tbuckley/cabot-search huggingface dataset:
Abstract 1622: Design and preclinical evaluation of single agents with tubulin and multiple receptor tyrosine kinase inhibition
Authors: Aleem Gangjee, Roheeth K. Pavana, Michael Ihnat, Ernest Hamel
Journal: Cancer Research (2014)

Abstract Vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors lead to the reduction of angiogenesis but are cytostatic, not tumoricidal. These inhibitors have shown significant promise in the clinic when used in combination with cytotoxic agents, and several clinical trials with such combinations are in progress. We have previously reported preclinical studies on AG119, a compound that inhibits both VEGFR2 and tubulin, thereby affording antiangiogenic and cytotoxic effects in a single agent. Structural modifications of AG119 afforded AG321, a unique compound with four separate mechanisms of action in a single agent. AG321 inhibits platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor (EGFR), in addition to VEGFR2 and tubulin. AG321 is a colchicine site binding agent with potency comparable with that of combretastatin A-4 against bovine brain tubulin assembly. AG321 has potency comparable with that of erlotinib in tumor cell lines overexpressing EGFR and potency comparable with those of erlotinib, PD153035 and DMBI and in cell lines overexpressing PDGFRβ. It also has potency comparable with those of sunitinib and semaxinib in cell lines overexpressing VEGFR2. AG321 reduced tumor size (control: 15.7 ± 2.9 mm3/day; AG321 treated: 5.7 ± 0.7 mm3/day; p &amp;lt; 0.01 by one way ANOVA with Tukey multiple comparisons post test) and the number of lung metastases in the 4T1 triple negative mouse breast cancer allograft model and was superior to docetaxel, without overt systemic toxicity. A range of potential therapies that target EGFR are currently in development or in clinical trials for the treatment of glioblastoma. Targeting both VEGFR2 and PDGFRβ, which are two key mediators of tumor angiogenesis, increases the antiangiogenic effect even in the often intractable late stage of solid tumors. Hence, AG321, a multiple receptor tyrosine kinase (RTK) inhibitor which may also be effective against EGFR-amplified glioblastoma [AG119 reduced tumor size and vascularity in vivo in the U251 glioma model]. In summary, AG321 with antiangiogenic effects via multiple RTK inhibition and cytotoxic effects via tubulin inhibition in a single entity may delay or prevent tumor cell resistance, circumvent pharmacokinetic problems that can occur with multiple agents, avoid drug-drug interactions, be used at lower doses to alleviate toxicity and be and have reduced toxicity. Citation Format: Aleem Gangjee, Roheeth K. Pavana, Michael Ihnat, Ernest Hamel. Design and preclinical evaluation of single agents with tubulin and multiple receptor tyrosine kinase inhibition. [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 1622. doi:10.1158/1538-7445.AM2014-1622
Abstract 2898: HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma
Authors: Ahmed M. Aref, Neil T. Hoa, Lisheng Ge, Anshu Agrawal, Maria Dacosta-Iyer, Nils Lambrecht, Yi Ouyang, Andrew N. Cornforth, Martin R. Jadus
Journal: Cancer Research (2014)

Abstract Immunotherapy for human hepatocellular cancer (HCC) is slowly making progress towards treating these fatal cancers. The identification of new antigens can improve this approach. We describe a possible new antigen, Hepatocellular Carcinoma-associated Antigen-519/ Targeting Protein for Xklp-2 [HCA519/Tpx2], for HCC that might be beneficial for T cell specific HCC immunotherapy. HCC was studied for the expression for 15 tumor-associated antigens considered useful for immunotherapy within three HCC cell lines (HepG2, Hep3B and PLC/PRF/5), lymphocytes, non-cancerous livers and clinical HCC. The expression of Tumor Antigenic Precursor Proteins (TAPPs) mRNA was first screened by quantitative real time PCR. Four antigens (alpha fetoprotein, aspartyl/asparaginyl β-hydroxylase, glypican-3 and HCA519/Tpx2) proved to be the best expressed TAPPs within the HCC specimens by molecular analyses. HCA519/Tpx2 was detected by intracellular cell flow cytometry within HCC cell lines by using a specific antibody towards this TAPP. This antibody also detected the protein within primary HCCs. We synthesized two HCA519/Tpx2 peptides (HCA519464-472 and HCA519351-359) which can bind to HLA-A*0201. Dendritic cells pulsed with these peptides stimulated cytolytic T lymphocytes (CTLs). These killer T cells lysed HLA-A*0201+ T2 cells exogenously loaded with the correct specific peptide. The CTLs killed HepG2 (HLA-A2+ and HCA519+), but not the Hep3B and PLC/PRF/5 cell lines, which are HCA519+ but HLA-A2-negative. In silico analysis reveals that HCA519/Tpx2 has the inherent ability to bind to a very wide variety of HLA antigens. HCA519/Tpx2 is a viable immunotarget that should be further investigated. Citation Format: Ahmed M. Aref, Neil T. Hoa, Lisheng Ge, Anshu Agrawal, Maria Dacosta-Iyer, Nils Lambrecht, Yi Ouyang, Andrew N. Cornforth, Martin R. Jadus. HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. [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 2898. doi:10.1158/1538-7445.AM2014-2898
Abstract 868: Characterization of LASEP3 as a serological and prognostic biomarker and a therapeutic target for lung cancer
Authors: Atsushi Takano, Yusuke Nakamura, Yataro Daigo
Journal: Cancer Research (2014)

Abstract This study aims to identify novel biomarkers or therapeutic targets for lung cancers. We used cDNA microarrays for screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers. During this process, we identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical staining of LASEP3 showed that LASEP3 expression was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP3 expression was associated with poor prognosis for NSCLC patients. (P=0.0183 by log-rank test). Serum LASEP3 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP3-positive cases was 160 (61.8%) of 259 NSCLCs (49.4% for stage I-II, 67.4% for stage III-IV), while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Moreover serum LASEP3 levels were significantly higher in breast and colon cancer patients than in healthy volunteers. LASEP3 protein was overexpressed in breast and colon cancer tissues. Furthermore, reduction of LASEP3 by siRNA suppressed lung cancer cell proliferation and invasion. Flow cytometric analysis of these tumor cells transfected with siRNAs for LASEP3 revealed a significant increase of the cells at the G1 phase. Furthermore, subsequent microarray analysis of these cancer cells identified several candidate downstream genes of LASEP3 that relate to cell growth signals. These data suggest that LASEP3 is a possible diagnostic and prognostic biomarker and therapeutic target for lung and various types of solid cancer. Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Characterization of LASEP3 as a serological and prognostic biomarker and a therapeutic target for lung 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 868. doi:10.1158/1538-7445.AM2014-868
Liver Catalase Activity in Rat Leukemia
Authors: Arthur A. Spector, Leonard Berwick, Peter C. Nowell
Journal: Cancer Research (1960)

Summary  Liver catalase activity in rats bearing a transplanted lymphocytic leukemia showed progressive changes that were similar to those reported for solid neoplasms in a rodent. There was an initial drop in the recipient9s liver catalase activity upon inoculation with blood from a leukemic donor. This was followed by a return to normal liver catalase activity levels and then by a further steady decline until the animal died. The early changes took place before there was any visible evidence of tumor growth either in the liver or elsewhere in the body.
Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the U.S. from 1990 through 1999
Authors: William J. Rogers, John G. Canto, Costas T. Lambrew, Alan J. Tiefenbrunn, Becky Kinkaid, David A. Shoultz, Paul D. Frederick, Nathan Every
Journal: Journal of the American College of Cardiology (2000)
267. Enhancement of T-Cell Immunity by CEA Delivery to Dendritic Cells with Adenovirus Retargeted Via sCAR-Fibritin-CD40L
Authors: Papia T. Banerjee, Stephan G. Klinz, Alexander V. Pereboev, Douglas R. Nelson, James S. Huston, David T. Curiel, Stephen D. Gillies
Journal: Molecular Therapy (2004)

Dendritic cells (DC) are excellent targets for antigen-specific immune intervention. However, several attempts to transfer genes of interest to DC by Adenovirus (Ad) have been disappointing, due to limited expression of the relevant receptors and limited uptake of the Ad into DC. Although successful gene transduction to DC has been achieved with very high doses of Ad, associated toxicity was too high for clinical use. Increased transduction efficiency with relatively lower adenoviral dose was previously documented by retargeting Ad to specific cell types using either a two-component targeting moiety or genetically modified adenovirus.
Primary Cutaneous Trichosporonosis Responsive to Voriconazole
Authors: Neetu Bhari, Immaculata Xess, Mragnayani Pandey, Sudheer Arava, M. Ramam
Journal: JAMA Dermatology (2015)

at that time (Figure 2A).Since it seemed difficult to heal the lesion completely with only antibiotics, she was given surgical debridement on day 20.The ulcer had a necrotic bed, with the Achilles tendon and the calcaneal bone exposed (Figure 2B).We started NPWT with V.A.C. Therapy System (Kinetics Concepts Inc [KCI]) as a pretreatment for skin grafting on day 42.The vacuum suction was maintained at 125 mm Hg, and the wound dressings were changed every third day for 24 days.By day 69, good granulation tissue covered the ulcer bed (Figure 2C).A mesh skin graft was successfully engrafted on day 78.By day 127, the ulcer was completely healed, and she was able to walk again by herself (Figure 2D).Treatment with antibiotics was continued throughout the 4-month treatment course.Discussion | Buruli ulcer should be considered in patients who present with chronic refractory ulcers or atypical cellulitis unresponsive to standard treatment.Its diagnosis relies primarily on PCR methods, 4 and PCR targeting of IS2404 is a highly sensitive and specific diagnostic test (sensitivity and specificity >90%). 5n this case, although the lesion extended deeply and required radical debridement, we were able to avoid amputation and achieve good wound healing by wound bed preparation with NPWT, which increases wound blood flow and granulation tissue growth and decreases local edema and bacterial flora at the wound site. 6Portable NPWT treatment devices are adaptable for outpatients and also can be used in developing countries.This treatment outcome suggests that NPWT might be appropriate for treatment of advanced BU cases.
A memorable patient: For want of a bag of blood
Authors: M. Yung
Journal: BMJ (2000)

I had been working in sub-Saharan Africa for a month, and it was the height of the malaria season. When I first arrived I asked what the transfusion threshold was, and was told, “A haemoglobin of 5 if they are sick; otherwise 3.5.” An otherwise perfectly normal little girl was admitted with a haemoglobin of 2.6 and malaria. Like any toddler, she was able to sit, look around, and resist examination. I tried to give her oxygen but, like most toddlers, she would not keep the mask on. However, she had the respiratory distress and metabolic acidosis of severe malaria, and needed blood urgently.

Most children with this life threatening syndrome did well with simple treatments: antimalarials, fluid, and blood. …
Medicine and Social Justice: Essays on the Distribution of Health Care
Authors: S. Gorovitz
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
SAM without ASH.
Authors: R M McCleskey
Journal: Circulation (1978)

To the Editor:We were interested in the article by Martins and colleagues on cardiac size and function in acromegaly,' because of our recent observations on left ventricular dynamics in this disease.Using echocardiography, we have studied a series of 24 patients, of whom seven were studied one year after elective surgery.All patients had markedly elevated growth hormone levels (16-380 ng/ml without suppression after glucose loading) in the preoperative assessment, with a normalization with postoperative data.Every case exhibited a marked concentric left ventricular hypertrophy (LVH) with a mean LV free wall thickness of 16 mm and absolute LV mass of 484 g, according to the ellipse approximation calculations.None had signs of asymmetric septal hypertrophy.In the postoperative group of seven patients the LV wall thickness was smaller (13 mm, P < 0.001) but the mean LV mass did not differ from the preoperative data (477 g; NS).The mean LV transversal diameter was 51.7 ± 5.1 mm in the preoperative studies and 57.4 ± 4.5 mm in the postoperative studies (P < 0.05).Asynergy was detected by multidirectional contraction cinetics analysis2 in only two patients.They also exhibited ischemic ST segment depressions upon exercise testing.The data suggest that the acromegalic heart disease consists of concentric hypertrophy without other structural or functional ab- normalities.It appears that normalization of the growth hormone levels postoperatively initiates dilatation with persistence of the in- creased LV mass.
Abstract 4026: Attenuation of pancreatic cancer cell migration and invasion through a targeted inhibition of the Rac GEF Vav1
Authors: Gina L. Razidlo, Christopher Magnine, Arthur C. Sletten, Rachel M. Hurley, Mark A. McNiven
Journal: Cancer Research (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of human cancer, due in large part to a high incidence of metastasis and resistance to conventional chemotherapies. As such, new therapies are needed to halt the metastatic process. The proto-oncogene Vav1 is ectopically expressed in over half of human pancreatic cancers, and its expression correlates with a poor prognosis in humans and promotes survival and transformation in isolated tumor cells. We have found that Vav1, through its GEF activity towards Rac1, also potently induces migration by pancreatic tumor cells. In addition, Vav1 also signals through Cdc42 to drive the formation of invadopodia and matrix degradation, which also promotes tumor cell invasion. Importantly, the activation of Vav1 circumvents the requirement for active Src in this process. Because Vav1 is ectopically expressed in pancreatic cancers and is a potent regulator of tumor cell survival, proliferation, and invasive migration, it could provide a specific therapeutic target for these tumors. Recently, the anti-inflammatory agent azathioprine was described as an inhibitor of Vav1/Rac1 activity in hematopoietic cells. Therefore, we hypothesized that azathioprine could also inhibit the Vav1-driven processes of proliferation and invasion in pancreatic tumor cells. Indeed, we have determined that azathioprine treatment of cultured human PDAC cells reduces viability and proliferation. Further, similar to siRNA-mediated depletion of Vav1, azathioprine treatment reduces cell migration, as well as the matrix degradation required for invasion. Vav1-expressing tumor cells were more sensitive to azathioprine than Vav1-negative cells, supporting the premise that the inhibitory effects of azathioprine are mediated through Vav1. Finally, azathioprine also reduces metastasis in a xenograft model of pancreatic cancer. Taken together, these data uncover a role for aberrantly expressed Vav1 in regulation of the cytoskeletal machinery required for migration and invasion, and in the promotion and metastasis of pancreatic cancer. Even with the expression of multiple Rho family GEFs, tumor cells that upregulate Vav1 have become dependent upon this exchange factor, implicating Vav1 as a potent node for therapeutic intervention. Supported by R01 CA104125 and R03 CA155778 to M.A.M. Citation Format: Gina L. Razidlo, Christopher Magnine, Arthur C. Sletten, Rachel M. Hurley, Mark A. McNiven. Attenuation of pancreatic cancer cell migration and invasion through a targeted inhibition of the Rac GEF Vav1. [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 4026. doi:10.1158/1538-7445.AM2014-4026
Hypertension in the Young and the Old.
Authors: Gaddo Onesti, Kwan Eun Kim
Journal: Annals of Internal Medicine (1981)

This is a well-presented book published soon after volumes I and II.Some problems have arisen in the series.The first chapter -The adult respiratory distress syndrome: pathogenesis and treatment - has been covered twice previously.As the current authors state this cramped their style, though they have risen manfully to the occasion, and produced an excellent chapter capped with a comprehensive reference list.The book selects several topics and attempts to deal with the growing points.Generally this is well accomplished, and the individual contributors are all suited to their task.To select one or two of the highlights, chapter 2 (Chronic obstructive pulmonary disease: cor pulmonale and left ventricular failure) gives a good physiological appraisal and review though not everyone would agree with the conclusion that left ventricular dysfunction probably does not result from cor pulmonale.In chapter 3 (Hypersensitivity lung disease) the summary is particularly good.Chapters 4, 5 and 6 dealing with tuberculosis, non- tuberculous non-fungal infections and fungal
Abstract 13253: Cost-effectiveness of CABG vs PCI for Treatment of Multivessel Coronary Disease among Unstable Angina Patients---A Secondary Analysis from ASCERT
Authors: Zugui Zhang, Paul Kolm, Maria V Grau-Sepulveda, Angelo Ponirakis, Sean M O’Brien, Lloyd W Klein, Richard E Shaw, Charles McKay, David M Shahian, Frederick L Grover, John E Mayer, Kirk N Garratt, Mark Hlatky, Fred H Edwards, William S Weintraub
Journal: Circulation (2014)

Background: The American College of Cardiology Foundation and The Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies (ASCERT) has demonstrated that coronary artery bypass graft (CABG) surgery was associated with reduced mortality compared to percutaneous coronary intervention (PCI) at 4 years. In this study, we examined the cost-effectiveness of CABG versus PCI for treatment of multivessel coronary artery disease (CAD) patients among unstable angina patients. Methods: Unstable angina age ≥65 year-old patients with stable 2 and 3-vessel disease undergoing revascularization from 2004 through 2008 were evaluated. Costs were assessed at index, study period from years 2004 to 2008 by Diagnosis Related Group for hospitalizations. The average Medicare participant per capita expenditure in 2004 was used to estimate cost beyond the study period. Effectiveness during the study period was measured via mortality rate. Costs and effectiveness comparisons were adjusted using propensity scores bin bootstrapping (PSBB) method. The incremental cost-effectiveness ratio (ICER) was expressed as cost per quality adjusted life year (QALY) gained. Analyses were also conducted for 1-to-1 matched analytic population. Results: Among unstable angina patients (24,630 of 86,244 in CABG group and 48,261 of 103,549 in PCI group) at least 65 years old with two or three vessel CAD, results from both matched analytic population (16,500 in each group) and PSBB adjusted approach were similar. Costs were higher for CABG by $10,389 (95% CI: $10,269 to $10,509) during the index hospitalization. Over the period from 2004 through 2008, average total costs were $69,476 for CABG versus $57, 037 for PCI, a difference of $12,439 (95% CI: $11,038 to $13,751); patients undergoing CABG gained an average of 0.4066 life-years relative to PCI; the ICER of CABG compared to PCI, was $30, 484 per LYG, with 37%, 100%, and 100% of bootstrap-derived estimates &lt;$30,000/ QALY, &lt;$50,000/ QALY , and &lt;$100,000/ QALY, respectively. Conclusions: Recognizing the limitations of an observational study, this study shows that over a period of 4 years or longer, CABG is associated with better outcomes but at higher cost than PCI in patients with unstable angina.