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1.
Article in English | WPRIM | ID: wpr-760645

ABSTRACT

The long-term survival of heavily pretreated patients with primary peritoneal cancer (PPC) is uncommon. Here, we report on a patient with PPC refractory to multiple lines of intravenous chemotherapy, namely, a combined regimen of paclitaxel and carboplatin, and single regimens of topotecan, docetaxel, cisplatin, and gemcitabine. However, after intraperitoneal (IP) chemotherapy with paclitaxel-cisplatin, the patient's condition improved, and she has been progression-free for more than 4 years. Interestingly, before the IP chemotherapy, the recurrences were limited to the peritoneal cavity. These results suggest that IP recurrence might be a predictor of a good response to IP chemotherapy.


Subject(s)
Carboplatin , Cisplatin , Drug Therapy , Humans , Infusions, Parenteral , Neoplasm Recurrence, Local , Ovarian Neoplasms , Paclitaxel , Peritoneal Cavity , Peritoneal Neoplasms , Recurrence , Topotecan
2.
Article in Chinese | WPRIM | ID: wpr-360078

ABSTRACT

<p><b>OBJECTIVE</b>To explore the clinical efficacy and toxicity of CLAT protocol (cladribine, cytarabine and topotecan) for treating patients with refractory acute myeloid leukemia (R-AML).</p><p><b>METHODS</b>A total of 18 patients with R-AML (median age 37 years, range 18 to 58 years; male n = 16, female n = 2) were treated with CLAT protocol, which consisted of cladribine 5 mg/m(2)/d, i.v. on days 1-5, cytarabine 1.5 g/m(2)/d, i.v. on days 1-5, topotecan 1.25 mg/m(2)/d, i.v. on days 1-5 and G-CSF 300 µg/d subcutaneous injection on day 6 until neutrophile granulocyte recovery.</p><p><b>RESULTS</b>Out of 18 patients 2 died of severe infection before the assessment. Among 16 evaluated patients, 10 (55.6%) achieved complete remission (CR), and 2 (11.1%) achieved partial remission (PR), the overall response rate was 66.7%, the rest 4 patients did not respond (NR). The median overall survival time and DFS for the CR patients was 9.5 months (95%CI: 6.7-16.64) and 9.5 months (95%CI: 6.1-16.7) respectively. The 1 year OS and DFS rates were 45% and 46.9%, respectively. All patients developed grade 4 of granulocytopenia and thrombocytopenia, the median duration was 13 (range 2 to 21) days and 12 days (range 2 to 21), respectively, all patients developed infection, 2 patients died of severe infection. The most common non-hematological side effects included nausea, vomiting, diarrhoea, rash, aminotransferase or bilirubin elevation and were grade 1 to 2.</p><p><b>CONCLUSION</b>The CLAT protocol seems to have promising for the treatment of refractory AML patients, and patients well tolerated. This CLAT protocol offers an alternative treatment for R-AML patients who received severe intensive treatment, especially with anthracycline-containing chemotherapy.</p>


Subject(s)
Adolescent , Adult , Agranulocytosis , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cladribine , Therapeutic Uses , Cytarabine , Therapeutic Uses , Female , Granulocyte Colony-Stimulating Factor , Therapeutic Uses , Humans , Leukemia, Myeloid, Acute , Drug Therapy , Male , Middle Aged , Remission Induction , Thrombocytopenia , Topotecan , Therapeutic Uses , Young Adult
3.
Chinese Journal of Oncology ; (12): 863-867, 2015.
Article in Chinese | WPRIM | ID: wpr-286707

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC).</p><p><b>METHODS</b>Clinical data of 251 patients with stage III (76 IIIA and 175 IIIB) NSCLC who received CCRT as initial treatment between Jan 2001 and Dec 2010 in our hospital were reviewed. A median total radiotherapy dose of 60 Gy (range, 50-74 Gy) were delivered. 174 patients were treated with IMRT, 51 with 3D-CRT and 26 with 2D-radiotherapy. EP chemotherapy regimen was administered in 112 patients, PC regimen in 99 patients, topotecan regimen in 18 patients and other regimens in the remaining 22 patients. The efficacy and toxicity of CCRT were retrospectively analyzed.</p><p><b>RESULTS</b>244 patients were assessable for response, including 6 (2.5%) patients with CR, 183 (75.0%) with PR, 42 (17.2%) with SD and 13 (5.3%) with PD. At a median follow-up period of 20 months, the 1-, 3-, 5- year OS were 69.2%, 31.2%, 23.2%, respectively, and the median OS was 21 months. The 1-, 3-, 5- year PFS were 40.9%, 22.1%, 17.7%, respectively, and the median PFS was 10 months. Patients with stage IIIA NSCLC achieved better 5-year OS than that with IIIB NSCLC (29.2% vs. 20.7%, χ2=2.254, P=0.133). Failure pattern was assessable in 244 patients, including 61 (25.0%) locoregional progression alone, 55 (22.5%) distant metastasis alone and 77 (31.6%) with both. The rates of grade≥3 radiation pneumonitis, esophagitis and hematologic toxicity were 4.4%, 11.2% and 26.4%, respectively.</p><p><b>CONCLUSIONS</b>CCRT provide stage III NSCLC patients favorable outcome with acceptable toxicity. CCRT is standard therapeutic approach for patients with unresectable locally advanced NSCLC.</p>


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Non-Small-Cell Lung , Pathology , Therapeutics , Chemoradiotherapy , Cisplatin , Cyclophosphamide , Esophagitis , Humans , Lung Neoplasms , Pathology , Therapeutics , Neoplasm Staging , Radiation Pneumonitis , Radiotherapy, Conformal , Retrospective Studies , Topotecan
4.
Chinese Medical Journal ; (24): 340-344, 2013.
Article in English | WPRIM | ID: wpr-331270

ABSTRACT

<p><b>BACKGROUND</b>Retinocytoma (RB) is a very common intraocular malignant tumor during infancy. Chemotherapy has gradually been used as the first-line treatment for intraocular RB in recent years. In this study, Livin and PTEN expressions were observed in the RB tissue, along with the growth-inhibiting and apoptosis-induced effects of topotecan (TPT) on RB HXO-Rb44 cell strain. This study aimed to investigate the antigrowth effects of TPT on RB cell strain HXO-Rb44.</p><p><b>METHODS</b>Max-Vision(TM) rapid immunohistochemistry was adopted to detect Livin and PTEN expressions in the normal retina and in RB, and their relationship with RB clinicopathologic features was analyzed. Human RB cell strain HXO-Rb44 was cultivated and passaged. MTT method was used to measure the survival rates of HXO-Rb44 cell strains under various TPT concentrations. IC50 values were calculated. Flow cytometry was used to detect the effects of various TPT concentrations on HXO-Rb44 cell apoptosis. Western blotting was used to detect the differences of Livin and PTEN protein expressions during cell apoptosis.</p><p><b>RESULTS</b>The positive expressions of Livin and PTEN in the RB group were obviously different from those in the normal control group. In RB tissue, Livin expression was relevant to PTEN expression. TPT could significantly induce the occurrence of cell apoptosis and had a dependent relationship with drug concentration. Livin and PTEN expression levels varied with the extension of the effect time of TPT based on Western blotting analysis.</p><p><b>CONCLUSIONS</b>Livin and PTEN have high and low expression levels in the RB tissue, respectively. Both of them have key roles in RB occurrence and development. TPT could induce human RB cell strain HXO-Rb44 cell apoptosis, and its mechanism is associated with the inhibition of Livin and PTEN expressions.</p>


Subject(s)
Adaptor Proteins, Signal Transducing , Apoptosis , Cell Line, Tumor , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Infant , Inhibitor of Apoptosis Proteins , Male , Neoplasm Proteins , PTEN Phosphohydrolase , Retinal Neoplasms , Drug Therapy , Pathology , Retinoblastoma , Drug Therapy , Pathology , Topoisomerase I Inhibitors , Pharmacology , Topotecan , Pharmacology
5.
Article in English | WPRIM | ID: wpr-319467

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate chemotherapy-related toxicity and the short-term efficacy of topotecan and cyclophosphamide as maintenance chemotherapy for stage IV neuroblastoma in complete remission.</p><p><b>METHODS</b>The clinical data of 16 children with stage IV neuroblastoma received 3 cycles of maintenance chemotherapy with topotecan (0.75 mg·m(-2)·day(-1), infused on days 0-4) and cyclophosphamide 250 mg·m(-2)·day(-1), infused on days 0-4). The two-year event-free survival after complete remission was recorded and the chemotherapy-related toxicities were evaluated according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute.</p><p><b>RESULTS</b>The most common chemotherapy-related toxicity was bone marrow suppression and suppressions of neutrophils, hemoglobin and platelets, which occurred in all the patients mostly of grade III and IV. All the patients experienced episodes of infections, which were controlled effectively with antibiotics. Impairment of gastrointestinal and liver functions in these cases was mostly mild (grade I and II) and recovered after corresponding treatments. None of the patients exhibited damages in the nervous system or the renal or cardiac functions. After complete remission, the two-year event-free survival rate of these patients was 68.75% (11/16).</p><p><b>CONCLUSION</b>Topotecan plus cyclophosphamide for maintenance chemotherapy can be effective and relative safe for stage IV neuroblastoma in complete remission, thus giving a chance to those patients who choose not to have stem cell transplantation.</p>


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Child , Child, Preschool , Cyclophosphamide , Female , Humans , Infant , Maintenance Chemotherapy , Male , Neoplasm Staging , Neuroblastoma , Drug Therapy , Pathology , Topotecan , Treatment Outcome
6.
Chinese Journal of Cancer ; (12): 150-158, 2012.
Article in English | WPRIM | ID: wpr-294426

ABSTRACT

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters , Metabolism , Adenosine , Pharmacology , Animals , Antineoplastic Agents , Pharmacology , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Cell Survival , Cisplatin , Pharmacology , Colonic Neoplasms , Metabolism , Pathology , Diketopiperazines , Doxorubicin , Metabolism , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Female , Heterocyclic Compounds, 4 or More Rings , Humans , Inhibitory Concentration 50 , KB Cells , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Mitoxantrone , Pharmacology , Neoplasm Proteins , Metabolism , Neoplasm Transplantation , Rhodamine 123 , Metabolism , Topotecan , Pharmacology
7.
Chinese Journal of Cancer ; (12): 690-700, 2011.
Article in English | WPRIM | ID: wpr-294475

ABSTRACT

Although the anti-malaria drug chloroquine (CQ) has been shown to enhance chemotherapy and radiation sensitivity in clinical trials, the potential mechanisms underlying this enhancement are still unclear. Here, we examined the relevant mechanisms by which the multipotent CQ enhanced the cytotoxicity of topotecan (TPT). The lung cancer cell line A549 was treated with TPT alone or TPT combined with CQ at non-cytotoxic concentrations. Cell viability was assessed using the MTT assay. The percentage of apoptotic cells and the presence of a side population of cells were both determined by flow cytometry. Autophagy and the expression of Bcl-2 family proteins were examined by Western blotting. The accumulation of YFP-LC3 dots and the formation of acidic vesicular organelles were examined by confocal microscopy. CQ sensitized A549 cells to TPT and enhanced TPT-induced apoptosis in a Bcl-2 family protein-independent fashion. CQ inhibited TPT-induced autophagy, which modified the cytotoxicity of TPT. However, CQ failed to modify the transfer of TPT across the cytoplasmic membrane and did not increase lysosomal permeability. This study showed that CQ at non-cytotoxic concentrations potentiated the cytotoxicity of TPT by interfering with autophagy, implying that CQ has significant potential as a chemotherapeutic enhancer.


Subject(s)
Apoptosis , Apoptosis Regulatory Proteins , Metabolism , Autophagy , Bcl-2-Like Protein 11 , Cell Line, Tumor , Cell Proliferation , Chloroquine , Pharmacology , Drug Synergism , Humans , Lung Neoplasms , Metabolism , Pathology , Membrane Proteins , Metabolism , Proto-Oncogene Proteins , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Topoisomerase I Inhibitors , Pharmacology , Topotecan , Pharmacology , bcl-2-Associated X Protein , Metabolism
8.
MEAJO-Middle East African Journal of Ophthalmology. 2010; 17 (3): 207-209
in English | IMEMR | ID: emr-123593

ABSTRACT

To describe an unusual clinical finding seen in children undergoing intra-arterial chemotherapy for retinoblastoma. A retrospective review of 69 eyes of 63 patients receiving intra-arterial chemotherapy over a 3-year period. Charts and photographs of 69 consecutive cases were reviewed, and data were collected on patients with clinical evidence of a hyperemic cutaneous periocular abnormality following the procedure. A blanching erythematous and edematous patch was noted in the periocular region in 16% [11 of 69] of the children who received intra-arterial chemotherapy. The plaque extended into the region of the supertrochlear and medial marginal artery distribution on the ipsilateral side of the intra-arterial chemotherapy. All patches of erythema spontaneously resolved within 3 months following completion of the intra-arterial chemotherapy. Periocular erythema and swelling is a self-limited clinical finding associated with intra-arterial chemotherapy in a small number of patients


Subject(s)
Humans , Erythema , Eye , Antineoplastic Agents , Infusions, Intra-Arterial , Retinal Neoplasms , Retrospective Studies , Topotecan , Melphalan , Skin
9.
Hematology, Oncology and Stem Cell Therapy. 2010; 3 (4): 199-202
in English | IMEMR | ID: emr-108576

ABSTRACT

Idiopathic hyperammonemia [IHA] had been reported in some patients with hematological malignancy after receiving intensive chemotherapy, following bone marrow transplantation, or after using 5-fluorouracil for some solid tumors. The chemotherapeutic agents involved include cytarabine, daunomycin, cyclophosphamide, vincristine, amsacrine, etoposide, asparaginase, busulfan, and methotraxate, all used for treating hematological malignancies. No previous reports have described the association between idiopathic hyperammonemia and combined chemotherapy with vinorelbine, topotecan, and cisplatin. We describe a 20-year-old girl with normal liver function and relapsed precursor B-lymphoblastic leukemia receiving the modified TVTG [topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine] protocol to control her disease. We used cisplatin [30 mg/m[2]/day] to replace thiotepa on day 3 because thiotepa was not available in Taiwan. The patient developed acute idiopathic hyperammonemia after 5 days of chemotherapy and died 9 days after chemotherapy. To our knowledge, this patient is the first report of the association of hyperammonemia and chemotherapy with vinorelbine, topotecan, and cisplatin in the English literature


Subject(s)
Humans , Female , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols , Vinblastine/adverse effects , Vinblastine , Topotecan/adverse effects , Topotecan , Cisplatin/adverse effects , Cisplatin , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Thiotepa , Dexamethasone
10.
Article in English | WPRIM | ID: wpr-6894

ABSTRACT

OBJECTIVE: Retrospective evaluation of the outcome of stage IVB, recurrent or persistent cervical cancer treated with cisplatin and generic topotecan (CT) in a tertiary care hospital in Thailand. METHODS: The medical records of patients treated with CT regimen at Chiang Mai University Hospital between January 2005 and December 2007 were reviewed and analyzed. The treatment protocol consisted of IV topotecan 0.75 mg/m2 on days 1, 2, and 3; combined with cisplatin 50 mg/m2 IV on day 1 and repeated every 21 days until progression or unacceptable toxicity for a maximum of 6 cycles. The outcomes were evaluated based on the response rate, progression free survival (PFS), and overall survival (OS) by using the World Health Organization criteria. The adverse effects of the treatments were also determined. RESULTS: Twenty-one cervical cancer patients received the CT regimen. The tumor response rate was 28.6%. The median PFS and OS was 4 and 11 months, respectively. With 87 cycles of chemotherapy, the most common grade 3 & 4 hematologic toxicity was neutropenia (57.9%). CONCLUSION: Advanced and recurrent cervical cancer patients treated with cisplatin and generic topotecan had a favorable outcome with manageable toxicity.


Subject(s)
Cisplatin , Clinical Protocols , Disease-Free Survival , Humans , Medical Records , Neutropenia , Recurrence , Retrospective Studies , Tertiary Healthcare , Thailand , Topotecan , Uterine Cervical Neoplasms , World Health Organization
11.
Article in Chinese | WPRIM | ID: wpr-237609

ABSTRACT

Mesenchymal stem cells (MSC) are important cellular component of the bone marrow microenvironment in supporting hemopoiesis. Li J et al reported previously that MSCs are resistant to chemotherapy commonly used in hematologic malignancies but are relatively sensitive to anti-microtubule agents. However, the response of MSCs to other chemotherapeutic agents commonly used in solid tumour settings remains unknown. This study was purposed to evaluate the acute direct effects of 4 individual chemotherapeutic agents on human MSCs (hMSC), including cisplatin, topotecan, daunorubicin and hydroxyurea. Using an in vitro culture system, the chemosensitivity of hMSC was determined by XTT assay and compared with NB-4 cells and normal peripheral blood mononuclear cells (PBMNC). The recovery of cell numbers following exposure to chemotherapeutic agents and apoptosis induced by chemotherapy in hMSC were evaluated. The results showed that although hMSCs were more resistant to the 4 agents above mentioned than NB-4 cells, they were sensitive to topotecan, cisplatin and daunorubicin than PBMNCs. The IC₅₀ values of hMSCs for topotecan, cisplatin, hydroxyurea and daunorubicin were 636, 24.8, > 20 and 2.4 times of those of NB-4 cells respectively. The IC₅₀ values of human PBMNCs for topotecan, cisplatin and daunorubicin were > 27, 1.9 and 1.4 times of those of hMSCs respectively. Reduction of cell number was observed in hMSCs treated with the 4 drugs in clinically relative concentrations. Sustained suppression in hMSCs was observed following 3 days exposure to the 4 agents. It is concluded that the cisplatin, topotecan, daunorubicin and hydroxyurea alone can induce apoptosis of hMSCs and exert persistent suppressive effect on the proliferation of hMSCs even with short term exposure.


Subject(s)
Antineoplastic Agents , Pharmacology , Bone Marrow Cells , Cell Biology , Cells, Cultured , Cisplatin , Pharmacology , Daunorubicin , Pharmacology , Humans , Hydroxyurea , Pharmacology , Inhibitory Concentration 50 , Mesenchymal Stem Cells , Cell Biology , Topotecan , Pharmacology
12.
Chinese Journal of Lung Cancer ; (12): 211-215, 2010.
Article in Chinese | WPRIM | ID: wpr-294833

ABSTRACT

<p><b>BACKGROUND AND OBJECTIVE</b>How to prolong progression free survival (PFS) and overall survival (OS) of patients with small cell lung cancer (SCLC) has been one of the hottest issues. We retrospectively reviewed our data to compare the survival of immediate with delayed topotecan after first-line therapy in SCLC.</p><p><b>METHODS</b>In our retrospective study, 53 patients with SCLC were divided into two groups as follow: patients receiving topotecan-containing regimen as maintenance/consolidation (maintenance/consolidation chemotherapy group) and salvage chemotherapy (salvage chemotherapy group). The Log-rank test was used to assess the difference in OS between two groups. Cox regression model was used for the multivariable analysis of independent prognostic factors.</p><p><b>RESULTS</b>Twenty-nine patients received topotecan as maintenance/consolidation treatment, whereas 24 patients salvage chemotherapy. The response rates were 51.7% and 41.7%, respectively. The median survival time were 20 months and 27 months respectively (P = 0.89). Multivariate Cox regression analyses identified sex and stage as independent prognostic factors.</p><p><b>CONCLUSION</b>Efficacy of first-line therapy was improved by topotecan maintenance/ consolidation treatment, which did not result in any significant survival benefits in SCLC.</p>


Subject(s)
Adult , Aged , Antineoplastic Agents , Therapeutic Uses , Female , Humans , Lung Neoplasms , Drug Therapy , Mortality , Male , Middle Aged , Retrospective Studies , Small Cell Lung Carcinoma , Drug Therapy , Mortality , Topotecan , Therapeutic Uses , Treatment Outcome
13.
Chinese Journal of Oncology ; (12): 855-858, 2010.
Article in Chinese | WPRIM | ID: wpr-293466

ABSTRACT

<p><b>OBJECTIVE</b>To explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity.</p><p><b>METHODS</b>Sixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method.</p><p><b>RESULTS</b>The results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P < 0.01).</p><p><b>CONCLUSION</b>The results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.</p>


Subject(s)
Adenosine Triphosphate , Metabolism , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , CA-125 Antigen , Blood , Carcinoma, Endometrioid , Blood , Drug Therapy , Metabolism , Cystadenocarcinoma, Serous , Blood , Drug Therapy , Metabolism , Deoxycytidine , Disease-Free Survival , Doxorubicin , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Methods , Etoposide , Female , Follow-Up Studies , Humans , Luminescent Measurements , Neoplasm Recurrence, Local , Ovarian Neoplasms , Blood , Drug Therapy , Metabolism , Paclitaxel , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Survival Rate , Topotecan
14.
Chinese Journal of Oncology ; (12): 143-147, 2009.
Article in Chinese | WPRIM | ID: wpr-255542

ABSTRACT

<p><b>OBJECTIVE</b>To retrospectively analyze the effects of different chemotherapy regimens for concurrent chemoradiation on locally advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The data from 106 patients diagnosed as locally advanced NSCLC (IIIa: 29, IIIb: 77), who received various chemotherapy regimens for concurrent chemoradiotherapy, were retrospectively analyzed. Paclitaxel-based chemotherapy regimen was administered in 55 patients, topotecan regimen in 21 patients, PE (cisplatin and etopside) regimen in 26 patients, and other regimens in the remaining 4 patients. The effect of different chemotherapy regimens on overall survival and toxicity was analyzed.</p><p><b>RESULTS</b>The median survival time was 18.6 months, and the overall 1- and 3-year survival rates were 72.2% and 27.5%, respectively. The median survival time of 102 patients treated with paclitaxel-containing, topotecan-containing or PE regimens was 16.3, 27.3 and 29.1 months, respectively. The overall survival times of topotecan and PE groups were superior to that of paclitaxol-based group, but not significantly different (P = 0.32). Both univariate and multivariate analysis showed that paclitaxol-based chemotherapy regimen was significantly associated with a poorer survival (P < 0.05). N stage was another significant prognostic factor determined by COX multivariate regression model. Compared with the other regimens (10.6%), paclitaxel-based regimen (27.3%) had more acute radiation pneumonitis (grade >or= 2, P = 0.03), but no significant differences were observed in blood toxicity and esophagitis.</p><p><b>CONCLUSION</b>There is a correlation between different chemotherapy regimens for concurrent chemoradiotherapy and the overall survival and acute radiation pneumonitis in patients with locally advanced NSCLC.</p>


Subject(s)
Adult , Aged , Antineoplastic Agents , Therapeutic Uses , Antineoplastic Agents, Phytogenic , Therapeutic Uses , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Pathology , Radiotherapy , Cisplatin , Therapeutic Uses , Combined Modality Therapy , Etoposide , Therapeutic Uses , Female , Follow-Up Studies , Humans , Lung Neoplasms , Drug Therapy , Pathology , Radiotherapy , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Paclitaxel , Therapeutic Uses , Proportional Hazards Models , Radiation Pneumonitis , Radiotherapy, Conformal , Retrospective Studies , Survival Rate , Topotecan , Therapeutic Uses
15.
Article in Korean | WPRIM | ID: wpr-129514

ABSTRACT

OBJECTIVE: Theoretically, chemotherapy sensitivity and resistance assays help to predict which sensitive agent will be effective for patients. Due to low correlation between in vitro assay results and in vivo responses, chemosensitivity test is not generally applied in actual clinical practices. The aim of this study is to evaluate the influence of cell cycle in the course of cell culture stage on chemosensitivity test as a disturbing factor. METHODS:After synchronization at G0, we conducted experiments on SKOV-3 cell line according to determined cell cycle span (G0, G0/G1, S, G2/M) with MTT (methylthiazolyl-diphenyl- tetrazolium bromide) chemosensitivity test. We evaluated the sensitivity changes of six chemotherapeutic agents (5-FU, Etoposide, Cisplatin, Topotecan, Paclitaxel, Doxorubicin) in each phase at target times. RESULTS: Each phase represented the various results of MTT sensitivity on six chemotherapeutic agents. The variation of sensitivity between experimental (cell cycle synchronized culture) group and reference (conventional culture) group was 21.3+/-5.1 (mean+/-.D)%. CONCLUSION: The cells in the each phase of cell cycle represent different levels of sensitivity to the same chemotherapeutic agent. The required cell culture stage of chemosensitivity test can blur the true candidate agent. This finding can be regarded as one of the reasons of mismatch between in vitro chemosensitivity and in vivo response of candidate chemotherapeutic agents.


Subject(s)
Cell Culture Techniques , Cell Cycle , Cell Line , Cisplatin , Etoposide , Humans , Ovarian Neoplasms , Paclitaxel , Topotecan
16.
Article in Korean | WPRIM | ID: wpr-129499

ABSTRACT

OBJECTIVE: Theoretically, chemotherapy sensitivity and resistance assays help to predict which sensitive agent will be effective for patients. Due to low correlation between in vitro assay results and in vivo responses, chemosensitivity test is not generally applied in actual clinical practices. The aim of this study is to evaluate the influence of cell cycle in the course of cell culture stage on chemosensitivity test as a disturbing factor. METHODS:After synchronization at G0, we conducted experiments on SKOV-3 cell line according to determined cell cycle span (G0, G0/G1, S, G2/M) with MTT (methylthiazolyl-diphenyl- tetrazolium bromide) chemosensitivity test. We evaluated the sensitivity changes of six chemotherapeutic agents (5-FU, Etoposide, Cisplatin, Topotecan, Paclitaxel, Doxorubicin) in each phase at target times. RESULTS: Each phase represented the various results of MTT sensitivity on six chemotherapeutic agents. The variation of sensitivity between experimental (cell cycle synchronized culture) group and reference (conventional culture) group was 21.3+/-5.1 (mean+/-.D)%. CONCLUSION: The cells in the each phase of cell cycle represent different levels of sensitivity to the same chemotherapeutic agent. The required cell culture stage of chemosensitivity test can blur the true candidate agent. This finding can be regarded as one of the reasons of mismatch between in vitro chemosensitivity and in vivo response of candidate chemotherapeutic agents.


Subject(s)
Cell Culture Techniques , Cell Cycle , Cell Line , Cisplatin , Etoposide , Humans , Ovarian Neoplasms , Paclitaxel , Topotecan
17.
Journal of Experimental Hematology ; (6): 1342-1346, 2009.
Article in Chinese | WPRIM | ID: wpr-343289

ABSTRACT

Up to now, no consensus has been reached on the standard salvage regimen for patients with refractory or relapsed acute myeloid leukemia (AML). This study was purposed to evaluate the efficacy and safety of combination chemotherapy composing of cyclophosphamide (Cy), cytosine arabinoside (Ara-C) and topotecan (CAT regimen) for 37 refractory or relapsed AML patients. The dosing regimen was as follows: Cy 300 mg/m2 by intravenous infusion, every 12 hours on days 1-3, topotecan 1.25 mg/m2 by intravenous continuous infusion over 6 hours daily on days 2 to 6, Ara-C 500 mg/m2 by intravenous infusion over 2 hours daily for 5 days on days 2-6. The results showed that all patients completed one cycle of chemotherapy. 12 patients (32.4%) achieved complete remission (CR), 2 (5.4%) achieved partial remission (PR), and the 23 remaining patients achieved no remission (NR). The overall response rate (RR) was 37.8%. Among 18 relapsed cases, 6 cases had CR (33.3%), 2 cases achieved PR (11.1%), and 10 cases were with NR (55.6%). Among 19 refractory cases, 6 had CR (31.6%), and 13 (68.4%) were with NR. There was no statistically significant difference in RR between refractory and relapsed groups (31.6% and 44.4%, respectively) (p=0.42). Myelosuppression was universal. Mild non-hematologic toxicities were mainly gastrointestinal, as nausea, vomiting, diarrhea. The incidence of severe (grade III-IV) non-hematologic toxicity, such as oral mucositis and infection was 37.8% and 86.5% respectively. Only one patient died of severe infection during the observation (within 28 days from start of chemotherapy). The time of median follow-up was 4 (0-33) months, the median overall survival (OS) was 4 (1.8-6.2) months. The median OS for responders was longer than that for non-responders (9 vs 2 months respectively, p=0.00). In conclusion, the CAT regimen of lower dose is well tolerated and has certain anti-leukemia effect, and worthy to be further investigated.


Subject(s)
Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Cyclophosphamide , Cytarabine , Female , Humans , Leukemia, Myeloid, Acute , Drug Therapy , Male , Middle Aged , Recurrence , Topotecan , Young Adult
18.
Article in Chinese | WPRIM | ID: wpr-304617

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether topotecan, a novel anti-tumor agent, down-regulates gene expression of melanoma antigen-encoding (MAGE) in HPB-AM cells.</p><p><b>METHODS</b>MAGE mRNA expression of HPB-AM cells was detected by RT-PCR 4, 8, 12 and 16 hrs after different concentrations (0.05, 0.10, 0.15 and 0.20 micromol/L) of topotecan treatment.</p><p><b>RESULTS</b>MAGE mRNA expression of HPB-AM cells decreased with increasing concentrations of topotecan 12 hrs after treatment. The MAGE mRNA expression of HPB-AM cells treated by 0.10, 0.15 and 0.20 micromol/L of topotecan was significantly lower than that in the blank control group (P<0.05). MAGE mRNA expression of HPB-AM cells was significantly reduced in a time-dependent manner after 0.10 micromol/L of topotecan treatment. The MAGE mRNA expression of HPB-AM cells treated by 0.10 micromol/L of topotecan was significantly lower than that in the blank control group 12 and 16 hrs after treatment (P<0.05).</p><p><b>CONCLUSIONS</b>Topotecan is capable of inhibiting the expression of MAGE mRNA of HPB-AM cells in a time- and dose-dependent manner.</p>


Subject(s)
Antigens, Neoplasm , Genetics , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Dose-Response Relationship, Drug , Gene Expression , Humans , Lymphoma , Drug Therapy , Metabolism , Pathology , Neoplasm Proteins , Genetics , RNA, Messenger , Topotecan , Pharmacology
19.
Acta Pharmaceutica Sinica ; (12): 565-569, 2008.
Article in Chinese | WPRIM | ID: wpr-277795

ABSTRACT

Hypoxia-inducible factor-1 (HIF-1), as a transcription factor, plays an important role in the adaptation to hypoxic microenvironment within tumors. It can induce a series of genes transcription that participate in angiogenesis, glucose metabolism, cell proliferation, and cell migration/invasion. Thus HIF-1 not only allows cancer cells to survive in hypoxic microenvironment, but also makes the tumor more aggressive. Moreover, HIF-1 also induces tumors to acquire resistance to chemo-/radio-therapy, and is related to poor prognosis. HIF-1 emerges gradually as a potential target to develop new antitumor drugs. This paper reviews recent progress in this field.


Subject(s)
Amphotericin B , Pharmacology , Animals , Antineoplastic Agents , Pharmacology , Echinomycin , Pharmacology , Humans , Hypoxia-Inducible Factor 1 , Genetics , Metabolism , Indazoles , Pharmacology , Sirolimus , Pharmacology , Topotecan , Pharmacology , Transcription, Genetic
20.
Acta Pharmaceutica Sinica ; (12): 811-818, 2008.
Article in Chinese | WPRIM | ID: wpr-277772

ABSTRACT

Antitumor activity and the mechanism of CPUY013, a novel Topo I inhibitor, on gastric adenocarcinoma BGC823 cells were studied in vitro and in vivo. The proliferation was investigated by MTT assay and colony formation assay. Apoptosis was determined by both dual fluorescence staining with AO and EB and DNA agarose gel electrophoresis analysis methods. Nude mice model of BGC823 xenograft tumor was established by subcutaneous inoculation. The suppression activity of the CPUY013 by intragastric administration on xenograft mice model was detected. The change of cell cycle was studied by flow cytometry assay. The expressions of Topo I, widetype p53, active caspase-3, bcl-2 and bax proteins were analyzed by Western blotting assay. Results showed that CPUY013 could inhibit BGC823 cell proliferation at a certain range of dose. The flow cytometry analysis showed that CPUY013 and topoecan (TPT) led to a decrease in the proportion of G1 phase cells and an increase in the proportion of S phase cells, suggesting that they arrested the transition of tumor cells from S phase to G2 phase. The sub-G1 group was analyzed by flow cytometry. Compared with control, after 48 h treatment with CPUY013 or TPT, the sub-G1 group significantly increased in a dose-dependent manner. CPUY013 and TPT induced apoptosis in tumor cells. Cells treated with CPUY013 for 48 h were stained with AO/EB mixture. Then the cells were observed under fluorescence microscope. And it was found that early and late apoptosis cells were identified by perinuclear condensation of chromatin stained by AO/EB, respectively. Necrotic cells were identified by uniform labeling with EB. With the increase of concentration of CPUY013 and TPT, these morphological changes under the fluorescence microscope become clearer, indicating that the proportion of apoptosis cells increased gradually. By using JC-1 kit, loss of deltapsim was also detected in BGC823 cells treated with CPUY013 and TPT, which represent mitochondria function. And characteristic DNA ladder was observed apparently in BGC823 cells treated with CPUY013. When the xenograft tumor mice were treated with 150 mg x kg(-1) CPUY013, the tumor growth inhibition rate was 62.1%. The expression of bax and p53 proteins increased significantly and bcl-2 and bcl-2/bax decreased after the treatment of the CPUY013. The CPUY013 down-regulated Topo I protein expression and up-regulated active caspase-3 protein expression. The novel Topo I inhibitor CPUY013 can significantly suppress the growth of BGC823 xenograft tumor in vivo and inhibit the proliferation by inducing apoptosis of BGC823 cells in vitro.


Subject(s)
Animals , Antineoplastic Agents , Pharmacology , Apoptosis , Caspase 3 , Metabolism , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Female , Fluoroquinolones , Pharmacology , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Oxazoles , Pharmacology , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Stomach Neoplasms , Metabolism , Pathology , Topoisomerase I Inhibitors , Topotecan , Pharmacology , Tumor Suppressor Protein p53 , Metabolism , bcl-2-Associated X Protein , Metabolism
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