Lefty promotes the proliferation and invasion of trophoblast cells by inhibiting nodal expression.

Trophoblast cells play a vital role in embryo implantation. Exploring cytokines secreted by trophoblast cells will be significant in revealing the molecular mechanism of embryo implantation. In vitro-cultured trophoblast cells treated with Lefty revealed that Lefty could downregulate the expression of Nodal while promoting the expression of MMP-2 and MMP-9. Thus, Lefty may promote the proliferation and invasion of trophoblast cells, thereby reducing the amount of apoptosis of these cells. Lefty siRNA knockdown or overexpression of Nodal showed opposite effects to treatment with Lefty. When trophoblast cells overexpressing Nodal were treated with Lefty, Nodal expression increased, and MMP-2 and MMP-9 expression was still promoted. Additionally, the proliferation and invasion of trophoblast cells were upregulated, and trophoblast apoptosis was reduced. Together, these data reveal that Lefty can promote the proliferation and invasion of trophoblast cells and inhibit their apoptosis by downregulating Nodal expression while promoting the expression of MMP-2 and MMP-9. This finding provides new proof for the mechanism of trophoblast cell invasion in decidua.

[Side effects of adjuvant chemotherapy and radiotherapy concurrently after conservative surgery for breast cancer].

OBJECTIVE: Observe the side effects of adjuvant chemotherapy and radiotherapy concurrently after breast conservative surgery and investigate it feasible. METHODS: 40 breast cancer patients of conservative surgery were divided into two groups randomizedly, 20 patients of the study group were given adjuvant chemotherapy and radiotherapy concurrently, 20 patients of the control group were given adjuvant thermotherapy and radiotherapy sequently. Observe the side effects of the patients in the two groups and follow them 6 months. RESULTS: The leukopenia within the third chemotherapeutic cycle and the oral mucitis within the fourth chemotherapeutic cycle in the study group were more severe than those in the control group (P < 0.05). The other side effects within every chemotherapeutic cycles were similar in both groups, including skin reaction in radiotherapeutic area, gastroenteric reaction, alopecia, arthralgia, neurotoxicity and abnormal hepatic function. Following the patients of the two groups in 6 months, there were no significance in hemogram, hepatic and renal function, electrocardiogram and chest x-ray. CONCLUSION: It is feasible and safe to give the adjuvant chemotherapy and radiotherapy concurrently to the breast cancer patients after conservative surgery.

[The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression in breast carcinoma].

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on estrogen receptor (ER) and progesterone receptor (PR) expression in breast carcinoma. METHODS: Samples were obtained from 31 patients with breast carcinoma who received neo-adjuvant chemotherapy, ER or PR expressions were analyzed in preoperative core biopsies and final surgical specimens. RESULTS: ER level was up-regulated in 13 (41.9%) out of 31 cases, PR level was up-regulated in 10 (32.3%). Both ER level and PR level were up-regulated in 8 (25.8%) out of 31 cases. CONCLUSIONS: Neoadjuvant chemotherapy may impact the hormone receptor status, ER and PR expression re-analysis in final surgical specimens is recommended.

[Feasibility of breast conservation surgery after neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the efficacy of neoadjuvant chemotherapy (NCT) and the feasibility of conservative breast surgery after reducing the size of a primary tumor by NCT in patients with operable breast cancer. METHODS: Thirty patients with stage IIB and IIIA breast cancer underwent NCT including epirubicin 60 mg/m(2) by intravenous injection on day 1 and paclitaxel 150 mg/m(2) by 3-hour continuous infusion on day 2 with 21 days as a cycle from July 2001 to April 2003. All patients received 3 - 4 cycles of NCT. Breast conservation treatment or modified mastectomy was performed after the tumor was reduced to less than 3 cm in diameter. The nonresponders received modified mastectomy. RESULTS: The overall response rate (ORR) was 93% (28/30) for the primary tumors of breast, Fifteen patients (50%) obtained clinical complete response (cCR), including 7 cases (23%) with pathologic complete response (pCR). Thirteen cases (43%) achieved clinical partial response (cPR), and 2 (7%) no change (NC). No case showed progression of disease. Twenty-six (87%) cases were downstaged according to the TNM system classification. The median initial tumor size was 4 cm (3 - 10 cm) before NCT and was reduced to 0.8 cm (0 - 6 cm) after NCT. All 30 patients received operation. Eighteen (60%) of them were candidates for breast conserving therapy, and actually only 11 (37%) selected such surgery. CONCLUSION: An effective treatment for operable breast cancer, NCT with epirubicin plus paclitaxel results in significant downstaging or eliminating of primary tumors in breast cancer, thus expanding the indication of breast conservation therapy.

[The effect of transfecting Stat3beta cDNA on human breast cancer].

OBJECTIVE: To study the effect of transfecting Stat3beta cDNA on human breast cancer. METHODS: Human breast cancer cells of the line SK-BR-3 were cultured and divided into 3 groups: Stat3beta transfection group (to be transfected with plasmid pIRES-Stat3beta containing Stat3beta by transient transfection technique), lipofectin reagent transfection group pIRES-EGFP transfection group, and control group. The positively transfected cells were isolated by fluorescence-activated cell sorter. Flow cytometry was used to analyze the cell cycles and cell apotosis. Western blotting was used to detect the expression of STAT3 protein. MTT method was used to examine the proliferation of the cells. RESULTS: Forty-eight hours after exposure to the plasmid pIRES-Stat3beta the transfection rate of the SK-BR-3 cells was 13.79%. SK-BR-3 cells expressed STA3 protein during proliferation. In comparison with the SK-BR-3 cells of other 3 group, the proliferation of the cells transfected with pIRES-Stat3beta was significantly decreased. Forty-eight hours after transfection, 81.09% of the cells transfected with the plasmid pIRES-Stat3beta accumulated at the G(0)/G(1) stage, a rate significantly higher than those of the other groups, and displayed a significantly higher rate of apoptosis. CONCLUSION: Transfection of plasmid pIRES-Stat3beta containing Stat3beta blocks the Stat3 pathway, thus inhibiting the proliferation and augment the apoptosis of human breast cancer cells and providing a novel gene therapy target.

[A prospective multicenter clinical trial of breast conserving therapy for early breast cancer in China].

OBJECTIVE: To demonstrate the feasibility of breast conserving therapy (BCT) and establish a multimodality BCT model for early breast cancer in China. METHODS: A prospective multicenter case control study consisting of 4461 patients was carried out by the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and nine other hospitals across China from November, 2001 to November, 2004, the result of BCT and mastectomy on early stage breast cancer were compared. Patients entry-primary tumor < or = 3 cm, primary tumor in periphery quadrant, pathology showed infiltrating carcinoma and clinical absence of locoregional lymphatic or distant metastasis. Patients rejection-multiple center cancer or diffused malignant calcified spots, previous radical radiation therapy in the chest, accompanying collogenolytic vascular granuloma and simultaneous pregnancy. RESULTS: Of these 4461 patients, breast conserving surgery was performed in 872 (19.5%) patients who were eligible for BCT, accounting for 9.0% of all operated breast cancer patients during the same period. The rates of local recurrence, metastasis and death were 1.0% (9/872), 1.3% (11/872) and 0.1% (1/872) in BCT group, versus 0.5% (18/3589), 1.4% (49/3589) and 0.1% (4/3589) in the mastectomy group. No statistical significant difference was found between these two groups (P > 0.05). Cosmetic evaluation of breast in BCT group was carried out postoperatively at points of six months, one year and two years with 89.7%, 91.1% and 86.6% of the patients assessed as excellent or fine cosmetic state respectively. CONCLUSION: Breast conserving therapy for early stage breast cancer is feasible in China, with no ominous effect on the survival and recurrence rate. Breast conserving therapy is able to improve not only the quality of life but also enhance the confidence of the patients, in addition to quasi-perfect cosmetic results. Standard comprehensive BCT involving multi-centers all concentrating on combination treatment should be widely adopted in China in the future. However, breast conserving surgery should selectively be used only for early stage breast cancer, and should be combined with postoperative radiotherapy, chemotherapy and hormone therapy in order to guarantee success.

[Expression and significance of estrogen receptor isoforms in the development of human breast carcinoma].

OBJECTIVE: To investigate the estrogen receptors (ER)alpha and ERbeta expression and their relationship with clinicopathological parameters in human breast carcinoma. METHODS: Samples were obtained from 30 breast carcinoma, reverse transcriptase polymerase chain reaction was used to measure the expression of ERalpha and ERbeta mRNA. RESULTS: ERalpha mRNA level was up-regulated in breast carcinoma tissue compared with adjacent normal tissue (t = 7.399, P < 0.01) while down-regulated in ERbeta. The relative ratio of ERalpha and ERbeta was decreased in normal tissue vs. carcinoma (t = 6.385, P < 0.01), in patients with lymph node metastasis vs. those without lymph node metastasis (t = 2.602, P < 0.05), in late stage carcinoma vs. early stage (t = 3.754, P < 0.05). CONCLUSION: ERalpha and ERbeta play divergent role in the development of human breast carcinoma.

[Significance of concentration of serum soluble vascular cell adhesion molecule-1 in epithelial ovarian carcinoma].

BACKGROUND & OBJECTIVE: It was reported that vascular cell adhesion molecule-1 (VCAM-1) was highly expressed in ovarian carcinoma samples. The latest research showed that the concentration of serum soluble VCAM-1 (sVCAM-1) was increased in the patients with various tumors. The aim of this study was to investigate the biological effects of sVCAM-1 on epithelial ovarian carcinoma. METHODS: The concentration of serum sVCAM-1 was assayed in 130 normal cases, 50 benign ovarian tumors, and 67 epithelial ovarian carcinoma cases using enzyme-linked immunoadsorbent assay(ELISA). RESULTS: The serum sVCAM-1 level in epithelial ovarian carcinoma[(897+/-54) g/L,83.6%] was higher than those in benign ovarian tumor [(435+/-43) g/L, 8.0%] and normal cases [(420+/-40) microg/L,6.2%] (P< 0.01), while the former dropped post-operation [(532+/-46) microg/L,37.3%]. The serum sVCAM-1 levels in stage II-IV [(899+/-71) microg/L,93.3%], grade III [(982+/-66) microg/L,94.8%], and the cases combined with lymphatic metastasis [(895+/-58) microg/L,95.1%] were higher than those in stage I[(571+/-49) microg/L,63.6%], grade I [(641+/-51)microg/L,69.2%], grade II[(768+/-47)microg/L,66.7%], and the cases without lymphatic metastasis[(728+/-47) microg/L,65.4%](P< 0.05, P< 0.01, and P< 0.01, respectively); while no correlation was found between serum sVCAM-1 levels and histological types (P >0.5). No correlation was found between concentration of sVCAM-1 and prognosis by multiple factor analysis. CONCLUSION: Dynamically monitoring the concentration of serum sVCAM-1 will hopefully become an index for early diagnosis and supervising the recurrence of epithelial ovarian carcinoma.