• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 16
  • 13
  • 3
  • 2
  • 1
  • 1
  • Tagged with
  • 37
  • 37
  • 12
  • 7
  • 6
  • 3
  • 3
  • 3
  • 3
  • 3
  • 3
  • 3
  • 3
  • 3
  • 3
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Studies toward the asymmetric total synthesis of mitomycin Cpdn

Chen, Wei, January 2003 (has links)
Thesis (Ph. D.)--Ohio State University, 2003. / Title from first page of PDF file. Document formatted into pages; contains xiii, 266 p.: ill. Includes abstract and vita. Advisor: Robert S. Coleman, Dept. of Chemistry. Includes bibliographical references (p. 208-222).
2

MITOMYCIN C METABOLISM AND INTERACTION WITH SULFUR NUCLEOPHILES IN BONE MARROW, DNA, AND CLONOGENIC TUMOR CELLS (ANTICANCER, ANTIBIOTIC).

Dorr, Robert Thomas January 1984 (has links)
A series of studies in mice were performed to determine the interaction of two sulfur nucleophiles, oral n-acetylcysteine (NAC) and intravenous sodium thiosulfate (Na₂S₂O₃) with the anticancer drug mitomycin C (MMC). Neither nucleophile reduced MMC lethality or hematopoietic toxicity. Both increased the antitumor activity of MMC in mice bearing P-388 and L-1210 leukemias. There was no nucleophile reduction of MMC effects on normal bone marrow stem cells (CFUs) using a murine spleen colony forming assay. In contrast, the nucleophiles significantly enhanced MMC bone marrow toxicity. Three clonogenic human tumor cell lines (HEC-1A endometrial, 8226 myeloma, WiDr colon) were relatively resistant to MMC and the nucleophiles did not increase activity. A human breast cancer cell line (MCF-7) was sensitive to MMC and this activity was blocked by glutathione. Oxygen free radical scavengers did not reduce MMC activity. A novel isocratic high performance liquid chromatography (HPLC) assay (48:52, methanol:0.01M phosphate buffer) using ultraviolet detection at 365 nm was used to characterize MMC-protein binding and murine pharmacokinetics. The k' for MMC was 7.91 and 9.86 for porfiromycin. Peaks were confirmed by mass spectroscopy. MMC was bound 30% to albumin and S-9 microsomal proteins and 60-70% to calf thymus DNA. MMC uptake into mouse bone marrow was enhanced by the nucleophiles and was rapidly cleared from the plasma (half-life 0.5 hours). In vitro MMC metabolism with rat liver S-9 microsomes demonstrated production of a polar eluting, putative MMC metabolite (K' = 4.486, lambda maximum 300 nm). This metabolite was inactive in the in vitro clonogenic tumor cell assay. Finally, molecular pharmacology studies using alkaline DNA elution showed that MMC causes both DNA-DNA and DNA-protein crosslinks. There was no evidence for free radical-induced DNA strand scission by MMC. There was also some evidence of moderate DNA protection with the sulfur nucleophiles.
3

Geschlechts-chromosomale Kopplung der Fanconi Anämie Gene FANCC und FANCG im Hühnergenom und die geschlechtsspezifische Sensibilität der Hühnerzellen gegenüber Mitomycin C / Sex-chromosomal linking of Fanconis Anemia gene FANCC and FANCG in chicken and gender-related sensibility to mitomycin C.

Buwe, Andrea January 2013 (has links) (PDF)
Fanconi Anämie ist eine seltene rezessiv vererbte Erkrankung, deren zu Grunde liegende Enzymdefekte in ein Netzwerk unterschiedlichster DNA-Reparaturproteine eingewoben sind. Phylogenetisch sind uns Vögel relativ nahe verwandt, was sie zu einem guten Modellorganismus jenseits der Säugetiermodelle macht. Eine von Hühnerzellen abgeleitete Zelllinie (DT40) wurde bereits schon breit eingesetzt um die Funktion des FA-Signalwegs zu erforschen. Nachdem auch das Hühnergenom vollständig entschlüsselt wurde, konnten zu fast allen FA-Genen Orthologe gefunden werden. Unter den zahlreichen FA-Genen sind für diese Arbeit vor allem FANCC und -G von Bedeutung, da beide Gene auf dem Z-Geschlechtschromosom des Huhns liegen und eine Inaktivierung des zweiten Z-Chromosoms beim Hahn äquivalent zur X-Inaktivierung beim Menschen nicht stattfindet. Somit sollte es ein ´natürliches´ Gendosisungleichgewicht zwischen den Geschlechtern geben. Im durchgeführten Southern Blot konnte keine geschlechtsspezifisch weibliche Bande (für FANCC und -G) gefunden werden. Somit ist davon auszugehen, dass die FA-Gene C und G ausschließlich auf dem Z-Chromosom lokalisiert sind. Dies wurde auch nochmals mittels FISH bestätigt - beide Gene fanden sich auf dem kurzen Arm des Z-Chromosoms (FANCC zentromernah, FANCG zentromerfern). Aus Studien mit DT40 Zellen ist bereits bekannt, dass FA defiziente Zellen ähnlich wie humane FA-Zellen eine Hypersensitivität gegenüber Substanzen zeigen, die DNA-crosslinks verursachen. In Anlehnung an die humane FA-Diagnostik wurden die neu etablierten embryonalen Fibroblasten mit unterschiedlichen Konzentrationen und Einwirkzeiten von MMC behandelt und die Schäden ausgewertet. In allen Untersuchungen trugen die weiblichen Zellen mehr Schäden davon als die männlichen. Bei niedrigen Konzentrationen zeigte sich dies nur als Trend, bei höheren MMC-Konzentrationen und längeren Einwirkzeiten fanden sich bei fast allen durchgeführten Untersuchungen auch statistisch signifikante Unterschiede. Somit ergibt sich aus dieser Arbeit ein deutlicher Hinweis auf ein funktionelles Ungleichgewicht zwischen Henne und Hahn was die DNA-Reparatur nach Schädigung durch MMC angeht. / Fanconi anemia is a rare recessive disorder whose underlying enzyme deficiencies are woven into a network of various DNA repair proteins. Phylogenetically related birds are relatively close to us, which makes it a good model organism beyond the mammalian models. A cell line derived from chicken cells (DT40) has already been widely used to study the FA pathway. Even after the chicken genome was completely decoded, orthologs could be found for almost all FA genes. Among the numerous FA genes are mainly FANCC and G of importance since both genes are located on the Z sex chromosome of chicken. An inactivation of the second Z chromosome as the inactivation of the x chromosom in human does not take place. Thus there should be a 'natural' imbalance of the gen dose between the sexes. Southern blot showed no gender female band (for FANCC and G). Thus it can be assumed that the FA genes C and G are exclusively localized on the Z chromosome. This was also confirmed by FISH, both genes were located on the short arm of the Z chromosome. From studies in DT40 cells is already known that FA deficient cells, similar to a human FA cell show hypersensitivity to substances that cause DNA crosslinks. Based on the human FA diagnosis, newly established embryonic fibroblasts were treated with different concentrations of MMC and chromosomal the damage was evaluated. In all studies, the female cells contributed more damage than the male. At low concentrations, this was only shown as a trend, at higher MMC concentrations and longer exposure times there was a significant differences. Thus, results from this study, a clear indication of a functional imbalance between hen and rooster in terms of DNA repair after damage by MMC.
4

Studies towards enantioselective synthesis of mitomycins

Gu, Qiangshuai, 顧強帥 January 2013 (has links)
published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy
5

SYNTHESIS AND STRUCTURE-ANTITUMOR RELATIONSHIPS OF 6-SUBSTITUTED MITOSENES (LIPOPHILICITY, BACTERIOPHAGE, QUINONE).

CASNER, MICHAEL LAWRENCE. January 1984 (has links)
Novel mitosenes substituted at the 6-position were synthesized for antineoplastic screening. More than 26 new compounds were made by two synthetic routes. A Nenitzescu-type synthesis provided ethyl 1-acetoxy-2,3-dihydro-5,8-dione-7-methoxy-1H-pyrrolo{1,2-a}indole-9-carboxylate. However, selective reduction of this ester could not be achieved satisfactorily. A more practical route via annelation of a commercially available indole was successful in completing the planned scheme of 6-substituted mitosene congeners. The third ring (pyrrolidine) was added by condensation of ethyl acrylate with ethyl 5-methoxyindole-2-carboxylate. After decarboxylation at position 2, the ketone at position 1 was reduced and acetylated. Then the carbon at the 9 position was introduced by Vilsmeier-Haack formylation and the quinone moiety was synthesized via a nitration, reduction, and oxidation sequence. Subsequently, the aldehyde was most satisfactorily reduced to an alcohol with sodium borohydride and the quinone was regenerated with Fremy's salt. 1-acetoxy-6-desmethyl-7-methoxymitosene was made by forming a carbamate at position 9 by treatment of the 9-alcohol with phenyl chloroformate and displacing the phenoxy group with ammonia. Other 1,6,7-substituted mitosene congeners were made using N-methylcarbamate formation via methyl isocyanate and the 9-alcohol. The 6-chloro and 6-bromo analogs were formed by treatment of the 6-H congener, 1-acetoxy-2,3-dihydro-5,8-dioxo-9-(hydroxymethyl)-7-methoxy-1H-pyrrolo{1,2-a}indole methylcarbamate, with the desired halogen in acetic acid and sodium acetate. The 7-methoxy group could be displaced by ammonia for the 6-bromo compound and by pyrrolidine for the 6-H compound to form respectively the 7-amino-6-bromo and 7-pyrrolidino-6-H 1-acetoxy-2,3-dihydro-5,8-dioxo-9-(hydroxymethyl)-1H-pyrrolo{1,2-a}indole methylcarbamates. The 6-methyl analog (1-acetoxy-7-methoxy-N-methyl-carbamoylmitosene) was made from a previously synthesized precursor. Attempted syntheses of the 6-azido and 6-amino analogs by displacing the 6-bromo substituent with sodium azide were met by gross rearrangement of the resulting adducts. Preliminary antitumor screening against P388 leukemia in mice showed these analogs to be too inactive for use as antineoplastic agents. The 6-methyl substituent was shown to be most potent in bacteriophage induction in E. coli for this series of 6-substituted mitosene analogs.
6

Primary viscocanalostomy versus mitomycin-C augmented trabeculectomy in patients with open-anle glaucoma: a randomized clinical trial

Williams, Susan Eileen IsabellaI 08 September 2009 (has links)
M.Med. Faculty of Health Sciences, University of the Witwatersrand, 2009 / Purpose To compare the outcomes of primary viscocanalostomy with trabeculectomy augmented with mitomycin C (MMC) in black South African patients with primary open-angle glaucoma (POAG). Method A prospective, randomized study was conducted over a four year period. Fifteen black South African patients with bilateral open-angle glaucoma requiring surgery that met the inclusion criteria and gave informed consent to participate in the trial were randomized to receive either a viscocanalostomy or a trabeculectomy with MMC in the first eye requiring surgery. The fellow eye then received the alternate procedure. Patients were followed up for two years postoperatively. Results There were no significant differences between the two surgical groups preoperatively. Twelve eyes in each group were followed for twenty-four months. In both groups the intraocular pressure (IOP) was significantly reduced post-operatively (p < 0.01) and the average number of medications used per eye was significantly reduced (p < 0.02). At twenty-four months, complete success (IOP less than or equal to 18mmHg without glaucoma medication and with no evidence of glaucoma progression) was seen in 75% of eyes undergoing trabeculectomy with MMC that completed the follow up, but in only 33% of eyes undergoing viscocanalostomy (p = 0.0498). Survival curves for both success and qualified success (IOP less than or equal to 18mmHg with glaucoma medications) in the two surgical procedures confirmed the superiority of trabeculectomy with MMC over viscocanalostomy. Conclusion Viscocanalostomy may offer some advantages because it is less invasive, but intraocular pressure control appears to be superior with trabeculectomy with MMC and this continues to be the filtering procedure of choice for the management of glaucoma in black South African patients.
7

Mitomycin C treatment improves pancreatic islet graft longevity in intraportal islet transplantation by suppressing proinflammatory response / マイトマイシンCによる膵島の移植前処置は炎症性反応を抑制することにより経門脈膵島移植の生着期間を延長させる

Yamane, Kei 25 January 2021 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22884号 / 医博第4678号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 羽賀 博典, 教授 椛島 健治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
8

Effekte von Hyper-IL-6 in der Vaccinia-Virus-vermittelten Krebstherapie / Effects of Hyper-IL-6 in vaccinia virus-mediated cancer therapy

Sturm, Julia January 2011 (has links) (PDF)
In der vorliegenden Arbeit wurde ein onkolytisches Vaccinia-Virus unter Ausnutzung seiner Eigenschaft als Vektorsystem mit dem Designer-Zytokin Hyper-IL-6 ausgestattet (GLV 1h90). Bei Hyper IL 6 handelt es sich um ein Fusionsprotein bestehend aus humanem Interleukin-6 und der Liganden-Bindungsdomäne des löslichen Interleukin-6-Rezeptors, welche kovalent über einen flexiblen Linker miteinander verbunden sind. Dieses chimäre Designer-Zytokin erlaubt die Untersuchung von IL-6-Effekten, welche über das IL-6-Trans-Signaling vermittelt werden. Daraus ergibt sich einerseits eine beträchtliche Erweiterung des Wirkspektrums und darüber hinaus weist Hyper-IL-6 sowohl in vitro als auch in vivo eine 100-1000fach verstärkte biologische Aktivität auf. Aufgrund der Tatsache, dass Hyper-IL-6, neben seiner Tumor-inhibierenden Wirkung, eine Vielzahl weiterer Effekte zugeschrieben wird, wurde in dieser Arbeit durch die Kombination des Designer-Zytokins mit einem onkolytischen Vaccinia-Virus nicht nur additive Effekte auf die Tumorregression, sondern darüber hinaus auch mögliche systemisch-vermittelte Hyper-IL-6-Effekte untersucht. Nach intravenöser Injektion von GLV-1h90 in DU-145-Tumor-tragende Mäuse konnte neben der intratumoralen Replikation des Virus und der Expression des Markerproteins Ruc-GFP zusätzlich die Expression des integrierten Designer-Zytokins Hyper-IL-6 im Tumor nachgewiesen werden. Von entscheidender Bedeutung war der zusätzliche Nachweis des Designer-Zytokins in Serum-Proben von GLV-1h90-injizierten Mäusen. Nach einer aktiven Hyper-IL-6-Sekretion von infizierten Tumorzellen, bildet der Transport in die Blutbahn die Voraussetzung für systemisch-vermittelte Hyper-IL-6-Effekte. In dieser Arbeit wurde untersucht, ob sich durch die Überexpression von Hyper-IL-6 im Tumor, zusätzlich zu den onkolytischen Eigenschaften des Vaccinia-Virus, additive anti-Tumor-Effekte ergeben. Eine systemische Injektion von GLV 1h90 bzw. GLV 1h68 in DU-145-Tumor-tragende Mäuse führte zu einer signifikanten Reduktion des Tumorvolumens im Vergleich zu PBS-injizierten Mäusen. Neben Effekten, welche mit Entzündungsprozessen assoziiert sind, wie eine Rotfärbung der Haut, eine signifikanten Vergrößerung der Leber sowie eine massive Stimulation der Akute-Phase-Antwort in der Leber, konnte in GLV-1h90-injizierten Mäusen ein verbesserter Gesundheitszustand auf der Basis einer signifikanten Gewichtszunahme, verbunden mit einer beschleunigten Wundheilung Virus-induzierter Schwanzläsionen, beobachtet werden. Darüber hinaus konnte für Hyper-IL-6 eine Stimulierung der Megakaryopoese im Knochenmark nachgewiesen werden, welche zu einer signifikanten Erhöhung der Thrombozyten-Zahl im Blutkreislauf von GLV-1h90-injizierten Mäusen führte. Es ist von entscheidender Bedeutung anzumerken, dass alle beobachteten systemischen Hyper-IL-6-Effekte eine zeitliche Limitierung aufwiesen, welche sich höchstwahrscheinlich auf die Virus-bedingte Zerstörung Hyper IL 6-produzierender Tumorzellen zurückführen lässt. Dies impliziert zudem, dass eventuelle Komplikationen, welche durch die Überexpression des Designer-Zytokins hervorgerufen werden können, ebenfalls selbstlimitierend sind. Es konnte bereits mehrfach gezeigt werden, dass eine Kombinationstherapie aus onkolytischen Viren und Chemotherapie über synergistische Effekte zu einer signifikant verbesserten Tumorregression führt. Allerdings kommt es in Folge einer Chemotherapie oft zu einer Vielzahl von gefährlichen Nebenwirkungen, da alle schnell proliferierenden Zellen des Körpers betroffen sind. Thrombozytopenie ist eine der am häufigsten vorkommenden Nebenwirkung und beschreibt eine massive Reduktion der Thrombozyten-Zahl im Blut. Im Hinblick auf eine mögliche klinische Anwendung von GLV 1h90 wurde deshalb untersucht, ob in einer Kombinationstherapie mit Mitomycin C, neben einer Verstärkung der therapeutischen Effekte des Virus, basierend auf den beobachteten Hyper-IL-6-Effekten, zusätzlich der Gesundheitszustand der behandelten Mäuse verbessert werden kann. Die Experimente belegen, dass eine Kombination onkolytischer Vaccinia-Virus-Konstrukte mit Mitomycin C zu einer signifikant verbesserten Tumorregression im Vergleich zu den jeweiligen Monotherapien führt. Von bedeutender Relevanz war die Beobachtung, dass in einer Kombinationstherapie von Mitomycin C und GLV-1h90, im Gegensatz zu GLV-1h68, eine signifikante zeitliche Verkürzung der auftretenden Thrombozytopenie erreicht wird. Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass eine systemische Injektion von GLV-1h90 zu einer funktionellen Expression des Designer-Zytokins Hyper-IL-6 führte, welches in der Lage ist eine erfolgreiche Kombinationstherapie aus einem onkolytischen Vaccinia-Virus und dem Chemotherapeutikum Mitomycin C durch eine Reduktion der Nebenwirkungen zusätzlich zu optimieren. / In this thesis, an oncolytic vaccinia virus was armed with the designer cytokine Hyper-IL-6 by recombinant integration (GLV-1h90), exploiting its features as a vector system. Hyper IL-6 is composed of human interleukin-6 (IL-6) and the cytokine-binding domain of its soluble receptor sIL-6R which are bond covalently by a flexible peptide linker. Hyper-IL-6 is a multifunctional cytokine which exhibits not only anti-tumor activity, but also a variety of other effects. For this reason, the combination of the designer cytokine and an oncolytic vaccinia virus was used to study possible improvements regarding tumor regression and more importantly additional systemically mediated Hyper IL-6 effects. In addition to intratumoral replication and visualization of the marker gene ruc-gfp, intratumoral expression of the inserted designer cytokine Hyper-IL-6 could be detected after systemic administration of GLV-1h90 into DU-145-tumor-bearing mice. Of special interest was the presence of hyper-IL-6 in blood serum samples of GLV-1h90-injected mice. Following active hyper-IL-6 secretion of infected tumor cells, the transport into the blood circulation is essential for its ability to induce signal transduction pathways outside the tumor. IL-6 is a pro-inflammatory cytokine which is postulated to exhibit both, tumor promoting as well as tumor inhibiting effects. However, growth or proliferation inhibition of tumors could only be observed after addition of soluble IL-6 receptor and is consequently associated with the IL 6-trans-signaling pathway. Therefore, the thesis deals with the question of whether overexpression of hyper-IL-6 can further enhance the pre-existing oncolytic effects of vaccinia virus. Systemic administration of either GLV-1h90 or GLV-1h68 led to significant tumor regression compared to PBS-treated mice. Comparison of the two viral constructs demonstrated a slightly increased oncolytic activity of GLV-1h90. However, further studies have to clarify to which extend this improvement is resulting from an intratumoral overexpression of hyper IL 6. Following the detection of hyper-IL-6 in the blood circulation as a consequence of GLV 1h90-mediated overexpression in the tumor, functionality of the designer cytokine was analyzed regarding systemically mediated effects. Besides effects which can be associated with inflammatory processes, such as red skin, significant enlargement of the liver as well as enormous stimulation of the acute-phase-response, GLV-1h90-injected mice showed improved healthiness. Health status was assessed by significant gain in body weight associated with accelerated epithelial barrier repair of virus-induced tail lesions. Moreover, it could be demonstrated that Hyper-IL-6 stimulates megakaryopoiesis in the bone marrow, which in turn leads to significantly elevated levels of blood platelets in GLV-1h90-injected mice. It is particularly important to note that all observed systemic Hyper-IL-6 effects occurred only temporarily, which could be explained by virus-mediated oncolysis, reducing the amount of viable Hyper-IL-6 producing tumor cells. The results also implicate that potential complications associated with the overexpression of the designer cytokine can be self-limiting due to the destruction of the virus replication site. Recently, we and others demonstrated that the combination of oncolytic virotherapy and chemotherapy could lead to synergistic interactions that ultimately result in enhanced tumor regression. On the other hand, chemotherapy is often associated with serious side effects, since all fast proliferating cells are affected. Among the most frequently observed adverse effects is thrombocytopenia, which is characterized by a massive reduction of blood platelets. With regard to a possible clinical application of GLV 1h90, combination therapy of the hyper IL 6 encoding vaccinia-virus strain and the chemotherapeutic agent mitomycin C was investigated. Besides therapeutic effects of the virus, the issue was addressed, whether the health status of mice can be improved based on the observed hyper-IL-6 effects. Experimental results clearly demonstrated that combination therapy of mitomycin C and oncolytic vaccinia viruses led to a significantly improved DU-145 tumor regression compared to the respective monotherapies. Of particular importance was the finding that as compared to GLV-1h68, a combination of GLV-1h90 and mitomycin C reduced the time interval during which treated mice suffered from thrombocytopenia significantly. Taken together, this thesis revealed that systemic injection of GLV-1h90 leads to functional expression of the designer cytokine hyper-IL-6, which is able to further optimize the already effective combination therapy of the oncolytic virus GLV-1h90 and the chemotherapeutic agent mitomycin C by reducing of serious adverse effects.
9

„Vergleich zweier Methoden zur intraoperativen Mitomycin C Applikation im Rahmen der Trabekulektomie“ / "Comparison of two methods of intraoperative application of mitomycin C during trabeculectomy"

Panidou, Ermioni January 2012 (has links) (PDF)
Das Ziel dieser Studie war der Vergleich zweier intraoperativer Applikationsmethoden von Mitomycin C (MMC) im Rahmen der Trabekulektomie. Zu diesem Zweck wurde eine retrospektive Analyse vorgenommen. 100 Patienten hatten intraoperativ eine MMC-Applikation mittels Schwämmchen und 100 Patienten mittels Streifen erhalten. Vor dem Beginn der Studie wurden Labormessungen durchgeführt, um die standartisierte Applikationsdosis von MMC zu bestimmen, die sich jeweils in einem Schwämmchen beziehungsweise in 4 Streifen befand. Die Laborergebnissen zeigten eine wirkliche MMC-Dosis von 17,59±3,15µg für die Schwämmchen und von 12,38 ±1,75µg für die Streifen. Überprüft wurde sowohl die absolute (= complete success, ohne lokale Medikation) als auch die relative Erfolgsrate (= qualified success, mit lokaler Medikation). Beide Methoden zeigten eine zufriedenstellende IOD-senkende Wirkung. Für die Erfolgskriterien ≤21+20%, <16, <12 mmHg gab es keinen statistisch signifikanten Unterschied zwischen den zwei Gruppen weder für die absolute noch für die relative Erfolgsrate 1 Jahr nach der Operation. Für das Erfolgskriterium <18 mmHg gab es einen statistisch signifikanten Unterschied bezüglich der relativen Erfolgsrate zugunsten der Streifen-Gruppe. Zwei Erklärungen dafür sind möglich: Zum einen könnte dies mit der höheren Anzahl von Interventionen (Faden-LKs) in der frühen postoperativen Phase zu tun haben. Zum anderen könnte sich die Behandlung eines größeren Areals mit MMC günstiger auf die Vernarbungsreaktion auswirken und damit auch auf die Erfolgsrate. Die Streifen-Gruppe hatte zudem – trotz weniger MMC – eine statistisch signifikant günstigere Sickerkissen-Morphologie 12 Monate nach der Operation. Auch dies ließe sich durch die größere Applikationsfläche von MMC bei den Streifen erklären. Die Schwämmchen-Gruppe hatte statistisch signifikant mehr Hornhaut-Erosiones in der frühen postoperativen Phase. Auf der anderen Seite hatte die Streifen-Gruppe zu dem Zeitpunkt eine bessere relative Erfolgsrate für die Erfolgskriterien <18 und <12 mmHg. Eine mögliche Erklärung wäre, dass die 8x8-mm-Schwämmchen mehr MMC aufnehmen und näher zur Hornhaut appliziert werden. Im Gegensatz zu den Streifen, die über eine breitere Applikationsfläche in der Peripherie weniger MMC abgeben. Möglich wäre aber auch, dass die Erosiones durch die in der Schwämmchen-Gruppe statistisch signifikant vermehrt vorhandenen Voroperationen erklärbar sind. Diese präoperativen Eingriffe können zu Augentrockenheit führen, welche eine Epitheliopathie der Hornhaut begünstigt. Im Bezug auf die Sickerkissen-Needlings und 5-FU-Injektionen hatten die Schwämmchen-Patienten statistisch signifikant mehr Interventionen als die Streifen-Patienten. Dass die Schwämmchen-Gruppe einen statistisch signifikanten höheren Bedarf an 5-FU-Injektionen zeigte, könnte durch die schlechtere Sickerkissen-Morphologie dieser Patienten erklärt werden. Abschließend sei erwähnt, dass die Schwämmchen-Gruppe statistisch signifikant mehr drucksenkende Augentropfen ein Jahr nach der Operation benötigten, damit der erwünschte IOD postoperativ erreicht werden könnte. Zusammenfassend zeigt die Streifen-Gruppe eine tendenziell etwas günstigere Erfolgsrate als die Schwämmchen-Gruppe und benötigte dafür eine geringere Anzahl von postoperativen Interventionen und weniger MMC. Diese Befunde sprechen für die These, dass die Streifen das MMC effektiver applizieren, indem sie eine größere Fläche behandeln. Aufgrund dieser positiven Tendenz hat die Würzburger Klinik den Einsatz der Schwämmchenapplikation eingestellt. / The aim of this study was to compare two methods of intraoperative application of mitomycin C (MMC ) during trabeculectomy . For this purpose, a retrospective analysis was performed. 100 patients received intraoperative MMC application through a sponge and 100 patients through stripes. Before the start of the study laboratory measurements were made to determine the standardized application dose of MMC which was in the sponge or in the 4 stripes. The laboratory results showed a real MMC dose of 17.59 ± 3.15 mcg for the sponge and of 12.38 ± 1.75 mcg for the stripes . The study tested both the absolute ( = complete success , without local medication) and the relative success rate ( = qualified success , with local medication) . Both methods showed a satisfactory IOP lowering effect. For the success criteria ≤ 21 +20 %, < 16, <12 mmHg , there was no statistically significant difference between the two groups for either the absolute or the relative success rate 1 year after surgery. For the success criterion <18 mmHg , there was a statistically significant difference in the relative success rate in favor of the strip Group. Two explanations are possible : At first, this might have to do in the early postoperative period with the higher number of interventions ( suturelysis). Secondly, the treatment of a larger area with MMC could be more beneficial in case of scaring and thus on the success rate . The stripes group - despite less MMC - had a statistically significant favorable bleb morphology 12 months after surgery. Again, this could be explained by the larger application area of MMC through the stripes. The sponge group had statistically significantly more corneal erosions in the early postoperative period . On the other hand, the stripes group had at that point a better success rate for the success criteria had < 18 and <12 mmHg at the time. A possible explanation could be that the 8x8-mm sponge apply more amount of MMC and nearer to the cornea . In contrast to the stripes, that apply less MMC in a wider area in the periphery. The sponge group had statistically significant more prior surgery and this could explain the number of corneal erosions. These preoperative interventions can lead to eye dryness and superficial punctate keratitis. The sponge group had statistically significant more interventions(needlings of the bleb and the subkonjunctival 5-FU injections) than the stripes group. The sponge group showed a statistically significant higher demand for 5-FU injections, which could be explained by the worse bleb morphology. Finally, it should be mentioned that the sponge group needed statistically significant more eye pressure lowering eye drops one year after trabeculectomy in order to reach the desired IOP postoperatively. In summary, the stripes group showed a better success rate than the sponge group and required a smaller number of post-surgical interventions and less MMC. These findings support the theory that the stripes applied MMC effectively over a larger area. Because of this positive trend, the Würzburg university eye hospital uses the application of MMC with stripes.
10

Immunohistochemical analysis of NAD(P)H:quinone oxidoreductase and NADPH cytochrome P450 reductase in human superficial bladder tumours: Relationship between tumour enzymology and clinical outcome following intravesical mitomycin C therapy

Phillips, Roger M., Basu, S., Gill, Jason H., Loadman, Paul M. 27 May 2009 (has links)
A central theme within the concept of enzyme-directed bioreductive drug development is the potential to predict tumour response based on the profiling of enzymes involved in the bioreductive activation process. Mitomycin C (MMC) is the prototypical bioreductive drug that is reduced to active intermediates by several reductases including NAD(P)H:quinone oxidoreductase (NQO1) and NADPH cytochrome P450 reductase (P450R). The purpose of our study was to determine whether NQO1 and P450R protein expression in a panel of low-grade, human superficial bladder tumours correlates with clinical response to MMC. A retrospective clinical study was conducted in which the response to MMC of 92 bladder cancer patients was compared to the immunohistochemical expression of NQO1 and P450R protein in archived paraffin-embedded bladder tumour specimens. A broad spectrum of NQO1 protein levels exists in bladder tumours between individual patients, ranging from intense to no immunohistochemical staining. In contrast, levels of P450R were similar with most tumours having moderate to high levels. All patients were chemotherapy naïve prior to receiving MMC and clinical response was defined as the time to first recurrence. A poor correlation exists between clinical response and NQO1, P450R or the expression patterns of various combinations of the 2 proteins. The results of our study demonstrate that the clinical response of superficial bladder cancers to MMC cannot be predicted on the basis of NQO1 and/or P450R protein expression and suggest that other factors (other reductases or post DNA damage events) have a significant bearing on tumour response.

Page generated in 0.1689 seconds