• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4531-4536
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• 2012

Objective: To study synergistic effects of nedaplatin and cisplatin on three human carcinoma cell lines (esophageal carcinoma cell line Eca-109, ovarian carcinoma Skov-3 and cervical carcinoma Hela). Methods: Inhibition effects were evaluated by MTT assay and cell apoptosis was detected by flow cytometry. In addition, changes of Ki-67, Bax and Bcl-2 at mRNA and protein levels were quantified by RT-PCR and Western blotting. Results: Growth inhibition in each cell lines was dose-dependent after exposure to nedaplatin or cisplatin alone. The interaction of the two drugs was synergistic at higher concentrations according to the median-effect principle. The inhibition rates with nedaplatin, cisplatin and combined treatment were $41.9{\pm}4.1%$, $47.4{\pm}2.9%$, $52.5{\pm}0.9%$(Eca-109), $39.0{\pm}1.26%$, $45.0{\pm}1.45%$, $56.2{\pm}1.44%$ (Skov-3) and $44.8{\pm}2.11%$, $46.9{\pm}0.99%$, $56.6{\pm}1.83%$ (Hela) respectively, with increase in apoptosis. Compared with the nedaplatin or cisplatin alone treatment group, the combinative treatment group's Ki-67 and bcl-2 mRNA (protein) expression was decreased while that of Bax mRNA (protein) was increased. Conclusion: Compared to the effects of nedaplatin or cisplatin alone at high concentrations, combination of nedaplatin and cisplatin at low concentrations proved to be much more effective for inhibition of proliferation and the induction of apoptosis in the Eca-109, Skov-3 and Hela cell lines.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7523-7527
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• 2013

Thymidylate synthase (TS) catalyzes the transfer of a methyl group from methylenetetrahydrofolate to dUMP to form dTMP. It is a primary target in the chemotherapy of colorectal cancers and some other neoplasms. In order to obtain pure protein for analysis of structure and biological function, an expression vector TS-pET28b (+) was constructed by inserting wild-type human thymidylate synthase (hTS) cDNA into pET28b (+). Then an expression strain was selected after transformation of the recombined plasmid into Rosetta (DE3). Fusion protein with His-tag was efficiently expressed in the form of inclusion bodies after IPTG induction and the content was approximately 40.0% of total bacteria proteins after optimizing expression conditions. When inclusion bodies were washed, dissolved and purified by Ni-NTA under denatured conditions, the purity was up to 90%. On SDS-PAGE and West-blotting, the protein band was found to match well with the predicted relative molecular mass-36kDa. Bioactivity was 0.1 U/mg. The results indicated that high-level expression of wild-type hTS cDNA can be achieved in prokaryotes with our novel method, facilitating research into related chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6663-6668
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• 2015

Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

• 대한두경부종양학회지
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• 제8권1호
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• pp.25-30
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• 1992

The causes of treatment failure in head and neck cancer are locoregional recurrence, distant metastasis and second primary cancer. The favorite sites of second primary cancer are head and neck, lung and esophagus. But, the incidence of stomach cancer in Korea is the highest of all, high incidence of stomach cancer is expected in head and neck cancer patients. We experienced 2 cases of stomach cancer after successful treatment of primary head and neck cancer at Kang Nam St. Mary's hospital. The first case was a 60-year-old male with nasopharyngeal non-keratinizing carcinoma(stage III, T1N1M0). He received three cycles of induction chemotherapy including cisplatin and 5-fluorouracil followed by radiotherapy which resulted in complete response. Five months after completion of radiotherapy. stomach adenocarcinoma(stage IV, T4N2M1) was diagnosed. He received one cycle of FAM chemotherapy and died 4 months after diagnosis of stomach cancer. The second case was a 50-year-old male with pyriform sinus squamous cell carcinoma(stage II, T2N0M0). He received curative partial pharyngolaryngectomy followed by radiotherapy which result in free of disease. Four months after completion of radiotherapy. stomach adenocarcinoma(stage IV, T4N2M1) was diagnosed. Bypass gastrojejunostomy was performed. The screening test for stomach cancer including upper gastrointestinal X-xay series and/or endoscope of the stomach should be performed periodically for the patients with head and neck cancer in Korea.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1487-1494
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• 2015

Background: To investigate the clinical efficacy of expanded activated autologous lymphocytes (EAAL) in patients with small cell lung cancer (SCLC). Materials and Methods: A total of 32 SCLC patients were selected and randomly divided into EAAL treatment and control groups, 16 cases in each. EAAL were obtained by proliferation of peripheral blood mononuclear cells (PBMCs) of patients followed by phenotype determination. Clinical data of all patients were recorded. Patients of both groups were followed up and the overall survival (OS) were compared retrospectively. Results: After culture and proliferation in vitro, the percentages of $CD3^+$, $CD3^+CD8^+$, $CD45RO^+$, $CD28^+$, $CD29^+$, $CD8^+CD28^+$ and $CD3^+CD16^+/CD56^+$ cells increased markedly (p<0.05). The OS of the EAAL treatment group was longer than that of control group, but the difference was not statistically significant (p=0.060, HR=0.487, 95%CI 0.228~1.037). 1- to 3-year survival rates in EAAL treatment group were longer than those in control group, but there was still no significant difference (p>0.05). COX multivariate regression analysis showed that the number of chemotherapy cycles and the application of EAAL immunotherapy were independent prognostic factors for SCLC patients. The OS in females and chemotherapy${\leq}6$ cycles were obviously prolonged after EAAL immunotherapy. Conclusions: In vitro induction and proliferation of EAAL is easy and biologically safe. Generally, EAAL adoptive immunotherapy can evidently prolong the OS of SCLC patients.

• Journal of Korean Neurosurgical Society
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• 제52권6호
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• pp.517-522
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• 2012

Objective : Meningiomas represent 18-20% of all intracranial tumors and have a 20-50% 10-year recurrence rate, despite aggressive surgery and irradiation. Hydroxyurea, an inhibitor of ribonucleotide reductase, is known to inhibit meningioma cells by induction of apoptosis. We report the long-term follow-up result of hydroxyurea therapy in the patients with recurrent meningiomas. Methods : Thirteen patients with recurrent WHO grade I or II meningioma were treated with hydroxyurea (1000 $mg/m^2/day$ orally divided twice per day) from June 1998 to February 2012. Nine female and 4 male, ranging in age from 32 to 83 years (median age 61.7 years), were included. Follow-up assessment included physical examination, computed tomography, and magnetic resonance imaging (MRI). Standard neuro-oncological response criteria (Macdonald criteria) were used to evaluate the follow-up MRI scans. The treatment was continued until there was objective disease progression or onset of unmanageable toxicity. Results : Ten of the 13 patients (76.9%) showed stable disease after treatment, with time to progression ranging from 8 to 128 months (median 72.4 months; 6 patients still accruing time). However, there was no complete response or partial response in any patients. Three patients had progressive disease after 88, 89, 36 months, respectively. There was no severe (Grade III-IV) blood systemic disorders and no episodes of non-hematological side effects. Conclusion : This study showed that hydroxyurea is a modestly active agent against recurrent meningiomas and can induce long-term stabilization of disease in some patients. We think that hydroxyurea treatment is well tolerated and convenient, and could be considered as an alternative treatment option in patients with recurrent meningiomas prior to reoperation or radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1089-1092
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• 2013

Background: Elderly patients with acute myeloid leukemia (AML) have a poor outcome because of co-morbidities, poor tolerance to intensive chemotherapy and inherently more resistant disease. Clofarabine is a second generation nucleoside analogue which has shown promising activity in elderly patients with AML. This study was conducted to review the outcome of treatment with clofarabine in a group of such patients. Methods: The records of 5 elderly patients who were diagnosed to have AML and treated with clofarabine over a 12 month period were reviewed retrospectively. Results: There were 2 female and 3 male patients with a median age of 68 years (range 65-82). At the time of treatment, 2 patients had newly diagnosed AML not considered suitable for intensive therapy, while 3 patients had partial or no response to conventional chemotherapy. The overall response rate was 100%, all patients achieving a complete remission. Induction and consolidation were well tolerated. All patients developed neutropenia with a median duration of 20 days (range 17-42). One patient developed hand and foot syndrome and a generalized rash but recovered. There was no mortality and all patients remained in remission after a median follow-up of 5.2 months (Range 3-10). Conclusion: Clofarabine (alone or in combination) is active in elderly AML patients with an acceptable safety profile and should be considered a potential option in this group.

• 대한약침학회지
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• 제20권3호
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• pp.207-212
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• 2017

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.776-784
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• 1997

서 론 : 비소세포폐암은 전체 폐암의 약 75%를 차지하고 있으며 조기 발견에 이은 외과적 절제가 유일한 완치방법으로 알려져 있다. 그러나 병기 III기에서는 정립된 치료방법이 없고 여러 종류 및 조합의 치료방법이 시도되고 있다. 이에 연구자들은 수술이 불가능한 병기 IIIA 및 악성흉수를 제외한 병기 IIIB의 과거 치료력이 없는 비소세포폐암 환자에서 cisplatin, etoposide 이용한 복합화학요법을 동시에 시행하여 그의 효과 및 순응성을 조사하였다. 대상 및 방법 : 1995년 10월부터 1996년 12월까지 원자력병원에 입원하여 조직학적으로 비소세포폐암으로 진단된 병기 III기의 환자중 수술이 불가능한 IIIA 및 IIIB의 환자를 대상으로 하였다. 복합화학요법은 cisplatin 30mg/$m^2$/D, etoposide 80mg/$m^2$/D를 방사선요법과 동시에 시작하여 3일간 투여후 4주 간격으로 총 3회 투여하였고, 방사선요법은 5940cGy까지 진행후 치료효과를 평가하였다. 결 과 : 총 대상환자 32명 중 조기종료한 3명을 제외한 29명에서 평가가 가능하였으며, 완전관해는 없었고 부분관해 22명(75.9%), 불변 5명(17.2%), 치료중 진행하였던 경우가 2명(6.9%)으로 전체관해율은 75.9%, 중앙 생존기간 12.1개월, 1년 생존률은 50.6%로 나타났다. 치료에 의한 주된 독성은 백혈구감소로 WHO기준으로 3등급이상이 13명(45%)에서 나타났고 혈소판감소는 3등급이상이 3명(11%)에서 나타났으나 모두 회복되었고, 그밖에 오심과 구토는 대부분의 환자에서 2등급이하이었으며 방사성폐렴은 13명(46%)에서 나타났다. 결 론 : 수술이 불가능한 병기 IIIA 및 악성흉수를 제외한 병기 IIIB기 비소세포폐암환자에서 EP 복합화학요법과 방사선요법을 동시 병행한 치료는 비교적 안전하면서 효과적이었으며, 이에 대한 평가는 방사선요법을 단독으로한 치료와의 3상 연구를 요할 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제26권3호
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• pp.328-334
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• 2018

Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an $IC_{50}$ of $15{\mu}M$ and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of $p21^{WAF1/Cip1}$ and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.