RESUMEN
Mulberry zonate leaf spot disease (MZLSD) is an important fungal disease of mulberry trees, which seriously affects the productivity and quality of mulberry leaves. MZLSD has been widely reported in sericultural production areas in Guangxi, China, in recent years. In this study, the causal agent of MZLSD was isolated from symptomatic samples and identified as Gonatophragmium mori (Acrospermaceae) based on morphological characterization and molecular analyses using nucleotide sequences of the internal transcribed spacer (ITS) and large subunit ribosomal DNA (LSU rDNA). Pathogenicity tests confirmed that G. mori is the pathogen responsible for MZLSD. Furthermore, we isolated antagonistic endophytic bacteria (AEB) from healthy mulberry leaves. Plate confrontation experiments showed that the lipopeptide crude extracts (LPCE) of three endophytic bacteria can inhibit the growth of G. mori, and the diameter of the antibacterial circle reaches more than 60 mm when their concentration of LPCE is 200 mg/ml. Light microscopy and scanning electron microscopy revealed that LPCE caused drastic changes in mycelial morphology. Fluorescence microscopy and transmission electron microscopy showed that the LPCE-induced apoptosis-like cell death in G. mori hyphae. Finally, based on morphological and molecular features, we identified the three isolates as Bacillus subtilis DS07, B. subtilis DS32, and B. velezensis Q6, respectively. To our knowledge, this is the first time to identify G. mori by combining characterization and molecular analyses, and we provide timely information about the use of biocontrol agents for suppression of G. mori.
Asunto(s)
Morus , China , Antibacterianos , ADN Ribosómico , FrutasRESUMEN
Transarterial interventional therapy combined with tyrosine kinase inhibitors (TKIs) and anti-Pd-1 antibodies (triplet regimen) has shown promising results in advanced HCC. However, the clinical utility of the triplet regimen in patients with HCC and major portal vein tumor thrombosis (PVTT) remains unclear. This study compared the efficacy and safety of the triplet regimen versus transarterial interventional therapy combined with TKIs (double regimen) for such patients. Thirty-nine patients treated with the triplet regimen were retrospectively compared with 37 patients treated with the double regimen. The objective response rate (ORR), the response rate of PVTT treatment, and safety were observed; progression-free survival (PFS) and overall survival (OS) were assessed using the KaplanâMeier method and log-rank test. Predictors of survival were identified using multivariate analysis. Median OS and median PFS were significantly improved in the Triplet Group compared with the Double Group (482 vs. 310 days; 208 vs. 85 days). The ORR and the response rate of PVTT were significantly higher in the Triplet Group than in the Double Group (59% vs. 35%; 62% vs. 35%). There was no significant difference in the incidence of grade 3/4 adverse events between the two groups (33% vs. 21%). The most frequent grade 3/4 adverse events were thrombocytopenia (10%) in the Triplet Group and hand-foot syndrome (14%) in the Double Group. Multivariable analysis showed that treatment method and PVTT treatment response were significant predictors of OS. The triplet regimen showed superiority over the doublet regimen in improving OS and PFS and had acceptable safety in patients with HCC and major PVTT.
Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Trombosis de la Vena , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Vena Porta , Quimioembolización Terapéutica/métodos , Resultado del Tratamiento , Trombosis de la Vena/etiología , Trombosis de la Vena/terapia , Trombosis de la Vena/patologíaRESUMEN
AIM: Hepatocellular carcinoma (HCC) has a poor prognosis. Moreover, large HCCs have been commonly observed. We aimed to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) combined with conventional TACE (cTACE) for the treatment of patients with unresectable large HCCs (main tumor ≥5 cm in diameter) compared with cTACE alone. METHODS: A retrospective matched cohort study was performed on consecutive patients with unresectable large HCCs who underwent TACE as the initial treatment at the Fujian Medical University Cancer Hospital from May 2017 and March 2019. Fifty-five patients who underwent DEB-TACE combined with cTACE were compared with a case-matched control group of 110 patients who received cTACE alone. We compared the tumor response at 1 and 3 months after TACE, time to progression (TTP), and adverse events between the groups. RESULTS: The objective response rate was higher for the DEB-TACE combined with cTACE group than for the cTACE alone group at 1 (39 of 55 [70.9%] vs. 57 of 110 [51.8%], p = 0.019) and 3 months (27 of 43 [62.8%] vs. 31 of 71 [43.7%], p = 0.048) post-treatment. The DEB-TACE combined with cTACE group also had a significantly longer median TTP than that of the cTACE group (7.2 vs. 5.3 months, p = 0.039). Compared with the cTACE group, occurrences of abdominal pain, nausea/vomiting, and constipation were significantly more frequent in the DEB-TACE combined with cTACE group (p < 0.05). CONCLUSION: Compared with cTACE alone, DEB-TACE combined with cTACE significantly increased the objective response rate at 1 and 3 months after the treatment of unresectable large HCCs, and had a longer TTP, without any significant increase in the number of severe complications.
RESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer worldwide, with a poor prognosis. Most patients are diagnosed at advanced stages and are only eligible for palliative therapy. Therefore, this study aimed to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with apatinib (TACE-apatinib) treatment and TACE-alone treatment for Barcelona Clinic Liver Cancer stage C HCC. METHODS: We retrospectively reviewed 80 consecutive patients with BCLC stage C HCC who received TACE-apatinib or TACE-alone as the initial treatment. We compared the clinical and laboratory outcomes, imaging findings at 1 and 3 months after TACE, tumor response, time to progression (TTP), overall survival (OS), and adverse events between both groups. RESULTS: The overall response rate was higher in the TACE-apatinib group than in the TACE-alone group at 1 and 3 months after treatment (66.7% vs 39.6%, respectively, P = 0.020; 45.8% vs 17.6%, respectively, P = 0.021). The median TTP and OS in the TACE-apatinib group were longer than those of the TACE-alone group (TTP: 6.3 months vs 3.5 months, respectively, P = 0.002; OS: 13.0 months vs 9.9 months, respectively, P = 0.041). Apatinib-associated side effects such as hypertension, hand-foot syndrome, oral ulcers, proteinuria, and diarrhea were more prevalent in the TACE-apatinib group than in TACE-alone group (P < 0.05). CONCLUSION: Compared to TACE-alone treatment, TACE-apatinib increased the TTP, OS, and tumor-response rate at 1 and 3 months after treatment of BCLC stage C HCC without any significant increase in severe adverse events.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Piridinas/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/patología , Terapia Combinada , Diarrea/inducido químicamente , Femenino , Humanos , Hipertensión/inducido químicamente , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Piridinas/efectos adversos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Background: Unresectable hepatocellular carcinoma (HCC) has a poor prognosis. According to the HCC management guidelines in China, the standard treatment of Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC with portal vein tumour thrombosis (PVTT) is chemoembolization. However, some patients with BCLC stage B or C HCC with PVTT respond poorly to chemoembolization. We aimed to compare tumour responses and survival benefits between patients with unresectable HCC with or without PVTT. Methods: We reviewed 119 consecutive patients with unresectable HCC with PVTT (n = 67) and without PVTT (n = 52) who underwent hepatic arterial infusion of oxaliplatin plus raltitrexed between January 2018 and April 2021. Overall survival, progression-free survival, tumour responses, and adverse events were compared between the groups. Results: There were no significant between-group differences in the objective response rates and median progression-free survival. The median overall survival was significantly longer in the group without PVTT than in that with PVTT (17.0 vs 10.4 months, respectively; P = 0.024). Conclusion: Hepatic arterial infusion of oxaliplatin plus raltitrexed may be efficacious in patients with unresectable HCC with or without PVTT.
RESUMEN
PURPOSE: To investigate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed in patients with intermediate stage and advanced stage hepatocellular carcinoma (HCC). METHODS: In this phase II, single-arm clinical trial, we enrolled patients aged 18-70 years with intermediate stage and advanced stage HCC, which included patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B who experienced transcatheter arterial chemoembolization failure/refractoriness, and those with BCLC stage C with portal vein invasion. We performed HAI with oxaliplatin and raltitrexed. Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon's two-stage design. The primary end-point was the objective response rate in accordance with the Response Evaluation Criteria in Solid Tumours. RESULTS: Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade IV adverse events or deaths were not reported, and the observed grade III adverse events were elevated aspartate aminotransferase levels (5 [12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopaenia (1 [2.6%]) and abdominal infection (1 [2.6%]). CONCLUSION: HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate and advanced stage HCC, and further evaluation is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Pronóstico , Estudios Prospectivos , Quinazolinas/administración & dosificación , Tasa de Supervivencia , Tiofenos/administración & dosificaciónRESUMEN
The aim of this study was to compare the efficacy and safety of 2 different embolic agents, namely gelatin sponge particle (GSP) and Lipiodol, for transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC).We retrospectively reviewed 87 consecutive patients with unresectable HCC who underwent Lipiodol TACE with lobaplatin and 87 consecutive patients with unresectable HCC who underwent GSP TACE with lobaplatin between January 2013 and June 2017 in our institution as the initial treatment. Both groups were compared considering the clinical and laboratory outcomes and imaging findings before and after TACE. Tumor response and adverse events were also evaluated.There was significant difference in the rate of complete and overall response between the groups (Pâ=â.029 and .001, respectively), specifically when the tumor size was >5âcm (Pâ=â.001). The disease control rate was significantly better in the GSP group than in the Lipiodol group (94.3% vs. 86.4%, Pâ=â.011). The response differences in higher stages were significant between the 2 groups (Pâ=â.035 and .007, respectively). The grades of adverse events were also significantly different between the groups (Pâ=â.000).GSP-as an embolic agent in TACE for HCC-could significantly increase the rate of tumor response 1 month after treatment, especially in large tumors, without any significant increase in severe adverse events, when compared to Lipiodol.
Asunto(s)
Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/diagnóstico por imagen , Quimioembolización Terapéutica/efectos adversos , Aceite Etiodizado/administración & dosificación , Aceite Etiodizado/efectos adversos , Aceite Etiodizado/uso terapéutico , Femenino , Esponja de Gelatina Absorbible/administración & dosificación , Esponja de Gelatina Absorbible/efectos adversos , Esponja de Gelatina Absorbible/uso terapéutico , Hemostáticos/administración & dosificación , Hemostáticos/efectos adversos , Hemostáticos/uso terapéutico , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomógrafos Computarizados por Rayos X , Resultado del Tratamiento , alfa-Fetoproteínas/análisisRESUMEN
This prospective study aimed to evaluate the efficacy and safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma (HCC).The patients with intermediate/advanced HCC, who met predetermined inclusion and exclusion criteria, underwent oral treatment of apatinib 500âmg daily. The drug-related adverse effects were monitored by regular follow-up and workup including laboratory tests and imaging examinations. Tumor response was assessed by response evaluation criteria in solid tumor criteria. The time to tumor progression (TTP) and overall survival rate (OS) were calculated using the Kaplan-Meier method.A total of 31 patients were enrolled in the study from October 28, 2015 to December 28, 2016. The number of patients with intermediate and advanced HCC was 4 (12.90%) and 27 (87.10%), respectively. The mean tumor size was 9.47 ± 5.48âcm (range: 1.2-19âcm). Vascular invasion was seen in 14 patients (45.16%). A total of 21 (67.74%) patients exhibited extrahepatic metastases. On the basis of first follow-up computed tomography and magnetic resonance imaging at 6 weeks after treatment, 10 (32.26%), 15 (48.39%), and 6 (19.35%) of 31 patients achieved a partial response, stable disease, and progression of disease, respectively. Response rate and disease control rate were 32.26% and 80.65%, respectively. The median TTP was 4.8 months (95% confidence interval: 3.75-5.86 months). Furthermore, 6- and 12-month OS rates were 73.8% and 55.4%, respectively. Grade 3 thrombocytopenia (6.45%) and hypertension (48.39%) were the most common hematologic and nonhematologic toxicities. Grade 3 elevation of either serum total bilirubin or aminotransferase (6.45%) was observed as the top incidence among important indexes of liver function.Our preliminary findings suggest apatinib is a safe and effective therapy in intermediate/advanced HCC patients with high tumor response and survival rates.