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Ravindra Amunugama, Smaranda Willcox, R Alex Wu, Ummi B Abdullah, Afaf H El-Sagheer, Tom Brown, Peter J McHugh, Jack D Griffith, Johannes C Walter
DNA interstrand crosslinks (ICLs) are extremely cytotoxic, but the mechanism of their repair remains incompletely understood. Using Xenopus egg extracts, we previously showed that repair of a cisplatin ICL is triggered when two replication forks converge on the lesion. After CDC45/MCM2-7/GINS (CMG) ubiquitylation and unloading by the p97 segregase, FANCI-FANCD2 promotes DNA incisions by XPF-ERCC1, leading to ICL unhooking. Here, we report that, during this cell-free ICL repair reaction, one of the two converged forks undergoes reversal...
June 19, 2018: Cell Reports
Penelope R Brock, Rudolf Maibach, Margaret Childs, Kaukab Rajput, Derek Roebuck, Michael J Sullivan, Véronique Laithier, Milind Ronghe, Patrizia Dall'Igna, Eiso Hiyama, Bénédicte Brichard, Jane Skeen, M Elena Mateos, Michael Capra, Arun A Rangaswami, Marc Ansari, Catherine Rechnitzer, Gareth J Veal, Anna Covezzoli, Laurence Brugières, Giorgio Perilongo, Piotr Czauderna, Bruce Morland, Edward A Neuwelt
Background Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. Methods We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses...
June 21, 2018: New England Journal of Medicine
Alibek Abdrakhmanov, Andrey V Kulikov, Ekaterina A Luchkina, Boris Zhivotovsky, Vladimir Gogvadze
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. The removal of malfunctioning or damaged mitochondria is essential for normal cellular physiology and tissue development. Stimulation of mitochondrial permeabilization and release of proapoptotic factors from the intermembrane space is an essential step in triggering the mitochondrial pathway of cell death. In this study, we analyzed the extent to which mitophagy interferes with cell death, attenuating the efficiency of cancer therapy...
June 1, 2018: Biological Chemistry
Hozumi Kumagai, Hitoshi Kusaba, Takeharu Yamanaka, Kenta Nio, Kyoko Inadomi, Kotoe Takayoshi, Mamoru Ito, Shingo Tamura, Akitaka Makiyama, Chinatsu Makiyama, Gen Hirano, Yoshihiro Shibata, Tsuyoshi Shirakawa, Kenji Mitsugi, Hiroshi Ariyama, Taito Esaki, Koichi Akashi, Eishi Baba
PURPOSE: Combination therapy of fosaprepitant, dexamethasone (DEX) and a serotonin (5-HT3) receptor antagonist is a standard antiemetic prophylaxis for patients receiving highly emetogenic chemotherapy (HEC). However, the appropriate dose of DEX has not been established in Japan. This study determined the efficacy and safety of triplet antiemetic prophylaxis in Japanese patients receiving HEC when administered the same doses of DEX as those given in a previous international phase 3 study on this drug...
June 2018: Medicine (Baltimore)
Hyae-Jin Kim, Hyeon-Jeong Lee, Eunsoo Kim, Jihwan Yun
RATIONALE: Intrapleural hyperthermic chemotherapy (IPHC) is the preferred method to locally treat lung cancer with pleural seeding. Anesthetic management during IPHC is a very challenging task for the anesthesiologist because of the hemodynamic instability associated with the procedure; however, there is no report on anesthetic considerations during the IPHC procedure. PATIENT CONCERNS: Three patients who diagnosed lung cancer with pleural invasion scheduled for IPHC were reported in this case series...
June 2018: Medicine (Baltimore)
Yun-Ho Jeong, Hyeon-Woo Shin, Ji-Yeong Kwon, Sang-Min Lee
Encapsulation of chemotherapeutic agents inside a nanoscale delivery platform can provide an attractive therapeutic strategy with many pharmaceutical benefits, such as increased plasma solubility, prolonged in vivo circulation, and reduced acute toxicity. Given that the biological activities of polymeric nanoparticles are highly dependent on their colloidal structures, the molecular geometry-regulated programming of self-assembled nanoscale architecture is of great interest for chemical design of an ideal delivery platform...
June 20, 2018: ACS Applied Materials & Interfaces
D V Kuzmin, A A Emel'yanova, M B Kalashnikova, P V Panteleev, T V Ovchinnikova
We studied combined effect of β-hairpin antimicrobial peptide tachyplesin I and cytotoxic agent cisplatin on tumor and normal human cell lines. MTT assay and flow cytometry showed that tachyplesin I selectively sensitized cancer cells to cisplatin in specified concentration ratios. In vitro experiments demonstrated that combined use of tachyplesin I and cisplatin allows decreasing the effective dose of the cytostatic thus reducing nonspecific toxicity.
June 19, 2018: Bulletin of Experimental Biology and Medicine
Fabienne Thomas, Gareth J Veal, Souleiman El Balkhi, Thierry Lafont, Nicolas Picard, Laurence Brugières, Etienne Chatelut, Christophe Piguet
PURPOSE: Chemotherapy dosing in neonates represents a major clinical challenge because of a lack of clinical pharmacology information in this patient population. In this study, we investigate the use of cisplatin dose adaptation based on therapeutic drug monitoring in a 2-week-old neonate with localized hepatoblastoma. METHODS: Cisplatin concentrations were determined in plasma and ultrafiltrate samples collected on each of six cycles of a monotherapy regimen, beginning with a dose of 1...
June 19, 2018: Cancer Chemotherapy and Pharmacology
Rongbo Han, Jingsun Wei, Honghong Zhang, Xinyu Su, Xia Chu, Yuetong Chen, Yang Gong, Xiujuan Wang, Junfeng Shi, Jinfei Chen
Background: This study aimed to explore the clinical correlation of single-nucleotide polymorphisms of thymidylate synthase (TS) and runt-related transcription factor 1 (RUNX1) in patients with postoperative stage II and III gastric cancer (GC). Patients and methods: Samples were obtained from 661 patients with postoperative stage II and III GC. TS (rs34743033) and RUNX1 (rs2014300) were genotyped in 261 patients who received postoperative basic platinum and fluorouracil chemotherapy regimens and 400 patients who did not accept chemotherapy...
2018: Cancer Management and Research
Duo Xu, Shun-Qing Liang, Haitang Yang, Ursina Lüthi, Carsten Riether, Sabina Berezowska, Thomas M Marti, Sean R R Hall, Rémy Bruggmann, Gregor J Kocher, Ralph A Schmid, Ren-Wang Peng
BACKGROUND: Standard treatment for advanced malignant pleural mesothelioma (MPM) is a cisplatin/pemetrexed (MTA) regimen; however, this is confronted by drug resistance. Proteotoxic stress in the endoplasmic reticulum (ER) is a hallmark of cancer and some rely on this stress signalling in response to cytotoxic chemotherapeutics. We hypothesise that ER stress and the adaptive unfolded protein response (UPR) play a role in chemotherapy resistance of MPM. METHODS: In vitro three-dimensional (3D) and ex vivo organotypic culture were used to enrich a chemotherapy-resistant population and recapitulate an in vivo MPM microenvironment, respectively...
June 20, 2018: British Journal of Cancer
Jialing Zhang, Tony Chen, Xinping Yang, Hui Cheng, Stephan S Späth, Paul E Clavijo, Jianhong Chen, Christopher Silvin, Natalia Issaeva, Xiulan Su, Wendell G Yarbrough, Christina M Annunziata, Zhong Chen, Carter Van Waes
Human papilloma viruses (HPV) are linked to an epidemic increase in oropharyngeal head and neck squamous cell carcinomas (HNSCC), which display viral inactivation of tumor suppressors TP53 and RB1 and rapid regional spread. However, the role of genomic alterations in enabling modulation of pathways that promote the aggressive phenotype of these cancers is unclear. Recently, a subset of HPV+ HNSCC has been shown to harbor novel genetic defects or decreased expression of TNF-receptor-associated-factor-3 (TRAF3)...
June 19, 2018: Cancer Research
Haiyan Xu, Fei Xu, Wenjie Zhu, Jianming Ying, Yan Wang
BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced pan-negative non-squamous (non-Sq) non-small cell lung cancer (NSCLC). However, it is unknown which chemotherapy regimen confers the greatest benefit in such patients. This study explored which chemotherapy regimens were advantageous in non-Sq NSCLC patients. METHODS: A retrospective study was conducted on 114 patients with advanced non-Sq NSCLC using platinum-based chemotherapy in a first-line setting between January 2013 and December 2015...
June 19, 2018: Thoracic Cancer
Yun Peng Shao, Qiao Zhou, Yun Peng Li, Si Cong Zhang, He Wei Xu, Shuo Wu, Bai Xin Shen, Liu Cheng Ding, Jun Xue, Zheng Sen Chen, Zhong Qing Wei
OBJECTIVES: The present work evaluated preventive effect of curcumin on cisplatin-induced bladder cystopathy. METHODS: Fifteen female rats were divided into (i) Control group administered with physiological saline solution for 5 days; (ii) Cis-P group injected with cisplatin (6 mg/kg); and (iii) Cis-Cur group given cisplatin (6 mg/kg) with curcumin for 5 consecutive days. The function of bladder was measured by means of urodynamic analysis. Furthermore, hematoxylin-eosin staining and Masson trichrome staining were performed for morphological analysis...
June 19, 2018: Neurourology and Urodynamics
Isabelle Martins, Syed Qasim Raza, Laurent Voisin, Haithem Dakhli, Awatef Allouch, Frédéric Law, Dora Sabino, Dorine De Jong, Maxime Thoreau, Elodie Mintet, Delphine Dugué, Mauro Piacentini, Marie-Lise Gougeon, Fanny Jaulin, Pascale Bertrand, Catherine Brenner, David M Ojcius, Guido Kroemer, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells...
June 18, 2018: Cell Death & Disease
Moon Jin Kim, Sung Min Kim, Hyun Ae Jung, Jung Yong Hong, Won Jin Chang, Moon Ki Choi, Hye Sook Kim, Jong-Mu Sun, Keunchil Park, Myung-Ju Ahn
Background/Aims: We investigated the efficacy and toxicity of a weekly schedule of docetaxel and cisplatin as a first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Methods: In this study, 18 patients with previously diagnosed R/M HNSCC were treated with combination chemotherapy of weekly docetaxel 35 mg/m2 (day 1 and 8) and cisplatin 70 mg/m2 (day 1) as first-line chemotherapy, repeated every 3 weeks. Results: Partial response and stable disease were observed in six patients (33...
June 20, 2018: Korean Journal of Internal Medicine
Marisol Gouveia, João Figueira, Manuel G Jardim, Rita Castro, Helena Tomás, Kari Rissanen, João Rodrigues
Here and for the first time, we show that the organometallic compound [Ru(η⁵-C₅H₅)(PPh₃)₂Cl] (RuCp) has potential to be used as a metallodrug in anticancer therapy, and further present a new approach for the cellular delivery of the [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragment via coordination on the periphery of low-generation poly(alkylidenimine) dendrimers through nitrile terminal groups. Importantly, both the RuCp and the dendrimers functionalized with [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragments present remarkable toxicity towards a wide set of cancer cells (Caco-2, MCF-7, CAL-72, and A2780 cells), including cisplatin-resistant human ovarian carcinoma cell lines (A2780 cis R cells)...
June 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Nan Jiang, Chengjie Meng, Xiao Han, Guo Jun, Haoming Li, Zhengquan Yu
Astrocytes are the most abundant cell type in the central nervous system. Defects in astrocyte function have been implicated in a variety of diseases. Cisplatin (CDDP) is a chemotherapeutic drug that is widely used to treat various cancers. However, it causes neurocognitive impairment in patients. Little is known about the damaging effects of chemotherapeutic drugs like CDDP on astrocytes. Presently, we found that a low dose of CDDP distinctly inhibited astrocyte proliferation and induced delayed cell death...
June 15, 2018: Neuroscience Letters
Min Dai, Ingegerd Hellstrom, Yuen Y Yip, Hans Olov Sjögren, Karl Erik Hellstrom
While immunomodulatory monoclonal antibodies (mAbs) have therapeutic efficacy against many tumors, few patients are cured. Attempting to improve their therapeutic efficacy we have applied the TC1 mouse lung carcinoma model and injected established subcutaneous tumors intratumorally with 3 weekly doses of various combinations of mAbs. Combinations of mAbs to CTLA4/PD1/CD137 (the 3 mAb combination) and to CTLA4/PD1/CD137/CD19 (the 4 mAb combination) were most efficacious to induce complete regression of both the injected tumor and an untreated tumor in the same mouse...
June 15, 2018: Journal of Immunotherapy
Brittany A Simone, Ajay Palagani, Kimberly Strickland, Kevin Ko, Lianjin Jin, Meng Kieng Lim, Tu D Dan, Mak Sarich, Daniel A Monti, Massimo Cristofanilli, Nicole L Simone
Triple negative breast cancer (TNBC) is a heterogeneous disease that has no available targeted therapies. Previously, we have shown that caloric restriction (CR) can augment the effects of radiation therapy in a TNBC mouse model. To build upon this, we now present data regarding the combination of chemotherapy and CR in the same 4T1 model. Chemotherapy can induce inflammation that breeds resistance to therapy. We propose CR as a mechanism to decrease chemotherapy-induced inflammation and increase efficacy of therapy...
June 18, 2018: Cell Cycle
Vítězslav Kolek, Stanislav Losse, Juraj Kultan, Petr Jakubec, Jaromir Zatloukal, Milan Sova, Marek Szkorupa, Čestmír Neoral, Josef Škarda, Tomáš Tichý, Zdeněk Kolář
OBJECTIVES: Adjuvant chemotherapy (AC) in non-small cell lung cancer (NSCLC) has become a standard of care in patients with stages IIA, IIB, and IIIA after complete tumor resection. Utilization and outcome of AC in routine practice is described in a few studies with non-conclusive results. MATERIAL AND METHODS: This retrospective study included consecutive patients with NSCLC who underwent curative-intent surgery. Data of AC uptake in stage IB (tumor of ≥4 cm in diameter), II and IIIA and reasons of AC omission were evaluated according to medical records...
June 18, 2018: Current Medical Research and Opinion
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