tbuckley/cabot-search huggingface dataset:
Abstract 464: Tumor derived vacuolar ATPase subunit promotes M2 type polarization of macrophages.
Authors: Gajendra K. Katara, Mukesh K. Jaiswal, Alice Gilmam-Sacks, Kenneth D. Beaman
Journal: Cancer Research (2013)

Abstract Tumors and tumor associated macrophages (TAMs) express a unique surface vacuolar ATPase (V-ATPase) on the plasma membrane. In tumor cells, a 20 kd peptide is cleaved from a2 isoform of V-ATPase and is referred to as a2NTD; it is associated with in vitro induction of pro-tumorigenic properties in monocytes and IL-β secretion. In this study, we evaluated the immuno-modulatory properties of a2NTD in inducing murine peritoneal macrophage polarization and activation of inflammasome components both ex vivo and in vivo. Peritoneal macrophages from BALB/c mice were stimulated with recombinant a2NTD and the mRNA and protein expression of M1 (CD11c, TNF-α), M2 (Mannose receptor-1, Arginase-1, IL-10) markers, IL-1β and NLRP3 (inflammasome marker) were analyzed using quantitative real time PCR and flow cytometry. Further, mice were injected with a2NTD i.p. and peritoneal cells were analyzed for M1/M2 specific markers. The results of both in vivo and ex vivo analysis showed an elevated population of M2 subtype in a2NTD-treated mice compared to control (P&amp;lt;0.05). a2NTD upregulated the expression of IL-1β and NLRP3 in macrophages. These data demonstrated that a2NTD modulates macrophage polarization towards the M2 subtype functionally similar to tumor associated macrophages (TAMs). Since, tumor progression requires sterile inflammation and maturation of resident macrophages into TAMs; our data provide evidence that the surface expression of V-ATPase in tumor cells has a role in inducing the unique inflammatory environment of tumors by modulating macrophage phenotype and inducing IL-1β production through the action of a2NTD. The study also provides indication for the involvement of a2NTD in NLRP3 mediated inflammasome activation. Citation Format: Gajendra K. Katara, Mukesh K. Jaiswal, Alice Gilmam-Sacks, Kenneth D. Beaman. Tumor derived vacuolar ATPase subunit promotes M2 type polarization of macrophages. [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 464. doi:10.1158/1538-7445.AM2013-464
P243 INVOLVEMENT OF MYOKINES AND ADIPOKINES IN LIVER STEATOSIS
Authors: M. Nakamuta, M. Kohjima, T. Yoshimoto, T. Nakamura, T. Ohashi, K. Fukuizumi, N. Fujimori, K. Kawabe, K. Haraguchi, A. Aso, Y. Sumida, N. Harada, T. Ryu, Y. Wada, Y. Takami, H. Saitsu, T. Utsunomiya, M. Shimada, K. Dohmen, H. Nomura, M. Enjoji
Journal: Journal of Hepatology (2014)
Adult-Onset Acid Maltase Deficiency
Authors: V. Askanas, W.K. Engel, S. DiMauro, B.R. Brooks, M. Mehler
Journal: New England Journal of Medicine (1976)

We established muscle-tissue cultures from biopsy of a patient with adult-onset acid maltase deficiency. Morphologically and biochemically, the newly grown fibers of the cultured muscle showed the same abnormalities as those of the biopsied muscle. Light microscopy showed multiple vacuoles filled with acid-phosphatase-positive material; on ultrastructural examination there was abnormal accumulation of glycogen in membrane-bound sacs (secondary lysosomes), some of which also contained dark membranous of homogeneous material. Acid maltase (pH 4.0), a lysosomal enzyme, was undetectable in either cultured or biopsied muscle by maltose hydrolysis, whereas acid phosphatase, also a lysosomal enzyme, was increased in both sources of muscle cells. Cultured muscle fibers demonstrate the same morphologic and biochemical abnormalities characteristic of biopsied muscle, supporting the concept of a biochemically distinct primary myopathy in man.
UEG Week 2014 highlights: putting endoscopy into perspective
Authors: Ioannis Papanikolaou, Peter Siersema
Journal: Endoscopy (2015)

The 22nd United European Gastroenterology (EUG) Week took place in Vienna in October 2014. The meeting offered a great opportunity to all those interested in gastrointestinal (GI) endoscopy to exchange clinical experiences, research trends, and scientific progress from all over the world. This report will highlight some of the most interesting topics of GI endoscopy that were presented over the 3 days, and will briefly comment on them in light of the latest bibliographic data.
Coronary Angioscopy in Patients with Unstable Angina Pectoris
Authors: C. Todd Sherman, Frank Litvack, Warren Grundfest, Myles Lee, Ann Hickey, Aurelio Chaux, Robert Kass, Carlos Blanche, Jack Matloff, Leon Morgenstern, William Ganz, H.J.C. Swan, James Forrester
Journal: New England Journal of Medicine (1986)

To visualize intracoronary lesions in patients with different clinical expressions of coronary disease, we performed coronary angioscopy during coronary-artery bypass surgery in 10 patients with unstable angina and 10 patients with stable coronary disease. We examined a total of 32 vessels, using flexible fiberoptic angioscopes. Twenty-two vessels had no acute intimal lesion; three had complex plaques, six had thrombi, and one had both. Coronary angiography correctly identified the absence of complex plaque and thrombus in 22 vessels, but it detected only one of four complex plaques and one of seven thrombi. On angioscopy, none of the 17 arteries in the patients with stable coronary disease had either a complex plaque or thrombus. In the "offending" arteries of the patients with unstable angina, all three patients with accelerated angina had complex plaques and all seven with angina at rest had thrombi. We conclude that angioscopy frequently reveals complex plaques or thrombi not detected by coronary angiography. Our observations suggest that anginal syndromes that are refractory to medical treatment can be caused by unstable pathologic processes in the intima. Ulceration of plaques may increase the frequency and severity of effort angina, and the subsequent development of partially occlusive thrombi may cause unstable rest angina.
AB0126 Regulation of embryonic bone development and fracture repair by SYNDECAN-4
Authors: J. Bertrand, R. Stange, H. Hidding, F. Echtermeyer, G. Nalesso, L. Godmann, F. Dell’Accio, T. Pap, R. Dreier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Syndecan-4 (Sdc4) is a heparan sulfate proteoglycan that has been strongly associated with osteoarthritis, a disease that mimics key aspects of early cartilage remodelling during endochondral ossification. The role of Sdc4 in embryonic and adult bone formation, however, remains unclear. <h3>Objectives</h3> In order to elucidate its function we used <i>Sdc4</i><sup>-/-</sup> mice to analyze the distribution and functional role of Scd4 in endochondral ossification of mouse embryos and in adult fracture repair, which recapitulates endochondral ossification, but like osteoarthritis involves an inflammatory component. <h3>Methods</h3> <i>Sdc4</i> promoter activity was anlysed in <i>Sdc4</i><sup>-/-</sup><i>/LacZ knock-in</i> animals using β-galactosidase stainings. E16.5 embyros were used for histological (alcian blue/alizarin red) and immunohistological (PCNA, Col10a1, A Disintegrin ADAMTS-4, BC-3, Sdc2) stainings. Calcified bone area was quantified using whole mount stainings. Histological (Masson-Goldner, alcian blue) and immunohistological (Col10a1, Sdc2, PCNA) stainings at day 7, 14 and 28 fracture calli were performed. Callus size and cartilage area were quantified. Chondrocytes were isolated from neonatal knee joints and embyronal cartilage. Proliferation was investigated using MTT assay. Gene expression analysis for Sdc-2, Sdc-4 with and without stimulation using TNFα and WNT3a was performed using quantitative real time-PCR. <h3>Results</h3> <i>Sdc4</i> promoter activity was detectable in all stages of chondrocyte differentiation, and <i>Sdc4</i> deficiency inhibited chondrocyte proliferation both <i>in vivo</i> and <i>in vitro</i>. Moreover, aggrecan turn over in the epiphysial cartilage was decreased transiently <i>in vivo,</i> but this did not lead to a growth phenotype at birth. In contrast, fracture healing in adult mice was markedly delayed in <i>Sdc4</i><sup>-/-</sup> animals and accompanied by increased callus formation. Analysing the discrepancy between the mild embryonic and the severe adult phenotype, we found a compensatory up-regulation of <i>Sdc2</i> in the developing cartilage of <i>sdc4</i><sup>-/-</sup> mice that was absent in adult tissue. Stimulation of chondrocytes with Wnt3a <i>in vitro</i>, led to an increased expression of <i>Sdc2</i>, while stimulation with TNFa resulted in an up-regulation of <i>Sdc4</i> but a decreased expression of <i>Sdc2</i>. <h3>Conclusions</h3> We conclude that Sdc4 is functionally involved in endochondral ossification and that the loss of Sdc4 impairs adult fracture healing due to the inhibition of compensatory mechanisms under inflammatory conditions. <h3>Disclosure of Interest</h3> None Declared
Parachutes and Preferences — A Trial of Knee Replacement
Authors: Jeffrey N. Katz
Journal: New England Journal of Medicine (2015)

The term parachute trial entered the medical lexicon to depict studies of treatments everyone already assumes to be effective. (In other words, do we need a trial to show that parachutes save the lives of persons who jump from airplanes?1) The parachute trial has been invoked to decry randomized trials of total joint replacement as senseless. After all, joint replacements are among the most significant advances of the 20th century; don’t we already know they are successful?Nearly 1 million elective total knee and hip replacements are performed annually in the United States; rates of total knee replacement tripled . . .
Comparison of Two Platelet Glycoprotein IIb/IIIa Inhibitors, Tirofiban and Abciximab, for the Prevention of Ischemic Events with Percutaneous Coronary Revascularization
Authors: Eric J. Topol, David J. Moliterno, Howard C. Herrmann, Eric R. Powers, Cindy L. Grines, David J. Cohen, Eric A. Cohen, Michel Bertrand, Franz-Josef Neumann, Gregg W. Stone, Peter M. DiBattiste, Steven J. Yakubov, Paul T. DeLucca, Laura Demopoulos
Journal: New England Journal of Medicine (2001)

In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab.
Comparative study of bipolar eletrocoagulation versus argon plasma coagulation for rectal bleeding due to chronic radiation coloproctopathy
Authors: L. Lenz, J. Tafarel, L. Correia, D. Bonilha, M. Santos, R. Rodrigues, G. Gomes, G. Andrade, F. Martins, M. Monaghan, F. Nakao, E. Libera, A. Ferrari, R. Rohr
Journal: Endoscopy (2011)

Background and study aim: Chronic radiation coloproctopathy (CRCP) is a well-recognized complication of radiotherapy, with rectal bleeding the most common presentation. It is frequently refractory to conservative management, but the optimal endoscopic treatment of bleeding secondary to CRCP is still controversial. The efficacy and safety of bipolar eletrocoagulation (BEC) and argon plasma coagulation (APC) in the management of bleeding from CRCP were evaluated and compared.
The Time Factor in the Development of Complications of Gallstones
Authors: Carl Bearse
Journal: New England Journal of Medicine (1945)

IF GALLSTONES remain in the gall bladder, according to Cheever,1 "sooner or later, if their host lives long enough, they will cause damage of a serious nature." With this statement there can be only general accord, but the phrase "sooner or later" is vague. The following statistical study was undertaken with the hope of establishing a more definite time relation between the original disease and the sequelae.It is generally acknowledged that gallstones may exist for many years without giving rise to symptoms,2 but once they have been demonstrated, one is obliged to assume that eventually such sequelae as acute . . .
Abstract 3413: A population of metastatic colorectal cancer (mCRC) patients with radiologically proven liver metastasis and EpCAM expressing primary tumors show low circulating tumor cell counts by Veridex Cellsearch
Authors: Avisnata Das, Jamal Joudeh, Kristi L. Peters, Joshua E. Allen, Siyang Zheng, David T. Dicker, Zhaohai Yang, Wafik S. El-Deiry
Journal: Cancer Research (2012)

Abstract Circulating tumor cells (CTCs) have prognostic significance for metastatic cancers including colorectal, breast and prostate cancer. We have been evaluating CTC numbers as well as molecular markers as prognostic, treatment and disease-monitoring tools. The FDA recommends a cutoff value of &amp;gt; 3 CTCs/7.5 ml of blood, using Johnson &amp; Johnson Veridex Cellsearch technology as indicator of poor prognosis for metastatic colorectal cancer (mCRC). We report identifying a population of patients who have advanced disease and liver metastases (shown by CT/MRI/PET scan) but the CTC count using our CLIA-certified Veridex Cellsearch laboratory was &amp;lt;3/7.5 ml of blood. As Cellsearch technology relies on Epithelial Cell Adhesion Molecule (EpCAM) expression for isolation of CTCs, we analysed the primary tumors for EpCAM positivity using immunostaining. All 5 patients we have identified so far showed moderate to strong EpCAM expression in their primary tumor. The low CTC count in these patients with reference to the FDA standard raises a question regarding use of CTC counts as an independent tool for measuring advanced disease as liver metastasis signifies progressive disease and is generally associated with poorer outcome. The epithelial-to-mesenchymal transition (EMT) in tumor cells in blood may provide a possible mechanism for loss of EpCAM expression in some CTCs although we have certainly detected similar patients with liver metastases from CRC with elevated levels of CTCs including about 10-15% of such CRC patients with very high levels at ∼10-20 times the cut-off of 3 CTCs/7.5 ml of blood. Technologies that involve detection of cancer cell proteins and do not rely on EpCAM-based isolation (eg. multiplex PCR) are not currently approved by the FDA for clinical application but may provide insights into this problem. Alternatively we are using microfluidic devices, that rely on size-based capture of CTCs in attempts to determine if such patients with liver metastases and no detectable CTCs by Veridex may have tumor cells that may be captured. We are particularly interested in determining whether the biology of the tumors varies among patients with liver metastases from CRC with no measurable CTCs versus those patients with high levels of CTCs. In this regard we are pursuing molecular characterization of primary tumors looking for possible molecular insights among these cohorts. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3413. doi:1538-7445.AM2012-3413
Abstract 2845: Candidate genes related to CagA signal transduction pathway and risk of gastric cancer: A nested case-control study
Authors: Jae Jeong Yang, Lisa Y. Cho, Kwang-Pil Ko, Boyoung Park, Aesun Shin, Jin Gwack, Soung-Hoon Chang, Hai-Rim Shin, Daehee Kang, Keun-Young Yoo, Sue K. Park
Journal: Cancer Research (2010)

Abstract Objectives: Cytotoxin-associated antigen (CagA) produced by Helicobacter pylori (H. pylori) plays a role in gastric carcinogenesis, but the role of genes coding proteins in the CagA pathway remains unclear. This genetic association study aimed to evaluate which genes involved in CagA signal transduction pathway are associated with gastric cancer development. Methods: By literature reviews, we selected 34 candidate genes involved in CagA signal transduction pathway and screened a total of 580 SNPs within +/- 5kbp of target gene location. Within the Korean Multi-Center Cancer Cohort (KMCC), a 100 incident gastric cancer cases were matched to a cancer-free subject by age, sex, residential area and enrollment. Both raw and permutated p-values by 10,000 permutation tests were computed using the LRT with 1 degree of freedom in the trend model. Gastric cancer risk was estimated as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, smoking status, H. pylori infection, and CagA IgG antibody positivity in each genetic model. Results: Twenty five SNPs in 8 genes, Erk, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk, were significantly associated with gastric cancer risk in the single SNP analysis (p&amp;lt;0.05). Specifically, Erk rs5999749 and Dock180 rs9418677 remained significant after correction of multiple comparisons. Except for Dock180 rs9418677 and Rap1 rs17028287, most SNPs downstream CagA/Crk signaling (Dock180, C3G, Rap1 and Mek) were significantly associated with a reduced risk for gastric cancer. Conclusions: Our findings indicate that genes involved in the CagA signal transduction pathway can be major susceptible factors related to tyrosine kinase action, especially interaction with Crk. Further replication studies with wider genomic coverage and a greater number of subjects are still needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2845.
Abstract 4215: Hypoxia regulates the breast cancer stem/progenitor cell population
Authors: Sarah Santos, Amber Heath, Max Wicha
Journal: Cancer Research (2010)

Abstract There is increasing evidence from our lab and others supporting the “cancer stem cell” hypothesis in breast cancer, which proposes that tumors are driven a small population of cells exhibiting stem cell properties. These cancer stem/progenitor cells may also be responsible for mediating tumor metastasis and resistance to cancer treatments. Recently, several new cancer therapies targeting tumor angiogenesis have been developed and validated in clinical trials. Specifically, the VEGFR and multikinase inhibitors sunitinib and sorafenib have been approved for treatment of some tumor types. However, clinical trials in breast cancer and other malignancies have demonstrated that these therapies ultimately result in drug resistance and only modestly prolong patient survival. Recent reports have suggested that these angiogenesis inhibitors may promote tumor invasiveness and metastasis in rodent breast cancer models. We hypothesize that the tumor stem/progenitor cell population increases in response to hypoxia in anti-angiogenic treated cancers, leading to increased tumor aggressiveness. We have used in vitro and in vivo assays to study the possible role of hypoxia in regulating mammary cancer stem/progenitor cells. We demonstrate that moderate hypoxia (2% oxygen) enriches for stem/progenitor cells in several breast cancer cell lines grown in vitro. The percentage of cells expressing ALDH as assessed by the Aldefluor assay approximately doubles in response to hypoxia. In vivo, sunitinib treatment increases the proportion of Aldefluor positive cells in SUM-159 and MDA-MB-231 breast cancer xenografts in NOD/SCID mice. In addition, tumor cells obtained from sunitinib treated mice exhibit enhanced tumor initiation and growth upon transplantation into secondary NOD/SCID mice. These studies indicate that tissue hypoxia results in expansion of the breast cancer stem/progenitor cell population. This may contribute to the increased aggressiveness and metastasis of cancers that evolve during therapy with angiogenesis inhibitors. If this is the case, then the addition of cancer stem cell targeting agents to antiangiogenic agents may reduce the development of treatment resistance and enhance treatment efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4215.
Abstract P5-06-06: The Safety and Tolerability of Panobinostat (LBH589) in Combination with Capecitabine +/− Lapatinib: A Phase I Study in HER2+ Breast Cancer
Authors: NW Peacock, SF Jones, DA Yardley, JC Bendell, JR Infante, PB Murphy, HA. Burris
Journal: Cancer Research (2010)

Abstract Background: Panobinostat is a histone deacetylase (HDAC) inhibitor, for which in vitro studies have suggested activity in breast cancer lines. This phase I study was designed to assess the safety, tolerability, and efficacy of panobinostat in combination with lapatinib and capecitabine in 3 parts. Part 1, for which we have previously reported findings (Peacock et al, ASCO 2010), established the maximum tolerated dose (MTD) of panobinostat (30mg twice weekly) in combination with capecitabine (1000mg/m2 BID). Part 2, reported here, was designed to assess the QTc prolongation and overall toxicity of panobinostat in combination with lapatinib in patients with HER2+ breast cancer. Part 3 will assess the tolerability and efficacy of the triplet combination based on doses defined in Parts 1 and 2. Method: Patients aged ≥18 years with incurable, locally recurrent or metastatic HER2+ breast cancer were eligible. Additional eligibility criteria included: &amp;lt; 3 prior treatments in the metastatic setting; ECOG PS 0-1; measurable disease by RECIST; no impairment of cardiac function; no prior treatment with HDAC inhibitors; informed consent. Lapatinib doses of 1000mg daily were administered with panobinostat doses of 15mg and 20mg three times weekly, following 1 week of 2 doses of panobinostat alone to assess QTc prolongation. Cycles were repeated every 21 days until disease progression or toxicity warranted drug discontinuation. Patients were reevaluated for response every 2 cycles. Results: 5 female patients with HER2+ metastatic breast cancer were accrued to Part 2, with a median age of 66 years (range: 64 — 67); 80% of patients were ECOG PS 0. To date, patients have received 17 cycles of treatment (median 4 cycles), and 2 patients have stable disease (progression1, unevaluable 1, and too early to assess 1), with one patient remaining on treatment. There have been no dose-limiting toxicities. One patient was hospitalized for grade 3 peripheral neuropathy (unrelated). No grade 2/3/4 toxicities have occurred in &amp;gt;1 patient; no QTc prolongation has been observed. Conclusions: Our preliminary findings suggest that the combination of panobinostat and lapatinib is safe and tolerable. No QTc prolongation or cardiotoxicity has been observed. Part 3 will evaluate the triplet combination using the dosages established in Parts 1 and 2. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-06-06.
Interim Adjusted Estimates of Seasonal Influenza Vaccine Effectiveness — United States, February 2013
Authors: Lisa Jackson, Michael L. Jackson, C. Hallie Phillips, Joyce Benoit, Edward A. Belongia, Deanna Cole, Sarah Kopitzke, Tamara A. Kronenwetter Koepel, Huong Q. McLean, Jennifer K. Meece, Sandra K. Strey, Maria E. Sundaram, Mary Vandermause, Manjusha Gaglani, Juhee Song, Lydia Clipper, Dean Kjar, Anne Robertson, Kempapura Murthy, Melinda Dunnahoo, Stephanie Oliver, Monica Weir, Hope Gonzales, Martha Zayed, Teresa Ponder, Jo Ann Nichols, Michael Reis, Cathleen Rivera, David Morgan, Pedro Piedra, Vasanthi Avadhanula, Arnold S. Monto, Suzanne E. Ohmit, Joshua G. Petrie, Emileigh Johnson, Rachel T. Cross, Casey Martens, Marcus Zervos, Lois Lamerato, Mary Ann Aubuchon, Gregory G. Wolff, Heather Eng, Mary Patricia Nowalk, Stephen R. Wisniewski, Richard K. Zimmerman, Charles R. Rinaldo, Arlene Bullotta, Joe Suyama, Evelyn Reis, Donald B. Middleton, Rachel Hess, Jonathan M. Raviotta, Mark G. Thompson, Alicia M. Fry, Swathi N. Thaker, Jill Ferdinands, Po Yung Cheng, Sarah Spencer, Erin Burns, La Shondra Berman, Wendy Sessions, Angie Foust, Joseph Bresee, Nancy Cox
Journal: MMWR Morbidity and Mortality Weekly Report (2013)