1,721,009 research outputs found
A Review of Non-Invasive Skin Imaging in Merkel Cell Carcinoma: Diagnostic Utility and Clinical Implications
Get PDFBackground/Objectives: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy characterized by its propensity for rapid growth and early regional and distant metastasis. Given its potentially lethal nature, accurate and timely diagnosis of MCC is of utmost importance. This review aims to describe non-invasive imaging methods that can serve as additional tools in the examination of MCC. Methods: In this narrative review, we describe the up-to-date spectrum of non-invasive skin-imaging methods that can serve as additional tools in the examination of MCC based on the available literature. Dermoscopy might enhance the clinical diagnosis of MCC, facilitate differentiation from other benign and malignant tumors, and help optimize the treatment plan. New imaging technologies might also provide useful information at a sub-macroscopic level and support clinical diagnosis. These techniques include high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). Results: Clinically, MCC typically presents as a rapidly growing, red, purple or skin-colored painless and firm nodule. Diagnosis is usually established with histopathological assessment and immunohistochemistry. However, dermoscopy and new imaging technologies might enhance the clinical diagnosis of MCC, facilitate differentiation from other benign and malignant tumors, and help optimize the treatment plan
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Wirkungsmechanismen von Bisphosphonaten in Melanomzelllinien in vitro
No full textTITLE PAGE AND TABLE OF CONTENTS
1\. INTRODUCTION
1
1.1 STRUCTURE PHARMACOLOGY AND MECHANISM OF ACTION OF BISPHOSPHONATES
1
1.1.1 Structure
1
1.1.2 Mechanism of action
4
1.1.3 Pharmacology
7
1.2 USE OF BISPHOSPHONATES IN TUMOR THERAPY
9
1.2.1 In vitro studies of anti-tumor effect of bisphosphonates
10
1.2.2 Antitumor effects of bisphosphonates in animal model
11
1.2.3 Clinical trials
12
1.3 MELANOMA: CLINICAL COURSE, PROGNOSTIC PARAMETERS, THERAPEUTIC MEASURES
14
1.3.1 Clinical course
14
1.3.2 Prognostic parameters
17
1.3.3 Therapeutic procedures
18
1.3.3.1 Surgical therapy
18
1.3.3.2 Elective lymph node dissection (ELND)
19
1.3.3.3 Adjuvant therapy
19
1.3.3.4 Palliative therapy of metastasing melanoma (stage IV)
21
1.3.3.5 Experimental therapeutic approach
22
1.4 OBJECTIVE OF THE STUDY
25
2. MATERIAL AND METHODS
26
2.1 Materials
26
2.1.1 Reagents
26
2.1.2 Cell culture materials
26
2.1.3 Antibodies
27
2.1.4 Cell lines
27
2.1.5 Equipment
28
2.2 Methods
29
2.2.1 Cell culture
29
2.2.1.1 Cell culture media and solutions
29
2.2.1.2 Cultivation of cells
30
2.2.1.3 Freezing and thawing of cells
30
2.2.2 Cell biological techniques
31
2.2.2.1 Measurement of cell proliferation
31
2.2.2.2 Cytoxicity assay
32
2.2.2.3 Detection of apoptosis
33
2.2.3 Protein analysis
35
2.2.3.1 Determination of protein concentration
35
2.2.3.2 SDS-polyacrylamide gel electrophoresis
36
2.2.3.3 Western blotting
40
2.2.3.4 Immunodetection of blotted poroteins
42
2.2.4 Cell fractionation
44
2.2.5 Cell cycle analysis
46
3. Results
49
3.1 Bisphosphonates inhibit melanoma cell proliferation in vitro
49
3.2 Bisphosphonates have no cytotoxic effect in melanoma cells in vitro
51
3.3 Bisphosphonates induce apoptosis in human melanoma cells in vitro
52
3.3.1 Bisphosphonates induce apoptosis in melanoma cells in vitro in time-
dependent manner
54
3.3.2 Bcl-2 overexpression does not prevent bisphosphonate-induced apoptosis
in cultured melanoma cells
55
3.3.3 Effect of short-time exposure of melanoma cells to bisphosphonates
56
3.3.4 Éffect of combination of pamidronate and DTIC in melanoma cells
58
3.3.5 Cytochrome c release is not involved in bisphosphonate-induces apoptosis
in vitro
59
3.4 Effects of bisphosphonates on cell cycle progression in melanoma cell in
vitro
61
4. DISCUSSION
65
SUMMARY
76
5. REFERENCES
78
6. LIST OF PUBLICATIONS
90
ABBREVIATIONS
91
ACKNOWLEDGMENTS
94Bisphosphonates are synthetic pyrophosphate-analogues well established in the
treatement of osteoclast -mediated resorbtive bone diseases including
osteoporosis, Paget's disease and tumor-induced osteolysis. Recent studies
suggest that , beside inhibiting bone resorbtion, bisphosphonates may also
exert a direct antitumor effect, and this class of drugs has been shown to
inhibit proliferation and to induce apoptosis in vitro in different human
tumor cell lines. For the nitrogen- containing sub- class of bisphosphonates,
this anti-neoplastic activity could be related to the inhibition of the
mevalonate pathway and, consequently, of the prenylation of signalling
proteins such as the small GTPases. The present study compared for the first
time the in vitro effects of different bisphosphonates on melanoma cell lines.
Three compounds with different mechanism of action and different
antiresorptive potency were analysed: a non-amino-bisphosphonate (clodronate)
and two amino- bisphosphonates, pamidronate and zoledronate, which is the most
potent antiresorptive agent known to date. Their effects on cell
proliferation, induction of apoptosis and cell cycle progression in the
melanoma cell lines A375 and M186 and in the Bcl-2 overexpressing cell line
A375/ Bcl-2 have been investigated in detail. In this experimental model, it
could be shown that the nitrogen-containing bisphosphonates inhibit cell
proliferation, induce apoptosis and alter cell cycle progression causing
accumulation of cells in the S phase of the cycle. The antiproliferative and
proapoptotic activity of the two compounds in vitro did not correlate well
with their known antiresorptive potency in vivo. Apoptosis induced by the
amino-bisphosphonates was dose and time dependent and acute exposure to
pamidronate over 6h was sufficient to induce apoptosis. The pro-apoptotic
effect of pamidronate and zoledronate was not inhibited by overexpression of
Bcl-2 protein and did not appear to involve of cytochrome c release from the
mitochondria, suggesting that these compounds may stimulate a mitochondria-
independent pathway for inducing apoptotosis. In contrast, the non-amino-
bishophonate clodronate had no effect on cell proliferation, apoptosis
induction or cell cycle progression in melanoma cell lines, even at high
concentrations. In conclusion, amino-bisphosphonates manifest a direct
antitumoral effect on melanoma cells in vitro, and may thus represent a
promising novel class of agents for the treatment/prevention of melanoma
metastasis. Further studies are required, in order to describe the exact
mechanism of action of these compounds, their most effective structures and
ultimately their potential place in new strategies for adjuvant therapy
schedules in malignant melanoma.Bisphosphonate stellen eine Klasse der synthetischen Analoga des endogenen
Pyrophosphats dar, die heutzutage einen breiten klinischen Einsatz in der
Therapie der Osteoklast-vermittelten Knochenstoffwechselerkrankungen wie
Morbus Paget, Osteoporose und Tumorosteolyse haben. Neuere Studien weisen
darauf hin, dass Bisphosphonate ausserhalb ihres osteoprotektiven Effekts,
auch eine direkte antitumorale Wirkung zeigen und antiproliferativ und pro-
apoptotisch in verschiedenen Typen von humanen Tumoren in vitro wirken. Im
Fall der stickstoffhaltigen Bisphosphonate könnte die antineoplasische Wirkung
durch die Hemmung der Enzyme des Mevalonat-Stoffwechselweges erklärt werden,
die zur Inhibition der Prenylierung und dadurch zur Inaktivierung
unterschiedlicher Signalmoleküle führt. In der vorliegenden Arbeit wurden die
Effekte von verschiedenen Bisphosphonaten mit unterschiedlichen
antiresorptiven Wirkungen und Wirkungsmechanismen in Melanom-Zelllinien in
vitro untersucht. Der Einfluss der Aminobisphosphonate Pamidronat und
Zoledronate sowie des Nichtaminobisphosphonates Clodronat auf die
Zellproliferation, Apoptoseinduktion und Zellzyklusprogression in der
Melanomzelllinien A 375, M186 und in der Bcl-2 überexprimierenden Zelllinie A
375/Bcl-2 wurde bestimmt. Es konnte gezeigt werden, dass die
stickstoffhaltigen Bisphosphonate die Zellproliferation hemmen, Apoptosis
auslösen und die Zellzyklusprogression durch eine Akkumulation der Zellen in
der S Phase beeinträchtigen. Diese Wirkungen waren konzentrationsabhängig und
korrelierten nicht mit der klinisch beschriebenen antiresorptiven Potenz der
Medikamente. Die durch stickstoffhaltige Bisphosphonate ausgelöste Apoptose
war zeitabhängig und konnte nach 6 Std Inkubation mit Pamidronat nachgewiesen
werden. Die proapoptotische Wirkung der Aminobisphosphonate lies sich durch
die Überexpression des Proteins Bcl-2 nicht hemmen und schien unabhängig von
der Cytochrome C-Freisetzung zu sein, so dass die Auslösung der Apoptose
mittels Amninobisphosphonate durch einen Mitochondrien-unabhängigen Weg
angenommen werden kann. Im Gegensatz dazu konnte der Einfluss des
Nichtaminobisphosphonates Clodronat auf die Zellproliferation,
Apoptoseinduktion oder Zellzyklusprogression in den untersuchten Zelllinien
nicht nachgewiesen werden. Diese Ergebnisse unterstützen weiterhin die
Hypothese, dass Amino-bzw Nichtaminobisphosphonate über unterschiedliche
Mechanismen ihre Wirkung entfalten können. Zusammenfassend kann festgehalten
werden, dass Aminobisphosphonate eine direkte antitumorale Wirkung in
Melanomzellen in vitro zeigen und dadurch eine interessante Möglichkeit für
die Entwicklung neuer Strategien für die Behandlung bzw. Prävention der
Melanom-Metastasen darstellen
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
