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Chemosensitivity Test

Daiha Shin, Eun Hye Kim, Jaewang Lee, Jong-Lyel Roh
Glutathione peroxidase 4 (GPX4) is a regulator of ferroptosis (iron-dependent, non-apoptotic cell death); its inhibition can render therapy-resistant cancer cells susceptible to ferroptosis. However, some cancer cells develop mechanisms protective against ferroptosis; understanding these mechanisms could help overcome chemoresistance. In this study, we investigated the molecular mechanisms underlying resistance to ferroptosis induced by GPX4 inhibition in head and neck cancer (HNC). The effects of two GPX4 inhibitors, (1S, 3R)-RSL3 and ML-162, and of trigonelline were tested in HNC cell lines, including cisplatin-resistant (HN3R) and acquired RSL3-resistant (HN3-rslR) cells...
October 16, 2018: Free Radical Biology & Medicine
Yasuyuki Shigematsu, Kentaro Inamura, Noriko Yamamoto, Yoshihiro Mise, Akio Saiura, Yuichi Ishikawa, Shunji Takahashi, Hiroaki Kanda
BACKGROUND: The prognostic biomarker for patients undergoing curative liver metastasectomy for colorectal cancer (CRC) is lacking. The purpose was to investigate the prognostic role of a lack of CDX2 expression, which has been proposed as a potential biomarker for high-risk relapse in early-stage CRC, in patients undergoing curative liver metastasectomy. METHODS: A total of 396 consecutive patients with CRC liver metastasis who underwent potentially curative liver metastasectomy at a single center in Japan between 2005 and 2015 were included...
October 16, 2018: BMC Cancer
Junko Johzuka, Toshihiro Ona, Masatoshi Nomura
In anti-cancer drug (candidate) screening, there is the need for evaluation at physiological concentrations similar to in vivo. This is often performed by three-dimensionally (3D) cultured cells; however, it requires a long culture period of 2 - 4 weeks with tedious experimental procedures. Here, we report on a high precision surface plasmon resonance (HP-SPR)-3D system. We developed the system with average fluctuation of 50 ndeg s-1 using two-dimensionally cultured cells attached onto a sensor chip by applying collagen on the top to change their activity into in vivo-like conditions without cell division...
2018: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Pallabita Chowdhury, Prashanth K B Nagesh, Elham Hatami, Santosh Wagh, Nirnoy Dan, Manish K Tripathi, Sheema Khan, Bilal B Hafeez, Bernd Meibohm, Subhash C Chauhan, Meena Jaggi, Murali M Yallapu
Paclitaxel (PTX) is a gold standard chemotherapeutic agent for breast, ovarian, pancreatic and non-small cell lung carcinoma. However, in clinical use PTX can have adverse side effects or inadequate pharmacodynamic parameters, limiting its use. Nanotechnology is often employed to reduce the therapeutic dosage required for effective therapy, while also minimizing the systemic side effects of chemotherapy drugs. However, there is no nanoformulation of paclitaxel with chemosensitization motifs built in. With this objective, we screened eleven pharmaceutical excipients to develop an alternative paclitaxel nanoformulation using a self-assembly method...
September 22, 2018: Journal of Colloid and Interface Science
Jia Chen, Gaojun Li
BACKGROUND: Chemotherapy is one of the commonest therapeutic method for cervical cancer. There are some common chemotherapy drugs, such as cisplatin, docetaxel, paclitaxel and selenium nanoparticle. microRNAs (miRNAs) have been verified to be regulators in various human cancers. This study aims to investigate the effects of miR-1284 on the cisplatin sensitivity of cervical cancer cells. METHODS: The levels of miR-1284 in different tissues and cell lines were detected through using qRT-PCR analysis...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Keith I Block, Penny B Block, Charlotte Gyllenhaal
A comprehensive approach to integrative treatment of colorectal cancer (CRC) patients involves three spheres of intervention: lifestyle, biology, and conventional treatment. Individualization of treatment is emphasized. The lifestyle sphere includes nutritional therapies, biobehavioral strategies with circadian interventions, and physical care modalities. The biology sphere comprises six host factors in the patient's internal biochemical environment or "terrain": inflammation, glycemia, oxidative stress, immune dysregulation, coagulopathy, and stress chemistries...
September 2018: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
Luke Rowsell, Keith K H Wong, Brendon J Yee, Danny J Eckert, Andrew A Somogyi, James Duffin, Ronald R Grunstein, David Wang
OBJECTIVE: Anaesthesiology guidelines suggest that opioids worsen obstructive sleep apnoea (OSA) despite no randomised controlled trial evidence. We therefore conducted a randomised controlled trial to evaluate the effects of a common clinical dose of morphine on OSA, and to identify clinical phenotype and genotype vulnerability to opioid-respiratory depression. METHODS: Under a double-blind, randomised, crossover design, 60 male patients with OSA attended two visits to the hospital sleep laboratory, at least 1 week apart...
August 30, 2018: Thorax
Fengbin Gao, Xiaojing Wang, Shanwen Chen, Tianyuan Xu, Xianjin Wang, Yifan Shen, Fan Dong, Shan Zhong, Zhoujun Shen
Poor response and chemotherapy resistance to cisplatin (DDP)‑based therapy frequently lead to treatment failure in advanced bladder cancer; however the underlying mechanism is extremely complex and unclear. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified human oncoprotein, has been shown to play important regulatory roles in cancer cell survival. The present study aimed to investigate the correlation of CIP2A with sensitivity to DDP in bladder cancer cells. In the present study, knockdown of CIP2A was performed using short hairpin‑RNA...
November 2018: Oncology Reports
Ana S Pires, Cláudia R Marques, João C Encarnação, Ana M Abrantes, Inês A Marques, Mafalda Laranjo, Rui Oliveira, João E Casalta-Lopes, Ana C Gonçalves, Ana B Sarmento-Ribeiro, Maria F Botelho
Colorectal cancer (CRC) is continuously classified as one of the most incidental and mortal types of cancer worldwide. The positive outcomes of the conventional chemotherapy are frequently associated with high toxicity, which often leads to the suspension of the treatment. Growing evidences consider the use of pharmacological concentrations of ascorbic acid (AA), better known as vitamin C, in the treatment of cancer. The use of AA in a clinical context is essentially related to the adoption of new therapeutic strategies based on combination regimens, where AA plays a chemosensitizing role...
2018: Frontiers in Physiology
Jie Dong, Xu Wang, Yu Yu, Xu Yan, Jiu-Wei Cui
Background: Base excision repair (BER) plays an important role in the maintenance of genome integrity and anticancer drug resistance. This study aimed to explore the role of BER gene polymorphisms in response to chemotherapy for advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Methods: During the period from November 2009 to January 2016, a total of 152 patients diagnosed with NSCLC Stage IIIB and IV in the First Hospital of Jilin University were admitted into this study...
August 20, 2018: Chinese Medical Journal
Elham Zokaei, Arastoo Badoei-Dalfrad, Mehdi Ansari, Zahra Karami, Touba Eslaminejad, Seyed Noureddin Nematollahi-Mahani
Commonly, acquired resistances to anticancer drug are mediated by overexpression of a membrane-associated protein that encode via multi-drug resistance gene-1 (MDR1). Herein, the mRNA-cleaving DNAzyme that targets the mRNA of MDR1 gene in doxorubicin-resistant breast cancer cell line (MCF-7/DR) loaded on the chitosan β-cyclodextrin complexes was used as a tropical agent. Chitosan/β-cyclodextrin complexes were used to deliver DNAzymes into cancer cells. Determination of the physicochemical characteristics of the particles was done by photon correlation spectroscopy and scanning electron microscopy...
July 24, 2018: Applied Biochemistry and Biotechnology
Jürgen Weinreich, Florian Struller, Iaroslav Sautkin, Shalva Giuashvili, Marc Reymond, Alfred Königsrainer, Timm C Schott
We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compared to oxaliplatin or to cisplatin plus doxorubicin. The experiments were designed to reflect the conditions of intraperitoneal chemotherapy. CASY® (Cell Analysis System) technology was used to compare the impact of incubation temperature/duration and drug concentration on the viability of the cancer cell lines versus normal human dermal fibroblasts...
July 18, 2018: Investigational New Drugs
João Anes, Marta Martins, Séamus Fanning
Eleven clinical Klebsiella pneumoniae fluoroquinolone-resistant isolates were tested to access the potential of adjuvant therapies to reduce antimicrobial resistance using fixed concentrations of the chemosensitizers chlorpromazine (CPZ), thioridazine (TZ), phenylalanine-arginine-β-naphthylamide (PAβN), and 1-(1-naphthylmethyl)-piperazine-(NMP) with varying concentrations of antimicrobial agents nalidixic acid (NAL), ciprofloxacin (CIP), moxifloxacin (MXF), tetracycline (TET), and chloramphenicol (CHL). Ethidium bromide dye was used together with the chemosensitizers to investigate permeabilization effects...
July 13, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Michelle E Bartman, Stephen M Johnson
During hypoxia, red-eared slider turtles increase ventilation and decrease episodic breathing, but whether these responses are due to central mechanisms is not known. To test this question, isolated adult turtle brainstems were exposed to 240 min of hypoxic solution (bath PO2  = 32.6 ± 1.2 mmHg) and spontaneous respiratory-related motor bursts (respiratory event) were recorded on hypoglossal nerve roots. During hypoxia, burst frequency increased during the first 15 min, and then decreased during the remaining 35-240 min of hypoxia...
November 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Yuyun Sun, Shuai Liu, Zheng Feng, Jingyi Cheng, Linjun Lu, Mingwei Wang, Huiyu Yuan, Junyan Xu, Yingjian Zhang
OBJECTIVE: The aim of this study was to explore the clinical and prognostic implication of preoperative fluorine-18-fluorodeoxyglucose uptake value of omental metastasis-related in advanced high-grade serous ovarian cancer patients (HGSC). PATIENTS AND METHODS: We retrospectively investigated HGSC patients with omental metastasis (International Federation of Gynecology and Obstetrics stage IIIB-IV) who underwent PET/CT before primary surgery in our hospital between January 2010 and January 2016...
August 2018: Nuclear Medicine Communications
Guodong Liu, Liandong Ji, Mujing Ke, Zhenglin Ou, Neng Tang, Yixiong Li
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and resistance to cytotoxic chemotherapy is the major cause of mortality in PDAC patients. miR-125a-3p was found to be down-regulated in PDAC cells; however, the function of miR-125a-3p in PDAC has been elusive. Here, we explored the role of miR-125a-3p in chemosensitivity in PDAC cells. METHODS: We used qRT-PCR to detect miR-125a-3p expression in two PDAC cell lines. And we measured cell viability and apoptosis by MTT assay and flow cytometry, respectively...
October 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hui Qiao, Yu-Feng Wang, Wen-Zhen Yuan, Bing-Dong Zhu, Lei Jiang, Quan-Lin Guan
α-Enolase is a significant subunit of enolase and acts as a glycolytic enzyme responsible for catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the anaerobic glycolysis pathway. The research about their role is known little in tumor invasion and metastasis. This research analyzed the effect of α-enolase in proliferation and progression of human gastric cancer. The constructed PLKO.1-ENO1 shRNA vector was transfected into 293 T cells and used to infect gastric cancer cells, MKN45, by using lentivirus method...
January 1, 2018: Technology in Cancer Research & Treatment
Hisatsugu Maekawa, Hiroyuki Miyoshi, Tadayoshi Yamaura, Yoshiro Itatani, Kenji Kawada, Yoshiharu Sakai, M Mark Taketo
Current genomic and gene expression analyses provide versatile tools to improve cancer chemotherapy. However, it is still difficult to predict whether each patient responds to a particular regimen or not. To predict chemosensitivity in each patient with colorectal cancer, we developed an evaluation method using the primary tumor-initiating cells (TIC, aka cancer stem cells) xenografted in nude mice subcutaneously (patient-derived spheroid xenografts; PDSX). Simultaneously, we also prepared the conventional patient-derived xenografts (PDX) from the same patients' tumors and compared the dosing results with those of PDSXs...
October 2018: Molecular Cancer Therapeutics
Dong-Mei Wu, Xiao-Wu Hong, Ling-Ling Wang, Xia-Feng Cui, Jun Lu, Gui-Quan Chen, Yuan-Lin Zheng
MicroRNAs (miRNAs), a novel class of important gene-regulatory molecules, correlates with tumor growth, invasion, metastasis, and chemo resistance in gastric cancer (GC). Microarray analysis revealed that aberrant expressed microRNA-17 (miR-17) and DEDD were identified in GC. DEDD has been found to act as an endogenous suppressor of tumor growth and metastasis through epithelial-mesenchymal transition (EMT) process. However, the role of miRNA-17 (miR-17) has not been clearly evaluated in GC, thereby a series of in vitro experiments were performed in this study...
September 2018: International Journal of Biochemistry & Cell Biology
Alice Lallo, Kristopher K Frese, Christopher J Morrow, Robert Sloane, Sakshi Gulati, Maximillian W Schenk, Francesca Trapani, Nicole Simms, Melanie Galvin, Stewart Brown, Cassandra L Hodgkinson, Lynsey Priest, Adina Hughes, Zhongwu Lai, Elaine Cadogan, Garima Khandelwal, Kathryn L Simpson, Crispin Miller, Fiona Blackhall, Mark J O'Connor, Caroline Dive
Purpose: Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity of tumor tissue to identify drug targets and patient-relevant models to interrogate novel therapies. Following our development of circulating tumor cell patient-derived explants (CDX) as models that faithfully mirror patient disease, here we exploit CDX to examine new therapeutic options for SCLC. Experimental Design: We investigated the efficacy of the PARP inhibitor olaparib alone or in combination with the WEE1 kinase inhibitor AZD1775 in 10 phenotypically distinct SCLC CDX in vivo and/or ex vivo These CDX represent chemosensitive and chemorefractory disease including the first reported paired CDX generated longitudinally before treatment and upon disease progression...
June 25, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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