Enhancing the Interaction of Carbon Nanotubes by Metal-Organic Decomposition with Improved Mechanical Strength and Ultra-Broadband EMI Shielding Performance.

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 105 S m-1, and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 µm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices.

Secondary coronary artery ostial lesions: Three case reports.

BACKGROUND: Atherosclerosis is one of the main causes of coronary artery ostial lesions seen clinically. Secondary coronary artery ostial lesions are rare, and cases reported previously were associated with syphilitic vasculitis and aortic dissection. Here, we report three rare cases of secondary coronary ostial lesions. Due to their rareness, these lesions can easily be neglected, which may lead to misdiagnosis and missed diagnosis. CASE SUMMARY: We present three patients with acute myocardial infarction and unstable angina caused by secondary coronary artery ostial lesions. In Case 1, coronary angiography (CAG) revealed 90% stenosis of the left main coronary ostium. Chest contrast computed tomography (CT) suggested thymic carcinoma invading the left main coronary ostium. Coronary artery bypass grafting and tumor resection were performed. In Case 2, echocardiography revealed a sinus of Valsalva aneurysm (SVA)-like dilatation. CAG showed a right coronary sinus giant aneurysm and complete obstruction of the right coronary artery (RCA) ostium. Aortic contrast CT confirmed these findings. The Bentall procedure was performed. In Case 3, CT CAG identified an anomalous origin of the right coronary artery (AORCA) from the left sinus of Valsalva coursing between the aorta and pulmonary trunk, causing severe RCA ostium stenosis by compression. Surgical correction of the AORCA was performed. CONCLUSION: The cases reported here suggest that we should consider other causes of coronary ostial lesions other than atherosclerosis.

Tumor-associated macrophages are associated with response to neoadjuvant chemotherapy and poor outcomes in patients with triple-negative breast cancer.

Background and objective: Tumor-associated macrophages (TAMs) play an essential role in tumor progression and metastasis. However, the role of TAMs in neoadjuvant chemotherapy (NAC) is unclear and need to be identified. The main subject of this study was to investigate whether TAMs are related to the chemotherapeutic response with triple-negative breast cancers (TNBC). Methods: We retrospectively analyzed pretreatment tissue from patients who received NAC and followed by a mastectomy or breast-conservation for stage II-III TNBC in this study. The association between TAMs and the pathological complete response (pCR) rate of TNBC to NAC was analyzed. In addition, the correlation of the TAMs with recurrence-free survival (RFS) in patients with TNBC was also evaluated. Results: Of the 91 patients, 31 (34.1%) patients experienced pathological complete response (pCR) after completion of NAC. Regarding the chemotheraptic response, patients with low infiltration of CD163+ macrophages achieved a significantly higher rate of pCR. Importantly, Kaplan-Meier survival shown that patients with high infiltration of CD163+ macrophages and non-pCR had poor OS and RFS. Conclusions: our data showed that TAMs may predict chemotherapeutic response and can be used as a promising prognostic candidate for poor survival in TNBC patients treated with NAC.

Elevated Expression of CAV1 is Associated with Unfavorable Prognosis of Patients with Breast Cancer Who Undergo Surgery and Neoadjuvant Chemotherapy.

INTRODUCTION: Neoadjuvant chemotherapy (NACT), which is standard treatment for locally advanced breast cancer, improves the resectability of patients with early breast cancer and reduces the extent of breast and axillary surgery. Caveolin-1 (CAV1) is implicated in human cancers, although its utility for cancer prognosis is unknown. Here, we investigated the expression of CAV1 in breast cancer tissues to evaluate its prognostic significance on patients with breast cancer administered NACT. METHODS: CAV1 expression in 80 breast cancer tissue samples was evaluated using immunohistochemistry (IHC). The association between CAV1 levels and clinical factors was analyzed using the chi-square test and that between CAV1 and prognosis was evaluated using multivariate Cox regression and Kaplan-Meier analyses. RESULTS: High levels of CAV1 were significantly associated with survival, and patients with overexpression of CAV1 had a poor prognosis. Adjusted multivariate Cox regression analyses revealed that a high level of CAV1 expression was an independent, significant prognostic factor for patients with breast cancer treated with NACT. DISCUSSION: Overexpression of CAV1 in patients with breast cancer administered NACT was associated with shorter disease-free survival and overall survival. Therefore, high levels of CAV1 may serve as a prognostic biomarker for such patients.

Proteomics Study on the Differentially Expressed Proteins in c-fos-silenced Cells Exposed to PM 2.5.

OBJECTIVE: To investigate the effect of c-fos gene silencing on differentially expressed proteins (DEPs) in human bronchial epithelial (HBE) cells after exposure to fine particulate matter (PM 2.5). METHODS: HBE cells and c-fos-silenced HBE cells were exposed to 50 µg/mL PM 2.5, LC-MS/MS and tandem mass tag (TMT) labeling methods were combined with bioinformatics methods, and DEPs and interaction networks were identified. RESULTS: In the HBE group, 414 DEPs were screened, of which 227 were up-regulated and 187 down-regulated. In the c-fos silenced HBE group, 480 DEPs were screened, including 240 up-regulated proteins and 240 down-regulated proteins. KEGG annotations showed that DEPs in the HBE group are mainly concentrated in the glycolysis/gluconeogenesis pathway and those in the c-fos silenced group are concentrated mainly in endoplasmic reticulum and the processing of proteins. Additionally, the abnormal expression of GPRC5C, DKK4, and UBE2C was identified in top 15 DEPs. After constructing the protein interaction network, 20 Hub proteins including HNRNPA2B1, HNRNPL, RPS15A, and RPS25 were screened from the HBE group and the c-fos silenced HBE group. CONCLUSION: c-fos gene affected the expression of cancer-related proteins. Our results provided a scientific basis for further study of PM 2.5-induced carcinogenesis mechanism.

Characteristics of Atmospheric Fine Particulate Matter (PM 2.5) Induced Differentially Expressed Proteins Determined by Proteomics and Bioinformatics Analyses.

OBJECTIVE: To screen the differentially expressed proteins (DEPs) in human bronchial epithelial cells (HBE) treated with atmospheric fine particulate matter (PM 2.5). METHODS: HBE cells were treated with PM 2.5 samples from Shenzhen and Taiyuan for 24 h. To detect overall protein expression, the Q Exactive mass spectrometer was used. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Perseus software were used to screen DEPs. RESULTS: Overall, 67 DEPs were screened in the Shenzhen sample-treated group, of which 46 were upregulated and 21 were downregulated. In total, 252 DEPs were screened in the Taiyuan sample-treated group, of which 134 were upregulated and 118 were downregulated. KEGG analysis demonstrated that DEPs were mainly enriched in ubiquitin-mediated proteolysis and HIF-1 signal pathways in Shenzhen PM 2.5 samples-treated group. The GO analysis demonstrated that Shenzhen sample-induced DEPs were mainly involved in the biological process for absorption of various metal ions and cell components. The Taiyuan PM 2.5-induced DEPs were mainly involved in biological processes of protein aggregation regulation and molecular function of oxidase activity. Additionally, three important DEPs, including ANXA2, DIABLO, and AIMP1, were screened. CONCLUSION: Our findings provide a valuable basis for further evaluation of PM 2.5-associated carcinogenesis.

Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients.

Background: Cancer-associated fibroblasts (CAFs) have been shown to be among the most prominent cells in tumor microenvironment and play a significant role in accelerating tumor metastasis by interacting with other type of cells. Tumor-associated macrophages (TAMs), the predominant tumor-infiltrating immune cells, also play important roles in cancer progression. Here, we aimed to evaluate the effects of CAFs on infiltration of TAMs and lymphatic metastasis in triple-negative breast cancer (TNBC). Material and methods: The study included 278 patients with histologically confirmed TNBC. Immunohistochemical staining of α-smooth muscle actin and fibroblast activation protein were used to identify CAFs. Polarized functional status of infiltrated TAMs was detected by expression of CD163. The clinicopathological features were assessed from all the patients' medical records. Results: The CAFs-related markers were found to be expressed more frequently in TNBC patents with aggressive behaviors, including recurrence and poor histological differentiation. High activation of CAFs was positively correlated with elevated infiltration of polarized CD163-positive TAMs and lymph node metastasis in TNBC patients. Multivariate Cox analysis revealed that the activation of CAFs, TAMs infiltration, and lymph node metastasis were independent prognostic factors for disease-free survival in TNBC patients. Conclusion: Cancer-associated fibroblasts were associated with infiltration of CD163-positive macrophages and lymphatic metastasis, and may be potential prognostic predictors of TNBC.

Tumor-associated macrophages correlate with phenomenon of epithelial-mesenchymal transition and contribute to poor prognosis in triple-negative breast cancer patients.

BACKGROUND: Tumor-associated macrophages (TAMs) are associated with poor outcomes in multiple solid cancers and play important roles in cancer progression. Epithelial-mesenchymal transition (EMT) may account for metastasis and recurrence. However, the association between TAMs and EMT is not clarified in triple-negative breast cancer (TNBC). The aim of this study was to investigate the effects of TAMs on EMT in TNBC. MATERIAL AND METHODS: We studied specimens from 278 patients with TNBC. TAMs marker cluster of differentiation 163 and EMT-related marker E-cadherin were detected by immunohistochemistry in TNBC tissues, and their clinical significance was evaluated from the patients' medical records. RESULTS: TNBC patients with polarized cluster of differentiation 163+ TAMs infiltration and low level of E-cadherin had a significantly higher risk of aggressive features, including recurrence, histologic differentiation, and lymph node metastasis. Infiltration of TAMs was also negatively correlated with E-cadherin in TNBC tissues. Multivariate analysis indicated that infiltration of TAMs and low expression of E-cadherin were independent prognostic factors of overall survival and disease-free survival in TNBC patients. CONCLUSIONS: High infiltration of TAMs was associated with low expression of E-cadherin and could be used as an unfavorable prognostic factor for patients with TNBC.

Hypoxia-inducible factor-1 alpha Correlates with Tumor-Associated Macrophages Infiltration, Influences Survival of Gastric Cancer Patients.

Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC. Clinical significance was assessed for all these patients. Results: High expression of HIF-1α was found in patients with aggressive features, especially for recurrent patients. High infiltration of TAMs and abnormal expression of EMT-marker were also related to aggressive characteristics and predicted poor prognosis in GC. Meanwwhile, there existed a significant correlation among expression of HIF-1α, infiltration of TAMs and EMT marker in GC tissues. Multivariate Cox analysis revealed that high expression of HIF-1α combined TAMs infiltration were independent prognostic factors for disease-specific survival rate. Conclusion: HIF-1α is an unfavorable indicator for prognosis, may promote tumor progression through the induction of EMT and establishment of a pro-tumor immunosuppressive microenvironment. Further investigation into the therapeutic effects of blocking hypoxia is possible a potential strategy for GC treatment.

High Infiltration of Polarized CD163+ Tumor-Associated Macrophages Correlates with Aberrant Expressions of CSCs Markers, and Predicts Prognosis in Patients with Recurrent Gastric Cancer.

Background: As the most predominant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are associated with poor outcome in multiple solid cancers and play important roles in cancer progression. Cancer stem cells (CSCs) may account for metastasis and recurrence after cancer therapy. However, the association between TAMs and CSCs is not clarified in gastric cancer (GC). The aim of the present study was to evaluate the effects of TAMs on CSCs in GC and find out the risk factors to predict recurrence and prognosis. Material and methods: This study included consecutive 236 patients with histologically confirmed primary GC. TAMs marker CD163 and CSCs-related proteins were detected by immunohistochemistry (IHC) in GC tissues and their prognostic values were all investigated. Results: High expression of CD163+ TAMs was found in patents with aggressive characteristics, especially for patents with recurrence. There existed a significant correlation between high expression of CD163 and CSCs-related markers in GC tissues. In patients with recurrence, high-expression of CD163 TAMs was an independent worse prognostic factor. Conclusion: High infiltration of TAMs was related to aggressive behavior, associated with aberrant expression of CSC markers, and an independent worse prognostic factor in GC. Targeting TAMs may be a potential treatment strategy for GC, including patients with recurrence.

Function characterization of a glyco-engineered anti-EGFR monoclonal antibody cetuximab in vitro.

AIM: To evaluate the biochemical features and activities of a glyco-engineered form of the anti-human epidermal growth factor receptor monoclonal antibody (EGFR mAb) cetuximab in vitro. METHODS: The genes encoding the Chinese hamster bisecting glycosylation enzyme (GnTIII) and anti-human EGFR mAb were cloned and coexpressed in CHO DG44 cells. The bisecting-glycosylated recombinant EGFR mAb (bisec-EGFR mAb) produced by these cells was characterized with regard to its glycan profile, antiproliferative activity, Fc receptor binding affinity and cell lysis capability. The content of galactose-α-1,3-galactose (α-Gal) in the bisec-EGFR mAb was measured using HPAEC-PAD. RESULTS: The bisec-EGFR mAb had a higher content of bisecting N-acetylglucosamine residues. Compared to the wild type EGFR mAb, the bisec-EGFR mAb exhibited 3-fold higher cell lysis capability in the antibody-dependent cellular cytotoxicity assay, and 1.36-fold higher antiproliferative activity against the human epidermoid carcinoma line A431. Furthermore, the bisec-EGFR mAb had a higher binding affinity for human FcγRIa and FcγRIIIa-158F than the wild type EGFR mAb. Moreover, α-Gal, which was responsible for cetuximab-induced hypersensitivity reactions, was not detected in the bisec-EGFR mAb. CONCLUSION: The glyco-engineered EGFR mAb with more bisecting modifications and lower α-Gal content than the approved therapeutic antibody Erbitux shows improved functionality in vitro, and requires in vivo validations.

Decreased core-fucosylation contributes to malignancy in gastric cancer.

The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human gastric cancer cells.

Copy number variation analysis based on AluScan sequences.

BACKGROUND: AluScan combines inter-Alu PCR using multiple Alu-based primers with opposite orientations and next-generation sequencing to capture a huge number of Alu-proximal genomic sequences for investigation. Its requirement of only sub-microgram quantities of DNA facilitates the examination of large numbers of samples. However, the special features of AluScan data rendered difficult the calling of copy number variation (CNV) directly using the calling algorithms designed for whole genome sequencing (WGS) or exome sequencing. RESULTS: In this study, an AluScanCNV package has been assembled for efficient CNV calling from AluScan sequencing data employing a Geary-Hinkley transformation (GHT) of read-depth ratios between either paired test-control samples, or between test samples and a reference template constructed from reference samples, to call the localized CNVs, followed by use of a GISTIC-like algorithm to identify recurrent CNVs and circular binary segmentation (CBS) to reveal large extended CNVs. To evaluate the utility of CNVs called from AluScan data, the AluScans from 23 non-cancer and 38 cancer genomes were analyzed in this study. The glioma samples analyzed yielded the familiar extended copy-number losses on chromosomes 1p and 9. Also, the recurrent somatic CNVs identified from liver cancer samples were similar to those reported for liver cancer WGS with respect to a striking enrichment of copy-number gains in chromosomes 1q and 8q. When localized or recurrent CNV-features capable of distinguishing between liver and non-liver cancer samples were selected by correlation-based machine learning, a highly accurate separation of the liver and non-liver cancer classes was attained. CONCLUSIONS: The results obtained from non-cancer and cancerous tissues indicated that the AluScanCNV package can be employed to call localized, recurrent and extended CNVs from AluScan sequences. Moreover, both the localized and recurrent CNVs identified by this method could be subjected to machine-learning selection to yield distinguishing CNV-features that were capable of separating between liver cancers and other types of cancers. Since the method is applicable to any human DNA sample with or without the availability of a paired control, it can also be employed to analyze the constitutional CNVs of individuals.

[Study on sperm damage caused by trichloroethylene in male rats].

OBJECTIVE: To study in vitro sperm damage caused by trichloroethylene in male rats. METHODS: Sperms of Sprague-Dawley (SD) rats were collected 4 hours after being contaminated by trichloroethylene of 0, 2, 4, 6, 8, and 10 mmol/L in vitro. Giemsa staining was performed to observe the morphological changes of sperms, and flow cytometer was used to detect the changes in mitochondrial membrane potential. RESULTS: The sperm motilities in 6, 8, and 10 mmol/L trichloroethylene groups decreased significantly compared with that in control group (P <0.01); the sperm aberration rates in 8 and 10 mmol/L trichloroethylene groups were significantly higher than that in control group (P<0.01). With the increase in exposure dose, the proportion of sperms with reduced mitochondrial membrane potential increased, and there were significant differences in sperm apoptosis rate between the 4, 6, 8, and 10 mmol/L trichloroethylene groups and control group (P<0.01). CONCLUSION: In vitro exposure to trichloroethylene can reduce sperm motility and increase the aberration rate and apoptosis rate of sperms in male SD rats.

[Effects of trichloroethylene on hepatotoxicity in cytochrome 2E1-silenced hepatocytes].

OBJECTIVE: To prepare cytochrome (CYP)2E1-silenced hepatocytes by lentivirus-mediated RNA interference technology and to investigate the hepatotoxicity of trichloroethylene (TCE) in CYP2E1-silenced hepatocytes. METHODS: Short hairpin RNA fragments were designed and synthesized and were then ligated into the lentiviral vector; single colonies were screened; the plasmid was extracted after PCR and sequence identification and then transferred into L02 hepatocytes; the CYP2E1-silenced hepatocytes were selected; real-time quantitative PCR and Western blot were used to evaluate the interference effects. The obtained CYP2E1-silenced hepatocytes, as well as normal L02 hepatocytes, were treated with TCE (0, 0.25, 0.50, 1.00, 2.00, and 4.00 mmol/L). The cell viability and half maximal inhibitory concentration (IC50) of TCE were measured; the apoptotic rate of cells was measured by flow cytometry; the mRNA expression levels of apoptosis genes and oncogenes were measured by real-time quantitative PCR. RESULTS: The IC50s of TCE for L02 hepatocytes and CYP2E1-silenced hepatocytes were 15.1 mmol/L and 23.6 mmol/L, respectively. The apoptotic rate increased as the dose of TCE rose in the two types of cells; the CYP2E1-silenced hepatocytes hada significantly lower apoptotic rate than L02 hepatocytes when they were exposed to 2.0 and 4.0 mmol/L TCE (P < 0.05 or P < 0.01). The mRNA expression level of bcl-2 (anti-apoptosis gene) in CYP2E1-silenced hepatocytes was 15% ∼ 60% higher than that in L02 hepatocytes (P < 0.01), while the mRNA expression levels of caspase-3 and caspase-9 (apoptosis genes) in CYP2E1-silenced hepatocytes were 30% ∼ 60% lower than those in L02 hepatocytes (P < 0.01). The mRNA expression level of p53 (cancer suppressor gene) in CYP2E1-silenced hepatocytes was 81 - 278% higher than that in L02 hepatocytes (P < 0.01), while the mRNA expression levels of c-fos and k-ras (oncogenes) in CYP2E1-silenced hepatocytes were 20-68% lower than those in L02 hepatocytes (P < 0.01). CONCLUSION: CYP2E1-silenced cells can be successfully prepared by lentivirus-mediated RNA interference technology. Silencing CYP2E1 gene can reduce the hepatotoxicity of TCE and inhibit the expression of some apoptosis genes and oncogenes, suggesting that CYP2E1 gene plays an important role in TCE metabolism and is related to the hepatotoxicity of TCE.

Proteome of melamine urinary bladder stones and implication for stone formation.

Melamine can cause urinary stones related to nephropathy of the kidney and hyperplasia or carcinoma of the bladder, but the mechanism of stone formation is not well understood. In this study, male rats were administered melamine for thirteen weeks to establish melamine bladder stone models and the stones were analysed by Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), energy dispersive X-ray (EDX) spectroscopy, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) and western blot, respectively, for the composition and proteome, and to explore the implication of proteins for stone formation. The results showed bladder stones were composed of predominant melamine and a few amount of proteins. The proteins had a wide range of molecular weights and 1051 proteins were identified. Gene Ontology (GO) classification of the identified proteins showed most proteins were from injured cells, involved in various metabolic processes and had binding functions. Of the identified proteins, there were a few inflammatory proteins and urinary proteins. Physicochemical characteristics of the identified proteins showed that 67.1% proteins' isoelectric points (pI) value was below 7.0, 91.1% proteins' grand average of hydropathicity (GRAVY) scores were below 0 and nearly half of the proteins were stable. Our data indicated proteins might play an important role in melamine bladder stone formation.

EGFR-mediated G1/S transition contributes to the multidrug resistance in breast cancer cells.

Despite the improvement of strategies against cancer therapy, the multidrug resistance (MDR)is the critical problem for successful cancer therapy. Recurrent cancers after initial treatment with chemotherapy are generally refractory to second treatments with these anticancer therapies. Therefore, it is necessary to elucidate the therapy-resistant mechanism for development of effective therapeutic modalities against tumors. Here we demonstrate a phase-specific chemotherapy resistance due to epidermal growth factor receptor (EGFR) in human breast cancer cells. Thymidine-induced G1-arrested cultures showed upregulated chemosensitivity, whereas S-phase arrested cells were more resistant to chemotherapeutic agents. Overexpression of EGFR promoted the MDR phenotypes in breast cancer cells via accelerating the G1/S phase transition, whereas depletion of EGFR exerted the opposite effects. Furthermore, CyclinD1, a protein related to cell cycle, was demonstrated to be involved in above EGFR-mediated effects since EGFR increased the expression of CyclinD1, and the specific RNA interference against CyclinD1 could primarily abolish the EGFR-induced MDR phenotypes. These data provide new insights into the mode by which MDR breast cancers evade cytoxic attacks from chemotherapeutic agents and also suggest a role for EGFR-CyclinD1 axis in this process.