2011 Vol.23(3)

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Review Article
XRCC1 Polymorphisms and Pancreatic Cancer: A Meta-Analysis
Wei-dong Shen, Hong-lin Chen, Peng-fei Liu
2011, 23(3): 165-170. doi: 10.1007/s11670-011-0165-5
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ObjectiveTo assess the association between X-ray repair cross-complementating group 1 (XRCC1) polymorphisms and pancreatic cancer.MethodsWe searched MEDLINE, Web of Science and HuGE Navigator at June 2010, and then quantitatively summarized associations of the XRCC1 polymorphisms with pancreatic cancer risk using meta-analysis.ResultsFour studies with 1343 cases and 2302 controls were included. Our analysis found: at codon 194, the Trp allele did not decrease pancreatic cancer risk (Arg/Arg versus Trp/Trp: OR=0.97; 95% CI: 0.48-1.96; P=0.97; Arg/Arg versus Arg/Trp: OR=0.89; 95% CI: 0.70-1.13; P=0.55; Arg/Trp versus Trp/Trp: OR=1.06; 95% CI: 0.52-2.16; P=0.90); at codon 280, only a study showed a nonsignificant association between single nucleotide polymorphism with pancreatic cancer risk; at codon 399, the Gln allele also showed no significant effect on pancreatic cancer compared to Arg allele (Arg/Arg versus Gln/Gln: OR=0.94; 95% CI: 0.74-1.18; Arg/Arg versus Arg/Gln: OR=0.97; 95% CI: 0.83-1.13; Arg/Gln versus Gln/Gln: OR=0.97; 95% CI: 0.77-1.22). The shape of the funnel plot and the Egger’s test did not detect any publication bias.ConclusionThere is no evidence that XRCC1 polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) are associated with pancreatic cancer risk.
Original Article
Attributable Causes of Cancer in China: Fruit and Vegetable
Hui-juan Xiao, Hao Liang, Jian-bing Wang, Cheng-Yu Huang, Wen-qiang Wei, Mathieu Boniol, You-lin Qiao, Paolo Boffetta
2011, 23(3): 171-176. doi: 10.1007/s11670-011-0171-7
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ObjectiveTo provide an evidence-based and consistent assessment of the burden of cancer attributable to inadequate fruit and vegetable intake in China in 2005.MethodsThe proportions of cancers attributable to low consumption of vegetable and fruit were calculated separately to estimate the burden of related cancers for the year 2005 in China. Data on the prevalence of exposure were derived from a Chinese nutrition and health survey. Data on relative risks were mainly derived from meta-analysis. Attributable fractions were calculated based on the counterfactual scenario which was a shift in the exposure distribution.ResultsThe total cancer burden attributable to inadequate consumption of fruit was up to 233,000 deaths (13.0% of all cancers) and 300,000 cases (11.6% of all cancers) in 2005. Increasing consumption of vegetable to the highest quintile could avoid total cancer deaths and cases by 3.6% (64,000 persons) and 3.4% (88,000 persons). The contributions to cancer burden were higher in rural areas than in urban areas. They have greater influence on men than on women. The largest proportions of cancer burden attributable to low fruit and vegetable intake were for oral and pharyngeal cancers.ConclusionThis study showed that inadequate intake of fruit and vegetable makes a significant contribution to the cancer burden. Increasing consumption of fruit and vegetable could prevent many cancer deaths and save many lives. Promoting the consumption of fruit and vegetable is an important component in diet-based strategies for preventing cancer.
Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Retrospective Cohort Study
Cai-xing Sun, Tao Li, Xiao Zheng, Ju-fen Cai, Xu-li Meng, Hong-jian Yang, Zheng Wang
2011, 23(3): 177-182. doi: 10.1007/s11670-011-0177-1
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ObjectiveTo assess prognostic factors and validate the effectiveness of recursive partitioning analysis (RPA) classes and graded prognostic assessment (GPA) in 290 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM).MethodsFrom Jan 2008 to Dec 2009, the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation, systemic chemotherapy and tyrosine kinase inhibitors (TKIs) in two institutes were analyzed. Survival was estimated by Kaplan-Meier method. The differences of survival rates in subgroups were assayed using log-rank test. Multivariate Cox’s regression method was used to analyze the impact of prognostic factors on survival. Two prognostic indexes models (RPA and GPA) were validated respectively.ResultsAll patients were followed up for 1-44 months, the median survival time after brain irradiation and its corresponding 95% confidence interval (95% CI) was 14 (12.3-15.8) months. 1-, 2- and 3-year survival rates in the whole group were 56.0%, 28.3%, and 12.0%, respectively. The survival curves of subgroups, stratified by both RPA and GPA, were significantly different (P<0.001). In the multivariate analysis as RPA and GPA entered Cox’s regression model, Karnofsky performance status (KPS) ≥ 70, adenocarcinoma subtype, longer administration of TKIs remained their prognostic significance, RPA classes and GPA also appeared in the prognostic model.ConclusionKPS ≥70, adenocarcinoma subtype, longer treatment of molecular targeted drug, and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.
Genetic Variants in MMP9 and TCF2 Contribute to Susceptibility to Lung Cancer
Jing-zhe Sun, Xue-xi Yang, Ni-ya Hu, Xin Li, Fen-xia Li, Ming Li
2011, 23(3): 183-187. doi: 10.1007/s11670-011-0183-3
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ObjectiveThe Wnt signaling pathway is crucial for pulmonary development and differentiation; dysregulation of the Wnt signaling pathway may impair lung function. Indeed, single nucleotide polymorphisms (SNPs) of Wnt pathway-related genes have been suggested as risk factors for certain types of cancers. In this study, we aimed to evaluate the influence of SNPs in Wnt-related genes (TCF2, MMP9) on susceptibility to lung cancer.MethodsPolymorphisms of TCF2 rs4430796, MMP9 rs2250889, and MMP9 rs17576 were studied in Han Chinese subjects, including 135 patients with lung cancer and 176 controls, using the Sequenom MassARRAY platform. The association of genotypes with susceptibility to lung cancer was analyzed using odds ratio (OR), with 95% confidence interval (95% CI) and χ2.ResultsThe three SNPs (rs4430796, rs2250889, and rs17576) were found to be significantly associated with an increased risk of lung cancer. The AA genotype and AG+AA genotype of rs4430796 showed a significantly increased susceptibility to lung cancer compared with the GG genotype (adjusted OR=6.03, 95% CI: 1.30-28.09, P=0.022; 5.55, 95% CI: 1.20-25.58, P=0.028). Compared with the rs17576 GG genotype, the AG and AG+AA genotypes were also associated with a significant risk (adjusted OR=2.65, 95% CI: 1.60-4.37, P≤0.001; 2.57, 95% CI: 1.59-4.19, P≤0.001) whereas the rs2250889 CG and CG+GG genotypes had 2.97-fold (95% CI: 1.81-4.85; P≤0.001) and 2.80-fold increased associations with lung cancer (95% CI: 1.73-4.54; P≤0.001), respectively, compared with the rs2250889 CC genotype. Furthermore, the association of rs4430796 with lung cancer became insignificant (P>0.05) after adjusting for gender and rs2250889.ConclusionThe three SNPs may play a role in the predisposition of members of the Han Chinese population to lung cancer.
Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma
Jin-luan Li, Yong Cai, Shan-wen Zhang, Shao-wen Xiao, Xiao-fan Li, You-jia Duan, Yong-heng Li, Bo Xu, Kun Yan
2011, 23(3): 194-200. doi: 10.1007/s11670-011-0194-0
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ObjectiveTo assess the safety and efficacy of the combination of recombinant adenovirus-p53 (rAd-p53) with radiochemotherapy for treating unresectable pancreatic carcinoma.MethodsThe eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy. Intratumoral injection of rAd-p53 was guided by B ultrasound. Radiochemotherapy consisted of intensity-modulated radiotherapy (IMRT) at two dose levels and intravenous gemcitabine (Gem). For radiotherapy, gross target volume (GTV) and clinical target volume (CTV) were 55-60 Gy and 45-55 Gy in 25-30 fractions, respectively. Concurrent intravenous gemcitabine was administered at 350 mg/m2, weekly, for 6 weeks. The primary end points included toxicity, clinical benefit response (CBR) and disease control rate (DCR). The secondary end points included progression-free survival (PFS) and overall survival (OS).ResultsFifteen eligible patients were enrolled. Eight patients (53.3%) were evaluated as CBR and 12 (80%) achieved DCR. The median PFS and OS were 6.7 and 13.8 months, respectively. One-year PFS and OS were 40.0% and 51.1%, respectively. There were 8 (53.3%) patients reported grade 3 toxicities including neutropenia (6 patients, 40%), fever (1 patient, 6.7%) and fatigue (1 patient, 6.7%). There was no grade 4 toxicity reported.ConclusionCombination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated. Long-term follow-up is needed to confirm the improvement of PFS and OS.
High Expression of p300 in Human Breast Cancer Correlates with Tumor Recurrence and Predicts Adverse Prognosis
Xiang-sheng Xiao, Mu-yan Cai, Jie-wei Chen, Xin-yuan Guan, Hsiang-fu Kung, Yi-xin Zeng, Dan Xie
2011, 23(3): 201-207. doi: 10.1007/s11670-011-0201-5
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ObjectiveTranscriptional coactivator p300 has been shown to play a variety of roles in the transcription process and mutation of p300 has been found in certain types of human cancers. However, the expression dynamics of p300 in breast cancer (BC) and its effect on BC patients’ prognosis are poorly understood.MethodsIn the present study, the methods of tissue microarray and immunohistochemistry (IHC) were used to investigate the protein expression of p300 in BCs. Receiver operating characteristic (ROC) curve analysis, Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were utilized to analyze the data.ResultsBased on the ROC curve analysis, the cutoff value for p300 high expression was defined when the H score for p300 was more than 105. High expression of p300 could be observed in 105/193 (54.4%) of BCs, in 6/25 (24.0%) of non-malignant breast tissues, respectively (P=0.004). Further correlation analysis showed that high expression of p300 was positively correlated with higher histological grade, advanced clinical stage and tumor recurrence (P<0.05). In univariate survival analysis, a significant association between high expression of p300 and shortened patients’ survival and poor progression-free survival was found (P<0.05). Importantly, p300 expression was evaluated as an independent prognostic factor in multivariate analysis (P<0.05).ConclusionOur findings provide a basis for the concept that high expression of p300 in BC may be important in the acquisition of a recurrence phenotype, suggesting that p300 high expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with BC.
Shu-Gan-Liang-Xue Decoction Simultaneously Down-regulates Expressions of Aromatase and Steroid Sulfatase in Estrogen Receptor Positive Breast Cancer Cells
Xue-song Fu, Ping-ping Li
2011, 23(3): 208-213. doi: 10.1007/s11670-011-0208-y
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ObjectiveEstradiol (E2) plays an important role in the development of breast cancer. In postmenopausal women, the estrogen can be synthesized via aromatase (CYP19) pathway and steroid-sulfatase (STS) pathway in peripheral tissues, when the production in ovary has ceased. The objective of our study was to explore the effects of Shu-Gan-Liang-Xue Decoction (SGLXD) on the expressions of CYP19 and STS in estrogen receptor positive breast cancer MCF-7 and T47D cells.MethodsThe effects of SGLXD on the cell viability of MCF-7 and T47D were analyzed by MTT assay. By quantitative real-time RT-PCR and Western blot, we evaluated the mRNA and protein expressions of CYP19 and STS in MCF-7 and T47D cells after SGLXD treatment.ResultsBy MTT assay, the cell viability rates of MCF-7 and T47D were significantly inhibited by SGLXD in a dose-dependent manner, the IC50 values were 40.07 mg/ml for MCF-7 cells and 25.62 mg/ml for T47D cells, respectively. As evidenced by real-time PCR and Western blot, the high concentrations of SGLXD significantly down-regulated the expressions of CYP19 and STS both in the transcript level and the protein level.ConclusionThe results suggest that SGLXD is a potential dual aromatase-sulfatase inhibitor by simultaneously down-regulating the expressions of CYP19 and STS in MCF-7 and T47D cells.
Diagnostic Value of Mini-laparoscopy in Patients with Abdominal Neoplasm
Jian Wang, Yan-jun Ni, Shi-yao Chen
2011, 23(3): 214-217. doi: 10.1007/s11670-011-0214-0
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ObjectiveBlood biochemistry, ascites tests, and imaging examinations have low sensitivities in abdominal neoplasm diagnoses. In addition, exploratory laparotomy is not suitable for final stage patients. Mini-laparoscopy has recently emerged as a new diagnostic technology for abdominal disease. The aim of this research was to evaluate the value of mini-laparoscopy in diagnosing abdominal neoplasms.MethodsClinical and operational data were retrospectively analyzed in 20 cases with pathologically confirmed abdominal malignancies. Of these, 10 cases were each diagnosed by mini-laparoscopy and exploratory laparotomy. The surgical and anesthesia expenses, perioperative nursing, monitoring and treating charges, postoperative hospital stay and complications were compared between groups.ResultsThe surgical and anesthesia costs were statistically lower in patients who received a mini-laparoscopy (P<0.01). Perioperative drug expenses and nursing and monitoring charges were also significantly decreased (P<0.05 and P<0.01, respectively). Further, the gastrointestinal function recovery time and postoperative hospital stay were significantly reduced in the mini-laparoscopy group. There was no significant difference between the two groups regarding the preoperative hospital stay and postoperative complications.ConclusionMini-laparoscopy effectively reduces surgical injury and treatment costs, and is capable of safely diagnosing abdominal tumors. Moreover, the procedure is also easy to perform.
Curcumin Prevents Induced Drug Resistance: A Novel Function?
Dong Xu, Wei Tian, Hong Shen
2011, 23(3): 218-223. doi: 10.1007/s11670-011-0218-9
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ObjectiveWe supposed that it will be a promising strategy to "prevent" multidrug resistance (MDR) instead of "reversing" it. This study was designed to investigate the potency of curcumin to prevent the acquired drug resistance induced by adriamycin (ADM) in native K562 cells.MethodsK562 cells were pretreated with curcumin or 0.5% DMSO for 24 h and then were co-incubated with ADM. P-glycoprotein (P-gp) and mdr1 mRNA levels were analyzed separately by flow cytometry and quantitative real-time RT-PCR. The intracellular Rh-123 accumulation was also detected by flow cytometer. Finally, we performed a MTT assay to determine the ADM-induced cytotoxicity with or without pretreatment of curcumin.ResultsP-gp and mdr1 mRNA expressions were elevated in the ADM alone group. While in the curcumin pretreated groups, the induced P-gp and mdr1 mRNA levels gradually decreased with increasing curcumin concentrations, and the Rh-123 accumulation level was almost recovered close to the control group's. Finally, the MTT colorimetric assay verified the enhanced effect of curcumin on ADM-induced cytotoxicity.ConclusionOur present study suggested that curcumin exhibits the novel ability to prevent the up-regulation of P-gp and its mRNA induced by ADM. The prevention capacity is also functionally associated with the elevated intracellular drug accumulation and parallel enhanced ADM cytotoxicity. We revealed a novel function of curcumin as a potential drug resistance preventor.
Determination of PDCD5 in Peripheral Blood Serum of Cancer Patients
Yue Wang, Guo-hong Wang, Qing-yun Zhang
2011, 23(3): 224-228. doi: 10.1007/s11670-011-0224-y
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ObjectiveProgrammed cell death 5 (PDCD5) is an apoptosis related gene and plays an important role in the pathogenesis and development of cancer. Whether PDCD5 is present in peripheral blood serum has not been reported. The aim of this study is to determine the contents of PDCD5 protein in peripheral blood serum of cancer patients, as well as normal subjects.MethodsELISA was used to detect the serum PDCD5 concentrations in 100 normal persons, 83 patients with breast cancer, 74 patients with gastrointestinal tract cancer and 41 patients with lung cancer. The results were statistically analyzed and discussed.ResultsPDCD5 could be detected in peripheral blood serum in both normal subjects and cancer patients. The serum PDCD5 contents in normal persons ranged from 3.8 to 6.1 ng/ml with a median of 4.70±0.68 ng/ml. For cancer patients the PDCD5 levels were 4.59±0.90, 4.79±1.14 and 10.43±22.34 ng/ml for breast cancer, gastrointestinal cancer and lung cancer patients respectively. There was no statistically significant difference between the serum PDCD5 concentrations of normal persons and cancer patients.ConclusionPDCD5 is present in peripheral blood. The PDCD5 levels in cancer patients are not statistically different from that of normal persons, though decreased expression of PDCD5 in malignant tissues has been found.
Brief Communication
Src Is Dephosphorylated at Tyrosine 530 in Human Colon Carcinomas
Shudong Zhu, Jeffrey D Bjorge, Donald J Fujita
2011, 23(3): 229-231. doi: 10.1007/s11670-011-0229-6
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ObjectiveSrc is a protein tyrosine kinase that plays important roles in cancer development, and Src kinase activity has been found to be elevated in several types of cancers. However, the cause of the elevation of Src kinase activity in the majority of human colon carcinomas is still largely unknown. We aim at finding the cause of elevated Src kinase activity in human colon carcinomas.MethodsWe employed normal colon epithelial FHC cells and examined Src activation in human colon carcinoma specimens from 8 patients. Protein expression levels were determined by Western blotting, and the activity of Src kinase by kinase assay.ResultsActin levels were different between tumor and normal tissues, demonstrating the complexities and inhomogeneities of the tissue samples. Src kinase activities were increased in the majority of the colon carcinomas as compared with normal colon epithelial cells (range 13-29). Src protein levels were reduced in the colon carcinomas. Src Y530 phosphorylation levels were reduced to a higher extent than protein levels in the carcinomas.ConclusionThe results suggest that Src specific activities were highly increased in human colon carcinomas; phosphorylation at Src Y530 was reduced, contributing to the highly elevated Src specific activity and Src kinase activity.
Case Report
Oxaliplatin-Induced Lung Injury with Allergic Reaction
Tetsuya Homma, Masatsugu Kurokawa, Yoshitaka Yamamoto, Satoshi Matsukura, Koushi Ieki, Shintaro Suzuki, Miho Odaka, Shin Watanabe, Munehiro Yamaguchi, Mitsuru Adachi
2011, 23(3): 232-235. doi: 10.1007/s11670-011-0232-y
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A 79-year-old man was diagnosed as stage IV colon cancer and treated with a modified FOLFOX6 (mFOLFOX6) regimen. On the 12th cycle, we observed erythema and dyspnea. Radiographs showed ground grass opacities. Blood tests showed elevated levels of eosinophils and immunoglobulin E. We diagnosed this finding as response to drug allergy and administered high-dose methylprednisolone. The treatment was successful and he was discharged. The drug lymphocyte stimulating test against oxaliplatin was positive, indicating a type I and IV allergic reaction due to oxaliplatin. Regimens including oxaliplatin must be carefully monitored and frequent blood tests and chest radiographs are needed.
Mosaic Trisomy 21 and Trisomy 14 as Acquired Cytogenetic Abnormalities without GATA1 Mutation in A Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia
Yi Xiao, Jia Wei, Jin-huan Xu, Jian-feng Zhou, Yi-cheng Zhang
2011, 23(3): 239-241. doi: 10.1007/s11670-011-0239-4
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One case of acute megakaryoblastic leukemia (AMKL) with trisomy 21, trisomy 14 and unmutated GATA1 gene in a phenotypically normal girl was reported. The patient experienced transient myelodysplasia before the onset of AMKL. The bone marrow blasts manifested typical morphology of megakaryoblast both by the May-Giemsa staining and under the electronic microscopy. Leukemic cells were positive for CD13, CD33, CD117, CD56, CD38, CD41 and CD61 in flow cytometry analysis. Cytogenetic study showed karyotype of 48, XX, +14, +21 in 40% metaphases. Known mutations of GATA1 gene in Down syndrome or acquired trisomy 21 were not detected in this case.
Pilomyxoid Astrocytoma in Cerebellum
Peng-fei Ge, Hai-feng Wang, Li-mei Qu, Bo Chen, Shuanglin Fu, Yinan Luo
2011, 23(3): 242-244. doi: 10.1007/s11670-011-0242-9
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Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma, and typically locates in the hypothalamic and chiasmatic region. Herein, we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum. MRI scanning showed a tumor involved the cerebellar vermis, tonsil, the forth ventricle and brainstem. It was homogeneous isointensity on T1WI, relative hyper-intensity on T2WI, hyper-intensity on fluid attenuated inversion recovery (FLAIR) images, and uniform enhancement on contrast T1WI. The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma. Follow-up at the 5th month, MRI showed the residual tumor enlarged at the brainstem. The patient survived 10 months after the operation, and finally died of respiration failure resulting from brainstem dysfunction.