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1.
2.
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.
Sylvie Pillet Julien Courtieux Sylvie Gonzalo Issam Bechri Thomas Bourlet Martine Valette Antonin Bal Bruno Pozzetto 《Viruses》2022,14(12)
Within the successive waves that occurred during the SARS-CoV-2 pandemic, recommendations arose to test symptomatic and contact subjects by using rapid antigen devices directed against the viral nucleocapsid protein with the aim to isolate contagious patients without delay. The objective of this study was to evaluate the ability of four rapid lateral-flow tests (RLFT) that were commercially available on the French market in 2022 to recognize various strains of SARS-CoV-2. Series of five-fold dilutions of seven viral suspensions belonging to different lineages of SARS-CoV-2 (19A, 20A, Alpha, Beta, Gamma, Delta and Omicron) were used to evaluate the analytical sensitivity of four commercially available RLFTs (manufacturers: Abbott, AAZ, Becton-Dickinson and Biospeedia). Cell culture and quantitative RT-PCR were used as references. Excellent correlations were observed for each lineage strain between the viral titer obtained via cell culture and the number of RNA copies measured by quantitative RT-PCR. Although the four tests were able to recognize all the tested variants, significant differences in terms of sensitivity were observed between the four RLFTs. Despite the limitation represented by the small number of devices and clinical isolates that were tested, this study contributed by rapidly comparing the sensitivity of SARS-CoV-2 RLFTs in the Omicron era. 相似文献
6.
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
7.
Hanna HA Raad II Hackett B Wallace SK Price KJ Coyle DE Parmley CL;M.D. Anderson Catheter Study Group 《Chest》2003,124(3):1030-1038
OBJECTIVE: To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU. DESIGN: Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999). SETTING: ICUs of a tertiary care hospital in Houston, TX. PATIENTS: Cancer patients in the medical ICU (MICU) and surgical ICU (SICU). INTERVENTIONS: ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999. Measurements and main results:The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999. CONCLUSIONS: The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays. 相似文献
8.
Issam Abushammala 《Saudi Pharmaceutical Journal》2015,23(2):177-181
Introduction
Drug–drug interactions can lead to serious and potentially lethal adverse events. In recent years, several drugs have been withdrawn from the market due to interaction-related adverse events. The objective of this study was to evaluate the pharmacokinetic interaction between pioglitazone (PG) and carbamazepine (CBZ) in healthy male rabbits.Methods
A randomized, two-crossover design study was conducted in six healthy male rabbits. The study consisted of two periods: period one, when each rabbit received a single dose of 70 mg CBZ-suspension. Period two, when each rabbit received a single dose of 70 mg CBZ-suspension co-administered with a single dose of 1.5 mg PG with a washout period of one week between the two periods. Serial blood samples were collected over a period of 48 h. Chemiluminescent enzyme immunoassay (CLEIA) was used to measure CBZ in serum. Pharmacokinetic (PK) parameters Cmax, Tmax, t 1/2, AUC0-t, AUC 0-∞, and ke were determined for the two periods using non-compartmental analysis.Results
In the two periods of treatment, Cmax, Tmax, AUC0-t, AUC0-∞, t ½ and ke for CBZ were administered alone and in combination with PG. Cmax, the mean peak plasma concentration was 4.33 ± 2.4 μg/mL versus 4.76 ± 2.1 μg/ml, tmax, time taken to reach, was 2.91 ± 1.11 h versus 3.6 ± 1.83 h, total area under the curve AUC0-t was 64.90 ± 43.6 μg·h/ml versus 102.90 ± 66.9 μg·h/ml, AUC0-∞ was 74.0 ± 52.6 μg·h/ml versus 124.3 ± 85 μg·h/mL, t ½ was 14.10 ± 2.5 h versus 16.43 ± 6.43 h and elimination rate constant ke was 0.050 ± 0.009 h−1 versus 0.057 ± 0.049 h−1, respectively. No statistical differences were found in pharmacokinetic of CBZ in both cases (P > 0.05).Conclusion
The result of the study demonstrated that PG does not affect pharmacokinetic parameters of CBZ. Therefore, no cautions regarding dose or administration pattern of CBZ with PG should be taken. 相似文献9.
Issam A. Halaby M.D. Peter C. Rantis M.D. Anthony M. Vernava III M.D. Dr. Walter E. Longo M.D. 《Diseases of the colon and rectum》1996,39(5):573-578
INTRODUCTION: Collagenous colitis is a rare disease of unknown etiology that primarily affects middle-aged women. It presents with chronic watery diarrhea and thickening of the subepithelial collagen layer of the colonic mucosa in the absence of endoscopic abnormalities. PURPOSE: This study was undertaken to review the current literature on clinical course, pathology, diagnosis, and current management of collagenous colitis. RESULTS: Collagenous colitis is an inflammatory disease of the colon, clinically characterized by a waxing and waning course of watery diarrhea, an inflammatory infiltration of the colonic mucosa, and a thickening of the subepithelial collagen layer. Its pathogenesis remains unclear, but there is evidence for an inflammatory process triggered possibly by an uncommon luminal agent. Diagnosis is established by colonic biopsies; in the setting of normal colonic mucosa, the disorder is primarily managed medically with virtually no role for surgery. CONCLUSIONS: Pathogenesis of collagenous colitis remains unclear. Current data favor an inflammatory etiology, possibly involving an initiating luminal insult. Guidelines for diagnosis are being established, and medical treatment options are variably effective in the majority of cases. Very unusual refractory cases may benefit from surgical management. 相似文献
10.
Nakhleh E. Abu-Yaghi Ahmad M. AlNawaiseh Issam M. Khourshid Tala J. AlRawashdeh Majd M. Al Rawashdeh Ayat M. Zghoul Abdallah N. Shafagoj Yousif A. Alomairi Sana' M. Muhsen SaifAldeen S. AlRyalat 《The Journal of international medical research》2021,49(4)
ObjectivesTo measure central macular thickness in Jordanian patients with sickle cell disease who did not have retinopathy and compare the findings with age- and sex-matched controls using spectral domain optical coherence tomography (SDOCT).MethodsIn this cross-sectional study, participants underwent visual acuity testing, slit-lamp bio-microscopy, dilated ophthalmoscopy, and SDOCT imaging to measure central macular thickness. Macular quadrant measurements and thickness difference indexes (TDIs) were compared between groups.ResultsTwenty eyes with sickle cell disease and 20 control eyes were enrolled. The median visual acuity in both groups was 20/20. The mean macular thickness was significantly lower in eyes with sickle cell disease than in matched controls (mean difference, 22.15 ± 6.44 µm). Peripheral quadrants were all significantly thinner in eyes with sickle cell disease, especially in superior and temporal quadrants. TDIs were lower in eyes with sickle cell disease than in control eyes.ConclusionsEyes with sickle cell disease that had no clinical evidence of retinopathy exhibited significantly lower central macular thickness in all quadrants, compared with eyes in age- and sex-matched controls. SDOCT is a non-invasive imaging modality that can detect preclinical changes in eyes with sickle cell disease and can be used to screen and monitor the disease process. 相似文献