Topotecan and Doxorubicin Combination to Treat Recurrent Ovarian Cancer: The Influence of Drug Exposure Time and Delivery Systems to Achieve Optimum Therapeutic Activity

Patankar, Nilesh A.; Pritchard, J. Frederick; Grinsven, Mariska carav Van; Osooly, Maryam; Bally, Marcel B.

doi:10.1158/1078-0432.ccr-12-2459

Cited by 26 publications

(16 citation statements)

References 46 publications

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“…The result revealed that RASSF1A is absent in SKOV-3 and OVCAR-3 cells, while it is present in the HO8910 and HO8910PM cells. Our findings are consistent with those of a previous study showing that SKOV-3 and OVCAR-3 cells represent an ovarian cancer, referred to as serous adenocarcinoma (28). We subsequently transfected SKOV-3 cells with an adenovirus with or without RASSF1A and the expression of RASSF1A in the differently treated SKOV-3 cells was analyzed.…”

Section: Discussionsupporting

confidence: 91%

RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells

Zhang

2014

International Journal of Molecular Medicine

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As the most lethal gynecological malignancy, ovarian cancer has attracted much attention over the past few decades; however, the early detection of this malignancy has been largely unsuccessful. The aim of this study was to determine the effects of Ras-association domain family 1, isoform A (RASSF1A) on ovarian cancer and to elucidate the molecular mechanisms responsible for these effects. The expression of RASSF1A in different ovarian cancer cells was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The morphology, structure, apoptosis and proliferation of differently treated SKOV-3 cells were then analyzed using a fluorescence microscope, transmission electron microscope, flow cytometer and by western blot analysis, respectively. Moreover, the GSE14407 affymetrix microarray data were downloaded from the Gene Expression Omnibus database and the expression of RASSF1A was quantified by Spotfire DecisionSite software. A RASSF1A related protein-protein interaction (PPI) network was then constructed using STRING and Cytoscape software. Finally, DAVID was utilized to perform KEGG pathway enrichment analysis of the network. RASSF1A was expressed in the HO8910, HO8910PM cells and the SKOV-3 cells transfected with RASSF1A, whereas it was absent in the other SKOV-3 cells and OVCAR-3 cells. Additionally, compared with the other SKOV-3 cells, the nucleus of SKOV-3 cells transfected with RASSF1A was vacuolated, apoptosis was increased, and the expression of cyclin D1 and survivin was decreased (P<0.05), and that of p27 and caspase-3 was increased (P<0.01). Additionally, 10 genes, including serine/threonine kinase (STK)3, STK4, Harvey rat sarcoma viral oncogene homolog (HRAS) and cell division cycle 20 (CDC20), were found to have close interactions with RASSF1A in the PPI network. Finally, a total of 8 enriched pathways, such as bladder cancer, non-small cell lung cancer and pathways in cancer were identified. To our knowledge, this is the first study to explore the biological functions and the underlying mechanisms of action of RASSF1A in the development of ovarian cancer. Our findings may provide a novel therapeutic target for ovarian cancer.

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Section: Discussionsupporting

confidence: 91%

RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells

Zhang

2014

International Journal of Molecular Medicine

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“… Li & Howell (2010) and Patankar et al (2013) used different doses of chemotherapeutics in the treatment group and control group. Therefore, it was tested whether these studies were responsible for the positive overall outcome.…”

Section: Resultsmentioning

confidence: 99%

Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies

Raavé

Vries

Massuger

et al. 2015

PeerJ

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Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To overcome these limitations, drug delivery systems (DDS) have been developed to encapsulate chemotherapeutics for delivery to tumor cells. However, no systematic assessment of the efficacy of chemotherapy by DDS compared to free chemotherapy (not in a DDS) has been performed for animal studies. Here, we assess the efficacy of chemotherapy in DDS on survival and tumor growth inhibition in animal studies. We searched PubMed and EMBASE (via OvidSP) to systematically identify studies evaluating chemotherapeutics encapsulated in DDS for ovarian cancer treatment in animal studies. Studies were assessed for quality and risk of bias. Study characteristics were collected and outcome data (survival/hazard ratio or tumor growth inhibition) were extracted and used for meta-analyses. Meta-analysis was performed to identify and explore which characteristics of DDS influenced treatment efficacy. A total of 44 studies were included after thorough literature screening (2,735 studies found after initial search). The risk of bias was difficult to assess, mainly because of incomplete reporting. A total of 17 studies (377 animals) and 16 studies (259 animals) could be included in the meta-analysis for survival and tumor growth inhibition, respectively. In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition. Subgroup analyses, however, revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin, although it did result in improved survival. Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics, which indicates that micelles may not be a suitable DDS for ovarian cancer treatment. Other subgroup analyses, such as targeted versus non-targeted DDS or IV versus IP administration route, did not identify specific characteristics of DDS that affected treatment efficacy. This systematic review shows the potential, but also the limitations of chemotherapy by drug delivery systems for ovarian cancer treatment. For future animal research, we emphasize that data need to be reported with ample attention to detailed reporting.

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“…According to the Drug Combination Database (DCDB) [ 4 ], there have been 330 FDA-approved and 1033 investigational drug combinations until the second version. With more and more researches on this new form of therapy, drug combinations have been proven a promising way to combat complex diseases [ 5 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Systematic synergy modeling: understanding drug synergy from a systems biology perspective

Chen

Yang

et al. 2015

BMC Syst Biol

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Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose–response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and “omic”-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.

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Topotecan and Doxorubicin Combination to Treat Recurrent Ovarian Cancer: The Influence of Drug Exposure Time and Delivery Systems to Achieve Optimum Therapeutic Activity

Cited by 26 publications

References 46 publications

RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells

RASSF1A promotes apoptosis and suppresses the proliferation of ovarian cancer cells

Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies

Systematic synergy modeling: understanding drug synergy from a systems biology perspective

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