The Key Laboratory of Cancer Prevention and Intervention

Fangqian, China

The Key Laboratory of Cancer Prevention and Intervention

Fangqian, China
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Zhang K.,Zhejiang University | Zhou J.,Zhejiang University | Zhou J.,The Key Laboratory of Cancer Prevention and Intervention | Zhu X.,Zhejiang University | And 9 more authors.
Breast Cancer Research and Treatment | Year: 2017

Background: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. To verify the utility of PALB2 genetic testing in Chinese population, we assessed the mutational frequency, spectrum, and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank. Methods: We examined breast cancer samples (n = 2279) collected from 2000 through 2016 from Chinese patients who agreed to participate in research DNA banking. To identify the mutations, complete coding sequence and intron–exon boundaries of PALB2 were screened with Next-Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. Results: Among the 2279 breast cancer patients, 305 patients were familial breast cancer cases and the rest 1967 patients were sporadic breast cancer cases. PALB2 loss-of-function mutation carriers accounted for 1.31% (n = 4) and 0.56% (n = 11) in familial and sporadic breast cancer cohort separately. In total, 30 missenses, four nonsenses, three frameshifts, three splicings, and one inframe deletions of PALB2 were identified in this study. Among the deleterious mutations, PALB2 c.1744C>T, c.2748+1G>A, c.2749−1G>C, c.3114−1G>A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, we found two potentially damaging missense variants with high frequency: c.1213C>G, c.3054G>C, and classified six new potentially damaging missense variants. Conclusions: Our data presented the germline mutation status of PALB2 in Chinese breast cancer patients, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, these data may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation. © 2017 Springer Science+Business Media, LLC

Zhang M.-W.,Zhejiang University | Zhang M.-W.,The Key Laboratory of Cancer Prevention and Intervention | Zhang M.-W.,Johns Hopkins University | Fujiwara K.,Johns Hopkins University | And 4 more authors.
Journal of Zhejiang University: Science B | Year: 2017

The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumorassociated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers. © 2017, Zhejiang University and Springer-Verlag Berlin Heidelberg.

Zhou J.,Zhejiang University | Zhou J.,The Key Laboratory of Cancer Prevention and Intervention | Zhang M.,Zhejiang University | Zhang M.,The Key Laboratory of Cancer Prevention and Intervention | And 11 more authors.
Cancer Letters | Year: 2015

Colorectal cancer metastasis is believed to be associated with microRNA dysregulation. However, little is known as to how microRNAs regulate colorectal cancer proliferation, invasion and metastasis. In the present study, we compared the microRNA expression profiles between patients of colorectal cancer at diagnosis with and without liver metastasis. MicroRNA-320b was found to be among those up-regulated in the patient group with metastasis. We subsequently found that microRNA-320b, opposite of its homolog, microRNA-320a that differs by only a single nucleotide, functions in promoting colorectal cancer cell proliferation and invasion. Moreover, we found that overexpression of exogenous microRNA-320b can up-regulate the target genes of microRNA-320a including β-catenin, Neuropilin-1 and Rac-1, which are all known to promote tumor proliferation, invasion and metastasis. These results suggest that microRNA-320b may function in competing with microRNA-320a. Thus, our study has proposed one novel mechanism for controlling colorectal cancer proliferation and invasion through homologous competition between microRNAs. This mechanism may be important for colorectal cancer metastasis. © 2014 Elsevier Ireland Ltd.

Hu Y.,Zhejiang University | Hu Y.,The Key Laboratory of Cancer Prevention and Intervention | Wang Z.,Zhejiang University | Wang Z.,The Key Laboratory of Cancer Prevention and Intervention | And 15 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2016

Purpose: Despite convergent evidence indicating a wide range of advantages for computed tomography angiography (CTA) for evaluating vascular anatomy prior to laparoscopic complete mesocolic excision (CME), the operative effects of CTA remain to be determined. In this study, we investigated alterations in operative outcomes caused by preoperative CTA. Methods: Based on CTA, arterial and venous vessels were reconstructed prior to laparoscopic CME (CTA group) in 84 patients with colon cancer. Sixteen of these patients were excluded from the analysis of the operative outcomes because of undergoing either laparoscopic surgery combined with resection of other organs or radiofrequency ablation. The remaining 68 patients were enrolled in the CTA group for the analysis of the operative outcomes. For comparison, 61 patients had the same surgery without preoperative CTA (Control group). Results: We found that the right colon artery (RCA) and the right colon vein (RCV) were absent in 42.9% and 23.8% of patients, respectively. Some patients, 17.9%, had one superior RCA (SRCA) and 1.1% had two SRCAs. Many patients, 40.5%, had one superior RCV (SRCV), and 2.4% had two. The gastrocolic trunk (GCT) was observed in 89.3% of patients in CTA group. Compared to the Control group, operative time declined in CTA group (181.0 vs. 159.8 mins), and the intraoperative blood loss in CTA group decreased (157.0 vs. 108.2 ml, P=0.001). Additionally, the intraoperative blood loss decreased more in laparoscopic CME for right-sided tumors, from 174.2±121.0 ml to 107.6±67.3 ml in the Control and CTA groups respectively (P<0.001). Conclusions: Preoperative CTA performed in colon cancer patients could help reduce the intraoperative blood loss during the laparoscopic CME. Preoperative CTA is a novel technique to assist surgeons in the evaluation of individual mesenteric vascular variations and could reduce the risk of vessel injury during surgery. © 2016, E-Century Publishing Corporation. All rights reserved.

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