• Nutritional Sciences
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• v.7 no.3
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• pp.144-150
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• 2004

We have investigated the effect of calcium spirulan(Ca-SP) isolated from a blue-green alga Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose and fructose, on invasion of both B16- BL6 melanoma cells, Colon 26 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters in a concentration-dependent manner. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no inhibitory effect on tumor cell migration to fibronectin-coated filters. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel- and laminin-substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin in a concentration-dependent fashion, while the pretreatment of laminin-substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contraset, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP in a dose-dependent manner. Seven intermittent ⅰ.ⅴ. injection of 100$\mu\textrm{g}$ of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung colonization of B16-BL6 melanoma cells in experimental metastasis model, by inhibiting the tumor invasion of basement membrane Matrigel, probably through the prevention of the adhesion and migration of tumor cells to laminin-substrate and of the heparanase activity.

• Safety and Health at Work
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• v.8 no.3
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• pp.258-266
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• 2017

Background: Welders are exposed to many known and suspected carcinogens. An excess lung cancer risk among welders is well established, but whether this is attributable to welding fumes is unclear. Excess risks of other cancers have been suggested, but not established. We investigated welding cancer risks in the population-based Canadian Census Health and Environmental Cohort. Methods: Among 1.1 million male workers, 12,845 welders were identified using Standard Occupational Classification codes and followed through retrospective linkage of 1991 Canadian Long Form Census and Canadian Cancer Registry (1992-2010) records. Hazard ratios (HRs) were calculated using Cox proportional hazards models based on estimated risks of lung cancer, mesothelioma, and nasal, brain, stomach, kidney, and bladder cancers, and ocular melanoma. Lung cancer histological subtypes and risks by industry group and for occasional welders were examined. Some analyses restricted comparisons to blue-collar workers to minimize effects of potential confounders. Results: Among welders, elevated risks were observed for lung cancer [HR: 1.16, 95% confidence interval (CI): 1.03-1.31], mesothelioma (HR: 1.78, 95% CI: 1.01-3.18), bladder cancer (HR: 1.40, 95% CI: 1.15-1.70), and kidney cancer (HR: 1.30, 95% CI: 1.01-1.67). When restricted to blue-collar workers, lung cancer and mesothelioma risks were attenuated, while bladder and kidney cancer risks increased. Conclusion: Excess risks of lung cancer and mesothelioma may be partly attributable to factors including smoking and asbestos. Welding-specific exposures may increase bladder and kidney cancer risks, and particular sources of exposure should be investigated. Studies that are able to disentangle welding effects from smoking and asbestos exposure are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5189-5193
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• 2012

Kemerovo is an industrial region of the Russian Federation characterized by highly developed mining, chemical, metallurgical and power industries. Many of the factories were closed down due to the socioeconomical crisis in the early 90's, and economic potential of the survivors has also decreased significantly. Paradoxically, this has led to the improvement of the ecological situation in the region and elimination of exposure to many chemical carcinogens. This factor, in combination with the improvement of oncological care, might be expected to have lead to a decline of cancer incidence and mortality in the region. To assess trends of cancer incidence and mortality in Kemerovo Region, we therefore carried out an analysis of relevant epidemiological data during 1991-2010. In fact, a significant increase of cancer incidence overall was revealed during 2001-2010. Male cancer incidence was significantly higher than female cancer incidence. Regarding gastric cancer incidence, statistically significant differences during 2001-2010 were found only for men, and male incidence exceeded female incidence. Concerning colorectal cancer incidence, it was lower during 2001-2005 and 2006-2010 as compared to the period of 1991-1996. Lung cancer incidence was significantly higher during 1991-2000 compared to 2001-2010. Among urban populations, cancer incidence was higher in comparison with rural population, but a gradual steady convergence of trends of cancer incidence among urban and rural populations was noted. Lung cancer, breast cancer, colorectal cancer, non-melanoma skin cancer, and gastric cancer are the most prevalent cancer forms in Kemerovo Region. There were no differences in cancer mortality between 2001-2005 and 2006-2010; however, male cancer mortality exceeded female cancer mortality. A similar situation was observed for gastric cancer, colorectal cancer, and lung cancer. Cancer mortality among urban populations exceeded mortality among rural population, for both genders. We suggest that these data can be used for development of modern programs of cancer prevention and early diagnostics in industrial regions of Siberia.

• Molecules and Cells
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• v.41 no.2
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• pp.73-82
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• 2018

Cancer preventive activities of green tea and its main constituent, (-)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as green tea extract and underlying molecular mechanisms. The first part of this review summarizes groundbreaking topics with EGCG and green tea extract: 1) Delayed cancer onset as revealed by a 10-year prospective cohort study, 2) Prevention of colorectal adenoma recurrence by a double-blind randomized clinical phase II trial, 3) Inhibition of metastasis of B16 melanoma cells to the lungs of mice, 4) Increase in the average value of Young's moduli, i.e., cell stiffness, for human lung cancer cell lines and inhibition of cell motility and 5) Synergistic enhancement of anticancer activity against human cancer cell lines with the combination of EGCG and anticancer compounds. In the second part, we became interested in cancer stem cells (CSCs). 1) Cancer stem cells in mouse skin carcinogenesis by way of introduction, after which we discuss two subjects from our review on human CSCs reported by other investigators gathered from a search of PubMed, 2) Expression of stemness markers of human CSCs compared with their parental cells, and 3) EGCG decreases or increases the expression of mRNA and protein in human CSCs. On this point, EGCG inhibited self-renewal and expression of pluripotency-maintaining transcription factors in human CSCs. Human CSCs are thus a target for cancer prevention and treatment with EGCG and green tea catechins.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6073-6080
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• 2015

Background: Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24), a unique tumor suppressor gene, has killing activity in a broad spectrum of cancer cells. Herein, plasmids producing mda-7 proteins fused to different RGD peptides (full RGD4C and shortened RGD, tRGD) were evaluated for apoptosis induction with a hepatocellular carcinoma cell line, Hep-G2. The study aim was to improve the apoptosis potency of mda-7 by tethering to RGD peptides. Materials and Methods: Three plasmids including mda-7, mda-7-RGD and mda-7-tRGD genes beside a control vector were transfected into Hep-G2 cells. After 72 hours incubation, cell viability was evaluated by MTT assay. In addition, the rate of apoptosis was analyzed by flow cytometry using PI/annexin staining. To detect early events in apoptosis, 18 hours after transfection, expression of the BAX gene was quantified by real time PCR. Modeling of proteins was also performed to extrapolate possible consequences of RGD modification on their structures and subsequent attachment to receptors. Results and Conclusions: In MTT assays, while all mda-7 forms showed measurable inhibition of proliferation, unmodified mda-7 protein exhibited most significant effect compared to control plasmid (P<0.001). Again, flow cytometry analysis showed a significant apoptosis induction by simple mda-7 gene but not for those RGD-fused mda-7 proteins. These findings were also supported by expression analysis of BAX gene (P<0.001). Protein modelling analysis revealed that tethering RGD at the end of IL-24/Mda7 disrupt attachment to cognate receptor, IL-20R1/IL-20R2. In conclusion, fusion of RGD4C and shortened RGD peptides to carboxyl terminal of mda7, not only reduce apoptosis property in vitro but also disrupt receptor attachment as demonstrated by protein modelling.

• Journal of Life Science
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• v.20 no.5
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• pp.736-744
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• 2010

The root of Playtcodon grandiflorum, called Platycodi radix, has been a favorite edible plant in Asia and contains a large amount of saponins. Melanoma cells (B16F10) were used to investigate the inhibitory effect of aged black Platycodi radix extract (ABPRE) on oxidative stress and matrix metalloproteinases (MMPs). Platycodon radix has been known to have a variety of medicinal effects such as prevention of gastric ulcers, antiallergenic activities, histamine release inhibition, and antioxidant effects. However, the mechanism of its action remains unclear in humans. ABPRE was prepared using ethanol extraction of aged black Platycodi radix. In an antioxidant effect study of ABPRE, it was observed that ABPRE specifically exhibited the scavenging activity of DPPH radical, but did not inhibit the production of malondialdehyde from lipid peroxidation. DNA oxidation was also blocked in the presence of ABPRE. In addition, ABPRE decreased the expression and activation of MMP-2 stimulated by phenazine methosulfate. Furthermore, ABPRE revealed the inhibitory effect on melanin production induced by L-dopa via antioxidant effect and the reduction of tyrosinase expression. Especially, the expression of antioxidant enzymes such as SOD-1 and SOD-2 regulated by Nrf2 was increased in the presence of ABPRE. Therefore, it appears that ABPRE may be a possible chemopreventive agent for the prevention of metastasis related to oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5887-5895
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• 2012

Background: To determine the effect of essential oil obtained from a traditionally used medicinal plant Tridax procumbens L, on lung metastasis developed by B16F-10 melanoma cells in C57BL/6 mice. Materials and Methods: Parameters studied were toxicity, lung tumor nodule count, histopathological features, tumor directed capillary vessel formation, apoptosis and expression levels of $P^{53}$ and caspase-3 proteins. Results: In vitro the MTT assay showed cytotoxicity was found to be high as 70.2% of cancer cell death within 24hrs for $50{\mu}g$. In vivo oil treatment significantly inhibited tumor nodule formation by 71.7% when compared with untreated mice. Formation of tumor directed new blood vessels was also found to be inhibited to about 39.5%. TUNEL assays also demonstrated a significant increase in the number of apoptotic positive cells after the treatment. $P^{53}$ and caspase-3 expression was also found to be greater in the essential oil treated group than the normal and cancer group. Conclusions: The present investigation showed significant effects of the essential oil of Tridax procumbens L in preventing lung metastasis by B16F-10 cell line in C57BL/6 mice. Its specific preventive effect on tumor directed angiogenesis and inducing effect on apoptosis warrant further studies at the molecular level to validate the significance of Tridax procumbens L for anticancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2303-2306
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• 2015

Objective: Skin tumors are the most commonly seen cancer type worldwide. Regarding pathogenesis, it is thought that disruption of kinetics through T lymphocyte-mediated development of chronic inflammation may be involved. The present study was intended to identify role of inflammatory cells such as neutrophils, monocytes and lymphocytes in the determination of risk for skin cancer. Materials and Methods: We retrospectively reviewed charts of 569 cases diagnosed as having primary skin tumors. Data regarding age, gender and histopathological subtype were recorded. Blood parameters studied on the day before surgery including WBCs, neutrophils, and lymphocyte counts, neutrophil:lymphocyte and neutrophil:monocyte ratios were also recorded. Two-hundred and two healthy individuals presented for check-up in an outpatient clinic were selected as the control group. Parameters studied in cases with skin cancer were compared to those healthy individuals. Findings: Of the cases with skin cancer, 401 were basal cell carcinoma (BCC) while 144 were squamous cell carcinoma (SCC) and 13 were malignant melanoma (MM). WBC, neutrophil and monocyte counts and the neutrophil:lymphocyte ratio were found to be lower in the patient group than in the healthy control group (p<0.001) while no significant difference was found in other parameters reviewed (p>0.05). No significant difference was found in WBC, neutrophil, neutrophil: monocyte ratio according to gender (p>0.05). Monocyte count was found to be $0.68{\pm}0.61$ in men and $0.55{\pm}0.25$ in women, indicating strong statistical significance (p<0.001). WBC, neutrophil and monocyte values were highest in control group while lowest in BCC. When BCC and SCC groups were compared to controls, significant differences found (p<0.001). There were no significant differences in lymphocyte counts among groups (p=0.976). Neutrophil:lymphocyte ratios were 3.24 in BCC, 3.59 in SCC, 3.44 in MM and 5.06 in control group (p<0.001). Conclusions: In our study, it was found that there were significant differences in complete blood count, neutrophil, monocyte and neutrophil:lymphocyte levels among groups. Neutrophil: lymphocyte ratio was found to be lowest in BCC among skin cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1093-1096
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• 2016

The tumor suppressor p16 is a biomarker for transforming human papilloma virus (HPV) infections that can lead to contradictory results in skin carcinomas. The aim of this study was to evaluate p16 expression and HPV-16 infection in the cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case-control study was performed on paraffin blocks of BCCs and SCCs and normal skin (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for groups were stained with hematoxylin and eosin (H & E). Immunohistochemistry was performed for p16 expression and human papilloma virus type 16 (HPV-16) infection. Normal group was skin of mammoplasty specimens and normal skin tissue in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4 years for normal, BCC and SCC groups, respectively. P16 positivity was more in SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all patients in three groups. Also, the mean age at diagnosis and P16-positivity were higher for the SCC group than the BCC group (P<0.005). In conclusion, in non-melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor but there is no correlation between HPV-16 and p16 in these tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7769-7779
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• 2015

Background: This study was conducted with the purpose of evaluating the effect of skin cancer training provided to maritime high school students on their knowledge and behaviour. Materials and Methods: The study had a quasi-experimental design with pre-test and post-test intervention and control groups. Two maritime high schools located in the city of Antalya were included within the scope of the study between March and June 2013, covering a total of 567 students. Results: While the knowledge mean scores of students regarding skin cancer and sun protection did not vary in the pre-test ($6.2{\pm}1.9$) and post-test ($6.8{\pm}1.9$) control group, the knowledge mean scores of students in the experimental group increased from $6.0{\pm}2.3$ to $10.6{\pm}1.2$ after the provided training. Some 25.4% of students in the experimental group had low knowledge level and 62.2% had medium knowledge level in the pre-test; whereas no students had low knowledge level and 94.3% had high knowledge level in the post-test. It was determined that tenth grade students, those who had previous knowledge on the subject, who considered themselves to be protecting from the sun better, had higher knowledge levels and their knowledge levels increased as the risk level increased. It was found that the provided training was effective and increased positively the knowledge, attitude and behaviour levels of students in the experimental group in terms of skin cancer and sun protection. Conclusions: Along with the provided training which started to form a lifestyle, appropriate attitudes and behaviours concerning skin cancer and sun protection could be brought to students who will work in outdoor spaces and are members of the maritime profession within the risk group.