tbuckley/cabot-search huggingface dataset:
The Pacific trial: A randomized phase II study of OGX-427 in men with metastatic castration-resistant prostate cancer (mCRPC) and PSA progression while receiving abiraterone acetate (AA).
Authors: Kim N. Chi, Christopher Sweeney, Cindy Jacobs, Patricia S. Stewart, Noah M. Hahn
Journal: Journal of Clinical Oncology (2013)

TPS5101 Background: Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone protein that regulates cell signaling and survival pathways implicated in cancer progression and over-expressed in many cancers including prostate, bladder, lung, and breast. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a second-generation antisense oligonucleotide designed to inhibit Hsp27 expression with in vitro and in vivo efficacy that increases apoptosis, inhibits tumor growth, sensitizes cells to chemotherapy and inhibits AR activity (Cancer Res 2007;67(21):10455). A phase 2 study of OGX-427 in patients with mCRPC reported preliminary activity with 50% of patients having a ≥50% PSA decline during treatment (J Clin Oncol 30, 2012 (suppl; abstr 4514)). The purpose of this study was to evaluate the clinical activity of OGX-427 in patients with mCRPC progressing on AA. Methods: In this randomized, phase 2 study, 74 evaluable patients with mCRPC who are currently receiving AA and have PSA progression despite a prior response are randomized 1:1 to receive either OGX-427 (600 mg IV x 3 loading doses in week 1 followed by 1000 mg IV weekly) with AA or continuing AA alone. Additional eligibility criteria include: ECOG performance status ≤1, no evidence of radiographic progression, adequate liver/kidney/bone marrow function, and ≤1 prior chemotherapy for CRPC. Protocol therapy is continued until disease progression, unacceptable toxicity, or patient withdrawal. Eligible control arm patients may cross over to receive OGX-427 following disease progression. The primary objective of the study is to evaluate the proportion of patients progression-free at Day 60 post randomization. Secondary objectives include comparisons between arms of PSA and disease response, progression free survival, time to disease progression, serial serum levels of Hsp27, and circulating tumor cell enumeration. The study is designed to detect a 25% improvement in the primary endpoint (α = 0.2, β = 0.1). The study was initiated December, 2012. Clinical trial information: NCT01681433.
Survey of &lt;italic&gt;int&lt;/italic&gt; Region DNA Rearrangements in C3H and BALB/cfC3H Mouse Mammary Tumor System&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: V. K. Pathak, R. Strange, L. J. T. Young, D. W. Morris, R. D. Cardiff
Journal: JNCI Journal of the National Cancer Institute (1987)

Rearrangement of the int-1 and int-2 regions of mouse chromosomes was compared in the C3H and BALB/cfC3H hyperplastic alveolar nodule and its hyperplastic outgrowth (HPO) model systems by examining the DNA of the different stages of the neoplastic progression, with use of the Southern blot technique. Rearrangement of int region DNAs associated with proviral amplification occurred more frequently in spontaneous tumors (19 of 27) than in tumors from HPOs (7 of 37) and rarely occurred in HPOs (1 of 29). However, the int-1 rearrangement maintained in 1 BALB/cfC3H HPO line through 11 transplant generations suggests that the int-1 rearrangement is neither sufficient nor necessary for progression to mouse mammary carcinoma.
Emerging prognostic biomarkers in non small cell lung cancer patients: Impact of treatment with nimesulide (COX-2 inhibitor) combined with chemotherapy
Authors: Soad Abdel-Ghany, Nagla Elmelegy, Aliae Mohamed-Hussein, Randa Hana
Journal: European Respiratory Journal (2011)

To date, the treatment outcome of non small cell lung cancer (NSCLC) is still not satisfactory and new treatment options are urgently needed. The present study was designed to: 1) evaluate the effects of the antiangiogenic drug; nimesulide (NSAID, a COX-2 inhibitor) combined with chemotherapy on NSCLC treatment progress, 2) Evaluate the role of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), as prognostic indicators in NSCLC, 3) Correlate the above parameters levels with the clinicopathological status of the patients during the therapy. The study included 30 NSCLC.

Methods: The patients were divided to: group I, included 17 patients received chemotherapy alone and group II included 13 patients received the same chemotherapy with Nimesulide and 10 as controls. Serum and biopsies were taken for all subjects on admission and 3 weeks after the completion of treatment.

Results: Serum and tissue levels of VEGF and bFGF, were significantly higher in NSCLC patients and decreased significantly after treatment specially in group II compared to group I. The serum and tissue levels of the studied parameters decreased significantly in the responders as compared to resistant cases. The response rate after combined therapy was 69% versus 53% after chemotherapy alone.

Conclusion: In conclusion, Nimesulide appears to boost the efficacy of the traditional chemotherapy as its co-administration showed encouraging effects on improving and normalization of the proangiogenic parameters levels and in turn the vascular supply of tumors. This may have good impact on the patient outcome, prolongation of their survival rate and prognosis.
A difficult diagnosis
Authors: Sanjiv Agarwal
Journal: BMJ (2006)

Mr Mahon's case1 shows the importance of carrying out investigations on the kidney in patients who have a recently diagnosed varicocele. Although Mr Mahon did not have occlusion of his renal vein, ultrasonography of the abdomen showed a previously undiagnosed abdominal aortic aneurysm that needed repair, renal cysts, and a solid renal lesion. Oncocytoma is difficult to …
P46 Vascular adhesion protein-1 promotes inflammation and fibrogenesis in murine steatohepatitis
Authors: L C Claridge, C J Weston, E L Haughton, N Westerlund, P F Lalor, D J Smith, D H Adams
Journal: Gut (2010)

Introduction  VAP-1 is an adhesion molecule which promotes lymphocyte recruitment to the liver. It is released in a soluble form (sVAP-1) from adipose tissue and the hepatic vascular bed. sVAP-1 has insulin-like effects, can initiate and propagate oxidative stress and is implicated in vascular complications of the metabolic syndrome. Our group has discovered that VAP-1 is expressed and secreted by hepatic stellate cells and we have reported that serum sVAP-1levelsareelevated in NAFLD and predict fibrosis. These observations suggest that VAP-1 may have a role in mediating interactions between lymphocytes and stromal cells to promote inflammation induced fibrosis in NAFLD.  Aim  To investigate a possible pathogenic role for VAP-1 in NAFLD by determining the effects of the inhibition or absence of VAP-1 in murine models of steatohepatitis.  Method  1. A high fat diet (HFD) was administered for 18 weeks in wild type (WT) C57Bl/6 mice (n=5) and VAP-1 null mice (n=5). 2. A methionine choline deficient (MCD) diet was administered for 6 weeks in WT mice (n=6), WT mice receiving an anti-VAP-1 antibody (n=6) and VAP-1 null mice (n=6).  Results  In the HFD model VAP-1 null mice developed less steatosis on quantitative analysis of Oil Red O staining (p  Conclusion  ElevatedsVAP-1 levels in NAFLD and increased hepatic VAP-1 expression in murine steatohepatitis suggest a role for VAP-1 in the pathogenesis of NAFLD. Inhibition and/or absence of VAP-1 are protective in two murine models of steatohepatitis implicating an important role for VAP-1 in hepatic fibrogenesis and suggesting it may be a potential therapeutic target in NAFLD.
Airway smooth muscle enlargement is associated with protease-activated receptor 2/ligand overexpression in patients with difficult-to-control severe asthma
Authors: Michel Aubier, Gabriel Thabut, Fatima Hamidi, Noëlline Guillou, Julien Brard, Marie-Christine Dombret, Keren Borensztajn, Brahim Aitilalne, Isabelle Poirier, Pascale Roland-Nicaise, Camille Taillé, Marina Pretolani
Journal: Journal of Allergy and Clinical Immunology (2016)
The new Cutaneous Lymphoma International Prognostic index (CLIPi) for early mycosis fungoides failed to identify prognostic groups in a cohort of Spanish patients
Authors: J. Sanz-Bueno, D. Lora, V. Monsálvez, L. Maroñas-Jiménez, C. Postigo, J.L. Rodríguez- Peralto, P.L. Ortiz-Romero
Journal: British Journal of Dermatology (2016)
Indicators for Remission of Suicidal Ideation Following Magnetic Seizure Therapy in Patients With Treatment-Resistant Depression
Authors: Yinming Sun, Faranak Farzan, Benoit H. Mulsant, Tarek K. Rajji, Paul B. Fitzgerald, Mera S. Barr, Jonathan Downar, Willy Wong, Daniel M. Blumberger, Zafiris J. Daskalakis
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder. <h3>Objective</h3> To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG). <h3>Design, Setting, and Participants</h3> Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site. <h3>Interventions</h3> The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used. <h3>Main Outcomes and Measures</h3> Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP. <h3>Results</h3> Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired<i>t</i><sub>26</sub> = 3.72;<i>P</i> = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex—but not in the motor cortex—were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90;<i>P</i> = .003). <h3>Conclusions and Relevance</h3> These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.
Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors
Authors: Shom Goel, Qi Wang, April C. Watt, Sara M. Tolaney, Deborah A. Dillon, Wei Li, Susanne Ramm, Adam C. Palmer, Haluk Yuzugullu, Vinay Varadan, David Tuck, Lyndsay N. Harris, Kwok-Kin Wong, X. Shirley Liu, Piotr Sicinski, Eric P. Winer, Ian E. Krop, Jean J. Zhao
Journal: Cancer Cell (2016)
Regulated expression of endothelin converting enzymes in glomerular endothelial cells.
Authors: K Uchida, S Uchida, K Nitta, W Yumura, H Nihei
Journal: Journal of the American Society of Nephrology (1997)

Endothelin converting enzyme (ECE) constitutes a potential regulatory site for the production of active mature endothelins. Two cDNAs (ECE-1 and -2) encoding ECE have recently been cloned, but the regulation of the expression of these ECE has not been clarified. In the study presented here, an attempt was made to determine whether or not glomerular endothelial cells (GEN) express ECE-1 and -2, and to learn how the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems. Ribonuclease protection assay revealed the expression of ECE-1 and -2 in cultured GEN, and the expression was increased approximately 2.5- and approximately 1.8-fold, respectively, by treatment with 10(-7) M 12-O-tetradecanocyl-phorbol-13-acetate (TPA) for 4 hours. These increases in ECE-1 and -2 expression with TPA were inhibited by cotreatment with calphostin C (10(-7) M). In contrast, 24-h treatment with 10(-7) M TPA significantly decreased the expression of ECE-1 and -2, indicating that the expression was tightly regulated by protein kinase C (PKC)-dependent mechanism(s). Actinomycin D (1 microgram/mL) abolished the TPA-induced increase of ECE-1 and -2 mRNA, whereas TPA treatment did not affect the mRNA stability of ECE-1 and -2, thus suggesting that TPA-induced increases of ECE-1 and -2 mRNA resulted from the transcriptional activation of ECE-1 and -2, gene, rather than from the increase of mRNA stability. In addition to the regulation by PKC, the effects of protein kinase A and G on ECE-1 and -2 expression were also examined. Treatment with chlorophenyl-thio cyclic AMP (200 microM) for 24 h decreased ECE-1 and -2 expression to approximately 50% and approximately 40% of the control value, respectively. 8-bromo-3', 5'-cyclic GMP also decreased ECE-1 and -2 expression to approximately 80% and approximately 25% of the control value, respectively. These results demonstrate that the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems, with the most prominent regulatory effect shown by protein kinase C.
Worsening of calcinosis cutis with teriparatide treatment in two osteoporotic patients
Authors: A.F. Echeverri, F.E. Ospina, C.A. Cañas, A. Agualimpia, J.P. Suso, G.J. Tobón, F. Bonilla-Abadía
Journal: British Journal of Dermatology (2016)

We present two cases of patients with systemic autoimmune diseases (one with dermatomyositis and one with CREST syndrome) who presented with a worsening of calcinosis cutis after treatment of osteoporosis with teriparatide. To our knowledge, this association is not described in the literature and might be considered in the spectrum of adverse reactions to teriparatide.
Phase I study of acupuncture as treatment of hot flashes for men with prostate cancer
Authors: H. Ashamalla, M. Jiang, A. Guirguis
Journal: Journal of Clinical Oncology (2008)

20678 Background: Up to 80% of men treated with androgen deprivation for prostate cancer suffer from hot flashes. Insomnia, fatigue, and irritability are often associated with hot flashes and adversely affect the quality of life for these patients. Several pharmacologic interventions can reduce hot flash frequency and intensity but have the potential for adverse effects. Acupuncture, a 23 century-old treatment modality, has been reported to substantially reduce hot flash frequency in postmenopausal women. We investigated the benefit of acupuncture in a group of men with hot flashes due to hormonal therapy for prostate cancer. Methods: Eight men with prostate cancer experiencing hot flashes more than three times/day were enrolled in an IRB approved protocol. The hot flashes were scored using 3 nationally accredited scoring systems; Hot Flash Score (HFS), Hot Flash Related Daily Interference Scale (HFRDIS) and Pittsburgh Sleep Quality Index (PSQI). Hot flashes were assessed on weekly basis and at one month post intervention. Interventions were given twice weekly for 4 consecutive weeks and once a week for the following 6 weeks. Pre- and post-acupuncture serum Serotonin is obtained. Results: Four patients completed the protocol with one month follow up. The mean pre-intervention hot flashes score was 12 for HFS, 59.2 for HFRIDS and 5 for PSQI. The post treatment scores were 4, 36.7 and 2.3 respectively. The overall mean reduction in hot flashes was 53%. The mean pretreatment serotonin level was 226 compared to 183 in post therapy estimation. No immediate adverse effects could be observed. Conclusions: The use of acupuncture reduced the intensity and frequency of hot flashes in men with prostate cancer secondary to androgen ablation by 53%. The intervention was safe with no immediate adverse effects. The study is still accruing patients. ClinicalTrials.gov ID#NCT00421902 No significant financial relationships to disclose.
Multicenter Study of Food Induced Anaphylaxis in Korean Infants
Authors: You Hoon Jeon, Soo-Young Lee, Kang Mo Ahn, So-Yeon Lee, Kyung Won Kim, Hyun Hee Kim, Jeong Hee Kim, Hye Young Yum, Woo Kyung Kim, Yong-Mean Park, Tae Won Song, Jihyun Kim, Yong Ju Lee, Gwang Cheon Jang, Kyoung Uk Jeong, Yoon Hee Kim, Taek Ki Min, Bok Yang Pyun
Journal: Journal of Allergy and Clinical Immunology (2016)
Detection of Tumorigenic Cells in Friend Virus-Infected Mice: An In Vivo Methodological Investigation2, 3
Authors: Françoise Moreau-Gachelin, Françoise Wendling, Paule Bucau-Varlet, Martine Charon, Pierre Tambourin
Journal: JNCI Journal of the National Cancer Institute (1981)

Tumor formation by subcutaneous transplants of spleens from erythroleukemic mice infected with Friend virus complex inducing polycythemia (FLV-P) is successful only during the late phase of the disease. To determine whether this observation is due to the absence of tumorigenic cells in the early phase of such leukemia or to the inability of standard procedures to detect these cells, the sensitivities of different routes of inoculation in sublethally irradiated or unirradiated syngeneic recipients were examined. The omentum of the sublethally irradiated mouse was found to be a suitable site for the homing and proliferation of recently isolated tumorigenic cells from FLV-P-infected mice, since it proved 1,000 times more sensitive than the usual subcutaneous sites in unirradiated mice. When this sensitive graft in the omentum was applied to detection of tumorigenic cells in the spleens of FLV-P-infected mice, the mean detection time was 20 days after virus infection, compared to 36 days with the usual subcutaneous graft method.
IMPS-19RETROVIRAL REPLICATING VECTOR-MEDIATED DELIVERY OF AN IMMUNODOMINANT NEO-ANTIGEN EPITOPE TARGET FOR VIRO-IMMUNOTHERAPY IN EXPERIMENTAL GLIOMA
Authors: Yuki Kato, Rudi Scharnweber, Akhito Inagaki, Shuichi Kamijima, Michelle Hickey, Dominique Lisiero, Kip Hermann, Horacio Soto, Joe Antonios, Shaina Sedighim, Hideho Okada, Linda Liau, David Klatzmann, Robert Prins, Noriyuki Kashara
Journal: Neuro-Oncology (2015)

Retroviral replicating vectors (RRV) show intrinsic tropism for actively dividing cells within the immunosuppressed tumor microenvironment, and viral replication significantly enhances transduction efficiency and therapeutic efficacy for cancer gene therapy. RRV-mediated prodrug activator gene therapy is currently being evaluated in clinical trials at multiple centers (www.clinicaltrials.gov, NCT01156584, NCT01470794) with highly encouraging results after local virus injection in patients with recurrent high grade glioma. In murine syngeneic intracranial glioma models, we have shown that RRV-mediated prodrug activator gene therapy can further induce immune responses leading to tumor clearance. We are now investigating the use of RRV for efficient and stable transduction of tumors in situ with an exogenous dominant foreign epitope, thereby xenogenizing the tumor. Here we developed a novel RRV displaying the lymphocytic choriomeningitis virus glycoprotein gp33-41 (gp33) epitope fused to the N-terminus of the viral env gene (RRV-gp33). We confirmed that insertion of the gp33 epitope does not affect RRV replication kinetics, genomic stability over serial passage, or transgene expression. In vitro cell viability measured by xCELLigence electrical impedance assay showed target cell-specific cytotoxicity by transgenic lymphocytes engineered with a T cell receptor recognizing the gp33 epitope (P14 cells) when co-cultured with glioma cells transduced with RRV-gp33. In vivo, adoptively transferred P14 cells selectively homed to RRV-gp33-transduced intracranial syngeneic gliomas in immunocompetent hosts, and mediated increased survival. These results indicate that RRV-mediated gene transfer can be effectively used to confer a new antigen to gliomas as a target for subsequent immunotherapy, and further studies are underway to investigate the therapeutic effect of combining RRV-mediated prodrug activator gene therapy and neo-antigen target delivery for adoptive immunotherapy.
Bioethicists Can and Should Contribute to Addressing Racism
Authors: Marion Danis, Yolonda Wilson, Amina White
Journal: The American Journal of Bioethics (2016)

The problems of racism and racially motivated violence in predominantly African American communities in the United States are complex, multifactorial, and historically rooted. While these problems are also deeply morally troubling, bioethicists have not contributed substantially to addressing them. Concern for justice has been one of the core commitments of bioethics. For this and other reasons, bioethicists should contribute to addressing these problems. We consider how bioethicists can offer meaningful contributions to the public discourse, research, teaching, training, policy development, and academic scholarship in response to the alarming and persistent patterns of racism and implicit biases associated with it. To make any useful contribution, bioethicists will require preparation and should expect to play a significant role through collaborative action with others.