The duration of ST segment depression as an indicator of the pathophysiology of myocardial ischemia.
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Angina Pectoris↗
Biomedical subjects
B Kong
Publications and source records attributed to B Kong.
Use of oral dipyridamole SPECT thallium-201 imaging in detection of coronary artery disease.
This study examined the merits of oral dipyridamole SPECT thallium-201 imaging in detecting CAD and multivessel CAD. The 65 patients included in this study (aged 62 +/- 11 years) were not candidates for exercise testing (for the usual reasons). Coronary arteriography revealed no significant CAD in 17 patients and greater than or equal to 50% narrowing of one or more vessels in 48 patients; 12 had one-vessel and 36 had multivessel CAD (high-risk group). Thallium-201 was injected intravenously 45 minutes after an oral dose of 375 mg of dipyridamole, and SPECT imaging was performed within 10 minutes and 4 hours after injection. There were no serious side effects; only six patients (8%) had ST segment depression and 18 patients (28%) had chest pain. The heart rate increased from 74 +/- 15 beats/min at rest to 84 +/- 14 beats/min at peak effect (p = 0.001); the systolic blood pressure did not change (130 +/- 18 and 128 +/- 20 mm Hg, respectively, p = NS). The thallium images were abnormal in 6 of 17 patients (35%) with no CAD, in 7 of 12 patients with one-vessel disease (58%), and in 34 of 36 patients with multivessel CAD (94%) (p = 0.001). Twenty-one of 25 patients (84%) with a perfusion abnormality in more than one vascular territory had multivessel CAD assessed by angiography. Thus oral dipyridamole SPECT thallium-201 imaging is a safe and inexpensive method for the detection of CAD in patients who are otherwise not candidates for exercise testing.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Angiographic demonstration of spasm in a left internal mammary artery used as a bypass to the left anterior descending coronary artery.
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Coronary Vasospasm↗
Elimination of amphotericin B in impaired renal function.
The influence of impaired renal function on the steady-state plasma clearance of amphotericin B was determined in seven patients with creatinine clearances ranging from zero to normal. Contrary to previous reports, steady-state plasma concentrations of total drug were lower in uremic patients than in patients with normal renal function. Total plasma clearance of amphotericin B ranged from 16.7 to 39.9 ml/min, correlated directly with the plasma creatinine concentration, and correlated inversely with the creatinine clearance. Urinary excretion of unchanged drug accounted for less than 10% of the dose. In 10 healthy subjects, mean percent of amphotericin B unbound in plasma was 3.55 +/- 0.32 (SD). Binding was determined in a further group of 10 uremic patients. Mean unbound percent (4.15 +/- 0.73, SD) was higher than in the healthy subjects, and the binding ratio (molar concentration of bound to unbound drug) correlated weakly with the creatinine clearance. This suggests that plasma clearance of unbound amphotericin B and, therefore, steady-state plasma concentrations of unbound drug are not affected by renal impairment, and that dosage requirements will be overestimated if based on measurements of total drug plasma concentration.
Adult↗
VP22 enhanced intercellular trafficking of HSV thymidine kinase reduced the level of ganciclovir needed to cause suicide cell death.
BACKGROUND: The inefficiency of herpes simplex virus thymidine kinase (TK) gene transfer and toxicity of ganciclovir (GCV) at high concentrations in vivo limits the use of this suicide gene therapy approach for the treatment of cancers in clinical settings. To overcome the problem, we have sought evidence of amplification of cytotoxicity by co-transfer of the TK gene fused with the gene encoding HSV-1 structural protein VP22 which has a remarkable ability for intercellular trafficking. METHODS: The expression of the fusion proteins from the chimeric VP22-TK or VP22-EGFP genes was shown by Western blot and VP22 promoted TK or EGFP intercellular trafficking by an indirect immunofluorescent assay. The cytotoxicity was demonstrated by a colorimetric cell proliferation assay followed by an assessment of the bystander effect on admixtures of transfected with non-transfected naive cells. RESULTS: Our results show the expression of the VP22 fusion proteins and their spread to varying numbers of bystander cells (up to 30, observed in viable cells with VP22-EGFP as well as after methanol fixation), confirming that VP22 assisted intercellular trafficking of the fusion proteins. This VP22 promoted TK spreading resulted in killing by 2.5 microg/ml GCV of virtually all cells in cultures that had been transfected at an efficiency of only 27.5%. In contrast, fewer than 80% of cells were killed when transfected with 'tk alone' at the same efficiency. The cell killing effect was exponentially dependent on GCV concentration in cells transfected with 'tk alone' at GCV concentrations between 0.25 and 0.5 microg/ml, but not those transfected with VP22-TK, probably due to the continuously variable, high sensitivity of about 50% of cells. Even at low concentration of GCV (0.2 microg/ml), the enhancement of cell killing by VP22 was four-fold higher in cells transfected with VP22-TK than in cells transfected with 'tk alone'. CONCLUSIONS: VP22 enhanced intercellular trafficking of TK and amplified the TK/GCV killing effect, especially in the lower range of GCV concentrations. This offers a new strategy to enhance the effectiveness of suicide gene therapy for the treatment of cancers.
Animals↗
Arsenic trioxide induces apoptosis in cisplatin-sensitive and -resistant ovarian cancer cell lines.
Arsenic trioxide (As(2)O(3)), has been used for centuries in traditional Chinese medicine; it has considerable efficacy in the treatment of relapsed acute promyelocytic leukemia, inducing partial differentiation and promoting apoptosis of malignant promyelocytes. Although a number of studies have demonstrated that As(2)O(3) has potent activity against cell growth in a series of leukemia cell lines, little information is available regarding this compound's effect on cell growth in solid tumor cell lines. In this study, we investigated the effects of As(2)O(3)in vitro on ovarian cancer cell lines sensitive (3AO) and resistant (3AO/CDDP) to cisplatin. The 3-(4,5-dimethy-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotoxicity. Flow cytometric analysis was used to determine the apoptosis, cell cycle distribution. We clearly demonstrated that As(2)O(3) induced cell apoptosis and inhibition of cell growth in both the cell lines. Furthermore, we identified that As(2)O(3)-induced apoptosis involved Fas pathway. As(2)O(3) is an active agent against ovarian cancer cells and could be effective in the clinical treatment of ovarian cancer.
Apoptosis↗
Ultrastructure alterations in adriamycin-resistant and cisplatin-resistant human ovarian cancer cell lines exposed to nonlethal ultrasound.
Human ovarian cancer cell lines, SKOV3 and its adriamycin-resistant substrain SKOV3/ADR and COC1 and its cisplatin-resistant substrain COC1/DDP, were exposed to nonlethal ultrasound. Ultrastructures in sham-insonated and insonated cells were inspected by transmission electron microscopy, and cytochrome C in cytosol was determined by enzyme-linked immunosorbent assay. Ultrasound exposure led to no significant changes in SKOV3/ADR cells, but tumid mitochondria occurred in SKOV3 cells. Mitochondria changes were also detected in some exposed COC1 and COC1/DDP cells. Apoptotic bodies could be detected in either control or insonated COC1/DDP cells. A few exposed COC1/DDP cells became reticular. Cytochrome C in cytosol in exposed SKOV3/ADR cells was increased but that in exposed COC1/DDP cells was decreased. These findings revealed that the bioeffect of ultrasound on chemosensitive cells was not identical to that of chemoresistant ones, and ultrasound was a potential approach for treatment of drug-resistant ovarian cancers.
Antibiotics, Antineoplastic↗
Procaspase-3 enhances the in vitro effect of cytosine deaminase-thymidine kinase disuicide gene therapy on human ovarian cancer.
Because the efficacy of genetic prodrug activation therapy (GPAT) using herpes simplex virus thymidine kinase (tk)/ganciclovir (GCV) or Escherichia coli cytosine deaminase (cd)/5-fluorocytosine (5-FC) is not satisfied in early clinical trials and the mechanism of both the GPATs have been shown to lead to the activation of cell apoptotic pathway, we hypothesized that coexpression of procaspase-3, a central downstream executioner of apoptotic pathways, with cd-tk gene leads to enhanced cell death in ovarian cancer cells in vitro. Following transfection with the vectors encoding cd and tk, 5-FC and GCV treatments lead to greater cell death in procaspase-3-expressing clones of 3AO (3AO-caspase-3) than control cells (3AO-pcDNA3), as well as more rapid activation of caspase-3 and more rapid cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). There is a greater degree of cell apoptotic rate in the procaspase-3-expressing clones than in control cells following the treatment with cd-tk/5-FC + GCV, and apoptosis is the main cell death form. None of these effects is seen following transfection with a control vector that does not encode tk and cd (pBTdel-279). The results strongly suggest that coexpression of procaspase-3 may lead to a significant enhancement of the efficacy of cd-tk/5-FC + GCV, and this strategy would be a novel and promising approach for the treatment of ovarian cancer.
Apoptosis↗