OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

OBJECTIVETo evaluate the combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) as primary treatment for gestational trophoblastic neoplasia (GTN).

METHODSClinical data and outcome of the patients with GTN from 1 January 2004 to 31 December 2009 were retrospectively reviewed. Totally 38 eligible patients had received at least one cycle of FAEV chemotherapy as primary treatment. The primary end points were response rate and toxicity of FAEV regimen.

RESULTSTotally 38 patients and 205 cycles of FAEV chemotherapy were included. Twenty-eight of these patients (73.6%) achieved serologic complete remission (SCR). Regimens were changed in 10 patients because of 5 with no response and 5 with intolerable toxicity. The most serious adverse events were greater than or equal to grade 3 neutropenia (31.6%), febrile neutropenia (7.9%), and greater than or equal to grade 3 thrombocytopenia (5.3%). During the follow-up, none relapsed.

CONCLUSIONFAEV is an effective regimen with manageable toxicity for patients with GTN as primary treatment, especially for patients with non-metastatic low or high risk GTN.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Dactinomycin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Floxuridine ; administration & dosage ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Middle Aged ; Pregnancy ; Retrospective Studies ; Treatment Outcome ; Vincristine ; administration & dosage ; Young Adult

OBJECTIVETo evaluate the role of lung lobectomy in the patients of tumor with lung metastases.

METHODSA total of 45 cases of trophoblastic tumor with pulmonary metastases treated by lung lobectomy from 1985-2002 at PUMC hospital was retrospectively analyzed. Seven cases were diagnosed as invasive mole and thirty-eight as choriocarcinoma.

RESULTSLung lobectomy was performed in all of these patients after several courses of chemotherapy. Seven cases of invasive mole reached complete remission. Eleven cases of choriocarcinoma with stage IIIa had received average 13 courses of chemotherapy, 10 of them reached complete remission. Seventeen cases of choriocarcinoma with stage IIIb had received average 14.3 courses of chemotherapy, 11 of them reached complete remission. Ten cases of choriocarcinoma with stage IV had received average 15 courses of chemotherapy, six of them reached complete remission. In the 45 patients, histologic examination disclosed haemorrhagic necrotic tissue in 27 patients, 17 of them reached complete remission (63%). Histologic examination also revealed fibrosis around the focus in 16 patients, 14 of them reached complete remission (88%). Tuberculosis was found in 2 patients.

CONCLUSIONSAlthough the development of effective chemotherapy has resulted in improved survival of patients with gestational trophoblastic tumor, lung lobectomy remains an important adjunct treatment in a selected subset of patients. Pathological examinations can help to estimate the prognosis.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Choriocarcinoma ; secondary ; surgery ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Dactinomycin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Humans ; Hydatidiform Mole, Invasive ; pathology ; secondary ; surgery ; Lung Neoplasms ; secondary ; surgery ; Male ; Methotrexate ; administration & dosage ; Middle Aged ; Pneumonectomy ; methods ; Pregnancy ; Prognosis ; Retrospective Studies ; Trophoblastic Neoplasms ; secondary ; surgery ; Uterine Neoplasms ; pathology ; surgery ; Vincristine ; administration & dosage

OBJECTIVETo analyse the efficacy of the floxuridine (FUDR)-containing regime (single agent or in combination) in the treatment of gestational trophoblastic tumor.

METHODSSeventy-four patients with gestational trophoblastic tumors (GTT), 47 invasive mole and 27 choriocarcinoma, were treated with FUDR-containing regime. The clinical staging of the disease were: 33 cases of stage I, 3 cases of stage II, 31 cases of stage IIIa, 6 cases of stage IIIb, and 1 case of stage IV.

RESULTSThe cure rate of FUDR-containing regime in the treatment of GTT was 91.9% (68 out of 74 cases). Twenty-one out of these 74 patients showed drug resistant to 5-FU-containing or MTX-containing regime and were cured after they changed to the FUDR-containing regime. All 7 patients of advanced stage (> or = III b) got cured. The major adverse event of FUDR-containing regime was myelodepression and gastrointestinal toxicity: III-IV degree granulopenia 26%, III-IV thrombopenia 6.2%, III degree vomiting 57.1%, and III degree diarrhea 4.3%.

CONCLUSIONFUDR-containing regime is efficient for the treatment of GTT, even for those with advanced stage or drug-resistant disease.

Adolescent ; Adult ; Antimetabolites, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Choriocarcinoma ; drug therapy ; Dactinomycin ; administration & dosage ; Drug Administration Schedule ; Female ; Floxuridine ; administration & dosage ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Hydatidiform Mole, Invasive ; drug therapy ; Middle Aged ; Pregnancy ; Uterine Neoplasms ; drug therapy ; Vincristine ; administration & dosage

BACKGROUND: The purpose of this study is to evaluate the disease-free survival (DFS) and overall survival (OS) of patients with stage IIB osteosarcoma at a single institution for 20 years and to compare the results according to the chemotherapy protocols. METHODS: From Jan 1988 to Nov 2008, 167 patients with osteosarcoma were treated at our hospital and among them, 117 patients (67 males and 50 females) with stage IIB osteosarcoma were evaluable. Their mean age was 22.6 years (range, 8 months to 71 years). Seventy-eight cases underwent the modified T10 (M-T10) protocol (group 1), 23 cases underwent the T20 protocol (group 2) and 16 cases underwent the T12 protocol (group 3). The DFS and OS were calculated and compared according to the chemotherapy protocols. RESULTS: At a mean follow-up of 78.9 months, 63 patients were continuously disease-free (63/117), 6 patients were alive after having metastatic lesions, 7 patients died of other cause and 41 patients died of their disease. The 5- and 10-year OS rates were 60.2% and 44.8%, respectively and the 5- and 10-year DFS rates were 53.5% and 41.4%, respectively. There was no significant difference of the OS and DFS between the chemotherapy protocols (p = 0.692, p = 0.113). CONCLUSIONS: At present, we achieved success rates close to the internationally accepted DFS and OS. We were able to achieve the higher survival rates using the M-T10 protocol over the 20 years. However, there was no significant difference of results between the chemotherapy protocols. We think the M-T10 protocol will achieve more favorable results in the near future.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use ; Bleomycin/administration & dosage ; Bone Neoplasms/*drug therapy/*mortality/surgery ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Cyclophosphamide/administration & dosage ; Dactinomycin/administration & dosage ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Infant ; Kaplan-Meier Estimate ; Leucovorin/administration & dosage ; Male ; Methotrexate/administration & dosage ; Middle Aged ; Neoadjuvant Therapy ; Osteosarcoma/*drug therapy/*mortality/surgery ; Survival Rate ; Vincristine/administration & dosage ; Young Adult

OBJECTIVETo improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery.

METHODSSixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI)-Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology.

RESULTSIn the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively.

CONCLUSIONThe present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoembolization, Therapeutic ; Child ; Child, Preschool ; Combined Modality Therapy ; Dactinomycin ; administration & dosage ; Disease-Free Survival ; Epirubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Infant ; Iodized Oil ; administration & dosage ; Kidney Neoplasms ; mortality ; pathology ; therapy ; Male ; Neoplasm Staging ; Nephrectomy ; Preoperative Care ; Survival Rate ; Treatment Outcome ; Vincristine ; administration & dosage ; Wilms Tumor ; pathology ; therapy

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child, Preschool ; Dactinomycin ; administration & dosage ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Infant ; Kidney Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rhabdoid Tumor ; drug therapy ; metabolism ; pathology ; surgery ; Rhabdomyosarcoma ; pathology ; Sarcoma, Clear Cell ; metabolism ; pathology ; Synaptophysin ; metabolism ; Vimentin ; metabolism ; Vincristine ; administration & dosage ; Wilms Tumor ; pathology

OBJECTIVETo study the inhibitory effect of antisense oligonucleotides against telomerase RNA on the growth of human choriocarcinoma transplant in nude mice.

METHODSChoriocarcinoma xenografts were established by transplanting JAR cells subcutaneously to female nude mice, and were treated with high and low doses of antisense oligonucleotides. Control groups were treated with NS, random sequence and actinomycin D (Act-D). Tumor growth was monitored once every other day. Telomerase relative activity was assayed by TRAP-ELISA. Western blotting was used to detect expression of hTERT.

RESULTSLow and high doses antisense oligonucleotides, and Act-D inhibited tumor growth by 76.6%, 93.8% and 85.4% respectively, which were significantly different when compared with random sequence and NS groups. Expression of telomerase relative activity and hTERT were decreased as well. But the differences among the first three groups had no significance.

CONCLUSIONTelomerase RNA antisense oligonucleotide inhibits growth of human choriocarcinoma xenografts in nude mice. It may be a novel approach to the treatment of choriocarcinoma.

Animals ; Antibiotics, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Choriocarcinoma ; enzymology ; pathology ; DNA-Binding Proteins ; metabolism ; Dactinomycin ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Oligonucleotides, Antisense ; administration & dosage ; pharmacology ; Pregnancy ; Telomerase ; genetics ; metabolism ; Uterine Neoplasms ; enzymology ; pathology

OBJECTIVE: To investigate the effect of sodium valproate (VPA) on activation of miR-34c-5p/ATG4B signaling pathway and autophagy in SH-SY5Y cells. METHODS: Routinely cultured SH-SY5Y cells were treated with VPA at different doses for 24 h, and the changes in the mRNA levels of ATG4B and miR-34c-5p and the protein expression of ATG4B were assessed using qRTPCR and immunoblotting, respectively. The effect of transfection with a plasmid containing ATG4B promoter on the promoter activity of ATG4B in VPA-treated SH-SY5Y cells was assessed using the reporter gene assay. The stability of ATG4B mRNA was analyzed with qPCR in SH-SY5Y cells treated with VPA alone or with VPA combined with the transcription inhibitor actinomycin D. The expression level of miR-34c-5p was detected using qPCR in SH-SY5Y cells treated with VPA alone or with VPA combined with miR-34c-5p mimics or antagonist, and the role of miR-34c-5p in VPA-induced ATG4B down-regulation was evaluated. The changes in the level of autophagy were evaluated by detecting LC3-Ⅱ expression in the cells after treatment with VPA or VPA combined with miR-34c-5p antagonist. RESULTS: VPA dose-dependently down-regulated the expression of ATG4B at both the mRNA and protein levels in SH-SY5Y cells. VPA treatment did not significantly affect the promoter activity of ATG4B, but obviously lowered the mRNA stability of ATG4B in SH-SY5Y cells. VPA treatment up-regulated the expression of miR-34c-5p, and the miR-34c-5p antagonist reversed VPA-induced down-regulation of ATG4B in SH-SY5Y cells. VPA also down-regulated the expression level of LC3-Ⅱ in SH-SY5Y cells. CONCLUSIONS VPA suppresses autophagy in SH-SY5Y cells possibly via activating miR-34c-5p/ATG4B signaling pathway.
Autophagy ; drug effects ; Autophagy-Related Proteins ; genetics ; metabolism ; Cell Line ; Cysteine Endopeptidases ; genetics ; metabolism ; Dactinomycin ; pharmacology ; Down-Regulation ; Genes, Reporter ; Humans ; MicroRNAs ; antagonists & inhibitors ; metabolism ; Microtubule-Associated Proteins ; metabolism ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Transfection ; Valproic Acid ; administration & dosage ; antagonists & inhibitors ; pharmacology