tbuckley/cabot-search huggingface dataset:
Abstract LB-231: p 190RhoGAP-B is required for rho down-regulation and ductal morphogenesis of breast epithelial cells in compliant collagen gels
Authors: Ponik Suzanne, Michele Wozniak, Patricia J. Keely
Journal: Cancer Research (2010)

Abstract Breast epithelial cells cultured in compliant (floating), but not stiff (attached), 3-dimensional collagen gels differentiate into tubules. While the mechanisms of breast ductal morphogenesis are not well understood, we have previously shown that this process requires down-regulation of the small GTPase Rho in compliant collagen gels. In this study we sought to better define the signaling pathways regulating Rho activity when epithelial cells are cultured in compliant vs. stiff 3D collagen gels. Of the known Rho regulators, expression of p190RhoGAP has been detected at the terminal end buds in the mouse mammary gland, suggesting that proper breast development in vivo requires Rho down-regulation through this protein. Therefore, we specifically investigated the role of p190RhoGAP in ductal morphogenesis. We found that shRNA against p190RhoGAP-B, but not p190RhoGAP-A, blocked down-regulation of Rho activity and inhibited tubule formation in T47D cells cultured in compliant 3D collagen gels. Additionally, both Rho and p190RhoGAP-B co-localized with the adherens junction protein, p120-catenin at sites of cell-cell adhesion when cultured in 3D collagen gels. Similar to our results with p190B knockdown, shRNA against p120-catenin resulted in disruption of ductal morphogenesis and disregulation of Rho activity in cells cultured in compliant 3D collagen gels. Interestingly, we found that the association between p190RhoGAP-B and p120-catenin, which has been shown by others to play a role in Rho regulation, increases in compliant vs. stiff collagen gels. Interaction between p190RhoGAP-B is not mediated by Rho, as it does not require the Rho binding domain of p120-catenin. Together these results demonstrate that p190RhoGAP-B is required for Rho regulation and ductal morphogenesis of breast epithelial cells in floating collagen gels through a mechanism that may involve p 120-catenin. 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 LB-231.
Revised International Prognostic Scoring System for Myelodysplastic Syndromes
Authors: Peter L. Greenberg, Heinz Tuechler, Julie Schanz, Guillermo Sanz, Guillermo Garcia-Manero, Francesc Solé, John M. Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Alessandro Levis, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M. Le Beau, Marilyn L. Slovak, Otto Krieger, Michael Luebbert, Jaroslaw Maciejewski, Silvia M. M. Magalhaes, Yasushi Miyazaki, Michael Pfeilstöcker, Mikkael Sekeres, Wolfgang R. Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A. van de Loosdrecht, Ulrich Germing, Detlef Haase
Journal: Blood (2012)
P768 PNPLA3 rs738409 C&gt;G SNP IS ASSOCIATED WITH HISTOLOGICAL FEATURES OF NASH IN GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS
Authors: S. Petta, D. Cabibi, C. Cammà, V. Di Marco, R. Fonte, F.S. Macaluso, M.G. Minissale, A. Craxì
Journal: Journal of Hepatology (2014)
Abstract 1776: Antitumor activity of Chk1 inhibitor LY2606368 as a single agent in SW1990 human pancreas orthotopic tumor model
Authors: Wenjuan Wu, Chen Bi, Aimee K. Bence, Suzane L. Um, Betty Yan, James J. Starling, Mark S. Marshall, Richard P. Beckmann
Journal: Cancer Research (2012)

Abstract ChK1 is a key kinase in the DNA damage response signaling network, including cell cycle checkpoints, DNA repair, apoptosis and transcription, thus emerging as an attractive target in anti-cancer therapy. LY2606368, a potent and selective ATP competitive inhibitor of the Chk1 protein kinase, is currently in clinical development. LY2606368 has been reported to inhibit Chk1 auto-phosphorylation activated by DNA damaging agents, and induce phosphorylation of H2AX, a DNA damage maker in multiple cancer cell lines in vitro. In addition, LY2606368 has demonstrated potent single agent activity and potentiates the anti-tumor activity of DNA damaging agents in vivo. Pancreatic cancer is one of the least curable cancers, with an approximate 5% overall 5-year survival for all patients. In the current study, we evaluated the efficacy of LY2606368 (as its methanesulfonate salt, hydrate; LY2606368.MeSO3H.H2O = LY2940930) in pancreatic cancer cell lines in vitro and xenograft tumors (including subcutaneous and orthotopic models) in vivo. LY2606368 alone significantly inhibited the cell proliferation in a variety of pancreatic cell lines (SW1990, SU86.86, Bx-PC3, AsPC-1, CFPAC-1, Capan-2, HPAF-II) with SW1990 being the most sensitive (IC50=1.5 nM). In SW1990 subcutaneous xenograft model, LY2606368 showed substantial dose-dependent inhibition of tumor growth. In SW1990 pancreas orthotopic model, which represents the local and metastatic growth pattern seen in pancreas cancer patients, LY2606368 treatment resulted in over 92% inhibition of primary tumor growth as well as 100% inhibition of metastasis to lymph node, spleen and intestine. The anti-tumor effect of LY2606368 treatment was further demonstrated in comparing with gemcitabine (the standard of care for pancreas cancer patient) in SW1990 orthotopic model. The anti-tumor and/or anti-metastasis mechanism of LY2606368 was also investigated, including phosphorylation of H2AX, cell proliferation, cell survival, and soft agar anchorage-independent growth. Together, our findings demonstrate the therapeutic potential of LY2606368 as a single agent in the treatment of pancreatic cancer patients. 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 1776. doi:1538-7445.AM2012-1776
P1087 ENTECAVIR AND TENOFOVIR MONOTHERAPY IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS B: A MULTICENTER TURKISH STUDY IN CLINICAL PRACTICE
Authors: R. Idilman, O. Keskin, F. Gunsar, M. Koruk, C.E. Meral, A. Tuzun, M. Gulsen, A.H. Elhan, U.S. Akarca, C. Yurdaydin
Journal: Journal of Hepatology (2014)
Breast Cancer Grants Spur New Research Programs
Authors: C. Nelson
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Breast Cancer Grants Spur New Research Programs Get access Corinna Nelson Corinna Nelson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 19, 5 October 1994, Pages 1447–1448, https://doi.org/10.1093/jnci/86.19.1447 Published: 05 October 1994
A phase II clinical trial of melanoma tumor-lysate-pulsed autologous dendritic cell vaccination in advanced colorectal cancer patients expressing the MAGE family antigen/s
Authors: Toh Han Chong, Peter Wang, Mai-Britt Zocca, Sun Li, Kelly Teo, Phoon Yee Peng, Yatanar Soe, Hee Siew Wan, Foo Kian Fong, Simon Ong, Koo Wen Hsin, Mogens Claesson
Journal: Clinical Cancer Research (2007)

LB01  We report the results of a single arm Phase II clinical trial of autologous dendritic cells (DC) pulsed ex vivo with tumor lysate from established melanoma cell lines (Dandrit Biotech) pre-treated with a demethylating agent to enhance immunogenicity. Twenty patients (9 males, 11 female) with advanced colorectal cancer who express one or more MAGE antigens were accrued and DC vaccine administered intradermally every 2 weeks for 10 injections.  The median age was 70 years (n = 20) and all patients had progressive disease (PD) prior to accrual. The commonest MAGE gene expressed by RT-PCR was MAGE A4 (60%) and 75% expressed only one MAGE gene. The patients had an average of 3 metastatic tumor sites each, 55% had baseline ECOG status of > 2 and the cohort had received a median of 3 prior chemotherapy and/or biologic agents. The average dose per vaccination was 4.20 x 106 DC vaccine and 12/20 completed all 10 injections. DC production analysis by a novel patented tumor-necrosis-factor-α-based method confirmed a high quality mature phenotype with median expression of HLA-D at 99.79%, CD86 at 99.76%, CCR7 at 60.24% and CD14 at 17.08%. There were no > Grade 2 toxicities.  At last follow up, the disease control rate was 35% with 6 stable disease (SD > 3 months) and 1 partial response (PR) by RECIST criteria. At 1 year post-DC vaccine, 40% of patients were alive. The overall median duration of response (including SD) was 201 days. In the single patient who achieved PR, time to response was 79 days, and further tumor regression was seen at 281 days. In a patient with prolonged SD, tumor shrinkage of 17.8% occurred after 464 days.  A significantly positive delayed-type hypersensitivity (DTH) reaction was demonstrated in more patients after X10 DC vaccinations (p
Apolipoprotein B–Gene DNA Polymorphisms Associated with Myocardial Infarction
Authors: Robert A. Hegele, Li-Shin Huang, Peter N. Herbert, Conrad B. Blum, Julie E. Buring, Charles H. Hennekens, Jan L. Breslow
Journal: New England Journal of Medicine (1986)

Levels of apolipoprotein B, the protein component of low-density lipoproteins, correlate with the risk of coronary heart disease. We examined whether genetic variation in apolipoprotein B is associated with myocardial infarction by studying apolipoprotein B-gene restriction-fragment-length polymorphisms in 84 patients with myocardial infarction and an equal number of matched controls. Southern blot analysis with apolipoprotein B-gene probes, performed after DNA was digested with the endonucleases XbaI and EcoRI, revealed alleles that we designated as X1, X2, and X3 and as R1 and R2, respectively. Similar studies with the endonuclease MspI revealed alleles of many different sizes (the difference was due to an insertion-deletion polymorphism), which we grouped as larger and smaller alleles and designated as ID1 and ID2, respectively. The frequencies of the X1, R1, and ID1 alleles were all significantly higher (P less than 0.01) in the cases than in the controls. None of the alleles, however, was significantly associated with variation in levels of low-density lipoprotein cholesterol or apolipoprotein B, and the functional importance of these alleles is therefore uncertain. Nonetheless, in addition to quantitative variation in apolipoprotein B levels in plasma, genetic variation at the apolipoprotein B locus may be a new and independent risk factor for myocardial infarction.
<i>Bacterium Alcaligines (Alcaligines faecalis)</i>Infections in Man
Authors: Louis Weinstein, Edward Wasserman
Journal: New England Journal of Medicine (1951)

BACTERIUM alcaligines (alcaligines faecalis) is usually a harmless saprophyte in the human intestinal tract. On occasion, however, it may invade the tissues of man and produce a wide variety of clinical syndromes; this paper is concerned with an infection of this type that occurred in a patient who had infectious mononucleosis, and with a review of the literature on this subject. Bact. alcaligines is a gram-negative rod that shows considerable variation in cell size but is usually longer and thinner than Escherichia coli. It is motile and fails to ferment any of the common carbohydrates. Litmus milk . . .
THU0398 Most Patients with a Recent Fracture after the Age of 50 Years are not Predicted to be at High Risk: The Fracture Prevention Paradox
Authors: P. Geusens, T. van Geel, S. Bours, J. Eisman, J. Center, J. van den Bergh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> For the purpose of improving fracture risk assessment over bone mineral density (BMD), the FRAX® fracture risk prediction algorithm has been developed. <h3>Objectives</h3> To evaluate BMD and FRAX® in patients at the time they presented with a clinical fracture after the age of 50 years. <h3>Methods</h3> In 479 consecutive patients (75% women) who were able and willing to participate, we measured BMD in spine and hip and calculated the 10-year fracture riskusing FRAX®(calibrated for the Netherlands and calculated without and with BMD) for major fractures (FRAXMajor), for hip fracture (FRAXHip). Also the percentages of patients were estimated who, before the current fracture, had a FRAXMajor score ≥20% and FRAXHip ≥3% according to US guidelines (1), and FRAXMajor score above age-dependent variable thresholds for assessment (FRAXMajor≥As), and intervention (FRAXMajor≥Int) according to the European guidance (2). <h3>Results</h3> In 214 patients with a low-trauma major fracture, osteoporosis (BMD T-score ≤ -2.5) was present in 40% of patients, FRAXMajor≥20% in 12%, FRAXHip≥3% in 49%, FRAXMajor≥As in 47% and FRAXMajor≥Int in 7%. Adding BMD lowered the percentage of patients with FRAXMajor≥20% to 9% (p&lt;0.05) and FRAXHip≥3% to 37% (p&lt;0.001), and increased the percentage of patients with FRAXMajor&gt;Int to 21% (p&lt;0.05). FRAXMajor&gt;Int was found in 43% of patients with a low-trauma hip fracture and in 21% of patients with a first low-trauma major fracture. Lower percentages were found in the 265 patients with other fractures than low-trauma major fractures. <h3>Conclusions</h3> More than half of all evaluated patients presenting with a clinical fracture are not estimated by FRAX®to be at high fracture risk before the current fracture, even when they have a low-trauma major or hip fracture. These results draw attention to the fracture prevention paradox, by which only limited patients with a fracture are estimated to be at high risk, whether using FRAX®, without or with BMD, or using BMD alone. <h3>References</h3> www.nofstore.org Kanis, Osteoporosis Int. 2013 Jan;24(1):23-57. <h3>Disclosure of Interest</h3> None Declared
GASTROSTOMÍA ENDOSCÓPICA PERCUTÁNEA (GEP): REGISTRO PROSPECTIVO DE INDICACIONES Y COMPLICACIONES A LARGO PLAZO
Authors: C Huertas-Nadal, M Hombrados, D Busquets, M Pérez, JO Miquel, F Mohamed-Embarec, M Figa, F González-Huix
Journal: Endoscopy (2010)

Introducción: La gastrostomía endoscópica percutánea (GEP) es un procedimiento considerado seguro como vía de acceso para la administración de nutrición enteral. Los objetivos del estudio fueron determinar las indicaciones, tasa de éxito en la colocación, mortalidad relacionada con el procedimiento y porcentaje de complicaciones
Press: Lessons from the HRT story
Authors: M. Sweet
Journal: BMJ (2003)

The media must become more critical of unproven interventions

One of the more fascinating medical stories of recent times was that surrounding the findings of the women's health initiative trial of hormone replacement therapy.

This was not simply because the findings were so significant, in challenging long held assumptions about the merits of hormone replacement therapy (HRT) in disease prevention. Of equal interest has been the diversity of the medical profession's response to the findings.

The trial, part of which was published last year ( JAMA 2002;288:321-33), showed increased risk of cardiovascular events from continuous combined oestrogen-progestogen hormone replacement, although it showed benefits for hip fractures and bowel cancer. The relative risks for invasive breast cancer, coronary heart disease, and stroke were increased, although the absolute risks were small.

Soon after the study's publication, Canadian epidemiologist Professor David Sackett wrote of the “arrogance” of preventive medicine in promoting unproven interventions and estimated that hundreds of thousands …
Intérêt de la dilatation endoscopique dans les sténoses caustiques de l'oesophage
Authors: M Dhooge, H Vuarnesson, J Lambert, C Baudry, M Chirica, N Lourenço, N Munoz Bongrand, M Allez, P Cattan, JM Gornet
Journal: Endoscopy (2012)

Les données concernant l'intérêt de la dilatation endoscopique dans les sténoses caustiques de l'oesophage sont peu nombreuses. De plus les résultats des différentes séries sont discordants et les critères de jugement utilisés souvent hétérogènes.
Treatment of locally advanced esophageal carcinoma with induction cisplatin-paclitaxel-5FU (PTF) before local therapy
Authors: R. Fernandez-Rodriguez, N. Ancizar, G. Lopez de Argumedo, A. Ruiz de Lobera, G. Lopez Vivanco, A. Gil Negrete, A. Sancho, S. Carrera, A. Munoz, J. M. Mane
Journal: Journal of Clinical Oncology (2007)

15174 Background: We analyse induction therapy with PTF before local definitive therapy in terms of response, resectability, toxicity and survival. Methods: Patients (pts) with locally advanced esophageal carcinoma were included. Treatment: Paclitaxel 175 mg/m2 and CDDP 75 mg/m2 on day 1 and 5FU 800 mg/m2/day, days 1–4, every 21 days. After 2–3 cycles surgery is considered. If unresectable, Radiotherapy (64 Gy) and concomitant Carboplatin (60 mg/m2, d 1–5 during 1 st and 4th week of RT) are planned. Results: From May-02 to October-06 31 pts were treated (28M, 3F) Age: 55 (32–70) PS 0–1: 6–25. Location: Upper 10, Middle 13, Distal 7, Whole 1. Pathology: Squamous 29, Adenocarcinoma 2. T3/4:14/17 N0/1:8/23 M1a: 3. Weight loss &gt;10 kg 12 pts. 87 cycles have been delivered. Range: 2–4. Mean 2,83. Median 3. Toxicity (episodes): hematological 3/4: no episodes. Emesis 3: 2. Mucositis 3: 2. Asthenia 2/3: 8. 2 pts died in remission due to gastrostomy complications and esophago-tracheal fistula, treatment related. Response: CR 5, PR 9, SD 13, PD 4. Treatment after PTF: Surgery 10 pts (1 upper, 5 middle, 4 distal). 1 distal unresectable at surgery, 2 middle not resected because of liver cirrhosis and liver metastases at surgery. pCR: 1. pPR 6 (R0: 3, R1: 3) Chemoradiation with concomitant Carboplatin: 19, making 3 SD in PR, 2 PR in CR and 1 SD in CR. One PR and 4 SD progressed after chemoradiation. Progression: 21 (local 7, systemic 7, both 7). Died: 19 (16 of disease, 2 of complications of gastrostomy, 1 unrelated) Median PFS: 48,28 weeks (95% CI 32,80 - 63,77). Median OS: 51,14 weeks (95% CI 28,81 - 73,47). Conclusions: This schedule has a good toxicity profile. Surgical rescue is possible in almost a half of middle and distal tumours. Chemoradiation is the best approach for unresectable tumours. Considering stage at diagnosis, survival curves are promising. No significant financial relationships to disclose.
Psychosis in a peasant society: social outcomes
Authors: J Westermeyer
Journal: American Journal of Psychiatry (1980)

Several clinicians have theorized that somatic and residential treatments have an untoward effect on the eventual outcome of major mental illness. To test this hypothesis, the author studied social coping behavior of mentally ill people in Laos, a predominantly peasant society with no psychiatrists or psychiatric hospitals. The Lao folk term baa ("crazy" or insane) was used in determining cases. Social factors studied included legal problems, family contact, sociability, friendship, communal activities, sexuality, and work. Results indicated that levels of social function in this sample were quite limited. The author concludes that social disability associated with chronic psychosis cannot be ascribed totally to diagnostic labeling or institutionalization.
Abstract P4-04-02: Tumor-initiated peripheral myeloid cell expansion is reversed by radiation therapy
Authors: MJ Gough, T Savage, KS Bahjat, W Redmond, S Bambina, M Kasiewicz, B Cottam, P Newell, MR Crittenden
Journal: Cancer Research (2012)

Abstract Myeloid lineage cells, particularly monocytes and macrophages, have an important role in the development and progression of cancer. Within established tumors, macrophages are critical for angiogenesis, invasion, metastasis, immunosuppression and response to therapy. In addition, both transplantable and transgenic mouse models of mammary cancer are associated with myeloid expansions detectible in the tumor, spleen and peripheral blood, and these myeloid cells are able to suppress T cell activation in vitro. Reducing the tumor burden through chemotherapy and resection has been shown to control the myeloid expansion. However, chemotherapies that reduce tumor burden also have direct effects on myeloid cells, and surgical trauma has been shown to mobilize myeloid cells. Radiation therapy is the third major option to treat cancer, but the consequence of radiation therapy to systemic myeloid populations has not been described. We applied tumor-specific radiation therapy to test the hypothesis that the frequency of myeloid lineage cells correlates with the primary tumor burden. We demonstrate in the MMTV-PyMT model of mammary cancer that myeloid expansion in the blood closely correlates with myeloid involvement in the tumor and with tumor progression. We demonstrate that radiation therapy of 4T1 mammary tumors leads to a decline in myeloid cell numbers in the blood and a decrease in spleen size. The frequency of myeloid cells does not decline to the level seen in tumor-free mice: we demonstrate that metastatic disease can prevent myeloid cell numbers from returning to baseline, and that tumor recurrence from residual disease correlates with re-expansion of myeloid lineage cells. Despite these changes in the frequency of myeloid lineage cells, T cell numbers in the blood and spleen remains constant. However, radiation therapy improves the myeloid cell:CD8+ T cell ratio and results in increased proliferation of T cells in the spleen. Finally, we demonstrate that T cell responses to foreign antigens are not altered by tumor burden or myeloid cell expansion, while T cell responses to tumor-associated antigens are increased after radiation therapy of the tumor. These data demonstrate that myeloid cell numbers are directly linked to primary tumor burden, that this population contracts following radiation therapy, and that radiation therapy may open a therapeutic window for immunotherapy of residual disease. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-04-02.
SAT0373 The role of the combination of bone and fall related risk factors on short-term subsequent fracture risk
Authors: K. Huntjens, T. van Geel, S. van Helden, J. van den Bergh, P. Geusens, S. Bours, P. Willems, B. Wilkens, P. Brink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Bone- and fall-related risk factors contribute to subsequent NVF risk and mortality <h3>Objectives</h3> We analysed whether a combination of bone-related and fall-related risk factors (RFs) in patients with a recent non-vertebral fracture (NVF) contributed to subsequent NVF risk and mortality during 2-years in patients who were offered after a mean of 3 months fall and fracture prevention according to their baseline risk and guidelines. <h3>Methods</h3> 834 consecutive patients aged ≥50 years with a recent NVF who were able and willing to participate were extensively evaluated for the presence of bone and fall RFs. We compared the yearly re-fracture risk and mortality in subgroups of patients according to the presence of bone RFs and/or fall RFs. <h3>Results</h3> Fifty seven patients (6.8%) had a subsequent NVF and 29 (3.5%) died within 2-years. During the first year the odds ratio for a subsequent fracture was 4.2 (95%CI:1.2-14.3) in patients with a combination of bone and fall RFs compared to patients with only bone RFs, and 2.8 (95%CI:1.4-5.8) compared to all patients without this combination. No differences in subsequent fracture risk were found in the second year. No significant differences in mortality were found between patients with or without bone and/or fall RFs. <h3>Conclusions</h3> Evaluation of fall RFs contributes to identifying patients with bone RFs at highest immediate risk of subsequent NVF. It should be further studied whether fall prevention immediately after a NVF can decrease fracture risk on top of anti-osteoporosis treatment in patients with a combination of bone and fall RFs. <h3>Disclosure of Interest</h3> None Declared