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https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#1
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550039/a-phase-1-2-study-of-the-oral-proteasome-inhibitor-ixazomib-in-relapsed-or-refractory-light-chain-al-amyloidosis
#2
Vaishali Sanchorawala, Giovanni Palladini, Vishal Kukreti, Jeffrey A Zonder, Adam D Cohen, David C Seldin, Angela Dispenzieri, Arnaud Jaccard, Stefan O Schönland, Deborah Berg, Huyuan Yang, Neeraj Gupta, Ai-Min Hui, Raymond L Comenzo, Giampaolo Merlini
This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory AL amyloidosis (RRAL). Ixazomib was administered to adult patients with RRAL after ≥1 prior line of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4. A 3+3 dose-escalation phase was followed by 2 expansion cohorts (PI-naïve and PI-exposed patients) at the maximum tolerated dose (MTD)...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28550029/pulmonary-function-changes-after-radiotherapy-for-lung-or-esophageal-cancer-a-systematic-review-focusing-on-dose-volume-parameters
#3
Anne G H Niezink, Renske A de Jong, Christina T Muijs, Johannes A Langendijk, Joachim Widder
BACKGROUND: Despite technical developments in treatment delivery, radiation-induced lung toxicity (RILT) remains a crucial problem in thoracic radiotherapy. Clinically based RILT scores have their limitations, and more objective measures such as pulmonary functions tests (PFTs) might help to improve treatment strategies. PURPOSE: To summarize the available evidence about the effect of dose to the lung in thoracic radiotherapy on forced expiratory volume in one second (FEV1) and diffusion capacity (DLCO) in patients with lung and esophageal cancer treated with curative intent...
May 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28549829/impact-of-chlorpyrifos-on-human-villous-trophoblasts-and-chorionic-villi
#4
M E Ridano, A C Racca, J B Flores-Martin, R Fretes, C L Bandeira, L Reyna, E Bevilacqua, S Genti-Raimondi, G M Panzetta-Dutari
Placental barrier regulates maternal-fetal interchange protecting the baby from damage caused by substances found in the uterine environment or circulating in the vascular system. Organophosphate (OP) pesticides are a paramount group of environmental pollutants used in intensive agriculture for protection against diseases and pests. While many studies have reported an increased risk of pregnancy alterations in pregnant women exposed to OPs, few have analyzed the effects caused by these pesticides in the placenta...
May 23, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28549783/irinotecan-temozolomide-with-temsirolimus-or-dinutuximab-in-children-with-refractory-or-relapsed-neuroblastoma-cog-anbl1221-an-open-label-randomised-phase-2-trial
#5
Rajen Mody, Arlene Naranjo, Collin Van Ryn, Alice L Yu, Wendy B London, Barry L Shulkin, Marguerite T Parisi, Sabah-E-Noor Servaes, Mitchell B Diccianni, Paul M Sondel, Julia G Bender, John M Maris, Julie R Park, Rochelle Bagatell
BACKGROUND: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma. METHODS: For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis...
May 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28549771/calcineurin-and-mtor-inhibitor-free-post-transplantation-cyclophosphamide-and-bortezomib-combination-for-graft-versus-host-disease-prevention-after-peripheral-blood-allogeneic-hematopoietic-stem-cell-transplantation-a-phase-i-ii-study
#6
A Samer Al-Homsi, Kelli Cole, Marlee Muilenburg, Austin Goodyke, Muneer Abidi, Ulrich Duffner, Stephanie Williams, Jessica Parker, Aly Abdel-Mageed
Graft-versus-host disease (GvHD) hampers the utility of allogeneic hematopoietic stem cell transplantation (AHSCT). The purpose of this study was to determine the feasibility, safety, and efficacy of a novel combination of post-transplantation cyclophosphamide (PTC) and bortezomib for the prevention of GvHD. Patients undergoing peripheral blood AHSCT for hematological malignancies following reduced-intensity conditioning with grafts from human leukocyte antigen (HLA)-matched related or unrelated donors were enrolled in a phase I-II clinical trial...
May 23, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28549676/exposure-response-relationship-of-regorafenib-efficacy-in-patients-with-hepatocellular-carcinoma
#7
Alexander Solms, Isabel Reinecke, Sabine Fiala-Buskies, Anne Keunecke, Henk-Jan Drenth, Jordi Bruix, Gerold Meinhardt, Adriaan Cleton, Bart Ploeger
PURPOSE: To explore the relationship between regorafenib exposure and efficacy in patients with hepatocellular carcinoma (HCC) who had disease progression during sorafenib treatment (RESORCE). METHODS: Exposure-response (ER) analyses for regorafenib were performed using data from a phase 3, randomized, placebo-controlled trial (RESORCE). Patients received 160mg regorafenib or placebo once daily (3weeks on/1week off in a 4-week cycle) with best supportive care until disease progression, death, or unacceptable toxicity...
May 23, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#8
Dai Sig Im, Hye Jin Shin, Keum Jin Yang, So Young Jung, Ho Yeon Song, Hyeon Seok Hwang, Hyo-Wook Gil
BACKGROUND: Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates P-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice...
May 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28549573/the-dose-makes-the-poison-nutritional-overload-determines-the-life-traits-of-blood-feeding-arthropods
#9
REVIEW
Marcos Sterkel, José Henrique M Oliveira, Vanessa Bottino-Rojas, Gabriela O Paiva-Silva, Pedro L Oliveira
Vertebrate blood composition is heavily biased towards proteins, and hemoglobin, which is a hemeprotein, is by far the most abundant protein. Typically, hematophagous insects ingest blood volumes several times their weight before the blood meal. This barbarian feast offers an abundance of nutrients, but the degradation of blood proteins generates toxic concentrations of amino acids and heme, along with unparalleled microbiota growth. Despite this challenge, hematophagous arthropods have successfully developed mechanisms that bypass the toxicity of these molecules...
May 23, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28549437/p-p-ddt-induces-testicular-oxidative-stress-induced-apoptosis-in-adult-rats
#10
Neila Marouani, Dorsaf Hallegue, Mohsen Sakly, Moncef Benkhalifa, Khémais Ben Rhouma, Olfa Tebourbi
BACKGROUND: The 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) is a known persistent organic pollutant and male reproductive toxicant. The present study is designed to test the hypothesis that oxidative stress mediates p,p'-DDT-induced apoptosis in testis. METHODS: Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The oxidative stress was evaluated by biomarkers such lipid peroxidation (LPO) and metallothioneins (MTs) levels...
May 26, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28549414/phase-i-ii-study-of-induction-chemotherapy-using-carboplatin-plus-irinotecan-and-sequential-thoracic-radiotherapy-trt-for-elderly-patients-with-limited-disease-small-cell-lung-cancer-ld-sclc-torg-0604
#11
Yuki Misumi, Hiroaki Okamoto, Jiichiro Sasaki, Noriyuki Masuda, Mari Ishii, Tsuneo Shimokawa, Yukio Hosomi, Yusuke Okuma, Makoto Nagamata, Takashi Ogura, Terufumi Kato, Masafumi Sata, Sakiko Otani, Akira Takakura, Koichi Minato, Yosuke Miura, Takuma Yokoyama, Saori Takata, Katsuhiko Naoki, Koshiro Watanabe
BACKGROUND: The role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated. METHODS: Patients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0-2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions)...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28549324/salinity-and-sensitivity-to-endocrine-disrupting-chemicals-a-comparison-of-reproductive-endpoints-in-small-bodied-fish-exposed-under-different-salinities
#12
Thijs Bosker, Giacomo Santoro, Steven D Melvin
The influence of salinity on toxicity outcomes has been demonstrated for various contaminants, but has received limited attention for endocrine disrupting chemicals (EDCs). Short-term laboratory tests using small-bodied fish are an important tool for evaluating impacts of EDCs on reproduction. Tests have been developed for both freshwater and estuarine/marine species, providing an opportunity to assess whether concentrations at which small-bodied fish respond to EDCs may be influenced by salinity. We conducted a semi-quantitative review of short-term laboratory tests with small-bodied fish exposed to EDCs, including 59 studies under freshwater conditions (7 species) and 23 studies conducted under saline conditions (5 species)...
May 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28548885/metformin-inhibits-p-gingivalis-lipopolysaccharide-lps-influenced-inflammatory-response-in-human-gingival-fibroblasts-via-regulating-activating-transcription-factor-3-atf3-expression
#13
Wenyan Kang, Ting Wang, Zhekai Hu, Feng Liu, Yundong Sun, Shaohua Ge
BACKGROUND: Chronic periodontitis is one of the most prevalent oral diseases, which is associated with Porphyromonas gingivalis (P. gingivalis) Lipopolysaccharide (LPS) infection, and has profound effects on type 2 diabetes mellitus (DM2). Metformin, a well-known antidiabetic agent, has been reported to exert anti-inflammatory effects on various cells. This study aimed to investigate the role of metformin on LPS-influenced inflammatory response in human gingival fibroblasts (HGFs). METHODS: Dose-dependent additive effects of metformin on LPS-influenced HGFs were detected...
May 26, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28548706/45-gy-is-not-sufficient-radiotherapy-dose-for-group-iii-orbital-embryonal-rhabdomyosarcoma-after-less-than-complete-response-to-12-weeks-of-arst0331-chemotherapy-a-report-from-the-soft-tissue-sarcoma-committee-of-the-children-s-oncology-group
#14
Ralph P Ermoian, John Breneman, David O Walterhouse, Yueh-Yun Chi, Jane Meza, James Anderson, Douglas S Hawkins, Andrea A Hayes-Jordan, David M Parham, Torunn I Yock, Sarah S Donaldson, Suzanne L Wolden
BACKGROUND: Recent Children's Oncology Group (COG) trials tested the efficacy of reduced therapy in an effort to lessen late effects compared to the Intergroup Rhabdomyosarcoma Study (IRS) IV regimen with associated hematologic and hepatic toxicity, and infertility. Here, we analyze the efficacy of 45 Gray (Gy) local radiotherapy (RT) in patients with Group III orbital embryonal rhabdomyosarcoma (ERMS) enrolled on the COG low-risk study ARST0331. PROCEDURE: Sixty-two patients with Group III orbital ERMS were treated on ARST0331 with four cycles of vincristine (VCR), dactinomycin (DACT), and cyclophosphamide (CPM; VAC, total cumulative CPM dose 4...
May 26, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28547856/prognostic-impact-of-the-cumulative-dose-and-dose-intensity-of-everolimus-in-patients-with-pancreatic-neuroendocrine-tumors
#15
Rossana Berardi, Mariangela Torniai, Sara Pusceddu, Francesca Spada, Toni Ibrahim, Maria Pia Brizzi, Lorenzo Antonuzzo, Piero Ferolla, Francesco Panzuto, Nicola Silvestris, Stefano Partelli, Benedetta Ferretti, Federica Freddari, Calogero Gucciardino, Enrica Testa, Laura Concas, Sabina Murgioni, Alberto Bongiovanni, Clizia Zichi, Nada Riva, Maria Rinzivillo, Oronzo Brunetti, Lucio Giustini, Francesco Di Costanzo, Gianfranco Delle Fave, Nicola Fazio, Filippo De Braud, Massimo Falconi, Stefano Cascinu
The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48)...
May 25, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28547525/neoadjuvant-chemotherapy-with-trastuzumab-docetaxel-and-carboplatin-administered-every-3%C3%A2-weeks-for-japanese-women-with-her2-positive-primary-breast-cancer-efficacy-and-safety
#16
Ikuko Sugitani, Shigeto Ueda, Takashi Sakurai, Takashi Shigekawa, Eiko Hirokawa, Hiroko Shimada, Hideki Takeuchi, Kazuo Matsuura, Misono Misumi, Nobuko Fujiuchi, Takao Takahashi, Takahiro Hasebe, Akihiko Osaki, Toshiaki Saeki
BACKGROUND: This phase II neoadjuvant study evaluated the efficacy and safety of a triweekly regimen of docetaxel and carboplatin in combination with trastuzumab (TCbH) in Japanese women with human epidermal growth factor receptor type2 (HER2)-positive primary breast cancer. METHODS: Patients with HER2-positive, stage I-III invasive breast cancer received six courses of trastuzumab (8 mg/kg loading dose, then 6 mg/kg, day 1), docetaxel (75 mg/m(2), day 1), and carboplatin (area under the curve: 6, day 1) every 3 weeks...
May 25, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28546951/common-chemotherapeutic-agents-modulate-fatty-acid-distribution-in-human-hepatocellular-carcinoma-and-colorectal-cancer-cells
#17
Amir Mehdizadeh, Morteza Bonyadi, Masoud Darabi, Reza Rahbarghazi, Soheila Montazersaheb, Kobra Velaei, Maghsood Shaaker, Mohammad-Hossein Somi
Introduction: Cancer cells are critically correlated with lipid molecules, particularly fatty acids, as structural blocks for membrane building, energy sources, and related signaling molecules. Therefore, cancer progression is in direct correlation with fatty acid metabolism. The aim of this study was to investigate the potential effects of common chemotherapeutic agents on the lipid metabolism of hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cells, with a focus on alterations in cellular fatty acid contents...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/28546541/protective-effect-of-low-dose-intra-articular-cadmium-on-inflammation-and-joint-destruction-in-arthritis
#18
Paola Bonaventura, Guillaume Courbon, Aline Lamboux, Fabien Lavocat, Hubert Marotte, Francis Albarède, Pierre Miossec
Synovium hyperplasia characterizes joint diseases, such as rheumatoid arthritis (RA). The cytotoxic effect of low-dose Cadmium (Cd) was tested in vitro and ex vivo on synoviocytes, the mesenchymal key effector cells of inflammation and proliferation in arthritis. The anti-inflammatory and anti-proliferative effects of Cd were tested in vivo by intra-articular injection in the adjuvant induced arthritis rat joints, where the clinical scores and the consequences of arthritis were evaluated. Cell death through apoptosis was highly induced by Cd in inflammatory synoviocytes (80% reduction of cell viability, p < 0...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546525/pazopanib-for-the-treatment-of-non-clear-cell-renal-cell-carcinoma-a-single-arm-open-label-multicenter-phase-ii-study
#19
Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim
Purpose: The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC. Materials and Methods: Patients with locally advanced or metastatic nccRCC, except for collecting duct or sarcomatoid type, received 800mg/day of pazopanib daily until progression of disease or intolerable toxicity...
May 22, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28546370/pediatric-oxygen-therapy-a-review-and-update
#20
Brian K Walsh, Craig D Smallwood
Oxygen is a colorless, odorless, tasteless gas that is utilized by the body for respiration. Oxygen has played a major role in respiratory care. Oxygen therapy is useful in treating hypoxemia but is often thought of as a benign therapy. After many years of study, we have learned a great deal of the benefits and potential risk of this powerful drug. Today oxygen gas is cheap, widely available, and easy to administer. Oxygen delivery devices vary in cost from a few cents for a simple nasal cannula to $25-$50 for some humidified systems...
June 2017: Respiratory Care
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