• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6417-6421
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• 2015

Viscum album var (VAV) also known as mistletoe, has long been categorized as a traditional herbal medicine in Asia. In addition to its immunomodulating activities, mistletoe has also been used in the treatment of chronic hepatic disorders in China and Korea. There are numerous reports showing that VAV possesses anti-cancer effects, however influence on human hepatocarcinoma has never been elucidated. In the present study, hot water extracts of VAV was evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were treated with VAV (50-400ug/ml) for both 24 and 48 hours then cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR and Western blot analysis were conducted to measure expression of cell cycle arrest related genes and proteins respectively. VAV dose dependently inhibited the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene expression were significantly down regulated while p21 was upregulated dose dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up regulation of p21 can result in cell death. These results indicate that VAV showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK-Hep1 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1581-1584
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• 2014

Background: The overall prognosis for cancers of unknown primary (CUP) is poor, median overall survival (OS) being 6-12 months. We evaluated our multicentric retrospective experience for CUP administered docetaxel and cisplatin combination therapy. Materials and Methods: A total of 29 patients that were pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel ($75mg/m^2$, day 1) and cisplatin ($75mg/m^2$, day 1) was performed as a first line regimen every 21 days. Results: The median age was 51 (range: 27-68). Some 17 patients had multimetastatic disease on the inital diagnosis. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Median number of cycles was 3 (range: 1-6). Objective response rate was 37.9% and clinical benefit was 58.6%. Median progression free survival (PFS) and overall survival (OS) were 6 months (range: 4.3-7.7 months) and 16 months (range: 8.1-30.9 months), respectively. Fourteen patients (60.8%) were treated in a second line setting. There was no treatment related death. Most common toxicities were nausia-vomiting (44.6%) and fatigue (34.7%), serious cases (grade 3/4) suffering nausia-vomiting (10.3%), neutropenia (13.8%) and febrile neutropenia (n=1). Conclusion: The combination of cisplatin and docetaxel is an effective regimen for selected patients with CUP.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.55-63
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• 2000

Soeumin Sibjeundaibo-tang (SJDBT) and Soyangin Sibimijihwang-tang (SMJHT) have been used traditionally to improve the systemic blood circulation and biological energy production in the patients with circulatory and neuronal diseases. The object of this study is to determine the protective effects of SJDBT and SMJHT extracts on the spontaneous and glutamate-induced neuronal damages in cultured cells derived from mice cerebral cortex. At 14 days after beginning the cultures, the activity of lactate dehydrogenase released into the culture media was significantly decreased by treatment of cerebroneuronal cells with SJDBT and SMJHT (0.1 mg/ml) for 7 days. By comparison with the normal cells, cerebroneuronal morphology was dramatically changed by treatment of glutamate (1 mM) for 12 hrs, and this was conspicuously recovered by pretreatment of cerebroneural cells with SJDBT and SMJHT (0.1-1.0 mg/ml) for 2 days. Moreover, glutamated-induced DNA fragmentation was also protected by pretreatment of cerebroneuronal cells with those extracts. These results suggest that naturally occurring and glutamate-induced degeneration of cultured cerebrocortical cells may be related, in part, to the process of apoptotic cell death. The pharmacological properties of SJDBT and SMJHT extracts to improve cerebroneuronal degeneration may be considered as one of useful medicines that can prevent cerebrocortical impairments resulted from age-dependent and excitotoxicity-induced neuronal degeneration in human brain.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6141-6147
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• 2015

Background: Cancer is a leading cause of death worldwide. A large proportion of cancer deaths are preventable through early detection but there are a range of social, emotional, cultural and financial dimensions that hinder the effectiveness of cancer prevention and treatment efforts. Cancer stigma is one such barrier and is increasingly recognized as an important factor influencing health awareness and promotion, and hence, disease prevention and control. The impact and extent of stigma on the cancer early detection and care continuum is poorly understood in India. Objectives: To evaluate cancer awareness and stigma from multiple stakeholder perspectives in North India, including men and women from the general population, health care professionals and educators, and cancer survivors. Materials and Methods: A qualitative study was conducted with in-depth interviews (IDIs) and focus group discussions (FGDs) among 39 individuals over a period of 3 months in 2014. Three groups of participants were chosen purposively - 1) men and women who attended cancer screening camps held by the Indian Cancer Society, Delhi; 2) health care providers and 3) cancer survivors. Results: Most participants were unaware of what cancers are in general, their causes and ways of prevention. Attitudes of families towards cancer patients were observed to be positive and caring. Nevertheless, stigma and its impact emerged as a cross cutting theme across all groups. Cost of treatment, lack of awarenes and beliefs in alternate medicines were identified as some of the major barriers to seeking care. Conclusions: This study suggests a need for spreading awareness, knowledge about cancers and assessing associated impact among the people. Also Future research is recommended to help eradicate stigma from the society and reduce cancer-related stigma in the Indian context.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2225-2228
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• 2012

Background: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy (CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Methods: A total of thirty patients who had received cisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500 $mg/m^2$ days 1-3, mesna 2500 $mg/m^2$ days 1-3, doxorubicin 60 mg/m2 day 1 (IMA), repeated every 21 days. Eligible patients had ECOG PS< 2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologic functions. Results: Median age was 47 (min-max; 17-60). Twenty six (86.7 %) were male. Median cycles of chemotherapy for each patient were 2 (range:1-6). Twenty patients were evaluable for toxicity and response. No patient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients. Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively. Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever after IMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT. No cardiotoxicity was observed after CT and treatments were generally well tolerated. Conclusion: Ifosfomide and doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPC patients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvage therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.707-711
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• 2013

Purpose: To investigate the clinical features and prognosis of papillary thyroid carcinoma (PTC) with a background of benign disease. Method: A total of 709 patients with papillary thyroid carcinoma undergoing surgical resection were analyzed retrospectively. In 147 patients who underwent surgery for benign thyroid disease, incidental PTC (IPC group) were identified by intraoperative or postoperative pathological examination of surgical specimens but were not detected by preoperative imaging studies. In the other group, according to the pathological examination with or without co-existing benign thyroid disease, 253 cases were clarified as concomitant PTC and 309 cases were clarified as dominant PTC. Results: Incidental PTC was more common in women, about 85.7%, the mean age was $47.6{\pm}11.3$ years old. Average tumor diameter was $4.4{\pm}2.2$ mm, multiple lesions accounted for 12.9% (19/147), and the cervical lymph node metastasis rate was 6.1% (9/147). After radical resection 8 cases recurred, the median time of recurrence was about 12 months (0.5 to 162), there was no tumor-related death. The tumor-free survival rates were 97.3%, 95.9%, 91.5%, and 79.3% in 1, 5, 10 and 14 year respectively. Conclusion: Incidental PTC with a background of benign lesions is common, and the generally good prognosis can be attributed to tumor early detection and early treatment. On the intraoperative finding of incidental PTC, lobectomy (unilateral) or total thyroidectomy (bilateral) should be the first choice, but with a postoperative pathologic finding of incidental PTC, further treatment, such as completion thyroidectomy or immediate lymph dissection is not necessary. Central lymph node dissection is also not needed unless lymphadenectasis is present.

• Proceedings of the Korean Vacuum Society Conference
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• 2014.02a
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• pp.262.1-262.1
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• 2014

Lipid peroxidation induces functional deterioration of cell membrane and induces cell death in extreme cases. These phenomena are known to be related generally to the change of physical properties of lipid membrane such as decreased lipid order or increased water penetration. Even though the electric property of lipid membrane is important, there has been no report about the change of electric properties after lipid peroxidation. Herein, we demonstrate the molecular energy band change in red blood cell membrane through peroxidation by air-based atmospheric pressure DBD plasma treatment. Ion-induced secondary electron emission coefficient (${\gamma}$ value) was measured by using home-made gamma-focused ion beam (${\gamma}$-FIB) system and electron energy band was calculated based on the quantum mechanical Auger neutralization theory. The oxidized lipids showed higher gamma values and lower electron work functions, which implies the change of surface charging or electrical conductance. This result suggests that modified electrical properties should play a role in cell signaling under oxidative stress.

• Nutrition Research and Practice
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• v.10 no.6
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• pp.569-574
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• 2016

BACKGROUND/OBJECTIVES: We investigated the anti-osteoarthritic effects of deer bone extract on the gene expressions of matrix metalloproteinases (MMPs) and collagen type II (COL2) in interleukin-$1{\beta}$-induced osteoarthritis (OA) chondrocytes. MATERIALS/METHODS: Primary rabbit chondrocytes were treated as follows: CON (PBS treatment), NC (IL-$1{\beta}$ treatment), PC (IL-$1{\beta}+100{\mu}g/mL$ glucosamine sulphate/chondroitin sulphate mixture), and DB (IL-$1{\beta}+100{\mu}g/mL$ deer bone extract). RESULTS: The results of the cell viability assay indicated that deer bone extract at doses ranging from 100 to $500{\mu}g/mL$ inhibits cell death in chondrocytes induced by IL-$1{\beta}$. Deer bone extract was able to significantly recover the mRNA expression of COL2 that was down-regulated by IL-$1{\beta}$ (NC: 0.79 vs. DB: 0.87, P < 0.05) and significantly decrease the mRNA expression of MMP-3 (NC: 2.24 vs. DB: 1.75) and -13 (NC: 1.28 vs. DB: 0.89) in OA chondrocytes (P < 0.05).CONCLUSIONS: We concluded that deer bone extract induces accumulation of COL2 through the down-regulation of MMPs in IL-$1{\beta}$-induced OA chondrocytes. Our results suggest that deer bone extract, which contains various components related to OA, including chondroitin sulphate, may possess anti-osteoarthritic properties and be of value in inhibiting the pathogenesis of OA.

• Toxicological Research
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• v.34 no.3
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• pp.267-279
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• 2018

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.