Search

Background: Breast cancer has become one of the leading causes of cancer deaths and is the most frequently diagnosed cancer among females worldwide. Despite advances in breast cancer therapy, metastatic disease in most patients will eventually progress due to the development of de novo or secondary resistance. Thus, it is extremely important to seek novel drugs with high effectiveness and low toxicity for systematic therapy., Methods: We applied a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in this study to analyze and evaluate the cytotoxic activity of oleanolic acid (OA) and its derivatives in three types of breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-453). A flow cytometry assay was performed to access the mechanisms of apoptosis and cell cycle analysis in SZC010 in MDA-MB-453 cells. Apoptosis- and cyclin-related proteins were evaluated by western blot. The key proteins of the NF-κB and PI3K-Akt-mTOR signaling pathway were also evaluated by western blot., Results: Our results revealed that all OA derivatives were more effective than OA in three types of breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-453). Among these seven OA derivatives, SZC010 exhibited the most potent cytotoxicity in MDA-MB-453 cells. Additionally, we observed that SZC010 treatment induced dose-and time-dependent growth inhibition in MDA-MB-453 cells. Furthermore, we demonstrated that SZC010 induced growth arrest in the G2/M phase and apoptosis by inhibition of NF-κB activation via the PI3K/Akt/mTOR signaling pathway., Conclusions: Our data indicate that the novel OA derivative, SZC010, has great potential in breast cancer therapy.

Breast carcinoma (BC) ranks as a predominant malignancy and constitutes the second principal cause of mortality among women globally. Epirubicin stands as the drug of choice for BC therapeutics. Nevertheless, the emergence of chemoresistance has significantly curtailed its therapeutic efficacy. The resistance mechanisms to Epirubicin remain not entirely elucidated, yet they are conjectured to stem from diminished tumor vascular perfusion and resultant hypoxia consequent to Epirubicin administration. In our investigation, we meticulously scrutinized the Gene Expression Omnibus database for EPDR1, a gene implicated in hypoxia and Epirubicin resistance in BC. Subsequently, we delineated the impact of EPDR1 on cellular proliferation, motility, invasive capabilities, and interstitial-related proteins in BC cells, employing methodologies such as the CCK-8 assay, Transwell assay, and western blot analysis. Our research further unveiled that hypoxia-induced miR-181a-5p orchestrates the regulation of BC cell duplication, migration, invasion, and interstitial-related protein expression via modulation of EPDR1. In addition, we identified TRPC1, a gene associated with EPDR1 expression in BC, and substantiated that EPDR1 influences BC cellular dynamics through TRPC1-mediated modulation of the PI3K/AKT signaling cascade. Our findings underscore the pivotal role of EPDR1 in the development of BC. EPDR1 was found to be expressed at subdued levels in BC tissues, Epirubicin-resistant BC cells, and hypoxic BC cells. The overexpression of EPDR1 curtailed BC cell proliferation, motility, invasiveness, and the expression of interstitial-related proteins. At a mechanistic level, the overexpression of hypoxia-induced miR-181a-5p was observed to inhibit the EPDR1/TRPC1 axis, thereby activating the PI3K/AKT signaling pathway and diminishing the sensitivity to Epirubicin in BC cells. In summation, our study demonstrates that the augmentation of hypoxia-induced miR-181a-5p diminishes Epirubicin sensitivity in BC cells by attenuating EPDR1/TRPC1 expression, thereby invigorating the PI3K/AKT signaling pathway. This exposition offers a theoretical foundation for the application of Epirubicin in BC therapy, marking a significant contribution to the existing body of oncological literature., (© 2024. The Author(s).)

Background: More than half of Chinese patients with hormone receptor positive (HR+) ductal carcinoma in situ (DCIS) are treated with mastectomy, and usually subjected to postoperative endocrine therapy (ET). Given that long-term ET can cause severe adverse effects it is important to determine the beneficial effect and safety of post-mastectomy ET on the disease-free survival (DFS) and adverse events in patients with HR+ DCIS., Methods: To explore beneficial effect and safety of post-mastectomy ET in patients with HR+ DCIS, we performed a multicenter, population-based study. This retrospective study analyzed the DFS and adverse events in 1037 HR+ DCIS Chinese patients with or without post-mastectomy ET from eight breast centers between 2006 and 2016. The median follow-up time period was 86 months., Results: There were 791 DCIS patients receiving ET (ET group). Those patients were followed up for a median of 86 months (range, 60-177 months). There were 23 cases with tumor recurrence or distant metastasis. There were similar 5-year DFS rates and DFS between the ET and non-ET groups, even for those with high-risk factors. Conversely, 37.04% of patients suffered from adverse events after ET, which were significantly higher than those in the non-ET group., Conclusions: ET after mastectomy did not benefit patients with HR+ DCIS for their DFS, rather increased adverse events in those patients. Therefore, ET after mastectomy may not be recommended for patients with HR+ DCIS, even for those with high-risk factors, such as multifocal, microinvasive, and higher T stage., Funding: This study was supported by grants from Outstanding Scientific Fund of Shengjing Hospital (201803) and Outstanding Young Scholars of Liaoning Province (2019-YQ-10)., Competing Interests: NN, YZ, YB, XW, SY, DS, HX, TL, BH, YZ, JL, XQ, JL, XZ, HC No competing interests declared, CL Senior editor, eLife, (© 2023, Niu, Zhang, Bai et al.)

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC., (© 2022. The Author(s).)

Introduction: Breast microcalcifications is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifications formation are not fully understood. Previous studies have shown that upregulation of bone morphogenetic protein 2 (BMP-2) is associated with the occurrence of microcalcifications and tumor-associated macrophages (TAMs) in the tumor microenvironment can secrete BMP-2. The aim of this study is to elucidate the role of secretion of BMP-2 by TAMs in promoting microcalcifications of breast cancer through immunohistochemical staining and co-culturing of breast cancer cells with TAMs., Methods: A total of 272 patients diagnosed with primary invasive breast cancer from January 2010 to January 2012 in the First Hospital of China Medical University were included in this study. Immunohistochemical staining of CD68 (marker of entire macrophages), CD168 (marker of the M2-like macrophages) and BMP-2 were performed on 4-μm tissue microarray (TMA) sections. Following induction, THP-1 cells were differentiated to M2-like TAMs and were then co-cultured with breast cancer cells (MCF-7). Calcifications and BMP-2 expression were analyzed by Alizarin Red S staining and western blot, respectively., Results: Immunohistochemical analysis showed that the expression of CD168 was significantly increased in tissues with microcalcifications and was correlated with the expression of BMP-2 and poor prognosis. The formation of cellular microcalcifications and BMP-2 expression were significantly increased in MCF-7 cells co-cultured with TAMs compared with MCF-7 cells alone., Conclusions: These findings support the hypothesis that TAMs secrete BMP-2 to induce microcalcifications in breast cancer cells and influence prognosis via multiple pathways including BMP-2 and its downstream factors., (© 2022. The Author(s).)

Background: Ovarian function suppression (OFS) is indicated in premenopausal women with early or metastasis breast cancer, which may be achieved with similar effect by gonadotropin-releasing hormone agonists (GnRHa) or ovarian ablation (OA). We examined whether there were differences in major depressive symptoms outcomes and its associated factors between gonadotropin-releasing hormone agonists (GnRHa) and ovarian ablation (OA) in premenopausal breast cancer patients., Methods: Premenopausal breast cancer patients from seven hospitals who received OFS participated in the study between June 2019 and June 2020. The correlated variable was the type of ovarian suppression, categorized as either OA (n = 174) or GnRHa (n = 389). Major depressive symptoms was evaluated using the Patient Health Questionnaire (PHQ-9), and the Female Sexual Function Index questionnaire was used to assess sexual function., Results: A total of 563 patients completed the surveys. The mean PHQ-9 sum score was slightly lower in the GnRHa cohort than in the OA cohort (11.4 ± 5.7 vs. 12.8 ± 5.8, P = 0.079). There were significantly fewer patients with major depressive symptoms (PHQ-9 ≥ 15) in the GnRHa cohort (31.1% vs. 40.2%, Exp (B)=1.805, P=0.004). Further, breast-conserving surgery and sexual dysfunction were negatively correlated with major depressive symptoms [mastectomy vs. breast-conserving: Exp (B) = 0.461, P <0.001;[sexual dysfunction vs. normal: Exp (B) = 0.512, P = 0.001]., Conclusions: This is the first study to demonstrate that GnRHa results in more favorable depressive symptoms outcomes than OA. Moreover, most patients preferred alternatives to their OFS treatment. These findings can contribute to improving and alleviating the adverse effects of OFS., (© 2021. The Author(s).)

Purpose: Current methods of judging whether HR+/HER2- breast cancer (BC) require adjuvant therapy, such as Ki67 and multigene prognostic tests, cannot balance accuracy with the price most patients can afford., Methods: A retrospective analysis of 330 HR+/HER2- BC patients was conducted. Six BC-related genes (Cathepsin L2, MMP11, CyclinB1, Aurora A, Survivin, and Ki67) were screened using univariate and multivariate COX regression, and correlate clinical follow-up with immunohistochemical expression (designated as 6-IHC). All the included patients were divided randomly at a 7:3 ratio into training and testing cohorts. The cutoff prognosis index (PI) of 6-IHC was determined by multivariate Cox risk regression analysis after calculating the PI of each patient in training cohort and confirmed in testing cohort. Kaplan-Meier (KM) method was used to analyze Disease-free survival (DFS) and overall survival (OS). Six-IHC score and other factors associated with survival benefit of adjuvant chemotherapy were compared with Ki67 index., Results: The receiver operating characteristic curve analysis showed that the patients can be divided into 6-IHC score "High" and "Low" risk groups. The 8-year DFS and OS of the KM curves showed that chemotherapy did not significantly improve the DFS in the 6-IHC score "Low" risk group (P= 0.830), but significantly improved the DFS in the 6-IHC score "High" risk group (P = 0.012)., Conclusions: Combined 6-IHC score could be a reliable tool in predicting cancer-specific recurrences and survival in HR+/HER2-breast cancer patients, with additional advantages over using immunohistochemical expression of Ki67., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The resistance to 5-FU often limits its clinical effectiveness on breast cancer treatment. Combination therapy thus is employed to overcome this treatment resistance. We here report a potent antitumor effect of Emodin at low dose on chemotherapy sensitivity of MCF-7 breast cancer cells., Methods: Cell viability, apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS) activity following Emodin and 5-FU treatment was assessed. Cellular senescence following combined treatment and silence of NRARP was examined by senescence-associated β-galactosidase analysis. Western blot analysis was used to determine changes in the expression of p21, p16, p27, E2F1 and NRARP., Results: Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in association with inhibition of NRARP, resulting in cellular senescence. RNA interference of NRARP induced cellular senescence in MCF-7 breast cancer cells. Furthermore, the cellular senescence induced by Emodin and 5-FU treatment could be reverted by pcDNA-NRARP., Conclusion: These findings provide preclinical evidence for repurposing use of Emodin in combination with chemotherapeutic agents to treat breast cancer as an alternative salvage regimen., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: This study aimed to explore the prognostic value of aldehyde dehydrogenase 1 (ALDH1) expression and vasculogenic mimicry (VM) in patients with breast cancer., Methods: ALDH1 expression and the presence of VM were examined by immunohistochemistry and CD31/PAS double staining, respectively, using formalin-fixed paraffin-embedded tissues from 202 breast cancer patients. The mean follow-up period ranged from 15 to 115 months. The Kaplan-Meier method was used to plot survival curves. Prognostic values were assessed by multivariate analysis using the Cox regression model., Results: ALDH1 expression was strongly associated with VM (P = 0.005). ALDH1 expression was positively correlated with histological grade (P = 0.011). Both ALDH1 expression and VM were negatively related to the status of the estrogen receptor and progesterone receptor and were statistically increased in triple-negative breast cancer. Patients with ALDH1 expression or VM displayed poorer disease-free survival (DFS) and overall survival (OS) than ALDH1-negative or VM-negative patients, with the worst OS and DFS observed in ALDH1/VM-double-positive patients. ALDH1-positive and VM-positive were independent survival risk factors for DFS and OS., Conclusion: ALDH1 expression and VM are correlated with the survival rate of patients with breast cancer. ALDH1 and VM, either alone or together, are prognostic factors in patients with breast cancer., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Transmembrane 4 L6 family member 1 (TM4SF1) belongs to the 4-transmembrane-domain family and functions as an oncogene in multiple human cancers. In this work, we aim to determine TM4SF1 expression and its prognostic impact on patients with invasive breast cancer.Overall, we enrolled 209 invasive breast cancer patients and immunohistochemically examined the expression of TM4SF1 in tumor specimens. The relationship between TM4SF1 expression and clinicopathological parameter and patient survival of breast cancer patients was analyzed.Among the 209 cases, 137 (65.6%) exhibited high expression of TM4SF1. High TM4SF1 expression was significantly associated with advanced histological grade and negative estrogen receptor and progesterone receptor status. Triple-negative breast cancer (TNBC) tumors were more likely to express high levels of TM4SF1 than non-TNBC cases. Patients with high tumoral expression of TM4SF1 had a significantly shorter disease-free survival (DFS; P = .00) and overall survival (OS; P = .01) than those with low expression of TM4SF1. When survival analysis was restricted to the 167 patients (79.9%) receiving adjuvant chemotherapy, TM4SF1 expression was also correlated with poorer DFS and OS (P = .00). In multiple Cox regression analysis TM4SF1 expression remained an independent prognostic indicator for OS and DFS.TM4SF1 is upregulated and serves as an independent poor prognostic indicator in invasive breast cancer., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Falcarindiol (FAD) is a natural polyyne have been found in many food and dietary plants. It has been found to have various beneficial biological activities. In this study, we demonstrated its anticancer function and mechanism in breast cancer cells. We found that FAD preferentially induces cell death in breast cancer cells. FAD-induced cell death is caspase-dependent. However, FAD induces autophagy to contribute to the cell death. Blocking autophagy by either chemical inhibitors or genetic knockout of autophagy signaling component inhibits FAD-induced cell death. We further found that FAD-induced cell death is mediated by the induction of endoplasmic reticulum stress. We also identified that FAD has synergistic effect with approved cancer drugs 5-FU and Bortezomib in killing breast cancer cells. Summarily, these data demonstrate that FAD has strong and specific anticancer effect in breast cancer cells, and provide some insights about the roles of autophagy in FAD-induced cell death.

Background: Suicide gene therapy in cancer can selectively kill tumors without damaging normal tissues. Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK), an original suicide kinase, makes use of the carcinomatous suicide gene therapy for broader substrate specificity and a higher catalytic rate., Methods: To enhance the anti-tumor efficacy of Dm-dNK and maintain its substrate specificity and safety control in the meantime, the conditionally replicative gene-viral system, ZD55-dNK (which contains the selective replication adenovirus, ZD55, encoded with Dm-dNK), was investigated in pushing a deeper development of this strategy. Selective replication, cell killing efficacy, and cytotoxicity, in combination with chemotherapy, were applied to two breast cell lines (MDA231 and MCF7 cells), two normal cell lines (WI38 and MRC5 cells), and the MCF7 xenograft model in vivo., Results: The preclinical study showed that ZD55-dNK, combined with 2',2'-difluorodeoxycytidine (DFDC), synergistically inhibited adenovirus replication in vitro but maintained specifically cancer cell killing efficacy. ZD55-dNK also greatly improved the antineoplastic effect in vitro and in breast cancer xenograft in vivo., Conclusion: The concomitant use of ZD55-dNK and DFDC is possibly a novel and promising approach to breast cancer treatment, and further investigation on the safe control of excessive virus replication and the efficacy of this approach in humans is warranted.

A 5-point breast imaging classification modified from the seven-category Breast Imaging-Reporting and Data System has been applied for mammographic and ultrasonographic examinations in patients with palpable breast masses. The aim of this study was to confirm the value of combined imaging assessment. We included 5,296 cases (3,002 benign and 2,294 cancer) from January 2004 to December 2011. Ultrasonography showed a significantly (P < 0.01) higher sensitivity and specificity and lower false-negative rate and false-negative predictive value (false-NPV) than mammography. The sensitivity of combined imaging was significantly (P < 0.01) increased and the false-negative rate and false-NPV were significantly (P < 0.01) reduced compared to mammography or ultrasonography alone. However, the specificity was significantly (P < 0.01) declined for combined imaging versus mammography or ultrasonography alone. Compared with combined imaging assessment, a significant (P < 0.01) improvement was noted with substratified scoring, with increased specificity and false-negative rate and decreased sensitivity. In conclusion, the substratified combined imaging score has the potential to provide additional value in the workup of palpable breast lesions.

Metaplastic breast carcinoma (MBC) is an uncommon malignancy characterized by the co-existence of two or more cellular types, commonly a mixture of epithelial and mesenchymal components. A case of a female patient aged 46 years with MBC (carcinosarcoma) is presented, including mammographic, ultrasonic, gross examination, and pathological findings. After undergoing modified radical mastectomy of the left breast and subsequent six courses of adjuvant chemotherapy and endocrine therapy, the patient is now doing well with no recurrence and metastasis. Conventional treatments for invasive ductal carcinoma (IDC) may appear to be less effective. Patients with MBC would be appropriate candidates for innovative or targeted therapy regimens.

Gene transfer using different viral vectors has demonstrated different antitumor effects in suicide gene therapy. In the present study, in order to optimize the efficacy of replication-defective adenoviral and lentiviral vectors for gene therapy, RT-PCR was used to evaluate the expression of Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK) in the Bcap37 human breast cancer cell line, dThd was used to determine the activity of Dm-dNK, cell cytotoxicity was evaluated by MTT assay and cell proliferation was assessed using a hemocytometer. Moreover, apoptosis induction was evaluated by the Annexin V-FITC-labeled FACS method. Furthermore, BALB/C nude mice bearing tumors were treated with Dm-dNK mediated with the pyrimidine nucleoside analog, brivudine [BVDU, (E)-5-(2-bromovinyl)-2'-deoxyuridine]. Our results indicated that the gene expression of Dm-dNK transfected by adenoviral and lentiviral vectors may be detected and that its long-term activity may be retained. Both vectors containing the Dm-dNK gene revealed high cytotoxicity and sensitized cell apoptosis from the BVDU prodrug. In tumor models, lentivirus-mediated gene therapy significantly inhibited the growth of tumors compared with adenovirus-mediated gene therapy. Although adenovirus- and lentivirus-transduced Dm-dNK reveal strong treatment efficacy in vitro, the latter has great potential due to the long-term expression of the therapeutic gene in vivo.

Currently, no curative treatments are available for late-stage metastatic or recurrent breast cancer, because the cancer tolerates both chemotherapy and endocrine therapy. In this study, we investigated the feasibility of a dual-regulated oncolytic adenoviral vector with a novel suicide gene to treat breast cancer. Following targeted gene virotherapy of conditionally replicating adenoviruses (CRAds), the novel suicide gene of multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-DNK) was inserted into the double-regulated oncolytic adenovirus SG500 to ensure more safety and enhanced antitumor activity against breast cancer both in vitro and in vivo. Selective replication, cell-killing efficacy, and cytotoxicity, combined with chemotherapeutics were investigated in several breast cell lines (MDA-MB-231 and MCF-7), normal cells (WI-38 and MRC-5), and human (MDA-MB-231) tumor models in vivo. The double-regulated SG500-dNK had high cell-killing activity in breast cancer. Replication was similar to wild-type in breast cells and was attenuated in normal cells. SG500-dNK combined with the chemotherapeutics (E)-5-(2-bromovinyl)-2'-deoxyuridine (Bvdu) and 2',2'-difluoro-deoxycytidine (dFdC) resulted in synergistically enhanced cell killing and greatly improved antitumor efficacy in vitro or in breast xenografts in vivo. These data suggest that the novel oncolytic variant SG500-dNK is a promising candidate for targeting breast tumors specifically when combined with chemotherapeutics., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The purpose of this analysis was to investigate the enzyme activity and specificity of using adenovirus-mediated Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK) mutants in combination with gemcitabine. Compared with herpes simplex type 1 thymidine kinase (HSV-TK) and other known dNKs, this Dm-dNK enzyme has a broader substrate specificity and a higher catalytic rate. We created the Dm-dNK mutants (dNKmu) by site-directed mutagenesis at the sites of 244E, 245S, 251S and 252R, with the last 10 amino acids in the amino acid sequence randomly mutated. We evaluated the enzyme activity and substrate specificity. The engineered enzymes showed a relative increase in phosphorylation in the nucleoside analogs of BVDU ((E)-5‑(2-Bromovinyl)-2'-deoxyuridine) or gemcitabine (DFDC, 2',2'-difluoro-deoxycytidine) compared with the wild-type enzyme. The dNKmu enzymes were expressed in the breast cancer cell lines MDA-MB-231 (ER-) and MCF7 (ER+). In studying the sensitivity of the cell lines to DFDC, conditionally replicative adenovirus (CRAd) SG500-dNKmu showed higher expression and enzymatic activity than the replication-defective adenovirus SG500 in cancer cells, but with less cytotoxicity to cancer cells than that of SG500. Our data suggest that the triple phosphorylated DFDC catalyzed by dNKmu inhibited the replication of adenovirus with a simultaneous positive therapeutic effect to cancer cells. Therefore, concomitant use of the SG500‑dNKmu and DFDC could be a novel targeted strategy in suicide gene therapy with safe control of excessive virus replication.

Background: As a known regulator of apoptosis, survivin has positive relationship with lymphatic metastasis in breast cancer. This study aims to detect the difference in expression between survivin and vascular endothelial growth factor-C (VEGF-C) in treated breast cancer cells and tissues, and to analyze the correlation among survivin, VEGF-C and lymphatic metastasis., Methods: Plasmid with survivin and VEGF-C shRNA and lentivirus with survivin gene were constructed and transfected into breast cancer cell ZR-75-30. Then the expressions of the two genes were examined using western blot analysis and real-time PCR. The change of invasiveness of breast cancer cells was assessed using matrigel invasion assay. Using immunohistochemistry, the expression of survivin and VEGF-C were analyzed in 108 clinical breast cancer cases with breast cancer tissue and lymph node., Results: Survivin regulated the expression of VEGF-C at both protein and mRNA levels in breast cancer cells. Immunohistochemical analysis showed that the level of VEGF-C expression was significantly related with that of survivin in breast cancer tissues (p<0.05). VEGF-C was found to participate in the process of breast cancer cells invasion mediated by survivin. The co-expression of the two and the single expression of any one took significant difference in positive lymph node (p<0.05)., Conclusions: Survivin takes an important part in regulating the expression of VEGF-C. VEGF-C could influence the invasive ability mediated by survivin. The co-expression of survivin and VEGF-C is more statistically significant to assess lymphatic metastasis in breast cancer., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9193530897100952.

Background: Breast cancer has a high incidence worldwide, while Chinese patients have some special characteristics compared to Western patients. A meta-analysis was carried out to determine the effectiveness of breast-conserving therapy (BCT) or mastectomy therapy (MT) for early-stage breast cancers in Chinese women., Methods: A fully recursive literature search was conducted in the Chinese Biomedical Literature Database. Case-control trials were considered for inclusion. Analyses were carried out using the Review Manager software (RevMan, version 5.0)., Results: The meta-analysis showed that the 3-year or 5-year overall survival, the locoregional recurrence rate, and the metastasis rate were not statistically different between the BCT group and the MT group, but the complication recurrence rate increased in the MT group. Subgroup analysis indicated that no significant differences were observed in the affected limb swelling recurrence rate between the BCT group and the MT group., Conclusions: BCT was the better choice than MT for Chinese women with early-stage breast cancer., (Copyright © 2012 S. Karger AG, Basel.)

Background: The multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) was investigated for its broader substrate specificity and higher catalytic rate as a suicide gene in a combined gene/chemotherapy of cancer., Methods: To evaluate the effects of nucleoside analog phosphorylation by Dm-dNK in vitro and in vivo, we generated a replication-deficient retroviral vector expressing Dm-dNK to transduce human breast cancer cells MCF7 (ER+) and MDA-MB-231 (ER-). We further determined the enzymatic activity and the sensitivity of the nontransduced and Dm-dNK-transduced 231/dNK and MCF7/dNK cells to the pyrimidine nucleoside analogs araC and araT., Results: The data obtained show that Dm-dNK is enzymatically active and its overexpression in the nuclei of breast cancer cells results in an increased sensitivity to the nucleoside analogs araC and araT in vitro. Furthermore, subcutaneously transplanted 231/dNK cells were significantly inhibited after araC treatment, whereas nontransduced cancer cells continued to grow and develop in vivo., Conclusions: These results suggest that the Dm-dNK/nucleoside analog system could be a novel therapeutic strategy for treating breast cancer and improving anti-tumor efficacy, as well as for optimizing approaches for suicide gene therapy., (Copyright © 2011 John Wiley & Sons, Ltd.)