Sung-Joon Kwon

Phospho-Stat3 expression and correlation with VEGF, p53, and Bcl-2 in gastric carcinoma using tissue microarray.

The signal transducer and activator of the transcription (Stat)‐family of proteins are latent cytoplasmic transcription factors that transmit signals from cytokines and growth‐factor receptors to the nucleus. Stat proteins, especially Stat3 and Stat5, are constitutively activated in various solid tumors and hematological malignancies. However, the role of Stat3 signaling in gastric carcinoma has not yet been fully determined. This study was conducted to investigate the clinical value of phospho‐Stat3 expression in gastric carcinoma. Expression of phospho‐Stat3 (Tyr705), vascular endothelial growth factor (VEGF), p53, and Bcl‐2 was determined by immunohistochemical staining of tissue microarrays from 137 cases of resected gastric cancer specimens. We evaluated the relationships among phospho‐Stat3, VEGF, p53, and Bcl‐2 expression and the correlation between expression of these proteins and various clinicopathological factors, including overall survival. Phospho‐Stat3 nuclear expression was observed in 18.2% of the cases. Of the total number of cases, 68.6% were positive for VEGF, 40.1% for p53, and 11.7% for Bcl‐2. Phospho‐Stat3 expression correlated with VEGF (p=0.021) and Bcl‐2 (p=0.005) expression. Positive phospho‐Stat3 staining was significantly associated with poor pathological grade. However, there was no significant difference in other clinicopathological parameters, such as tumor stage (T, N, M), pathological type, relapse‐free survival, and overall survival between the phospho‐Stat3‐positive and ‐negative groups. Co‐expression of phospho‐Stat3 and VEGF was found in many patients with N3 and Stage IV disease. These results suggest that phospho‐Stat3 expression might be associated with angiogenesis, anti‐apoptosis, and tumor progression. Further studies are needed to determine the role of phospho‐Stat3 in gastric cancer.

Bronchobiliary Fistula after Radiofrequency Thermal Ablation of Hepatic Tumor

A broad spectrum of complications can occur after radiofrequency (RF) ablation of hepatic tumors, even though it has been accepted as a safe and effective technique for unresectable hepatic tumors. Recently, the rare complication of brochobiliary fistula was encountered after RF ablation in a patient with a metastatic tumor from stomach cancer. It was assumed to have developed from collateral damage to the adjacent diaphragm and lung base as well as biloma formation at the ablation zone. Symptomatic improvement was achieved by conservative management with an external drainage catheter, but the fistula was still persistent on a 2-month follow-up image.

Overexpression of phospholipase D suppresses taxotere-induced cell death in stomach cancer cells

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid (PA) and choline. There are at least two PLD isozymes, PLD1 and PLD2. Genetic and pharmacological approaches implicate both PLD isozymes in a diverse range of cellular processes, including receptor signaling, membrane transport control, and actin cytoskeleton reorganization. Several recent studies reported that PLD has a role in signaling pathways that oppose apoptosis and promote cell survival in cancer. In this study, we examined the role of PLD in taxotere-induced apoptosis in stomach cell lines; normal stomach (NSC) and stomach cancer cells (SNU 484). Taxotere treatment resulted in increase of PLD activity. To confirm the role of PLD in taxotere-induced apoptosis, PLDs were transfected into SNU 484 cells. Overexpression of PLD isozymes resulted in inhibition of taxotere-induced apoptotic cell death, evidenced by decreased degradation of chromosomal DNA, and increased cell viability. Concurrently, Bcl-2 expression was upregulated, and taxotere-induced activation of procaspase 3 was inhibited after PLDs transfection. However, when PLD was selectively inhibited by specific siRNA-PLD1 or -PLD2, taxotere-induced apoptosis was exacerbated in SNU 484 cells. On top of this, PA -- the product of PLDs, also resulted in upregulation of Bcl-2 in SNU 484. Although PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of phospholipase A(2) (PLA(2)), increased Bcl-2 expression by PA was not abrogated by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Taken together, PLD1 and PLD2 are closely related with Bcl-2 expression together with PLA(2), but not with PAP, during taxotere-induced apoptosis in SNU 484 cells.

Effects of bridging groups on electronic structures of conjugated cyclic polymers

Summary form only given. Theoretical investigation was performed to elucidate effects of the bridging groups on the band gaps of conjugated cyclic polymers. In addition to poly(para-phenylene) and heterocyclic polymers such as polythiophene, polypyrrole, and polyfuran, the polymers concerned in this study include the conjugated cyclic polymers which contain bridging groups of an XY/sub 2/ form (CH/sub 2/, CF/sub 2/, SiH/sub 2/ and SiF/sub 2/) or an X=Y form (C=CH/sub 2/, C=O and C=S). Geometrical structures of the polymers were optimized through semiempirical band calculations with AM1 Hamiltonians. A modified extended Huckel method was employed to obtain electronic structures of the polymers. Effects of the bridging groups on band gaps of the polymers were analyzed in terms of geometrical relaxations and electronic perturbations.

The TSP motif in AP180 inhibits phospholipase D1 activity resulting in increased efficacy of anticancer drug via its direct binding to carboxyl terminal of phospholipase D1

Phospholipase D (PLD) has two isoforms, PLD1 and PLD2. Both isoforms are possible candidates for the development of anticancer drugs, since PLDs in several cancer cells act as survival factors. The aim of this study was to elucidate the inhibitory mechanism of PLD1 by AP180 in human cancer cells. Transfection of the human AP180 (hAP180) gene markedly inhibited phobol-12-myristate 13-acetate-induced PLD activity resulting in exacerbation of anticancer drug-induced cell death. Experiments using deletion mutants of hAP180 showed that three amino acids (Thr312-Pro314) are critical for inhibition of PLD1 activity by binding directly to PLD1, and, of these, Ser313 was the most important residue for both binding to and inhibiting PLD1. However, this inhibitory relationship did not exist between hAP180 and PLD2. In addition, the C-terminal region of PLD1 is important for the interaction with hAP180. These results indicated that Thr312-Pro314 (especially Ser313 as a phosphorylation residue) of hAP180 can regulate hPLD1 activity through binding with the C-terminal region of PLD1.

Combination chemotherapy of heptaplatin, paclitaxel and 5-fluorouracil in patients with advanced gastric cancer: a pilot study.

PURPOSE To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. MATERIALS AND METHODS Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m(2) iv on day 1, heptaplatin 400 mg/m(2) iv on day 2 and 5-fluorouracil 800 mg/m(2) on day 2 approximately 4 were administered and the regimen was repeated every 3 weeks. RESULTS The median age of the patients was 60 years (range: 32 approximately 74) and the most common sites of metastasis were liver and lymph nodes. In the 16 evaluated patients, the overall response rate was 43.8%, but this was without any complete response. The median time to disease progression was 3.93 months (range: 0.26 approximately 8.1) and the median response duration for the 7 responding patients was 3.83 months (range: 1.48 approximately 6.07). The median overall survival for 19 patients was 7.01 months (range: 0.26 approximately 17.44). A median of 3 cycles (range: 1 approximately 7) and a total of 65 cycles were administered and evaluated for toxicity. The most common hematologic toxicities were NCI grade I/II anemia (47.7%), neutropenia (9.2%) and thrombocytopenia (6.2%). The most common non-hematologic toxicities more than grade II were nausea/vomiting (30.8%/9.2%). One elderly patient with ECOG 2 had a life-threatening complication of pneumonia. CONCLUSION The combination of heptaplatin, paclitaxel, and 5-fluorouracil showed significant activity and favorable toxicity profiles in patients with advanced gastric cancer. However, one elderly patient who had poor performance experienced a life-threatening toxicity/complication. Our results suggest that the efficacy of this combination chemotherapy can be maximized when administered to the patients with good performance status. Further studies with large numbers of patients and long-term follow-up study will be needed.

Metastasis to Minute Lymph Node in Gastric Cancer, Its Significance for Indication of Endoscopic or Local Surgical Treatments

In a recent case of limited gastric resection for early gastric cancer with submucosal invasion, we found metastatic carcinoma in a minute lymph node at the gastric serosa. In a prospective study to determine the incidence of such metastases, we studied 200 consecutive patients. Our data showed that minute gastric serosal lymph nodes occurred in 43 cases(22%). However metastatic carcinoma in early gastric cancer to these nodes was uncommon, occurring in 1 case(2.3%). It is concluded that even if metastasis to minute lymph nodes at the gastric serosa had been previously missed,they would not have affected the data base for the management of early gastric cancer, particularly for endoscopic or local surgical treatment, because of the rarity of metastasis to these lymph nodes. Nevertheless it should be noted that metastasis to minute gastric serosal lymph nodes can sometimes occur.