tbuckley/cabot-search huggingface dataset:
When Quality of Life Is the Major Challenge
Authors: Odile Oberlin
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.14.3051 Journal of Clinical Oncology - published online before print November 1, 2016 PMID: 12118017 When Quality of Life Is the Major Challenge Odile OberlinxOdile OberlinSearch for articles by this author Show More Institut Gustave-Roussy, Villejuif Cedex, France https://doi.org/10.1200/JCO.2002.20.14.3051 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Phase I/II multicenter trial of S-1 plus paclitaxel in patients with metastatic gastric cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group Study (OGSG 0105)
Authors: H. Narahara, K. Fujitani, T. Tsujinaka, H. Takiuchi, K. Nakane, M. Kato, Y. Kimura, H. Tsukuma, H. Furukawa, T. Taguchi
Journal: Journal of Clinical Oncology (2004)

4249 Background: S-1 is one of key drugs for gastric cancer and paclitaxel was recently approved in Japan. We conducted a new combination therapy of S-1 plus paclitaxel for metastatic gastric cancer. The aim of this study is to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with a fixed dose of S-1 in step 1, and to evaluate the efficacy in step 2. Methods: The eligibility is as follows; histologically proven gastric cancer with measurable metastatic lesions, PS 0–2, life expectancydepends on document reviewof more than 3 months, age 20–75, normal organ functions, and written informed consent. S-1 was administered orally (80 mg/m2/day) for 14 consecutive days. Paclitaxel was injected intravenously for 60 minutes (level 1,2,3,4: 50,60,70,80 mg/m2) on day 1 and 8.This schedule was repeated every 3 weeks. DLT were determined as grade 4 hematological and grade 3 non-hematological. Critical toxicity was defined as the observation of DLT, more than 15 days of rest, and the discontinuation of the 2nd administration of paclitaxel during the first and second courses. MTD was defined as a dose with 33.3% (2/6) critical toxicities. At RD (n=5), the pharmacokinetic study was performed on day 7 and 8. Results: Thirty-three patients were enrolled in this study from October 2002 to August 2003. Step 1: At level 1, no patients developed DLT. At level 2, two patients developed DLT. Level 2 was determined as the MTD and the dose at level 1 was determined as the RD. The response rate of RD was 62.5%. Step 2: Overall response rate was 50%. This regimen was effective especially for lymph node metastases in 60%. Pharmacokinetic study suggested no drug interactions between S-1 and paclitaxel. No grade 4 toxicities were observed in any patients. Conclusions:The MTD of this combination is estimated at paclitaxel 60mg/m2. The RD of this combination is determined to be paclitaxel 50mg/m2/day. The response results are promising. These results warrant further investigation. No significant financial relationships to disclose.
SUCCESSFUL PLASMA INFUSION TREATMENT OF A PATIENT WITH C2 DEFICIENCY AND SYSTEMIC LUPUS ERYTHEMATOSUS: CLINICAL EXPERIENCE OVER FORTY‐FIVE MONTHS
Authors: Kristján Steinsson, Kristján Erlendsson, Helgi Valdimarsson
Journal: Arthritis & Rheumatology (1989)

We describe a patient with C2 deficiency and severe systemic lupus erythematosus (SLE) that did not respond to conventional therapy. Over a period of 45 months, she was given 22 cycles of plasma therapy. For 6–8 weeks after each plasma infusion, there was a full clinical remission of the SLE, and a brief restoration of hemolytic complement activity. However, there were more prolonged increases in the activities of the complement components that are believed to be more directly involved in the clearance of immune complexes. Because of the theoretical risk that the infused complement might enhance inflammatory tissue damage, there has been some reluctance to try plasma replacement therapy in SLE patients with complement deficiency. We have not observed any adverse effects with the long‐term use of this treatment, and our experience indicates that this therapeutic approach can be beneficial.
No further clues from global investigation
Authors: E E Castilla
Journal: BMJ (1994)

born infants.In comparison, the crude prevalence in the total population born in 1981-91, according to the medical birth registry, was 0-43/10000 newborn infants (26 cases, population 602 301).In all four cases the infants had been singletons born alive at full term with birth weights over 3500g.One had additional birth defects.The four families lived at farms in different parts of Norway, with no temporal clustering of the pregnancies (conceptions between 1971 and 1988).None of the families had a greenhouse or an orchard.Of the 21843 infants potentially exposed to benomyl, one was diagnosed as having microphthalmia (0 46/ 10 000).This child came from a farm that grew field vegetables.Our data do not indicate that parental agricultural activity is a specific risk for anophthalmia in children.Even with this large cohort, comprising roughly a seventh of all births in Norway during the period studied, no firm conclusions concerning this rare birth defect can be drawn.The use ofproxies as exposure variables adds to the uncertainty.Nevertheless, our data do not support the suggestion that benomyl is a risk factor.
New insights into folliculotropic mycosis fungoides (FMF): A single-center experience
Authors: Emmilia Hodak, Iris Amitay-Laish, Lihi Atzmony, Hadas Prag-Naveh, Natalia Yanichkin, Aviv Barzilai, Ruben Kershenovich, Meora Feinmesser
Journal: Journal of the American Academy of Dermatology (2016)
Granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim) as adjuvant therapy of melanoma
Authors: L. E. Spitler, R. W. Weber, S. Cruickshank, J. F. Thompson, H. Lin, S. J. Soong, E. Garbe, M. S. Ernstoff, M. L. Grossbard, S. N. Markovic, T. L. Whiteside
Journal: Journal of Clinical Oncology (2008)

20006 Background: Our previous study suggested that administration of GM-CSF for 1 year to melanoma patients at very high risk for recurrence may prolong survival (JCO 18(8):1614–1621, 2000) and led to a prospective randomized trial, which has completed accrual and follow-up is now ongoing (E4697). We conducted a series of follow-on studies to gain further information about the effects of GM-CSF as adjuvant therapy of melanoma. Methods: The dose of GM-CSF used in all studies was the same: 125 μg/m2 administered subcutaneously in 28-day cycles of 14 days followed by 14 days off therapy. Three studies were done: 1) Analysis of survival in 98 high-risk melanoma patients given GM-CSF for 3 years; 2) Comparison of survival in 4 studies in which patients were given 1- year (n = 142) or 3- years (n = 98) of therapy; 3) Determination of immunologic responses before and after 14 days of GM-CSF therapy and throughout the course of 1 year of treatment. Results: In 98 high-risk patients treated with GM-CSF for 3 years, the 5-year melanoma-specific survival rate was 60%. For patients with Stage III disease, survival was significantly prolonged in those who received GM-CSF compared to matched historical controls and this was due to a significant benefit in patients with Stage IIIC disease. Two of the 98 patients treated with GM-CSF for 3 years subsequently developed AML. Survival in patients with Stage IIIC and IV melanoma was significantly prolonged in patients who received 3 years of therapy as compared to those who received 1 year of therapy (HR = 0.61, p = 0.047). Immunologic studies showed an increase in neopterin levels following GM-CSF administration. There was also an increase in activated and regulatory T cells. Conclusions: Adjuvant therapy with GM-CSF for 3 years may prolong survival in patients with melanoma who are at high risk for recurrence. Survival improved in patients given 3 vs. 1 year of therapy, but 3 years of therapy may pose a risk for development of AML. The increase in neopterin levels is consistent with macrophage activation as the potential mechanism of action. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Schering Pharma Bayer Schering Pharma Bayer Schering Pharma
Case 48-1965
Authors: Alexander Leaf, Sanford I. Roth
Journal: New England Journal of Medicine (1965)

Presentation of CaseA seventy-nine-year-old man was admitted to the hospital because of a mass in the jaw.He had been well until eight months previously, when a swelling appeared beneath his lower denture. Examination at the Tumor Clinic two months later revealed a fungating lesion on the anterior portion of the lower gingiva and 2 hard lymph nodes, 1 by 2 cm., in the left submandibular area; a biopsy disclosed a squamous-cell carcinoma. Irradiation resulted in temporary regression, but during the three months before entry the mass increased in size.The patient had lost 17 pounds in weight during . . .
Robot-assisted Radical Prostatectomy and Extended Pelvic Lymph Node Dissection in Patients with Locally-advanced Prostate Cancer
Authors: Giorgio Gandaglia, Elisa De Lorenzis, Giacomo Novara, Nicola Fossati, Ruben De Groote, Zach Dovey, Nazareno Suardi, Francesco Montorsi, Alberto Briganti, Bernardo Rocco, Alexandre Mottrie
Journal: European Urology (2016)
Acid-Phosphatase Activity in the Gastric Content of Patients with Carcinoma of the Stomach<xref ref-type="fn" rid="fn1"><sup>1</sup></xref><xref ref-type="fn" rid="fn2"><sup>2</sup></xref><xref ref-type="fn" rid="fn3"><sup>3</sup></xref>
Authors: George W. Changus, Charles E. Dunlap
Journal: JNCI Journal of the National Cancer Institute (1949)

Acid-Phosphatase Activity in the Gastric Content of Patients with Carcinoma of the Stomach George W. Changus, George W. Changus Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles E. Dunlap Charles E. Dunlap Department of Pathology, School of Medicine, Tulane University, Charity Hospital of Louisiana at New Orleans and U. S. Marine Hospital, New Orleans, La. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 2, October 1949, Pages 481–487, https://doi.org/10.1093/jnci/10.2.481 Published: 01 October 1949
ODM-204: A novel dual inhibitor of CYP17A1 and androgen receptor for the treatment of castration-resistant prostate cancer—Preclinical data.
Authors: Riikka Oksala, Anu Moilanen, Reetta Riikonen, Petteri Rummakko, Riikka Huhtaniemi, Pekka Kallio
Journal: Journal of Clinical Oncology (2015)

221 Background: Castration-resistant prostate cancer (CRPC) is characterized by high androgen receptor (AR) expression and persistent activation of AR signaling axis by residual tissue/tumor androgens. Targeting AR and androgen biosynthesis together may be more effective than either alone. ODM-204 is a novel, non-steroidal dual inhibitor of CYP17A1 and AR, which has shown promising results in preclinical studies. Methods: The binding affinity of ODM-204 to wild type AR was determined in rat prostate cytosolic lysates. The potency and functional activity of ODM-204 to human AR were demonstrated in cells stably transfected with the full-length AR and androgen-responsive reporter gene constructs. In addition, assays for AR nuclear translocation and the transactivation of human AR mutants T877A, W741L, and F876L were conducted. The effects of ODM-204 on the growth of androgen-dependent VCaP and LNCaP cells in vitro and subcutaneously grafted VCaP cells in vivo with the oral dose of 50 mg/kg/day were studied. The inhibition of CYP17A1 by ODM-204 was studied in vitro by using human and rat testicular microsomes and a human adrenal cortex cell line, and in vivo in male rats coadministered with luteinizing hormone releasing hormone agonist leuprolide acetate to mimic clinical situation. Results: ODM-204 is a potent inhibitor of both AR and CYP17A1. It binds to AR with a high affinity (Ki=47 nM) and selectivity and has a high potency towards CYP17A1 (IC 50 =22 nM). In addition, ODM-204 inhibited testosterone-mediated nuclear translocation of AR and the mutant ARs (IC 50 values for AR(T877A), AR(W741L), and AR(F876L) were 95, 277, and 6 nM, respectively), and suppressed androgen-induced cell proliferation of LNCaP (IC 50 =170 nM) and VCaP (IC 50 =280 nM) cells. In a VCaP xenograft model, ODM-204 showed significant antitumor activity (tumor growth inhibition=66%). In rats, inhibitory effects of leuprolide acetate on testosterone production and androgen-sensitive organ weights were potentiated by ODM-204. Conclusions: ODM-204 is a promising new dual CYP17A1 and AR inhibitor for the treatment of CRPC. Clinical trials in patients with mCRPC will be started in early 2015.
Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity
Authors: Laurent Beziaud, Laura Mansi, Patrice Ravel, Elodie Lauret Marie-Joseph, Caroline Laheurte, Laurie Rangan, Francis Bonnefoy, Jean-René Pallandre, Laura Boullerot, Clémentine Gamonet, Sindy Vrecko, Lise Queiroz, Tristan Maurina, Guillaume Mouillet, Thierry Nguyen Tan Hon, Elsa Curtit, Bernard Royer, Béatrice Gaugler, Jagadeesh Bayry, Eric Tartour, Antoine Thiery-Vuillemin, Xavier Pivot, Christophe Borg, Yann Godet, Olivier Adotévi
Journal: Cancer Research (2016)

Abstract The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3+Helios+Ki67+ regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred. Furthermore, a high rate of Eomes+CD8+ T cells was detected in patients after a long-term mTOR inhibition. We found that early changes in the Tregs/antitumor Th1 balance can differentially shape the treatment efficacy. Patients presenting a shift toward decreased Tregs levels and high expansion of antitumor Th1 cells showed better clinical responses. Studies conducted in tumor-bearing mice confirmed the deleterious effect of rapalogs-induced Tregs via a mechanism involving the inhibition of antitumor T-cell immunity. Consequently, the combination of temsirolimus plus CCR4 antagonist, a receptor highly expressed on rapalogs-exposed Tregs, was more effective than monotherapy. Altogether, our results describe for the first time a dual impact of host adaptive antitumor T-cell immunity on the clinical effectiveness of rapalogs and prompt their association with immunotherapies. Cancer Res; 76(14); 4100–12. ©2016 AACR.
Recapitulating the Size and Cargo of Tumor Exosomes in a Tissue-Engineered Model
Authors: Aranzazu Villasante, Alessandro Marturano-Kruik, Srikanth R. Ambati, Zen Liu, Amandine Godier-Furnemont, Hesam Parsa, Benjamin W. Lee, Malcolm A.S. Moore, Gordana Vunjak-Novakovic
Journal: Theranostics (2016)

There is a growing interest in the pivotal role of exosomes in cancer and in their use as biomarkers.However, despite the importance of the microenvironment for cancer initiation and progression, monolayer cultures of tumor cells still represent the main in vitro source of exosomes.As a result, their environmental regulation remains largely unknown.Here, we report a three-dimensional tumor model for studying exosomes, using Ewing's sarcoma type 1 as a clinically relevant example.The bioengineered model was designed based on the hypothesis that the 3-dimensionality, composition and stiffness of the tumor matrix are the critical determinants of the size and cargo of exosomes released by the cancer cells.We analyzed the effects of the tumor microenvironment on exosomes, and the effects of exosomes on the non-cancer cells from the bone niche.Exosomes from the tissue-engineered tumor had similar size distribution as those in the patients' plasma, and were markedly smaller than those in monolayer cultures.Bioengineered tumors and the patients' plasma contained high levels of the Polycomb histone methyltransferase EZH2 mRNA relatively to their monolayer counterparts.Notably, EZH2 mRNA, a potential tumor biomarker detectable in blood plasma, could be transferred to the surrounding mesenchymal stem cells.This study provides the first evidence that an in vitro culture environment can recapitulate some properties of tumor exosomes.
EGFR Status in Mesothelioma: Possible Implications for the Efficacy of Anti-EGFR and Anti-MET Therapies
Authors: Sandra Salvi, Serena Varesano, Simona Boccardo, Jean Louis Ravetti, Pier Aldo Canessa, Maria Pia Pistillo, Paola Ferro, Franco Fedeli, Silvio Roncella
Journal: Journal of Thoracic Oncology (2016)
NCCN Guidelines Update for Multiple Myeloma
Authors: Kenneth C. Anderson
Journal: Journal of the National Comprehensive Cancer Network (2016)

The updated NCCN Guidelines for Multiple Myeloma feature several changes in the diagnosis and management of this disease. Criteria for treatment initiation have been broadened, new staging has been recommended, and new classes of agents and combinations are included as recommended treatment. Monoclonal antibodies are among the expanded therapeutic choices, along with a histone deacetylase inhibitor and third-generation proteosome inhibitor, and there is excitement about exploring new immune-based approaches.
Low-dose neuroleptic therapy for children with childhood-onset pervasive developmental disorder
Authors: P T Joshi, J A Capozzoli, J T Coyle
Journal: American Journal of Psychiatry (1988)

An open study of the therapeutic effects of low-dose neuroleptic treatment was performed on 12 consecutively hospitalized children, aged 7-11, who satisfied DSM-III criteria for childhood-onset pervasive developmental disorder. While receiving an average dose of 0.04 mg/kg per day of haloperidol or fluphenazine hydrochloride, the patients exhibited significant reductions in hyperactivity and aggressive symptoms and significant improvement in peer relations. This dose of neuroleptic was associated with minimal side effects. The authors conclude that low doses of potent neuroleptics may be effective treatment for some patients suffering from childhood-onset pervasive developmental disorder.
Abstract 14866: Athletic Heart Screening: Usefulness of Echocardiography and Economic Impact
Authors: Edgard Bendaly
Journal: Circulation (2015)

Background: The athletic heart screen (AS) for sudden cardiac death (SD) detection is controversial in the USA. EKG use is common in AS programs but ECHO is uncommon. Our study aims to determine the effectiveness of ECHO in identifying athletes at risk for SD that would have been missed without ECHO and to evaluate the cost of AS. Methods: AS and medical records were reviewed. AS consisted of a self-completed questionnaire, EKG and limited ECHO. AS were abnormal at the discretion of the reader at the time they were reviewed. Data is expressed as percentage. Cost is calculated using average reimbursement for the ensuing initial cardiac evaluation. Results: In 10 years, 2016 AS were randomly assigned to 5 pediatric cardiologists. There were 336 (16.7%) abnormal AS. The rate of abnormal AS was 79/244 (12.1%), 19/190 (10%), 82/630 (31.2%), 7/63 (11%), and 164/889 (18.4%) for the reviewers, representing a wide variability in the percentage of abnormal AS among reviewers. This resulted in 166 (49.4%) initial cardiac evaluations leading to 207 noninvasive testing in addition to repeat EKG in some cases. Testing included ECHO, Holter, stress test and cardiac CT and MRI. Initial evaluation was normal in 103 (62.0%) cases. Invasive interventions included: 3 small ASD closures, 1 moderate PDA closure, an EP ablation for WPW, and 1 surgery for abnormal right coronary artery origin (ARCA). In the remaining 57 (34.3%) cases, the cardiac abnormalities identified were mild including: prominent aortic root, premature complexes, and mild left-sided valve abnormalities in asymptomatic individuals. Conservatively, 2 diagnoses would be low risk for SD: WPW and ARCA representing &lt;0.1% of all AS performed. An abnormal AS was made by ECHO in 184/336 (54.8%) cases leading to 105 evaluations: 55 (52.4%) were normal, 45 (42.8%) had mild abnormalities, and 5 (4.8%) had the ASD and PDA closures, and the coronary surgery. The cost of 2016 AS was $100,000. The cost of the 166 first evaluations performed including noninvasive testing was $160,462. Conclusions: AS results are reviewer-dependent and low yield for detecting conditions at high risk for SD. The addition of ECHO can identify mild congenital heart disease and coronary abnormalities at the expense of increasing costs, acutely and long term.
Risk of Myocardial Infarction and Stroke in Patients With Granulomatosis With Polyangiitis (Wegener's): A Population‐Based Study
Authors: J. Antonio Aviña‐Zubieta, Alice Mai, Neda Amiri, Natasha Dehghan, Ju Ann Tan, Eric C. Sayre, Hyon K. Choi
Journal: Arthritis & Rheumatology (2016)

To assess the relative risk of myocardial infarction (MI) and ischemic stroke in patients with newly diagnosed granulomatosis with polyangiitis (Wegener's) (GPA) compared with that in controls from the general population.Using a population-based database from the province of British Columbia, Canada, we conducted a matched cohort study in which each patient with incident GPA was matched for age, sex, and entry time with up to 10 individuals from the general population. Patients in the GPA cohort were required to have received at least 1 prescription for oral glucocorticoids, methotrexate, cyclophosphamide, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil, or rituximab within 1 month before or 6 months after the index date. We compared the incidence rates of MI and ischemic stroke between the 2 groups and calculated hazard ratios (HRs), adjusting for confounders.Among 504 patients with incident GPA (53.4% female, mean age 57.4 years), MI developed in 23 patients, and ischemic stroke developed in 18 patients (incidence rates of 11.7 per 1,000 person-years and 8.9 per 1,000 person-years, respectively). The incidence rates among 5,222 subjects without GPA were 5.2 per 1,000 person-years and 4.3 per 1,000 person-years, respectively. The multivariable HRs among GPA patients were 1.86 (95% confidence interval [95% CI] 1.05-3.31) for MI and 1.50 (95% CI 0.78-2.89) for ischemic stroke. The age-, sex-, and entry time-matched HR for cardiovascular disease (composite outcome of MI or stroke) was highest during the first year after GPA diagnosis (HR 2.88, 95% CI 1.37-6.08).Patients with GPA have a significantly increased risk of MI and a non-statistically significant trend toward an increased risk of ischemic stroke. Monitoring for this complication and vigilance in modifying risk factors are particularly warranted in this patient population, especially early after the diagnosis of GPA.