• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6149-6154
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• 2015

Background: There is no suggested molecular indicator for the determination of which patients will benefit from anti-angiogenetic treatment in metastatic colorectal cancers. Materials and Methods: In this study, VEGF and $HIF-1{\alpha}$ expression and their clinical significance were studied in tumor tissues of patients with colorectal cancer receiving bevacizumab-based treatment. VEGF and $HIF-1{\alpha}$ were assessed by immunohistochemistry in the primary tumors of 53 metastatic colorectal cancer patients receiving chemotherapy in combination with first line bevacizumab. Results: The clinical benefit rate in the low-VEGF expression group was 38%, while it was 62% in the high expression group. While the median progression-free survival (PFS) was 10 months in the high-VEGF expression group, it was 8 months in the low-VEGF expression group (p = 0.009). The median overall survival (OS) was found to be 26 months vs 15 months. Thus, when VEGF was strongly expressed it was in favor of that group and the difference was statistically significant (p = 0.03). High VEGF expression rate was an independent factor that correlated with OS or PFS (p=0.016 and 0.009, respectively). Conclusions: The data showed that VEGF may have predictive value for determining the treatment of CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3191-3194
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• 2014

Adenocarcinoma of lung has high incidence and a poor prognosis, woith chemotherapy as the main therapeutic tool, most commonly with cisplatin. However, chemotherapy resistance develops in the majority of patients during clinic treatment. Mechanisms of resistance are complex and still unclear. Although annexin play important roles in various tumor resistance mechanisms, their actions in cisplatin-resistant lung adenocarcinoma remain unclear. Preliminary studies by our group found that in cisplatin-resistant lung cancer A549 cells and lung adenocarcinoma tissues, both mRNA and protein expression of annexins A1, A2 and A3 is increased. Using a library of annexin A1, A2 and A3 targeting combined molecules already established by ourselves we found that specific targeting decreased cisplatin-resistance. Taken together, the underlined effects of annexins A1, A2 and A3 on drug resistance and suggest molecular mechanisms in cisplatin-resistant A549 cells both in vivo and in vitro. Furthermore, the study points to improved research on occurrence and development of lung adenocarcinoma, with provision of effective targets and programmes for lung adenocarcinoma therapy in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3741-3745
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• 2014

Background: Emerging evidence implicates the platelet-derived growth factor-D (PDGF-D) in many types of human solid tumors. We investigated whether PDGF-D plays an important role in endometrial cancer (EC) in relation to clinicopathologic phenotype, angiogenesis, and patient prognosis. Materials and Methods: We analyzed PDGF-D protein expression by Western blotting in twenty-seven human endometrial cancer tissues, and matched normal endometrial controls collected at the third Affiliated hospital of Sun Yat-sen University during 2012-2013 (n=27). Immunohistochemical staining was performed using a human PDGF-D antibody on the endometrial cancer patients collected in the same facility during January 2001 and October 2013 (n=152). Patients were followed from the time of primary surgery in 2001-2013 until death or last follow-up. We correlated the PDGF-D expression levels with clinicopathologic parameters and prognosis in human endometrial cancer patients. Results: Compared with matched normal endometrial cases, PDGF-D was up-regulated in endometrial cancer. Expression of PDGF-D protein, found in 78% of the cases, was associated with nonendometrioid histologic type (p=0.028), FIGO stage III/IV (p=0.039), >50% solid tumor growth (p=0.048), pelvic LN metastasis (p=0.035) and ER and PR negativity (p=0.04 and 0.002). PDGF-D expression was also significantly associated with expression of VEGF-A (p=0.021). In multivariate analysis, PDGF-D expression proved to be an independent prognostic factor in addition to histologic grade and FIGO stage. Patients with high expression levels of PDGF-D had a significantly poorer overall survival rate compared with patients with no expression. Conclusions: PDGF-D expression is frequently up-regulated in endometrial cancer, and is associated with aggressive features and poor prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1925-1929
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• 2014

Background: Vascular endothelial growth factor-C (VEGF-C), which contributes to lymphatic metastasis (LM) in malignant disease, is one of the most important factors involved in physical and pathological lymphangiogenesis. Some VEGF-C related factors such as sine oculis homeobox homolog (SIX) 1, contactin (CNTN) 1 and dual specificity phosphatase (DUSP) 6 have been extensively studied in malignancies, but their expression levels and associations have still to be elucidated in stomach cancer. Methods: We detected their expression levels in 30 paired stomach cancer tissues using quantitative real-time reverse transcription-PCR (qRT-PCR). The expression and clinical significance of each factor was analyzed using Wilcoxon signed rank sum test. The correlation among all the factors was performed by Spearman rank correlation analysis. Results: The results suggest that VEGF-C and CNTN1 are significantly correlated with tumor size, SIX1 with the age and CNTN1 also with the cTNM stage. There are significant correlations of expression levels among VEGF-C, SIX1, CNTN1 and DUSP6. Conclusions: There exists an important regulatory crosstalk involving SIX1, VEGF-C, CNTN1 and DUSP6 in stomach cancer.

• ALGAE
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• v.32 no.3
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• pp.261-273
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• 2017

Fine dust (FD) particles have become a major contributor to air pollution causing detrimental effects on the respiratory system and skin. Although some studies have investigated the effects of FD on the respiratory system, their possible effects on the skin remain under-explored. We investigated the FD mediated inflammatory responses in keratinocytes, present in the outer layers of skin tissues and the transfer of inflammatory potential to macrophages. We further evaluated the anti-inflammatory effects of the polyphenolic derivative, diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae against FD-induced inflammation. Size distribution of FD particles was analyzed by scanning electron microscopy. FD particles induced the production of cyclooxygenase-2, prostaglandin E2 ($PGE_2$), interleukin (IL)-$1{\beta}$, and IL-6 in HaCaT keratinocytes and the expression of nitric oxide (NO), inducible nitric oxide synthases (iNOS), $PGE_2$, tumor necrosis factor-${\alpha}$ expression in RAW 264.7 macrophages. Further, we evaluated the inflammatory potential of the culture medium of inflammation-induced HaCaT cells in RAW 264.7 macrophages and observed a marked increase in the expression of NO, iNOS, $PGE_2$, and proinflammatory cytokines. DPHC treatment markedly attenuated the inflammatory responses, indicating its effectiveness in suppressing a broad range of inflammatory responses. It also showed anti-inflammatory potential in in-vivo experiments using FD-stimulated zebrafish embryos by decreasing NO and reactive oxygen species production, while eventing cell death caused by inflammation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3419-3423
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• 2015

Background: Liposarcoma of the spermatic cord is rare and frequently misdiagnosed. The standard therapeutic approach has been radical inguinal orchiectomy with wide local resection of surrounding soft tissues. The current trend of organ preservation in the treatment of several cancers has started to evolve. Herein we present our testis-sparing surgery experience in the treatment of spermatic cord liposarcoma and a pooled analysis on this topic. Materials and Methods: Clinical information from patient receiving organ-sparing surgery was described. Clinical studies evaluating this issue were identified by using a predefined search strategy, e.g., Pubmed database with no restriction on date of published papers. The literature search used the following terms: epidemiology, surgery, chemotherapy, radiotherapy, testis sparing surgery, spermatic cord sarcomas/liposarcomas. Results: Patient received a complete excision of the lesion, preserving the spermatic cord and the testis. The final pathological report showed a well differentiated liposarcoma with negative surgical margins and no signs of local invasion. After 2-year of follow-up, there was no evidence of local recurrence. Since the first case reported in 1952, a total of about 200 well-documented spermatic cord liposarcoma cases have been published in English literature. Among these patients, only three instances were reported to have received an organ-sparing surgery in the treatment of spermatic cord liposarcoma. Conclusions: Radical inguinal orchiectomy and resection of the tumor with a negative microscopic margin is the recommended treatment for liposarcoma of the spermatic cord. But for small, especially well-differentiated, lesions, testis-sparing surgery might be a good option if an adequate negative surgical margin is assured.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1391-1395
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• 2015

Breast cancer is one of the most common and letal cancers in all over the world. Since there have been significant improvements in treatment of breast cancer, there is still a big need for alternative approaches. In this study, we aimed to investigate protective role of hydatid disease against breast cancer. Twenty Wistar rats were divided into two groups of 10 rats each Group I (control) and Group II. In Group II intraperitoneal hydatidosis was performed. Then DMBA was applied to mammary tissues of all rats. Immunohistochemistry studies for Ki-67 and S-100 in the tumoral tissue sections of DMBA induced mammary tumor in rats were performed. TUNEL Assay was used to detect apoptotic cells of tumoral tissue. In vivo anticancer activity testing was carried out by preventing the tumorigenesis by DMBA in mammary tissue of rats. The expressions of the Ki-67 and S-100 protein decreased in rats who had Hydatid Disease (HD) (Group II), compared with the control rats (Group I). TUNEL positive cells were higher in rats with HD (Group II), compared with the control rats (Group I). In vivo studies showed that HD prevented the tumorigenesis by DMBA in mammary tissue of rats with 50 percent.In the light of the evidence the present study showed that HD may have chemopreventive effects on DMBA induced breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4169-4172
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• 2015

Background: Oral carcinoma (OC) remains as one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties on various human cancer cells, although the mechanisms of action remain to be addressed. This study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of p53 as a main prognosticator of OC. Materials and Methods: 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500 mg/kg body weight of Hesa-A three times a day. The two other groups considered as treated and untreated healthy groups. At the end of experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results indicated that compared to healthy group, p53 over expressed ~ 40% in untreated carcinoma group. After treatment with 250mg/kg and 500mg/kg body weights of Hesa-A, p53 level dropped by 53.4% and 13.6 %, respectively, compared to untreated carcinoma group (p<0.05, p<0.0001). Moreover, there was a significant relation between p53 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insights into the mechanism(s) by which Hesa-A improves clinical outcome of oral carcinoma by modulation of p53 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10917-10922
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• 2015

Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (${\geq}4cm$), alpha-fetoprotein (${\geq}100ng/ml$), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041-2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01-2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10773-10777
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• 2015

Background: Treatment for breast cancer is mainly performed by surgical resection of primary tumors and chemotherapy. However, after tumor invasion and metastases, breast cancer is hard to control. Clarification of the pathogenic mechanisms would be helpful to the prognosis or therapy for the breast cancer. The aim of this study is to investigate the clinical and prognostic implications of legumain protein Materials and Methods: In this study, we examined mastectomy specimens from 114 breast cancer and matching, 26 adjacent non-cancerous tissues using immunohistochemistry. Results: The results indicated that positive expression of legumain protein in breast cancer was 51.8 % (59/114) and the positive expression of legumain protein in adjacent non-cancerous tissue was 11.5% (3/26). It appeared to be related with lymph node metastasis of breast cancer (p=0.02) and correlation analysis indicated that legumain expression was correlated positively with the estrogen receptor (ER) and mutant-type p53 expression (both p<0.05). Positive legumain expression was significantly associated with shorter overall survival time in breast cancer patients (log-rank p<0.01). Multivariate survival analysis suggested that the positive legumain expression was an independent predictor of poorer overall survival in patients with breast cancer (HR=0.24; 95%CI 0.11-0.65, p=0.03). Conclusions: Legumain might be a new potential biomarker for breast cancer, which may reflect the prognosis and overall survival.