- Influence of social conditions on the quality of life of female breast cancer survivors. [Journal Article]
- BJBreast J 2018 Dec 17
- Axillary web syndrome: What the radiologist needs to know. [Journal Article]
- BJBreast J 2018 Dec 17
- Non-canonical AR activity facilitates endocrine resistance in breast cancer. [Journal Article]
- EREndocr Relat Cancer 2019 Feb 01; 26(2):251-264
- The role of androgen receptor (AR) in endocrine-resistant breast cancer is controversial and clinical trials targeting AR with an AR antagonist (e.g., enzalutamide) have been initiated. Here, we inve...
The role of androgen receptor (AR) in endocrine-resistant breast cancer is controversial and clinical trials targeting AR with an AR antagonist (e.g., enzalutamide) have been initiated. Here, we investigated the consequence of AR antagonism using in vitro and in vivo models of endocrine resistance. AR antagonism in MCF7-derived tamoxifen-resistant (TamR) and long-term estrogen-deprived breast cancer cell lines were achieved using siRNA-mediated knockdown or pharmacological inhibition with enzalutamide. The efficacy of enzalutamide was further assessed in vivo in an estrogen-independent endocrine-resistant patient-derived xenograft (PDX) model. Knockdown of AR inhibited the growth of the endocrine-resistant cell line models. Microarray gene expression profiling of the TamR cells following AR knockdown revealed perturbations in proliferative signaling pathways upregulated in endocrine resistance. AR loss also increased some canonical ER signaling events and restored sensitivity of TamR cells to tamoxifen. In contrast, enzalutamide did not recapitulate the effect of AR knockdown in vitro, even though it inhibited canonical AR signaling, which suggests that it is the non-canonical AR activity that facilitated endocrine resistance. Enzalutamide had demonstrable efficacy in inhibiting AR activity in vivo but did not affect the growth of the endocrine-resistant PDX model. Our findings implicate non-canonical AR activity in facilitating an endocrine-resistant phenotype in breast cancer. Unlike canonical AR signaling which is inhibited by enzalutamide, non-canonical AR activity is not effectively antagonized by enzalutamide, and this has important implications in the design of future AR-targeted clinical trials in endocrine-resistant breast cancer.
- Metabolic perturbation, proliferation and reactive oxygen species jointly contribute to cytotoxicity of human breast cancer cell induced by tetrabromo and tetrachloro bisphenol A. [Journal Article]
- EEEcotoxicol Environ Saf 2018 Dec 14; 170:495-501
- Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and mol...
Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and molecular mechanism remain under-explored. In this study, we employed human breast cancer cell as a model to investigate the concentration-dependent toxicity and underlying mechanisms of tetrabromo bisphenol A (TBBPA) and tetrachloro bisphenol A (TCBPA). An integrated method involving molecular toxicology and mass spectrometry (MS)-based global metabolomics was applied to evaluate the toxicity of TCBPA and TBBPA on cell viability, reactive oxygen species (ROS), and metabolic alterations. The results demonstrated that low micromolar levels (0-10 μM) of TCBPA/TBBPA exposure induced cell proliferation and activated the energy metabolism of both glycolysis and amino acid. On the other hand, high micromolar levels (10-50 μM) of TCBPA/TBBPA exposure perturbed the balance between ROS and antioxidative defense process by promoting the ROS generation via the down-regulation of glutathione biosynthesis and up-regulation of nucleotide metabolism. This study, for the first time, provides evidence and mechanism for better understanding the cytotoxicity of TCBPA and TBBPA by regulating the specific metabolic pathways.
- Dissolvable microneedle patch containing doxorubicin and docetaxel is effective in 4T1 xenografted breast cancer mouse model. [Journal Article]
- IJInt J Pharm 2018 Dec 14
- Microneedle-devices provide a promising alternative to syringe-injection-based administration of chemotherapeutics. Dissolvable polymeric microneedles provide possibility of carrying greater payload ...
Microneedle-devices provide a promising alternative to syringe-injection-based administration of chemotherapeutics. Dissolvable polymeric microneedles provide possibility of carrying greater payload and dual drugs. Here, we report development of polyvinyl pyrrolidone and polyvinyl alcohol composite dissolvable polymeric microneedle system for co-delivery of doxorubicin HCl and docetaxel. Microneedle patches were characterized using stereomicroscope, scanning electron microscope, texture analyzer and confocal microscope. The greatest amount of doxorubicin and docetaxel loaded within one microneedle patch was 533±65 and 227±23 µg, respectively. Ex-vivo studies in excised murine skin revealed insertion of microneedles and permeation of chemotherapeutics without lag time. Microneedles dissolved within 1 h of insertion in excised skin. Effectiveness of the delivery system was determined in 4T1 breast cancer cells xenografted athymic Balb/c mouse model. Intra-tumoral injection of doxorubicin and doxorubicin + docetaxel combination showed significant toxicity to animals evidenced by drastic reduction in the body weight and 100 percent death within 9-days and after 2-dose administration. Interestingly, doxorubicin and docetaxel administered using microneedles either alone or in combination showed significantly greater survival (100% survival after 16-days and 4-dose administration) compared with intratumoral injections. The normalized body weight, tumor volume and DNA fragmentation assay indicated superior effect of microneedle patch application. Furthermore, co-delivery of doxorubicin and docetaxel, controlled the tumor growth better than the administration of single molecules. Taken together, minimally invasive dissolvable microneedle patch application could compliment painful catheter assisted syringe injections to deliver combination chemotherapeutics.
- A papilloma in a large cyst of the breast: A case report. [Journal Article]
- IJInt J Surg Case Rep 2018 Nov 16; 55:1-3
- CONCLUSIONS: Tumors in a large cyst of the breast is difficult in distinguish benign from malignancy by preoperative imaging, cytological and histological study.Excisional biopsy should be performed before cancer surgery such as mastectomy to manage the cysts with intracystic growths.
- Tumor suppressor RARRES1- A novel regulator of fatty acid metabolism in epithelial cells. [Journal Article]
- PlosPLoS One 2018; 13(12):e0208756
- Retinoic acid receptor responder 1 (RARRES1) is silenced in many cancers and is differentially expressed in metabolism associated diseases, such as hepatic steatosis, hyperinsulinemia and obesity. He...
Retinoic acid receptor responder 1 (RARRES1) is silenced in many cancers and is differentially expressed in metabolism associated diseases, such as hepatic steatosis, hyperinsulinemia and obesity. Here we report a novel function of RARRES1 in metabolic reprogramming of epithelial cells. Using non-targeted LC-MS, we discovered that RARRES1 depletion in epithelial cells caused a global increase in lipid synthesis. RARRES1-depleted cells rewire glucose metabolism by switching from aerobic glycolysis to glucose-dependent de novo lipogenesis (DNL). Treatment with fatty acid synthase (FASN) inhibitor, C75, reversed the effects of RARRES1 depletion. The increased DNL in RARRES1-depleted normal breast and prostate epithelial cells proved advantageous to the cells during starvation, as the increase in fatty acid availability lead to more oxidized fatty acids (FAO), which were used for mitochondrial respiration. Expression of RARRES1 in several common solid tumors is also contextually correlated with expression of fatty acid metabolism genes and fatty acid-regulated transcription factors. Pathway enrichment analysis led us to determine that RARRES1 is regulated by peroxisome proliferating activated receptor (PPAR) signaling. These findings open up a new avenue for metabolic reprogramming and identify RARRES1 as a potential target for cancers and other diseases with impaired fatty acid metabolism.
- regQTLs: Single nucleotide polymorphisms that modulate microRNA regulation of gene expression in tumors. [Journal Article]
- PGPLoS Genet 2018 Dec 17; 14(12):e1007837
- Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with trait diversity and disease susceptibility, yet their functional properties often remain ...
Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with trait diversity and disease susceptibility, yet their functional properties often remain unclear. It has been hypothesized that SNPs in microRNA binding sites may disrupt gene regulation by microRNAs (miRNAs), short non-coding RNAs that bind to mRNA and downregulate the target gene. While several studies have predicted the location of SNPs in miRNA binding sites, to date there has been no comprehensive analysis of their impact on miRNA regulation. Here we investigate the functional properties of genetic variants and their effects on miRNA regulation of gene expression in cancer. Our analysis is motivated by the hypothesis that distinct alleles may cause differential binding (from miRNAs to mRNAs or from transcription factors to DNA) and change the expression of genes. We previously identified pathways-systems of genes conferring specific cell functions-that are dysregulated by miRNAs in cancer, by comparing miRNA-pathway associations between healthy and tumor tissue. We draw on these results as a starting point to assess whether SNPs on dysregulated pathways are responsible for miRNA dysregulation of individual genes in tumors. Using an integrative regression analysis that incorporates miRNA expression, mRNA expression, and SNP genotype data, we identify functional SNPs that we term "regulatory QTLs (regQTLs)": loci whose alleles impact the regulation of genes by miRNAs. We apply the method to breast, liver, lung, and prostate cancer data from The Cancer Genome Atlas, and provide a tool to explore the findings.
- Correlation Between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases After Neoadjuvant Systemic Therapy. [Journal Article]
- AnnSAnn Surg 2018 Dec 13
- CONCLUSIONS: Breast pCR achieved after NST is strongly correlated with ypN0 in cN0 patients, especially in ER+HER2+, ER-HER2+, and triple negative subtypes. These results provide data to proceed with future clinical trials to investigate if axillary surgery can be safely omitted in these selected patients when image-guided tissue sampling identifies a breast pCR.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
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- Prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia with lipegfilgrastim in 2489 cancer patients: final results from the non-interventional study NADIR. [Journal Article]
- CMCurr Med Res Opin 2018 Dec 17; :1-27
- CONCLUSIONS: Lipegfilgrastim administered to patients with solid tumor/NHL undergoing chemotherapy in routine clinical practice showed similar effectiveness and safety compared to the pivotal trials.