Protection effect of hepatocyte growth factor on tumor cells from apoptosis and its mechanism / 中国药学杂志

OBJECTIVE: To investigate the protection of hepatocyte growth factor (HGF) on 5 kinds of tumor cells (B cell lymphoma cell line Raji, human acute myeloid leukemia cell line HL-60, cervical cancer cell line HeLa, prostate cancer cell line PC-3, and non-small cell lung cancer cell line A549) from apoptosis induced by etoposide (VP-16). METHODS: Normal control group, drug group, and HGF protection group were set. CCK-8 assay was used to measure proliferation inhibition on 5 kinds of tumor cells by VP-16. Quantitative and qualitative analysis on 5 kinds of tumor cells was performed through acridine orange (AO) fluorescent staining, flow cytometry, HE staining, and transmission electron microscopy. RESULTS: CCK-8 assay revealed that the concentrations of VP-16, which can significantly inhibit the proliferation of Raji, HL-60, PC-3, HeLa, and A549 cell lines, were 100, 1,400, 200, and 200 μg·mL-1, respectively. The typical morphologic changes of cell apoptosis were observed under transmission electronic microscope. Flow cytometry showed that the apoptotic rates of tumor cells in the drug groups were significantly higher than those in normal control group (P>0.01, P>0.05) and in HGF protection groups (P>0.01, P>0.05). AO and HE staining revealed that cells in normal control group appeared to have regular cell morphology, but the cells apoptotic rates in the drug groups were significantly higher than those in normal control groups (P>0.01, P>0.05) and in HGF protection groups (P>0.01, P>0.05). CONCLUSION: HGF can significantly protect 5 kinds of tumor cells from apoptosis induced by VP-16. The mechanism need further investigation.

A Phase 2 Study of VP-16 , Ifosfamide , and Cisplatin ( VIP ) Combination Chemotherapy Plus Concurrent Thoracic Irradiation for Limited Small Cell Lung Cancer / 대한암학회지

PURPOSE: A phase II study of etoposide, ifosfamide, cisplatin combination chemotherapy and concurrent thoracic irradiation in patients with untreated limited small cell lung cancer (SCLC) was conducted to assess toxicities, response rate, response duration, and median survival. MATERIALS AND METHODS: Patients with histologically confirmed SCLC with a ECOG criteria 2 and adequate renal function and bone marrow reserve were eligible. Each cycle consisted of VP-16 100 mg/m i.v, days 1-3, ifosfamide 1,200 mg/m i.v. days 1-3 with Mesna, and cisplatin 30 mg/m i.v. days 1-3. Cycles were repeated every 21 days. Concutrent thoracic itradiation was given as total 40-45 Gy for 4-5 weeks beginning within 24 hours of the third cycle. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle. RESULT: Forty two patients with limited SCLC were treated at Seoul National University Hospital between December 1993 and August 1996. Three patients were not evaluable because of lost to follow up (2 patients) and one treatment-related early death. Of 39 evaluable patients, responses were seen in 38 (97%) patients including 22 (56%) complete responses and 16 (41%) partial responses. The median remission duration was 65 wks. The median disease free survival was 60 wks. The median overall survival was not reached and 2-year survival was 69% with median duration of follow up of 63.5 wks. Hematologic side effects (WHO Gr>III/IV) of evaluable 228 cycles of chemotherapy were leukopenia in 34%, thrombocytopenia in 16%. One patient expired after prolonged leukopenia and sepsis. Nonhematologic side effects (WHO Gr>II) included nausea and vomiting (17%) and peripheral neuropathy (2%). CONCLUSION: VIP combination chemotherapy with concurrent thoracic irradiation is effective and tolerable in limited SCLC.

Combination Chemotherapy with Etoposide, Ifosfamide, and Cisplatin (VIP) in Small Cell Lung Cancer / 대한암학회지

PURPOSE: A prospective phase II trial was conducted in patients with small cell lung cancer (SCLC) to determine whether the response rate, duration of response, and overall survival can be improved by a combination chemotherapy with etoposide, ifosfamide, and cisplatin (VIP). MATERIALS AND METHODS: From May 1994 to April 1997, thirty-three previously untreated patients with SCLC received individualized treatment tailored to disease extent. Twenty-one patients with limited disease (LD) received six cycles of chemotherapy consisting of etoposide 120 mg/m2, ifosfamide 1,500 mg/m2, and cisplatin 25 mg/m2 all given intravenously on days 1, 3 and 5. Cycles were repeated every 3 weeks for six cycles. Thoracic radiotherapy was administered to 15 patients with LD of SCLC subsequently after initial two or three cycles of chemotherapy. Prophylactic cranial irradiation was given to complete responders of SCLC. Chemotherapy alone was administered to 12 patients with extensive disease (ED) of SCLC. RESULTS: Complete response (CR) rate was 51% (LD 67%, ED 25%) and overall response rate was 94% (LD 95%, ED 92, p=0.022). And the median duration of response of all patients was 8 months (11 months in LD, 6.5 months in ED, p=0.042). With a median follow-up period of 13 months (3+~36), the median survival of all patients was 12 months (16 months in LD, 9.5 months in ED, p=0.006), and the median disease-free survival (DFS) of 17 CR patients was 12 months. Stage and performance status score were important prognostic factor, but sex, age, and LDH level did not affect the outcome significantly. Among 21 patients with LD, 15 patients received radiotherapy and 6 did not. The overall response rate of patients who received radiotherapy was significantly higher than that of patients who did not (p=0.045). But there were no significant differences in duration of response and OS between them (p=0.055, p=0.068, respectively). The major side effects (greater than grade 2 of WHO criteria) of evaluable 154 cycles of chemotherapy were alopecia (76%), nausea/vomiting (54%), leukopenia (27%), anemia (19%), and thrombocytopenia (15%). CONCLUSION: VIP chemotherapy has produced a high complete remission rate and it is a safe and well-tolerated regimen in SCLC. However, compared to previous reports, it has not improved overall survival significantly. Further phase II and III studies are warranted to confirm the efficacy of VIP chemotherapy.