Report on the first meeting of the International Collaborative Group on Hereditary Gastric Cancer.
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Humans↗
Biomedical subjects
H K Yang
Publications and source records attributed to H K Yang.
Dissociation between plasma adrenocorticotropin and serum cortisol level during the early postoperative period after gastrectomy.
We demonstrated the dissociation between plasma adrenocorticotropin (ACTH) and serum cortisol levels during the early recovery period after radical gastrectomy in 9 of 31 patients with gastric adenocarcinoma. Patients with the dissociation between plasma ACTH and serum cortisol levels (DAC) showed a sustained elevation of serum cortisol level on the first or second postoperative day, while the plasma ACTH level returned to its preoperative state. These patients also had more advanced cancers (p < 0.05) and suffered from more postoperative complications (p < 0.05) than those without DAC. In these patients with DAC, serum cortisol and interleukin (IL)-6 levels remained higher on the second postoperative day than in those of the patients without DAC (21.80 +/- 1.57 vs. 13.68 +/- 0.72 microg/dl, p < 0.001, and 74.31 +/- 15.65 vs. 18.75 +/- 3.14 pg/ml, p < 0.001, respectively). On the second postoperative day, serum IL-6 levels showed a significant correlation with serum cortisol levels in all patients (r = 0.511, p < 0.01). These results suggest that the DAC during the early postoperative period after radical gastrectomy is associated with advanced stage of cancer and postoperative complication, and that the increased serum IL-6 level is at least in part responsible for maintaining the elevated serum cortisol.
Adenocarcinoma↗
Result of 11,946 gastric cancer treatment with immunochemosurgery.
Although the therapeutic results of gastric cancer have markedly improved, it still remains the most common of cancer deaths in Korea. Annually more than 700, and all together 11,946, gastric cancer patients were surgically treated from 1970 to 1998 at Seoul National University Hospital. Stage III gastric cancer is already a systemic disease, Radical surgery alone cannot cure the patient, and about 35% recurred within 2-3 years. To improve the prognosis of advanced gastric cancer, systemic treatment such as immunotherapy and chemotherapy is required in the early postoperative period to kill the micrometastatic or remaining cancer cells after curative resection. We evaluated the survival rate and prognostic factors for 9,262 consecutive patients from 1981 to 1996. The clinicopathologic variables used for evaluating prognostic values were classified into patient, -tumor- and treatment-related factors. The prognostic significance of treatment modality was evaluated in stage III gastric cancer. The five-year survival rates were 55.9% for overall patients and 64.8% for patients who received curative resection. Radical lymph node dissection was found to produce survival gains in patients with stage II and IIIa. For postoperative adjuvant therapy, immunochemotherapy was most effective in patients with stage III. In multivariate analysis, curability of operation, depth of invasion, and ratio of involved-to-resected lymph nodes were the significant prognostic factors. Consequently, early detection and real curative resection with radical lymph node dissection, followed by immunochemotherapy (particularly in patients with stage III gastric cancer) should be recommended as a standard treatment principle for patients with gastric cancer.
Adult↗
Transcriptional repression of the transforming growth factor-beta type I receptor gene by DNA methylation results in the development of TGF-beta resistance in human gastric cancer.
The transforming growth factor-beta (TGF-beta) signaling pathway subserves an essential tumor suppressor function in various cell types. A heteromeric complex composed of TGF-beta type I (RI) and type II (RII) receptors is required for TGF-beta signaling. We have identified a subset of human gastric cancer cell lines which are insensitive to TGF-beta and which express a low level of TGF-beta type I receptor mRNA relative to a gastric cancer cell line which is highly responsive to TGF-beta. Using these cells, we show that hypermethylation of a CpG island in the 5' region of the TGF-beta RI gene provides another potentially important mechanism of escape from negative growth control by TGF-beta. This hypermethylation was found in four of five human gastric cancer cell lines and five out of 40 (12.5%) primary tumors examined. In human gastric cancer cell lines, treatment with the demethylating agent, 5-aza-2'-deoxycytidine, resulted in increased expression of the TGF-beta RI gene, but not the RII gene. Transient transfection of an RI expression vector into the TGF-beta resistant SNU-601 cell line restores TGF-beta responsiveness. These findings suggest that one of the mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve aberrant methylation of CpG islands in the 5' region of the TGF-beta RI gene.
DNA Methylation↗
Truncation of the TGF-beta type II receptor gene results in insensitivity to TGF-beta in human gastric cancer cells.
The transforming growth factor-beta (TGF-beta receptor system has been implicated in the development of resistance to the growth-inhibitory effects of TGF-beta. It has been reported that resistance to TGF-beta correlates with inactivation of the TGF-beta type II receptor (RII). In the present report, we examine the genetic changes in the TGF-beta RII gene of human gastric cancer cell lines, SNU-5 and SNU-668, which we had previously reported to express truncated TGF-beta RII transcripts. By independent PCR and Southern hybridization analysis of genomic DNA, we found that the genomic sequence of TGF-beta RII is truncated after exon 2 in SNU-5 and after exon 3 in SNU-668. This was confirmed by sequencing the TGF-beta RII cDNA cloned from a SNU-5 cDNA library. Predicted TGF-beta RII protein of SNU-5 cells based on sequencing data contains only a part of extracellular domain of TGF-beta RII. We demonstrate that cotransfection of 3TP-Lux and wild type TGF-beta RII restores the TGF-beta responsiveness in SNU-5 cells, suggesting that genetic changes in the TGF-beta RII gene of SNU-5 cells are responsible for the loss of sensitivity to TGF-beta. This is the first report demonstrating that truncation of the TGF-beta RII gene is an alternative mechanism to inactivate the TGF-beta signal transduction pathways.
Amino Acid Sequence↗
Germline mutations of E-cadherin gene in Korean familial gastric cancer patients.
Gastric cancer is the most common cancer in Korea. Germline mutations of the E-cadherin gene have recently been identified in familial gastric cancer patients. We screened five Korean familial gastric cancer patients to investigate germline mutations of the E-cadherin gene. These patients fulfilled the following criteria: presence of at least two gastric cancer patients within first-degree relatives and one patient diagnosed before the age of 50 years. Abnormal band patterns were found in exons 6 and 10 in two familial gastric cancer patients by polymerase chain reaction-single strand conformation polymorphism analysis (probands from the SNU-G2 and SNU-G1001 families, respectively). DNA sequencing analysis of the E-cadherin gene of these two patients revealed missense mutations in each exon. The SNU-G2 proband harbored a missense mutation from aspartic acid (GAT) to glycine (GGT) at codon 244 in exon 6 of the E-cadherin gene, and the SNU-G1001 proband had a missense mutation from valine (GTG) to alanine (GCG) at codon 487 in exon 10. The SNU-G2 proband was diagnosed with gastric cancer at the age of 38; three brothers and two sisters had died of gastric cancer under the age of 50, and their mother had died of gastric cancer at the age of 63. The SNU-G1001 proband was diagnosed with gastric cancer at the age of 42 and one brother had died of gastric cancer at the age of 49. In summary, we found germline mutations of the E-cadherin gene in two of five Korean familial gastric cancer patients screened.
Adenocarcinoma↗
Detection of methylation damage in DNA of gastric cancer tissues using 32P postlabelling assay.
Gastric cancer is the most common cancer in Korea. The causes are still unknown but it has been speculated that gastric cancer is associated with consumption of foods rich in nitrates/nitrites or a high dietary intake of salt or pickled food. In the present study, we studied the level of alkylated DNA adducts formed in gastric cancer tissues in comparison with that in normal gastric mucosa. DNA was extracted from surgically removed gastric cancer tissues and patient-matched normal gastric mucosa. The level of N7-methyldeoxyguanosine was measured by 32P-postlabelling assay after high performance liquid chromatography (HPLC) enrichment. We found that the level of N7-methyldeoxyguanosine of gastric cancerous tissues was significantly higher than that of normal gastric mucosa (P=0.01685).
Adenocarcinoma↗
A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor.
A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system. The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain. Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter. A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay. Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region. Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene.
Cloning, Molecular↗
Nutritional status of gastric cancer patients after total gastrectomy.
A number of causes of malnutrition after total gastrectomy have been proposed. The purpose of this study was to assess nutritional status and to determine the cause of malnutrition after total gastrectomy. We studied 20 gastric cancer patients who had undergone total gastrectomy and immunochemotherapy and 6 normal controls. Nutritional status was assessed by dietary history, anthropometric methods, and serologic measurements. Malabsorption tests included the fecal fat excretion test, D-xylose absorption test, glucose tolerance test, vitamin B12 absorption test using dual isotopes, bacterial culture of jejunal aspirates, and jejunal biopsy. Weight loss was compared to the preoperative status in all patients (average 15%: 59.0 +/- 9.9 vs. 50.2 +/- 7.8 kg, preoperatively vs. postoperatively). Average daily calorie intake was 1586.2 kcal, which is lower than the normal intake of Korean adults (1838 kcal). Malnutrition of skeletal and visceral protein was not found. There was, however, severe fat malnutrition and a deficit of body fat. Postoperatively the body mass index was considerably lower than that preoperatively (22.2 +/- 0.4 vs. 18.9 +/- 0.4 kg/m2; preoperatively vs. postoperatively). With malabsorption tests, the daily excreted amount of fecal fat was 28.6 +/- 3.4 g (mean +/- SD) in patients and 6.9 +/- 0.2 g in controls. There was no significant malabsorption of carbohydrates. In 64.3% (9/14) of patients, vitamin B12 absorption was abnormal; and the serum concentration of vitamin B12, which was significantly related to malabsorption of this vitamin, was lower than normal in 73.7% (14/19). Bacterial overgrowth was not found, and there were no abnormal histologic findings in the jejunal mucosa. These results suggest that poor oral intake and fat malabsorption following total gastrectomy cause malnutrition and that fat malabsorption may be related to relative pancreatic insufficiency.
Body Weight↗
Correlation of expression of bombesin-like peptides and receptors with growth inhibition by an anti-bombesin antibody in small-cell lung cancer cell lines.
The murine anti-bombesin monoclonal antibody, 2A11, has been demonstrated to inhibit growth of some small-cell lung cancer (SCLC) cells in nude mice xenografts and in a clinical trial. To determine if the expression of bombesin-like peptides (BLP) and their receptors (GRP-R and NMB-R) correlate with an in vitro response to 2A11, we measured these parameters in seven SCLC cell lines. Gastrin releasing peptide (GRP) mRNA was detected in three of seven cell lines (NCI-H69, NCI-H345, NCI-H510) and neuromedin B (NMB) mRNA was detected in all seven lines using an RNase protection assay (RPA). Immunoreactive BLP was detected in the cell pellets of all lines (range 0.11-59.90 pmol/mg protein) by a solid phase GRP radioimmunoassay (RIA) using 125I-labeled 2A11. RPA detected GRP-receptor mRNA in two cell lines (NCI-H69 and NCI-H345) and NMB-receptor in three lines (NCI-H345, NCI-H510, and NCI-H660). Reverse transcriptase-PCR confirmed the presence of receptor mRNA in these lines and detected NMB-receptor in an additional three lines (NCI-H69, NCI-H82, and NCI-H187). Calcium mobilization in response to BLP stimulation was detected in the six cell lines expressing either GRP-R or NMB-R mRNA but not in NCI-N417, which had no detectable BLP-receptor. 2A11 (5 microg/ml) inhibited colony formation by 26-61% after 2 weeks in all cell lines except NCI-N417. Thus, growth inhibition by 2A11 requires the presence of at least one BLP-receptor. These findings may be useful in selecting patients with SCLC for treatment with 2A11.
Animals↗
Establishment and characterization of human gastric carcinoma cell lines.
We report 8 newly established gastric-carcinoma cell lines (SNU-216, 484, 520, 601, 620, 638, 668, 719) from Korean patients. Morphologic study was carried out using light and electron microscopes. CEA, alpha FP, and CA 19-9 and TPA in supernatant and in cell lysate were measured by radioimmunoassay. p53 and c-Ki-ras gene mutations were screened and confirmed by sequencing. The cell lines, derived from tumors with moderate differentiation, grew as a diffuse monolayer, and those from tumors with poor differentiation and minimal desmoplasia grew exclusively as non-adherent. Out of the 8 gastric-cancer cell lines, 5 had detectable levels of CEA both in supernatant and in cell lysate; there was no expression or secretion of alpha FP in these cells; 4 cell lines showed high levels of CA 19-9 in cell pellets. All cell lines except SNU-484 had high concentrations of TPA both in cell lysate and in supernatants. p53 mutation was found in 6 cell lines (75%): 2 (SNU-216 and SNU-668) had mutations in exon 6, and other 3 in exon 8. The c-Ki-ras mutation was found in 2 cell lines (25%), SNU-601 and SNU-668. The former showed GGT-to-GAT transition mutation at codon 12, while the latter showed CAA-to-AAA transversion mutation at codon 61. DNA profiles using restriction endonuclease HinfI and polymorphic DNA probes ChdTC-15 and ChdTC-114 showed different unique patterns; which suggests that these cell lines are unique and not cross-contaminated. We believe that the newly characterized gastric-cancer cell lines presented in this paper will provide a useful in vitro model for studies related to human gastric cancer.
Adult↗
A case of bilateral cavernous hemangioma associated with intracerebral hemangioma.
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Adult↗
Laparoscopic cholecystostomy for acute acalculous cholecystitis.
Acute acalculous cholecystitis (AAC) can occur in up to 18% of severely injured patients. Diagnosis is made by positive ultrasound findings of gallbladder sludge, hydrox, and wall thickening. There may also be recent-onset jaundice, positive ultrasound induced Murphy's sign, and unexplained sepsis. Mortality can be as high as 50%. Laparoscopic confirmation was obtained in six ICU trauma patients when omentum was drawn up over a distended gallbladder. Laparoscopic cholecystectomy (LC) was done by first directly decompressing the gallbladder through the fundus. This trocar was replaced by a 16 French Foley catheter passed through an Endoloop into the gallbladder and secured by tightening the loop around a cuff of gallbladder. Sepsis resolved in all cases. Only one required subsequent laparoscopic cholecystectomy. LC has a low morbidity and may be life saving during the early stages of AAC. It is not indicated in gangrene or perforation of the gallbladder.
Acute Disease↗
Overexpression of the 67 kD laminin receptor correlates with the progression of gastric carcinoma.
This retrospective study was designed to investigate the relationship between overexpression of the 67 kD laminin receptor (67LR) using immunohistochemistry, and several clinicopathological parameters including overall survival in human gastric adenocarcinoma. We stained paraffin-embedded sections of 93 resected primary gastric adenocarcinomas using a polyclonal antibody specific for the 67LR as well as monoclonal antibodies for p53 protein, epidermal growth factor receptor, proliferating cell nuclear antigen, carcinoembryonic antigen and chromagranin. The results showed statistically significant correlations between overexpression of the 67LR and types of early or advanced gastric carcinoma (p < 0.001), depth of invasion (p < 0.001), WHO histopathologic classification (p < 0.001), stage (p = 0.001), expression of p53 protein (p = 0.019), expression of epidermal growth factor receptor (p < 0.001) and proliferating cell nuclear antigen labeling index (p = 0.002). A lower proportion of signet ring cells revealed a higher percentage of overexpression of 67LR in both early (p < 0.002) and advanced (p < 0.001) gastric carcinomas. Intestinal type adenocarcinoma (according to Lauren's classification) revealed a higher percentage of overexpression of the 67LR than the diffuse type in both early (p = 0.057) and advanced (p < 0.001) gastric carcinomas. The correlations between overexpression of the 67LR and lymph node metastasis were statistically significant (p < 0.07). Although the overexpression of the 67LR tended to correlate with lower survival rates, the correlation was not statistically significant due to the limited sample size. Our data revealed that overexpression of the 67LR is correlated with the progression of gastric carcinoma. The expression of the 67LR may be important as one of the steps which determines invasiveness during the progression of cancer.
Adenocarcinoma↗
Iatrogenic "respiratory acidosis" during laparoscopic preperitoneal hernia repair.
This is the first report, to our knowledge, of a case of massive subcutaneous emphysema during totally preperitoneal laparoscopic hernia repair causing a "respiratory acidosis" with a systemic pH 7.20 and a pCO2 of 64 and PO2 of 84. The acidosis was corrected by increased mechanical ventilation. It appears that because of its lack of defined borders, the preperitoneal space is particularly vulnerable to the formation of massive subcutaneous emphysema. Thus, there is a large potential surface area for CO2 absorption. The complication may be prevented by increased attention to the length of fascial incisions, inflation of balloon expanding devices, and securing gripping devices in the port sites.
Acidosis, Respiratory↗
Resection of Dieulafoy's lesion by a combined endoscopic and laparoscopic approach.
Dieulafoy's lesion is a vascular malformation, usually of the stomach but occasionally of the small or large bowel. It is an uncommon but clinically significant source of massive upper gastrointestinal (GI) hemorrhage. The lesion is generally located high on the lesser curvature in the proximal stomach. Although most bleeding can be controlled endoscopically, surgery is occasionally required. The traditional approach was open laparotomy, gastrotomy to localize the lesion, followed by partial gastrectomy or wedge resection. The following case report describes and illustrates a method of intraluminal endoscopic localization of the lesion followed by laparoscopic gastric wedge resection using a 3-port technique.
Aged↗
Laparoscopic management of peritonitis in the setting of an infected Tenckhoff catheter: a case report and description of technique.
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Adult↗
TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract.
Patients who initially develop an upper aerodigestive tract cancer have an increased risk of second primary cancers. We examined TP53 and RAS mutations and p53 protein in 21 tumors from 10 patients with upper aerodigestive tract cancer who developed a metachronous tumor, to assess the genetic changes that occur in multiple primary tumors from the same individual. Thirteen of 21 (62%) tumors were found to have mis-sense mutations of either TP53 or RAS. Six tumors had TP53 mutations in codons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K-RAS. Only one patient had concordance of a mutation in 2 tumors; this mutation occurred in K-RAS and was accompanied by discordance of TP53 mutation. Three patients had tumors discordant for both TP53 and RAS mutations. Smoking-related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and transitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohistochemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations are discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, supporting the concept that these cancers arise independently.
Adenocarcinoma↗