tbuckley/cabot-search huggingface dataset:
Prolonged disease-free survival (DFS) is possible in locally advanced biliary cancers (LABC): Results of a phase II trial
Authors: V. J. Picozzi, N. K. Boone-Hill, L. W. Traverso, R. E. Kozarek
Journal: Journal of Clinical Oncology (2005)

4130 Background: LABC are a rare, infrequently studied cancer group typified by poor (median < 1 year) overall survival. To test the impact of intensive chemoradiation on survival in LABC, we developed a novel chemoradiation regimen using mitomycin C (MITO C), 5-fluorouracil (5-FU), and alpha interferon (IFN). These drugs share properties of 1) radiosensitiztion and 2) potential for synergistic cytotoxicity. Methods: From 1995 and 2003 we accrued 23 patients (pts) to a phase II study using treatment as follows: external beam XRT 4500–5000 cGy/25 fx d1–35; MITO C 10mg/m2 IV d1, 29; 5-FU 200mg/m2 IVCI d1–35 and IFN 3,000,000U sq qod d1–35. 5-FU 200mg/m2 IVCI d64–105 and 120–161 completed the regimen.Site of cancer origin was extrahepatic cholangiocarcinoma (n=16), gallbladder cancer (n=5) and intrahepatic cholangiocarcinoma (n=2). 9/23 (39%) of pts underwent partial tumor resection prior to XRT. The primary tool for tumor staging/assessment was helical CT scanning. Results: Acute toxicity was moderate. Reported grade 3 or higher toxicity included thrombocytopenia (4/23 pts, 17%), and neutropenia, GI bleeding, anorexia and dehdration (all 3/23 pts, 13%). There was 1 episode of grade 4 toxicity (GI bleeding due to duodenal ulcer) and no treatment death due to acute toxicity. Biliary stricture formation potentially attributable (at least in part) to therapy occurred in 3/23 pts (13%) as a long-term complication. In 14 relapsing pts, inital relapse was equally divided between local (n=7) and sytemic (peritoneum=5, liver =2) sites, all within 2 years of start of therapy. With median followup of approximately 5 years, median DFS for this patient cohort is 19 months (Kaplan -Meier method). 1-year, 2-year and 5-year DFS are 66%,37% and 33%, respectively. 9/23 (39%) of pts have been in continuous complete remission following this treament (duration 15–102+ months). Conclusions: We conclude this regimen applied to pts with LABC 1) can be delivered successfully with moderate toxicity, 2) was associated with longer DFS than typically seen in LABC, and 3) offers potential for prolonged DFS in LABC. Subsequent phase II work is in progress at our institution based upon these results. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
ERK mediated upregulation of death receptor 5 overcomes the lack of p53 functionality in the diaminothiazole DAT1 induced apoptosis in colon cancer models: efficiency of DAT1 in Ras-Raf mutated cells
Authors: Reshma Thamkachy, Rohith Kumar, K. N. Rajasekharan, Suparna Sengupta
Journal: Molecular Cancer (2016)

p53 is a tumour suppressor protein that plays a key role in many steps of apoptosis, and malfunctioning of this transcription factor leads to tumorigenesis. Prognosis of many tumours also depends upon the p53 status. Most of the clinically used anticancer compounds activate p53 dependent pathway of apoptosis and hence require p53 for their mechanism of action. Further, Ras/Raf/MEK/ERK axis is an important signaling pathway activated in many cancers. Dependence of diaminothiazoles, compounds that have gained importance recently due to their anticancer and anti angiogenic activities, were tested in cancer models with varying p53 or Ras/Raf mutational status. In this study we have used p53 mutated and knock out colon cancer cells and xenograft tumours to study the role of p53 in apoptosis mediated by diaminothiazoles. Colon cancer cell lines with varying mutational status for Ras or Raf were also used. We have also examined the toxicity and in vivo efficacy of a lead diaminothiazole 4-Amino-5-benzoyl-2-(4-methoxy phenylamino)thiazole (DAT1) in colon cancer xenografts. We have found that DAT1 is active in both in vitro and in vivo models with nonfunctional p53. Earlier studies have shown that extrinsic pathway plays major role in DAT1 mediated apoptosis. In this study, we have found that DAT1 is causing p53 independent upregulation of the death receptor 5 by activating the Ras/Raf/MEK/ERK signaling pathway both in wild type and p53 suppressed colon cancer cells. These findings are also confirmed by the in vivo results. Further, DAT1 is more efficient to induce apoptosis in colon cancer cells with mutated Ras or Raf. Minimal toxicity in both acute and subacute studies along with the in vitro and in vivo efficacy of DAT1 in cancers with both wild type and nonfunctional p53 place it as a highly beneficial candidate for cancer chemotherapy. Besides, efficiency in cancer cells with mutations in the Ras oncoprotein or its downstream kinase Raf raise interest in diaminothiazole class of compounds for further follow-up.
Thalidomide use in patients with relapsed, refractory, low-grade lymphoma
Authors: E. A. Lowenthal, L. D. Camp-Sorrell, J. A. Lingenfelter
Journal: Journal of Clinical Oncology (2004)

6672 Background: Low grade B-cell lymphomas are a heterogenous group characterized by advanced stage at presentation and an indolent course that inexorably ends in death after several years of treatment. With the recent demonstration that NF-kappa beta is expressed in Bcell lymphomas, and the knowledge that thalidomide impacts this growth factor in myeloma, we offered thalidomide to a series of 4 symptomatic patients who had exhausted all other therapeutic options. Methods: 3 men and 1 woman (mean age 56) diagnosed with Stage IV, CD20+ transformed low grade lymphoma were enrolled in the STEPS program for thalidomide access over the last 2 years. They were started on a thalidomide dose of 100 mg hs. All patients had developed progressive symptomatic disease after sequential treatment with chlorambucil, followed by fludarabine, followed by CHOP plus Rituxan, followed by salvage Rituxan alone for 8 weekly treatments. In addition, two patients had relapsed after participation in a Bexar clinical trial. Results: 3 of the 4 patients have had a CR that has been durable for a mean duration of follow up of 17 months (range 16–21 mos). The 4th patient was unable to tolerate the medication due to anasarca and had a transient partial response of only 4 months. This doseage of thalidomide has been associated with minimal side effects in these patients for a sustained treatment duration. Conclusions: Thalidomide has demonstrated compelling efficacy in the treatment of a small group of patients with refractory low grade lymphoma with minimal toxicity. Larger studies are needed to confirm these results, to define the most appropriate time to initiate this agent, and to define the optimum duration of therapy. No significant financial relationships to disclose.
Hepatitis B : Risk of hepatitis B virus reactivation according to viral status and treatment intensity in patients with hepatocellular carcinoma (초)
Authors: Jeong Won Jang, Byong Sun Oh, Jung Hyun Kwon, Chan Ran You, Jin Dong Kim, Hyun Young Woo, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Kyu Won Chung
Journal: Clinical and Molecular Hepatology (2011)
Targeting of BMI-1 with PTC-209 shows potent anti-myeloma activity and impairs the tumour microenvironment
Authors: Arnold Bolomsky, Karin Schlangen, Wolfgang Schreiner, Niklas Zojer, Heinz Ludwig
Journal: Journal of Hematology & Oncology (2016)

The polycomb complex protein BMI-1 (BMI-1) is a putative oncogene reported to be overexpressed in multiple myeloma (MM). Silencing of BMI-1 was shown to impair the growth and survival of MM cells. However, therapeutic agents specifically targeting BMI-1 were not available so far. Here, we investigated PTC-209, a novel small molecule inhibitor of BMI-1, for its activity in MM. BMI-1 expression was analysed in human MM cell lines and primary MM cells by using publically available gene expression profiling (GEP) data. The anti-MM activity of PTC-209 was investigated by viability testing, cell cycle analysis, annexin V and 7-AAD staining, quantification of cleaved poly(ADP-ribose) polymerase (PARP), JC-1 as well as colony formation assays. Deregulation of central myeloma growth and survival genes was studied by quantitative PCR and flow cytometry, respectively. In addition, the impact of PTC-209 on in vitro osteoclast, osteoblast and tube formation was analysed. We confirmed overexpression of BMI-1 in MM patients by using publically available GEP datasets. Of note, BMI-1 expression was further increased at relapse which translated into significantly shorter overall survival in relapsed/refractory patients treated with bortezomib or dexamethasone. Treatment with PTC-209 significantly decreased viable cell numbers in human MM cell lines, induced a G1 cell cycle arrest, promoted apoptosis and demonstrated synergistic activity with pomalidomide and carfilzomib. The anti-MM activity of PTC-209 was accompanied by a significant decrease of cyclin D1 (CCND1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) expression as well as upregulation of cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1B (CDKN1B). We also observed upregulation of NOXA (up to 3.6 ± 1.2-fold induction, P = 0.009) and subsequent downregulation of myeloid cell leukemia 1 (MCL-1) protein levels, which likely mediates the apoptotic effects of PTC-209. Importantly, the anti-MM activity was upheld in the presence of stromal support or myeloma growth factors insulin-like growth factor 1 (IGF-1) and interleukin 6 (IL-6). In the MM microenvironment, PTC-209 impaired tube formation, impaired osteoclast development and decreased osteoblast formation in a dose-dependent manner (P < 0.01 at 1 μM, respectively). The latter might be attributed to an induction of DKK1 and was reversed by concurrent anti-DKK1 antibody treatment. We confirmed overexpression of BMI-1 in MM highlighting its role as an attractive drug target and reveal therapeutic targeting of BMI-1 by PTC-209 as a promising novel therapeutic intervention for MM.
Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis
Authors: Mira M Wouters, Sander Van Wanrooy, Anh Nguyen, James Dooley, Javier Aguilera-Lizarraga, Winde Van Brabant, Josselyn E Garcia-Perez, Lukas Van Oudenhove, Marc Van Ranst, Jan Verhaegen, Adrian Liston, Guy Boeckxstaens
Journal: Gut (2015)

<h3>Objective</h3> Psychological factors increase the risk to develop postinfectious IBS (PI-IBS), but the mechanisms involved are unclear. As stress affects the immune system, we investigated the potential interaction between psychological factors, the immune response against infectious gastroenteritis (IGE) and the development of IGE and PI-IBS in a large cohort exposed to contaminated drinking water. <h3>Design</h3> 18 620 people exposed to contaminated drinking water (norovirus, <i>Giardia lamblia</i>, <i>Campylobacter jejuni</i>) were invited to participate in a prospective controlled cohort study. They were asked to complete questionnaires assessing demographic, psychological and clinical data during the outbreak and 1 year later. At both time points, in-depth immune function (peripheral blood and rectal biopsies) was studied in a subgroup of subjects. <h3>Results</h3> 1379 subjects completed the questionnaires during the outbreak, of which 271 developed IGE. Risk factors for IGE included younger age, pre-existing dyspepsia-like symptoms, anxiety and drinking contaminated tap water. Anxiety scores before the outbreak inversely correlated with interleukin-2-expressing CD4+ T cells (r=0.6, p=0.01, n=23). At follow-up, 34 of 172 (20%) IGE subjects developed IBS compared with 24/366 exposed participants (7%, p&lt;0.0001, χ<sup>2</sup> test). A Th2 cytokine phenotype at time of infection was associated with increased risk for PI-IBS 1 year later. Except for increased B cell numbers, no evidence for systemic or rectal mucosal immune activation in PI-IBS was demonstrated at follow-up. <h3>Conclusions</h3> Our study shows that the increased risk of patients with psychological comorbidity to develop PI-IBS may partly result from an increased susceptibility to develop IGE, possibly resulting from a Th2-immune bias. <h3>Trial registration number</h3> (ClinicalTrials.gov NCT01497847).
Deregulated methionine adenosyltransferase α1, c‐Myc, and Maf proteins together promote cholangiocarcinoma growth in mice and humans‡
Authors: Heping Yang, Ting Liu, Jiaohong Wang, Tony W.H. Li, Wei Fan, Hui Peng, Anuradha Krishnan, Gregory J. Gores, Jose M. Mato, Shelly C. Lu
Journal: Hepatology (2016)

c‐Myc induction drives cholestatic liver injury and cholangiocarcinoma (CCA) in mice, and induction of Maf proteins (MafG and c‐Maf) contributes to cholestatic liver injury, whereas S‐adenosylmethionine (SAMe) administration is protective. Here, we determined whether there is interplay between c‐Myc, Maf proteins, and methionine adenosyltransferase α1 (MATα1), which is responsible for SAMe biosynthesis in the liver. We used bile duct ligation (BDL) and lithocholic acid (LCA) treatment in mice as chronic cholestasis models, a murine CCA model, human CCA cell lines KMCH and Huh‐28, human liver cancer HepG2, and human CCA specimens to study gene and protein expression, protein‐protein interactions, molecular mechanisms, and functional outcomes. We found that c‐Myc, MATα1 (encoded by MAT1A), MafG, and c‐Maf interact with one another directly. MAT1A expression fell in hepatocytes and bile duct epithelial cells during chronic cholestasis and in murine and human CCA. The opposite occurred with c‐Myc, MafG, and c‐Maf expression. MATα1 interacts mainly with Mnt in normal liver, but this switches to c‐Maf, MafG, and c‐Myc in cholestatic livers and CCA. Promoter regions of these genes have E‐boxes that are bound by MATα1 and Mnt in normal liver and benign bile duct epithelial cells that switched to c‐Myc, c‐Maf, and MafG in cholestasis and CCA cells. E‐box positively regulates c‐Myc, MafG, and c‐Maf, but it negatively regulates MAT1A. MATα1 represses, whereas c‐Myc, MafG, and c‐Maf enhance, E‐box‐driven promoter activity. Knocking down MAT1A or overexpressing MafG or c‐Maf enhanced CCA growth and invasion in vivo . Conclusion: There is a novel interplay between MATα1, c‐Myc, and Maf proteins, and their deregulation during chronic cholestasis may facilitate CCA oncogenesis. (H epatology 2016;64:439‐455)
Autopsy Analysis On Epidemiology and Site of Involvement Of Invasive Fungal Infections (IFI) In Hematological Malignancies : A Retrospective Study at Hematologic Tertiary Care Department
Authors: Anna Chierichini, Francesca Monardo, Barbara Anaclerico, Paola Anticoli Borza, Velia Bongarzoni, Domenico Campagna, Michele Cedrone, Susanna Fenu, Marianna Norata, Francesca Paoloni, Benedetto Ronci, Luciana Annino
Journal: Blood (2013)
Observations on the theoretical bases for seclusion of the psychiatric inpatient
Authors: T G Gutheil
Journal: American Journal of Psychiatry (1978)

Contemporary controversy concerning the seclusion of psychiatric inpatients is focused primarily on the issues of civil rights and behavior control. The author believes that we are in danger of losing sight of the therapeutic aspects of this treatment modality. He offers a brief review of the theoretical and clinical rationale for seclusion.
Cytogenetic Study of a New Ph1-Positive Cell line (NALM-1)2
Authors: Shin-ichi Sonta, Jun Minowada, Teruhiko Tsubota, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1977)

The chromosomes of a cell line (NALM-1) derived from the leukocytes of a patient with chronic myelocytic leukemia (CML) were examined with several banding techniques. The modal chromosome number was 46 and the cells contained a Philadelphia chromosome (Ph1), due to the standard translocation of the missing segment of the long arm of chromosome #22 onto the distal end of the long arm of chromosome #9, i.e., t(9;22) (q34;q11). The Ph1-positive modal cells of the NALM-1 line also had two common marker chromosomes, an extra X-chromosome, and missing chromosomes in groups #7, 9, and 15. Immunologic examination of the NALM-1 cells revealed them to have non-T-non-B (null) surface characteristics. An antigen specific for cells of acute leukemia and a human la-like antigen were detected. These facts suggested that the NALM-1 cell line originated from CML cells and maintained the cytogenetic and Immunologic characteristics of such cells.
Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study
Authors: B. Pérez-Valderrama, J.A. Arranz Arija, A. Rodríguez Sánchez, A. Pinto Marín, P. Borrega García, D.E. Castellano Gaunas, G. Rubio Romero, C. Maximiano Alonso, J.C. Villa Guzmán, J.L. Puertas Álvarez, I. Chirivella González, M.J. Méndez Vidal, M.J. Juan Fita, L. León-Mateos, M. Lázaro Quintela, R. García Domínguez, J.M. Jurado García, E. Vélez de Mendizábal, J.J. Lambea Sorrosal, I. García Carbonero, A. González del Alba, C. Suárez Rodríguez, P. Jiménez Gallego, J.A. Meana García, R.D. García Marrero, P. Gajate Borau, C. Santander Lobera, C. Molins Palau, M. López Brea, E.M. Fernández Parra, O. Reig Torras, L. Basterretxea Badiola, S. Vázquez Estévez, J.L. González Larriba
Journal: Annals of Oncology (2015)
Micro-RNAs in abdominal aortic aneurysms: insights from animal models and relevance to human disease
Authors: Juliette Raffort, Fabien Lareyre, Marc Clement, Ziad Mallat
Journal: Cardiovascular Research (2016)

Abdominal aortic aneurysm (AAA) is a major health concern and may be associated with high rates of mortality linked to acute complications. Diagnosis and treatment are, respectively, based on imaging and surgical techniques. Drug-based therapies are still mostly ineffective, which highlight a real unmet need. Major pathophysiological mechanisms leading to aneurysm formation involve inflammatory processes, degradation of the extracellular matrix, and loss of smooth muscle cells. However, the precise cellular and molecular pathways are still poorly understood. Recently, microRNAs have emerged as major intracellular players in a wide range of biological processes, and their stability in extracellular medium within microvesicles has led to propose them as mediators of intercellular crosstalk and as potential biomarkers and therapeutic targets in a variety of disease settings. To date, several studies have been performed to address the involvement of micro-RNAs (miRs) in aneurysm formation and complications. Here, we discuss the roles and implications of miRs in animal models and their relevance to human AAA.
The Role of Physicians in Asylum Evaluation
Authors: Jenna M. Peart, Elisabeth H. Tracey, Jules B. Lipoff
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Decline in HIV infections in Thailand [letter]
Authors: Brody S
Journal: New England Journal of Medicine (1996)

Nelson et al. report that seropositivity for the human immunodeficiency virus (HIV) declined among Thai military conscripts from a range of 10.4-12.5% in the period 1991-93 to 6.7% in 1995 and they attribute the decline to the increased use of condoms.  The authors rely on the post hoc ergo propter hoc fallacy attributing causation on the basis of the temporal sequence (of a single pair of events).  Among Ugandan men of comparable age the prevalence of HIV declined from 11.8% in 1989 to 2.7% in 1994 in the absence of either a major program of condom distribution or a behavioral intervention.  Thus the decline in seroprevalence in Thailand might best be attributed to the natural course of epidemics rather than to the distribution of condoms.  Table 3 of Nelson et al. shows that the use of condoms with prostitutes was not significantly related to protection from HIV in 1993 or 1995 and was associated with an increased risk in the 1991 cohort.  As in most studies of risk factors for HIV infection no attempt was made to verify the self-reports of the soldiers even though there is frequent misreporting by respondents in such investigations and other reasons for the misclassification of risk.  One trend that may be observed in Table 4 of the article is a cohort effect of increasing risk of infection attributable to injection-drug use and homosexual contact and a decreasing risk attributable to heterosexual prostitution.  This may be due to seropositive persons becoming more forthcoming about their more serious risk factors.  (full text)
Prognostic Factors in Primary Cutaneous Lymphomas Other Than Mycosis Fungoides and the Sézary Syndrome
Authors: F. Grange, G. Hedelin, P. Joly, M. Beylot-Barry, M. D’Incan, M. Delaunay, L. Vaillant, M.F. Avril, J. Bosq, J. Wechsler, S. Dalac, C. Grosieux, N. Franck, E. Esteve, C. Michel, C. Bodemer, B. Vergier, L. Laroche, M. Bagot
Journal: Blood (1999)
Poster Exhibition : Add on Lamivudine to Adefovir Monotherapy for the Treatment of Lamivudine-Resistant Chronic Hepatitis B Patients (초)
Authors: Young Ju Cho, Jae Youn Cheong, Myoung Hee Lee, Su Jin Jeon, Yoon Chul Lee, Sung Hwan Kang, Chang Joon Kang, Jae Chun Song, Sung Won Cho
Journal: Clinical and Molecular Hepatology (2009)
Identifying Children and Adolescents at Risk for Persistent Postconcussion Symptoms
Authors: Lynn Babcock, Brad G. Kurowski
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal