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https://www.readbyqxmd.com/read/28637003/structural-recognition-of-tubulysin-b-derivatives-by-multidrug-resistance-efflux-transporters-in-human-cancer-cells
#1
Michal Stark, Yehuda G Assaraf
Multidrug resistance (MDR) is a major hindrance to curative chemotherapy of various human malignancies. Hence, novel chemotherapeutics must be evaluated for their recognition by MDR efflux transporters. Herein we explored the cytotoxic activity of synthetic tubulysin B (Tub-B, EC1009) derivatives (Tub-B-hydrazide/EC0347 and Tub-B bis-ether/EC1820), and their recognition by the MDR efflux transporters P-glycoprotein 1 (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636760/successful-management-of-refractory-diabetic-gastroparesis-with-long-term-aprepitant-treatment
#2
N Fountoulakis, J Dunn, S Thomas, J Karalliedde
BACKGROUND: People with gastroparesis who develop treatment-resistant (refractory) disease pose a difficult challenge, especially in the setting of end-stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin-receptor antagonist) is licensed for the short-term treatment of chemotherapy-induced nausea. There is lack of information on its long-term efficacy and safety in people with diabetic gastroparesis. CASE REPORT: Case 1 was 73-year-old man with Type 2 diabetes of 25 years' duration and ESRD requiring dialysis...
June 21, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28636040/tamoxifen-like-metallocifens-target-the-thioredoxin-system-determining-mitochondrial-impairment-leading-to-apoptosis-in-jurkat-cells
#3
Valeria Scalcon, Michèle Salmain, Alessandra Folda, Siden Top, Pascal Pigeon, Hui Zhi Shirley Lee, Gérard Jaouen, Alberto Bindoli, Anne Vessières, Maria Pia Rigobello
Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, and Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. In contrast, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types resistant to standard chemotherapies. Therefore, we investigated the effect of these three TLMs on the thioredoxin system and evaluated the input of the metallocene unit in comparison with structurally related organic tamoxifens...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28635633/new-insights-in-thyroid-cancer-and-p53-family-proteins
#4
REVIEW
Livia Manzella, Stefania Stella, Maria Stella Pennisi, Elena Tirrò, Michele Massimino, Chiara Romano, Adriana Puma, Martina Tavarelli, Paolo Vigneri
Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634711/%C3%AE-pyrone-derivatives-from-a-streptomyces-strain-resensitize-tamoxifen-resistance-in-breast-cancer-cells
#5
Rui-Min Yang, Xiu-Lei Zhang, Li Wang, Jian-Ping Huang, Jing Yang, Yi-Jun Yan, Jian-Ying Luo, Xiang-Ting Wang, Sheng-Xiong Huang
Tamoxifen resistance (TamR) is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen. In order to look for noncytotoxic natural products with the ability to reverse TamR, an extract from strain Streptomyces sp. KIB-H0495 was detected to be active. Subsequent large scale fermentation and isolation led to the isolation of four α-pyrone derivatives including two new compounds, violapyrones J (2) and K (3), and two known analogues, violapyrones B (1) and I (4). Further bioactivity assays indicated that only 1 and 3 exerted potent resensitization effects on MCF-7/TamR cells at a concentration of 1 μM...
June 20, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28632486/randomized-noncomparative-phase-ii-trial-of-early-switch-from-docetaxel-to-cabazitaxel-or-vice-versa-with-integrated-biomarker-analysis-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#6
Emmanuel S Antonarakis, Scott T Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B Lannin, Shalu Suri, Conor N Gruber, Erica D Pratt, Brian J Kirby, Mario A Eisenberger, David M Nanus, Fred Saad, Paraskevi Giannakakou
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327)...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28632134/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#7
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
June 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#8
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28629530/novel-natural-product-therapeutics-targeting-both-inflammation-and-cancer
#9
Jiangjiang Qin, Wei Wang, Ruiwen Zhang
Inflammation is recently recognized as one of the hallmarks of human cancer. Chronic inflammatory response plays a critical role in cancer development, progression, metastasis, and resistance to chemotherapy. Conversely, the oncogenic aberrations also generate an inflammatory microenvironment, enabling the development and progression of cancer. The molecular mechanisms of action that are responsible for inflammatory cancer and cancer-associated inflammation are not fully understood due to the complex crosstalk between oncogenic and pro-inflammatory genes...
June 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28628492/complete-remission-of-intrathecal-metastases-with-lorlatinib-therapy-in-a-heavily-pretreated-alk-positive-lung-cancer-patient
#10
Maximilian J Hochmair, Sophia Schwab, Helmut Prosch
Patients with lung cancer who show EML4-ALK translocation are routinely treated with ALK tyrosine kinase inhibitors, although in the majority of cases, these patients develop resistance over time. The central nervous system is a common of site of recurrence in this population, which calls for next-generation drugs that can penetrate into the brain and achieve clinically meaningful central nervous system activity. Here, I report the case of a female patient diagnosed with adenocarcinoma of the lung in 2005, at the age of 46 years, who underwent lobectomy and then experienced a series of progression episodes 6 years later...
June 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28628491/calcein-acetoxymethy-ester-enhances-the-antitumor-effects-of-doxorubicin-in-nonsmall-cell-lung-cancer-by-regulating-the-topbp1-p53rr-pathway
#11
Yinxiang Lv, Rongrong Liu, Shangzhi Xie, Xiaoxiao Zheng, Jiayan Mao, Ying Cai, Wei Chen
Calcein acetoxymethyl ester (calcein-AM) treatment has been reported to exert antitumor effects in certain cancer cells; however, the detailed mechanism of action of calcein-AM in cancers remains unclear, especially in nonsmall cell lung cancer (NSCLC). This study focused on the function and mechanism of action of calcein-AM in NSCLC. We used cell viability assays, western blotting, and EdU proliferation assay combined with calcein-AM treatment or siRNA interference to investigate the role of topoisomerase IIβ binding protein 1 (TopBP1) and p53 in NSCLC chemotherapy...
June 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28628188/silencing-of-bag3-promotes-the-sensitivity-of-ovarian-cancer-cells-to-cisplatin-via-inhibition-of-autophagy
#12
Shuang Qiu, Liang Sun, Ye Jin, Qi An, Changjiang Weng, Jianhua Zheng
Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin‑based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28627658/shikonin-promotes-adriamycin%C3%A2-induced-apoptosis-by-upregulating-caspase%C3%A2-3-and-caspase%C3%A2-8-in-osteosarcoma
#13
Qing Yang, Suoyuan Li, Zeze Fu, Binhui Lin, Zifei Zhou, Zhuoying Wang, Yingqi Hua, Zhengdong Cai
Osteosarcoma is the most common primary malignant bone tumor. Cancer cells employ a host of mechanisms to develop resistance to adriamycin (ADM) or other chemotherapeutic drugs. Shikonin (SK), an active constituent extracted from a Chinese medicinal herb, has been shown to cooperate with ADM in the treatment of osteosarcoma and certain other types of cancer by contributing to the response rate of chemotherapy and the side effects. The aim of the present study was to investigate the role and underlying mechanism of SK in chemotherapy for osteosarcoma...
June 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626736/enterococcus-spp-and-s-aureus-colonization-in-neutropenic-febrile-children-with-cancer
#14
Julia R Spinardi, Rodrigo Berea, Patricia A Orioli, Marina M Gabriele, Alessandra Navarini, Marina T Marques, Milton N Neto, Marcelo J Mimica
INTRODUCTION: Febrile neutropenia is one of the most serious treatment-related complications in cancer patients. Susceptible to rapidly progressing infections, which result in prolonged hospitalization and use of broad-spectrum antibiotics, neutropenic patients are subject to colonization by multiresistant agents, which enhances the risk of infections. METHODS: In this study we included samples collected with nasal, oropharyngeal and anal swabs from hospitalized children with febrile neutropenia following chemotherapy, between March 2014 and 2015, aiming to elucidate colonization by S...
June 2017: Germs
https://www.readbyqxmd.com/read/28626727/mast-cell-infiltration-in-human-brain-metastases-modulates-the-microenvironment-and-contributes-to-the-metastatic-potential
#15
Ananya Roy, Sylwia Libard, Holger Weishaupt, Ida Gustavsson, Lene Uhrbom, Göran Hesselager, Fredrik J Swartling, Fredrik Pontén, Irina Alafuzoff, Elena Tchougounova
Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs) are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs) in a large cohort of human BM samples with different tissues of origin for primary cancer...
2017: Frontiers in Oncology
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
#16
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/28624848/-177-lu-psma-617-radioligand-therapy-and-outcome-in-patients-with-metastasized-castration-resistant-prostate-cancer
#17
Axel Bräuer, Lena Sophie Grubert, Wolfgang Roll, Andres Jan Schrader, Michael Schäfers, Martin Bögemann, Kambiz Rahbar
PURPOSE: Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with (177)Lu-PSMA-617. METHODS: Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study...
June 17, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28624793/bufalin-reverses-abcb1-mediated-drug-resistance-in-colorectal-cancer
#18
Ze-Ting Yuan, Xiao-Jing Shi, Yu-Xia Yuan, Yan-Yan Qiu, Yu Zou, Cheng Liu, Hui Yu, Xue He, Ke Xu, Pei-Hao Yin
Multidrug resistance (MDR), mainly mediated by ABCB1 transporter, is a major cause for chemotherapy failure. Bufalin (BU), an active component of the traditional Chinese medicine chan'su, has been reported to have antitumor effects on various types of cancer cells. The purpose of this present study was to investigate the reversal effect of BU on ABCB1-mediated multidrug resistance in colorectal cancer. BU at safe concentration (5, 10, 20 nM) could reverse chemosensitivity of ABCB1-overexpression HCT8/ADR, LoVo/ADR and HCT8/ABCB1 nearly back to their parental cells level...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624791/epha2-affects-the-sensitivity-of-oxaliplatin-by-inducing-emt-in-oxaliplatin-resistant-gastric-cancer-cells
#19
Qiaocheng Wen, Zihua Chen, Zhikang Chen, Jinxiang Chen, Ran Wang, Changhao Huang, Weijie Yuan
Erythropoietin-producing hepatocellular receptor A2 (EphA2) is upregulated in gastric cancer tissues and cells, which is accompanied by epithelial-mesenchymal transition (EMT). The current study was designed to establish the oxaliplatin-resistant human gastric cancer cell line SGC-7901/L-OHP, to determine if EMT in these cells could be reversed, and to determine if the susceptibility of these cells to oxaliplatin was affected by silencing EphA2 expression. We found that EphA2 expression levels were upregulated in gastric cancer and associated with chemotherapy sensitivity...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624784/mitochondrial-pyruvate-carrier-function-determines-cell-stemness-and-metabolic-reprogramming-in-cancer-cells
#20
Xiaoli Li, Gaoyang Han, Xiaoran Li, Quancheng Kan, Zhirui Fan, Yaqing Li, Yasai Ji, Jing Zhao, Mingzhi Zhang, Mantas Grigalavicius, Viktor Berge, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo
One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout...
May 25, 2017: Oncotarget
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