2012 Vol.24(1)

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Original Article
Cancer Incidence and Mortality in China, 2007
Wan-qing Chen, Hong-mei Zeng, Rong-shou Zheng, Si-wei Zhang, Jie He
2012, 24(1): 1-8. doi: 10.1007/s11670-012-0001-6
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ObjectiveCancer incidence and mortality data collected from population-based cancer registries were analyzed to present the overall cancer statistics in Chinese registration areas by age, sex and geographic area in 2007.MethodsIn 2010, 48 cancer registries reported cancer incidence and mortality data of 2007 to National Central Cancer Registry of China. Of them, 38 registries’ data met the national criteria. Incidence and mortality were calculated by cancer sites, age, gender, and area. Age-standardized rates were described by China and World population.ResultsThe crude incidence rate for all cancers was 276.16/100,000 (305.22/100,000 for male and 246.46/100,000 for female; 284.71/100,000 in urban and 251.07/100,000 in rural). Age-standardized incidence rates by China and World population were 145.39/100,000 and 189.46/100,000 respectively. The crude mortality rate for all cancers was 177.09/100,000 (219.15/100,000 for male and 134.10/100,000 for female; 173.55/100,000 in urban and 187.49/100,000 in rural). Age-standardized mortality rates by China and World population were 86.06/100,000 and 116.46/100,000, respectively. The top 10 most frequently common cancer sites were the lung, stomach, colon and rectum, liver, breast, esophagus, pancreas, bladder, brain and lymphoma, accounting for 76.12% of the total cancer cases. The top 10 causes of cancer death were cancers of the lung, liver, stomach, esophagus, colon and rectum, pancreas, breast, leukemia, brain and lymphoma, accounting for 84.37% of the total cancer deaths.ConclusionCancer remains a major disease threatening people’s health in China. Prevention and control should be enhanced, especially for the main cancers.
Attributable Causes of Breast Cancer and Ovarian Cancer in China: Reproductive Factors, Oral Contraceptives and Hormone Replacement Therapy
Li Li, Jia Ji, Jian-bing Wang, Mayineur Niyazi, You-lin Qiao, Paolo Boffetta
2012, 24(1): 9-17. doi: 10.1007/s11670-012-0009-y
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ObjectiveTo provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors (RFs, including nulliparity, mean number of children, age at first birth and breastfeeding), use of oral contraceptives (OCs, restricted to the age group of 15-49 years), and hormone replacement therapy (HRT), as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005.MethodsWe derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure.ResultsExposure of RFs in 2001 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer (711 cases, 294 deaths). The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction (PAF) of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths.ConclusionRFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.
Value of c-Met for Predicting Progression of Precancerous Gastric Lesions in Rural Chinese Population
Yu Sun, Meng-meng Tian, Li-xin Zhou, Wei-cheng You, Ji-you Li
2012, 24(1): 18-22. doi: 10.1007/s11670-012-0018-x
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ObjectiveTo investigate the value of c-Met in predicting progression of precancerous gastric lesions.MethodsA population-based study was conducted to detect the overexpression of c-Met by immunohisto- chemical analysis in 124 subjects with precancerous gastric lesions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for the association of c-Met overexpression with the risk of advanced gastric lesions.ResultsThe positive rates of c-Met were 55.7% in intestinal metaplasia (IM) and 64.8% in dysplasia (DYS), respectively. Stratified analysis indicated that the proportion of c-Met overexpression was 71.4% for IM progressive group, significantly higher than that for IM persistent group (40.0%, P<0.05). Compared to the IM persistent group, unconditional logistic regression showed that OR of c-Met overexpression for the IM progressive group was 7.416 (95% CI: 2.084-26.398).Conclusionc-Met plays an important role in gastric carcinogenesis. Detection of c-Met is of value in predicting progression of precancerous gastric lesions from IM to DYS.
Caveolin-1, E-cadherin and β-catenin in Gastric Carcinoma, Precancerous Tissues and Chronic Non-atrophic Gastritis
Guo-yang Sun, Jun-xia Wu, Jian-sheng Wu, Yu-ting Pan, Rong Jin
2012, 24(1): 23-28. doi: 10.1007/s11670-012-0023-0
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ObjectiveTo investigate the expressions of caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressions with the development of gastric cancer.MethodsThe expressions of caveolin-1, E-cadherin and β-catenin were detected by biotin-streptavidin- peroxidase (SP) immunohistochemistry on 58 gastric cancer tissues, 40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues. The correlation between the expressions of caveolin-1, E-cadherin and β-catenin, and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.ResultsThe positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01). An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues (P<0.01). Moreover, low expressions of caveolin-1, E-cadherin and β-catenin correlated with tumor size, depth of invasion, lymph node metastasis and TNM stage (P<0.05). The positive rates of caveolin-1 and E-cadherin expressions decreased (P<0.01), while an abnormal rate of β-catenin expression increased inversely, with the degree of atypical hyperplasia (P<0.01). Caveolin-1 expression correlated positively with E-cadherin (r=0.41, P<0.05). Caveolin-1 (r=-0.36, P<0.05) and E-cadherin (r=-0.45, P<0.05) expressions negatively correlated with abnormal β-catenin expression.ConclusionThese results suggested that dysregulated expressions of caveolin-1, E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.
Single-Nucleotide Polymorphism Associations for Colorectal Cancer in Southern Chinese Population
Fen-xia Li, Xue-xi Yang, Ni-ya Hu, Hong-yan Du, Qiang Ma, Ming Li
2012, 24(1): 29-35. doi: 10.1007/s11670-012-0029-7
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ObjectiveGenome-wide association studies (GWAS) have identified 11 loci that influence the risk of developing colorectal cancer (CRC). Given that these studies were conducted in European Caucasian populations, it is not clear whether the results are relevant for populations with different ethnicities. The aim of this study was to examine these associations in a southern Chinese population.MethodsEleven single-nucleotide polymorphisms (SNPs), rs12701937, rs16892766, rs7014346, rs6983267, rs719725, rs10795668, rs3802842, rs4444235, rs9929218, rs10411210, and rs961253, were genotyped in 229 CRC patients and 267 controls using the MassArray SNP genotyping system.ResultsEvidence of an association with CRC was found for four of the 11 loci. The strongest associations were with rs4444235 and rs961253, with significant odds ratios close to those reported in previous GWAS. Among these four loci, rs719725 and rs4444235 were significantly associated with female gender, rs3802842, rs961253, and rs4444235 with early disease onset, and rs3802842 with later disease onset. However, no associations with CRC risk were detected for six other loci (rs9929218, rs10411210, rs12701937, rs7014346, rs6983267, and rs10795668), and one SNP, rs16892766, was not polymorphic in any of the study participants.ConclusionThe rs4444235 and rs961253 loci are strongly associated with the risk of CRC in southern Chinese.
Impact of Serum Vascular Endothelial Growth Factor on Prognosis in Patients with Unresectable Hepatocellular Carcinoma after Transarterial Chemoembolization
Jian-hai Guo, Xu Zhu, Xiao-ting Li, Ren-jie Yang
2012, 24(1): 36-43. doi: 10.1007/s11670-012-0036-8
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ObjectiveTo investigate the expression level of serum vascular endothelial growth factor (VEGF) in patients with unresectable hepatocellular carcinoma (HCC) and its relationship with the clinicopathological characteristics, and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization (TACE) treatments.MethodsSerum VEGF levels were measured using enzyme-linked immunosorbent assay (ELISA) in 60 random patients who underwent TACE or transarterial infusion (TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control. All patients’ clinicopathological features were retrospectively analyzed. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The patients’ survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test. The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.ResultsThe median serum VEGF level in the HCC patients was 285 pg/ml (range 14-1,207 pg/ml), significantly higher than that of healthy controls (P=0.021). The serum VEGF levels were significantly correlated with platelet counts (r=0.396, P=0.002) but not other clinicopathological features. Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml (P=0.002). By multivariate analysis, the serum VEGF level was a significant prognostic factor.ConclusionHigh serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.
Role of Contrast Enhanced Ultrasound in Radiofrequency Ablation of Metastatic Liver Carcinoma
Jin-yu Wu, Min-hua Chen, Wei Yang, Shu-zhi Lin, Wei Wu, Shan-shan Yin, Hui Zhang, Kun Yan
2012, 24(1): 44-51. doi: 10.1007/s11670-012-0044-8
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ObjectiveTo investigate the application of contrast enhanced ultrasound (CEUS) in planning and guiding for radiofrequency ablation (RFA) for metastatic liver carcinoma (MLC).MethodsOne hundred and thirty-five patients with clinically and pathologically diagnosed MLC (from gastrointestinal tumors) were included in the present study, and 104 of them had received CEUS prior to RFA to assess the number, size, shape, infiltration, location and enhancing features of the lesions. Among the 104 patients, 21 (20.1%) were excluded from RFA treatment due to too many lesions or large infiltrative range based on CEUS. The remaining 83 patients with 147 lesions underwent RFA (group A). During the same period, other 31 patients with 102 lesions serving as control group were treated based on findings of conventional ultrasound without contrast (group B). The patients underwent follow-up enhanced CT at the 1st month, and then every 3–6 months after RFA. The tumor was considered as early necrosis if no contrast enhancement was detected in the treated area on the CT scan at the 1st month.ResultsIn group A, 72 of 147 MLC lesions (48.9%) showed increased sizes on CEUS. Among them, 48 lesions (66.6%) appeared enlarged in arterial phase, and 24 (33.3%) showed enlarged hypoechoic area in parenchymal phase. CEUS showed total 61 additional lesions in 35 patients (42.1%) (ranged from 8 to 15 mm) compared with conventional ultrasound (US), and 42 (68.8%) of them were visualized in parenchymal phase only. There were total 208 lesions in group A underwent RFA with CEUS planning, and the tumor necrosis rate was 94.2% (196/208). In this group, local recurrence was found in 16 lesions (7.7%) during 3–42 months’ following up, and new metastases were seen in 30 cases (36.1%). For group B, the tumor necrosis rate was 86.3% (88/102), local recurrence in 17 lesions (16.7%), and new metastases in 13 cases (41.9%). Tumor early necrosis and recurrence rates were significantly different between the two groups (P=0.018, P=0.016, respectively).ConclusionCEUS played an important role in RFA for liver metastases by candidate selecting and therapy planning, which helped to improve the outcome of the treatment.
Use of Radioiodinated Peptide Arg-Arg-Leu Targeted to Neovasculari- zation as well as Tumor Cells in Molecular Tumor Imaging
Xia Lu, Ping Yan, Rong-fu Wang, Meng Liu, Ming-ming Yu, Chun-li Zhang
2012, 24(1): 52-59. doi: 10.1007/s11670-012-0052-8
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ObjectiveTo explore a tumor peptide imaging agent Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg- Leu-Gly-Gly-Cys, tripeptide RRL [tRRL]) that targeted to tumor cells and tumor-derived endothelial cells (TDECs) and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 (VEGFR-2).MethodsThe tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs. Tyrosine was conjugated to the amino terminal of RRL (Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys) for labeling with radionuclide iodine-131 (131I-tRRL). The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro. Whether VEGFR-2 is the binging site of tRRL was investigated. Biodistribution and single-photon emission computed tomography (SPECT) imaging of 131I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice.ResultsIn vitro cellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells. VEGFR-2, which is highly expressed on TDECs, was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium. 131I-tRRL mainly accumulated in tumors in vivo, not other organs at 24 h after injection. SPECT imaging with 131I-tRRL clearly visualized tumors in nude mice, especially at 24 h.ConclusionRadioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors targeted to neovascularization, and may be a promising candidate for tumor radioimmunotherapeutic carrier.
Combined Detection of Serum Matrix Metalloproteinase 9, Acetyl Heparinase and Cathepsin L in Diagnosis of Ovarian Cancer
Wei Zhang, Xiao-xia Hu, Xing-zhi Yang, Qi Wang, Hong Cheng, Shu-mei Wang, Yan-ling Hu, Zhi-jun Yang, Li Li
2012, 24(1): 67-71. doi: 10.1007/s11670-012-0067-1
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ObjectiveTo investigate the clinic values of combining test of serum matrix metalloproteinase 9 (MMP-9), acetyl heparinase (Hpa) and Cathepsin L (CL) in diagnosis of ovarian cancer.MethodsSerum levels of MMP-9, Hpa and CL were detected in a total of 418 cases, including 217 cases with ovarian malignant tumor, 100 cases with ovarian benign tumor and 101 healthy controls, by using enzyme-linked immunosorbent assay (ELISA). Their correlation with clinicopathologic feature of ovarian malignant tumor was analyzed and their diagnosis performance was evaluated by receiver operating characteristic (ROC). The combined diagnosis model was established by logistic regression analysis.ResultsThe serum levels of MMP-9, Hpa and CL were significantly higher in patients with ovarian malignant tumor than in benign tumor and healthy control, the serum levels of CL and Hpa were higher in epithelial cancer than in non-epithelial tumor, and MMP-9, Hpa and CL were elevated in low grade and advanced stage compared to high grade and early stage. The sensitivity for diagnosis of ovarian malignant tumor from high to low was CL, Hpa and MMP-9, and the specificity was MMP-9, CL and Hpa. The united diagnosis model was established and showed the sensitivity and specificity of combined detection were 84.6% and 82.1%, respectively, which were significantly higher than a single tumor marker.ConclusionSerum MMP-9, Hpa and CL were correlated with ovarian malignant tumor and the combined detection of which may be valuable for clinical diagnosis of ovarian malignant tumor.
JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis
Jun Xia, Mi-ze Lu, Yuan-qiang Jiang, Guo-hua Yang, Yun Zhuang, Hong-li Sun, Yun-feng Shen
2012, 24(1): 72-76. doi: 10.1007/s11670-012-0072-4
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ObjectiveJAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF).MethodsWe introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF.ResultsFifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls.ConclusionMPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.
HLA Class I Expressions on Peripheral Blood Mononuclear Cells in Colorectal Cancer Patients
Zhi-mian Zhang, Xiao Guan, Ying-jie Li, Ming-chen Zhu, Xiao-jing Yang, Xiong Zou
2012, 24(1): 77-82. doi: 10.1007/s11670-012-0077-z
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ObjectiveTo investigate the expression change of human leukocyte antigen (HLA) class I on human peripheral blood mononuclear cells (PBMCs) at both mRNA and protein levels, and to evaluate its roles in the development of colorectal cancer (CRC).MethodsIn the present study, 50 patients with CRC, 35 patients with benign colorectal lesion and 42 healthy volunteers were enrolled. Expression levels of HLA class I mRNA and protein were determined using real-time quantitative reverse transcription PCR (RT-PCR) and flow cytometry analysis, respectively.ResultsThe expression levels of HLA class I mRNA and proteins were not influenced by age and gender. The relative ratios of HLA class I mRNA were 0.99±0.27 in healthy controls, 0.76±0.19 in benign patients, and 0.48±0.21 in CRC patients. Mean fluorescence intensities of HLA class I were 145.58±38.14 in healthy controls, 102.05±35.98 in benign patients and 87.44±34.01 in CRC patients. HLA class I on PBMCs was significantly down-regulated at both mRNA and protein levels in patients with stage III and IV CRC. CRC patients with lymph node metastasis also showed a decreased HLA class I expression at protein level.ConclusionHLA class I expressions on PBMCs are associated with staging of CRC and lymph node metastasis. Monitoring the expression of HLA class I on PBMCs may provide useful information for diagnosis and metastasis judgement of CRC.