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Chemotherapy neurotoxicity

Benjamin Anon, Bérenger Largeau, Alban Girault, Aurélie Chantome, Morgane Caulet, Clémence Perray, Driffa Moussata, Christophe Vandier, Chantal Barin-Le Guellec, Thierry Lecomte
INTRODUCTION: Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. MATERIALS AND METHODS: We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density...
May 17, 2018: Cancer Chemotherapy and Pharmacology
Tetsuhiko Okabe, Taiki Nozaki, Noriko Aida, Jay Starkey, Mikako Enokizono, Tetsu Niwa, Atsuhiko Handa, Yuji Numaguchi, Yasuyuki Kurihara
Neurological complications of paediatric cancers are a substantial problem. Complications can be primary from central nervous system (CNS) spread or secondary from indirect or remote effects of cancer, as well as cancer treatments such as chemotherapy and radiation therapy. In this review, we present the clinical and imaging findings of rare but important neurological complications in paediatric patients with cancer. Neurological complications are classified into three phases: pre-treatment, treatment and post-remission...
May 15, 2018: Insights Into Imaging
Nobuyoshi Fukumitsu, Skye Hsin-Hsien Yeh, Leo Garcia Flores Ii, Uday Mukhopadhyay, Daniel Young, Kazuma Ogawa, Hwan-Jeong Jeong, William Tong, Juri G Gelovani
Background: Histone deacetylases (HDACs) regulate gene expression by changing histone deacetylation status. Neurotoxicity is one of the major side effects of cisplatin, which reacts with deoxyribonucleic acid (DNA) and has excellent antitumor effects. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor with neuroprotective effects against cisplatin-induced neurotoxicity. Purpose: We investigated how cisplatin with and without SAHA pretreatment affects HDAC expression/activity in the brain by using 6-([18 F]fluoroacetamido)-1-hexanoicanilide ([18 F]FAHA) as a positron emission tomography (PET) imaging agent for HDAC IIa...
2018: Contrast Media & Molecular Imaging
Shunsuke Kato, Hiroo Imai, Makio Gamoh, Takenori Takahata, Hisatsugu Ohori, Katsuhiro Yasuda, Tomohito Niitani, Yasuko Murakawa, Kenji Amagai, Hideki Isobe, Yoshiaki Shindo, Michio Kuroki, Yasuhiro Sakamoto, Hideki Shimodaira, Takashi Yoshioka, Chikashi Ishioka
Oxaliplatin-based chemotherapy is a well-established regimen for patients with inoperable and metastatic colorectal cancer. However, one of the major limitations of oxaliplatin-based chemotherapy is sensory neuropathy. It was previously reported that introduction of intermittent oxaliplatin treatment to an oxaliplatin-based regimen has a significant benefit on efficacy or safety. Here, we prospectively assessed whether efficacy and safety of first-line chemotherapy for advanced colorectal cancer are achieved by introduction of withdrawal of oxaliplatin treatment for a certain period (intermittent oxaliplatin treatment)...
2018: Tohoku Journal of Experimental Medicine
Clemens B Tempfer, Urs Giger-Pabst, Veronika Seebacher, Miriam Petersen, Askin Dogan, Günther A Rezniczek
OBJECTIVE: We performed a phase I, single-arm, non-randomized, open-label, dose-escalation trial to determine the dose-limiting toxicity of intraperitoneal cisplatin and doxorubicin applied as pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with recurrent ovarian cancer. METHODS: We used a standard 3 + 3 dose-escalation design with doxorubicin 1.5 mg/m2 , cisplatin 7.5 mg/m2 q 4 to 6 weeks for 3 cycles and subsequent dose escalation steps (20% increment per step) in patients with recurrent ovarian cancer and peritoneal carcinomatosis...
May 6, 2018: Gynecologic Oncology
Daniela Almeida, Rita Pinho, Verónica Correia, Jorge Soares, Maria de Lourdes Bastos, Félix Carvalho, João Paulo Capela, Vera Marisa Costa
The potential neurotoxic effects of anticancer drugs, like doxorubicin (DOX) and mitoxantrone (MTX; also used in multiple sclerosis), are presently important reasons for concern, following epidemiological data indicating that cancer survivors submitted to chemotherapy may suffer cognitive deficits. We evaluated the in vitro neurotoxicity of two commonly used chemotherapeutic drugs, DOX and MTX, and study their underlying mechanisms in the SH-SY5Y human neuronal cell model. Undifferentiated human SH-SY5Y cells were exposed to DOX or MTX (0...
May 5, 2018: Pharmaceuticals
T G Fonseca, M Auguste, F Ribeiro, C Cardoso, N C Mestre, D M S Abessa, M J Bebianno
Cytotoxic drugs applied in chemotherapy enter the aquatic environment after patient's metabolism and excretion, in both main compounds and their respective metabolites. The increased consumption and discharge of these drugs raise concern on the genotoxic burden to non-target aquatic species, due to their unselective action on DNA. Settlement and adsorption of cytotoxic drugs to aquatic sediments pose risks to benthic species through chronic exposure. The aim of the present study was to assess the effects induced by the anticancer drug cyclophosphamide (CP) on the polychaete Nereis diversicolor, after 14 days of exposure to environmental relevant concentrations (10, 100, 500 and 1000 ng L-1 )...
May 1, 2018: Science of the Total Environment
Ming Zhuo, Murat F Gorgun, Ella W Englander
Peripheral Nervous System (PNS) neurotoxicity caused by cancer drugs hinders attainment of chemotherapy goals. Due to leakiness of the blood nerve barrier, circulating chemotherapeutic drugs reach PNS neurons and adversely affect their function. Chemotherapeutic drugs are designed to target dividing cancer cells and mechanisms underlying their toxicity in postmitotic neurons remain to be fully clarified. The objective of this work was to elucidate progression of events triggered by antimitotic drugs in postmitotic neurons...
April 23, 2018: Free Radical Biology & Medicine
Alissar El Chediak, Ali A Haydar, Ayman Hakim, Sarah Abdel Massih, Lara Hilal, Deborah Mukherji, Sally Temraz, Ali Shamseddine
Background: Oxaliplatin is a nonconventional third-generation platinum compound. It is an important chemotherapeutic agent in regimens used in gastrointestinal carcinomas as well as other malignancies. Oxaliplatin toxicity profile includes neurotoxicity, hepatotoxicity, and splenomegaly. The primary aim of this study was to measure the spleen volume of patients on oxaliplatin therapy before and during chemotherapy to detect any increase in splenic size as a biomarker for early oxaliplatin toxicity...
2018: Therapeutics and Clinical Risk Management
Oliver A Cornely, Dimitrios P Kontoyiannis
Although the benefit for any type of antifungal prophylaxis in patients with acute myelogenous leukemia is well accepted, less is known about the risk for invasive fungal infections (IFIs) and the optimal prophylaxis strategies in patients with acute lymphocytic leukemia (ALL). Based on recent studies, ALL is a disease that appears to be associated with significant risk for IFIs. The pharmacokinetic interactions between azoles and vincristine, an antineoplastic agent that is part of modern combination chemotherapies in ALL, results in clinically significant neurotoxicity that makes the use of azoles problematic...
April 25, 2018: Mycoses
Chun-Tang Chiou, Kaw-Chen Wang, Ying-Chen Yang, Chuen-Lin Huang, Sien-Hung Yang, Yao-Haur Kuo, Nai-Kuei Huang
Liu Jun Zi Tang (LJZT) has been used to treat functional dyspepsia and depression, suggesting its effects on gastrointestinal and neurological functions. LJZT is currently used as a complementary therapy to attenuate cisplatin-induced side effects, such as dyspepsia. However, its effect on chemotherapy-induced neuropathic pain or neurotoxicity has rarely been studied. Thus, we explored potential mechanisms underlying LJZT protection against cisplatin-induced neurotoxicity. We observed that LJZT attenuated cisplatin-induced thermal hyperalgesia in mice and apoptosis in human neuroblastoma SH-SY5Y cells...
April 23, 2018: International Journal of Molecular Sciences
Stefanie Brehmer, Mario Alexander Grimm, Alex Förster, Marcel Seiz-Rosenhagen, Grit Welzel, Florian Stieler, Frederik Wenz, Christoph Groden, Sabine Mai, Daniel Hänggi, Frank Anton Giordano
BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE: To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor...
April 24, 2018: Neurosurgery
Eva Battaglini, Susanna B Park, Elizabeth H Barnes, David Goldstein
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment...
April 19, 2018: Contemporary Clinical Trials
Shilan Ding, Min Wang, Song Fang, Huibo Xu, Huiting Fan, Yu Tian, Yadong Zhai, Shan Lu, Xin Qi, Fei Wei, Guibo Sun, Xiaobo Sun
Life-threatening chemotherapy-induced thrombocytopenia can increase the risk of bleeding due to a dramatic low platelet count, which may limit or delay treatment schedules in cancer patients. The pressing need for the rapid alleviation of the symptoms of thrombocytopenia has prompted us to search for novel highly effective and safe thrombopoietic agents. Pharmacological investigations have indicated that dencichine can prevent and treat blood loss and increase the number of platelets. On the basis of the neurotoxicity of dencichine, D-dencichine is artificially synthesized in the laboratory...
2018: Frontiers in Pharmacology
Ellen M Lavoie Smith, Tanima Banerjee, James J Yang, Celia M Bridges, Paola Alberti, Jeff A Sloan, Charles Loprinzi
BACKGROUND: No criterion-standard patient-reported outcome measure of chemotherapy-induced peripheral neuropathy (CIPN) exists. OBJECTIVES: The aims of this study were to reevaluate the sensitivity, reliability, and validity of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (QLQ-CIPN20) measure and suggest possible revisions that could strengthen it. METHODS: Cross-sectional QLQ-CIPN20 data from 8 European countries (n = 271) were pooled with data from 4 North American multisite CIPN intervention trials (n = 884)...
April 12, 2018: Cancer Nursing
Hidemitsu Nakagawa, Yoshihiro Yui, Satoru Sasagawa, Kazuyuki Itoh
INTRODUCTION: The prognosis for leptomeningeal metastasis (LM) remains extremely poor regardless of intrathecal chemotherapy with various drugs, and thus, new treatments are necessary. Butyrate is an endogenous 4-carbon saturated fatty acid, has been investigated as an anti-tumor agent because of its multiple suppressive effects on several tumors. In this study, we investigated the cellular basis of sodium butyrate (SB), a sodium salt compound of butyrate, in vitro and evaluated the clinical potential of intrathecal SB administration for LM in vivo...
April 6, 2018: Journal of Neuro-oncology
Jae-Joon Kim, Jihoon Kang, Yong Sang Hong, Kyu-Pyo Kim, Sun Young Kim, Tae Won Kim, Jeong Eun Kim
Because the number of cytotoxic agents available for the treatment of metastatic colorectal cancer (mCRC) is limited, rechallenge with the same chemotherapy agents can provide a continuum of treatment. This study investigated the efficacy and feasibility of oxaliplatin rechallenge in mCRC patients who had been previously exposed to oxaliplatin-based chemotherapy. Patients were included if they had mCRC and evaluable disease, had remained disease-free or progression-free for at least 6 months after the last dose of prior oxaliplatin-based therapy, and were retreated with oxaliplatin therapy...
April 5, 2018: Medical Oncology
Ali Amidi, S M Hadi Hosseini, Alexander Leemans, Shelli R Kesler, Mads Agerbæk, Lisa M Wu, Robert Zachariae
Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore whether possible changes are related to decline in cognitive functioning. Methods: Sixty-four newly orchiectomized TC patients underwent structural magnetic resonance imaging (T1-weighted and diffusion-weighted imaging) and cognitive testing at baseline prior to further treatment and again at a six-month follow-up...
December 1, 2017: Journal of the National Cancer Institute
Yin Ting Cheung, Raja B Khan, Wei Liu, Tara M Brinkman, Michelle N Edelmann, Wilburn E Reddick, Deqing Pei, Angela Panoskaltsis-Mortari, Deokumar Srivastava, Cheng Cheng, Leslie L Robison, Melissa M Hudson, Ching-Hon Pui, Kevin R Krull
Importance: Little is known about treatment-related neurotoxic mechanisms in children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only. Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of brain injury at ALL diagnosis and during cancer therapy and to evaluate associations with long-term neurocognitive and neuroimaging outcomes and relevant genetic polymorphisms. Design, Setting, and Participants: This prospective cohort study included 235 patients with ALL who received a chemotherapy-only protocol...
March 29, 2018: JAMA Oncology
Paola Alberti, Emanuela Rossi, Andreas A Argyriou, Haralabos P Kalofonos, Chiara Briani, Mario Cacciavillani, Marta Campagnolo, Jordi Bruna, Roser Velasco, Marina E Cazzaniga, Diego Cortinovis, Maria G Valsecchi, Guido Cavaletti
PURPOSE: We aimed to verify the predictiveness of dorsal sural nerve neurophysiological monitoring in obtaining risk stratification for oxaliplatin-induced peripheral neurotoxicity (OXAPN). METHODS: We conducted a secondary analysis on a cohort of 110 colorectal cancer patients who were evaluated clinically and neurophysiologically before chemotherapy, at mid-treatment and at discontinuation. We applied the classification tree analysis method to predict the end-of-treatment OXAPN neurophysiological diagnosis, using data recorded at mid-treatment...
March 29, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
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