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Targeted therapy in breast cancer

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https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#1
Theodosia Maina, Aikaterini Kaloudi, Ibai E Valverde, Thomas L Mindt, Berthold A Nock
INTRODUCTION: Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG4-[Nle(14)]BBN(7-14) (1) was reported to improve the in vitro stability of resulting (177)Lu-radioligands...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28632938/mek-inhibitors-induce-akt-activation-and-drug-resistance-by-suppressing-negative-feedback-erk-mediated-her2-phosphorylation-at-thr701
#2
Chia-Hung Chen, Te-Chun Hsia, Ming-Hsin Yeh, Tsung-Wei Chen, Yun-Ju Chen, Jung-Tsu Chen, Ya-Ling Wei, Chih-Yen Tu, Wei-Chien Huang
Targeting the MEK/ERK pathway has been viewed as a promising strategy for cancer therapy. However, MEK inhibition leads to the compensatory PI3K/AKT activation and thus contributes to the desensitization of cancer cells to MEK inhibitors. The underlying molecular mechanism of this event is not yet understood. In this study, our data showed that the induction of Akt activity by MEK inhibitors was specifically observed in HER2-positive breast cancer cells. Silence of HER2, or overexpression of HER2 kinase-dead mutant, prevents the induction of Akt activation in response to MEK inhibition, indicating HER2 as a critical regulator for this event...
June 20, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28629427/targeting-vegfr-3-2-signaling-pathways-with-ad0157-a-potential-strategy-against-tumor-associated-lymphangiogenesis-and-lymphatic-metastases
#3
Melissa García-Caballero, Jenny Paupert, Silvia Blacher, Maureen Van de Velde, Ana Rodríguez Quesada, Miguel Angel Medina, Agnès Noël
BACKGROUND: Lymphatic metastasis is one of the leading causes of death in patients with different types of cancer and is the main prognostic factor for the disease survival. The formation of new lymphatic vessels (lymphangiogenesis) in primary tumors facilitates tumor cell dissemination to regional lymph nodes and correlates with distant metastases. Lymphangiogenesis has thus emerged as a suitable therapeutic target to block metastases, but no anti-lymphangiogenic compounds have been approved for clinical use to date...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28628857/identification-of-b-and-t-cell-epitope-based-peptide-vaccine-from-igf-1-receptor-in-breast-cancer
#4
Manijeh Mahdavi, Violaine Moreau, Majid Kheirollahi
The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28627677/integrated-analysis-of-the-potential-roles-of-mirna%C3%A2-mrna-networks-in-triple-negative-breast-cancer
#5
Huiru Zhu, Meiyu Dai, Xiaoli Chen, Xiang Chen, Shini Qin, Shengming Dai
Triple negative breast cancer (TNBC) is a type of breast cancer where the tumor cells are negative for the estrogen, progesterone and human epidermal growth factor 2 receptors. To date, expression profiling of microRNA (miRNA/miR) and mRNA sequences have been widely applied for the diagnosis of TNBC. In the present study, an integrated analysis of miRNA‑mRNA profiling arrays was performed. A total of five dysregulated miRNAs in patients with TNBC were identified, including upregulated miR‑558 expression and downregulated miR‑320d‑1, miR‑548v, miR‑99a and miR‑21 expression...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627610/silencing-dek-downregulates-cervical-cancer-tumorigenesis-and-metastasis-via-the-dek-p-ser9-gsk-3%C3%AE-p-tyr216-gsk-3%C3%AE-%C3%AE-catenin-axis
#6
Xiaoyang Xu, Lin Zou, Qiuhui Yao, Yanbo Zhang, Li Gan, Liangdan Tang
Cervical cancer is the second most common gynecological malignancy. The mechanisms of the genesis and progression of cervical cancer are complicated and not thoroughly understood. DEK is reported as an oncogene in various cancers, such as acute myeloid leukemia, bladder cancer, breast cancer and hepatocellular cancer. However, its role in cervical cancer has not been well studied. In our study, we confirmed the DEK protein as an oncoprotein in cervical cancer tissues which is correlated to cervical cancer FIGO staging and tumor type...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627503/three-layered-polyplex-as-a-microrna-targeted-delivery-system-for-breast-cancer-gene-therapy
#7
Yan Li, Yu Dai, Xiaojin Zhang, Jihua Chen
MicroRNAs (miRNAs), small non-coding RNAs, play an important role in modulating cell proliferation, migration, and differentiation. Since miRNAs can regulate multiple cancer-related genes simultaneously, regulating miRNAs could target a set of related oncogenic genes or pathways. Owing to their reduced immune response and low toxicity, miRNAs with small size and low molecular weight have become increasingly promising therapeutic drugs in cancer therapy. However, one of the major challenges of miRNAs-based cancer therapy is to achieve specific, effective, and safe delivery of therapeutic miRNAs into cancer cells...
June 19, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28627385/advances-in-antibody-drug-conjugates-a-new-era-of-targeted-cancer-therapy
#8
REVIEW
Samaresh Sau, Hashem O Alsaab, Sushil Kumar Kashaw, Katyayani Tatiparti, Arun K Iyer
Antibody-drug conjugates (ADCs), a potent class of anticancer therapeutics, comprise a high-affinity antibody (Ab) and cytotoxic payload coupled via a suitable linker for selective tumor cell killing. In the initial phase of their development, two ADCs, Mylotarg(®), and Adcetris(®) were approved by the US Food and Drug Administration (FDA) for treating hematological cancer, but the real breakthrough came with the discovery of the breast cancer-targeting ADC, Kadcyla(®). With advances in bioengineering, linker chemistry, and potent cytotoxic payload, ADC technology has become a more powerful tool for targeted cancer therapy...
June 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28626876/optical-molecular-imaging-guided-radiation-therapy-part-2-integrated-x-ray-and-fluorescence-molecular-tomography
#9
Junwei Shi, Thirupandiyur S Udayakumar, Zhiqun Wang, Nesrin Dogan, Alan Pollack, Yidong Yang
PURPOSE: Differentiating tumor from its surrounding soft tissues is challenging for x-ray computed tomography (CT). Fluorescence molecular tomography (FMT) can directly localize the internal tumors targeted with specific fluorescent probes. A FMT system was developed and integrated onto a CT guided irradiator to improve tumor localization for image guided radiation. METHODS: The FMT system was aligned orthogonal to the cone beam CT onboard our previously developed image guided small animal arc radiation treatment system (iSMAART)...
June 19, 2017: Medical Physics
https://www.readbyqxmd.com/read/28626426/potential-of-central-eastern-and-western-africa-medicinal-plants-for-cancer-therapy-spotlight-on-resistant-cells-and-molecular-targets
#10
REVIEW
Armelle T Mbaveng, Victor Kuete, Thomas Efferth
Cancer remains a major health hurdle worldwide and has moved from the third leading cause of death in the year 1990 to second place after cardiovascular disease since 2013. Chemotherapy is one of the most widely used treatment modes; however, its efficiency is limited due to the resistance of cancer cells to cytotoxic agents. The present overview deals with the potential of the flora of Central, Eastern and Western African (CEWA) regions as resource for anticancer drug discovery. It also reviews the molecular targets of phytochemicals of these plants such as ABC transporters, namely P-glycoprotein (P-gp), multi drug-resistance-related proteins (MRPs), breast cancer resistance protein (BCRP, ABCG2) as well as the epidermal growth factor receptor (EGFR/ErbB-1/HER1), human tumor suppressor protein p53, caspases, mitochondria, angiogenesis, and components of MAP kinase signaling pathways...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28625953/the-relationship-between-the-expressions-of-tumor-associated-fibroblasts-cav-1-and-mct4-and-the-prognosis-of-papillary-carcinoma-of-breast
#11
Yuanyuan Zhai, Lijun Chai, Jianzhong Chen
The aim of this study was to evaluate the expression levels of Cav-1 and MCT4 in the tumor stroma CAFs. Immunohistochemical method was used to detect the expression of Cav-1 and MCT4 in 86 cases of IMPC, with 105 cases of non-specific invasive ductal carcinoma (IDC-NOS) as control. Their differential expression in different histological types were compared and relationship between the expression of Cav-1 and IMPC in the MCT4 and the main pathological features such as age, tumor size and histological grades were analyzed...
January 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28625568/the-olive-oil-phenolic-oleocanthal-modulates-estrogen-receptor-expression-in-luminal-breast-cancer-in-vitro-and-in-vivo-and-synergizes-with-tamoxifen-treatment
#12
Nehad M Ayoub, Abu Bakar Siddique, Hassan Y Ebrahim, Mohamed M Mohyeldin, Khalid A El Sayed
Luminal breast cancer represents a therapeutic challenge in terms of aggressive disease and emerging resistance to targeted therapy. (-)-Oleocanthal has demonstrated anticancer activity in multiple human cancers. The goal of this study was to explore the effect of (-)-oleocanthal treatment on growth of luminal breast cancer cells and to examine the effect of combination of (-)-oleocanthal with tamoxifen. Results showed that (-)-oleocanthal inhibited growth of BT-474, MCF-7, and T-47D human breast cancer cells in mitogen-free media with IC50 values of 32...
June 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28625320/expression-of-jagged1-notch3-signaling-pathway-and-their-relationship-with-the-tumor-angiogenesis-in-tnbc
#13
Siliang Xue, Lang He, Xiao Zhang, Jin Zhou, Fanghua Li, Xiaoshan Wang
BACKGROUND AND AIMS: Jagged1/Notch3 signaling pathway plays a key role in angiogenesis of breast cancer, but little is known in TNBC. This study was designed to investigate the expression of Jagged1/Notch3 mRNA and protein in TNBC, analyze their correlations with clinicopathological characteristics and prognosis. Moreover, the interrelationship among Jagged1/Notch3 and VEGF was initially evaluated. METHODS: Jagged1/Notch3 mRNA and protein expression levels were determined by Q-RT-PCR and Western blotting...
February 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28624192/stimuli-responsive-mesoporous-silica-nps-as-non-viral-dual-sirna-chemotherapy-carriers-for-triple-negative-breast-cancer
#14
REVIEW
Behrad Darvishi, Leila Farahmand, Keivan Majidzadeh-A
Triple negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. It is associated with a very poor prognosis and intrinsically resistant to several conventional and targeted chemotherapy agents and has a 5-year survival rate of less than 25%. Because the treatment options for TNBC are very limited and not efficient enough for achieving minimum desired goals, shifting toward a new generation of anti-cancer agents appears to be very critical. Among recent alternative approaches being proposed, small interfering RNA (siRNA) gene therapy can potently suppress Bcl-2 proto-oncogene and p-glycoprotein gene expression, the most important chemotherapy resistance inducers in TNBC...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623955/precision-medicine-in-breast-cancer-reality-or-utopia
#15
REVIEW
Ali Bettaieb, Catherine Paul, Stéphanie Plenchette, Jingxuan Shan, Lotfi Chouchane, François Ghiringhelli
Many cancers, including breast cancer, have demonstrated prognosis and support advantages thanks to the discovery of targeted therapies. The advent of these new approaches marked the rise of precision medicine, which leads to improve the diagnosis, prognosis and treatment of cancer. Precision medicine takes into account the molecular and biological specificities of the patient and their tumors that will influence the treatment determined by physicians. This new era of medicine is accessible through molecular genetics platforms, the development of high-speed sequencers and means of analysis of these data...
June 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28623645/psmb5-is-associated-with-proliferation-and-drug-resistance-in-triple-negative-breast-cancer
#16
Wensong Wei, Yufeng Zou, Qihua Jiang, Zhibin Zhou, Haolong Ding, Liping Yan, Shixin Yang
BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies. METHODS: To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development...
June 15, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28622695/mir-23a-promotes-tgf-%C3%AE-1-induced-emt-and-tumor-metastasis-in-breast-cancer-cells-by-directly-targeting-cdh1-and-activating-wnt-%C3%AE-catenin-signaling
#17
Fei Ma, Wenjie Li, Chunxiao Liu, Wei Li, Haining Yu, Bo Lei, Yanlv Ren, Zhigao Li, Da Pang, Cheng Qian
TGF-β1-induced epithelial-mesenchymal transition (EMT) has been proved to be associated with metastasis of breast cancer cells. We attempted to detect a novel mechanism that microRNAs mediated the TGF-β1-induced EMT in the process of breast cancer metastasis. Here we reported that the expression of miR-23a was higher in breast cancer cells with high metastasis ability and patients with lymph node metastasis and the treatment of TGF-β1 significantly upregulated the expression of miR-23a in breast cancer cells...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622693/release-of-her2-repression-of-trefoil-factor-3-tff3-expression-mediates-trastuzumab-resistance-in-her2-er-mammary-carcinoma
#18
Qing-Yun Chong, Ming-Liang You, Vijay Pandey, Arindam Banerjee, Yi-Jun Chen, Han-Ming Poh, Mengyi Zhang, Lan Ma, Tao Zhu, Basappa, Liang Liu, Peter E Lobie
HER2+/ER+ breast cancer, a subset of the luminal B subtype, makes up approximately 10% of all breast cancers. The bidirectional crosstalk between HER2 and estrogen receptor (ER) in HER2+/ER+ breast cancer contributes to resistance towards both anti-estrogens and HER2-targeted therapies. TFF3 promotes breast cancer progression and has been implicated in anti-estrogen resistance in breast cancer. Herein, we investigated the cross-regulation between HER2 and estrogen-responsive TFF3, and the role of TFF3 in mediating trastuzumab resistance in HER2+/ER+ breast cancer...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621523/mussel-inspired-hyaluronic-acid-derivative-nanostructures-for-improved-tumor-targeting-and-penetration
#19
Song Yi Lee, Ju-Hwan Park, Seung-Hak Ko, Jae-Seong Shim, Dae-Duk Kim, Hyun-Jong Cho
An amphiphilic hyaluronic acid-ceramide-dopamine (HACE-d) conjugate was prepared and HACE-d-based nanoparticles (NPs) including phloretin (as an inhibitor of glucose transporter (GLUT1)) were fabricated. Mussel-inspired property of d was introduced to HACE NPs and it may improve tumor targetability and penetration in addition to passive (based on enhanced permeability and retention effect) and active (interaction between HA and CD44 receptor) tumor targeting effects. HACE-d/phloretin NPs with 279 nm mean diameter, ~0...
June 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28621239/a-microrna-signature-associated-with-pathological-complete-response-to-novel-neoadjuvant-therapy-regimen-in-triple-negative-breast-cancer
#20
Raúl García-Vazquez, Erika Ruiz-García, Abelardo Meneses García, Horacio Astudillo-de la Vega, Fernando Lara-Medina, Alberto Alvarado-Miranda, Héctor Maldonado-Martínez, Juan A González-Barrios, Alma D Campos-Parra, Sergio Rodríguez Cuevas, Laurence A Marchat, César López-Camarillo
Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker for the prediction of long-term clinical benefits; however, 50%-85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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