• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3997-4002
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• 2015

Background: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. Results: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ${\geq}3.24$) and PNI (<49.5 or ${\geq}49.5$). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). Conclusions: NLR (${\geq}3.24$) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5681-5686
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• 2015

Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstline chemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6569-6572
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• 2013

In cervical cancer, one of the most common malignant tumors in women worldwide, miR-126 has been reported to exhibit decreased expression. However, its role in cervical cancer cell proliferation and drug sensitivity has remained relatively unexplored. Here, we compared the expression of miR-126 in cervical cancer tissues (n = 20) with that in normal cervical tissue (n = 20) using quantitative RT-PCR. The viability of Siha cervical cancer cells was further measured by MTT assay after transfection with miR-126 mimic (Siha-miR-126 mimic) or microRNA mimic negative control (Siha-miR mimic NC) and after treatment with various concentrations of bleomycin (BLM). IC50s were calculated, and the survival rates (SRs) of Siha cells were calculated. miR-126 expression in cervical cancer tissue was significantly decreased compared with that in normal cervical tissue (P < 0.01). The relative SRs of Siha-miR-126 mimic cells were also significantly decreased compared with those of Siha-miR mimic NC cells at 24-96 h after transfection. The IC50 of BLM in Siha-miR-126 mimic cells ($50.3{\pm}2.02{\mu}g/mL$) was decreased compared with that in Siha-miR mimic NC cells ($70.5{\pm}4.33{\mu}g/mL$) at 48 h after transfection (P < 0.05). Finally, the SRs of Siha-miR-126 mimic cells were significantly lower than those of SihamiR mimic NC cells after cultured in medium containing 40 ${\mu}g/mL$ BLM for 24-96 h (P < 0.05). These results suggest that miR-126 is expressed at low levels in cervical cancer. Upregulation of miR-126 inhibited cervical cancer cell proliferation and enhanced the sensitivity to BLM. Thus, miR-126 may represent a novel approach to cervical cancer treatment.

• Plant Biotechnology Reports
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• 제2권2호
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• pp.163-169
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• 2008

Roots of Ophiorrhiza prostrata D. Don serve as a rich source of camptothecin (CPT), an anticancer drug. Because of the large-scale collection of its roots, the plant has become a threatened species. The present study accomplishes the induction of adventitious roots as a means for the production of CPT as well as for the large-scale propagation of this anticancer drug plant using leaf and internode explants. The biomass yield and CPT content of adventitious roots induced from different explants were compared to roots developed on ex vitro rooted stem cuttings. Adventitious roots were produced on half-strength Murashige and Skoog (MS) medium supplemented with $10.74{\mu}M$ ${\alpha}-naphthaleneacetic$ acid and $2.32{\mu}M$ kinetin at mean fresh weights of 0.753, 0.739 and 0.748 g roots from leaf, internode and shoot, respectively. CPT yield from in vitro derived roots after 50, 80 and 120 days of incubation (0.028, 0.06 and 0.1% dry weight, respectively) was not significantly different from those harvested at the same age from ex vitro rooted (0.03, 0.06 and 0.13%, respectively) stem cuttings. CPT from subcultured roots derived from solid (0.08%) medium was lower than from suspension culture medium (0.12%). Subsequent cultures of the adventitious roots showed a stable production of CPT (0.16%). The yield of CPT from 360-day-old plant-derived roots was 0.19%. Elicitation using methyl jasmonate and acetyl salicylic acid exhibited no enhancement in CPT yield. In vitro propagation through direct shoot regeneration was achieved from the adventitious roots upon transfer to MS medium with $8.87{\mu}M$ $N^6-benzyladenine$ (BA) and $2.46{\mu}M$ indole-3-butyric acid (IBA) with a mean of 21.2 shoots per culture in 50 days. The shoots upon subculture on medium having the same level of BA and IBA underwent rapid proliferation. The shoots transferred to field conditions after in vitro rooting exhibited 95% survival. Adventitious root induction, from leaf and internode explants, enables the feasible production of CPT as well as the large-scale rapid propagation of this species which can safeguard it from extinction.

• 한국균학회소식:학술대회논문집
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• 한국균학회 2018년도 춘계학술대회 및 임시총회
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• pp.33-33
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• 2018

Air-borne plant pathogenic fungus Fusarium graminearum and seed-borne plant pathogenic bacterium Burkholderia glumae are cause similar disease symptoms in rice heads. Here we showed that two pathogens frequently co-isolated in rice heads and F. graminearum is resistant to toxoflavin produced by B. glumae while other fungal genera are sensitive to the toxin. We have tried to clarify the resistant mechanism of F. graminearum against toxoflavin and the ecological reason of co-existence of the two pathogens in rice. We found that F. graminearum carries resistance to toxoflavin as accumulating lipid in fungal cells. Co-cultivation of two pathogens resulted in increased conidia and enhanced chemical attraction and attachment of the bacterial cells to the fungal conidia. Bacteria physically attached to fungal conidia, which protected bacterium cells from UV light and allowed disease dispersal. Chemotaxis analysis showed that bacterial cells moved toward the fungal exudation compared to a control. Even enhanced the production of phytotoxic trichothecene by the fungal under presence of toxoflavin and disease severity on rice heads was significantly increased by co-inoculation rather than single inoculation. This study suggested that the undisclosed potentiality of air-born infection of bacteria using the fungal spores for survival and dispersal.

• Journal of Ginseng Research
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• 제47권5호
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Journal of Medicine and Life Science
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• 제17권2호
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• pp.41-46
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• 2020

Metformin, a predominantly prescribed anti-diabetic drug for decades, has gained new insights for its anti-tumor activity in a variety of cancer cells. Our previous studies also showed the obvious pro-apoptotic activity of metformin and the underlying action mechanisms in hepatocellular carcinoma cells. Together with apoptosis, autophagy is a crucial intracellular process to determine the survival or death of cells under some stressful environments. The present study aimed to determine the role of autophagy in metformin-induced death of H4IIE hepatocellular carcinoma cells. Metformin blocked the formation of autophagosome and the expression of LC3A, generally described as a biomarker of autophagy. Inhibition of AMPK reversed the metformin-induced blockade of autophagy. Antioxidant (NAC) suppressed the metformin-induced cell death but not affected LC3A. The inhibition of protein kinase C totally restored the metformin-suppressed expression of LC3A. In summary, our present study suggests that autophagy is an anti-apoptotic player in metformin-induced apoptosis in H4IIE cells.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• 생약학회지
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• 제48권3호
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• pp.173-178
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• 2017

We investigated the efficacy of single compound of plant extract in coxsackievirus B3 (CVB3) infection. CVB3 is a main cause of Hand-foot-mouth diseases (HFMD) and viral myocarditis in children and adult. Several single compounds of plant extract were purified by HPLC and tested as antiviral drug candidate. Among them, kaempferol was selected to effective anti-enterovirus compound by HeLa cells survival assay. CVB3 infected HeLa cells were treated with kaempferol ($100{\mu}g/ml-100ng/ml$) and their antiviral effect was confirmed. After 16 hours of treatment, HeLa cells were lysed and proteins were extracted for western blot analysis. CVB3 viral capsid protein VP1 production and transcription factor eIF4G-1 cleavage was significantly decreased in $100{\mu}g/ml$ kaempferol treatment. Virus replication was observed by virus RNA amplification. Kaempferol strongly reduced virus positive and negative strand RNA amplification. Moreover, MAPK signal induced by CVB3 infection, pERK and pmTOR, kaempferol treatment significantly inhibited the activity. Plant extract single compound, kaempferol, is a strong candidate to be developed non-toxic anti-enterovirus treatment agent.