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International Journal of Gynecological... Aug 2023This study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after...
OBJECTIVE
This study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy.
METHODS
This study recruited premenopausal women aged 15 to 45 with a newly diagnosed low-risk gestational trophoblastic neoplasia needing actinomycin D. AMH was measured at baseline, during chemotherapy, and 1, 3, and 6 months after the last chemotherapy. The reproductive outcomes were also documented.
RESULTS
Of the 42 women recruited, we analyzed 37 (median: 29 years; range 19-45) with a complete dataset. The follow-up was 36 months (range 34-39). Actinomycin D significantly decreased AMH concentrations during treatment, from 2.38±0.92 ng/mL to 1.02±0.96 ng/mL (p<0.05). Partial recovery was seen at 1 month and 3 months after treatment. Full recovery was reached 6 months after treatment among patients younger than 35 years. The only factor correlated with the extent of AMH reduction at 3 months was age (r=0.447, p<0.05). Notably, the number of courses of actinomycin D was not associated with the extent of AMH reduction. A total of 18 (90%) of 20 patients who had a desire to conceive had live births with no adverse pregnancy outcomes.
CONCLUSION
Actinomycin D has a transient and minor effect on ovarian function. Age is the only factor that impacts the patient's rate of recovery. Patients will achieve favorable reproductive outcomes after actinomycin D treatment.
Topics: Pregnancy; Humans; Female; Dactinomycin; Ovarian Reserve; Gestational Trophoblastic Disease; Pregnancy Outcome; Anti-Mullerian Hormone
PubMed: 37290904
DOI: 10.1136/ijgc-2023-004292 -
BMC Microbiology Jun 2023Klebsiella pneumoniae is one of the main pathogens of clinical isolation and nosocomial infections, as K. pneumoniae show broad-spectrum resistance to β-lactam and...
BACKGROUND
Klebsiella pneumoniae is one of the main pathogens of clinical isolation and nosocomial infections, as K. pneumoniae show broad-spectrum resistance to β-lactam and carbapenem antibiotics. It is emerging clinical need for a safe and effective drug to anti-K. pneumoniae. At present, Achromobacter mainly focused on its degradation of petroleum hydrocarbons, polycyclic aromatic hydrocarbons, assisting insects to decompose, degrade heavy metals and utilize organic matter, but there were few reports on the antibacterial activity of the secondary metabolites of Achromobacter.
RESULTS
In this study, a strain WA5-4-31 from the intestinal tract of Periplaneta americana exhibited strong activity against K. Pneumoniae through preliminary screening. The strain was determined to be Achromobacter sp. through the morphological characteristics, genotyping and phylogenetic tree analysis, which is homologous to Achromobacter ruhlandii by 99%, its accession numbe in GenBank at National Center for Biotechnology Information (NCBI) is MN007235, and its deposit number was GDMCC NO.1.2520. Six compounds (Actinomycin D, Actinomycin X2, Collismycin A, Citrinin, Neoechinulin A and Cytochalasin E) were isolated and determined by activity tracking, chemical separation, nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. Among them, Actinomycin D, Actinomycin X2, Collismycin A, Citrinin and Cytochalasin E showed a good effect on anti-K. pneumoniae, with MIC values of 16-64 µg/mL.
CONCLUSIONS
The study reported Achromobacter, which was from the intestinal tract of Periplaneta americana with the activity against K. Pneumoniae, can produce antibacterial compounds for the first time. It lays the foundation for development of secondary metabolites of insect intestinal microorganisms.
Topics: Animals; Periplaneta; Dactinomycin; Citrinin; Klebsiella pneumoniae; Phylogeny; Secondary Metabolism; Anti-Bacterial Agents; Achromobacter; Intestines; Klebsiella Infections; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 37277707
DOI: 10.1186/s12866-023-02909-7 -
International Journal of Molecular... Mar 2023Actinomycin is a family of chromogenic lactone peptides that differ in their peptide portions of the molecule. An antimicrobial peptide, actinomycin X2 (Ac.X2), was...
Actinomycin is a family of chromogenic lactone peptides that differ in their peptide portions of the molecule. An antimicrobial peptide, actinomycin X2 (Ac.X2), was produced through the fermentation of a strain. Immobilization of Ac.X2 onto a prepared silk fibroin (SF) film was done through a carbodiimide reaction. The physical properties of immobilized Ac.X2 (antimicrobial films, AMFs) were analyzed by ATR-FTIR, SEM, AFM, and WCA. The findings from an in vitro study showed that AMFs had a more broad-spectrum antibacterial activity against both and compared with free Ac.X2, which showed no apparent strong effect against These AMFs showed a suitable degradation rate, good hemocompatibility, and reduced cytotoxicity in the biocompatibility assay. The results of in vivo bacterially infected wound healing experiments indicated that wound inflammation was prevented by AMFs, which promoted wound repair and improved the wound microenvironment. This study revealed that Ac.X2 transformation is a potential candidate for skin wound healing.
Topics: Dactinomycin; Fibroins; Immobilized Proteins; Wound Healing; Antimicrobial Peptides; Streptomyces; Escherichia coli; Staphylococcus aureus; Spectroscopy, Fourier Transform Infrared; Microscopy, Atomic Force; Fermentation; Materials Testing; Biocompatible Materials; Animals; Rats; Male; Rats, Sprague-Dawley
PubMed: 37047243
DOI: 10.3390/ijms24076269 -
PeerJ 2023Multidrug-resistant tuberculosis (MDR-TB) is one of the world's most devastating contagious diseases and is caused by the MDR- (MDR-Mtb) bacteria. It is therefore...
BACKGROUND
Multidrug-resistant tuberculosis (MDR-TB) is one of the world's most devastating contagious diseases and is caused by the MDR- (MDR-Mtb) bacteria. It is therefore essential to identify novel anti-TB drug candidates and target proteins to treat MDR-TB. Here, and studies were used to investigate the anti-TB potential of two newly sourced actinomycins, actinomycin-X (act-X) and actinomycin-D (act-D), from the strain UKAQ_23 (isolated from the Jubail industrial city of Saudi Arabia).
METHODS
The anti-TB activity of the isolated actinomycins was assessed using the Mtb H37Ra, (BCG), and Mtb H37Rv bacterial strains, using the Microplate Alamar Blue Assay (MABA) method. molecular docking studies were conducted using sixteen anti-TB drug target proteins using the AutoDock Vina 1.1.2 tool. The molecular dynamics (MD) simulations for both actinomycins were then performed with the most suitable target proteins, using the GROningen MAchine For Chemical Simulations (GROMACS) simulation software (GROMACS 2020.4), with the Chemistry at HARvard Macromolecular Mechanics 36m (CHARMM36m) forcefield for proteins and the CHARMM General Force Field (CGenFF) for ligands.
RESULTS
results for the Mtb H37Ra, BCG, and Mtb H37Rv strains showed that act-X had minimum inhibitory concentration (MIC) values of 1.56 ± 0.0, 1.56 ± 0.0, and 2.64 ± 0.07 µg/mL and act-D had MIC values of 1.56 ± 0.0, 1.56 ± 0.0, and 1.80 ± 0.24 µg/mL respectively. The molecular docking results showed that protein kinase PknB was the preferred target for both actinomycins, while KasA and pantothenate synthetase were the least preferred targets for act-Xand act-D respectively. The molecular dynamics (MD) results demonstrated that act-X and act-D remained stable inside the binding region of PknB throughout the simulation period. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding energy calculations showed that act-X was more potent than act-D.
CONCLUSION
In conclusion, our results suggest that both actinomycins X and D are highly potent anti-TB drug candidates. We show that act-Xis better able to antagonistically interact with the protein kinase PknB target than act-D, and thus has more potential as a new anti-TB drug candidate.
Topics: Humans; Antitubercular Agents; BCG Vaccine; Dactinomycin; Molecular Docking Simulation; Protein Kinases; Tuberculosis, Multidrug-Resistant
PubMed: 36935926
DOI: 10.7717/peerj.14502 -
Nucleic Acids Research May 2023Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here,...
Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.
Topics: Humans; Animals; Mice; Dactinomycin; Echinomycin; Thymine; Base Sequence; Binding Sites; Nucleic Acid Conformation; DNA; Colorectal Neoplasms
PubMed: 36919604
DOI: 10.1093/nar/gkad156 -
The Journal of International Medical... Mar 2023To date, only 34 cases of primary pulmonary rhabdomyosarcoma (PPRMS) in the middle-aged and elderly population have been published. However, analyses of the... (Review)
Review
To date, only 34 cases of primary pulmonary rhabdomyosarcoma (PPRMS) in the middle-aged and elderly population have been published. However, analyses of the clinicopathological characteristics and prognosis of PPRMS in this population have not been performed. A 75-year-old man visited our hospital because of abdominal pain and discomfort. His serum lactate dehydrogenase, neuron specific enolase, and progastrin-releasing peptide levels were elevated. Positron emission tomography-computed tomography revealed a lobulated mass of 7.6 × 5.5 cm in the lower lobe of the left lung with abnormally high fluoro-2-deoxy-d-glucose metabolism. Histologically, the tumor cells were small with little cytoplasm, deep nuclear staining, and heavily stained nuclear chromatin. Immunohistochemically, the tumor cells were positive for desmin, MyoD1 myogenin, synaptophysin, and CD56. Cytogenetic analysis for FOXO1A translocation was negative. Finally, the patient was diagnosed with PPRMS. He received combined chemotherapy with vincristine 1 mg, actinomycin 0.4 mg, cyclophosphamide 0.8 mg; however, only one course of chemotherapy was completed, and the patient died 2 months after diagnosis. PPRMS in middle-aged and elderly people is a highly malignant soft tissue tumor with significant clinicopathological characteristics.
Topics: Aged; Humans; Male; Middle Aged; Cyclophosphamide; Lung Neoplasms; Prognosis; Rhabdomyosarcoma; Vincristine; Dactinomycin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36883437
DOI: 10.1177/03000605231159782 -
BMC Women's Health Feb 2023Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare... (Review)
Review
BACKGROUND
Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare clinical case of GTN combined with primary lung cancer and mesenchymal tumor of the sigmoid colon, followed with literature review.
CASE PRESENTATION
The patient was hospitalized due to diagnosis of GTN with primary lung cancer. Firstly, two cycles of chemotherapy including 5-fluorouracil (5-FU) and actinomycin-D(Act-D) was given. Laparoscopic total hysterectomy and right salpingo-oophorectomy was performed during the third chemotherapy. During the operation, a 3*2 cm nodule was removed which was protruded from the serous surface of the sigmoid colon, and the nodule was confirmed mesenchymal tumor pathologically, in accord with gastrointestinal stromal tumor. During the treatment of GTN, Icotinib tablets were taken orally to control the progression of lung cancer. After 2 cycles of consolidation chemotherapy of GTN, she received thoracoscopic lower lobe of right lung lobectomy and the mediastinum lymph nodes removal. She undertook gastroscopy and colonoscopy and the tubular adenoma of the descending colon was removed. At present, the regular follow-up is taken and she remains free of tumors.
CONCLUSIONS
GTN combined with primary malignant tumors in other organs are extremely rare in clinical practice. When imaging examination reveals a mass in other organs, clinicians should be aware of the possibility of a second primary tumor. It will increase the difficulty of GTN staging and treatment. We emphasis the importance of the collaboration of multidisciplinary teams. Clinicians should choose a reasonable treatment plan according to the priorities of different tumors.
Topics: Pregnancy; Female; Humans; Colon, Sigmoid; Retrospective Studies; Gestational Trophoblastic Disease; Dactinomycin; Lung Neoplasms
PubMed: 36803691
DOI: 10.1186/s12905-023-02204-7 -
International Journal of Molecular... Jan 2023The opportunistic fungus causes a set of diseases ranging from allergy to lethal invasive mycosis. Within the human airways, is embedded in a biofilm that forms not...
The opportunistic fungus causes a set of diseases ranging from allergy to lethal invasive mycosis. Within the human airways, is embedded in a biofilm that forms not only a barrier against the host immune defense system, but also creates a physical barrier protecting the fungi from chemicals such as antifungal drugs. Novel therapeutic strategies aim at combining drugs that inhibit biofilm synthesis or disrupt existing biofilm with classical antimicrobials. One of the major constituents of biofilm is the polysaccharide galactosaminogalactan (GAG) composed of α1,4-linked N-acetylgalactosamine, galactosamine, and galactose residues. GAG is synthesized on the cytosolic face of the plasma membrane and is extruded in the extracellular space, where it is partially deacetylated. The deacetylase Agd3 that mediates this last step is essential for the biofilm formation and full virulence of the fungus. In this work, a previously described enzyme-linked lectin assay, based on the adhesion of deacetylated GAG to negatively charged plates and quantification with biotinylated soybean agglutinin was adapted to screen microbial natural compounds, as well as compounds identified in in silico screening of drug libraries. Actinomycin X2, actinomycin D, rifaximin, and imatinib were shown to inhibit Agd3 activity in vitro. At a concentration of 100 µM, actinomycin D and imatinib showed a clear reduction in the biofilm biomass without affecting the fungal growth. Finally, imatinib reduced the virulence of in a infection model in an Agd3-dependent manner.
Topics: Humans; Dactinomycin; Imatinib Mesylate; Polysaccharides; Aspergillus fumigatus; Biofilms
PubMed: 36768176
DOI: 10.3390/ijms24031851 -
Caspian Journal of Internal Medicine 2023Methotrexate (MTX) and actinomycin D (ActD) have been used as first-line chemotherapy agents in the treatment of low-risk gestational trophoblastic neoplasia (GTN)....
BACKGROUND
Methotrexate (MTX) and actinomycin D (ActD) have been used as first-line chemotherapy agents in the treatment of low-risk gestational trophoblastic neoplasia (GTN). Although low-risk GTN is considered a curable disease, its reported primary remission rates of 49 to 93% reflect the difficulties of treatment and different factors influencing it. Hence, this study aimed to determine the remission rates and related factors of single-agent chemotherapy resistance in low-risk GTN patients.
METHODS
This retrospective study included patients with diagnosed low-risk GTN who received either MTX once a week (IM, 30mg/m2) or ActD once every two weeks (pulsed IV, 1.25mg/m2). Then, the patients were followed-up until complete remission or single-agent treatment failure to assess resistance rate and related factors.
RESULTS
Eighty-four patients were included in the study (18 patients were receiving MTX and 66 patients were receiving ActD). 85.7% of all participants achieved complete remission after first-line chemotherapy (72.2% in MTX vs 89.4% in ActD). There was a significant association for higher tumor size (P=0.046), the occurrence of metastasis (P=0.019), and pretreatment β-HCG levels (P=0.005) with resistance to treatment.
CONCLUSION
This study demonstrated higher tumor size, the occurrence of metastasis, and pretreatment β-HCG levels have been associated with increased resistance to first-line chemotherapy agents.
PubMed: 36741497
DOI: 10.22088/cjim.14.1.47 -
Journal of the Formosan Medical... Aug 2023The purpose of this study was to clarify the effect of ZC3H13 on the growth of papillary thyroid carcinoma (PTC).
PURPOSE
The purpose of this study was to clarify the effect of ZC3H13 on the growth of papillary thyroid carcinoma (PTC).
METHODS
Firstly, we used qRT-PCR and Western blot to compare the difference in the expression of ZC3H13 between normal thyroid epithelial cells and PTC cell lines. Then, ZC3H13 overexpression/knockout thyroid cancer cells were constructed by lentivirus transfection, and the effects of overexpression of ZC3H13 on the proliferation, migration and invasion of PTC cells were detected by CCK8 and transwell experiments. Lastly, MeRIP-qPCR, RIP and o Actinomycin D were used to verify that ZC3H13 regulated the expression of downstream target gene IQGAP1 through m6A modification.
RESULTS
ZC3H13 expression was decreased in PTC cell lines BCPAP, KTC-1, k1, HTH83, and TPC-1. Proliferation, invasion, and migration of PTC cells were inhibited by overexpressed ZC3H13 but increased by knockdown of ZC3H13. IQGAP1 expression was suppressed by ZC3H13 overexpression but enhanced by ZC3H13 knockdown. In ZC3H13-overexpressed PTC cells, the m6A level of IQGAP1 mRNA was increased, and the IQGAP1 mRNA expression was decreased with the increasing time of Actinomycin D treatment. YTHDF2 enriched more IQGAP1 mRNA than IgG and knockdown of YTHDF2 reversed the effect of ZC3H13 overexpression on IQGAP1 mRNA stability. The xenograft tumor experiment in nude mice confirmed that the overexpression of ZC3H13 inhibited tumor growth, while overexpression of IQGAP1 could reverse the inhibitory effect of ZC3H13 overexpression on tumor growth.
CONCLUSION
ZC3H13 mediates IQGAP1 mRNA degradation by promoting m6A modification of IQGAP1 mRNA, this provides a prospective therapeutic target for PTC.
Topics: Mice; Animals; Humans; Thyroid Cancer, Papillary; MicroRNAs; Mice, Nude; Dactinomycin; Cell Line, Tumor; Cell Proliferation; Neoplasm Invasiveness; Cell Movement; Thyroid Neoplasms; RNA, Messenger; Gene Expression Regulation, Neoplastic; Nuclear Proteins; RNA-Binding Proteins
PubMed: 36739231
DOI: 10.1016/j.jfma.2022.12.019