Significance of Nuclear Glutathione S‐Transferase π in Resistance to Anti‐cancer Drugs

Goto, Shinji; Kamada, Kensaku; Soh, Yoko; Ihara, Yoshito; Kondo, Takahito

doi:10.1111/j.1349-7006.2002.tb02482.x

Cited by 52 publications

(35 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[15][16][17] It is already wellknown that GST-p overexpression is associated with increased resistance to platinum-based chemotherapy and poor outcome in NSCLC. 18,19 RCN is an endoplasmic reticulum-resident Ca 21 -binding protein with 6 repeats of a domain containing the EF-hand motif.…”

Section: Discussionmentioning

confidence: 99%

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

Hirano

Kato

Maeda

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Cisplatin-based (CDDP-based) adjuvant chemotherapy of nonsmall cell lung cancer (NSCLC) was reported to yield 5-15% improvement in 5-year survival compared to complete resection alone. The importance of information concerning preselection of good responders has become increasingly evident. The purpose of our study is the establishment of a preselection of good responders for CDDP-based adjuvant chemotherapy. We investigated protein expressions comparing intensity between parent strains (H69 and PC14 lung cancer cultured cells) and resistant strains against CDDP using 2-dimensional polyacrylamide gel electrophoresis (2-DE). Immunohistochemically, we evaluated the relationship between protein expression associated with CDDP-resistance and the clinical effects of platinum-based postoperative adjuvant chemotherapy using 126 surgically-resected NCLC materials. We detected 2 kinds of polypeptides that changed expression levels on 2-DE gels. The analyses of the amino acid sequence showed that these polypeptides were reticulocalbin (RCN) and glutathione-Stransferase-p (GST-p). The 2-DE analysis showed decreased expression in RCN and overexpression in GST-p with the acquisition of CDDP-drug resistance. RCN-transfectant of H69 CDDPresistant strain showed intermediate sensitivity between the parent strain and the CDDP-resistant strain. RCN-positive cases showed a statistically significant better disease-free survival only in the cases receiving postoperative platinum-based adjuvant chemotherapy after curative resection (p 5 0.007). In addition, cases that were both RCN-positive and GST-p-negative showed a statistically significantly better outcome (p 5 0.0150). In the cases without postoperative adjuvant chemotherapy no relationship between the outcome and these expressions was seen. The evaluation of RCN and GST-p might provide valuable information concerning postoperatively therapeutic strategy from the standpoint of individualized postoperative therapy. ' 2005 Wiley-Liss, Inc.Key words: reticulocalbin; glutathione-S-transferase-p; cisplatin; individual therapy; non-small cell lung cancer Death due to lung cancer is still increasing in Japan and most Western countries, despite intensive application of various therapeutic strategies, and it is still the leading cause of cancer death in Japan. Though the opportunities of relatively early detection and treatment increase, still more than half of cases of primary lung cancer show advanced stage at the initial definitive diagnoses. Several years ago, we routinely carried out postoperative adjuvant chemotherapy using platinum (cisplatin [CDDP] or carboplatin) for patients with advanced stage non-small cell lung carcinoma (NSCLC) because distant metastasis occurred frequently after surgical treatment only. Clinically favorable outcome was not obtained, however, and the 5-year survival of Stage IIIA was approximately 25%, despite postoperative adjuvant chemotherapy. It had been believed that the efficacy of adjuvant chemotherapy in surgically resected lung cancer was controvers...

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

Hirano

Kato

Maeda

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…40 Evidence suggests that GSTs are involved in the detoxification of chemotherapeutic drugs, like Topo I inhibitors or platinum compounds and are important mediators of drug resistance. 22,41 In vitro studies by Goto et al found that CPT-11 treatment induces an upregulation of GST-P1 expression, and a specific inhibitor of this enzyme partially increases sensitivity to CPT-11. 22 Therefore, we expected that high expression levels of GST-P1 in our study would correlate with response to CPT-11-based chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…22,41 In vitro studies by Goto et al found that CPT-11 treatment induces an upregulation of GST-P1 expression, and a specific inhibitor of this enzyme partially increases sensitivity to CPT-11. 22 Therefore, we expected that high expression levels of GST-P1 in our study would correlate with response to CPT-11-based chemotherapy. We found that patients with high intratumoral GST-P1 gene expression levels were associated with response to CPT-11 based chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…21 Finally, preclinical data from Goto et al, analyzing the significance of glutathione S-transferase pi (GST-P1) in resistance to anticancer drugs, imply that these factors of the DNA repair system influence CPT-11 sensitivity. 22 On the premise of these limited and controversial data, the goal of our study was to identify potential predictive molecular markers in patients with metastatic CRC treated with first line CPT-11 based chemotherapy. We tested our hypothesis that mRNA levels of drug targets [TS, Topo I] and enzymes involved in critical pathways of drug resistance such as the 5-FU metabolism [dihydropyrimidine dehydrogenase (DPD)], the EGFR signaling pathway [epidermal growth factor receptor (EGFR)], interleukin 8 (IL-8), vascular endothelial growth factor (VEGF) and DNA-repair/drug detoxification [excision repair cross-complementing 1 (ERCC1), GST-P1] will be When comparing the 31 patients who were enrolled in the 2 clinical trials with the 23 patients who were not enrolled, there were no statistically significant differences in demographic characteristics (age, sex and race) and clinical outcome variables (tumor response, toxicity, progression-free survival and overall survival).…”

mentioning

confidence: 99%

“…[14][15][16][17] Other studies determining predictive markers of CPT-11 efficacy have been highly controversial. [18][19][20][21][22] In vitro studies in colon cancer cell lines have suggested that Topo I activity may be a potential determinant of CPT-11 sensitivity. 18,19 Saltz et al described a significant correlation between mRNA levels of Topo I and response to CPT-11 based treatment in a small group of patients with metastatic CRC.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Molecular determinants of irinotecan efficacy

Vallböhmer

Iqbal

Yang

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Molecular markers predicting the efficacy of CPT‐11 based chemotherapies in patients with colorectal cancer (CRC) are unknown. Therefore, we investigated whether mRNA levels of drug targets (Topoisomerase I, TS), enzymes involved in 5‐FU metabolism (DPD), in angiogenesis (EGFR, IL‐8, VEGF) and in DNA‐repair/drug detoxification (ERCC1, GST‐P1) are associated with the clinical outcome of patients with CRC treated with first‐line CPT‐11 based chemotherapy. Thirty three patients with metastatic CRC were included in the study. Intratumoral gene expression levels were assessed from paraffin‐embedded tissue samples, using laser capture microdissection and quantitative Real‐Time PCR. Complete response was observed in 1 patient, partial response in 12 patients, stable disease in 13 patients and progressive disease in 6 patients. Response was inevaluable for 1 patient. Patients with complete response or partial response were classified as responders, while patients with stable disease or progressive disease were classified as nonresponders. High intratumoral mRNA levels of EGFR, ERCC1 and GSPT‐P1 were each significantly associated with response to CPT‐11 based chemotherapy. Recursive partitioning analysis showed that mRNA levels of EGFR and ERCC1 are primarily responsible for delineating responders from nonresponders. Also, the combination of high intratumoral gene expression levels of both EGFR and ERCC1 was significantly associated with progression‐free survival. The mRNA levels of EGFR had a significant correlation with expression levels of ERCC1, GST‐P1 and VEGF. This small retrospective study suggests that gene expression levels of EGFR, ERCC1 and GST‐P1 may be useful in predicting the clinical outcome of patients with metastatic CRC treated with first‐line CPT‐11 based chemotherapy. © 2006 Wiley‐Liss, Inc.

show abstract

Cloning and Heterologous Expression of Three Type II PKS Gene Clusters from Streptomyces bottropensis

Yan¹,

Probst²,

Linnenbrink³

et al. 2011

ChemBioChem

View full text Add to dashboard Cite

Mensacarcin is a potent cytotoxic agent isolated from Streptomyces bottropensis. It possesses a high content of oxygen atoms and two epoxide groups, and shows cytostatic and cytotoxic activity comparable to that of doxorubicin, a widely used drug for antitumor therapy. Another natural compound, rishirilide A, was also isolated from the fermentation broth of S. bottropensis. Screening a cosmid library of S. bottropensis with minimal PKS-gene-specific primers revealed the presence of three different type II polyketide synthase (PKS) gene clusters in this strain: the msn cluster (mensacarcin biosynthesis), the rsl cluster (rishirilide biosynthesis), and the mec cluster (putative spore pigment biosynthesis). Interestingly, luciferase-like oxygenases, which are very rare in Streptomyces species, are enriched in both the msn cluster and the rsl cluster. Three cosmids, cos2 (containing the major part of the msn cluster), cos3 (harboring the mec cluster), and cos4 (spanning probably the whole rsl cluster) were introduced into the general heterologous host Streptomyces albus by intergeneric conjugation. Expression of cos2 and cos4 in S. albus led to the production of didesmethylmensacarcin (DDMM, a precursor of mensacarcin) and the production of rishirilide A and B (a precursor of rishirilide A), respectively. However, no product was detected from the expression of cos3. In addition, based on the results of isotope-feeding experiments in S. bottropensis, a putative biosynthesis pathway for mensacarcin is proposed.

show abstract

Significance of Nuclear Glutathione S‐Transferase π in Resistance to Anti‐cancer Drugs

Cited by 52 publications

References 38 publications

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

Molecular determinants of irinotecan efficacy

Cloning and Heterologous Expression of Three Type II PKS Gene Clusters from Streptomyces bottropensis

Contact Info

Product

Resources

About