M. Spina, M. Zaccarelli, F. Aiuti, M. Moroni, S. Monfardini, D. Greco, F. Ancarani, G. Angarano, C. Baroni, A. Borri, A. Barelli, G. Cagnoni, A. Cajozzo, A. Carbone, A. Cargnel, F. Confalonieri, P. Costigliola, P. Crocchiolo, A. De Agostini, M. Della Santa, M. Fasan, F. Figoli, G.P. Fiore, P.L. Garavelli, F. Giannelli, S. Galâ, M.G. Giudici, F.M. Gritti, G. Luzi, R. Luzzati, G. Magnani, Malena M., A. Malfitano, F. Mazzotta, P. Meraviglia, F. Milazzo, D. Milo, L. Ortona, A. Paladini, N. Piersantelli, R. Pristerà, G. Raineri, E. Raise, L. Repetto, G. Rezza, E. Rinaldi, E. Ricchi, G. Riccio, G. Rizzardini, M. Rizzi, F. Rizzo, R. Rosso, B. Salassa, G. Saliva, E. Savalli, G. Scalise, A. Scasso, A. Sinicco, M.L. Soranzo, M. Spina, R. Stellini, L. Sueri, E. Sulis, F. Suter, A. Terragna, T. Troiano, A. Vaglia, G. Visco, R. Foà, F. Gavosto
Journal: Annals of Oncology (1991)
High Cure Rates and Reduced Long-Term Toxicity in Pediatric Hodgkin's Disease: The German-Austrian Multicenter Trial DAL-HD-90
Authors: Günther Schellong, Richard Pötter, Jürgen Brämswig, Wolfgang Wagner, Franz-Josef Prott, Wolfgang Dörffel, Dieter Körholz, Georg Mann, Bettina Rath, Alfred Reiter, Gerhard Weissbach, Marianne Riepenhausen, Markus Thiemann, Ernst-Wilhelm Schwarze
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To further reduce therapy-related late effects in patients with pediatric Hodgkin's disease (HD) while maintaining the high cure rates achieved with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OPPA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemotherapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the induction therapy for boys. Radiation doses and fields were further reduced. PATIENTS AND METHODS: Three hundred nineteen boys and 259 girls younger than 18 years with previously untreated HD, enrolled onto the study between 1990 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (intermediate stages), or TG3 (advanced stages). All groups underwent two cycles of OEPA (boys) or OPPA (girls) for induction chemotherapy. TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involved fields. RESULTS: Initial response to OPPA or OEPA induction was virtually identical. Eight of 578 patients experienced early progression of HD. Thirty-seven relapses, three secondary tumors, and no secondary leukemias have been recorded, with a median follow-up duration of 5.1 years (maximum, 8.1 years). Thirteen of 578 patients died. The probability of 5-year event-free survival/overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/98% with OEPA induction therapy. Risk factor analysis showed two significant prognostic factors: histologic subtype NS2 and “B” symptoms. OEPA induction therapy, large mediastinal tumor, and age were not significant. Preliminary studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA. CONCLUSION: OEPA is a satisfactory alternative to OPPA. Radiotherapy can be confined to involved sites when combined with appropriate chemotherapy. The DAL-HD-90 regimen represents a comprehensive treatment program for all stages of pediatric HD and offers a favorable benefit/risk ratio, combining excellent disease control, moderate acute toxicity, and reduced long-term toxicity.