• Title/Summary/Keyword: carcinoma, hepatocellular

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HGFK1 is Associated with a Better Prognostis and Reverses Inhibition by Gefitinib in NSCLC Cases

  • Zhou, Xiao-Hui;Tang, Li-Na;Yue, Lu;Min, Da-Liu;Yang, Yi;Huang, Jian-An;Shen, Zan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1457-1461
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    • 2012
  • Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

Heterogenous Clinical Manifestations in Adult Patients with Late Diagnosis of Glycogen Storage Disease type Ia (성인기에 진단된 당원병 제 Ia형의 다양한 임상 양상)

  • Kim, Yoo-Mi;Cheon, Chong Kun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.1
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    • pp.9-17
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    • 2015
  • Glycogen storage disease (GSD) type Ia is rare inborn metabolic disorder, caused by glucose-6-phosphatase deficiency. It characterized by hepatomegaly, hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia and it is usually manifested in the infantile period. In addition, it is also associated with growth failure, pubertal delay, anemia, platelet dysfunction, osteopenia, and pulmonary hypertension. Hepatocellular adenoma and renal dysfunction are frequent late complications. Delayed diagnosis and inappropriate therapy lead to many complications such as growth failure, osteoporosis, refractory gout, renal failure, hepatocellular carcinoma (HCC), and pulmonary hypertension. Here, two Korean sisters diagnosed with GSD Ia, aged 33 and 36 respectively, were described and compared to recent articles about four adults with late diagnosis of GSD Ia. One sister had typical manifestations of GSD Ia including short stature (height, 145 cm), multiple hepatic adenoma, chronic kidney disease stage IV, and severe osteoporosis, whereas the older sister had normal stature (162 cm), one tiny hepatic nodule, and normal renal function. Direct sequencing of G6PC in two sisters identified a homozygous splicing mutation, c.645G>T, which is a prevalent mutation in Korea. Interestingly, our cases and four adults from recent reports had asymptomatic mild hypoglycemia and various manifestations including renal failure, HCC, fatty liver, or uncontrolled hyperlipidemia. These adult cases represent not only heterogenous phenotype to genotype within family members with GSD Ia but also long-term complications such as gouty arthritis, renal failure, and osteoporosis in untreated adult GSD Ia patients. In addition, lactic academia and hypertriglyceridemia are good markers of GSD Ia to distinguish from metabolic disease.

Comparative Study Between Respiratory Gated Conventional 2-D Plan and 3-D Conformal Plan for Predicting Radiation Hepatitis (간암에서 호흡주기를 고려한 2-차원 방사선 치료 방법과 3-차원 입체조형 치료방법에서 방사선 간염 예측의 비교연구)

  • Lee Sang-wook;Kim Gwi Eon;Chung Kap Soo;Lee Chang Geol;Seong Jinsil;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.455-467
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    • 1998
  • Purpose : To evaluate influences associated with radiation treatment planning obtained with the patient breathing freely. Materials and Methods : We compared reduction or elimination of planning target volume (PTV) margins with 2-D conventional plan with inclusion of PTV margins associated with breathing with 3-D conformal therapy. The respiratory non gated 3-D conformal treatment plans were compared with respiratory gated conventional 2-D plans in 4 patients with hepatocellular carcinomas. Isodose distribution, dose statistics, and dose volume histogram (DVH) of PTVs were used to evaluate differences between respiratory gated conventional 2-D plans and respiratory non gated 3-D conformal treatment plans. In addition. the risk of radiation exposure of surrounding normal liver and organs are evaluated by means of DVH and normal tissue complication probabilities (NTCPs). Results : The vertical movement of liver ranged 2-3 cm in all patients. We found no difference between respiratory gated 2-D plans and 3-D conformal treatment plans with the patients breathing freely. Treatment planning using DVH analysis of PTV and the normal liver was used for all patients. DVH and calculated NTCP showed no difference in respiratory gated 2-D plans and respiratory non gated 3-D conformal treatment plans. Conclusion : Respiratory gated radiation therapy was very important in hepatic tumors because radiation induced hepatitis was dependent on remaining normal liver volume. Further investigational studies for respiratory gated radiation.

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Validation of the OncoHepa test, a multigene expression profile test, and the tumor marker-volume score to predict postresection outcome in small solitary hepatocellular carcinomas

  • Ha, Su-Min;Hwang, Shin;Park, Jin Young;Lee, Young-Joo;Kim, Ki-Hun;Song, Gi-Won;Jung, Dong-Hwan;Yu, Yun-Suk;Kim, Jinpyo;Lee, Kyoung-Jin;Tak, Eunyoung;Park, Yo-Han;Lee, Sung-Gyu
    • Annals of Surgical Treatment and Research
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    • v.95 no.6
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    • pp.303-311
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    • 2018
  • Purpose: OncoHepa test is a multigene expression profile test developed for assessment of hepatocellular carcinoma (HCC) prognosis. Multiplication of ${\alpha}$-FP, des-${\gamma}$-carboxy prothrombin (DCP) and tumor volume (TV) gives the ${\alpha}$-FP-DCP-volume (ADV) score, which is also developed for assessment of HCC prognosis. Methods: The predictive powers of OncoHepa test and ADV score were validated in 35 patients who underwent curative hepatic resection for naïve solitary HCCs ${\leq}5cm$. Results: Median tumor diameter was 3.0 cm. Tumor recurrence and patient survival rates were 28.6% and 100% at 1 year, 48.6% and 82.9% at 3 years, and 54.3% and 71.4% at 5 years, respectively. The site of first tumor recurrence was the remnant liver in 18, lung in 1, and the peritoneum in 1. All patients with HCC recurrence received locoregional treatment. OncoHepa test showed marginal prognostic significance for tumor recurrence and patient survival. ADV score at 4log also showed marginal prognostic difference with respect to tumor recurrence and patient survival. Combination of these 2 tests resulted in greater prognostic significance for both tumor recurrence (P = 0.046) and patient survival (P = 0.048). Conclusion: Both OncoHepa test and ADV score have considerably strong prognostic power, thus individual and combined findings of OncoHepa test and ADV score will be helpful to guide postresection surveillance in patients with solitary HCCs ${\leq}5cm$.

Safety and Anticancer Effects of Platycodon grandiflorum Extracts (도라지 추출물의 안전성 및 항암 효과)

  • Kim, Soo-Hyun;Chung, Mi Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.4
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    • pp.516-523
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    • 2015
  • This study investigated the antimutagenic and anticancer effects of Platycodon grandiflorum extract (PGE) and its fractions against carcinogenic N-nitrosodimethylamine (NDMA) and genotoxicity. The Ames Salmonella mutagenicity test employing histidine mutants of Salmonella Typhimurium TA98 and TA100 was used to examine the mutagenicity of PGE and its fractions. Bacterial reversion assay with S. Typhimurium TA98 and TA100 did not show a significantly increased number of revertant colonies. The same test was used to examine the ability of PGE and its fractions to prevent acquisition of N-methyl-N'-nitro-N-nitrosoguanidine- and 4-introquino-line-1-oxide-induced mutations. PGE and its fractions inhibited mutagenesis in a dose-dependent manner. Among the fractions, ethyl acetate fraction from PGE (PGEA) exhibited a higher antimutagenic effect than other fractions. PGE and its fractions suppressed the growth of cancer cell lines, including human cervical adenocarcinoma, human hepatocellular carcinoma, human breast adenocarcinoma, human lung carcinoma, and transformed primary human embryonic kidney cells. In addition, we evaluated the antitumor activity of PGEA and its fractions in sacorma-180 solid tumor-bearing mice. In vivo anticancer activity results showed that PGE and its fractions could more effectively suppress tumor growth than the control. PGEA showed higher in vitro and in vivo anticancer effects than PGE and other fractions, and PGEA inhibited NDMA formation. Thus, we showed that PGEA has antimutagenic and anticancer activities, making it a candidate anticancer material under these experimental conditions.

Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

  • Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.5917-5935
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    • 2012
  • Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

A Case-Control Study of Primary Liver Cancer and Liver Disease History (간 질환력과 원발성 간암에 관한 환자-대조군 연구)

  • Kim, Dong-Hyun;Park, Byung-Joo;Yoo, Keun-Young;Ahn, Yoon-Ok;Lee, Hyo-Suk;Kim, Chung-Yong;Lee, Sang-Il;Lee, Moo-Song;Ahn, Hyung-Sik;Kim, Heon;Park, Tae-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.2 s.46
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    • pp.217-225
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    • 1994
  • The relationship between past liver disease history and the risk of primary liver cancer was analyzed in a hospital-based case-control study conducted in Seoul on 165 patients with histologically or serologically confirmed hepatocellular carcinoma and individually age- and sex-matched 165 controls in hospital for ophthalmologic, otologic, or nasopharyngeal problems. Significant association were observed for liver deseases occurring 5 or more years before liver cancer diagnosis [OR,4.9;95% confidence interval (CI), $1.6{\sim}14.0$) and family history of liver disease(OR, 9.0;95% CI, $2.1{\sim}38.8$). These associations were not appreciably modified by allowance for major identified potential confounding factors. From these results, it is possible to speculate that liver cell injuries caused by various factors might be a common pathway to developing primary liver carcinoma. Considering the significant effect of family history of liver diseases on PLCA risk after adjusting past liver disease history, there might be genetic susceptibility in the carcinogenic mechanism of liver cancer. Further investigations are needed to clarify the effect of family history of liver disease on PLCA risk.

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Effect of Clonorchis sinensis infection on hepatic oval cell proliferation in rats (랫트에서 Clonorchis sinensis 감염이 간 oval cell 의 증식에 미치는 영향)

  • Lee, Jae-Hyun;Yoon, Byung-Il;Park, Min-Kyung;Kim, Shin-A;Lee, Joon-Sang;Joo, Kyoung-Hwan;Kim, Han-Jong
    • Korean Journal of Veterinary Pathology
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    • v.2 no.2
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    • pp.95-106
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    • 1998
  • The prevalence of primary liver carcinoma (PLC) is relatively high in Clonorchis sinensis (CS) endemic areas in Korea. PLC is a malignant tumor which can be subclassified into hepatocellular carcinoma and cholangiocarcinoma(CC). CC has been associated with clonorchiasis, but it is unclear whether clonorchiasis is associated with hepatocarcinogenesis. This experiment was designed to investigate relationships between clonorchiasis and early changes of hepatocarcinogenesis. Sixteen Sprague-Dawley rats weighing 150g were divided into two groups of 8 rats in each. All rats were fed choline-devoid(CD) diet for 4 weeks. Group 1 was given 0.015-0.020% diethylnitrosamine(DEN) as drinking water for 1 week. After one week, the rats were treated orally with 1% N-acetylaminofluorene(AAF) (5 times per week for 2 weeks). Group 2 was treated equally to group 1 except for CS infection during AAF treatment. Two rats in each group were sacrificed at 4th, 5th, 6th and 7th week of the experiment. Livers were stained with OV -6, proliferating cell nuclear antigen(PCNA) and GST-p. Results were as follows: Group 2 livers showed more oval cell proliferation in parenchyma and portal areas at the 4th, 5th, 6th and 7th weeks than did livers of group 1 (p<0.01). PCNA was mostly localized in oval cell populations, rather than hepatocytes and biliary cells. The ratio of oval cells to hepatocytes was much higher in group 2 than in group l(p<0.01 The ratio of hepatocytes to biliary cells is higher in group 2 than in group 1 (p<0.05), More group 2 acidophilic foci reacted to GST-p monoclonal antibody than in the noninfected group. It appeared that CS infection promoted potentially precancerous acidophilic foci and oval cell proliferation.

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Effect on Antimutagenic and Cancer cell growth inhibition of Ixeris dentata Nakai (씀바귀의 항돌연변이성 및 암세포 성장억제효과)

  • Kim, Myong-Jo;Kim, Ju-Sung;Kang, Won-Hee;Jeong, Dong-Myong
    • Korean Journal of Medicinal Crop Science
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    • v.10 no.2
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    • pp.139-143
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    • 2002
  • Ixeris dentate was used to extract the natural compounds with methanol and then the extracts were further fractionated using n-hexane, ethyl acetate, butanol and aqueous fraction. The methanol extract of Ixeris dentate had strong antimutagenic effect in Ames mutagenicity test. Among the extracts fractioned from the methanol extract, the butanol fraction exhibited the greatest antimutagenic effect suppressing the mutagenicity of Salmonella typhimurium TA100 with inhibition rate of 88.93%. Cancer cell lines include human lung carcinoma(A549), human breast adenocarcinoma(MCF-7) and human hepatocellular carcinoma(Hep3B). Hexane fraction showed the strongest effect against A549, MCF-7 and Hep3B at the same concentration compared to those of other fractions.

Multiple Molecular Targets of Sensitizers in Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL/Apo2L)-Mediated Apoptosis (TRAIL 매개의 세포사멸 유도를 위한 다양한 분자적 타깃)

  • Min, Kyoung-Jin;Kwon, Taeg-Kyu
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1641-1651
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    • 2011
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a recently identified member of the TNF ligand family that can initiate apoptosis through the activation of their death receptors. TRAIL has been paid attention as a potential anti-cancer drug, because it selectively induces apoptosis in tumor cells in vitro and in vivo but not in most normal cells. However, recent studies have shown that some cancer cells including malignant renal cell carcinoma and hepatocellular carcinoma, are resistant to the apoptotic effects of TRAIL. Therefore, single treatment with TRAIL may not be sufficient for the treatment of various malignant tumor cells. Understanding the molecular mechanisms of TRAIL resistance and identification of sensitizers capable of overcoming TRAIL resistance in cancer cells is needed for the establishment of more effective TRAIL-based cancer therapies. Chemotherapeutic drugs induce apoptosis and the upregulation of death receptors or activation of intracellular signaling pathways of TRAIL. Numerous chemotherapeutic drugs have been shown to sensitize tumor cells to TRAIL-mediated apoptosis. In this study, we summarize biological agents and drugs that sensitize tumors to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.