Spelling suggestions: "subject:"recombinations"" "subject:"orcombinations""
11 |
Accelerated induction of etorphine immobilization in blue wildebeest (Connochaetes taurinus) by the addition of hyaluronidaseDittberner, Mark 16 July 2013 (has links)
Wild animal capture has progressed over the years from trapping or physical capture, which was dangerous to both animal and man, to chemical immobilization. Opioids and butyrophenones are the most common classes of drugs used for ungulate immobilization; however newer drugs and drug combinations are commonly used in an attempt to reduce time to immobilization in wildlife. The enzyme hyaluronidase is often added to drug combinations in the belief that it reduces time to immobilization by improving drug absorption. The primary objective of this study was to ascertain if the addition of hyaluronidase to an etorphine and azaperone drug combination would be of value in reducing time to immobilization in blue wildebeest. The study also tried to ascertain if the added hyaluronidase enabled one to reduce the etorphine and azaperone doses required to immobilize blue wildebeest, without affecting time to immobilization. The study made use of a four-way cross-over study design, with four treatment groups, four sequences and four periods. The four treatment groups were etorphine and azaperone; etorphine, azaperone and 5000 international units (IU) hyaluronidase; etorphine, azaperone and 7500 IU hyaluronidase; and 75 % of the original etorphine dose, 75% of the original azaperone dose and 7500 IU hyaluronidase. Each animal was immobilized with each of the above four drug combinations randomly over an eight week period with a two week interval between each period. The times to first effect, first down and immobilization were recorded. The etorphine and azaperone treatment group was used as the control group. The difference in time to first effect between the control group and the etorphine, azaperone and 7500 IU hyaluronidase treatment group was statistically significant (95 seconds versus 67 seconds; p = 0.007). When compared to the time to immobilization in the control group (323 seconds) the time to immobilization in the etrophine, azaperone and 5000 IU hyaluronidase (228 seconds); etorphine, azaperone and 7500 IU hyaluronidase (210 seconds) and the low dose etorphine, low dose azaperone and 7500 IU hyaluronidase (268 seconds) groups were statistically significantly reduced (p=0.002, p=0.001 and p=0.045 respectively). It is therefore concluded that the addition of 5000 or 7500 IU hyaluronidase to an etorphine and azaperone combination significantly reduced the time to immobilization in blue wildebeest. The unexpected decrease in time to immobilization in the low dose etorphine, low dose azaperone and 7500 IU hyaluronidase treatment group requires further investigation. / Dissertation (MMedVet)--University of Pretoria, 2011. / Production Animal Studies / unrestricted
|
12 |
Panacea: Predicting anti-aging combinations from expression analysisJatti, Ashwini January 2023 (has links)
Identifying interventions, such as drugs, that can counteract the effects of aging is crucial due to the complex nature of the aging process, which involves multiple biological processes. By targeting these processes, interventions have the potential to promote healthy aging. Utilizing pairs of drugs that exhibit synergistic effects becomes particularly effective as they can simultaneously impact multiple pathways associated with aging and reprogramming, enhancing their anti-aging potential. The Panacea (predicting anti-aging combinations from expression analysis) framework was developed to facilitate the discovery of such drug combinations. Deep generative models were incorporated into the Panacea framework to effectively capture complex patterns in gene expression data, leveraging their non-linear nature for an accurate representation of relationships and interactions. This makes them ideal for predicting drug combinations. The trained models, using the CMap dataset, demonstrated an improved performance to predict the effect of drugs. The age effect of these drug combinations was evaluated using an age-predictive model, revealing that synergistic anti-aging combinations mainly comprised reprogramming (the process of transforming one type of cell into another by altering its gene expression and properties), apoptosis (programmed cell death mechanism), and chemotherapy drugs, while pro-aging combinations involved cellular growth-limiting, longevity-extending, and chemotherapy drugs. These results emphasize the capability of deep generative models in predicting potent drug combinations for anti-aging and anti-cancer interventions.
|
13 |
Avaliação farmacoeconômica dos tratamentos para leishmaniose visceral no Estado de SergipeSantos, João Luiz Alves dos 31 August 2015 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Search for new therapeutic alternatives for leishmaniasis is considered essential by the World Health Organization, due to the high toxicity of the drugs currently used, its high
cost and the risk of resistance. In Brazil, it is used three drugs to treat leishmaniasis: meglumine antimoniate and two formulations of amphotericin B (deoxycholate and
liposomal). This study is a piggy-back evaluation linked to a multicentric clinical trial with the objective to perform a decision analysis between the treatment regimens for
visceral leishmaniasis, for both adults and children. For this end, it was performed analysis of the data obtained in the state of Sergipe from 62 patients randomized to treatment with meglumine antimoniate (group A), considered the first line treatment in Brazil, amphotericin B deoxycholate (group B), liposomal amphotericin B (group C) and the combined regimen of meglumine antimoniate with liposomal amphotericin B
(group D), in order to conduct a decision analysis from among these therapeutic regimens for both adults and children. To this end, two scenarios were considered: scenario 1 is the currently prevailing in Brazil, where patients are always treated as
possible on an outpatient basis with meglumine antimoniate, although with a smaller monitoring on its potentially lethal side effects and a possible lower adherence to treatment. In the scenario 2, patients are hospitalized during the treatment period, with a better monitoring of clinical and laboratory parameters of the patient, although with a higher risk of nosocomial infections and increasing treatment costs. In terms of security, there is an emphasis on amphotericin B deoxycholate as the one that presents a greater amount of serious and potentially lethal adverse reactions, with an average of 2 severe reactions per patient. From the viewpoint of cost-efficacy, for scenario 1 the meglumine antimoniate remains the treatment of choice for both adults and children. However, in
scenario 2, the combination of drugs (group D) presented itself as the most costeffective for both adults and children. From this study it became clear, from a safety point of view for the patient, the need to evaluate both therapeutic regimens, particularly amphotericin B deoxycholate, such as the treatment scenarios for visceral leishmaniasis. / A busca por novas alternativas terapêuticas para as leishmanioses é considerada essencial pela Organização Mundial da Saúde, em virtude da elevada toxicidade dos
medicamentos atualmente utilizados, seu alto custo e o risco de resistência. No Brasil, utilizam-se três drogas para o tratamento da leishmaniose: o antimoniato de meglumina e as formulações de anfotericina B (desoxicolato e lipossomal). Este estudo é uma
análise econômica atrelada a um ensaio clínico multicêntrico, com o objetivo de se realizar uma análise de decisão entre os esquemas terapêuticos para a leishmaniose visceral, tanto para adultos como para crianças. Para tal, foram utilizados os dados
obtidos do estado de Sergipe, onde foram acompanhados 62 pacientes, randomizados para tratamento com antimoniato de meglumina (grupo A), considerado o esquema de primeira escolha no Brasil, anfotericina B desoxicolato (grupo B), anfotericina B lipossomal (grupo C) e o esquema terapêutico combinado de antimoniato de meglumina com anfotericina B lipossomal (grupo D). Na análise de decisão, foram considerados
dois cenários: o cenário 1, atualmente existente no Brasil, no qual os pacientes são tratados sempre que possível ambulatorialmente com o antimoniato de meglumina,
porém com um menor acompanhamento de suas reações adversas potencialmente letais e uma possível menor adesão ao tratamento. Já no cenário 2, os pacientes são internados
durante todo o período do tratamento, com um melhor monitoramento dos parâmetros clínicos e laboratoriais do paciente, porém com um risco maior de infecções
hospitalares e aumento de custos do tratamento. No quesito segurança, há um destaque para a anfotericina B desoxicolato como sendo a que apresenta uma maior quantidade
de reações adversas graves e potencialmente letais, com uma média de 2 reações graves/paciente. Já no ponto de vista de custo-eficácia, para o cenário 1 o antimoniato de meglumina continua sendo o tratamento de primeira escolha, tanto para adultos como para crianças. Porém, no cenário 2, a combinação de medicamentos (grupo D) se apresentou como o mais custo-eficaz tanto para adultos como para crianças. Deste
estudo evidenciou-se, do ponto de vista de segurança ao paciente, a necessidade de reavaliação tanto dos esquemas terapêuticos, particularmente a anfotericina B
desoxicolato, como dos cenários de tratamento para a leishmaniose visceral.
|
14 |
Efeitos da imunossupressão sobre a depuração mucociliar de ratos: comparação entre dois esquemas de terapia tríplice / Effects of immunosuppression on mucociliary clearance of rats: comparison between two triple therapy regimensSilva, Maristela Prado e 05 April 2016 (has links)
INTRODUÇÃO: O transplante de pulmão é parte fundamental no tratamento das doenças terminais do pulmão, constituindo uma modalidade terapêutica eficaz para pacientes com doença pulmonar incapacitante, progressiva e em estágio final. No entanto, as drogas imunossupressoras usadas para evitar a rejeição do enxerto podem causar efeitos colaterais em diversos tecidos. O sistema mucociliar, presente nas vias aéreas, é um dos principais mecanismos de defesa do trato respiratório e pode ser alterado por ação das drogas imunossupressoras. Desta forma, o objetivo deste estudo foi avaliar o sistema mucociliar traqueobrônquico de ratos submetidos a dois esquemas de terapia tríplice imunossupressora. MÉTODOS: Foram utilizados 90 ratos machos Wistar distribuídos em 3 grupos conforme o tratamento: controle (C) = solução salina; terapia 1 (TI) = tacrolimus + micofenolato de mofetil + prednisona; terapia 2 (TII) = ciclosporina + azatioprina + prednisona. Após o período de tratamento (7, 15 ou 30 dias), os animais foram sacrificados e realizadas as seguintes medidas: transportabilidade do muco (TM), frequência de batimento ciliar (FBC), quantificação de muco neutro e ácido, velocidade de transporte mucociliar (VTMC), e contagem total e diferencial de células no lavado broncoalveolar (LBA). RESULTADOS: A TM não foi afetada pelas terapias em nenhum dos tempos estudados. Ambas as terapias causaram significativa redução da FBC dos animais tratados por 7 e 15 dias. A produção de muco neutro foi menor nos animais tratados com a TI por 7, 15 e 30 dias. Porém, com a TII, essa redução ocorreu apenas aos 7 dias. Por outro lado, a quantidade de muco ácido foi significativamente maior em todos os animais tratados com as duas terapias. Todos os animais tratados com as terapias imunossupressoras apresentaram redução da VTMC nos três tempos. Houve aumento do número total de células e de macrófagos e neutrófilos no grupo TI em 7 dias. CONCLUSÕES: Ambas as terapias imunossupressoras foram prejudiciais ao transporte mucociliar das vias aéreas de ratos, tanto pela redução da FBC e da VTMC, quanto pela maior produção de muco ácido e menor produção de muco neutro. A TI foi mais prejudicial ao sistema mucociliar em comparação à TII / INTRODUCTION: Lung transplantation is an essential part in the treatment of terminal lung diseases, providing an effective therapeutic modality for patients with disabling, progressive and final stage lung disease. However, the immunosuppressant drugs used to prevent graft rejection may cause side effects in several tissues. The mucociliary system, present in the airways, is a major defense mechanism of the respiratory tract and can be changed by action of immunosuppressive drugs. Thus, the aim of this study was to evaluate the tracheobronchial mucociliary system of rats submitted to two triple immunosuppressive therapy regimens. METHODS: We used 90 male Wistar rats divided into 3 groups according to treatment: control (C) = saline solution; therapy 1 (TI) = tacrolimus + mycophenolate mofetil + prednisone therapy; therapy 2 (TII) = cyclosporine + azathioprine + prednisone. After the period of treatment (7, 15, or 30 days), the animals were sacrificed and the following measures taken: mucus transportability (MT), ciliary beating frequency (CBF), quantification of neutral and acid mucus, mucociliary transport velocity (MCTV), and total and differential counting of cells in bronchoalveolar lavage (BAL). RESULTS: MT was not affected by treatments in any of the periods studied. Both therapies have caused significant reduction of CBF of animals treated for 7 and 15 days. The neutral mucus production was lower in animals treated with TI for 7, 15 and 30 days. But with TII, this reduction occurred only at 7 days. Moreover, the amount of acid mucus was significantly higher in all animals treated with both therapies. All animals treated with immunosuppressive therapies had reduced MCTV at the three times. There was an increase of total cells and macrophages and neutrophils in the TI group in 7 days. CONCLUSIONS: Both immunosuppressive therapies were harmful to the mucociliary clearance of the airways of rats, either by reducing the CBF and MCTV, as by the increased production of acid mucus and decreased production of neutral mucus. TI was more harmful to the mucociliary system in comparison to TII
|
15 |
Efeitos da imunossupressão sobre a depuração mucociliar de ratos: comparação entre dois esquemas de terapia tríplice / Effects of immunosuppression on mucociliary clearance of rats: comparison between two triple therapy regimensMaristela Prado e Silva 05 April 2016 (has links)
INTRODUÇÃO: O transplante de pulmão é parte fundamental no tratamento das doenças terminais do pulmão, constituindo uma modalidade terapêutica eficaz para pacientes com doença pulmonar incapacitante, progressiva e em estágio final. No entanto, as drogas imunossupressoras usadas para evitar a rejeição do enxerto podem causar efeitos colaterais em diversos tecidos. O sistema mucociliar, presente nas vias aéreas, é um dos principais mecanismos de defesa do trato respiratório e pode ser alterado por ação das drogas imunossupressoras. Desta forma, o objetivo deste estudo foi avaliar o sistema mucociliar traqueobrônquico de ratos submetidos a dois esquemas de terapia tríplice imunossupressora. MÉTODOS: Foram utilizados 90 ratos machos Wistar distribuídos em 3 grupos conforme o tratamento: controle (C) = solução salina; terapia 1 (TI) = tacrolimus + micofenolato de mofetil + prednisona; terapia 2 (TII) = ciclosporina + azatioprina + prednisona. Após o período de tratamento (7, 15 ou 30 dias), os animais foram sacrificados e realizadas as seguintes medidas: transportabilidade do muco (TM), frequência de batimento ciliar (FBC), quantificação de muco neutro e ácido, velocidade de transporte mucociliar (VTMC), e contagem total e diferencial de células no lavado broncoalveolar (LBA). RESULTADOS: A TM não foi afetada pelas terapias em nenhum dos tempos estudados. Ambas as terapias causaram significativa redução da FBC dos animais tratados por 7 e 15 dias. A produção de muco neutro foi menor nos animais tratados com a TI por 7, 15 e 30 dias. Porém, com a TII, essa redução ocorreu apenas aos 7 dias. Por outro lado, a quantidade de muco ácido foi significativamente maior em todos os animais tratados com as duas terapias. Todos os animais tratados com as terapias imunossupressoras apresentaram redução da VTMC nos três tempos. Houve aumento do número total de células e de macrófagos e neutrófilos no grupo TI em 7 dias. CONCLUSÕES: Ambas as terapias imunossupressoras foram prejudiciais ao transporte mucociliar das vias aéreas de ratos, tanto pela redução da FBC e da VTMC, quanto pela maior produção de muco ácido e menor produção de muco neutro. A TI foi mais prejudicial ao sistema mucociliar em comparação à TII / INTRODUCTION: Lung transplantation is an essential part in the treatment of terminal lung diseases, providing an effective therapeutic modality for patients with disabling, progressive and final stage lung disease. However, the immunosuppressant drugs used to prevent graft rejection may cause side effects in several tissues. The mucociliary system, present in the airways, is a major defense mechanism of the respiratory tract and can be changed by action of immunosuppressive drugs. Thus, the aim of this study was to evaluate the tracheobronchial mucociliary system of rats submitted to two triple immunosuppressive therapy regimens. METHODS: We used 90 male Wistar rats divided into 3 groups according to treatment: control (C) = saline solution; therapy 1 (TI) = tacrolimus + mycophenolate mofetil + prednisone therapy; therapy 2 (TII) = cyclosporine + azathioprine + prednisone. After the period of treatment (7, 15, or 30 days), the animals were sacrificed and the following measures taken: mucus transportability (MT), ciliary beating frequency (CBF), quantification of neutral and acid mucus, mucociliary transport velocity (MCTV), and total and differential counting of cells in bronchoalveolar lavage (BAL). RESULTS: MT was not affected by treatments in any of the periods studied. Both therapies have caused significant reduction of CBF of animals treated for 7 and 15 days. The neutral mucus production was lower in animals treated with TI for 7, 15 and 30 days. But with TII, this reduction occurred only at 7 days. Moreover, the amount of acid mucus was significantly higher in all animals treated with both therapies. All animals treated with immunosuppressive therapies had reduced MCTV at the three times. There was an increase of total cells and macrophages and neutrophils in the TI group in 7 days. CONCLUSIONS: Both immunosuppressive therapies were harmful to the mucociliary clearance of the airways of rats, either by reducing the CBF and MCTV, as by the increased production of acid mucus and decreased production of neutral mucus. TI was more harmful to the mucociliary system in comparison to TII
|
16 |
Cooperative Drug Combinations Target Oncogenes and Tumor Suppressors in CancerTyler John Peat (11790659) 19 December 2021 (has links)
<p>Multiple myeloma (MM) is a neoplasm
involving plasma cells in the bone marrow. Drug resistance and progression are
common, underscoring the need for new drug combinations. Utilizing a high-throughput
screen of tool compounds to limit growth of human MM cell lines and <i>i</i><i>n silico</i> robust regression analysis of
drug responses, potential synergistic combinations were identified. Further
selection of effective combinations that reduce oncogenic MYC expression and enhance
tumor suppressor p16 activity was based on earlier genetic and drug studies that
identified MYC and p16 as appropriate targets in MM. Furthermore, the top three
combinations synergistically reduced drug sensitive and resistant cell
viability <i>in vitro</i> and the were effective in <i>ex vivo</i> treated patient cells Combination-associated survival was also
prolonged in a transplantable Ras-driven allograft model of advanced MM that closely
recapitulates MM in humans. One top drug combination was selected for further
preclinical development. Targets, mechanism of action, and efficacy of the
combination were evaluated through several <i>in vitro</i> and <i>in vivo </i>models,
as well as <i>ex vivo</i> in myeloma patient cells. Effective targeting of the
combination resulted in synergistic inhibition of proteasome inhibitor (PI) sensitive
MM cells, as well as cell with induced PI resistance. Additionally, the
combination was effective at delaying L363 MM xenograft growth in NSG mice and
prolonging survival compared to single agent therapy. Finally, a cooperative
signature of combined targeting was elucidated via RNA sequencing. These data
identify potentially useful drug combinations for preclinical evaluation in
drug-resistant MM and may ultimately reveal novel mechanisms of combined drug
sensitivity.</p>
|
17 |
New Molecular Approaches to Glioblastoma TherapyBaskaran, Sathishkumar January 2017 (has links)
Glioblastoma (GBM) is the most common high-grade brain tumor diagnosed in patients who are more than 50 years of age. The standard of care treatment is surgery, followed by radiotherapy and chemotherapy. The median life expectancy of patients is only between 12 to 15 months after receiving current treatment regimes. Hence, identification of new therapeutic compounds and gene targets are highly warranted. This thesis describes four interlinked studies to attain this goal. In study 1, we explored drug combination effects in a material of 41 patient-derived GBM cell (GC) cultures. Synergies between three compounds, pterostilbene, gefitinib, and sertraline, resulted in effective killing of GC and can be predicted by biomarkers. In study 2, we performed a large-scale screening of FDA approved compounds (n=1544) in a larger panel of GCs (n=106). By combining the large-scale drug response data with GCs genomics data, we built a novel computational model to predict the sensitivity of each compound for a given GC. A notable finding was that GCs respond very differently to proteasome inhibitors in both in-vitro and in-vivo. In study 3, we explored new gene targets by RNAi (n=1112) in a panel of GC cells. We found that loss of transcription factor ZBTB16/PLZF inhibits GC cell viability, proliferation, migration, and invasion. These effects were due to downregulation of c-MYC and Cyclin B1 after the treatment. In study 4, we tested the genomic stability of three GCs upon multiple passaging. Using molecular and mathematical analyses, we showed that the GCs undergo both systematic adaptations and sequential clonal takeovers. Such changes tend to affect a broad spectrum of pathways. Therefore, a systematic analysis of cell culture stability will be essential to make use of primary cells for translational oncology. Taken together, these studies deepen our knowledge of the weak points of GBM and provide several targets and biomarkers for further investigation. The work in this thesis can potentially facilitate the development of targeted therapies and result in more accurate tools for patient diagnostics and stratification.
|
18 |
Caractérisation des activités épigénétiques et anticancéreuses de la proscillaridine A dans les cancers pédiatriquesDa Costa, Elodie 11 1900 (has links)
Les glycosides cardiotoniques sont des inhibiteurs des pompes sodium / potassium utilisés
pour le traitements des insuffisances cardiaques, qui détiennent également des activités
anticancéreuses et épigénétiques récemment caractérisées. Toutefois, dans l’objectif de
repositionner ces médicaments comme traitement anticancéreux, les mécanismes sousjacents
aux activités anticancéreuses et épigénétiques des glycosides cardiotoniques restent à
être déterminés. Dans nos travaux, nous révélons que la proscillaridine A est le glycoside
cardiotonique qui détient des activités anticancéreuses et épigénétiques les plus puissantes
dans des lignées de cancer du côlon, de leucémies et de sarcomes pédiatrique. De plus, nous
avons identifié que l’activité anticancéreuse de la proscillaridine A corrèle positivement avec le
niveau d’expression protéique du proto-oncogène MYC dans un panel de 14 lignées cellulaires
cancéreuses. Dans les lignées cellulaires exprimants un haut niveau de MYC telles que les
lignées leucémiques, la proscillaridine A agit comme un inhibiteur de MYC et module sa
stabilité protéique ainsi que la régulation transcriptionnelle et translationnelle de ces cibles.
Cette inhibition est induite par la baisse significative de l’expression des enzymes
épigénétiques les lysines acétyltransférases (KATs), qui contrôlent l’ajout des résidus d’acétylcoenzyme
A sur les histones et sur d'autres protéines dont MYC. La baisse d’expression des
KATs résultent à une baisse de l’acétylation des résidus de l’histone 3 et à une
reprogrammation de l’acétylome des cellules cancéreuses surexprimant MYC. Ces
changements au niveau de la chromatine induisent une reprogrammation transcriptionnelle et
phénotypique des cellules surexprimant MYC, qui se traduit par une perte de la transcription
des programmes oncogéniques et l’induction des programmes associés à la différenciation
cellulaire. Pour finir, nous avons évalué le potentiel synergique anticancéreux et épigénétique
de la proscillaridine A avec le médicament épigénétique la décitabine dans des lignées
cancéreuses exprimants des niveaux différentiels de MYC. Dans une lignée résistante à la
proscillaridine A et exprimant de faible niveau de MYC (lignée de cancer de côlon), la
décitabine et la proscillaridine A démontrent des activités épigénétiques synergiques tandis
que dans une lignée sensible à la proscillaridine A et surexprimant MYC (lignée de sarcome
pédiatrique), la décitabine et la proscillaridine A démontrent des activités antiprolifératives
synergiques. Dans ces travaux, nous avons donc démontré le potentiel de repositionner la
proscillaridine A dans les cancers surexprimant MYC. Également, nous démontrons le potentiel
synergique anticancéreux et épigénétique de la proscillaridine A avec la décitabine et nous
suggérons d’étudier cette combinaison de médicaments dans les cancers plus résistants à la
proscillaridine A. / Cardiac glycosides are sodium/potassium pomps’ inhibitors used for the treatment of heart
failure, and whose anticancer and epigenetic activities have been recently characterized.
However, in order to repurpose cardiac glycosides as anticancer drugs, mechanistic studies
are required to identify the anticancer and epigenetic mechanism of actions. In our
experiments, proscillaridin A exhibited the most powerful anticancer and epigenetic activities in
colon cancer, leukemia, and sarcoma cell lines. Moreover, we demonstrated that in a panel of
14 cancer cell lines, proscillaridin A anticancer activities positively correlated with MYC protooncogene
expression level. In high MYC expressing cell lines such as leukemia, proscillaridin A
inhibited MYC expression through protein destabilization and through transcriptomic and
translational regulation of MYC targets. Theses inhibitions are induced by the loss of lysine
acetylatransferase (KAT) expressions, which are epigenetic enzymes controlling the addition of
acetyl-coenzyme A on histones and other proteins such as MYC. KAT inhibitions are responsible
for the global loss of histone 3 acetylation and acetylome reprogrammation in high MYC expressing
cancer cells. These chromatin changes induced transcriptomic and phenotypic
reprogrammation, defined by a loss of the transcription of oncogenic programs and the
induction of cell differentiation. To finish, we evaluated the anticancer and epigenetic synergic
potential of proscillaridin A in combination with the epigenetic drug the decitabine in cancer
cell lines expressing different MYC levels. In a cancer cell line resistant to proscillaridin A
treatments and expressing low MYC level (colon cancer cell line), the combination of
decitabine and proscillaridin A demonstrated synergistic epigenetic activity although, in a cell
line sensitive to proscillaridin A treatments and expressing high MYC level (sarcoma cell line),
the combination of decitabine and proscillaridin A exhibited synergistic anti-proliferative
activity. To conclude, we highlighted the potential of repurposing proscillaridin A as an anticancer
treatment in high MYC expressing cells. Furthermore, we demonstrated the anticancer and
epigenetic synergistic potential of proscillaridin A in combination with decitabine and we
propose to study the drug combination in cancers that are resistant to proscillaridin A
treatment.
|
Page generated in 0.0746 seconds