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British Journal of Cancer Sep 1990Menogaril is an anthracycline presently in Phase II clinical trials. Menogaril-resistant mouse leukaemia P388 cells were developed in vitro by 4 months of exposure to...
Menogaril is an anthracycline presently in Phase II clinical trials. Menogaril-resistant mouse leukaemia P388 cells were developed in vitro by 4 months of exposure to step-wise increasing concentrations of menogaril after which resistant cells (P388/MEN) were cloned in 320 ng ml-1 menogaril. P388/MEN cells were 40-fold more resistant to menogaril in vitro compared to P388/O and were also resistant in vivo. Resistance to menogaril was stable for at least 2 months in the absence of the drug. The results indicate that P388/MEN, although resistant to an anthracycline, did not display the typical multidrug resistant phenotype. It was not cross-resistant to several structurally unrelated drugs such as actinomycin D, cisplatin, or vinblastine, but it was cross-resistant to the anthracycline, adriamycin. Uptake and efflux of menogaril was similar in sensitive and resistant cell lines. Also, resistance was not reversed by verapamil. No major karyotypic difference was noted between P388/O and P388/MEN. There was no significant amplification or overexpression of the mdr gene in P388/MEN compared to P388/O. In contrast to P388/MEN, P388 cells resistant to adriamycin displayed the typical multidrug resistant phenotype. Glutathione content of P388/MEN cells was similar to that of P388/O and depletion of glutathione did not potentiate menogaril cytotoxicity. Therefore, we conclude that glutathione is not likely to be involved in menogaril resistance to P388/MEN cells.
Topics: Animals; Antineoplastic Agents; Cell Division; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance; Drug Synergism; Glutathione; In Vitro Techniques; Leukemia P388; Menogaril; Mice; Nogalamycin; Verapamil
PubMed: 2145026
DOI: 10.1038/bjc.1990.302 -
Advanced Science (Weinheim,... Apr 2024Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor growth and dissemination, motivating a search for key targets to interfere with the activation...
Tumor-associated macrophages (TAMs) play a crucial role in promoting tumor growth and dissemination, motivating a search for key targets to interfere with the activation of TAMs or reprogram TAMs into the tumor-suppressive type. To gain insight into the mechanisms of macrophage polarization, a designed co-culture system is established, allowing for the education of macrophages in a manner that closely mimics the intricacies of TAMs in the tumor immune microenvironment (TIME). Through database mining, exosomal miR-1246 is identified and is then validated. Exosomal miR-1246-driven polarization of TAMs disrupts the infiltration and function of CD8 T cells. Mechanically, the amassment of exosomal miR-1246 stems from TUT7-mediated degradation of small noncoding RNA, a process stabilized by SNRPB, but not the precursor of miR-1246. Moreover, an Exo-motif is present in the exosomal miR-1246 sequence, enabling it to bind with the exosomal sorting protein hnRNPA2B1. RNA-seq analysis reveals that exogenous miR-1246 modulates the polarization of TAMs at a post-transcriptional level, emphasizing the pivotal role of the NLRP3 in macrophage polarization. In conclusion, the findings underscore the importance of exosomal miR-1246 as a trigger of macrophage reprogramming and uncover a novel mechanism for its enhanced presence in the TIME.
Topics: Tumor-Associated Macrophages; Menogaril; CD8-Positive T-Lymphocytes; MicroRNAs; Macrophages
PubMed: 38342611
DOI: 10.1002/advs.202304222 -
RNA (New York, N.Y.) Nov 2022Metazoan histone mRNAs are the only cellular eukaryotic mRNAs that are not polyadenylated, ending instead in a conserved stem-loop. SLBP is bound to the 3' end of...
Metazoan histone mRNAs are the only cellular eukaryotic mRNAs that are not polyadenylated, ending instead in a conserved stem-loop. SLBP is bound to the 3' end of histone mRNAs and is required for translation of histone mRNA. The expression of histone mRNAs is tightly cell-cycle regulated. A major regulatory step is rapid degradation of histone mRNA at the end of S-phase or when DNA synthesis is inhibited in S-phase. 3'hExo, a 3' to 5' exonuclease, binds to the SLBP/SL complex and trims histone mRNA to 3 nt after the stem-loop. Together with a terminal uridyl transferase, 3'hExo maintains the length of the histone mRNA during S-phase. 3'hExo is essential for initiating histone mRNA degradation on polyribosomes, initiating degradation into the 3' side of the stem-loop. There is extensive uridylation of degradation intermediates in the 3' side of the stem when histone mRNA is degraded. Here, we knocked out TUT7 and 3'hExo and we show that both modification of histone mRNA during S-phase and degradation of histone mRNA involve the interaction of 3'hExo, and a specific TUTase, TENT3B (TUT7, ZCCHC6). Knockout of 3'hExo prevents the initiation of 3' to 5' degradation, stabilizing histone mRNA, whereas knockout of TUT7 prevents uridylation of the mRNA degradation intermediates, slowing the rate of degradation. In synchronized 3'hExo KO cells, histone mRNA degradation is delayed, but the histone mRNA is degraded prior to mitosis by a different pathway.
Topics: Animals; Humans; Histones; Menogaril; HeLa Cells; RNA Stability; RNA, Messenger; mRNA Cleavage and Polyadenylation Factors
PubMed: 36041871
DOI: 10.1261/rna.079233.122 -
Oxidative Medicine and Cellular... 2020This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating,...
This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating, rat heart myocytes. Doxorubicin produced a dose-dependent increase in the rate of cyanide-resistant respiration by beating myocytes. The anthracycline analogs 4-demethoxydaunorubicin, 4'-epidoxorubicin, 4'-deoxydoxorubicin, and menogaril, as well as the anticancer quinones mitomycin C and menadione, also significantly increased oxygen consumption by cardiac myocytes. However, 5-iminodaunorubicin (which has a substituted quinone group) and mitoxantrone (which is not easily reduced by flavin dehydrogenases) had no effect on cardiac respiration. Both catalase (43%) and acetylated cytochrome c (19%) significantly decreased oxygen consumption that had been stimulated by doxorubicin; furthermore, extracellular hydrogen peroxide production was increased from undetectable control levels to 1.30 ± 0.02 nmol/min/10 myocytes ( = 4, < 0.01) in the presence of 400 M doxorubicin. These experiments suggest that the anthracycline antibiotics and other anticancer quinones stimulate cardiac oxygen radical production in intact heart myocytes; such a free radical cascade could contribute to the cardiac toxicity of these drugs.
Topics: Aging; Animals; Antineoplastic Agents; Benzoquinones; Cell Respiration; Cyanides; Doxorubicin; Free Radical Scavengers; Hydrogen Peroxide; Male; Myocytes, Cardiac; Oxygen Consumption; Rats, Sprague-Dawley; Reactive Oxygen Species
PubMed: 33144915
DOI: 10.1155/2020/8877100 -
Sensors (Basel, Switzerland) Jun 2021Underlying topography plays an important role in the national economic construction, military security, resource exploration and investigation. Since synthetic aperture...
Underlying topography plays an important role in the national economic construction, military security, resource exploration and investigation. Since synthetic aperture radar tomography (TomoSAR) can achieve the three-dimensional imaging of forests, it has been widely used in underlying topography estimation. At present, there are two kinds of TomoSAR based on the applied datasets: single polarimetric TomoSAR (SP-TomoSAR) and fully polarimetric TomoSAR (FP-TomoSAR). However, SP-TomoSAR cannot obtain the underlying topography accurately due to the lack of enough observations. FP-TomoSAR can improve the estimation accuracy of underlying topography. However, it requires high-cost data acquisition for the large-scale application. Thus, this paper proposes the dual polarimetric TomoSAR (DP-TomoSAR) as another suitable candidate to estimate the underlying topography because of its wide swath and multiple polarimetric observations. Moreover, three frequently used spectral estimation algorithms, namely, Beamforming, Capon and MUSIC, are used in DP-TomoSAR. For validation, a series of simulated experiments was carried out, and the airborne P-band multiple polarimetric SAR data over the Lope, Gabon was also acquired to estimate the underlying topography. The results suggest that DP-TomoSAR in HH & HV combination is more suitable to estimate underlying topography over forest areas than other DP combinations. Moreover, the estimation accuracy of DP-TomoSAR is slightly lower than that of FP-TomoSAR but is higher than that of SP-TomoSAR.
Topics: Environmental Monitoring; Forests; Menogaril; Radar; Tomography
PubMed: 34203846
DOI: 10.3390/s21124117 -
Annals of Oncology : Official Journal... Mar 1992
Topics: Administration, Oral; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Female; Humans; Idarubicin; Menogaril; Neoplasms; Nogalamycin
PubMed: 1534020
DOI: 10.1093/oxfordjournals.annonc.a058144 -
Sensors (Basel, Switzerland) Jan 2023Building reconstruction using high-resolution satellite-based synthetic SAR tomography (TomoSAR) is of great importance in urban planning and city modeling applications....
Building reconstruction using high-resolution satellite-based synthetic SAR tomography (TomoSAR) is of great importance in urban planning and city modeling applications. However, since the imaging mode of SAR is side-by-side, the TomoSAR point cloud of a single orbit cannot achieve a complete observation of buildings. It is difficult for existing methods to extract the same features, as well as to use the overlap rate to achieve the alignment of the homologous TomoSAR point cloud and the cross-source TomoSAR point cloud. Therefore, this paper proposes a robust alignment method for TomoSAR point clouds in urban areas. First, noise points and outlier points are filtered by statistical filtering, and density of projection point (DoPP)-based projection is used to extract TomoSAR building point clouds and obtain the facade points for subsequent calculations based on density clustering. Subsequently, coarse alignment of source and target point clouds was performed using principal component analysis (PCA). Lastly, the rotation and translation coefficients were calculated using the angle of the normal vector of the opposite facade of the building and the distance of the outer end of the facade projection. The experimental results verify the feasibility and robustness of the proposed method. For the homologous TomoSAR point cloud, the experimental results show that the average rotation error of the proposed method was less than 0.1°, and the average translation error was less than 0.25 m. The alignment accuracy of the cross-source TomoSAR point cloud was evaluated for the defined angle and distance, whose values were less than 0.2° and 0.25 m.
Topics: Menogaril; Tomography, X-Ray Computed; City Planning; Cluster Analysis; Principal Component Analysis
PubMed: 36679649
DOI: 10.3390/s23020852 -
Japanese Journal of Cancer Research :... Aug 1990Menogaril, an anthracycline compound possessing a significant antitumor activity after both po and iv administration, has been introduced into clinical trials. However,...
Menogaril, an anthracycline compound possessing a significant antitumor activity after both po and iv administration, has been introduced into clinical trials. However, its mechanism of action has not been clarified yet. This study revealed that its cytotoxicity correlated very well with the inhibition of macromolecular synthesis, indicating the involvement of interaction with DNA. The spectrophotometric study showed a weaker binding of this compound to calf thymus DNA when compared to that of doxorubicin (adriamycin). Despite the lower binding affinity of menogaril to DNA, pronounced DNA cleavage was observed in an intact cell system, indicating that the character of the interaction with DNA is different from intercalation. In contrast to doxorubicin, menogaril is extensively localized in the cytoplasm. The cytoplasmic localization prompted us to study its effect on cytoskeleton proteins. It was found that menogaril inhibited the initial polymerization rate of tubulin, indicating a possible contribution of this process to the overall cytotoxicity of menogaril.
Topics: Animals; Antineoplastic Agents; DNA Damage; DNA, Neoplasm; Daunorubicin; Doxorubicin; Leukemia L1210; Menogaril; Microtubule Proteins; Neoplasm Proteins; Nogalamycin; Polyphosphates; RNA, Neoplasm; Tubulin
PubMed: 2144516
DOI: 10.1111/j.1349-7006.1990.tb02654.x -
Neuro-oncology Oct 1999In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II... (Clinical Trial)
Clinical Trial
In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II chemotherapy trials. We reviewed the records of patients from 8 consecutive phase II trials, including 225 patients with recurrent glioblastoma multiforme and 150 with recurrent anaplastic astrocytoma. Median age was 45 years (range, 15-82) and median Karnofsky performance score was 80 (range, 60-100). Forty-one patients (11%) had more than two prior resections and/or more than two prior chemotherapy regimens. Best response was complete (n = 1) or partial (n = 33) in 34 patients (9%). Median time to response was 14 weeks, and median response duration was 44 weeks. Simon-Makuch estimates for 52-week progression-free survival for patients progression-free at 13 weeks were 48% for response and 28% for nonresponse. When response was treated as a time-dependent covariate in a Cox proportional hazards regression analysis, response was associated with significantly lower failure rates (hazard ratio 0.5; 95% confidence interval 0.3-0.8; P = 0.0016). This study showed that response in recurrent glioma is associated with a significant reduction in progression rates.
Topics: Actuarial Analysis; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Carboplatin; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Eflornithine; Female; Fluorouracil; Glioblastoma; Glioma; Humans; Interferon-beta; Male; Menogaril; Middle Aged; Neoplasm Recurrence, Local; Procarbazine; Prognosis; Proportional Hazards Models; Texas; Treatment Outcome; Tretinoin
PubMed: 11550320
DOI: 10.1093/neuonc/1.4.282 -
Annals of Oncology : Official Journal... Mar 1992The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of weekly oral menogaril as first-line therapy in 51 patients with... (Clinical Trial)
Clinical Trial
The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of weekly oral menogaril as first-line therapy in 51 patients with incurable, metastatic or locally advanced breast cancer. While no prior chemotherapy for metastatic disease was permitted, prior adjuvant chemotherapy was allowed provided that no anthracycline or anthracene had been given. Forty-eight patients were evaluable for response. Two patients (4%) achieved complete remissions, 9 patients (19%) achieved partial remissions, 26 patients (54%) were stable and 11 patients (23%) failed. At the initial menogaril dose of 275 mg/m2 per week, 13 of 14 patients required a dose reduction and/or a treatment delay of one or more weeks. Therefore, the menogaril dose was reduced to 225 mg/m2 per week for the last 37 patients. At that those, 20 of 37 patients developed grade 3 or 4 granulocytopenia and 22 required dosage delays. At the initial starting dose, the average dose intensity actually delivered was 169 mg/m2 per week. At 225 mg/m2 the average dose intensity actually delivered was 197 mg/m2 per week. Toxic effects included mild to moderate nausea and vomiting, diarrhea, hair loss and occasional hyperpigmentation. In summary, menogaril is an anthracycline derivative that has modest activity when administered orally to minimally pretreated patients with breast cancer.
Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Female; Humans; Menogaril; Middle Aged; Nogalamycin
PubMed: 1534021
DOI: 10.1093/oxfordjournals.annonc.a058152