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Biomedical subjects

N K Kim

Publications and source records attributed to N K Kim.

At least 73 records · Page 4Linked to original sources
PubMed1998

Preimplantation diagnosis of non-deletion Duchenne muscular dystrophy (DMD) by linkage polymerase chain reaction analysis.

The use of preimplantation diagnosis for sex determination and detection of exon deletion means that unaffected babies can be born to parents suffering from Duchenne muscular dystrophy (DMD). However, those who do not have exon deletion should also be considered for further investigation. A new method, known as linkage analysis, has been developed to diagnose the presence of non-deletion DMD in preimplantation embryos. Linkage analysis uses informative intragenic and flanking markers to track the chromosome bearing the mutated gene. The present study reports the analysis of two polymorphic sites, in blastomeres biopsied from embryos from a female carrier of DMD. A single male embryo was obtained who had inherited alternate maternal alleles to the woman's affected surviving son, and this embryo was transferred.

Adult↗
PubMed1997

Alterations of p16INK4A and p15INK4B genes in gastric carcinomas.

BACKGROUND: It has been suggested that cyclin-dependent kinase inhibitors (CDKIs), including p16 and p15, are tumor suppressor genes. Alterations of CDKIs have been found in most types of cancer. However, little is known about the status of p16 and p15 genes, including methylation of the promoter region, in gastric carcinoma. METHODS: Thirty-six primary gastric tumors and 9 gastric carcinoma cell lines were examined for alterations of the p16 and p15 genes. Deletion of the p16 and p15 genes was assessed by Southern blot analysis, expression by Northern blot analysis, and mutation by polymerase chain reaction-single strand conformation polymorphism followed by direct sequencing. The methylation status of the 5' CpG island of the p16 gene was evaluated using methylation-sensitive restriction enzymes, and reversal of the transcriptional block of the p16 gene was determined by Northern blot analysis after treatment with 5-aza-2'-deoxycytidine. RESULTS: Homozygous deletions of the p16 and 15 genes from 2 of 9 gastric carcinoma cell lines were found. In contrast, no deletions were detected in 36 primary gastric tumors, and one primary tumor showed rearrangements of the p16 and p15 genes. Two gastric carcinoma cell lines showed a point mutation and an insertional mutation of the p16 gene, respectively; however, no point mutations were noted for the p16 and p15 genes in any of the primary gastric tumors. Constitutive levels of p16 mRNA expression in gastric carcinoma cell lines were quite heterogeneous; four gastric carcinoma cell lines had no detectable p16 mRNA and 6 gastric carcinoma cell lines had negligible expression of p15 mRNA. Of 10 primary gastric tumors, only 1 tumor expressed p16 mRNA. Furthermore, abnormal DNA methylation patterns of the p16 gene were found in 2 gastric carcinoma cell lines through the use of methylation-sensitive restriction enzymes. These cell lines lacked expression of p16 mRNA without deletions of the p16 gene. These transcriptional blocks were reversed by treatment with 5-aza-2'-deoxycytidine. CONCLUSIONS: Deletions or mutations of the p16 and p15 genes are uncommon in primary gastric carcinomas. However, defective mRNA transcription, sometimes by aberrant DNA methylation, might be one of the pathways of inactivation of the p16 gene that leads to the development of gastric carcinoma.

Adenocarcinoma↗
PubMed1997

Adjuvant radiation therapy in resectable rectal cancer: should local recurrence rates affect the decision?

Adjuvant external beam pelvic radiotherapy (XRT) for resectable rectal cancer has been mandated by the National Cancer Institute because of reported 20 to 50 per cent reductions in local recurrence rates. However, these series' reported local recurrence rates are 18 to 39 per cent in the nonradiated patients, which seems extraordinarily high compared to the 3 to 5 per cent rates reported by surgeons advocating proctectomy with complete mesorectal excision. This fact, coupled with the high cost of XRT ($11,000-$14,000), the risk of radiation injury to small bowel and the neo-rectum, and the failure of XRT to provide any survival advantage, raises questions as to the precise role of XRT for rectal cancer. The purpose of this study was to perform a review of 212 consecutive patients undergoing curative resection via low anterior resection (LAR) or abdominoperineal resection (APR) for rectal cancer between 1989 and 1993, focusing on local and distant recurrence rates and survival. The choice of surgery alone (SUR), preoperative radiation (PRE) (45 Gy), or postoperative radiation (POST) (45-50 Gy) was at the surgeon's discretion. There were no significant differences in male:female ratio (SUR, 83:60; PRE, 14:8; POST, 34:13) or type of procedure (SUR-LAR, 112:APR, 31; PRE-LAR, 5:APR, 17; POST-LAR, 30:APR, 17) between the groups. There were no significant differences in age between the preoperative and postoperative radiation groups (PRE, 64.0 +/- 2.4; POST, 59.2 +/- 1.7); however, age was significantly different (P < 0.05) between the surgery-alone and the postoperative radiation groups (SUR, 68.5 +/- 0.8; POST, 59.2 +/- 1.7). With a median follow-up of 49 months, there were no significant differences in local recurrence (SUR, 4.2%; PRE, 4.5%; POST, 2.1%); however, there was a significantly longer survival for the SUR group compared to the other groups (SUR, 45.9 months; PRE, 36.4 months; POST, 39.3 months; P < 0.05 least significant difference). The PRE group also had shorter survival compared to the other groups when only Stage II and III lesions were studied (S, 40.0 months; PRE, 28.3 months; POST, 39.3 months). Local recurrences based on TNM stage were: T1N0 (S, 0 of 27; PRE, 0 of 3); T2N0 (S, 4 of 4S; PRE, 0 of 7); T2N1 (S, 0 of 9; POST, 1 of 5); T3,4N0 (S, 2 of 37; PRE, 1 of 9; POST, 0 of 10); and T3,4N1,2 (S, 0 of 21; PRE, 0 of 3; POST, 0 of 30). The results of this series support the contention that proctectomy with complete mesorectal excision yields a 4.2 per cent local recurrence rate without the need for adjuvant XRT. In this series, if all the patients had received adjuvant radiation, an additional $2.2 million would have been added to the costs of medical care. Therefore, the potential risks, costs, and benefits of adjuvant pelvic XRT for rectal cancer must be weighed against optimal benchmarks for local recurrence rate for surgery alone.

Adult↗
PubMed1997

Long-term outcome after ileocecal resection for Crohn's disease.

The decision to operate on ileocecal Crohn's disease is usually tempered by concern for early recurrence and the potential for multiple small bowel resections that will render the patients a gastroenterological cripple. However, delays in surgical management may unnecessarily prolong the patient's disease state and risk complications from both medications and unchecked disease. The aim of this study was to report the long-term clinical outcome of patients undergoing ileocecal resection for Crohn's disease between 1970 and 1993. One hundred eighty-one patients underwent ileocecal resection for Crohn's disease during the study period, with a median follow-up of 14.3 years. The mean age at the first resection was 32.7 +/- 0.9 years, and the male female ratio was 79:102. The indications for the initial resection were intractability in 119 (68.4%), obstruction in 45 (25.9%), enteric fistula in 27 (15.5%), perforation in 16 (9.2%), intra-abdominal abscess in 7 (4.0%), and hemorrhage in 5 (2.9%). Postoperative complications included prolonged ileus in 13 (7.5%), pneumonia/atelectasis in 15 (8.6%), wound infection in 11 (6.3%), urinary tract infection in 10 (5.7%), intra-abdominal abscess in 7 (4.0%), and wound dehiscence in 1 (0.6%). There were no operative mortalities. Fifty-six (30.9%) developed a recurrence requiring further surgery, with the mean time interval between initial ileocecal resection and operation for recurrence being 72.3 +/- 7.6 months. A second recurrence developed in 19 patients (10.5%) with a mean time interval of 52.3 +/- 8.3 months. The most frequent sites of first recurrence were the preanastomotic ileum in 49 (87.3%), the postanastomotic colon in 10 (17.9%), other colonic sites in 16 (28.6%), and other small bowel sites in 2 (3.6%) and other sites in 4 (7.1%). The types of resection for first recurrence were ileal resection in 28 (50%), right hemicolectomy in 17 (30.4%), segmental colectomy in 6 (10.7%), total proctocolectomy in 3 (5.4%), and proximal small bowel resection in 2 (3.6%). The long-term follow-up of this patient cohort indicated that 125 (69.1%) had only one resection, 37 (20.4%) required two resections, 15 (8.3%) required three resections, 4 (2.2%) required four resections. The results indicate that ileocecal resection of Crohn's disease had a high rate of disease control obtained with low morbidity, and a low frequency of three or more bowel resections (2.2%). Therefore, surgical resection of ileocecal Crohn's disease should not be unduly delayed for fear of risking short bowel syndrome. This approach should minimize overall disease-related patient morbidity by avoiding long periods of chronic illness.

Adult↗
PubMed1996

Efficacy of in vitro treatment of chronic myelogenous leukemia cell line, K562 cells, using 4-hydroperoxycyclophosphamide, alpha-interferon and gamma-interferon.

Alpha-interferon (alpha-IFN) and gamma-interferon (gamma-IFN) are highly effective biologic agents in the treatment of chronic myelogenous leukemia (CML). 4-hydroperoxycyclophosphamide (4-HC) is the most commonly used chemotherapeutic drug when purging bone marrow contaminated with malignant cells. To investigate the efficacy of alpha-IFN, gamma-IFN and 4-HC as purging agents in CML patients, K562 cells, a human CML cell line, were treated in vitro with these drugs singly or in combination. The cytotoxic effect was evaluated by MTT assay. Data were analyzed for synergism by the median effect principle of Chou and Talalay. Using Southern blot analysis, the effect of purging on the suppression of bcr gene rearrangement was also evaluated. Alpha-IFN, gamma-IFN and 4-HC all showed good concentration-dependent cytotoxic effect. Median cytotoxic doses of alpha-IFN gamma-IFN and 4-HC were 0.03 microM 0.20 microM and 1.97 microM respectively, and molar ratios of median doses of alpha-IFN to 4-HC, gamma-IFN to 4-HC and alpha-IFN to gamma-IFN were 1:80, 1:10 and 1:8, respectively. The combination treatment of alpha-IFN and 4-HC, and gamma-IFN and 4-HC showed significant synergistic cytotoxic activities, but combination of alpha-IFN and gamma-IFN was antagonistic. Status of bcr gene rearrangements in K562 cells was not changed after the treatments. Our results appear to provide an efficient method for removing CML cells from the bone marrow of CML patients.

Antineoplastic Agents↗
PubMed1996

Prognostic factors of patients with thymoma.

OBJECTIVES: To analyze the prognostic factors influencing the survival of patients with thymoma, clinical characteristics, treatment modalities and survival of patients were evaluated. The efficacy of chemotherapy was also determined. METHODS: Retrospective study was done on one hundred patients whose diagnosis was confirmed pathologically at Seoul National University Hospital from 1981 to 1994. The staging was carried out according to the Masaoka system. Survival rate was calculated by the Kaplan-Meier method and prognostic factors were analyzed by a multivariate analysis (Weibull model). RESULTS: The stage of 100 patients was as follows: Stage I-50, II-6, III-27, IV A-10, IV B-7. The overall survival rates at 5 and 10 years after diagnosis were 73.1% and 58.7%, respectively. The 5-year survival differences, according to various prognostic factors, were as follows: 1) Stage: I-92.8%, II-100%, III-71.6%, IVA-25.9% and IVB-32.9% (p = 0.0029). 2) Age: < 60 years-79.5% and > or = 60 years-41.5% (p = 0.0489). 3) Extent of resection: Total patients: complete resection-87.6% and incomplete resection-50.5% (p > 0.05) Stage III: complete resection-66.7% and incomplete resection-75.5% (p > 0.05) 4) Myasthenia gravis: present-71.6% and absent-74.9% (p > 0.05) Seventeen patients were treated with a combination chemotherapy of Cyclophosphamide, Adriamycin and cisplatin(CAP). Two complete responses and seven partial responses (overall response rate of 53%) were observed with a median response duration of fourteen months. Combination chemotherapy with CAP was effective. CONCLUSIONS: Stage and age were the independent prognostic factors in patients with thymoma. However, the presence of myasthenia gravis or the extent of resection in stage III patients was not associated with the survival time.

Adolescent↗
PubMed1995

Differential expression of TIS21 and TIS1 genes in the various organs of Balb/c mice, thymic carcinoma tissues and human cancer cell lines.

As a part of a series of investigations on the functions of TIS21 and TIS1 genes, we measured in vivo 12-O-tetradecanoylphorbol-13-acetate (TPA) inducibility of primary response genes (TIS21, TIS8 and TIS1) in the Balb/c mice and the changes of TIS gene expression in thymic carcinoma tissues and A549 and NCIH69 human lung cancer cell lines. In vivo induction of the TIS genes (TIS21, -8 and -1) by intraperitoneal injection of TPA was dramatic only at the needle contact site, i.e. in the abdominal muscle, not in the thigh muscle. Expression of TIS21 and TIS1 in the Balb/c mice thymus, lung, stomach and spleen was very strong (Lim IK et al. 1994a), regardless of TPA injection. Thymic carcinoma tissues developed in SV40-T-antigen-containing transgenic mice did not express TIS21 and TIS1, and expressed TIS8 weakly. Interestingly, induction of TIS21 expression was obliterated in the human lung cancer cells; A549 cells completely lost the ability to express TIS21 after a combined treatment of TPA and cycloheximide. We also measured the induction of TIS genes by TPA and/or cycloheximide in Raw264.7 mouse macrophage cells and U937 human histiocytic lymphoma cells. However, the induction profile was quite different; repressed and deregulated expression in the U937 cells as compared to rapid and transient induction of TIS genes in the Raw264.7 cells. These data may suggest a repressed expression of TIS21 and TIS1 in the cancer tissues and cells derived from the organs that constitutively express TIS21 in mice and in human cancer cells.

Animals↗
PubMed1995

Structural organization of the mouse DNA repair gene, N-methylpurine-DNA glycosylase.

N-Methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, removes N-alkylpurines and other purine lesions induced in DNA by simple alkylating carcinogens. A mouse MPG cDNA clone was isolated from a lambda recombinant phage library of BALB/c mouse lung cell and characterized. Using the mouse MPG cDNA as a probe, the complete mouse MPG gene was isolated in two overlapping lambda recombinant genomic clones. The 6-kb gene has four exons containing 1,002 bp of coding sequence. The transcription start site was identified in the genomic sequence by primer extension of MPG mRNA from a mouse lung fibroblast cell line. The location of this transcription start site was confirmed by in vitro transcription with the promoter-containing plasmid template. Promoter function of the sequence 5' upstream of the transcription initiation site was shown by transient expression of the firefly luciferase reporter gene under the control of this sequence in transfected human and mouse cells. The mouse MPG promoter contains no TATA box, but has a CAAT element and is G.C-rich with putative AP2 elements and SP1-complementary sequences.

3T3 Cells↗
PubMed1995

Evaluation of bone metastases by Tc-99m MDP imaging in patients with stomach cancer.

The authors conducted a retrospective review of 234 bone scans of stomach cancer patients who had been diagnosed at the Seoul National University Hospital. In 106 of the 234 cases (45.3%), there were abnormal bone scan results, suggestive of bone metastases. The most common site of bone metastases was the spine, followed by the ribs, pelvis, femur, and skull. These sites were similar to those known for other malignant diseases. The incidence of bone metastases increased according to the duration of disease, especially within 12 months after diagnosis in patients with stage III gastric cancer. The incidence of bone metastases increased as the clinical stage increased. However, the incidence of metastases did not relate to gastric cancer pathologic type. The authors found 6 cases of "superscan" in the 234 bone scans (2.6%). The bone scan findings correlated positively with the level of serum alkaline phosphatase.

Bone Neoplasms↗
PubMed1995

The first documentation of Li-Fraumeni syndrome in Korea.

Li-Fraumeni syndrome(LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast cancer, soft tissue sarcoma, brain tumor, osteosarcoma, leukemia, and adrenocortical carcinoma. Recently, germ-line mutation of the p53 tumor suppressor gene has been implicated in this familial disorder. We report a case of a 25-year old woman who presented with bilateral breast cancer and uterine leiomyoma. Her mother had died of early-onset bilateral breast cancer. And her younger sister had breast carcinoma as well, which was identified at the age of 22, indicating her strong familial history. To test for the presence of the p53 germ-line mutation, we analyzed the genomic DNA from the peripheral blood of the proband and her sister by PCR-SSCP analysis of exon 5 through exon 8 of the p53 gene. As a result, a p53 mutation in exon 7 was detected in an allele, and it was shared with her sister as the same pattern. Sequencing analysis determined the altered nucleotide at codon 248(CGG > TGG) which is one of the most frequent mutation sites related to LFS. Therefore, this patient has the most consistent characteristic features of LFS phenotype and it is believed that this case is the first report of a family with Li-Fraumeni syndrome carrying the p53 germ-line mutation in Korea.

Adult↗
PubMed1995

Technetium-99m-labeled antigranulocyte antibody bone marrow scintigraphy.

UNLABELLED: Although bone scintigraphy is a sensitive method for detecting skeletal metastases, it is often equivocal for metastases due to poor specificity. This study evaluates 99mTc-antigranulocyte antibody (AGA) bone marrow scintigraphy in differentiating malignant from benign lesions, in 42 patients with skeletal tumors who had equivocal bone scans. METHODS: AGA scans performed approximately 1 wk after 99mTc-MDP bone imaging were visually assessed for the presence of concordant marrow defects. Final diagnoses were made from radiological results, follow-up bone scans or clinical evaluation for 12 mo or longer. RESULTS: The final diagnoses were: skeletal metastasis (19 patients), no metastasis (20 patients) and unconfirmed (3 patients). AGA scans could not determine the presence of a concordant defect in three patients because of overlying liver activity or previous irradiation of the region. Seventeen patients had bone marrow defects concordant with bone scan lesions, whereas 15/19 patients without metastasis had normal AGA scans. The sensitivity and specificity of AGA for detecting skeletal metastases were 100% and 79%, respectively. CONCLUSION: AGA scans had a low incidence of skeletal metastases in patients who had equivocal bone scans. Although a concordant marrow defect increases the possibility of metastasis, further radiological investigation to exclude benign disease is warranted.

Antibodies, Monoclonal↗
PubMed1994

Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta.

We have found several genetic changes in the TGF-beta-type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-beta. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-beta showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-beta express either truncated or no detectable TGF-beta type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-beta expresses a full-size type II receptor mRNA. Immunoprecipitation followed by Western blot analysis showed parallel changes in TGF-beta type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve genetic changes in the TGF-beta type II receptor gene itself or altered expression of its mRNA.

Carcinoma↗
PubMed1994

Transrectal ultrasonography in preoperative staging of rectal cancer.

A precise knowledge of the depth of invasion of tumor is essential for the planning of treatment of rectal cancer. Transrectal ultrasonography is a new diagnostic modality that has become useful in determining the depth of invasion preoperatively and the presence or absence of metastatic lymph nodes. Transrectal ultrasonography was used in preoperative staging of 36 patients with rectal cancer. Thirty three patients had a radical resection (17 low anterior resection, 15 abdominoperineal resection and 1 pelvic exenteration), one patient had a local excision. Two among these thirty four patients had preoperative radiotherapy. Preoperative transrectal ultrasonographic staging was compared with pathologic findings. In staging depth of invasion, the overall accuracy was 88.8 percent, overstaged in 5.8 percent, understaged in 5.8 percent. Transrectal ultrasonography is the more accurate method than CT in staging of depth of tumor invasion (61.8% vs 88.8%). In staging of lymph nodes, the overall accuracy of transrectal ultrasonography was 85.3 percent, sensitivity was 71.7 percent and specificity was 88.8 percent. Transrectal ultrasonography is a safe, inexpensive and accurate staging method in the assessment of both depth of invasion and nodal status.

Adult↗
PubMed1994

Multiple myeloma presenting as a testicular mass.

Primary testicular plasmacytoma is extremely rare and only a few cases have been reported. Testicular involvement in the course of multiple myeloma is just as rare and it implies a poor prognosis, expressing an acceleration of the malignant process. We present the case of a patient with multiple myeloma presenting as a testicular mass. The literature is reviewed and testicular involvement in plasma cell neoplasms is discussed.

Humans↗
PubMed1993

A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer.

BACKGROUND: With the introduction of cisplatin-containing regimens in the treatment of advanced gastric cancer, promising clinical results have been reported. A 61.5% response rate was observed with a combination of 5-fluorouracil (5-FU) infusion and bolus cisplatin; however, the superiority of cisplatin-containing regimens to other regimens has not been clearly verified in any randomized controlled studies. A prospective, randomized study of 5-FU and cisplatin (FP) versus 5-FU, doxorubicin, and mitomycin C (FAM) versus 5-FU alone (FU) in previously untreated patients with advanced gastric cancer is reported. METHODS: A total of 324 patients were entered into the trial and 295 patients (103 for FP, 98 for FAM, 94 for FU) were evaluable. The patients were randomized to receive FP, FAM, or FU after stratifying by the following factors: performance status, presence of measurable disease, and resection of the primary tumor. RESULTS: The overall response rate for patients with measurable disease in the FP arm was significantly higher than in the FAM and FU arms (51% for FP; 25% for FAM; 26% for FU). The durations of response for each arm, however, were not significantly different. Even though the median time to progression for the FP arm (21.8 weeks) was longer than that for the FAM arm (12 weeks; P < 0.05) and for the FU arm (9.1 weeks; P < 0.005), there was no statistical difference in overall survival among the three arms. Toxicity for all three regimens was moderate and consisted primarily of myelosuppression, nausea, vomiting, and alopecia. CONCLUSIONS: Although the FP regimen showed a significantly higher response rate and a longer time to progression than the FAM or FU regimens, a survival benefit was not observed.

Adenocarcinoma↗
PubMed1993

Radioimmunoscintigraphy of advanced gastrointestinal carcinomas employing I-131 labeled CEA-79 monoclonal antibody.

CEA-79 is a murine IgG2a type monoclonal antibody (MoAb) generated using purified CEA from culture supernatants of a human colon cancer cell line, LS174T. The association constant and immunoreactivity of the I-131 labeled CEA-79 ranged from 2.0 to 3.2 x 10(9) l/mole, and from 54 to 74%, respectively. The purpose of this study was to evaluate the feasibility of radioimmunoscintigraphy employing MoAb CEA-79 in patients with advanced gastrointestinal carcinomas. Two mgs of MoAb CEA-79 was labeled with 111 MBq (3 mCi) of I-131, and infused intravenously in 6 stomach cancer and 16 colon cancer patients. Out of 6 patients with stomach cancer, immunoscintigraphy was able to detect the tumors in 4 cases. However, immunoscintigraphy found out tumors in all patients with colon cancer. Moreover, 1 patient with stomach cancer and 2 patients with colon cancer showed increased uptake of MoAb in the tumor lesions despite normal serum levels of CEA. We could conclude that this antibody has a potential as a new imaging agent for the diagnosis of gastrointestinal carcinoma.

Adult↗