Abstract:
:Pathophysiological factors exist within solid tumors that lead to a low pH environment. Therefore, pH-sensitive cancer chemotherapeutic agents may selectively target and kill tumor cells while sparing the normal tissue from toxicity. Using colony forming assays to assess cell survival, we found that EMT6 mouse mammary tumor cells were more sensitive to cisplatin cytotoxicity when cultured in pH 6.0 medium than in pH 7.2, 6.8, or 6.4 medium. The pH-dependent cytotoxicity of cisplatin resulted from an increase in cisplatin accumulation and an increase in the amount of DNA cross-links at pH 6.0 compared with pH 7.2. Because DNA is the cytotoxic target of cisplatin, intracellular pH (pHi) may be an important factor in determining the cytotoxicity of anticancer drugs at low extracellular pH (pHe). Therefore, manipulating the pHi of cells could be one method to enhance the effectiveness of the pH-sensitive chemotherapeutic agents. The pHi of EMT6 cells varied with pHe: at pHe 7.2, pHi was 7.54; at pHe 6.8, pHi was 7.29; at pHe 6.4, pHi was 7.02; and at pHe 6.0, pHi was 6.64. Using inhibitors to the ion transport mechanisms which regulate pHi, 5-N,N-hexamethylene amiloride (NHMA) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), the pHi and pHe of EMT6 cells were equilibrated. To evaluate the importance of pHi in determining drug toxicity, cell survival was determined for cells treated with cisplatin in the presence of NHMA and SITS. Cells cultured with NHMA and SITS were less sensitive to cisplatin. The cisplatin resistance obtained was independent of pH and could be attributed to the presence of SITS.
journal_name
Oncol Resjournal_title
Oncology researchauthors
Laurencot CM,Kennedy KAsubject
Has Abstractpub_date
1995-01-01 00:00:00pages
371-9issue
7-8eissn
0965-0407issn
1555-3906journal_volume
7pub_type
杂志文章abstract::A series of bis-aziridinylnaphthoquinone derivatives has been prepared. The cytotoxic activities and DNA alkylation abilities of these synthetic bis-aziridinylnaphthoquinone derivatives were investigated. They displayed significant cytotoxicity against human carcinomna cell lines and weak cytotoxic activities against ...
journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00
abstract::A1, a member of the Bcl-2 gene family, was originally identified as a hemopoietic-specific early response gene. Later it was found that A1 was overexpressed in human stomach cancer tissues and was induced by tumor necrosis factor-alpha (TNF-alpha) in human vascular endothelial cells. However, its expression in human c...
journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Lung cancer is the leading cause of deaths due to cancer. Studies suggest an important role of microRNAs (miRNAs) in a variety of cancers, including lung cancer. In the present study, we evaluated the role of miR-641 in human lung cancer A549 cells. Quantitative RT-PCR and Western blot were used to measure mRNA and pr...
journal_title:Oncology research
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journal_title:Oncology research
pub_type: 杂志文章
doi:10.3727/096504016X14816352324532
更新日期:2017-07-05 00:00:00
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journal_title:Oncology research
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journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Oncology research
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journal_title:Oncology research
pub_type: 杂志文章
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更新日期:1995-01-01 00:00:00
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journal_title:Oncology research
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journal_title:Oncology research
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-01-01 00:00:00
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journal_title:Oncology research
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Oncology research
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doi:10.3727/096504016X14641336229602
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doi:10.3727/096504020X15907428281601
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journal_title:Oncology research
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doi:10.3727/096504012x13285365944337
更新日期:2011-01-01 00:00:00
abstract::MicroRNAs (miRNAs) play important roles in the carcinogenesis of cervical cancer. However, the expression and underlying mechanisms of miRNA in cervical cancer progression remain unclear. In the present study, our data showed that the expression of miR-138-5p was significantly downregulated in cervical cancer tissues,...
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journal_title:Oncology research
pub_type: 杂志文章
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journal_title:Oncology research
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更新日期:1993-01-01 00:00:00
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journal_title:Oncology research
pub_type: 杂志文章
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journal_title:Oncology research
pub_type: 杂志文章
doi:
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journal_title:Oncology research
pub_type: 杂志文章
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