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In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

  • Yin, Hai-Tao;Zhang, De-Geng;Wu, Xiao-Li;Huang, Xin-En;Chen, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.409-412
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    • 2013
  • Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

Clinical Study on Safety of Cantharidin Sodium and Shenmai Injection Combined with Chemotherapy in Treating Patients with Breast Cancer Postoperatively

  • Wang, Lin;Huang, Xin-En;Cao, Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5597-5600
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    • 2014
  • Objectives: To assess side effects on Cantharidin sodium and Shenmai injection combined with chemotherapy in treating patients with breast cancer postoperatively. Method: Patients with breast cancer receiving postoperative chemotherapy were retrospectively collected, and divided into four groups: group A with cantharidin sodium injection combined with chemotherapy; group B with Shenmai injection combined with chemotherapy; group C with both cantharidin sodium and Shenmai injection combined with chemotherapy; while group D (control group) received chemotherapy alone. All patients were administered docetaxel at a dose of $75mg/m^2$ on day 1, epirubicin hydrochloride at a dose of $60mg/m^2$ on day 1, and cyclophosphamide at a dose of $500mg/m^2$ on day 1 for 3 cycles (repeated at 21 day intervals). After ${\geq}$ three courses of treatment, quality of life and side effects were evaluated. Results: There were a total of 78 patients in this study, and the incidence of leukopenia and gastrointestinal reactions in groups A and B were lower than those in the control group and lowest in group C (p<0.05). Conclusions: Thus cantharidin sodium and Shenmai injection combined with chemotherapy reduce side effects and deserve to be further investigated in randomized clinical control trials.

A Clinical Study on Juheli (Recombinant Human Interleukin - 11) in the Second Prevention of Chemotherapy Induced Thrombocytopenia

  • Xiao, Yang;Liu, Jun;Huang, Xin-En;Guo, Jian-Xiong;Fu, Peng-Chao;Huang, Xiao-Hong;Zhou, Juan;Ye, Ai-Qin
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.485-489
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    • 2016
  • Objective: to investigate the effect and side effects of recombinant human interleukin - 11 (rhIL - 11, in Chinese Juheli, produced by Qi Lu Biotechnology CO., LTD) in the second prevention of chemotherapy induced thrombocytopenia (CIT). Methods: Cancer patients with CIT were recruited and were treated with rhIL - 11 (treatment phase, TP), and in the following cycle, all these patients administered with rhIL - 11 24 hours immediately after chemotherapy (preventive treatment phase, PTP). Duration and severity of thrombocytopenia between two phases were compared. Results: for patients in TP or PTP, nadir values of platelet were ($29.28{\pm}20.08){\times}10^9/L$ and ($45.24{\pm}19.66){\times}10^9/L$, duration of thrombocytopenia in TP and PTP was ($11.52{\pm}4.33$) and ($8.20{\pm}+2.77$)days, recovery time was ($19.40{\pm}3.89$)and ($13.44{\pm}3.02$)days, duration of rhIL - 11 administration was ($10.68{\pm}2.46$)and ($6.28{\pm}1.77$)days, number of patients needing platelet infusion was 16and4 respectively, all differences were statistically significant (p value were 0.007, 0.002, 0.000, 0.000, 0.034 respectively). For TP and PTP, number of patients with hemorrhage was 8 and 4, duration of bleeding was ($5.00{\pm}0.82$) and ($4.50{\pm}0.71$) days respectively, with no statistically significant difference. Adverse reactions mainly included fever, edema, arrhythmia, joint pain, fatigue, skin rash, headache, dizziness, etc., all were not statistically significant between TP and PTP. Conclusion: rhIL - 11 could be well tolerated and is effective that could reduce the duration, severity of CIT, platelet transfusion, and incidence of bleeding, as well as shorten the recovery time, duration of rhIL - 11 administration. Thus, rhIL - 11 could be commended in the second prevention of CIT for patients with cancer.

Phase II Study on Dose Escalating Schedule of Paclitaxel Concurrent with Radiotherapy in Treating Patients with Locally Advanced Non-small Cell Lung Cancer

  • Cui, Lin;Liu, Xing-Xiang;Jiang, Yong;Liu, Jian-Jun;Zhou, Xiang-Rong;He, Xue-Jun;Chen, Jue;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1699-1702
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    • 2014
  • Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

Association Between C-reactive Protein and Risk of Cancer: A Meta-analysis of Prospective Cohort Studies

  • Guo, Yong-Zhong;Pan, Lei;Du, Chang-Jun;Ren, Dun-Qiang;Xie, Xiao-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.243-248
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    • 2013
  • Background: Associations between elevated C-reactive protein (CRP) and cancer risk have been reported for many years, but the results from prospective cohort studies remains controversial. A meta-analysis of prospective cohort studies was therefore conducted to address this issue. Methods: Eligible studies were identified by searching the PubMed and EMBASE up to October 2012. Pooled hazard ratios (HR) was calculated by using random effects model. Results: Eleven prospective cohort studies involving a total of 194,796 participants and 11,459 cancer cases were included in this meta-analysis. The pooled HR per natural log unit change in CRP was 1.105 (95% confidence interval (CI): 1.033-1.178) for all-cancer, 1.308 (95% CI: 1.097-1.519) for lung cancer, 1.040 (95% CI: 0.910-1.170) for breast cancer, 1.063 (95% CI: 0.965-1.161) for prostate cancer, and 1.055 (95% CI: 0.925-1.184) for colorectal cancer. Dose-response analysis showed that the exponentiated linear trend for a change of one natural log unit in CRP was 1.012 (95% CI: 1.006-1.018) for all-cancer. No evidence of publication bias was observed. Conclusions: The results of this meta-analysis showed that the elevated levels of CRP are associated with an increased risk of all-cancer, lung cancer, and possibly breast, prostate and colorectal cancer. The result supports a role of chronic inflammation in carcinogenesis. Further research effort should be performed to identify whether CRP, as a marker of inflammation, has a direct role in carcinogenesis.

Production of IL-1β and Inflammasome with Up-Regulated Expressions of NOD-Like Receptor Related Genes in Toxoplasma gondii-Infected THP-1 Macrophages

  • Chu, Jia-Qi;Shi, Ge;Fan, Yi-Ming;Choi, In-Wook;Cha, Guang-Ho;Zhou, Yu;Lee, Young-Ha;Quan, Juan-Hua
    • 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.

Cantharidin Overcomes Imatinib Resistance by Depleting BCR-ABL in Chronic Myeloid Leukemia

  • Sun, Xiaoyan;Cai, Xueting;Yang, Jie;Chen, Jiao;Guo, Caixia;Cao, Peng
    • Molecules and Cells
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    • v.39 no.12
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    • pp.869-876
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    • 2016
  • Cantharidin (CTD) is an active compound isolated from the traditional Chinese medicine blister beetle and displayed anticancer properties against various types of cancer cells. However, little is known about its effect on human chronic myeloid leukemia (CML) cells, including imatinib-resistant CML cells. The objective of this study was to investigate whether CTD could overcome imatinib resistance in imatinib-resistant CML cells and to explore the possible underlying mechanisms associated with the effect. Our results showed that CTD strongly inhibited the growth of both imatinib-sensitive and imatinib-resistant CML cells. CTD induced cell cycle arrest at mitotic phase and triggered DNA damage in CML cells. The ATM/ATR inhibitor CGK733 abrogated CTD-induced mitotic arrest but promoted the cytotoxic effects of CTD. In addition, we demonstrated that CTD downregulated the expression of the BCR-ABL protein and suppressed its downstream signal transduction. Real-time quantitative PCR revealed that CTD inhibited BCR-ABL at transcriptional level. Knockdown of BCR-ABL increased the cell-killing effects of CTD in K562 cells. These findings indicated that CTD overcomes imatinib resistance through depletion of BCR-ABL. Taken together, CTD is an important new candidate agent for CML therapy.

Characterization of the Microbial Diversity in a Korean Solar Saltern by 16S rRNA Gene Analysis

  • Park, Soo-Je;Kang, Cheol-Hee;Rhee, Sung-Keun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.10
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    • pp.1640-1645
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    • 2006
  • We studied the diversity of the halophilic archaea and bacteria in crystallizer ponds of a Korean solar saltern by analyzing 16S rRNA gene libraries. Although diverse halophilic archaeal lineages were detected, the majority (56%) were affiliated with the uncultured and cultured Halorubrum group. Halophilic archaea that have been frequently observed in solar saltern environments previously, such as Halogeometricum, Halococcus, Haloarcula, and Haloferax, were not detected in our samples. The majority of clones (53%) belonged to the Cytophaga-Flavobacterium-Bacteroides and ${\alpha}-,\;{\gamma}-,\;and\;{\delta}-Proteobacteria$ groups, with 47% of the clones being affiliated with ${\gamma}-Proteobacteria$. We also identified new ${\delta}-Proteobacteria$-related bacteria that have not been observed in hypersaline environments previously. Our data show that the diversity of the halophilic archaea and bacteria in our Korean saltern differs from that of solar salterns found in other geographic locations. We also showed by quantitative real-time PCR analysis that bacteria can form a significant component of the microbial community in solar salterns.

MRI-guided Wire Localization Open Biopsy is Safe and Effective for Suspicious Cancer on Breast MRI

  • Wang, Hai-Yi;Zhao, Yu-Nian;Wu, Jian-Zhong;Wang, Zheng;Tang, Jing-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1715-1718
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    • 2015
  • Background: Magnetic resonance imaging of breast, reported to be a high sensitivity of 94% to 100%, is the most sensitive method for detection of breast cancer. The purpose of this study was to investigate our clinical experience in MRI-guided breast lesion wire localization in Chinese women. Materials and Methods: A total of 44 patients with 46 lesions undergoing MRI-guided breast lesion localization were prospectively entered into this study between November 2013 and September 2014. Samples were collected using a 1.5-T magnet with a special MR biopsy positioning frame device. We evaluated clinical lesion characteristics on pre-biopsy MRI, pathologic results, and dynamic curve type baseline analysis. Results: Of the total of 46 wire localization excision biopsied lesions carried out in 44 female patients, pathology revealed fourteen malignancies (14/46, 30.4%) and thirty-two benign lesions (32/46, 69.6%). All lesions were successfully localized followed by excision biopsy and assessed for morphologic features highly suggestive of malignancy according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) category of MRI (C4a=18, C4b=17, C4c=8,C5=3). Of 46 lesions, 37 were masses and 9 were non-mass enhancement lesions. Thirty-two lesions showed a continuous kinetics curve, 11 were plateau and 3 were washout. Conclusions: Our study showed success in MRI-guided breast lesion wire localization with a satisfactory cancer diagnosis rate of 30.4%. MRI-guided wire localization breast lesion open biopsy is a safe and effective tool for the workup of suspicious lesions seen on breast MRI alone without major complications. This may contribute to increasing the diagnosis rate of early breast cancer and improve the prognosis in Chinese women.

Research Progress in Potential Urinary Markers for the Early Detection, Diagnosis and Follow-up of Human Bladder Cancer

  • Wang, Hai-Feng;Wang, Jian-Song
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1723-1726
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    • 2012
  • Objective: To summarize and evaluate various urinary markers for early detection, diagnosis and follow-up of human bladder cancer. Methods: A MEDLINE and PUBMED search of the latest literature on urinary markers for bladder cancer was performed. We reviewed these published reports and made a critical analysis. Results: Most urinary markers tend to be less specific than cytology, yielding more false-positive results, but demonstrating an advantage in terms of sensitivity, especially for detecting low grade, superficial tumors. Some tumor markers appear to be good candidates for early detection, diagnosis, and follow-up of human bladder cancer. Conclusion: A number of urinary markers are currently available that appear to be a applicable for clinical detection, diagnosis, and follow-up of bladder cancer. However, further studies are required to determine their accuracy and widespread applicability.