Clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 & SATB1 in HER-2-Positive breast cancer patients.

Objective: To evaluate the clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 and SATB1 in HER-2-positive breast cancer patients. Methods: The subjects of study were 80 patients with HER-2-positive breast cancer. Enrolled patients were randomly divided into two groups, with 40 cases in each group at The Fourth Affiliated Hospital of Hebei Medical University from March 2018 from March 2021. Patients in the control group were provided with neoadjuvant chemotherapy using TAC regimen merely; while those in the study group received oral administration of Apatinib Mesylate (500mg/d; three weeks a cycle) on the basis of the TAC regimen. Further comparative analysis was performed focusing on the therapeutic effect and adverse drug reaction rate of the two groups; levels of CD3+, CD4+, CD8+ and CD4+/CD8+ of T lymphocyte subsets in the two groups before and after treatment; as well as the expressions of ER, PR, HER-2 and SATB1 in the two groups before and after treatment. Results: The total response rate was 77.5% and 55% in the study group and the control group, respectively, with an obviously better outcome in the former group than that in the latter group (p=0.03). Meanwhile, the incidence of adverse reactions was 40% in the study group and 45% in the control group, without statistical difference (p=0.65). There were statistically significant differences that the levels of CD3+, CD4+, and CD4+/CD8+ in the study group were significantly higher when compared with those in the control group after treatment (CD3+, p=0.00; CD4+, p=0.02; CD4+/CD8+, p=0.00); while no evident change was observed in the level of CD8+ (p=0.88). After treatment, the positive expression rates of ER, HER-2 and SATB1 were remarkably lower in the study group than those in the control group, showing statistically significant differences (ER, HER-2, p=0.03; SATB1, p=0.02). However, there was no statistically significant difference in the positive expression rate of PR between the study group and the control group (P=0.80). Conclusions: Neoadjuvant chemotherapy combined with immunotherapy has significant effect on the treatment of HER-2-positive breast cancer patients. It can result in the significant enhancement of T lymphocyte function, obvious improvement in the negative converse rates of ER, HER-2 and SATB1, and no evident increase in the adverse drug reactions. The proposed therapeutic approach is safe, effective, and have certain clinical value.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer.

BACKGROUND: Breast cancer (BC) remains a public health problem. Tamoxifen (TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear. AIM: To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients. METHODS: High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1. RESULTS: EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance. CONCLUSION: This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

MicroRNA-409 regulates the proliferation and invasion of breast cancer cell lines by targeting special AT-rich sequence-binding protein 1 (SATB1).

This study aims to determine the cellular functions and clinical significance of microRNA-409 (miR-409) in breast cancer by targeting special AT-rich sequence-binding protein 1 (SATB1). Breast cancer tissues and adjacent normal tissues, breast cancer cell lines (MDA-MB-453, MDA-MB-231, BT-549, BR3, and MCF-7) were used. miR-409 mimics, miR-409 inhibitor, SATB1, and siSATB1 were transiently transduced into cancer cells independently or together. RT-qPCR, Western blot, Cell Counting Kit-8 (CCK8), and Transwell assays were carried out to analyze the expression, cellular proliferation, and invasion. The results showed that the expression of miR-409 in breast cancer tissues is lower than that in adjacent tissues. The application of a target prediction algorithm predicts that the candidate gene regulated by miR-409 may be SATB1. The expression level of miR-409 in MDA-MB-453 cells is lower, while in BT-549 cells it is higher, when compared with MDA-MB-231, BR3, and MCF-7. The proliferation rate and invasive ability of MDA-MB-453 cells transfected with the miR-409 mimic was significantly lower than that of the miRNA negative control (miR-NC) cells, while the proliferation rate and invasive ability of BT-549 cells transfected with the miR-409 inhibitor were significantly increased. Cell proliferation and invasion of miR-409 mimic and SATB1 co-transfected MDA-MB-453 cells increased compared with that of miR-409 mimic-transfected cells, while miR-409 inhibitor and siSATB1 co-transfected BT-549 cells showed the opposite result. All these results indicated that miR-409 regulates breast cancer proliferation and invasion by targeting SATB1 and might be a potential therapeutic target for the treatment of breast cancer.

Low-dose epirubicin inhibits ezrin-mediated metastatic behavior of breast cancer cells.

AIMS AND BACKGROUND: Overexpression of ezrin contributes to the progression and invasiveness of several human cancers; however, its role in breast cancer metastasis has not been investigated in detail. METHODS: Ezrin expression in tissue samples from patients with invasive ductal carcinoma of the breast was detected by immunohistochemistry. Ezrin expression in a breast cancer cell line was evaluated using Western blot and RT-PCR. RESULTS: Elevated expression of ezrin was associated with lymph node metastasis and poor prognosis in patients with invasive ductal carcinoma. Ezrin expression was related to the invasiveness of breast cancer cells in vitro. Low-dose epirubicin inhibited the migration of breast cancer cells in a concentration-dependent manner without promoting cytotoxicity in vitro and decreased the expression of ezrin in a concentration-dependent manner. CONCLUSIONS: Low-dose epirubicin may be antimetastatic without promoting cytotoxic effects and could serve as a target for the development of therapeutics for breast carcinoma.

The effect of childbirth on carcinogenesis of DMBA-induced breast cancer in female SD rats.

Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divided them into control or experimental (DMBA-treated) nulliparous, early childbirth, and late childbirth groups to observe the incidence, latency, and size of breast cancer. Argyrophilic nucleolar organizer regions (AgNOR) count and the expression of C-erbB-2, proliferating cell nuclear antigen (PCNA), Ki-67, and minichromosome maintenance protein 2 (MCM2) in breast cancer tissues were detected by immunohistochemistry. The breast cancer incidences were 95.0%, 16.7%, and 58.8% in the experimental nulliparous, early childbirth, and late childbirth groups, respectively (all P < 0.05). Between any two of these groups, the latency was significantly different, but tumor size was similar. AgNOR count and the expression of C-erbB-2, PCNA, Ki-67, and MCM2 were significantly higher in the experimental nulliparous group than in the experimental early or late childbirth groups (P < 0.05), but no significant differences were observed between the latter two groups. Taken together, the results suggest that childbirth, especially early childbirth, can reduce the incidence and postpone the onset of DMBA-induced breast cancer.

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.

The value of radiotherapy in patients with T1 and T2 breast cancer with one to three positive nodes after modified radical mastectomy.

BACKGROUND AND OBJECTIVE: The role of adjuvant radiotherapy to the regional nodes in women with T1 to T2 breast cancer and one to three positive nodes is controversial. This study compared and analyzed the prognosis of patients with T1-T2 breast cancer with one to three positive nodes after modified radical mastectomy with or without postoperative radiotherapy. METHODS: The cases of 434 women patients with T1 to T2 breast cancer with one to three positive lymph nodes after modified radical mastectomy were reviewed, of which 196 patients received postoperative radiotherapy and 238 patients did not. The ipsilateral chest wall and supraclavicular fossa were irradiated with doses of 46-50 Gy in 23-25 fractions. RESULTS: For all patients, the 3- and 5-year rates of overall survival (OS) were 94.7% and 85.7% respectively, local control (LC) 96.5% and 95.6%;, and disease-free survival (DFS) 89.3% and 82.3% respectively. The 3- and 5-year OS rates for patients without radiotherapy were 92.7% and 97.1% and for those with radiotherapy were 82.4% and 89.2%, both with significant differences (P = 0.039). The 3- and 5-year LC rates for patients without radiotherapy were 94.8% and 98.4% and for those with radiotherapy were 93.6% and 97.7%, again with significant differences (P = 0.041). The 3- and 5-year DFS rates for patients without radiotherapy were 87.8% and 91.3% and for patients with radiotherapy were 78.5% vs 86.1% (P = 0.047). CONCLUSIONS: Postoperative radiotherapy confers better rates of OS, LC, and DFS in patients with T1 to T2 breast cancer with one to three positive nodes after modified radical mastectomy.

Molecular fingerprint of precancerous lesions in breast atypical hyperplasia.

OBJECTIVE: To identify atypical hyperplasia (AH) of the breast by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and to explore the molecular fingerprinting characteristics of breast AH. METHODS: Breast hyperplasia was studied in 11 hospitals across China from January 2015 to December 2016. All patients completed questionnaires on women's health. The differences between patients with and without breast AH were compared. AH breast lesions were detected by Raman spectroscopy followed by the SHINERS technique. RESULTS: There were no significant differences in clinical features and risk-related factors between patients with breast AH (n = 37) and the control group (n = 2576). Fifteen cases of breast AH lesions were detected by Raman spectroscopy. The main different Raman peaks in patients with AH appeared at 880, 1001, 1086, 1156, 1260, and 1610 cm-1, attributed to the different vibrational modes of nucleic acids, ß-carotene, and proteins. Shell-isolated nanoparticles had different enhancement effects on the nucleic acid, protein, and lipid components in AH. CONCLUSION: Raman spectroscopy can detect characteristic molecular changes in breast AH lesions, and may thus be useful for the non-invasive early diagnosis and for investigating the mechanism of tumorigenesis in patients with breast AH.

[Clinicopathologic features and prognosis of triple negative breast cancer].

OBJECTIVE: To analyze the clinicopathologic features and prognosis of triple negative breast cancer. METHODS: The clinical datas of 477 patients of primary breast cancer which were diagnosed by pathology in the 4th Hospital of Hebei Medical University from Jan. 2004 to Dec. 2004 were analyzed. All of the patients were divided into two groups according to the results of immunohistochemistry: one was triple negative breast cancer (TNBC) which included estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor (HER2) negative and other was non-triple negative breast cancer. We compared TNBC with the group of non-triple negative breast cancer in the clinicopathologic features. The disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier method. RESULTS: Of the 477 patients, 12.6% (60/477) was TNBC patients in which 76.7% of age was younger than fifty years(46/60), 28.3% of T > 5 cm (17/60), 68.3% of lymph nodes metastasis (41/60), 31.7% of grade III (19/60) and 13.3% of family history of breast cancer (8/60), (P < 0. 05). Till June 2008, the median time of follow-up was 48 months (42-54 months). Local recurrence or distant metastasis were 26.7% (16/60) of TNBC which was higher than 15.3% (64/417) of non-triple negative cases; DFS was 68.3% in TNBC group and 79.6% in the non-triple negative breast cancer group. The OS was 81.7% in TNBC group and 90.9% in the non-triple negative breast cancer group (Log-Rank = 3.917, P = 0.048; Log-Rank = 4.838, P = 0.028). CONCLUSION: These patients of triple negative breast carcinoma were usually young (age < 50), with tumor growth fast, much more invasion and poorly prognosis.

Undifferentiated embryonal sarcoma of liver in an old female: case report and review of the literature.

The clinical characteristics of undifferentiated (embryonal) sarcoma of the liver (UESL) were investigated and the best treatment modalities were recommended. Both histology and immuno-histochemistry demonstrated the cellular features of this peculiar tumor. The tumor size was 12 cm multiply 9 cm multiply 8 cm in the right liver lobe. The patient underwent surgical resection of the tumor. The postoperative recovery was uneventful and she died eight months after diagnosis. The tumor showed mixed spindle and polygonal cells within the myxoid matrix. Some tumor cells contained eosinophilic hyaline globules that were positive for resistant diastase. Immunohistochemistry showed positive vimentin. Stellate and spindle cells were positively stained with alpha-1-antichymotrypsin (AACT) and CD68. This case indicates that UESL is not obviously differentiated in old-aged adults.

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.

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma.

Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta-1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK-HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN-bearing non-treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

Biomarkers for EMT and MET in breast cancer: An update.

Metastasis and recurrence are the leading cause of mortality due to breast cancer, but the underlying mechanisms are still poorly understood. Understanding the breast cancer metastasis mechanism is important for early diagnosis and treatment of breast cancer. The seeding and growth of breast cancer cells at sites distinct from the primary tumor is a complex and multistage process. Recently, it has been reported that the epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET) are the main mechanisms for breast cancer metastasis. During EMT, carcinoma cells shed their differentiated epithelial characteristics, including cell-cell adhesion, polarity and lack of motility, and acquire mesenchymal traits, including motility and invasiveness. This review has summarized the studies of known EMT biomarkers in the context of breast cancer progression. These biomarkers include EMT-related genes, proteins, microRNAs and kinases. In general, the findings of these studies suggest that EMT markers are associated with the invasion and metastasis of breast cancer. Further studies on the link between EMT markers and breast cancer will contribute to identify biomarkers for predicting early breast cancer metastasis as well as to provide new ideas for the treatment of breast cancer.

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.

Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism.

BACKGROUND AND AIMS: The MAGE gene encodes cancer/testis antigens that are selectively expressed in various types of human neoplasms but not in normal tissues other than testis and placenta. However, the expression pattern of MAGE-A9 and MAGE-A11 in breast cancer patients is still unclear. The purpose of our study is to investigate the expression pattern and mechanism of MAGE-A9 and MAGE-A11 in breast cancer patients. METHODS: The expression of MAGE-A9 and MAGE-A11 was investigated in 60 breast benign diseases specimens, 60 tumor-free breast specimens and 60 breast cancer specimens by RT-PCR, and their correlation with clinicopathological parameters was elucidated. We examined the influence of the DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) together with the histone deacetylase inhibitor trichostatin A (TSA) on the expression of MAGE-A9 and MAGE-A11 genes in two breast cancer cell lines. RESULTS: The expression rates of MAGE-A9 and MAGE-A11 in breast cancer specimens were 45 and 66.7%, respectively. MAGE-A9 and MAGE-A11 expression was positively associated with estrogen-receptor (ER) and HER-2 expression (p <0.05). 5-Aza-CdR treatment alone could induce the expression of MAGE-A9 and MAGE-A11 in cell lines that did not express this antigen. TSA treatment alone had no influence on MAGE-A9 and MAGE-A11 gene expression. However, TSA was able synergistically to enhance 5-aza-CdR-mediated MAGE-A transcription (p <0.05). CONCLUSIONS: Our data show that MAGE-A9 and MAGE-A11 are tumor-specific antigens and not only DNA hypermethylation but also histone deacetylation is responsible for the mechanism underlying MAGE-A9 and MAGE-A11 gene silencing.

Preventive effect of hydrazinocurcumin on carcinogenesis of diethylnitrosamine-induced hepatocarcinoma in male SD rats.

The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DEN- induced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

Relationship of RhoA signaling activity with ezrin expression and its significance in the prognosis for breast cancer patients.

BACKGROUND: We have recently reported that RhoA may regulate the invasion and metastasis of breast cancer cells as an upstream signal of ezrin in vitro. In this study, we examined the relationship of RhoA signaling activity with ezrin expression in breast cancer and its prognostic significance in patients with breast cancer. METHODS: Paraffin tumor sections of breast cancer were collected retrospectively from 487 patients diagnosed between 2001 and 2004. Immunohistochemical methods were used to detect the expression of RhoA, phosphorylated (activated) RhoA, and ezrin. RESULTS: Ezrin overexpression was detectable in 15.2% of 487 invasive breast cancers. The majority (85.1%) of ezrin-overexpressing tumors coexpressed phosphorylated RhoA; 78.8% of tumors with phosphorylated RhoA cooverexpressed ezrin. Patients whose cancers showed overexpression of ezrin or expression of phosphorylated RhoA had shorter survival rates. CONCLUSIONS: RhoA activation is important in human breast cancer due to its upregulation of ezrin; thus, agents that target phosphorylated RhoA may be useful in the treatment of tumors with ezrin overexpression.

Risk factors related to female breast cancer in regions of Northeast China: a 1:3 matched case-control population-based study.

BACKGROUND: There has been an increase in the incidence of breast cancer in China, but no definite risk and protective factors for breast cancer have been identified in Chinese females. This study was designed to identify the risk factors for female breast cancer in North and East China. METHODS: A 1:3 matched, case-control study was conducted. All of the subjects in the case and control groups were selected from a previous epidemiological survey of 122 058 females aged 25 to 70 years. Single and multiple Logistic regression analyses were used to study potential factors in the development of breast cancer. RESULTS: Significant differences at the level of α=0.20 between case and control groups were observed for the following factors: economic status, social status, family annual income, bean product consumption, body mass index (BMI), family history of breast cancer in the first or second degree, number of miscarriages, menstrual pattern, benign breast disease history, nipple leakage, inverted nipple, history of diabetes mellitus, history of hypertension, history of ovarian cyst, physical exercise, current and global quality of life satisfaction, healthy behavior and prevention, and scores of breast cancer-related knowledge. After Cox-regression model analysis (α=0.10), six factors were found to be significantly related to breast cancer, of which the ORs and 95%CIs were: BMI, 1.696 (1.169-2.460, P=0.005); benign breast disease history, 2.672 (0.848-8.416, P=0.093); family history of breast cancer, 7.080 (1.758-28.551, P=0.006); number of miscarriages, 1.738 (1.014-2.978, P=0.044); global quality of life satisfaction, 3.044 (1.804-5.136, P=0.000); healthy behavior and prevention, 3.294 (1.692-6.412, P=0.000). CONCLUSIONS: A comprehensive range of factors related to breast cancer was identified. Women should be educated about a healthy lifestyle, especially those with a family history of breast cancer or a personal history of benign breast disease.