tbuckley/cabot-search huggingface dataset:
The role of matrix metalloproteinases (MMP-9) in the proliferation of colorectal cancer metastases to the liver.
Authors: Lee Gorden, Barbara Fingleton, Conor Lynch, Saul Juliao, Lynn M. Matrisian
Journal: Cancer Research (2004)

2417  Aim: To determine the role of MMP-9 in the proliferation and invasion of colorectal cancer metastases to the liver. Background: MMPs have been shown to play a role in tumorigenesis of primary epithelial tumors such as those of colon and breast origin. The majority of patients who succumb to colorectal cancer, die with a significant burden of metastatic disease in the liver. The role of specific MMPs in the proliferation and growth of metastatic colorectal tumor cells in the liver remains to be elucidated. MMP-9 is known to play a role in the angiogenic switch and in the growth of other tumor types. Through a better understanding of the roles of tumor and stroma derived MMPs at the earliest stages of tumor metastasis, we hope to identify specific, rational targets for future therapies. Methods and Results: We have adapted the murine splenic injection model of colorectal metastases. This orthotopic model is used to recapitulate the latter stages of colorectal metastases. Wild type (WT) C57BL/6 mice and C57BL/6 mice genetically deficient in MMP-9 underwent splenic injection of 1X 105 syngeneic MC38 colon cancer cells. This technique reproducibly resulted in liver metastases in the mice injected. MC38 cells were stably transfected with a luciferase reporter construct to allow in vivo monitoring of the growth of metastatic tumors. RTPCR analysis of MC38 cells shows that these epithelial tumors produce MMP-9. After splenic injection, mice genetically deficient in MMP-9 consistently show minimal metastatic growth in the liver by gross examination as well as bioluminescence imaging when compared to WT controls. After 14 days, the control mice showed more than a 2 fold increase in liver weight with their tumor burden when compared to MMP-9 null mice (p value 0.01). Serial bioluminescence imaging during the 14 day post splenic injection period shows decreased signal intensity in the MMP-9 null mice when compared to WT controls. In addition, we have imaged the same mice at successive time points (days 7 and 14) using MRI. This technique gives spatial and anatomic resolution that corroborates the markedly decreased burden of liver metastases in the MMP-9 null mice as compared to WT controls. Conclusions: To our knowledge this is the first example of bioluminescence imaging of metastatic tumors in an orthotopic model. We have demonstrated that host stromal MMP-9, and not tumor derived MMP-9, is important for the proliferation of colorectal metastases to the liver in this orthotopic murine model. Understanding the role of specific MMPs in colorectal cancer metastases will allow targeted modulation of these enzymes in therapeutic strategies.
Abstract 1129: Obesity-related Elevations in Soluble P-selectin are Derived From Endothelium and Dependent on Expression of Leukocyte P-selectin Glycoprotein Ligand-1
Authors: Kevin J Wickenheiser, Peter F Bodary, Kristina Bahrou, Daniel T Eitzman
Journal: Circulation (2007)

Background : Obesity is associated with proinflammatory changes and an increased risk for vascular disease complications. The tissue source and mechanism by which soluble P-selectin (sPsel) is generated in obesity are unclear. Methods and Results : Soluble p-selectin (sPsel) levels were measured in the circulation from lean wild type and obese leptin receptor deficient mice (LepR−/−) at 4 and 10 weeks of age. In wild-type mice body weight increases from 13+/−2 to 20+/−3 grams over this time period while the body weight increases from 15+/−2 to 38+/−5 grams in LepR−/− mice. At 4 weeks of age sPsel levels were 103+/−8mg/mL in wild-type mice vs. 138+/−9 ng/mL in LepR−/− mice, p=0.048. By 10 wks of age sPsel increased to 112 +/− 2 in wild-type mice and 182 +/− 9 in LepR−/− mice, p=0.00005. In order to determine if the obesity-induced rise in sPsel is regulated by leukocyte Psgl-1, bone marrow transplantation was performed from Psgl+/+ or Psgl−/− donors into irradiated LepR−/−recipients. At 4 weeks post-transplant, sPsel levels were 166 +/−6 ng/mL in LepR−/− mice receiving Psgl+/+ marrow and 45 +/− 4 ng/mL in LepR−/− mice receiving Psgl−/− marrow, p=0.0000004. In order to determine if the sPsel in LepR−/− mice originated from the endothelium versus platelets, we transplanted Psel−/− bone marrow into irradiated LepR−/−mice. At 4 weeks post transplant, sPsel levels were 153 +/−3 ng/mL in LepR−/− mice receiving Psel−/− bone marrow and were not significantly different from LepR−/− mice receiving Psel+/+ bone marrow (166 +/−6 ng/mL, p=0.06). By 10 weeks post transplant, mice gained even more weight and levels were 377+/−51 ng/mL in LepR−/− mice receiving Psel+/+ bone marrow and 370+/−73 ng/mL in LepR−/− mice receiving Psel−/− bone marrow, p=0.87. Conclusions : These data suggest that the increase in sPsel observed in obesity is primarily derived from the endothelium and that this process is regulated by leukocyte Psgl-1.
Constraints on CD4 Recovery Postchemotherapy in Adults: Thymic Insufficiency and Apoptotic Decline of Expanded Peripheral CD4 Cells
Authors: Frances T. Hakim, Rosemarie Cepeda, Song Kaimei, Crystal L. Mackall, Nanette McAtee, JoAnne Zujewski, Kenneth Cowan, Ronald E. Gress
Journal: Blood (1997)
BMP and Wnt Induce Embryonic Blood Fate by Activation of the Cdx-Hox Pathway.
Authors: Claudia Lengerke, Sabine Schmitt, Teresa Bowman, Leila Maouche-Chretien, Shannon L. McKinney-Freeman, Il Ho Jang, Alan J. Davidson, Matthias Hammerschmidt, Fabian Rentzsch, Jeremy B. Green, Leonard I. Zon, George Q. Daley
Journal: Blood (2007)
(R)-roscovitine inhibits proliferation and induces apoptosis in DLBCL through Stat3 signaling and inhibition of myc-mediated glycolysis
Authors: Anthony Faber, Purna Mukherjee, Thomas Chiles
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4367 

(R)-roscovitine (CYC202, Seliciclib) is a CDK (cyclin-dependent kinase)-specific inhibitor belonging to the family of purines and is currently in clinical trials for a number of different cancers. Diffuse large B cell lymphoma (DLBCL) is the second fastest growing cancer in the Western world and a number of recent reports have implicated over expression and aberrant activation of CDKs in the pathogenesis of DBLCL. There is no in vitro or in vivo report on the effect of (R)-roscovitine on DLBCL viability. Here, we report (R)-roscovitine inhibits proliferation and induces time-dependent apoptosis in a panel of DLBCL cell lines. Coinciding with arrest of proliferation and induction of apoptosis in (R)-roscovitine-treated cells, we found that expression of the transcription factor c-myc was inhibited. Several c-myc targets, including genes encoding rate-limiting enzymes in the glycolytic pathway ( e.g., hexokinase II and phosphofructokinase 1) were reduced. In keeping with this, glycolysis was inhibited following treatment of DLBCLs with (R)-roscovitine, and this proceeded apoptosis. Inhibition of glycolytic flux with 3-bromopyruvate also resulted in growth arrest. Further, (R)-roscovitine inhibited Stat3/Pim-1 signaling in DLBCL cells that displayed constitutive activation of this pathway. Treatment with the Stat3 inhibitors tryphostinAG490 or cucurbitacin I resulted in similar effects on cell viability, c-myc expression, transcription of glycolytic enzymes, and glycolytic flux as (R)-roscovitine, suggesting involvement of this pathway. This study provides novel insight into the mechanisms in which (R)-roscovitine exerts its therapeutic effectiveness and we suggest (R)-roscovitine may be a promising therapy in treating DLBCL.
Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring
Authors: M.L. Manca, I. Castangia, M. Zaru, A. Nácher, D. Valenti, X. Fernàndez-Busquets, A.M. Fadda, M. Manconi
Journal: Biomaterials (2015)
A research agenda for aging in China in the 21st century
Authors: Evandro Fei Fang, Morten Scheibye-Knudsen, Heiko J Jahn, Juan Li, Li Ling, Hongwei Guo, Xinqiang Zhu, Victor Preedy, Huiming Lu, Vilhelm A Bohr, Wai Yee Chan, Yuanli Liu, Tzi Bun Ng
Journal: Ageing Research Reviews (2015)
Breast cancer prevention with grape seed phytochemicals
Authors: Gene Hur, Sheryl Phung, Sei-Ryang Oh, Sharon Kwok, Barbara Sarter, Melanie Palomares, Jeffrey Weitzel, Shiuan Chen
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4278 

Suppression of aromatase/estrogen biosynthesis is thought to have potential for chemoprevention of breast cancer. Aromatase is the enzyme that converts androgen to estrogen. An abnormal expression of aromatase in breast tissue is considered to be a risk factor for breast cancer. In our laboratory, we found that of seven fruit juices tested, grape juice was the most effective in inhibiting the activity of human placental aromatase activity. During the last several years, we have learned that (1) the methanol extract of grape juice and red wine suppresses aromatase in a dose-dependent manner; (2) the extract suppresses the proliferation of an aromatase over-expressing and estrogen receptor-positive breast cancer cell line - MCF-7aro; (3) oral administration of the extract completely abrogates aromatase-induced hyperplasia and other changes in the mammary tissue of aromatase transgenic mice; (4) procyanidin B dimers, the major phytochemicals in the seeds and skins of grapes, are the chemicals responsible for the anti-aromatase activity; and (5) oral feeding of procyanidin B dimers reduces androgen-dependent MCF-7aro tumor growth in nude mice. The tumors of mice treated with the extract enriched with procyanidin B dimers showed a minimal increase in apoptotic cells compared with tumors of control mice, suggesting that the reduction in tumor growth in the treated mice was due to inhibition of aromatase and not due to a non-specific cytotoxic effect. Further, results from the feeding experiments indicate that these procyanidin B dimers are orally active and maintain their activity after ingestion. Recently, we have examined the content of procyanidin B dimers in commercially available grape seed extract formulations and determined that grape seed extract may be a useful chemopreventive agent against breast cancer. The mass spectral analysis has revealed that grape seed extract contains high levels of procyanidin B dimers, oligomers and gallate esters of procyanidins. Further testing in the nude mouse model revealed suppression of MCF-7aro tumor shrinkage when they were fed 700μg/day for 6 weeks. Based on this preclinical data, we hypothesize that postmenopausal women could reduce their breast cancer risk with a grape seed extract dietary supplement, containing phytochemicals that have been shown to be effective aromatase inhibitors. A Phase I chemoprevention trial to evaluate the in vivo anti-aromatase activity of grape seed extract in postmenopausal women has been initiated at the City of Hope. The design and progress of this clinical trial will be discussed.
Social phobia in adults with stuttering
Authors: M B Stein, A Baird, J R Walker
Journal: American Journal of Psychiatry (1996)

The authors evaluated features of social anxiety in a group of adult stutterers to explore the soundness of the DSM-IV requirement that social phobia not be diagnosed in patients who stutter if their phobia relates to their stuttering.They conducted diagnostic interviews and verbal fluency assessments with 16 consecutive adults seeking speech therapy for stuttering. Patients also completed scales measuring social phobia symptoms and associated disability.When DSM-IV criteria were modified to permit a diagnosis of social phobia if phobic symptoms were clearly excessive in relation to the severity of stuttering, seven of the 16 patients were given a diagnosis of social phobia. All seven identified social anxiety as an important source of role impairment. Three of the seven patients entered cognitive-behavioral group therapy and benefited from this intervention.Many adults seeking treatment for stuttering have salient difficulties with social anxiety that may prove amenable to cognitive-behavioral interventions. By precluding a diagnosis of social phobia in these patients, DSM-IV may hinder the identification of social anxiety as a source of disability and may limit access to treatment.
Health and Illness
Authors: Joseph T. Young
Journal: JAMA (2005)

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
Abstract 5560: Quercetin overcomes chemotherapy resistance in triple negative breast cancer
Authors: Asha Srinivasan, Chellappagounder Thangavel, Yi Liu, Sunday Shoyele, Robert B. Den, Ponniah Selvakumar, Ashakumary Lakshmikuttyamma
Journal: Cancer Research (2015)

Abstract Triple negative breast cancer (TNBC) is one of the most aggressive breast cancers and is characterized by poor prognosis and high possibilities of tumor relapse. TNBC lacks specific receptors that are targets for breast cancer treatment options. Plant flavonoids have been identified to inhibit tumor growth and metastasis in various cancers. Our study revealed that quercetin, one of the major flavonoids present in fruits, vegetables, green tea, and red wine inhibit TNBC migration and invasion. Our data indicate that quercetin is able to induce the expression of E-cadherin and also down regulate vimentin levels in TNBC cells. Further the cellular localization of β-catenin is also altered by quercetin treatment. Also, studies identified that quercetin is capable of inhibiting the chemotherapy induced TGF-β signaling in TNBC cells, and that it would decrease the development of chemotherapy resistance in TNBC. Quercetin inhibits the TGF-β induced phosphorylation status of smad-2 in drug resistant cells. Further, quercetin is able to inhibit the enhanced migration and mammosphere formation of chemoresistant TNBC cells. Taken together, our findings revealed that quercetin is a promising natural product that increases the anti-cancer effect of chemotherapy drug in TNBC. Future studies in TNBC animal models are needed to confirm the therapeutic efficacy of quercetin in TNBC. Citation Format: Asha Srinivasan, Chellappagounder Thangavel, Yi Liu, Sunday Shoyele, Robert B. Den, Ponniah Selvakumar, Ashakumary Lakshmikuttyamma. Quercetin overcomes chemotherapy resistance in triple negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5560. doi:10.1158/1538-7445.AM2015-5560
Abstract 19032: Performance of Euroscore I, Euroscore II and STS Score for Risk Stratification of Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Augusto D'Onofrio, Valeria Gasparetto, Giulio Rizzoli, Massimo Napodano, Giuseppe Tarantini, Roberto Bianco, Chiara Tessari, Giambattista Isabella, Gino Gerosa
Journal: Circulation (2012)

Purpose: Objective of this single center study was to assess and compare the performance of logistic Euroscore I (ES I), logistic Euroscore II (ES II) and the Society of Thoracic Surgeons (STS) mortality score for risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR). Methods: We analyzed data of 235 consecutive patients who underwent TAVR from June 2007 through January 2011. We calculated STS, ES1 and ES2 of each patient. Performance of the risk scores was evaluated by means of ROC curves. A logistic multivariable analysis was performed including confounding factors (age, sex) and access: percutaneous (trans-femoral and trans-subclavian) vs. surgical (trans-apical and trans-aortic) TAVI. Results: Surgical and percutaneous TAVI were performed in 78 (33.2%) and 157 (66.8%) patients, respectively. Mean age was 80.5 ± 6.6 years. Median ES1, ES2 and STS scores were: 17.6%, 5.4% and 6.8% respectively. Thirty-day mortality was 4.3%, the incidence of combined safety events, according to VARC definitions, was 17%. The area under the ROC curve (AUC) for thirty-day mortality was 0.68, 0.66 and 0.60 for ES1, ES2 and STS, respectively (p=0.79). The AUC for combined safety events was 0.57, 0.60 and 0.57 for ES1, ES2 and STS, respectively (p=0.71). After correction for age, sex and approach the AUC for thirty-day mortality was 0.84, 0.75 and 0.74 for ES I, ES II and STS scores, respectively while the AUC for combined safety events was 0.68, 0.66 and 0.65 for ES I, ES II and STS scores, respectively. ES2 and STS performed better in predicting thirty-day mortality in surgical cases (0.75 and 0.74) while ES1 performed better in percutaneous cases (0.76). Conclusion: According to our analysis, in patients undergoing TAVR, ES1, ES2 and STS scores for thirty-day mortality and for combined safety events provide similar but poor performance (less than 0.75). After correction for confounding factors and approach, ES1 was the only that showed AUC greater than 0.75.
Abstract 3234: New-onset Post-operative Atrial Fibrillation Following Aortic Valve Replacement Surgery and Long-term Survival
Authors: Giovanni Filardo, Cody Hamilton, Baron Hamman, Robert Hebeler, Paul Grayburn
Journal: Circulation (2009)

Background: Atrial fibrillation (AFIB) is a common complication of open cardiac surgery, occurring in up to 65% of patients. The advancing age and increasing risk profile of patients receiving aort...
Good quality research demands consent
Authors: Paul Thornton
Journal: BMJ (2015)

Darzi perpetuates the narrative that ran the national NHS database into the buffers, wasting billions of pounds, and that has derailed the care.data programme.1

There is no conspiracy against research—just explicit and deliberate protection for patient information, with the transfer of identifiable information requiring consent.

Nor has there ever been any barrier in law to the transfer of information between health …
An Arterial Based Complexity (ABC) Scoring System to Assess the Morbidity Profile of Partial Nephrectomy
Authors: Massimiliano Spaliviero, Bing Ying Poon, Christoph A. Karlo, Giuliano B. Guglielmetti, Pier Luigi Di Paolo, Renato Beluco Corradi, Alexandre G. Martin-Malburet, Felix Campos-Juanatey, Eva Escudero-Fontano, Daniel D. Sjoberg, Paul Russo, Jonathan A. Coleman, Oguz Akin, Karim A. Touijer
Journal: European Urology (2015)
Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor–mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation
Authors: Douglas R. Adkins, Lawrence T. Goodnough, Shalini Shenoy, Randy Brown, Jennifer Moellering, Hanna Khoury, Ravi Vij, John DiPersio
Journal: Blood (2000)
Enzastaurin (ENZ) before and concomitant with radiation therapy (RTX), followed by ENZ maintenance therapy in patients with newly diagnosed glioblastoma (GBM) without hypermethylation of the O6-methylguanyl DNA-methyltransferase (MGMT) promoter: A multicenter, open-label, uncontrolled phase II study
Authors: W. Wick Wolfgang, S. E. Combs, M. Platten, M. Weller, U. Ohnmacht, C. Stoffregen, D. Thornton
Journal: Journal of Clinical Oncology (2009)

e13038 Background: There is an unmet need to improve efficacy outcome for GBM patients without hypermethylation of the MGMT promoter. Preclinical data indicated a potential benefit of ENZ, an oral serine/threonine kinase inhibitor, together with RTX (Tabatabai et al; Ann Neurol 61: 2007). In a run-in phase of this phase II study the feasibility of once or twice daily ENZ dosing was evaluated. The split dose results in higher exposure. The results of the run-in phase are presented. Methods: Patients (pts) with newly diagnosed supratentorial GBM were entered. The first regimen administered once daily ENZ (500 mg QD) before and concomitant with standard radiotherapy at a dose of 60 Gy (2 Gy, 5 days a week). As no dose-limiting toxicities occurred in the first 3 pts, another 6 pts were enrolled into the second regimen, twice daily ENZ (250 mg BID) with RTX. ENZ is given until progression afterward. Results: Between 10/07 and 07/08 a total of 9 pts were enrolled. Mean treatment duration was 9.3 weeks for ENZ, and 6.3 weeks for RTX. No drug-related grade 3/4 toxicity was reported. The only laboratory toxicity CTC grade 3 (low potassium) and 1 serious adverse event (erysipelas) were reported in the BID regimen. No pts discontinued in the first 9 weeks, no deaths in this period. Conclusions: Following the results of the run-in phase, the BID regimen was chosen for the ongoing study. [Table: see text] [Table: see text]
Electrical Alternans with Pericardial Tamponade
Authors: Waqas Jehangir, Mohamed Osman
Journal: New England Journal of Medicine (2015)

A 56-year-old woman with a history of stage II cancer of the left breast presented with progressive shortness of breath and fatigue. Transthoracic echocardiography revealed a large pericardial effusion with the heart freely swinging in an anterior–posterior fashion, shown in a video.
DSM-IV and the disappearance of agoraphobia without a history of panic disorder: new data on a controversial diagnosis
Authors: R M Goisman, M G Warshaw, G S Steketee, E J Fierman, M P Rogers, I Goldenberg, N J Weinshenker, R G Vasile, M B Keller
Journal: American Journal of Psychiatry (1995)

This analysis describes subjects who met rigorous criteria for DSM-III-R agoraphobia without a history of panic disorder and makes inferences from these data regarding relationships among agoraphobia without a history of panic disorder, panic disorder, and panic disorder with agoraphobia.Twenty-six subjects (seven men and 19 women) with agoraphobia without a history of panic disorder were identified from among 711 subjects recruited for a multicenter, longitudinal anxiety disorder study. Narrative transcripts prepared by raters from study evaluations were coded for limited symptom attacks, situational panic, catastrophic cognitions, and possible precipitants and stressors, course, and somatic and psychosocial treatments received.Sixty-five percent of the subjects reported experiences consistent with situational panic attacks, and 57% had definite or probable limited symptom attacks; these attacks usually preceded or appeared at the same time as avoidance behavior. Eighty-one percent had catastrophic cognitions associated with agoraphobia. Twenty-six percent reported a likely precipitating factor for symptom onset, and 30% reported a definite or probable major life stressor within 6 months before symptom onset. Cognitive-behavioral treatments were relatively infrequently used. Course was relatively unchanged across the follow-up period.These data support a view of agoraphobia without a history of panic disorder on a continuum with uncomplicated panic disorder and with panic disorder and agoraphobia, rather than as a separate diagnosis.