tbuckley/cabot-search huggingface dataset:
Abstract 4473: Development of ceramide liposomes for tumor interstitial and vascular drug targeting
Authors: Shaohua Cheng, William Crall, Bryan Nguyen, Charles Dang, Musaed Alkholief, Robert B. Campbell
Journal: Cancer Research (2014)

Abstract Background: Interstitial and vascular targeting with cytotoxic agents has proven to be an effective approach for cancer therapy (1). Ceramide, a sphingolipid, plays an important role in apoptosis, regulation of differentiation, growth suppression, and in cell senescence (2). Liposomes containing ceramide exert an anti-proliferative effect against the growth of tumor cells in vitro (3). In this study, we attempted to apply a rational approach to the development of ceramide liposomes for tumor targeting. Methods: We first determined the relative amounts of ceramide produced by cells normally found in the tumor interstitial matrix (ZR-75-1- human breast cancer cells), and by those lining tumor endothelia (HMEC-1 -human microvascular endothelial cells). For this experiment we measured sphingomyelinase activity. We next determined the cytotoxic effects of various liposome systems containing 0 to 20% ceramide (C6:1) content. The optimal ceramide content was determined from this study, and 2-methoxyestradiol (2-ME) was loaded in the optimal ceramide liposome preparation type. We next evaluated cytotoxic effects of the drug-loaded liposomes compared to ceramide liposomes alone. Results: ZR-75-1 cells showed a higher level of sphingomyelinase activity (4.4 fold) as compared to that of HMEC-1. The 20% ceramide formulation demonstrated the most significant anti-proliferative effect, regardless of the cell line. The cytotoxic drug effects were favorably influenced by the ceramide content. Finally, preliminary studies suggest that the overall effectiveness of ceramide liposomes against the growth of proliferating tumor cells correlated with the sphingomyelinase activity expressed by the target cells. Conclusion: Future studies will determine whether sphingomyelinase activity can be used to determine the population of cells (i.e., interstitial vs vascular) most likely to benefit from ceramide (cytotoxic) drug-loaded liposomes as a therapeutic approach. Citation Format: Shaohua Cheng, William Crall, Bryan Nguyen, Charles Dang, Musaed Alkholief, Robert B. Campbell. Development of ceramide liposomes for tumor interstitial and vascular drug targeting. [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 4473. doi:10.1158/1538-7445.AM2014-4473
478. Preinjection of Free DiC14-Amidine Liposome and Dexamethasone Synergistically Enhance the Intravenous Transfection Efficiency of Cationic Lipid/DNA Lipoplex
Authors: Marc A. Ilies, Betty H. Johnson, William A. Seitz, Edward L. Ezell, Aaron Miller, E. Brad Thompson, Alexandru T. Balaban
Journal: Molecular Therapy (2004)

A new approach for generating cationic lipids for gene delivery bearing pyridinium polar heads was described recently 1. It is based on the reaction of pyrylium salts with primary amines thus generating the polar head and the linker of the non-viral transfection vector in a single, high yield step. The versatility of the synthesis allows the choice of a large variety of aliphatic or aromatic linkers, yielding cationic lipids such as 1–4, some of which act better than commercial transfection systems. The method also allows the easy access to the class of gemini surfactants such as 5 and congeners, and the facile choice of the counterion of the final positively charged species. Additionally, the use of styryl pyrylium salts can yield fluorescent transfection systems and membrane markers such as 6. Detailed insights into their chemical synthesis and transfection properties on different tumor cell lines are presented, together with a complete structure - activity relationship study for each class of lipophilic pyridinium compounds Figure 1.
Studies on Cyclophosphamide, Antitumor Alkylating Compound. I. Effects on Mouse Leukemias&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: E. T. Kovacs, S. Ohno, R. Kinosita
Journal: JNCI Journal of the National Cancer Institute (1960)

Cyclophosphamide, administered intramuscularly, showed a strong inhibitory effect on growth of L4946 and C1498 ascites tumors. Repeated injections and even a single administration caused a considerable decrease in the ascites tumor-cell population. First the mitotic index dropped sharply, and then it gradually rose. At this stage, abnormal mitoses with multiple breaks predominated. Some tumor cells in ascitic fluid and especially those in other sites survived. Later, regular mitoses, with the chromosome complement of the stem-cell lineage, increased in frequency and led to generalized regrowth which finally caused death.
The molecular basis of chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and docetaxel.
Authors: Ian A. Cree, Sharon Glaysher, Louise A. Knight, Francis G. Gabriel, Paul Modi, Dennis Yiannakis, Joe Rahamin, Mark Smith, Khalid Amer, Bruce Addis, Peter John Davies, Peter E. Andreotti
Journal: Clinical Cancer Research (2006)

B64   Introduction: NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy. This study has tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients9 tumors.Methods: The chemosensitivity of a series of 29 tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA)against cisplatin, and docetaxel, alone and in combination. The results were correlated with quantitative expression of resistance genes measured by RT-PCR in a Taqman Low Density Array (Applied Biosystems) following extraction of mRNA from formalin-fixed paraffin-processed tissue using the AB 6100 extraction system. The results were standardised against the least variable housekeeping gene (PBGD) of those tested. The relationship between chemosensitivity and gene expression was assessed by multiple linear regression analysis.Results: No individual gene expression showed direct correlation with activity in the ATP-TCA. However, docetaxel activity showed some dependence on the expression of Beta-tubulin III, BCRP, MDR1, MRP2 and GSTpi, while cisplatin activity showed some dependence on DNA repair enzyme expression (e.g. ERCC1, MLH1, MSH6). Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel (p
Abstract 910: NOTCH3 expression is predictive of efficacy in pancreas tumor models treated with OMP-59R5, a monoclonal antibody targeting the NOTCH2 and NOTCH3 receptors
Authors: Belinda Cancilla, Wan-Ching Yen, Chun Zhang, Marcus M. Fischer, May Ji, Tracy Tang, Yu-Wang Liu, Raymond S. Tam, Min Wang, Austin Gurney, Timothy Hoey, John Lewicki, Ann M. Kapoun
Journal: Cancer Research (2014)

Abstract The Notch signaling pathway regulates key functions during embryonic development, stem cell maintenance and differentiation in adult tissues, and is implicated in many human cancers. OMP-59R5 is a ligand-blocking antibody targeting both the NOTCH2 and NOTCH3 receptors. We have developed a series of primary human xenograft models from patients with pancreatic cancer and used these models to examine efficacy response to OMP-59R5. We found that anti-NOTCH2/3, either as a single agent or in combination with chemotherapeutic agents, was efficacious in pancreatic tumor models. Expression of NOTCH3 mRNA by next-generation sequencing in ten baseline pancreatic tumors correlates with response to OMP-59R5, where growth of tumors with moderate to high expression of NOTCH3 was significantly reduced compared to tumors with low expression. We developed a Research-Use-Only (RUO) qPCR assay for measuring NOTCH3 mRNA expression using Formalin-Fixed, Paraffin-Embedded (FFPE) samples. This assay shows consistent NOTCH3 expression data with the next-generation sequencing data in the ten pancreatic xenograft tumors. Expression levels of NOTCH3 were also examined in ∼120 human metastatic pancreatic specimens to determine the reportable range of the assay and to identify association with clinical factors. This analysis showed that NOTCH3 gene expression maintained the same distribution across different specimen types, such as biopsy, surgical biopsy and surgical resection, etc. Samples with clinically relevant sites of recurrence also showed a similar range in NOTCH3 gene expression. Moreover, we developed an immunohistochemistry (IHC) assay for NOTCH3 protein expression. The correlation between the IHC assay and the qPCR assay was examined in both the metastatic pancreatic human specimens and the primary human pancreatic xenograft models. A significant correlation was found between the gene and protein levels, suggesting that both NOTCH3 gene expression and protein expression may predict the response to OMP-59R5 in pancreatic cancer. We are evaluating NOTCH3 levels and patient response in ALPINE, a Ph1b/2 Anti-NOTCH2/3 trial in first-line advanced pancreatic cancer patients. Citation Format: Belinda Cancilla, Wan-Ching Yen, Chun Zhang, Marcus M. Fischer, May Ji, Tracy Tang, Yu-Wang Liu, Raymond S. Tam, Min Wang, Austin Gurney, Timothy Hoey, John Lewicki, Ann M. Kapoun. NOTCH3 expression is predictive of efficacy in pancreas tumor models treated with OMP-59R5, a monoclonal antibody targeting the NOTCH2 and NOTCH3 receptors. [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 910. doi:10.1158/1538-7445.AM2014-910
Proteomic Profiling and Intra-amniotic Infection—Reply
Authors: Michael G. Gravett, Srinivasa R. Nagalla
Journal: JAMA (2004)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
262. Dendritic Cell (DC) Vaccine Loaded with Apoptotic Tumor Fragments Effectively Suppress Preestablished Malignant Melanoma in Mice
Authors: Hidetsugu Asada, Tsunao Kishida, Hideyo Hirai, Jiro Imanishi, Osam Mazda
Journal: Molecular Therapy (2004)

The central issue of cancer immunotherapy is to active tumor-specific T cell immune responses. Dendritic cells (DCs) are the most prominent antigen presenting cells characterized by their high ability to engulf, process, and present antigens to T lymphocytes, playing crucial roles in triggering antigen-specific T cell activation. Previous studies attempted to introduce tumor antigens into DCs ex vivo, by means of genetic transduction into DCs, tumor cell-DC fusion, and pulsing DCs with peptide antigen or tumor cell lysate. We hypothesized that DCs allowed to ingest cell fragments from apoptotic tumor cells may effectively process and present tumor antigen to T cells, which may subsequently recognize and attack the tumor cells. Here we engineered autologuous DCs to phagocytose apoptotic body of B16 melanoma and assessed their efficacy as therapeutic vaccine to treat preestablished B16 solid tumor in mice. Co-immunization of T subset populations with the DCs was also examined.
THE PERNICIOUS TYPE OF NERVOUS DYSPEPSIA
Authors: Edward C. Klein
Journal: Annals of Internal Medicine (1934)

Article1 February 1934THE PERNICIOUS TYPE OF NERVOUS DYSPEPSIAEDWARD C. KLEIN JR., M.D., F.A.C.P.EDWARD C. KLEIN JR., M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-7-8-960 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThat there is such a nosological entity as nervous dyspepsia is generally admitted. It constitutes a large proportion of the practitioner's clinical office material. The real difficulty begins when an attempt is made to define it. Alvarez in his classic book,Nervous Indigestion,describes it as a convenient term by which to designate all those gastrointestinal disturbances for which no organic cause can be found. Leube thought that the symptoms of nervous dyspepsia depended on a morbid supersensitivity at the beginning of digestion of the gastric nervous mechanism. He believed that to make the diagnosis it was necessary to exclude...References ALVAREZ WC: Nervous indigestion, 1930, Paul B. Hoeber, New York. Google Scholar BERKMAN JM: Anorexia nervosa, anorexia, inanition and low basal metabolic rate, Am. Jr. Med. Sci., 1930, clxxx, 411-424. CrossrefGoogle Scholar BULATAOCARLSON EAJ: Contributions to physiology of stomach; influence of experimental changes in blood sugar level on gastric hunger contractions, Am. Jr. Physiol., 1924, lxix, 107-115. CrossrefGoogle Scholar CLOW FE: Anorexia nervosa, New Eng. Jr. Med., 1932, ccvii, 613-617. CrossrefGoogle Scholar FALTA W: Insulin treatment and adipositas, Wien klin. Wchnschr., 1925, xxxviii, 757-758. Google Scholar GULL WW: Anorexia nervosa (apepsia hysterica), Trans. Clin. Soc. London, 1888, vii, 22. Google Scholar LABARRE J: Les fonctions contractiles et sécrétoires de l'estomac en rapport avec les variations du métabolisme glucidique, Bull. Acad. roy. de méd. de Belgique, 1931, xi, 598-651. Google Scholar LEEDE CS: Anorexia nervosa; hypoglycemia or hypoadrenia, Northwest Med., 1928, xxvii, 233-238. Google Scholar NAHUMHIMWICH LHHE: Insulin and appetite; method for increasing weight in thin patients, Am. Jr. Med. Sci., 1932, clxxxiii, 608-613. CrossrefGoogle Scholar VENABLES JF: Anorexia nervosa; study of pathogenesis and treatment of nine cases, Guy's Hosp. Rep., 1930, lxxx, 213-226. Google Scholar VENABLES JF: Anorexia nervosa, Clin. Jr., 1930, lix, 544-548. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Newark, New Jersey*Read before the Section on Medicine and Pediatrics, Academy of Medicine of Northern New Jersey, February 14, 1933. Received for publication March 29, 1933. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1934Volume 7, Issue 8Page: 960-965KeywordsDigestionPediatrics ePublished: 1 December 2008 Issue Published: 1 February 1934 PDF downloadLoading ...
<i>At Her Ease</i>
Authors: M. Therese Southgate
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Does Reduced Vascular Stiffening Fully Explain Preserved Cardiovagal Baroreflex Function in Older Physically Active Men?
Authors: Michael F. O’Rourke, Wilmer W. Nichols
Journal: Circulation (2002)

The article on change in vascular stiffening and baroreflex function by Hunt et al 1 contains a serious flaw that may have substantially influenced the results and interpretations.The authors used elegant methods to determine pulsatile carotid artery diameter change and to analyze data, but they related this diameter change to pulse pressure in the finger for determination of carotid artery stiffness.The finger artery pressure waveform is quite different in contour and amplitude to that in the carotid artery, and the relationship between the two varies markedly with age and vasoactive interventions. 2 The authors studied change in cardiovagal baroreflex function in young untrained men, older untrained men, and older physically active men given nitroprusside and phenylephrine; no allowance was made for alteration in pressure wave transmission, and the carotid pressure wave amplitude was considered to be identical to the finger pressure wave amplitude under all conditions and at all ages.This is not a reasonable assumption because amplification can vary between unity and over 2.0 under different conditions.We agree with others 3,4 that pulse wave amplification must be taken into account when studying cardiovagal baroreflex function by noninvasive methods or serious errors will result in arterial compliance calculations.
Blazing the pharmacologic audit trail: Pharmacodynamic biomarkers in early drug development
Authors: Chris H. Takimoto
Journal: Clinical Cancer Research (2010)

Abstract Pharmacodynamic (PD) biomarkers of drug action are common components of early clinical trials in oncology. However, how to optimally apply biomarker endpoints to rationale decision making is less clear cut. As a consequence, many biomarker programs represent expensive scientific investments in drug development infrastructure yielding little or no practical advantage at the end of the day. The Pharmacologic Audit Trail (PhAT), first proposed by Workman and colleagues, represents a well designed strategic paradigm for the rationale incorporation of PD and mechanism of action biomarkers into early drug development. The PhAT is comprised of a series of key questions addressed sequentially in early clinical trials to assess the pharmacological behavior of an experimental agent. It includes evaluation of target expression, pharmacokinetics, pharmacodynamics, target engagement, pathway modulation, biological effects and, ultimately, clinical activity in early clinical trials. This approach promotes rigorous scientific evaluation and rational decision making in early oncology drug development, culminating in the demonstration of proof of concept. However, success application of this process requires a substantial investment in target evaluation and in vivo preclinical studies. A detailed discussion of the PhAT and its application to the early drug development in oncology therapeutics will be described.
The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression
Authors: Arnav Mehta, Jimmy L. Zhao, Nikita Sinha, Georgi K. Marinov, Mati Mann, Monika S. Kowalczyk, Rachel P. Galimidi, Xiaomi Du, Erdem Erikci, Aviv Regev, Kamal Chowdhury, David Baltimore
Journal: Immunity (2015)
Multiple Cutaneous Melanomas and Clinically Atypical Moles in a Patient With a Novel Germline<i>BAP1</i>Mutation
Authors: Pedram Gerami, Oriol Yélamos, Christina Y. Lee, Roxana Obregon, Pedram Yazdan, Lauren M. Sholl, Gerta E. Guitart, Ching-Ni Njauw, Hensin Tsao
Journal: JAMA Dermatology (2015)

Several kindreds having germline BAP1 mutations with a propensity for uveal and cutaneous melanomas and other internal malignancies have been described in an autosomal dominant tumor predisposition syndrome. However, clinically atypical moles have not been previously recognized as a component of this syndrome, to our knowledge. We describe the first kindred to date with a germline mutation in BAP1 associated with multiple cutaneous melanomas and classic dysplastic nevus syndrome.We describe a 53-year-old man who was initially seen in 2003 with dysplastic nevus syndrome, multiple atypical melanocytic proliferations showing loss of immunostaining for BAP1, and 7 cutaneous melanomas. Germline testing was performed in the proband, his 16-year-old son, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X) in the proband and in his 16-year-old son. CDKN2A and CDK4 genes were wild type. No members of this kindred reported a history of uveal melanoma.To our knowledge, this is the first report of a patient with multiple melanomas, dysplastic nevus syndrome, and an inactivating germline BAP1 mutation. The coexistence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor predisposition syndrome and may confer a greater risk for cutaneous melanomas.
Seeing what you want to see in randomised controlled trials
Authors: R. Holman
Journal: BMJ (2000)

Impact of NHS Direct on demand for immediate care Target communities show poor awareness of NHS DirectEditor-Munro et al found that NHS Direct had no discernible effect on the use of emergency ambulances or accident and emergency departments in the first year of operation, leading to a suggestion that this service may not prove cost effective. 1 The study is limited by an assumption that the population studied had complete awareness of the service.Six months after the introduction of East Midlands NHS Direct we had anecdotal evidence to suggest that many patients attending our accident and emergency department were unaware of the telephone advisory service.Consequently we undertook a survey of 300 consecutive ambulatory patients (or their parents) who referred themselves to the accident and emergency department and had not contacted NHS Direct.We wanted to find out whether they were aware of the service.Altogether 266 (89%) questionnaires were completed, with 166 (62%) patients claiming to have had no previous awareness of NHS Direct.Furthermore, of the 100 patients who were aware of the service, only 36 were aware of the telephone charge while 51 thought that calls were taken by doctors.Only eight "aware" patients, however, said that they would distrust advice given by a nurse, a finding that supports a study by O'Cathain et al. 2 The survey also determined which sections of the community were unaware of NHS Direct.Patients aged over 65 (all 9), patients from ethnic minorities (41/59; 69%), patients from predominantly less affluent postcodes (101/129; 78%), and young men (20/28; 71%) were overrepresented.The survey also found that 240 (90%) patients claimed to have access to a telephone and that 56 (21%) might have been redirected away from our department by NHS Direct.In the light of these findings we would say that NHS Direct has failed to market its existence to those members of the community who frequently access urgent health care.The results of NHS Direct impact studies have consequently been confounded by this oversight.Whether a proper national publicity campaign can improve the impact of this beleaguered service remains to be seen.