tbuckley/cabot-search huggingface dataset:
Abstract 1036: Cbl-independent degradation of Met: Ways to avoid agonism of bivalent Met targeting antibody.
Authors: Ji Min Lee, Bogyou Kim, Kyung-Ah Kim
Journal: Cancer Research (2013)

Abstract The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met down-regulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Cbl E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met over-expressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met targeting antibody demonstrated intrinsic agonistic activity while capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to down-regulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies. Citation Format: Ji Min Lee, Bogyou Kim, Kyung-Ah Kim. Cbl-independent degradation of Met: Ways to avoid agonism of bivalent Met targeting antibody. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1036. doi:10.1158/1538-7445.AM2013-1036
Why the findings of published multiple treatment comparison meta-analyses of biologic treatments for rheumatoid arthritis are different: an overview of recurrent methodological shortcomings
Authors: Kristian Thorlund, Eric Druyts, J Antonio Aviña-Zubieta, Ping Wu, Edward J Mills
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate the quality of published multiple treatment comparison (MTC) meta-analyses on biologic disease modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA), and to identify methodological issues that can explain the discrepancies in the findings of these MTCs.We searched MEDLINE for MTCs of bDMARDs for RA. Following the PRISMA guidelines, we extracted a large set of methodological items. These comprised of inclusion/exclusion criteria, information sources, reported results and outcomes measures, approaches to dealing with differing response profiles to available treatments, monotherapies versus combination therapies, and potential sources of heterogeneity.We identified 13 published MTCs, of which nine were published since 2009. Despite similar stated eligibility criteria and objectives across MTCs, we identified major discrepancies in the estimated treatment effects, the inclusion of trials and analytic approaches. The number of included trials was typically much smaller than the number of eligible trials at the time of publication. Three out of six MTCs including patients of differing response profiles inappropriately combined DMARD-naive and DMARD-inadequate responder patients in the analyses. Four out of eight MTCs that considered both monotherapy and combination therapy (ie, concomitant DMARD) did not adjust for the potential effect modification. Half of the identified MTCs did not explore potential sources of heterogeneity, and the explored sources varied considerably. Last, most MTCs only included one or two efficacy outcomes (eg, ACR50) and only two considered health related quality of life outcomes (eg, HAQ).The identified methodological shortcomings and inconsistencies most likely explain the observed discrepancies in findings across MTCs.
GASTRIC EXCRETION OF NEUTRAL RED
Authors: PERCY B. DAVIDSON
Journal: JAMA (1925)

The application of neutral red as a vital stain has been a wide one since its introduction by Ehrlich into medicine. Its use in the study of gastric secretory functions dates from Fuld's<sup>1</sup>work on dogs with Pawlow pouches in 1908, in which he demonstrated its excretion into the pouch, when the dye was instilled into the main stomach. Finkelstein,<sup>2</sup>in 1922, injecting neutral red and other dyes subcutaneously, studied the excretion into Pawlow pouches and substantiated Fuld's earlier observations. Glaessner and Wittgenstein,<sup>3</sup>in 1923, applied this knowledge to the formulation of a "gastric function test," using as their criterion the appearance time of the dye in the stomach after intra-muscular injection. Subsequently, publications by Simici and Dumitriu,<sup>4</sup>Koopman,<sup>5</sup>and Carnot and Gaehlinger<sup>6</sup>have emphasized the usefulness of this procedure. The studies reported here aim particularly to consider the clinical usefulness of determining the
Human Anatomy: Text and Colour Atlas
Authors: John E. Skandalakis
Journal: JAMA (1991)

<b>Visualizing Muscle: A New Ecorché Approach to Surface Anatomy,</b>by John Cody, 231 pp, with illus, $35, ISBN 0-7006-0425-1, paper $25, ISBN 0-7006-0426-X, Lawrence, University Press of Kansas, 1990.
Molecular Mechanisms of Tamoxifen Therapy for Cholangiocarcinoma: Role of Calmodulin
Authors: Pritish Pawar, Liping Ma, Chang Hyun Byon, Hui Liu, Eun-Young Ahn, Nirag Jhala, Juan P. Arnoletti, Jay M. McDonald, Yabing Chen
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Cholangiocarcinoma is a fatal tumor with limited therapeutic options. We have reported that calmodulin antagonists tamoxifen and trifluoperazine induced apoptosis in cholangiocarcinoma cells. Here, we determined the effects of tamoxifen on tumorigenesis and the molecular mechanisms of tamoxifen-induced apoptosis. Experimental Design: Nude mice xenograft model of cholangiocarcinoma was used and tamoxifen was given i.p. and intratumorally. Cholangiocarcinoma cells were used to characterize molecular mechanisms of tamoxifen-induced apoptosis in vitro. Results: I.p. or intratumoral injection of tamoxifen decreased cholangiocarcinoma tumorigenesis by 40% to 80% in nude mice. In cells isolated from tumor xenografts, tamoxifen inhibited phosphorylation of AKT (pAKT) and cellular FLICE like inhibitory protein (c-FLIP). Immunohistochemical analysis further showed that pAKT was identified in all nontreated tumors but was absent in tamoxifen-treated tumors. In vitro, tamoxifen activated caspase-8 and caspase-10, and their respective inhibitors partially blocked tamoxifen-induced apoptosis. Overexpression of c-FLIP inhibited tamoxifen-induced apoptosis and enhanced tumorigenesis of cholangiocarcinoma cells in nude mice, whereas deletion of the calmodulin-binding domain on c-FLIP restored the sensitivity to tamoxifen and inhibited tumorigenesis. With two additional cholangiocarcinoma cell lines, we confirmed that the expression of FLIP is an important factor in mediating spontaneous and tamoxifen-induced apoptosis. Conclusions: Thus, tamoxifen inhibits cholangiocarcinoma tumorigenesis in nude mice. Tamoxifen-induced apoptosis is partially dependent on caspases, inhibition of pAKT, and FLIP expression. Further, calmodulin-FLIP binding seems to be important in FLIP-mediated resistance to tamoxifen. Therefore, the present studies support the concept that tamoxifen may be used as a therapy for cholangiocarcinoma and possibly other malignancies in which the calmodulin targets AKT and c-FLIP play important roles in the tumor pathogenesis.
PolioPlus: Poliomyelitis Eradication by Year 2005
Authors: Phil Gunby
Journal: JAMA (1993)

IF SOMALIA'S SITUATION symbolizes what the United Nations will do for a less fortunate world neighbor's health, "PolioPlus" is an indication of what the private sector can do internationally. Rotary International apparently is the first international private sector organization to make a major commitment to child immunization in developing nations and, as 1993 gets under way, there is an expanded energy evident in this "PolioPlus" effort (<i>JAMA</i>. 1992;267:479). This fall, Rotary International and Foundation officials met at the 1.1million-member service-club association's Evanston, Ill, headquarters with representatives of the World Health Organization, United Nations Children's Fund, Pan American Health Organization, Centers for Disease Control and Prevention, and Carter Center (Emory University, Atlanta, Ga) Task Force for Child Survival and Development. This group has been heartened by news that no polio has been reported in the western hemisphere for more than 16 months (<i>JAMA</i>. 1992;268:1650). Now, since hosting that fall meeting, the
B lymphocyte stimulator expression in patients with rheumatoid arthritis treated with tumour necrosis factor antagonists: differential effects between good and poor clinical responders
Authors: D T La, C E Collins, H-T Yang, T-S Migone, W Stohl
Journal: Annals of the Rheumatic Diseases (2007)

To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA).Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS protein levels, blood leukocyte BLyS mRNA levels and disease activity were longitudinally monitored. Twelve patients with RA who either refused or were felt not to be candidates for TNF antagonist therapy and five normal healthy volunteers served as TNF antagonist-naïve controls.Baseline plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were elevated in patients with RA. Plasma BLyS protein levels declined following initiation of TNF antagonist therapy in good responders (GR) to TNF antagonist therapy but not in poor responders (PR). By contrast, the erythrocyte sedimentation rate (ESR) declined in response to TNF antagonist therapy in GR and PR. TNF antagonist therapy did not promote change in blood leukocyte BLyS mRNA levels in either GR or PR, suggesting that the TNF antagonist-associated changes in circulating BLyS protein levels reflected changes in local BLyS production in the affected joints rather than changes in systemic BLyS production. BLyS expression did not change over time in either the normal or RA control groups.A good clinical response to TNF antagonist therapy in patients with RA is associated with a decline in plasma BLyS protein levels. Increased BLyS expression in affected joints may contribute to ongoing disease activity, and reduction of such expression may help promote a favourable clinical response to TNF antagonist therapy.
Nimbolide, a Limonoid Triterpene, Inhibits Growth of Human Colorectal Cancer Xenografts by Suppressing the Proinflammatory Microenvironment
Authors: Subash C. Gupta, Sahdeo Prasad, Dhanya R. Sethumadhavan, Mangalam S. Nair, Yin-Yuan Mo, Bharat B. Aggarwal
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Extensive research over the past decade has revealed that the proinflammatory microenvironment plays a critical role in the development of colorectal cancer. Whether nimbolide, a limonoid triterpene, can inhibit the growth of colorectal cancer was investigated in the present study. Experimental Design: The effect of nimbolide on proliferation of colorectal cancer cell lines was examined by MTT assay, apoptosis by caspase activation and poly-ADP ribose polymerase cleavage, NF-κB activation by DNA-binding assay, and protein expression by Western blotting. The effect of nimbolide on the tumor growth in vivo was examined in colorectal cancer xenografts in a nude mouse model. Results: Nimbolide inhibited proliferation, induced apoptosis, and suppressed NF-κB activation and NF-κB–regulated tumorigenic proteins in colorectal cancer cells. The suppression of NF-κB activation by nimbolide was caused by sequential inhibition of IκB kinase (IKK) activation, IκBα phosphorylation, and p65 nuclear translocation. Furthermore, the effect of nimbolide on IKK activity was found to be direct. In vivo, nimbolide (at 5 and 20 mg/kg body weight), injected intraperitoneally after tumor inoculation, significantly decreased the volume of colorectal cancer xenografts. The limonoid-treated xenografts exhibited significant downregulation in the expression of proteins involved in tumor cell survival (Bcl-2, Bcl-xL, c-IAP-1, survivin, and Mcl-1), proliferation (c-Myc and cyclin D1), invasion (MMP-9, ICAM-1), metastasis (CXCR4), and angiogenesis (VEGF). The limonoid was found to be bioavailable in the blood plasma and tumor tissues of treated mice. Conclusions: Our studies provide evidence that nimbolide can suppress the growth of human colorectal cancer through modulation of the proinflammatory microenvironment. Clin Cancer Res; 19(16); 4465–76. ©2013 AACR.
Abstract 1073: Significant association of neutrophils in regional lymph nodes with lymphangiogenesis and micrometastasis by gastric cancer
Authors: Mao Tokumoto, Hiroaki Tanaka, Masaichi Ohira, Yukie Go, Yoshihiro Okita, Katunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Kazuya Muguruma, Kiyoshi Maeda, Tetsuji Sawada, Kosei Hirakawa
Journal: Cancer Research (2014)

Abstract Recent evidences indicate that inflammation is the seventh hallmark of cancer. Several researches reported that tumor-associated neutrophils (TANs) promote tumor invasion or tumor-induced angiogenesis in the tumor microenvironment. However, the relation between TANs and lymph node metastasis remains unclear. We previously reported that increasing of intranodal lymphatic vessel density (LVD) was significantly correlated to tumor progression, lymph node metastasis and poor prognosis of the patients with gastric cancer. In this study, we aimed to reveal the affect of TANs in regional lymph nodes in terms of micrometastasis and the prognostic impact. TANs and micrometastasis were immunohistochemically estimated by anti-CD15 and anti-pan cytokeratin antibody in 1596 lymph nodes from 52 patients who were underwent gastrectomy with lymphadenectomy. We investigated the association of the density of TANs in regional lymph nodes with clinicopathological factors. The number of TANs in regional lymph nodes had a positive correlation with accumulation of intranodal LVD and micrometastasis. Furthermore we divided another 96 patients into two groups according to median TAN number of 39 to investigate the prognostic value. Patients in high CD15+TANs group had significantly poorer prognosis compared with low group. Our results suggested that TANs in regional lymph nodes promote the invasion of cancer cells to lymph nodes by augmentation of lymphangiogenesis and contribute to tumor progression. In conclusion, TANs might be an attractive target of novel bioloigical therapies of gastric cancer. Citation Format: Mao Tokumoto, Hiroaki Tanaka, Masaichi Ohira, Yukie Go, Yoshihiro Okita, Katunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Kazuya Muguruma, Kiyoshi Maeda, Tetsuji Sawada, Kosei Hirakawa. Significant association of neutrophils in regional lymph nodes with lymphangiogenesis and micrometastasis by gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1073. doi:10.1158/1538-7445.AM2014-1073
Randomized, placebo‐controlled trial of <i>Lactobacillus rhamnosus</i> GG as treatment of atopic dermatitis in infancy
Authors: C. Grüber, M. Wendt, C. Sulser, S. Lau, M. Kulig, U. Wahn, T. Werfel, B. Niggemann
Journal: Allergy (2007)

Background: Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis. Methods: Infants aged 3–12 months suffering from mild‐to‐moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15–40) without current antiinflammatory treatment were randomized to receive LGG (5 × 10 9 colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL). Results: Fifty‐four infants (LGG group, mean ± SD SCORAD index 24.6 ± 8.8) and 48 infants (placebo group, SCORAD index 23.6 ± 7.8) were randomized and completed the treatment period (intention‐to‐treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 ± 12.4 vs 20.6 ± 9.9), 8 weeks (22.5 ± 14.6 vs 17.9 ± 13.1), and 12 weeks (19.6 ± 15.4 vs 15.1 ± 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 ± 45.0 g vs 3.5 ± 29.8 g), increase in mean logarithmic total serum IgE (0.17 ± 0.30 kU/l vs 0.26 ± 0.45 kU/l), and newly developed allergic sensitization against hen’s egg or cow’s milk (18.8% vs 10.0%). Conclusion: This placebo‐controlled trial showed no therapeutic effect of LGG against mild‐to‐moderate atopic dermatitis in infancy.
A 42-Year-Old Man Considering Whether to Drink Alcohol for His Health
Authors: Kenneth J. Mukamal
Journal: JAMA (2010)

Alcohol consumption is widespread and, in excess, a leading cause of morbidity and mortality worldwide. At the same time, a consistent body of observational evidence has found that individuals who consume alcohol within recommended limits have a lower risk of coronary heart disease than do abstainers. These observations have led many to consider small amounts of alcohol as a cardioprotective strategy. Mr Q, a 42-year-old man who has consistently sought ways to preserve his health, is at a crossroads in his discussions with his physicians about the health effects of his regular, limited alcohol intake. The discussion reviews the epidemiology of drinking in the United States, the established effects of moderate alcohol intake on key pathophysiological biomarkers and pathways, the strengths and limitations of observational evidence linking alcohol intake to lower risk of coronary heart disease, other chronic diseases linked to moderate alcohol intake, and a framework in which Mr Q can discuss the potential risks and benefits of alcohol consumption with his physicians.
67Ga???Citrate Scanning in Gastrointestinal Malignancies
Authors: HOWARD N. DOUDS, SANFORD V. BERENS, ROBERT F. LONG, GERALD E. CAPLAN
Journal: Clinical Nuclear Medicine (1978)

The value of 67 Ga-citrate scanning in cases of gastrointestinal malignancies is discussed. Seven cases are presented, including lymphomas of the stomach, small bowel, and rectum, and adenocarcinomas of the stomach and colon. In a review of the literature, there is general pessimism regarding the use of 67Ga scans in GI malignancies. Based on previous reports and our own experience, specific clinical situations are cited in which the scan is of considerable value for diagnosis and followup of GI malignancy.
Characterization of a rituximab variant with potent antitumor activity against rituximab-resistant B-cell lymphoma
Authors: Bohua Li, Lei Zhao, Huaizu Guo, Chong Wang, Xunming Zhang, Lan Wu, Lin Chen, Qing Tong, Weizhu Qian, Hao Wang, Yajun Guo
Journal: Blood (2009)
Correlation between ultrasound imaging of major salivary glands and histopathological findings of labial gland biopsy samples in Sjogren's syndrome
Authors: Shabnum Ali, Jackie Brown, Rose Ngu, Troy Daniels, John Greenspan, Edward Odell, Penelope J Shirlaw, Kuldipsinh G Gohil, Bruce Kirkham, Genevieve Larkin, Stephen J Challacombe
Journal: The Lancet (2013)
CHANGES INDUCED IN THE BLOOD OF RABBITS BY LIVING IN AN ATMOSPHERE OF WATER GAS
Authors: George G. Nasmith, F. C. Harrison
Journal: The Journal of Experimental Medicine (1910)

1. Rabbits living in an atmosphere of carbon monoxide react in general as guinea-pigs react. 2. The increased specific gravity of the blood in " carbon monoxide " rabbits is due wholly to the increase in the number of erythrocytes and of hemoglobin, and not to any change in the plasma. 3. Weigert's law of inertia, that production would continue after the stimulus has ceased to act, does not hold in the case of carbon monoxide stimulated rabbits. 4. Hemolysins, precipitins and agglutinins towards normal rabbit corpuscles and sera were not present in carbon monoxide rabbits. 5. " Hemopoeitin " or anything of a similar nature was not found in rabbits in any stage of erythrocyte degeneration or regeneration.
Vaccination and Disease Prevention for Adults
Authors: Richard A. Goodman
Journal: JAMA (1982)

BECAUSE vaccination of children is now considered to be routine in the United States, it is taken for granted that adults are immunized. A recent review of the role of the periodic health examination depicted some of the uncertainties concerning routine immunization practices for adults.<sup>1</sup>Many "childhood" diseases are no longer diseases of childhood because of the widespread immunization of children in the United States. In recent years, several of the vaccine-preventable diseases have become diseases of adults: during 1980, for example, 91.6% of tetanus cases and more than one third of rubella cases occurred in persons older than 15 years.<sup>2</sup>The purposes of this commentary are to remind physicians and other health care workers who treat adults to incorporate vaccination questions into the medical history and to review immunizing agents that might be indicated for adults. The medical history of a patient is an important tool used