• Environmental Analysis Health and Toxicology
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• v.25 no.2
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• pp.111-120
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• 2010

DEPs (diesel exhaust particles) like any other particles can be also inhaled into lung to participate in a damaging reaction to the organ. Possible damages might be apoptosis and inflammatory responses to the cells in respiratory track. The aim of this study was cytotoxicity evaluation of DEPs from five in-use diesel vehicles using a murine macrophage cell (RAW 254.7). We found that most DEPs have a considerable cytotoxicity compared to the control and SRM 2975. When measured by MTT assay and extents of apoptosis, DEPs of two highmileage vehicles had higher toxicity than those of the other three low-mileage vehicles tested. Although mRNA expression level of TNF-${\alpha$ somewhat explains the trend of cytotoxicity and apoptosis, that of IL-1$\beta$ did not. Correlation studies among the extents of MTT assay, apoptosis, and TNF-$\alpha$ expression showed that the extents between apoptosis and TNF-$\alpha$ expression was most highly correlated (r=0.96). These results suggest that cytotoxicity of various DEPs could be compared easily by measuring the extent of apoptosis or TNF-$\alpha$ expression by DEPs.

• Journal of Forest and Environmental Science
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• v.33 no.2
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• pp.113-121
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• 2017

In flight particulate matter particularly emissions generated by incomplete combustion processes has become a subject of global concern due to the health problems and environmental impacts associated with them. This has compelled most countries to set standards for coarse and fine particles due to their conspicuous impacts on environment and public health. This contribution therefore explores forest fire emissions and how its particulates affects air quality, damage to vegetation, water bodies and biological functions as architects for lung diseases and other degenerative illnesses such as oxidative stress and aging. Soot was collected from simulated forest fire using a clean glass surface and carefully transferred into amber vials for analysis. Volatile components of soot were collected over 10 mL dichloromethane and analyzed using a QTOF Premier-Water Corp Liquid Chromatography hyphenated to a mass selective detector (MSD), and Gas Chromatograph coupled to a mass spectrometer (GC-MS). To characterize the size and surface morphology of soot, a scanning electron microscope (SEM) was used. The characterization of molecular volatiles from simulated forest fire emissions revealed long chain compounds including octadec-9-enoic acid, octadec-6-enoic acid, cyclotetracosane, cyclotetradecane, and a few aromatic hydrocarbons (benzene and naphthalene). Special classes of organics (dibenzo-p-dioxin and 2H-benzopyran) were also detected as minor products. Dibenzo-p-dioxin for instance in chlorinated form is one of the deadliest environmental organic toxins. The average particulate size of emissions using SEM was found to be $11.51{\pm}4.91{\mu}m$. This study has shown that most of the emissions from simulated forest fire fall within $PM_{10}$ particulate size. The molecular by-products of forest fire and particulate emissions may be toxic to both human and natural ecosystems, and are possible precursors for various respiratory ailments and cancers. The burning of a forest by natural disasters or man-made fires results in the destruction of natural habitats and serious air pollution.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.2
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• pp.76-96
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• 2008

Purpose: This study was performed to evaluate anti-inflammatory effects of Jogantanggagambang(JGTG). Methods: In the study of anti-oxidant activities, JGTG was investigated by DPPH radical scavenger activity, superoxide dismutase activity and superoxide anion radical scavenger activity. In the study of anti-inflammatory effects, JGTG was investigated using cultured cells and murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were measured in mouse lung fibroblast cells(mLFCs) and RAW264.7 cells. Results: 1. JGTG showed a safety in cytotoxicity and toxicity of liver. 2. JGTG effected scavenging activity on DPPH free radical, superoxide dismutase and superoxide anion radical. 3. JGTG in RAW 264.7 cell decreased IL-$1{\beta}$ mRNA expression, IL-6 mRNA expression, TNF-${\alpha}$ mRNA expression at 50, $100{\mu}g/m{\ell}$ and also decreased NOS-II mRNA expression at $100{\mu}g/m{\ell}$, and decreased COX-2 mRNA expression at 10, 50, $100{\mu}g/m{\ell}$. 4. JGTG in RAW 264.7 cell decreased significantly IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ at 50, $100{\mu}g/m{\ell}$. 5. JGTG inhibited significantly IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in serum of acute inflammation-induced mice. 6. JGTG decreased significantly IL-$1{\beta}$ mRNA production in spleen tissue. Conclusion: These results suggest that JGTG can be used for treating diverse female diseases caused by inflammation

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.65-75
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• 2018

Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5703-5707
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8603-8605
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• 2014

Objective: To assess the safety of Brucea javanica and Cantharidin combined with chemotherapy in treating patients with non-small-cell lung carcinoma. Method: A consecutive cohort of patients with NSCLC were divided into four groups: experimental group A treated with Brucea javanica injection combined with chemotherapy; experimental group B with Cantharidin injection combined with chemotherapy; experimental group C treated with Brucea javanica and Cantharidin injection combined with chemotherapy; and the control group receiving only chemotherapy. After more than two courses of treatment, safety, quality of life and side effects were evaluated. Results: The incidences of myelosuppression in groups A, B and C were lower than that in Control group (p<0.05), but without significant differences among A, B and C. Adverse effects on the gastrointestinal tract also were lower than in controls (p<0.05) without variation amnog the combined treatment groups. Conclusions: Brucea javanica or Cantharidin combined with chemotherapy could in both cases improve quality of life in our cohort of NSCLC patients without any increase in toxicity. However, further clinical experiments should be conducted to evaluate the efficacy of Brucea javanica and Cantharidin combined with chemotherapy for patients with NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.617-622
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• 2014

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MPI fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3161-3166
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• 2016

Background: Metastatic renal cell carcinoma (mRCC) status as poor prognosis improved with the introduction of tyrosine-kinase inhibitors, especially sunitinib. There is sparse data reporting from our region on use of sunitinib in metastatic RCC. Thus the present study explores sunitinib usage at our institute. Materials and Methods: An unselected population of patients with metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. Results: Fourty-nine patients with a median age of 50.5 years (range 21-71 years) were included. Most were male (61.2%). Twenty‑one (42.9%) had metastatic disease at presentation. Sunitinib was first line therapy in 45. Conventional clear cell carcinoma was the most common pathology present (39 patients; 79.59 %). The most common site of metastasis was the lung (75.5%). Most patients (30) were started at a dose of 50 mg once a day for 4 weeks and then 2 weeks rest. Clinical benefit rate was 73.5% (n= 36), and 22.5% (n= 11) demonstrated progressive disease at first imaging evaluation within the first 3-6 months. The following objective response performed for patients was 48.9% (n=24) and progression at 24.5 % (n=12). The median follow‑up was 16 months (range, 4-34 months), the overall estimated median PFS was 9 months and the estimated median OS was 15 months. Conclusions: This study demonstrated sunitinib is tolerable and effective in advanced/metastatic RCC Egyptian patients and indicates we should further seek second and third lines to increase survival equivalence as reported in the worldwide literature.

• Herbal Formula Science
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• v.12 no.1
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• pp.131-148
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• 2004

In order to evaluate the anti-tumor and synergic effect of Bojungikkeehapdaechilkitang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Bojungikkeehapdaechilkitang with their concomitant treatment against 3LL(Lewis lung carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to 3LL cell lines. Bojungikkeehapdaechilkitang has only mimic direct anti-tumor effect against to 3LL cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Bojungikkeehapdaechilkitang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and Bojungikkeehapdaechilkitang extracts.