• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1889-1894
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• 2013

Background: Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a rare and distinctive tumor with no standard treatment. This study aimed to explore treatment in relation to prognosis of the disease. Methods: A total of 142 patients with BSCCE that underwent treatment in our hospital from March 1999 to July 2010 were retrospectively analyzed. All patients received surgery, 42 postoperative radiotherapy and 28 patients chemotherapy. Results: There were 26 patients included in stage I, 60 in stage II, 53 in stage III and 3 in stage IV. The clinical symptoms and macroscopic performances of BSCCE did not differ from those of typical esophageal squamous cell carcinoma. Among 118 patients receiving endoscopic biopsy, only 12 were diagnosed with BSCCE. The median survival time (MST) of the entire group was 32 months, with 1-, 3- and 5-year overall survival (OS) of 81.4%, 46.8% and 31.0%, respectively. The 5-year OS of stage I and II patients was significantly longer than that of stages III/IV, at 60.3%, 36.1% and 10.9%, respectively (p<0.001, p=0.001). The MST and 5-year OS were 59.0 months and 47.4% in patients with tumors located in the lower thoracic esophagus, and 27.0 months and 18.1% in those with lesions in the upper/middle esophagus (p=0.002). However, the survival was not significantly improved in patients undegoing adjunctive therapy. Multivariate analysis showed TNM stage and tumor location to be independent prognostic factors. Furthermore, distant metastasis was the most frequent failure pattern, with a median recurrence time of 10 months. Conclusion: BSCCE is an aggressive disease with rapid progression and a propensity for distant metastasis. It is difficult to make a definitive diagnosis via preoperative biopsy. Multidisciplinary therapy including radical esophagectomy with extended lymphadenectomy should be recommended, while the effectiveness of radiochemotherapy requires further validation for BSCCE.

• Molecules and Cells
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• v.26 no.6
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• pp.536-547
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• 2008

Anthocyanidin synthase (ANS, leucoanthocyanidin oxygenase), a 2-oxoglutarate iron-dependent oxygenase, catalyzed the penultimate step in the biosynthesis of the anthocyanin class of flavonoids, from the colorless leucoanthocyanidins to the colored anthocyanidins. The full-length cDNA and genomic DNA sequences of ANS gene (designated as GbANS) were isolated from Ginkgo biloba for the first time. The full-length cDNA of GbANS contained a 1062-bp open reading frame (ORF) encoding a 354-amino-acid protein. The genomic DNA analysis showed that GbANS gene had three exons and two introns. The deduced GbANS protein showed high identities to other plant ANSs. The conserved amino acids (H-X-D) ligating ferrous iron and residues (R-X-S) participating in 2-oxoglutarate binding were found in GbANS at the similar positions like other ANSs. Southern blot analysis indicated that GbANS belonged to a multi-gene family. The expression analysis by real-time PCR showed that GbANS expressed in a tissue-specific manner in G. biloba. GbANS was also found to be up-regulated by all of the six tested abiotic stresses, UV-B, abscisic acid, sucrose, salicylic acid, cold and ethylene, consistent with the promoter region analysis of GbANS. The recombinant protein was successfully expressed in E. coli strain with pET-28a vector. The in vitro enzyme activity assay by HPLC indicated that recombinant GbANS protein could catalyze the formation the cyanidin from leucocyanidin and conversion of dihydroquercetin to quercetin, suggesting GbANS is a bifunctional enzyme within the anthocyanidin and flavonol biosynthetic pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1693-1697
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• 2012

Objective: To explore the effect on radiosensitivity of arsenic trioxide ($As_20_3$) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of $As_20_3$ was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of $IC_{50}$ value and choice of 20% of the $IC_{50}$ as the experimental drug concentration. Blank control, $As_20_3$, hyperthermia, radiotherapy group, $As_20_3$ + hyperthermia, $As_20_3$ + radiotherapy, hyperthermia + radiotherapy and $As_20_3$ + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: $As_20_3$ exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an $IC_{50}$ of 18.7 ${\mu}mol/L$. After joint therapy of $As_20_3$ + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the $G_2$/M phase, and as the ratio of cells in $G_0/G_1$ and S phases decreased, cell death became more pronounced. Conclusion: $As_20_3$ and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, $As_20_3$ and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3931-3936
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• 2012

Background: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. Methods: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. Results: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). Conclusion: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1567-1574
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• 2014

The incidence and mortality rates of liver and nasopharyngeal cancer in Guangxi province of China have always been among the highest in the world, and cancer is one of the major diseases that pose a threat to the health of residents in Guangxi. However, no systematic study has been performed to evaluate the time trends in the structure of cancer-related deaths and cancer mortality. In this study, we reveal sex, age and geography differences of cancers mortality between three death surveys (1971 to 1973, 1990 to 1992, and 2004 to 2005). The results show that the standardized mortality rate of cancer in Guangxi residents has risen from 43.3/100,000 to 84.2/100,000, the share of cancer deaths in all-cause deaths has increased from 13.3% to 20.7%, and cancer has become the second most common cause of death. The five major cancers, liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and colorectal cancer, account for 60% of all the cancer deaths. Cancers with growing mortality rates over the past 30 years include lung cancer, colorectal cancer, liver cancer and female breast cancer, of which lung cancer is associated with the sharpest rise in mortality, with a more than 600% rise in both men and women. Cancer death in Guangxi residents occurs mainly in the elderly population above 45 years of age, especially in people over the age of 65. The areas with the highest mortality rates for liver cancer and nasopharyngeal cancer, which feature regional high incidences, include Chongzuo and Wuzhou. Therefore, for major cancers such as liver cancer, lung cancer, gastric cancer, nasopharyngeal cancer and female breast cancer in Guangxi, we can select high-risk age groups as the target population for cancer prevention and control efforts in high-prevalence areas in a bid to achieve the ultimate goal of lowering cancer mortality in Guangxi.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6427-6431
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• 2013

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world and deeply threatens people's health, especially in China. Techniques of early diagnosis, prevention and prediction are still being discovered, among which the approaches based on single nucleotide polymorphisms in microRNA genes (miRNA SNPs) are newly proposed and show prospective potential. In particular, the association between SNPs in miRNA196a-2 (rs11614913) and miRNA146a (rs2910164) and HCC has been investigated. However, the conclusions made were conflicting, possibly due to insufficient sample size or population stratification. Further confirmations in well-designed large samples are still required. In this study, we verified the association between these two SNPs and the susceptibility to HCC by MassARRAY assay in a 2,000 large Chinese case-control sample. Significant association between rs11614913 and HCC was confirmed. Subjects with the genotype of CT+TT or T allele in rs11614913 were more resistant to HCC (CT+TT: OR (95% CI)=0.73 (0.57-0.92), P=0.01; T allele: OR (95% CI)=0.85 (0.75-0.97), P=0.02) and HBV-related HCC (CT+TT: OR (95% CI)=0.69 (0.53-0.90), P=0.01; T allele: OR (95% CI)=0.82 (0.71-0.95), P=0.01). The affected carriers of CT or TT also tended to have lower levels of serum AFP (P=0.01). This study demonstrated a role of rs11614913 in the etiology of HCC. Further research should focus on the clinical use of this miRNA SNP, so as to facilitate conquering HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4061-4066
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• 2013

The extranodal natural killer/T-cell lymphoma (ENKTL) shows high local or systemic failure rates when radiotherapy (RT) is taken as the primary treatment, suggesting a role for chemotherapy (CT) added to RT for this disease. However, the appropriate mode of combined modality therapy (CMT) has not been fully defined. A total of one hundred and twenty-one patients with ENKTL receiving sandwich CT with RT were reviewed between January 2003 and August 2012. The primary endpoints were the response rate, progression-free survival (PFS), overall survival (OS), and the relapse rate. After the initial CT, there were 84 (69.4%) patients in CR, 22 (18.2%) patients in PR, 9 (7.4%) patients in SD, and 6 (5%) patients in PD, respectively. At the end of RT, the CR, PR, SD, and PD rates for all patients were 90.9% (n=110), 1.7% (n=2), 4.1% (n=5), and 3.3% (n=4), respectively. After a median follow-up of 42.3 months (3.5~112.3 months), the 5-year PFS was 74.7% (95% CI 70.4%~79.0%), and 5-year OS was 77.3% (95% CI 67.9%~86.7%). Disease progression was documented in 25 (20.7%) patients. The rates of systemic failure, local failure, and regional failure were 18.2%, 5.8%, 1.7%, respectively. Twenty death events (16.5%) were observed for the entire group of patients (18 deaths related to PD). Furthermore, CR to the initial CT and low Korean Prognostic Index (KPI) can independently predict long PFS and OS. The sandwich CMT achieved an excellent outcome for localized ENKTL with acceptable toxicity. We recommend it can be applied as the optimal choice for localized ENKTL.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.12
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• pp.1601-1607
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• 2010

Two experiments were carried out to investigate i) the effects of four levels of lactic acid bacteria inoculants (LAB; 0, $2{\times}10^5$, $3{\times}10^5$ and $4{\times}10^5$ cfu/g fresh forage) and two physical forms of rice straw (whole and chopped rice straw) on silage fermentation quality and nutritive value of rice straw (RS) silage for lactating Holsteins and ii) the effects of the replacement of corn silage (CS) with different inclusion levels (0, 25 and 50%) of LAB treated RS on lactating performance of Holstein dairy cows. Rice straw packed with stretch film was ensiled for 45 d. The results showed that the higher level of LAB inoculants in the silage quadratically decreased pH, $NH_3$-N and acetic acid concentrations and increased the contents of lactic acid and total organic acids. The CP content and DM losses in the silage declined linearly as the level of LAB addition was increased. Compared with whole-plant rice straw silage (WRS), chopped rice straw silage (CRS) dramatically reduced pH by 0.83. The concentrations of $NH_3$-N were similar in WRS and CRS and both were less than 50 g/kg of total N. Chopping rice straw before ensiling significantly enhanced the lactic acid concentration and total organic acids content whereas the concentration of acetic acid declined. The CP, NDF and ADF content of CRS was 13.4, 5.9 and 10.2% lower than in WRS, respectively. Except for butyric acid concentration, significant interaction effects of inoculation level and physical form of RS were found on all fermentation end-products. Our findings indicated that milk yield and composition were not affected by different level of RS inclusion. However, because of the lower cost of WRS, cows consuming a ration in which WRS was partially substituted for CS had 3.48 Yuan (75% CS+25% WRS) and 4.56 Yuan (50% CS+50% WRS) more economic benefit over those fed a CS-based ration. It was concluded that the chopping process and LAB addition could improve the silage quality, and that substitution of corn silage with RS silage lowered the cost of the dairy cow ration without impairing lactation performance.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5835-5842
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• 2015

Background: Melatonin, which is mainly produced by the pineal gland, has a good inhibitory effect on cell growth of multiple cancer types. However, the underlying molecular mechanisms of anti-tumor activity for colon cancer have not been fully elucidated. In this study, we investigated the effects of melatonin on migration in human colon cancer RKO cells and the potential molecular mechanisms. Materials and Methods: The viability of RKO cells was investigated by MTT assay after treatment with melatonin, SB203580 (p38 inhibitor) and phorbol 12-myristate 13-acetate (PMA, MAPK activator) alone or in combination for 48h. The effects of melatonin, and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, and PMA on the migration of RKO cells were analyzed by in vitro scratch-wound assay. The relative mRNA levels of MLCK was assessed by real-time quantitative RT-PCR. Western blotting analysis was performed to examine the expression of MLCK, phosphorylation of myosin light chain (pMLC) and p38 (pp38). Results: The proliferation and migration of human colon cancer RKO cells were inhibited significantly after treatment with melatonin. The expression levels of MLCK and phosphorylation of MLC of RKO cells were reduced, and real-time quantitative RT-PCR showed that melatonin had significant effects on suppressing the expression of MLCK. Furthermore, the phosphorylation level of p38, which showed the same trend, was also reduced when cells were treated by melatonin. In addition, ML-7 (25umol/l) could down-regulate the phosphorylation of p38. Conclusions: Melatonin could inhibit the proliferation and migration of RKO cells, and further experiments confirmed that p38 MAPK plays an important role in regulating melatonin-induced migration inhibition through down-regulating the expression and activity of MLCK.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.125-131
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• 2015

Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first-level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were $0.1-1.0{\mu}g/ml$, $0.001-0.01{\mu}g/ml$ and $0.01-0.1{\mu}g/ml$, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the $0.01-1.0{\mu}g/ml$ had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.