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Retrospektive Analyse der operativ versorgten Patienten mit Ösophaguskarzinomen und Karzinomen des ösophagogastralen Übergangs der Jahre 2007 bis 2011 an der Universitätsklinik LeipzigSchein, Julia 08 December 2015 (has links)
Jährlich werden in Deutschland 5190 Neuerkrankungen an einem Ösophaguskarzinom registriert. Diese Tumorentität steht bei Männern an 13. Stelle der Häufigkeiten der Krebserkrankungen und bei den Frauen an 17. Stelle. Die Fünfjahresüberlebensrate wird in der Literatur für männliche Patienten mit 11-22% und für Frauen mit 15-20% angegeben. Somit hat das Ösophaguskarzinom nach wie vor eine schlechte Prognose. Ziel der durchgeführten Studie war es, retrospektiv einen Überblick über die Patienten zu erstellen, welche im Zeitraum von 2007 bis 2011 aufgrund eines Ösophaguskarzinoms in der Klinik für Viszeral-, Transplantations-, Thorax-, und Gefäßchirurgie der Universitätsklinik Leipzig operativ behandelt wurden und die gewonnenen deskriptiven Statistiken und Überlebenszeitanalysen mit denen der Fachliteratur zu vergleichen, sowie gegebenenfalls Rückschlüsse zur Therapieoptimierung zu ziehen. Insgesamt lag die mediane Überlebenszeit der Patienten bei 23,7 Monaten (95%KI 13,7-33,6). Die 5-Jahres-Überlebensrate lag bei 30,3%. Zusammenfassend konnten signifikante Überlebensvorteile für das männliche Geschlecht, eine niedrigere lokale Infiltrationstiefe des Tumors (pT), das Fehlen von regionalen Lymphknotenmetastasen im Gesamtkollektiv und in der Gruppe der Adenokarzinome (pN), ein niedrigeres pUICC-Stadium ebenfalls im Gesamtkollektiv und in der Gruppe der Adenokarzinome, eine R0-Resektion und in der Subgruppe der Plattenepithelkarzinom die alleinige Operation ohne neoadjuvante Therapie festgestellt werden.
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Tissue Damage in the Canine Normal Esophagus by Photoactivation with Talaporfin Sodium (Laserphyrin): A Preclinical Study / タラポルフィリンナトリウムを用いた光化学反応における正常犬食道の組織障害について: 前臨床試験Horimatsu, Takahiro 25 November 2014 (has links)
Horimatsu T, Muto M, Yoda Y, Yano T, Ezoe Y, et al. (2012) Tissue Damage in the Canine Normal Esophagus by Photoactivation with Talaporfin Sodium (Laserphyrin): A Preclinical Study. PLoS ONE 7(6): e38308. doi:10.1371/journal.pone.0038308 / 京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12870号 / 論医博第2086号 / 新制||医||1006(附属図書館) / 31588 / (主査)教授 羽賀 博典, 教授 坂井 義治, 教授 平岡 眞寛 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
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A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer. / 食道癌に対する化学放射線療法後または放射線療法後局所遺残再発病変に対するタラポルフィンナトリウムと半導体レーザーを用いた光線力学療法の多施設第II相試験Yano, Tomonori 24 November 2017 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13132号 / 論医博第2136号 / 新制||医||1024(附属図書館) / (主査)教授 溝脇 尚志, 教授 坂井 義治, 教授 山田 泰広 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
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SIX1 maintains tumor basal cells via transforming growth factor-β pathway and associates with poor prognosis in esophageal cancer / SIX1は食道癌においてTGF-β経路を介して悪性基底細胞を維持し不良な予後と関連するNishimura, Takao 23 January 2019 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13219号 / 論医博第2166号 / 新制||医||1033(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 妹尾 浩, 教授 小川 修, 教授 戸口田 淳也 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Design, formulation, characterization, and evaluation of polymeric nanoparticles for local chemotherapySabatelle III, Robert C. 24 May 2023 (has links)
Chemotherapy, whether in combination therapies or as a monotherapy, is the standard treatment for most cancer subtypes. However, these regimens are administered systemically, resulting in poor pharmacokinetics and reducing the overall efficacy. Additionally, most chemotherapeutics, such as paclitaxel (PTX), are hydrophobic necessitating the use of solvents such as polyethoxylated castor oils, which are inherently toxic. Local delivery can mitigate these off-target toxicities while increasing the bioavailability of the payload. This was confirmed in studies by Dr. Paul Sugarbaker, showing that local paclitaxel, in the setting of multimodal therapy, can improve disease-free survival for peritoneal mesothelioma. However, this regimen is associated with high postoperative morbidities, due to the inherent toxicities. These studies establish the validity of local chemotherapy while also confirming the need for a novel delivery platform to allow for safe delivery of higher doses. Nanoparticles (NPs) have long been investigated to enhance chemotherapeutic delivery, increasing bioavailability, prolonging exposure durations, and mitigating off-target side effects. To address the unmet need for a local, sustained drug delivery system, this thesis discusses the formulation and validation of ultra-high loaded polymeric nanoparticles. Specifically, we use a biodegradable polymer comprised of glycerol, CO2, succinic acid, and paclitaxel building blocks, termed poly(1,2-glycerol carbonate)-graft-succinic acid-paclitaxel (PGC-PTX), to form NPs. By additionally entrapping free PTX within the NP core, we create ultra-high loaded “PGC-PTX+PTX NPs”. These NPs encapsulate over 75 wt% PTX, as the mass of the drug is greater than the mass of the carrier, and generate the desired greater initial release, while simultaneously maintaining therapeutic levels long-term due to cleavage of the chemically conjugated PTX over time. These nanoparticles demonstrate efficacy both in vitro and in vivo against murine models of both mesothelioma and metastatic breast cancer. Locally delivery ablates the primary tumor, while also decreasing metastasis to the lungs. This thesis validates the ability to deliver local chemotherapies utilizing the ultra- high loaded nanoparticles safely and effectively.
Mesothelioma and breast cancer are both ideal models for local chemotherapy delivery due to their confined biology. However, more difficult biologies such as tumors in the GI tract suffer from significant fluid movement and peristalsis. Mucoadhesive materials, such as naturally occurring polysaccharides (chitosan and alginate) and positively charged synthetic polymers (poly(allylamine) hydrochloride and poly((2-dimethylamino)ethyl methacrylate) have been investigated for mucosal delivery, yet suffer from high variability and/or toxicities. Amine-functionalized poly-amido-saccharides (AmPASs) offer a unique solution, as they have exquisite control of molecular weight, high cationic charge density, are water soluble, and exhibit low toxicities due to their sugar backbone. Synthesizing an amphiphilic diblock copolymer was accomplished with AmPAS as the hydrophilic portion and poly(lactic acid) as the hydrophobic portion. When placed in aqueous conditions, this polymer forms 200nm diameter particles with a zeta potential of +25mV (mucoNPs). Utilizing a mini-emulsion technique, nanoparticles are loaded with ultra-high levels of paclitaxel, encapsulating both free drug, and drug conjugated to a hydrophobic core polymer (PGC-PTX). The mucoNPs release drug over the span of 28 days, with varying pharmacokinetics depending on encapsulation of free drug, conjugated drug, or both. These NPs rapidly enter OE19 and OE33 esophageal cancer cells, resulting in pronounced cytotoxicity when coupled with the ultra-high paclitaxel loading. Most importantly, the mucoNPs display greater adhesion to porcine gastric mucin and porcine esophageal tissue compared to non-mucoadhesive PEG nanoparticles. This work indicates the need for future in vivo studies with the mucoNPs, and ultimately enhance local mucosal delivery. / 2025-05-24T00:00:00Z
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ROLE OF CHEMOTHERAPY IN IMPROVING DYSPHAGIA FREE SURVIVAL IN PATIENTS WITH ADVANCED ESOPHAGEAL CANCER TREATED WITH HIGH DOSE RATE BRACHYTHERAPYTimotin, Emilia Olimpia 06 February 2015 (has links)
BACKGROUND
High dose rate Intraluminal Brachytherapy (HDRILBT) is one of the most used palliative treatment options for advanced esophageal cancer. The present study evaluates the role of additional chemotherapy in improving dysphagia free survival (DFS) and overall survival (OS) in patients with inoperable advanced esophageal cancer treated with brachytherapy.
MATERIAL and METHODS
132 patients with advanced metastatic esophageal cancer with total or near total dysphagia were given HDRILBT to a dose of 18 Gray (Gy) in 3 fractions on alternate days. Intraluminal brachytherapy alone was performed on 98 patients. 34 patients received Epirubicin, 5-Fluorouracil, and Cisplatin (ECF) chemotherapy regimen after HDRILBT. The mean age of the whole group was 65 years (HDRILBT-71.41, HDRILBT+ECF-59.98; p<0.0001). Male: Female was 101:31 (HDRILBT 72:26; HDRILBT +ECF 29:5; p>0.05). The location incidence was GEJ: Lower Esophagus: Mid Esophagus: Cervical Esophagus 24:81:17:5 respectively; for the whole group HDRILBT- 17:57:16:4; HDRILBT+ECF-7:24:1:1; p>0.05. 78 patients presented with co-morbidities (cardiac) (HDRILBT- 59; HDRILBT+ECF- 19; p>0.05). 74 patients presented with distant metastasis (54 with HDRILBT and 20 with HDRILBT+ECF; p>0.05). The ECOG scores were as follows 0:1:2:3:4 15:52:51:12:2 (HDRILBT- 10:35:41:10:2; HDRILBT+ECF- 5:17:10:2:0; p=0.0014). All patients completed 3 fractions of HDRILBT. 34 patients received additional chemotherapy with ECF regimen. Selection of patients was done by the medical oncologist. Statistical analysis of data was done using the SAS statistical analysis software system. Univariate and multivariate analysis was done using the log rang test.
RESULTS
Patients who received additional ECF were younger (p< 0.001) and with a better performance status than those who received HDRILBT alone (p=0.0014). Mean DFS was higher for patients who had further chemotherapy treatment (232 days) vs. patients who had HDRILBT only (155 days) (p>0.05). The mean OS for HDRILBT + ECF was 266 days (p = 0.0010) compare with HDRILBT alone which was 155 days, when the effect of 10 prognostic factors was analyzed for DFS and OS. Only additional ECF after brachytherapy impacted on DFS while age (p<0.001) and performance status (p=0.0014) impacted on overall survival on univariate analysis. On multivariate analysis tumor length and nodal presentation (p<0.000) impacted on OS. The incidence of stricture and fistulae were similar. Chemotherapy related side effects: gastrointestinal tract (25 patients), neurotoxicities (2) and nephrotoxicities (2) were seen as a result of 5-FU and Cisplatin respectively. 18 patients completed at least 3 cycles of ECF.
CONCLUSION
Additional chemotherapy with ECF after HDRILBT improves the DFS and OS in selected patients with advanced esophageal cancer. These patients tend to be younger with better performance status, small tumor length and nodal metastasis. The incidence of complications is similar with more than 50% patients completing at least 3 cycles of chemotherapy. / Thesis / Master of Science (MSc)
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Differential Expression of Integrin α<sub>3</sub>β<sub>1</sub> and α<sub>6</sub>β<sub>4</sub> Molecules on a Panel of Rat Esophageal Cell LinesChakraborty, Arup Ratan 09 November 2005 (has links)
No description available.
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Prospective Development and Validation of a Malignancy Scoring System During Endobronchial Ultrasound Evaluation of Mediastinal Lymph Nodes for Lung and Esophageal Cancer / Clinical Utility of Lymph Node Features during EBUSHylton, Danielle A. January 2018 (has links)
Background: At the time of endobronchial ultrasound (EBUS) staging, ultrasonographic features can be used to predict mediastinal lymph node (LN) malignancy. Predictive tools have been developed, however they have not gained widespread use due to lack of research demonstrating validity and reliability. We sought to develop a novel predictive tool, the Canada Score, capable of predicting malignancy and potentially guide LN biopsy decision making.
Methods: We prospectively analyzed the ultrasonographic features of LNs from patients with NSCLC. Ultrasonographic features were identified by a single experienced endoscopist, this data was used to develop the Canada Score. Pathological specimens were used as the gold standard for determination of malignancy. Videos were then circulated to endoscopists across Canada, who were also asked to identify ultrasonographic features for each LN. Hosmer- Lemeshow test, logistic regression, receiver operator characteristic (ROC) curve, and Gwet’s AC1 analyses were used to test the performance, discriminatory capacity, and inter-rater reliability of the Canada Score.
Results: A total of 300 LNs from 140 patients were analyzed by 12 endoscopists across 7 Canadian centres. Backwards elimination was used to create a multivariate model. Hosmer-Lemeshow test and ROC curves indicated the model was well-calibrated (chi2=11.86, p=0.1567) with good discriminatory power (c- statistic= 0.72 ±0.042, 95%CI: 0.64-0.80). Beta-coefficients were used to create a simplified score out of four. Evaluation of the tool showed that LNs scoring 3 or 4 had odds ratios of 15.17 (p<0.0001) and 50.56 (p=0.001), respectively for predicting malignancy. A score of 4/4 was associated with 99.59% specificity and a positive likelihood ratio of 22.78. Inter-rater reliability for a score ≥ 3 was 0.81 ± 0.02 (95%CI: 0.77-0.85).
Conclusions: The Canada Score shows excellent performance in identifying malignant LN at the time of EBUS. A cut-off of ≥ 3 has the potential to inform decision-making regarding biopsy or repeat/mediastinoscopy if the initial results are inconclusive. / Thesis / Master of Science (MSc) / During lymph node staging for lung and esophageal cancer, specific features of lymph nodes can be seen. Using diagnostic tools these features can be used to predict whether a lymph node is cancerous or benign. However, many of these diagnostic tools are inaccurate or unreliable. To address this, this thesis aimed to develop a novel diagnostic tool based on lymph node features seen during staging procedures and determine its clinical usefulness and application to the wider lung and esophageal cancer population. This thesis also aimed to use improved methods to develop this diagnostic tool such that patient and clinician experiences would be significantly improved. The results of this thesis may contribute to a reduction in the number of repeat procedures required for patients undergoing staging prior to their treatment for lung and esophageal cancers.
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Design of Confocal Microendscopy for Fallopian Tube Imaging and Detection of Esophageal CancerWu, Tzu-Yu January 2015 (has links)
This work presents several major developments related to a fluorescence confocal microendoscope technology that can provide instantaneous cellular level images from selected depths of tissue inside the human body. The confocal microendoscope systems discussed employ fiber-optic based imaging catheters coupled to custom built slit-scan confocal microscopes. One major new development involves the design, development, and testing of a new flexible confocal microgastroscope (CMG) system for imaging the esophagus. This new system has the potential to aid in the early detection of esophageal cancer. It consists of a new optical scan unit mounted on an endoscopy cart and a new flexible catheter that can be inserted through the instrument channel of a commercial gastroscope. The CMG system has higher spatial resolution and larger field of view than the previous generation clinical confocal microendoscopes in our lab. In addition, the new CMG system can be operated over a greater wavelength range than its predecessor. Central to the CMG system is the design, construction, and testing of a new distal miniature objective that enables high-quality microendoscopy. The miniature objective, built with all glass spherical surfaces, achieves diffraction-limited performance over a 486 to 1000 nm spectral range. The wide achromatic range of this lens allows the CMG system to be used with a variety of contrast agents including agents in the NIR region. In addition, the new miniature objective can be mounted on existing confocal microendoscopes in our lab such as the ovarian clinical confocal microlaparoscope and our laboratory based experimental system. Finally, a new confocal microlaparoscope with an articulating catheter capable of imaging inside the distal portion of fallopian tubes is presented. This instrument is intended to allow the detection of early stage ovarian cancer originating inside the fallopian tube. The new microlaparoscope is compatible with 5 mm trocars and includes a thin 2.2 mm diameter articulating distal tip consisting of a bare fiber bundle and an automated dye delivery system. The distal tip of this new endoscope can be articulated through simple wrist movements and locked in place at a given angle if desired. The thin distal tip and the ability to control the angle of the tip provide the size and flexibility needed to image inside the curved and delicate structures of the fallopian tube. Preliminary imaging results from the new CMG system, the achromatized miniature objective, and the new articulating confocal microlaparoscope are presented to demonstrate the performance and the potential of each system towards the overall goal of in vivo imaging and disease diagnosis.
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Nucleotide sequence variation and expression levels of TP53 in cancers of the upper gastro-intestinal tractBarnard, Desire 03 1900 (has links)
Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: The work presented in this thesis deals with the association between cancers of
the upper gastro-intestinal tract and the tumor suppressor gene, TP53, and can
be divided into three parts: (i) the analysis of the mutational spectrum of TP53
with respect to laryngeal cancer, (ii) the analysis of the mutational spectrum of
TP53 with respect to esophageal cancer and (iii) the analysis of TP53
transcriptional levels in esophageal cancer.
Laryngeal cancer (LC) is the 6th most common cancer in the world and the 2nd
most common respiratory cancer, with approximately 500 000 new cases per
annum detected worldwide. Over the last few years, LC has become
increasingly prevalent within the Coloured Community of the Western Cape. The
mechanisms of tumorigenesis in LC remain unknown, although smoking and
alcohol consumption are considered to be major risk factors. Mutations within
the gene TP53 have been strongly implicated as playing a role in cancer
development, as they are frequently found in several cancer types. We therefore
screened exons 5 - 8 of TP53 for mutations in DNA from tumor biopsies (n=44)
and blood samples (n=42) from Coloured LC patients, using polymerase chain
reaction - single strand conformation polymorphism (PCR-SSCP) analysis and
direct sequencing. Blood samples from a healthy, matched control group (n=40)
were included in the study as controls. Significant correlations were found
between the occurrence of LC and age and smoking, whereas daily meat
consumption was a possible protective factor. In tumor-derived samples,
mutations were found in 3 of the exons under investigation, representing 25% of
the samples. The mutations were unique to the tumor biopsies, indicating a
somatic origin for mutations. The data confirms that the region between codons
175 and 273 of TP53 is a mutational hotspot for cancers in general. This study
reports 6 novel mutations within this same region. Esophageal cancer (EC) has a very high incidence in South Africa, relative to the
rest of the world, and is particularly common amongst the Black Transkei
population. The goal of this study was to determine whether there are
differences in the TP53 mutational pattern observed in the Coloured Western
Cape community as compared to that observed in the Black Transkei community.
This required the analysis of the molecular structure of TP53, specifically exons 5
- 8, in a group of Coloured EC patients (n=44) treated at Tygerberg Hospital,
Cape Town, South Africa. DNA obtained from tumor biopsies and blood (from
patients) as well as from apparently healthy surrounding tissue was screened via
PCR-SSCP and direct sequencing analysis. Only 4 nucleotide changes were
observed from a total of 124 sequences obtained, of which two were novel to
esophageal squamous cell carcinoma. These 4 nucleotide alterations were
found only within the tumor biopsy sample set, representing 9% of the tumors
investigated. This study revealed that the mutational spectrum of TP53 within
the Coloured population of the Western Cape greatly differs from that of the
Black community of the Transkei. This suggests that a different set of etiological
factors are involved in the tumorigenic process for each of these distinct
geographical communities, which is the subject of an epidemiological study
undertaken by the MRC.
The final part of this thesis deals with the quantification and comparison of TP53
transcription levels in esophageal cancer tumor tissue to the TP53 levels in
healthy esophageal tissue obtained from patients from a unique geographical
and ethnic background. The cohort used in this study consisted of Coloured
patients (n=2) treated at Tygerberg Hospital. The LightCycler system was
implemented in order to try to accurately quantify TP53 mRNA levels.
Unfortunately, the desired results were unattainable due to unforeseen difficulties
encountered during the study. These difficulties included the insufficient
preservation of samples for RNA based studies. Several recommendations were
made concerning future similar studies, including an improved planning strategy
as well as the employment of an RNA stabilizing agent. Additionally, a few important contributions were made through this study, including the design and
optimization of TP53 primers specifically intended for future RNA studies. These
primers would enable the identification of the presence of TP53 RNA species as
well as the absence of DNA contamination in a single PCR amplification step.
Other contributions include the development of a well-optimized RNA extraction
method for the extraction of RNA from tough tissues (such as the human
esophageal tissue used in this study). This method makes the extraction of large
quantities of RNA from small amounts of tough tissue types possible.
In conclusion, this study has made a significant contribution to the field of cancer
research, by shedding light on the TP53 mutational spectrum with regards to
laryngeal as well as esophageal cancer in a population unique to the Western
Cape.
The first part of this thesis has been published in Cancer Genetics and
Cytogenetics (Barnard, D., K. Lehmann, E.G. Haal, P.O. van Heiden, and l.C.
Victor. 2003. The spectrum of mutations in TP53 in laryngeal cancer patients
from a high-incidence population shows similarities to many of the known
mutational hotspots. Cancer Genetics and Cytogenetics 145:126-132), of which
a copy can be found in Appendix I. This work has also been presented (by D.
Barnard) at an international conference entitled "Cancer of the Esophagus and
Gastric Cardia: From Gene to Cure", held in Amsterdam, the Netherlands during
the period 13 - 15 December 2002. / AFRIKAANSE OPSOMMING: Die werk wat in hierdie tesis voorgelê word handel oor die assosiasie tussen
kankers van die boonste gastrointestinale weg en die tumor suppressor geen,
TP53, en kan in 3 dele gedeel word, (i) die analise van die mutasiespektrum van
TP53 in laringiale kanker (LK), (ii) die analise van die mutasiespektrum van TP53
in slukderm kanker (SK) en (iii) die analise van die transkripsievlakke van TP53
in SK.
Laringeal kanker (LK) is die 6de algemeenste kanker in die wêreld en die 2de
algemeenste respiratoriese kanker, met "n benaderde 500 000 nuwe gevalle
jaarliks wêreldwyd. Oor die afgelope paar jare het LK "n toenemende probleem
geraak, veral in die Kleurling gemeenskap van die Wes Kaap. Die meganismes
van die tumorvorming in LK is onbekend, alhoewel rook-en alkoholgebruik
vername risiko faktore is. Die voorkoms van mutasies in TP53 is verskeie kere
aangetoon in verskillende kanker tipes en daar word vermoed dat dit "n rol speel
in tumorvorming. In hierdie studie is dus na mutasies in eksons 5 - 8 van TP53
gesoek in tumor biopsie weefsel (n=44) en bloed isolate (n=42) van Kleurling LK
pasiënte d.m.v. polimerase ketting reaksie - enkelstring konformasie
polimorfisme (PKR-ESKP) analisering en direkte volgorde bepaling. Bloed
monsters van "n vergelykbare groep (n=40) is ook in die studie ingesluit as "n
kontrole. Betekenisvolle positiewe korrelasies is gevind tussen die voorkoms van
LK en ouderdom sowel as rook. Daarmee saam is daaglikse vleisinname as
potensiële beskermende faktor gevind. In tumor biopsies is mutasies in 3 van
die ondersoekte eksons gevind, wat 25% van die biopsie monsters
verteenwoordig. Hierdie mutasies is uniek aan die tumor biopsie weefsels en dui
op "n somatiese oorsprong van mutasies. Hierdie bevindinge bevestig dat die
gedeelte tussen kodons 173 - 273 van TP53 "n hipermuteerbare gebied
geassosieer met kankers is. Hierdie studie bevestig 6 nuwe mutasies.
Daar is 'n hoë insidensie van slukderm kanker (SK) in Suid Afrika relatief tot die
res van die wêreld. Hierdie soort kanker word veral gevind by die Swart
populasie van die Transkei. Die doel van hierdie studie was om verskille tussen
die TP53 mutasie patroon van die Kleurling gemeenskap van die Wes Kaap en
die Swart gemeenskap van die Transkei te vergelyk. Hiervoor is die molekulêre
struktuur van TP53, veral eksons 5 - 8, in 'n groep Kleurling SK pasiënte (n=42)
wat behandel is by Tygerberg Hospitaal, Kaapstad, Suid Afrika, geanaliseer.
Analisering is gedoen deur DNS van tumor, bloed en ook oënskynlike gesonde
aangrensende weefsel van dieselfde pasiënte te onderwerp aan PKR-ESKP
analise en direkte volgorde bepaling. Slegs 4 nukleotied veranderings is gevind
in 124 volgorde bepalings, waarvan 2 nuwe veranderings is in SK. Hierdie 4
nukleotied veranderinge verteenwoordig 9% van al die tumors wat ondersoek is
in die studie. Hierdie studie bewys dat die mutasiespektrum van TP53 in die
Kleurling gemeenskap van die Wes Kaap grootliks verskil van die Swart
gemeenskap van die Transkei. Dit impliseer dat verskillende etiologiese faktore
moontlik 'n rol mag speel op die tumorvormingsproses in die 2 afsonderlike
geografiese gemeenskappe. Hierdie is die onderwerp van 'n epidemiologiese
studie wat deur die MNR onderneem word.
Die laaste deel van hierdie tesis handel oor die kwantifisering en vergelyking van
TP53 transkripsievlakke in SK tumor weefsel teenoor TP53 vlakke in gesonde
slukderm weefsel van pasiënte in 'n unieke geografiese en etniese agtergrond.
Die studie populasie in hierdie projek het bestaan uit Kleurling pasiënte (n=2) wat
by Tygerberg hospitaal behandel is. Die "LightCycler" sisteem is gebruik vir die
akkurate kwantifisering van TP53 boodskapper RNS vlakke. Ongelukkig is die
verlangde resultate nie gekry nie as gevolg van onvoorsiene probleme wat
ondervind is tydens die studie. Hierdie probleme sluit in die onvoldoende
preserv RNS studies. Hierdie inleiers maak dit nou moontlik om die teenwoordigheid van
TP53 RNS spesies sowel as die afwesigheid van DNS kontaminasie in een PKR
amplifikasie stap te kan identifiseer. 'n Ander belangrike bydrae is die
ontwikkeling van 'n goed geoptimaliseerde RNS ekstraksie metode vir moeilike
starre weelfsel tipes (soos menslike slukderm weefsel in hierdie studie) en maak
die ekstraksie van groot hoeveelhede RNS uit klein hoeveelhede van moeilik
hanteerbare weefsel tipes moontlik.
Om saam te vat, hierdie studie het betekenisvolle bydraes gemaak tot die veld
van kankernavorsing deur die ontrafeling van die TP53 mutasiespektrum in beide
laringeale sowel as slukderm kanker, in 'n populasie uniek aan die Wes Kaap.
Die eerste deel van hierdie tesis is gepubliseer in Cancer Geneties and
Cytogenetics (Barnard, D., K. Lehmann, E. G. Hoal, P. D. van Heiden, and T. C.
Victor. 2003. The spectrum of mutations in TP53 in laryngeal cancer patients
from a high-incidence population shows similarites to many of the known
mutational hotspots. Cancer Genetics and Cytogenetics 145: 126-132) en 'n
afskrif van die artikel is ingesluit in Appendix I. Hierdie werk is ook voorgedra
(deur D. Barnard) by 'n internasionale kongres getiteld "Cancer of the
Esophagus and Gastric Cardia: From Gene to Cure", wat in Amsterdam,
Nederland gehou is gedurende 13 - 15 Desember 2002
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