• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.785-789
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• 2016

A key drug for treatment of EGFR mutation-positive non-small cell lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). While the dosage of many general anti-tumor drugs is adjusted according to the patient body surface area, one uniform dose of most TKIs is recommended regardless of body size. In many cases, dose reduction or drug cessation is necessary due to adverse effects. Disease control, however, is frequently still effective, even after dose reduction. In this study, we retrospectively reviewed the characteristics of 26 patients at Fukuoka University Hospital between January 2004 and January 2015 in whom the EGFR-TKI dose was reduced with respect to progression free survival and overall survival. There were 10 and 16 patients in the gefitinib group and the erlotinib group, respectively. The median progression-free survival in the gefitinib group and the erlotinib group was 22.4 months and 14.1 months, respectively, and the median overall survival was 30.5 months and 32.4 months, respectively. After stratification of patients by body surface area, the overall median progression-free survival was significantly more prolonged in the low body surface area (<1.45 m2) group (25.6 months) compared to the high body surface area (>1.45 m2) group (9.7 months) (p=0.0131). These results indicate that low-dose EGFR-TKI may sufficiently control disease without side effects in lung cancer patients with a small body size.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2619-2623
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• 2014

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6433-6438
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• 2013

In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We studied the effect of the demethylating reagent 5-aza-2'-deoxycitidine (5-Aza-CdR) on MAT1A gene expression, DNA methylation and S-adenosylmethionine (SAMe) production in the HCC cell line Huh7. We found that MAT1A mRNA and protein expression were activated in Huh7 cells with the treatment of 5-Aza-CdR; the status of promoter hypermethylation was reversed. At the same time, MAT2A mRNA and protein expression was significantly reduced in Huh7 cells treated with 5-Aza-CdR, while SAMe production was significantly induced. However, 5-Aza-CdR showed no effects on MAT2A methylation. Furthermore, 5-Aza-CdR inhibited the growth of Huh7 cells and induced apoptosis and through down-regulation of Bcl-2, up-regulation of Bax and caspase-3. Our observations suggest that 5-Aza-CdR exerts its anti-tumor effects in Huh7 cells through an epigenetic change involving increased expression of the methionine adenosyltransferase 1A gene and induction of S-adenosylmethionine production.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4759-4763
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• 2013

Background: Prognostic factors of postoperative early and late recurrence in patients with hepatocellular carcinoma (HCC) undergoing curative resection remain to be clarified. The aim of this study was to identify risk factors for postoperative early (${\leq}$ 2 year) and late (> 2 year) intrahepatic recurrences in patients with single HCCs without macrovascular invasion. Methods: A total of 280 patients from December 2004 to December 2007 were retrospectively included in this study. Intrahepatic recurrence was classified into early (${\leq}$ 2 year) and late (> 2 year) and the Chi-Square test or Fisher's exact test and multivariate logistic regression analysis were performed to determine significant risk factors. Results: During the follow-up, 124 patients had intrahepatic recurrence, early and late in 82 and 42 patients, respectively. Multivariate logistic regression analysis showed that microvascular invasion (p=0.006, HR: 2.397, 95% CI: 1.290-4.451) was the only independent risk factor for early recurrence, while being female (p = 0.031, HR: 0.326, 95% CI: 0.118-0.901), and having a high degree of cirrhosis (P=0.001, HR: 2.483, 95% CI: 1.417-4.349) were independent risk factors for late recurrence. Conclusions: Early and late recurrence of HCC is linked to different risk factors in patients with single HCC without macrovascular invasion. This results suggested different emphases of strategies for prevent of recurrence after curative resection, more active intervention including adjuvant therapy, anti-cirrhosis drugs and careful follow-up being necessary for patients with relevant risk factors.

• Molecules and Cells
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• v.41 no.5
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• pp.465-475
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• 2018

The advent of massively parallel sequencing, also called next-generation sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AML-related genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as "hot-zone" analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1663-1669
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• 2007

Acute transverse myelitis(ATM) is defined as an acute intramedullary dysfunction of the spinal cord, ascendng or static involving both halves of the cord and appearing without any history of previous neurological diseases due to traumatic accident, tumor of all kind, encephalitis and of course excluding all possible viral, bacterial and fungal infection. It is mainly characterized by acute motor disorder of both limbs in respect to which spinal segments are affected as well as sensory disorder and dysuria & dyschezia. The exact cause is unknown, however it is recently suggested that immunological factors are highly involved. It has been reported by several reliable sources that it is often accompanied by immunological diseases such as systemic lupus erythematosus(SLE). As treatments non steroid anti-inflammatory drugs(NSAIDS) are primarily recommended as to steroids, limited doses are injected only with the proper prescription from the physician. Operative methods are not options as traumatic accidents and tumors are excluded as factors. To enhance muscle strength and prevent articular contracture physical therapy and passive exercise is imperative. The following patient whose chief complaints were mainly about hypoesthesia of Rt. lower limb and stiffness of phalanges of both fingers as well as to weakness of lower extermity. Therefore it has been diagnosed as arthalgia syndrome. In oriental medicine factors such as wind evil heat-evil, dampness-heat evil, cold evil cause the arthalgia syndrome. In this case the patient was diagnosed as dampness-heat evil and herbal medicine Chunglijagam-Tang and Dong-Qi acupuncture was applied to treat bladder disorder.

• Herbal Formula Science
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• v.31 no.4
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• pp.295-313
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• 2023

Objectives : While treatments for cancer are advancing, the development of effective treatments for cancer metastasis, the main cause of cancer patient death, remains insufficient. Recent studies on Dichroae Radix have revealed that its active ingredients have the potential to inhibit cancer metastasis. This study aimed to investigate the cancer metastasis inhibitory effect of Dichroae Radix using network pharmacological analysis. Methods : The active compounds of Dichroae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : In total, 25 active compounds and their 62 non-redundant targets were selected through the TCMSP database and analysis platform. The target genes underwent gene ontology and pathway enrichment analysis. The gene list applied to the gene ontology analysis revealed associations with various biological processes, including signal transduction, chemical synaptic transmission, G-protein-coupled receptor signaling pathways, response to xenobiotic stimulus, and response to drugs, among others. A total of eleven genes, including HSP90AB1, CALM1, F2, AR, PAKACA, PTGS2, NOS2, RXRA, ESR1, ESR2, and NCOA1, were found to be associated with biological pathways related to cancer metastasis. Furthermore, nineteen of the active compounds from Dichroae Radix were confirmed to interact with these genes. Conclusions : The results provide valuable insights into the mechanism of action and molecular targets of Dichroae Radix. Notably, Berberine, the main active ingredient of Dichroae Radix, plays a significant role in degrading AR proteins in advanced prostate cancer. Further studies and validations can provide crucial data to advance cancer metastasis prevention and treatment strategies.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.83-91
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• 2024

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

• Food Science and Industry
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• v.51 no.4
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• pp.278-301
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• 2018

Although more than 80% of living organisms are found in marine ecosystems, only less than 10% of marine resources have been utilized for human food consumptions and other usages. It is well known that marine resources (fish, shellfish and algae) have exceptional nutritional properties; however, their functional characteristic has not been completely discovered. It is believed that metabolites (organic compounds, proteins, peptides, lipids, minerals, etc.) play an important role to show its biological properties. Marine proteins and peptides are considered to be future drugs due to their excellent biological activities with a fewer adverse side effect. Marine peptides show several biological activities, including antimicrobial, antioxidant, anti-inflammatory, anti-cancer, anti-viral, anti-tumor, anti-diabetic, anti-hypertensive, anti-coagulant, immunomodulatory, appetite suppressing and neuroprotective effects. Therefore, the pharmaceutical, nutraceutical, and cosmeceutical companies have been paid attention to the marine peptides to commercialize into products. This current review mainly focused on the above mentioned biological activities of marine peptides and protein hydrolysates as a functional food and pharmaceutical applications. To commercialize these materials in industrial level required large quantity in high-purity level, and it is complicated to produce huge quantity from the marine resources due to insufficient raw materials, unavailability of raw materials through a year, hinder the growth with geographical variations, and availability of compounds in extreme small quantities. The best solution for these issues is to introduce new modern technologies such as artificial intelligence robots, drones, submersibles and automated raw material harvesting vessels in farming industries instead of man power, which will lead to 4th industrial revolution.

• 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.