We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Dactinomycin/adverse effects* ; Female ; Gestational Trophoblastic Disease/drug therapy* ; Humans ; Methotrexate/therapeutic use* ; Pregnancy ; Retrospective Studies

Background: Recent studies have shown poorer outcomes for patients with prognostic score above 12. Authors have proposed categorizing these patients as ultra high-risk to emphasize the need for a different treatment regimen. Objectives: This study was conducted to compare the clinical response of high-risk and ultra high-risk Gestational Trophoblastic Neoplasia (GTN) patients who were managed at the Philippine General Hospital, from January 1, 2010 to December 31, 2015, after receiving the EMACO regimen as first line treatment. Methods: All patients diagnosed with metastatic high-risk GTN who were managed at the Philippine General Hospital from January 1, 2010 to December 31, 2015 and given the EMACO regimen as first-line treatment were included in the study. Patients were divided into high-risk disease or patients with a WHO prognostic score of 7-11 and ultra high-risk disease or patients with WHO prognostic score of 12 and above. Using the Z-test on two proportion, treatment outcome between the two groups were compared. Results: A total of 57 patients diagnosed with metastatic high-risk GTN were included in the study. Of these, 35 or 61% were classified as high-risk while 22 or 39% were ultra high-risk. The primary remission rate of the high-risk group was 89% compared to 77% for the ultra high-risk group. The difference was not statistically significant (p=0.2542). Out of the 57 patients included in the study, 48 patients achieved remission after being treated with EMACO. An additional 4 patients achieved remission after being shifted to EPEMA due to resistance to the first line agent. All patients were alive after one year of follow-up, giving a one-year survival rate of 91.2%. Conclusion The result of this study showed a relatively higher remission rate for high-risk (89%) than ultra highrisk GTN (77%) with EMACO as first line chemotherapy regimen, but statistical analysis revealed no significant difference. This finding suggests that EMACO may still be used as first line regimen for ultra high-risk GTN to attain remission.
Gestational Trophoblastic Disease ; EMA-CO protocol ; Etoposide ; Dactinomycin ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Methotrexate ; Vincristine

Ewing sarcoma is the second most frequently occurring malignant tumor of the bone and soft tissue in adolescents and young adults. Genetically, Ewing sarcoma is characterized by balanced chromosomal translocation in which a member of FET gene family is fused with an ETS transcription factor, with the most common fusion being EWSR1-FLI1 (85% of cases). Treatment of Ewing sarcoma is based on multidisciplinary approach (local surgery, radiotherapy and multiagent chemotherapy), which are associated with chronic late effects that may compromise quality of life of survivors. First line treatment includes combination of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin. The beneficial role of high dose chemotherapy has been suggested in high-risk localized Ewing sarcoma patients, and the studies are being performed to investigate the role in metastatic disease. The 5-year overall survival for localized Ewing sarcoma has improved to reach 65% to 75%. But patients with metastatic disease have a 5-year survival rate of <30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrent tumor have a dismal prognosis. Novel therapeutic strategies based on understanding of molecular mechanisms are needed to improve the outcome of Ewing sarcoma and to lessen the treatment-related late effects.
Adolescent ; Cyclophosphamide ; Dactinomycin ; Doxorubicin ; Drug Therapy ; Etoposide ; Humans ; Ifosfamide ; Neoplasm Metastasis ; Neuroectodermal Tumors, Primitive, Peripheral ; Prognosis ; Quality of Life ; Radiotherapy ; Sarcoma, Ewing ; Survival Rate ; Survivors ; Transcription Factors ; Translocation, Genetic ; Vincristine ; Young Adult

No abstract available.
Dactinomycin ; Gestational Trophoblastic Disease

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

OBJECTIVE: The aim of this study was to compare responses to single-agent chemotherapies and evaluate the predictive factors of resistance in low risk (LR) gestational trophoblastic disease (GTD). The chemotherapy agents included methotrexate (MTX) and actinomycin D (ACT-D). METHODS: We conducted a retrospective study of 126 patients with GTD who were treated between 2000 and 2013. A total of 71 patients with LR GTD were treated with MTX (8-day regimen or weekly regimen, n=53) or ACT-D (bi-weekly pulsed regimen or 5-day regimen, n=18). The successful treatment group and the failed treatment group were compared and analyzed to identify prognostic factors. RESULTS: The complete response rates were 83.3% for ACT-D and 62.2% for MTX, with no statistically significant difference. There was no severe adverse effect reported for either group. Longer interval durations from the index pregnancy (>2 months, p=0.040) and larger tumor size (>3 cm, p=0.020) were more common in non-responders than in responders; these results were statistically significant. CONCLUSION: Based on our results, ACT-D may be a better option than MTX as a first-line single chemotherapy agent for LR GTD. The bi-weekly pulsed ACT-D regimen had minimal, or at least the same, toxicities compared with MTX. However, due to the lack of strong supporting evidence, it cannot be conclusively stated that this is the best single agent for first-line chemotherapy in LR GTD patients. Further larger controlled trials will be necessary to establish the best guidelines for GTD treatment.
Dactinomycin* ; Drug Therapy* ; Gestational Trophoblastic Disease* ; Humans ; Methotrexate* ; Pregnancy ; Retrospective Studies

This paper reports a case of a 19 year-old born with ambiguous genitalia, who presented with abdominopelvic mass diagnosed to have Ovotesticular Disorder of Sexual Development (OT-DSD) 46, XY with Malignant Mixed Germ Cell Tumor (Yolk Sac Tumor, Dysgerminoma, Mature Cystic Teratoma,). She underwent two surgeries and had gone through six cycles of Vincristine, Dactinomycin and Cyclophosphamide chemotherapy.

OT-DSD is a rare condition by the presence of both histologically proven testis and ovary in the same individual. The report describes the clinical, biochemical, imaging, and histopathologic findings and outcomes of OT-DSD complicated with gonadal tumor. Diagnostic work up, pre-operative preparations, intra operative management, post-operative follow up and chemotherapy along with psychiatric support for gender identity and assignment are discussed. This paper emphasizes the importance of multidisciplinary effort from the different fields of medicine namely reproductive endocrinology, gynecologic oncology, surgery, psychiatry, and anesthesiology.

Human ; Female ; Adult ; Dysgerminoma ; Testis ; Vincristine ; Dactinomycin ; Endodermal Sinus Tumor ; Gender Identity ; Anesthesiology ; Sexual Development ; Psychiatry ; Endocrinology ; Cyclophosphamide ; Teratoma

PURPOSE: Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor beta (TGF-beta) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-beta can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-beta-responsive and overexpress COX-2. MATERIALS AND METHODS: Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-beta. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference. RESULTS: We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-beta. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-beta, suggesting that TGF-beta-induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-beta rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-beta. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-beta. CONCLUSION: The results of this study show that TGF-beta down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.
Adenocarcinoma ; Blotting, Northern ; Blotting, Western ; Cyclooxygenase 2 ; Dactinomycin ; Down-Regulation ; Epithelial Cells ; Humans ; Lung ; Lung Neoplasms* ; RNA Interference ; RNA Stability ; RNA* ; RNA, Messenger ; Transforming Growth Factor beta* ; Tristetraprolin

OBJECTIVETo evaluate the efficacy and safety of MAC regimen in the treatment of acute myeloid leukemia(AML) patients older than 55 years.

METHODSA total of 33 relapsed or non-remission AML patients older than 55 years were enrolled in this research. MAC regimen was given as the salvage treatment. Complete remission rate(CR), partial remission rate(PR), overall survival(OS), relapse-free survival(RFS) and adverse effect were analysed.

RESULTSCR rate after the salvage therapy with MAC was 51.1%, partial remission (PR) rate was 6.1%, the overall response rate (ORR) was 57.6%, the median OS was 8 months (1.0-66.0 months), the median relapse-free survival (RFS) was 10.1 months (2.3-40.4 months). Mortality related with salvage treatment in 30 days was 9.1%. Low incidence of severe organ damage were found.

CONCLUSIONMAC can be used as a relative effective and safe regimen for the salvage treatment of the older AML patients.

Antineoplastic Combined Chemotherapy Protocols ; Chlorambucil ; Cytarabine ; Dactinomycin ; Humans ; Leukemia, Myeloid, Acute ; Methotrexate ; Middle Aged ; Recurrence ; Remission Induction ; Salvage Therapy

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