• Asian Pacific Journal of Cancer Prevention
• /
• 제15권2호
• /
• pp.1063-1063
• /
• 2014

• Journal of Gastric Cancer
• /
• 제13권1호
• /
• pp.58-64
• /
• 2013

Alpha-fetoprotein-producing gastric cancer is associated with poor prognosis because of frequent liver and lymph node metastasis. We present a case with synchronous liver metastasis who survived for 5 years. A 69-year-old man with upper abdominal pain was referred to our hospital. Gastrointestinal endoscopy revealed a Borrmann II-like tumor in the lower part of the stomach. Computed tomography revealed a tumor in the left lobe of the liver. Serum alpha-fetoprotein levels were markedly increased. We performed distal gastrectomy after administering oral tegafur/gimeracil/oteracil potassium and administered hepatic intra-arterial cisplatin injection. Liver metastasis showed partial response on computed tomography. Despite left hepatic lobectomy, further metastases to the liver and mediastinal lymph nodes became difficult to control. After sorafenib tosylate administration, stabilization of the disease was observed for 4 months. We conclude that hepatic intra-arterial chemotherapy and oral administration of sorafenib tosylate may potentially improve the prognosis in such cases.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권16호
• /
• pp.6929-6934
• /
• 2015

Background: Real life management of hepatocellular carcinoma occasionally deviates from guidelines for recommended therapy. Aims: To evaluate how frequent this deviation happens in our center and assess its impact on outcome. Materials and Methods: The treatment of 770 patients (87% males, mean age 57.8 years) was analyzed and the effect of deviation on outcome over 36 months was examined. Results: Of Barcelona Clinic liver cancer stages 0 and A patients, 65.8% received resection, ablation, liver transplantation or transarterial chemoembolisation for unresectable tumors more than 5 cm in diameter, and 34.2% received treatment recommended for later stages. Of stage B patients, 62.2% received recommended therapy, 34.3% of patients received supportive therapy or sorafenib and 3.5% received upward treatment stage migration. Among stage C patients, 7.6% received sorafenib, and most (79.2%) were given supportive care. Deviation from recommended therapy occurred in 34.2%, 37.7%, and 92.4% in stages 0-A, B and C. Survival of stage 0-A patients who received downwards treatment stage migration was lower than those who received recommended treatment (p <0.001). Upward treatment stage migration in stages B, C and D did not improve survival compared to those who received recommended treatment. Conclusions: Deviation from recommended therapy had a negative impact on survival in Barcelona Clinic liver cancer stage A patients.

• Journal of Life Science
• /
• 제22권11호
• /
• pp.1456-1462
• /
• 2012

Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권5호
• /
• pp.2539-2543
• /
• 2016

Background: In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. Materials and Methods: Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. Results: Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (p<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (p<0.001). Conclusions: Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended.

• Journal of Yeungnam Medical Science
• /
• 제30권2호
• /
• pp.152-155
• /
• 2013

Orbital metastasis from hepatocellular carcinoma is very rare, with only 14 biopsy-proven cases from hepa tocellular carcinoma cases reported in English literature and three cases reported in Korea. Common symptoms of orbital metastasis are proptosis, visual loss, ocular pain and oculomotor dysfunction. For its precise diagnosis, we can perform fine needle aspiration biopsy, orbit CT or MRI, and ultrasonography. Radiotherapy is the mainstay in the treatment of orbital metastasis. In addition, chemotherapy, hormonal therapy and surgical intervention can play a role in the treatment of orbital metastasis according to the primary cancer and symptoms. However, the prognosis of orbital metastasis is poor. We report herein a rare case of a patient with orbital metastasis from hepatocellular carcinoma, which was treated with various modalities that included resection, and who had good clinical and radiological responses to radiation therapy and sorafenib (Nexavar, Bayer HealthCare).

• The Korean Journal of Physiology and Pharmacology
• /
• 제26권5호
• /
• pp.367-375
• /
• 2022

Gastric cancer stem cells (GCSCs) are a major cause of radioresistance and chemoresistance in gastric cancer (GC). Therefore, targeting GCSCs is regarded as a powerful strategy for the effective treatment of GC. Atorvastatin is a widely prescribed cholesterol-lowering drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the mevalonate pathway. The anticancer activity of atorvastatin, a repurposed drug, is being investigated; however, its therapeutic effect and molecular mechanism of action against GCSCs remain unknown. In this study, we evaluated the anticancer effects of atorvastatin on MKN45-derived GCSCs. Atorvastatin significantly inhibited the proliferative and tumorsphere-forming abilities of MKN45 GCSCs in a mevalonate pathway-independent manner. Atorvastatin induced cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade. Furthermore, atorvastatin exerted an antiproliferative effect against MKN45 GCSCs by inhibiting the expression of cancer stemness markers, such as CD133, CD44, integrin α6, aldehyde dehydrogenase 1A1, Oct4, Sox2, and Nanog, through the downregulation of β-catenin, signal transducer and activator of transcription 3, and protein kinase B activities. Additionally, the combined treatment of atorvastatin and sorafenib, a multi-kinase targeted anticancer drug, synergistically suppressed not only the proliferation and tumorsphere formation of MKN45 GCSCs but also the in vivo tumor growth in a chick chorioallantoic membrane model implanted with MKN45 GCSCs. These findings suggest that atorvastatin can therapeutically eliminate GCSCs.

• Bulletin of the Korean Chemical Society
• /
• 제33권5호
• /
• pp.1571-1576
• /
• 2012

A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.

• Bulletin of the Korean Chemical Society
• /
• 제33권9호
• /
• pp.2991-2998
• /
• 2012

A series of new diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was synthesized and their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 9, 11, 12, 14, and 17-21 showed superior potency against A375P to Sorafenib. Over the NCI-60 cancer cell line panel, compound 14 possessing a methoxy group, amide linker, and 4-chloro-3-(trifluoromethyl)phenyl terminal ring showed the highest potency and broad-spectrum anticancer activity. Compound 13 showed high selectivity towards leukemia subpanel over other cancer types.

• Journal of the Korean Applied Science and Technology
• /
• 제26권1호
• /
• pp.29-37
• /
• 2009

This study is focused on the synthesis of urea and amide derivatives particularly, since the amide moiety is an essential binding group at the binding site. Urea derivatives 3-7 and 13-14 were obtained by reaction of 2-aminopyrimidines and other amines with diverse isocyanates in pyridine as a solvent under reflux. The urea derivatives were obtained in low yield because of the highly electron deficient nature of the amino group of the 2-aminopyrimidine. Amide derivatives 8-10 were obtained in moderate yields by reaction of compound 1 with aryl chloride derivatives. Also, arylamine 11 was synthesized by Buchwald-Hartwig amination in moderate yields. Most of the compound did not show good activity against A375P melanoma cells, compared with Sorafenib as control compound.