tbuckley/cabot-search huggingface dataset:
Abstract 477: Long-term protection against B16F1 melanoma upon vaccination with tumor cell lysate combined with LTX-315 as a novel adjuvant.
Authors: Gerd Berge, Ketil Andre Camilio, Øystein Rekdal, Ali Areffard
Journal: Cancer Research (2013)

Abstract Here, we demonstrate the potency of LTX-315 as a novel adjuvant in combination with B16F1 tumor cell lysate vaccine. LTX-315 is a chemically modified cationic peptide derived from a family of molecules called host defense peptides. Through its cytolytic activity, the main mechanism of LTX-315 is the induction of immunogenic cell death which leads to local inflammation by recruitment and activation of the immune system at the injection site. This is important to obtain strong vaccine-specific immune responses. We have selected the B16F1 melanoma model for this study since this tumor model is poorly immunogenic and have been described for being notoriously difficult to treat. Mice were vaccinated once a week for 4 weeks and challenged with viable B16F1 cells s.c. two weeks after the last vaccination. Tumor protected mice were re-challenged 10 weeks post primary challenge. In contrast to other studies where tumor growth inhibition is observed for this model, our results not only demonstrate complete tumor regression, but also long-term protection against the B16F1 melanoma. In total, 14/18 animals had established long-term protection which indicates induction of immunological memory against B16F1 melanoma. In conclusion, LTX-315 is a novel adjuvant with substantial potency to induce strong and durable immune responses against the poorly immunogenic B16F1 in vivo. The efficacy of vaccinations to further document the potency of LTX-315 as an adjuvant are currently studied in therapeutic and metastatic B16 models and other orthotopic models. The present results indicate the potential of LTX-315 to be a next generation adjuvant for therapeutic vaccines based on tumor-associated antigens (TAA). Citation Format: Gerd Berge, Ketil Andre Camilio, Øystein Rekdal, Ali Areffard. Long-term protection against B16F1 melanoma upon vaccination with tumor cell lysate combined with LTX-315 as a novel adjuvant. [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 477. doi:10.1158/1538-7445.AM2013-477
RANDOMIZED COMPARISON OF VASCULAR HEALING RESPONSE BETWEEN SELF-EXPANDING NITINOL STENT AND SELF-EXPANDING PACLITAXEL-ELUTING STENT IN THE SUPERFICIAL FEMORAL ARTERY: AN OPTICAL FREQUENCY DOMAIN IMAGING STUDY
Authors: Kojiro Miki, Kenichi Fujii, Masashi Fukunaga, Takahiro Imanaka, Hiroto Tamaru, Akinori Sumiyoshi, Tetsuo Horimatsu, Machiko Nishimura, Ten Saita, Masahiko Shibuya, Tohru Masuyama, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2015)
PTH-114 Skin Pathology Associated with Anti-Tumour Necrosis Factor (ANTI-TNF) Therapy- a Single UK IBD Centre Experience
Authors: T C Shepherd, E Cronin, K Greveson, O Epstein, G Erian, F Jaboli, E Despott, M Hamilton, C Murray
Journal: Gut (2013)

<h3>Introduction</h3> With the increasing use of biologic therapy in the treatment of inflammatory bowel disease (IBD) there has been a reported increase in dermatological conditions associated with therapy in patients with IBD. We carried out a prospective audit to identify the proportion of IBD patients at The Royal Free Hospital on anti-TNF therapy developing therapy related inflammatory skin pathology <h3>Methods</h3> 141 IBD patients on anti-TNF therapy (either infliximab or adalimumab) were sent a postal questionnaire to identify patients who had experienced identifiable and associated skin conditions. The questionnaire included information regarding the body site affected, dermatology opinion and whether therapy had to be stopped. Data for infliximab and adalimumab were analysed. <h3>Results</h3> Of 141 patients, 105 replied (71 (74%) infliximab and 34 (74%)adalimumab).In both groups 32% of patients described new skin complaints attributable to anti-TNF therapy (n = 23 in infliximab group, n = 11 in adalimumab group). Sites of skin inflammation were common to both groups; face (29%), trunk (21%), legs (14%) and arms (14%). Combined data showed only 44% of patients were reviewed by a dermatologist and received a formal diagnosis. No patients on adalimumab stopped treatment, while 3 stopped therapy in the infliximab group (9% overall). <h3>Conclusion</h3> Although IBD is itself associated with skin pathology, recent studies have demonstrated that patients on anti-TNF therapy develop inflammation of the skin (1), and our data support the concept that paradoxical skin inflammation related to anti-TNF therapy is a class effect. [c1] In our cohort few patients had to stop therapy which is similar to some (1), but not all reported studies (2,3). Less than half of affected patients received consultant dermatological review. [c1]Can’t just give a figure ‘if’ they had responded. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Cleynen I, Vermeire S. Paradoxical inflammation induced by anti-TNF agents in patients with IBD. Nat Rev Gastroenterol Hepatol. 2012 Sep; 9(9):496–503. Cullen, G., Kroshinsky, D., Cheifetz, A. S. &amp; Korzenik, J. R. Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120cases from the literature. Aliment. Pharmacol. Ther. 34, 1318–1327 (2011). Baumgart, D. C., Grittner, U., Steingraber, A., Azzaro, M. &amp; Philipp, S. Frequency, phenotype, outcome, and therapeutic impact of skin reactions following initiation of adalimumab therapy: experience from a consecutive cohort of inflammatory bowel disease patients. Inflamm. Bowel Dis. 17, 2512–2520 (2011).
Viral Load and Heterosexual Transmission of Human Immunodeficiency Virus Type 1
Authors: Thomas C. Quinn, Maria J. Wawer, Nelson Sewankambo, David Serwadda, Chuanjun Li, Fred Wabwire-Mangen, Mary O. Meehan, Thomas Lutalo, Ronald H. Gray
Journal: New England Journal of Medicine (2000)

We examined the influence of viral load in relation to other risk factors for the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1). In a community-based study of 15,127 persons in a rural district of Uganda, we identified 415 couples in which one partner was HIV-1–positive and one was initially HIV-1–negative and followed them prospectively for up to 30 months. The incidence of HIV-1 infection per 100 person-years among the initially seronegative partners was examined in relation to behavioral and biologic variables.
Abstract 5700: Preparation and evaluation of glycosylated paclitaxel loaded in tastuzumab-immunoliposome
Authors: Masaharu Murakami, Tomonari Kasai, Masashi Okada, Katsuhiko Mikuni, Naoyoshi Egashira, Masaharu Seno, Hiroki Hamada
Journal: Cancer Research (2012)

Abstract Targeted drug delivery is considered to enhance the therapeutic effects of anti-cancer agents because high amount could be administered with least side effects. However, water-insoluble hydrophobic chemical compounds such as paclitaxel are not suitable for efficient drug delivery. We conferred water-solubility of paclitaxel by coupling glucose at 7-OH to produce 7-alpha-glucosyloxyacetylpaclitaxel (7-GLG-PT). Although the 7-GLG-PT showed lower cytotoxicity than paclitaxel, encapsulation of 7-GLG-PT into liposomes was more efficient than that of paclitaxel. In our experiment, paclitaxel encapsulated liposomes was not detectable. Trastuzumab was then conjugated on the surface of 7-GLG-PT liposomes to prepare immunoliposome (GLG-PT-IL). The GLG-PT-IL exhibited cytotoxicity on SK-BR-3 cells overexpressing HER2. The IC50 values of paclitaxel, 7-GLG-PT, 7-GLG-PT liposome and GLG-PT-IL were 6, 126, 130 and 94 nM, respectively. From this evaluation, the concentration of each formula to suppress the cell growth completely was estimated around 30 to 300 nM. At these concentrations, the time required for each formula to suppress the growth at the half maximal level was evaluated. GLG-PT-IL showed the shortest time of 5 hours, which was one third of the others when compared with paclitaxel, 7-GLG-PT and 7-GLG-PT liposome. The specific targeting potential of the immunoliposome on SK-BR-3 cells was assessed. The accumulation on the cell surface was competitively inhibited by the excess amount of free tastuzumab. The endocytosis of the immunoliposomes was simultaneously confirmed by time-lapse imaging. Thus GLG-PT-IL has been successfully demonstrated to target the HER2-overexpressing cancer cells specifically suppressing their growth. Trastumab itself is considered to induce the antibody dependent cellular cytotoxicity, so that the endocytosis of HER2 may not be always necessary. However, HER2-mediated endocytosis was induced by the immunoliposomes while single trastuzumab did not show the endocytosis in SK-BR-3 cells. In this context together with the results demonstrated in this study, the 7-GLG-PT immunoliposome should be a promising candidate of highly efficient drug delivery system of cancer treatment targeting HER2. 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 5700. doi:1538-7445.AM2012-5700
Tripelennamine Dysuria in Chronic Nephritic Uremia
Authors: Ralph M. Sussman, Niel Wald
Journal: New England Journal of Medicine (1952)

ACCORDING to recent estimates as many as 10,000,000 people will be taking antihistamines in the United States this year,1 and 6 to 16 per cent of them will experience side-reactions.2 Among the less well known reactions accompanying the use of these agents is difficulty in initiating and maintaining the urinary stream, with associated symptoms of urinary obstruction. In 1949 Wolfson3 reported the occurrence of urinary obstruction in a patient who received tripelennamine. Although reference has been made to this untoward effect1 , 2 , 4 5 6 7 8 in the literature, no other case reports for this agent were found. Physicians' awareness of this disturbing symptom may . . .
The Importance of Being Empathic
Authors: Thomas F. Hughes
Journal: JAMA (1992)

To the Editor.  —I wish to commend Drs Bellet and Maloney on their excellent article reviewing the importance of empathy as a tool in medical practice.1In total, it was a timely review of a critical issue in medicine. Unfortunately, I fear that the authors may have inadvertently prejudiced the character of empathy when they limited their comments to the nature of compassion as a clinical device.  The social revolution that is rapidly enveloping the field of medicine is not designed to produce physicians who are merely aware of the mechanism for acting in an empathetic manner, but, rather, it hopes to develop physicians who can remain both profoundly human and professionally competent in the clinical setting. Patients cannot be satisfied by a physician who is merely capable of offering some sort of placebo perfunctory conciliation in times of crises for, as with any placebo, when patients realize
P1042 EFFICACY OF ENTECAVIR MONOTHERAPY VERSUS ENTECAVIR PLUS ADEFOVIR COMBINATION THERAPY AS RESCUE THERAPY FOR rt181 MUTANTS OF HEPATITIS B VIRUS: 48 WEEKS RESULTS
Authors: M.J. Oh, H.J. Lee, K.H. Kim, K.O. Kim, S.H. Lee, B.I. Jang, T.N. Kim
Journal: Journal of Hepatology (2014)
Diversity Outbred Mice Identify Population-Based Exposure Thresholds and Genetic Factors that Influence Benzene-Induced Genotoxicity
Authors: John E. French, Daniel M. Gatti, Daniel L. Morgan, Grace E. Kissling, Keith R. Shockley, Gabriel A. Knudsen, Kim G. Shepard, Herman C. Price, Deborah King, Kristine L. Witt, Lars C. Pedersen, Steven C. Munger, Karen L. Svenson, Gary A. Churchill
Journal: Environmental Health Perspectives (2014)

BackgroundInhalation of benzene at levels below the current exposure limit values leads to hematotoxicity in occupationally exposed workers.ObjectiveWe sought to evaluate Diversity Outbred (DO) mice as a tool for exposure threshold assessment and to identify genetic factors that influence benzene-induced genotoxicity.MethodsWe exposed male DO mice to benzene (0, 1, 10, or 100 ppm; 75 mice/exposure group) via inhalation for 28 days (6 hr/day for 5 days/week). The study was repeated using two independent cohorts of 300 animals each. We measured micronuclei frequency in reticulocytes from peripheral blood and bone marrow and applied benchmark concentration modeling to estimate exposure thresholds. We genotyped the mice and performed linkage analysis.ResultsWe observed a dose-dependent increase in benzene-induced chromosomal damage and estimated a benchmark concentration limit of 0.205 ppm benzene using DO mice. This estimate is an order of magnitude below the value estimated using B6C3F1 mice. We identified a locus on Chr 10 (31.87 Mb) that contained a pair of overexpressed sulfotransferases that were inversely correlated with genotoxicity.ConclusionsThe genetically diverse DO mice provided a reproducible response to benzene exposure. The DO mice display interindividual variation in toxicity response and, as such, may more accurately reflect the range of response that is observed in human populations. Studies using DO mice can localize genetic associations with high precision. The identification of sulfotransferases as candidate genes suggests that DO mice may provide additional insight into benzene-induced genotoxicity.CitationFrench JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA. 2015. Diversity Outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. Environ Health Perspect 123:237–245; http://dx.doi.org/10.1289/ehp.1408202
Evaluation of adjuvant chemotherapy-induced anemia in colon cancer patients (pts)
Authors: H. Engin, F. C. Sökmen, A. G. Aköz, Y. Üstündağ, H. Ankaralı
Journal: Journal of Clinical Oncology (2008)

20741 Background: Patients (pts) with colon cancer receiving adjuvant chemotherapy often develop chemotherapy-induced anemia and reduced quality of life. In this study we aimed to evaluate hemoglobin (Hb), MCV, RDW values both before and after adjuvant chemotherapy and the influence of duration of chemotherapy administration, development of metastasis and blood transfusion on these values. Methods: In this retrospective study Hb, MCV, RDW values and clinical characteristics of 57 colon cancer pts who received adjuvant chemotherapy between February 2003 and April 2007 were obtained by reviewing consecutive medical records of pts at Medical Oncology Department. Results: Hb levels after adjuvant chemotherapy were found to be significantly decreased compared to the levels before adjuvant chemotherapy (p=0.002) and this decrease was more pronounced in non-transfused pts. Development of metastasis (p=0.776) and duration of chemotherapy administration (p=0.476) had no effect on Hb levels. MCV values after adjuvant chemotherapy were also found to be significantly decreased compared to the values before adjuvant chemotherapy (p=0.001) and the magnitude of this decrease was the same independent of duration of chemotherapy administration, development of metastasis and blood transfusion. RDW values after adjuvant chemotherapy were observed to be increased compared to the levels before adjuvant chemotherapy (p=0.001) and development of metastasis (p=0.935), blood transfusion (p=0.222) and duration of chemotherapy administration (p=0.522) had no influence on RDW values. Conclusions: In colon cancer pts adjuvant chemotherapy can cause significant anemia and reduced quality of life and prospective studies should be planned to determine what measures should be taken to prevent the development of this anemia. No significant financial relationships to disclose.
BLEEDING RISK AND MAJOR ADVERSE EVENTS IN PATIENTS WITH PREVIOUS ULCER ON ORAL ANTICOAGULATION THERAPY: A MULTICENTER STUDY
Authors: Seung-Jun Lee, Jong-Yun Kim, Jin-Bae Kim, Min-Soo Ahn, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyoung Lee, Jung-Hoon Sung, Boyoung Joung
Journal: Journal of the American College of Cardiology (2015)
Abstract 3901: Estrogen receptor conformation sensing small molecules as novel anti-cancer agents
Authors: Bethany Rankin, Rajendram V. Rajnarayanan, Marc Koyack
Journal: Cancer Research (2012)

Abstract Estrogen mediated signaling affects cell proliferation, differentiation and mammary gland function. The human Estrogen Receptor (hER) is present in 70% of breast cancers. Consequently, estrogen mediated hER signaling plays a critical role in breast cancer diagnosis, prognosis, and treatment.Anti-estrogen, Tamoxifen, targets the LBD and transitions the hER from “agonist” conformation into a structurally unique “antagonist” conformation, which is distinctly recognizable by the position of helix XII. Antiestrogen tamoxifen is a known treatment for hER positive breast cancers. However, due to mutations and hormone-independent activation of/in the hER, breast cancers develop resistance to tamoxifen, and resume growth and malignant progression. Estrogen's action at hER is regulated not only by estrogen, but also by other small molecules and coregulators. A closer look at the compliment of coregulators during acquired tamoxifen resistance shows a significant decrease in the corepressor breast cancer susceptibility (BRCA1) protein expression. BRCA1 directly interacts, from amino acids 67-200, with the hER, from 338-379 and 420-495, LBD/AF2 domain. The interface region of BRCA1 containing the binding motif (amino acids 86-93), which specifically contain two essential chemical features, a hydrophobic core and a charged carboxylic acid is necessary for high affinity binding and hER repression. Here we present several small molecules identified based on these pharmacophoric features as well as ER molecular profiles of conformation sensing peptides. Discovery of conformation sensing protein/peptides would open new avenues for drug development and would lead to advanced clinical studies of hER-conformation sensing small molecules as an entirely new class of anticancer therapy especially in tamoxifen-resistant tumors. Acknowledgements: This research was supported via funds from the New York State, National Institutes of Health (5P20MD002725), through the NCMHD -RIMI program (RVR) and NSF LSAMP Bridge to Doctorate grant (BR). 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 3901. doi:1538-7445.AM2012-3901
Abstract 2346: Switching from an ROR1-positive phenotype to an ROR2-positive phenotype promotes melanoma progression
Authors: Michael P. O'Connell, Janelle L. Nelson, Jennifer L. Fiori, Sarah S. Subaran, Fred E. Indig, Ashani T. Weeraratna
Journal: Cancer Research (2011)

Abstract The orphan tyrosine kinase receptors, ROR1 and ROR2, make up a superfamily of receptors that, until recently, had no known signal pathway association or ligand identification. ROR2 has since been shown to play a role in Wnt signal transduction and studies from our laboratory have demonstrated an important role for ROR2 in increasing the metastatic potential of melanoma cells. Here, we demonstrate, that, despite significant homology, ROR1 expression is inversely correlated to that of ROR2 in melanoma and decreasing ROR1 expression increases overall metastatic potential. ROR1 is expressed on the cell surface in the hydrophobic region of the cell membrane and in the cytoplasm of less metastatic melanoma cells. Treatment of less metastatic melanoma cells with recombinant Wnt5A decreased the levels of ROR1 in these cells. We have previously demonstrated that increases in Wnt5A result in an increase in metastatic capacity of melanoma cells, and a decrease in the melanoma differentiation antigens MART1 and gp100. These data have been supported by several other laboratories, giving rise to the phenotype switching model of melanoma progression that suggests that melanomas express a “proliferative” gene expression signature governed by the transcription factor MITF, and its targets MART1, gp100, DCT, etc., during the initial stages of melanoma development, and an “invasive” gene expression signature governed by Wnt5A in the later stages of melanoma progression. In keeping with these data, reduction of ROR1 by siRNA demonstrates a decrease in the melanoma differentiation markers MART1 and GP100, and motility, and an increase in the invasive capability of melanoma cells. In addition, siRNA knockdown of ROR1 expression increased WNT5A expression, implying that downregulation of ROR1 may be a step in the progression towards melanoma metastasis. Further, WNT5A knockdown in cells that have high levels of WNT5A, but low levels of ROR1, increases ROR1 expression and knockdown of ROR2 increases ROR1 expression. These data suggest that melanoma receptors in the ROR superfamily can influence the expression of one another and the switch from ROR1 positivity to ROR2 positivity can contribute to metastatic potential. The search for the micro-environmental factors that can initiate this switch is currently under investigation in our laboratory. (This work was supported in part by the Intramural Research Program of the National Institute on Aging, Baltimore, MD). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2346. doi:10.1158/1538-7445.AM2011-2346
Cytokine Production and Function in c-mpl–Deficient Mice: No Physiologic Role for Interleukin-3 in Residual Megakaryocyte and Platelet Production
Authors: Timothy Gainsford, Andrew W. Roberts, Shinya Kimura, Donald Metcalf, Glenn Dranoff, Richard C. Mulligan, C. Glenn Begley, Lorraine Robb, Warren S. Alexander
Journal: Blood (1998)
Association of Silent Mitral Stenosis with Massive Thrombi in the Left Atrium
Authors: Borys Surawicz, Marvin A. Nierenberg
Journal: New England Journal of Medicine (1960)

WE have had an opportunity to study over the past five years 4 patients who had mitral stenosis without diastolic murmurs concomitant with massive thrombi in the left atrium. The coexistence of these relatively infrequent clinical findings appeared to us more than coincidental. We have found several case reports in which the coexistence of mitral stenosis without diastolic murmurs with massive thrombosis of the left atrium was mentioned.1 2 3 4 5 In 3 cases the authors commented on this association briefly.3 4 5 It is our purpose, by presenting the 4 cases in detail, to call wider attention to this group of patients in whom . . .