tbuckley/cabot-search huggingface dataset:
Acute lymphatic leukemia: Peruvian experience
Authors: W. Rodriguez, C. Castañeda, C. Vallejos, L. Casanova, C. Carracedo, J. León, H. Gómez, G. Ferreyros, C. Flores, L. Mas
Journal: Journal of Clinical Oncology (2005)

6726 Background: Acute lymphatic leukemia (ALL) is one of the most curable neoplasia in children, but the results in adults are poor. We evaluated the response, relapse, disease-free survival (DFS) and overall survival (OS) in adults pts with ALL who received treatment with Induction, Intensification, CNS Prophylaxis, Consolidation and Maintenance chemotherapy (9904 Regimen). Induction phase included Cyclophosphamide, Daunomicine, Vincristine, L-asparaginase and Prednisone. Methods: Clinical prospective trial of 9904 Regimen in pts with ALL treated in our institution between 1999–2003. It included pts older than 14y without previous treatment, neither chronic illness of kidney nor liver. We described clinical characteristics of patients; response and relapse rates to treatment. Survival rate was estimated by Kaplan-Meier. Results: We included 231 pts in the present trial. Pts characteristics were: Median age: 18y (14–57) and relationship Male/female: 1.4/1. Extramedullary deposit: 164 (72%) pts. including Lymph nodes involvement:105 (46%) and Hepatosplenomegaly: 49(21%). Median hemoglobin: 7.2gr/L (1.6- 15), median leucocytes count: 12900/L (0.1- 798000) and platelets count: 42000/L (1000- 669000). Signs of DIC in 7%. Characteristics of induction treatment were: Median neutropenia: 30 days, leucocytes nadir: 0.4/L and median number of febrile events: 1 episode (1–11). Toxicity in 105 (45%) pts: including liver toxicity: 79 (35%), hypofibrinogenemia: 75 (33%), hyperamylasemia: 14 (6%).Complete remission (CR) was achieved in 183/231 (79%) pts. Characteristics of failure to induction were: relative resistance to drugs in 50%, death in bone hypoplasia in 19% and persistence of illness at extramedullary deposit in 17% of pts. Until now there are 86/183 pts (47%) with relapses. The median of following was 13.5 months, reaching a 3 year rate DFS of 32% and OS of 55%. Conclusions: This regimen of chemotherapy repeat the results reported in literature for pts with Adult ALL. The induction is effective for reaching CR, but relapses are often. Toxicity was tolerated. No significant financial relationships to disclose.
Cetuximab and irinotecan in patients with EGFR+ colorectal cancer refactory to oxaliplatin and irinotecan: A single institution experience
Authors: A. Herrero, V. Alonso, J. Lao, A. Ruiz de Lobera, R. Pazo, J. Martinez-Trufero, T. Puertolas, V. Calderero, A. Artal, A. Anton
Journal: Journal of Clinical Oncology (2005)

3726 Background: Cetuximab is a IgG1 chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR), that has demonstrated activity in patients with metastatic colorectal cancer expressing EGFR. This activity has been shown in irinotecan refractory as a single agent and in combination. Methods: 22 patients who have showed progression to both irinotecan and oxaliplatin were treated with irinotecan (the same schedule as previously: 180 mg/m2 every two weeks) with cetuximab at standard doses 400 mg/m2 loading dose over 2 hours, then 250 mg/m2 over 1 hour weekly. Results: From February to November 2004, 22 patients with EGFR+ metastatic colorectal carcinoma who have failed both oxaliplatin and irinotecan were enrolled. Median age 58,5 years. Male/Female: 10/12. ECOG perfomance status 0/1/2: 8/8/4. Median CEA level was 214 ng/ml (11–2628). Metastatic sites: 1 in 8p, 2 in 9p and >2 in 5p. Median treatment lines administered previously 3. The most commonly adverse effects were mild to moderate, including: acne-like skin eruption (81% any grade, 9% grade 3), fatigue-malaise (54% any grade, 22% grade 3), diarrhea (68% any grade, 22% grade 3–4). Neither grade 3–4 hematological toxicity nor grade 3–4 allergic reaction were observed. 14 patients presented decreased in CEA levels (4p >75%, 6p 50–75%, 4p <50%). Partial responses were observed in 6 patients (27%), and stable disease for at least 6 weeks in 4 patients (18%) bringing the disease control rate to 45%. Conclusions: The combination of cetuximab and irinotecan in heavily pretreated patients refractory to both irinotecan and oxaliplatin produced objective responses in 27% of patients. This results are consistent with previously published (Cunningham NEJM 2004). No significant financial relationships to disclose.
Activation of Human T Cells by Major Histocompatability Complex Class II Expressing Neutrophils: Proliferation in the Presence of Superantigen, But Not Tetanus Toxoid
Authors: Neil A. Fanger, Chunlei Liu, Paul M. Guyre, Kathleen Wardwell, Jerome O'Neil, Tai L. Guo, Todd P. Christian, Stanley P. Mudzinski, Edmund J. Gosselin
Journal: Blood (1997)

Abstract The primary function of polymorphonuclear neutrophils (PMN) in the immune response appears to be acute phagocytic clearance of foreign pathogens and release of inflammatory mediators. Consistent with their assumed lack of major histocompatibility complex (MHC) class II expression, PMN have not been considered to play a role in antigen presentation and T-cell activation. However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF ) or interferon-γ (IFN-γ). Thus, under appropriate conditions, PMN could play a significant role in immune regulation, including T-cell activation. In this report, we demonstrate that human class II–expressing PMN can serve as accessory cells in superantigen (SAg)-mediated T-cell activation. This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-γ, which acted synergistically to induce MHC class II molecules on PMN. Moreover, the level of MHC class II expression and the magnitude of SAg-induced T-cell responses were found to be highly correlated and distinctly donor dependent, with PMN from some donors repeatedly showing fivefold higher responses than PMN from other donors. On the other hand, culture of PMN with GM-CSF plus IFN-γ under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide. These results delineate a new pathway for T-cell activation by SAg that may play an important role in the severity of SAg-induced inflammatory responses. They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-γ.
<u>F</u>luorouracil, <u>o</u>xaliplatin and <u>C</u>PT-11 (irinotecan), <u>u</u>se and <u>s</u>equencing (MRC FOCUS): A 2135-patient randomized trial in advanced colorectal cancer (ACRC)
Authors: M. T. Seymour
Journal: Journal of Clinical Oncology (2005)

3518 Background: This multicenter, open randomized trial assesses the effect on overall survival (OS) and quality of life of the planned sequencing of the first two cytotoxic drugs (fluorouracil (FU) plus one other) received by patients (pts) with inoperable ACRC. It compares three approaches: sequential single agents (FU first then change to second drug); sequential single/combination (FU then add a second drug); or 1st-line combination. It also compares irinotecan (Ir) and oxaliplatin (Ox) combinations. Methods: Pts had PS 0–2; GFR >50; ALP <5 x ULN; bili <1.25 x ULN. Randomization was 2:1:1:1:1 to: Plan A (reference): MdG (Modified de Gramont: leucovorin; FU bolus + 48 hr infusion; q2w) until treatment failure, then 2nd-line Ir; Plans Bir and Box: MdG until treatment failure, then 2nd-line IrMdG or OxMdG respectively; Plans Cir and Cox: 1st-line IrMdG or OxMdG. Primary endpoint was OS, 2100 pts giving 80% power (α = 0.01) to detect a difference of 22.5% vs 15% in 2 yr OS of each plan against Plan A. Results: 2135 pts entered, May’00 - Dec’03, at 61 centres, median age 64 yrs; 92% PS 0–1. With 1435 deaths to date, the primary comparisons, of OS for each plan (Bir, Box, Cir, Cox) versus Plan A, show trends to improvement (HR 0.92, 0.91, 0.86, 0.96 respectively) but all are non-significant (all p > 0.05). Grouped comparison of OS in Plans B (712 pts) with Plan A (710 pts) has a HR of 0.91, 95% CI (0.81, 1.04) p=0.157 in favour of B. The comparison of OS in grouped Plans C (713 pts) with Plan A has a HR of 0.91 (0.80, 1.03) p=0.134 favouring C. Comparison of Plans B with Plans C has a HR of 1.00 (0.88, 1.14) p=0.993. OS does not differ significantly between Ox and Ir in plans B and C. Compared with Plan B, Plan C gave a higher 1st-line RR (54% vs 29%) and PFS (median 8.7 vs 6.6 months) but shorter time to failure of the Plan (median 9.1 vs 11.6 months) (all p<0.001). Conclusions: Slightly increased survival was seen with combination chemotherapy, whether given 1st line or 2nd line, but this does not reach conventional levels of statistical significance. However, 1st-line combination chemotherapy did not improve OS compared with the same combinations deferred until 2nd line. Mature data will be presented at the meeting. No significant financial relationships to disclose.
Measurement of physical activity in older adult interventions: a systematic review
Authors: Ryan S Falck, Samantha M McDonald, Michael W Beets, Keith Brazendale, Teresa Liu-Ambrose
Journal: British Journal of Sports Medicine (2015)

Background Interventions to promote physical activity (PA) among older adults can positively impact PA behaviour and other health outcomes. Measurement of PA must be valid and reliable; however, the degree to which studies employ valid and reliable measures of PA is unclear. The purpose of this systematic review was to evaluate the measurement tools used in interventions to increase PA among older adults (65+ years), including both self-report measures and objective measures. In addition, the implications of these different measurement tools on study results were evaluated and discussed. Methods Four electronic research databases (MEDLINE, PsychINFO, Web of Science and EBSCO) were used to identify published intervention studies measuring the PA behaviour of adults over 65 years of age. Studies were eligible if: (1) PA was an outcome; (2) there was a comparison group and (3) the manuscript was published in English. Data describing measurement methods and properties were extracted and reviewed. Results Of the 44 studies included in this systematic review, 32 used self-report measures, 9 used objective measures and 3 used both measures. 29% of studies used a PA measure that had neither established validity nor reliability, and only 63% of measures in the interventions had established both validity and reliability. Only 57% of measures had population-specific reliability and 66% had population-specific validity. Conclusions A majority of intervention studies to help increase older adult PA used self-report measures, even though many have little evidence of validity and reliability. We recommend that future researchers utilise valid and reliable measures of PA with well-established evidence of psychometric properties such as hip-accelerometers and the Community Health Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults.
Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome
Authors: Larry A. Greenbaum, Marc Fila, Gianluigi Ardissino, Samhar I. Al-Akash, Jonathan Evans, Paul Henning, Kenneth V. Lieberman, Silvio Maringhini, Lars Pape, Lesley Rees, Nicole C.A.J. van de Kar, Johan Vande Walle, Masayo Ogawa, Camille L. Bedrosian, Christoph Licht
Journal: Kidney International (2016)

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months–17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.
Development a set of reagents for real-time PCR diagnostics and surveillance of infections caused by B. pertussis, B. parapertussis and B. bronchiseptica
Authors: Maria Praded, Tatiana Selezneva, Svetlana Yatsyshina
Journal: European Respiratory Journal (2011)

Pertussis is a Vaccine-preventable disease, but the goal to reduce the incidences of whooping cough by 2010 to 1 case cases per 100,000, has not been achieved in any country. Causative agent of whooping cough is  B.pertussis , but  B.parapertussis , cause of about 45% of clinical whooping cough cases. Cross-immunity against B.parapertussis is absent. Our goal was to develop a set of reagents for Real-Time PCR differential identification of  B.pertussis ,  B.parapertussis  and  B.bronchiseptica . The complexity is that genomes of these species are very similar. To solve this problem specific primers and probes have been chosen for detection of four targets in one tube. One of the targets is pertussis toxin (ptx) gene, which presents in genomes of B.pertussis, B.parapertussis and B.bronchiseptica. The second one is gene unique for Bordetella pertussis, the third one is gene unique for B.bronchiseptica. Fourth target is an exogenous internal control for assessment the efficacy of all stages of PCR analysis. Analytical sensitivity of developed set of reagents is 5*10 2  genomic units/ml of the sample. 51 Bordetella cultures isolated from children clinical samples with whooping cough in Russia in 1967 - 2011 and 6 Bordetella strains from animal were tested. The specificity of Bordetella species identification has been proved by sequencing of pertussis toxin gene promoter region. Preliminary results on 188 clinical samples have revealed high diagnostic efficacy of developed set of reagents.
The effect of compensatory induction of various PTEN mutants against TGFβ-induced translocation of β-catenin in lung cancer cells
Authors: Masaaki Kusunose, Naozumi Hashimoto, Daisuke Aoyama, Yoshinori Hasegawa
Journal: European Respiratory Journal (2013)

Background

Transforming growth factor β(TGFβ)-induced β-catenin translocation into cytoplasm is involved in epithelial-mesenchymal

transition(EMT). In this congress, we also show that modulation of phosphorylation sites in the PTEN C-terminus (PTEN4A) inhibits TGFβ-induced EMT via blockade of β-catenin translocation. Nevertheless, how PTEN4A could exert the inhibitory effect on β-catenin translocation remains elusive.

Objectives

We aimed to illuminate the underlying mechanisms, by using several PTEN constructs with deletion mutants.

Methods

We prepared four deletion mutants with the phosphatase domain, the C2 domain, and/or the PTEN C-terminus. Thus, we established lung cancer cells with a Dox-dependent gene expression system, in which these mutants were induced only when Dox is added. To evaluate the localization of β-catenin, immunofluorescence and confocal laser scanning microscopy were performed.

Results

Immunofluorescence images suggested that the PTEN C-terminus did not appear to directly inhibit TGFβ-induced β-catenin translocation into cytoplasm. We showed that the phosphatase domain might be important to block the β-catenin translocation.

Conclusions

Inhibition of phosphorylation of the PTEN C-terminus, by which the phosphatase domain could retain the PTEN phosphatase activity, might blunt TGFβ-induced β-catenin translocation as well as EMT.
No Seasonality in the Diagnosis of Acute Leukemia in the United States&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A M Walker, P A van Noord
Journal: JNCI Journal of the National Cancer Institute (1982)

Dates of diagnosis of 7,000 cases of acute leukemia occurring in the United States between 1969 and 1981 were reviewed for detection of seasonal patterns. No strong evidence was found for seasonality in the diagnosis of acute leukemias as a whole or for subgroups based on cell type, age, or geography. Previous indications of seasonal fluctuation may represent the selective reporting of chance events.
Far Too Often
Authors: Stanley Cohen
Journal: Annals of Internal Medicine (2016)

Ad Libitum2 February 2016Far Too OftenStanley Cohen, MDStanley Cohen, MDFrom Atlanta, Georgia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2105 Audio Reading - “Far Too Often” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Far Too Often," by S. Cohen. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail (Idiopathic thrombocytopenic purpura)Too often purple saturates your skinfar too many places, playinga twisted game, connecting dotsalong the path of edges and elbowsthat left their memory on yours.Too often tears drain your eyes.Those war wounds from everykitchen you enter, some doorclosing, a child's ill manners,a moment misspent, a hand mislaid.Too often you wear long sleeves,high collars, pants instead of skirts,hoping to hide the ripe or fadingcolors from eyes that questionand contend—perhaps your own.from running your ... Author, Article, and Disclosure InformationAffiliations: From Atlanta, Georgia.Current Author Address: Stanley Cohen, MD, Children's Center for Digestive Health Care, 993D Johnson Ferry Road, #440, Atlanta, GA 30342; e-mail, [email protected]com PreviousarticleNextarticle Advertisement Audio Reading - “Far Too Often” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Far Too Often," by S. Cohen. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 2 February 2016Volume 164, Issue 3Page: 183KeywordsElbowGamesHealth careHeartIdiopathic thrombocytopenic purpuraMemoryRiversRunningSaltsTaste ePublished: 2 February 2016 Issue Published: 2 February 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A phase II study of carboplatin plus paclitaxel in advanced thymoma or thymic carcinoma: E1C99
Authors: G. L. Lemma, P. J. Loehrer, J. W. Lee, C. J. Langer, W. J. Tester, D. H. Johnson
Journal: Journal of Clinical Oncology (2008)

8018 Background: Thymoma (THY) and thymic carcinoma (TC) are the most common tumors of the anterior mediastinum. Anthracycline-based combination chemotherapies have yielded response rates ranging from 50–90% in previously untreated patients (pts). The primary endpoint of this trial was to evaluate the objective response rate of paclitaxel plus carboplatin in previously untreated pts with advanced THYor TC. Secondary endpoints include the duration of response and toxicity for this regimen. Methods: Patients (pts) with histologically proven, unresectable THY or TC, PS <2, without prior systemic chemotherapy for thymic malignancies were eligible. Pts were treated with carboplatin (AUC = 5) plus paclitaxel (225 mg/m2) every 3 weeks for a maximum of six cycles of therapy. Results: From February, 2001 to December, 2007, 46 pts were enrolled (THY= 25; TC= 21). One pt was ineligible and never received therapy ( in THY). All treated pts were included in the toxicity analysis and all eligible were included in the survival analysis. Over 62 % of pts had Stage IV disease (most common metastasis sites were pleura and lung). Five pts had preexisting autoimmune disease including myasthenia gravis. Thirteen pts had ≥Grade 4 toxicity, most commonly, neutropenia. Using RECIST criteria, 3 CR and 5 PR (CR + PR= 33%, 90% CI 18–52%) were observed in 24 pts with THY; fifteen had stable disease. For the 21 pts with TC, no CR and 5 PRs (24%; 90% CI 10–44%) were observed; seven had stable disease. The progression-free survivals were 19.8 and 6.2 mos for THY and TC respectively. To date, only 3 (12%) pts with THY have died compared to 16 (76%) pts with TC. The median survival time is 15 mos for TC pts, but has not been reached for pts with THY. Conclusions: This represents one of the largest prospective trials in previously untreated, advanced thymic malignancies. Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies that appears less than expected with cisplatin plus anthracycline-based therapy. Patients with thymic carcinoma have a poorer progression free survival and overall survival than patients with thymoma. No significant financial relationships to disclose.