Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.

[Analysis of clinicopathological factors associated with false-negative rate of sentinel lymph node biopsy in breast cancer patients: experience of a single center].

OBJECTIVE: The purpose of this study was to investigate the clinicopathologic factors associated with false-negative rate of sentinel lymph node biopsy (SLNB) in breast cancer, and to explore how to reduce the false-negative rate of SLNB. METHODS: The clinicopathological data of 2265 patients with invasive breast carcinoma who underwent sentinel lymph nodes biopsy (SLNB) in Shandong Cancer Hospital between November 1999 and December 2011 were retrospectively analyzed. We screened 1228 patients who received axillary lymph node dissection after SLNB, and studied the clinicopathological factors that could be associated with false-negative rate of SLNB. RESULTS: The false negative rate of this group was 10.7% (73/683), accuracy rate was 94.1% (1155/1228), and negative predictive value was 88.2% (545/618). Clinical tumor size (all P < 0.05), calendar year of surgery (all P < 0.05) and numbers of detected SLNs (all P < 0.05) were significantly related with false negative rate and accuracy rate of SLNB, determined by single factor analysis. Logistic regression model analysis showed that calendar year of surgery (P = 0.034) and numbers of detected SLNs (P = 0.012) were independent predictive factors for the false negative rate of SLNB. CONCLUSIONS: False negative rate and accuracy rate of SLNB are significantly related to the calendar year of surgery and number of detected SLNs. Strict case selection, standard operation procedure, increaseing numbers of detected SLNs, and improvement of the skill of operators are effective measures to reduce the false negative rate of SLNB.

[Value of sentinel lymph node metastasis status in predicting the presence of residual disease in the non-sentinel lymph node of breast cancer patients].

OBJECTIVE: To explore the value of sentinel lymph nodes (SLN) metastasis status in predicting the presence of residual disease in non-sentinel lymph nodes (nSLN) and the feasibility of avoiding or reducing the scope of axillary lymph node dissection (ALND) for patients with single positive SLN. METHODS: A retrospective study was conducted for 2265 patients with invasive breast carcinomas undergoing sentinel lymph nodes biopsy (SLNB) at Shandong Cancer Hospital between November 1999 and December 2011. And 1228 patients with axillary dissection were screened and divided into 5 groups of (-), (1/n), (1/1), (n/N), (n/n) (n ≥ 2, N ≥ 3, N > n) according to the status of SLN metastasis. RESULTS: The nSLN metastasis rate of SLN(-), (1/n), (1/1), (n/N) and (n/n) groups was 11.8%(73/618), 25.2%(65/258), 49.6%(67/135), 48.4%(60/124)and 65.6%(61/93)respectively. A comparison of SLN(-), (1/n), (1/1), (n/N), and (n/n) groups of nSLN metastasis showed a significant difference (P = 0.000). The differences of nSLN metastasis between SLN(-) and other groups (including 1/n, 1/1, n/N, n/n group) were significant (P = 0.000). This difference was also significant between SLN (1/n) and other positive groups (include 1/1, n/N, n/n group) (P = 0.000), but not significant between SLN(1/1), (n/N) and (n/n) groups (P = 0.842, 0.017, 0.042 respectively, Chi-square segmentation). No significant difference existed between axillary lymph node metastasis on Level II and III of SLN 1/n group and SLN(-) group (P = 0.012, 0.570,χ(2) segmentation). CONCLUSIONS: The status of SLN metastasis is one of influencing factors for the nSLN metastasis of patients with invasive breast cancer. The possibility of non-sentinel lymph node involvement for patients with single SLN metastasis was smaller than that of other SLN-positive patients. It is safe for some SLN 1/n patients to undergo low lymph node dissection. But ALND is not avoided for patients with single positive SLN (SLN 1/n n ≥ 2). Their clinicopathological variables should be also considered.

[Systematic review of validation phase of breast cancer sentinel lymph node biopsy results in China].

OBJECTIVE: To explore the studies and application status of sentinel lymph node biopsy (SLNB) in breast cancer in China by statistically analyzing the relevant domestic literature. METHODS: The literatures published from January 1999 to December 2005 were searched in the databases of China, Info, CBM and CNKI retrieval system with "breast tumor, SLN and SLNB" as the key words. A total of 88 manuscripts were selected with 2 new reports of SLNB. The successful rate, accuracy, false-negative rate and sensitivity of SLNB were analyzed by SPSS 10.0 statistical analysis software. RESULTS: Among a total of 6282 patients, the detection rate of SLNB was 90.82% (5705/6282) and the overall false-negative rate 9.69% (259/2671). The prediction sensitivity, specificity, false positive rate, accuracy, negative and positive predictive value of SLN for axillary lymph nodes status were 90.30%, 99.64%, 0.41%, 86.52%, 92.11% and 99.55% respectively. CONCLUSION: SLNB can accurately predict the axillary lymph node metastasis. And its detection rate is correlated with patient age and tumor location. The detection rate and false-negative rate has nothing to do with the tracer injection site. A combined regimen has a higher detection rate and a low false negative rate. Affecting the whole breast, SLN is not correlated with a particular area of breast. The validation phase of SLNB in breast cancer is currently feasible in China.

Relationship Between Lifestyle Habits and Health-Related Quality of Life of Recently Diagnosed Breast Cancer Patients: A Comparison Between Younger and Older Women in China.

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.

XRCC5/6 polymorphisms and their interactions with smoking, alcohol consumption, and sleep satisfaction in breast cancer risk: A Chinese multi-center study.

BACKGROUND: X-ray repair cross-complementary 5 (XRCC5) and 6 (XRCC6) are critical for DNA repair. Few studies have assessed their association with breast cancer risk, and related gene-environment interactions remain poorly understood. This study aimed to determine the influence of XRCC5/6 polymorphisms on breast cancer risk, and their interactions with cigarette smoking, alcohol consumption, and sleep satisfaction. METHODS: The study included 1039 patients with breast cancer and 1040 controls. Four single-nucleotide polymorphisms of XRCC5 and two of XRCC6 were genotyped. Information about smoking, alcohol consumption, and sleep satisfaction was collected through questionnaires. Odds ratios (OR) and related 95% confidence intervals (95% CI) were assessed using unconditional logistic regression models. Gene-environment interactions were analyzed using logistic regression with multiplicative interaction models. RESULTS: XRCC5 rs16855458 was associated with increased breast cancer risk in the co-dominant (ptrend  = 0.003) and dominant (CA + AA vs. CC, OR = 1.29, 95% CI = 1.07-1.56, p = 0.008) genetic models after Bonferroni correction. The CG + GG genotype of XRCC6 rs2267437 was associated with an increased risk of estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancer (CG + GG vs. CC: OR = 1.54, 95% CI = 1.12-2.13, p = 0.008) after Bonferroni correction. Moreover, an antagonistic interaction between XRCC5 rs16855458 and alcohol consumption (pinteraction  = 0.017), and a synergistic interaction between XRCC6 rs2267437 and sleep satisfaction were associated with breast cancer risk (pinteraction  = 0.0497). However, these interactions became insignificant after Bonferroni correction. CONCLUSION: XRCC5 rs16855458 was associated with breast cancer risk, and XRCC6 rs2267437 was associated with the risk of ER-/PR- breast cancer. Breast cancer risk associated with XRCC5 and XRCC6 polymorphisms might vary according to alcohol consumption and sleep satisfaction, respectively, and merit further investigation.

[Expressions of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma and their relationship with clinicopathological factors].

OBJECTIVE: The purpose of this study was to explore the clinical significance of expression of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma. METHODS: Semi-quantitative reverse transcriptive polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the three genes in tumor tissues from 60 patients with primary breast cancer and normal breast tissues of 30 cases. The relationship between gene expression and clinicopathological factors were analyzed and determined. RESULTS: The relative expression levels (gray scale ratio between target gene and internal reference gene) of Fas, CTLA-4 and RhoBTB2 genes in breast carcinoma tissues were 0.699 +/- 0.285, 1.045 +/- 0.302 and 0.625 +/- 0.160, respectively. In the normal breast tissues, they were 0.502 +/- 0.178, 0.418 +/- 0.140 and 0.843 +/- 0.218, respectively. There were statistically significant differences of the expression of those three genes between carcinoma tissues and normal breast tissues (P < 0.01). The expression level of Fas in carcinoma tissues was significantly higher in lymph node matastasis positive patients (0.782 +/- 0.313) than that in node-negative patients (0.557 +/- 0.146, P < 0.01). The expression level of CTLA-4 gene in carcinoma tissues was lower in II stage patients (0.978 +/- 0.330) than that in III stage patients (1.134 +/- 0.240, P < 0.05). The expression level of RhoBTB2 gene was lower in invasive ductal carcinoma (0.597 +/- 0.157) than that in invasive lobular carcinoma (0.717 +/- 0.145, P < 0.05). There were no correlations of expression of the three genes at mRNA level and age, ER, PR, HER2 status and survival time. Furthermore, no correlation was seen among the three genes expression (P > 0.05). CONCLUSION: The expression of all the three genes at mRNA level is involved in genesis and progression of breast cancer. There exist correlations between Fas expression and axillary lymph node matastasis, CTLA-4 expression and disease stage, and RhoBTB2 expression and pathological type of breast cancer.

miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer.

Cancer stem cell (CSC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in tumor cell invasion and metastasis. They have been shown to occur in resistance to tamoxifen. Moreover, microRNAs (miRNAs) have been associated with CSCs, EMT as well as tamoxifen resistance. Studying molecular mechanism of CSCs, EMT as well as tamoxifen resistance will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that miR-375 inhibits CSC traits in breast cancer MCF-7 cells. Bioinformatics analysis and experimental validation identified HOXB3 as a direct target of miR-375. Overexpressing miR-375 degraded HOXB3 mRNA in MCF-7 cells. Moreover, overexpression of HOXB3 induced formation of CSC phenotypes, EMT and tamoxifen-resistance as well as enhanced ability of migration and invasion in MCF-7 cells. Most ER-positive breast cancer-related deaths occur, because of resistance to standard therapies and metastasis, restoring miR-375 or targeting HOXB3 might serve as potential therapeutic approaches for the treatment of tamoxifen-resistant breast cancer.

A case-control study on risk factors of breast cancer in Han Chinese women.

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P<0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

[Expression of CD80, CD86, TGF-beta1 and IL-10 mRNA in the esophageal carcinoma].

OBJECTIVE: To investigate the correlation of CD80 and CD86 mRNA expression with the expression of transforming growth factor-beta1 mRNA (TGF-beta1) and interleukin-10 mRNA (IL-10) in the esophageal cancer. To explore the reason of impaired immunological function of dentritic cell (DC) and the mechanism of cancer cell escaption from body immunity system in the esophageal cancer patient. METHODS: Expression of CD80, CD86, TGF-beta1 and IL-10R mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in specimens of 62 esophageal carcinoma and 16 normal esophageal mucosal tissues used as normal control. RESULTS: Expression of CD80 and CD86 mRNA in the esophageal cancer tissue was significantly lower than that in the normal esophageal mucosal tissue (CD80: P = 0.038; CD86: P = 0.0002). It was significantly higher in stage I or II than that in stage III or IV (CD80: P = 0.029; CD86: P = 0.045); and also higher in paitents with high or moderate differentiation than that with poor differentiation (CD80: P = 0.046; CD86: P = 0.044). Furthermore, it was found to be reversely correlated with expression of TGF-beta1, IL-10 mRNA by multiple regression analysis (P = 0. 0001) respectively, the more TGF-beta1 and IL-10 mRNA expressed in the tumor tissue, the less CD80 and CD86 mRNA expressed by dendritic cells. CONCLUSION: The expression of CD80 and CD86 mRNA in the tissues of esophageal cancer are found to be weak, and reversely correlated with the expression of TGF-beta1 and IL-10 mRNA. High level expression of TGF-beta1 and IL-10 mRNA may be an important influential factor to the weak expression of CD80 and CD86 mRNA, which may be one of the reasons leading to impaired function of dendritic cells and immune escape of cancer cells in the esophageal cancer patient.

[Flow cytometric quantitative analysis of multiple tumor suppressor gene 1 (MTS1) and cyclooxygenase-2 (COX-2) gene expressions in invasive breast cancers and their clinical significance].

OBJECTIVE: The purpose of the present study was to explore the expression and clinical significance of multiple tumor suppressor gene 1 (MTS1) and cyclooxygenase-2 (COX-2) gene in invasive breast cancers. METHODS: Flow cytometry was used to analyze the expression level of MTS1 and COX-2 in cancer tissues and corresponding para-cancer tissues from 66 cases of primary invasive breast cancers. RESULTS: In breast cancer tissues, the expression of MTS1 and COX-2 assessed by relative fluorescence intensity were 0.84 and 10.54, respectively, and were 1.61 and 4.00 in corresponding para-cancer tissues, respectively. There was a significant difference between MTS1 and COX-2 expressions in cancer and corresponding para-cancer tissues (P <0.05). The differences of MTS1 and COX-2 expression of different ages, pathological types, tumor sizes or clinical stages of the breast cancer patients were not significant (P > 0.05). The MTS1 and COX-2 expressions were 1.12 and 5.94, respectively, in lymph node metastasis positive patients, and 0.79 and 13.05, respectively, in lymph node metastasis negative patients. The differences were significant (P <0.05). CONCLUSION: The preliminary research results suggest that MTS1 and COX-2 gene expressions play fairly important role in tumorigenesis and progression of breast cancers. MTS1 and COX-2 protein expressions have correlation with lymph node metastasis. This study provides theoretical basis for use of COX-2 selective inhibitors in prevention and treatment for breast cancer patients.

[The clinical significance of P-glycoprotein, lung resistance protein and multidrug resistance related protein expressions in infiltrating breast carcinoma tissues].

OBJECTIVE: Our purpose was to explore clinical significance of three kinds of drug resistance related proteins, including P-glycoprotein (P-gp), lung resistance protein (LRP), multidrug resistance related protein (MRP) expressions in infiltrating breast carcinoma tissues. METHODS: Flow cytometry was used to analyze the expression of drug resistance related proteins in carcinoma tissues and corresponding para-carcinoma tissues from 68 primary infiltrating breast carcinoma patients. RESULTS: The relative fluorescence intensity (RFI) expressed by median (M) of P-gp, LRP and MRP in breast carcinoma tissues were 0.58, 0.51and 0.56 respectively. In corresponding para-carcinoma tissues, their expression level were 0.26, 0.33 and 0.30. Their difference were obvious (P < 0.05). There were not notable differences of drug resistance related protein expressions in different ages, different tumor sizes, different pathological types, different clinical stages, estrogen receptor or progestin receptor negative and positive patients (P > 0.05). The expressions of P-gp and MRP in lymph node metastasis positive patients were 0.61and 0.69, in lymph node metastasis negative patients they were 0.54 and 0.45. There were no notable differences of P-gp and MRP expression in lymph node metastasis negative and positive patients. The expression of LRP (M = 1.49) was higher in lymph node metastasis positive patients than that in negative patients (M = 0.50, P < 0.05). The correlation analysis showed that there was positive correlation between the expression of LRP and MRP in breast carcinoma tissues (P < 0.05). CONCLUSION: The clinical significance of three kinds of drug resistance related protein expressions had differences in infiltrating breast carcinoma tissues. The expression of LRP had related with lymph node metastasis status and had positive correlation with MRP expression. It can become a target in forecasting breast carcinoma prognosis.

Prospective study found that peripheral lymph node sampling reduced the false-negative rate of sentinel lymph node biopsy for breast cancer.

BACKGROUND: Although sentinel lymph node biopsy (SLNB) can accurately predict the status of axillary lymph node (ALN) metastasis, the high false-negative rate (FNR) of SLNB is still the main obstacle for the treatment of patients who receive SLNB instead of ALN dissection (ALND). The purpose of this study was to evaluate the clinical significance of SLNB combined with peripheral lymph node (PLN) sampling for reducing the FNR for breast cancer and to discuss the effect of "skip metastasis" on the FNR of SLNB. METHODS: At Shandong Cancer Hospital Affiliated to Shandong University between March 1, 2012 and June 30, 2015, the sentinel lymph nodes (SLNs) of 596 patients with breast cancer were examined using radiocolloids with blue dye tracer. First, the SLNs were removed; then, the area surrounding the original SLNs was selected, and the visible lymph nodes in a field of 3-5 cm in diameter around the center (i.e., PLNs) were removed, avoiding damage to the structure of the breast. Finally, ALND was performed. The SLNs, PLNs, and remaining ALNs underwent pathologic examination, and the relationship between them was analyzed. RESULTS: The identification rate of SLNs in the 596 patients was 95.1% (567/596); the metastasis rate of ALNs was 33.7% (191/567); the FNR of pure SLNB was 9.9% (19/191); and after the SLNs and PLNs were eliminated, the FNR was 4.2% (8/191), which was significantly decreased compared with the FNR before removal of PLNs (P = 0.028). According to the detected number (N) of SLNs, the patients were divided into four groups of N = 1, 2, 3, and ≥4; the FNR in these groups was 19.6, 9.8, 7.3, and 2.3%, respectively. For the patients with ≤2 or ≤3 detected SLNs, the FNR after removal of PLNs was significantly decreased compared with that before removal of PLNs (N ≤ 2: 14.0% vs. 4.7%, P = 0.019; N ≤ 3: 12.2% vs. 4.7%, P = 0.021), whereas for patients with ≥4 detected SLNs, the decrease in FNR was not statistically significant (P = 1.000). In the entire cohorts, the "skip metastasis" rate was 2.5% (15/596); the FNR caused by "skip metastasis" was 2.1% (4/191). CONCLUSIONS: The FNR of SLNB was associated with the number of SLNs. For patients with ≤3 detected SLNs, PLN sampling can reduce the FNR of SLNB to an acceptable level of less than 5%. Because of the existence of the "skip metastasis" and distinct metastasis patterns, the FNR of SLNB cannot be completely eliminated.

The Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Prospective Studies.

OBJECTIVE: The axillary reverse mapping (ARM) technique has recently been developed to prevent lymphedema by preserving the arm lymphatic drainage during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) procedures. The objective of this systematic review and meta-analysis was to evaluate the feasibility and oncological safety of ARM. METHODS: We searched Medline, Embase, Web of science, Scopus, and the Cochrane Library for relevant prospective studies. The identification rate of ARM nodes, the crossover rate of SLN-ARM nodes, the proportion of metastatic ARM nodes, and the incidence of complications were pooled into meta-analyses by the random-effects model. RESULTS: A total of 24 prospective studies were included into meta-analyses, of which 11 studies reported ARM during SLNB, and 18 studies reported ARM during SLNB. The overall identification rate of ARM nodes was 38.2% (95% CI 32.9%-43.8%) during SLNB and 82.8% (78.0%-86.6%) during ALND, respectively. The crossover rate of SLN-ARM nodes was 19.6% (95% CI 14.4%-26.1%). The metastatic rate of ARM nodes was 16.9% (95% CI 14.2%-20.1%). The pooled incidence of lymphedema was 4.1% (95% CI 2.9-5.9%) for patients undergoing ARM procedure. CONCLUSIONS: The ARM procedure was feasible during ALND. Nevertheless, it was restricted by low identification rate of ARM nodes during SLNB. ARM was beneficial for preventing lymphedema. However, this technique should be performed with caution given the possibility of crossover SLN-ARM nodes and metastatic ARM nodes. ARM appeared to be unsuitable for patients with clinically positive breast cancer due to oncological safety concern.

[Expression of osteopontin mRNA and its clinical significance in gastric cancer].

OBJECTIVE: To investigate the expression of osteopontin mRNA and its correlation with clinicopathologic features of gastric cancer and elucidate its role in tumor invasion and distant metastasis. METHODS: The expression of OPN mRNA was detected by semi-quantitive RT-PCR. The relationship between the relative content of OPN mRNA and clinicopathologic features of gastric cancer was analyzed. RESULTS: In 66 cancer tissue samples, a 330 bp band was detected in 50 cases, the positive rate of OPN mRNA expression was 75.8% (50/66). The expression in all 20 cases of normal gastric mucosa was negative. The expression was associated with the depth of tumor invasion, diameter, lymph node metastasis and but had no correlation with differentiation grades. The 66 patients were followed up for 10 approximately 27 months (mean 16 months). The OPN mRNA expression positive group (50 cases) had recurrence in 15 patients and the negative group (16 cases) had only 1 case with recurrence (P = 0.05); 10 patients died in OPN mRNA expression positive group but no patient died in OPN staining negative group (P = 0.05). CONCLUSION: OPN mRNA is over-expressed in gastric cancer. It reflects the progression of disease and association with poor prognosis of gastric cancer. OPN may play an important role in the process of distant metastasis in gastric cancer.

[Primary research on arsenic trioxide inhibiting human breast cancer cells growth and its mechanisms].

OBJECTIVE: The study was to research the biological effect and mechanisms of arsenic trioxide (As2O3) on human breast cancer cell line MDA-MB-231. METHODS: The cytotoxicity was observed by MTT assay. Apoptosis was detected with Annexin V-FITC + PI dual parameter. Cell cycle and positive rate of proliferation cell nuclear antigen (PCNA), apoptosis associated protein Fas and bcl-2 and intracellular calcium ions (IECa(2+)) levels were measured by flow cytometry. RESULTS: As2O3 could inhibit the growth of MDA-MB-231 cells dramatically. There was obvious dosage-effect correlation (r = 0.99, P < 0.01), its half inhibitory concentration (IC(50)) was 6.65 micromol/L. Apoptosis was observed in MDA-MB-231 cells treated with As2O3. As2O3 could increase Fas expression and IECa(2+) levels and decrease PCNA expression in MDA-MB-231 cells (P < 0.01). Cell cycle was arrested in S + G(2)/M phase, but bcl-2 protein expression were not affected (P > 0.05). CONCLUSION: As2O3 could inhibit the growth of MDA-MB-231 cells dramatically and induce apoptosis. We proposed that its mechanisms were probably associated with the improved Fas expression and IECa(2+) levels and decreased PCNA expression and cell cycle arrest.

[Inhibitory and apoptosis regulating effects of adriamycin on different human breast cancer cell lines].

OBJECTIVE: To investigate the inhibitory and apoptosis regulating effects of adriamycin (ADM) on different human breast cancer cell lines and to evaluate the value of apoptosis in breast cancer treatment. METHODS: Human breast cancer cells of the lines Bcap37 and MDA-MB-231 were cultured. ADM of different concentrations was added into the culture fluid. MTT method was used to detect the inhibition rate. Flow cytometry was used to detect the proliferation and apoptosis of the cells. To examine the expression of apoptosis-related molecules: Fas, mutant p53, and Bcl-2 proteins. RESULTS: ADM inhibited the proliferation of Bcap37 cells and MDA-MB-231 cells dose and time-dependently, however, the inhibitory effect of ADM was stronger on the Bcap37 cells than on the MDA-MB-231 cells. After being treated by ADM the expression of Fas was increased and the expression of Bcl-2 was decreased in the Bcap37 cells. However, after being treated by ADM the expressions of Fas, Bcl-2, and mutant p53 in the MDA-MB-231 cells remained almost unchanged. Treated by ADM for 24 hours the apoptotic rate of the Bcap37 cells was increased from 0% to 5.8% (P < 0.05), however, no apoptosis was detected in the MDA-MB-231 cells after treatment of ADM at any time pint. CONCLUSION: With different molecular and biological characteristics, different breast cancer lines are different in chemosensitivity and drug-resistance, which are related to their apoptotic abilities induced by chemotherapeutic drugs.

Evaluation of hormone receptor, human epidermal growth factor receptor-2 and Ki-67 with core needle biopsy and neoadjuvant chemotherapy effects in breast cancer patients.

BACKGROUND: We investigated the reliability of core needle biopsy (CNB) in evaluating the status of hormone receptor (HR), human epidermal growth factor receptor (HER)-2, and Ki-67 status, and the effect of neoadjuvant chemotherapy (NAC) on the expression of these immunohistochemical markers. METHODS: Among 177 patients with breast adenocarcinoma, 95 patients underwent NAC and the remaining 82 patients made up the control group. Immunohistochemistry (IHC) was used to evaluate the expression status of estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 in the specimens obtained by surgical excision or CNB. RESULTS: In the control group, the expression of ER, PR, HER-2, and Ki-67 was highly consistent between samples from surgical excision or CNB (all r > 0.8, P < 0.05). In the NAC group, the proportions of samples with changes in ER, PR, HER-2, and Ki-67 expression were 12.7%, 24.1%, 5.1%, and 38.0%, respectively; the figures in the control group were 2.4%, 4.9%, 2.4%, and 7.3%, respectively, which significantly differed in ER, PR, and Ki-67 (P < 0.05), but not HER-2 (P > 0.05). In the NAC group, pre- and post-treatment ER(+) rates did not significantly differ (P > 0.05), although PR(+) and high Ki-67 expression rates did significantly differ (P < 0.05). CONCLUSION: Neither CNB nor surgical excision samples gave highly consistent results in HR, HER-2, and Ki-67 status. NAC can alter HR and Ki-67 status in breast adenocarcinoma patients. NAC decreased PR(+) rate and Ki-67 expression. The mean ER(+) rate exhibited a decreasing, but insignificant trend after NAC treatment. NAC had no significant effect on HER-2 expression.

Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study.

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

Sentinel lymph node biopsy does not apply to all axillary lymph node-positive breast cancer patients after neoadjuvant chemotherapy.

BACKGROUND: The aim of this study was to investigate the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuant chemotherapy (NAC) in breast cancer patients with confirmed axillary nodal metastases. METHODS: We enrolled 51 patients with breast cancer who received NAC. All patients were proven to have axillary nodal metastases by histopathology biopsy prior to NAC. They all underwent SLNB before breast surgery, and complete axillary lymph node dissection immediately followed. RESULTS: The identification rate for SLNB was 87.5% (84/96); the false negative rate was 24.5% (12/49). The clinicopathological factors were not significantly correlated with the identification and false negative rate of the SLNB. Lymphatic mapping, blue dye or radionuclide methods tended to decrease the identification rate of SLNB (P = 0.073). Clinical nodal status before NAC has a trend to increase the false-negative rates of the SLNB (P = 0.059). For patients with N1 clinical axillary lymph nodal status, the identification rate was 93.9%, and the false negative rate was 5.9%, compared with N2-3 patients with 73.9% and 38.9%, respectively. CONCLUSIONS: SLNB is feasible for the patients whose axillary lymph nodal status before NAC is N1. However, for N2-3 patients, SLNB cannot be used as an infallible indicator of non-SLN status.