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https://www.readbyqxmd.com/read/29454062/laser-assisted-delivery-of-synergistic-combination-chemotherapy-in-in-vivo-skin
#1
Emily Wenande, Joshua Tam, Brijesh Bhayana, Steven Kyle Schlosser, Emily Ishak, William A Farinelli, Agata Chlopik, Mai P Hoang, Omar R Pinkhasov, Peter Caravan, R Rox Anderson, Merete Haedersdal
The effectiveness of topical drugs for treatment of non-melanoma skin cancer is greatly reduced by insufficient penetration to deep skin layers. Ablative fractional lasers (AFLs) are known to enhance topical drug uptake by generating narrow microchannels through the skin, but information on AFL-drug delivery in in vivo conditions is limited. In this study, we examined pharmacokinetics, biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in combination in in vivo porcine skin...
February 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29454061/activation-of-nlrx1-mediated-autophagy-accelerates-the-ototoxic-potential-of-cisplatin-in-auditory-cells
#2
Haiyan Yin, Qianqian Yang, Zhixin Cao, Hongrui Li, Zhaoyan Yu, Guodong Zhang, Gaoying Sun, Rongjun Man, Haibo Wang, Jianfeng Li
To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member ×1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus...
February 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29452770/single-arm-phase-2-trial-of-elective-nodal-dose-reduction-for-patients-with-locoregionally-advanced-squamous-cell-carcinoma-of-the-head-and-neck
#3
Patrick D Maguire, Charles R Neal, Stuart M Hardy, Andrew M Schreiber
PURPOSE: To evaluate a novel chemoradiation therapy (CRT) regimen for patients with squamous cell carcinoma of the head and neck (SCCHN) incorporating a lower intensity modulated radiation therapy dose to electively treated neck lymph nodes than is currently standard. METHODS AND MATERIALS: Eligible patients had locally advanced SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx. The 7-week CRT course consisted of weekly cisplatin at 35 mg/m 2 concurrently with sequential-boost intensity modulated radiation therapy: 36 Gy to high- and low-risk planning target volumes followed by a sequential boost to the high-risk planning target volume to 70 Gy...
December 28, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29452344/overexpression-of-blm-promotes-dna-damage-and-increased-sensitivity-to-platinum-salts-in-triple-negative-breast-and-serous-ovarian-cancers
#4
N J Birkbak, Y Li, S Pathania, A Greene-Colozzi, M Dreze, C Bowman-Colin, Z Sztupinszki, M Krzystanek, M Diossy, N Tung, P D Ryan, J E Garber, D P Silver, J D Iglehart, Z C Wang, D Szuts, Z Szallasi, A L Richardson
Background: Platinum based therapy is an effective treatment for a subset of triple negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed. Patients and methods: We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared to resistant triple negative breast cancers in two independent neoadjuvant cisplatin treated cohorts...
February 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29452161/c33-a-cells-transfected-with-e6-i-or-e6-ii-the-short-forms-of-hpv-16-e6-displayed-opposite-effects-on-cisplatin-induced-apoptosis
#5
Carolina E Vaisman, Oscar Del Moral-Hernandez, Samadhi Moreno-Campuzano, Elena Aréchaga-Ocampo, Raul Bonilla-Moreno, Israel Garcia-Aguiar, Leticia Cedillo-Barron, Jaime Berumen, Porfirio Nava, Nicolas Villegas-Sepúlveda
The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7 pre-mRNA product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death, while the transfection with the E6*I-GFP construct showed only a 25% of diminution of cell death, compared to the control cells...
February 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29451951/time-course-and-clinical-characterization-of-cisplatin-induced-ototoxicity-after-treatment-for-nasopharyngeal-carcinoma-in-a-south-east-asian-population
#6
Sze Ling Chan, Li Shia Ng, Xueying Goh, Chor Hiang Siow, Han Lee Goh, Boon Cher Goh, Timothy Cheo, Kwok Seng Loh, Liam R Brunham
BACKGROUND: The purpose of this study was to characterize the clinical course of hearing loss in patients with nasopharyngeal carcinoma (NPC) and the clinical factors affecting its severity. METHODS: The time course of hearing loss in patients with NPC was assessed using threshold shift from baseline and Common Terminology Criteria for Adverse Events (CTCAE) grade. RESULTS: In the chemoradiotherapy (CRT) groups, the threshold shift was significantly higher from 3 months at 4 kHz (P = 2...
February 16, 2018: Head & Neck
https://www.readbyqxmd.com/read/29451302/comparing-cytotoxic-backbones-for-first-line-trastuzumab-containing-regimens-in-her2-positive-advanced-esophagogastric-cancer-a-meta-analysis
#7
Emil Ter Veer, Aafke Creemers, Laura de Waal, Martijn G H van Oijen, Hanneke W M van Laarhoven
According to the ToGA study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for HER2-positive advanced esophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive esophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in-situ-hybridisation...
February 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29449735/alk-positive-adenocarcinoma-of-the-lung-expressing-neuroendocrine-markers-and-presenting-as-a-pituitary-adenoma
#8
M C Mengoli, F Bertolini, M Maur, F Barbieri, L Longo, P Gasparri, M Tiseo, G Rossi
We report an ALK-rearranged adenocarcinoma of the lung presenting as a pituitary metastasis, clinically simulating a pituitary adenoma. The patient, a 50 year-old, former-smoking woman was admitted with a Parinaud's syndrome characterized by progressive oculomotor impairment of visual verticality, bitemporal hemianopsia and nystagmus. Imaging studies showed a sellar tumor and the biopsy revealed a TTF-1 and napsin positive lung adenocarcinoma strongly expressing synaptophysin and CD56, also harboring ALK rearrangement...
December 2017: Pathologica
https://www.readbyqxmd.com/read/29449612/ixr1-regulates-ribosomal-gene-transcription-and-yeast-response-to-cisplatin
#9
Ángel Vizoso-Vázquez, Mónica Lamas-Maceiras, M Isabel González-Siso, M Esperanza Cerdán
Ixr1 is a Saccharomyces cerevisiae HMGB protein that regulates the hypoxic regulon and also controls the expression of other genes involved in the oxidative stress response or re-adaptation of catabolic and anabolic fluxes when oxygen is limiting. Ixr1 also binds with high affinity to cisplatin-DNA adducts and modulates DNA repair. The influence of Ixr1 on transcription in the absence or presence of cisplatin has been analyzed in this work. Ixr1 regulates other transcriptional factors that respond to nutrient availability or extracellular and intracellular stress stimuli, some controlled by the TOR pathway and PKA signaling...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449555/intravenous-injections-of-the-oncolytic-virus-m1-as-a-novel-therapy-for-muscle-invasive-bladder-cancer
#10
Cheng Hu, Ying Liu, Yuan Lin, Jian-Kai Liang, Wen-Wen Zhong, Ke Li, Wen-Tao Huang, De-Juan Wang, Guang-Mei Yan, Wen-Bo Zhu, Jian-Guang Qiu, Xin Gao
Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449532/senescence-associated-secretory-factors-induced-by-cisplatin-in-melanoma-cells-promote-non-senescent-melanoma-cell-growth-through-activation-of-the-erk1-2-rsk1-pathway
#11
Xuerong Sun, Benyan Shi, Huiling Zheng, Ling Min, Jie Yang, Xiaoyi Li, Xiaoxin Liao, Weixing Huang, Mingmeng Zhang, Shun Xu, Zhe Zhu, Hongjing Cui, Xinguang Liu
Although targeted therapy and immunotherapy greatly improve the outcome of melanoma, drug resistance and low response rates still maintain the unsubstitutability of traditional chemotherapy. Cisplatin (CDDP) is widely used in different types of tumours with high response rates, but it generally has low efficiency in melanoma. The mechanisms underpinning the phenomena are not sufficiently understood. Here we demonstrated that various melanoma cell lines adopted senescence phenotype after CDDP treatment in contrast to the other types of tumour cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449217/zfp36l2-is-a-cell-cycle-regulated-ccch-protein-necessary-for-dna-lesion-induced-s-phase-arrest
#12
Aya Noguchi, Shungo Adachi, Naoto Yokota, Tomohisa Hatta, Tohru Natsume, Hiroyuki Kawahara
ZFP36L2 promotes the destruction of AU-rich element-containing transcripts, while its regulation and functional significance in cell cycle control are scarcely identified. We show that ZFP36L2 is a cell cycle-regulated CCCH protein whose abundance is regulated post-translationally at the respective stages of the cell cycle. Indeed, ZFP36L2 protein was eliminated after release from M phase, and ZYG11B-based E3 ligase plays a role in its polyubiquitination in interphase. Although ZFP36L2 is dispensable for normal cell cycle progression, we found that endogenous ZFP36L2 played a key role in cisplatin-induced S-phase arrest, a process in which the suppression of G1/S cyclins is necessary...
February 15, 2018: Biology Open
https://www.readbyqxmd.com/read/29449189/adjuvant-chemoradiotherapy-versus-radiotherapy-alone-for-women-with-high-risk-endometrial-cancer-portec-3-final-results-of-an-international-open-label-multicentre-randomised-phase-3-trial
#13
Stephanie M de Boer, Melanie E Powell, Linda Mileshkin, Dionyssios Katsaros, Paul Bessette, Christine Haie-Meder, Petronella B Ottevanger, Jonathan A Ledermann, Pearly Khaw, Alessandro Colombo, Anthony Fyles, Marie-Helene Baron, Ina M Jürgenliemk-Schulz, Henry C Kitchener, Hans W Nijman, Godfrey Wilson, Susan Brooks, Silvestro Carinelli, Diane Provencher, Chantal Hanzen, Ludy C H W Lutgens, Vincent T H B M Smit, Naveena Singh, Viet Do, Romerai D'Amico, Remi A Nout, Amanda Feeney, Karen W Verhoeven-Adema, Hein Putter, Carien L Creutzberg
BACKGROUND: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup...
February 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29448138/dual-targeting-antitumor-hybrids-derived-from-pt-iv-species-and-millepachine-analogues
#14
Xiaochao Huang, Shixian Hua, Rizhen Huang, Zhikun Liu, Shaohua Gou, Zhimei Wang, Zhixin Liao, Hengshan Wang
Many strategies have been developed to circumvent the shortcomings of Pt(II)-based chemotherapy, but the inherent problems still have not been effectively resolved. Here we report a new series of dual-targeting Pt(IV) prodrugs, conjugates of millepachine analogues with the related Pt(IV) complexes derived from cisplatin or oxaliplatin, respectively, which can inhibit tubulin polymerization and induce DNA damage. Among them, compound 19 possessed excellent antitumor activities against the tested human cancer cell lines, and arrested the cell cycle at the G2/M phases and ultimately induced cell apoptosis...
February 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29447961/a-physiologically-relevant-3d-collagen-based-scaffold-neuroblastoma-cell-system-exhibits-chemosensitivity-similar-to-orthotopic-xenograft-models
#15
C Curtin, J C Nolan, R Conlon, L Deneweth, C Gallagher, Y J Tan, B L Cavanagh, A Z Asraf, H Harvey, S Miller-Delaney, J Shohet, I Bray, F J O'Brien, R L Stallings, O Piskareva
3D scaffold-based in vitro cell culturing is a recent technological advancement in cancer research bridging the gap between conventional 2D culture and in vivo tumours. The main challenge in treating neuroblastoma, a paediatric cancer of the sympathetic nervous system, is to combat tumour metastasis and resistance to multiple chemotherapeutic drugs. The aim of this study was to establish a physiologically relevant 3D neuroblastoma tissue-engineered system and explore its therapeutic relevance. Two neuroblastoma cell lines, chemotherapeutic sensitive Kelly and chemotherapeutic resistant KellyCis83 were cultured in a 3D in vitro model on two collagen-based scaffolds containing either glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) and compared to 2D cell culture and an orthotopic murine model...
February 12, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29446648/electromagnetic-field-could-protect-sh-sy5y-cells-against-cisplatin-cytotoxicity-but-not-mcf-7-cells
#16
Hamideh Mahmoudinasab, Mostafa Saadat
Cisplatin [cis-dichlorodiammine platinum (II), CDDP], morphine (Mor), and electromagnetic field (EMF) induced oxidative stress. In this study, we tried to increase the cytotoxicity of CDDP in combination with Mor and/or EMF in MCF-7 and SH-SY5Y cells. Furthermore, we evaluate the expression levels of 11 antioxidant genes in both cell lines. We designed four treatments: CDDP alone, "CDDP+Mor," "CDDP+EMF," and "CDDP+Mor+EMF." Serial dilutions of CDDP, Mor (5.0 μM), and EMF (50 Hz, 0...
February 15, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29446148/efficacy-of-low-dose-5-fluorouracil-cisplatin-therapy-for-invasive-extramammary-paget-s-disease
#17
Hiroshi Kato, Shoichi Watanabe, Kiyonori Kariya, Motoki Nakamura, Akimichi Morita
Extramammary Paget's disease (EMPD) is one of the cutaneous adenocarcinomas. The effective chemotherapy for advanced EMPD has not been established. This study was designed to evaluate the efficacy of combination 5-fluorouracil (500 mg/body, 7 days/week) and cisplatin (5 mg/body 5 days/week) for invasive EMPD. Seventeen EMPD patients with multiple metastases who visited our dermatology clinic between October 2004 and May 2016 (mean age, 76.9 years; 10 men, seven women) were retrospectively analyzed. Eight EMPD patients underwent low-dose 5-fluorouracil/cisplatin therapy and nine patients chose best supportive care...
February 14, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29445340/inhibition-of-glucose-6-phosphate-dehydrogenase-reverses-cisplatin-resistance-in-lung-cancer-cells-via-the-redox-system
#18
Weipeng Hong, Peiheng Cai, Chuncao Xu, Di Cao, Weibang Yu, Zhongxiang Zhao, Min Huang, Jing Jin
The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29445029/pantoprazole-an-inhibitor-of-the-organic-cation-transporter-2-does-not-ameliorate-cisplatin-related-ototoxicity-or-nephrotoxicity-in-children-and-adolescents-with-newly-diagnosed-osteosarcoma-treated-with-methotrexate-doxorubicin-and-cisplatin
#19
Elizabeth Fox, Kristin Levin, Yan Zhu, Blair Segers, Naomi Balamuth, Richard Womer, Rochelle Bagatell, Frank Balis
LESSONS LEARNED: Using a randomized crossover design and continuous variables such as change in hearing threshold and biomarkers of acute renal injury as short-term endpoints, it was determined that pantoprazole, an organic cation transporter 2 inhibitor, did not ameliorate cisplatin-associated nephrotoxicity or ototoxicity.Cystatin C is a robust method to estimate glomerular filtration rate in patients with cancer. Using a patient-reported outcome survey, all patients identified tinnitus and subjective hearing loss occurring "at least rarely" after cycle 1, prior to objective high-frequency hearing loss measured by audiograms...
February 14, 2018: Oncologist
https://www.readbyqxmd.com/read/29444512/a-phase-ii-study-of-irinotecan-for-patients-with-previously-treated-small-cell-lung-cancer
#20
Rie Kondo, Satoshi Watanabe, Satoshi Shoji, Kosuke Ichikawa, Tetsuya Abe, Junko Baba, Junta Tanaka, Hiroki Tsukada, Masaki Terada, Kazuhiro Sato, Yoshie Maruyama, Masato Makino, Akira Hirata, Hiroshi Tanaka, Toshiyuki Koya, Hirohisa Yoshizawa, Toshiaki Kikuchi
OBJECTIVE: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. METHODS: Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression...
February 14, 2018: Oncology
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