To Man Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 85-105). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / (in Chinese) --- p.iv / Acknowledgements --- p.vi / Publications --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xii / List of Figures --- p.xiii / List of Abbreviations --- p.xiv / Chapter CHAPTER 1: --- General Introduction --- p.1 / Chapter Section 1.1 --- Background and Clinical Application of Anthracylines --- p.1 / Chapter Section 1.2 --- DOX-induced Cardiotoxicity --- p.3 / Chapter 1.2.1 --- Types of Cardiotoxicity --- p.4 / Chapter 1.2.1.1 --- Acute Cardiotoxicity --- p.4 / Chapter 1.2.1.2 --- Chronic Cardiotoxicity --- p.5 / Chapter 1.2.2 --- Subcellular Effects of DOX --- p.6 / Chapter 1.2.2.1 --- Ultrastructural Lesions --- p.6 / Chapter 1.2.2.2 --- Effects on Mitochondrial Functions --- p.7 / Chapter 1.2.2.3 --- Effects on Sarcoplasmic reticulum (SR) Functions --- p.8 / Chapter Section 1.3 --- Mechanisms of DOX-induced Cardiotoxicity --- p.8 / Chapter 1.3.1 --- Formation of Free Radicals --- p.9 / Chapter 1.3.1.1 --- Generation of Free Radicals by DOX --- p.10 / Chapter 1.3.1.2 --- Cardiac damage by Free radicals --- p.12 / Chapter 1.3.2 --- Induction of Apoptosis --- p.14 / Chapter 1.3.2.1 --- Characteristics and Pathway of Apoptosis --- p.14 / Chapter 1.3.2.2 --- Mitochondria and Apoptosis --- p.15 / Chapter 1.3.2.3 --- Caspases and Apoptosis --- p.17 / Chapter 1.3.2.4 --- Apoptosis and DOX-induced Cardiotoxicity --- p.18 / Chapter Section 1.4 --- Strategies to Reduce DOX-induced Cardiotoxicity --- p.19 / Chapter 1.4.1 --- Dosage optimization and Schedule modification --- p.19 / Chapter 1.4.2 --- Anthracycline Analogues --- p.21 / Chapter 1.4.3 --- Cardioprotective Agents --- p.21 / Chapter Section 1.5 --- Thrombopoietin --- p.23 / Chapter CHAPTER 2: --- Hypotheses and Objectives --- p.30 / Chapter CHAPTER 3: --- Methodology --- p.33 / Chapter Section 3.1 --- Methods --- p.33 / Chapter 3.1.1 --- Culture of Rat H9C2 Myoblast Cell Line and Primary Neonatal Rat Cardiomyocytes --- p.33 / Chapter 3.1.1.1 --- Maintenance of Cell Line --- p.33 / Chapter 3.1.1.2 --- Culture of Primary Neonatal Rat Cardiomyocytes --- p.34 / Chapter 3.1.2 --- Effects of Thrombopoietin on Cell Viability of Rat H9C2 Myoblast Cell Line and Beating Rates of Primary Rat Cardiomyocytes --- p.35 / Chapter 3.1.2.1 --- Cell Viability assay --- p.35 / Chapter 3.1.2.2 --- Beating Rate of Primary Beating Cardiomyocytes --- p.36 / Chapter 3.1.3 --- Effects of Thrombopoietin on the Protection against DOX-induced Heart Injury In Vivo --- p.36 / Chapter 3.1.3.1 --- Animals --- p.36 / Chapter 3.1.3.2 --- Experimental Protocol --- p.37 / Chapter 3.1.3.3 --- Echocardiography --- p.38 / Chapter 3.1.3.4 --- Blood Cell Counts --- p.39 / Chapter 3.1.3.5 --- Histopathology --- p.39 / Chapter 3.1.4 --- Effects of Thrombopoietin on Apoptosis and Mitochondrial Integrity of Rat H9C2 Myoblast Cell Line and Apoptosis In Vivo --- p.40 / Chapter 3.1.4.1 --- Determination of Externalized Phosphatidylserine --- p.40 / Chapter 3.1.4.2 --- Determination of Active Caspase-3 Expression --- p.41 / Chapter 3.1.4.3 --- Assessment of Mitochondrial Integrity --- p.42 / Chapter 3.1.4.4 --- TUNEL assay --- p.43 / Chapter 3.1.5 --- Statistical Analysis --- p.44 / Chapter CHAPTER 4: --- Effects of Thrombopoietin on Cell Viability of Rat H9C2 Myoblast Cell Line and Beating Rates of Primary Neonatal Rat Cardiomyocytes --- p.46 / Chapter Section 4.1 --- Results --- p.46 / Chapter 4.1.1 --- Effects of TPO on DOX-induced Cell Death --- p.46 / Chapter 4.1.2 --- Effects of TPO on the Beating Rates of Primary Cardiomyocytes --- p.47 / Chapter Section 4.2 --- Discussion --- p.47 / Chapter CHAPTER 5： --- Effects of Thrombopoietin on the Protection Against DOX-induced Heart Injury In Vivo --- p.54 / Chapter Section 5.1 --- Results --- p.54 / Chapter 5.1.1 --- General Observations and Survival --- p.54 / Chapter 5.1.2 --- Blood Cell Counts --- p.55 / Chapter 5.1.3 --- Cardiac Functions by Echocardiography --- p.56 / Chapter 5.1.4 --- Gross Anatomic Changes and Pathology of the Myocardium --- p.57 / Chapter Section 5.2 --- Discussion --- p.58 / Chapter CHAPTER 6: --- Effects of Thrombopoietin on Apoptosis and Mitochondrial Integrity of H9C2 Cell Line and Apoptosis In Vico --- p.69 / Chapter Section 6.1 --- Results --- p.69 / Chapter 6.1.1 --- Determination of Externalized Phosphatidylserine --- p.69 / Chapter 6.1.2 --- Determination of Active Caspase-3 Activity --- p.70 / Chapter 6.1.3 --- Assessment of Mitochondrial Membrane Potential --- p.70 / Chapter 6.1.4 --- Determination of Apoptosis by TUNEL assay --- p.72 / Chapter Section 6.2 --- Discussion --- p.72 / Chapter CHAPTER 7： --- General Discussion and Conclusion --- p.83 / References --- p.85

Malignant brain tumor is one of the most lethal forms of cancers. In the United States alone, approximately 20,500 new cases of primary malignant brain and central nervous system tumors are expected to be diagnosed in 2007 with 12,740 deaths estimated. Treatment of malignant brain tumor remains a major challenge despite recent advance in surgery and other adjuvant therapies, such as chemotherapy. The failure of potential effective chemotherapeutics for brain tumor treatment is usually not due to the lack of potency of the drug, but rather can be attributed to lack of therapeutic strategies capable of overcoming blood brain barrier for effective delivery of drug to the brain tumor. In this thesis, we developed a minimally invasive sustained release system for glioma therapy. The present study was initiated in an effort to incorporated Doxorubicin (DOX) loaded PLGA particle into an agarose gel, which can provide a continuous release of DOX locally to the tumor site. DOX, a toposiomearase II inhibitor, is not currently used clinically for brain tumor treatment because when delivered systemically it does not cross BBB. Our hydrogel particle system can overcome this shortcoming of DOX. The results from this study demonstrate that the DOX/PLGA particle gel system can maintain the bioactivity of DOX and sustained release DOX for at least 15 day in vitro. The result of in vivo study showed the DOX/PLGA particle gel treated group had significantly extend the medium survival of 9L glioma bearing rat from 21 days to 29 days. Therefore, the success experience of this local and sustained delivery device might benefit the development of future glioma therapy strategy.

No description available.

Neuroblastom är en barncancer som uppstår ur det sympatiska nervsystemet och drabbar omkring 15 barn i Sverige varje år. Högriskvarianten är associerad med mycket hög dödlighet och risk för återfall, vilket tros ha att göra med att tumörernas ovanligt heterogena sammansättning tillåter resistenta subpopulationer att motstå konventionella behandlingsmetoder. Tidigare forskning har identifierat rubbade mekanismer för celldelning som ett tillvägagångssätt för tumörcellerna att överleva DNA-skador som kemoterapeutiska droger orsakar. I detta masterprojekt analyserades fem ultra-högrisk neuroblastomcellinjer i syfte att belysa deras progression genom celldelningen efter behandling med doxorubicin och/eller gemcitabin. Vidare identifierades ataxia telangesia mutated (ATM) serine/threonine kinase som ett essentiellt protein vid inhibering av celldelningen och i samband med reparation av DNA-skador, vilket bekräftades av förhöjt uttryck av fosforylerat ATM i alla fem cellinjer efter behandling med doxorubicin, gemcitabin, och/eller en kombination av båda. Återväxt av tumörcellerna efter inhibering av fosforylerat ATM i kombination med doxorubicin och gemcitabin analyserades sedan, och fördröjd återväxt noterades i en av cellinjerna efter kombinationsbehandling. Sammantaget har nya mekanismer för behandlingsresistens hos tumörceller identifierats och alternativa kombinationsbehandlingar har visat effekt på en av fem testade neuroblastomcellinjer. / Neuroblastoma is a pediatric cancer of the sympathetic nervous system that afflicts around 15 children annually in Sweden. Despite aggressive treatment, high-risk neuroblastoma is associated with a mortality of 50% and relapse rate of up to 60%, emphasizing the need for novel treatment options. In this study, fluoresce activated cell sorting was used to analyze cell cycle progression in five ultra-high-risk neuroblastoma cell lines: BE(2)-C, Kelly, SK-N-AS, SK-N-DZ, and SK-N-FI, post-treatment with doxorubicin and gemcitabine. In line with previous research, doxorubicin primarily induced cell cycle arrest in G2/M-phase and gemcitabine in the S-phase. Combined, the compounds induced varied effects, with accumulation primarily in the G1-and S-phase. Immunoblotting revealed elevated levels of phosphorylated ATM (pATM), a key regulator of cell cycle arrest and DNA damage signaling, across all five cell lines post-treatment to doxorubicin, gemcitabine, and/or the combination, indicating its vital role in their survival. Kelly stood out in both cell cycle progression and ATM phosphorylation, exhibiting minimal to no changes in cell cycle accumulation or pATM expression when exposed to the combined treatment, despite reacting to both monotherapies. These results may indicate that Kelly might implement an alternative mechanism of regulation compared to the remaining cell lines. To explore targeted inhibition of pATM, we employed the ATM kinase inhibitor KU-55933, which in BE(2)-C cells reduced expression levels of pATM when combined with doxorubicin, but not gemcitabine or the combination. Regrowth assays showed increased efficacy of doxorubicin and gemcitabine upon addition of the ATM kinase inhibitor KU-55933 in one of the tested cell lines in comparison to doxorubicin alone. However, longer incubation time is needed before the effect can be fully evaluated. These findings shed light on the differential cell cycle behavior in high-risk neuroblastoma cell lines exposed to combination therapy and suggest a vital role of ATM in the DNA damage response following doxorubicin and gemcitabine treatment. Further investigations are warranted to explore alternative strategies for enhancing the effectiveness of doxorubicin and gemcitabine in the treatment of this aggressive cancer subtype.

Chau, Kin Fan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 106-119). / Abstract also in Chinese. / Abstract --- p.II / 摘要 --- p.VI / Acknowledgements --- p.IX / List of figures --- p.X / List of Abbreviations --- p.XII / Table of Contents --- p.XV / Chapter Chapter 1: --- Introduction / Chapter 1.1 --- Incidence and etiology of hepatocellular carcinoma (HCC) --- p.1 / Chapter 1.2 --- Structure of Hepatitis B Virus (HBV) --- p.2 / Chapter 1.3 --- Hepatitis B X protein (HBx) and HCC --- p.5 / Chapter 1.4 --- HBx and Apoptosis --- p.8 / Chapter 1.5 --- The role of Bcl-2 family in apoptosis and cell survival --- p.10 / Chapter 1.6 --- "Bid, the BH3-domain only protein" --- p.14 / Chapter 1.7 --- Dual Functions of Bid --- p.16 / Chapter 1.8 --- The relationship between Bid and HBx --- p.19 / Chapter 1.9 --- Hypoxia and HCC --- p.21 / Chapter 1.10 --- Hypoxia and HBx --- p.25 / Chapter 1.11 --- Hypoxia and Bid --- p.28 / Chapter 1.12 --- Aim of study --- p.29 / Chapter Chapter 2: --- Methods and materials / Chapter 2.1 --- Confirmation of the culture of the stable cell lines --- p.30 / Chapter 2.2 --- Doxorubicin treatment to the cell lines --- p.34 / Chapter 2.3 --- Culture of the cell lines under hypoxic conditions --- p.35 / Chapter 2.4 --- Protein sample preparations --- p.37 / Chapter 2.5 --- Determination of protein samples --- p.38 / Chapter 2.6 --- Sodium dodecyl sulfate 226}0ؤ polyacrylamide gel electrophoresis (SDS- PAGE) --- p.39 / Chapter 2.7 --- Transfer of protein to nitrocellulose membranes --- p.39 / Chapter 2.8 --- Western blot analysis of proteins --- p.41 / Chapter 2.8.1. --- Antibodies --- p.41 / Chapter 2.8.2. --- Determination of expression profiles of desired proteins by immunoblotting --- p.45 / Chapter 2.9 --- "Measurement of cell viability by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay" --- p.46 / Chapter 2.10 --- Determination of cell proliferation by BrdU proliferation assay --- p.47 / Chapter 2.11 --- Detection of apoptosis of the cell lines by TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling) --- p.50 / Chapter 2.12 --- Determination of the involvement of p38 MAPK in the generation of truncated Bid by p38 MAPK inhibitor SB203580 --- p.52 / Chapter Chapter 3: --- Results / Chapter 3.1 --- Confirmation of plasmids and the stable cell lines --- p.53 / Chapter 3.2 --- Morphology and the basic parameters of the cells with full-length HBx or mutant HBx --- p.53 / Chapter 3.3 --- Cell viability under doxorubicin treatment with or without hypoxia --- p.59 / Chapter 3.4 --- Determination of cell proliferation under stress --- p.70 / Chapter 3.5 --- Expression profiles of various proteins in the stable cell lines under doxorubicin treatment with or without hypoxia --- p.74 / Chapter 3.5.1. --- Verification of hypoxia --- p.74 / Chapter 3.5.2. --- Pro-apoptotic proteins --- p.74 / Chapter 3.5.3. --- Anti-apoptotic proteins --- p.74 / Chapter 3.6 --- Determination of apoptosis of various cell lines under stress --- p.82 / Chapter 3.7 --- "p38 MAPK, but not Akt, was activated by doxorubicin" --- p.87 / Chapter 3.8 --- The p38 MAPK inhibitor SB203580 could attenuate the cleavage of Bid --- p.89 / Chapter Chapter 4: --- Discussion --- p.92 / Chapter Chapter 5: --- Conclusion and future prospective --- p.103 / Chapter Chapter 6: --- References --- p.106

Objetivo:Investigar "in vivo" la supervivencia de las motoneuronas del núcleo del VI par craneal tras la inyección intramuscular de toxina botulínica tipo A (TxBA) y doxorrubicina (DXR). Método: En el músculo recto lateral de las ratas se inyectó fluorogold(FG) y se determinó el número de motoneuronas del núcleo del VI par craneal. Tras el marcaje con FG de dichas motoneuronas se realizó la inyección intramuscular de diferentes dosis de TxBA y de DXR. Resultados: El número de motoneuronas marcadas con FG en los animales que fueron inyectados con TxBA fue similar al encontrado en los animales control. Sin embargo, era menor el número de motoneuronas marcadas en los animales inyectados con DXR. Conclusiones: La inyección intramuscular de TxBA no induce muerte de motoneuronas. La inyección intramuscular de DXR induce una muerte neuronal dosis dependiente en las motoneuronas del núcleo del VI par craneal. / Purpose: To investigate "in vivo" the survival of abducens motoneurons (AMNs) after a single intramuscular injection of the botulinum toxin A (BTxA) or doxorubicin (DXR). Methods: In rats, the AMNs were labeled with fluorogold (FG), which was applied intramuscularly in the lateral rectus muscle. The number of labeled neurons were determined in control animals; in animals that had received intramuscular injections of BTxA; and in rats that had received DXR. Result: The numbers of FG-labeled neurons in the animals that had been injected with BTxA were similar to those found in control animals. However, there were fewer FG-labeled neurons in the animals injected with DXR. Conclusion: The intramuscular injection of BTxA does not induce significant motoneuron death. Doxorubicin injected intramuscularly causes variable amounts of motoneuron death that is related to the amount of DXR injected.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

I ett försök att förstå orsakerna bakom de kardio-, metaboliska- och muskuloskeletala sjukdomar hos barn som överlevt akut lymfatisk leukemi (ALL) har vi studerat den adipogena differentieringen hos mesenkymala stromaceller från benmärg (BM MSCs). Det komplexa nätverket av faktorer som påverkar adipogenes är hittills inte helt kartlagt. Därför är vårt övergripande mål att få en bättre förståelse för den cellulära och molekylära grunden bakom utvecklingen av dessa tillstånd hos ALL-överlevare. Vi undersökte om behandling av BM MSC in vitro med cancerläkemedel, Doxorubicin och Dexamethason, kan påverka differentieringen mot adipogenes. BM MSCs analyserades med avseende på lipidackumulering, genuttryck och adipokinproduktion. Vår hypotes kunde inte bekräftas. Inga lipidackumuleringar kunde detekteras i cellerna. Vid analys av genuttryck av de adipogena transkriptionsfaktorerna PPARγ och C/EBPα sågs vissa förändringar; men på grund av brist på biologiska replikat kunde inga statistiska analyser tillämpas på resultaten. Slutligen sågs en liten ökning i den inflammation- och adipogenes-associerade cytokinen IL-6, medan cytokinerna IL-8 och TNF-a inte gick att detektera alls. / In an effort to understand the cause of late onset cardiac, metabolic, and musculoskeletal conditions in paediatric acute lymphoblastic leukaemia (ALL) survivors, the adipogenic differentiation of bone marrow (BM) mesenchymal stromal cells (MSCs) has been studied. There is a complex network of factors influencing adipogenesis, which to date is not completely understood. Hence, the overall aim is to better understand the cellular and molecular basis behind the development of these conditions in survivors. To this end, we asked whether treating BM MSCs in vitro with cancer drugs, Doxorubicin and Dexamethasone, will initiate a skewed differentiation towards adipogenesis. BM MSCs were analysed with respect to lipid accumulation, gene expression, and adipokine production. In general, our hypothesis was not confirmed. No lipid accumulations were detected in the cells. In analysis of gene expression of the adipogenic transcription factors PPARγ and C/EBPα, certain changes were seen; however, due to lack of biological replicates, no statistical analyses could be applied to the results. Lastly, the inflammation and adipogenesis associated cytokine IL-6 displayed a slight increase, whereas the cytokines IL-8 and TNF-α were undetectable.

The childhood cancer neuroblastoma mostly affects children under the age of 2 and comprises 6% of all childhood cancers. Neuroblastoma has very diverse phenotypes caused by both inter- and intra-tumour heterogeneities. The phenotypes are classified as being either low- or high-risk. This project focuses on high-risk NB cell lines with various chemotherapy sensitivity. Titration studies with chemotherapy agents cisplatin or doxorubicin showed a proneness of p53 mutated cell lines to arrest in either the S- and/or the G2/M-phase, depending on the drug and the drug dosage, indicating on a dose-dependent cell cycle response. To potentially inhibit the cells from arresting a treatment assay with 3 cell cycle key-components, pATM, Chk1 and Wee1 inhibitors was done. An initial immunocytochemistry staining of the expression levels of pATM and Wee1 showed that pATM was upregulated for 5 out 7 tested cell lines, namely SK-N-SH, SK-N-FI, Kelly, SK-N-DZ and BE(2)-C, upon chemotherapy treatment with doxorubicin. Wee1 was however only upregulated for 3 out 7 cell lines; Kelly, SK-N-DZ and BE(2)-C. The upregulation of pATM and Wee1 showed a potential confirmation of their involvement in CT induced cell cycle arrest. Upon inhibition of pATM, Chk1 and Wee1 diverse effects were observed for each cell line (SK-N-SH, SK-N-AS, SK-N-FI, Kelly, SK-N-DZ and BE(2)-C). Wee1 showed the most promising results were the cell viability decreased for all 5 p53 mutated cell lines and the confluency over time decreased for 4 out 5 p53 mutated cell lines. The p53 wild type cell line SK-N-SH was less sensitive towards Chk1 and Wee1 inhibition indicating that cell lines with functional p53 might not be as dependent on the Chk1 and Wee1 pathways compared to cell lines with non-functional p53. Thus, targeting the cell cycle arrest might be a promising therapeutic target for high-risk neuroblastoma. / Barndomscancern neuroblastom utgör 6% av all barncancer. Majoriteten av de drabbade är under 2 år. Neuroblastom har en stor mångfald av fenotypiska utryck som orsakas av dess inter- och intra-tumör heterogenitet. Fenotyperna klassificeras antigen som låg- eller högrisk. Här har 7 högrisks-neutoblastom cellinjer med varierande grad av känslighet mot kemoterapi analyserats. Titreringsstudier med kemoterapierna cisplatin och doxorubicin påvisade en benägenhet för de p53 muterade cellinjerna att arrestera i S- och/eller i G2/M-fasen, beroende på behandlingen samt behandlingsdosen, vilket indikerar på en dos-beroende cellcykel respons. En behandlingsanalys med de 3 nyckelkomponenterna fosforylerat ATM, Chk1 samt Wee1 gjordes för att potentiellt inhibera cellerna från att arrestera. Efter en initial immunocytokemi infärgning av pATM samt Wee1 visade 5 av 7 cellinjer (SK-N-SH, SK-N-FI, Kelly, SK-N-DZ samt BE(2)-C) en uppreglering av pATM-uttryck till följd av doxorubicin behandling. Däremot var Wee1 endast uppreglerat för 3 av 7 cell linjer (Kelly, SK-N-DZ samt BE(2)-C). Uppregleringen av pATM och Wee1 påvisar ett potentiellt samband mellan kemoterapi-inducerad cellcykelarrest och ökat utryck av pATM och Wee1. Vid inhibering av pATM, Chk1 samt Wee1 gav Wee1 de mest lovande resultaten där cellviabiliteten minskade för samtliga 5 p53-muterade cellinjer och där konfluensen över tid minskade för 4 av 5 p53-muterade cellinjer. SK-N-SH med funktionerande p53 var mindre känslig gentemot Chk1 och Wee1 inhibering, vilket indikerar att cellinjer med funktionerande p53 inte är lika beroende av reaktionsvägarna för Chk1 och Wee1 jämfört med cellinjer som har icke-funktionerande p53. Därmed kan riktad behandling mot cellcykelarrest vara en lovande behandling för högrisks-neuroblastom.

I ett försök att förstå orsakerna bakom de kardio-, metaboliska- och muskuloskeletala sjukdomar hos barn som överlevt akut lymfatisk leukemi (ALL) har vi studerat den adipogena differentieringen hos mesenkymala stromaceller från benmärg (BM MSCs). Det komplexa nätverket av faktorer som påverkar adipogenes är hittills inte helt kartlagt. Därför är vårt övergripande mål att få en bättre förståelse för den cellulära och molekylära grunden bakom utvecklingen av dessa tillstånd hos ALL-överlevare. Vi undersökte om behandling av BM MSC in vitro med cancerläkemedel, Doxorubicin och Dexamethason, kan påverka differentieringen mot adipogenes. BM MSCs analyserades med avseende på lipidackumulering, genuttryck och adipokinproduktion. Vår hypotes kunde inte bekräftas. Inga lipidackumuleringar kunde detekteras i cellerna. Vid analys av genuttryck av de adipogena transkriptionsfaktorerna PPARγ och C/EBPα sågs vissa förändringar; men på grund av brist på biologiska replikat kunde inga statistiska analyser tillämpas på resultaten. Slutligen sågs en liten ökning i den inflammation- och adipogenes-associerade cytokinen IL-6, medan cytokinerna IL-8 och TNF-a inte gick att detektera alls. / In an effort to understand the cause of late onset cardiac, metabolic, and musculoskeletal conditions in paediatric acute lymphoblastic leukaemia (ALL) survivors, the adipogenic differentiation of bone marrow (BM) mesenchymal stromal cells (MSCs) has been studied. There is a complex network of factors influencing adipogenesis, which to date is not completely understood. Hence, the overall aim is to better understand the cellular and molecular basis behind the development of these conditions in survivors. To this end, we asked whether treating BM MSCs in vitro with cancer drugs, Doxorubicin and Dexamethasone, will initiate a skewed differentiation towards adipogenesis. BM MSCs were analysed with respect to lipid accumulation, gene expression, and adipokine production. In general, our hypothesis was not confirmed. No lipid accumulations were detected in the cells. In analysis of gene expression of the adipogenic transcription factors PPARγ and C/EBPα, certain changes were seen; however, due to lack of biological replicates, no statistical analyses could be applied to the results. Lastly, the inflammation and adipogenesis associated cytokine IL-6 displayed a slight increase, whereas the cytokines IL-8 and TNF-α were undetectable.