| Title |
Changes in the in vitro activity of platinum drugs when administered in two aliquots
|
|---|---|
| Published in |
BMC Cancer, August 2016
|
| DOI | 10.1186/s12885-016-2731-1 |
| Pubmed ID | |
| Authors |
Zaynab Al-Eisawi, Philip Beale, Charles Chan, Jun Qing Yu, Nicholas Proschogo, Mark Molloy, Fazlul Huq |
| Abstract |
The management of ovarian cancer remains a challenge. Because of the lack of early symptoms, it is often diagnosed at a late stage when it is likely to have metastasized beyond ovaries. Currently, platinum based chemotherapy is the primary treatment for the disease. However acquired drug resistance remains an on-going problem. As cisplatin brings about apoptosis by intrinsic and extrinsic pathways, this study aimed to determine changes in activity of platinum drugs when administered in two aliquots as against a bolus and sought to determine association with changes in GSH, speciation of platinum drugs and changes in protein expression. The efficacy of administering cisplatin, carboplatin and oxaliplatin in two aliquots with a time gap was investigated in ovarian A2780, A2780(cisR), A2780(ZD0473R) and SKOV-3 cell lines. The cellular accumulation of platinum, level of platinum - DNA binding and cellular glutathione level were determined, and proteomic studies were carried out to identify key proteins associated with platinum resistance in ovarian A2780(cisR) cancer cell line. Much greater cell kill was observed with solutions left standing at room temperature than with freshly prepared solutions, indicating that the increase in activity on ageing was related to speciation of the drug in solution. Proteomic studies identified 72 proteins that were differentially expressed in A2780 and A2780(cisR) cell lines; 22 of them were restored back to normal levels as a result of synergistic treatments, indicating their relevance in enhanced drug action. The proteins identified are relevant to several different cellular functions including invasion and metastasis, cell cycle regulation and proliferation, metabolic and biosynthesis processes, stress-related proteins and molecular chaperones, mRNA processing, cellular organization/cytoskeleton, cellular communication and signal transduction. This highlights the multifactorial nature of platinum resistance in which many different proteins with diverse functions play key roles. This means multiple strategies can be harnessed to overcome platinum resistance in ovarian cancer. The results of the studies can be significant both from fundamental and clinical view points. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 3 | 19% |
| Student > Doctoral Student | 2 | 13% |
| Professor | 2 | 13% |
| Researcher | 2 | 13% |
| Professor > Associate Professor | 2 | 13% |
| Other | 4 | 25% |
| Unknown | 1 | 6% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 38% |
| Medicine and Dentistry | 6 | 38% |
| Chemistry | 1 | 6% |
| Agricultural and Biological Sciences | 1 | 6% |
| Unknown | 2 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 September 2016.
All research outputs
#15,381,871
of 22,884,315 outputs
Outputs from BMC Cancer
#4,123
of 8,326 outputs
Outputs of similar age
#216,032
of 338,621 outputs
Outputs of similar age from BMC Cancer
#102
of 246 outputs
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