• Korean Journal of Plant Resources
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• v.1 no.1
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• pp.8-22
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• 1988

Vincristine and vinblastine isolated from Vinco spp. , and podophyllotoxine derivatives isolated from Podophyllum spp. are usefulas anticancerous components obtaned from higher plants. More thanten antineoplastic compounds are now following them as anticancerousagents from higher plants. In my laboratory, Sarcoma 180A has beenused as the first screening test. By this method, I have found outsome kinds of antineoplastic constituents from active plants extracts .For instance, bisaborane type compounds were isolated from Curcumaxanthorrhiza, one of Indonesian plants; a morphinane type compoundfromCocculus trilobus; cyclic hexapeptides from Rubia akane and R.cordiorta. Seven components having antineoplastic actirity wereisolated from Rubia spp. except. R. tinctoria. Their structures wereelucidated except RA-Vl by chemical reaction and variovs instrumentalanalysis as shown in Fig. Among of them, RA-Vll showed strong activityagainst P388 Lymphocytic leukemia, L2O, B16 melanoma, Lewis lungcarcinoma, colon 38 and Ehrlich carcinoma. RA-V revealed excellentactivity against MM2 mammary carcinoma. The· value of acute LD5O ofRA-ViI were 10. Omg/kg( iP) and 16.5mg/kg( po ) respectiveIy . Therapruticratio was 400, compared with 10 of mitomycin C. QSAR was also appliedto these compounds by elongation of ether and ester side chains atR'. Mechanism of action of RA-Vll was also investigated and wasassumed to be inhibition of protein biosynthesis .

• Korean Journal of Pharmacognosy
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• v.26 no.4
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• pp.344-348
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• 1995

Preliminary screening test of modulators for multidrug resistance with 400 medicinal plants was carried out by using human multidrug resistance cell line, KB-V1. Among active medicinal plants, the unripe fruits of Evodia officinalis showed a potent modulating activity of MDR. From MeOH extract of this plant, we isolated two indole alkaloids, rutaecarpine (1) and evodiamine (2), by repeated silicagel column chromatography. Rutaecarpine increased the cytotoxicities of vinblastine and taxol against multidrug resistance cells, but evodiamine showed no modulating activity in spite of its potent cytotoxic activities.

• Archives of Pharmacal Research
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• v.19 no.5
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• pp.342-347
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• 1996

Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of its parental cells, and it also revealed cross-resistance to actinomycin D, etoposide and vinblastine but not to displatin and tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin against both HCT15 and GCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the tosicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex mechanisms for MDR.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.183-189
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• 2008

The present study compared the feasibility of Caco-2 and MDCK cells as an efficient in-vitro model for the drug classification based on Biopharmaceutics Classification System (BCS) as well as an in-vitro model for drug interactions mediated by P-gp inhibition or P-gp induction. Thirteen model drugs were selected to cover BCS Class I{\sim}IV$ and their membrane permeability values were evaluated in both Caco-2 and MDCK cells. P-gp inhibition studies were conducted by using vinblastine and verapamil in MDCK cells. P-gp induction studies were also performed in MDCK cells using rifampin and the P-gp expression level was determined by western blot analysis. Compared to Caco-2 cells, MDCK cells required shorter period of time to culture cells before running the transport study. Both Caco-2 and MDCK cells exhibited the same rank order relationship between in-vitro permeability values and human permeability values of all tested model compounds, implying that those in-vitro models may be useful in the prediction of human permeability (rank order) of new chemical entities at the early drug discovery stage. However, in the case of BCS drug classification, Caco-2 cells appeared to be more suitable than MDCK cells. P-gp induction by rifampin was negligible in MDCK-cells while MDCK cells appeared to be feasible for P-gp inhibition studies. Taken all together, the present study suggests that Caco-2 cells might be more applicable to the BCS drug classification than MDCK-cells, although MDCK cells may provide some advantage in terms of capacity and speed in early ADME screening process.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6519-6524
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• 2014

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033) but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1381-1387
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• 2001

Objective : Endodermal sinus tumor or yolk sac tumor is an uncommon malignant germ-cell neoplasm. This tumor was originally described as a germ cell tumor of the ovary or the testis. Intracranial endodermal sinus tumor is extremely rare and usually develop in the pineal or suprasellar regions. The authors evaluated the effect of adjuvant therapy(chemotherapy combined with radiotherapy) and radical removal of intracranial endodermal sinus tumors. Material and Methods : Between 1996 and 2001, four patients of intracranial endodermal sinus tumor were diagnosed with tumor marker(AFP) and biopsy. Three patients were treated with surgical removal and chemotherapy with cisplatin($20mg/m^2$), etoposide($100mg/m^2$) and bleomycin($15mg/m^2$) as well as external beam radiation therapy. We compared the management problems for these tumors. Result : In all three patients the tumor size and the level of tumor marker decresed during initial adjuvant therapy. However, Tumors showed regrowth with elevated AFP of serum and CSF possibly related to delayed chemotherapeutic treatment or inadequate administration of chemotherapeutic drugs due to severe bone marrow suppression. An additional chemotherapy and external radiation therapy were given, but tumors could not be controlled with leptomeningeal seeding. Conclusion : Radiotherapy is considered to be less effective. The combination chemotherapy with PVB(cisplatin, vinblastine, bleomycine) or PE(cisplatin, etoposide) is considered to be value in prolongation of the survival rate. But the role of chemotherapy in this tumor has not yet been clarified due to bone marrow suppression and drug resistance. Further study with large series of this tumor is necessary to establish the optimal management.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8715-8718
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• 2014

Background: ABVD (doxorubicin, bleomycin, vinblastine (Vb) and dacarbazine) is the standard regimen in Hodgkin's lymphoma (HL).Vincristine (O) is a mitotic spindle agent like Vb. We aimed to evaluate the efficacy and safety of O as a part of ABOD in HL. Materials and Methods: Patients who had ABOD were enrolled. Stage I-II HL were evaluated for unfavorable risk factors according to NCCN. National Cancer Institute Common Toxicity Criteria was used for toxicity. Results: Seventy-nine HL patients in our center between 2003 and 2007 were evaluated retrospectively. Median follow-up was 54 months. Most of the patients were male in their third decade. Median ABOD cycles were 6 (2-8). Primary refractory disease rate was 17.7% whereas it was 5.1% for early relapse and 5.1% for late relapse disease. Response rates were as 82.3% for complete response, 11.4% for partial response, 5.1% for stable disease and 1.3% for progressive disease. Half of relapsed patients had autologous stem cell transplantation. Estimated 5-year failure-free survival was 71% and significantly longer in early stage patients without risk factors, bulky disease or radiotherapy (RT) (p=0.05, p<0.0001, p=0.02; respectively). Estimated 5-year overall survival was 74% and significantly longer in those who had no RT (p=0.001). Dose modification rate was 5.1% and chemotherapy delay rate was 19%. There were no toxicity-related deaths. Conclusions: ABOD seems to be effective with managable toxicity in HL, even in those with poor prognostic factors.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.409-413
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• 1999

Malignant melanoma develops from the melanocyte and the most common primary site is skin, followed by mucosa and retina. Even though any other tissue where melanocytes reside could be the primary site of the malignant melanoma, the one developed in the mediastinum is rarely reported. We experienced a patients of 54 years old woman whose initial symptom was progressive dyspnea for one month, and proved to have the anterior mediastinal mass with pleural effusion and the small mass in the abdominal soft tissue. The needle aspiration biopsy from the mediastinal mass showed the consistent findings with malignant melanoma. We concluded the mediastinum was the primary site of the malignant melanoma of this patient because we couldn't find any other evidence of primary tumor in skin, oral and gastrointestinal mucosa, and retina. She has been treated with combined chemotherapy with dacarbazine, cisplatin and vinblastine. Her symptom was improved after chemotherapy and follow up chest CT after three cycles of chemotherapy showed the decreased tumor size in the mediastinum.

• YAKHAK HOEJI
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• v.35 no.3
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• pp.203-215
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• 1991

Using the calorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT)assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin (Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of ($\pm$)-ar-turmerone and the extracts of the crude drugs {Lithospermum eythrorhizon(LE) and Scutellaria baicalensis (SB)} on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50%, while VP-16, ara-C, Bleo, and CYC were less effective. ($\pm$)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID$_{50}$ values of 11.730 $\mu\textrm{g}$/ml and 0.292 $\mu\textrm{g}$/ml for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID$_{50}$ values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing ($\pm$)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing ($\pm$)-ar-turmerone, two, three and three times by combining wilth the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of ($\pm$)-ar-turmerone and the extracts of LE and SB roots against HL-60 cell were greater than KG-1 cell.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.215-219
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• 1991

To evaluate the effect of MVP chemotherapy and hyperfractionated radiotherapy in Stage III unresectable non small cell lung cancer (NSCLC), authors have conducted a prospective randomized study since January 1991, Stage IIIa or IIIb unresectable NSCLC patients were treated with hyperfractionated radiotherapy (120 cGy/fx BID) up to 6500 cGy following 3 cycles of induction MVP (Mitomycin C 6 mg/$m^2$, Vinblastine 6 mg/$m^2$, Cisplatin 60 mg/$m^2$) and randomized for either observation or 3 cycles of maintenance MVP chemotherapy. Until August 1991, 18 patients were registered to this study. 4 cases were stage IIIa and 14 were stage IIIb. Among 18 cases 2 were lost after 2 cycles of chemotherapy, and 46 were analyzed for this preliminary report. The response rate of induction chemotherapy was $62.5\%$ : partial response, $50\%$ and minimal response, $12.5\%$. Residual tumor of the one partial responder was completely disappeared after radiotherapy. Among 6 cases who were progressed during induction chemotherapy, 4 of them were also progressed after radiotherapy. All patients were tolerated BID radiotherapy without definite increase of acute complications, compared with conventional radiotherapy group. But at the time of this report, one patient expired in two month after the completion of the radiotherapy because of treatment related complication. Although the longer follow up is needed, authors are encouraged with higher response rate and acceptable toxicity of this treatment. Authors believe that this study is worthwhile to continue.