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https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#1
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210763/artemisinin-and-its-derivatives-in-cancer-therapy-status-of-progress-mechanism-of-action-and-future-perspectives
#2
REVIEW
Archana Bhaw-Luximon, Dhanjay Jhurry
Since the late 1990s, there has been rapid multiplication of data on the anti-cancer properties of artemisinins. This article reviews the status of progress of artemisinin and its derivatives as anti-cancer agents in clinical trials, case reports, and in vitro/in vivo studies. Particular attention is laid on the combinations of artemisinins and synthetic chemodrugs to enhance the latter's efficacy. An attempt is here made to rationalize the synergistic effects of a few common anti-cancer drugs of the anthracycline, taxane, anti-metabolite, and platinum-based drug families...
February 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28209757/cdk4-6-therapeutic-intervention-and-viable-alternative-to-taxanes-in-crpc
#3
James P Stice, Suzanne E Wardell, John D Norris, Alexander P Yllanes, Holly M Alley, Victoria O Haney, Hannah S White, Rachid Safi, Peter S Winter, Kimberly J Cocce, Rigel J Kishton, Scott A Lawrence, Jay C Strum, Donald P McDonnell
: Resistance to second generation AR antagonists and CYP17 inhibitors in patients with castrationresistant prostate cancer (CRPC) develops rapidly through reactivation of the androgen signaling axis and has been attributed to androgen receptor (AR) overexpression, production of constitutively active AR splice variants, or the selection for AR mutants with altered ligand binding specificity. It has been established that androgens induce cell cycle progression, in part, through upregulation of cyclin D1 (CCND1) expression and subsequent activation of cyclin-dependent kinases 4 and 6 (CDK4/6)...
February 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28209298/utidelone-plus-capecitabine-versus-capecitabine-alone-for-heavily-pretreated-metastatic-breast-cancer-refractory-to-anthracyclines-and-taxanes-a-multicentre-open-label-superiority-phase-3-randomised-controlled-trial
#4
Pin Zhang, Tao Sun, Qingyuan Zhang, Zhongyu Yuan, Zefei Jiang, Xiao Jia Wang, Shude Cui, Yuee Teng, Xi-Chun Hu, Junlan Yang, Hongming Pan, Zhongsheng Tong, Huiping Li, Qiang Yao, Yongsheng Wang, Yongmei Yin, Ping Sun, Hong Zheng, Jing Cheng, Jinsong Lu, Baochun Zhang, Cuizhi Geng, Jian Liu, Roujun Peng, Min Yan, Shaohua Zhang, Jian Huang, Li Tang, Rongguo Qiu, Binghe Xu
BACKGROUND: Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer. METHODS: We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens...
February 10, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28207984/structural-basis-of-microtubule-stabilization-by-discodermolide
#5
Andrea E Prota, Katja Bargsten, Mariano Redondo, Amos B Smith Iii, Chia-Ping H Yang, Hayley M McDaid, Ian Paterson, Susan B Horwitz, José Fernando Díaz, Michel O Steinmetz
Microtubule-stabilizing agents (MSAs) are widely used in chemotherapy. Here, using X-ray crystallography we describe the detailed binding modes of two potent MSAs, (+)-discodermolide (DDM) and the DDM-paclitaxel-hybrid KS-1-199-32, in the taxane pocket of ß-tubulin. Both compounds bind in a very similar hairpin conformation as previously observed in solution. However, they differentially stabilize the M-loop of ß-tubulin: KS-1-199-32 induces an M-loop helical conformation that is not observed for DDM. In the context of the microtubule structure, both MSAs connect the ß-tubulin helices H6 and H7 and loop S9-S10 with the M-loop, which is similar to the structural effects elicited by epothilone A, but distinct from paclitaxel...
February 16, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28205193/new-therapeutic-strategies-for-triple-negative-breast-cancer
#6
REVIEW
Borbála Székely, Andrea L M Silber, Lajos Pusztai
Relatively few clinically important therapeutic advances have occurred in the treatment of triple-negative breast cancer (TNBC) since the introduction of taxanes as adjuvant therapy over 20 years ago. However, this is rapidly changing due to a variety of conceptually important clinical trials and emerging new options such as immune checkpoint inhibitors and antibody-drug conjugates. Evidence also increasingly supports that platinum drugs and inhibitors of poly (ADP-ribose) polymerase, or PARP, are particularly effective in the treatment of germline BRCA-mutant cancers, including TNBC...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28204996/incidence-of-taxane-induced-peripheral-neuropathy-receiving-treatment-and-prescription-patterns-in-patients-with-breast-cancer
#7
Su Jeong Song, Ji Min, Sung Yun Suh, Sun Hoi Jung, Hyeon Joo Hahn, Seock-Ah Im, Ju-Yeun Lee
PURPOSE: Taxane-induced peripheral neuropathy (TIPN) can affect quality of life and treatment outcomes in breast cancer patients. Despite the high incidence, treatment of PN has not been established. This study aimed to evaluate the incidence, risk factors, and prescribing pattern of TIPN receiving pharmacologic treatment in real-world practice. METHODS: We conducted a retrospective chart review of 1629 breast cancer patients who received taxanes at the Seoul National University Hospital from July 2012 to June 2014...
February 16, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28204994/prevalence-of-aromatase-inhibitor-induced-arthralgia-in-breast-cancer-a-systematic-review-and-meta-analysis
#8
REVIEW
David Beckwée, Laurence Leysen, Kaipo Meuwis, Nele Adriaenssens
BACKGROUND: Although aromatase inhibitors have proven to be an effective treatment of hormone receptor-positive breast cancer in postmenopausal women, aromatase inhibitor-induced arthralgia (AIA) is an adverse event associated with low compliance with treatment. The aim of this literature study is to assess the prevalence of AIA and to provide an overview of significant predictors for the development of AIA. METHODS: A systematic review was conducted using PubMed, Cochrane Library and Web of Science...
February 15, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28197640/sb-t-121205-a-next-generation-taxane-enhances-apoptosis-and-inhibits-migration-invasion-in-mcf-7-ptx-cells
#9
Xiaowei Zheng, Changwei Wang, Yuanming Xing, Siying Chen, Ti Meng, Haisheng You, Iwao Ojima, Yalin Dong
Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. the aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28196257/association-between-use-of-a-scalp-cooling-device-and-alopecia-after-chemotherapy-for-breast-cancer
#10
Hope S Rugo, Paula Klein, Susan Anitra Melin, Sara A Hurvitz, Michelle E Melisko, Anne Moore, Glen Park, Jules Mitchel, Erika Bågeman, Ralph B D'Agostino, Elizabeth S Ver Hoeve, Laura Esserman, Tessa Cigler
Importance: Chemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited. Objectives: To evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life. Design, Setting, and Participants: A prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen)...
February 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28196254/effect-of-a-scalp-cooling-device-on-alopecia-in-women-undergoing-chemotherapy-for-breast-cancer-the-scalp-randomized-clinical-trial
#11
Julie Nangia, Tao Wang, Cynthia Osborne, Polly Niravath, Kristen Otte, Steven Papish, Frankie Holmes, Jame Abraham, Mario Lacouture, Jay Courtright, Richard Paxman, Mari Rude, Susan Hilsenbeck, C Kent Osborne, Mothaffar Rimawi
Importance: Chemotherapy may induce alopecia. Although scalp cooling devices have been used to prevent this alopecia, efficacy has not been assessed in a randomized clinical trial. Objectives: To assess whether a scalp cooling device is effective at reducing chemotherapy-induced alopecia and to assess adverse treatment effects. Design, Setting, and Participants: Multicenter randomized clinical trial of women with breast cancer undergoing chemotherapy...
February 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28191807/neo-adjuvant-chemotherapy-in-locally-advanced-breast-cancer-a-retrospective-analysis-from-tertiary-care-centre
#12
Deepti Sharma, Garima Singh
INTRODUCTION: Breast cancer is the most common cancer in women in India. The incidence of LABC is 30%-40% in developing countries as compared to developed countries, lack of awareness and screening programmes in developing countries are supposed to be main contributor of this increase incidence. The use of neoadjuvant chemotherapy in locally advanced breast cancer has shown benefits in down staging of tumors, and increases the rate of breast conserving surgeries. AIM: The aim was to compare response rate (clinical and pathological), the disease free survival, and overall survival in two chemotherapy regime...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28187446/targeting-of-apoptotic-pathways-by-smac-or-bh3-mimetics-distinctly-sensitizes-paclitaxel-resistant-triple-negative-breast-cancer-cells
#13
Effrosini G Panayotopoulou, Anna-Katharina Müller, Melanie Börries, Hauke Busch, Guohong Hu, Sima Lev
Standard chemotherapy is the only systemic treatment for triple-negative breast cancer (TNBC), and despite the good initial response, resistance remains a major therapeutic obstacle. Here, we employed a High-Throughput Screen to identify targeted therapies that overcome chemoresistance in TNBC. We applied short-term paclitaxel treatment and screened 320 small-molecule inhibitors of known targets to identify drugs that preferentially and efficiently target paclitaxel-treated TNBC cells. Among these compounds the SMAC mimetics (BV6, Birinapant) and BH3-mimetics (ABT-737/263) were recognized as potent targeted therapy for multiple paclitaxel-residual TNBC cell lines...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181130/micrornas-mir-7-and-mir-340-predict-response-to-neoadjuvant-chemotherapy-in-breast-cancer
#14
Mithu Raychaudhuri, Holger Bronger, Theresa Buchner, Marion Kiechle, Wilko Weichert, Stefanie Avril
PURPOSE: miRNAs have been linked to chemosensitivity of breast cancer cells in vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether (I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and (II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients...
February 8, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28176956/docetaxel-associated-myalgia-arthralgia-syndrome-in-patients-with-breast-cancer
#15
Chelsea Seguin, Natalie Kovacevich, Ioannis A Voutsadakis
BACKGROUND: As taxanes are increasingly used in oncology, the myalgia-arthralgia syndrome (M-AS) that represents an adverse effect of these drugs is becoming more common. Nevertheless, information regarding predisposing factors, prevention, and therapy of the syndrome is still lacking. PATIENTS AND METHODS: Women who had received docetaxel as part of the FEC-D(T) regimen for the adjuvant treatment of breast cancer were retrospectively identified from the records of our oncology department...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28174294/trastuzumab-in-human-epidermal-growth-factor-receptor-2-positive-early-breast-cancer-results-of-a-prospective-noninterventional-study-on-routine-treatment-between-2006-and-2012-in-germany
#16
Peter Dall, Thorsten Koch, Thomas Göhler, Johannes Selbach, Andreas Ammon, Jochen Eggert, Nidal Gazawi, Daniela Rezek, Arthur Wischnik, Carsten Hielscher, Stella Keitel, Ursula Cirrincione, Axel Hinke, Gabriele Feisel-Schwickardi
PURPOSE: Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies. PATIENTS AND METHODS: Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy...
February 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28164759/neoadjuvant-therapy-for-her2-positive-breast-cancer
#17
Rachel Wuerstlein, Nadia Harbeck
In HER2-positive early breast cancer, neoadjuvant treatment with a combination of sequential chemotherapy and HER2-targeted therapy is currently the standard of care. This is followed by breast surgery, radiotherapy (if indicated), completion of 12 months of HER2-directed therapy, and -depending on the tumor biology - endocrine adjuvant therapy, and ultimately follow up. 10-year survival rates in the HER2-positive subgroup of breast cancer do reach now more than 75% with the introduction of first adjvuant and later neoadjuvant HER2-targeted therapies over the last 15 years...
February 2, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28161993/eribulin-in-non-small-cell-lung-cancer-challenges-and-potential-strategies
#18
Umang Swami, Umang Shah, Sanjay Goel
Eribulin is a non-taxane, macrocyclic, synthetic, ketone analog of Halichondrin B with a microtubule inhibitory action specific towards plus ends. It is approved by United States Food and Drug Administration (USFDA) for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen. It is also approved as a third line therapy for patients with metastatic breast cancer who have received a prior treatment with anthracycline and taxane in either adjuvant or metastatic setting...
February 6, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28161682/preclinical-evaluation-of-taxane-binding-peptide-modified-polymeric-micelles-loaded-with-docetaxel-in-an-orthotopic-breast-cancer-mouse-model
#19
Jennifer Logie, Ahil N Ganesh, Ahmed M Aman, Rima S Al-Awar, Molly S Shoichet
We developed a novel taxane-binding peptide (TBP) modified, biodegradable polymeric micelle that overcomes limitations of drug loading and poor serum stability typically seen with particle delivery, leading to enhanced pharmacokinetics and tumor distribution of docetaxel (DTX). The use of the taxane-binding peptide to increase docetaxel loading is particularly compelling as it takes advantage of a known intracellular binding mechanism in a new way. Docetaxel is a potent chemotherapeutic with a therapeutic index often limited by the toxicity of the excipients that are necessary to enhance its solubility for intravenous delivery...
January 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#20
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
January 23, 2017: Cancer Treatment Reviews
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