Biomedical subjects

Zhen-Zhou Shen

Publications and source records attributed to Zhen-Zhou Shen.

7 recordsLinked to original sources

PubMed2003

The analysis of BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives.

To study the BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives, 41 patients' genomic DNA from peripheral mononuclear blood cells was studied by using single strand conformational polymorphism (SSCP) and DNA sequencing. The BRCA1 mutations were detected in the whole gene sequence. Three novel disease-causing mutations (c.582C>T, c.735C>T and c.2790delT) occurred in all the patients. Two occurred in the patients younger than 35 years old (9.1%) and one in the patients with affected relatives (5%). Additional sequence variants identified included a novel missense mutation of unknown significance and six polymorphisms. The prevalence of BRCA1 mutations in Chinese patients in Shanghai with early onset breast cancer is similar to that observed in western women, but the incidence of mutations in breast cancer patients in Shanghai with affected relatives isn't as high as that in western women.

Adult↗

PubMed2003

Addition of adjuvant tamoxifen to cyclophosphamide, methotrexate and 5-fluorouracil for premenopausal women with oestrogen receptor-positive breast cancer.

OBJECTIVE: To study the value of adjuvant tamoxifen (TAM) in premenopausal women with oestrogen receptor (ER)-positive breast cancer who received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) polychemotherapy. METHODS: Four hundred and two premenopausal ER-positive breast cancer patients who received CMF chemotherapy between January 1990 and December 1999 were retrospectively studied. Disease-free survival (DFS) and overall survival (OS) were used to evaluate the clinical value of TAM therapy. The relationships between nodal status and TAM were also analysed. RESULTS: After a mean of 41 months of follow-up, 43 (13.7%) patients died of breast cancer and 68 (19.9%) patients suffered recurrence. There was a significant difference between TAM and non-TAM treatment groups for DFS (p=0.0058), but no significant difference for OS. For node-negative patients, there was no significant difference between the TAM and non-TAM treatment groups for either DFS or OS. For node-positive patients, the difference between TAM and non-TAM treatment groups was significant for both DFS and OS (p=0.0497 and p=0.0285, respectively). CONCLUSION: TAM resulted in additional benefit to premenopausal patients with node-positive ER-positive breast cancer who received the CMF polychemotherapy regimen.

Adult↗

PubMed2002

Curcumin exerts multiple suppressive effects on human breast carcinoma cells.

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)-positive MCF-7 cells, being more pronounced in estrogen-containing media and in the presence of exogenous 17-beta estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-beta (transforming growth factor) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)-CAT activities induced by 17-beta estradiol. In addition, we demonstrate that curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231 cells.

Antineoplastic Agents↗

PubMed2002

The tumor suppressor gene LKB1 is associated with prognosis in human breast carcinoma.

PURPOSE: LKB1 (also called STK11) is a recently identified tumor suppressor gene in which its mutation can lead to Peutz-Jeghers syndrome, characterized by gastrointestinal polyps and cancers of different organ systems. Weak expression of this gene does occur at a certain frequency in sporadic breast cancer. This indicates that LKB1 gene may relate to the tumorigenesis of breast cancer. EXPERIMENTAL DESIGN: To investigate the function of the LKB1 gene in sporadic breast cancer, we reintroduced LKB1 into breast cancer cell lines which lack the LKB1 gene. Also, we examined the LKB1 protein expression in human breast cancer samples. RESULTS: We found that reintroducing LKB1 into breast cancer cell lines suppresses cell growth by G(1) cell cycle block. The LKB1-mediated G(1) cell cycle arrest is caused by up-regulation of the expression of p21(WAF1/CIP1) in breast cancer MDA-MB-435 cells. We also demonstrated that low LKB1 protein expression correlates with higher histological grade (P = 0.013), larger tumor size (P = 0.001), progesterone receptor status (P = 0.048), and presence of lymph node metastasis (P = 0.003). Furthermore, LKB1 low expression was associated with a higher relapse rate (P = 0.002) and a worse OS (P = 0.008). CONCLUSIONS: LKB1 plays a role in tumor suppressor function in human breast cancer. LKB1 expression may be a useful prognostic marker in human breast cancer.

AMP-Activated Protein Kinase Kinases↗

PubMed2002

Retraction.

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Retraction Notice↗

PubMed2000

Significance of Apoptosis and Apoptotic-Related Proteins, Bcl-2, and Bax in Primary Breast Cancer.

Apoptosis and expression of apoptosis-regulating proteins, Bcl-2 and Bax, have been observed in human breast carcinomas. The authors investigated whether expression of Bcl-2 and Bax proteins and apoptotic index (AI) had significance in cases of primary breast cancer. The authors evaluated Bcl-2 and Bax immunoreactivity and AI in primary breast cancers with the ApopTag method in 91 breast cancer patients retrospectively with long-term follow-up (median 60 months). Bcl-2 expression was seen in 60 (65.9%) cases and Bax expression was observed in 59 (64.8%) cases. Increased Bcl-2 and absence or low Bax immunoreactivity were significantly associated with low AI, high tumor grade, axillary lymph node involvement, postoperative recurrence, and metastasis. Thirty-five (38.5%) samples expressed high AI, which correlated with low tumor grade, absent axillary lymph node metastasis, and low levels of Bcl-2 with Bax overexpression. In univariate analysis, the variables associated with short relapse-free survival (RFS) and overall survival (OS) were large tumor size, axillary lymph node involvement, high histologic grade, low AI, high Bcl-2 expression, and absence or low Bax expression. In multivariate analysis, only Bcl-2 expression, lymph node status, and histologic grade were of independent prognostic value with respect to RFS and OS. Because the vast majority of the patients in this study received chemotherapy, it can be concluded that these apoptotic markers were also predictive of response to chemotherapy. Immunostaining of apoptosis-related genes, Bcl-2 and Bax, together with AI, may stratify high- versus low-risk breast cancer patients.

Journal Article↗

PubMedDate not supplied

The expression of ER beta protein correlates with vascular endothelial growth factor and its prognostic significance in human breast cancer.

Although cloning of ER beta has prompted a reevaluation of the role of ERs in human breast cancer and there have been many studies focusing on the clinical value of ER beta detection, however, few reports evaluated the prognostic significance of ER beta based on follow-up data. The VEGF gene transcription may be mediated by different ER subtypes directly. The aim of this study was to evaluate the relationship of angiogenesis factor VEGF with different ER subtypes and the prognostic value of ER beta and VEGF in 116 human breast cancer patients. Of these patients, 40 (34.5%) were ER beta protein high expressed and 76 (65.5%) were ER beta protein low expressed. When correlated the ER beta protein levels with other clinical characteristics, statistical significance (p<0.05) was found between ER beta protein expression and menopausal status, and tumor grade. No significance was found between ER beta protein level and node status, stage, or tumor size. Inverse relationship was found between ER beta protein expression and PR status (p<0.05). When comparing the VEGF levels with different ER subtypes a significant difference between ERs and VEGF was found. In ER beta protein high expression group, the VEGF protein was highly expressed (p<0.01), inverse relationship was also found between ER alpha and VEGF. In univariate analysis ER alpha, ER beta and VEGF levels had prognostic value for both relapse-free survival and overall survival (p<0.05). However, in a multivariate study, ER beta and ER alpha protein levels lost the prognostic value either to relapse-free survival or to overall survival. Only VEGF levels acted as an independent prognostic factor to disease-free survival. The result suggested that ER beta protein may have important prognostic value in human breast cancer patients. VEGF expression may be mediated through different ER subtypes.

Adult↗