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 we...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.展开更多
AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines ...AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.展开更多
Background: Use of Chemotherapy is a double edged sword apart from destroying malignant cells it also has life threatening complications, so clinician should be ready to counter the complication while also dealing wit...Background: Use of Chemotherapy is a double edged sword apart from destroying malignant cells it also has life threatening complications, so clinician should be ready to counter the complication while also dealing with malignancies. Case Report: We report a case of Invasive Mole who after initiation of first cycle of chemotherapy (5 Fluorouracil and Dactinomycin) developed Gastrointestinal and Myelosuppression related complications. Conclusion: Extreme Knowledge of Clinicians is a must to deal with infections and other potential complications while using chemotherapy.展开更多
文摘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.
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.
文摘Background: Use of Chemotherapy is a double edged sword apart from destroying malignant cells it also has life threatening complications, so clinician should be ready to counter the complication while also dealing with malignancies. Case Report: We report a case of Invasive Mole who after initiation of first cycle of chemotherapy (5 Fluorouracil and Dactinomycin) developed Gastrointestinal and Myelosuppression related complications. Conclusion: Extreme Knowledge of Clinicians is a must to deal with infections and other potential complications while using chemotherapy.
