Cancer Institute Key Laboratory of Cancer Prevention and Intervention

Laboratory of, China

Cancer Institute Key Laboratory of Cancer Prevention and Intervention

Laboratory of, China
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Wang Z.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Zhao J.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Chen W.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Wu D.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Huang J.,Zhejiang University
Molecular Medicine Reports | Year: 2017

Colorectal cancer (CRC) is one of most common cancers and causes of cancer-associated mortality worldwide, due to its recurrence, metastasis and therapy resistance. Cancer stem cells (CSC) have been demonstrated to be vital for tumor initiation and recurrence. microRNAs may act as an oncogenes or tumor suppressors in numerous cancers. The present study demonstrated that microRNA-141 (miR-141) was downregulated in CSC compared with differentiated cancer cells, and in tumor compared with healthy tissue. MIR-141 may inhibit CRC cell proliferation and the maintenance of CSC stemness, thereby enhancing drug susceptibility. In addition, the present study identified cyclin D2 as a novel target gene of MIR-141. In conclusion, the antitumor role of MIR-141 and its target cyclin D2 may suggest the development of MIR-141 as a potential therapeutic agent.


Fu J.,Zhejiang University | Wu L.,Zhejiang University | Fu W.,Johns Hopkins University | Tan Y.,Zhejiang University | And 5 more authors.
Clinical Breast Cancer | Year: 2017

Background: There is no uniformly adopted cutoff value to define "young patients" with breast cancer. This study was designed to determine an optimal cutoff value, to investigate prognostic factors and to explore gene expression profiles of young female breast cancer. Materials and Methods: The Surveillance, Epidemiology, and End Results database was examined to identify cases of female breast cancer diagnosed between 2000 and 2007. The optimal cutoff value for young age was determined using the X-tile program (Yale University, version 3.6.1). Age-specific gene expression profiles were explored using RNA sequence data from the Cancer Genome Atlas database. Results: The age of 40 years was determined as the optimal cutoff value. Among 94,087 patients, 12,755 were aged 40 years or younger (younger group), and 81,332 were older (older group). The 5- and 10-year cancer-specific survival rates in younger and older groups were 88.74% and 80.65%, respectively, and 93.22% and 88.43%, respectively (P < .001). Univariate and multivariate analyses indicated younger patients had worse prognosis. Subgroup analysis according to estrogen receptor (ER) showed the risk for cancer-specific death of ER-positive (ER+) younger patients increased by approximately 2 times (hazard ratio, 1.96) compared with ER+ older patients. We failed to find any age-related gene in 509 patients after adjusting according to subtype (50-gene prediction analysis of a microarray) and histological type. Conclusion: The age of 40 years is a reasonable cutoff value for defining "young." Young patients with breast cancer, especially those in the ER+ subgroup, have worse prognosis. However, we found that young breast cancer is not a unique biological entity, and therefore, a lack of new potential targets. © 2017 Elsevier Inc.


Fu J.,Zhejiang University | Wu L.,Zhejiang University | Jiang M.,Zhejiang Chinese Medical University | Li D.,Zhejiang University | And 5 more authors.
Cancer | Year: 2017

BACKGROUND: The real-world occurrence rate of non–breast cancer–specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized. METHODS: Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer–specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model. RESULTS: There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor–positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model. CONCLUSIONS: OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432–43. © 2017 American Cancer Society. © 2017 American Cancer Society


Ruan S.-Q.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Ruan S.-Q.,Zhejiang University | Wang Z.-H.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Wang Z.-H.,Zhejiang University | And 7 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-β1 (HRG-β1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-β1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2-ErbB3 heterodimerization and activating the downstream MAPK-ERK signaling pathway. Moreover, GPR30 boosts HRG-β1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-β1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2-ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer. © 2012 Elsevier Inc.


Huang Y.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Huang Y.,Zhejiang University | Ge W.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Ge W.,Zhejiang University | And 7 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2013

Background: There is currently very little data available on the consistency of quantitative and qualitative faecal immunochemical test (FIT) for colorectal cancer screening. Methods: A representative random population (n=1889, 40-74 year olds) in Jiashan, China was invited for FIT screening in 2012. Faecal samples were collected by a single specimen collection device and simultaneously tested by a quantitative FIT (OC-SENSOR, OC) and two qualitative FITs (FIT A and FIT B with intrinsic positive haemoglobin cut-off concentrations of 20 μg Hb/g faeces and 40 μg Hb/g faeces, respectively). The observational criteria for a positive result of the qualitative FIT were set according to the density of the colour appearing in the test strip. The results produced by the quantitative and qualitative FIT for each sample were compared. κ coefficient was used to measure consistency. Results: A total of 1368 (72.4%) individuals returned faecal samples. Both FIT A and FIT B precisely identified all faecal samples with haemoglobin concentration above 100 μg Hb/g faeces, but the overall consistency was poor for OC & FIT A (κ=0.32, 95% CI 0.20-0.44) and was moderate for OC & FIT B (κ=0.74, 95% CI 0.64-0.85). A more favourable consistency (κ=0.64, 95% CI 0.57-0.72) was achieved when a different positive criterion was employed for FIT A. Conclusions: The diagnostic inconsistency between quantitative and qualitative FITs mainly exists in the faecal samples with low haemoglobin concentrations. Refining the criterion for a positive result may be a feasible way to improve the accuracy of qualitative FIT. © 2013 by Walter de Gruyter Berlin Boston.


Huang Y.Q.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2013

To compare the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening. A representative random population of 9000 subjects aging between 40 and 74 years old were selected from Xuxiang, Haining city, Zhejiang province, by random cluster sampling method in year 2011. The fecal samples from each subject were separately detected by the two methods, namely fecal occult blood quantitive testing instrument and colloidal gold strip method. The positive result was standardized by hemoglobin concentration (HGB) ≥ 100 ng/ml under the application of quantitive testing instrument, or color-developing by colloidal gold strip method. The positive subjects from either method would be provided a further colonoscopy examination for pathological diagnosis. The positive rate and consistency of the two methods were compared, as well as the positive predictive value and population detecting rate of the colorectal cancer and adenoma. A total of 6475 (71.9%) subjects submitted their two fecal samples according to our requirement in 9000 subjects. There were separately 319 positive cases (4.9%) and 146 positive cases (2.3%) by the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method, including 45 positive in both tests (Kappa = 0.168, 95%CI:0.119-0.217).184 out of the 319 positive cases (57.7%) in the test by quantitive testing instrument and 89 out of 146 positive cases (61.0%) in the test by colloidal gold strip method received the colonoscopy examination. There were no significant statistical differences between the two methods in the positive predictive value of colorectal cancer (P > 0.05) , developing adenoma and non-developing adenoma.However, the population detecting rate of the colorectal cancer and developing adenoma were higher in the test by quantitive testing instrument (26 cases, 0.402%) than it in the test by colloidal gold strip method (10 cases, 0.154%). The difference showed statistical significance (χ(2) = 7.131, P < 0.01). The performances of fecal occult blood quantitive testing instrument might be better than colloidal gold strip method in colorectal cancer screening. However, the results need to be further verified.


Wang K.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention
International journal of nanomedicine | Year: 2011

The failure of cancer treatments is partly due to the enrichment of cancer stem-like cells (CSLCs) that are resistant to conventional chemotherapy. A novel micelle formulation of oxaliplatin (OXA) encapsulated in chitosan vesicle was developed. The authors postulate that micelle encapsulation of OXA would eliminate both CSLCs and bulk cancer cells in colorectal cancer (CRC). In this study, using stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles as a drug-delivery system, OXA-loaded CSO-SA micelles (CSO-SA/OXA) were prepared. Intracellular uptake of CSO-SA/OXA micelles was assessed by confocal microscope. The effects of free OXA, the empty carrier, and CSO-SA/OXA micelles were tested using human CRC cell lines in vitro and in vivo. The micelles showed excellent internalization ability that increased OXA accumulation both in CRC cells and tissues. Furthermore, CSO-SA/OXA micelles could either increase the cytotoxicity of OXA against the bulk cancer cells or reverse chemoresistance of CSLC subpopulations in vitro. Intravenous administration of CSO-SA/OXA micelles effectively suppressed the tumor growth and reduced CD133+/CD24+ cell (putative CRC CSLC markers) compared with free OXA treatment, which caused CSLC enrichment in xenograft tumors (P < 0.05). The results of this study indicate that CSO-SA micelle as a drug-delivery carrier is effective for eradicating CSLCs and may act as a new option for CRC therapy.


Wang Y.K.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Zhu Y.L.,Zhejiang University | Qiu F.M.,Zhejiang University | Zhang T.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | And 4 more authors.
Carcinogenesis | Year: 2010

Cancer stem cells (CSCs) play an important role in carcinogenesis, resistance to treatment and may lead to cancer recurrence and metastasis. However, the molecular mechanism of CSC involved in these events needs to be further elucidated. In this study, CD133+ colon cancer cells were cultured, which showed CSC properties both in vitro and in vivo from metastatic tissue. Upstream molecules in Akt and mitogen-activated protein kinase (MAPK) pathways were preferentially expressed in these CD133+ cells, as revealed by a global gene chip. The kinase activities of Akt and extracellular signal-regulated kinase (Erk)1/2 were also significantly upregulated in CD133+ cells. In addition, the clonogenic growth of CD133+ cell was reduced greatly by inhibiting the activity of Akt and Erk1/2. The results revealed the Akt and MAPK pathways were involved in the tumorigenesis of CD133+ colon cancer cells, suggesting that molecules in these two pathways might be potential targets in the future therapy. © The Author 2010. Published by Oxford University Press. All rights reserved.


Wang K.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Xu J.,Zhejiang University of Finance and Economics | Zhang J.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention | Huang J.,Cancer Institute Key Laboratory of Cancer Prevention and Intervention
BMC Cancer | Year: 2012

Background: CD133 has been identified as a putative cancer stem cell marker in colorectal cancer (CRC). However, the clinical and prognostic significance of CD133 in CRC remains controversial.Methods: Publications were identified which assessed the clinical or prognostic significance of CD133 in CRC up to October 2012. A meta-analysis was performed to clarify the association between CD133 expression and clinical outcomes.Results: A total of 12 studies met the inclusion criteria, and comprised 3652 cases. Analysis of these data showed that CD133 was not significantly associated with the depth of CRC invasion (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 0.77-2.68, Z = 1.15, P = 0.252) or tumor differentiation (OR = 0.63, 95% CI: 0.28-1.46, Z = -1.06, P = 0.286). Also, there was no statistically significant association of CD133 with lymph node metastasis (OR = 1.16, 95% CI: 0.87-1.54, Z = 1.05, P = 0.315) or lymphatic invasion (OR = 1.08, 95% CI: 0.81-1.43, Z = 0.53, P = 0.594). However, in identified studies, overexpression of CD133 was highly correlated with reduced overall survival (relative risk [RR] = 2.14, 95% CI: 1.45-3.17, Z = 3.81, P = 0.0001).Conclusions: CD133 may play an important role in the progression of CRC, and overexpression of CD133 is closely related with poorer patient survival. If these findings are confirmed by well-designed prospective studies, CD133 may be a useful maker for clinical applications. © 2012 Wang et al.; licensee BioMed Central Ltd.


PubMed | Cancer Institute Key Laboratory of Cancer Prevention and Intervention
Type: Comparative Study | Journal: Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | Year: 2013

To compare the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening.A representative random population of 9000 subjects aging between 40 and 74 years old were selected from Xuxiang, Haining city, Zhejiang province, by random cluster sampling method in year 2011. The fecal samples from each subject were separately detected by the two methods, namely fecal occult blood quantitive testing instrument and colloidal gold strip method. The positive result was standardized by hemoglobin concentration (HGB) 100 ng/ml under the application of quantitive testing instrument, or color-developing by colloidal gold strip method. The positive subjects from either method would be provided a further colonoscopy examination for pathological diagnosis. The positive rate and consistency of the two methods were compared, as well as the positive predictive value and population detecting rate of the colorectal cancer and adenoma.A total of 6475 (71.9%) subjects submitted their two fecal samples according to our requirement in 9000 subjects. There were separately 319 positive cases (4.9%) and 146 positive cases (2.3%) by the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method, including 45 positive in both tests (Kappa = 0.168, 95%CI:0.119-0.217).184 out of the 319 positive cases (57.7%) in the test by quantitive testing instrument and 89 out of 146 positive cases (61.0%) in the test by colloidal gold strip method received the colonoscopy examination. There were no significant statistical differences between the two methods in the positive predictive value of colorectal cancer (P > 0.05) , developing adenoma and non-developing adenoma.However, the population detecting rate of the colorectal cancer and developing adenoma were higher in the test by quantitive testing instrument (26 cases, 0.402%) than it in the test by colloidal gold strip method (10 cases, 0.154%). The difference showed statistical significance ((2) = 7.131, P < 0.01).The performances of fecal occult blood quantitive testing instrument might be better than colloidal gold strip method in colorectal cancer screening. However, the results need to be further verified.

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