Hugh C. Kim

Bio: Hugh C. Kim is an academic researcher from Ajou University. The author has contributed to research in topics: Leukemia & Stem cell. The author has an hindex of 27, co-authored 98 publications receiving 2381 citations. Previous affiliations of Hugh C. Kim include Rutgers University & University of Vermont.

Increased expression of cyclooxygenase-2 protein in human gastric carcinoma.

Abstract: Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein over-expression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.

Docetaxel 75 mg/m2 is Active and Well Tolerated in Patients with Metastatic or Recurrent Gastric Cancer: a Phase II Trial

Abstract: Objective: The aim of the present study was to confirm the efficacy and tolerability of docetaxel 75 mg/m 2 in a population of Korean patients with advanced gastric cancer. Methods: Patients with metastatic or locally recurrent gastric cancer received docetaxel 75 mg/m 2 by intravenous infusion every 3 weeks. Objective response rate was the primary endpoint. Results: Forty-five patients were enrolled. Most showed adenocarcinomas of the gastric antrum and/or body of the stomach. All showed metastases and two-thirds retained the primary tumour. Forty-four patients received at least one docetaxel infusion (‘treated’ population), with 40 patients evaluable for response. A total of 159 cycles (median three cycles) were administered, with mean duration of treatment 10.9 weeks. The objective response rate in the treated population was 15.9% (17.5% in the per protocol population), with stable disease in 25.0% of patients and progressive disease in 50.0%. Grade 3–4 neutropenia occurred in 36 (81.8%) patients and 36.1% of cycles. However, febrile neutropenia occurred in only two (4.5%) patients and 1.3% of cycles. Grade 3 anorexia, experienced by two patients (4.5%) and during 1.9% of cycles, was the most frequent non-haematological adverse event possibly or probably related to docetaxel. No grade 4 non-haematological events occurred. Conclusion: This study suggests that docetaxel 75 mg/m 2 is active in metastatic or locally recurrent adenocarcinoma with a low incidence of grade 3–4 adverse events. Docetaxel warrants further study in combination regimens for advanced gastric cancer.

Selective induction of apoptosis with proton pump inhibitor in gastric cancer cells.

Abstract: Purpose: To survive in an ischemic microenvironment with a lower extracellular pH, ability to up-regulate proton extrusion is critical for cancer cell survival. Gastric H + /K + -ATPase exchanges luminal K + for cytoplasmic H + and is the enzyme primarily responsible for gastric acidification. On the basis of the fact that blocking the clearance of acidic metabolites are known to induce the cell death, we hypothesized that pantoprazole (PPZ), one of gastric H + /K + -ATPase inhibitors used frequently to treat acid-related diseases, could inhibit growth of tumor cells. Experimental Design: Genomic DNA fragmentation, terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling assay, and annexin V staining were performed to detect PPZ-induced apoptosis. Mitogen-activated protein kinase activation and heat shock proteins expression were determined by immunoblot with specific antibodies. The antitumor effect of PPZ was evaluated in vivo by a xenograft model of nude mice. Results: After PPZ treatment, apoptotic cell death was seen selectively in cancer cells and was accompanied with extracellular signal-regulated kinase deactivation. By contrast, normal gastric mucosal cells showed the resistance to PPZ-induced apoptosis through the overexpression of antiapoptotic regulators including HSP70 and HSP27. In a xenograft model of nude mice, administration of PPZ significantly inhibited tumorigenesis and induced large-scale apoptosis of tumor cells. Conclusions: PPZ selectively induced in vivo and in vitro apoptotic cell death in gastric cancer, suggesting that proton pump inhibitors could be used for selective anticancer effects.