JM216-, JM118-, and cisplatin-induced cytotoxicity in relation to platinum-DNA adduct formation, glutathione levels and p53 status in human tumour cell lines with different sensitivities to cisplatin

Fokkema, Eelco; Groen, Harry J.M.; Helder, Marco N.; Vries, Elisabeth G.E. de; Meijer, Coby

doi:10.1016/s0006-2952(02)00983-8

Cited by 61 publications

(35 citation statements)

References 20 publications

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“…This has prompted extensive studies to investigate the cellular and molecular mechanisms of platinum resistance in various cancer cells. Development of platinum resistance has been attributed to decreased drug accumulation, enhanced detoxification capability, aberrant apoptosis pathway, and increased repair of drug-induced DNA damage (1)(2)(3)(4)(5)(6)(7)(8). It has been reported that metallothioneins (9), glutathione S-transferase π (10), p53 (11), ERCC1 (12), copper transporters (13), and XIAP (14) can be responsible for these changes in cells.…”

Section: Introductionmentioning

confidence: 99%

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

et al. 2010

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Resistance to platinum drugs has emerged as a major obstacle in the treatment of ovarian cancers. Through proteomic analysis, we have found that the expression of annexin A3, a member of the Ca 2+ and phospholipidbinding annexin family, is significantly increased in platinum-resistant ovarian cell lines. Anti-annexin A3 immunostaining indicated that cancers from platinum-resistant patients also possess higher levels of annexin A3 than those from platinum-sensitive patients. Although expression of annexin A3 made susceptible ovarian cancer cells more resistant to platinum, expression of antisense annexin A3 downregulated its expression and rendered the resistant cells more sensitive to platinum. In athymic mice, the growth of tumors from inoculated SKOV3 cells was inhibited by the administration of platinum, whereas tumors from annexin A3-expressing SKOV3/Ann were resistant to platinum treatment. Interestingly, the intracellular platinum concentration and platinum-DNA binding are significantly lower in annexin A3-overexpressing cells than those in parental cells. The lower cisplatin concentration was also accompanied by reduced induction of p53, which could be restored by downregulation of annexin A3. These results indicate that increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. It seems to act by preventing uptake or accumulation of platinum in cells. Therefore, it is conceivable that annexin A3 could be a target for therapeutic intervention and may also serve as a biomarker for drug resistance in ovarian cancer patients. Cancer Res; 70(4); 1616-24. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

et al. 2010

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“…Satraplatin [bisacetatoammine-dichloro-cyclohexylamine-platinum(IV)] is a novel, orally bioavailable, platinum agent (5). It was selected from a series of oral platinum compounds because of promising preclinical features including in vitro antitumor activity, in vivo antitumor activity at least comparable with cisplatin and carboplatin in a diversity of murine and human tumor models, and finally its ability to partially circumvent intrinsic and acquired resistance to cisplatin (5)(6)(7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Satraplatin, an Oral Platinum, Administered on a Five-day Every-Five-Week Schedule: a Pharmacokinetic and Food Effect Study

Ricart

Sarantopoulos

Calvo

et al. 2009

Clinical Cancer Research

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Purpose: The study aimed to assess the pharmacokinetic behavior of satraplatin under fasted and fed conditions, and its safety and preliminary antitumor activity in adults with advanced solid tumors. Experimental Design: Satraplatin was administered orally at 80 mg/m 2 once daily with prophylactic antiemetics for 5 consecutive days every 5 weeks. Patients were randomized to receive day 1 and day 5 doses of satraplatin in either the fed or fasted state, the order being reversed for cycle 2. Pharmacokinetic sampling was done during the first two cycles. For all subsequent cycles, patients received satraplatin in the fasted state. Results: Seventeen patients were treated with 60 total cycles of satraplatin. There was no dose-limiting toxicity during cycle 1. Severe hematologic toxicity was rare and the hematologic nadir occurred during week 4. Nausea, vomiting, and diarrhea were grade 1/2. No significant cardiac, renal, hepatic, or neurologic toxicity was observed. The hypothesis that food decreased ultrafiltrate platinum bioavailability could not be rejected, as the lower limit of the 90% confidence intervals for peak plasma concentration and area under the concentration-time curve from time 0 to 24 hours were 56.14% and 73.53%, respectively, both below the 80% bioequivalence acceptance criterion. One partial response (hormone refractory prostate cancer) and four durable stable diseases (breast, ovarian, parotid, and hormone refractory prostate cancer) were confirmed. Conclusions: There is an effect of food on the pharmacokinetics of satraplatin, the clinical significance of which is unclear. It is recommended that satraplatin be administered in the fasting state. This 5-week interval schedule of satraplatin was well tolerated in heavily pretreated patients.Platinum analogs form the mainstay of treatment for a number of cancers, including bladder, head and neck, lung, ovarian, and testicular cancer, and a usual first option against colorectal and esophagogastric cancer. All approved platinum anticancer drugs are administered i.v., with aggressive hydration to avoid acute nephrotoxicity in the case of cisplatin (1, 2). In addition, their efficacy is often limited by cumulative toxicity, particularly neurotoxicity and ototoxicity (1,3,4). Satraplatin [bisacetatoammine-dichloro-cyclohexylamine-platinum(IV)] is a novel, orally bioavailable, platinum agent (5). It was selected from a series of oral platinum compounds because of promising preclinical features including in vitro antitumor activity, in vivo antitumor activity at least comparable with cisplatin and carboplatin in a diversity of murine and human tumor models, and finally its ability to partially circumvent intrinsic and acquired resistance to cisplatin (5-12).When satraplatin was administered every three to four weeks, nonlinear pharmacokinetics, probably due to saturable absorption, were observed (13,14). Subsequently, a daily schedule for five consecutive days was developed, with the dose utilized for phase II and III studies varying between 100 ...

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“…One of the anti-tumor Pt(IV) drugs, which is an analogue of cisplatin, is bisacetatoamminedichloro(cyclohexylamine)platinum(IV) (JM216, Figure 25.5) the first orally administrable platinum complex that has entered the clinic. 48 The DNA-binding properties of JM216 on naked DNA or within tumor cells are similar to those of cisplatin, although there are some differences in the nature of the adducts. 49 The search for a clinically useful orally available anti-tumor platinum drug also led to the design of several Pt(IV) compounds with trans-leaving ligands.…”

Section: Platinum(iv) Compoundsmentioning

confidence: 97%

₇₈ Pt Platinum‐Based Drugs

Brabec

Kašpárková

2005

Metallotherapeutic Drugs and Metal‐Based Diagnostic Agents

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JM216-, JM118-, and cisplatin-induced cytotoxicity in relation to platinum-DNA adduct formation, glutathione levels and p53 status in human tumour cell lines with different sensitivities to cisplatin

Cited by 61 publications

References 20 publications

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

Satraplatin, an Oral Platinum, Administered on a Five-day Every-Five-Week Schedule: a Pharmacokinetic and Food Effect Study

₇₈ Pt Platinum‐Based Drugs

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JM216-, JM118-, and cisplatin-induced cytotoxicity in relation to platinum-DNA adduct formation, glutathione levels and p53 status in human tumour cell lines with different sensitivities to cisplatin

Cited by 61 publications

References 20 publications

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer

Satraplatin, an Oral Platinum, Administered on a Five-day Every-Five-Week Schedule: a Pharmacokinetic and Food Effect Study

78 Pt Platinum‐Based Drugs

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₇₈ Pt Platinum‐Based Drugs