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Biomedical subjects

M Sung

Publications and source records attributed to M Sung.

At least 19 recordsLinked to original sources

IFNgamma secretion following stimulation with total tumor peptides from autologous human tumors.

Several issues remain to be resolved before the efficacy of various approaches to elicit anti-tumor immunity in patients can be evaluated. First, in vitro assays able to detect responses by T cells primed in vivo are needed. Second, a source of tumor antigen to stimulate patients' lymphocytes in vitro is required. The ELISPOT assay is attractive, because it can be performed with a small numbers of cells and requires only short-term culture in vitro. A source of tumor antigen is more problematic, since for most tumors, tumor-associated antigens (TAA) have not been identified and/or cloned. In this report we demonstrate that autologous antigen-presenting cells (APC) pulsed with total tumor peptides from autologous tumor tissue can stimulate IFNgamma release by patients' lymphocytes in the ELISPOT assay. Thus, this approach should be considered for monitoring immune responses in clinical immunotherapy trials.

Antigen Presentation↗

Asp 280 residue is important in the activity of the Escherichia coli leader peptidase.

Leader peptidase is a novel serine protease in Escherichia coli, which catalyzes the cleavage of amino-terminal signal sequences from exported proteins. It is an integral membrane protein containing two transmembrane segments with its carboxy-terminal catalytic domain residing in the periplasmic space. Recently, the x-ray crystal structure of signal peptidase-inhibitor complex showed that Asp 280, a highly conserved consensus sequence of E. coli leader peptidase is the closest charged residue in the vicinity of two catalytic dyad, Ser 90 and Lys 145, and it is likely held in place by a salt bridge to Arg 282. Possible roles of Asp 280 and Arg 282 in the structure-catalytic function relationship were investigated by the site-directed mutagenesis of Asp 280 substituted with alanine, glutamic acid, glycine, or asparagine and of Arg 282 with methionine. All of mutants purified with nickel affinity chromatography were inactive using in vitro assay. It is surprising to find complete lose of activity by an extension of one carbon units in the mutant where Asp 280 is substituted with glutamic acid. These results suggest that Asp 280 and Arg 282 are in a sequence which constitutes catalytic crevice of leader peptidase and are essential for maintaining the conformation of catalytic pocket.

Aspartic Acid↗

Cryoablation of unresectable malignant liver tumors.

BACKGROUND: Unresectable malignant liver tumors, particularly metastases of gastrointestinal origin, are rapidly lethal in a vast majority of patients, regardless of treatment. PATIENTS AND METHODS: We evaluated 58 patients by laparoscopy and/or laparotomy. Thirty-nine were treated with cryoablation of liver tumors using a liquid-nitrogen cryoprobe delivering a tumoricidal temperature of -196 degrees C with intraoperative ultrasound monitoring. Histologic evaluation showed that 25 patients had colorectal metastases, 3 had gastric tumors, 4 hepatocellular carcinomas, 6 carcinoids, and 1 gastrinoma. RESULTS: All patients who received complete cryoablation are alive with a mean follow-up of 14 months. Five whose treatment could not be completed died between 3 and 9 months postoperatively. Thirteen patients (28%) have recurrent disease and 20 (51%) have no evidence of disease. There were no operative mortalities. Postoperative transient elevation of liver function tests and thrombocytopenia were noted. All patients received postoperative chemotherapy. CONCLUSION: Cryoablation is an active and safe treatment for advanced liver malignancies.

Adult↗

Surgical treatment of spinal cord compression from epidural metastasis.

PURPOSE: A retrospective study of the results of neoplastic cord compression was undertaken to determine the effectiveness of surgical treatment and to assess quality of life in patients undergoing extensive procedures with potential morbidity. PATIENTS AND METHODS: Over a 5-year period (1989 to 1993), a total of 110 patients underwent surgery. Fifty-five patients (50%) had undergone prior treatment, including 47 (43%) who had failed to respond to prior irradiation (RT). Before surgery, 48 patients (44%) were nonambulatory, with severe paresis being present in 20. Surgery included staged anterior-posterior resections in 53 patients (48%), anterior resections in 33 (30%), and posterior resection in six (5%), all of whom required spinal instrumentation for reconstruction; only 18 patients underwent resection without instrumentation. RESULTS: Postoperatively, 90 patients (82%) were improved, both in terms of pain relief and ambulatory status. Fifty-three patients (48%) experienced postoperative complications, related statistically to the following three factors: age over 65 years, prior treatment, and presence of paraparesis. The overall median survival duration was 16 months, with 46% alive at 2 years. Apart from primary tumor, the presence of preoperative paraparesis had the most significant impact on survival. CONCLUSION: Our data suggest that the effective surgical treatment of neoplastic compression requires anterior-posterior resection in most patients to achieve the goal of total tumor resection, with the majority requiring instrumentation. Long-term survival is feasible in a subset of patients with this aggressive surgical approach.

Adult↗

A multidisciplinary approach to hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: A multidisciplinary approach has been developed to evaluate and treat patients with cirrhosis and hepatocellular carcinoma (HCC). STUDY DESIGN: We evaluated 153 patients with cirrhosis and HCC. Fourteen patients with Child's A cirrhosis underwent resection. Transplantation was performed in 40 patients with HCC less than 5 cm (32 incidental, eight recognized preoperatively), in six patients with HCC 5 cm or greater not recognized preoperatively, and in 11 patients with recognized HCC 5 cm or greater; the latter 11 underwent transplantation in a multimodality protocol using pretransplant chemoembolization and intraoperative and postoperative chemotherapy. RESULTS: Among the 14 patients who underwent resection, the three-year survival rate was 39 percent. Among the 40 patients with HCC less than 5 cm who underwent transplantation, no tumor recurrence was observed. Among the six with HCC 5 cm or greater unrecognized preoperatively, three had tumor recurrence. Among the 11 with HCC 5 cm or greater enrolled in the protocol, there were no deaths and one recurrence at a mean of 433 days follow-up. The four-year survival rate for all patients who underwent transplantation with HCC was 56 percent (66 percent excluding the six patients with unrecognized HCC 5 cm or larger). CONCLUSIONS: Hepatocellular carcinoma less than 5 cm in patients with cirrhosis (Child's B or C) is an indication for hepatic transplantation. Hepatocellular carcinoma less than 5 cm in patients with cirrhosis (Child's A), although resectable, may in some cases be better treated by hepatic transplantation. Transplantation for HCC 5 cm or greater within a multimodality protocol has yielded excellent results at two years.

Aged↗