Biomedical subjects

J K Roh

Publications and source records attributed to J K Roh.

At least 109 records · Page 6Linked to original sources

PubMed1993

Combined use of tamoxifen, cyclosporin A, and verapamil for modulating multidrug resistance in human hepatocellular carcinoma cell lines.

The intensive use of chemotherapeutic agents for the treatment of cancer has resulted in the cure or improved survival of many patients. But unfortunately, many cancers including human hepatocellular carcinoma (HCC) don't respond to chemotherapy. One of the major mechanisms for the drug resistance in the HCC is an elevated MDR1 RNA expression which makes cells become multidrug resistant. To overcome the multidrug resistance (MDR) phenotype, a high dose of verapamil is required both clinically and experimentally. Accordingly we have examined the MDR modulating effects with combinations of tamoxifen, cyclosporin A, and verapamil in vitro with the physiologically achievable concentrations of each agent, i.e., 2.0 microM/L for tamoxifen, 1.6 microM/L for cyclosporin A, and 2.5 microM/L for verapamil respectively in HCC lines. As expected, verapamil alone with the physiologically achievable concentration at which we tested didn't enhance the doxorubicin cytotoxicity in the HCC lines. Furthermore, any verapamil combination with cyclosporin A or tamoxifen was not effective in overcoming the doxorubicin resistance in the high MDR1 expressor (Hep-G2) line. However tamoxifen reduced the IC50 of doxorubicin by a factor of 1.9 in the low MDR1 expressor (SK-Hep1) and 1.1 in the high MDR1 expressor line (p < 10(-5) respectively). Of interest, combinations of tamoxifen and cyclosporin A showed a significant reduction in the IC50 of doxorubicin in both HCC lines. The IC50 of doxorubicin was reduced by a factor of 3.9 and 1.3, i.e., from 0.023943 micrograms/ml to 0.006157 micrograms/ml (p < 10(-5)) in the SK-Hep1 cell line, and 0.068819 micrograms/ml to 0.052442 micrograms/ml (p < 10(-5)) in Hep-G2 respectively when tamoxifen and cyclosporin A were administered together. Both the estrogen and progesterone receptors in the SK-Hep1 and Hep-G2 lines were less than 0.01 fmol/mg of cytosol protein, respectively. It is therefore suggested that the reversal of doxorubicin resistance is unrelated to their anti-estrogenic activity in the HCC lines. Three modulator combinations of tamoxifen, cyclosporin A, and verapamil were not more effective than the combination of tamoxifen and cyclosporin A on the sensitivity to doxorubicin. MDR modulators of tamoxifen, cyclosporin A, and verapamil didn't reduce the IC50 of cisplatin to the clinically achievable concentration range in HCC lines. In summary, the combination of tamoxifen and cyclosporin A at the concentrations normally seen after clinical administration of these modulators showed significant synergism on the sensitivity to doxorubicin in both low and high MDR1 expressor HCC lines. These data indicate the need for in vivo trials.

Antineoplastic Agents↗

PubMed1992

High-performance liquid chromatographic determination of rifapentine in serum using column switching.

A high-performance liquid chromatographic method with column switching has been developed for the determination of rifapentine in serum. The serum samples were injected onto a precolumn packed with Corasil RP C18 (37-50 microns) after simple dilution with an internal standard in a 1% ascorbic acid solution. Polar serum components were washed out using 0.05 M phosphate buffer. After valve switching, the concentrated drugs were eluted in the back-flush mode and separated by a mu Bondapak C18 column with acetonitrile-tetrahydrofuran-0.05 M phosphate buffer (pH 7.0) (42:5:53, v/v/v) as the mobile phase. The method showed excellent precision with good sensitivity and speed, and a detection limit of 0.1 microgram/ml. The total analysis time was less than 25 min and the mean coefficients of variation for intra- and inter-assay were less than 4.8%. The method has been successfully applied to serum samples from dogs after the oral administration of rifapentine.

Animals↗

PubMed1992

The effect of hyperglycemia on lipid peroxidation in the global cerebral ischemia of the rat.

To investigate the influence of hyperglycemia on ischemic brain damage, we measured brain ATP, lactate and malondialdehyde (MDA) levels in global cerebral ischemic models of Wistar rats. We induced global cerebral ischemia by the 4-vessel occlusion method. After 30 or 60 min of occlusion, and after 30 min of reperfusion, we measured brain ATP, lactate and MDA levels. During the ischemic period, brain ATP levels decreased to 30-70% of sham groups both in normoglycemic and hyperglycemic groups. But during the reperfusion period, the recovery rate of ATP levels was significantly lower in the hyperglycemic than in the normoglycemic groups (p less than 0.05). After 60 min of global ischemia, brain lactate increased much more in the hyperglycemic than in the normoglycemic group, and, during reperfusion, was washed out slowly in the hyperglycemic group. The MDA level, a parameter of lipid peroxidation, increased more in the hyperglycemic group than in the normoglycemic group during reperfusion periods (p less than 0.05). We conclude that hyperglycemia increases lactate accumulation, delays the recovery of energy metabolism, and enhances the lipid peroxidation in the transient global ischemia of rat brain. These findings may suggest the harmfulness of hyperglycemia in clinical cerebral ischemia.

3,4-Methylenedioxyamphetamine↗

PubMed1992

MR imaging of the internal carotid artery in ischemic cerebrovascular disorders--clinical and angiographic correlation.

This study was intended to correlate the appearance of the cavernous segment of the carotid artery on MR images with the presence of significant stenosis or occlusion of the cervical carotid artery as seen on angiograms in 37 patients with cerebrovascular disorders who had brain MRI and arteriography. Three patients demonstrated an isointense signal within the carotid artery's cavernous segment, correlating with complete carotid occlusion as seen angiographically. Ten patients had variable signal intensity and/or luminal narrowing in the carotid siphon; seven of these findings correlated with angiographic evidence of carotid occlusion, while carotid branch occlusion was seen angiographically in the other three. The demonstration of normal signal void within a normal-appearing cavernous segment of the internal carotid artery in the remaining 24 patients correlated with an absence of significant stenosis within the cervical segment in 21 patients. In the remaining three, significant disease of the internal carotid artery was found. Isointensity or luminal irregularity within the intracranial carotid artery can indicate complete occlusion or slow flow. The presence of normal flow void in the intracranial segment does not exclude significant abnormality of the cervical segment of the carotid artery.

Adolescent↗

PubMed1992

The value of immunohistochemical detection of P-glycoprotein in breast cancer before and after induction chemotherapy.

We have studied the patterns of P-glycoprotein expression before and after 3 cycles of induction chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) using immunohistochemically stained paraffin-embedded specimen of 28 patients with locally advanced breast cancer. The frequency of P-glycoprotein expression in untreated breast cancer turned out to be very low: only one out of 28 untreated, biopsy specimen at the time of diagnosis was positive. The frequency of P-glycoprotein expression was markedly increased from 9.1% before chemotherapy to 63.6% after induction chemotherapy (p = 0.006). After 3 cycles of induction chemotherapy, 25 patients had obtained clinical response to chemotherapy (4, CR; 21, PR). Eleven out of 25 tumors (44%) showing clinical response and all three tumors (100%) with minimal response have expressed P-glycoprotein. One out of 6 patients (16.7%) with microscopic residual tumor seen in mastectomy specimen expressed P-glycoprotein, whereas 13 of 22 patients (59.1%) with gross residual tumor showed the presence of P-glycoprotein (p = 0.08). The frequency of intrinsic P-glycoprotein expression in untreated breast cancer was quite low, but approximately half of the patients do acquire P-glycoprotein expression during the cycles of induction chemotherapy. Therefore, the results suggest that the immunohistochemical detection of P-glycoprotein on residual tumor cells after induction chemotherapy can predict acquired drug resistance in breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer?

Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended.

Adult↗

PubMed1992

Overexpression of erbB-2 protein in gastric adenocarcinoma--a potential role in therapeutic response to adjuvant 5-FU-doxorubicin regimen.

In order to study the influence of erbB-2 protein overexpression on outcome of patients with gastric cancer after attempted curative resection with or without adjuvant chemotherapy, paraffin embedded sections from 109 cases of primary gastric cancer with defined treatments have been immunostained for erbB-2 protein in a retrospective study. Thirty four cases (31%) showed strong membrane staining of tumor cells. erbB-2 overexpression did not show significant effect on outcome when all patients were considered. However, erbB-2 overexpression was an indicator for poor disease free survival (p = 0.0474), local relapse free survival (p = 0.0293), and overall survival (p = 0.0310) of the patients treated with surgery only (N = 51), while it did not show any effect on outcome of patients treated with 5-FU plus Doxorubicin (FA) as adjuvant chemotherapy (N = 58). Furthermore, the apparent therapeutic benefit from FA regimen was restricted to patients with erbB-2 positive tumors. Combined predictive value of erbB-2 and FA regimen was found to be significant in predicting local relapse in multivariate analysis (p = 0.0439). The data suggests that erbB-2 may be associated with an improved response to FA regimen and that erbB-2 should be included as a potential confounding variable in the analysis of the data from the clinical trials for gastric cancer.

Adenocarcinoma↗

PubMed1991

Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines.

We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from primary tumors and in all five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma.

Amino Acid Sequence↗

PubMed1991

Assessment of regional cerebral blood flow (rCBF) in ischemic stroke using Tc-99m HMPAO SPECT--comparison with CT and MR findings.

To assess the regional cerebral blood flow (rCBF) in ischemic stroke, we analyzed the findings of single photon emission computed tomography (SPECT) using technetium-99m hexamethyl propyleneamine oxime (Tc-99m HMPAO). The SPECT images revealed abnormal areas of decreased perfusion in 29 out of 31 subjects (93.5%), which represented a higher detection rate than those for CT and MR (89.5%, respectively). Also, the areas of decreased perfusion were frequently larger than the lesions on CT and MR. Areas of decreased perfusion remote from the CT/MR lesions were found in 10 patients, including 8 with crossed cerebellar diaschisis (CCD). Thus, studies of rCBF by Tc-99m HMPAO SPECT can be useful in the assessment of ischemic stroke.

Adolescent↗

PubMed1991

Alternating dissociated nystagmus with palatal myoclonus--a case report.

An extraordinary eye movement was seen in a vegetative patient. His eyeballs were exotropic in the primary position and showed dissociated nystagmus which appeared alternately in each eye every few seconds. He also had palatal myoclonus quite asynchronous with the nystagmus. To our knowledge, there has been no such nystagmus documented in the literature. We report the new nystagmus with his EOG and brain MRI.

Electrooculography↗

PubMed1991

Magnetic resonance imaging in brainstem ischemic stroke.

To evaluate the efficacy of magnetic resonance imaging in brainstem stroke, we studied 21 cases of clinically definite brainstem ischemic stroke with brain magnetic resonance imaging (MRI) and conventional computed tomography (CT). MRI demonstrated brainstem lesions in 79% of the cases (16.5 out of 21), while CT revealed 33% (7 out of 21) when cases with suspicious lesions counted as 0.5. Although MRI was done a few days later than CT in most cases, MRI was superior to CT in detecting the number and the size of ischemic lesions, with clear delineation of anatomy and visualization of the status of the blood flow in the vertebral-basilar artery. Disappearance of the flow signal void in the basilar artery can be an important clue in diagnosing occlusion or thrombus of the basilar artery. By delineating the extent and the location of the infarction, MRI findings allowed an interpretation of whether the ischemic vessel is a small basilar branch or a large vessel vertebral or basilar artery.

Adult↗

PubMed1991

Expression of prognostic factors (EGFR, ER) by immunohistochemical staining method in male breast cancer.

Twelve male patients with operable breast cancer were evaluated for the expression of prognostic factors by immunohistochemical staining assay. Seven patients were stage I & II, and five patients were stage III. Axillary lymph node positivity was 42%. Nine patients were nuclear grade I, three were nuclear grade II, and none were nuclear grade III. The expression rate of EGFR (epidermal growth factor receptor), ER (estrogen receptor) were 8.3%, 70.0% respectively. This limited data suggest better tumor behavior in male than in female breast cancer. Adjuvant treatment should be considered in male breast cancer just as in females, based on axillary lymph node and ER states.

Breast Neoplasms↗

PubMed1991

Coexisting mycosis fungoides and Hodgkin's disease as a composite lymphoma: a case report.

Within the past few years, an increasing number of reports of Hodgkin's disease following the diagnosis of, and frequently coexisting with, mycosis fungoides have appeared. Previously, Hodgkin's disease found in the lymph nodes of the patient diagnosed as mycosis fungoides was considered as a transformed form of the mycosis fungoides. But, now it has been proven that Hodgkin's disease and mycosis fungoides are histologically and immunohistochemically distinct disease entities. We report a well-documented case of a man who developed Hodgkin's disease and mycosis fungoides simultaneously as a composite lymphoma. Our case emphasizes the importance of considering the diagnosis of another lymphoma in patients with mycosis fungoides who have lymphadenopathy. The cutaneous mycosis fungoides and the Hodgkin's disease should be treated as an independent disease.

Adult↗

PubMed1990

Gd-DTPA enhanced MR imaging in intracranial tuberculosis.

Twenty-six patients with intracranial tuberculosis (Tb) (10 with acute meningitis, 5 with chronic meningitis, 5 with meningitic sequelae and 6 with localized tuberculoma(s)) were examined with MR before and after Gd-DTPA enhancement (0.1 mmol/kg), using 2.0T superconducting unit, and the images were retrospectively analyzed and compared with CT scans. Without Gd-DTPA enhancement, the MR images were generally insensitive to detection of active meningeal inflammation and granulomas. The signal intensity of granulomas was usually isointense to gray matter on both T1- and T2-weighted images, whether they were associated with diffuse meningitis or presented as localized tuberculoma(s). A few granulomas showed focal hypointensity on T2-weighted images. Calcifications seen on CT of the meningitic sequelae group usually appeared markedly hypointense on all spin-echo sequences. On Gd-DTPA enhanced T1-weighted images, abnormal meningeal enhancement indicating active inflammation was conspicuous, and the granulomas often appeared as conglomerated ring-enhancing nodules, which seems to be characteristic of granulomas. Thin rim enhancement around the suprasellar calcifications were observed in two out of 5 patients with meningitic sequelae. Compared with CT, MR detected a few more ischemic infarcts, hemorrhagic infarcts, meningeal enhancement and granulomas in the acute meningitis group, but missed small calcifications in the basal cisterns well shown on CT in the sequelae group. Otherwise, MR generally matched CT scans. MR imaging appears to be superior to CT in evaluation of active intracranial Tb only if Gd-DTPA is used, while CT is better than MR in evaluating meningitic sequelae with calcification.

Adolescent↗

PubMed1990

Adjuvant treatment of operable stomach cancer with polyadenylic.polyuridylic acid in addition to chemotherapeutic agents: a preliminary report.

A randomized trial of polyadenylic.polyuridylic acid [poly(A).poly(U)] in addition to chemotherapy was undertaken in patients with stomach cancer following curative gastrectomy. They were randomized into a group of 108 patients receiving chemotherapy plus poly(A).poly(U) and a control group of 116 patients receiving chemotherapy alone. Chemotherapy consisted of injections of 5-fluorouracil, 12 mg/kg once weekly and adriamycin, 40 mg/m2 once every 3 weeks, continuously after operation. Poly(A).poly(U) was infused in a 100 mg dose, once a week six times from 5 days after the first injection of chemotherapeutic agents and 6 months later in a half dose similarly. At 55 months after initiation of the trial, the mean follow-up periods were 24 months for both groups. It has been revealed that patients who received the combined treatment postoperatively showed a lesser mortality and lower rate of recurrence, both reflecting significant increases in overall (P less than 0.05) and relapse-free (P less than 0.02) survivals as compared to those who received chemotherapy alone. This effect is more pronounced in patients having moderately advanced lymphnode involvement (N1) than in patients without (N0) or more advanced (N2) involvement. Thus, poly(A).poly(U) appears to be an effective agent when used postoperatively with chemotherapy in stomach cancers.

Aged↗

PubMed1990

A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin.

We have treated 14 cancer patients with liposome-encapsulated doxorubicin (LED) at doses of 30, 45, 60, and 90 mg/m2. Nausea and vomiting, phlebitis, and stomatitis were minimal or absent at each dose, but dose-limiting granulocytopenia occurred at 90 mg/m2. Thrombocytopenia and/or anemia also occurred in all patients treated at 60 or 90 mg/m2. Complete alopecia was seen in one of three cases at 60 mg/m2 and all cases at 90 mg/m2. No hepatic, renal, or other major organ toxicities were encountered. Clinical cardiac toxicity did not occur in any patient, but the cumulative doxorubicin doses in 13 cases were less than 400 mg/m2. The plasma elimination of LED out to 24 hours was analyzed in terms of a two-compartment model. Depending upon the dose and the infusion time, maximum plasma concentrations ranged from 2.6 mumol/L to 36.89 mumol/L and the area under the plasma concentration x time curve (AUC) values ranged from 1.86 mumol/L x h/L to 49.57 mumol x h/L. These values are significantly higher than those expected for free doxorubicin. Urinary excretion of LED was approximately 10% after 24 hours. Doxorubicinol and doxorubicinone appeared at low levels in plasma 12 to 24 hours after injection. LED pharmacokinetics differ from those of free drug by the higher plasma levels and AUC of doxorubicin achieved, and by the low conversion of LED to metabolites. Overall, LED was well tolerated and produced only moderate nausea and vomiting and little stomatitis at myelosuppressive doses. The study also suggested that LED produces less venous sclerosis than free doxorubicin, but this requires further clinical verification.

Adult↗

PubMed1990

Gd-DTPA-enhanced MR imaging of the brain in patients with meningitis: comparison with CT.

Plain and Gd-DTPA-enhanced MR images of the brain were obtained in 18 consecutive patients with meningitis (eight with tuberculous, five with bacterial, three with viral, and two with fungal infections); the MR images were compared with CT scans. MR images were obtained on a 2.0-T superconducting unit with both T1- and T2-weighted pulse sequences before injection and with a T1-weighted sequence after injection of Gd-DTPA (0.1 mmol/kg) in all patients. In tuberculous meningitis, MR imaging depicted ischemia/infarct, hemorrhagic infarct of basal ganglia, meningeal enhancement at either basal cistern or convexity surface of brain, and associated small granulomas in a few more patients than CT did. In bacterial meningitis, primary foci of extracranial inflammation (i.e., mastoid, paranasal sinuses) and adjacent intracranial lesions including localized dural inflammation, subdural fluid collection, and/or brain parenchymal lesions were demonstrated much better on MR than on CT. Otherwise, MR images generally matched the CT scan. Although the plain MR images, both T1- and T2-weighted, were the most sensitive in delineating ischemia/infarct, hemorrhage, and edema, they were not as specific as Gd-DTPA-enhanced T1-weighted images and postcontrast CT scans in defining the active inflammatory process of the meninges and focal lesions precisely. We conclude that if Gd-DTPA is used, MR imaging appears to be superior to CT in the evaluation of patients with suspected meningitis. Precontrast MR is needed to delineate ischemia/infarct, edema, and subacute hemorrhage.

Adolescent↗

PubMed1990

Kinetics of isoniazid transfer into cerebrospinal fluid in patients with tuberculous meningitis.

For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively.

Administration, Oral↗