tbuckley/cabot-search huggingface dataset:
Catalytic inactivation of capases by legumain confers resistance to multiple apoptotic pathways
Authors: Yuan Liu, Wenyuan Wu, Fang Guo, Zhiyong Chen, Subhash Sinha, Cheng Liu
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4367 

The caspase cascade plays fundamental roles in apoptosis. Here, we describe catalytic inactivation of caspase by legumain as a basic mechanism of cell resistance to apoptosis. Cells over-expressing legumain are highly resistant to both receptor-mediated and mitochondria-mediated pathways of apoptosis. Expression of legumain completely eliminates TNF receptor inducded active caspase 8 in early endosomes. In the early stage of apoptosis, lysosome permeability changes and Legumain is released from the lysosome into the cytoplasm where legumain selectively depletes active caspase 7 and 9 thus preventing activation of downstream caspase 3. In addition, legumain binds directly to cathepsin B and suppresses its auto-activation and activation of BID therefore contributing to preservation of mitochondria membrane potential. Legumain expression is up-regulated in cancer cells and addition of cell permeable Legumain inhibitor (AEPI-5) enhances cancer cell apoptosis in vitro and vivo, suggesting that legumain protects cancer cells against programmed cell death. In conclusion, legumain is responsible for a comprehensive anti-apoptotic mechanism and has significant implications in tumorigenesis as well as autoimmune and neural degenerative diseases.
Abstract 4494: A clinical candidate anti-mesothelin-MMAE antibody-drug conjugate (ADC) for therapy of mesothelin-expressing cancers
Authors: Suzie J. Scales, Nidhi Gupta, Glenn Pacheco, Ron Firestein, Dorothy M. French, Josefa Chuh, Yin Zhang, Leanne Berry, Jenny Bostrom, Elizabeth Luis, Aimee Fourie O'Donohue, Katherine R. Kozak, Sarajane Ross, Mark S. Dennis, Jay Tibbitts, Susan D. Spencer
Journal: Cancer Research (2014)

Abstract Mesothelin (MSLN) is a cell surface glycoprotein widely expressed in a variety of cancers, with prevalence levels by IHC of 85% in ovarian, 75% in pancreatic and 45% in mesothelioma, and normal expression limited to the mesothelia, suggesting it could be an ideal target for antibody-drug conjugate therapy of these cancers. We have generated a high affinity (subnanomolar), humanized antibody to MSLN and conjugated it to auristatin anti-mitotic drugs (monomethylauristatin E and F, Seattle Genetics) via an uncleavable linker (anti-MSLN-mc-MMAF) or a cathepsin-cleavable valine-citrulline linker (anti-MSLN-mc-vc-PAB-MMAE/F) for comparison. The in vivo efficacy obtained in an ovarian transplant model was superior with the anti-MSLN-MMAE ADC. Anti-MSLN-MMAE was specifically internalized by MSLN-expressing cells in vitro, resulting in cell death compared to control ADCs. Pancreatic, ovarian and mesothelioma tumor cell lines endogenously expressing physiological levels of MSLN were identified and established as xenografts in mice. A single dose of anti-MSLN ADC was sufficient to inhibit or shrink tumor growth in models of each of the three indications in vivo, as well as inducing complete regressions in primary human pancreatic models, even those expressing low levels of MSLN typical of most human pancreatic tumors. Additionally, anti-MSLN-MMAE (at suboptimal doses) appeared to synergize with gemcitabine at clinically relevant doses in an HPAC xenograft model. Furthermore, anti-MSLN-MMAE was well tolerated in non-clinical toxicity studies (see accompanying abstract by Gupta et al.). Our data suggest that anti-MSLN-vc-MMAE is a promising clinical candidate for the treatment of several types of mesothelin-positive cancers. Citation Format: Suzie J. Scales, Nidhi Gupta, Glenn Pacheco, Ron Firestein, Dorothy M. French, Josefa Chuh, Yin Zhang, Leanne Berry, Jenny Bostrom, Elizabeth Luis, Aimee Fourie O'Donohue, Katherine R. Kozak, Sarajane Ross, Mark S. Dennis, Jay Tibbitts, Susan D. Spencer. A clinical candidate anti-mesothelin-MMAE antibody-drug conjugate (ADC) for therapy of mesothelin-expressing cancers. [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 4494. doi:10.1158/1538-7445.AM2014-4494
Comparison of cryotherapy with curettage in the treatment of Bowen’s disease: a prospective study
Authors: I. Ahmed, J. Berth-Jones, S. Charles-Holmes, C.J. O’Callaghan, A. Ilchyshyn
Journal: British Journal of Dermatology (2000)

Background In our departments, curettage and cautery (C&C) and liquid nitrogen cryotherapy are the preferred methods of treatment for Bowen's disease (BD). Objectives We aimed to compare these two treatments with regard to efficacy, time to heal, morbidity and recurrence rate. Methods Cryotherapy was performed using a liquid nitrogen spray giving two freeze–thaw cycles, each freeze cycle being maintained for 5–10 s after the formation of an ice ball to the intended margin. Curettage was performed with a conventional disposable curette under local anaesthesia, and electrocautery was then used for haemostasis. Results Eighty lesions in 67 patients (55 female) were analysed. The mean age of the patients was 74 years (range 46–89). The most frequent site was the lower leg, below the knee (n = 59, 74%). The average time taken for complete healing after the procedure was 60 days. The mean size of the lesions was 336 mm2 (range 30–1890). The patients were followed up for a mean of 22 months (range 6–24, median 2 years). In the cryotherapy group (n = 36 lesions), the median time to complete healing was 46 days (range 14–210; mean 69). Twelve lesions took more than 90 days to heal. Infection requiring antibiotics developed in four patients. Thirteen of the treated lesions had recurred by 24 months. In the C&C group (n = 44 lesions), the median time to healing was 35 days (range 14–330; mean 53). Six of the lesions took more than 90 days to heal. Infection developed in two patients. Recurrence occurred in four lesions over the follow‐up period. Considering BD on the lower legs separately, lesions took on average 90 days to heal in the cryotherapy group (n = 23), whereas in the C&C group (n = 36) they took 39 days to heal (P < 0·001). During the procedure and the subsequent 24 h, patients were 10·4 times more likely to report pain of any degree for lesions treated by cryotherapy than by C&C (P < 0·001). Conclusions This study suggests a superiority of C&C over cryotherapy in the treatment of BD, especially for lesions on the lower leg. Curettage of lesions of BD is associated with a significantly shorter healing time, less pain, fewer complications and a lower recurrence rate when compared with cryotherapy.
Sebum excretion rates in mothers and neonates
Authors: C.A. Henderson, J. Taylor, W.J. Cunliffe
Journal: British Journal of Dermatology (2000)

As neonates have a high sebum production compared with 6-month-old babies, we wished to investigate the relationship of sebum production in mother and neonate. The sebum excretion rate (SER) was therefore measured in 10 mothers prenatally, and in each mother and baby as soon after birth as possible, and again 5-12 weeks postnatally. There was a significant correlation between the maternal and neonatal SER perinatally. The perinatal SER in the babies was markedly higher than the postnatal sample. These observations suggest an important role for the maternal hormonal environment on the infant sebaceous glands. There is animal evidence which suggests that the endocrine environment of the neonate influences the sebaceous gland development in puberty, but it is not known whether babies with a high SER are more prone to seborrhoea and acne in later life.
904. Lentiviral Transduction of Wiskott-Aldrich Syndrome (WAS) Deficient, T-Cells Leads to Long-Term and Progressive WAS Protein Expression and Functional Reconstitution
Authors: Monique N. Kierlin, Jonghoe Byun, Ning Lan, Meredith Long, Bruce Sullenger
Journal: Molecular Therapy (2004)

Top of pageAbstract
Previous work has shown that both group I ribozymes and SMaRT™ pre-trans-splicing molecules (PTMs) can be designed to trans-splice into mutant RNA targets and subsequently correct these transcripts. The technology's therapeutic potential hinges on specific and efficient trans-splicing with the intended transcript. We are using quantitative PCR to assess these two parameters with a β-globin target in mammalian cells. Both ribozyme and PTM RNA repair approaches are being used and the results will provide the first direct comparison between these two potential therapeutics. Preliminary efficiency experiments using co-transfection of β-globin target and ribozyme expression vectors into 293T cells followed by QC-RT-PCR resulted in 5–50% trans-splicing levels depending on the promoter used. We are now testing 3' and 5' PTM constructs against the same β-globin target and assessing trans-splicing levels in 293T cells.
The Clinician's Guide to Diagnostic Imaging.
Authors: Zachary D. Grossman, David A. Ellis, Stephen C. Brigham
Journal: Annals of Internal Medicine (1984)

''Contains accurate and essential information on the imaging work-up of many clinical problems. It is best suited for medical students, house staff, and general practitioners who need a quick and easy basic reference when choosing among the various imaging modalities.'' -Radiology ''A practical manual designed for clinicians at any level....Provides a clear working framework.'' -Lancet ''The clarity of the text...is refreshing...It should be read by both referring physicians and imaging specialists.'' This pocket manual provides clinicians, house officers, and medical students with the first practical guide to the most appropriate, cost-effective use of computed tomography, ultrasound, nuclear medicine, and radiography. For each of 42 medical, surgical, and pediatric problems whose workup depends upon imaging, the text presents a logical, step-by-step imaging sequence, outlining the most direct, least invasive route to a diagnosis.
Management of tuberculosis (TB) at a district general hospital: An audit of practice
Authors: Amiera Awad, Mark Juniper
Journal: European Respiratory Journal (2013)

Background  : An initial audit of TB management in 2009 highlighted areas of our service that required improvement. In 2011, a TB Community Nurse Specialist was appointed to address these issues.   Objective  : To re-assess our management of TB in four key areas: microbiological diagnosis, case reporting to Consultant in Communicable Disease Control, contact tracing and appropriate treatment.   Methods  : Retrospective analysis of new cases of TB from January 2011 to December 2011. Eligible patients were identified using departmental and micorbiological databases.   Results  : 30 patients were diagnosed (15 males, 14 females). Mean age was 42 years (range 20-80). There were 19 cases of pulmonary TB, 7 cases of TB lymphadenopathy, 2 pelvic/peritoneal and 2 bone/joint cases of TB. Notification rates improved from 69% to 87% and the number of patients undergoing contact tracing also improved from 69% to 83%. Knowledge of HIV status also improved from 62% to 70%. 77% of patients had a microbiological diagnosis in 2011. This was less than the 100% achieved in 2009. Reasons for this included a patient dying prior to diagnosis and failure to obtain positive culture in a patient who was felt to clinically have TB. 90% of patients were on track to complete treatment and were started on the appropriate regimen.   Discussion  : Initial results from the 2009 audit are likely to be similar to experiences in TB management in other hospitals. This audit clearly demonstrates the benefits of enlisting a Community Team to help ensure that Physicians are meeting the standards for TB management set out by the British Thoracic Society and National Institute for Clinical Excellence.
Abstract 617: Repression of cell proliferation and androgen receptor activity by 2’-hydroxyflavanone in prostate cancer cells
Authors: Atsushi Mizokami, Mitsuo Ofude, Misako Kumaki, Kouji Izumi, Hiroyuki Konaka, Yoshifumi Kadono, Minkyoung Shin, Jian Zhang, Evan T. Keller, Mikio Namiki
Journal: Cancer Research (2014)

Abstract Background: Since androgen-androgen receptor (AR) axis is the main stream for development and progression of prostate cancer, androgen-deprivation therapy (ADT) is conducted as a first line hormonal therapy using medical castration, such as LH-RH agonists, LH-RH antagonist, and antiandrogen for advanced PCa. After an initial response to ADT, however, PCa eventually loses responsiveness to ADT and progresses into castration-resistant prostate cancer (CRPC). Prevention of the development of castration-resistant from hormone-naïve prostate cancer is an important issue in maintaining the quality of life of the patients. We explored the effect of 2’-hydroxyflavanone on proliferation and androgen responsiveness using prostate cancer cell lines. Materials and Methods: To investigate the effect of 2’ -hydroxyflavanone on proliferation, prostate cancer cells were treated with 2’-hydroxyflavanone. Androgen-responsiveness in LNCaP cells was confirmed by luciferase assay after transfection of luciferase reporter driven by prostate specific antigen promoter. To detect androgen receptor (AR) expression, reverse transcriptase polymerase chain reaction and western blot analysis were conducted. Results: 2’ -Hydroxyflavanone inhibited the proliferation of PC-3 and DU145 cells by induction of apoptosis. 2’ -Hydroxyflavanone inhibited the proliferation of LNCaP cells stimulated by androgens and attenuated androgen-responsiveness through down-regulation of AR protein. Conclusion: 2’ -Hydroxyflavanone not only inhibited proliferation of prostate cancer cells, but also repressed androgen-responsiveness, suggesting that it might be an useful agent in preventing recurrence of prostate cancer. Citation Format: Atsushi Mizokami, Mitsuo Ofude, Misako Kumaki, Kouji Izumi, Hiroyuki Konaka, Yoshifumi Kadono, Minkyoung Shin, Jian Zhang, Evan T. Keller, Mikio Namiki. Repression of cell proliferation and androgen receptor activity by 2’-hydroxyflavanone in prostate cancer cells. [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 617. doi:10.1158/1538-7445.AM2014-617
Discordant expression of matriptase, prostasin and their endogenous inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1) is associated with placental labyrinth defects in mice
Authors: Bin Fan, Jane Brennan, Deanna Grant, Franklin Peale, Daniel Kirchhofer
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4378 

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a membrane-associated bi-Kunitz type serine protease inhibitor that regulates cell surface and extracellular serine proteases involved in tissue remodeling and tumorigenesis, such as prostasin, matriptase, hepsin and HGFA. The importance of HAI-1 during early development was demonstrated in HAI-1 deficient mice, which displayed a defective placental labyrinth morphology resulting in embryolethality. In order to gain insight into the underlying molecular mechanisms, we characterized HAI-1 deficient mice (generated by Lexicon Genetics). The homozygous HAI-1−/− embryos died between E10.5 and E11.5 due to attenuated vascularization of the placental labyrinth, consistent with the phenotype reported previously. HAI-1 was expressed in the trophoblast cell lineage in the chorionic placenta, as well as in the branchial arches, otic vesicles and limb buds in the embryo at E9.5. However, the vascularization in the HAI-1−/− embryo appeared normal, indicating that HAI-1 did not regulate vascularization directly. In-situ hybridization using cell type-specific markers showed that the trophoblast cells in the HAI-1−/− placenta failed to form a branching morphology. The expression of glial cell missing-1 (Gcm1), a transcription factor defining trophoblast branching sites, was not altered in the trophoblast cells along the chorioallantoic interface. examination of HAI-1 target protease expression by RT-PCR revealed that matriptase and prostasin were expressed in both wildtype and HAI-1−/− placentas, whereas neither HGFA nor hepsin were detectable. In-situ hybridization experiments showed matriptase and prostasin expression to co-localize with HAI-1 on the chorionic trophoblast cells of the placental labyrinth. Both the localization and expression of the two proteases remained unchanged in HAI-1−/− placentas, indicating that matriptase and prostasin were no longer regulated by their endogenous inhibitor. Since tight regulation of these proteases by HAI-1 is considered paramount for their physiological function, the complete absence of HAI-1 may have resulted in uncontrolled proteolytic activity towards extracellular matrix components detrimental to branching morphogenesis. These results provide new evidence to further support the concept that the matriptase/prostasin/HAI-1 system plays a critical role in physiological and in pathological processes.
Abstract 15951: Palmitate, Not Oleate, is the Preferred Fatty Acid for Cardiac Triacylglycerol Synthesis
Authors: Stephen C Kolwicz, Rong Tian
Journal: Circulation (2014)

Introduction: Previous studies using cell culture models identified cyto-toxic effects of palmitate and that supplementation with oleate was protective by redirecting palmitate into triacylglycerol (TAG) stores. However, other cull culture studies reported that diacylglycerol transferase 1 (DGAT1), the last enzyme in TAG synthesis, demonstrated a preference for oleate. At present, it is not clear whether the supply of exogenous fatty acids (FA) to the heart is differentially allocated into the endogenous TAG pool. Therefore, the purpose of the present study is to examine the influence of palmitate and/or oleate on cardiac TAG incorporation. METHODS/RESULTS: Hearts were isolated from DGAT1-transgenic (DGAT) and control littermates (CON) and perfused in Langendorff mode with a mixed substrate buffer consisting of glucose, lactate, insulin, and FAs. The FA supply was varied with 0.2mM of both labeled (13C) and unlabeled (12C) FAs in 4 different experiments: 1) 13C/12C palmitate; 2) 13C/12C oleate; 3) 13C palmitate/12C oleate; 4) 13C oleate/12C palmitate. The incorporation of 13C palmitate or 13C oleate into the TAG pool was monitored by 13C NMR spectroscopy. In CON hearts (n=3), the incorporation of palmitate was ~65% higher than oleate when the perfusate contained a homogenous supply of FA. This was also observed in DGAT hearts (n=4) although the incorporation of both palmitate and oleate was ~75% higher compared to CON (P &lt;0.05). In the presence of oleate, palmitate incorporation decreased 25-30% in both CON and DGAT hearts. In contrast, oleate incorporation was diminished by ~50% and ~100% in CON and DGAT hearts, respectively, in the presence of palmitate. CONCLUSIONS: These data suggest that when palmitate and oleate are provided in equal concentrations, palmitate is more readily utilized in the synthesis of endogenous TAG stores in the heart. Furthermore, although overexpression of DGAT increases both oleate and palmitate incorporation, the DGAT1 enzyme demonstrates a preference for palmitate. These findings provide insight into the relationship between exogenous FA supply and endogenous TAG dynamics in the contracting heart.
THE CLINICAL VALUE OF THE PRESUMPTIVE KAHN TEST
Authors: Tomas Cajigas
Journal: Annals of Internal Medicine (1933)

Article1 July 1933THE CLINICAL VALUE OF THE PRESUMPTIVE KAHN TESTTOMAS CAJIGAS, M.S., M.D., F.A.C.P.TOMAS CAJIGAS, M.S., M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-7-1-114 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSoon after the development of the standard Kahn reaction in 1923, Dr. Kahn proposed a more sensitive method, which he named the Presumptive test, to be employed as a check on the standard method.1Since that time the standard reaction has become an accepted method throughout the world. The same cannot be said, however, in the case of the presumptive reaction. One finds comparatively few reports in the literature on this reaction, indicating that it is relatively little used. The reason for this may be the fact that serologists who often employ the Kahn with the Wassermann test have the...References1. KAHN RL: Serum diagnosis of syphilis by precipitation; governing principles, procedure and clinical application of the Kahn precipitation test, 1925, Williams and Wilkins Company, Baltimore, Maryland.—The Kahn test, a practical guide, 1928, Williams and Wilkins Company, Baltimore, Maryland. Google Scholar2. MCDERMOTT EB: Presumptive Kahn procedure in syphilis based on 15,000 examinations, Arch. Path., 1929, viii, 661-663.—Kahn presumptive procedure with spinal fluids, Arch. Neurol. and Psychiat., 1930, xxiii, 531-535. Google Scholar3. DAVENPORT KM: Clinical value of Kahn test with spinal fluids, Am. Jr. Syph., 1929, xiii, 570-574.—Clinical value of presumptive Kahn test with spinal fluids, Am. Jr. Syph., 1929, xiii, 575-582. Google Scholar4. Report of Laboratory Conference on Serodiagnosis of Syphilis convened at Montevideo, Geneva, League of Nations Health Organization, 1931. Google Scholar5. WARTHIN AS: Eleventh Pasteur Lecture (November 21, 1930), Institute of Medicine, Chicago. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D. C.*Received for publication January 23, 1933. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byKlassische Serologie der Syphilis 1 July 1933Volume 7, Issue 1Page: 114-119 Issue Published: 1 July 1933 PDF downloadLoading ...
Abnormalities of the Left Temporal Lobe and Thought Disorder in Schizophrenia
Authors: Martha E. Shenton, Ron Kikinis, Ferenc A. Jolesz, Seth D. Pollak, Marjorie LeMay, Cynthia G. Wible, Hiroto Hokama, John Martin, Dave Metcalf, Michael Coleman, Robert W. McCarley
Journal: New England Journal of Medicine (1992)

Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia.
Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research
Authors: Joost Willebrords, Isabel Veloso Alves Pereira, Michaël Maes, Sara Crespo Yanguas, Isabelle Colle, Bert Van Den Bossche, Tereza Cristina Da Silva, Cláudia Pinto Marques Souza de Oliveira, Wellington Andraus, Venâncio Avancini Alves, Bruno Cogliati, Mathieu Vinken
Journal: Progress in Lipid Research (2015)
Quantitative Genetics of Skeletal Variations in the Mouse. I. Crosses Between Three Short-Ear Strains (P, NB, SEC/2)<xref ref-type="fn" rid="fn1">1</xref><xref ref-type="fn" rid="fn2">2</xref>
Authors: E L GREEN
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Quantitative Genetics of Skeletal Variations in the Mouse. I. Crosses Between Three Short-Ear Strains (P, NB, SEC/2) Get access Earl L. Green Earl L. Green Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 607–627, https://doi.org/10.1093/jnci/15.3.607 Published: 01 December 1954