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Microbiology Spectrum Dec 2023As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential...
As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found and were highly virulent against the insects. After infective juvenile injection, quickly turned black and softened with increasing esterase activity. Simultaneously, attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of , indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.
Topics: Animals; Dactinomycin; Insecta; Diptera; Rhabditida; Symbiosis; Sepsis
PubMed: 37787562
DOI: 10.1128/spectrum.01422-23 -
Clinical Case Reports Oct 2023Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are...
KEY CLINICAL MESSAGE
Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are the same, and all patients with ectopic pregnancy should be evaluated for choriocarcinoma based on histopathological findings. Adjuvant chemotherapy (after surgery) is the proposed treatment for tubal choriocarcinoma.
ABSTRACT
Choriocarcinoma is a malignant epithelial tumor of the chorionic villi that often manifests after a normal or molar pregnancy. The primary tubal choriocarcinoma associated with ectopic pregnancy is extremely rare and can be misdiagnosed as an ectopic pregnancy since symptoms including vaginal bleeding, amenorrhea, elevated beta-human chorionic gonadotropin (BHCG) levels, and pelvic pain are shared. A 34-year-old G4P3003 woman presented with a one-week history of vaginal bleeding and right lower abdominal pain, which had intensified a day before admission. Clinical and paraclinical examinations pointed to a ruptured tubal pregnancy; hence, an emergency laparotomy was performed, and a right salpingectomy was carried out on the patient. However, a nonsignificant decline in BHCG level was observed, and histological examination revealed tubal choriocarcinoma; hence, a metastasis workup was carried out, yet no metastasis was detected. Six sessions of chemotherapy consisting of Etoposide, Methotrexate, Dactinomycin, Cyclophosphamide, and Vincristine (EMA-CO) were administered without complication, in such a way that the BHCG level normalized after three sessions of chemotherapy. Evaluations after 1 year from the completion of chemotherapy revealed that the patient had no subsequent problems. Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are the same, and all patients with ectopic pregnancy should be evaluated for choriocarcinoma based on histopathological findings. Metastasis workup should be considered for all individuals with choriocarcinoma. Adjuvant chemotherapy (after surgery) is the proposed treatment for tubal choriocarcinoma.
PubMed: 37780932
DOI: 10.1002/ccr3.7977 -
International Journal of Gynecological... Nov 2023International societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of...
OBJECTIVE
International societies advocate for gestational trophoblastic neoplasia referral to designated expert centers. This study assessed the impact of centralization of trophoblastic care on clinical outcomes.
METHODS
A centralized program was implemented in 2018 at two affiliated academic hospitals, Princess Margaret Cancer Center and Mount Sinai Hospital. A retrospective analysis of patients treated between 2000 and 2022 was performed and the clinical outcomes were compared before (2000-2017) and after (2018-2022) centralization. Statistical analyses were performed with significance set as p<0.05.
RESULTS
A total of 94 patients with trophoblastic neoplasia were included: 60 pre-centralization and 34 post-centralization, 79.8% low-risk and 18.1% high-risk. Centralization led to significant improvement for: (1) accurate score documentation (from 37.9% to 89.3%,); (2) contraception counseling (from 67.2% to 96.7%); (3) median time from diagnosis to chemotherapy (from 9 days to 1 day); and (4) incomplete follow-up (from 20.7% to 3.3%) (all p<0.05). First-line chemotherapy for low-risk neoplasia was dactinomycin in 47.9% and 87.0% pre- and post-centralization, respectively (p=0.005). The median number of chemotherapy cycles decreased from seven to four (p=0.01), and the median number of consolidation cycles increased from two to three (p<0.001). Serum human chorionic gonadotropin (hCG) levels of 10 000-100 000 IU/L were significantly associated with longer time to hCG normalization and higher risk of resistance to first-line chemotherapy compared with hCG levels <1000 IU/L.
CONCLUSION
Centralization of trophoblastic neoplasia care leads to greater guideline compliance, faster chemotherapy initiation, fewer chemotherapy cycles with optimized consolidation, and enhanced surveillance completion. This supports the establishment of trophoblastic neoplasia expert centers.
Topics: Pregnancy; Female; Humans; Retrospective Studies; Gestational Trophoblastic Disease; Chorionic Gonadotropin; Hydatidiform Mole; Uterine Neoplasms
PubMed: 37723102
DOI: 10.1136/ijgc-2023-004526 -
Molecules (Basel, Switzerland) Aug 2023Actinobacteria produce a broad spectrum of bioactive substances that are used in the pharmaceutical, agricultural, and biotechnology industries. This study investigates...
Actinobacteria produce a broad spectrum of bioactive substances that are used in the pharmaceutical, agricultural, and biotechnology industries. This study investigates the production of bioactive substances in , isolated from soil under five tropical plants, focusing on their potential as natural antibacterial dyes for silk fabrics. Out of 194 isolates, 44 produced pigments on broken rice as a solid substrate culture. Eight antibacterial pigmented isolates from under (TBRC 15924, TBRC 15927, TBRC 15931), (TBRC 15925, TBRC 15926, TBRC 15928, TBRC 15930), and (TBRC 15929) were studied in more detail. TBRC 15927 was the only isolate where all the crude extracts inhibited the growth of the test organisms, TISTR 518 and DMST 4745. The bioactive compounds present in TBRC 15927 were identified through LC-MS/MS analysis as belonging to the actinomycin group, actinomycin D (or X), X, and X. Also, the ethyl acetate crude extract exhibited non-toxicity at an IC value of 0.029 ± 0.008 µg/mL on the mouse fibroblast L-929 assay. From the 16S rRNA gene sequence analysis, TBRC 15927 had 100% identity with JR-43. Raw silk dyed with the positive antimicrobial TBRC 15927 extract (8.35 mg/mL) had significant (>99.99%) antibacterial properties. TBRC 15927 is the first actinomycin-producing strain reported to grow on broken rice and shows promise for antibacterial silk dyeing.
Topics: Animals; Mice; Dactinomycin; Soil; Silk; Chromatography, Liquid; RNA, Ribosomal, 16S; Staphylococcus aureus; Tandem Mass Spectrometry; Anti-Bacterial Agents; Streptomyces
PubMed: 37630201
DOI: 10.3390/molecules28165949 -
BMC Cancer Aug 2023Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various...
Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.
BACKGROUND
Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens.
METHODS
We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life.
DISCUSSION
Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).
Topics: Humans; Pregnancy; Female; Dactinomycin; Methotrexate; Prospective Studies; Quality of Life; Gestational Trophoblastic Disease; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37612621
DOI: 10.1186/s12885-023-11225-2 -
Clinics (Sao Paulo, Brazil) 2023To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as...
OBJECTIVE
To evaluate the efficacy of immunotherapy for GTN treatment after methotrexate-resistance or in cases of multiresistant disease, through a systematic review, as well as to present the first 4 Brazilian cases of immunotherapy for GTN treatment.
METHODS
Three independent researchers searched five electronic databases (EMBASE, LILACS, Medline, CENTRAL and Web of Science), for relevant articles up to February/2023 (PROSPERO CRD42023401453). The quality assessment was performed using the Newcastle Ottawa scale for case series and case reports. The primary outcome of this study was the occurrence of complete remission. The presentation of the case reports was approved by the Institutional Review Board.
RESULTS
Of the 4 cases presented, the first was a low-risk GTN with methotrexate resistance unsuccessfully treated with avelumab, which achieved remission with sequential multiagent chemotherapy. The remaining 3 cases were high-risk multiagent-resistant GTN that were successfully treated with pembrolizumab, among which there were two subsequent gestations, one of them with normal pregnancy and healthy conceptus. Regarding the systematic review, 12 studies were included, only one of them on avelumab, showing a 46.7% complete remission rate. The remaining 11 studies were on pembrolizumab, showing an 86.7% complete remission rate, regardless of tumor histology. Both immunotherapies showed good tolerability, with two healthy pregnancies being recorded: one after avelumb and another after pembrolizumab.
CONCLUSION
Immunotherapy showed effectiveness for GTN treatment and may be especially useful in cases of high-risk disease, where pembrolizumab achieves a high therapeutic response, regardless of the histological type, and despite prior chemoresistance to multiple lines of treatment.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Brazil; Gestational Trophoblastic Disease; Immunotherapy; Retrospective Studies
PubMed: 37523979
DOI: 10.1016/j.clinsp.2023.100260 -
Bulletin of Experimental Biology and... May 2023We studied the possibility of inhibition of histone deacetylases (HDAC) in the nuclear extract of HeLa cells by N1-hydroxy-N4-(pyridin-4-yl)succinamide (compound 1)....
We studied the possibility of inhibition of histone deacetylases (HDAC) in the nuclear extract of HeLa cells by N1-hydroxy-N4-(pyridin-4-yl)succinamide (compound 1). Compound 1 inhibits HDAC and showed low toxicity for A-172, HepG2, HeLa, MCF-7, and Vero cells. HeLa cells were most sensitive to the compound. Increasing the interval between administration of compound 1 and the chemotherapeutic agent to 8 h led to an increase in the cytotoxic effect of cisplatin (actinomycin D) on HeLa cells. The combination of compound 1 with cisplatin (actinomycin D) reduced the cytotoxic effect of these drugs for non-tumor Vero cells.
Topics: Animals; Chlorocebus aethiops; Humans; Cisplatin; Dactinomycin; Succinic Acid; HeLa Cells; Vero Cells; Antineoplastic Agents; Pyridines; Histone Deacetylase Inhibitors; Cell Line, Tumor
PubMed: 37338757
DOI: 10.1007/s10517-023-05803-4 -
Gynecologic Oncology Aug 2023Approximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0-6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment...
BACKGROUND
Approximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0-6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment with either actinomycin-D (ActD) or multi-agent combination chemotherapy has depended on whether the hCG was above or below an hCG threshold. To reduce exposure to combination chemotherapy (CC), over the years the UK service has raised this threshold as well as using single-agent carboplatin AUC6 3-weekly at MTX-R instead of CC. Updated results for carboplatin demonstrate an 86% complete hCG response (hCG CR) but associated with haematological dose-limiting toxicity.
METHODS
In 2017, single-agent carboplatin became the national standard second-line treatment following MTX-R at hCG of >3000 IU/L. Carboplatin was changed to two-weekly AUC4 scheduling and continued until normal hCG plus 3 consolidation cycles. For patients failing to respond, CC (Etoposide-Actinomycin-D or EMA-CO) was introduced.
RESULTS
22 evaluable patients with a median hCG at MTX-R of 10,147 IU/L (IQR 5527-19,639) received carboplatin AUC4 2-weekly (median no. of cycles = 6, IQR 2-8). Of these, 36% achieved a hCG CR. All 14 non-CR patients were cured with subsequent CC; 11 and 2 patients with 3rd line and 4th line CC respectively and 1 patient following 5th line CC and hysterectomy. Overall survival remains 100%.
CONCLUSION
Carboplatin is not sufficiently active in the second-line treatment of low-risk MTX-resistant GTN. New strategies are required to increase hCG CR and spare more toxic CC regimens.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Carboplatin; Antineoplastic Combined Chemotherapy Protocols; Gestational Trophoblastic Disease; Retrospective Studies
PubMed: 37327541
DOI: 10.1016/j.ygyno.2023.05.072 -
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