tbuckley/cabot-search huggingface dataset:
TC1(C8orf4) Correlates with Wnt/β-Catenin Target Genes and Aggressive Biological Behavior in Gastric Cancer
Authors: Byungsik Kim, Hyunlyoung Koo, Seunghee Yang, Seunghyun Bang, Yusun Jung, Youngmi Kim, Jungtae Kim, Juhee Park, Randall T. Moon, Kyuyoung Song, Inchul Lee
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have recently reported that TC1(C8orf4), a small protein present in vertebrates, functions as a novel regulator of the Wnt/β-catenin pathway. TC1 up-regulates β-catenin target genes that are implicated in the aggressive behavior of cancers. Our aim was to investigate the clinical and pathobiological relevance of TC1 in gastric cancer. Experimental Design: The expression of TC1 was analyzed using tissue microarray in correlation with clinicopathologic variables and β-catenin target genes in 299 gastric cancers. The biological effects of TC1 on Matrigel invasiveness and the proliferation of cancer cells were analyzed. TC1 expression was analyzed in gastric cancer cells after serial peritoneal implantation in nude mice. Results: TC1 expression was present in 111 carcinomas (37.1%), correlating with tumor stage (P &amp;lt; 0.002), poor differentiation (P &amp;lt; 0.001), lymphatic infiltration (P &amp;lt; 0.005), and lymph node metastasis (P &amp;lt; 0.006). TC1 also correlated with poor survival in diffuse type carcinomas (P &amp;lt; 0.0001), and even in patients with lymph node metastasis (P &amp;lt; 0.0014). TC1 also correlated with the expression of β-catenin target genes including laminin γ2, metalloproteinase-7 and metalloproteinase-14, cyclin D1, c-Met, and CD44. TC1 enhanced Matrigel invasiveness and proliferation, supporting its role in the aggressive biological behavior of cancers. The expression of TC1 increased in MKN45 cells after serial peritoneal seeding in nude mice. Conclusions: Our data suggests that TC1 coordinates the up-regulation of Wnt/β-catenin target genes that are implicated in the aggressive biological behavior of cancers. The strong clinical relevance, even in patients with lymph node metastasis, suggested that TC1 could be a potential therapeutic target of advanced gastric cancers.
Phase II Study of Oxaliplatin and Fluorouracil in Taxane- and Anthracycline-Pretreated Breast Cancer Patients
Authors: L. Zelek, P. Cottu, M. Tubiana-Hulin, J.-M. Vannetzel, Ph. Chollet, J.-L. Misset, N. Chouaki, M. Marty, E. Gamelin, S. Culine, V. Dieras, S. Mackenzie, M. Spielmann
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m 2 (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m 2 /d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.
Gastritis due to spiral shaped bacteria other than Helicobacter pylori: clinical, histological, and ultrastructural findings.
Authors: K L Heilmann, F Borchard
Journal: Gut (1991)

An intensive histological search for Helicobacter pylori in gastric biopsy specimens has led to the detection of other spiral shaped bacteria in the human gastric mucosa. The clinical and morphological findings of 39 cases (0.25% of all gastric biopsies performed in the observation period) are reported for 34 patients (87.2%) complaining of upper abdominal discomfort. Five patients (12.8%) had chronic gastritis and 34 (87.2%) chronic active gastritis. The organisms were seen by light microscopy deep in the gastric foveolae and intracellularly. The scanning and transmission electron microscopic findings show bacteria which invade and damage gastric mucosal cells. These organisms are similar to the spiral shaped bacteria found in the stomachs of cats and dogs and non-human primates. In eight patients organisms were not detected after four weeks of treatment with bismuth salts. The disappearance of the organisms coincided with resolution of the chronic active gastritis and the symptoms.
Renal Stone Disease: Pathogenesis, Prevention, and Treatment
Authors: Charles Y. C. Pak
Journal: Annals of Internal Medicine (1988)

1. Physiochemistry of urinary stone formation.- 2. Pathogenesis of Hypercalciuria.- 3. Pathophysiology of nonhypercalciuric causes of stones.- 4. Nutritional aspects of stone disease.- 5. Radiologic considerations.- 6. Diagnostic considerations.- 7. Prevention of recurrent nephrolithiasis.- 8. Potassium citrate therapy of nephrolithiasis.- 9. Struvite stones.- 10. Contemporary approaches to removal of renal and ureteral calculi.
Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection
Authors: Bruce C.V. Campbell, Peter J. Mitchell, Timothy J. Kleinig, Helen M. Dewey, Leonid Churilov, Nawaf Yassi, Bernard Yan, Richard J. Dowling, Mark W. Parsons, Thomas J. Oxley, Teddy Y. Wu, Mark Brooks, Marion A. Simpson, Ferdinand Miteff, Christopher R. Levi, Martin Krause, Timothy J. Harrington, Kenneth C. Faulder, Brendan S. Steinfort, Miriam Priglinger, Timothy Ang, Rebecca Scroop, P. Alan Barber, Ben McGuinness, Tissa Wijeratne, Thanh G. Phan, Winston Chong, Ronil V. Chandra, Christopher F. Bladin, Monica Badve, Henry Rice, Laetitia de Villiers, Henry Ma, Patricia M. Desmond, Geoffrey A. Donnan, Stephen M. Davis
Journal: New England Journal of Medicine (2015)

Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes.We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days.The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).
Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells.
Authors: R D Cardin, J W Brooks, S R Sarawar, P C Doherty
Journal: The Journal of Experimental Medicine (1996)

A unique experimental model has been developed for dissecting the integrity of CD8+ T cell-mediated immunity to a persistent gammaherpesvirus under conditions of CD4+ T cell deficiency. Respiratory challenge of major histocompatibility complex class II -/- and +/+ C57BL/6J mice with the murine gammaherpesvirus 68 (MHV-68) leads to productive infection of both lung and adrenal epithelial cells. Virus titers peak within 5-10 d, and are no longer detected after day 15. Persistent, latent infection is established concurrently in splenic and lymph node B cells, with higher numbers of MHV-68+ lymphocytes being found in all lymphoid sites analyzed from the +/+ mice concurrent with the massive, but transient splenomegaly that occurred only in this group. From day 17, however, the numbers of infected B lymphocytes were consistently higher in the -/- group, while the frequency of this population diminished progressively in the +/+ controls. Infectious MHV-68 was again detected in the respiratory tract and the adrenals of the -/- (but not the +/+) mice from day 22 after infection. The titers in these sites rose progressively, with the majority of the -/- mice dying between days 120 and 133. Even so, some CD8+ effectors were still functioning as late as 100 d after infection. Depletion of CD8+ T cells at this stage led to higher virus titers in the -/- lung, and to the development of wasting in some of the -/- mice. Elimination of the CD8+ T cells from the +/+ group (day 80) increased the numbers of MHV-68+ cells in the spleen, but did not reactivate the infection in the respiratory tract. The results are consistent with the interpretation that CD8+ T cell-mediated control of this persistent gammaherpesvirus is progressively lost in the absence of the CD4+ T cell subset. This parallels what may be happening in AIDS patients who develop Kaposi's sarcoma and various Epstein Barr virus associated disease processes.
RUNX3 Is Frequently Inactivated by Dual Mechanisms of Protein Mislocalization and Promoter Hypermethylation in Breast Cancer
Authors: Quek Choon Lau, Erna Raja, Manuel Salto-Tellez, Qiang Liu, Kosei Ito, Masafumi Inoue, Thomas Choudary Putti, Marie Loh, Tun Kiat Ko, Canhua Huang, Kapil N. Bhalla, Tao Zhu, Yoshiaki Ito, Saraswati Sukumar
Journal: Cancer Research (2006)

Abstract A tumor suppressor function has been attributed to RUNX3, a member of the RUNX family of transcription factors. Here, we examined alterations in the expression of three members, RUNX1, RUNX2, and RUNX3, and their interacting partner, CBF-β, in breast cancer. Among them, RUNX3 was consistently underexpressed in breast cancer cell lines and primary tumors. Fifty percent of the breast cancer cell lines (n = 19) showed hypermethylation at the promoter region and displayed significantly lower levels of RUNX3 mRNA expression (P &amp;lt; 0.0001) and protein (P &amp;lt; 0.001). In primary Singaporean breast cancers, 9 of 44 specimens showed undetectable levels of RUNX3 by immunohistochemistry. In 35 of 44 tumors, however, low levels of RUNX3 protein were present. Remarkably, in each case, protein was mislocalized to the cytoplasm. In primary tumors, hypermethylation of RUNX3 was observed in 23 of 44 cases (52%) and was undetectable in matched adjacent normal breast epithelium. Mislocalization of the protein, with or without methylation, seems to account for RUNX3 inactivation in the vast majority of the tumors. In in vitro and in vivo assays, RUNX3 behaved as a growth suppressor in breast cancer cells. Stable expression of RUNX3 in MDA-MB-231 breast cancer cells led to a more cuboidal phenotype, significantly reduced invasiveness in Matrigel invasion assays, and suppressed tumor formation in immunodeficient mice. This study provides biological and mechanistic insights into RUNX3 as the key member of the family that plays a role in breast cancer. Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment. (Cancer Res 2006; 66(13): 6512-20)
Palliative side-to-side oesophagogastrostomy for unresectable carcinoma of the oesophagus and cardia.
Authors: K Kwun, P A Kirschner
Journal: Thorax (1981)

The distressingly low resectability rate of carcinoma of the oesophagus and gastric cardia emphasises the need for palliative restoration of the act of swallowing. Side-to-side oesophagogastrostomy was performed in 10 cases of unresectable tumours. Eight anastomoses were made low in the left chest for lower third oesophageal and cardiac lesions and two high on the right for midoesophageal tumours. There were no anastomotic leaks or other complications, and no postoperative deaths. All patients swallowed well for an average of five months until their deaths. The decision to use this procedure is made at the time of thoracotomy when resection of the cancer is impossible because of local invasion and when sufficient proximal oesophagus is available for the anastomosis. The operation involves a single suture line only. It provides immediate palliation of dysphagia and makes unnecessary additional technical manoeuvres such as preparation of colonic or jejunal loops insertion of endoluminal tubes, or even transection of the oesophagus, pyloroplasty, gastrostomy or cervical oesophagostomy. It does not interfere with any subsequent radiotherapy or chemotherapy.
Postexposure Protection of Macaques from Vaginal SHIV Infection by Topical Integrase Inhibitors
Authors: Charles Dobard, Sunita Sharma, Urvi M. Parikh, Rolieria West, Andrew Taylor, Amy Martin, Chou-Pong Pau, Debra L. Hanson, Jonathan Lipscomb, James Smith, Francis Novembre, Daria Hazuda, J. Gerardo Garcia-Lerma, Walid Heneine
Journal: Science Translational Medicine (2014)

Postexposure protection of macaques from SHIV infection by a gel containing integrase inhibitors.
Acceleration of Ventricular Pacemakers by Transient Increases in Heart Rate in Dogs during Ouabain Administration
Authors: STEPHEN M. WITTENBERG, FRITZ STREULI, FRANCIS J. KLOCKE
Journal: Circulation Research (1970)

The present experiments describe effects of transient increases in heart rate on ventricular pacemakers during digitalization. Fifteen anesthetized, vagotomized dogs were studied during ouabain infusion or after recovery from ouabain-induced ventricular tachycardia. Vagal stimulation was used to assess baseline ventricular automaticity and 30-second periods of atrial pacing were utilized to evaluate the response of ventricular pacemakers following different increments in rate. After an average dose of 45 ± 3 (SE) µg/kg of ouabain, vagal stimulation unmasked an automatic ventricular focus in 14 animals and pacing was followed by ventricular acceleration in all 15 animals. The Degrees of ventricular acceleration varied directly with the pacing rate. The increment in ventricular rate above the level unmasked by vagal stimulation averaged 59 ± 4% of the increment in atrial rate. At the higher driving rates, a transient postpacing depression was present before the emergence of a rapid ventricular focus. These findings were unaffected by beta-receptor blockade with 4-(2-hydroxy-3-isopropylamino propoxy) acetanilide (AY21,011). The results indicate that transient increases in heart rate may accelerate rather than depress ventricular pacemakers during digitalization.
A New Spin on Research Translation: The Boston Consensus Conference on Human Biomonitoring
Authors: Jessica W. Nelson, Madeleine Kangsen Scammell, Rebecca Gasior Altman, Thomas F. Webster, David M. Ozonoff
Journal: Environmental Health Perspectives (2008)

BackgroundTranslating research to make it more understandable and effective (research translation) has been declared a priority in environmental health but does not always include communication to the public or residents of communities affected by environmental hazards. Their unique perspectives are also commonly missing from discussions about science and technology policy. The consensus conference process, developed in Denmark, offers a way to address this gap.ObjectivesThe Boston Consensus Conference on Human Biomonitoring, held in Boston, Massachusetts, in the fall of 2006, was designed to educate and elicit input from 15 Boston-area residents on the scientifically complex topic of human biomonitoring for environmental chemicals. This lay panel considered the many ethical, legal, and scientific issues surrounding biomonitoring and prepared a report expressing their views.DiscussionThe lay panel's findings provide a distinct and important voice on the expanding use of biomonitoring. In some cases, such as a call for opt-in reporting of biomonitoring results to study participants, they mirror recommendations raised elsewhere. Other conclusions have not been heard previously, including the recommendation that an individual's results should be statutorily exempted from the medical record unless permission is granted, and the opportunity to use biomonitoring data to stimulate green chemistry.ConclusionThe consensus conference model addresses both aspects of a broader conception of research translation: engaging the public in scientific questions, and bringing their unique perspectives to bear on public health research, practice, and policy. In this specific application, a lay panel's recommendations on biomonitoring surveillance, communication, and ethics have practical implications for the conduct of biomonitoring studies and surveillance programs.
The Hunterian Oration
Authors: T. S. Wells
Journal: BMJ (1883)

IMIUST now obey the other direction in the trust deced, and en- deavour to express something as to the "merits, in comparative anatomy, physiology and surgery," of John Hunter.The direction seems a happy one, for Hunter based his surgery upon physiology, and his physiology upon comparative anatomy.What can more strikingly illustrate this than his greatest improvement in practical surgery?-the abolition of amputation for popliteal aneurysm, and the practice of tying the artery in a sound part at a distance from the seat of disease.
36 OPTIMIZATION OF DONOR-RECIPIENT MATCH AND IDENTIFICATION OF THE FUTILE MATCH CUTOFF. A NATIONAL ITALIAN STUDY ON LIVER TRANSPLANTATION
Authors: A.W. Avolio, S. Agnes, M.C. Lirosi, M. Salizzoni, A.D. Pinna, B. Gridelli, L. De Carlis, M. Colledan, G.E. Gerunda, U. Valente, G. Rossi, G.M. Ettorre, A. Risaliti, V. Mazzaferro, F. Bresadola, M. Rossi, G. Tisone, F. Zamboni, L. Lupo, O. Cuomo, F. Calise, M. Donataccio, N. Nicolotti, A. Vitale, R. Romagnoli, F. Lupo, A. Cucchetti, S. Gruttadauria, I. Mangoni, D. Pinelli, R. Montalti, M. Gelli, L. Caccamo, G. Vennarecci, D. Nicolini, E. Regalia, U. Baccarani, Q. Lai, T. Manzia, E. Tondolo, M. Rendina, M. Barone, A. Perrella, M. Romano, C. de Waure, P. Burra, A. Gasbarrini, U. Cillo
Journal: Journal of Hepatology (2011)
Association of pretreatment serum interferon inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C
Authors: M Diago
Journal: Gut (2005)

<b>Background:</b> Increased serum and intrahepatic interferon γ inducible protein 10 (IP-10) levels in patients with chronic hepatitis C (CHC) have been described. <b>Aim:</b> To analyse the possible association of serum IP-10 levels with different outcomes to antiviral therapy. <b>Patients:</b> A total of 137 CHC patients treated with peginterferon plus ribavirin. <b>Methods:</b> Serum IP-10 levels were determined by enzyme linked immunosorbent assay before therapy, after 12 weeks of treatment, and 24 weeks after cessation of therapy. Variables significantly associated with a sustained virological response (SVR) on univariate analysis were included in a multivariate logistic regression model. <b>Results:</b> Pretreatment serum IP-10 levels in patients with SVR were significantly lower than in non-responders (NR) (332.4 (222.1) <i>v</i> 476.8 (305.3) pg/ml, respectively; p = 0.004). Serum IP-10 concentrations significantly decreased in patients with SVR (pretreatment: 332.4 (222.1) pg/ml; post-treatment: 170.2 (140.1) pg/ml; p&lt;0.001) but not in NR (pretreatment: 476.8 (305.3) pg/ml; post treatment: 387.3 (268.1) pg/ml; p = 0.06). By multivariate analysis, non-1 genotype (odds ratio (OR) 3.5 (95% confidence interval (CI) 1.1–10.4); p = 0.003) and low viral load at baseline (OR 0.34 (95% CI 0.14–0.79); p = 0.01) were independent predictors of SVR in all patients. When multivariate analysis was restricted to patients with genotype 1, only baseline viral load (OR 0.38 (95% CI 0.155–0.96); p = 0.04) and pretreatment serum IP-10 levels (OR 0.99 (95% CI 0.996–0.999); p = 0.03) were identified as predictive factors of SVR. <b>Conclusion:</b> Pretreatment serum IP-10 behaves as a predictive factor of SVR to peginterferon plus ribavirin therapy in genotype 1 infected patients.
Matrix mechanics and regulation of the fibroblast phenotype
Authors: Boris Hinz
Journal: Periodontology 2000 (2013)

Abstract The oral cavity hosts a variety of different fibroblast populations that are generally responsible for maintaining homeostasis of the soft connective tissue. In addition to regulating the turnover and structural arrangement of collagen and other proteins of the extracellular matrix, fibroblasts perform a number of specialized functions. Certain fibroblast subpopulations in the gingiva, oral mucosa and periodontal ligament serve as progenitor cells with multilineage differentiation and self‐renewal characteristics. In the periodontal ligament, fibroblasts further appear to function as mechanosensing entities that regulate collagen‐secretory and collagen‐remodeling activities according to the level of strain in the ligament. Mechanical challenge also plays an important role during the activation of periodontal fibroblasts in response to injury. Dysregulation of this activation process can lead either to poor healing and chronic wounds or to overly healed wounds with fibrosis. This review will elaborate on the roles of mechanical factors and mechanoperception in fibroblast activation, the molecular features of activated fibroblasts and the regulation mechanisms of fibroblast contraction. Pharmacological interference at each level is currently being pursued to improve the outcome of healing of injured periodontal tissue.