tbuckley/cabot-search huggingface dataset:
Abstract 376: P-cadherin overexpression is associated with poor prognosis in pancreatic carcinoma and is regulated by its promoter hypomethylation
Authors: Keita Sakamoto, Katsunori Imai, Shigeki Nakagawa, Hidetoshi Nitta, Hiromitsu Hayashi, Akira Chikamoto, Takatoshi Ishiko, Toru Beppu, Hideo BaBa
Journal: Cancer Research (2014)

Abstract [Background] P-cadherin belongs to the family of classic cadherin, and accumulating evidences shows hat P-cadherin is strongly associated with carcinogenesis and confers alignant phenotype of various cancers. Pancreatic cancer has a poor prognosis, with an overall 5-year survival rate of only 5%. Despite advances in therapy recently, its survival rate still remains poor. This study aimed to analyze P-cadherin expression and its prognostic value in pancreatic carcinoma and to validate the P-cadherin gene (CDH3) promoter methylation status as the mechanism of this gene regulation. [Methods] Seventy-three patients diagnosed with pancreatic cancer were enrolled in this study. P-cadherin expression was examined by immunohistochemistry, and correlated with various clinicopathological features and prognosis. Furthermore, P-cadherin expression and its promoter methylation status were analyzed in pancreatic cancer cell lines. [Results] In pancreatic tissues, 50.7% (37/73) of cases shows a high expression of P-cadherin by immunohistochemical analysis, and high expression of P-cadherin was significantly correlated with gender, posterior tissue invasion and other organs invasion. In multivariate analyses, P-cadherin expression was the independent prognostic factors for disease-free survival (relative risk:2.68, p=0.005). P-cadherin expression was found to be related to its promoter methylation status in pancreatic cancer cell lines. Furthermore, when P-cadherin was down-regulated by specific siRNA, cell migration and invasion were significantly reduced. [Conclusion] These results suggested that expression of P-cadherin is a useful prognostic marker and seems to be important in the malignant behavior in pancreatic cancer. We are now conducting experiments to validate the CDH3 methylation status in the cancerous tissues and their adjacent normal counterpart, and investigating the biological role of P-cadherin in pancreatic cancer. Note: This abstract was not presented at the meeting. Citation Format: Keita Sakamoto, Katsunori Imai, Shigeki Nakagawa, Hidetoshi Nitta, Hiromitsu Hayashi, Akira Chikamoto, Takatoshi Ishiko, Toru Beppu, Hideo BaBa. P-cadherin overexpression is associated with poor prognosis in pancreatic carcinoma and is regulated by its promoter hypomethylation. [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 376. doi:10.1158/1538-7445.AM2014-376
Selection of Elderly Patients for Colorectal Cancer Screening
Authors: Bechien U. Wu
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Preclinical and early clinical study of forodesine hydrochloride (FH) in chronic lymphocytic leukemia (CLL).
Authors: Kumudha Balakrishnan, Ramadevi Nimmanapalli, Michael J. Keating, Farhad Ravandi, Varsha Gandhi
Journal: Cancer Research (2006)

5657  Mammalian purine nucleoside phosphorylase (PNP) deficiency in humans produces a relatively selective depletion of T cells. FH, a potent inhibitor of PNP, was designed based on the transition-state analog structure stabilized by the enzyme. Previous studies demonstrated that FH with dGuo inhibits the proliferation of T-lymphocytes (PNAS 98:4593, 2001). Based on these observations, we conducted a phase I clinical trial of FH in patients with advanced T-cell malignancies. Significant antileukemic activity was correlated with an increase in plasma FH (median 5 μM), dGuo (median 14 μM), and an accumulation of intracellular dGuo triphosphate (dGTP) (Gandhi et al, Blood, Aug 30, 2005 Epub). High accumulation of dGTP in T-cells may be dependant on activity of deoxynucleoside kinases. Deoxycytidine kinase (dCK) is an enzyme that catalyses the conversion of dGuo to its monophosphate, which is then converted to dGTP. Because B-CLL cells have high dCK activity, we hypothesized that they would be sensitive to FH. This postulate was tested in primary CLL lymphocytes during in vitro investigations. Lymphocytes from 11 patients with CLL were incubated with FH (2 μM) in the presence of 10 μM dGuo. These CLL cells showed a wide variation in the endogenous dGTP levels (0.3 μM –4 μM). After incubation with FH and dGuo, cells from 8 of these 11 patients had an elevation in the intracellular dGTP to a median 15 μM at 8 hr (range, 6-119 μM), without any effect on other deoxynucleotides. This increase in dGTP was associated with DNA damage-induced p53 stabilization, phosphoryla tion of p53 at ser15, and increase in the expression level of p21 protein. The dGTP accumulation was related to induction of apoptosis measured by activation of caspase 3 and cleavage of PARP. Based on these results, availability of oral formulation, and to validate these in vitro data during clinical trial, a phase II study of FH in patients with fludarabine-refractory CLL has been initiated. FH is administered orally at a dose of 200 mg/day for 7 days each wk for 4 wks. So far, 2 patients have been enrolled in this protocol, and one has been studied for pharmacodynamic end points prior to treatment and at 24, 48, 72, and 96 hrs after start of therapy. There was a significant increase in the intracellular dGTP, which achieved a plateau of about 80 μM by 3 days. This was associated with a dramatic increase in the loss of mitochondrial membrane potential and induction of apoptosis as measured by annexin V. In conclusion, in vitro studies with FH suggested that CLL cells accumulate dGTP and undergo apoptosis. Furthermore, preliminary results of the pharmacodynamic studies in this first clinical trial of a PNP inhibitor in CLL demonstrate the potential clinical efficacy of oral FH.
Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency
Authors: Irène Netchine, Marie-Laure Sobrier, Heiko Krude, Dirk Schnabel, Mohamed Maghnie, Elisabeth Marcos, Bénédicte Duriez, Valère Cacheux, Arpard v. Moers, Michel Goossens, Annette Grüters, Serge Amselem
Journal: Nature Genetics (2000)
Medicare Wrangling Continues
Authors: Brian Vastag
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
Abstract 3814: FAK inhibition targets nucleostemin, a nucleolar protein, impacting breast cancer spheroid growth and tumor progression
Authors: Isabelle Tancioni, Sean Uryu, Nichol L. G. Miller, Christine Lawson, Christine Jean, Xiao Lei Chen, David D. Schlaepfer
Journal: Cancer Research (2014)

Abstract Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that controls cell proliferation and survival downstream of integrin-matrix receptors. However, under deprivation of anchorage, FAK translocates to the nucleus. The nucleolus, a non-membrane structure within the nucleus, is important in the control of ribosome biogenesis, regulates the sequestration of nuclear proteins, and increased nucleolar size is a marker of aggressive tumors. Nucleostemin, a nucleolar-localized protein, acts to modulate cell cycle progression and anchorage-independent cell growth. Although many drugs have low efficacy on tumor cells cultured in suspension, nanomolar small molecule FAK inhibitor (PF-271 or PND-1186) addition can prevent anchorage-independent growth of tumor cells as spheroids through mechanism(s) that remain unresolved. Here, we show that pharmacological FAK inhibitor (FAK-I) treatment or kinase-dead (KD) FAK re-expression analyses reduced breast cancer (MDA-MB-231 and 4T1-L) anchorage-independent cell growth with a G0/G1 cell cycle block. This was associated with a specific decrease in nucleostemin protein levels. As FAK-KD forms a complex with nucleostemin, and proteasome inhibitor treatment increased nucleostemin levels in FAK-KD cells, FAK-KD may function as a scaffold to facilitate nucleostemin degradation. In orthotopic breast cancer mouse tumor models, oral FAK-I administration or FAK-KD expression resulted in smaller tumors, decreased Ki67 positive cells, and lower levels of tumor-associated nucleostemin. Ongoing experiments are focused on understanding the molecular mechanisms of FAK nucleolar localization and the regulation of nucleostemin protein levels. Our results point to a novel function of FAK in nucleolar function, spheroid growth, and breast cancer progression. Supported by NIH CA102310 and Susan G. Komen for the Cure (KG111237). Citation Format: Isabelle Tancioni, Sean Uryu, Nichol L. G. Miller, Christine Lawson, Christine Jean, Xiao Lei Chen, David D. Schlaepfer. FAK inhibition targets nucleostemin, a nucleolar protein, impacting breast cancer spheroid growth and tumor progression. [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 3814. doi:10.1158/1538-7445.AM2014-3814
Abstract 2523: Mechanism-based inhibitors of HGFA, matriptase and hepsin for breast cancer treatment
Authors: James Janetka, Zhenfu Han, Peter Harris, Scott Wildman
Journal: Cancer Research (2014)

Abstract Hepatocyte Growth Factor Activator (HGFA) is a member of the S1 family of trypsin-like serine proteases. Its biological function is to proteolytically process the inactive single-chain zymogen precursors of the receptor tyrosine kinase ligands HGF (hepatocyte growth factor) and MSP (macrophage stimulating protein) resulting in formation of their active heterodimeric forms which initiate ligand-dependent c-MET and RON kinase cell signaling, respectively. We have discovered the first small molecular weight mechanism-based ketothiazole inhibitors of HGFA. The compounds were evaluated for HGFA, matriptase and hepsin inhibition in a protease competition assay using a chromogenic peptide substrate. We have identified several sub-micromolar inhibitors of HGFA and demonstrate they inhibit conversion of the native pro-HGF and pro-MSP substrates into active heterodimers. Finally, we show that HGFA inhibitors cause a dose-dependent decrease c-MET phosphorylation in invasive MDA-MB-231 breast cancer cells. This investigation provides preliminary validation of HGFA as a novel therapeutic target for breast cancer. These initial peptides serve as templates for lead optimization and the structure-based design of other small-molecule inhibitors. Optimized inhibitors will be used to study the role of HGFA in the regulation of growth factors, kinase receptor activation, cell signaling, invasion, and breast cancer metastasis. Citation Format: James Janetka, Zhenfu Han, Peter Harris, Scott Wildman. Mechanism-based inhibitors of HGFA, matriptase and hepsin for breast cancer treatment. [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 2523. doi:10.1158/1538-7445.AM2014-2523
THE CLINICAL SIGNIFICANCE AND TREATMENT OF PYURIA
Authors: William F. Braasch
Journal: Annals of Internal Medicine (1942)

Article1 December 1942THE CLINICAL SIGNIFICANCE AND TREATMENT OF PYURIAWILLIAM F. BRAASCH, M.D.WILLIAM F. BRAASCH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-6-943 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe physician of today, whatever may be the nature of his practice, must know something about progress in all fields of medicine. Much progress has been made in recent years in knowledge concerning infection in the urinary tract. It is appropriate, therefore, to discuss before internists some of the clinical phases of urinary infection and its treatment. I take it for granted that most patients who come to the internist have symptoms other than those referable to the urinary tract, and that pyuria, when present, is discovered in the course of routine urinalysis. If it were otherwise, the modern sophisticated... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota*Read before the meeting of the American College of Physicians, St. Paul, Minnesota, April 24, 1942. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1942Volume 17, Issue 6Page: 943-951KeywordsUrinary tract infections ePublished: 1 December 2008 Issue Published: 1 December 1942 PDF downloadLoading ...
Congenital pulmonary airway malformation in a 10 year old male adolescent
Authors: Maria Niña Banque
Journal: European Respiratory Journal (2011)

Congenital pulmonary airway malformation (CPAM), more commonly and previously termed congenital cystic adenomatoid malformation is an uncommon anomaly characterized by multicystic lesions due to proliferation of the respiratory bronchioles. This lung anomaly has an incidence of 1:25,000-35,000 and 90% of this number occurs in children below 2 years old. Late-onset CPAM is an infrequent illness and requires a high level of suspicion. It usually presents in the form of repeated infections but very rarely remains to be asymptomatic until its diagnosis. This is a case of a previously healthy, apparently asymptomatic 10 year old male adolescent who had an incidental finding of a pulmonary bulla on chest radiograph taken while he was worked up because of a high grade fever which eventually he was diagnosed of dengue fever. He underwent elective right upper lobe lobectomy and was discharged improved on the 4th post-operative day. The final histopathologic result is consistent with a congenital pulmonary airway malformation, type 1.
Conjunctival effects of a selective nasal pollen provocation
Authors: I. Callebaut, L. Spielberg, V. Hox, S. Bobic, M. Jorissen, I. Stalmans, G. Scadding, J. L. Ceuppens, P. W. Hellings
Journal: Allergy (2010)

To cite this article: Callebaut I, Spielberg L, Hox V, Bobic S, Jorissen M, Stalmans I, Scadding G, Ceuppens JL, Hellings PW. Conjunctival effects of a selective nasal pollen provocation. Allergy 2010; 65 : 1173–1181. Abstract Background: Several clinical and experimental observations suggest that allergen deposition in the nose may partially be responsible for the induction of conjunctival symptoms in allergic rhinitis. The aims of this study were to evaluate the induction of conjunctival symptoms by selective nasal allergen provocation and to assess the feasibility of the different tools for evaluation of conjunctival allergic inflammation. Methods: Grass pollen allergic subjects with rhinoconjunctivitis symptoms during the pollen season ( n = 12) underwent a nasal sham and grass pollen provocation extra‐seasonally. Nasal and conjunctival symptoms were scored using the Visual Analogue Scale (VAS) system at baseline, 15 min, 1 h and 24 h after provocation. In addition to Peak Nasal Inspiratory flow (PNIF) measurements, conjunctival inflammation and vascular congestion were evaluated and histamine and substance P levels in tear fluid were measured. Results: Selective nasal grass pollen provocation induced ocular pruritus, lacrimation and conjunctival vascular congestion. PNIF values correlated inversely with lacrimation ( r = −0.71, P &lt; 0.001) and ocular pruritus ( r = −0.41, P &lt; 0.05). Four out of 11 patients showed a conjunctival eosinophilic inflammation and levels of histamine ( r = 0.73, P &lt; 0.05) and substance P ( r = 0.67, P = 0.05) in tear fluid correlated with conjunctival symptoms. Conclusion: Selective nasal grass pollen provocation induced conjunctival inflammation, ocular pruritus and lacrimation, which correlated with histamine and substance P levels in tear fluid and inversely with the PNIF values. These data show a naso‐ocular interaction in allergic rhinitis and offer objective tools for evaluation of conjunctival inflammation in allergic rhinoconjunctivitis.
A Reference Allergen Preparation of the House Dust Mite D. <i>pteronyssinus</i>, Produced from Whole Mite Culture — A Part of the DAS 76* Study
Authors: Peter Lind, Bent Weeke, Henning Løwenstein
Journal: Allergy (1984)

A D. pteronyssinus , whole culture allergen preparation contained 49 antigens as revealed by crossed immunoelectrophoresis (CIE), using polyspecific rabbit antibodies. Crossed radio‐immunoelectrophoresis (CRIE) with sera from 30 patients revealed nine allergens, antigens 42, X, Y and 23 (in rank order) showing the most frequent and intense IgE‐uptake. Nine antigens originated from the culture medium (human dander + yeast), but none of these gave rise to specific IgE‐uptake. Extremely few and weak reactions were observed in radioallergosorbent (RAST) with 129 sera, using media extracts on the discs. Purified mite body extract (PMB) contained less ag 42 and more ag Y and ag 23 than whole mite culture extract (WMC), whereas an acetone‐extracted mile excreta preparation (AML) contained 5 times more ag 42, but was devoid of ag Y and ag 23. Ag X was present in all preparations. The RAST‐inhibitory potency of PMB was best correlated with the content of ag X. Preparations with properties similar to WMC and PMB were judged as suitable for clinical application.
Abstract 13596: The Prognostic Impact of Spontaneous Coronary Artery Dissection in Younger Female Patients with Acute Myocardial Infarction; Report from Angina Pectoris-Myocardial Infarction Multicenter Investigations in Japan
Authors: Takahiro Nakashima, Satoshi Yasuda, Teruo Noguchi, Seiichi Haruta, Yusuke Yamamoto, Shuichi Oshima, Koichi Nakao, Atsushi Seki, Tatsuro Uchida, Nobuhiro Omura, Junichi Yamaguchi, Yasuyo Taniguchi, Migaku Kikuchi, Kazufumi Tsuchihashi, Kazuo Kimura, Hisao Ogawa, Shunichi Miyazaki
Journal: Circulation (2014)

Introduction: Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial infarction (AMI). It is postulated that the patients with SCAD have good clinical prognosis because they have few coronary risk factors (CRF). However, a recent report studying the US patients with SCAD aged 18~78 years suggested that the rate of recurrence was higher than we expected. In the present study, we therefore have focused on prognostic impact of SCAD on younger female populations. Methods: A total of 16,233 AMI patients registered by 10 institutes from 1991 to 2012 were retrospectively studied. The definition of SCAD was based on the presence of medial dissection or intramural hematoma that was recognized by angiography before any catheter intervention. Results: There were 27 patients diagnosed as SCAD (male/female 1/26, age 45±9 [SD] years). The overall prevalence of SCAD was 0.17% of AMI patients. SCAD developed after physical or emotional stress in 11 patients (40.7%). The left anterior descending artery was involved in 17 patients (62.9%), among whom 4 patients had multi-vessel SCAD (14.8%). Recurrences of SCAD were shown in 9 patients (33.3%). In 4 of 9, recurrence was seen in previously unaffected coronary arteries. In young population of AMI patients (age &lt;50), we compared clinical parameters of SCAD (n=21) with those of Non-SCAD groups (atherosclerotic, n=35). In SCAD group, the number of CRF was significantly lower than in Non-SCAD groups (SCAD, 1.0+/-0.8 vs Non-SCAD, 2.2+/-1.1, P&lt;0.0001). In Kaplan-Meier analysis, younger female AMI patients with SCAD showed significantly higher rate of cardiac event (death, AMI and heart failure) in comparison with those without SCAD (SCAD, 11/21 vs Non-SCAD, 4/34; P=0.0002) during a median follow-up of 1557 (1-8172) days. Conclusions: The present multicenter study demonstrated that younger female AMI patients with SCAD, characterized as minimum accumulation of CRF, seem to be prone to cardiac events.