• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.381-386
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• 2013

Aims: The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis. Methods: A total of 128 patients with gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5-fluorouracil, according to a defined schedule, were divided into three groups according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6 cycles); and Group III (>6 cycles). Results: The 5-year overall survival (OS) was 20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow-up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40% in Group II, and 40% in Group III. The OS and RFS in Groups II and III were significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between Groups II and III. Multivariate Cox hazard analysis determined that the number of adjuvant chemotherapy cycles was an independent factor that influenced OS and RFS. Conclusion: Six cycles of adjuvant chemotherapy gave encouraging outcomes in patients with resectable gastric cancer. Further prospective randomized controlled investigations are warranted in a multi-center setting.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.494-498
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• 2009

The emergence and spread of drug-resistant malaria parasites is a serious public health problem in the tropical world. Useful antimalarial drugs such as chloroquine have resistance in the world now. Moreover, other antimalarialdrugs such as mefloquine, halofantrine, atovaquone, proguanil, artemether and lumefantrine retain efficacy but have limitations, one of which is their high cost. New antimalarial drugs are clearly needed now. Cytotoxicity assay and susceptibility assay were performed for the selectivity of herb extracts in vitro. On the basis of high selectivity, 4-day suppressive test and survival test were progressed in Plasmodium berghei-infected mice. The selectivity of Areca catechu L. (ACL) and butanol extract of ACL (ACL-BuOH extract) were 3.4 and 3.0 in vitro, respectively. Moreover in vivo, 4-day suppressive test showed 39.1 % inhibition effect after treated with 150 mg/kg/day ACL-BuOH to P. berghei-infected mice. Survival test also showed 60% survival rate with ACL-BuOH-treated group while all other group mice died. In this study, ACL and ACL-BuOH were investigated for antimalarial activity in vitro and in vivo and they showed a potent antimalarial activity. In particular,ACL-BuOH could specifically lead higher survival rate of mice in vivo. Therefore ACL-BuOH would be a candidate of antimalarial drugs.

• Parasites, Hosts and Diseases
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• v.52 no.6
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• pp.595-603
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• 2014

Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time-and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite.

• Parasites, Hosts and Diseases
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• v.54 no.6
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• pp.711-717
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• 2016

Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of $pro-IL-1{\beta}$. To elucidate the role of inflammasome components in T. gondiiinfected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine $IL-1{\beta}$ secretion. The results revealed a significant upregulation of $IL-1{\beta}$ after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6017-6022
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• 2012

Background: Resveratrol has been reported to have potential chemopreventive and apoptosis-inducing properties in a variety of tumor cell lines. Objective: In this study, to investigate the effects of resveratrol on protein kinase C (PKC) activity and apoptosis in human colon carcinoma cells, we used HT-29 cells and examined the $PKC{\alpha}$ and ERK1/2 signaling pathways. Methods: To test the effects of resveratrol on the growth of HT-29 cells, the cells were exposed to varying concentrations and assessed with the the MTT cell-viability assay. Fluorescence-activated cell sorter (FACS) analysis was applieded to determine the effects of resveratrol on cell apoptosis. Western blotting was performed to determine the protein levels of $PKC{\alpha}$ and ERK1/2. In inhibition experiments, HT-29 cells were treated with G$\ddot{o}$6976 or PD98059 for 30 min, followed by exposure to $200{\mu}M$ resveratrol for 72 h. Results: Resveratrol had a significant inhibitory effect on HT-29 cell growth. FACS revealed that resveratrol induced apoptosis. Western blotting showed that e phosphorylation of $PKC{\alpha}$ and ERK1/2 was significantly increased in response to resveratrol treatment. Pre-treatment with $PKC{\alpha}$ and ERK1/2 inhibitors (G$\ddot{o}$6976 and PD98059) promoted apoptosis. Conclusion: Resveratrol has significant anti-proliferative effects on the colon cancer cell line HT-29. The PKC-ERK1/2 signaling pathway can partially mediate resveratrol-induced apoptosis of HT-29 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1447-1452
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• 2012

Aim: To evaluate the differential diagnostic potential of lesion stiffness assessed by the sonoelastographic strain index ratio (SR) and elastographic color scoring system (UE) for breast lesions. Materials and Methods: Three hundred and forty two breast masses (158 benign and 184 malignant) from 325 consecutive patients (mean age 44.2 years; range 16-81)who had been scheduled for a sonographically guided core biopsy were examined proposed by Itoh et al, with scoring 1-3=benign and 4-5=malignant. Strain and area ratios of each lesion were calculated within the same machine. Histological diagnosis was used as the reference standard. The area under the curve (AUC) and cut-off point were obtained by receiver operating curve and the cross table Fischer Test was carried out for assessing diagnostic value. Sensitivity, specificity, PPV, NPV, accuracy and false-discovery rates were compared. Results: The mean strain ratios for benign and malignant lesions were 1.87 and 7.9 respectively. (P<0.0001). When a cutoff point of 3.54 was used, SR had a sensitivity of 94.6%, a specificity 94.3%, a PPV of 95.1%, an NPV of 93.7% and an accuracy of 94.4%. The AUC values were 0.90 for the 5 point scoring system (UE) and 0.96 for the strain index ratio. The overall diagnostic performance was SR method was better (P<0.05). Conclusions: Strain ratio measurement could be another effective predictor in elastography imaging besides 5 the point scoring system for differential diagnosis of breast lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1487-1489
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• 2012

Objective: To compare the clinical efficacy of concurrent chemoradiotherapy, neoadjuvant chemotherapy, and intracavity brachytherapy in comprehensive treatment for young patients with stage Ib2 cervical cancer. Methods: One hundred and twelve young patients with stage Ib2 cervical cancer were enrolled retrospectively in our hospital from January 2003 to June 2005. They were categorized into three groups according to preoperative regimens, including the concurrent chemoradiotherapy group (Group 1, n=38), the neoadjuvant chemotherapy (Group 2, n=49), and the intracavity brachytherapy group (Group 3, n=25). Radical hysterectomy was performed following these regimens. Chemotherapy and radiotherapy were given according to pelvic lymph node metastasis, deep cervical stromal invasion, intravascular cancer emboli, histological grading, vaginal stump and positive surgical margin. Results: The cancer disappearance and superficial muscle invasion rates were statistically significantly better in the concurrent chemoradiotherapy group than in the other two groups (P<0.01). No statistically significant difference was noted in the deep muscle invasion rate, surgical time and intraoperative blood loss among three groups, but significantly more postoperative complications occurred in the concurrent chemoradiotherapy group. The 2-year pelvic recurrence was statistically significantly lower in the concurrent chemoradiotherapy group compared to other two groups, while the 5-year survival was higher. Conclusion: Concurrent chemoradiotherapy is efficacious for young patients with stage Ib2 cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7357-7362
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• 2014

Interleukin-6 (IL-6), a central proinflammatory cytokine, maintains immune homeostasis and also plays important roles in cervical cancer. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms at positions -174 and -572 with predisposition to cervical cancer in a Chinese population. The present hospital-based case-control study comprised 518 patients with cervical cancer and 518 healthy controls. Polymorphisms of the IL-6 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients with cervical cancer had a significantly higher frequency of the IL-6 -174 CC genotype [odds ratio (OR) =1.52, 95% confidence interval (CI) = 1.06-2.19; p=0.02], IL-6 -572 CC genotype (OR =1.91, 95% CI = 1.16-3.13; p=0.01) and IL-6 -174 C allele (OR =1.21, 95% CI = 1.02-1.44; p=0.03) compared to healthy controls. When stratifying by the FIGO stage, patients with III-IV cervical cancer had a significantly higher frequency of IL-6 -174 CC genotype (OR =1.64, 95% CI =1.04-2.61; p=0.04). The CC genotypes of the IL-6 gene polymorphisms at positions -174 and -572 may confer a high risk of cervical cancer. Additional studies with detailed human papillomavirus (HPV) infection data are warranted to validate our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7919-7923
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• 2014

20(S)-Protopanaxadiol (PPD), a ginsenoside isolated from Pananx quinquefolium L., has been shown to inhibit growth and proliferation in several cancer cell lines. The aim of this study was to evaluate its anticancer activity in human breast cancer cells. MCF-7 cells were incubated with different concentrations of 20(S)-PPD and cytotoxicity was evaluated by MTT assay. Occurrence of apoptosis was detected by DAPI and Annexin V-FITC/PI double staining. Mitochondrial membrane potential was measured with Rhodamine 123. The Bcl-2 and Bax expression were determined by Western blot analysis. Caspase activity was measured by colorimetric assay. 20(S)-PPD dose-dependently inhibited cell proliferation in MCF-7 cells, with an $IC_{50}$ value of $33.3{\mu}M$ at 24h. MCF-7 cells treated with 20(S)-PPD presented typical apoptosis, as observed by morphological analysis in cell stained with DAPI. The percentages of annexin V-FITC positive cells were 8.92%, 17.8%, 24.5% and 30.5% in MCF-7 cells treated with 0, 15, 30 and $60{\mu}M$ of 20(S)-PPD, respectively. Moreover, 20(S)-PPD could induce mitochondrial membrane potential loss, up-regulate Bax expression and down-regulate Bcl-2 expression. These events paralleled activation of caspase-9, -3 and PARP cleavage. Apoptosis induced by 20(S)-PPD was blocked by z-VAD-fmk, a pan-caspase inhibitor, suggesting induction of caspase-mediated apoptotic cell death. In conclusion, the 20(S)-PPD investigated is able to inhibit cell proliferation and to induce cancer cell death by a caspase-mediated apoptosis pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6439-6443
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• 2013

Objective: To investigate whether the expression level of valosin-containing protein (VCP) is correlated with the prognosis of primary orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: VCP expression in 58 samples from primary orbital MALT lymphoma patients was determined by immunohistochemisty using monoclonal antibodies. Correlations between VCP expression level and prognosis were clarified by statistical analysis. Results: It was found that the percentage of VCP positive cells in samples of primary orbital MALT lymphoma ranged from 32% to 95%. The samples were divided into two groups (level 1 and level 2) according to the median value (45%) of the percentage of VCP positive cells. It was found that the expression level of VCP was significantly correlated with recurrence (P=0.003) and tumor size (P=0.008). At the same time, the 5-year disease-free and overall survival rate of patients of level 1 was significantly better than that of level 2 (P=0.001; P=0.032). There was no observed correlation between the expression level of VCP and other clinical features. Conclusion: VCP could be a useful marker for predicting the prognosis of primary orbital MALT lymphoma.