tbuckley/cabot-search huggingface dataset:
Phase II Trial of Karenitecin in Patients with Malignant Melanoma: Clinical and Translational Study
Authors: Adil Daud, Nikola Valkov, Barbara Centeno, Jennifer Derderian, Patricia Sullivan, Pamela Munster, Patricia Urbas, Ronald C. DeConti, Elmer Berghorn, Zhenmei Liu, Frederick Hausheer, Daniel Sullivan
Journal: Clinical Cancer Research (2005)

Abstract Purpose: A phase II trial of the novel camptothecin karenitecin (BNP1350) was conducted to determine its efficacy and tolerability in patients with metastatic melanoma. Patients were biopsied to determine topoisomerase expression at baseline and response to therapy. Patients and Methods: Eligible patients had metastatic melanoma with up to three prior chemotherapy and/or any number of immunotherapy regimens. Treatment consisted of an i.v. infusion of 1 mg/m2 karenitecin daily for 5 days with cycles repeated every 3 weeks. Fine-needle aspiration biopsies were done before treatment and on day 3 to determine topoisomerase expression from patients' tumors. Results: Forty-three patients were evaluable for response and toxicity. Most patients (72%) had stage M1C disease and were previously exposed to chemotherapy (56%). The investigational agent was well tolerated with limited gastrointestinal side effects or fatigue. The major toxicity seen was reversible noncumulative myelosuppression. One patient had a complete response after 11 months of therapy. No partial responses were seen, but 33% of the patients had disease stabilization lasting ≥3 months. Topoisomerase I, IIα, and IIβ expression and localization were determined in a subset of patients. Topoisomerase I expression was highest, followed by topoisomerase IIβ and topoisomerase IIα. Conclusion: Karenitecin was a well-tolerated investigational agent in this phase II study; side effects were generally mild and mostly hematologic. Karenitecin has significant activity in metastatic melanoma. Melanoma metastases express high levels of topoisomerase I. We did not observe any compensatory increase in topoisomerase II upon treatment with karenitecin.
In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency
Authors: Silvia Selleri, Immacolata Brigida, Miriam Casiraghi, Samantha Scaramuzza, Barbara Cappelli, Barbara Cassani, Francesca Ferrua, Memet Aker, Shimon Slavin, Alessia Scarselli, Caterina Cancrini, Sarah Marktel, Maria Grazia Roncarolo, Alessandro Aiuti
Journal: Journal of Allergy and Clinical Immunology (2011)
Localization of melanin pigmentation in the skin with Wood's lamp
Authors: BARBARA A. GILCHREST, THOMAS B. FITZPATRICK, R.ROX ANDERSON, JOHN A. PARRISH
Journal: British Journal of Dermatology (1977)

Examination of the skin or hair with Wood's lamp has long been used to aid in the clinical diagnosis of some cutaneous disorders. A new observation reported here illustrates that Wood's light can be used to determine the depth of melanin pigmentation in the skin: contrast in epidermal pigmentation is increased while contrast in dermal pigmentation is decreased under Wood's lamp illumination compared to ambient visible light. The principles underlying this phenomenon are discussed. Use of the Wood's lamp to localize abnormal melanin pigmentation in the skin can be a guide to clinical diagnosis of hypermelanosis.
What effects might anti-TNF treatment be expected to have on cardiovascular morbidity and mortality in rheumatoid arthritis? A review of the role of TNF in cardiovascular pathophysiology
Authors: W G Dixon, D P M Symmons
Journal: Annals of the Rheumatic Diseases (2007)

Patients with rheumatoid arthritis (RA) have an increased burden of atherosclerotic cardiovascular disease which cannot be explained by an increased prevalence of traditional cardiovascular risk factors alone. Atherosclerosis is now being viewed as an inflammatory condition and the cumulative inflammation experienced in RA may contribute to accelerated atherosclerosis. It has been hypothesised that treatment with anti-tumour necrosis factor (TNF) α in RA may reduce both intra-articular inflammation and the inflammation associated with atherosclerosis. Thus, TNFα blockade may reduce the cardiovascular morbidity and mortality associated with RA. This review examines the pathophysiological role of TNFα in atherosclerosis and the evidence to date that anti-TNFα treatment modifies this process in RA.
Oncology Micro-Cap Stocks: Caveat Emptor!
Authors: A. Feuerstein, M. J. Ratain
Journal: JNCI Journal of the National Cancer Institute (2011)

JNCI Vol. 103, Issue 20 | October 19, 2011 Trading based on material nonpublic information is a criminal violation of the Federal Securities Exchange Act of 1934 and is punishable by a maximum sentence of 20 years and a fine of $5 million. Thus, the suggestion by Rothenstein et al. (1) in this issue of the Journal that insider trading is the cause of observed differences in company stock prices before and after public announcements related to oncology drugs is of grave concern. Specifically, Rothenstein et al. (1) analyzed the stock prices in the 120 days leading up to public announcements regarding phase III trials, and they appear to reject the null hypothesis that the outcome of the trial is unrelated to the stock price behavior before the announcement. Indeed, companies that reported a positive trial demonstrated better price performance (an increase of approximately 14%) during that period compared with companies Oncology Micro-Cap Stocks: Caveat Emptor!
Mechanisms of Transendothelial Migration of Leukocytes
Authors: William A. Muller
Journal: Circulation Research (2009)

A great deal of progress has been made recently in understanding the molecules and mechanisms that regulate transendothelial migration of leukocytes, or diapedesis, a critical step in the inflammatory response. This review focuses mainly on the active role of the endothelial cell in this process as it occurs at endothelial cell borders. It discusses some of the many molecules that have been reported to play a role in transendothelial migration and asks why so many molecules seem to be involved. The concept is emerging that diapedesis itself can be dissected into sequential steps controlled by specific molecule(s) at the endothelial cell border. Several mechanisms have been shown to play a critical role in transendothelial migration including signals derived from clustering of apically disposed intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, disruption or loosening of adherens junctions, and targeted recycling of platelet/endothelial cell adhesion molecule and other molecules from the recently described lateral border recycling compartment. A hypothesis that integrates the various known mechanisms is proposed.
Type II collagen-induced arthritis in rats. Passive transfer with serum and evidence that IgG anticollagen antibodies can cause arthritis.
Authors: J M Stuart, M A Cremer, A S Townes, A H Kang
Journal: The Journal of Experimental Medicine (1982)

We have found that serum from rats with type II collagen-induced arthritis, when fractionated with 50% ammonium sulfate and concentrated, would transfer arthritis to nonimmunized recipients. The arthritis in recipients developed within 18-72 h and displayed all of the major histopathologic characteristics of the early lesion in immunized animals but was transient and less severe. Although consideration was given to the possibility that a circulating immune complex was involved, no evidence of such a complex was detected. Further fractionation of the serum yielded an IgG anticollagen antibody that was fully active in transferring disease. The antibody's reaction was inhibited by the native bovine type II collagen used for immunization of donors and the antibody strongly cross-reacted with homologous type II collage but not with denatured collagen. These studies demonstrate that arthritis in rats can be induced with anti-type II collagen antibodies and suggest that an autoimmune process is involved. Because antibodies to collagen have also been detected in human rheumatic diseases, further investigation of the characteristics of collagen antibodies capable of inducing arthritis seems warranted.
Human Leukocyte Antigen Class II Alleles Associated With Human T-Cell Lymphotropic Virus Type I Infection and Adult T-Cell Leukemia/Lymphoma in a Black Population
Authors: Angela Manns, Jun-mo Nam, William Blattner, Barrie Hanchard, Owen St. C. Morgan, Rainford Wilks, Beverly Cranston, Michelle Blank, Masahiro Kuwayama, Shinji Yashiki, Toshinobu Fujiyoshi, Shunro Sonoda
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. Methods: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reactionbased methods to examine HLA class II DRB1 and DQB1 alleles. Results: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio {OR} = 2.7; 95% confidence interval {CI} = 1.0- 7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. Conclusions: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.
Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study
Authors: J. Young
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART). <b>Design</b> Prospective cohort study of adults with HIV (Swiss HIV cohort study). <b>Setting</b> Seven outpatient clinics throughout Switzerland. <b>Participants</b> The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years). <b>Main outcome measures</b> Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound. <b>Results</b> During follow up 2985 (80%) participants reported a stable partnership on at least one occasion. When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/μl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression. <b>Conclusions</b> A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.
Effects of a 5-Lipoxygenase–Activating Protein Inhibitor on Biomarkers Associated With Risk of Myocardial Infarction
Authors: Hakon Hakonarson, Sverrir Thorvaldsson, Anna Helgadottir, Daniel Gudbjartsson, Florian Zink, Margret Andresdottir, Andrei Manolescu, David O. Arnar, Karl Andersen, Axel Sigurdsson, Gestur Thorgeirsson, Asgeir Jonsson, Uggi Agnarsson, Halldora Bjornsdottir, Gizur Gottskalksson, Atli Einarsson, Hrefna Gudmundsdottir, Asdis E. Adalsteinsdottir, Kolbeinn Gudmundsson, Kristleifur Kristjansson, Thordur Hardarson, Arni Kristinsson, Eric J. Topol, Jeffrey Gulcher, Augustine Kong, Mark Gurney, Gudmundur Thorgeirsson, Kari Stefansson
Journal: JAMA (2005)

Myocardial infarction (MI) is the leading cause of death in the world. Variants in the 5-lipoxygenase-activating protein (FLAP) gene are associated with risk of MI.To determine the effect of an inhibitor of FLAP on levels of biomarkers associated with MI risk.A randomized, prospective, placebo-controlled, crossover trial of an inhibitor of FLAP (DG-031) in MI patients who carry at-risk variants in the FLAP gene or in the leukotriene A4 hydrolase gene. Of 268 patients screened, 191 were carriers of at-risk variants in FLAP (87%) or leukotriene A4 hydrolase (13%). Individuals were enrolled in April 2004 and were followed up by designated cardiologists from a university hospital in Iceland until September 2004.Patients were first randomized to receive 250 mg/d of DG-031, 500 mg/d of DG-031, 750 mg/d of DG-031, or placebo. After a 2-week washout period, patients received DG-031 if they had received placebo first or placebo if they had received DG-031 first. Treatment periods lasted for 4 weeks.Changes in levels of biomarkers associated with risk of MI.In response to 750 mg/d of DG-031, production of leukotriene B4 was significantly reduced by 26% (95% confidence interval [CI], 10%-39%; P = .003) and myeloperoxidase was significantly reduced by 12% (95% CI, 2%-21%; P = .02). The higher 2 doses of DG-031 produced a nonsignificant reduction in C-reactive protein (16%; 95% CI, -2% to 31%; P = .07) at 2 weeks. However, there was a more pronounced reduction (25%; 95% CI, 5%-40%; P = .02) in C-reactive protein at the end of the washout period that persisted for another 4 weeks thereafter. The FLAP inhibitor DG-031 was well tolerated and was not associated with any serious adverse events.In patients with specific at-risk variants of 2 genes in the leukotriene pathway, DG-031 led to significant and dose-dependent suppression of biomarkers that are associated with increased risk of MI events.
Determination of UVA protection factors by means of immediate pigment darkening in normal skin
Authors: Kays H. Kaidbey, Angelit Barnes
Journal: Journal of the American Academy of Dermatology (1991)

A method is described for screening potentially useful photoprotective agents against UVA radiation by the use of immediate pigment darkening as an end point. Threshold doses of immediate pigment darkening showed a log normal distribution and the response was found to obey dose-reciprocity at irradiance levels below 50 mW/cm2. With this procedure, several marketed sunscreens containing benzophenone-3 as the only UVA absorber were found to have poor UVA protection factors, whereas those containing combinations of benzophenone-3 and butyl methoxydibenzoyl methane or melanin were more effective. There was no correlation between the sun protection factor cited on the label and the calculated immediate pigment darkening-protection factor.
Haplotypes of SNPs associated with COX-2 and their comparison with histopathological features of breast cancer patients
Authors: Muniba Aban, Imran Siddqui, Muhammad Saboor, Shahid Pervez, Tariq Moatter
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In breast cancer, increased cyclooxygenase-2 expressions is associated with poor prognosis. COX-2 expression influences production of pro-inflammatory prostaglandins. The present study investigated association between COX-2 promoter polymorphisms (rs689465, rs689466, rs20417) and
Translational Phase I Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytarabine and Etoposide in Patients with Relapsed, Refractory, or High-Risk Acute Myeloid Leukemia
Authors: Ivana Gojo, Ming Tan, Hong-Bin Fang, Mariola Sadowska, Rena Lapidus, Maria R. Baer, France Carrier, Jan H. Beumer, Bean N. Anyang, Rakesh K. Srivastava, Igor Espinoza-Delgado, Douglas D. Ross
Journal: Clinical Cancer Research (2013)

To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts.In this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m(2)) and cytarabine (1 or 2 g/m(2) twice a day if ≥65 or <65 years old, respectively) were given. The study used a standard 3+3 dose escalation design.Eighteen of 21 patients with acute myelogenous leukemia (AML) treated on study completed planned therapy. Dose-limiting toxicities [hyperbilirubinemia/septic death (1) and anorexia/fatigue (1)] were encountered at the 200 mg three times a day level; thus, the MTD was established to be vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment.Vorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings.
Interobserver agreement in a community skin cancer screening setting
Authors: David J. Leffell, Ya-Ting Chen, Marianne Berwick, Jean L. Bolognia
Journal: Journal of the American Academy of Dermatology (1993)

To evaluate the appropriateness of screening as a preventive health tool, it is necessary to estimate its validity (or accuracy) and reliability (or reproducibility). Accuracy is determined by measures of sensitivity, specificity, and positive predictive value, whereas reliability reflects the consistency of results when the test is performed more than once on the same person under the same conditions. l The accuracy and reliability of skin cancer screening have not been examined extensively. A few studies have assessed positive predictive value by correlating histopathologic findings with screening diagnoses2-6; although one study addressed the reproducibility of the screening examination itself, it reported interobserver agreement between dermatologists and dermatology nurses.6 Our study examines interobserver agreement between dermatologists in a community skin cancer screening setting.
TGF-β1 inhibits expression and activity of hENT1 in a nitric oxide-dependent manner in human umbilical vein endothelium
Authors: José L. Vega, Carlos Puebla, Rodrigo Vásquez, Marcelo Farías, Julio Alarcón, Marçal Pastor-Anglada, Bernardo Krause, Paola Casanello, Luis Sobrevia
Journal: Cardiovascular Research (2009)

AimsWe studied whether transforming growth factor β1 (TGF-β1) modulates human equilibrative nucleoside transporters 1 (hENT1) expression and activity in human umbilical vein endothelial cells (HUVECs). hENT1-mediated adenosine transport and expression are reduced in gestational diabetes and hyperglycaemia, conditions associated with increased synthesis and release of nitric oxide (NO) and TGF-β1 in this cell type. TGF-β1 increases NO synthesis via activation of TGF-β receptor type II (TβRII), and NO inhibits hENT1 expression and activity in HUVECs.
Epigenetic Silencing of Interferon-κ in Human Papillomavirus Type 16–Positive Cells
Authors: Bladimiro Rincon-Orozco, Gordana Halec, Simone Rosenberger, Dorothea Muschik, Ingo Nindl, Anastasia Bachmann, Tina Maria Ritter, Bolormaa Dondog, Regina Ly, Franz X. Bosch, Rainer Zawatzky, Frank Rösl
Journal: Cancer Research (2009)

We have investigated interferon-kappa (IFN-kappa) regulation in the context of human papillomavirus (HPV)-induced carcinogenesis using primary human foreskin keratinocytes (HFK), immortalized HFKs encoding individual oncoproteins of HPV16 (E6, E7, and E6/E7), and cervical carcinoma cells. Here, IFN-kappa was suppressed in the presence of E6, whereas its expression was not affected in HFKs or E7-immortalized HFKs. Transcription could be reactivated after DNA demethylation but was decreased again upon drug removal. Partial reactivation could also be accomplished when E6 was knocked down, suggesting a contribution of E6 in IFN-kappa de novo methylation. We identified a single CpG island near the transcriptional start site as being involved in selective IFN-kappa expression. To prove the functional relevance of IFN-kappa in building up an antiviral response, IFN-kappa was ectopically expressed in cervical carcinoma cells where protection against vesicular stomatitis virus-mediated cytolysis could be achieved. Reconstitution of IFN-kappa was accompanied by an increase of p53, MxA, and IFN-regulatory factors, which was reversed by knocking down either IFN-kappa or p53 by small interfering RNA. This suggests the existence of a positive feedback loop between IFN-kappa, p53, and components of IFN signaling pathway to maintain an antiviral state. Our in vitro findings were further corroborated in biopsy samples of cervical cancer patients, in which IFN-kappa was also downregulated when compared with normal donor tissue. This is the first report showing an epigenetic silencing of type I IFN after HPV16 oncogene expression and revealing a novel strategy on how high-risk HPVs can abolish the innate immune response in their genuine host cells.
The dangers of LSD. Analysis of seven months' experience in a university hospital's psychiatric service
Authors: J. T. Ungerleider
Journal: JAMA (1966)

The symptoms, diagnostic categories, and general characteristics of patients in 70 cases of adverse reactions to lysergic acid diethylamide tartrate (LSD) are varied. Psychiatric side effects ranged from depressive reaction to psychotic states. In all cases, LSD ingestion occurred separately and apart from medical-experimental and psychiatric-therapeutic models of LSD usage. Findings based on these cases and from observations made on LSD users in the community indicate that widespread use of LSD is a cause for concern.