tbuckley/cabot-search huggingface dataset:
Abstract 3922: TFEB translocation renal carcinoma: Two cases of novel isoforms with unique clinicopathological features
Authors: Kentaro Inamura, Yuki Togashi, Mutsunori Fujiwara, Shinya Yamamoto, Junji Yonese, Iwao Fukui, Yuichi Ishikawa
Journal: Cancer Research (2011)

Abstract Renal cell carcinoma (RCC) with t(6;11) translocation, involving the transcription factor EB (TFEB), is an extremely rare neoplasm with only 20 cases reported to date. According to the available clinical histories, TFEB translocation renal carcinoma (TFEB RC) is predominantly seen in children and young adults and generally indolent. So far, only two TFEB RC cases have been reported to result in metastases and patient death. We herein present two cases of novel isoforms of TFEB RC with unique clinicopathological features, involving a 37-year-old man and a 47-year-old man. Whereas the former case had an aggressive course, the latter case had the borderline features between TFEB RC and chromophobe type RCC histologically and immunohistochemically except for the nuclear staining of TFEB. Genetically, the former case had two variants of mRNA in RT-PCR analysis, one of which directly connected to the exon 3 of TFEB in sequencing analysis. The latter case had the fusion point of TFEB downstream of the wild-type ATG in exon 3, although the nuclear staining of TFEB was detected. Our data including the molecular characterization contribute to clarify this tumor entity genetically and clinicopathologically. Further investigations with additional new cases are required. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3922. doi:10.1158/1538-7445.AM2011-3922
M30 Neoepitope Expression in Epithelial Cancer: Quantification of Apoptosis in Circulating Tumor Cells by CellSearch Analysis
Authors: Elisabetta Rossi, Umberto Basso, Romina Celadin, Francesca Zilio, Salvatore Pucciarelli, Michele Aieta, Carmen Barile, Teodoro Sava, Giorgio Bonciarelli, Salvatore Tumolo, Cristina Ghiotto, Cristina Magro, Antonio Jirillo, Stefano Indraccolo, Alberto Amadori, Rita Zamarchi
Journal: Clinical Cancer Research (2010)

This study aimed to detect the M30 neoepitope on circulating tumor cells (CTC) as a tool for quantifying apoptotic CTC throughout disease course and treatment.An automated sample preparation and analysis platform for computing CTC (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The assay was validated using cell lines and blood samples from healthy volunteers and patients with epithelial cancer.M30-positive CTC could be detected in >70% of CTC-positive carcinoma patients, which were free for both chemotherapy and radiologic treatments. The fraction of M30-positive CTC varied from 50% to 80%, depending on the histotype. To investigate the potential application of the M30 CTC assay for the evaluation of response in early phase trials, CTC and M30-positive CTC were enumerated in a small case series of breast cancer patients during treatment. Results indicate that changes in the balance of M30-negative/positive CTC may be used as a dynamic parameter indicating an active disease, as documented by consistent radiologic findings.M30 expression on CTC is detectable by immunofluorescence. The M30-integrated test has potential for monitoring dynamic changes in the quote of apoptotic CTC (in addition to CTC count) to evaluate response in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research, in which there is a pressing need for informative circulating biomarkers.
Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.
Authors: M Markman, E Rowinsky, T Hakes, B Reichman, W Jones, J L Lewis, S Rubin, J Curtin, R Barakat, M Phillips
Journal: Journal of Clinical Oncology (1992)

PURPOSE To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.
Predicting the Glycemic Response to Gastric Bypass Surgery in Patients With Type 2 Diabetes
Authors: John B. Dixon, Lee-Ming Chuang, Keong Chong, Shu-Chun Chen, Gavin W. Lambert, Nora E. Straznicky, Elisabeth A. Lambert, Wei-Jei Lee
Journal: Diabetes Care (2012)

To find clinically meaningful preoperative predictors of diabetes remission and conversely inadequate glycemic control after gastric bypass surgery. Predicting the improvement in glycemic control in those with type 2 diabetes after bariatric surgery may help in patient selection.Preoperative details of 154 ethnic Chinese subjects with type 2 diabetes were examined for their influence on glycemic outcomes at 1 year after gastric bypass. Remission was defined as HbA(1c) ≤6%. Analysis involved binary logistic regression to identify predictors and provide regression equations and receiver operating characteristic curves to determine clinically useful cutoff values.Remission was achieved in 107 subjects (69.5%) at 12 months. Diabetes duration <4 years, body mass >35 kg/m(2), and fasting C-peptide concentration >2.9 ng/mL provided three independent preoperative predictors and three clinically useful cutoffs. The regression equation classification plot derived from continuous data correctly assigned 84% of participants. A combination of two or three of these predictors allows a sensitivity of 82% and specificity of 87% for remission. Duration of diabetes (with different cutoff points) and C-peptide also predicted those cases in which HbA(1c) ≤7% was not attained. Percentage weight loss after surgery was also predictive of remission and of less satisfactory outcomes.The glycemic response to gastric bypass is related to BMI, duration of diabetes, fasting C-peptide (influenced by insulin resistance and residual β-cell function), and weight loss. These data support and refine previous findings in non-Asian populations. Specific ethnic and procedural regression equations and cutoff points may vary.
Genetics and genomics of radiotherapy toxicity: towards prediction
Authors: Catharine M West, Gillian C Barnett
Journal: Genome Medicine (2011)

Radiotherapy is involved in many curative treatments of cancer; millions of survivors live with the consequences of treatment, and toxicity in a minority limits the radiation doses that can be safely prescribed to the majority. Radiogenomics is the whole genome application of radiogenetics, which studies the influence of genetic variation on radiation response. Work in the area focuses on uncovering the underlying genetic causes of individual variation in sensitivity to radiation, which is important for effective, safe treatment. In this review, we highlight recent advances in radiotherapy and discuss results from four genome-wide studies of radiotoxicity.
Celecoxib-induced apoptosis in rat cholangiocarcinoma cells mediated by Akt inactivation and Bax translocation
Authors: Zichen Zhang, Guan-Hua Lai, Alphonse E. Sirica
Journal: Hepatology (2004)

Recently, we demonstrated that the cyclooxygenase-2 (COX-2) inhibitor celecoxib acts to significantly suppress the growth of rat C611B cholangiocarcinoma (ChC) cells in vitro. To establish a molecular mechanism for this growth suppression, we investigated the effects of celecoxib on apoptotic signaling pathways in cultured rat C611B ChC cells. Celecoxib and another COX-2 inhibitor, rofecoxib, at 5 μM were almost equally effective in inhibiting prostaglandin E2 (PGE2) production by these cells, but at this low concentration, neither inhibitor suppressed growth or induced apoptosis. Celecoxib at 50 μM induced prominent apoptosis in these cells, whereas rofecoxib at 50 μM was without effect in either suppressing growth or inducing apoptosis. Celecoxib (50 μM) did not alter Bcl-2, Bcl-xL, or COX-2 protein levels, nor did it inhibit p42/44 mitogen-activated protein kinase (MAPK) phosphorylation; however, it significantly suppressed serine/threonine kinase Akt/PKB (Akt) phosphorylation and kinase activity in cultured C611B cells. This effect, in turn, directly correlated with Bax translocation to mitochondria, cytochrome c release into cytosol, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Addition of 25 μM PGE2 to C611B cell cultures blocked the apoptotic actions of celecoxib. Rofecoxib (50 μM) was without effect in suppressing Akt phosphorylation and caspase-3 activation. In vivo, celecoxib partially suppressed tumorigenic growth of C611B ChC cells. In conclusion, our results indicate that celecoxib preferentially acts in vitro to induce apoptosis in ChC cells through a mechanism involving Akt inactivation, Bax translocation, and cytochrome c release. Our in vivo results further suggest celecoxib might have potential therapeutic or chemopreventive value against ChC. (HEPATOLOGY 2004;39:1028–1037.)
Equity in financing and use of health care in Ghana, South Africa, and Tanzania: implications for paths to universal coverage
Authors: Anne Mills, John E Ataguba, James Akazili, Jo Borghi, Bertha Garshong, Suzan Makawia, Gemini Mtei, Bronwyn Harris, Jane Macha, Filip Meheus, Di McIntyre
Journal: The Lancet (2012)
Induction and properties of cytoplasmic factor(s) which enhance nuclear nonhistone protein phosphorylation in lymphocytes stimulated by anti-Ig.
Authors: Y Nishizawa, T Kishimoto, H Kikutani, Y Yamamura
Journal: The Journal of Experimental Medicine (1977)

An increased in vitro phosphorylation of nonhistone nuclear proteins (NHP) was observed in the nuclei isolated from rabbit lymphocytes which had been stimulated with anti-Ig for 4 h. No concomitant increase of phosphorylation in histones or 0.14 M NaCl-soluble proteins was observed. The increase of in vitro phosphorylation of NHP was also observed in the nuclei isolated from nonstimulated cells when these nuclei were preincubated for 2 h with cell-free extracts from anti-Ig-stimulated cells. The active substance in cell-free extracts was maximally induced when lymphocytes were stimulated with anti-Ig for 2 h. The induction of an increased phosphorylation of NHP in nonstimulated nuclei with the cell-free extracts was not due to decrease of the adenosine triphosphate pool in the extracts from anti-Ig-stimulated cells. The active substance in cell-free extracts was not NHP-protein kinase itself, but it probably activated NHP-protein kinase in quiescent nuclei. The active substance was nondialyzable and probably protein. It was resistant against heating at 56 degrees C for 30 min, but the activity was completely destroyed by heating at 90 degrees C for 30 min. The active substance may be responsible for the transduction of the membrane-mediated signals given through Ig receptors to nuclei.
Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo
Authors: M. Pilar Gil, Rachelle Salomon, Jennifer Louten, Christine A. Biron
Journal: Blood (2005)

Abstract Type 1 interferons (IFNs) are induced in vivo, administered therapeutically, and potential targets for amelioration of autoimmune diseases. The cytokines mediate profound antiproliferative effects. Signal transducer and activator of transcription 1 (STAT1)-dependent signaling pathways are required for inhibition of proliferation, and viral infections can elicit high levels of type 1 IFNs as well as total STAT1 protein expression. Thus, a mechanism must be in place to help antigen-specific T cells overcome IFN-induced inhibition of proliferation. The studies reported here demonstrate that total CD8 T-cell proliferation in the presence of IFNs, ex vivo in response to cytokines and in vivo during viral infection, is inhibited through a STAT1-dependent mechanism. In contrast, major proportions of antigen-specific CD8, but not CD4, T cells are rendered less sensitive to this inhibition, express lower endogenous levels of total STAT1, and are selectively proliferating in the presence of type 1 IFN, at key times after viral challenge. Taken together, these novel results show that differential STAT1 expression is used by the immune system to modify cytokine-mediated effects on T-cell expansion and have implications for the consequences of therapeutic intervention in cytokine function.
Immunoglobulin A in the skin of patients with ankylosing spondylitis.
Authors: A Collado, R Sanmarti, I Bielsa, T Castel, E Kanterewicz, J.D Cañete, M.A Brancós, J Rotes-Querol
Journal: Annals of the Rheumatic Diseases (1988)

Cutaneous immunofluorescence studies were carried out in 21 patients with ankylosing spondylitis (AS) and the results compared with those for 18 healthy subjects. The most prominent finding was the presence of IgA in dermal vessels of patients with AS (71% compared with 17% of the control group). IgG and IgM cutaneous deposits were also observed in patients with AS, but these results did not differ from those of the control group. A renal biopsy was performed in three of the patients presenting with unexplained microscopic haematuria. One of them had an IgA nephropathy, but no correlation was found between kidney and skin deposits of IgA. These findings suggest that IgA cutaneous deposits in AS are not a marker of IgA nephropathy but stress the role of immunoglobulin A in the pathogenesis of this disease.
Antiremodeling Effects of Iloprost and the Dual-Selective Phosphodiesterase 3/4 Inhibitor Tolafentrine in Chronic Experimental Pulmonary Hypertension
Authors: Ralph Theo Schermuly, Klaus Peter Kreisselmeier, Hossein Ardeschir Ghofrani, Arun Samidurai, Soni Pullamsetti, Norbert Weissmann, Christian Schudt, Leander Ermert, Werner Seeger, Friedrich Grimminger
Journal: Circulation Research (2004)

Severe pulmonary hypertension is a disabling disease with high mortality. We investigated acute and chronic effects of iloprost, a long-acting prostacyclin analogue, and the dual-selective phosphodiesterase 3/4 inhibitor tolafentrine in monocrotaline-induced pulmonary hypertension in rats. Twenty-eight and 42 days after administration of the alkaloid, right ventricular systolic pressure increased from 25.8+/-2.0 to 62.9+/-3.4 and 70.5+/-7.4 mm Hg, with concomitant decline in cardiac index, central venous oxygen saturation, and arterial oxygenation. Marked right heart hypertrophy was demonstrated by the strongly elevated ratio of right ventricle/left ventricle plus septum weight, and massive thickening of the precapillary artery smooth muscle layer was shown histologically. Western blot analysis demonstrated increased levels of matrix metalloproteinases (MMPs) -2 and -9 and increased gelatinolytic activities in isolated pulmonary arteries. In these animals, both intravenous iloprost and tolafentrine displayed characteristic features of pulmonary vasodilators. When chronically infused from days 14 to 28, both agents significantly attenuated all monocrotaline-induced hemodynamic and gas exchange abnormalities as well as right heart hypertrophy. Full normalization of all variables including right ventricle size was achieved on combined administration of both agents during this period. This was also true for MMP-2 and MMP-9 expression and activity. Moreover, when iloprost plus tolafentrine was used for late therapeutic intervention, with infusion from days 28 to 42 after full establishment of severe pulmonary hypertension and cor pulmonale, hemodynamic, gas exchange, and cardiac and pulmonary vascular remodeling changes were significantly reversed. We conclude that the combined administration of iloprost and a dual-selective phosphodiesterase 3/4 inhibitor prevents and reverses the development of pulmonary hypertension and cor pulmonale in response to monocrotaline in rats. This regimen may therefore offer a possible antiremodeling therapy in severe pulmonary hypertension.
Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells
Authors: Nicole Bacher, Verena Raker, Claudia Hofmann, Edith Graulich, Melanie Schwenk, Ria Baumgrass, Tobias Bopp, Ulrich Zechner, Luzie Merten, Christian Becker, Kerstin Steinbrink
Journal: Cancer Research (2013)

IFN-α is an antineoplastic agent in the treatment of several solid and hematologic malignancies that exerts strong immune- and autoimmune-stimulating activity. However, the mechanisms of immune activation by IFN-α remain incompletely understood, particularly with regard to CD4(+)CD25(high)Foxp(+) regulatory T cells (Treg). Here, we show that IFN-α deactivates the suppressive function of human Treg by downregulating their intracellular cAMP level. IFN-α-mediated Treg inactivation increased CD4(+) effector T-cell activation and natural killer cell tumor cytotoxicity. Mechanistically, repression of cAMP in Treg was caused by IFN-α-induced MAP-ERK kinase (MEK)/extracellular signal-regulated kinase (ERK)-mediated phosphodiesterase 4 (PDE4) activation and accompanied by downregulation of IFN receptor (IFNAR)-2 and negative regulation of T-cell receptor signaling. IFN-α did not affect the anergic state, cytokine production, Foxp3 expression, or methylation state of the Treg-specific demethylated region (TSDR) within the FOXP3 locus associated with a stable imprinted phenotype of human Treg. Abrogated protection by IFN-α-treated Treg in a humanized mouse model of xenogeneic graft-versus-host disease confirmed IFN-α-dependent regulation of Treg activity in vivo. Collectively, the present study unravels Treg inactivation as a novel IFN-α activity that provides a conceivable explanation for the immune-promoting effect and induction of autoimmunity by IFN-α treatment in patients with cancer and suggests IFN-α for concomitant Treg blockade in the context of therapeutic vaccination against tumor antigens.
A model patient
Authors: Nicola Thomas
Journal: BMJ (2007)

Mary wasn't feeling very well according to the nurse on the other end of the telephone. The nurse said that Mary “came over a bit funny” at the dinner table and was found to have an irregular pulse with a rate of about 30 beats/minute—enough to make anyone come over a bit funny. I went to see Mary, examined her, and performed electrocardiography, which confirmed slow atrial fibrillation. 

I contacted the cardiology registrar, who listened patiently while I presented my case. At the end …
Controlled trial of methylprednisolone therapy in severe acute alcoholic hepatitis.
Authors: A Theodossi, A L Eddleston, R Williams
Journal: Gut (1982)

The efficacy of methylprednisolone (1 g daily or three days), which is effective in reversing transplant rejection, was assessed in a randomised controlled trial of 55 patients with severe acute alcoholic hepatitis, 34 of whom had encephalopathy. The clinical progress, frequency of bleeding and sepsis, and cause of death were similar in the treatment (27 patients) and control groups (28 patients). There was no significant difference in mortality rate between the two groups: 57% of the control group and 63% of the treatment group died during the study. Patients9 survival depended on the presence of absence of the following features: encephalopathy, serum bilirubin concentration more than 340 micromol/l, serum creatinine concentration more than 250 micromol/l, and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis.
Acute HIV revisited: new opportunities for treatment and prevention
Authors: Christopher D. Pilcher, Joseph J. Eron, Shannon Galvin, Cynthia Gay, Myron S. Cohen
Journal: Journal of Clinical Investigation (2004)

Inability to recognize incident infection has traditionally limited both scientific and public health approaches to HIV disease. Recently, some laboratories have begun adding HIV nucleic acid amplification testing to HIV diagnostic testing algorithms so that acute (antibody-negative) HIV infections can be routinely detected within the first 1–3 weeks of exposure. In this review article, we will highlight critical opportunities for HIV treatment and prevention that are presented by these diagnostic strategies.
A possible role for elastin ligands in the proteolytic degradation of arterial elastic lamellae in the rabbit.
Authors: H M Kagan, P E Milbury, D M Kramsch
Journal: Circulation Research (1979)

Thoracic aortae of normal rabbits were perfused with pancreatic elastase in vitro at 37 degrees C and 70 mm Hg pressure in the presence or absence of elastin ligands previously shown to stimulate or inhibit the enzymatic degradation of elastin. Perfusion with elastase results in an average of 3.6 lamellae degraded, whereas addition of sodium linoleate before and during the perfusion with elastase increases this value to 7.9 (P less than 0.001). Conversely, perfusion with the cationic detergent, dodecyltrimethylammonium chloride, completely prevents the degradation of elastic lamellae by elastase. These effects do not reflect alterations of the intrinsic catalytic activity of elastase, but apparently indicate the formation of complexes between the elastin ligands and arterial elastic lamellae, as is consistent with prior studies indicating such interactions between fatty acids or detergents and purified elastin. These studies suggest that agents such as fatty acids may significantly alter the metabolic susceptibility of elastin in vivo and possibly contribute to the degradation of elastic lamellae seen in arteries with advanced atherosclerosis.
Randomised comparison of primary stent placement versus primary angioplasty followed by selective stent placement in patients with iliac-artery occlusive disease
Authors: Eric Tetteroo, Yolanda van der Graaf, Johanna L Bosch, Andries D van Engelen, Maria GM Hunink, Bert C Eikelboom, Willem P Th M Mali
Journal: The Lancet (1998)