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https://www.readbyqxmd.com/read/27915168/interactions-of-long-chain-homologues-of-colchicine-with-tubulin
#1
Ana Marzo-Mas, Pascale Barbier, Gilles Breuzard, Diane Allegro, Eva Falomir, Juan Murga, Miguel Carda, Vincent Peyrot, J Alberto Marco
Several colchicine analogues in which the N-acetyl residue has been replaced by aliphatic, straight-chain acyl moieties, have been synthesized. These compounds show high cytotoxic activity at the nanomolar level against the tumoral cell lines HT-29, MCF-7 and A549. Some of them exhibit activities in the picomolar range against the HT-29 line and are thus two to three orders of magnitude more cytotoxic than colchicine. In this specific cell line, the activities were found to be closely related to the length of the acyl carbon chain, an increase in the latter giving rise to an increase in the cytotoxicity with a maximum in the range of 10-12 carbon atoms, followed by a decrease in activity with still longer chains...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27914971/once-weekly-ofatumumab-in-untreated-or-relapsed-waldenstr%C3%A3-m-s-macroglobulinaemia-an-open-label-single-arm-phase-2-study
#2
Richard R Furman, Herbert A Eradat, Christine G DiRienzo, Craig C Hofmeister, Suzanne R Hayman, John P Leonard, Morton Coleman, Ranjana Advani, Asher Chanan-Khan, Julie Switzky, Qiming M Liao, Damini Shah, Roxanne C Jewell, Steen Lisby, Thomas S Lin
BACKGROUND: The development of more effective and safer treatments, especially non-chemotherapeutics, is needed for patients with Waldenström's macroglobulinaemia. The aim of the study was to assess the safety and clinical activity of intravenous ofatumumab monotherapy for untreated and relapsed Waldenström's macroglobulinaemia. METHODS: We did a phase 2, open-label, single-arm study at six centres (hospitals and cancer clinics) in the USA. Patients aged at least 18 years who were diagnosed with untreated or relapsed Waldenström's macroglobulinaemia and required treatment, received up to three cycles of weekly ofatumumab for 5 weeks...
November 30, 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27914243/efficacy-and-safety-of-bevacizumab-containing-neoadjuvant-therapy-followed-by-interval-debulking-surgery-in-advanced-ovarian-cancer-results-from-the-anthalya-trial
#3
Roman Rouzier, Sébastien Gouy, Frédéric Selle, Eric Lambaudie, Anne Floquet, Virginie Fourchotte, Christophe Pomel, Pierre-Emmanuel Colombo, Elsa Kalbacher, Sandrine Martin-Francoise, Raffaele Fauvet, Philippe Follana, Anne Lesoin, Fabrice Lecuru, Youssef Ghazi, Julien Dupin, Elisabeth Chereau, Sarah Zohar, Paul Cottu, Florence Joly
AIM: To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma. METHODS: Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS...
November 30, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27913927/the-number-of-cycles-of-neoadjuvant-chemotherapy-is-associated-with-prognosis-of-stage-iiic-iv-high-grade-serous-ovarian-cancer
#4
Xia Xu, Fei Deng, Mengmeng Lv, Xiaoxiang Chen
OBJECTIVE: No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). MATERIALS AND METHODS: A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed...
December 3, 2016: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/27913497/response-adapted-frontline-therapy-for-hodgkin-lymphoma-are-we-there-yet
#5
Peter W M Johnson
Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913198/argininosuccinate-synthetase-1-ass1-is-a-common-metabolic-marker-of-chemosensitivity-for-targeted-arginine-and-glutamine-starvation-therapy
#6
Yan Long, Wen-Bin Tsai, Dajuan Wang, David H Hawke, Niramol Savaraj, Lynn G Feun, Mien-Chie Hung, Helen H W Chen, Macus Tien Kuo
Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme that catalyzes the biosynthesis of arginine (Arg). Many malignant human tumors are auxotrophic for Arg because ASS1 is silenced. ASS1 has been established as a sensor of Arg auxotrophic response and a chemosensitivity marker for Arg starvation therapy. Here, we report that ASS1 is also a sensor for glutamine (Gln)-deprivation response, and that upregulation of ASS1 expression is associated with resistance to Gln-starvation treatments. Knockdown of ASS1 expression resulted in increased sensitivity to both Arg- and Gln-starvation, whereas increased ASS1 expression by ectopic transfection is associated with resistance to both Arg- and Gln-starvation...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913098/succinyl-coa-synthetase-sucla2-deficiency-in-two-siblings-with-impaired-activity-of-other-mitochondrial-oxidative-enzymes-in-skeletal-muscle-without-mitochondrial-dna-depletion
#7
Xiaoping Huang, Jirair K Bedoyan, Didem Demirbas, David J Harris, Alexander Miron, Simone Edelheit, George Grahame, Suzanne D DeBrosse, Lee-Jun Wong, Charles L Hoppel, Douglas S Kerr, Irina Anselm, Gerard T Berry
Mutations in SUCLA2 result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) (A-SCS) deficiency, a mitochondrial tricarboxylic acid cycle disorder. The phenotype associated with this gene defect is largely encephalomyopathy. We describe two siblings compound heterozygous for SUCLA2 mutations, c.985A>G (p.M329V) and c.920C>T (p.A307V), with parents confirmed as carriers of each mutation. We developed a new LC-MS/MS based enzyme assay to demonstrate the decreased SCS activity in the siblings with this unique genotype...
November 12, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27912880/combination-of-baicalein-and-10-hydroxy-camptothecin-exerts-remarkable-synergetic-anti-cancer-effects
#8
Qin Tang, Fangling Ji, Wenhui Sun, Jingyun Wang, Jianli Guo, Lianying Guo, Yachen Li, Yongming Bao
BACKGROUND: 10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy. Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis. The synergistic anti-cancer effect of BA and HCPT has not been reported. PURPOSE: To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells. METHODS: Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912832/neoadjuvant-and-adjuvant-therapy-for-non-small-cell-lung-cancer
#9
REVIEW
Jody C Chuang, Ying Liang, Heather A Wakelee
The use of 4 cycles of cisplatin-based adjuvant chemotherapy is now the standard of care for patients with resected stage II and IIIA non-small cell lung cancer. Neoadjuvant chemotherapy lacks the same level of data as adjuvant treatment, but meta-analyses of this approach support its use. Selection of patients who are most likely to benefit from chemotherapy remain elusive. Ongoing adjuvant trials are exploring biomarkers, molecularly targeted agents, postoperative radiation therapy, and immunotherapy.
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912776/improving-stroke-prevention-therapy-for-patients-with-atrial-fibrillation-in-primary-care-protocol-for-a-pragmatic-cluster-randomized-trial
#10
Theresa M Lee, Noah M Ivers, Sacha Bhatia, Debra A Butt, Paul Dorian, Liisa Jaakkimainen, Kori Leblanc, Dan Legge, Dante Morra, Alissia Valentinis, Laura Wing, Jacqueline Young, Karen Tu
BACKGROUND: The prevalence of atrial fibrillation (AF) is growing as the population ages, and at least 15% of ischemic strokes are attributed to AF. However, many high-risk AF patients are not offered guideline-recommended stroke prevention therapy due to a variety of system, provider, and patient-level barriers. METHODS: We will conduct a pragmatic, cluster-randomized controlled trial randomizing primary care clinics to test a "toolkit" of quality improvement interventions in primary care...
December 3, 2016: Implementation Science: IS
https://www.readbyqxmd.com/read/27911951/body-surface-area-and-baseline-blood-pressure-predict-subclinical-anthracycline-cardiotoxicity-in-women-treated-for-early-breast-cancer
#11
Paul Kotwinski, Gillian Smith, Jackie Cooper, Julie Sanders, Louise Ma, Albert Teis, David Kotwinski, Michael Mythen, Dudley J Pennell, Alison Jones, Hugh Montgomery
BACKGROUND AND AIMS: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. METHODS: Subjects were women with early breast cancer, free of pre-existing cardiac disease...
2016: PloS One
https://www.readbyqxmd.com/read/27911860/id4-regulates-transcriptional-activity-of-wild-type-and-mutant-p53-via-k373-acetylation
#12
Derrick J Morton, Divya Patel, Jugal Joshi, Aisha Hunt, Ashley E Knowell, Jaideep Chaudhary
Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911852/long-non-coding-rna-xist-promotes-cell-growth-and-invasion-through-regulating-mir-497-macc1-axis-in-gastric-cancer
#13
Lei Ma, Yongjian Zhou, Xiaojun Luo, Hai Gao, Xubin Deng, Yingjie Jiang
Abnormal expression of long non-coding RNA (lncRNAs) often contributes to unrestricted growth and invasion of cancer cells. LncRNA XIST expression is up-regulated in several cancers, however, its modulatory mechanism in gastric cancer (GC) has not been elucidated. In the present study, we found that XIST expression was significantly increased in GC tissues and cell lines. LncRNA XIST promoted cell cycle progression from the G1 phase to the S phase and protected cells from apoptosis, which contributed to GC cell growth...
November 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910068/endometrial-carcinoma-specific-targeted-pathways
#14
Nuria Eritja, Andree Yeramian, Bo-Juen Chen, David Llobet-Navas, Eugenia Ortega, Eva Colas, Miguel Abal, Xavier Dolcet, Jaume Reventos, Xavier Matias-Guiu
Endometrial cancer (EC) is the most common gynecologic malignancy in the western world with more than 280,000 cases per year worldwide. Prognosis for EC at early stages, when primary surgical resection is the most common initial treatment, is excellent. Five-year survival rate is around 70 %.Several molecular alterations have been described in the different types of EC. They occur in genes involved in important signaling pathways. In this chapter, we will review the most relevant altered pathways in EC, including PI3K/AKT/mTOR, RAS-RAF-MEK-ERK, Tyrosine kinase, WNT/β-Catenin, cell cycle, and TGF-β signaling pathways...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27909065/cdk5-directly-targets-nuclear-p21cip1-and-promotes-cancer-cell-growth
#15
Pao-Hsuan Huang, Mei-Chih Chen, Yu-Ting Peng, Wei-Hsiang Kao, Chih-Hsiang Chang, Yun-Chi Wang, Chih-Ho Lai, Jer-Tsong Hsieh, Jo-Hsin Wang, Yueh-Tsung Lee, Eugene Lin, Chia-Herng Yue, Hsin-Yi Wang, Shuen-Chi You, Ho Lin
The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21(CIP1) from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21(CIP1) through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21(CIP1) protein degradation...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27909037/safety-and-efficacy-of-stereotactic-body-radiation-therapy-combined-with-s-1-simultaneously-followed-by-sequential-s-1-as-an-initial-treatment-for-locally-advanced-pancreatic-cancer-silapanc-trial-study-design-and-rationale-of-a-phase-ii-clinical-trial
#16
Xiaofei Zhu, Xiaoping Ju, Fei Cao, Fang Fang, Shuiwang Qing, Yuxin Shen, Zhen Jia, Yangsen Cao, Huojun Zhang
INTRODUCTION: Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine...
December 1, 2016: BMJ Open
https://www.readbyqxmd.com/read/27908178/a-probability-based-multi-cycle-sorting-method-for-4d-mri-a-simulation-study
#17
Xiao Liang, Fang-Fang Yin, Yilin Liu, Jing Cai
PURPOSE: To develop a novel probability-based sorting method capable of generating multiple breathing cycles of 4D-MRI images and to evaluate performance of this new method by comparing with conventional phase-based methods in terms of image quality and tumor motion measurement. METHODS: Based on previous findings that breathing motion probability density function (PDF) of a single breathing cycle is dramatically different from true stabilized PDF that resulted from many breathing cycles, it is expected that a probability-based sorting method capable of generating multiple breathing cycles of 4D images may capture breathing variation information missing from conventional single-cycle sorting methods...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27908159/a-preclinical-microbeam-facility-with-a-conventional-x-ray-tube
#18
Stefan Bartzsch, Craig Cummings, Stephan Eismann, Uwe Oelfke
PURPOSE: Microbeam radiation therapy is an innovative treatment approach in radiation therapy that uses arrays of a few tens of micrometer wide and a few hundreds of micrometer spaced planar x-ray beams as treatment fields. In preclinical studies these fields efficiently eradicated tumors while normal tissue could effectively be spared. However, development and clinical application of microbeam radiation therapy is impeded by a lack of suitable small scale sources. Until now, only large synchrotrons provide appropriate beam properties for the production of microbeams...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27906748/evolving-therapies-for-hepatitis-c-virus-in-chronic-kidney-disease-the-beginning-of-a-new-era
#19
Craig E Gordon, Claudia Nader
PURPOSE OF REVIEW: The current review highlights recent advances in treatment of chronic hepatitis C virus infection using new classes of agents, direct-acting antivirals (DAAs), with a focus on the evidence for their use in the setting of chronic kidney disease (CKD) stages 4-5, hemodialysis, and kidney transplantation. RECENT FINDINGS: DAA agents target-specific proteins involved in the hepatitis C virus life cycle and interrupt viral replication. Sustained virologic response, a marker of viral eradication, occurs in more than 90% of patients treated with DAA agents in the general population...
November 30, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27906655/methodology-considerations-in-phase-mapping-of-human-cardiac-arrhythmias
#20
Ramya Vijayakumar, Sunil K Vasireddi, Phillip S Cuculich, Mitchell N Faddis, Yoram Rudy
BACKGROUND: Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping. METHODS AND RESULTS: Seven subjects were enrolled...
November 2016: Circulation. Arrhythmia and Electrophysiology
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