• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05b
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• pp.88.2-98
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• 2002

A wide arry of naturally occurring substances particularly those present in dietary and medicinal plants, have been reported to possess substantial cancer chemopreventive properties. Certain phytochemicals retain strong antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activities. Inducible cyclooxygenase(COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. There is some evidence that expression of both COX-2 and iNOS is co-regulated by the eukaryotic transcription factor NF-$textsc{k}$B. Increased expression of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory diseases. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activies are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. An example is curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), that strongly occurring diaryl heptanoids structurally related to curcumin have substantial anti-tumor promotional activities in two-stage mouse skin carcinogenesis. Thus, yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3heptanone] and yakuchinone B [1-(4'-hydroxy-3'methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberacease) attenuate phorbol ester-induced inflammation and papilloma formation in female ICR mice. These diarylheptanoids also suppressed phorbol ester-induced activation of epdermal ornithine decarboxylase and its mRNA expression when applied onto shaven backs of mice. Yakuchinone A and B as well as curcumin inhibited phorbol ester-induced expression of COX-2 and iNOS and their mRNA in mouse skin via inactivation of NF-$textsc{k}$B. Capsaicin, a major pungent ingredient of red pepper also attenuated phorbol ester-induced NF-$textsc{k}$B activation. Similar suppression of COX-2 and iNOS and down-regulation of NF-$textsc{k}$B activation for its DNA binding were observed with the ginsenosied Rg3 and the ethanol extract of Artemisia asiatica. We have also found that certain anti-inflammatory phytochemicals exert inhibitory effects on phorbol ester-induced COX-2 expression and NF-$textsc{k}$B activation in immortalized human breast epithelial (MCF-10A) cells in culture. One of the plausible mechanisms undelying inhibition by aforementioned phytochemicals of phorbol ester-induced NF-$textsc{k}$B activation involves interference with degragation of the inhibitory unit, I$textsc{k}$Ba, which blocks subsequent nuclear translocation of the functionally active p65 subunit of NF-$textsc{k}$B. the activation of epidermal NF-$textsc{k}$B by phorbol ester and subsequent induction of COX-2 hence appear to play an important role in intracellular signaling pathwasy leading to tumor promotion and targeted inhibition of NF-$textsc{k}$B may provide a new promising cancer chemopreventive strategy.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.347-354
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• 2014

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8699-8703
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• 2014

18-fluoro-2-deoxyglucose positron emission tomography-computed tomography ($^{18}F$-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate $^{18}F$-FDG uptake on PET/CT scans. We reviewed $^{18}F$-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between $^{18}F$-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. $^{18}F$-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on $^{18}F$-FDG PET/CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5965-5972
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• 2013

PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.

• Biomedical Science Letters
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• v.3 no.2
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• pp.125-130
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• 1997

Taxol, an anticancer drug that has diterpenoid conformation, has been used as an effective chemotherapeutical agent in the treatment of breast and ovarian cancers. Because of its toxicity like other anticancer drugs, monitoring the taxol level in serum is important procedure during cancer therapy. The various monitoring methods using HPLC, ELISA, and RIA have been adopted, and RIA technique is known to be superior than other methods in trems of sensitivity and convenience. In this study, in order to develope taxol RIA system using $^{125}$I labelled antigen, first of all we synthesized taxol derivatives. 2'-hemisuccinyltaxol was obtained with about 80％ yield by esterification of taxol at C-2' hydroxyl group on C-13 carbon with succinic anhydride. [$^{125}$I]iodotyramine was prepared with 58％ labelling yield by radioiodination of tyramine and purified by gel chromatography. 2'-[$^{125}$I]iodotyramine-hemisuninyltaxol, $^{125}$I labelled antigen for taxol RIA, was synthesized with 96% yield from conjugation of 2'-hemisuccinyltaxol and [$^{125}$I]iodotyramine. Anti-taxol serum was produced from the rabbit immunized with 2'-hemisuccinyltaxol-BSA synthesized by 2'-hemisuccinyltaxol and BSA. The antiserum titer was determined by RIA using 2'-[$^{125}$I]iodotyramine-hemisuccinyltaxol. The titer of 1:20 was obtained with about 40% of B/T. The results suggest that taxol RIA using $^{125}$I labelled antigen can be applied to monitor the taxol level in serum.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10613-10619
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• 2015

Background: Both alcohol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, the dried root tuber of which is named Baifuzi in Chinese, have been used for folklore treatment of cancer in Northeast of China. However, little is known about which is most suitable to the cancer therapy. Materials and Methods: Serum pharmacology and MTT assays were adopted to detect the effects of ethanol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, prepared by heat reflux methods, on proliferation of different cancer cells. Results: Cancer cells treated with medium supplemented with 10%, 20%, 40% serum(v/v) containing ethanol extract had a decline in viability, with inhibition rates of 7.69%, 21.8%, 41.9% in MCF-7 cells, 42.8%, 48.1%, 51.8% in SGC-7901 cells, 44.1%, 49.2%, 53.7% in SMMC-7721 cells, 6.8%, 15.2%, 39.8% in HepG2 cells, 7.57%, 16.3%, 36.2% in HeLa cells, 6.24%, 12.5%, 27.4% in A549 cells, and 7.20%, 17.5%, 31.3% in MDA-MB-231 cells, respectively. Viability in the aqueous extract groups was no different with that of controls. Conclusions: An ethanol extract of Sauromatum giganteum(Engl.) Cusimano and Hett inhibited the proliferation of SMMC-7721, SGC-7901 and MCF-7 cells, which supports the use of alcoholic but not aqueous extracts for control of sensive cancers, which might include hepatocarcinoma, gastric cancer and breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5435-5440
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• 2013

Background: Recent estimates suggest that in the Lao People's Democratic Republic (Lao PDR) the burden of cancer in terms of DALYs lost is amongst the highest in South East Asia. As such, increasingly cancer is becoming an important public health concern in the country. Lao PDR however has no population-based cancer registry and only one hospital-based registry. Cancer treatment within the country is extremely limited. Patients who can, may travel to neighboring countries for treatment, but little information about this is available in the country. The aim of this study was to estimate some of the otherwise largely unknown parameters of the cancer burden in Lao PDR. Materials and Methods: This is a retrospective, descriptive study based on the records of 847 Lao cancer cases treated with surgery, radiation and chemotherapy at Srinagarind Hospital, Khon Kaen University, in Thailand between 1988 and 2010. Results: The annual rate of registration of Lao cancer cases fluctuated, but showed an increasing trend. Most cancers were diagnosed by histology (65.2%), and a combination of endoscopy and radiology (15.6%). In most cases (70.2%) the stage of cancer at diagnosis could not be determined. In those whose stage could be identified, 54.0% were at the final stage (Stage IV). Among males, the commonest cancer sites were the liver (16.1%), blood (12.3%) and nasopharynx (10.6%). Those in female patients were the cervix (22.2%), breast (14.6%) and blood (8.1%). Conclusions: This study indicates that despite some fluctuations, the number of Lao cancer patients presenting at Srinagarind Hospital, Khon Kaen, gradually increased between 1988 and 2010. The unfavorable pattern of late-stage cancer diagnosis among male and female patients suggests a need for cancer control interventions and the establishment of cancer registration and treatment facilities within Lao PDR.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.5
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• pp.343-349
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• 2007

Radioiodide transport has been extensively and successfully used in the evaluation and management of thyroid disease. The molecular characterization of the sodium/iodide symporter (NIS) and cloning of the NIS gene has led to the recent expansion of the use of radioiodide to cancers of the breast and other nonthyroidal tissues exogenously transduced with the NIS gene. More recently, discoveries regarding the functional analysis and regulatory processes of the NIS molecule are opening up exciting opportunities for new research and applications for NIS and radio iodide. The success of NIS based cancer therapy is dependent on achievement of maximal radioiodide transport sufficient to allow delivery of effective radiation doses. This in turn relies on high transcription rates of the NIS gene. However, newer discoveries indicate that nontranscriptional processes that regulate NIS trafficking to cell membrane are also critical determinants of radioiodide uptake. In this review, molecular mechanisms that underlie regulation of NIS transcription and stimuli that augment membrane trafficking and functional activation of NIS molecules will be discussed. A better understanding of how the expression and cell surface targeting of NIS proteins is controlled will hopefully aid in optimizing NIS gene based cancer treatment as well as NIS based reporter-gene imaging strategies.

• Journal of Preventive Medicine and Public Health
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• v.35 no.1
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• pp.24-32
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• 2002

Objective : Few studies have examined the relationship between the risk of cancer and exposure to pesticides in Korea or in other East Asian that have until recently used chlorophenoxy herbicides. The aim of this study was to evaluate the relationship between the exposure to pesticides and cancer incidence. Methods : We conducted a prospective cohort study with a follow-up period of 13 years (1985-1998). The subjects included 2,687 male and 3,589 female Kangwha Island residents, Koreans aged fifty-five or more as of March 1985, who received a personal health interview and completed a health examination survey. A Cox proportional hazards models were used to estimate relative risks(RR). Results : At baseline, the mean age of the study participants in 1985 was 66.4 for males and 67.1 for females. During the 13 years follow-up, a total of 300 incidents of cancer in males and 140 in females developed. In males, the total cancer incidence in the highest group was RR, 1.4 (95%. CI=1.0-1.9), p for trend=0.041, for digestive organ cancer Incidence in the highest group, RR, 1.5 (95% CI=1.0-2.3), p for trend=0.057, for stomach cancer, incidence in the highest group, RR, 1.6 (95% CI=0.9-2.8), p for trend=0.094, for gallbladder cancer incidence in the highest group, RR, 9.1 (95% CI=1.1-77.0), p for trend=0.014 were elevated according to the higher frequency of pesticide use per year. In particular, the risk of gallbladder cancer was very high. Although not significant, the risk of liver cancer was higher than in the non-exposed group (in the highest group, RR, 2.0(95% CI=0.7-5.9)). In females, although not significant, breast cancer incidence in the highest exposure group was higher than in the non-exposed group (in the highest group, RR, 4.7 (95% CI=0.5-27.9)). Conclusions : This study demonstrates that Korean farmers who use pesticides, particularly males, have a significantly higher total cancer incidence, particularly from digestive organ cancers such as, stomach, gallbladder, and liver cancer. In particular, the risk of gallbladder cancer was very high.

• Journal of Life Science
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• v.22 no.9
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• pp.1145-1151
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• 2012

Aspirin and its deacetylated form, sodium salicylate (NaSal), have been shown to exert chemopreventive activities against many human cancers including those of the colon, lung, and breast. Previously, we showed that combined treatment of NaSal and genistein synergistically induced apoptosis in A549 lung cancer cells, indicating that these two natural chemicals could be used in combination for cancer therapy. In this study, we examined effects of NaSal/genistein combined treatment on other cancer cells and in three-dimensional multicellular tumor spheroid (MTS) and in an in vitro solid tumor model. We found that the combined treatment induces apoptosis in the HCT116 cells and the A549 cells, but not in the MCF-7 cells. Interestingly, the MCF-7 cells responded to the NaSal/genistein combined treatment by undergoing cell death when they were cultivated as MTS. The combined treatment induced apoptosis at an earlier stage in the MCF-7 MTS culture. However, when the MCF-7 MTS was cultivated for a longer period, it induced necrosis rather than apoptosis. We further found that the apoptotic pattern observed in MCF-7 MTS was incomplete: the chromatins were condensed and fragmented, but the nuclear membrane was still intact. Taken together, these results demonstrate that the NaSal/genistein combined treatment induces incomplete apoptosis and necrosis in the MCF-7 MTS culture system.