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M. Abdellah Alaoui Jamali Ming-biao Yin Alessandra Mazzoni Issam Bankusli Youcef M. Rustum 《Cancer chemotherapy and pharmacology》1989,25(2):77-83
Summary The effect ofN-(3,4-dimethoxyphenyl)N-methyl-2-(naphthyl)-m-dithiane-2-propylamine hydrochloride (RO11-2933), an analog of the calcium channel blocker tiapamil, on doxorubicin (DOX)-induced cytotoxicity and DNA damage in human ovarian cancer cells sensitive and resistant to DOX was investigated. A2780-DX2, A2780-DX3, and A2780-DX6 cell sublines were characterized by 7-, 26-, and 48-fold resistance after 2 h DOX exposure and 30-, 50-, and 500-fold resistance after 72 h DOX exposure, respectively. Increased drug efflux resulting in a lower intracellular drug accumulation, decreased DOX-induced DNA single-strand breaks (DNA SSBs), and rapid DNA repair correlated with the degree of resistance. In addition, DNA SSBs were rapidly repaired within 8 h in A2780-DX3 cells, whereas no significant repair of DNA SSBs was observed in sensitive cells. In comparison with verapamil, RO11-2933 was found to reverse DOX resistance at lower and nontoxic concentrations (2 M as compared with 10 M verapamil). This reversion was complete in cells with a low degree of resistance (A2780-DX1 and A2780-DX2) but partial in highly resistant cells (A2780-DX3 and A2780-DX6), and continuous exposure to RO11-2933 was essential for optimal reversal of drug resistance. Interestingly, RO11-2933 was found to inhibit the repair of DNA SSBs induced by DOX but not those induced by X-ray. These results suggest that the potentiation of DNA SSBs and the specific inhibition of DNA repair by RO11-2933 in multidrug-resistant cells could be of particular value in overcoming MDR in the clinic.Abbreviations RO11-2933
N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl)-m-dithiane-2-propylamine hydrochloride
- DOX
doxorubicin-HCl
- SSBs
single-strand breaks
- MDR
multidrug resistance
This work was supported in part by CA 18420 and CA 21071 相似文献
3.
Lu W Parikh PJ El Naqa IM Nystrom MM Hubenschmidt JP Wahab SH Mutic S Singh AK Christensen GE Bradley JD Low DA 《Medical physics》2005,32(4):890-901
We have developed a four-dimensional computed tomography (4D CT) technique for mapping breathing motion in radiotherapy treatment planning. A multislice CT scanner (1.5 mm slices) operated in ciné mode was used to acquire 12 contiguous slices in each couch position for 15 consecutive scans (0.5 s rotation, 0.25 s between scans) while the patient underwent simultaneous quantitative spirometry measurements to provide a sorting metric. The spirometry-sorted scans were used to reconstruct a 4D data set. A critical factor for 4D CT is quantifying the reconstructed data set quality which we measure by correlating the metric used relative to internal-object motion. For this study, the internal air content within the lung was used as a surrogate for internal motion measurements. Thresholding and image morphological operations were applied to delineate the air-containing tissues (lungs, trachea) from each CT slice. The Hounsfield values were converted to the internal air content (V). The relationship between the air content and spirometer-measured tidal volume (v) was found to be quite linear throughout the lungs and was used to estimate the overall accuracy and precision of tidal volume-sorted 4D CT. Inspection of the CT-scan air content as a function of tidal volume showed excellent correlations (typically r>0.99) throughout the lung volume. Because of the discovered linear relationship, the ratio of internal air content to tidal volume was indicative of the fraction of air change in each couch position. Theoretically, due to air density differences within the lung and in room, the sum of these ratios would equal 1.11. For 12 patients, the mean value was 1.08 +/- 0.06, indicating the high quality of spirometry-based image sorting. The residual of a first-order fit between v and V was used to estimate the process precision. For all patients, the precision was better than 8%, with a mean value of 5.1% +/- 1.9%. This quantitative analysis highlights the value of using spirometry as the metric in sorting CT scans. The 4D reconstruction provides the CT data required to measure the three-dimensional trajectory of tumor and lung tissue during free breathing. 相似文献
4.
Depolarization thresholds for hippocampal damage, ischemic preconditioning, and changes in gene expression after global ischemia in the rat 总被引:1,自引:0,他引:1
Induced ischemic tolerance in rat hippocampus was investigated in a forebrain ischemia model of repeated 4-vessel occlusion (4-VO). Ischemic insult variability was reduced by the use of dc potential measurements to determine the duration of ischemic depolarization in hippocampus. The results demonstrate a depolarization threshold for ischemic injury to CA1 neurons of 4-6 min and a window for optimal preconditioning of 2.5-3.5 min. Levels of induced mRNAs encoding hsp72 and several immediate-early genes were also shown to vary with depolarization interval. Immediate-early genes were maximally induced after depolarization periods inducing optimal preconditioning, while hsp72 expression increased with insult severity over the range leading to neuron loss. These results are similar to those obtained in gerbil studies indicating that preconditioning does not require large increases in hsp72 expression, and demonstrate the fundamental comparability of rodent global ischemia models when monitored by this approach. 相似文献
5.
Fatina W. Dahadhah Mayyas Saleh Jaweesh Mazhar Salim Al Zoubi Manal Issam Abu Alarjah Mohamad Eid Hammadeh Houda Amor 《Andrologia》2021,53(8):e14139
Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation. 相似文献
6.
H. Rejab W. Ben Kridis H. Ben Ameur J. Feki M. Frikha M. Issam Beyrouti 《Pathologie-biologie》2013,61(3):134-137
Gastro-intestinal stromal tumors are uncommon mesenchymal tumors. There are localized preferentially in the stomach. The rectal localization is exceedingly rare. Through a new case of rectal stromal tumour as well as a review of the literature, we propose to focus on clinical, radiological and therapeutic particularities of this rare entity. 相似文献
7.
Issam Saliba Musaed Alzahrani Xiaoduan Weng Alain Bestavros 《Acta oto-laryngologica》2018,138(2):110-115
Objectives: (1) To assess the ability of flow cytometric immunophenotyping to detect and quantitate eosinophils in patients with eosinophilic otitis media (EOM). (2) to evaluate the association of EOM to bronchial asthma.Methods: Twenty-one patients with chronic otorrhea or middle ear effusion (MEE) were included in this prospective cohort study. Group I composed of 10 patients (14 ears) and associated to bronchial asthma. Group II included 11 patients (11 ears) without bronchial asthma. Samples of MEE were sent for flow cytometric analysis at initial presentation. Patients with positive eosinophils on flow cytometric immunophenotyping were analyzed after one-month course of dexamethasone eardrops.Results: EOM was diagnosed in all patients of group I and in three patients of group II. The mean eosinophils percentage was 43.5% and 14.2% for group I and group II, respectively (p?=?.006). Those patients showed a significant response to dexamethasone eardrops, both on clinical examination and on flow cytometric analysis with a decrease in eosinophil levels post-treatment. However, this improvement was temporary and symptoms recurred after treatment cessation. Bronchial asthma was not associated to all patients with EOM.Conclusion: Diagnosis of EOM remained mostly clinical; flow cytometry immunophenotyping of MEE may be helpful as an additional tool in diagnosis and monitoring the response to treatment, particularly in non-asthmatic patients. 相似文献
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Halima Al-tamimi Alia A. Al-Hadi Al-Hareth Al-Khater Issam Al-bozom Najla Al-sayed 《Archives of gynecology and obstetrics》2009,280(3):465-468
Abstract A case report and review of an extraskeletal neuroectodermal tumour of the vagina.
Background Ewing’s sarcoma (ES) and primitive neuroectodermal tumours (PNETs) account for approximately 6–10% of primary malignant bone
tumours and, following osteosarcoma, are the second most common group of bone sarcomas in children. Ewing’s sarcoma rarely
affects the genitourinary tract.
Case summary We report a rare case of extraskeletal Ewing’s sarcoma diagnosed in a 47-year-old Indian woman presenting with a simple cystic
lesion in the posterior wall of the vagina. The histopathology revealed a rare presentation of a primitive malignant extraskeletal
neuroectodermal tumour.
Conclusion As our PubMed review found only six previously reported cases of vaginal extraskeletal Ewing’s sarcoma. Presentation as vaginal
masses helped in early disease detection. 相似文献