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Biomedical subjects

Z Z Shen

Publications and source records attributed to Z Z Shen.

At least 19 recordsLinked to original sources
PubMed2005

Over expression of aromatase protein is highly related to MMPs levels in human breast carcinomas.

Estrogens can play a critical role in the development of breast cancer. Aromatase which catalyzes the formation of aromatic C18 estrogens from C19 androgens is regarded to be responsible for the cancer local production of estrogen. Studies not only from aromatase transfected breast cancer cells, but also transgenic mouse, which overexpressed aromatase, demonstrated that in situ produced estrogen plays more important roles than circulating estrogens in breast tumor promotion and progression. Matrix-metalloproteinases (MMPs) have been implicated in the proeolytic process, which play important roles in the aggressiveness of cancer cells including invasion of adjacent tissue and metastasis to distant sites. Expression of MMP2 and 9 may be stimulated by estrogens in hormonal dependent breast cancers, since tumor aromatase can stimulate breast cancer growth and progression in both an autocrine and a paracrine manner. Theoretically aromatase overexpression, that causes relatively high estrogen concentration in situ, may be positively related to MMP2 and 9 expression, indicate worse prognosis in breast cancers, and maybe insensitive to tamoxifen therapy. In the present study, we studied the expression of aromatase activity and MMPs in human breast carcinoma both in vitro and in vivo. In human breast carcinoma cell lines including MCF-7, MDA-MB-231 and MDA-MB-435, the expression of aromatase levels both in mRNA and protein activity was related to MMP2 and MMP9. In humam breast cancer samples, we demonstrated that aromatase expressions were strongly associated with MMP2 and MMP9 levels. It was interesting to observe that the positive relationship was only present in the ER and/or PR positive patients. This may indicate that both MMP2 and MMP9 were up regulated by estrogen produced by aromatase through ER. So in endocrine therapy, either blocking the ER by tamoxifen or inhibiting the aromatase by aromatase inhibitors for example letrozole, may both inhibit tumor growth and lower the metastatic potential especially in ER positive breast cancer patients by means of down-regulation of MMP2/9.

Adult↗
PubMed2004

Sentinel lymph node biopsy in breast cancer patients after overnight migration of radiolabelled sulphur colloid.

OBJECTIVE: To evaluate the performance and feasibility of sentinel lymph node biopsy in breast cancer patients using technetium-99m (99mTc) sulphur colloid and gamma probe. METHODS: From May 2000 to March 2001, 70 patients with a tumour less than 5 cm with clinically negative axillary lymph nodes underwent sentinel node biopsy followed by standard axillary dissection. 99mTc sulphur colloid was injected around the primary tumour the day before surgery and a gamma probe was used to detect the sentinel lymph node during the surgical procedure. Sentinel lymph node biopsy was compared with standard axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes. RESULTS: The sentinel lymph node was successfully identified in 67 of 70 patients (95.71%). The number of sentinel lymph nodes ranged from 1-5 (mean 1.5) and non-sentinel nodes ranged from 5-22 (mean 13.3). Of the 67 patients with successfully identified sentinel lymph nodes, 43.28% (29/67) were histologically positive. Sensitivity of the sentinel lymph node to predict axilla was 82.75%; specificity was 100%. Positive and negative predictive values were 100% and 88.3% respectively. The sentinel lymph node was falsely negative in five patients, yielding an accuracy of 92.53%. Sentinel lymph node biopsy was more accurate for T1 tumours than for T2 tumours. CONCLUSIONS: The gamma probe guided method after overnight migration of 99mTc sulphur colloid is technically feasible for detecting sentinel lymph nodes in most breast cancer patients, accurately predicting the axillary lymph node status, and appears more accurate for T1 lesions than for larger lesions. This minimally invasive axillary staging procedure represents a major advance in the surgical treatment of breast cancer.

Adult↗
PubMed2003

Pregnancy-associated breast cancer: a case control and long-term follow-up study in China.

Pregnancy associated (PA) breast cancer is defined when diagnosed during pregnancy or within one year afterwards. To analyze the prognostic factors related to this disease and assess the impact of pregnancy on breast cancer patients, 88 PA breast cancer patients initially treated in the Shanghai Cancer Hospital from 1957 to 1990 were reviewed. A non-PA group including 176 patients individually well matched to the PA group was also analyzed. Univariate analysis suggested prognostic value for clinical tumor size, TNM stage, and breast feeding time among the classic prognostic factors, pregnancy associated factors and treatment modalities were evaluated. Multivariate analysis demonstrated clinical tumor size, TNM stage and axillary lymph node metastasis as independent prognostic factors. Compared with the non-PA group, the PA group was significantly correlated with delay at diagnosis, large size of the tumor, late TNM stage, extension to the skin or chest wall and administration with oophorectomy. The overall survival rates of 5-year, 10-year and 20-year were 40.39%, 36.29% and 30.70%, respectively, which were worse than those in the non-PA group, but did not reach a significant difference (p=0.0536). We are conducting further basic research to analyze the biologic characteristics of PA breast cancer.

Adult↗
PubMed2001

Fiberoptic ductoscopy for breast cancer patients with nipple discharge.

BACKGROUND: Breast cancer and precancer are thought to originate in the lining of the milk duct, but until recently, we have not had direct access to this area other than in tissue removed blindly by core biopsy or fine-needle aspiration. Fiberoptic ductoscopy (FDS) is an emerging technique that allows direct visual access of the ductal system of the breast through nipple orifice cannulation and exploration. To date, this technique has been used only in pilot studies. Previously, we have demonstrated that fiberoptic ductoscopy in patients with and without nipple discharge is a safe and effective means of visualizing the intraductal lesion. When combined with cytology, it is a screening technique that has high predictive value. METHODS: We applied ductoscopy to 415 women with nipple discharge with the specific intent of detecting those patients with nipple discharge who had intraductal carcinoma (DCIS) as the basis of their discharge. RESULTS: In this cohort of patients, ductoscopy was successful in visualizing an intraductal lesion in 166 patients (40%). In these cases, ductal lavage following ductoscopy increased the yield of cytologically interpretable ductal epithelial cells 100-fold compared to discharge fluid alone. In the majority of these patients, FDS examination detected lesions that had the appearance of typical papillomas. However, in 10 patients, the intraductal lesion exhibited one of several atypical features, including bleeding, circumferential obstruction, and gross fungating projections. In eight of these patients, the subsequent histopathology turned out to be DCIS. In two of these eight patients, endoscopic biopsy revealed cytologically malignant cells; in two others, ductal lavage (washings) revealed cytologically malignant cells. In three additional patients, although FDS examination uncovered a typical papilloma that was not biopsied, ductal lavage (washings) revealed cytologically malignant cells. On surgical pathology review of the extirpated lesions, all 11 patients were subsequently shown to have DCIS. Of these 11 cases of DCIS that were initially detected with a combination of FDS and ductal lavage cytology, six were completely negative on mammogram and physical exam. CONCLUSION: Although nipple discharge is an unusual presentation for DCIS, in patients with nipple discharge, FDS with ductal lavage cytology is a useful technique for diagnosing DCIS prior to definitive surgery.

Biopsy, Needle↗
PubMed2001

p53 mutation in plasma DNA and its prognostic value in breast cancer patients.

PURPOSE: Tumor-specific DNA has recently been detected in the plasma of lung, head and neck, breast, and colon cancer patients. Detection of tumor-specific genetic materials in cancer patients at sites distant from the tumor, such as in the blood, may provide a unique and valuable tumor marker for diagnosis and prognosis. EXPERIMENTAL DESIGN: The present investigation was aimed at determining the presence of p53 mutations in the peripheral blood of breast cancer patients and its prognostic value in these patients. RESULTS: In this study, we found that the mean concentration of plasma DNA in healthy women was 21 ng/ml, whereas in patients with breast cancer the mean concentration was 211 ng/ml (P < 0.01). p53 mutations were detected in the primary tumors of 46 of 126 (36.5%) breast cancer patients. Of these 46 patients, 30 (65.1%) were found to have p53 mutations in their plasma DNA. p53 mutations in plasma DNA were strongly correlated with clinical stage, tumor size, lymph node (LN) metastasis, and estrogen receptor status (P < 0.05). After a median follow-up of 29 months, univariate and multivariate analysis revealed that both primary tumor and plasma DNA p53 mutations were significant prognostic factors for both relapse-free and overall survival. Furthermore, we demonstrated that patients with both primary tumor and plasma p53 mutations have the worst survival. This outcome occurs in both LN-positive and LN-negative groups. Thirteen of the 22 (59%) patients with recurrence and/or metastasis later had detectable p53 mutations in their plasma DNA. CONCLUSIONS: Detection of p53 mutations in plasma DNA may be used as a prognostic factor and an early marker to indicate recurrence or distant metastasis.

Adult↗
PubMed2000

Fiberoptic ductoscopy for patients with nipple discharge.

BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of the milk duct or lobule, yet until recently, we have not had direct access to this area other than by blindly removing tissue by core biopsy or fine-needle aspiration. Fiberoptic ductoscopy (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast through nipple orifice exploration. METHODS: We applied ductoscopy to 259 women who had nipple discharge, and we analyzed the visual findings, the cytological washings, and the subsequent histopathology. RESULTS: In 92 (36%) of these women, fiberoptic ductoscopy was successful in detecting an intraductal papillary lesion. Of these observed lesions, 68 (74%) were single papilloma, 21 (23%) were multiple discrete papillomas, and 3 (3%) were diffuse intraductal thickening which corresponded to diffuse papillomatosis on histopathological analysis. The overall positive predictive value of FDS screening was 83%. Of the lesions observed, 29.8% were located in the main (segmental) duct, 43.9% lesions in the first branch, 17.5% lesions in the second branch, 7.9% in the third branch, and 0.9% in the fourth branch. These lesions had an overall average distance of 2.7 cm from the nipple orifice. Ductal washings performed at the time of ductoscopy were effective at obtaining representative exfoliated ductal cells which could be evaluated for the presence of clumps (> 50 cells), clumps with atypia or single ductal cells. The presence of clumps with positive FDS increased the positive predictive value to 86%. CONCLUSIONS: Fiberoptic ductoscopy currently offers a safe alternative to ductography in guiding subsequent breast surgery in the treatment of nipple discharge.

Adult↗
PubMed2000

Somatic polyploidization and cellular proliferation drive body size evolution in nematodes.

Most of the hypodermis of a rhabditid nematode such as Caenorhabditis elegans is a single syncytium. The size of this syncytium (as measured by body size) has evolved repeatedly in the rhabditid nematodes. Two cellular mechanisms are important in the evolution of body size: changes in the numbers of cells that fuse with the syncytium, and the extent of its acellular growth. Thus nematodes differ from mammals and other invertebrates in which body size evolution is caused by changes in cell number alone. The evolution of acellular syncytial growth in nematodes is also associated with changes in the ploidy of hypodermal nuclei. These nuclei are polyploid as a consequence of iterative rounds of endoreduplication, and this endocycle has evolved repeatedly. The association between acellular growth and endoreduplication is also seen in C. elegans mutations that interrupt transforming growth factor-beta signaling and that result in dwarfism and deficiencies in hypodermal ploidy. The transforming growth factor-beta pathway is a candidate for being involved in nematode body size evolution.

Animals↗
PubMed1999

Neo-adjuvant chemotherapy for operable breast cancer induces apoptosis.

The use of neo-adjuvant chemotherapy (often referred to as pre-operative or primary chemotherapy) represents a major change in the management of breast cancer as a systemic disease. Laboratory studies have shown that many anti-cancer agents with differing modes of action achieve cytotoxic effects by inducing apoptosis. In this study, we investigated the induction of apoptosis by neo-adjuvant chemotherapy in human breast cancer. The aim was to determine whether a correlation existed between post chemotherapy apoptotic index (AI) and clinical response and patients' survival. Our results indicate that apoptosis is induced by neo-adjuvant chemotherapy and that the response is variable. Our data show that post chemotherapy AI correlated with clinical response and increased patient survival, including both relapse (disease) free survival and overall survival. Post-neo-adjuvant chemotherapy AI levels in primary breast cancer may possibly predict an individual patient's overall response.

Adult↗
PubMed1999

Prognostic role of p27Kip1 and apoptosis in human breast cancer.

Human breast carcinoma is biologically heterogeneous, and its clinical course may vary from an indolent slowly progressive one to a course associated with rapid progression and metastatic spread. It is important to establish prognostic factors which will define subgroups of patients with low vs high risk of recurrence so as to better define the need for additional therapy. Additional characterization of the molecular make-up of breast cancer phenotypes should provide important insights into the biology of breast cancer. In the present study, we investigated apoptosis, expression of p27Kip1 and p53 retrospectively in 181 human breast cancer specimens. In addition, their relevance to the biological behaviour of breast cancer was examined. Our studies found a significant association among high histological grade, high p53, low apoptosis and low p27. Our results also demonstrated that, in human breast cancer, low levels of p27 and apoptotic index (AI) strongly correlated with the presence of lymph node metastasis and decreased patient survival. In node-negative patients, however, p27 also had prognostic value for relapse-free and overall survival in multivariate analysis. Furthermore p27 and AI had predictive value for the benefits of chemotherapy. These latter observations should prompt prospective randomized studies designed to investigate the predictive role of p27 and AI in determining who should receive chemotherapy in node-negative patients.

Analysis of Variance↗
PubMed1998

Genistein exerts multiple suppressive effects on human breast carcinoma cells.

Dietary genistein, a natural flavone compound found in soy, has been proposed to be responsible for the low rate of breast cancer in Asian women. The cellular mechanisms of genistein's chemopreventive effects in vio have been largely unexplored. In our previous studies, we found that genistein exerted pronounced antiproliferative effects on both estrogen receptor-positive and -negative human breast carcinoma cells through G2-M arrest, induction of p21WAF1/CIP1 expression, and apoptosis. Because chemopreventive effects need not be limited to antiproliferation, we decided to examine whether genistein exerted other suppressive effects on breast carcinoma progression. Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1. These in vitro and in vivo studies demonstrate that genistein exerts multiple suppressive effects on breast carcinoma cells, suggesting that its mechanism of chemoprevention is pleiotropic.

Animals↗
PubMed1997

p21/waf1/cip1 and mdm-2 expression in breast carcinoma patients as related to prognosis.

p21/waf1/cip1 and mdm-2 are downstream effectors of p53. p21 plays a major role in negatively regulating cell-cycle progression, while mdm-2 inhibits p53 effects, and its role has been implicated in oncogenesis. In this study, we investigated the expression profiles of p21, mdm-2 and p53 in human breast-carcinoma tissues. The aim was to determine whether a correlation exists between the expression profiles of these markers and tumor differentiation, ER status and prognosis. We studied tumor specimens obtained from 106 patients and found a highly significant association among low histology grade, p53 over-expression, high mdm-2 expression and lack of p21 expression. Our studies also demonstrate that, in human breast cancer, low levels of p21 and higher mdm-2 levels directly correlate with the onset of lymph-node metastases and shortened patient survival. Furthermore, the expression profiles of p21, mdm-2 and p53 were independently correlated with patient survival.

Adult↗
PubMed1994

Treatment of locally recurrent soft tissue sarcomas of the retroperitoneum: report of 30 cases.

To assess the results in treating locally recurrent soft tissue sarcomas of the retroperitoneum, we reviewed the clinical, therapeutic, and pathologic characteristics of 30 patients who underwent surgical exploration. Complete resection was achieved in 18 patients (60%), 6 with en bloc resection of adjacent organs involved by the tumors. Following the first operation for recurrent lesions, the median survival was 33 months for those undergoing complete resection and 14 months for those undergoing partial resection or biopsy (P = 0.04). Patients with a disease-free interval (DFI) of > 24 months were associated with better prognosis than those with DFI of < or = 24 months (median survival: 40 months vs. 17 months, P = 0.03). Patients with tumor size of < or = 20 cm had longer survival than those with tumor size of > 20 cm (median survival: 39 months vs. 23 months, P = 0.04). Among 14 patients who received adjuvant radiation therapy, four patients whose tumors had been considered unresectable at first exploration for recurrence underwent complete resection after preoperative radiation therapy. An aggressive surgery aimed at complete resection in treating recurrent retroperitoneal sarcomas is strongly recommended. We suggest that in large tumors preoperative radiation therapy should be used to reduce the tumor volume and therefore a higher rate of complete resection may be achieved.

Adult↗
PubMed1994

[Expression of WT1mRNA: relation to histology in Wilm's tumor].

UNLABELLED: The mRNA expression of WT1 gene was examined by Northern blot and Dot blot hybridization in 13 Wilm's tumors of varying histology, 2 normal kidneys (1 and 5 years of age) and 1 fetal kidney (5 months of gestation). RESULTS: (1) WT1 gene expression was much higher in fetal kidney than in normal kidney of children; (2) Wilm's tumors which were predominantly epithelial or blastemal expressed high amounts of WT1mRNA, whereas predominantly stromal tumors expressed low amounts (P < 0.01). The data suggests that (1) there is a relationship between WT1 gene expression and cellular differentiation in kidney development; (2) low level expression of WT1mRNA results in disruption of cell differentiation and development of Wilms' tumor which shows stromal-predominant histology.

Blotting, Northern↗
PubMed1994

[Genetic epidemiology and a matched case-control study of bilateral breast cancer in Shanghai].

A matched case-control study on breast cancer was conducted in Shanghai from September 1990 to April 1992. Forty-six cases of bilateral breast cancer and 67 unilateral cases were studied. Results indicated that family history of breast cancer, personal history of benign breast diseases, high-level education, earlier menarche, and heavier body weight were the risk factors for breast cancer with conditional logistic regression analysis. Transmission of bilateral and unilateral breast cancer maybe conformed to Medellian recessive heredity model in simple segregation analysis, and all bilateral breast cancer, asynchronous bilateral breast cancer and asynchronous premenopausal bilateral breast cancer conformed to Medellian dominant heredity, and all unilateral breast cancer conformed to Medellian co-dominant heredity in complex segregation analysis.

Breast Neoplasms↗
PubMed1991

The gene for von Recklinghausen neurofibromatosis (NF1) maps to the pericentromeric region of chromosome 17 in Chinese families.

Linkage analysis of six Chinese families with neurofibromatosis type 1 (NF1) confirms the location of the NF1 gene to the region of the proximal long arm of chromosome 17, as in Caucasian populations. The diagnosis of NF1 was made according to internationally accepted criteria. The markers used were D17S71, D17S58, D17S33, and EVI2A. The overall odds in favor of NF1 lying within this linkage group in the families studied are over 150,000:1, with a maximum location score of 5.112 for the interval D17S58-EVI2A.

Centromere↗
PubMed1991

[Relation of tumor size, lymph node status and prognosis in breast cancer].

Tumor size and the extent of axillary lymph node involvement are the two most important prognostic factors for breast cancer, but their relation is not clear. Data on 2189 cases of radical surgery from 1956-1985 showed a linear relation between tumor size and percentage of cases with positive lymph node involvement. A negative relation was noted between tumor size, the extent of lymph node involvement and prognosis. There was a significance difference in survival rate between one group, two group or more lymph nodes involve. The worst prognosis was seen in those patients with level 3 lymph nodes involve. Tumor size and lymph node status were found to be independent but additive prognostic indicators. If there was no lymph node involvement, the survival rate was decreased because of tumor size. In cases of 1-3 and 4-6 lymph nodes involved, the survival rate was not different when tumor size was less than 5 cm, but there was a significant difference when tumor size large than 5 cm. In cases of more than 7 nodes involved, the survival rate decreased regardless of tumor size. Lymph node metastasis was more important than tumor size in prognosis. The relation of different TNM combination with prognosis was investigated, and the importance of the treatment of internal mammary lymph node in breast cancer was emphasized.

Breast Neoplasms↗