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Target in cancer breast

Behjatolah Monzavi-Karbassi, Fariba Jousheghany, Thomas Kieber-Emmons
Development of cancer vaccines targeting tumor-associated antigens (TAAs) is an alternative approach to chemotherapy with sustained anti-tumor effects. The success of active immunotherapy has been hampered by tumor-induced immune suppressors. Regulatory T cells (Tregs) are a population of immune suppressors with a proven role in regulating anti-tumor immune responses. Removing or subduing Tregs activity leads to more robust anti-tumor immune responses. Here, we used a cell-based vaccination strategy in the 4T1 murine mammary model to examine whether bulk removal of certain TAAs, using their glycan profile, can affect the immunogenicity of the vaccine...
October 19, 2016: Immunological Investigations
Deeksha Pal, Venkatesh Kolluru, Balaji Chanderashekar, Becca V Baby, Mazzy Aman, Suman Suman, Suman Sirimulla, Mary Ann Sanders, Praveen Seshabhatter, Houda Alatassi, Murali K Ankem, Chendil Damodaran
We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues...
October 18, 2016: Molecular Carcinogenesis
Saeed Zavareh, Milad Mahdi, Soheyla Erfanian, Hamid Hashemi-Moghaddam
PURPOSE: Carrier-mediated drug delivery systems can be used to increase the intracellular concentration of drugs in cancerous cells, thereby improving drug biodistribution and minimizing unwanted side effects. This study aimed to investigate the effect of synthesized magnetic molecularly imprinted polydopamine for controlled doxorubicin (DOX) delivery in a breast adenocarcinoma model of BALB/c mice with an external magnetic field. METHODS: The synthesized DOX-imprinted polydopamine (DOX-IP) was characterized using Fourier transform infrared spectroscopy and scanning electron microscopy...
October 17, 2016: Cancer Chemotherapy and Pharmacology
Schammim Ray Amith, Krista Marie Vincent, Jodi Marie Wilkinson, Lynne Marie Postovit, Larry Fliegel
Mounting evidence supports a major role for the Na(+)/H(+) exchanger NHE1 in cancer progression and metastasis. NHE1 is hyperactive at the onset of oncogenic transformation, resulting in intracellular alkalinization and extracellular microenvironmental acidification. These conditions promote invasion and facilitate metastasis. However, the signal pathways governing the regulation of exchanger activity are still unclear. This is especially important in the aggressively metastatic, triple-negative basal breast cancer subtype...
October 14, 2016: Cellular Signalling
Domenico Ribatti, Beatrice Nico, Simona Ruggieri, Roberto Tamma, Giovanni Simone, Anita Mangia
Several data support a central role for angiogenesis in breast cancer growth and metastasis. Observational studies have demonstrated that microvascular density (MVD) is a prognostic factor in invasive breast cancer, whereas others reached the opposite conclusion. Vascular endothelial growth factor is the most important angiogenic factor with proven significance in breast cancer, as it has been assessed in both experimental and clinical studies. Triple-negative breast cancer (TNBC) is a type of breast cancer which lacks estrogen, progesterone, and HER-2/neu receptors...
October 2016: Translational Oncology
Yasunori Minami, Tomohiro Minami, Hirokazu Chishina, Masashi Kono, Tadaaki Arizumi, Masahiro Takita, Norihisa Yada, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVE: Radiofrequency ablation (RFA) induces gas bubbles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immediately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liver metastasis. METHODS: RFA guided by US-US fusion imaging was performed on 12 targeted tumors in 10 patients. Secondary hepatic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1)...
2016: Digestive Diseases
Michael Rehman, Sreeharsha Gurrapu, Gabriella Cagnoni, Lorena Capparuccia, Luca Tamagnone
The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays...
2016: PloS One
Shanmei Du, Helou Li, Xiaochun Sun, Dongsheng Li, Yong Yang, Zehua Tao, Qian Li, Kui Liu
MicroRNA (miRNA) is a type of endogenous non‑coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines...
October 11, 2016: Oncology Reports
Tianhui Wu, Xin Chen, Rui Peng, Handeng Liu, Pin Yin, Huimin Peng, Yujian Zhou, Yan Sun, Li Wen, Hong Yi, Ailing Li, Zheng Zhang
Cervical cancer is the second most commonly diagnosed type of cancer among women after breast cancer. Recent research has addressed the role of microRNAs in cervical cancer. In the present study, we aimed to determine the effect of let‑7a on the regulation of the cell proliferation of cervical cancer and the related signaling pathway. Real‑time RT‑PCR was used to detect the expression of let‑7a in the blood of cervical cancer patients and normal controls. The expression of let‑7a was also assessed in cervical cancer cell lines: HeLa, SiHa and normal human immortalized keratinocyes HaCaT...
October 11, 2016: Oncology Reports
A L R Bordinhão, A F Evangelista, R J S Oliveira, T Macedo, H C Silveira, R M Reis, M M Marques
Cediranib, a pan-tyrosine kinase inhibitor is showing promising results for the treatment of several solid tumours. In breast cancer, its effects remain unclear, and there are no predictive biomarkers. Several studies have examined the expression profiles of microRNAs (miRNAs) in response to different chemotherapy treatments and found that the expression patterns may be associated with the treatment response. Therefore, our aim was to evaluate the cellular behaviour and differential expression profiles of miRNAs in breast cancer cell lines exposed to cediranib...
October 7, 2016: Oncology Reports
Sarah A Altınoğlu, Ming Wang, Kathleen Q Li, Yuyang Li, Qiaobing Xu
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor, mutated or inactive in a large percentage of human cancers. Restoring PTEN activity in cancer cells through gene therapy has shown to inhibit cell growth and induce apoptosis, particularly in cells with a PTEN deficiency. Gene therapy, however, comes with some inherent risks such as triggering an immune response and permanent off target effects. Nanoparticle assisted protein delivery could mitigate these liabilities while maintaining therapeutic integrity...
October 17, 2016: Biomaterials Science
C Yang, Z Li, T Bhatt, M Dickler, D Giri, M Scaltriti, J Baselga, N Rosen, S Chandarlapaty
Dysregulated activation of the CDK4/6 kinases is a hallmark of most mammary-derived carcinomas. ATP-competitive inhibitors against this complex have been recently advanced in the clinic and have shown significant activity, particularly against tumors driven by the estrogen receptor (ER). However, resistance to these compounds has begun to emerge often months to years after their initiation. We investigated potential mechanisms of resistance using cell line models that are highly sensitive to this class of drugs...
October 17, 2016: Oncogene
Farha Naz, Neha Sami, Abu Turab Naqvi, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human microtubule affinity-regulating kinase 4 (MARK4) is considered as an encouraging drug target for the design and development of inhibitors to cure several life threatening diseases such as Alzheimer disease, cancer, obesity and type-II diabetes. Recently, we have reported four ligands namely, BX-912, BX-795, PKR-inhibitor and OTSSP167 (hydrochloride) which bind preferentially to the two different constructs of human MARK4 containing kinase domain. To ensure the role of ubiquitin associated (UBA) domain in the ligand binding, we made a newer construct of MARK4 which contain both kinase and UBA domains, named as MARK4-F3...
October 16, 2016: Journal of Biomolecular Structure & Dynamics
Egidio Iorio, Maria José Caramujo, Serena Cecchetti, Francesca Spadaro, Giulia Carpinelli, Rossella Canese, Franca Podo
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. (1)H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment...
2016: Frontiers in Oncology
Ciara M Kelly, Yelena Y Janjigian
Gastric cancer is a biologically heterogeneous tumor. The identification of human epidermal growth factor receptor-2 (HER2) biomarker overexpression in gastric cancer represented a significant step towards unraveling the molecular complexity of this disease. Trastuzumab in combination with chemotherapy, in the first-line setting of patients with metastatic, HER2-positive gastric and gastroesophageal, represents the first targeted therapeutic to demonstrate improvement in response rate and survival in gastric cancer...
October 2016: Journal of Gastrointestinal Oncology
Peng Zou, Longhua Liu, Louise D Zheng, Kyle K Payne, Masoud H Manjili, Michael O Idowu, Jinfeng Zhang, Eva M Schmelz, Zhiyong Cheng
Overactive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1α, NRF1, and Tfam) in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in breast cancer cells...
2016: Oxidative Medicine and Cellular Longevity
Shivani Sharma, Praveen K Patnaik, Stella Aronov, Ritu Kulshreshtha
Apoptosis, a form of programmed cell death, is a highly regulated process, the deregulation of which has been associated with the tumor initiation, progression, and metastasis in various cancers including breast cancer. Induction of apoptosis is a popular target of various therapies currently being tested or used for breast cancer treatment. Thus, identifying apoptotic mediators and regulators is imperative for molecular biologists and clinicians for benefit of patients. The regulation of apoptosis is complex and involves a tight equilibrium between the pro- and anti-apoptotic factors...
2016: Frontiers in Genetics
Hongyu Shen, Dandan Wang, Liangpeng Li, Sujin Yang, Xiu Chen, Siying Zhou, Shanliang Zhong, Jianhua Zhao, Jinhai Tang
BACKGROUND AND PURPOSE: Acquisition of resistance to adriamycin (ADR) is one of the most important clinical obstacles in the treatment of breast cancer, but the molecular mechanisms underlying sensitivity to ADR remain elusive. In our previous study, through miRNA microarray and experiments, we have emphasized that miR-222 could promote the ADR-resistance in breast cancer cells. The aim of this study was to explore the possible mechanism by which miR-222 affects sensitivity to ADR. METHODS: Through pathway enrichment analyses for miR-222, we found that PTEN/Akt/FOXO1 signaling pathway may be of importance...
October 13, 2016: Gene
Xiu Chen, Peng Lu, Dan-Dan Wang, Su-Jin Yang, Ying Wu, Hong-Yu Shen, Shan-Liang Zhong, Jian-Hua Zhao, Jin-Hai Tang
PURPOSE: Chemoresistance mediated by miRNAs in breast cancer have been already validated by previous studies in vitro, while little is known concerning the expression of them in vivo. The aim of this study was to investigate the role of miR-222, miR-29a, miR-34a, miR-130a, miR-90b, miR-200b, miR-452, miR-197, miR-138, miR-210, miR-423, miR-4298, miR-4644, miR-139, miR-1246, miR-1268a, miR-140, miR-149, miR-3178, miR-3613, miR-4258, miR-574, miR-671, miR-6780b, miR-7107, miR-744 and miR-7847 linked to drug resistance in breast cancer formalin-fixed paraffin-embedded tissues and the association of prognosis with miRNAs, thus providing effective targets in chemotherapy, as well as potential biomarkers for guiding effective treatments of breast cancer...
October 13, 2016: Gene
Yanan Gao, Xuejing Qi, Yiping Zheng, Hongyu Ji, LinhuaWu, Nannan Zheng, Jingling Tang
The vitamin E analogue, α-tocopherol succinate (α-TOS), has a broad anti-tumor effect. α-TOS can induce cancer cells apoptosis and suppress tumor growth by targeting mitochondria. Low bioavailability of α-TOS is the major problem encountered with formulation development. In our study, α-TOS nanoemulsion (α-TOS-NE) was demonstrated as a new drug delivery system of α-TOS to increase the bioavailability. MTT-based cytotoxicity assay and mitochondrial membrane potential (ΔY) were performed on human breast cancer cell lines MCF-7 and human oral epithelial cancer cell lines KB to evaluate in vitro anticancer efficacy of α-TOS-NE...
October 13, 2016: International Journal of Pharmaceutics
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