• BMB Reports
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• v.32 no.2
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• pp.112-118
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• 1999

The presence of hypoxic cells in solid tumors has long been considered a problem in cancer treatment such as in radiation therapy or treatment with some anticancer drugs. It has been suggested that hypoxic cells are involved in the development of a more aggressive phenotype and contribute to metastasis. In this study, as an attempt to understand how tumor cells adapt to hypoxic stress, we investigated the regulation of the hypoxia-induced expression of proteins that control essential processes of tumor cell survival and angiogenesis. We first examined whether hypoxia induces stress protein gene expression of murine solid tumor RIF cells. We also examined hypoxia-induced changes in angiogenic gene expression in these cells. Finally, we investigated the association of the elevated levels of stress proteins with the regulation of hypoxia-induced angiogenic gene expression. Results demonstrated that hypoxia induced the expression of the erythropoietin (EPO) gene and at least two major members of stress proteins, heat shock protein 70 (HSP70) and 25 (HSP25) in RIF tumor cells. Evidence that the expression of EPO gene was greatly potentiated in TR cells suggested that the elevated levels of HSPs may play an important role in the regulation of the hypoxia-induced EPO gene expression. One of the RIF variant cell lines, TR, displays elevated levels of HSPs constitutively. Taken together, our results suggest that a hypoxic tumor microenvironment may promote the survival and malignant progression of the tumor cells by temporarily increasing the level of stress proteins and expressing angiogenic genes. We suspect that stress proteins may be associated with the increase of the angiogenic potential of tumor cells under hypoxia.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.385-392
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• 2006

Paclitaxel is an important chemotherapeutic agent for the treatment of human solid tumors. Multicellular resistance(MCR) is considered to be a major mechanism of resistance of human solid tumors to chemotherapeutic agent such as paclitaxel, which includes barriers to drug penetration through tumor tissues. Multicellular layers(MCL) cultures resemble in vivo tumor condition in terms of MCR and has been used successfully to produce clinically relevant data. In the present study, we evaluated the penetration characteristics and post-penetration anti-proliferative activity of paclitaxel using MCL of human colorectal cancer cells(DLD-1 and HT-29) grown in Transwell inserts. The penetration of $[^{14}C]-paclitaxel$ was slower than that of mannitol which penetrates via paracellular pathway in DLD-1 MCL. The penetration of $[^{14}C]-paclitaxel$ was faster in HT-29 MCL compared to DLD-1 MCL, i.e., at 10 ${\mu}M$ 100% and 40% penetration were observed after 48 hr incubation for HT-29 and DLD-1 cells, respectively. When calculated using anti-proliferative activity in the conditioned media of bottom chamber, the penetration after 24 hr was very limited(less than 50%) and concentration-dependent at the concentrations tested in both MCL's. These results suggest that limited and differential penetration of paclitaxel in tumor tissues may contribute to lower and differential efficacy against human solid tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7085-7090
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• 2014

Objective: To make the clinical evaluation of a solid-state human papillomavirus (HPV) sampling medium in combination with an economical HPV testing method ($careHPV^{TM}$) for cervical cancer screening. Methods: 396 women aged 25-65 years were enrolled for cervical cancer screening, and four samples were collected. Two samples were collected by woman themselves, among which one was stored in DCM preservative solution (called "liquid sample") and the other was applied on the Whatman Indicating FTA $Elute^{(R)}$ card (FTA card). Another two samples were collected by physician and stored in DCM preservative solution and FTA card, respectively. All the samples were detected by $careHPV^{TM}$ test. All the women were administered a colposcopy examination, and biopsies were taken for pathological confirmation if necessary. Results: FTA card demonstrated a comparable sensitivity of detecting high grade Cervical Intraepithelial Neoplasia (CIN) with the liquid sample carrier for self and physician-sampling, but showed a higher specificity than that of liquid sample carrier for self-sampling (FTA vs Liquid: 79.0% vs 71.6%, p=0.02). Generally, the FTA card had a comparable accuracy with that of Liquid-based medium by different sampling operators, with an area under the curve of 0.807 for physician &FTA, 0.781 for physician &Liquid, 0.728 for self & FTA, and 0.733 for self &Liquid (p>0.05). Conclusions: FTA card is a promising sample carrier for cervical cancer screening. With appropriate education programmes and further optimization of the experimental workflow, FTA card based self-collection in combination with centralized $careHPV^{TM}$ testing can help expand the coverage of cervical cancer screening in low-resource areas.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7587-7593
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• 2013

Background: Cancers of gastric and esophagus are the most frequent gastrointestinal (GI) tract cancers in Iran. This study aimed to analyze time trends of GI tract cancers in Guilan province by gender and age to provide solid scientific evidence for cancer prevention and control. Materials and Methods: The data were obtained from the Guilan Cancer Registry System and Guilan Provincial Health Center, over the 15 year period between 1997 and 2011. Crude incidence and age standardized (AS)incidence rates were calculated and annual percent change was estimated by Joinpoint software for long term trend analysis. Results: During the study period, 8,332 cases of GI malignances with a male to female ratio of 1:1.73 were registered in Guilan province. The AS rates for esophageal, gastric, colon and rectal cancers were 5.97, 14.5, 7.59 and 3.58 per 105 respectively. While the trend was declining and relatively constant for esophageal and gastric cancer, respectively, the incidence trend for colon and rectal cancers was of increase over the period of the study. Conclusions: The results indicated that the incidence of GI cancers was relatively low in Guilan province compared to neighboring provinces. An effective cancer control program including prevention measures, early detection and effective treatment needs to be implemented to reduce cancer morbidity and mortality.

• BMB Reports
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• v.42 no.6
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• pp.344-349
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• 2009

Angiogenesis is crucial for solid tumor growth. By secreting angiogenic factors, tumor cells induce angiogenesis. However, targeting these angiogenic factors for cancer therapy is not always successful, suggesting that other factors may be involved in tumor angiogenesis. This work shows that 25 protein spots were differentially expressed by two-dimensional gel electrophoretic analysis when HepG2 cells induced endothelial cell differentiation to tube in vitro, and most of them were upregulated. Twenty-one proteins were identified with MALDITOF-MS, and the other four were identified by LTQ-MS/MS. Keratins were identified as one class of these upregulated proteins. Further study indicated that the expression of keratin 17 in cultured endothelial cells is likely microenvironment regulated, because its expression can be induced by HepG2 cells and bFGF as well as serum in culture media. Increased expression of keratins in endothelial cells, such as keratin 17, may contribute to the angiogenesis induced by HepG2 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.23-29
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• 2015

Background: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge-scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3259-3263
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• 2016

Aims: To determine suitable food textures for videofluoroscopic study of swallowing (VFSS), in order to predict and prevent subsequent aspiration pneumonia in esophageal cancer patients with dysphagia after surgery. Materials and Methods: We evaluated 45 hospitalized esophageal cancer patients who underwent surgery between January 2012 and December 2013. The control group consisted of 43 patients treatmed from January 2010 until December 2011 and were not examined by VFSS. Test foods, which were presented in order of increasing thickness, included thin barium sulfate (Ba) liquid (3 or 10 ml), slightly thickened Ba liquid (3 or 10 ml), a spoonful of Ba jelly, and a spoonful of Ba puree. Results: Patients could most safely swallow puree, followed by jelly. The 3-mL samples of both the thin and thick liquids put patients at risk for aspiration pneumonia, with incidence rates of 13% and 11%, respectively. While 64.4% of patients could swallow all test foods and liquids safely, 35.6% were at risk for aspiration pneumonia when swallowing liquids. Even though >30% of patients were at risk, only 1 (2.2%) in the VFSS group developed aspiration pneumonia, which occurred at the time of admission. Following VFSS, no incidence of aspiration pneumonia was observed. However, aspiration pneumonia occurred in 4 (9.3%) control patients during hospitalization. Conclusions: Postoperative esophageal cancer patients were more likely to aspirate any kind of liquid than solid foods, such as jellies. VFSS is very useful in determining suitable food textures for postoperative esophageal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1067-1072
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• 2013

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of $SSC^{lo}\;Alde^{br}$ cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell $SSC^{lo}\;Alde^{br}$ cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

• Journal of Korean Traditional Oncology
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• v.20 no.2
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• pp.37-49
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• 2015

Objectives : Retroperitoneal liposarcoma (RPS) is a rare solid tumor and has a high recurrence rate after surgery. New complementary and alternative medicine is required to manage symptoms of RPS and side effects of surgery, chemotherapy and radiation therapy. The purpose of this case report is to report two cases of reduction of side effects of surgery and radiation therapy in RPS treated with Wheel Balanced Therapy (WBT) which is a traditional Korean medicine treatment program for patients with cancer. Methods : Two patients with RPS were treated with WBT. Each of patients received personalized WBT schedule including acupuncture. The changes in clinical and laboratory findings were evaluated. Results : The symptoms of patients were improved after about 2 weeks hospitalization. Conclusions : This case report suggests that WBT has a potential to treat side effects of surgery and radiation therapy in patients with RPS. Further rigorous studies are necessary to investigate the therapeutic effects of WBT on RPS.

• 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.