Randomized phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer: cross-over analysis from the SHIVA trial
ConclusionsThe cross-over analysis of the SHIVA trial identified 37% of patients who crossed-over from TPC to MTA with a PFSMTA/PFSTPC ratio exceeding 1.3. (Source: Annals of Oncology)
Source: Annals of Oncology - December 19, 2016 Category: Cancer & Oncology Source Type: research

The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC)
Conclusion: The combination of PG plus MTA was superior to PG alone in terms of PFS and ORR but not in OS. The combination chemotherapy also showed a higher frequency of grade 3 or higher toxic effects in patients with advanced NSCLC than PG chemotherapy. (Source: Medicine)
Source: Medicine - December 1, 2016 Category: Internal Medicine Tags: Research Article: Systematic Review and Meta-Analysis Source Type: research

Genome-wide association mapping of resistance to eyespot disease (Pseudocercosporella herpotrichoides) in European winter wheat (Triticum aestivum L.) and fine-mapping of Pch1.
;der MS Abstract KEY MESSAGE: Genotypes with recombination events in the Triticum ventricosum introgression on chromosome 7D allowed to fine-map resistance gene Pch1, the main source of eyespot resistance in European winter wheat cultivars. Eyespot (also called Strawbreaker) is a common and serious fungal disease of winter wheat caused by the necrotrophic fungi Oculimacula yallundae and Oculimacula acuformis (former name Pseudocercosporella herpotrichoides). A genome-wide association study (GWAS) for eyespot was performed with 732 microsatellite markers (SSR) and 7761 mapped SNP markers derived from the 90 K ...
Source: TAG. Theoretical and Applied Genetics - November 19, 2016 Category: Genetics & Stem Cells Authors: Zanke CD, Rodemann B, Ling J, Muqaddasi QH, Plieske J, Polley A, Kollers S, Ebmeyer E, Korzun V, Argillier O, Stiewe G, Zschäckel T, Ganal MW, Röder MS Tags: Theor Appl Genet Source Type: research

Discovery and preclinical evaluation of 7-benzyl-N-(substituted)-pyrrolo[3,2-d]pyrimidin-4-amines as single agents with microtubule targeting effects along with triple-acting angiokinase inhibition as antitumor agents.
Abstract The utility of cytostatic antiangiogenic agents (AA) in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of AA with microtubule targeting agents (MTAs) have been particularly successful. The discovery, synthesis and biological evaluations of a series of 7-benzyl-N-substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported. Novel compounds which inhibit proangiogenic receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth fa...
Source: Bioorganic and Medicinal Chemistry - November 15, 2016 Category: Chemistry Authors: Pavana RK, Choudhary S, Bastian A, Ihnat MA, Bai R, Hamel E, Gangjee A Tags: Bioorg Med Chem Source Type: research

Belinostat and Vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma.
Abstract Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy that has a 60 percent five-year survival rate, highlighting a need for new therapeutic approaches. Histone deacetylase inhibitors (HDACi) are novel therapeutics being clinically-evaluated in combination with a variety of other drugs. However, rational selection of companion therapeutics for HDACi is difficult due to their poorly-understood, cell-type specific mechanisms of action. To address this, we developed a pre-clinical model system of sensitivity and resistance to the HDACi belinostat using DLBCL cell lines. In the current study, we d...
Source: Cancer Biology and Therapy - October 28, 2016 Category: Cancer & Oncology Authors: Havas AP, Rodrigues KB, Bhakta A, Demirjian JA, Hahn S, Tran J, Scavello M, Tula-Sanchez AA, Zeng Y, Schmelz M, Smith CL Tags: Cancer Biol Ther Source Type: research

Hydration behaviors of calcium silicate-based biomaterials
Conclusion Mineral oxides might not result in significant changes in the crystal phases or microstructures during the hydration of CS-based biomaterials, but these compounds affected the hydration behavior at the molecular level. (Source: Journal of the Formosan Medical Association)
Source: Journal of the Formosan Medical Association - September 20, 2016 Category: Journals (General) Source Type: research

Hydration behaviors of calcium silicate-based biomaterials.
CONCLUSION: Mineral oxides might not result in significant changes in the crystal phases or microstructures during the hydration of CS-based biomaterials, but these compounds affected the hydration behavior at the molecular level. PMID: 27663276 [PubMed - as supplied by publisher] (Source: J Formos Med Assoc)
Source: J Formos Med Assoc - September 20, 2016 Category: Journals (General) Authors: Lee YL, Wang WH, Lin FH, Lin CP Tags: J Formos Med Assoc Source Type: research

Optimal sequential enrichment designs for phase II clinical trials
In the early phase development of molecularly targeted agents (MTAs), a commonly encountered situation is that the MTA is expected to be more effective for a certain biomarker subgroup, say marker‐positive patients, but there is no adequate evidence to show that the MTA does not work for the other subgroup, that is, marker‐negative patients. After establishing that marker‐positive patients benefit from the treatment, it is often of great clinical interest to determine whether the treatment benefit extends to marker‐negative patients. The authors propose optimal sequential enrichment (OSE) designs to address this pr...
Source: Statistics in Medicine - September 19, 2016 Category: Statistics Authors: Yong Zang, Ying Yuan Tags: Research Article Source Type: research

Combination treatment including targeted therapy for advanced hepatocellular carcinoma.
Authors: Lin J, Wu L, Bai X, Xie Y, Wang A, Zhang H, Yang X, Wan X, Lu X, Sang X, Zhao H Abstract Management of advanced hepatocellular carcinoma (HCC), one of the most lethal cancers worldwide, has presented a therapeutic challenge over past decades. Most patients with advanced HCC and a low possibility of surgical resection have limited treatment options and no alternative but to accept local or palliative treatment. In the new era of cancer therapy, increasing numbers of molecular targeted agents (MTAs) have been applied in the treatment of advanced HCC. However, mono-targeted therapy has shown disappointing out...
Source: Oncotarget - September 16, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Raising concern about the information provided on medical travel agency websites: A place for policy
This study examined the information provided by European MTA websites using a modified version of the Health on the Net (HON) code. A content analysis of the information collected assessed how the MTA websites promoted their services and communicated the risks, benefits and other issues related to medical travel. Twenty-seven websites based in thirteen different European countries were identified and coded using a modified version of the HON tool. Considerable inconsistencies across websites were noted on all domains assessed and no single item of the tool was addressed by all websites. The most frequently included item on...
Source: Health Policy and Technology - August 31, 2016 Category: Health Management Source Type: research

Genome wide association mapping of stripe rust resistance in Afghan wheat landraces
Publication date: Available online 1 August 2016 Source:Plant Science Author(s): Alagu Manickavelu, Reem Joukhadar, Abdulqader Jighly, Caixia Lan, Julio Huerta-Espino, Ahmad Shah Stanikzai, Andrzej Kilian, Ravi P. Singh, Tomohiro Ban Mining of new genetic resources is of paramount importance to combat the alarming spread of stripe rust disease and breakdown of major resistance genes in wheat. We conducted a genome wide association study on 352 un-utilized Afghan wheat landraces against stripe rust resistance in eight locations. High level of disease variation was observed among locations and a core-set of germplasm showed...
Source: Plant Science - August 3, 2016 Category: Biology Source Type: research

Vincristine-Induced Interphase Death in Leukemia Cells
In this study, we sought to develop and characterize an experimental system in which to test the hypothesis that MTAs induce cell death during interphase. Primary adult acute lymphoblastic leukemia (ALL) cells treated with vincristine only weakly exhibited colocalization between mitotic and apoptotic markers and major characteristics of mitotic death, such as an increase in cells with 4N DNA content before the appearance of cells with (Source: Cancer Research)
Source: Cancer Research - June 14, 2016 Category: Cancer & Oncology Authors: Kothari, A., Hittelman, W. N., Chambers, T. C. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

An adaptive dose‐finding method using a change‐point model for molecularly targeted agents in phase I trials
In this study, we propose a novel adaptive dose‐finding approach based on binary efficacy and toxicity outcomes in phase I trials for monotherapy using an MTA. We develop a dose–efficacy model, the parameters of which are allowed to change in the vicinity of the change point of the dose level, in order to consider the non‐monotonic pattern of the dose–efficacy relationship. The change point is obtained as the dose that maximizes the log‐likelihood of the assumed dose–efficacy and dose‐toxicity models. The dose‐finding algorithm is based on the weighted Mahalanobis distance, calculated using the ...
Source: Statistics in Medicine - May 11, 2016 Category: Statistics Authors: Hiroyuki Sato, Akihiro Hirakawa, Chikuma Hamada Tags: Research Article Source Type: research

An adaptive dose ‐finding method using a change‐point model for molecularly targeted agents in phase I trials
In this study, we propose a novel adaptive dose‐finding approach based on binary efficacy and toxicity outcomes in phase I trials for monotherapy using an MTA. We develop a dose–efficacy model, the parameters of which are allowed to change in the vicinity of the change point of the dose level, in order to consider the non‐monotonic pattern of the dose–efficacy relationship. The change point is obtained as the dose that maximizes the log‐likelihood of the assumed dose–efficacy and dose‐toxicity models. The dose‐finding algorithm is based on the weighted Mahalanobis distance, calculated using the ...
Source: Statistics in Medicine - May 11, 2016 Category: Statistics Authors: Hiroyuki Sato, Akihiro Hirakawa, Chikuma Hamada Tags: Research Article Source Type: research

Push-out Bond Strength of Root-end Filling Materials.
Abstract The aim of this study was to evaluate the bond strength of root-end filling materials. Forty 2-mm-thick slices were obtained from human single-rooted teeth. After root canal preparation using a 1.5 mm diameter cylindrical drill, the dentinal walls were prepared by diamond ultrasonic tip (CVD T0F-2). The specimens were divided according the material (n=10): MTA Angelus (MTAA), MTA Sealer (MTAS, experimental), Sealer 26 (S26) and zinc oxide and eugenol cement (ZOE). The push-out test was performed in a mechanical test machine (EMIC DL 2000) at 1 mm/min speed. The failure type was evaluated by stereomicrosco...
Source: Braz Dent J - May 1, 2016 Category: Dentistry Authors: Vivan RR, Guerreiro-Tanomaru JM, Bosso-Martelo R, Costa BC, Duarte MA, Tanomaru-Filho M Tags: Braz Dent J Source Type: research

Ubiquinol and plastoquinol triphenylphosphonium conjugates can carry electrons through phospholipid membranes.
Abstract Many mitochondria-targeted antioxidants (MTAs) that comprise a quinol moiety covalently attached through an aliphatic carbon chain to the lipophilic triphenylphosphonium cation are widely used for evaluating the role of mitochondria in pathological processes involving oxidative stress. The potency of MTAs to carry electrons across biological membranes and thereby mediate transmembrane redox processes was unknown. To assess this, we measured the rate of ferricyanide reduction inside liposomes by external ascorbate. Here, we show that MTAs containing ubiquinone (MitoQ series) or plastoquinone (SkQ series) c...
Source: Bioelectrochemistry - April 28, 2016 Category: Biochemistry Authors: Rokitskaya TI, Murphy MP, Skulachev VP, Antonenko YN Tags: Bioelectrochemistry Source Type: research

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials [Statistical Analysis]
Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. (Source: Journal of Clinical Oncology)
Source: Journal of Clinical Oncology - April 13, 2016 Category: Cancer & Oncology Authors: Lee, Backenroth, Cheung, Hershman, Vulih, Anderson, Ivy, Minasian Tags: Clinical Trials, Phase I and Clinical Pharmacology, Statistics in Oncology Statistical Analysis Source Type: research

The Many Faces of MTA3 Protein in Normal Development and Cancers.
Abstract As a family of chromatin remodeling proteins, metastasis-associated proteins (MTAs) have shown to be the master regulators in both physiological and pathological context. Although MTA3 is the latest being identified in MTA family, it has started to draw as much attention as the other family members. MTA3 is expressed in various tissues and is associated with different physiological functions. In cancerous context, both MTA1 and MTA2 are generally considered as oncogenes because they are capable of enhancing metastasis. However, MTA3 appears to play more complicated roles in cancers depending on the contex...
Source: Current Protein and Peptide Science - April 1, 2016 Category: Biochemistry Authors: Ma L, Yao Z, Deng W, Zhang D, Zhang H Tags: Curr Protein Pept Sci Source Type: research

Targeting of tubulin polymerization and induction of mitotic blockage by Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) in human cervical cancer HeLa cell
Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are widely used in the treatment of various cancers. As with most chemotherapeutic agents, adverse effects and drug resi... (Source: Journal of Experimental and Clinical Cancer Research)
Source: Journal of Experimental and Clinical Cancer Research - March 31, 2016 Category: Cancer & Oncology Authors: Mohadeseh Hasanpourghadi, Chandrabose Karthikeyan, Ashok Kumar Pandurangan, Chung Yeng Looi, Piyush Trivedi, Kinue Kobayashi, Kozo Tanaka, Won Fen Wong and Mohd Rais Mustafa Source Type: research

Beyond the dose‐limiting toxicity period: Dermatologic adverse events of patients on phase 1 trials of the Cancer Therapeutics Evaluation Program
BACKGROUNDDermatologic adverse events (AEs) can be key determinants of overall drug tolerability and of the maximum tolerated and recommended phase 2 doses in phase 1 trials. The authors present the largest dedicated analysis of dermatologic AEs on phase 1 trials to date. METHODSData from a prospectively maintained database of patients with solid tumors who were enrolled onto Cancer Therapeutics Evaluation Program (CTEP)‐sponsored phase 1 trials of cytotoxic or molecularly targeted agents (MTAs) from 2000 to 2010 were analyzed. Cumulative incidence, site, and type of drug‐related dermatologic AEs were described and com...
Source: Cancer - February 25, 2016 Category: Cancer & Oncology Authors: Alexander Drilon, Anne A. Eaton, Katja Schindler, Mrinal M. Gounder, David R. Spriggs, Pamela Harris, S. Percy Ivy, Alexia Iasonos, Mario E. Lacouture, David M. Hyman Tags: Original Article Source Type: research

Abstract P5-03-08: Eribulin impairs the transport of TGF-{beta} type I receptor leading to inhibition of downstream non-canonical TGF-{beta} signaling necessary for cancer metastasis and survival
Microtubule targeting agents (MTAs) continue to be some of the most valuable drugs used in the treatment of breast cancers. While decades of research have shown that these drugs cause mitotic arrest in cells by suppressing the dynamic instability of microtubules, recent evidence demonstrates that the ability of MTAs to disrupt microtubule-dependent transport of key signaling components, including proteins and microRNAs, in interphase cells likely contributes to their anticancer actions. TGF-β receptors are known to undergo constant cycling from the plasma membrane to intracellular portions of the cell, a process which...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Rohena, C., Kaul, R., Risinger, A., Mooberry, S. Tags: Poster Session Abstracts Source Type: research

Abstract P5-03-09: Eribulin affects E-cadherin localization consistent with a reversal of the epithelial-to-mesenchymal transition
Microtubule targeting agents (MTAs) are some of the most important compounds used to treat breast cancer. While both microtubule stabilizers and destabilizers have utility against breast cancers, not all patients respond and there are differences among the agents. Eribulin is a microtubule depolymerizer used to treat patients with locally advanced or metastatic breast cancerwho have previously received at least two chemotherapeutic regimens, including an anthracycline and a taxane. Our goal was to compare the effects of eribulin to four other clinically relevant MTAs on signaling processes important for cancer cell metasta...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Dybdal-Hargreaves, N., Rohena, C., Risinger, A., Mooberry, S. Tags: Poster Session Abstracts Source Type: research

Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.
Abstract Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivi...
Source: Experimental Neurology - February 13, 2016 Category: Neurology Authors: Pittman SK, Gracias NG, Fehrenbacher JC Tags: Exp Neurol Source Type: research

Effect of ultrasonic tip and root-end filling material on bond strength
Conclusions The CVD tip favored higher bond strength of the root-end filling materials. MTA Angelus and experimental MTAS presented bond strength to dentin prepared with ultrasonic tips. Clinical relevance Root-end preparation with the CVD tip positively influences the bond strength of root-end filling materials. MTA Angelus and experimental MTAS present bond strength to be used as root-end filling materials. (Source: Clinical Oral Investigations)
Source: Clinical Oral Investigations - January 9, 2016 Category: Dentistry Source Type: research

Abstract B34: Coordinated delivery of anticancer drug combinations incorporating molecularly targeted agents provides markedly increased plasma drug exposure, decreased toxicity and increased efficacy in preclinical tumor models
Conclusions: HPN-mediated coordinated delivery of drug combinations incorporating molecularly targeted agents can favorably shift the PK/PD profile resulting in an improved therapeutic index. Initial results suggest this may expand the utility of combinations that to date have been limited by toxicities associated with dosing regimens aimed at ensuring simultaneous and durable multi-target inhibition.Citation Format: Lawrence D. Mayer, Paul Tardi, Sherwin Xie, Barry Liboiron, Winnie Lui, Leon Wan. Coordinated delivery of anticancer drug combinations incorporating molecularly targeted agents provides markedly increased plas...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Mayer, L. D., Tardi, P., Xie, S., Liboiron, B., Lui, W., Wan, L. Tags: Drug Delivery: Poster Presentations - Proffered Abstracts Source Type: research

Changing first degrees of OMFS trainees and specialists 1996–2020
Introduction: For most of its history, oral and maxillofacial surgery has been a surgical specialty for those who have trained in dentistry. Even when dual medical and dental qualifications became mandated, most trainees undertook medicine as their second degree. In the last decade two major changes in training had a joint impact on OMFS training, availability and access to shortened dental degrees for medical graduates and the training earthquake of the Medical Training Appointment Service (MTAS). (Source: The British Journal of Oral and Maxillofacial Surgery)
Source: The British Journal of Oral and Maxillofacial Surgery - December 1, 2015 Category: ENT & OMF Authors: P. Magennis, A. Begley, S. Dover Tags: PP 116 Source Type: research

Meta-analysis of molecular targetted agents in the treatment of elderly patients with metastatic colorectal cancer: does the age matter?
Authors: Zhao C, Li S, Liu Q Abstract AIM: Patients aged 65 years and older are often under-represented in clinical trials of metastatic colorectal cancer (mCRC) and probably undertreated in clinical practice. We performed a meta-analysis of randomized controlled trials to assess the efficacy of molecular targetted agents (MTAs) in this population. METHODS: A comprehensive literature search for studies published up to December 2014 was performed. The endpoints were overall survival (OS) and progression-free survival (PFS). The pooled hazard ratio (HR) and 95% confidence intervals (CI) were calculated employin...
Source: Journal of Chemotherapy - November 18, 2015 Category: Cancer & Oncology Tags: J Chemother Source Type: research

Efficacy and toxicity of molecular targeted therapies in combination with docetaxel for metastatic castration-resistant prostate cancer: a meta-analysis of phase III randomized controlled trials.
CONCLUSIONS: The findings of this study suggest that the palliation of CRPC with MTAs and docetaxel does not provide a significant survival benefit and is associated with increased severe toxicities. PMID: 25492160 [PubMed - in process] (Source: Journal of Chemotherapy)
Source: Journal of Chemotherapy - November 18, 2015 Category: Cancer & Oncology Tags: J Chemother Source Type: research

"are doses and schedules of small molecule targeted anticancer drugs recommended by phase i studies realistic?"
"ARE DOSES AND SCHEDULES OF SMALL MOLECULE TARGETED ANTICANCER DRUGS RECOMMENDED BY PHASE I STUDIES REALISTIC?" Clin Cancer Res. 2015 Nov 18; Authors: Roda D, Jimenez B, Banerji U Abstract Tolerability of molecularly targeted agents (MTA) used in cancer therapeutics are determined in phase I trials. We reviewed the reported incidence of toxicity in phase III trials at doses and schedules recommended by phase I trials to evaluate if these recommendations are realistic when drugs are used in larger populations of patients. We systematically reviewed a safety profile of small molecule (SM-MTA) ...
Source: Clinical Cancer Research - November 18, 2015 Category: Cancer & Oncology Authors: Roda D, Jimenez B, Banerji U Tags: Clin Cancer Res Source Type: research

Withdrawal of anticancer therapy in advanced disease: a systematic literature review
Conclusions: Oncologists report that decisions around stopping chemotherapy treatment are challenging, with limited evidence-based guidance outside of clinical trial protocols. The increasing availability of oral MTAs is transforming the management of incurable cancer; blurring boundaries between active treatment and palliative care. No studies specifically addressing decision-making around stopping MTAs in clinical practice were identified. There is a need to develop an evidence base to support physicians and patients with decision-making around the withdrawal of these high cost treatments. (Source: BMC Cancer)
Source: BMC Cancer - November 11, 2015 Category: Cancer & Oncology Authors: G. ClarkeS. JohnstonP. CorrieI. KuhnS. Barclay Source Type: research

The changing landscape of phase I trials in oncology
Nature Reviews Clinical Oncology 13, 106 (2016). doi:10.1038/nrclinonc.2015.194 Authors: Kit Man Wong, Anna Capasso & S. Gail Eckhardt Advances in our knowledge of the molecular pathogenesis of cancer have led to increased interest in molecularly targeted agents (MTAs), which target specific oncogenic drivers and are now a major focus of cancer drug development. MTAs differ from traditional cytotoxic agents in various aspects, including (Source: Nature Clinical Practice Oncology)
Source: Nature Clinical Practice Oncology - November 10, 2015 Category: Cancer & Oncology Authors: Kit Man WongAnna CapassoS. Gail Eckhardt Tags: Review Source Type: research

Abstract 657: Microtubule stabilizers inhibit the cellular transport and signaling of EGFR in breast cancer cells
Breast cancer is the second most diagnosed cancer in women and it is estimated that approximately 40,000 women die every year from this disease in this country alone. The overexpression of EGFR in breast cancer is associated with drug resistance and an aggressive nature resulting in an overall poor outcome. The EGFR signaling pathway requires internalization of the receptor, endosomal translocation and in some cases nuclear accumulation of the receptor. These processes are dependent on functional microtubules. Microtubule targeting agents (MTAs) have been used with great success in the treatment of breast cancer alone and ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rohena, C. C., Dybdal-Hargreaves, N. F., Mooberry, S. L. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 2609: Disruption of CAS scaffolds: A novel mechanism for microtubule targeting agents
Microtubule targeting agents (MTAs) are an important class of anticancer drugs. While their anticancer mechanisms were considered exclusively as antimitotic for decades, evidence now suggests that the ability of MTAs to inhibit functions of interphase microtubules likely plays an essential role in their clinical anticancer actions. Interphase microtubules are responsible for intracellular trafficking of many constituents including proteins involved in signal transduction. Efficient signal transduction requires precise coordination of signaling partners through their appropriate localization. Scaffold proteins regulate sign...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dybdal-Hargreaves, N. F., Rohena, C. C., Risinger, A. L., Mooberry, S. L. Tags: Experimental and Molecular Therapeutics Source Type: research

Towards using a full spectrum of early clinical trial data: a retrospective analysis to compare potential longitudinal categorical models for molecular targeted therapies in oncology
Following the pattern of phase I clinical trials for cytotoxic drugs, dose‐finding clinical trials in oncology of molecularly targeted agents (MTA) aim at determining the maximum tolerated dose (MTD). In classical phase I clinical trials, MTD is generally defined by the number of patients with short‐term major treatment toxicities (usually called dose‐limiting toxicities, DLT), occurring during the first cycle of study treatment (e.g. within the first 3weeks of treatment). However, S. Postel‐Vinay (2011) highlighted that half of grade 3 to 4 toxicities, usually considered as DLT, occur after the first cycle of MTA ...
Source: Statistics in Medicine - June 9, 2015 Category: Statistics Authors: Pierre Colin, Sandrine Micallef, Maud Delattre, Pierre Mancini, Eric Parent Tags: Special Issue Paper Source Type: research

Assessment of Simplified Blood Dose Protocols for the Estimation of the Maximum Tolerable Activity in Thyroid Cancer Patients Undergoing Radioiodine Therapy Using 124I
Conclusion: The pretherapy blood dosimetry protocol can be substantially shortened and may be beneficial to patients and patient management while reducing the radiation exposure to medical staff. (Source: Journal of Nuclear Medicine)
Source: Journal of Nuclear Medicine - June 1, 2015 Category: Nuclear Medicine Authors: Jentzen, W., Bockisch, A., Ruhlmann, M. Tags: Clinical Investigations Source Type: research

Marker-trait association study for protein content in chickpea (Cicer arietinum L.).
The objective of the present study was to study variation for protein content in chickpea germplasm, and to find markers associated with it. A set of 187 genotypes comprising both international and exotic collections, and representing both desi and kabuli types with protein content ranging from 13.25% to 26.77% was used. Twenty-three SSR markers representing all eight linkage groups (LG) amplifying 153 loci were used for the analysis. Population structure analysis identified three subpopulations, and corresponding Q values of principal components were used to take care of population structure in the analysis which was perf...
Source: Journal of Genetics - June 1, 2015 Category: Genetics & Stem Cells Authors: Jadhav AA, Rayate SJ, Mhase LB, Thudi M, Chitikineni A, Harer PN, Jadhav AS, Varshney RK, Kulwal PL Tags: J Genet Source Type: research

Antiproliferative effects of mitochondria-targeted cationic antioxidants and analogs: role of mitochondrial bioenergetics and energy-sensing mechanism
• Mitochondria-targeted antioxidants (MTAs) inhibit proliferation of cancer cells.• Radical scavenging properties are not necessary for antiproliferative effects of MTAs.• Inhibition of bioenergetic function is a common feature of different MTAs. (Source: Cancer Letters)
Source: Cancer Letters - May 21, 2015 Category: Cancer & Oncology Authors: Gang Cheng, Jacek Zielonka, Donna McAllister, Micael Hardy, Olivier Ouari, Joy Joseph, Michael B. Dwinell, Balaraman Kalyanaraman Tags: Original Articles Source Type: research

Orientated Guidance of Peripheral Nerve Regeneration Using Conduits with a Microtube Array Sheet (MTAS)
ACS Applied Materials & InterfacesDOI: 10.1021/acsami.5b00215 (Source: ACS Applied Materials and Interfaces)
Source: ACS Applied Materials and Interfaces - April 17, 2015 Category: Materials Science Authors: Yueming Wang, Wenjin Wang, Yan Wo, Ting Gui, Hao Zhu, Xiumei Mo, Chien-Chung Chen, Qingfeng Li and Wenlong Ding Source Type: research

O3.4 * A first-in-human study of intravenous BAL101553, a novel microtubule inhibitor, in patients with advanced solid tumors
Conclusions: The MTD for BAL101553 administered as 2-h IV infusion at days 1, 8 and 15 of 28-day cycles was 60 mg/m2. Clinical activity observed at dose levels of 15-30 mg/m2 together with preclinical evidence of reduced tumour disposition at high vascular-disrupting doses indicate that a lower dose may be preferable by providing cytotoxic and intermediate anti-vascular effects without major toxicity. A randomised Phase 2a study in patients with advanced solid tumors with treatment at MTD and at 50% MTD is ongoing. (NCT01397929). (Source: Annals of Oncology)
Source: Annals of Oncology - March 20, 2015 Category: Cancer & Oncology Authors: Rhoda Molife, L., King, J., Smith, A., D'arcangelo, M., Brown, N., Diamantis, N., Lane, H., Schmitt Hoffmann, A. H., Engelhardt, M., Plummer, R., Kristeleit, R. Tags: Plenary session 3: Phase 1 studies: Miscellaneous drugs & amp; targets Source Type: research

Managing Human Tissue Transfer Across National Boundaries – An Approach from an Institution in South Africa
This article will examine three significantly important ethico‐legal concepts that were deliberated and carefully adapted by a South African Institution to suit the transfer of Human Biological Materials (HBMs) and associated data for biobank research, namely: informed consent; benefit sharing arrangements; and ownership together with intellectual property rights in human tissues. The discussion includes an analysis of current practice; the ethico‐legal challenges in the South African/African context; the decisions made with regard to how the related ethico‐legal challenges were addressed in the MTA; and justificatio...
Source: Developing World Bioethics - February 17, 2015 Category: Medical Ethics Authors: Safia Mahomed, Kevin Behrens, Melodie Slabbert, Ian Sanne Tags: Original Article Source Type: research

Microtubule inhibitors impede DNA repair proteins [Medical Sciences]
The paradigm that microtubule-targeting agents (MTAs) cause cell death via mitotic arrest applies to rapidly dividing cells but cannot explain MTA activity in slowly growing human cancers. Many preferred cancer regimens combine a MTA with a DNA-damaging agent (DDA). We hypothesized that MTAs synergize with DDAs by interfering with trafficking... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 3, 2015 Category: Science Authors: Poruchynsky, M. S., Komlodi-Pasztor, E., Trostel, S., Wilkerson, J., Regairaz, M., Pommier, Y., Zhang, X., Kumar Maity, T., Robey, R., Burotto, M., Sackett, D., Guha, U., Fojo, A. T. Tags: Biological Sciences Source Type: research

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.
Authors: Hur EM, Lee BD Abstract Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been p...
Source: International Neurourology Journal - January 10, 2015 Category: Urology & Nephrology Tags: Int Neurourol J Source Type: research

Different Effects of antimitotic drug on mechanical behaviors of Cancer cytoskeleton: Investigating distinct Grades of "colon Cancer cell lines"
Biomechanical behaviors of cells alter during cancer progression which strongly depends on changes in the main cytoskeletal proteins. Microtubules have a vital role in mitosis and in supporting the integrity of the cell due to their ability to withstand high compressive loads. Accordingly, microtubule-targeting agents (MTAs) have become one of the most promising classes of drugs in cancer therapy. In the present study, alterations of viscoelastic parameters induced by an appropriate concentration of an antimitotic drug on two different grades of colon cancer cells were evaluated. (Source: Journal of Biomechanics)
Source: Journal of Biomechanics - December 12, 2014 Category: Biomedical Science Authors: S.M. Seyedpour, M. Pachenari, M. Janmaleki, M. Alizadeh, H. Hosseinkhani Source Type: research

Effects of an antimitotic drug on mechanical behaviours of the cytoskeleton in distinct grades of colon cancer cells
This study evaluated changes in visco-elastic parameters induced by an appropriate concentration of an antimitotic drug in two different grades of colon cancer cells. (Source: Journal of Biomechanics)
Source: Journal of Biomechanics - December 12, 2014 Category: Biomedical Science Authors: S.M. Seyedpour, M. Pachenari, M. Janmaleki, M. Alizadeh, H. Hosseinkhani Source Type: research

Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents.
ute;ñez MJ Abstract Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents (MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues of slippages and resistance, and cause significant side effects. The advances in the identification of other mitosis-related targets led to the development of new mitotic regulators aimed to perturb mitosis without interfering with microtubule dynamics in non-dividing cells trying to reduce side effects in patients. Some of these compounds like those targeted to entry and mitotic kinase...
Source: Current Topics in Medicinal Chemistry - November 29, 2014 Category: Chemistry Authors: Novío S, Freire-Garabal M, Núñez MJ Tags: Curr Top Med Chem Source Type: research

Bayesian dose‐finding designs for combination of molecularly targeted agents assuming partial stochastic ordering
Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose‐finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as the lowest dose combinations (in a certain sense) that are safe and have the highest efficacy level meeting a prespecified target. The limited existing designs for these trials use parametric dose–efficacy and dose–toxic...
Source: Statistics in Medicine - November 21, 2014 Category: Statistics Authors: Beibei Guo, Yisheng Li Tags: Research Article Source Type: research

Disease resistance breeding in rose: Current status and potential of biotechnological tools
Publication date: November 2014 Source:Plant Science, Volume 228 Author(s): Thomas Debener , David H. Byrne The cultivated rose is a multispecies complex for which a high level of disease protection is needed due to the low tolerance of blemishes in ornamental plants. The most important fungal diseases are black spot, powdery mildew, botrytis and downy mildew. Rose rosette, a lethal viral pathogen, is emerging as a devastating disease in North America. Currently rose breeders use a recurrent phenotypic selection approach and perform selection for disease resistance for most pathogen issues in a 2–3 year field trial...
Source: Plant Science - November 9, 2014 Category: Biology Source Type: research

Making Sense of Nice's ‘New' MTA and STA Process Guide: A Narrative Synthesis
The objective of this analysis was to identify the number and type of amendments within the guides in order to highlight the most important changes for consultees and commentators. (Source: Value in Health)
Source: Value in Health - November 1, 2014 Category: Global & Universal Authors: M. Urbich, M. Mildred Source Type: research

Metastatic tumor antigen in hepatocellular carcinoma: golden roads toward personalized medicine
Abstract Hepatocellular carcinoma (HCC), a prototype of hypervascular tumors, is one of the most common malignancies in the world, especially hyperendemic in the Far East where chronic hepatitis B virus (HBV) infection is highly prevalent. It is characterized by the clinical feature of a poor prognosis or a high mortality due to its already far advanced stages at diagnosis. It is so multifactorial that hepatocarcinogenesis cannot be explained by a single molecular mechanism. To date, a number of pathways have been known to contribute to the development, growth, angiogenesis, and even metastasis of HCC. Among the v...
Source: Cancer and Metastasis Reviews - October 18, 2014 Category: Cancer & Oncology Source Type: research

Abstract LB-106: Microtubule-targeting agents (MTAs) disrupt intracellular trafficking of DNA repair proteins and augment the toxicity of DNA damaging agents (DDAs)
MTAs have long been thought to cause cell death primarily by inducing mitotic arrest, a paradigm that applies to rapidly dividing cells in preclinical models. However, mitotic arrest cannot explain the activity of MTAs in much more slowly growing human cancers. In the latter, we have proposed interference with trafficking on interphase microtubules (MTs) as the principal mechanism of cytotoxicity. Satisfying this paradigm requires identification of the proteins whose trafficking on MTs, when disrupted, leads to cytotoxicity. MTAs in combination with DNA-damaging agents (DDAs) have emerged as preferred regimens for the trea...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Poruchynsky, M. S., Komlodi-Pasztor, E., Wilkerson, J., Trostel, S., Burroto-Pichun, M., Fojo, T. Tags: Experimental and Molecular Therapeutics Source Type: research