Biomedical subjects

J K Roh

Publications and source records attributed to J K Roh.

137 records · Page 8Linked to original sources

PubMedDate not supplied

Embryotoxic effects of SKI 2053R, a new potential anticancer agent, in rats.

SKI 2053R, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolan e] platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. The potential of SKI 2053R to induce embryotoxicity was investigated in the Sprague-Dawley rat. One hundred mated rats (sperm in vaginal lavage = Day 0) were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rats from Days 6 to 16 of gestation at dose levels of 0, 0.75, 1.5, and 3.0 mg/kg/d. All dams were subjected to caesarean section on Day 20 of gestation. At 3 mg/kg, reduced food intake, reduced body weight, and decreased liver weight were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of visceral and skeletal malformations occurred at an incidence of 18.5 and 6.0%, respectively. Characteristic malformations included dilated cerebral ventricle, anophthalmia, microphthalmia, fused or absent cervical arch, fused thoracic arch, fused thoracic centrum, and fused rib, among others. Delayed ossification of both sternebrae and metatarsals was also observed. There were no signs of maternal toxicity or embryotoxicity at 0.75 and 1.5 mg/kg. The results show that SKI 2053R is embryotoxic at a minimally maternally toxic dose in rats.

Animals↗

PubMedDate not supplied

Effects of 2-bromopropane on spermatogenesis in the Sprague-Dawley rat.

In 1995, 2-bromopropane (2-BP) was associated with occupational reproductive and hematopoietic toxicity in Korea. The effect of 2-BP on spermatogenesis, or Leydig cells, has not been determined in adult rats. In the present study, 40 ten-week-old Sprague-Dawley (SD) rats were treated orally with 3.5 g/kg/d of 2-BP for 3 consecutive days. At 1, 3, 5, 7, 14, 28, 42, and 70 d after treatment, testes were perfused with Karnovsky's solution or immersed in Bouin's solution, embedded in plastic or Epon and evaluated with light and electron microscopy. DNA ploidy distributions of testicular suspensions were determined by flow cytometry, which allowed comparison of quantitative spermatogenesis with histopathologic observations. Degeneration of spermatogonia was observed during Stages I-IV in seminiferous tubules on Day 1 after treatment. Spermatocytes, spermatids, Sertoli cells, and Leydig cells appeared normal in the early stage of the study. Whereas spermatid retention in Stages IX-XI was observed on Day 7 after treatment, depletion of spermatocytes and spermatids continued over time, followed by a marked increase of germ cells on Day 42 after treatment. However, the seminiferous tubules did not completely recover by study termination. Leydig cell cellularity increased mildly without any significant morphologic modification at the end of the study. Immunohistochemistry using an antibody against proliferating cell nuclear antigen (PCNA), showed an increased number of immunoreactive Leydig cells in the interstitium. In the flow cytometry analysis, proportions of diploid and tetraploid cells gradually decreased time-dependently until Day 28 after treatment, but showed an increase on Day 42, followed by a decrease on Day 70 after treatment. These data are strengthened by qualitative descriptions of lesions observed by histopathology. These results suggest that a high dose of 2-BP can decrease spermatogenesis by adversely affecting spermatogonia followed by depletion of spermatocytes, spermatids, and spermatozoa, with subsequent testicular atrophy. The atrophied testes may not regenerate completely. The number of Leydig cells may increase mildly with 10 weeks of recovery.

Animals↗

PubMedDate not supplied

Perioperative blood transfusions and prognosis in patients with curatively resected locally advanced gastric cancer.

Several reports have demonstrated an adverse effect of perioperative blood transfusions on the survival of patients with various solid tumors treated surgically. We retrospectively investigated the relationship between perioperative blood transfusions and the survival of 501 patients who underwent radical subtotal gastrectomy for locally advanced gastric cancer (stage II-IIIB) from January 1984 to December 1989. Three hundred and fifty-two patients (70.3%) received blood transfusions within the perioperative period. The transfused group included patients with tumors of larger size (5.1 vs. 4.4 cm, p = 0.001) and more advanced stage (stage IIIB: 27.6 vs. 10.7%, p = 0.0001) than the nontransfused group. Although the 5-year overall survival rate was significantly lower (52.9 vs. 66.7%, p = 0.026) in the transfused patients than the nontransfused, subgroup analysis according to the pathologic stage showed no statistically significant difference in survival in each stage between the two groups. In conclusion, we could not find any causal relationships between transfusion and prognosis in patients with curatively resected locally advanced gastric cancer. Circumstances such as advanced stage necessitating transfusions may be more important prognostic factors.

Blood Transfusion↗

PubMedDate not supplied

Overexpression of c-ErbB-2 protein in gastric cancer by immunohistochemical stain.

An immunohistochemical stain to the c-ErbB-2 protein was performed in 225 paraffin-embedded tissue blocks from patients with locally advanced gastric cancer who underwent curative resection. The overexpression of the c-ErbB-2 protein was observed in 27.4% of the patients. The c-ErbB-2 positivity showed a statistically significant correlation with nodal status and stage. The patients with an overexpression of the c-ErbB-2 protein had a tendency to a shorter survival than those without, but it was not statistically significant (p = 0.08). The 5-year survival rate after surgery was 54% in the negative staining group to the c-ErbB-2 protein and 49% in the positive staining group. This suggests that the c-ErbB-2 protein has a possible role in lymph node metastasis. Therefore overexpression of the c-ErbB-2 protein is a useful indicator of disease progression in gastric carcinoma patients who received curative surgery.

Adult↗

PubMedDate not supplied

Relationship between p53 overexpression and gastric cancer progression.

The relationship between p53 overexpression and clinicopathologic variables in gastric cancer was evaluated using 304 paraffin-embedded gastric tumor tissues. DO7, a murine monoclonal antiserum to p53 protein, was used for the immunohistochemical analysis. Positive staining was found in 129 tumors (42.2% of all tumors). Overexpression of p53 was not associated with sex, location of the tumor in the stomach or the type of Borrman's tumor. The overexpression rate of p53 protein was 30.4% (28/92) in stage II and 47.6% (101/212) in stage III (p = 0.007). While there was no significant association between p53 protein accumulation and T stage, there was a significant association with N stage, i.e. p53 overexpression was 27.4% (17/62) in the node-negative group and 46.3% (112/242) in the node-positive group (p = 0.011). In 79 patients, in whom corresponding primary gastric tumor and regional lymph node metastases were available, overexpression was found in 34 (43%) primary tumors and in 38 (48.1%) node samples, with a concordance rate of 67.1% in terms of p53 expression. Mean numbers of regional lymph node involvement by the tumor were 6.1 in the group with p53 overexpression and 5.2 in the group showing no immunoreactivity (p = 0.051). These findings suggest that p53 overexpression is related to gastric cancer progression and that immunoreactivity in the metastatic lymph nodes show the dependency on p53 expression in the primary tumor.

Adenocarcinoma↗

PubMedDate not supplied

Different expression patterns of MMP-2 and MMP-9 in breast cancer.

Among the many biological characteristics of cancer, the matrix metalloproteinase (MMPs) is essential for tumor invasion and metastasis. The relationship between MMP-2 and MMP-9 according to tumor progression has not been studied yet. We evaluated the synchronous expression and activation rate of MMP-2 and MMP-9 in breast cancer tissues and compared them to the clinical parameters in order to determine the clinical significance of MMPs and the possibilities of using them as a therapeutic target. The activity of MMPs was evaluated in 121 breast cancer tissues using zymography and the area of activation was calculated by computer-assisted densitometry in comparison to the activity of a positive control (HT-1080). In 121 tumor tissues, 32 (26.4%) did not express any form of MMPs and 19 (15.7%) showed both expression of MMP-2 and MMP-9. We observed that only one tissue expressed MMP-9 alone, while MMP-2 alone was expressed in 69 tissues. In 88 patients with MMP-2 and/or MMP-9 expression, we were unable to observe any correlation between the activity of MMPs expression or activation rate and the clinical parameters. But MMP-2 and MMP-9 activity increased according to T factor. Rapid production of MMP-9 occurred from T2 (p=0.046), while that of MMP-2 occurred from T3 (p=0.004). In conclusion, MMPs activity was organ specific. The major MMPs in breast cancer was MMP-2 and MMPs activity was different with tumor progression. When MMPs are a specific therapeutic target, we should use different inhibitors according to tumor size, in patients at the same stage.

Adult↗

PubMedDate not supplied

Alpha-fetoprotein-producing gastric cancer.

We measured the sero-positivity rate of serum alpha-fetoprotein (alphaFP) of gastric cancer patients by ELISA assay; forty-two curatively resected patients, 14 palliatively resected patients, 8 who received explo-laparotomy or bypass surgery and 18 patients with systemic metastasis. The sero-positive rate was 9.8% (8/82) and the positivity increased with cancer progression. Sex, age and pathological type were similar between alphaFP-positive and -negative patients. The overall synchronous hepatic metastasis rates in alphaFP-positive and alphaFP-negative groups were 37.5% (3/8) and 12.2% (9/74), respectively (p=0.08). The predictability of synchronous liver metastasis in eight alphaFP-positive patients were as follows: 37. 5% of total patients (3/8), 50.0% (3/6) of unresectable patients, and 60.0% (3/5) of patients with systemic metastasis. In three alphaFP-positive patient with liver metastasis, all the hepatic lesions were intrahepatic and multiple, while in alphaFP-negative patients, 67% (6/9) of the hepatic lesions was single intrahepatic lesion or surface nodule. The predictability of both synchronous and metachronous liver metastasis in alphaFP-positive gastric cancer patients was 75%. These findings suggested that, in advanced stomach cancer patients, especially in stage IV, alphaFP can be used in predicting liver metastasis during follow-up.

Adult↗

PubMedDate not supplied

Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma.

Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 were female with median age of 16 years (range 8-41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.

Adolescent↗

PubMedDate not supplied

Enhancement of gene transfer efficiency into human cancer cells by modification of retroviral vectors and addition of chemicals.

Retroviral vectors have recently experienced limited use in cancer gene therapy mainly due to poor transduction efficiency. To overcome this drawback, we attempted to enhance the transduction efficiency by employing different retroviral packaging cell lines and chemical additives. The retrovirus from the PG13 packaging cell line gave mostly higher or similar transduction efficiencies in a variety of human cancer cell lines compared to the retrovirus from the PA317, Bing, or FLYRD18 packaging cell line. A cationic liposome, especially Lipofectamine, significantly enhanced the transduction efficiency of a retrovirus. However, the retrovirus derived from the PG13 cell line could not infect the murine cell line efficiently even after Lipofectamine treatment. Furthermore, chloroquine did not improve the transduction efficiency regardless of the presence of chemical additives. These results, therefore, suggested that the transduction efficiency of a retrovirus in human cancer cells can certainly be improved when a proper packaging cell line is chosen. In addition, this study implied that Lipofectamine is a superb additive to enhance the transduction efficiency of a retrovirus via a specific virus envelope protein-receptor interaction for virus entry, and that receptor-mediated endocytosis does not seem to be the leading route of virus delivery to liberate a virus genome.

3T3 Cells↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Effects of interleukin-2 transduction on the human hepatoma cell lines using retroviral vector.

Gene therapy, using cytokine gene transduction, aims to increase the antigenicity of tumor cells, and to activate the immune effector cells, and thereby inducing tumor regression. With regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity we compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus. IL-2 secretion was 186 pg/10(6) cells/24 h in SK-Hep1 cell line and 147 pg/106 cells/24 h in Hep-3B cell line with N2A/IL-2 retroviral vector and was 55,000 pg/10(6) cells/24 h in Hep-3B cell line with LNC/IL-2 retroviral vector. in vitro sensitivity to peripheral blood monocytes was increased by 163.8-254% in IL-2 transduced hepatoma cell lines (Hep-3B/LNC/IL-2, Hep-G2/LNC/IL-2) compared to those of the parent cell lines. The tumor was formed in 1 of 3 BALB/c mice and all 3 nude mice with the injection of 1x107 cells. Simultaneous injection of 1x10(7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5x10(5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. After injection of 1x10(7) cells into five other nude mice, the tumor of the IL-2 transduced hepatoma cells (Hep-3B/LNC/IL-2) gradually disappeared, however, the tumor of the parent hepatoma cell line initially decreased and then gradually regrew 20 days later. In conclusion, IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes. IL-2 secretion by LNC/IL-2 retrovirus from the hepatoma cell lines was more prominent compared with that by N2A/IL-2 retrovirus. IL-2 transduction into the hepatoma cells resulted in increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, which leads the regression of the tumors. However, the higher the tumor burden, the less efficient tumor regression by IL-2 transduction into the hepatoma cell line in nude mice was observed.

Animals↗