tbuckley/cabot-search huggingface dataset:
Cyclic Adenosine 3′,5′-Monophosphate-Independent Phosphorylation of Externally Oriented Plasma Membrane Proteins in Transformed and Nontransformed Mouse Embryo Cell Lines2
Authors: Robert E. Scott
Journal: JNCI Journal of the National Cancer Institute (1980)

Thirty transformed and nontransformed mouse embryo cell lines were analyzed to determine if increased plasma membrane phosphorylation is a characteristic of all transformed cell lines. Nontransformed, virally and chemically transformed, and smooth surface-transformed cell lines derived from Swiss, BALB/c, AKR, or C3H mice were studied. Cyclic AMP-independent phosphorylation of plasma membrane proteins was comparable in nontransformed and simian virus 40 (SV40)-transformed Balb/3T3 cells, in nontransformed and 3-methylcholanthrene (MCA)-transformed C3H/10T½ cells, and in nontransformed and MCA-transformed AKR-2B cells. In contrast, increased plasma membrane phosphorylation was observed in MCA- and smooth surface-transformed Balb/3T3 cells and in SV40-transformed Swiss 3T3 cells compared to the respective nontransformed parent cell lines. These observations suggest that increased cyclic AMP-independent phosphorylation of externally oriented plasma membrane proteins is not a universal marker for the transformed phenotype.
A Near Infrared Light Triggered Hydrogenated Black TiO<sub>2</sub> for Cancer Photothermal Therapy
Authors: Wenzhi Ren, Yong Yan, Leyong Zeng, Zhenzhi Shi, An Gong, Peter Schaaf, Dong Wang, Jinshun Zhao, Baobo Zou, Hongsheng Yu, Ge Chen, Eric Michael Bratsolias Brown, Aiguo Wu
Journal: Advanced Healthcare Materials (2015)

White TiO 2 nanoparticles (NPs) have been widely used for cancer photodynamic therapy based on their ultraviolet light–triggered properties. To date, biomedical applications using white TiO 2 NPs have been limited, since ultraviolet light is a well‐known mutagen and shallow penetration. This work is the first report about hydrogenated black TiO 2 (H‐TiO 2 ) NPs with near infrared absorption explored as photothermal agent for cancer photothermal therapy to circumvent the obstacle of ultraviolet light excitation. Here, it is shown that photothermal effect of H‐TiO 2 NPs can be attributed to their dramatically enhanced nonradiative recombination. After polyethylene glycol (PEG) coating, H‐TiO 2 ‐PEG NPs exhibit high photothermal conversion efficiency of 40.8%, and stable size distribution in serum solution. The toxicity and cancer therapy effect of H‐TiO 2 ‐PEG NPs are relative systemically evaluated in vitro and in vivo. The findings herein demonstrate that infrared‐irradiated H‐TiO 2 ‐PEG NPs exhibit low toxicity, high efficiency as a photothermal agent for cancer therapy, and are promising for further biomedical applications.
Gene expression profiling of tumours derived from rasV12/E1A-transformed mouse embryonic fibroblasts to identify genes required for tumour development.
Authors: Sophie Vasseur, Cédric Malicet, Ezequiel L Calvo, Jean Dagorn, Juan L Iovanna
Journal: Molecular Cancer (2005)

In cancer, cellular transformation is followed by tumour development. Knowledge on the mechanisms of transformation, involving activation of proto-oncogenes and inactivation of tumour-suppressor genes has considerably improved whereas tumour development remains poorly understood. An interesting way of gaining information on tumour progression mechanisms would be to identify genes whose expression is altered during tumour formation. We used the Affymetrix-based DNA microarray technology to analyze gene expression profiles of tumours derived from rasV12/E1A-transformed mouse embryo fibroblasts in order to identify the genes that could be involved in tumour development.Among the 12,000 genes analyzed in this study, only 489 showed altered expression during tumour development, 213 being up-regulated and 276 down-regulated. The genes differentially expressed are involved in a variety of cellular functions, including control of transcription, regulation of mRNA maturation and processing, regulation of protein translation, activation of interferon-induced genes, intracellular signalling, apoptosis, cell growth, angiogenesis, cytoskeleton, cell-to-cell interaction, extracellular matrix formation, metabolism and production of secretory factors.Some of the genes identified in this work, whose expression is altered upon rasV12/E1A transformation of MEFs, could be new cancer therapeutic targets.
Abstract 8592: Cross-Talk Between the Toll-Like Receptor 4 and Notch1 Pathways Augments the Inflammatory Response to Endotoxin in the Interstitial Cells of Stenotic Human Aortic Valves
Authors: Qingchun Zeng, Chunhua Jin, Lihua Ao, Joon Lee, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
Journal: Circulation (2011)

Due to limited knowledge of the mechanisms of aortic valve stenosis, pharmacological intervention of this cardiovascular disease remains unavailable. Aortic valve stenosis is a chronic inflammatory disease, and aortic valve interstitial cells (AVICs) play an important role in the valvular inflammatory response. Oral bacteria have been found in stenotic aortic valve leaflets, and we recently found that stimulation of TLR4 in human AVICs induces the expression of ICAM-1 and BMP-2. While AVICs from stenotic aortic valves has an enhanced response to the TLR4 agonist endotoxin, the mechanism underlying the enhanced response is unknown. Activated Notch1 is found to modulate NF-κB activity in human leukemic T-cells, and endotoxin induces Notch1 activation in cultured macrophages. We tested the hypothesis that xcessive cross-talk between the TLR4 and Notch1 pathways augments the inflammatory response to endotoxin in diseased AVICs. The purposes of this study were to investigate: 1) whether TLR4 stimulation results in enhanced Notch1 activation in diseased AVICs, 2) whether inhibition of Notch1 attenuates the inflammatory response to TLR4 stimulation in diseased cells and 3) whether activation of Notch1 augments the inflammatory response to TLR4 stimulation in healthy AVICs. Methods and results: Human AVICs were isolated from normal and stenotic aortic valve leaflets. IL-6, MCP-1 and ICAM-1 were analyzed following treatment with endotoxin. Cells from diseased valves produced greater levels of cytokines and ICAM-1, and exhibited enhanced Jagged1 release and Notch1 activation after TLR4 stimulation. Inhibition of Notch1 greatly reduced the inflammatory response in diseased cells. Stimulation of Notch1 with Jagged1 or over-expression of Notch1 intracellular domain in healthy AVICs enhanced the production of cytokines and ICAM-1 induced by TLR4 stimulation. Conclusion: Notch1 enhances the inflammatory response to TLR4 stimulation in human AVICs. Excessive crosstalk between the TLR4 and Notch1 pathways is responsible, at least in part, for the augmentation of the inflammatory response to TLR4 agonist in AVICs of stenotic aortic valves. The Notch1 and TLR4 pathways could be therapeutic targets for regulation of aortic valve inflammatory response.
Study supports more aggressive blood pressure treatment targets, US officials say
Authors: Michael McCarthy
Journal: BMJ (2015)

US health officials have halted a large hypertension treatment trial ahead of schedule after finding strong evidence to support more aggressive treatment of high blood pressure. Initially, the trial, called the Systolic Blood Pressure Intervention Trial (SPRINT), was expected to be completed in 2017.

Officials said on 9 September that they decided to halt the study after an interim analysis of the data indicated that treating patients to achieve a target systolic blood …
Combination chemotherapy with mastectomy or radiotherapy for stage III breast carcinoma: a Cancer and Leukemia Group B study.
Authors: M Perloff, G J Lesnick, A Korzun, F Chu, J F Holland, M P Thirlwell, R R Ellison, R W Carey, L Leone, V Weinberg
Journal: Journal of Clinical Oncology (1988)

One hundred thirteen evaluable patients with previously untreated stage III breast carcinoma were treated with three monthly cycles of cyclophosphamide (CYC), doxorubicin (DOX), 5-fluorouracil (5-FU), vincristine (VCR), and prednisone (PRED) (CAFVP). Subsequently, 91 (81%) were deemed operable. Patients were then randomized to receive surgery or radiotherapy (RT) to determine which of these modalities afforded better local tumor control. All patients also received 2 additional years of CAFVP in a further attempt to eradicate local disease and systemic micrometastases. Forty-one of the randomized patients have relapsed. Approximately half of the initial relapses in each arm were local. The overall duration of disease control was similar following either modality, with a median of 29.2 months for surgery patients and 24.4 months for RT patients. Similarly, there was no major difference in survival related to randomized treatment with an overall median of 39 months (median follow-up 37 months). Pre- or perimenopausal status and inflammatory disease were associated with shorter disease control and survival. Treatment was generally well tolerated and toxicity was acceptable. This study demonstrates that prolonged control of stage III breast carcinoma can be achieved with combined modality therapy in which cytotoxic chemotherapy precedes and follows treatment directly primarily at the breast tumor, using either surgery or RT. Nevertheless, new regimens must be designed if significant advances that may lead to the cure of this disease are to be achieved.
Effect of imipramine on mood and enumerative measures of immune status in depressed patients with HIV illness
Authors: J G Rabkin, R Rabkin, W Harrison, G Wagner
Journal: American Journal of Psychiatry (1994)

The authors' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness. Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate standard doses of imipramine. Second, the authors sought to determine whether imipramine treatment is associated with changes in immune status.A double-blind, randomized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic. After 6 weeks of treatment, responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly. All patients were offered 26 weeks of treatment. Of the 97 patients who were randomly assigned to placebo or imipramine, 80 completed the 6-week phase. Main outcome measures included the Clinical Global Impression, the Hamilton Depression Rating Scale, the Brief Symptom Inventory, and CD4 cell count.Among study completers, 31 (39%) had AIDS. The response rate to imipramine was 74% and the response rate to placebo was 26%. There was no difference in depression response between patients with more or less severe immunodeficiency, nor was there a difference in medication dose or side effects. Neither type nor duration of treatment influenced CD4 cell count during the course of treatment.Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients. Severity of immunosuppression is not associated with imipramine treatment outcome. There is no evidence that imipramine has negative effects on enumerative measures of immune status.
Fibrin Sealing in Laparoscopic Colorectal Surgery
Authors: T. Reck, C. Schneider, I. Schneider, I. Gastinger, F. Köckerling
Journal: Endoscopy (1995)

Successful laparoscopic colorectal surgery depends essentially on the following requirements: (a) a reliable anastomotic technique, (b) lymph node dissection according to the principles of oncological radicality and (c) the specimen removal technique. In extensive animal studies we have developed a laparoscopic operative method for deep rectal carcinoma by abdominoperineal rectum extirpation with high ligation of the inferior mesenteric artery. The first clinical use of the method was in January 1992. From January to October we successfully operated on ten patients using the new technique; no severe complications were observed. Although Well's transabdominal rectopexy to correct rectum prolapse is technically simple and yields good results, a minimally invasive procedure is desirable in the treatment of this benign condition. Therefore we developed a laparoscopic rectopexy technique based on Well's method in animal models. In principle, laparoscopic rectopexy does not differ greatly from the intra-abdominal approach used in Well's rectopexy, but the techniques applied in the individual steps must be adapted for laparoscopic application. We have successfully performed this operation without any complications in six patients with complete prolapse of the rectum. For the treatment of residual bleeding in the pelvic region and for additional fixation of the rectum to the sacrum in Well's procedure, fibrin sealing has been found very useful.
Digoxin Use and Subsequent Outcomes Among Patients in a Contemporary Atrial Fibrillation Cohort
Authors: Larry A. Allen, Gregg C. Fonarow, DaJuanicia N. Simon, Laine E. Thomas, Lucas N. Marzec, Sean D. Pokorney, Bernard J. Gersh, Alan S. Go, Elaine M. Hylek, Peter R. Kowey, Kenneth W. Mahaffey, Paul Chang, Eric D. Peterson, Jonathan P. Piccini
Journal: Journal of the American College of Cardiology (2015)
A randomized phase III trial comparing sorafenib plus best supportive care (BSC) versus BSC alone in Child-Pugh B patients (pts) with advanced hepatocellular carcinoma (HCC): The BOOST study.
Authors: Bruno Daniele, Massimo Di Maio, Ciro Gallo, Antonio Gasbarrini, Giacomo Carteni, Giovan Giuseppe Di Costanzo, Antonio Craxi, Giuseppe Cabibbo, Luigi Bolondi, Alessandro Granito, Gabriele Missale, Antonio Frassoldati, Mario Angelico, Mario Roselli, Gennaro Daniele, Francesco Perrone
Journal: Journal of Clinical Oncology (2012)

TPS4151 Background: The efficacy of sorafenib in pts with advanced HCC has been demonstrated in two randomized phase III trials (Llovet JM, NEJM 2008;359:378; Cheng AL, Lancet Oncol 2009;10:25), both restricted to pts with well-preserved liver function (Child-Pugh A). Child-Pugh B (CPB) pts, that represent a relevant proportion of pts with advanced HCC in clinical practice, were not eligible. Despite this limitation, the marketing authorization of sorafenib by the main regulatory agencies was not restricted to Child A pts. CPB pts are different in terms of prognosis, and are potentially different in terms of balance between treatment efficacy and toxicity. Large observational studies [Marrero JA, ASCO 2011 (abstr 4001)] are producing quite reassuring data about sorafenib tolerability in CPB pts, but the real efficacy of the drug in this setting remains substantially unknown, due to the lack of randomized trials. Methods: BOOST (B Child HCC patients – Optimization Of Sorafenib Treatment) is a randomized phase III trial comparing sorafenib + best supportive care (BSC) vs. BSC alone in CPB pts with advanced HCC. Pts are eligible if older than 18, with ECOG performance status 0-2. Pts assigned to experimental arm receive sorafenib 400 mg twice daily, with dose reductions and interruptions according to toxicity. Overall survival (OS) is the primary endpoint. In order to demonstrate a Hazard Ratio of death 0.70 in favor of sorafenib (2-month improvement in median OS, from 4.5 to 6.5 months), with 80% power and α 0.05, 320 pts have to be randomized, 160 per arm. The BOOST trial (ClinicalTrials.gov Identifier NCT01405573; Eudract number 2009-013870-42) is approved by the Ethical Committee of the National Cancer Institute, Napoli, Italy, as coordinating centre, and is currently under evaluation by several other Institutions. BOOST is a non-profit, academic trial. The trial has received a financial support by Italian Ministry of Health (FARM84SA2X), although the support is not enough to supply sorafenib to participating centers. BOOST is partially supported by AIRC (grant IG2009-9316). The study is open to all international Centers wishing to participate.
Abstract 5794: Geometric Changes of Mitral Annulus Assessed by Real-Time 3-Dimensional Transesophageal Echocardiography
Authors: Yoshiki Matsumura, Manatomo Toyono, Neil L Greenberg, Tetsuhiro Yamano, Kunitsugu Takasaki, Roberto M Saraiva, Takahiro Shiota
Journal: Circulation (2008)

Background: The mitral annular (MA) geometric changes have been reported in patients with various cardiac diseases such as atrial fibrillation (Af), mitral regurgitation (MR) and dilated cardiomyopathy (DCM). The advances of real-time 3D transesophageal echocardiography (TEE) enable us to analyze the MA geometry more accurately and reliably than 3D transthoracic echocardiography (TTE). We sought to determine the independent predictors for MA geometric changes in patients with Af, significant MR, and DCM by 3D TEE. Methods: We examined 32 subjects by 3D TEE and 2D TTE; 6 with lone Af, 9 with mitral valve prolapse (MVP), 3 with organic MR, 6 with DCM, and 8 normal subjects. Left ventricular (LV) end-diastolic and end-systolic volume indices (EDVI and ESVI), ejection fraction (EF), left atrial volume index (LAVI), and MR severity were assessed by 2D TTE. We measured MA area index, commissural length, and MA height (Figure 1 ). For the index of the saddle-shaped MA geometry, MA shape index was calculated as the (MA height)/(commissural length). Results: Patients with MVP and those with DCM had larger MA area index and lower MA shape index than normal subjects (all, P &lt;0.05). MA area index was associated with LAVI, MR severity, and LV EDVI (all, P &lt;0.05) (Figure 2 ). MA shape index was associated with LV EF, ESVI, and the presence of Af (all, P &lt;0.05) (Figure 3 ). In multivariate analysis, LAVI, MR severity, and LV EDVI independently predicted for MA area index, and LV EF was independent predictor for MA shape index (all, P &lt;0.05). Conclusion: MA dilatation was independently associated with larger LA and LV volumes and severer MR, not LV EF, while the saddle-shaped MA geometry was associated with LV EF. Figure 1 Figure 2 Figure 3
Genetics and Pathogenesis of Inflammatory Bowel Disease
Authors: Ta-Chiang Liu, Thaddeus S. Stappenbeck
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

We are currently in an exciting time when our understanding of genetic underpinnings of inflammatory bowel disease (IBD) has undergone a revolution, based in large part on novel genotyping and sequencing technologies. With &gt;160 susceptible loci identified for IBD, the goal is now to understand at a fundamental level the function of these susceptibility alleles. Determining the clinical relevance of how these susceptible genes shape the development of IBD is also a high priority. The main challenge is to understand how the environment and microbiome play a role in triggering disease in genetically susceptible individuals, as the interactions may be complex. To advance the field, novel in vitro and mouse models that are designed to interrogate complex genetics and functionally test hypotheses are needed. Ultimately, the goal of genetics studies will be to translate genetics to patients with IBD and improve their care.
Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.
Authors: P Percivale, S Bertoglio, P Meszaros, G Canavese, F Cafiero, M Gipponi, E Campora, M Gasco, F Badellino
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.
Ultrastructure and Distribution of Intracellular Spicules in Rat Lung Following Chronic Tobacco Smoke Exposure&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: C A Heckman, G L Lehman
Journal: JNCI Journal of the National Cancer Institute (1985)

Factors that contribute to the induction of lung tumors in F344 rats by chronic tobacco smoke exposure were studied. Previous studies had shown that tobacco smoke exposures of 1–2 years duration induced only one major type of lesion involving the respiratory airways, i.e., fibrotic and cellular enlargement of peribronchiolar alveolar septa. The airway epithelium in these areas was metaplastic and in some of the lesions, the airway lining epithelium advanced out onto the surfaces of adjacent alveoli. Epithelial cells in these lesions frequently contained elongated cytoplasmic inclusions which were oriented with their long dimensions roughly in the same plane as the long axis of the cell. Macrophages contained similar but larger inclusions. Because the composition of the inclusions could be indicative of their origin, we subjected samples of treated and control lung tissues concurrently to transmission electron microscopy and energy-dispersive X-ray fluorescence spectrometry. Spectra from inclusions of macrophages indicated the presence of the elements sulfur, phosphorus, aluminum, silicon, and iron. Spectra from type II cells, however, which did not contain inclusions, showed a different elemental composition. The results suggested that spicules were present in epithelial cells throughout the airways. Minor lesions corresponding to “microinvasion” of epithelium into the lamina propria and of capillaries into the epithelial layer were also found in the trachea.
Abstract 2839: Alpha1 Actions of Epinephrine Reduce Cerebral Perfusion During Cardiopulmonary Resuscitation
Authors: Giuseppe Ristagno, Shijie Sun, Wanchun Tang, Max H Weil
Journal: Circulation (2007)

Introduction. Epinephrine is the primary drug for CPR. The rationale is to restore threshold levels of myocardial blood flows through its alpha1 (α1) and alpha2 (α2)-adrenergic actions. Hypothesis....