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American Journal of Clinical Oncology Feb 2020
Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cyclophosphamide; Doxorubicin; Drug Substitution; Humans; Leukemia; Liposomes; Lymphoma; Prednisone; Vinblastine; Vincristine; Vindesine
PubMed: 31977507
DOI: 10.1097/COC.0000000000000648 -
Journal of Medicinal Chemistry Apr 2018The Ebola virus (EBOV) causes severe human infection that lacks effective treatment. A recent screen identified a series of compounds that block EBOV-like particle entry...
The Ebola virus (EBOV) causes severe human infection that lacks effective treatment. A recent screen identified a series of compounds that block EBOV-like particle entry into human cells. Using data from this screen, quantitative structure-activity relationship models were built and employed for virtual screening of a ∼17 million compound library. Experimental testing of 102 hits yielded 14 compounds with IC values under 10 μM, including several sub-micromolar inhibitors, and more than 10-fold selectivity against host cytotoxicity. These confirmed hits include FDA-approved drugs and clinical candidates with non-antiviral indications, as well as compounds with novel scaffolds and no previously known bioactivity. Five selected hits inhibited BSL-4 live-EBOV infection in a dose-dependent manner, including vindesine (0.34 μM). Additional studies of these novel anti-EBOV compounds revealed their mechanisms of action, including the inhibition of NPC1 protein, cathepsin B/L, and lysosomal function. Compounds identified in this study are among the most potent and well-characterized anti-EBOV inhibitors reported to date.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Drug Discovery; Drug Evaluation, Preclinical; Ebolavirus; HeLa Cells; Humans; Molecular Structure; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Virus Internalization
PubMed: 29624387
DOI: 10.1021/acs.jmedchem.8b00035 -
Blood Advances Aug 2023Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and... (Clinical Trial)
Clinical Trial
Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients with progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in frontline therapy has not been systematically investigated in this context. To this end, we analyzed a large cohort of 2203 younger patients with DLBCL treated on 10 German (German Lymphoma Alliance [GLA]/The German High Grade Non-Hodgkin's Lymphoma Study Group [DSHNHL]) and French (The Lymphoma Study Association [LYSA]) prospective phase 2 and 3 trials after first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone) followed by consolidation including multiple drugs crossing the blood-brain barrier (BBB). Patients with DLBCL with an age-adjusted International Prognostic Index (aaIPI) of 0 to 1 showed very low cumulative incidence rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year cumulative incidences 0%-1%). Younger high-risk patients with aaIPI of 2 to 3 had 3-year cumulative incidence rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (hazard ratio 2.4; 95% confidence interval: 0.8-7.4; P = .118). Thus, for younger high-risk patients, frontline regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.
Topics: Humans; Rituximab; Prednisone; Prospective Studies; Antibodies, Monoclonal, Murine-Derived; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Vincristine; Chronic Disease; Central Nervous System; Cyclophosphamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36716220
DOI: 10.1182/bloodadvances.2022008888 -
Turkish Journal of Haematology :... Aug 2023
Acute and Persistent Remission of Aggressive Natural Killer Cell Leukemia in an Older Patient Induced by Chidamide Combined with Cyclophosphamide, Vindesine, Prednisone, and Etoposide Therapy.
Topics: Humans; Prednisone; Etoposide; Vindesine; Leukemia, Large Granular Lymphocytic; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Vincristine
PubMed: 37464744
DOI: 10.4274/tjh.galenos.2023.2023.0227 -
Current Cancer Drug Targets 2018Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy...
BACKGROUND
Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy. The role of autophagy in nephroblastoma is largely uninvestigated.
OBJECTIVE
This study is to investigate the change of autophagy level in nephroblastoma, and whether autophagy could be a therapeutic target in anaplastic nephroblastoma.
METHOD
In clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Use of autophagy inhibitors alone and in combination with conventional chemotherapeutics, was studied both in vivo and in vitro.
RESULTS
In nephroblastoma, there was decrease in the Beclin 1 level and the number of autophagosomes, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, an inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved.
CONCLUSION
Our results suggest that autophagy deregulation is involved in nephroblastoma, and targeting autophagy can serve as a potential adjuvant strategy for the highly malignant cases.
Topics: Animals; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Cell Proliferation; Child; Child, Preschool; Chloroquine; Cisplatin; Drug Therapy, Combination; Female; Humans; Infant; Kidney Neoplasms; Male; Mice; Mice, Nude; Tumor Cells, Cultured; Vincristine; Wilms Tumor; Xenograft Model Antitumor Assays
PubMed: 28359249
DOI: 10.2174/1568009617666170330105433 -
World Journal of Clinical Cases Jul 2022Germ cell tumors (GCTs) account for 2% of human malignancies but are the most common malignant tumors among males aged 15-35. Since 1983, an association between...
BACKGROUND
Germ cell tumors (GCTs) account for 2% of human malignancies but are the most common malignant tumors among males aged 15-35. Since 1983, an association between mediastinal GCT (MGCT) and hematologic malignancies has been recognized.
CASE SUMMARY
We report a case in which malignant histiocytosis was associated with mediastinal GCTs. The clinical data of a male patient with MGCT admitted to Beijing Children's Hospital were collected retrospectively. The patient was first diagnosed according to imaging and pathological features as having MGCT, and was treated with surgery and chemotherapy. One year after stopping chemotherapy, imaging showed metastases in the right supraclavicular, mediastinum, hilar region and retroperitoneal lymph node, right pleura, right lung, and right para-cardiac margin. Pathological diagnosis of the liver nodular and hilar lymph nodes included systemic juvenile xanthogranuloma and Rosai-Dorfman lesions with malignant transformation ( morphological characteristics and immunophenotype of histiocytic sarcoma). Following diagnosis, the patient accepted chemotherapy with vindesine, cytarabine and dexamethasone. Positron emission tomography-computed tomography showed partial remission. The patient was followed-up for 10 mo after the diagnosis of malignant histiocytosis, and no sign of progression or relapse was observed.
CONCLUSION
Physicians should recognize the possibility of hematologic malignancies being associated with MGCT. Suitable sites should be selected for pathological examination.
PubMed: 36051154
DOI: 10.12998/wjcc.v10.i20.7116 -
Annals of Hematology May 2024In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy...
Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.
In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .
PubMed: 38805037
DOI: 10.1007/s00277-024-05708-w -
Translational Cancer Research Nov 2021To explore the stability of a mixture of three drugs including vindesine, etoposide, and epirubicin, assigned to infusion in an EPOCH chemotherapy regimen and provide a...
BACKGROUND
To explore the stability of a mixture of three drugs including vindesine, etoposide, and epirubicin, assigned to infusion in an EPOCH chemotherapy regimen and provide a basis for clinical use.
METHODS
After mixing the three chemotherapy drugs with 500 mL of 0.9% sodium chloride or 5% glucose injection, respectively, they were divided into four groups of test solution. According to the Pharmacopoeia of the people's Republic of China, 2020 Edition, injection fluid should be tested for content, osmolarity, insoluble microparticles and pH, as well as for sterility, bacterial endotoxin and pyrogen, etc. since this experiment focuses on the compatibility of the mixture of the three drugs, sterility and the detection of bacterial endotoxin and pyrogen, etc. were not performed. The test solutions were placed at room temperature, the content was determined using high-performance liquid chromatography, and the pH, osmolarity, and insoluble microparticle changes of the mixed solution were determined. Both imported and domestic epirubicin was used.
RESULTS
The four groups of test solution have no significant changes in pH, osmolarity, and insoluble microparticles were observed within 48 h, with the contents changing by less than 5%. Compared with the other three groups, the imported epirubicin saline group achieved better results with significant differences in insoluble microparticle detection items of ≥10 and ≥25 µM (P<0.05).
CONCLUSIONS
The stability of the three drugs in 500 mL 0.9% sodium chloride and 5% glucose injection at room temperature was good. Imported epirubicin had some advantages in the number of insoluble microparticles and its pH was more suitable when normal saline was used as a vehicle. To reduce irritation to blood vessels by infusion, it is recommended to choose imported epirubicin with 0.9% sodium chloride mixed deployment.
PubMed: 35116335
DOI: 10.21037/tcr-21-1819 -
Medicine Dec 2022Embryonal rhabdomyosarcoma (ERMS) is a major subtype of rhabdomyosarcoma, mainly affect children. There is seldom report for perineal ERMS in adults, since its rare...
RATIONALE
Embryonal rhabdomyosarcoma (ERMS) is a major subtype of rhabdomyosarcoma, mainly affect children. There is seldom report for perineal ERMS in adults, since its rare location and the age.
PATIENT CONCERNS
A 20-year old male adult was admitted due to the perineal mass.
DIAGNOSES
Diagnosis by histopathological examination of the biopsy sample was ERMS. Magnetic resonance imaging showed the tumor was found in the perineal region, with metastasis to pelvic cavity, right testis, lymph nodes and bone.
INTERVENTIONS
The patient received Isophosphamide and Epirubicin for 4 cycles, followed by Irinotecan and Vindesine Sulfate for 2 cycles, then cisplatin, Dacarbazine and Apatinib for 3 cycles.
OUTCOME
The patient showed no response to chemotherapy.
LESSONS
Perineal ERMS in adults is very rare. There is still no standard therapy for adult ERMS. Personalized therapy might be promising treatment for each individual.
Topics: Male; Child; Humans; Adult; Young Adult; Rhabdomyosarcoma, Embryonal; Rhabdomyosarcoma; Ifosfamide; Irinotecan; Perineum
PubMed: 36596039
DOI: 10.1097/MD.0000000000032529 -
Orphanet Journal of Rare Diseases Apr 2022Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a...
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients.
RESULTS
LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034).
CONCLUSIONS
LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.
Topics: Child; Child, Preschool; Histiocytosis, Langerhans-Cell; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Mutation; Retrospective Studies; Treatment Outcome
PubMed: 35379272
DOI: 10.1186/s13023-022-02276-y