• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6423-6427
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• 2012

Background: Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. Methods: A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. Results: A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum-based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. Conclusion: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.851-856
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• 2012

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.27-34
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• 1992

Cis-Platinum (DDP) was utilized as a radiosensitizer in a pilot study for stage III and IV squamous cell carcinoma between 1984-1987, and DDP 20 $mg/M^2$/day was administered for 4 days at 3 week interval with concurrent radiotherapy. This study consisted of three phases: cytoreduction phase, eradicative treatment phase and adjuvant phase. Total 59 patients were subjected to evaluate a tumor response and its toxicity. During the eradicative phase,27 patients underwent surgery (group I ), 29 patients were treated with radiotherapy only (group II) and 3 patients did not complete the second phase of therapy. At the cytoreduction phase, $95\%$ response rate with complete response (CR) $47.5\%$ and partial response (PR) $47.5\%$ was observed. Complete tumor clearance (CTC) rate following 2nd phase of therapy was $84\%$ (47/56) with 26/27($96\%$) in group I achieved CTC with surgery and 21/29 ($72\%$) patients In group II achieved CTC following 2nd phase. $67\%$ of primary lesions and $70\%$ of nodal diseases in group I showed no tumor in the surgical specimen. $34\%$ of patiets who achieved CTC at 2nd phase developed recurrence and median time to recur was 8 months. Actuarial disease free survival at 4 years was $59\%$ and $51\%$(24/27) of patients who achieved CTC at 2nd phase were alive without any evidence of disease at median follow-up 31 months (range, 10-48 months). There was no significant difference in overall and disease free survival between group I and II between CR and PR group following 1st Phase. Only significant Prognostic factor in this study was the complete tumor clearance following 2nd phase theapy. In general, toxicity was not excessive. Author concludes that this study confirmed the significant radiosensitizing effect of DDP with the acceptable toxicity and warrant the prospective study to determine optimum scheduling for DDP and radiotherapy which maximizes the therapeutic gain.

• Environmental Analysis Health and Toxicology
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• v.14 no.1_2
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• pp.13-19
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• 1999

Cisplatin is an inorganic complex formed by a central atom of platinum surrounded by chlorine and ammonia atoms in the cis position in the horizontal plane, Cisplatin is one of the most effective anticancer drug, widely used against various tumor such as testicular tumor, brain tumor, ovary tumor, bladder carcinoma, colon cancer etc. However its clinical use has been limited by nephrotoxicity, ototoxicity , gastrointestinal disturbances, myeloscrppression and allergic reactions. In these toxicities, dose related and cumulative nephrotoxicity is the major dose limit factor. So, to evaluate the protective effect of aspalactone on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally, Protective effects of aspalactone against nephrotoxicity of cisplatin were observed when aspalactone was administered to rats 1hr beforecisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and aspalactone was not observed. The present results indicate that aspalactone may provide protection against cisplatin nephrotoxicity, when it is given 1hr before cisplatin injection.

• Journal of Chest Surgery
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• v.17 no.3
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• pp.497-504
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• 1984

The malignant germ cell tumor found in the gonad can originate in the anterior mediastinum. Endodermal sinus tumor[Yolk sac tumor] is a kind of malignant germ cell tumor and is derived from extra-embryonic mesoderm. We experienced a case of primary mediastinal endodermal sinus tumor occurred in 22 year old male patient. His chief complaint was anterior chest pain for 2 days. The tumor located in the anterior mediastinum and invaded upper lobe of the deft lung and pericardium. A left upper lobe resection including phrenic nerve and pericardium was performed and the tumor in the anterior mediastinum was excised. The patient has been treated with combination chemotherapy[Cis-platinum, Vincristine, Actinomycin-D, & Cyclophosphamide} and followed up for 4 months with partial remission.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1987.05a
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• pp.5.1-5
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• 1987

Cisplatin (cis-dichlorodiamine platinum II)은 두경부 및 고환의 악성종양에 아주 효과적이라고 알려져 있다. 그러나 이 약물은 이독성 및 신독성이 이미 임상연구로 발표되어 있으며 신독성은 cisplatin 투여시 이뇨제 및 수액의 투여로 그 정도 및 빈도는 감소시킬 수 있지만 이독성은 감소시키지 못한다. Cisplatin에 의한 이독성은 보통 자각적으로 나타나지 않는데 이는 내이 와우각의 회전중 저부에서 일어나며 또한 외유모세포의 최외측열에서 일어난다고 동물실험에서 밝혀진 바 있다. 본 교실에서는 cisplatin의 이독성을 관찰하기 위하여 1회에 cisplatin 60~80 mg/$m^2$을 투여한 두경부 악성종양환자를 대상으로 투여전후의 청력을 비교 관찰하였다. 1) 청력은 대부분 10㏈ 이내의 손실례가 많았다. 2) 최대청력손실이 있는 주파수는 8KHz, 4KHz의 순으로 주로 고음역에서 발생하였다. 3) 신독성은 전례에서 관찰되지 않았다.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3123-3128
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• 2014

The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.147-152
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• 2004

A wide variety of cancer chemotherapeutic agents have been shown to induce programmed cell death (PCD, APOPTOSIS) in various tumor cell lines in vitro. cis-Malonato [(4R,5R)-4,5-bis(aminomethyl)-2-isoprpopyl-1,3-dioxolane] platinum(II) (heptaplatin), which is a new drug approved by KFDA in 1999, in a novel platinum-based antitumor agent with clinical potential against stomach cancer and the 3rd generation of the cisplatin. This study was performed to know how heptaplatin and cisplatin and sunpla (mixture of heptaplatin and mannitol) affect on SK-MEL-28 cell line, and how they induce the apoptosis. At EM analysis, the morphology of the cell was changed by treatment of the cisplatin, heptaplatin and sunpla. Apoptotic body formed around plasma membrane, and chromatin condensation represented in nucleus. This phenomenon is one of the characteristic of the apoptosis. The DNA of SK-MEL-28 cell line truncated by cisplatin and sunpla treatment was identified on 2% agarose gel electrophoresis. TUNEL assay was performed to know whether SK-MEL-28 cell die as apoptosis or necrosis by cisplatin, heptaplatin and sunpla. At this result, fluorescence intensity increased according to increase of time and concentration. Therefore, it was identified that cislatin, heptaplatin and sunpla induced apoptosis. Fas expressed on SK-MEL-28 cell membrane by cisplatin, heptaplatin and sunpla was identified by using flow cytometer and the expression of bcl-2(anti-apoptotic gene) decreased according to increase of concentration of the cisplatin, heptaplatin and sunpla. Cisplatin, heptaplatin and sunpla induced apoptosis against SK-MEL-28 cell line, and the apoptotic mechanism was identified as Fas-mediated apoptosis and decreased bcl-2 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5941-5944
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• 2014

Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.

• Advances in Traditional Medicine
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• v.4 no.1
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• pp.22-27
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• 2004

Cisplatin is a highly effective and extensively used anticancer drug. Higher doses of cisplatin manifest acute nephrotoxicity and this is one of the limiting factors of this drug in cancer chemotherapy. The effect of the oyster mushroom extract to ameliorate cisplatin ( cis platinum (II) diammine dichloride) induced nephrotoxicity and restoration of antioxidant defence system in mice was investigated. The investigations showed that prior administration of methanolic extract of Pleurotus florida at a dose of 500 and 1000mg/Kg body weight significantly reduced elevated serum creatinine and urea levels and increased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the kidney, consequent to cisplatin treatment, in a dose dependent manner. The extract restored the decreased reduced glutathione (GSH) activity and increased malondialdehyde (MDA) level due to cisplatin administration. The results thus indicated that oyster mushroom extract rendered significant protection against cisplatin induced nephrotoxicity and depletion of antioxidant defence system in a dose dependent manner. Since oyster mushrooms are excellently edible and non-toxic, the finding reported here is of significant use in cancer chemotherapy.