tbuckley/cabot-search huggingface dataset:
Abstract 5705: Orally delivery alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine protect against murine breast cancer
Authors: Ze Liu, Shu Liu, Rong Xiang, Xiaoyue Tan
Journal: Cancer Research (2012)

Abstract Legumain DNA vaccine has been proven to be a potential treatment approach to protect against breast cancer. However, absence of safe and efficient oral delivery system highly restricts its clinical application. Here, we aim to develop a novel oral delivery system for legumain DNA vaccine with better biocompatibility and efficiency. We constructed alginic acid-coated chitosan NPs (A.C.NPs) and tested its anti-acid characteristics in vitro. DNA agrose electrophoresis data showed that compared to chitosan NPs (C.NPs), A.C.NPs significantly protected DNA from degradation in the condition of pH=1.5. Furthermore, size distribution anlysis showed that when pH&amp;lt;3.0, A.C.NPs aggregated to form the micrometer scale complex and dispersed to nanoparticle sized about 314 nm with the increased pH value. To visualize DNA expression, mice were treated by gavage with the A.C.NPs carrying EGFP expression plasmid. Significant EGFP expression can be detected in the intestinal peryer's patch of mice. Immunoflurescence staining showed that overlapping existed in EGFP and F4/80 (CD11b) positive cells. Full length legumain plasmids were loaded into different delivery systems including chitosan NPs (CL), Salmonella typhi (SL), A.C.NPs (ACL). PBS and A.C.NPs loaded with empty plasmid was also set as control groups (n=5 each group). Oral vaccination was performed in murine orthotropic 4T1 breast cancer model. Animals were scarified when the average tumor size in the PBS group reached 500 mm3. Our data showed that tumor volume was significantly smaller in ACL and SL groups compared to other groups. Further, we isolated splenocytes from mice and co-cultured with 4T1 cells pre-stimulated with hypoxia, which intrigued the translocation of legumain from cytoplasm to membrane. FACS assay showed that active cytotoxic T lymphocytes (CD3+/CD8+/CD25+) in ACL group increased 4.5 folds compared to PBS group and 2.3 folds compared to CL group respectively. Our study suggests that chitosan NPs modified with alginic acid could be a potential safe and efficient tool for oral delivery plasmid DNA. Alginic acid-coated chitosan NPs loaded with legumain DNA vaccine can effectively improve auto-immune response and protect against breast cancer. 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 5705. doi:1538-7445.AM2012-5705
Abstract 2026: Targeted delivery of therapeutic NefM1 peptide with single-walled carbon nanotubes (SWNTs) suppresses growth of 3-D cultures of breast and colon cancers
Authors: Dasharatham G. Janagama, Marc D. Basson, Harvey L. Bumpers
Journal: Cancer Research (2012)

Abstract Background and Objectives: In vitro studies with NefM1 peptide demonstrated apoptotic effects on a number of cancer cell lines containing CXCR4 receptors. This suggests that NefM1 apoptotic peptides can be used as a therapeutic agent for breast and colon cancers. In this study we hypothesized these cancers cultured as 3-D tumor spheres will undergo greater regression and destruction after treatment with NefM1 peptide- linked-carbon nanotubes (SWNTs) particles than with NefM1 peptide alone. Material and Methods: Human breast cancer (MDA-MB-231, MDA-MB-468) and colon cancer (HT-29, WiDr, SW 480) cells were cultured with 1% Sea Prep hydrogel in supplemented RPMI1640 medium. After 3 weeks the 3-D cultures developed as tumor spheres. Like in vivo conditions these 3-D cultures had cell-cell interactions and the sphere is held together by an extracellular matrix. The cultures were treated with NefM1 peptide and NefM1 carbon nanotubes (SWNTs) to compare their relative effects on the growth of the tumor spheres. The viability status of the tumor spheres was established using ethidium bromide and acridine stain and fluorescent microscopy. The Nef peptide was linked to SWNTs using thionine and binding was verified by gel electrophoresis. Transmission electron microscopy (TEM) showed internalization of NefM1-SWNTs nanoparticles. Results: In 3-D cultures, the SeaPrep hydrogel facilitated the growth of tumor spheres. All breast (MDA-MB-231, MDA-MB-468) and colon (HT-29, WiDr, SW-480) tumor spheres showed reduction and disintegration with nefM1 administration. This was enhanced with the NefM1- SWNTs conjugate which destroyed all cells in the culture. This indicated effective delivery of NefM1 into the cells via SWNTs. This is novel in that not only were these growing tumor spheres killed by the peptide binding to the CXCR-4 receptors, but the nanoparticles allowed for increased internalization of the peptide into the cells. The NefM1-SWNT's will undergo further study regarding its ability to enhance suppression of these tumors in SCID mice models. Conclusion: An apoptotic peptide (NefM1) can be linked to a nanoparticle which enhances its cytotoxicity to breast and colorectal cancers in vitro. Using 3-D cultured tumor spheres to evaluate the suppression of cancer growth is convenient and cost effective for drug delivery and drug discovery. 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 2026. doi:1538-7445.AM2012-2026
Abstract 2846: Exploring ERBB3 as novel drug target in lung cancer
Authors: Alessia Noto, Luigi Aurisicchio, Claudia De Vitis, Emanuele Marra, Giuseppe Roscilli, Rita Mancini, Gennaro Ciliberto
Journal: Cancer Research (2012)

Abstract Recent evidences point to ERBB3 as a critical activator of the PI3K/Akt signaling axis and suggest that its trans-phosphorylation is linked to the occurrence of drug resistance in several cancers. Because of the absence of a functional tyrosine kinase, the best approach to target this receptor is through the development of selective monoclonal antibodies. For this purpose, our group has recently generated a set of mouse monoclonals with low nM affinity for human ERBB3. We have started to assess the effect of these antibodies in lung cancer using two systems: a) PC9 cells, known to be highly sensitive to gefitinib (IC50 0,03 uM), for the DelE746A750 in exon 19 of EGFR and its gefitinib-resistant counterpart PC9-ZD (Koizumi et al, 2005 Int J. Cancer 116, 36); b) primary lung adenocarcinoma cells isolated in our laboratory from Malignant Pleural Effusions (MPEs) and capable of efficient tumor propagation in vivo (Mancini et al, 2011, PlosONE 6: e21320). In PC9 cells anti-ERBB3 mabs, A3 and A4, strongly inhibit ligand-induced pHER3 and pAKT and induce receptor downmodulation. Furthermore, A3 and A4 potentiate the antiproliferative effect of gefitinib in a clonogenic assay, induce G0/G1 arrest, and increase the percentage of cells that undergo apoptosis. In the human primary MPE-derived lung adenocarcinoma culture PEd10, we observed that the expression of ERBB3 and its ligand are upregulated when cells are grown in spheroid vs adherent conditions. In this system, A3 and A4 antibodies significantly downmodulate spheroid propagation. Studies are ongoing to provide further insights as to the mechanism of action of anti-ERBB3 antibodies and to confirm efficacy in in vivo tumor models. Our results suggest that in a subset of lung adenocarcinomas which express high levels of ERBB3, this receptor contributes to cell growth and propagation and that targeting ERBB3 with antibodies capable of inducing receptor downmodulation can be considered a promising therapeutic approach. 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 2846. doi:1538-7445.AM2012-2846
New Distributor of<i>Morbidity and Mortality Weekly Report</i>
Authors: Arnoll S. Relman
Journal: New England Journal of Medicine (1983)

Readers will note an ad on the inside back cover of this issue announcing that beginning July 1 the Publications Committee of the Massachusetts Medical Society will use the facilities of The New England Journal of Medicine to reprint and distribute the Centers for Disease Control's Morbidity and Mortality Weekly Report (MMWR).MMWR is the weekly bulletin that many physicians and public-health workers have found invaluable in keeping them current on the latest epidemiologic and public-health developments, including vital statistics on epidemic diseases and environmental hazards. For years it was mailed to anyone for the asking, free of charge. At . . .
ACTION OF STRONGER SOLUTIONS OF MERCUROCHROME IN EARLY GONORRHEAL INFECTIONS
Authors: ERNEST RUPEL
Journal: JAMA (1923)

The advancement in the treatment of gonorrhea has not kept pace with that of many diseases. It is generally agreed that efforts to improve on the more or less standard forms of treatment have been relatively unavailing. The introduction of the colloidal silver preparations marked the biggest advancement in recent years and, still more recently, the development of the mercury derivatives, as carried on by Young and his associates, 1 offered hope for an immediate sterilizing injection. As in the case of arsphenamin, the chemicals did not effect a cure in a single injection, though Frontz 2 has about eight well developed cases in which the process was absorbed after two or three injections of 1: 1,000 acriflavine.  In spite of adverse criticism, mercurochrome-220 soluble possesses some commendable qualifications. It is a solution and not a colloidal suspension, and therefore penetrates animal tissues better. It has great germicidal value, a
Hyperparathyroidism and Radiation Therapy
Authors: TONY CHRISTENSSON
Journal: Annals of Internal Medicine (1978)

Hypercalcaemic hyperparathyroidism has been diagnosed more commonly in recent years. This reflects an increasing awareness of and a growing interest in the disease. In the search for possible aetiologic mechanisms behind the development of parathyroid adenomata, certain environmental factors have been suggested. This study indicates that a significantly (p < 0.01) greater number of patients who had parathyroid adenomata had previously undergone radiation therapy involving the neck region compared with normocalcaemic control subjects. The observed and controlled cases originate from a medical screening programme done as part of a health check-up including almost 16 000 persons in the Stockholm area. It is recommended that special attention to a past history of possible neck irradiation be paid in subjects suspected of suffering from hyperparathyroidism.
Successful treatment of cytomegalovirus‐associated hemophagocytic syndrome by intravenous immunoglobulins
Authors: Arnaud Hot, Marie Hélène Girard Madoux, Jean P. Viard, Brigitte Coppéré, Jacques Ninet
Journal: American Journal of Hematology (2007)

Virus-associated hemophagocytic syndrome (VAHS) is a rare complication in early cytomegalovirus (CMV) infection. There is no standard therapy for VAHS and the clinical course is variable. Data on the use of intravenous immunoglobulin (IVIG) in the treatment of CMV-associated VAHS are limited. We report a previously healthy, 32-year-old woman who presented with general malaise, fever, chills, and splenomegaly. Laboratory examination showed marked elevation of aminotransferase, leucopoenia, and thrombocytopenia. Acute CMV-infection was documented by the presence of immunoglobulin M anti-CMV and positive viremia in blood sample. Bone marrow examination revealed extensive hemophagocytosis. IVIG was administered after the diagnosis of CMV-associated VAHS. Her symptoms and laboratory abnormalities improved dramatically after the onset of the treatment and she did not require antiviral agent.
Survival in Childhood Pulmonary Arterial Hypertension
Authors: Robyn J. Barst, Michael D. McGoon, C. Gregory Elliott, Aimee J. Foreman, Dave P. Miller, D. Dunbar Ivy
Journal: Circulation (2011)

Background— Pulmonary arterial hypertension (PAH) is a rare but important cause of morbidity and mortality in children. Methods and Results— We analyzed data from 216 patients ≤18 years of age at diagnosis who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Median age at diagnosis and enrollment was 7 and 15 years, respectively. The most frequent presenting symptom was dyspnea (idiopathic/familial PAH, 53%; PAH associated with congenital heart disease, 30%). Presyncope/syncope was more frequent in patients with idiopathic PAH/familial PAH (36%) than in those with PAH associated with congenital heart disease (4%). At diagnosis, mean pulmonary artery pressure and pulmonary vascular resistance index were 56 mm Hg and 17 Wood units · m 2 , respectively. Five-year survival from diagnosis for the overall cohort was 74±6%, with no significant difference between the idiopathic PAH/familial PAH (n=122, 75±7%) and PAH associated with congenital heart disease (n=77, 71±13%) cohorts ( P =0.53). Older age at diagnosis was the only variable significantly associated with decreased survival from diagnosis. Variables at enrollment that were significantly associated with decreased survival from enrollment included higher pulmonary vascular resistance index, lower-weight z scores, and familial PAH. Additional variables at enrollment, identified in a secondary analysis, that were marginally associated with increased survival from enrollment included acute vasoreactivity (adaptation of conventional pediatric definition; P =0.087) and lower brain natriuretic peptide ( P =0.060). None of the 22 patients who were acute responders treated with high-dose calcium channel blockade as monotherapy or combination therapy died within 5 years of diagnosis. Conclusion— Using REVEAL, we identified key predictors of survival in childhood PAH. Refining these prognostic parameters should help clinicians improve outcomes. Clinical Trial Registration— URL: www.clinicaltrials.gov . Unique identifier: NCT00370214.
Mediterranean diet and hepatocellular carcinoma
Authors: Federica Turati, Dimitrios Trichopoulos, Jerry Polesel, Francesca Bravi, Marta Rossi, Renato Talamini, Silvia Franceschi, Maurizio Montella, Antonia Trichopoulou, Carlo La Vecchia, Pagona Lagiou
Journal: Journal of Hepatology (2013)
Carrier Rates in the Midwestern United States for &lt;EMPH TYPE="ITAL"&gt;GJB2&lt;/EMPH&gt; Mutations Causing Inherited Deafness
Authors: Glenn E. Green
Journal: JAMA (1999)

Mutations in the GJB2 gene are the most common known cause of inherited congenital severe-to-profound deafness. The carrier frequency of these mutations is not known.To determine the carrier rate of deafness-causing mutations in GJB2 in the midwestern United States and the prevalence of these mutations in persons with congenital sensorineural hearing loss ranging in severity from moderate to profound, and to derive revised data for counseling purposes.Laboratory analysis, performed in 1998, of samples from probands with hearing loss for mutations in GJB2 using an allele-specific polymerase chain reaction assay, single-strand conformation polymorphism analysis, and direct sequencing.Fifty-two subjects younger than 19 years sequentially referred to a midwestern tertiary referral center for hearing loss or cochlear implantation, with moderate-to-profound congenital hearing loss of unknown cause, parental nonconsanguinity, and nonsyndromic deafness with hearing loss limited to a single generation; 560 control neonates were screened for the 35delG mutation.Prevalence of mutations in the GJB2 gene by congenital deafness status.Of 52 sequential probands referred for congenital sensorineural hearing loss, 22 (42%) were found to have GJB2 mutations. The 35delG mutation was identified in 29 of the 41 mutant alleles. Of probands' sibs, all homozygotes and compound heterozygotes had deafness. Fourteen of 560 controls were 35delG heterozygotes, for a carrier rate expressed as a mean (SE) of 2.5% (0.66%). The carrier rate for all recessive deafness-causing GJB2 mutations was determined to be 3.01% (probable range, 2.54%-3.56%). Calculated sensitivity and specificity for a screening test based on 35delG mutation alone were 96.9% and 97.4%, respectively, and observed values were 94% and 97%, respectively.Our data suggest that mutations in GJB2 are the leading cause of moderate-to-profound congenital inherited deafness in the midwestern United States. Screening of the GJB2 mutation can be offered to individuals with congenital deafness with high sensitivity and specificity by screening only for the 35delG mutation. A positive finding should establish an etiologic diagnosis and affect genetic counseling.
Systemic Delivery of Liposomal Short-Chain Ceramide Limits Solid Tumor Growth in Murine Models of Breast Adenocarcinoma
Authors: Thomas C. Stover, Arati Sharma, Gavin P. Robertson, Mark Kester
Journal: Clinical Cancer Research (2005)

Abstract In vitro tumor cell culture models have illuminated the potential therapeutic utility of elevating the intracellular concentration of the antimitogenic and proapoptotic sphingolipid, ceramide. However, although cell-permeable, short-chain ceramide is an effective apoptotic agent in vitro, its use as an in vivo, systemically delivered therapeutic is limited by its inherent lipid hydrophobicity and physicochemical properties. Here, we report that the systemic i.v. delivery of C6-ceramide (C6) in a pegylated liposomal formulation significantly limited the growth of solid tumors in a syngeneic BALB/c mouse tumor model of breast adenocarcinoma. Over a 3-week treatment period, a well-tolerated dose of 36 mg/kg liposomal-C6 elicited a &amp;gt;6-fold reduction in tumor size compared with empty ghost liposomes. Histologic analyses of solid tumors from liposomal-C6-treated mice showed a marked increase in the presence of apoptotic cells, with a coincident decrease in cellular proliferation and in the development of a microvessel network. Liposomal-C6 accumulated within caveolae and mitochondria, suggesting putative mechanisms by which ceramide induces selective cancer cell cytotoxicity. A pharmacokinetic analysis of systemic liposomal-C6 delivery showed that the pegylated liposomal formulation follows first-order kinetics in the blood and achieves a steady-state concentration in tumor tissue. Confirming the therapeutic utility of i.v. liposomal-C6 administration, we also shown diminution of solid tumor growth in a human xenograft model of breast cancer. Together, these results indicate that bioactive ceramide analogues can be incorporated into pegylated liposomal vehicles for improved solubility, drug delivery, and antineoplastic efficacy.
The Sociological Aspects of the Treatment of Arthritis: Notes on a Visit to the United States
Authors: J. J. R. Duthie
Journal: Annals of the Rheumatic Diseases (1939)

BY means of a grant made to him by the Empire Rheumatism Council the writer was enabled to spend some months in the United States studying various problems connected with the care and treatment of sufferers from the chronic rheumatic diseases.The greater part of the time was spent at the Robert Brigham Hospital, Boston.The writer would like to take this opportunity of expressing his gratitude to the members of the staff for their kindness in granting him free access to the various departments of the hospital, and also to record his appreciation of the courtesy and consideration which were shown to him at all the centres visited.This report is concerned mainly.with certain aspects of the organisation and methods of treatment in clinics for chronic rheumatic diseases which were visited.Before any attempt is made to discuss treatment, it might serve a useful purpose to say something regarding the study of the aetiology and clinical course of the various forms of chronic arthritis.Many physicians in America believe that until sufficient knowledge is acquired of the natural course of the disease, it will not be possible to forecast with any degree of certainty the particular course which an individual case will follow.Likewise it will be impossible to assess accurately the significance of the various aetiological factors concerned or the value of any form of treatment employed.Only by studying large groups of patients over prolonged periods (throughout life if possible) can such knowledge be acquired.Such study includes details of family history, the anatomical and physiological make-up of the patient, environment, type of onset, factors believed to be of aetiological significance, the course of the disease before the patient was first examined, and a complete investigation, clinical and laboratory, which is repeated at regular intervals for as long as circumstances 201 copyright.
Exposure to Asbestos and Mesothelioma of the Pleura
Authors: P. B. S. Fowler, J. C. Sloper, E. C. Warner
Journal: BMJ (1964)

Two cases of mesothelioma were the subjects of fairly recent coroners' inquests.In neither instance was it accepted that the tumour was attributable to inhalation of asbestos fibre; yet in one case there was a known and severe occupational history of exposure to asbestos, while in both cases " asbestos bodies " were found in the lung.A point made at both inquests was the difficulty of attributing a tumour to asbestos-inhalation in the absence of the diffuse pulmonary fibrosis so long recognized (Murray, 1907) as characteristic of " asbestosis."Recently, however, it has become clear, at least in South Africa (Wagner, Sleggs, and Marchand, 1960; Thomson, Kaschula, and MacDonald, 1963), that the association between mesotheliomata and asbestos-inhalation can scarcely be for- tuitous.The studies initiated by Wagner in Great Britain (1963, unpublished) suggest that the same may apply here.Our two cases of this rare tumour illustrate the practical implications of his investigations.
Oxygen method for calculation of right to left shunt: new application in presence of right to left shunting through the ductus arteriosus
Authors: W. M. GERSONY, G. V. DUC, R. B. DELL, J. C. SINCLAIR
Journal: Cardiovascular Research (1972)

Journal Article Oxygen method for calculation of right to left shunt: new application in presence of right to left shunting through the ductus arteriosus Get access WELTON M. GERSONY, WELTON M. GERSONY From the Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, N.Y., U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar GABRIEL V. DUC, GABRIEL V. DUC From the Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, N.Y., U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar RALPH B. DELL, RALPH B. DELL 2 From the Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, N.Y., U.S.A. 2 Recipient of a Research Career Development Award No. 5 K03 GM-19, 779 from the National Institutes of Health. Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHN C. SINCLAIR JOHN C. SINCLAIR From the Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, N.Y., U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 4, July 1972, Pages 423–438, https://doi.org/10.1093/cvr/6.4.423 Published: 01 July 1972