tbuckley/cabot-search huggingface dataset:
Erythropoietin Induces Tyrosine Phosphorylation of Jak2, STAT5A, and STAT5B in Primary Cultured Human Erythroid Precursors
Authors: Atsushi Oda, Kenichi Sawada, Brian J. Druker, Katsutoshi Ozaki, Hina Takano, Kazuki Koizumi, Yoshikazu Fukada, Makoto Handa, Takao Koike, Yasuo Ikeda
Journal: Blood (1998)
Age related outcome in acute myocardial infarction
Authors: S. R McMechan, A A J. Adgey
Journal: BMJ (1998)

Patients older than 70 account for a third to a half of patients with acute myocardial infarction admitted to hospital,1 and 80% of deaths due to acute myocardial infarction occur in those aged over 65 years, 60% of them in people aged 75 or more.2 Despite extensive studies of thrombolytic treatments in large numbers of patients, we lack data on elderly subjects over 75 and particularly among those over 85. The size of the elderly population is growing: between 1982 and 1992 the Nottingham heart attack register recorded a 70% increase in patients aged 70-74 admitted with myocardial infarction anda 200% increase in those aged 75 or over.3 Hence we must be able to assess the optimal therapeutic strategies for such patients.

The application of trial results to clinical practice is hampered by the fact that such patients, although accounting for up to half of cases of myocardial infarction and having a disproportionately high mortality, are significantly underrepresented in clinical trials. Over …
Pulmonary dysfunction in cocaine smokers
Authors: R D Weiss, P D Goldenheim, S M Mirin, C A Hales, J H Mendelson
Journal: American Journal of Psychiatry (1981)

The authors report another complication of freebase cocaine smoking. They found a significant reduction in the carbon monoxide diffusing capacity in the lungs of two patients. This suggests that inhalation of the freebase of cocaine may damage the pulmonary gas exchange surface.
Pathogenic NLRP3 Inflammasome Activity during Candida Infection Is Negatively Regulated by IL-22 via Activation of NLRC4 and IL-1Ra
Authors: Monica Borghi, Antonella De Luca, Matteo Puccetti, Martin Jaeger, Antonella Mencacci, Vasilis Oikonomou, Marilena Pariano, Cecilia Garlanda, Silvia Moretti, Andrea Bartoli, Jack Sobel, Frank L. van de Veerdonk, Charles A. Dinarello, Mihai G. Netea, Luigina Romani
Journal: Cell Host & Microbe (2015)
Particularity of Local Immunity in the Nasopharynx
Authors: Renata Maźguran, Sabina Rabatić, A. Sabioncello, D. Dekaris
Journal: Allergy (1979)

Immunological functions of the pharyngeal tonsil, palatine tonsils and blood leucocytes of children undergoing tonsillectomy were evaluated by determining T or B lymphocytes, the response to mitogens, and the cell‐mediated immunological responses to tuberculin. In all the test systems used similar results were obtained with cells derived from either the palatine or pharyngeal tonsils. The mean percentage of T lymphocytes was significantly higher in the peripheral blood than in tonsils, but the reverse was true of B lymphocytes. The reaction to PHA was lower in tonsillar cell culture than in blood cell culture, but tonsillar cells reacted better to Con A than blood cells. In lymphocyte transformation tests tonsillar cells reacted to specific antigen (tuberculin) and this reaction was significantly higher than that of the parallelly tested blood lymphocytes. Further, in about 50% of the children tested, tuberculin caused migration inhibition of the mixture containing tonsillar cells and guinea pig peritoneal cells. Surprisingly, nearly identical results were obtained if migration inhibition test was performed with tonsillar cells alone. Consequently, poorly migrating tonsillar cells are nevertheless usable for direct migration inhibition testing.
Abstract 14927: Everolimus versus Mycophenolate for Cardiac Transplantation
Authors: Saurabh Aggarwal, Navdeep Gupta, Rohit S Loomba, Nawfal Al-Khafaji, Anushree Agarwal, Imtiaz Ismail, Manu Kaushik, Alok Saurav, Venkata Alla, Rohit R Arora
Journal: Circulation (2014)

The role of everolimus in cardiac transplantation is being increasingly recognized.Multiple studies have been published comparing the use of everolimus and mycophenolate with varying results. We aimed to perform a meta-analysis of the published literature. We searched Pubmed, EBSCO and Cochrane databases for terms “everolimus”, “mycophenolate”, “heart transplantation”, “cardiac transplantation” and their combinations. All studies in which everolimus was compared to mycophenolate were included. Studies in language other than English were excluded. Rates of biopsy proven acute rejection (OR 0.82 CI 0.67 to 1.00, p = 0.05), hemodynamically significant rejection (OR 0.76, CI 0.39 to 1.50, p = 0.43)or change in glomerular filtration rate (GFR) (mean difference -1.91, CI -6.90 to 3.08, p = 0.45) were similar between everolimus and mycophenolate groups. Everolimus use was associated with significant reduction in average maximal intimal thickness (mean difference -0.04 CI -0.06 to -0.02, p = 0.001) and cytomegalovirus antigenemia (OR 0.38, CI 0.28 to 0.53, p &lt; 0.00001). There was no significant heterogeneity for any endpoint except change in GFR. As compared to mycophenolate, everolimus use is associated with similar antirejection outcomes after cardiac transplantation but with reduced maximal intimal thickness and cytomegalovirus antigenemia.
Dietary Risk Factors for Gastric Carcinoma
Authors: John H Weisburger
Journal: JAMA (2004)

1. Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: Gefitinib (ZD1839) (Iressa(R)) tablets. Oncologist. 2003;8:303-306. 2. Bailey R, Kris M, Wolf M, et al. Tumor epidermal growth factor receptor (EGFR) expression levels does not predict for response in patients (pts) receiving gefitinib (“Iressa,” ZD1839) monotherapy for pretreated advanced non-small-cell lung cancer (NSCLC): IDEAL 1 and 2. Proc Am Assn Cancer Res. 2003;44:1362.
589. Therapeutic Efficacy and Cellular Mechanism Mediated by Intratumoral and Intramuscular IL-12 Electrogenetherapy
Authors: Eli Gilboa, Sandra Santulli-Marotto, Smita K. Nair, David Boczkowski, Yanbing Zhao
Journal: Molecular Therapy (2004)

The dendritic cell (DC) is a newly discovered member of the immune system specialized in presenting antigen to naive T cells, and consequently playing a central role in the induction of T cell, as well as B-cell, immunity. Immunization with DC loaded with tumor antigens could, therefore, represent a powerful method of inducing antitumor immunity. Studies in our laboratory have shown that DC transfected with mRNA encoding tumor antigens are effective inducers of cytotoxic T cells (CTL) and tumor immunity. Tumor RNA can be amplified from microscopic amounts of tumor tissue obtained by microdissection from needle biopsies or fixed tissue sections providing virtually inexhaustible amounts of tumor antigens without the need to identify the relevant antigens in each patient. Phase I/II clinical studies in patients with prostate and renal cancer have established the safety, and feasibility of this approach and despite the advanced nature of the disease, the majority of the patients exhibited specific immunological responses. To enhance the therapeutic impact of this vaccination strategy antisense and siRNA technology are used to induce CD4+ T cell immunity by inhibiting Invariant chain expression in the (mRNA transfected) DC, and CTLA-4 binding RNA aptamers are used to enhance the persistence of vaccine-induced antitumor immunity.
SNS-595, a novel S-phase active cytotoxic, exhibits potent in vitro and in vivo activities, and has the potential for treating advanced hematologic malignancies
Authors: Chris E. Lawrence, Jennifer P. Arbitrario, Jeffrey L. Kumer, Jasmin Wright
Journal: Cancer Research (2006)

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SNS-595 is a novel naphthyridine analog that acts specifically during the S-phase to induce rapid apoptosis of cells that are actively synthesizing DNA, resulting in cell cycle arrest in the G2 phase. SNS-595 is being developed for the treatment of both solid and hematologic malignancies. Current treatment of relapsed or refractory acute leukemias and advanced chronic myelogenous leukemia remains suboptimal. In patients with acute myelogenous leukemia (AML), failure to achieve a complete remission (CR) after induction chemotherapy or relapse occurring within the first year after diagnosis is associated with a poor prognosis. In patients with accelerated or blast-phase chronic myelogenous leukemia (CML) the response rates to intensive chemotherapy regimens are less than 30%, and in responding patients the median remission duration averages 4 to 6 months. SNS-595 has potent anti-proliferative effects on human leukemic cell lines in vitro. IC50 values, determined by MTT assay in four human promyelocytic, and acute lymphoblastic leukemia cell lines, range from 40 to 170 nM. Intravenous administration of SNS-595 to nu/nu mice with LM-3 Jck hematologic xenograft tumors resulted in 97 to 99% tumor growth inhibition. All mice treated with SNS-595 had significant reductions in tumor volume, with a complete response rate of 67%. Similarly, SNS-595 also showed 98% tumor growth inhibition in mice bearing CCRF-CEM xenograft tumors. The effect of IV administered SNS-595 on bone-marrow cellularity and circulating levels of leukocytes in CD-1 mice was measured after drug administration on days 0 and 4. Two days after the second administration of SNS-595, bone marrow isolated from femurs showed a dose-dependent reduction in cellularity. At 20 mg/kg, cellularity was reduced to 7.5%, while circulating neutrophils were reduced from a pre-dose level of 1244 ±55 cells/μL to a nadir of 51 ±24 cells/μL blood on day 8. Absolute neutrophil counts subsequently rebounded and soon returned to normal levels. Total WBCs also reached a nadir on day 8, but returned to normal levels. In conclusion, in vitro and in vivo data show that SNS-595 has potent anti-proliferative activity on human leukemic cell lines, inhibits tumor growth in hematologic xenografts, and reversibly ablates murine bone marrow cells. These data suggest that SNS-595 has the potential to demonstrate important clinical activity in patients with hematologic malignancies.
609. Highly Active, Cancer Specific Promoters for Gene Therapy of Small Cell Lung Cancer
Authors: Nina Pedersen, Mikkel W. Pedersen, Thomas T. Poulsen, Hans S. Poulsen
Journal: Molecular Therapy (2004)

One of the major problems in conventional, non-invasive cancer treatment is the lack of specific targeting to the cancer cells. For targeted gene therapy, the lack of cancer specific receptors has proven a major obstacle and therefore new strategies are being developed to increase the therapeutic index. This can be achieved by having the expression of the therapeutic gene regulated by a cancer specific promoter and will permit the use of less specific receptors for targeting. Most cancer specific promoters identified to date do not confer sufficient expression levels needed for effective therapy. Therefore the identification of novel highly active, cancer specific promoters would improve the potential of cancer gene therapy.
Abstract 3828: An 18-gene signature for vascular invasion is associated with aggressive features and reduced survival in breast cancer
Authors: Monica Mannelqvist, Elisabeth Wik, Ingunn M. Stefansson, Lars A. Akslen
Journal: Cancer Research (2014)

Abstract Introduction: Vascular invasion, i.e. tumor cells entering the vascular system, is considered to be an early step in the metastatic process and important for the progress of malignant tumors. By microarray and qPCR, we previously constructed an 18-gene signature in relation to vascular invasion among endometrial cancer patients. Here, we wanted to investigate the vascular invasion signature (VIS) among breast cancers patients. Methods: The 18-gene signature was studied in 11 gene expression data sets of breast cancer including information on 2423 patients. The genes in the signature were investigated in the external data sets and related to clinical data and follow-up information. We also wanted to examine if our signature was associated with other published signatures related to tumor progression. Results and Conclusions: High VIS showed associations with aggressive features of breast cancer such as high tumor grade, hormone receptor negativity, HER2 positive tumors, presence of a basal-like phenotype, reduced patient survival and response to cytostatic treatment. Correlations between VIS and other signatures for tumor progression indicate an involvement in similar biological processes. In conclusion, the vascular invasion signature showed strong and consistent associations with aggressive features of breast cancer. Citation Format: Monica Mannelqvist, Elisabeth Wik, Ingunn M. Stefansson, Lars A. Akslen. An 18-gene signature for vascular invasion is associated with aggressive features and reduced survival in breast 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 3828. doi:10.1158/1538-7445.AM2014-3828
Abstract 2541: Differential trafficking of dendritic cells after immunization determines establishment of systemic anti-tumor responses
Authors: Noriko Sato, Kingsley Asiedu, Peter L. Choyke
Journal: Cancer Research (2014)

Abstract Systemic immune activation and memory cell generation is desired in dendritic cell (DC)-based therapies against cancers, especially with metastasis. Migration properties of DCs, however, could limit the responses regionally constrained. Clinically, DC-vaccines are often given subcutaneously (s.c.), intravenously (i.v.) or intradermally (i.d.), without monitoring the migration of DCs. In this study, we visualized trafficking of DCs labeled with In-111 oxine using a whole-body micro-SPECT imager after immunization via different routes and examined induction of immune activation and memory cell generation in mice. Bone marrow-derived DCs were used. Surprisingly, most of s.c. transferred DCs failed to migrate to the adjacent lymph nodes (LNs) and died at the injection site, irrespective of their maturation status. DCs injected i.v. were initially trapped in the lungs, but gradually migrated to the spleen, liver and, to a lesser extent, LNs. In contrast, DCs administered i.d. and intraperitoneally (i.p.) quickly entered lymphatic system and distributed to LNs. Proliferation of CMFDA labeled OT-1 CD8 T cells pre-transferred to mice receiving ovalbumin loaded DCs (OVA-DCs) indicated that i.v. and i.p. immunizations triggered stronger and more systemic expansion of effector T cells than s.c. and i.d. immunizations. To examine the establishment of long-term defense, we next immunized mice with OVA-DCs and challenged them with OVA-expressing tumors intramuscularly, contra-lateral to the s.c. and i.d. injection site. Intriguingly, i.v. immunization seemed less effective than the others in developing long-term antigen-specific immunity, despite its capability to induce an extensive acute responses. These results might suggest that difference in the microenvironment of organs where CD8 T cells encounter the antigen (i.e., spleen or LNs) controls the generation of long-lived memory cells. Collectively, immunization route would be a critical factor that determines the spatial distribution of immune activation and generation of functional memory cells in DC-based therapies. Citation Format: Noriko Sato, Kingsley Asiedu, Peter L. Choyke. Differential trafficking of dendritic cells after immunization determines establishment of systemic anti-tumor responses. [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 2541. doi:10.1158/1538-7445.AM2014-2541
Disrupting the notch pathway with gamma-secretase inhibitors suppresses growth and induces apoptosis of sarcoma cell lines with constitutively active ras and notch signaling pathways
Authors: Raymond D. Meng, C. Chad Shelton, Yueming Li, Gary K. Schwartz
Journal: Cancer Research (2006)

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An urgent need exists for novel therapies to treat soft tissue sarcomas. Not only has the mortality rate remained unchanged for the past twenty years, but the incidence rate has increased annually as well. Of the sarcoma subtypes, a highly aggressive form is the malignant peripheral nerve sheath tumor (MPNST), which usually presents at an advanced stage, limiting therapeutic options. Notch signaling has been implicated in ras transformation, and MPNSTs may be especially susceptible to notch inhibition as they have active ras and notch signaling. The notch pathway may be disrupted by inhibiting the cleavage of notch into its transcriptionally active form by the gamma-secretase protein complex. We hypothesized that inhibition of notch signaling by gamma-secretase inhibitors (GSIs) would cause growth suppression of MPNSTs, despite constitutive ras activation. In two MPNST cell lines, MPNST and ST88, which have activated ras and mutant p53, the Notch1 pathway is also activated, as indicated by expression of Notch1 intracellular domain (NICD). The Notch1 ligand Jagged1 is also over-expressed. When treated with two novel GSIs (JC34 and JC18) identified in a screening library, both MPNST cell lines show decreased cell viability up to 50%, as assessed by a sulforhodamine B assay. This effect was both time- and dose-dependent with concentrations ranging from 10 to 25 μM. The selectivity of the GSIs upon the notch pathway was then examined. Using an NICD-specific antibody, we show that the NICD decreased in MPNST and ST88 at 24 hours after treatment with GSIs (10 to 25 μM). As a negative control, Jagged1 was not affected. The activity of Hes1, a transcriptional downstream target of Notch1, was also examined, using a luciferase reporter with the Hes1 promoter. Hes1 activity decreased 40% following GSIs for 24 hours. The decrease in viability resulted from apoptosis, as shown by PARP cleavage and nuclear fragmentation by DAPI staining. The apoptotic mechanism was attributed to up-regulation of pro-apoptotic NoxA in a p53-independent manner and down-regulation of the pro-survival protein Akt. Therefore, notch disruption results in growth inhibition and apoptosis in MPNST cell lines with constitutively active ras signaling. Studies are on-going to examine the combination of ras inhibitors with GSIs. Targeting the notch pathway with GSIs represents a novel approach to treating MPNSTs and has implications for developing new therapeutic strategies in the treatment of solid tumors with activated ras and notch pathways.
LARGE INTERAURICULAR SEPTAL DEFECT ASSOCIATED WITH TUBERCULOSIS AND AMYLOIDOSIS
Authors: Benjamin J. Elwood, Isadore E. Gerber
Journal: Annals of Internal Medicine (1944)

Case Reports1 September 1944LARGE INTERAURICULAR SEPTAL DEFECT ASSOCIATED WITH TUBERCULOSIS AND AMYLOIDOSISBENJAMIN J. ELWOOD, M.D., ISADORE E. GERBER, M.D.BENJAMIN J. ELWOOD, M.D.Search for more papers by this author, ISADORE E. GERBER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-21-3-485 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA developmental defect of the interauricular septum may vary from a small patency of the foramen ovale to complete arrest of formation of the septum. When the interauricular communication is one or more centimeters in diameter the defect may be considered sufficiently large to permit a considerable shunt of blood from the left to the right side of the heart. As a result, there ensues a significant alteration in circulatory dynamics with consequent anatomic changes in the heart and pulmonary vessels. Modern contributions to the knowledge of interauricular septal defects have been made by Abbott,1Assman,2Roesler,3McGinn and White,4...Bibliography1. ABBOTT ME: Congenital heart disease, Nelson Loose Leaf Medicine, Thomas Nelson & Sons, New York, 1929, Vol. IV. Google Scholar2. ASSMAN H: Klinische Röntgendiagnostik der inneren Erkrankungen, Ed. IV, 1928, F. C. W. Vogel, Leipzig. Google Scholar3. ROESLER H: Interatrial septal defect, Arch. Int. Med., 1934, liv, 339. CrossrefGoogle Scholar4. MCGINNWHITE SPD: Interauricular septal defect associated with mitral stenosis, Am. Heart Jr., 1933, ix, 1. CrossrefGoogle Scholar5. TINNEY WS: Interauricular septal defect, Arch. Int. Med., 1940, lxvi, 807. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Jersey City, N. J.*Received for publication January 18, 1943.From the Departments of Medicine and Pathology, Hudson County Tuberculosis Hospital, B. S. Pollak, M.D., Medical Director, Jersey City, N. J. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1944Volume 21, Issue 3Page: 485-493KeywordsAmyloidosisBloodHeartHospital medicine ePublished: 1 December 2008 Issue Published: 1 September 1944 PDF downloadLoading ...
Abstract 3506: Heregulin induces transformation of mammary epithelial cells via HER3 activation
Authors: Ruth Lupu, Ashwani Khurana, Ghiara Lugo, Anatilde Gonzalez Guerrico
Journal: Cancer Research (2014)

Abstract Heregulin (HRG)s are high-affinity combinatorial ligands for the HER family of tyrosine kinase receptors. HRG induces heterodimerization and cross-talk between members of the HER tyrosine kinase receptor family. HRG interaction with HER3 induces heterodimerization between HER3 and other HER receptors, including epidermal growth factor receptor (EGFR) and HER2, resulting in cross-talk-induced tyrosine phosphorylation. Several studies have revealed that HRG is expressed in about 40% of invasive breast carcinomas, many of which are triple negative breast carcinomas. We have previously demonstrated that HRG expression induces tumorigenesis and metastasis of MCF-7 cells. We tested the effect of HRG on non-committed MCF10A cells. MCF-10A cell line is an immortalized, non-transformed epithelial cell line derived from human fibrocystic mammary tissue. These cells lack the ability to form tumors in nude mice and the ability to grow in anchorage-independent assays. We found that forced expression of HRG in MCF10A induced cellular transformation, while the control MCF10A/Vector cells did not growth. MCF10A/HRG cells express constitutive phosphorylation of HER3 and induction of the signaling cascade. HER3 phosphorylation occurs as a result of HRG induction of HER3 heterodimerization with EGFR in an autocrine manner. Lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2 and EGFR pathways, blocked HER3 phosphorylation and the resulted signaling in MCF10A/HRG cells and prevented their anchorage-independent growth demonstrating that HER3 phosphorylation is responsible, at least in part, for the transformation of MCF10A/HRG cells. This study provides an alternate targeting prospective for breast carcinomas that express HER3 and HRG by targeting the autocrine-loop (HRG/HER3) and thus preventing HRG from binding to HER3, disrupting the possible receptor heterodimerization, and leading to blockage of the proliferative signals and promoting inhibition of growth. Citation Format: Ruth Lupu, Ashwani Khurana, Ghiara Lugo, Anatilde Gonzalez Guerrico. Heregulin induces transformation of mammary epithelial cells via HER3 activation. [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 3506. doi:10.1158/1538-7445.AM2014-3506