A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases.

Intraabdominal tuberculosis found by abnormal finding of ampulla of Vater / 대한내과학회지

No abstract available.

Effect of Ionizing Radiation on Homotypic Cell Adhesion, Cell-Matrix Adhesion, Matrix Metalloproteinases Excretion of High Mucin Producing HM7 Colon Cancer Cells

PURPOSE: To investigate the effect of ionizing radiation on high mucin-producing colon cancer cells, we evaluated homotypic cell adhesion, cell-matrix adhesion, and matrix metalloproteinases (MMPs) on HM7 cells. METHODS: After an irradiation of 60 Gy for 48 hours on HM7 cells, we evaluated cellular proliferation, colony-forming ability, homotypic adhesion, cell-matrix binding, and integrin subunit expressions. Also, alterations of MMPs expression were analyzed by using zymography. RESULTS: Cell proliferation of HM7 colon cancer cells was not remarkably affected even after high doses of radiation; however, clonogenic cell growth was significantly affected. Homotypic cell-cell adhesion and cell adhesion to ECM components and basement membrane protein matrigel were significantly increased after irradiation. Radiation induced expressions of cell surface integrin alpha2, alpha3, and beta1 subunits of HM7 cells. The activities of secreted MMPs (MMP-9 and MMP-2) were remarkably inhibited by radiation. CONCLUSIONS: These finding suggest the biologic characteristics of high-mucin-producing colorectal carcinomas. Even though the radiation-associated cellular alterations of HM7 cells with or without matrix proteins were not remarkably different from other cancer cell types studied, the radio-resistant behavior of high mucin producing HM7 cells may explain the aggressive characteristics of mucinous colorectal carcinomas.

Is the Invasive Approach for All the Upper Gastrointestinal Mesenchymal Tumors Necessary? / 대한소화기학회지

BACKGROUND/AIMS: Mesenchymal tumors are the most frequent submucosal tumors in gastrointestinal trail. We reviewed the mesenchymal tumors which are confirmed by pathology to examine whether the invasive approach of all mesenchymal tumors is necessary. METHODS: This study was performed on fifty-nine patients who has mesenchymal tumors confirmed by endoscopic or surgical resection from January 2000 to June 2004. RESULTS: Mesenchymal tumors consisted of thirty-six gastrointestinal stromal tumors (GISTs), 20 leiomyomas and 3 schwannomas. All the esophageal tumors were leiomyoma (12/12, 100%). In stomach, there were 32 GISTs (76.2%), 7 leiomyomas (16.7%) and 3 schwannomas (7.1%). And there were 4 GISTs (80.0%) and 1 leiomyoma (20.0%) in duodenum. Tumors less than 1 cm in maximal diameter were leiomyoma or GISTs with very low risk of aggressive behavior. 56.1% of the tumors larger than 1 cm consisted of low, intermediate or high risk GISTs. CONCLUSIONS: Biopsy must be considered according to its size and anatomic location of mesenchymal tumors. The invasive approach for every esophageal submucosal tumor is not necessary unless the size is very large, because most of them are benign in nature. However, the gastric submucosal tumor with more than 1 cm in diameter should be carefully and regularly followed up or biopsied because it cannot be assumed to be benign for any GIST more than 1 cm in size at the present time, safely.

Two Cases of Metronidazole-induced Encephalopathy / 대한소화기학회지

Metronidazole is a 5-nitroimidazole compound known as an antimicrobial agent widely used for the treatment of protozoal infection, anaerobic infection, Helicobacter pylori infection and hepatic encephalopathy. It may produce a number of neurologic side effects including peripheral neuropathy, seizure, encephalopathy, ataxic gait and dysarthritic speech. There have been ten or more reports of metronidazole-induced encephalopathy in the literatures including a few reports of brain imaging changes by magnetic resonance images (MRI). However, none of the case of metronidazole-induced encephalopathy in patients with hepatic encephalopathy has been reported yet. Recently, we experienced two cases of metronidazole-induced encephalopathy in patients with liver cirrhosis caused by chronic hepatitis B, which were diagnosed by brain MRI and MR spectroscopy. In this report, we present 2 cases of metronidazole-induced encephalopathy with MR imaging and MR spectroscopic changes including follow- up imaging performed after the discontinuation of the metronidazole with a review of the literatures.

Expression of Cdx2 Protein in Colorectal Cancer / 대한소화기학회지

BACKGROUND/AIMS: The caudal-related homeobox transcription factor, Cdx2, plays an important role in proliferation and differentiation of intestinal epithelial cells. Its expression is confined to normal and neoplastic intestinal epithelium. We evaluated Cdx2 expression in advanced colorectal cancers to determine the correlation between Cdx2 expression and clinicopathologic characteristics. METHODS: Four hundreds twenty consecutive colorectal cancers were included in the study. Cdx2 expression was investigated by immunohistochemistry using tissue microarrays constructed from surgically resected specimens. 145 invasive breast cancers, normal tissues from gastric mucosa, liver, lung, kidney and ovary were used as control. Nuclear staining was considered to be positive and the result was divided into 3 categories. RESULTS: In the colorectal cancers, Cdx2 was expressed in 380 of 420 (90.5%) cases, and 349 of 380 (83%) cases showed strong and diffuse staining and 31 of 420 (7.5%) cases showed weakly positive staining. Forty patients (9.5%) of colorectal cancer were negative for Cdx2. All of the invasive breast cancers and all non-neoplastic control tissues except the regions of intestinal metaplasia in gastric mucosa, which showed strong Cdx2 expression, were negative for Cdx2. Loss of Cdx2 expression was observed more frequently in cases with deeper invasion (p<0.05), lymph node metastasis (p<0.05), poor histologic differentiation (p<0.001), and distant metastasis (p<0.05). CONCLUSIONS: Cdx2 could be a highly sensitive marker to detect metastasis from intestine and might be useful as a novel prognostic marker in colorectal cancers.

Clinical Characteristics of Pancreatic Cancer According to the Presence of Diabetes Mellitus / 대한소화기학회지

BACKGROUND/AIMS: Pancreatic cancer is fatal with a dismal 6-month median survival from diagnosis. Diabetes mellitus is reported to be present up to 33.3 percent of patients with pancreatic cancer. The reason for the high frequency of diabetes is unknown. We studied the prevalence and duration of diabetes in patients with pancreatic cancer and the relationship between the two diseases. METHODS: A total of 152 patients with pancreatic cancer diagnosed at Yeungnam University Hospital from January 1999 to December 2001 were enrolled in this study. Clinical features, family history, smoking history, and characteristics of the tumor were compared between diabetic and non-diabetic groups. RESULTS: Among 152 patients with pancreatic cancer, 43 patients (28.3%) had diabetes. In diabetic group, mean age of diagnosis was significantly younger than non- diabetic group (62.0 +/- 7.2 vs. 65.0 +/- 8.8, p<0.05). Most of the patients with diabetes had non-insulin dependent diabetes mellitus (NIDDM) and did not have family history. Diabetes was diagnosed within 2 years after the diagnosis of pancreatic cancer in 35 patients (74.3%) of the diabetic group. There were no differences in the location and stage of tumor, chief complaints, presence of weight loss, and body mass index between the two groups. CONCLUSIONS: Diabetes mellitus occurs frequently in patients with pancreatic cancer and does not influence clinical features of pancreatic cancer. Pancreatic cancer should be suspected in patients with recent onset diabetes, especially in patients without family history of diabetes and with type of NIDDM.

Is Routine Second-Look Endoscopy Necessary for All Bleeding Peptic Ulcers? / 대한소화기내시경학회지

BACKGROUND/AIMS: Second-look endoscopy is generally performed to prevent rebleeding in patients with bleeding peptic ulcers. However, considering recent technologic advances of endoscopic hemostasis and decreasing rate of rebleeding, a small benefit with second-look endoscopy is suggested. Prospective study was carried out to evaluate the efficacy of second-look endoscopic examinations. METHODS AND RESULTS: One hundred thirty six patients with bleeding from peptic ulcer were included. Emergency endoscopic treatments consisting of the injection of hypertonic saline-epinephrine (HSE), band ligation and/or clipping were performed in patients with Forrest class I-IIb. They were scheduled to receive second-look endoscopy in 48 hours after initial endoscopy. Nine patients (6.6%) received endoscopic retreatment during second-look endoscopy and emergency endoscopic retreatment was required before scheduled endoscopy in six patients (4.4%) because of the evidence of rebleeding. Factors influencing retreatment were Forrest classification of initial endoscopy and methods of hemostasis. None of the patients with Forrest class IIb-III and the patients receiving endoscopic band ligation or clipping on initial endoscopy required retreatment during follow-up endoscopy. CONCLUSION: Routine second-look endoscopy may not be recommended after initial successful endoscopic treatment of peptic ulcer bleeding, especially in case of Forrest class IIb, IIc or III and in the patients treated with band ligation or clipping.

Ulcer healing effect of Helicobacter pylori eradication in patients with Helicobacter pylori-associated peptic ulcer / 대한내과학회지

BACKGROUND: Proton pump inhibitor-based triple therapy is effective first line treatment for Helicobacter pylori (H. pylori) infection. However, it is unclear that additional acid-suppression therapy should be continued for ulcer healing after eradication of H. pylori in patients with peptic ulcer diseases. We evaluated the effect of H. pylori eradication in the treatment of H. pylori-associated peptic ulcer diseases. METHODS: Eighty patients with endoscopically proven active peptic ulcers with H. pylori infection were randomized to receive either 1 week therapy of omeprazole 20 mg bid plus clarithromycin 500 mg bid plus amoxicillin 1000 mg bid alone (OCA group) or same regimen followed by 3 weeks of ranitidine 150 mg bid (OCAR group). Endoscopy, clinical assessments and urea breath test were performed after treatment. RESULTS: Overall healing rates of peptic ulcer after 4 weeks and 8 weeks of treatment were 89.7% and 97.4% in OCA group and 85.5% and 97.6% in OCAR group, respectively (p>0.05). The H. pylori eradication rates in OCA and OCAR group were 84.6% and 82.9%, respectively (p>0.05). Symptomatic relief rate after 4 weeks of treatment was 89.2% in OCA group and 92.5% in OCAR group (p>0.05). CONCLUSION: One-week OCA therapy without additional acid suppressing therapy seemed to be effective for the treatment of non-complicated H. pylori-associated peptic ulcer diseases. Further study will be necessary to evaluate the effect of H. pylori eradication in the treatment of peptic ulcer disease and factors affecting healing of the ulcer.

Epidermal Growth Factor Dependent Expression of Plasminogen Activator and Plasminogen Activator Inhibitor in Rat Hepatocytes in Primary Culture

PURPOSE: In order to clarify the the role of epidermal growth factor (EGF) in the regulation of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) during liver regeneration, we investigated the EGF-dependent gene expression of PA and PAI-1 in rat hepatocytes in primary culture. METHODS: Hepatocytes were isolated from rats using a two step perfusion technique and cultivated in dishes precoated with rat tail collagen. DNA synthesis of the hepatocytes by EGF treatment was measured with (3)H-thymidine incorporation. Gene expression for PAI-1, uPA and tPA was examined using Northern blot hybridization analysis. RESULTS: EGF treatment increased the (3)H-thymidine incorporation of the hepatocytes up to 36 hours and normal polygonal hepatocyte morphology was achieved simultaneously. tPA and PAI-1 mRNA were detected in the control hepatocytes. With the EGF treatment, the tPA mRNA level increased with time up to 48 hours, however the PAI-1 mRNA level rapidly increased to 1 hour and then decreased quickly to the control level. On the contrary, uPA mRNA was not detected in hepatocytes with or without treatment of EGF. The EGF-dependent induction of tPA and PAI-1 mRNA was a protein synthesis independent process. CONCLUSION: These results suggest that differential expression of tPA and PAI-1 mRNA by EGF in hepatocytes may play an important role in the regulation of liver regeneration. Among PAs, tPA seemed to be more important in EGF dependent growth or regeneration of primary hepatocytes in the rat since uPA mRNA was not induced in primary hepatocyte cultures in spite of EGF treatment.

Occipital Chondroid Chordoma

The authors present a case of occipital chondroid chordoma in a 12 year-old boy who presented with occipital mass amd mild tenderness but no neurologic symptoms or signs. On plain skull X-rays, there was an irregular calcific mass at the left occipital area. The CT scan revealed irregular extracranial calcific mass with intracranial extradural lentiform low density lesion at the left occipital area. Also, the occipital bone was thickened. Angiography showed hypervascular mass feeded by occipital artery of left ECA.

Clinical Analysis of Acute Subdural Hematoma

The outcome of acute subdural hematoma(SDH) had been generally unsatisfactory. The authors have analyzed the factors influencing the outcome of 70 patients who underwent acute SDH evacuation. Thirty five patients(50%) died and twenty two(31.4%) had a favorable outcome. A significant correlation was found between the outcome and the motor score at operation, the time interval to operation papillary response, type of operation and the Glasgow Coma Scale(GCS) at operation. But the patient's age, the mode of injury, the skull fracture, the degree of midline shift, the hematoma location, the type of brain swelling, the hematoma thickness, and the systolic blood pressure did not correlate with the outcome scale.

A Case of Intracerebral Sparganum Mansoni

A patient is reported with sparganosis of the intracerebral region involving sparganum mansoni. This 40-year-old man had complained of focal motor seizure in right exitremities during the 18 months before operation. Brain CT scan revealed worm-like linear enhancement in left frontoparietal area. Left frontoparietal osteoplastic craniotomy was performed and a live sparganum mansoni was successfully removed from intracerebral region. This is very rare case in which a live sparganum mansoni was removed from the intracerebral region.