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1.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献2.
U. Ravens Michael O. Flüß Q. Li Herbert M. Himmel Erich Wettwer Michael Klockow Inge Lues 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(6):733-742
The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4
-thiadiazine-2-on) is a Ca2+-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological
effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca2+-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC50 of Ca2+ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective.
In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative
inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure.
The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to
113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however,
both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly
activating component IKr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling
the effects of the antiarrhythmic agent E-4031 which had been originally used to define IKr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca2+-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the IKr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions
are clearly independent of sterical configuration. The combination of Ca2+-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic
use.
Received: 7 January 1997 / Accepted: 25 February 1997 相似文献
3.
Dr. Erich Traub 《European journal of pediatrics》1937,58(6):769-789
Zusammenfassung Die Auffassung des akuten Gelenksrheumatismus als allergische Krankheit bedingt auch die Deutung der diese Erkrankung begleitenden Hauterscheinungen als allergische Phänomene. Das Erythema annulare und die Urticaria rheumatica werden im Sinne toxisch-allergischer Effloreszenzen erklärt, und der Rheumatismus nodosus diesen beiden Hautveränderungen als periphere hyperergische Entzündung bei einer bestimmten Reaktionslage des sensibilisierten Organismus symptomatologisch und prognostisch nahegestellt. An Hand mehrerer Fälle werden Beobachtungen gebracht, daß die erwähnten peripheren Erscheinungen klinisch ähnliches Geschehen begleiten und somit ihre engere innere Verwandtschaft als wahrscheinlich angenommen. Erythema annulare, Urticaria rheumatica und Rheumatismus nodosus begleiten eine Generalisation der rheumatischen Infektion und treten meist dann auf, wenn die Herzklappen, das Nervensystem oder die serösen Häute ergriffen werden. Alle drei Phänomene haben auch gemeinsame Beziehungen zu Allergieschwankungen im Organismus. In diesem Sinne werden die erwähnten Erscheinungen als Symptome eines allergischen Sekundärstadiums der akuten Polyarthritis aufgefaßt (ähnlich den sekundären Hauteffloreszenzen bei der Tuberkulose) und ihnen als Indikatoren der Generalisation der rheumatischen Noxe, besondere prognostische Bedeutung zugemessen. 相似文献
4.
5.
Walter S Speidl Markus Exner Jasmin Amighi Wolfgang Mlekusch Schila Sabeti Stefan P Kastl Gerlinde Zorn Gerald Maurer Oswald Wagner Kurt Huber Erich Minar Johann Wojta Martin Schillinger 《Journal of endovascular therapy》2007,14(1):62-69
PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates. 相似文献
6.
Über Familiäre Tieflandstruma mit Untersuchungen Über den Deuterium-Oxydgehalt Eines „Kropfbrunnens“
Dr. Hans Ehrenwald Dr. Erich Kolisch 《Journal of molecular medicine (Berlin, Germany)》1937,16(13):462-464
Ohne ZusammenfassungDie Arbeit wurde vom Gesundheitsdepartement des Landesamtes für die Slovakei (Reg.-RatDr. Kohut undDoz. Dr. Tománek) subventioniert, wofür auch an dieser Stelle ergebenst gedankt sei. 相似文献
7.
8.
Claudia E E Noffke Erich J Raubenheimer Ntombizonke J Chabikuli Michael M R Bouckaert 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2007,104(1):101-109
OBJECTIVE: The purpose of the study was to analyze the clinical and radiographic features of central odontogenic myxomas (OM) of the jaws diagnosed over 23 years in a black South African patient sample. STUDY DESIGN: Records of 30 cases of OMs with radiographs of diagnostic quality were retrieved from 52 cases of histopathologically verified OMs from the archives of the Oral Health Center at the University of Limpopo, South Africa. The age, sex, size, location, and radiographic features were compared with the literature. RESULTS: The study consisted of 21 females and 9 males. The correlation between age and size of the tumor was found to be statistically significant (P = .004). Septa were shown to be either reorientated cortical bone or sheets of dense fibrous connective tissue. Indistinct borders mimicked malignancy. The most common radiographic feature was the tennis-racket appearance. CONCLUSIONS: Variations in radiographic presentation make a radiological differential interpretation of OM challenging because the radiographic features overlap with those of other benign and malignant neoplasms. 相似文献
9.
Paul Richter Erich Ebstein M. Gildemeister Mendel Eisner Koenigsfeld Schnabel C. Prausnitz Dessecker Edens Friedberg Oppenheimer Neisser Deusch Königsfeld Simon Lichtenberg Gniesbach Koch Valentin Zinn J. Rothberger Lipschitz A. W. Fischer Nick Henning Frik Euler Holthusen Gaupp Lange Cohn 《Journal of molecular medicine (Berlin, Germany)》1922,1(14):697-703
Ohne Zusammenfassung 相似文献
10.
Erich Engel 《European journal of pediatrics》1937,59(3):359-378
Ohne ZusammenfassungMit 5 Textabbildungen. 相似文献