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Chemotherapy resistance

Michail Mitsis, George A Alexiou, Evrysthenis Vartholomatos, Georgios Markopoulos, Diamanto Lazari, Entela Hodaj, Dimitrios Nastos, Panagiota Zagorianakou, Vasiliki Galani, Athanasios P Kyritsis
PURPOSE: Breast cancer is the most commonly diagnosed malignancy among women. Breast cancer cells may develop resistance to current chemotherapy, thus new chemotherapeutic agents are urgently needed. METHODS: A major number of drugs with anticancer activity have been isolated from plants. Herewith, we investigated for the first time the effect of N-(p-coumaroyl) serotonin (CS), isolated from Centaurea seed on a drug-resistant breast carcinoma (MCF-7) cells. Viability and proliferation of the cells were examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
JinYing Liu, Xiaokang Liu, Wei Ma, Wei Kou, CaiLi Li, Jin Zhao
PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Katarzyna Mieszala, Malgorzata Rudewicz, Agnieszka Gomulkiewicz, Katarzyna Ratajczak-Wielgomas, Jedrzej Grzegrzolka, Piotr Dziegiel, Sylwia Borska
Multidrug resistance (MDR) is a notable problem in the use of chemotherapy. Therefore, studies aimed at identifying substances capable of overcoming resistance of cancer cells are required. Examples of these compounds are polyphenols, including resveratrol, that exert a range of various biological activities. The aim of the present study was to demonstrate the effect of 3,5,4'-trihydroxy- trans -stilbene (resveratrol) on the expression of ATP binding cassette subfamily B member 1, Annexin A1 ( ANXA1 ) and thioredoxin ( TXN ) genes, and the proteins encoded by these genes, which are associated with MDR...
April 2018: Oncology Letters
Hongyang Lu, Bo Chen, Jing Qin, Fajun Xie, Na Han, Zhiyu Huang
The present study describes the case of a 48-year-old man who was diagnosed with lung adenocarcinoma with an epidermal growth factor receptor (EGFR) 21 L858R mutation. The patient received surgery and adjuvant chemotherapy. When multiple lung metastases appeared, icotinib was administered. Following resistance to icotinib, biopsy by endobroncheal ultrasonography for a right lung hilar lymph node revealed transformation to a neuroendocrine morphology. Neuron-specific enolase (NSE) levels were elevated, accompanied with disease progression following transformation to the neuroendocrine morphology...
April 2018: Oncology Letters
Maha S Al-Keilani, Dua H Alsmadi, Ruba S Darweesh, Karem H Alzoubi
Background: Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus. Objectives: To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53...
2018: Clinical Pharmacology: Advances and Applications
Yan Chen, Yao Cheng, Pengxuan Zhao, Shasha Zhang, Minsi Li, Chuanchuan He, Xiaojuan Zhang, Tan Yang, Ruicong Yan, Peng Ye, Xiang Ma, Guangya Xiang
Multidrug resistance to chemotherapeutic drugs is a major obstacle to breast cancer treatment. In this study, doxorubicin (DOX) and imatinib (IM) were co-loaded into folate receptor targeted (FR-targeted) pH-sensitive liposomes (denoted as FPL-DOX/IM) to fulfill intracellular acid-sensitive release and reverse drug resistance. FPL-DOX/IM could maintain stability in blood circulation with approximate diameters of 100 nm and rapidly release encapsulated drugs in tumor acidic microenvironment. Moreover, the IM in combination therapy could overcome chemoresistance associated with DOX effectively by inhibiting ABC transporter function and improving chemotherapy sensitivity...
March 15, 2018: International Journal of Pharmaceutics
Liliya Tyutyunyk-Massey, Syed U Haqqani, Reshma Mandava, Kirubel Kentiba, Mallika Dammalapati, Nga Dao, Joshua Haueis, David Gewirtz, Joseph W Landry
Cancer chemotherapeutic drugs have greatly advanced our ability to successfully treat a variety of human malignancies. The different forms of stress produced by these agents in cancer cells result in both cell autonomous and cell nonautonomous effects. Desirable cell autonomous effects include reduced proliferative potential, cellular senescence, and cell death. More recently recognized cell nonautonomous effects, usually in the form of stimulating an antitumor immune response, have significant roles in therapeutic efficiency for a select number of chemotherapies...
2018: Advances in Cancer Research
Lucia Tortorella, Carrie L Langstraat, Amy L Weaver, Michaela E McGree, Jamie N Bakkum-Gamez, Sean C Dowdy, William A Cliby, Gary L Keeney, Mark E Sherman, Saravut J Weroha, Andrea Mariani, Karl C Podratz
OBJECTIVE: Two randomized trials failed to demonstrate efficacy of platinum-based chemotherapy (PbCT) for uterine serous carcinoma (USC). Our objective was to reassess the value of PbCT for patients with microscopic residuum (R0). METHODS: Progression-free survival (PFS) after surgery was analyzed for 409 patients and correlated with adjuvant therapies: vaginal brachytherapy (VBRT), external beam radiotherapy (EBRT), PbCT, or combinations. RESULTS: The estimated 5-year PFS for stage I (n=209) USC was 65...
March 14, 2018: Gynecologic Oncology
Somedeb Ball, Kenneth Nugent
Microparticles (MP) are submicron vesicles released from various cells in response to activation, injury or apoptosis. They contain different structural and functional proteins and RNAs, which contribute to physiological intercellular "crosstalk" and to the pathogenesis of various diseases including cancer. In hematological malignancies, these MPs participate in the initiation and propagation of thrombosis through different pathways. They have a role in the angiogenesis, malignant cell survival and metastasis...
March 2018: American Journal of the Medical Sciences
Yu Liu, Jing Tang, Duanyang Liu, Lei Zhang, Yan He, Jing Li, Lei Gao, Dai Tang, Xiaoming Jin, Dan Kong
As the major and preferred treatment for ovarian cancer ascites, chemotherapy can reduce or inhibit recurrent ascites (hereafter re-ascites); however, some patients still experience re-ascites. Therefore, this study investigated cases in which epithelial ovarian cancer (EOC) patients experienced re-ascites. In re-ascites cases, CA125, MDR1, LC-3, and Beclin-1 were highly expressed. In addition, CASP-9 and c-CASP-3 expression levels were decreased, and serum CA125 levels (highest 4348 U/ml) were increased compared to chemosensitive cases...
March 16, 2018: Cell Death & Disease
Adam J Camblin, Emily A Pace, Sharlene Adams, Michael D Curley, Victoria Rimkunas, Lin Nie, Gege Tan, Troy Bloom, Sergio Iadevaia, Jason Baum, Charlene Minx, Akos Czibere, Chrystal U Louis, Daryl C Drummond, Ulrik B Nielsen, Birgit Schoeberl, J Marc Pipas, Robert M Straubinger, Vasileios Askoxylakis, Alexey A Lugovskoy
PURPOSE: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elena Piretto, Marcello Delitala, Mario Ferraro
Drug resistance is one of the major obstacles to a successful treatment of cancer and, in turn, has been recognized to be linked to intratumoral heterogeneity, which increases the probability of the emergence of a cancer clones refractory to treatment. Combination therapies have been introduced to overcome resistance, but the design of successful combined protocols is still an open problem. In order to provide some indications on the effectiveness of medical treatments, a mathematical model is proposed, comprising two cancer populations competing for resources and with different susceptibilities to the action of immune system cells and therapies: the focus is on the effects of chemotherapy and immunotherapy, used singularly or in combination...
March 13, 2018: Journal of Theoretical Biology
Menglong Liu, Danfeng He, Tao Yang, Wei Liu, Li Mao, Yang Zhu, Jun Wu, Gaoxing Luo, Jun Deng
BACKGROUND: Silver and photothermal therapy (PTT) have been widely used for eradicating the drug-resistant bacteria. However, the risks of excess of silver for humans and the low efficiency of PTT still limit their in vivo therapeutic application. Integration of two distinctive bactericides into one entity is a promising platform to improve the efficiency of antimicrobial agents. RESULTS: In this study, a chemo-photothermal therapeutic platform based on polydopamine (PDA)-coated gold nanorods (GNRs) was developed...
March 16, 2018: Journal of Nanobiotechnology
Michael K Krapf, Jennifer Gallus, Sahel Vahdati, Michael Wiese
Multidrug resistance occurring during cancer chemotherapy is a major obstacle for effectiveness and response to therapy and is often caused by ATP-binding cassette (ABC) efflux transporters. Belonging to the family of ABC transporters, breast cancer resistance protein is getting more and more in the spotlight of research. As a strategy to overcome multidrug resistance, inhibitors of ABC transporters were synthesized, which could be applied in combination with cytostatic drugs. For this purpose, 2,4-disubstituted pyridopyrimidine derivatives were synthesized...
March 16, 2018: Journal of Medicinal Chemistry
Jacob B Williams, Clara G Buchanan, William G Pitt
Background - Patients undergoing chemotherapy can develop resistance not only to the administered drug, but also to many other unrelated types of drugs, a phenomenon known as multidrug resistance. One of the most common mechanisms of multidrug resistance is an elevated expression of drug efflux pumps. Co-delivery of an efflux pump inhibitor with a chemotherapeutic can increase the killing of multidrug resistant cancer cells. Objective - Our hypothesis was that delivering doxorubicin directly to the cytosol of multidrug resistant cancer cells via a folate-targeted liposome loaded with a perfluoropentane emulsion droplet and doxorubicin (folated eLipoDox), along with the delivery of verapamil to block the efflux pumps will prove to be more effective at killing multidrug resistant cancer cells compared to conventional drug delivery...
March 16, 2018: Pharmaceutical Nanotechnology
Midori Tanaka, Hidenobu Ishii, Hayato Moribuchi, Yoshiko Naito, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Koichi Azuma, Kazuhiko Yamada, Tomoaki Hoshino
Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...
March 15, 2018: Investigational New Drugs
Yaming Xi, Zhuanzhen Ma, Hao Zhang, Maowen Yuan, Lina Wang
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit...
April 2018: Oncology Letters
S Wang, Z Zou, X Luo, Y Mi, H Chang, D Xing
Liver receptor homolog-1 (LRH1) has been shown to promote tumor proliferation and development. However, the functions of LRH1 in mediating cancer cells chemoresistance are still not clear. Here, we found LRH1 levels were significantly elevated in primary breast cancer tissues in patients who developed early recurrence. Similarly, adriamycin (ADR)-resistant breast cancer cell lines also exerted high LRH1 expression. Indeed, overexpression of LRH1 attenuated cytotoxicity of chemotherapeutic drugs ADR and cisplatin (DDP) in breast cancer cells in vitro and in nude mice tumor model...
March 16, 2018: Oncogene
Zhiqi Xie, Wangwei Guo, Ningning Guo, Mingyi Huangfu, Huina Liu, Mengting Lin, WenHong Xu, Jiejian Chen, TianTian Wang, Qichun Wei, Min Han, Jianqing Gao
Although existing nanomedicines have focused on the tumor microenvironment with the goal of improving the effectiveness of conventional chemotherapy, the penetration of a tumor's core still represents a formidable barrier for existing drug delivery systems. Therefore, a novel multifunctional hypoxia-induced size-shrinkable nanoparticle has been designed to increase the penetration of drugs, nucleic acids, or probes into tumors. This cooperative strategy relies on three aspects: (i) the responsiveness of nanoparticles to hypoxia, which shrink when triggered by low oxygen concentrations; (ii) the core of a nanoparticle involves an internal cavity and strong positive charges on the surface to deliver both doxorubicin and siRNA; and (iii) a reactive oxygen species (ROS) probe is incorporated in the nanoparticle to monitor its preliminary therapeutic response in real time, which is expected to realize the enhanced efficacy together with the ability to self-monitor the anticancer activity...
March 12, 2018: Acta Biomaterialia
María Paula Ceballos, Giulia Decándido, Ariel Darío Quiroga, Carla Gabriela Comanzo, Verónica Inés Livore, Florencia Lorenzetti, Flavia Lambertucci, Lorena Chazarreta-Cifre, Claudia Banchio, María de Luján Alvarez, Aldo Domingo Mottino, María Cristina Carrillo
Sirtuins (SIRTs) 1 and 2 deacetylases are overexpressed in hepatocellular carcinoma (HCC) and are associated with tumoral progression and multidrug resistance (MDR). In this study we analyzed whether SIRTs 1 and 2 activities blockage was able to affect cellular survival and migration and to modulate p53 and FoxO1 acetylation in HepG2 and Huh7 cells. Moreover, we analyzed ABC transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 3 (MRP3) expression. We used cambinol and EX-527 as SIRTs inhibitors...
March 12, 2018: Toxicology Letters
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