Rozprawy doktorskie na temat „Cancer treatment”
Kliknij ten link, aby zobaczyć inne rodzaje publikacji na ten temat: Cancer treatment.
Utwórz poprawne odniesienie w stylach APA, MLA, Chicago, Harvard i wielu innych
Sprawdź 50 najlepszych rozpraw doktorskich naukowych na temat „Cancer treatment”.
Przycisk „Dodaj do bibliografii” jest dostępny obok każdej pracy w bibliografii. Użyj go – a my automatycznie utworzymy odniesienie bibliograficzne do wybranej pracy w stylu cytowania, którego potrzebujesz: APA, MLA, Harvard, Chicago, Vancouver itp.
Możesz również pobrać pełny tekst publikacji naukowej w formacie „.pdf” i przeczytać adnotację do pracy online, jeśli odpowiednie parametry są dostępne w metadanych.
Przeglądaj rozprawy doktorskie z różnych dziedzin i twórz odpowiednie bibliografie.
1
Tong, Ka-keung. "Cancer Treatment Centre". Click to view the E-thesis via HKUTO, 1996. http://sunzi.lib.hku.hk/hkuto/record/B31983066.
Pełny tekst źródłaStreszczenie:
Thesis (M.Arch.)--University of Hong Kong, 1996.Includes special report study entitled : Hospital planning study for the cancer treatment centre. Includes bibliographical references. Also available in print.
2
Tong, Ka-keung, i 唐家強. "Cancer Treatment Centre". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31983066.
Pełny tekst źródła
3
Cha, Kyungduck. "Cancer treatment optimization". Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/22604.
Pełny tekst źródłaStreszczenie:
Thesis (Ph. D.)--Industrial and Systems Engineering, Georgia Institute of Technology, 2008.Committee Chair: Lee, Eva K.; Committee Member: Barnes, Earl; Committee Member: Hertel, Nolan E.; Committee Member: Johnson, Ellis; Committee Member: Monteiro, Renato D.C.
4
Горобченко, Неля Георгіївна, Неля Георгиевна Горобченко, Nelia Heorhiivna Horobchenko i T. Loboda. "Progress in cancer treatment". Thesis, Вид-во СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/16753.
Pełny tekst źródła
5
Горобченко, Неля Георгіївна, Неля Георгиевна Горобченко, Nelia Heorhiivna Horobchenko i T. Loboda. "Progress in cancer treatment". Thesis, Видавництво СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/7209.
Pełny tekst źródła
6
Reuille, Kristina M. "Cancer Treatment-Related Fatigue: Psychometric Testing of the Cancer Treatment-Related Fatigue Representation Scale (CTRFRep) in Patients Undergoing Radiation Treatment for Cancer". Thesis, Connect to resource online, 2009. http://hdl.handle.net/1805/2069.
Pełny tekst źródłaStreszczenie:
Thesis (Ph.D.)--Indiana University, 2009.Title from screen (viewed on February 2, 2010). School of Nursing, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Janet L. Welch, Juanita F. Keck, Janet S. Fulton, Barbara Manz Friesth. Includes vitae. Includes bibliographical references (leaves 150-164).
7
Aubert-Jürgens, Ana. "STAT3 inhibitors for cancer treatment". [S.l.] : [s.n.], 2005. http://elib.tu-darmstadt.de/diss/000563.
Pełny tekst źródła
8
Johansson, David. "Bacterial toxins for cancer treatment". Doctoral thesis, Umeå universitet, Medicinsk biovetenskap, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1637.
Pełny tekst źródłaStreszczenie:
Even though anti‐cancer chemotherapy has been continuously improved during the last decades. problems with adverse effects and drug resistance still constitutes a considerable obstacle and sets a demand for new effective treatment options. Tissue homeostasis in multi‐cellular organisms is maintained through intrinsic cell death, apoptosis, which removes unwanted or damaged cells. Disrupted apoptosis is an important factor in tumorgenesis and drug resistance, therefore induction or restoration of apoptotic pathways is also important for the treatment of cancer. Several naturally occurring bacterial toxins have the ability to induce apoptosis and could thus be candidates to complement or improve the therapeutic effect of other anticancer drugs. The bacterial toxins, adenylate cyclase (AC) toxin from Bordetella pertussis, α‐toxin from Staphylococcus aureus and verotoxin‐1 (VT‐1) from Escherichia coli were investigated for their ability to induce apoptosis in different tumor cell lines. Toxin induction of cell death was investigated by cell viability assays, end‐stage apoptosis induction by DNA‐fregmentation (TUNEL) assay. Toxin receptor expression and signal transduction pathways to apoptosis were investigated by flow cytometry, caspase enzyme activity assays and western blot. Immunohistochemistry was used for identification of toxin receptor expression in tumor tissue samples. AC‐toxin was cytotoxic and induced apoptosis in cultured malignant plural mesothelioma (MPM) and small‐cell lung cancer (SCLC) cells. Low‐toxic concentrations of AC‐toxin enhanced cisplatin cytotoxicity and apoptosis in both cell lines. MPM‐cells with acquired cisplatin resistance were more sensitive to α‐toxin than the less resistant parental MPM cell line. A low‐toxic concentration of α‐toxin re‐sensitized resistant MPM cells to cisplatin cytotoxicity by apoptosis induced through the mitochondrial pathway without detectable activation of common up‐stream apoptosis signalling proteins. VT‐1 was highly cytotoxic and induced apoptosis in globotriosylceramide (Gb3) ‐expressing glioma, breast cancer and non‐small‐cell lung cancer (NSCLC) cells but was not cytotoxic to non‐Gb3‐expressing cells. PPMP, an inhibitor of glucosylceramide synthesis which makes exposed cells unable to synthesize Gb3 rendered Gb3‐expressing cells resistant to VT‐1. MPM cells with acquired‐cisplatin resistance expressed Gb3 in contrast to the absent of expression in the less resistant parental cell line. Gb3, could however be up‐regulated by cisplatin in Gb3‐negative MPM‐cells. Presence of a low‐toxic concentration of VT‐1 potentiated cisplatin‐induced cytotoxicity and apoptosis in the cisplatin‐resistance MPM cell line. VT‐1 was a potent inducer of apoptosis, probably via stress‐induced Mitogen‐activated protein kinase (MAPK)‐signaling involving c‐Jun N‐terminal kinase (JNK) and p38, leading to disruption of the mitochondrial membrane integrety, activation of caspase‐9 and ‐3, and ultimately DNA fragmentation and cell death. Gb3 expression was demonstrated in clinical specimens of glioblastoma and breast cancer making these tumor types interesting for further VT‐1 studies. We conclude that bacterial toxins may be used to induce apoptosis in several types of cancer cells. Low concentrations of verotoxin‐1 and α‐toxin may potentially be used to overcome acquired cisplatin‐resistance in cancer patients.
9
Basran, Parminder S. "Optimisation of lung cancer treatment". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq22568.pdf.
Pełny tekst źródła
10
Wirth, Manfred P., i Oliver W. Hakenberg. "Curative Treatment of Prostate Cancer". Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133890.
Pełny tekst źródłaStreszczenie:
The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes availableDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
11
Abusara, Osama. "Neuropeptide antagonists for cancer treatment". Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/neuropeptide-antagonists-for-cancer-treatment(e2f22b9f-f0a7-432d-89c4-7e65a2c71b69).html.
Pełny tekst źródłaStreszczenie:
Small Cell Lung Cancer (SCLC) is an aggressive form of cancer accounting for 25% of lung cancer deaths worldwide. Treatment relies on combination chemotherapy (etoposide and cisplatin or carboplatin) with or without radiation therapy. However, disease relapse and resistance occurs quickly, prompting unmet need for alternative treatment options. One such option is the use of broad-spectrum antagonists, known as Substance P (SP) analogues. Historically, these analogues have not succeeded clinically due to low potency and bioavailability. In this project, novel SP analogues were developed to address these shortfalls. A chemical strategy was designed to synthesise novel short peptides including DMePhe-DTrp-Phe-DTrp-Leu-NH2 (25) as the new lead. Fmoc and Boc D-Trp derivatives with indole nitrogen having substituents (methyl, ethyl, propyl, butyl, pentyl, propargyl, benzyl and tert-prenyl) were made and characterised by 1H and 13C NMR spectroscopy and mass spectrometry (MS). These building blocks were incorporated into the first series of peptides, substituting the D-Trp residue located near the C-terminal of 25, via solid and/or liquid phase procedures. Final products were purified by RP-HPLC to >90% purity and structures verified by MS and/or 1H NMR. Cell viability assays were conducted to evaluate cytotoxicity against two SCLC cell lines: H69 (chemo-naive) and DMS79 (from a patient after treatment). The IC50 values for the D-Trp residue modified peptides were < 5 μM. One of the earliest candidates to emerge from this work was DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2 (33). Subsequently, the most potent peptide was the one bearing D-Trp(N-butyl) (29) with IC50 values of 1.0 μM (H69) and 1.4 μM (DMS79), compared to the lead 25 with IC50 values of 30.7 μM (H69) and 23.0 μM (DMS79). A second series of peptides were produced to optimise 29 by incorporating a D-Trp(N-butyl) residue. The study focused on peptides by (a) modifying the N-terminal D-Trp residue, (b) modifying both D-Trp residues, (c) changing the C-terminal amide to free carboxylic acid, and (d) adding a charged amino acid (arginine) or removing a hydrophobic amino acid (leucine) to additionally aid in solubility. The most potent candidate was found to bear dual D-Trp(N-butyl) residues (35) with IC50 value of 0.6 μM (H69) and 2.3 μM (DMS79). Peptides 29 and 35 were at least 26 times more potent than SP antagonist G (SPG, previously subjected to a Phase I clinical trial), as revealed by in vitro screening in this project. Both sequences induced apoptosis as evident from fluorescence staining. Flow cytometric analysis of 29 with the DMS79 cell line showed that the level of late apoptotic cells rose from 36% at 2 μM to 96% at 6 μM, compared to 25 that exhibited no effect. Efficacy of peptide 33 was separately evaluated in vivo using DMS79 xenografts. A low dose (1.5 mg/kg) was found to reduce tumour growth by ~ 30% (p < 0.05) at day 7, relative to the control group. Higher doses could not be used due to limited aqueous solubility. Furthermore, these peptides were shown to have improved stability. Exposed to neat mouse plasma for 48 hours, 29 and 35 remained intact by 68.5% and 81.0%, respectively, compared to 59.0% for 25 and 35.9% for 33. Complete metabolic stability of 29 and 35 was observed after 3 hours incubation in mouse S9 liver fraction. Aqueous solubility issues were overcome in feasibility studies incorporating 29 into liposomes for future in vivo efficacy testing. Finally, due to the high potency and stability of 29, a liposomal formulation of it may have a profound effect in in vivo efficacy studies against chemo-resistant SCLC.
12
Wirth, Manfred P., i Oliver W. Hakenberg. "Curative Treatment of Prostate Cancer". Karger, 1999. https://tud.qucosa.de/id/qucosa%3A27546.
Pełny tekst źródłaStreszczenie:
The guidelines for the curative treatment of prostate cancer presented by the German Society of Urology are discussed. They are based on the current knowledge of the outcomes of surgical and radiotherapeutic treatment for prostate cancer. Radical prostatectomy is recommended as the first-line treatment for organ-confined prostate cancer in patients with an individual life expectancy of at least 10 years. Radiotherapy can be considered as an alternative treatment modality, although current knowledge does not allow a definite assessment of the relative value of radiotherapy compared to radical prostatectomy. Locally advanced cT3 prostate cancer is overstaged in about 20% and curative treatment is possible in selected cases. Guidelines represent rules based on the available evidence. This implies that exceptions must be made whenever appropriate and that guidelines have to be reviewed regularly as new information becomes available.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
13
Whitehouse, Pauline Amanda. "Integrated individualised treatment of colorectal cancer". Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446884/.
Pełny tekst źródłaStreszczenie:
Introduction: Advanced colorectal cancer (CRC) has a poor prognosis with a 5-year survival of only 5% despite treatment with chemotherapeutic agents. The ATP- Tumour Chemosensitivity Assay (ATP-TCA) has been used to demonstrate heterogeneity of chemosensitivity between tumours of the same tissue type, but this has been difficult to establish in colorectal cancer due to infection of cells in culture. Methods: The ex vivo ATP-TCA was modified with antibiotics for use in CRC, and with immunohistochemistry and quantitative RT-PCR, has been used to assess the chemosensitivity and resistance of CRC tumour-derived cells. Results: (a) The addition of 2.5 mug/ml amphotericin B and 1 mug/ml metronidazole to culture media did not effect the cytotoxicity of all drugs tested on SK-MEL-28 melanoma cell lines. (b) The metabolite of irinotecan, SN38, was found to be inactive in the ATP-TCA (c) The ATP-TCA was performed on 71 CRC samples, 58 of which were evaluable (82%). There was considerable heterogeneity for individual samples and drugs tested. (d) Mitomycin C + gemcitabine was the most effective combination in 78% of specimens, with all but one sample showing sensitivity. The synergistic effect between these two drugs was not found to be schedule-specific. (e) Molecular studies determined the expression of a number of molecular targets which were correlated with the ATP-TCA results. The only correlation found was between positive staining for topoisomerase I and sensitivity to irinotecan. (f) Using qRT-PCR it was found that cyclo-oxgenase2 is up-regulated by short-term exposure to 5-fluorouracil (3-fold), but down-regulated by irinotecan (2.5-fold). Conclusion: The results show that it is possible to perform the ATP-TCA on CRC tumour-derived cells with a high evaluability rate. The changes in gene expression after short-term drug exposure have important implications for the use of sequential therapy in the treatment of colorectal and cancers.
14
Li, Pei-Xiang. "Molecular approaches to breast cancer treatment". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0023/NQ50092.pdf.
Pełny tekst źródła
15
Abraham, J. E. "The pharmacogenetics of breast cancer treatment". Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.595327.
Pełny tekst źródłaStreszczenie:
The core project in this thesis is the translational study PGSNPS, which aimed to investigate the pharmacogenetics of breast cancer chemotherapy in the adjuvant setting. Blood or saliva samples were collected from over 2300 patients, who were recruited during a 4 year period. The trial design was adapted to a GWAS approach. The combination of high quality genotype data and detailed clinical information allows this collection to be a useful resource not only for pharmacogenetic analysis but for investigation of prognosis and susceptibility in future analyses. I also examined the role of candidate gene analysis in the identification of variants associated with survival and susceptibility analysis. Candidate gene analysis of the prostaglandin pathway investigated the potential role of key genes in this pathway and their association with breast cancer susceptibility and survival. There was little evidence that common variants are associated with modest risks of breast cancers and no evidence for association with overall survival (OS) for any tagSNP studied. The metabolic enzyme cytochrome P450 2D6, (CYP2D6), is involved in the metabolism of tamoxifen to its active metabolites. I examined the role of the CYP2D6 gene in breast cancer specific survival (BCSS) and OS in tamoxifen treated breast cancer patients. One putative poor metaboliser (PM) CYP2D6*6 may be associated with decreased BCSS and OS, but the prior probability of such an association is low. All other putative functional variants showed no association. The evidence from this study does not support implementation of routine CYP2D6 testing pre-treatment to guide choice of hormone therapy.
16
Cunningham, David. "Gastric cancer : natural history and treatment". Thesis, University of Glasgow, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293449.
Pełny tekst źródła
17
Linardakis, Emmanouela. "Developing immunotherapy strategies for cancer treatment". Thesis, Open University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396819.
Pełny tekst źródła
18
Ullal, Adeeti (Adeeti Vedantham). "Micro and nanotechnology for cancer treatment". Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/83968.
Pełny tekst źródłaStreszczenie:
Thesis (Ph. D. in Biomedical Engineering)--Harvard-MIT Program in Health Sciences and Technology, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 92-101).
Cancer is responsible for over 7.6 million deaths worldwide; the majority of patients fail to respond to drugs or become resistant over time. In order to gain a better understanding of drug efficacy in patients, we developed three diagnostic technologies to address limitations in sample acquisition and improve the scale and sensitivity of current cancer diagnostic tools. In the first section, we describe a hybrid magnetic and size sorting microfluidic device that isolates rare circulating tumor cells from peripheral blood. The self-assembled magnetic sorter creates strong magnetic fields and effectively removes leukocytes tagged with magnetic nanoparticles. The size sorting region retains the remaining cells in single cell capture sites, while allowing small red blood cells to pass through 5pm gaps. The device achieves over 103 enrichment, up to 96% recovery of cancer cells and allows for on-chip molecular profiling. In the second section we use a magnetic nanoparticle decorated with small molecule drugs to assay target expression and drug binding in mock clinical samples of cancer cells spiked into whole blood. Specifically, we modify a PARP inhibitor (Olabarib) and conjugate it to a dextran coated iron oxide nanoparticle. We measure the presence of the drug nanosensor based on the change in T2 relaxation time using a miniaturized, handheld NMR sensor for point-of-care diagnosis. In the final section, we detail a photocleavable DNA barcoding method for understanding treatment response via multiplexed profiling of cancer cells. We validate our method with a 94 marker panel on different cell lines with varying treatments, showing high correlations to gold standard methods such as immunofluorescence and flow cytometry. Furthermore, we demonstrate single cell sensitivity, and identify a number of expected biomarkers in response to cell treatments. Finally, we demonstrate the potential of our method to help in clinical monitoring of patients by examining intra- and inter-patient heterogeneity, and by correlating pre and post-treatment tumor profiles to patient response. Together, we show how these technologies can help overcome clinical limitations and expedite advancements in cancer treatment.
by Adeeti Ullal
Ph.D.in Biomedical Engineering
19
Kho, Sunn Sunn Patricia. "Optimising Adjuvant Treatment for Colorectal Cancer". Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/9470.
Pełny tekst źródłaStreszczenie:
The aim of the thesis is to optimize adjuvant treatment for colorectal cancer (CRC) patients. CRC treatment has improved over the decades resulting in improved overall survival of patients. The 5-year overall survival for CRC in the US between 1975 – 1979 was 50.6% while by 2004; it had improved to 65.9%. This is largely due to improvements in surgical and radiation techniques, screening initiatives and more effective chemotherapy drugs. However, when compared to the 5-year overall survival for breast cancer in 2004 of 89.9% (SEER data), it is clear that further improvements in CRC treatment are needed. This thesis evaluated different approaches to further improve overall survival rates and to reduce the acute and late toxicities associated with adjuvant treatment. One of the approaches was to attempt to personalize treatment for colorectal cancer patients using prognostic and predictive biomarkers. The group of patients selected for review were Stage C colon and rectal patients as the risk of recurrence is very high and the 5 year overall survival remains poor at 28% for colon cancer and 33% for rectal cancer. In this era of personalized medicine, the hope is to be able to tailor treatment regimens according to the patient and disease stage to reduce toxicity and improve efficacy. A retrospective analysis of the survival of Stage C rectal cancer patients in a public teaching hospital who received adjuvant chemotherapy after a curative resection was conducted to evaluate the role of adjuvant chemotherapy alone without radiotherapy. An original research study evaluating the role of a candidate marker, s100A4 in the treatment of Stage C colon cancer was also performed to evaluate the possible role of a new candidate biomarker s100A4 in the prognostication of Stage C colon cancer.
20
Chen, Zong-Ping. "Three-dimensional hyperthermia cancer treatment simulation". Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184852.
Pełny tekst źródłaStreszczenie:
A simulation program to study the three dimensional temperature distributions produced by hyperthermia in anatomically realistic inhomogeneous tissue models has been developed. The anatomical data for the inhomogeneous tissues of the human body are entered on a digitizing tablet from serial CT scans. The program not only predicts temperature distributions in regions dominated by blood perfusion (with large number of small capillaries), but it can also predict the temperatures inside of and at the vicinity of large blood vessels. The program can be used for different power deposition patterns from various heating modalities, but they must be calculated independently. In this study, the author's attention has been focused on ferromagnetic implants. The program has been used to comparatively evaluate two and three dimensional simulations in a series of parametric calculations based on simple tissue models for both uniform power deposition and ferromagnetic implants. The conclusions drawn from these studies are that two dimensional simulations can lead to significant errors in many situations, and therefore three dimensional simulations will be necessary for accurate patient treatment planning. The conclusion from the geometrically simple model is substantiated by the results obtained using the full 3D model for actual patient anatomical simulations. The program has also been used for several parametric studies. The effect of the thermal conductivity used in the models on the temperature field has been studied, and the results show that its value in the range of 0.4 to 0.6 W/m/°C (valid for most soft tissues) has only a slight effect on the resultant temperature fields. The heating ability of the ferromagnetic implants has also been investigated for different blood perfusions. The effects of the Curie point of the ferromagnetic seeds, and seed spacing are also studied. Finally, the impact of large blood vessels on the resultant temperatures are studied, and the results show that the effect is dramatic and therefore it must be included in the simulations in order to predict accurate temperature fields. Finally, the program has been used to analyze a previously performed dog experiment, and a previously performed clinical treatment. A comparison between the predicted temperatures and the measured ones show that good agreement has been achieved for the clinical treatment, but not for the dog experiment. These results are studied in detail, and the conditions under which this program can be used as a hyperthermia patient treatment planning tool is discussed.
21
Ebeid, Kareem Atef Nassar. "Nanoparticles for targeted treatment of cancer". Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6567.
Pełny tekst źródłaStreszczenie:
Cancer is the second leading cause of death in the USA, following cardiovascular disease. Treating cancer using conventional therapies is associated with low response rates and high toxicity, because these therapies usually lack specific tumor accumulation. Loading anticancer drugs into intelligently designed polymeric nanoparticles (NPs) can serve in delivering these drugs specifically to the tumor site, thus boosting their efficacy and reducing any associated off target toxicity. Targeting NPs to the tumor site can occur through either passive or active means. In passive targeting, NPs of specific size and surface characteristics can exploit the tumor’s erratic vasculature and occluded lymphatic drainage to extravasate the systemic circulation and accumulate preferentially at the tumor site. Active targeting mandates grafting the surface of NPs with a ligand that specifically interacts with a protein expressed at higher levels at the tumor site, in comparison to elsewhere in the body. In the current research, we independently investigated the utilization of passive and active targeting strategies to treat aggressive forms of cancer.
Initially, passively targeted poly(lactic-co-glycolic acid) (PLGA) NPs to treat aggressive forms of endometrial cancer (EC) were investigated. A novel combination of soluble paclitaxel (PTX), a first line chemotherapy for EC, and soluble BIBF1120 (BIBF, nintedanib), an antiangiogenic molecular inhibitor, was first tested against three EC cell lines bearing different p53 mutations. The results showed that only EC cells with loss of function (LOF) p53 were sensitive to the combination therapy, indicating the potential of this combination to engender synthetic lethality to PTX. Next, NPs loaded with PTX were investigated with respect to the impact of varying the polymer lactic acid to glycolic acid ratio and the surfactant type on the major physicochemical properties of the prepared nanoparticles, drug loading, cellular uptake, cytotoxicity, and drug release. The optimum formulation was then loaded with BIBF and the combination of independently loaded passively targeted NPs were further evaluated for in vivo activity against a xenograft model of LOF p53 EC. The combination of independently loaded NPs exhibited the highest reduction in tumor volume and prolonged survival when compared to soluble PTX, PTX NPs or untreated control. These data highlight this specific combination of NPs as a novel promising therapy for LOF p53 EC.
In a second study, the use of actively targeted NPs to treat liver cancer was explored. In this study, a combination of small interfering RNA (siRNA) against astrocyte elevated gene-1 (AEG-1), and all-trans retinoic acid (ATRA) was investigated as a new therapy for hepatocellular carcinoma (HCC). AEG-1 is a highly expressed oncogene that is directly involved in HCC progression and aggressiveness, in addition to reducing the ability of retinoic acid to induce apoptosis in HCC cells. First, a new conjugate was synthesized that was capable of delivering siRNA selectively to HCC cells, using galactose as a targeting moiety. The conjugate was prepared by linking poly(amidoamine) (PAMAM) dendrimers, polyethylene glycol (PEG) and lactobionic acid (Gal, disaccharide containing galactose) (PAMAM-PEG-Gal). We confirmed the synthesis of the conjugate using 1H-NMR, Mass spectrometry and Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry. Next, nanoplexes of the synthesized conjugate, PAMAM-PEG-Gal, and AEG-1 siRNA were prepared. Nanoplexes were further characterized for their size, surface charge, morphology, and electrophoretic mobility to identify the optimum complexation ratio between PAMAM-PEG-Gal and the siRNA. Then, mice bearing orthotopic luciferase expressing HCC cells were treated with the optimum nanoplex formulation. Results showed that a combination of AEG-1 nanoplexes and ATRA results in a significant reduction in luciferase expression, reduced liver weight, lower AEG-1 mRNA levels and increased apoptosis, when compared to utilizing nanoplexes with silencing control (siCon), siCon+ATRA, or AEG-1 nanoplexes alone. The results indicate that the combination of liver-targeted AEG-1 nanoplexes and ATRA may be a potential treatment for aggressive HCC.
These data place targeted NPs as a promising efficient delivery system for cancer treatment.
22
Jakobi, Annika. "Evaluation of proton treatment strategies for head and neck cancer and lung cancer based on treatment planning studies". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-207484.
Pełny tekst źródłaStreszczenie:
The clinical introduction of proton therapy requires an extensive analysis of its benefits compared to conventional radiotherapy and a detailed analysis of possible uncertainties which might have serious consequences for patient treatment. In the first part of the presented thesis, the expected toxicities were evaluated for a treatment of head and neck cancer patients using a biologically adapted dose escalation schedule with photon and proton therapy. The feasibility of the dose escalation schedule could be demonstrated for both photon and proton therapy, since only a small increase in toxicity risk occurred for most toxicities. However, the expected toxicity risks were in most cases smaller with proton therapy. Furthermore, a higher benefit was found for patients with primary tumour locations in the upper head and neck area, who thus might be preferably referred to proton therapy. In the second part of this thesis, an extensive analysis of the impact of tumour motion in lung cancer treatment with active-scanning proton therapy was conducted. It could be shown, that dose degradations were small for tumour motion amplitudes below 5 mm. Parameters like the target volume concept, the optimisation approach, changes in the motion pattern and application sequence times had additional impact on the dose degradation. However, their magnitude was patient specific. Since not all parameters can be assessed before treatment, e.g. the motion pattern during treatment, prospective estimations should be supplemented by retrospective analysesDie Einführung der Protonentherapie in die klinische Praxis erfordert umfassende Analysen ihrer Vor- und Nachteile im Vergleich zur konventionellen Photonentherapie sowie detaillierte Untersuchungen der Auswirkungen von Unsicherheiten in der Therapieapplikation. Im ersten Teil der vorliegenden Arbeit wurden die zu erwartenden Nebenwirkungen bei der Behandlung von Patienten mit Kopf-Hals-Tumoren mit einem biologisch-adaptierten Fraktionierungsschema inklusive Dosiseskalation mit Photonen- und Protonentherapie evaluiert. Dabei konnte gezeigt werden, dass die Dosiseskalation sowohl mit Photonen- als auch Protonentherapie angewandt werden kann, da die Wahrscheinlichkeit für das Auftreten von Nebenwirkungen in den meisten Fällen kaum erhöht wurde. Weiterhin wurden die Nebenwirkungswahrscheinlichkeiten mit der Protonentherapie im Vergleich zur Photonentherapie reduziert. Dies war vor allem für Patienten mit Tumoren im oberen Kopf-Hals-Bereich der Fall. Diese könnten daher bevorzugt zur Protonentherapie überwiesen werden. Darüber hinaus wurde im zweiten Teil der Arbeit eine umfassende Analyse des Einflusses der Tumorbewegung auf die Dosisverteilung bei Behandlung von Lungentumoren mit aktiver Protonenstrahlformierung durchgeführt. Dabei zeigte sich, dass Dosisdegradierungen bei Bewegungsamplituden unter 5mm gering sind. Parameter wie das Zielvolumenkonzept, Veränderungen des Bewegungsmusters oder der Applikationszeiten nehmen zusätzlich Einfluss auf die Dosisdegradierung, allerdings in unterschiedlichem Maß für individuelle Patienten. Da nicht alle Parameter vor Behandlung bekannt sein können, sollten prospektive Dosisabschätzungen durch retrospektive Analysen ergänzt werden
23
Chiwakata, Maynard Tendai. "The synthesis and breast cancer inhibitory activity of cinnamic acid analogues based on the halogenated monoterpene pharmacophore". Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1016129.
Pełny tekst źródłaStreszczenie:
Breast cancer is one of the leading causes of death, with mortality rate estimates of 465 000 deaths per annum. It is estimated that 1.3 million women are diagnosed with the disease each year especially in the developing countries. Current chemotherapy relies on the use of high doses of non-specific toxic agents that possess adverse side effects and compromise patient’s compliance and adherence to treatment. Paclitaxel, one of the common drugs used in breast cancer chemotherapy results in sensory and motor neuropathy, whilst hormonal therapy e.g. Herceptin causes severe cardiovascular, gastrointestinal and cutaneous side effects. There has been a demand in developing newer cancer agents that demonstrate selective cytoxicity with minimal effect on normal body tissue. Numerous studies have shown that marine organisms produce a wide range of halogenated compounds that possess cytotoxic properties, and hence can be a source of new drug hits or leads for cancer therapy. Halomon, a polyhalogenated monoterpene from Portieria hornemannii, displayed interesting activity against brain, renal and lung cancer tumours with selective/differential cytotoxicity. This inspired us to focus our project on halogenated monoterpenes isolated from the same Rhodophyta class as P. hornemannii but with particular attention to Plocamium species. Several metabolites have been isolated from P. cornutum, P. corallorhiza and P. suhrii that possess interesting cytotoxicities against a breast cancer cell line (MCF7) and an oesophageal cancer line (WHCO1). The aim of the project was therefore centred at isolating target compounds for preliminary structure-activity studies against a breast cancer cell line, and use this information to synthesize a series of analogues that are more stable than the natural products and yet as active using a fragment-based type approach to map out pharmacophoric elements. Five metabolites were isolated from P. cornutum and five from P. corallorhiza. Cell-based assays were conducted using an MTT assay kit against MCF7 and MDA-MB-231 breast cancer cell lines and (1E,3E,5S,6R)-1,5,6-trichloro-2-(dichloromethyl)-6-methylocta-1,3,7-triene, isolated from P. cornutum was the most active with IC50 values of 3.0 μM and 6.15 μM respectively. Introduction of a terminal aromatic ring to enhance stability, together with varying substituents (H, CH3, CF3, Br, CN, CHO, CHCl2) on position 7 of the molecule, gave rise to a series of cinnamate ester derivatives inspired by (1E,3E,5S,6R)-1,5,6-trichloro-2-(dichloromethyl)-6-methylocta-1,3,7-triene. The analogues were synthesized from their benzaldehyde precursors via Aldol condensation, esterification and Wittig reactions. Their carboxylic acid counterparts were synthesized by hydrolysis of the parent esters in an attempt to promote water solubilities of the analogues. Biological activity assays were then conducted with the cinnamate analogues against the MDA-MB-231 breast cancer cell line using an MTT assay kit. Ester derivatives with -CHO and -CHCl2 functionalities had IC50 values of 43.45 μM and 100.01 μM respectively whilst the other ester derivatives were inactive. It was concluded that either an aldehyde (-CHO) or gem-dichlorides (-CHCl2) is specifically required for cytotoxic activity to be observed. None of the carboxylic acids were active which could have been due to failure of the compounds to enter the breast cancer cells and reach the target site because of their polar nature. Compounds with -CHO and -CHCl2 functionalities were therefore selected for future SARs studies.
24
Kikkawa, Fumitaka, Akihiro Nawa, Kazuhiko Ino, Kiyosumi Sibata, Hiroaki Kajiyama, Seiji Nomura, 史隆 吉川 i in. "Advances in treatment of epithelial ovarian cancer". Nagoya University School of Medicine, 2006. http://hdl.handle.net/2237/6129.
Pełny tekst źródła
25
Thanoon, David. "Computational framework for local breast cancer treatment". Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14387/document.
Pełny tekst źródłaStreszczenie:
Le cancer du sein est le cancer le plus fréquent chez les femmes. Il y a une multitude de solutions proposées concernant une éventuelle intervention médicale pour le cancer du sein ‐ une en particulier est la chirurgie mammaire conservatrice (tumoréctomie). Le but de la tumoréctomie est de parvenir à un contrôle local du cancer, ainsi que de préserver une forme du sein qui satisfait les besoins esthétiques de la femme. Bien que ces objectifs sont généralement atteint, il reste encore parfois des résultats inattendus,tels qu'une tumeur récurrence locale, ou des résultats cosmétiques insuffisants.L'objectif de cette thèse est de proposer une plateforme de calcul, qui contribue à la tumoréctomie. Cela comprend:1) Une étude de la dynamique de croissance des tumeurs du sein.2) Une étude sur la prédiction du contour du sein grâce a la chirurgie virtuelle.3) Un modèle de calcul de la forme finale du sein après cicatrisationBreast cancer is the most common cancer among women in the developed as well as the developing countries. There are a plethora of proposed solutions regarding possible medical interventions for breast cancer–one in particular is Breast Conserving Therapy (BCT). BCT comprises of complete surgical excision of the tumor (partialmastectomy), and post-operative radiotherapy for the remaining breast tissue. This is a feasible treatment for most women with breast cancer. The goal of BCT is toachieve local control of the cancer, as well as to preserve breast shape that appeases awoman’s cosmetic concerns. Although these goals are usually achieved, there are still occasional unexpected results, such as reexcision of the tumor due to a positive margin assessment, tumor local recurrence, unsatisfactory cosmetic results, and breastpain. Other than surgical experience and judgment, there are currently no toolswhich can predict the outcome of partial mastectomy on the contour and deformity of the treated breast. The objective of this dissertation is to propose computational framework, which contributes to BCT operations, this was achieve by exploring two areas.On the one hand we developed a multiscale model adapted for breast cancer tumor growth, ductal carcinoma in situ (DCIS). The model features included: nutrients growth limitation, wall degradation enzyme and HER2 chemical expression tumor phenotype. Our model successfully simulate some pattern of DCIS carcinoma.Among the interesting result we showed that the enzyme contributed to a greater tumor size and that when HER2 was over expressed, the growth limiting factor wasthe EGFR. On the other hand, we developed a virtual surgery box to simulate BCT surgery. The box will input MRI patient data and will output cosmetic and functional indicator to rate the impact of the surgery. It appears that stiffness of the tissue, resection radius as well as the lump quadrant location are the most sensitive parameters to the indicators. A healing model was also embedded to simulate the wound closure after resection, this model was stress dependent and illustrate anasymmetric wound closure progression.The tools developed in this research allows a new type of field convergence between the surgery and computation field. At the local level it will allow surgeons and patient to be able to communicate on the pertinence and necessity of performing alumpectomy surgery, enabling to anticipate the possible outcome of the operation.On the global aspect this type of tool gives birth to a new type of field: computational surgery, where computer scientist and surgeons work hand in hand to provide the best and the most reliable service to the patients
26
Roxburgh, Patricia. "Manipulating the p53 pathway for cancer treatment". Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4576/.
Pełny tekst źródłaStreszczenie:
p53 is a tumour suppressor that is dysfunctional in most cancers. In some cancers, mutation of the TP53 gene results in expression of a mutant protein or loss of p53 expression, while in others wild-type p53 is retained but there is a defect in the mechanisms that allow for the activation of p53, including, but not limited to, upregulation of p53’s negative regulators (MDM2 and MDMX). Restoration of wild-type p53 function can lead to tumour regression and is therefore an attractive anti-cancer therapy. Several small molecule compounds that activate wild-type p53 have been described, and in this study the functions of two new compounds that stabilise p53 are described. While these drugs may be useful to activate p53-dependent apoptosis or senescence in wild-type p53 tumours, an alternative approach that depends on the use of transient p53 activation to protect normal cells while leaving p53 null or mutant tumour cells vulnerable to cytotoxic drugs is also explored. Finally, the identification of pharmacodynamic biomarkers for p53 stabilisation is described. In chapter 3 a new class of MDM2 inhibitor (MPD compounds) is described. The compounds are capable of stabilising and activating p53 in cells by inhibiting the E3 ligase activity of MDM2 in a mechanism that involves compound binding to the RING-tail of MDM2. Although the MPD compounds have limitations in terms of solubility and potency they have demonstrated a new method of achieving MDM2 inhibition and support design of further RING-tail binding compounds with more favourable chemical properties. In chapter 4 the function of a dual inhibitor of MDM2 and MDMX has been explored (HLI373). This compound is shown to activate p53 in cells and in vivo by interfering with ribosomal biogenesis, causing ribosomal stress and inhibiting MDM2. In addition it is capable of reducing MDMX expression at the promoter level by a mechanism that requires intact MDM2-p53 binding. Further work is required to fully define the mechanism of action of this compound and demonstrate its anticancer activity in xenograft and transgenic mouse models. In chapter 5 a chemoprotective approach for p53 activation, which might be applied to situations where tumours express mutant p53, is explored in cell lines. Low-dose actinomycin D treatment can activate p53 without occult DNA damage via the ribosomal stress pathway, thereby protecting wild-type p53 expressing cells from the cytotoxic effects of paclitaxel. Low-dose actinomycin D may therefore be used to limit chemotherapy-induced toxicity to normal cells while targeting a mutant p53 expressing tumour. In chapter 6 the potential for developing pharmacodynamic biomarkers for MDM2 inhibition in serum, peripheral blood mononuclear cells and hair follicles taken from patients prior to and following chemotherapy was examined. Measurement of serum MIC-1 level showed most promise, although further evaluation of this marker is needed before it could be used as a pharmacodynamic endpoint in a clinical study.
27
Wirth, Manfred P., i Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer". Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133839.
Pełny tekst źródła
28
Whitman, Birgit. "Breast cancer : patient narratives and treatment methods". Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/2969/.
Pełny tekst źródłaStreszczenie:
This thesis concentrates on the treatment of women with breast cancer in the 19th and 20th century. It analyses written published patient narratives linking them with clinical developments. Medical history holds a rich source of information providing the view of the clinician. This includes case reports and case series from one surgeon or one hospital for the earlier period of the study and has progressed to the double blind randomised controlled trial that dominates comparative research today. There is an imbalance in the material available for the analysis of patients’ perceptions of their treatment. The patient view is not represented well in the history of medicine. This thesis attempts to provide a more complete assessment of the developments in breast cancer treatment by including the patient’s view. Three narratives provide an insight into the perception of women who were treated with breast cancer prior to the introduction of anaesthesia and infection control. The novelist, Fanny Burney (1752-1840), underwent a mastectomy in 1811. In a letter to her sister she wrote about her experience providing details of her diagnosis and treatment. In comparison, Emily Gosse (1806-1857) refused a mastectomy for her breast cancer and sought alternative treatment with caustics. Her husband, Phillip Gosse and friend, Anna Shipton, wrote narratives about Emily’s suffering. A third narrative provides the view of a woman with breast cancer who received no treatment and died of metastatic breast cancer; Zelie Martin died in 1877. These narratives were linked to a case report by Lorenz Heister (1683-1758). Heister described the procedure for amputation of the breast in detail. His method prevailed until new scientific developments in surgery such as anaesthesia and infection control improved the short-term survival of patients and enabled surgeons to operate sooner with a greater attention to detail.
29
Silberholz, John. "Analytics for Improved Cancer Screening and Treatment". Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/101290.
Pełny tekst źródłaStreszczenie:
Thesis: Ph. D., Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2015.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 139-156).
Cancer is a leading cause of death both in the United States and worldwide. In this thesis we use machine learning and optimization to identify effective treatments for advanced cancers and to identify effective screening strategies for detecting early-stage disease. In Part I, we propose a methodology for designing combination drug therapies for advanced cancer, evaluating our approach using advanced gastric cancer. First, we build a database of 414 clinical trials testing chemotherapy regimens for this cancer, extracting information about patient demographics, study characteristics, chemotherapy regimens tested, and outcomes. We use this database to build statistical models to predict trial efficacy and toxicity outcomes. We propose models that use machine learning and optimization to suggest regimens to be tested in Phase II and III clinical trials, evaluating our suggestions with both simulated outcomes and the outcomes of clinical trials testing similar regimens. In Part II, we evaluate how well the methodology from Part I generalizes to advanced breast cancer. We build a database of 1,490 clinical trials testing drug therapies for breast cancer, train statistical models to predict trial efficacy and toxicity outcomes, and suggest combination drug therapies to be tested in Phase II and III studies. In this work we model differences in drug effects based on the receptor status of patients in a clinical trial, and we evaluate whether combining clinical trial databases of different cancers can improve clinical trial toxicity predictions. In Part III, we propose a methodology for decision making when multiple mathematical models have been proposed for a phenomenon of interest, using our approach to identify effective population screening strategies for prostate cancer. We implement three published mathematical models of prostate cancer screening strategy outcomes, using optimization to identify strategies that all models find to be effective.
by John Silberholz.
Ph. D.
30
Madani, S. Y. "Application of carbon nanotubes for cancer treatment". Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1402742/.
Pełny tekst źródłaStreszczenie:
There are two classifications of carbon nanotubes (CNT), firstly single walled carbon nanotubes (SWCNT) and secondly multiwall carbon nanotubes (MWCNT). CNTs have the ability of absorbing near infra-red light and generating heat along with the ability to deliver drugs to the site of action. Different application of CNT has so far studied on the in vitro and in vivo models. This thesis is looking into the application of SWCNT on different in vitro models. These models include human breast cancer cell line (MCF7), human colorectal cancer cell line (HT29 and SW480), human pancreatic cancer cell lines (PANC-1) and mouse fibroblast cell line (3T3). In this research, the functionalization techniques of SWCNT have been investigated. In addition, a detailed observation on the application of SWCNT for thermal treatment and the delivery of anti-cancer drugs to the site of action has been obtained. The thesis also looks into conjugation techniques of other materials to the surface of SWCNT for the purpose of both directing the SWCNT to the site of action and tracking their movement through the cells. Finally yet importantly, a detailed investigation has been performed into the effect of SWCNT size and the conjugation of different functional groups to the SWCNT’s surface on its toxicity. From the results, it can be concluded that treating SWCNT in acid solution and further functionalization with OctaAmmonium-POSS will significantly increase the biocompatibility of the SWCNT. Using functionalized SWCNT could be used for the delivery of anticancer drugs to the site of action and thermal treatment of cancer. It has been demonstrated that attachment of QDs to the SWCNT’s surface can be used for tracking the SWCNT’s movement. Finally, it can be concluded that the smaller length SWCNT with a higher coating concentration of OctaAmmonium-POSS will decrease the toxicity of the SWCNT.
31
Masalla, S. G., Waal K. De i H. S. Friedrich-Nel. "Perceptions about cancer treatment : a Bloemfontein perspective". Interim : Interdisciplinary Journal: Vol 9, Issue 1: Central University of Technology Free State Bloemfontein, 2010. http://hdl.handle.net/11462/344.
Pełny tekst źródłaStreszczenie:
Published ArticleCancer patients have varying perceptions about their treatment. The aim of the study was to investigate the different perceptions that patients have about their treatment, and how these perceptions are influenced by their social and cultural backgrounds. The impact of these perceptions on patient responses was also investigated. Eighty-five patients were selected for the study and interviewed using a questionnaire to explore their perceptions and the possible impact of these perceptions on their responses to treatment. An analysis of the perceptions is provided.
32
Zhu, Yanting. "Exploring alternative cytotoxic strategies for cancer treatment". HKBU Institutional Repository, 2014. https://repository.hkbu.edu.hk/etd_oa/65.
Pełny tekst źródłaStreszczenie:
Triggering direct cytotoxicity has been the most common strategy for developing cancer treatments. The cytotoxic regimens currently used in the clinic mainly include radiation therapy, classic chemotherapeutic drugs (e.g. DNA damaging drugs and anti-mitotic drugs) and selected new targeted drugs. Although these therapies are the standard of care for most cancer patients, they suffer significant limitations: responses to these therapies vary significantly between cancer types and patients; sensitive cancers tend to acquire resistance; and they cause serious toxicity, particularly to dividing cells in the bone marrow and gut, and to neurons. It is not clear whether major improvements in cytotoxic anticancer therapies are possible; if they are, progress is likely to come from either new methods for identifying sub-populations of patients that respond well to current drugs, or developing new therapies with novel cytotoxic mechanisms. To pursue the above two avenues towards potential improvement of cytotoxic therapies, this thesis investigates: biomarkers that determine the sensitivity of distinct cancer cell types to common anti-mitotic chemotherapeutics; and the mechanistic basis to employ alternating electric field and Natural Killer cells as alternative methods to trigger cancer cell death. The study uses time-lapse microscopy as the major technique to characterize and quantify response dynamics to the different cytotoxic treatments, and the results provide important new insight not only for understanding existing cytotoxic anticancer drugs but also for developing novel cytotoxic regimens.
33
Wirth, Manfred P., i Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer". Karger, 2002. https://tud.qucosa.de/id/qucosa%3A27540.
Pełny tekst źródła
34
Reyad, Mariam M., i O. Kravchuk. "Nanoparticles: creating and using in cancer treatment". Thesis, ХНУРЕ, 2021. https://openarchive.nure.ua/handle/document/15689.
Pełny tekst źródłaStreszczenie:
This paper is about nanoparticles and which nano is better used for cancer treatment and their differences. Now a nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometers in diameter. Nanoparticles contains a drug molecule called interleukins are attached to immune cells (T-cells).
35
Elshafae, Said Mohammed Abbas. "Pathogenesis and Treatment of Canine Prostate Cancer". The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492081831172341.
Pełny tekst źródła
36
Bispo, Mafalda Alves Fernandes. "Galacto-silicon phthalocyanines for bladder cancer treatment". Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/19029.
Pełny tekst źródłaStreszczenie:
Mestrado em Bioquímica - Bioquímica ClínicaA terapia fotodinâmica (PhotodynamicTherapy, PDT) é uma metodologia emergente no tratamento de diversas doenças oncológicas e tem por base o uso de oxigénio molecular, luz e um fotossensibilizador (FS) para seletivamente destruir as células tumorais. Em oncologia, a PDT leva à indução de espécies reativas de oxigénio (reactive oxygen species, ROS) no tecido tumoral, no qual ocorreu previamente o uptake preferencial e/ou a retenção de um FS. As ftalocianinas têm-se vindo a revelar FSs promissores na PDT devido às suas propriedades foto-físicas. Contudo, estes compostos para além de pouco solúveis em água, têm problemas de agregação e de especificidade para os tecidos tumorais. Assim, o trabalho apresentado nesta tese teve como objetivo principal conjugar co-axialmente ftalocianinas de silício (silicon phthalocyanines, SiPcs) com duas moléculas de galactose (SiPcGal2) e com duas unidades dendríticas de galactose (SiPcGal4) para que estes FSs fossem reconhecidos por galectinas (e.g. galectina-1) sobrexpressas em células tumorais. Contudo, os compostos desejados finais não foram obtidos, uma vez que a remoção dos grupos isopropilideno, protetores dos grupos hidroxilo das unidades de galactose, não foi conseguida. Assim, foram avaliadas as propriedades foto-físicas e foto-químicas das SiPcs com as galactoses protegidas, comparando com a SiPc dihidróxido (SiPc(OH)2), de forma a estudar a influência da conjugação co-axial de biomoléculas no core destes tipo de FSs. Infelizmente, a solubilidade das SiPcs em solventes aquosos não foi conseguida, contudo o seu espectro de absorção UV-visível evidenciou elevada absorção a altos comprimentos de onda (650-700 nm), janela espectrofotométrica onde ocorre uma penetração mais profunda da luz nos tecidos. Para além disso, estes FSs demonstraram-se excelentes marcadores fluorescentes, estáveis após irradiação e bons geradores de 1O2. Foram ainda realizados estudos in vitro com o objetivo de validar o seu potencial fotodinâmico no tratamento do cancro da bexiga, sendo que a SiPcGal4 e a SiPcGal2 agregaram nas células, tendo assim um baixo uptake, baixa toxicidade após foto-ativação e baixa produção de ROS. No geral, as SiPcs demonstraram um grande potencial como futuros FSs para a PDT, dado as suas excelentes propriedades foto-físicas, o que nos incentiva na descoberta de novas técnicas que diminuam a sua agregação nas células, como a utilização de bio-formulações estáveis e a desproteção das moléculas de galactose, que também irá aumentar a sua especificidade para células tumorais.
Photodynamic Therapy (PDT) relies on the combination of a photosensitizer (PS), light and molecular oxygen (O2) to generate reactive oxygen species (ROS), which can trigger cell death pathways. In oncology, the PS needs to be preferentially accumulated in cancer cells and a good generator of ROS (especially singlet oxygen, 1O2). Phthalocyanines (Pcs) are promising PSs in PDT due to their photochemical and photophysical properties. However, Pcs present solubility and aggregation problems, as well as low selectivity to the cancer tissue. Therefore, it will be conjugated a silicon phthalocyanine (SiPc) with two galactose molecules (SiPcGal2) and another with two galacto-dendritic units (SiPcGal4), both in axial positions. The aim of that conjugation is to promote the binding of the PS with galactose-binding proteins such as galectins (e.g. galectin-1) which are found to be overexpressed in cancer cells. Nevertheless, the desired compound were not obtained, once the hydrolysis of the isopropylidene galactose-protective groups didn’t work. Thereby, the photophysical and photochemical properties of those two SiPcs with the galactose-protective groups were studied in comparison with the SiPc dihydroxide (SiPc(OH)2), in order to study the SiPc core properties as well as the influence of an axial conjugation of biomolecules. The PSs solubility was compromised in an aqueous solution, however their absorption UV-Visible spectra showed high absorption peaks at a high wavelengths range (650–700 nm), which is the ideal therapeutical window where there is a higher penetration of light into the tissues. Furthermore, these SiPcs demonstrated to be good fluorescence labels, photostable and good 1O2 generators. In vitro studies were performed with the aim of validating them as photodynamic therapeutic agents against bladder cancer cells, however SiPcGal4 and SiPcGal2 aggregated on cells, having a low uptake, phototoxicity and ROS production. Overall, SiPcs have demonstrated a great potential as future PSs for PDT, thanks to their excellent photophysical properties, which prompt us in the discovery of different approaches that diminished their aggregation on cells, such as the incorporation of PSs into bio-stable formulations and the deprotection of the galactose molecules, which will also increase their specificity to tumoral cells.
37
Keim, Rebecca. "Treatment-Induced Breast Cancer Dormancy and Relapse". VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3500.
Pełny tekst źródłaStreszczenie:
When breast tumor cells encounter stress due to cancer therapies, they may enter a dormant state, escaping from treatment-induced apoptosis. Dormant cells may eventually regain proliferative capabilities and cause recurrent metastatic disease, which is the leading cause of mortality in breast cancer patients. We sought to determine if a high dose of radiation therapy (RT) or combined chemo-immunotherapy, with and without the blockade of autophagy by chloroquine (CQ), could overcome treatment-induced tumor dormancy or relapse. We found that autophagy contributes in part to treatment-induced tumor dormancy. We also found that three therapeutic strategies were successful in inhibiting or preventing tumor relapse. These include: 18Gy/day RT, chemotherapy combined with the blockade of autophagy, and combined chemo-immunotherapy. Follow-up studies are needed to determine the feasibility of preventing tumor relapse by prolonging tumor dormancy versus eliminating dormant tumor cells.
38
Campbell, Neil Crawford. "Rural factors in cancer treatment and survival". Thesis, University of Aberdeen, 2003. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU177129.
Pełny tekst źródłaStreszczenie:
Treatment of cancer is becoming increasingly successful, particularly if conducted in specialist centres. For 20% of the UK population who live in rural areas, however, there may be difficulties accessing this care. The aim of the research in this thesis was to establish whether people in rural areas are disadvantaged in cancer care. Two studies were conducted. In the first, survival rates from six common cancers were analysed for 63 976 people with cancer diagnosed between 1991 and 1995 in Scotland. Living further from a cancer centre was associated with higher chance of early death (on the date of diagnosis) for stomach (adjusted odds ratio 3.92, 95% confidence intervals 2.17 to 7.08), breast (2.87, 1.74 to 4.74) and colorectal cancers (1.78, 1.19 to 2.67). After diagnosis, increasing distance was associated with poorer survival for prostate (proportional hazard ratio 1.23; 95% confidence intervals 1.02 to 1.48) and lung (1.09, 1.01 to 1.18) cancers. The second study compared disease stage at diagnosis, modes of cancer treatment and time between referral and treatment for 1323 patients diagnosed with lung or colorectal cancer in 1995 or 1996 in north and northeast Scotland. People living more than 58 kilometres from a cancer centre were 56% more likely to have disseminated disease at diagnosis (P = 0.046). The proportions of patients receiving surgery, chemotherapy and radiotherapy were similar for rural and urban patients although, fewer outlying rural patients received radiotherapy for colorectal cancer. Times between first referral and treatment also appeared similar in urban and rural groups. To conclude, rural patients, who live further from cities with specialist cancer facilities, have more advanced cancer at the diagnosis and poorer survival. This suggests there may be delays before diagnosis, but these must occur before initial referral perhaps related to consulting behaviour.
39
Smeenk, Henri Gerard. "Surgical and adjuvant treatment of pancreatic cancer". [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13713.
Pełny tekst źródła
40
Kim, Hannah Yejin. "Personalised Medicine in the Treatment of Cancer". Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20103.
Pełny tekst źródłaStreszczenie:
Understanding of pharmacokinetic-pharmacodynamic relationship for a given drug, and factors determining this, is an important part of personalised medicine in terms of choosing the correct regimen and maximising the therapeutic benefit with minimal toxicity. In the field of cancer, diversity of disease characteristics, complexity of regimens, as well as limited understanding of PK-PD profiles of rapidly-progressing anticancer drugs, create challenges for clinicians and patients to achieve the optimal outcome. This thesis addresses areas of cancer treatment where there is a need for identification of pharmacokinetic (PK), pharmacogenetic (PG) or physiological contributors, which may explain the observed variability, pharmacokinetics or toxicity of the studied drugs. The first component of the work aimed to investigate pharmacogenetic factors determining pharmacokinetics of actinomycin D. The study involves identification of the candidate transporters through in vitro uptake assays, which then led to clinical PK-PG analysis to determine clinically-significant transporter genotype influencing actinomycin D pharmacokinetics. The second component of the work explores pharmacodynamic associations between toxicity (pyrexia: body temperature > 38C) and exposure to dabrafenib and trametinib (CombiDT) used in the treatment of patients with melanoma expressing the common BRAF V600E/K mutation. A biomarker analysis using a panel of cytokines was also conducted to investigate their role in predicting or indicating the incidence of this toxicity. The significant findings of our study include identification of involvement of Solute Carrier (SLC) transporters (OAT4 and PEPT2) in actinomycin D uptake in vitro and the potentially predictive role of cytokines (IL-1B and IL-6) in CombiDT-induced pyrexia. Some of the results, such as the role of SLC transporters in clinical pharmacokinetics of actinomycin D in paediatric cancer patients, and drug exposure-pyrexia relationship for CombiDT treatment, lacked definitive conclusions due to study limitations, and provide areas of further research. Overall, we believe that our study has made valuable contributions to the enhanced understanding of these drugs, and a step closer to personalised medicine in the treatment of cancer.
41
Martinez, De Pinillos Bayona A. "Light-based therapies in prostate cancer treatment". Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1532467/.
Pełny tekst źródłaStreszczenie:
Photodynamic Therapy (PDT) and Photochemical Internalisation (PCI) are both light-based therapies which can be used for the focal treatment of cancer. Both PDT and PCI require the combination of photosensitisers, light and molecular oxygen to induce photooxidative reactions that damage biomolecules. However, while PDT employs a photosensitiser as the sole therapeutic agent, PCI combines low-dose PDT with another therapeutic agent to enable the improved delivery of this agent to its intended subcellular targets. The overall aim of this study was to investigate PDT and PCI for prostate cancer in both in vitro and in vivo tumour models. In the PCI procedures, the ribosome inactivating protein type 1 saporin was used as a model chemotherapy agent. We have concluded an enhancement in cell killing in prostate carcinoma cells after PCI compared to PDT in 2-dimensional models, i.e. 80% cell death, compared to 32% killing after PDT. Similar observations resulted from qualitative observations in the 3-dimensional model. Moreover, conjugation of a photosensitiser to cell penetrating peptides (TAT or Antp), resulted in a similar difference in cytotoxicity after PCI and PDT using lower concentrations of the conjugates - 76% and 14% respectively. These data confirm the synergistic effect of drug and photosensitiser in PCI. Three different clinically relevant photosensitisers were used in vivo in a subcutaneous rat model. Vascular-targeted PDT resulted in the most efficient treatment, and photosensitisers targeting a cellular effect, showed a better outcome with shorter drug-light intervals. The analysis of tumour samples through immunohistochemistry and molecular analysis revealed an innate inflammatory response that led to an adaptive immune response. A highly suppressive tumour microenvironment was suggested by the infiltration of regulatory T cells (FoxP3+), up-regulation of PD-L1 and down-regulation of cytolytic proteins (i.e. Perforin). Moreover, the beneficial effect of using immunoadjuvants (cyclophosphamide) was investigated. Light based therapies could play an important role in prostate cancer treatment both eradicating tumours and generating long-term immune protection against secondary tumour deposits.
42
Bossaer, John B., i Christian M. Thomas. "Adjuvant Treatment of Newly Diagnosed Breast Cancer". Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/2313.
Pełny tekst źródła
43
Khalaf, Rossa, John B. Bossaer i Elnora N. Spradling. "Individualized Cancer Treatment based on Pharmacogenomics Analysis". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/2345.
Pełny tekst źródłaStreszczenie:
5-Fluorouracil (5-FU) is one of most frequently used chemotherapeutic medications for the treatment of many types of cancer in curative and palliative setting. It is important to recognize chemotherapy side effects and toxicities because some of these symptoms may indicate a clinical syndrome needing evaluation for a principal cause. We discuss a patient who developed severe mucositis requiring hospitalization after first use of Fluorouracil. Dihydropyrimidine dehydrogenase ( DPD) deficiency was suspected and was proven to be a cause of severe drug-related toxicity. Our patient is fifty six year old gentleman with stage III nasopharyngeal squamous cell carcinoma who developed two masses on right side of the neck and large posterior right nasopharyngeal mass. Patient was treated with concurrent chemotherapy with high dose of cisplatin along with radiation. Once completion of concurrent chemotherapy and radiation he was started on combination of 5-Fluorouracil and cisplatin. Three days after completion of ninety six hour continuous 5-flurouracil infusion patient developed severe mucositis. Clinical exam was consistent with swollen tongue and mouth and inability to clear oral secretions. Patient was tested for DPYD gene mutation. Testing showed heterozygous for the c.1679T>G(*13) variant in the DPYD gene consistent with predicted intermediate DPD activity (30-70% enzyme activity). About 80% of administered 5-fluorouracil is normally inactivated by DPD. A decrease in DPD enzymatic activity may lead to increased concentrations of 5-FU and elevated risk for severe toxicities. Standard dose of 5-FU was decreased by 50% with second cycle of chemotherapy. Patient tolerated the second cycle of chemotherapy well. Variants in the DPD gene can lead to reduced 5-FU catabolism resulting in severe toxicities. Some of the toxicities can cause death. It is important to screen for this deficiency and closely observe patients during chemotherapy treatment.
44
Valetti, Sabrina. "Targeted squalenoyl nanomedicines for pancreatic cancer treatment". Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114805/document.
Pełny tekst źródłaStreszczenie:
Le cancer pancréatique représente la cinquième cause de décès par cancer dans les pays occidentaux. Son mauvais pronostic (survie à 5 ans inférieure à 3,5 % des cas) est dû à l’absence de facteurs de risques spécifiques interdisant une prévention efficace, et à un diagnostic tardif qui révèle un cancer agressif chez environ 90% des patients. Actuellement, le seul traitement curatif de ce cancer est la chirurgie, mais celle-ci ne peut être envisagée que dans 10 à 15 % des cas. L’adressage de molécules thérapeutiques vers l’organe, le tissu ou la cellule malade constitue aujourd’hui un défi majeur pour le traitement des maladies humaines notamment infectieuses, cancéreuses ou d’origine génétique. C’est pour ces raisons que le développement de nanotechnologies, en tant que vecteurs de médicaments, a pris un essor considérable au cours des dernières années. Dans ce contexte, le concept de squalènisation repose sur le couplage chimique entre le squalène (SQ), un lipide naturel précurseur de la synthèse du cholestérol, et des principes actifs (notamment des molécules anticancéreuses). Les bioconjugués ainsi formés sont alors capables de s’auto-assembler en solution aqueuse pour former des nanoparticules stables de diamètres compris entre 100 et 300 nm. L’exemple de référence dans ce domaine est la nanoparticule de gemcitabine-squalène (SQdFdC) qui a donné lieu à des résultats spectaculaires in vitro sur des lignées de cellules cancéreuses humaines In vivo, les nanoparticules de gemcitabine-squalène se sont avérées beaucoup plus efficaces que la gemcitabine libre sur des tumeurs solides greffées par voie sous-cutanée ainsi que sur des modèles murins de leucémies agressives métastatiques.Au vu de ces résultats encourageants, le projet de thèse a été développé autour de deux axes de recherche. (I) Dans un premier temps, les nanoparticules de gemcitabine-squalène ont été fonctionnalisées par un peptide capable de reconnaître et de cibler spécifiquement les cellules cancéreuses pancréatiques. (II) Le deuxième axe de recherche a visé l’encapsulation d’un second principe actif au sein des nanoparticules de gemcitabine-squalène afin de développer le concept de nanoparticule « multi-thérapeutique »Pancreatic cancer is a lethal disease with the worst prognosis among all solid tumors. In the last decades, progresses in pancreatic cancer therapy had remained exceedingly slow and disappointing offering minimal benefits in median survival which remains of less than 6 months and the maximum of 5 years in the 6% of patients. One of the major requirements for a successful cancer therapy is its ability to selectively kill cancer cells with minimal damage to healthy tissues. In this context, a great deal of attention focused on advanced nanoscale systems (i.e., nanomedicines) with the aim to overcome the limits associated to the traditional drug delivery modalities. Nanomedicines can indeed enhance drug properties by (i) offering protection from degradation, (ii) enabling controlled release and distribution and increasing bioavailability while reducing undesired side effects.In the current work we aimed to propose novel nanoscale-based strategies to optimize pancreatic cancer treatment taking into account the specific physio-pathology of this tumor. The first approach relied on the design of a targeted nanomedicine able to specifically bind receptors mainly expressed onto pancreatic cancer cells in order to selectively increase drug accumulation in these cells saving healthy ones.In a second approach, by combining two therapeutic agents in the same nanoparticle we constructed a multi-therapeutic drug delivery system capable to increase the therapeutic index of the combined therapy. In particular, taking advantages from the “squalenoylation prodrug approach”, the research activity of this Ph.D. work lead to the to design of (i) a novel peptide-functionalized squalenoyl gemcitabine nanoparticle and (ii) a tyrosine kinase inhibitor-loaded squalenoyl gemcitabine nanoparticle. Obtained nanoparticles were investigated with respect to their physico-chemical properties and in vitro antitumor activity. The efficacy of peptide-functionalized nanoparticles in impairing tumor growth was assessed in vivo on an experimental model of pancreatic cancer
45
Kemp, Patrice. "Cancer Treatment Decision Making in Aging Minorities". ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/6342.
Pełny tekst źródłaStreszczenie:
Cancer incidence is high for aging minority and underserved populations, yet research is limited about patient-provider communications with aging racial and ethnic minority populations. Achieving high-quality cancer care is crucial to reducing health disparities for this population. However, potential shortages in professional health personnel, the cost to treat cancer, a strained health care system, and large aging populations contribute to the problem. The purpose of this qualitative study was to understand the personal experiences of aging minorities during cancer treatment decision making when communicating with their cancer care providers. Purposive sampling methods were used to recruit 10 minority women and men born between 1946 and 1964 who had experienced communicating with providers and making cancer treatment decisions. In-depth semi-structured interviews and thematic analysis of qualitative data was conducted. Important findings were barriers related to miscommunication with providers, the need for more time with the cancer doctor, and mistrust of the medical profession. Participants perceived poor interpersonal communication with providers as causing a lack of understanding regarding their cancer treatment options, which affected their decision making regarding their treatment. Barriers to communication included long wait times at public or teaching health care systems for follow up cancer care services. The findings of this study could be useful to assist health care providers in improving communication with their cancer patients, reducing cancer health disparities, and increasing the quality of cancer care for this population.
46
Biason, Paola. "Pharmacogenetics of cytochromes in breast cancer treatment". Doctoral thesis, Università degli studi di Padova, 2008. http://hdl.handle.net/11577/3425652.
Pełny tekst źródłaStreszczenie:
Pharmacogenetic focuses on intersubject variations in therapeutic drug effects and toxicity depending on genetic polymorphisms. In defining the treatment strategies for breast cancer several factors are considered: patients with estrogen-positive breast cancer are treated with anti-estrogens (exemestane) whereas locally advanced or metastatic disease is treated with cytotoxic agents, including cyclophosphamide. In both cases, the presence of genetic alterations of cytochrome P450 (CYP) could influence the absorption, distribution, bioactivation, metabolism, elimination and drug action and thus have consequences in the efficacy and toxicity of treatment. This study is focused on the analysis of genetic polymorphisms of several CYP isoforms involved in cyclophosphamide bioactivation or as exemestane target.
The aim of this research is to point out a predictive role of genetic alterations in terms of toxicity and of overall survival after pharmacological treatment in breast cancer patients. Since the difficulty of the enrollment of patients treated with exemestane did not allow us to drawn the same pharmacogenetic/pharmacodynamic correlations. For this subgroup we have assessed only the relative risk to develop breast cancer for all the polymorphisms analysed.
One hundred ninty-five patients treated with cyclophosphamide in association with methotrexate and 5-fluorouracil (CMF regimen) were genotypized for a set of genetic polymorphisms of CYP2B6, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 involved in bioactivation of the drug. In the group of 121 patients treated with exemestane the analysis were performed for aromatase (CYP19) gene, which is also the target of the drug. Genotyping was performed using PCR based methods, such as Restriction Fragment Length Polymorphism (RFLP), fragment analysis, Pyrosequencing technology and TaqMan technology. Clinical parameters of toxicity (according with NCI-CTC scale) and Overall Survival were monitored by an oncologist.
Interesting results were obtained for the correlations between the genotypic and the pharmacodynamic profiles of subgroup of patients treated with cyclophosphamide. The study underlined the significant role of CYP2C9 isoforms involved in bioactivation of cyclophosphamide both in overall survival and in the development of toxicity. Patients carrying at least one mutant allele of CYP2C9*2 (C430T) polymorphism showed an higher risk to develop hepatic toxicity with respect to wild type patients after the 1st cycle of chemotherapy. Similar results were obtained with CYP2C9*3 (A1075C): the presence of at least one mutated allele was found significantly correlated with the development of hepatic toxicity (grade 1-3) after the entire course of treatment. A reduction of enzyme activity due by polymorphism could determine an impaired bioactivation of the prodrug with a consequent accumulation in the liver. Moreover, CYP2C9*3 polymorphism has showed an impact in the overall survival: the presence of at least one mutated allele is related to a reduced survival. This is probably due to a lesser bioavailability of the active molecule.
The presence of CYP2C19 G681A polymorphism was correlated with an higher risk to develop severe (grade 3-4) hematological toxicity at the end of the therapy. This variant characterizes the poor metaboliser (PM) allele and thus could be responsible for a reduction in the bioactivation of cyclophosphamide.
In conclusion, interesting molecular markers with a predictive value on pharmacodynamics of cyclophosphamide were identified, but their role has to be confirmed in a larger group of patients. A possible application of these parameters in the clinical practice, could be useful to design a tailored treatment based on the peculiar genetic characteristics of each breast cancer patient.La farmacogenetica studia l’impatto di polimorfismi genetici nella variabilità interindividuale dell’effetto terapeutico, in termini di risposta e tossicità, al trattamento farmacologico. Nella definizione del trattamento per il tumore della mammella si tiene conto di numerosi fattori tra cui la condizione ormonale delle pazienti stesse: la presenza di recettori per gli estrogeni a livello tumorale prevede il trattamento con farmaci anti-estrogenici (exemestane) mentre la malattia localmente avanzata o metastatica viene trattata con chemioterapia citotossica (ciclofosfamide). In entrambi i casi, la presenza di alterazioni genetiche a carico dei citocromi P450 (CYP) potrebbe influenzare la terapia in termini di risposta o di sviluppo di tossicità. Lo studio ha previsto l’arruolamento di due gruppi di pazienti sottoposte a terapia farmacologica (ciclofosfamide in regime CMF) o a terapia ormonale (exemestane) per le quali è stato fatto il profilo genetico di alcune particolari isoforme di CYP. Lo scopo dello studio è stato quello di valutare l’effetto dei polimorfismi individuati sull’outcome clinico delle pazienti in modo da fornire delle indicazioni su una possibile “personalizzazione” della terapia in relazione al profilo genetico della paziente. Lo studio si può definire completo per il gruppo di pazienti in trattamento farmacologico in quanto è stato possibile raccogliere i dati farmacodinamici di tossicità e sopravvivenza. Al contrario, per il gruppo in trattamento ormonale l’arruolamento non è stato completato quindi è stato possibile solo avere dei dati preliminari di frequenza dei polimorfismi. Lo scopo principale dello studio è stato quindi quello di valutare l’impatto di polimorfismi a carico dei CYP (siano essi coinvolti nel metabolismo della ciclofosfamide o rappresentino l’enzima target per exemestane) sulla sopravvivenza e sullo sviluppo di tossicità al trattamento. Inoltre, è stato possibile effettuare anche delle correlazioni di tipo caso/controllo per la valutazione del rischio relativo di sviluppo del tumore in relazione alla presenza dei polimorfismi studiati. Sono state quindi individuate le varianti genetiche a carico delle isoforme CYP2B6, CYP2C9, CYP2C19, CYP3A4 e CYP3A5 coinvolte nella bioattivazione della ciclofosfamide e dell’isoforma CYP19 enzima target di exemestane. La genotipizzazione delle pazienti (195 con trattamento farmacologico e 121 con trattamento anti-estrogenico) si è basata su tecniche che utilizzano l’amplificazione del DNA tramite PCR, quali il Restriction Fragment Length Polymorphism (RFLP), l’analisi automatizzata dei frammenti, la tecnologia del Pyrosequencing e la tecnologia TaqMan. I dati clinici di tossicità sono stati valutati da un oncologo medico secondo la classificazione NCI-CTC mentre il dato di sopravvivenza è stato considerato l’Overall Survival. Dati interessanti e significativi sono emersi per il gruppo di pazienti in trattamento farmacologico con ciclofosfamide in quanto è stato possibile valutare le relazioni tra profilo genetico e profilo farmacodinamico. Lo studio ha infatti evidenziato un ruolo significativo dei polimorfismi dell’isoforma CYP2C9 coinvolti nella bioattivazione epatica della ciclofosfamide sia per quanto riguarda la sopravvivenza che la tossicità. La presenza di almeno un allele mutato per il polimorfismo CYP2C9*2 (C430T) è correlata con un maggior rischio di sviluppo di tossicità epatica alla fine del primo ciclo di trattamento. La riduzione di attività enzimatica conseguente alla variazione genica potrebbe determinare una minore bioattivazione del profarmaco con un suo accumulo a livello epatico. Inoltre anche il polimorfismo CYP2C9*3 (A1075C) ha evidenziato un impatto non solo sulla tossicità epatica ma anche sulla sopravvivenza. La presenza di almeno un allele mutato riduce la sopravvivenza probabilmente in relazione alla minore disponibilità di farmaco attivo. Inoltre è emersa una correlazione significativa anche tra la presenza di un polimorfismo a carico di CYP2C19 (G681A) e lo sviluppo di tossicità ematologica severa (grado 3-4) alla fine della terapia. La presenza del polimorfismo è associata ad una riduzione nell’attività metabolica dell’enzima quindi potrebbe spiegare una riduzione nella bioattivazione della ciclofosfamide con sviluppo di tossicità. In conclusione, durante questo lavoro di tesi, sono stati evidenziati interessanti marcatori molecolari che potrebbero avere un valore prognostico nel trattamento del carcinoma della mammella con ciclofosfamide se confermati in una casistica più ampia. L’applicazione di questi parametri nella pratica clinica potrebbe essere utile per progettare una personalizzazione del trattamento basato su specifiche caratteristiche genetiche del paziente con carcinoma della mammella.
47
Mielcarek, Angelika Maria. "Surface engineered hybrid nanocarriers for cancer treatment". Electronic Thesis or Diss., Université Paris sciences et lettres, 2020. http://www.theses.fr/2020UPSLE033.
Pełny tekst źródłaStreszczenie:
Les nanoparticules métallo-organiques (nanoMOFs) sont des matériaux cristallins poreux à fort potentiel en biomédecine. Les nanoparticules (NP) de carboxylate de fer MIL-100(Fe) sont particulièrement intéressantes. Cependant, malgré de nombreux avantages, ces NP ont tendance à s'agréger dans les milieux physiologiques et à s'accumuler dans les organes après administration intraveineuse. Dans ce travail, nous avons étudié l'impact de différentes voies de modification de surface (covalente et non covalente) sur la stabilité des NP de MIL-100(Fe) dans les milieux physiologiques et la capacité des revêtements à ajuster la biodistribution in vivo et la pharmacocinétique des NP. Nous avons également entrepris de développer une voie de synthèse pour diminuer la taille des NP afin de réduire la capture par les macrophages. Enfin, nous avons étudié l'encapsulation et la libération du méthotrexate (MTX), un médicament anticancéreux dans des NP de MIL-100(Fe) dans deux types d'applications : NP cœur-coquille nanoMOF-oxyde de fer et l’évaluation de la toxicité de molécules par des vers C. elegansMetal-Organic Frameworks nanoparticles (nanoMOFs) are porous crystalline materials of interest for biomedicine applications. Particularly attractive ones are MIL-100(Fe) iron carboxylate nanoparticles (NPs). Despite many advantages, these NPs tend to aggregate in physiological media and accumulate in organs after intravenous administration. In this work, we investigated the impact of different surface modifications route (covalent and non-covalent) on the colloidal stability of MIL-100(Fe) NPs in physiological media and the ability of the coatings to tune the in vivo biodistribution and pharmacokinetics of NPs. We also investigated different synthesis route to decrease the size of the NPs, in a view of reducing the macrophage recognition. Finally, we studied the encapsulation and release of anticancer drug, Methotrexate (MTX), into magnetic core-shell nanoMOFs-iron oxide NPs and the toxicity evaluation of molecules based on C. elegans worms
48
Lyu, Zhenbin. "Fluorinated supramolecular dendrimer nanosystems for cancer treatment". Electronic Thesis or Diss., Aix-Marseille, 2020. http://www.theses.fr/2020AIXM0404.
Pełny tekst źródłaStreszczenie:
Le cancer est l'une des principales causes de décès et reste une maladie difficile à traiter. Dans ce contexte, l'application de la nanotechnologie apporte une percée et crée de nouvelles thérapies pour un diagnostic précoce et précis ainsi qu'un traitement sûr et efficace dans la thérapie du cancer. Les dendrimères sont des systèmes idéaux pour la nanomédecine en raison de leur structure bien définie et de leur coopérativité multivalente. Dans cette thèse de doctorat, nous avons développé des nanosystèmes innovants formés par des dendrimères amphiphiles portant des entités fluorées spécifiques pour la délivrance de médicaments, d’acides nucléiques et d'agents d'imagerie. Certains de ces nanosystèmes ont montré des propriétés particulièrement intéressantes pour l'encapsulation de médicaments, la délivrance d’acides nucléiques et la bio-imagerie avec un profil de bio-distribution favorable. En particulier, les entités fluorées confèrent également la capacité d’étudier le cancer par l'imagerie par résonance magnétique (IRM) du 19F. En conclusion, ces nanosystèmes innovants de dendrimères supramoléculaires fluorés constituent une plateforme prometteuse pour des applications biomédicales dans le traitement du cancerCancer is one of the leading causes of death and remains a difficult disease to treat. The application of nanotechnology is widely expected to bring breakthrough and create novel therapeutics for early and precise diagnosis as well as safe and effective treatment in cancer therapy. Dendrimers are ideal systems for nanomedicine by virtue of their uniquely well-defined structure and multivalent cooperativity. In this PhD thesis, we have developed innovative self-assembling supramolecular dendrimer nanosystems carrying specific fluorinated entities for the delivery of drug, nucleic acid therapeutics and imaging agents. Some of the established fluorinated supramolecular dendrimer nanosystems showed particularly interesting properties for drug encapsulation, nucleic acid delivery and bioimaging with favorable biodistribution profile. In particular, the fluorinated entities also offer the unique opportunity for in vivo 19F magnetic resonance imaging (MRI). Collectively, our innovative fluorinated supramolecular dendrimer nanosystems constitute promising platforms for biomedical applications in cancer treatment
49
Lyu, Jun Fang. "Discovery of cholesterol trafficking inhibitors as novel anti-angiogenic and anti-cancer agents". Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953967.
Pełny tekst źródła
50
Wirth, Manfred P., i Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program". Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133551.
Pełny tekst źródłaStreszczenie:
Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantageDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich