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Cancer Cell International Jun 2022Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and... (Review)
Review
Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies. Plant-based drugs have evolved as promising preventive chemo options both in developing and developed nations. The secondary plant metabolites such as alkaloids have proven efficacy and acceptability for cancer treatment. Apropos, this review deals with a spectrum of promising alkaloids such as colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine within different domains of comprehensive information on these molecules such as their medical applications (contemporary/traditional), mechanism of antitumor action, and potential scale-up biotechnological studies on an in-vitro scale. The comprehensive information provided in the review will be a valuable resource to develop an effective, affordable, and cost effective cancer management program using these alkaloids.
PubMed: 35655306
DOI: 10.1186/s12935-022-02624-9 -
Frontiers in Genetics 2022Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart...
Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare. We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved. Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA. We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement.
PubMed: 35495149
DOI: 10.3389/fgene.2022.856552 -
Journal of Healthcare Engineering 2022To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL).
OBJECTIVE
To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL).
METHODS
A total of 107 hospitalized children with AL were enrolled in this study and assigned to one group in each of the following categories: infected group ( = 52) and noninfected group ( = 55); treatment remission group ( = 56) and nonremission group ( = 51); high-risk (HR) group ( = 44), intermediate risk (IR) group ( = 53), and slight risk (SR) group ( = 8); cyclophosphamide + cytosine arabinoside+6-mercaptopurine + pegaspargase group (CAML, = 15); methotrexate group (MTX, = 9); and vindesine + daunomycin + L-asparaginasum + prednisone (VALP, = 38). Hematological and serological parameters, hepatic and renal function, and changes in vitamins A, B1, B2, B6, B9, B12, C, D, and E serum content in children with AL were analyzed to investigate their relationship with AL disease-related factors.
RESULTS
The vitamin D level was significantly higher in the noninfected group than in the infected group ( < 0.05). Compared with the nonremission group, the level of vitamin B1 in the treatment remission group was significantly higher, while the levels of vitamin B6 and B12 were notably lower ( < 0.05). The levels of vitamins B6 and B12 were notably different among the treatment groups. Multivariate analysis showed that hemoglobin (Hb) and C-reactive protein (CRP) were predisposing factors of AL in children. The disease type (acute lymphoblastic leukemia/acute myelogenous leukemia) was the factor affecting remission in AL children. Abnormal kidney function and the occurrence of icterus were the influencing factors for the risk degree in AL children. Platelet (PLT) count, activated partial thromboplastin time (APTT), neutrophils (N), and immunophenotype were shown to affect the choice of therapeutic regimens.
CONCLUSION
There are notable vitamins imbalances in children with AL. The imbalances influence disease-related factors and therefore provide some references for the prognosis and treatment of AL.
Topics: Causality; Child; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Vitamins
PubMed: 35463661
DOI: 10.1155/2022/5330563 -
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 -
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 -
Frontiers in Oncology 2021Angioimmunoblastic T-cell lymphoma (AITL) is a kind of peripheral T-cell lymphomas (PTCLs) with a highly invasive feature. At present, patients are often treated with...
Angioimmunoblastic T-cell lymphoma (AITL) is a kind of peripheral T-cell lymphomas (PTCLs) with a highly invasive feature. At present, patients are often treated with CHOP or CHOP-like regimens which is of poor prognosis whilst having high recurrence rate. Once the patient fails to achieve remission or relapse after the first-line treatment, many salvage chemotherapy regimens are always ineffective, and the long-term survival will be difficult to achieve for them. In this circumstance, more effective therapy methods are needed. In this study, two patients with relapsed/refractory AITL were treated with the CAOLD regimen [cyclophosphamide 400 mg/m qd d1, cytarabine 30 mg/m qd d1-d4, vindesine 2 mg/m qd d1, pegaspargase (PEG-ASP) 2,500 IU/m qd d2, dexamethasone 7.5 mg/m qd d1-d5], and long-term remission was achieved after chemotherapy. One is still alive after achieving complete remission (CR) after two cycles of chemotherapy, who has been followed up for 82 months. Besides, another patient achieved partial remission (PR) after the first course of chemotherapy. Then, CR was obtained after four courses of consolidation chemotherapy. The patient has been followed up for 63 months and is still alive. Both of them achieved long-time survival. These two successful cases demonstrated that the CAOLD regimen can be a better choice for relapsed/refractory AITL and offers hope of breakthrough in this medical field.
PubMed: 35047389
DOI: 10.3389/fonc.2021.758445 -
Frontiers in Medicine 2021The standardized treatment plan for patients with plasmablastic lymphoma (PBL) remains controversial. Taking morphological characteristics and immunophenotypes into...
Case Report: Bortezomib Plus CDOP Followed by Sequential Autologous Hematopoietic Stem Cell Transplantation and Lenalidomide-Based Maintenance Therapy in Plasmablastic Lymphoma.
The standardized treatment plan for patients with plasmablastic lymphoma (PBL) remains controversial. Taking morphological characteristics and immunophenotypes into consideration may provide superior options for the treatment of PBL. In this case, we report that a myeloma-type regimen containing bortezomib plus cyclophosphamide, epirubicin, vindesine and prednisolone (CDOP) followed by sequential autologous hematopoietic stem cell transplantation (ASCT) and lenalidomide-based maintenance therapy to treat PBL may represent a promising regimen to improve the prognosis.
PubMed: 34926499
DOI: 10.3389/fmed.2021.749863 -
Blood Advances Oct 2021Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains...
Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Large B-Cell, Diffuse; Retrospective Studies; Transplantation, Autologous; Treatment Outcome
PubMed: 34461634
DOI: 10.1182/bloodadvances.2021004778 -
British Journal of Haematology Nov 2021Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different... (Comparative Study)
Comparative Study
Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion-deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.
Topics: Adult; Aged; Aged, 80 and over; Allografts; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; CD28 Antigens; Carboplatin; Cyclophosphamide; DNA Copy Number Variations; Doxorubicin; Etoposide; Female; Genes, p53; Hematopoietic Stem Cell Transplantation; Humans; INDEL Mutation; Kaplan-Meier Estimate; Lenalidomide; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Mutation; Nitrosourea Compounds; Polymorphism, Single Nucleotide; Prednisolone; Prednisone; Prognosis; Receptors, CCR4; Vincristine; Vindesine
PubMed: 34405395
DOI: 10.1111/bjh.17749 -
Human Genomics Aug 2021Skin cutaneous melanoma (SKCM) is one of the most highly prevalent and complicated malignancies. Glycolysis and cholesterogenesis pathways both play important roles in...
BACKGROUND
Skin cutaneous melanoma (SKCM) is one of the most highly prevalent and complicated malignancies. Glycolysis and cholesterogenesis pathways both play important roles in cancer metabolic adaptations. The main aims of this study are to subtype SKCM based on glycolytic and cholesterogenic genes and to build a clinical outcome predictive algorithm based on the subtypes.
METHODS
A dataset with 471 SKCM specimens was downloaded from The Cancer Genome Atlas (TCGA) database. We extracted and clustered genes from the Molecular Signatures Database v7.2 and acquired co-expressed glycolytic and cholesterogenic genes. We then subtyped the SKCM samples and validated the efficacy of subtypes with respect to simple nucleotide variations (SNVs), copy number variation (CNV), patients' survival statuses, tumor microenvironment, and proliferation scores. We also constructed a risk score model based on metabolic subclassification and verified the model using validating datasets. Finally, we explored potential drugs for high-risk SKCM patients.
RESULTS
SKCM patients were divided into four subtype groups: glycolytic, cholesterogenic, mixed, and quiescent subgroups. The glycolytic subtype had the worst prognosis and MGAM SNV extent. Compared with the cholesterogenic subgroup, the glycolytic subgroup had higher rates of DDR2 and TPR CNV and higher proliferation scores and MK167 expression levels, but a lower tumor purity proportion. We constructed a forty-four-gene predictive signature and identified MST-321, SB-743921, Neuronal Differentiation Inducer III, romidepsin, vindesine, and YM-155 as high-sensitive drugs for high-risk SKCM patients.
CONCLUSIONS
Subtyping SKCM patients via glycolytic and cholesterogenic genes was effective, and patients in the glycolytic-gene enriched group were found to have the worst outcome. A robust prognostic algorithm was developed to enhance clinical decisions in relation to drug administration.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Cholesterol; DNA Copy Number Variations; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Glycolysis; Humans; Male; Melanoma; Middle Aged; Prognosis; Signal Transduction; Skin Neoplasms; Tumor Microenvironment; Young Adult; Melanoma, Cutaneous Malignant
PubMed: 34384498
DOI: 10.1186/s40246-021-00350-3