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https://www.readbyqxmd.com/read/28214890/a-new-perspective-for-osteosarcoma-therapy-proteasome-inhibition-by-mln9708-2238-successfully-induces-apoptosis-and-cell-cycle-arrest-and-attenuates-the-invasion-ability-of-osteosarcoma-cells-in-vitro
#1
Renhao Liu, Chunjiang Fu, Jiabing Sun, Xvming Wang, Shuo Geng, Xiaoyu Wang, Jilong Zou, Zhenggang Bi, Chenglin Yang
BACKGROUND: The proteasome exists in all eukaryotic cells and provides the main route of intracellular proteins degradation involved in cell growth and apoptosis. Proteasome inhibition could block protein degradation pathways and disturb regulatory networks, possibly leading to profound effects on cell growth, particularly in cancer cells. A proteasome inhibitor with an appropriate toxicity index for malignant cells rather than normal cells would be an attractive anticancer therapy. METHODS: The human osteosarcoma (OS) cell lines MG-63 and Saos-2 and normal osteoblast cells were used to study the antitumour activity of the proteasome inhibitor MLN9708/2238...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214724/where-biomedicalisation-and-magic-meet-therapeutic-innovations-of-elite-sports-injury-in-british-professional-football-and-cycling
#2
Alex Faulkner, Michael McNamee, Catherine Coveney, Jonathan Gabe
Injury is a conspicuous feature of the practice and public spectacle of contemporary elite sports. The paper argues that the 'biomedicalisation' thesis (medico-industrial nexus, techno-scientific drivers, medical optimisation, biologisation, the rise of evidence and health surveillance) goes some way to capturing the use in elite sports injury of some highly specialised mainstream therapies and some highly maverick biological therapies, which are described. Nevertheless, these main strands of biomedicalisation do not capture the full range of these phenomena in the contexts of sports medicine and athletes' practices in accessing innovative, controversial therapies...
February 9, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28213914/novel-method-to-assess-intrinsic-heart-rate-recovery-in-ambulatory-ecg-recordings-tracks-cardioprotective-effects-of-chronic-autonomic-regulation-therapy-in-patients-enrolled-in-the-anthem-hf-study
#3
Gerrard M Carlson, Imad Libbus, Badri Amurthur, Bruce H KenKnight, Richard L Verrier
BACKGROUND: Postexercise heart rate recovery (HRR) is a powerful and independent predictor of mortality. Autonomic regulation therapy (ART) with chronic vagus nerve stimulation (VNS) has been shown to improve ventricular function in patients with chronic heart failure. However, the effect of ART on HRR in patients with heart failure remains unknown. METHODS: A new measure involving quantification of intrinsic HRR was developed for 24-hr ambulatory ECG (AECG) recordings based on spontaneous heart rate changes observed during daily activity in patients with symptomatic heart failure and reduced ejection fraction...
February 17, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28213701/ursolic-acid-mediated-changes-in-glycolytic-pathway-promote-cytotoxic-autophagy-and-apoptosis-in-phenotypically-different-breast-cancer-cells
#4
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Plant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5-20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)). UA-mediated response was more potent than BA-mediated response...
February 17, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28213595/qualitative-study-of-the-breather-trial-short-cycle-antiretroviral-therapy-is-it-acceptable-to-young-people-living-with-hiv
#5
Sarah Bernays, Sara Paparini, Janet Seeley, Stella Namukwaya Kihika, Diana Gibb, Tim Rhodes
OBJECTIVES: A qualitative study of the BREATHER (PENTA 16) randomised clinical trial, which compared virological control of Short Cycle Therapy (SCT) (5 days on: 2 days off) with continuous efavirenz (EFV)-based antiretroviral therapy (CT) in children and young people (aged 8-24) living with HIV with viral load <50 c/mL to examine adaptation, acceptability and experience of SCT to inform intervention development. SETTING: Paediatric HIV clinics in the UK (2), Ireland (1), the USA (1) and Uganda (1)...
February 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28213365/fda-approval-summary-tas-102
#6
Leigh Marcus, Steven J Lemery, Sachia Khasar, Emily Wearne, Whitney S Helms, Weishi Yuan, Kun He, Xianhua Cao, Jingyu Yu, Hong Zhao, Yaning Wang, Olen Stephens, Erika Englund, Rajiv Agarwal, Patricia Keegan, Richard Pazdur
FDA approved TAS-102 (Lonsurf, Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In an international, multicenter, double-blinded, placebo-controlled trial (TPU-TAS-102-301, herein referred to as RECOURSE), 800 patients with previously treated mCRC were randomly allocated (2:1) to receive either TAS-102 35mg/m2 orally twice daily after meals on Days 1-5 and 8-12 of each 28-day cycle (n=534) or matching placebo (n=266)...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213006/a-prospective-multi-institutional-phase-ii-study-of-induction-chemoradiotherapy-followed-by-surgery-in-patients-with-non-small-cell-lung-cancer-involving-the-chest-wall-cjlsg0801
#7
Koji Kawaguchi, Kohei Yokoi, Hiroshi Niwa, Yasuhisa Ohde, Shoichi Mori, Sakae Okumura, Satoshi Shiono, Hiroyuki Ito, Motoki Yano, Kikuo Shigemitsu, Yoshinori Hiramatsu, Jiro Okami, Hideo Saka
OBJECTIVES: The standard therapy for patients with T3N0-1M0 non-small cell lung cancer (NSCLC) involving the chest wall is considered surgical resection and adjuvant therapy. However, the compliance of adjuvant therapy is relatively low, and the prognosis for those patients has been unsatisfactory. Therefore, we conducted a phase II study of induction chemoradiotherapy followed by surgery with the aim of improving the survival. PATIENTS AND METHODS: This treatment strategy consisted of induction chemotherapy (two cycles of cisplatin at 80mg/m(2) on Day 1 and vinorelbine at 20mg/m(2) on Days 1 and 8) concurrent with radiotherapy (40Gy in 20 fractions) followed by surgery...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28213002/a-phase-ii-trial-of-dovitinib-in-previously-treated-advanced-pleural-mesothelioma-the-ontario-clinical-oncology-group
#8
Scott A Laurie, Desiree Hao, Natasha B Leighl, John Goffin, Abderrahim Khomani, Ashish Gupta, Christina L Addison, Anita Bane, Jean Seely, Marc L Filion, Gregory R Pond, Mark N Levine
OBJECTIVES: Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM. METHODS: This open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#9
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212730/the-integrated-stress-response-and-proteotoxicity-in-cancer-therapy
#10
REVIEW
David J McConkey
A variety of different forms of cellular stress can cause protein misfolding and aggregation and proteotoxicity. The cytoprotective response to proteotoxicity is termed the integrated stress response and involves 4 distinct serine/threonine protein kinases that converge on the translation initiation factor eIF2α, resulting in phosphorylation at S51, cell cycle arrest, and a general inhibition of global protein synthesis. Phosphorylation of eIF2α also promotes translation of ATF4 and the expression of ATF4 target genes that ameliorate proteotoxic stress but can also promote apoptosis...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212559/the-selective-mek1-inhibitor-selumetinib-enhances-the-antitumor-activity-of-everolimus-against-renal-cell-carcinoma-in-vitro-and-in-vivo
#11
Yun Zou, Jianfeng Wang, Xuejiao Leng, Jiwei Huang, Wei Xue, Jin Zhang, Yiran Huang
Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by Selumetinib, a selective MEK1 inhibitor...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#12
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28211941/upfront-window-vincristine-irinotecan-treatment-of-high-risk-hepatoblastoma-a-report-from-the-children-s-oncology-group-ahep0731-study-committee
#13
Howard M Katzenstein, Wayne L Furman, Marcio H Malogolowkin, Mark D Krailo, M Beth McCarville, Alexander J Towbin, Greg M Tiao, Milton J Finegold, Sarangarajan Ranganathan, Stephen P Dunn, Max R Langham, Eugene D McGahren, Carlos Rodriguez-Galindo, Rebecka L Meyers
BACKGROUND: The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Children's Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma. METHODS: Patients with newly diagnosed metastatic hepatoblastoma or those with a serum α-fetoprotein (AFP) level <100 ng/mL were eligible...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28211936/reduction-of-cyclophosphamide-dose-for-patients-with-subset-2-low-risk-rhabdomyosarcoma-is-associated-with-an-increased-risk-of-recurrence-a-report-from-the-soft-tissue-sarcoma-committee-of-the-children-s-oncology-group
#14
David O Walterhouse, Alberto S Pappo, Jane L Meza, John C Breneman, Andrea Hayes-Jordan, David M Parham, Timothy P Cripe, James R Anderson, William H Meyer, Douglas S Hawkins
BACKGROUND: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cyclophosphamide dose of 26.4 g/m(2) ) to the combination of vincristine and dactinomycin (VAC). The goal of Children's Oncology Group ARST0331 for subset 2 low-risk patients was to reduce the total cumulative cyclophosphamide dose without compromising FFS...
February 17, 2017: Cancer
https://www.readbyqxmd.com/read/28211162/efficacy-of-the-oral-mtorc1-inhibitor-everolimus-in-relapsed-or-refractory-indolent-lymphoma
#15
N Nora Bennani, Betsy R LaPlant, Stephen M Ansell, Thomas M Habermann, David J Inwards, Ivana N Micallef, Patrick B Johnston, Luis F Porrata, Joseph P Colgan, Svetomir N Markovic, Grzegorz S Nowakowski, William R Macon, Craig B Reeder, Joseph R Mikhael, Donald W Northfelt, Irene M Ghobrial, Thomas E Witzig
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas...
February 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28211058/a-feasibility-study-of-a-hybrid-breast-immobilization-system-for-early-breast-cancer-in-proton-beam-therapy
#16
Takeshi Arimura, Takashi Ogino, Takashi Yoshiura, Mitsugi Matsuyama, Naoaki Kondo, Hideki Miyazaki, Akari Sakuragi, Takayuki Ohara, Etsuyo Ogo, Yoshio Hishikawa
PURPOSE: We aimed to develop a new breast-immobilizing system for proton beam therapy (PBT) of early breast cancer (EBC) that would provide the optimum breast shape during the treatment as well as increased fixation reliability by reducing the influence of respiratory movement. METHODS: The breast-immobilizing system (HyBIS; Hybrid Breast-Immobilizing System) consists of a whole body immobilization system (WBIS), position converting device (to change patient position), photo scanning system, breast cup (made using a three-dimensional printer), breast cup fitting apparatus, breast cup holding device (to ensure the breast remains lifted in the supine position), and dedicated stretcher fixed to the WBIS (to carry the patient)...
February 16, 2017: Medical Physics
https://www.readbyqxmd.com/read/28211049/low-dose-rituximab-and-concurrent-adjuvant-therapy-for-pemphigus-protocol-and-single-centre-long-term-review-of-nine-patients
#17
Aaron J Robinson, Mi Vu, Gary A Unglik, George A Varigos, Laura Scardamaglia
Pemphigus is an autoimmune B-cell mediated blistering disease associated with significant morbidity and mortality. Rituximab has proven effective for the treatment of steroid-refractory pemphigus, although there is controversy over the optimum dosing protocol. Additionally, effective disease control often requires long-term immunosuppression, even in disease-free periods. We present a case series of a single-centre long-term follow up of nine patients with pemphigus, treated with two 500-mg doses of rituximab separated by 14 days along with concurrent adjuvant therapy...
February 17, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/28210903/role-of-exchange-protein-directly-activated-by-camp-epac1-in-breast-cancer-cell-migration-and-apoptosis
#18
Naveen Kumar, Sonal Gupta, Surbhi Dabral, Shailja Singh, Seema Sehrawat
Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28210763/artemisinin-and-its-derivatives-in-cancer-therapy-status-of-progress-mechanism-of-action-and-future-perspectives
#19
REVIEW
Archana Bhaw-Luximon, Dhanjay Jhurry
Since the late 1990s, there has been rapid multiplication of data on the anti-cancer properties of artemisinins. This article reviews the status of progress of artemisinin and its derivatives as anti-cancer agents in clinical trials, case reports, and in vitro/in vivo studies. Particular attention is laid on the combinations of artemisinins and synthetic chemodrugs to enhance the latter's efficacy. An attempt is here made to rationalize the synergistic effects of a few common anti-cancer drugs of the anthracycline, taxane, anti-metabolite, and platinum-based drug families...
February 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28210100/the-cost-effectiveness-of-a-nsclc-patient-assistance-program-for-pemetrexed-maintenance-therapy-in-people-s-republic-of-china
#20
Qiang Shi, Shanlian Hu, Wesley E Furnback, Gregory F Guzauskas, Jiejing Shen, Bruce Cm Wang
BACKGROUND: Eli Lilly and the China Primary Health Care Foundation are currently implementing a patient assistance program (PAP) in China, which allows first-line nonsquamous non-small-cell lung cancer (NSCLC) patients who complete four cycles of pemetrexed induction therapy to receive free, continuous pemetrexed maintenance therapy. OBJECTIVE: To estimate the cost-effectiveness of pemetrexed maintenance therapy vs basic standard care (BSC) and the economic impacts of providing a PAP for pemetrexed maintenance therapy to NSCLC patients who have completed pemetrexed induction therapy in a Chinese health care setting...
2017: ClinicoEconomics and Outcomes Research: CEOR
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