Sensitivity of testis tumour cells to chemotherapeutic drugs: Role of detoxifying pathways

Masters, J. R. W.; Thomas, Robert Paul; Hall, Amy B.; Hogarth, Linda; Matheson, Elizabeth; Cattan, A; Lohrer, Horst D.

doi:10.1016/0959-8049(96)00033-0

Cited by 62 publications

(38 citation statements)

References 35 publications

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“…Several reports have shown that the level of DNA adducts upon initial exposure to cisplatin is similar in TGCT cell lines compared to other cancer lines [89,96]. This supports the notion that increased access of cisplatin to DNA in TGCTs via greater drug accumulation or activation is not associated with hypersensitivity per se.…”

Section: Recognition and Repair Of Dna Adductssupporting

confidence: 74%

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Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells

Giuliano

Freemantle

Spinella

2006

CCTR

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Treatment of testicular germ cell tumors (TGCTs) has been a success primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based therapy. Despite the promise of cure for the majority of TGCT patients, the effectiveness of therapy for some patients is limited by toxicity and the problem of resistance. There is compelling rationale to further understand the biology of TGCTs in order to better treat other solid tumors and to address the shortcomings of present TGCT therapies. TGCTs contain undifferentiated pluripotent stem cells, known as embryonal carcinoma, that share many properties with human embryonic stem cells. The importance of cancer stem cells in the initiation, progression and treatment of solid tumors is beginning to emerge. We discuss TGCTs in the context of solid tumor curability and targeted cancer stem cell therapy.

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Section: Recognition and Repair Of Dna Adductssupporting

confidence: 74%

“…Although not universally reported, in general it appears that the level of these detoxifiers are low in TGCTs compared to some other tumor types [96]. Interestingly, one study noted high levels of a gluatione-S-transfersase, the enzyme that conjugates glutathione, only in inherently resistant teratoma [95].…”

Section: Drug Transport and Detoxificationmentioning

confidence: 99%

Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells

Giuliano

Freemantle

Spinella

2006

CCTR

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“…The mice in control groups were treated with saline. Tumors were measured across three dimensions twice a week, and the tumor volume (mm 3 ) was calculated using the following formula: tumor volume = π (length × width × thickness) / 6. Inhibition of tumor growth was calculated according to the following formula: (1− the mean tumor volume of the treated group / the mean tumor volume of the control group at the time point of observation) × 100%.…”

Section: Methodsmentioning

confidence: 99%

“…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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“…The biochemical mechanisms underlying the exquisite sensitivity of germ-cell tumours for CDDP still has to be defined. Understanding of the mechanisms underlying sensitivity or resistance to CDDP is derived predominantly from studies using cell lines selected for CDDP resistance in vitro (for review, see Andrews and Howell, 1990) and from studies using unselected cell lines (Bedford et al, 1988;Sark et al, 1995;Masters et al, 1996). These studies revealed that several mechanisms can be involved in resistance to CDDP, including decreased drug accumulation, increased detoxification, decreased DNA-platination, increased DNA repair, tolerance to DNA damage and/or the occurrence of apoptosis (balance suppressor/oncogene expression).…”

mentioning

confidence: 99%

Role of metallothionein in cisplatin sensitivity of germ-cell tumours

Meijer

Timmer²,

Vries

et al. 2000

Int. J. Cancer

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Sensitivity of testis tumour cells to chemotherapeutic drugs: Role of detoxifying pathways

Cited by 62 publications

References 35 publications

Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells

Testicular Germ Cell Tumors: A Paradigm for the Successful Treatment of Solid Tumor Stem Cells

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

Role of metallothionein in cisplatin sensitivity of germ-cell tumours

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